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Acta Neurochirurgica

Supplements
Editor: H.-J. Reulen
Assistant Editor: H.-J. Steiger

Neurosurgical Management
of Aneurysmal Subarachnoid Haemorrhage
Edited by
I. A. Langmoen, T. Lundar, R. Aaslid,
H.-J. Reulen
Acta Neurochirurgica
Supplement 72

Springer-Verlag Wien GmbH

Iver A. Langmoen, M.D., Ph.D.


Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden

Tryggve Lundar
Department of Neurosurgery, Rikshospitalet, The National Hospital, Oslo, Norway

Rune Aaslid, Ph.D.


Department of Neurological Surgery, Harborview Medical Center, Seattle, U.S.A.

Hans-J. Reulen, M.D.


Department of Neurosurgery, Klinikum GroBhadern, Munich, Germany
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1999 Springer-Verlag Wien


Originally published by Springer-Verlag/Wien in 1999
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With 66 Figures

Library of Congress Cataloging-in-Publication Data


Management of aneurysmal subarachnoid haemorrhage / edited by
I.A.Langmoen ... let al.].
p.
cm. - (Acta neurochirurgica. Supplement, ISSN 0065-1419
; 72)
Includes index.
ISBN 978-3-7091-6377-1 (eBook)
ISBN 978-3-7091-7309-1
DOI 10.1007/978-3-7091-6377-1
1. Intracranial aneurysms-Surgery. 2. Subarachnoid hemorrhage.
3. Brain-Blood-vessels-Surgery. I. Langmoen, Iver Ame.
II. Series.
[DNLM: 1. Cerebral Aneurysm-therapy. 2. Subarachnoid Hemorrhage-therapy. WI AC8661 no. 72 1999]
RD594.2M35 1999
617.4'81-dc21
DNLMlDLC
99-19266
for Library of Congress
CIP

ISSN 0065-1419

ISBN 978-3-7091-7309-1

Preface

The small neck of the aneurysm afforded an easy surgical attack. An ordinary flat silver clip was placed over the
sac and tightly compressed obliterated it completely. The clip was flush with the wall of the carotid artery. The sac,
lateral to the silver clip, was then picked up with the forceps and thrombosed by the electocautery.
Walter Dandy reporting his successful operation of a posterior
communicating aneurysm on March 23, 1937.

Walter Dandy's patient left the hospital in good health 2 weeks later, and from his report one may gain the
impression that the operation was an easy task. Despite continuous developments during the following decades, it
was not until the introduction of the operating microscope and microsurgical techniques that surgical treatment
was generally accepted.
During the microsurgical era surgical results have continued to improve due to diagnostical, neuroanaesthesiological, and microsurgical refinements, and improved neurointensive care. Endovascular obliteration has
become an important treatment alternative but this has not been included in this particular volume.
The purpose of the present supplement of the ACTA NEUROCHIRURGICA is to review some of the elements
in the neurosurgical management of patients with aneurysmal subarachnoid haemorrhage that are important for a
successful outcome. Professor Helge Nornes has been a major force in the development of new techniques and
research strategies in this area for a number of years and has recently retired from the National Hospital in Oslo.
Helge Nornes has been a Co-Editor of ACTA NEUROCHIRURGICA since 1987. In this position he cooperated
closely with Fritz Loew and Luc Calliauw, the former and the present Chief Editor. With his strong engagement
and influence he played an important part in making ACTA NEUROCHIRURGICA one of the leading neurosurgical journals.
Some of his pupils, friends and colleagues decided to express their friendship, gratitude and respect by
dedicating this volume to him. He has all our good wishes.
Iver A. Langmoen
Tryggve Lundar
Rune Aaslid
Hans-J. Reulen
Luc Calliauw

Contents

Langmoen, I.A., Lundar, T.:


A Tribute to Helge Nornes .............................................................. .
Le Roux, P. D., Winn, H. R.:
Intracranial Aneurysms and Subarachnoid Hemorrhage Management of the Poor Grade Patient

Weir, B., Loch Macdonald, R., Stoodley, M.:


Etiology of Cerebral Vasospasm ..........................................................

27

Aaslid, R.:
Hemodynamics of Cerebrovascular Spasm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

47

Lindegaard, K.-F.:
The Role of Transcranial Doppler in the Management of Patients with Subarachnoid Haemorrhage a Review.............................................................................

59

Persson, L., Enblad, P.:


Neurointensive Care of Aneurysmal SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

73

Steiger, H.-f., van Loon, f. f. L.:


Virtues and Drawbacks of Titanium Alloy Aneurysm Clips

81

Dolenc, v. V.:
A Combined Transorbital-Transclinoid and Transsylvian Approach to Carotid-Ophthalmic Aneurysms
Without Retraction of the Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

89

Dolenc, V. V.:
Extradural Approach to Intracavemous ICA Aneurysms

99

Langmoen, I. A., Ekseth, K., Hauglie-Hanssen, E., Nomes, H.:


Surgical Treatment of Anterior Circulation Aneurysms ........................................

107

Yonekawa, Y., Kaku, Y., Imhof, H. G., Kiss, M., Curcic, M., Taub, E., Roth, P.:
Posterior Circulation Aneurysms. Technical Strategies Based on Angiographic Anatomical Findings
and the Results of 60 Recent Consecutive Cases .............................................

123

Lawton, M. T., Spetzler, R. F.:


Surgical Strategies for Giant Intracranial Aneurysms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..

141

Hiitter, B. 0., Kreitschmann-Andermahr, I., Mayfrank, L., Rohde, V., Spetzger, U., Gilsbach, f. M.:
Functional Outcome After Aneurysmal Subarachnoid Hemorrhage ..............................

157

Author Index .........................................................................

175

Index of Keywords ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..

177

Listed in Current Contents

Acta Neurochir (1999) [Suppl]72: 1-5


Springer-Verlag 1999

A Tribute to Helge Nornes


I. A. Langmoen 1 and T. Lundar 2
1 Department
2

of Neurosurgery, Karolinska Hospital and Karolinska Institute Stockholm, Sweden


Department of Neurosurgery, National Hospital, Oslo, Norway

Summary
This supplement of the Acta Neurochirurgica is dedicated to
professor Helge Nornes on the occasion of his retirement. Helge
Nornes started his neurosurgical training in Oslo in 1965. In 1980 he
was offered the neurosurgical chair of Bern, Switzerland, where he
stayed until 1983 when his old university called him back to the chair
at the National Hospital in Oslo, a position he filled until he retired
last year.
The present paper briefly reviews examples of his contributions to
neurosurgery and to the understanding of intracranial pathophysiology, including the transcranial doppler, the miniature transducer
for intracranial pressure monitoring, his observations on intracranial
pressure and internal carotid blood flow during subarachnoid haemorrhage, intracranial arterial blood flow in patients undergoing
aneurysm surgery, his studies of the pathophysiology of arteriovenous malformations, the introduction of intraoperative Doppler
recordings during surgery for aneurysms and arteriovenous malformations, and his methods for evaluating collateral circulation prior
to internal carotid artery occlusion.
Keywords: Cerebral aneurysm; subarachnoid haemorrhage; cerebral arteriovenous malformations; cerebral pathophysiology; transcranial Doppler; neurosurgery; biography.

1983 when the University of Oslo called him to the


chair at the National Hospital, a position he filled until
he retired last year.
Quite characteristically Helge Nomes' first contribution to neurosurgery was a technical device - a
miniature transducer for intracranial pressure (lCP)
monitoring [31]. Equally characteristic was the fact
that he, following the invention of the device itself,
started a long series of major investigations of intracranial pathophysiology utilizing his new tool. The
transducer and the first observations on its clinical use
was presented at the Annual Meeting of the Scandinavian Neurosurgical Society in 1968, with Tormod
Hauge as co-author. In order to evaluate his innovation he collaborated with G. Sundbarg in Lund,
Sweden. They conducted a combined experimental/

Introduction
Helge Nomes grew up in Telemark, Norway where
he was born on July 26, 1930. In his young days he was
a fencing master with several national championships.
He graduated from the University of Oslo Medical
School in 1955, and thereafter focused on general surgery. While complementing his surgical training with a
short-term period in the Neurosurgical service at the
National Hospital in Oslo, his extraordinary talents
were soon appreciated by professor Tormod Hauge.
He therefore started his neurosurgical training in 1965
and became vice-chairman of the department in 1971.
In 1980 he was offered the position as professor and
director of the Neurosurgical Department in the University of Bern, Switzerland, where he stayed until

Fig. I. Helge Nornes

clinical investigation and published the first comparisons of intraventricular and epidural pressure recordings in 1972.
Subarachnoid Haemorrhage (SAH) and Intracranial
Aneurysms

In his initial series of 468 aneurysms in 463 patients


he reported a postoperative mortality of 4.5%, and
good results in 74.5% [33]. He systematically monitored blood flow and ICP in his patients and made
several important contributions to the understanding
of intracranial pathophysiology. Together with Bj0rn
Magnres he reported three different patterns of acute
ICP increase in patients awaiting surgery following
aneurysmal subarachnoid haemorrhage (SAH) [30]. In
SAH type 1 the ICP acutely increased to 900-2200 mm
H 20 and thereafter fell to a considerably lower level
before it was followed by a second slowly increasing
rise in the ICP. In SAH type 2 the ICP abruptly increased to 1850-2200 mm H20. This pressure pattern
was associated with severe deterioration of the clinical
condition, and was irreversible and fatal in 4 out of 5
cases. A third pressure pattern - warning episode consisted of short-lasting peaks in the ICP. It was
associated with transient clinical deterioration and
increased risk of subsequent major bleeding, but not
with detectable amounts of blood in the cerebrospinal
fluid.
In a subsequent study of ICP and internal carotid
artery blood flow he observed that most repeated haemorrhages are stopped at ICP levels close to the diastolic blood pressure and that arrest of blood flow only
occurred during the end of the diastole [18, 22]. This
led him to conclude that the pressure gradient across
the aneurysm was important in the arrest of the haemorrhage and maintenance of haemostasis. He further reported that the risk of rebleeding increased as
the ICP normalized.
Following an experimental study of electromagnetic
blood flowmetry in small vessel surgery [20] he turned
to recording intracranial arterial blood flow with
electromagnetic flow probes in patients undergoing
aneurysm surgery together with dr. Per Wikeby [28,
32]. They found that average internal carotid artery
(lCA) flow was 144 ml/min (range 100-175), middle
cerebral artery (MCA) flow 97 ml/min (75-120) and
proximal anterior cerebral artery (ACA) flow 65 ml/
min (30-110). During test occlusion of the terminal
ICA retrograde flow in the proximal ACA to the MCA

I. A. Langmoen and Tryggve Lundar

was 78 (15-125). They further found that flow monitoring of the parent vessel was useful in some patients
in order to assess patency following occlusion of the
aneurysm neck. The average lower level of autoregulation was 62 mm Hg (35-85) in Grade I and II
patients and 76 mm (60-95) in grade III patients.
There was also a significant difference in control arterial blood pressure (110 vs 124 mm Hg). The average
lower autoregulatory range (the difference between
control blood pressure and lower level of autoregulation) was practically the same in the two groups.
The upper limit of autoregulation could not be studied
systematically but observations in a few patients
showing spontaneous blood pressure increases during
surgery indicated an upper limit of 150 mm Hg with a
total autoregulatory capacity of about 75 mm Hg.

Surgery and Pathophysiology of Intracranial AVMs

In 1979 he reported his first series of 63 patients with


cerebral arteriovenous malformation (AVM) [29].
When he resigned last year he had operated by far
more than 200 cases, most of them elective. The mortality in elective patients during his 30 years of A VM
surgery is 0%. Despite excellent surgical results he
clearly saw the need for adjunct endovascular treatment, accelerated the implementation of interventiona1
neuroradiology at the National Hospital in Oslo and
published the first series of patients undergoing combined treatment with the neuroradiologist professor
Per Nakstad [16].
In a later study 31 consecutive patients underwent
detailed neuropsychological testing pre-operatively,
and 4 and 12 months following surgery [39]. Pre-operatively the test pattern was very close to the average
performance of age-equivalent normative samples.
Although neither the patients nor their relatives reported definite emotional or affective changes after
surgery, neuropsychological testing revealed mild to
moderate deterioration of both cognitive and perceptual tasks in the postoperative period with return to
preoperative levels by 12 months. A moderate focal
impact was found in six patients (19%), and statistically significant improvement of test performance in
one.
During surgery he took the opportunity to study
A VMpathophysiology [25] and found that the arterial
pressure in feeding vessels ranged from 40 to 77 mm
Hg (average 56 mm Hg), instantly rising to from 55

A Tribute to Helge Nornes

to 95 mm Hg (average 76 mm Hg) during temporary


occlusion. Draining vein pressure before occlusion
ranged from 8 to 23 mm Hg (average 15 mm Hg), and
fell to zero in all patients when the A VM was occluded. In nine patients he was able to estimate total
AVM flow, which ranged from 150 to more than 900
ml/min (average 490 ml/min).
After they developed the transcranial Doppler he
and his collaborators demonstrated the possibility of
non-invasive identification and evaluation of A VMs
by this technique [9]. Feeding arteries could be identified by their high flow velocity and low pulsatility, and
their localization by the TCD technique provided good
definition of the anatomical localization of individual
AVM's.
Intraoperative Doppler Monitoring
In order to facilitate surgery of intracranial aneurysms and AVMS he introduced an intraoperative
pulsed echo Doppler technique. In A VM surgery this
allowed identification of involved vessels, precise location of deep-seated malformations not visible at the
brain surface, as well as determination of the depth of
the A VM, thus facilitating the planning of the cortical
incision and microsurgical strategy [26].
He described the effect of parent artery lumen reduction on flow velocity during aneurysm occlusion
and reported the use of the Doppler technique to evaluate parent artery patency. He further used the technique to study intra-aneurysmal flow patterns as well
as cognate and collateral blood flow [27].
Transcranial Doppler
Together with Rune Aaslid who worked with him
both in Oslo and in Bern, he developed the transcranial
Doppler (TCD) [4]. This methodology has had major
impact on the study of cerebrovascular physiology and
pathophysiology in man, as well as on the evaluation
of different clinical conditions, and since their original
publication of this method almost 2000 papers utilizing the technique have appeared in peer reviewed
journals.
Helge himself, together with his research group in
Bern and later in Oslo, has studied several aspects of
intracranial physiology and pathophysiology using the
TCD technique. This includes the relation between
flow volume and blood velocity [10], side-to-side and
day-to-day variations in normal subjects [38], cerebral

vasoreactivity and autoregulation [3, 5], vasospasms


[1, 2, 11, 34], diagnosis of intracranial and extacranial
occlusive disorders [9], and evaluation of intracranial
haemodynamics in occlusive carotid artery disease [6,
36, 37], as well as investigation of intracranial haemodynamics during cardiac bypass procedures [12-15].
Carotid Artery Occlusion
One of his early papers addressed the role of the
circle of Willis in graded occlusion of the internal
carotid artery [19]. In ten patients undergoing graded
carotid occlusion due to infraclinoid aneurysms, he
monitored bilateral internal carotid flow and concluded that increased contralateral flow in excess of
140-150% of pre-occlusive level indicated sufficient
collateral capacity. In his - so far -last publication he
returned to the same problem using TCD. Intracranial
haemodynamics were studied in a group of patients
with surgically inaccessible lesions affecting the ICA
[35]. Seven patients underwent ICA trapping procedures. While none of five patients with a drop ofMCA
blood flow velocity to less than 60% developed haemodynamic complications, two patients experienced
haemodynamic stroke. Based on these and other observations that cannot be detailed here, they suggested
that TCD investigation during short-lasting temporary
occlusion seems to be a potentially reliable method for
the evaluation of collateral capacity prior to permanent ICA occlusion.
Another interesting aspect of his studies regarding
carotid occlusion dealt with flow measurements during
surgery for carotid cavernous fistula [17]. He made
simultaneous measurements of extra- and intracranial
ICA blood flow prior to and during temporary extraand intracranial ICA occlusion, and was in this way
able to estimate both flow through the fistula, and
antero- and retrograde flow during ICA occlusion and coined the term Index of collateral capacity
A Tribute to Helge Nornes
Helge Nornes' contributions cannot be detailed in a
brief review. A number of them has not been covered.
Just to mention his studies of ICA blood flow during
cerebral angiography [21], intracranial pulse pressure
dynamics in patients with intracranial hypertension
[23], and pre-cerebral arterial blood flow pattern in
brain tamponade [7, 8, 24]. His scientific work on
TCD is continued with Karl Fredrik Lindegaard and
Wilhelm Sorteberg.

Helge Nornes is an innovative scientist with a sharp


intellect, he is an excellent surgeon, and has a well developed sense of humour. He is a warm human being
and a good doctor who always has taken extraordinary good care of his patients. The present supplement
of the Acta Neurochirurgica is therefore dedicated to
him. His international stature is reflected by the names
of the contributing authors.
Helge presently enjoys his retirement in Oslo. He is
married to Ellen. They have two daughters.

References
1. Aaslid R, Huber P, Nomes H (1984) Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. J
Neurosurg 60: 37-41
2. Aaslid R, Huber P, Nomes H (1986) A transcranial Doppler
method in the evaluation of cerebrovascular spasm. Neuroradiology 28: 11-16
3. Aaslid R, Lindegaard KF, Sorteberg W, Nomes H (1989)
Cerebral autoregulation dynamics in humans. Stroke 20: 45-52
4. Aaslid R, Markwalder TM, Nomes H (1982) Noninvasive
transcranial Doppler ultrasound recording of flow velocity in
basal cerebral arteries. J Neurosurg 57: 769-774
5. Dahl A, Lindegaard KF, Russell D, Nyberg-Hansen R,
Rootwelt K, Sorteberg W, Nomes H (1992) A comparison of
transcranial Doppler and cerebral blood flow studies to assess
cerebral vasoreactivity. Stroke 23: 15-19
6. Lindegaard KF, Bakke SJ, Grolimund P, Aaslid R, Huber P,
Nomes H (1985) Assessment of intracranial hemodynamics in
carotid artery disease by transcranial Doppler ultrasound. J
Neurosurg 63: 890-898
7. Lindegaard KF, Grip A, Nome~H (1980) Precerebral haemodynamics in brain tamponade, part 1: clinical studies on blood
flow velocity. Neurochirurgia 23: 133-142
8. Lindegaard KF, Grip A, Nomes H (1980) Precerebra1 haemodynamics in brain tamponade, part 2: experimental studies.
Neurochirurgia 23: 187-196
9. Lindegaard KF, Grolimund P, Aaslid R, Nomes H (1986)
Evaluation of cerebral AVM's using transcranial Doppler ultrasound. J Neurosurg 65: 335-344
10. Lindegaard KF, Lundar T, Wiberg J, Sjoberg D, Aaslid R,
Nomes H (1987) Variations in middle cerebral artery blood flow
investigated with noninvasive transcranial blood velocity measurements. Stroke 18: 1025-1030
11. Lindegaard KF, Nomes H, Bakke SJ, Sorteberg W, Nakstad P
(1988) Cerebral vasospasm after subarachnoid haemorrhage
investigated by means of transcranial Doppler ultrasound. Acta
Neurochir [Suppl) (Wien) 42: 81-84
12. Lundar T, Lindberg H, Lindegaard KF, Tjonneland S, Rian R,
Bo G, Nomes H (1987) Cerebral perfusion during major cardiac
surgery in children. Ped Cardiol8: 161-165
13. Lundar T, Lindegaard KF, Froysaker T, Aaslid R, Grip A,
Nomes H (1985) Dissociation between cerebral autoregulation
and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. Ann Thor Surg 40: 582-587
14. Lundar T, Lindegaard KF, Froysaker T, Aaslid R, Wiberg J,
Nomes H (1985) Cerebral perfusion during nonpulsatile cardiopulmonary bypass. Ann Thor Surg 40: 144-150
15. Lundar T, Lindegaard KF, Froysaker T, Grip A, Bergman M,

I. A. Langmoen and Tryggve Lundar

16.

17.
18.

19.

20.

21.
22.
23.

24.

25.
26.

27.

28.

29.

30.
31.

32.
33.
34.

35.

36.

37.

Am-Holen E, Nomes H (1986) Cerebral carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. Ann Thor
Surg41: 525-530
Nakstad PH, Nomes H (1994) Superselective angiography,
embolisation and surgery in treatment of arteriovenous malformations of the brain. Neuroradiology 36: 410-413
Nomes H (1972) Hemodynamic aspects in the management of
carotid-cavernous fistula. J Neurosurg 37: 687-694
Nomes H (1973) The role of intracranial pressure in the arrest of
hemorrhage in patients with ruptured intracranial aneurysm. J
Neurosurg 39: 226-234
Nomes H (1973) The role of the circle of Willis in graded occlusion of the internal carotid artery in man. Acta Neurochir
(Wien) 28: 165-177
Nomes H (1976) Electromagnetic blood flowmetry in small
vessel surgery. An experimental study. Scand J Thor Cardiovasc
Surg 10: 144-148
Nomes H (1977) Internal carotid artery blood flow during cerebral angiography. Neuroradiology 12: 219-225
Nomes H (1978) Cerebral arterial flow dynamics during aneurysm haemorrhage. Acta Neurochir (Wien) 41: 39-48
Nomes H, Aaslid R, Lindegaard KF (1977) Intracranial pulse
pressure dynamics in patients with intracranial hypertension.
Acta Neurochir (Wien) 38: 177-186
Nomes H, Angelsen B, Lindegaard KF (1977) Precerebral arterial blood flow pattern in intracranial hypertension with cerebral blood flow arrest. Acta Neurochir (Wien) 38: 187-194
Nomes H, Grip A (1980) Hemodynamic aspects of cerebral
arteriovenous malformations. J Neurosurg 53: 456-464
Nomes H, Grip A, Wikeby P (1979) Intraoperative evaluation
of cerebral hemodynamics using directional Doppler technique,
part 1: arteriovenous malformations. J Neurosurg 50: 145-151
Nomes H, Grip A, Wikeby P (1979) Intraoperative evaluation
of cerebral hemodynamics using directional Doppler technique,
part 2: saccular aneurysms. J Neurosurg 50: 570-577
Nomes H, Knutzen HB, Wikeby P (1977) Cerebral arterial
blood flow and aneurysm surgery, part 2: induced hypotension
and autoregulatory capacity. J Neurosurg 47: 819-827
Nomes H, Lundar T, Wikeby P (1979) Cerebral arteriovenous
malformations; results of microsurgical management. Acta
Neurochir (Wien) 50: 243-257
Nomes H, Magnaes B (1972) Intracranial pressure in patients
with ruptured saccular aneurysm. J Neurosurg 36: 537-547
Nomes H, Serck-Hanssen F (1970) Miniature transducer for
intracranial pressure monitoring in man. Acta Neurol Scand 46:
203-214
Nomes H, Wikeby P (1977) Cerebral arterial blood flow and
aneurysm surgery, part 1: local arterial flow dynamics. J Neurosurg 47: 810-818
Nomes H, Wikeby P (1979) Results of microsurgical management of intracranial aneurysms. J Neurosurg 51: 608-614
Seiler RW, Grolimund P, Aaslid R, Huber P, Nomes H (1986)
Cerebral vasospasm evaluated by transcranial ultrasound correlated with clinical grade and CT-visualized subarachnoid
hemorrhage. J Neurosurg 64: 594-600
Sorteberg A, Sorteberg W, Bakke SJ, Lindegaard KF, Boysen
M, Nomes H (1997) Cerebral haemodynamics in internal carotid artery trial occlusion. Acta Neurochir (Wien) 139: 10661073
Sorteberg A, Sorteberg W, Lindegaard KF, Bakke JS, Nomes H
(1996) Haemodynamic classification of symptomatic obstructive carotid artery disease. Acta Neurochir (Wien) 138: 10791086
Sorteberg A, Sorteberg W, Lindegaard KF, Nomes H (1996)

A Tribute to He1ge Nomes


Cerebral haemodynarnic considerations in obstructive carotid
artery disease. Acta Neurochir (Wien) 138: 68-75
38. Sorteberg W, Langmoen lA, Lindegaard KF, Nomes H (1990)
Side-to-side differences and day-to-day variations of transcranial Doppler parameters in normal sUbjects. J Ultrasound
Med 9: 403-409

5
39. Stabell KE, Nomes H (1994) Prospective neuropsychological
investigation of patients with supratentorial arteriovenous malformations. Acta Neurochir (Wien) 131: 32-44
Correspondence: Professor Iver A. Langmoen, M.D., Ph.D., Department of Neurosurgery, Karolinska Hospital, S-171 76 Sweden.

Acta Neurochir (1999) [Suppl]72: 7-26


Springer-Verlag 1999

Intracranial Aneurysms and Subarachnoid Hemorrhage


Management of the Poor Grade Patient
P. D. Le Roux 1 and H. R. Winn 2
1 Department
2 Department

of Neurosurgery, New York University, New York


of Neurosurgery, Harborview Medical Center, University of Washington, Seattle, USA

Abstract
Between 20 and 30% of patients who suffer cerebral aneurysm
rupture are in poor clinical grade when first evaluated. Management
of these patients is controversial and challenging but can be successful with an aggressive proactive approach that begins with in the field
resuscitation and continues through rehabilitation. In this article we
review the epidemiology, pathology and pathophysiology, clinical
features, evaluation, surgical and endovascular management, critical
care, cost, and outcome prediction of patients in poor clinical grade
after subarachnoid hemorrhage.
Keywords: Aneurysm; clinical grade; subarachnoid hemorrhage.

Introduction
Epidemiological, population based and community
based studies demonstrate that less than one third of
people who suffer rupture of a cerebral aneurysm
return to their premorbid state. The effects of the initial
hemorrhage contribute to 60% of this death and disability following aneurysm rupture [11, 13, 117]. In
particular patients in poor clinical condition with a
depressed level of consciousness are expected to do
poorly. For example, in the International Cooperative
Study on the Timing of Aneurysm Surgery (COSTAS;

73), which collected data between 1980 and 1983,


74.3% of patients who were alert at admission (n =
1722) subsequently experienced a good outcome and
13.1 % died. By contrast, if the patient was comatose
at admission (n = 315), 11.1 % subsequently made a
good recovery and 72.1 % died (Table 1). In the last
decade the management of cerebral aneurysms has
advanced by an increased understanding of the pathophysiology of subarachnoid hemorrhage (SAH), use of
critical care techniques, the development of innovative
neuroimaging and interventional techniques and technical advances in surgical management. These advances have improved the outlook for patients in poor
clinical condition after aneurysm rupture. This article
will review current management of poor grade subarachnoid hemorrhage.
Clinical Grading and Definition of Poor Grade
Many variables affect outcome following aneurysm
rupture, however, the single most important independent outcome predictor is the patients admission clinical status [13, 57, 63, 73, 89, 110, 134]. Two grading

Table 1. The International Cooperative Study on the Timing of Aneurysm Surgery: Admission Level of Consciousness is Associated with Outcome*
Consciousness
level

Good
recovery %

Moderately
disabled %

Severely
disabled %

Vegetative
%

Dead %

Total, n

Alert
Drowsy
Stuporous
Comatose
Total

74.3
53.5
30.2
11.1
57.6

7.5
11.0
13.8
5.4
9.1

4.1
6.3
8.0
7.9
5.5

1.0
1.7
4.3
3.5
1.8

13.1
27.6
43.7
72.1
26.0

1722
1136
348
315
3521

Relationship between admission level of consciousness and outcome: X2 = 720.5; P

< 0.001. Modified from Kassell et al. [73].

P. D. Le Roux and H. R. Winn

Table 2. Common Clinical Grading Scales Used After Subarachnoid


hemorrhage
Hunt and Hess Scale [63 J

Grade

o
II

III
IV
V

clinical findings
no SAH
asymptomatic or mild headache, mild nuchal rigidity
moderate to severe headache, nuchal rigidity, no neurologic deficit, except cranial nerve palsy
drowsiness, confusion, or mild focal deficit
stupor or mild to moderate hemiparesis; possible early
decerebrate rigidity
deep coma, decerebrate posturing, moribund

World Federation of Neurosurgical Societies Scale [23 J

Grade

o
I

3
4
5

GCS* score
15
15
13-14
13-14
7-12

3-6

motor deficit
absent and no SAH
absent
absent
present
present or absent
present or absent

GCS Glasgow Coma Scale.

systems: the Hunt and Hess system [63] and the World
Federation of Neurological Surgeons Scale (WFNS;
23) based on the Glasgow Coma Scale (GCS; Table 2)
are most frequently used by clinicians to describe the
clinical severity of SAH. These two scales are comparable as predictors of outcome.
Poor grade patients are those classified as grade IV
or V in the Hunt and Hess or WFNS Scale. Clinical
grading should be performed at admission after initial
cardiopulmonary resuscitation and stabilization. Using the Hunt and Hess scale grade IV patients are
stuporous and have moderate or severe hemiparesis
whereas those in deep coma who exhibit extensor posturing and a moribund appearance are classified grade
V. When using the WFNS scale, grade IV patients
have GCS score between 7 and 12, and grade V patients a GCS between 3 and 6. In the original classification described by Hunt and Hess [63], patient grade
was increased by one level in the presence of a serious
medical condition such as heart disease or advanced
pulmonary disease. We do not reclassify grade III patients as grade IV in the presence of serious underlying
medical disorders since we believe this reflects anesthetic risk rather than the severity of SAH.
Epidemiology and Selection Bias

Between 20 and 30% of patients who suffer SAH can


be classified as grade IV or V. In the original study by
Hunt and Hess 17% of their 275 patients were grade
IV or V [63]. In the recent International Cooperative

Study on the Timing of Aneurysm Surgery, 662 (19%)


of 3251 patients were either stuporous or comatose on
admission [73]. Population based studies that eliminate
the referral bias inherent in hospital based studies,
however, demonstrate that the incidence of poor grade
SAH is greater. For example, Longstreth et al. [89] reviewed SAH patients in Kings County and found that
47 (28%) of 166 hospitalized patients were grade IV or
V at admission. The true incidence of poor grade SAH
may be even greater since epidemiologic and population based studies demonstrate. that 15% of patients
who suffer aneurysm rupture die before reaching hospital [11, 13, 34, 89, 117]. Consistent with these observations are forensic studies that suggest that 5% of
unexpected deaths may be attributed to aneurysm
rupture.
Most information describing SAH management is
derived from studies conducted at large referral centers
whose referral pattern can influence outcome. For example, when management of community based patients or patients referred from outside the community
and treated at the same institution are compared, significantly more referral patients (83%) than community based patients (59%) survive the first 30 days [172].
Most of this difference is observed within 2 days of
aneurysm rupture, during which two thirds of deaths
following SAH occur [11, 13]. Analysis of referral
patterns, however, indicates that approximately one
third of patients are referred to a center capable of
managing SAH within 48 hours of aneurysm rupture
[72, 140]. Which patients are selected for admission to,
or treatment at a neurosurgical center also can influence outcome. For example, Maurice-Williams and
Marsh [96] observed that mortality in the same group
of patients was reduced from 35.5% to 16.1% when the
results were analyzed according to a non-selective or
selective admission policy. Similarly, Edner et al. [24]
observed that in the same series of patients, favorable
outcomes were observed in 46% of patients when total
outcome, including those who did not reach hospital
was reported. When management outcome was recorded, 58% of patients experienced a favorable outcome whereas 69% experienced a similar outcome
when only surgical outcome was reported. Admission
and treatment of select patients is frequent. For example, in the 1980's fewer than one third of British
neurosurgeons provided an "open door policy" [92]
whereas in COSTAS, 83% of all patients were treated
surgically, but only 58% of stuporous patients and 35%
of comatose patients underwent surgery [73, 74]. It is

Intracranial Aneurysms and Subarachnoid Hemorrhage

important to consider referral and selection bias to


make valid comparisons between results at different
centers and derive meaningful conclusions how management benefits overall patient outcome.
Pathology

In general poor grade patients are more likely to


demonstrate severe SAH on head computed tomography (CT) scan or other consequences of aneurysm
rupture such as intracerebral hemorrhage (lCH), intraventricular hemorrhage (IVH), hydrocephalus, or
vasospasm than patients in good clinical grade. These
findings are often associated with increased intracranial pressure (ICP; 7, 51, 169). In autopsy studies of
patients dying from ruptured cerebral aneurysms,
SAH, ICH, IVH, infarction and cerebral edema are
found.
Intracerebral hematoma complicates between 5 and
40% of SAH and is most prevalent in poor grade patients. About half cause mass effect. Autopsy studies
suggest that aneurysmal ICH occurs when the aneurysm lies between cerebral surfaces, adhesions exist
from a previous rupture or when the aneurysm is embedded in the parenchyma. Anterior and middle cerebral artery aneurysms are most frequently associated
with ICH, usually in the frontal lobe or external capsule respectively [52,120,171]. Temporal lobe hematomas may be seen after rupture of posterior communicating artery aneurysms. Posterior circulation
aneurysms are rarely associated with ICH although
distal posterior cerebral or superior cerebellar artery
aneurysms may be associated with temporal, occipital
or cerebellar ICH. Hematomas less than 50 ml produce little neurologic deterioration whereas those
greater than 50 ml in volume invariably cause coma.
Intracerebral hematoma adversely affects outcome in
all grades, particularly if midline shift is observed on
head CT scan [7, 50, 52, 114, 120, 139, 163, 173]. In
addition, patients with parietal and frontal ICH experience greater mortality than those with temporal ICH
[152]. Subdural hematomas (SDH) are infrequent after
aneurysm rupture but can be seen in poor grade patients. For example, Kamiya et al. [70], reviewed 484
patients suffering SAH; 15 had SDH. Ten of these patients were grade IV or V. The associated SAH is usually small and the SDH is most frequently associated
with ruptured internal carotid and middle cerebral
artery aneurysms when the dome is closely approximated to the arachnoid membrane.

Intraventricular hemorrhage occurs in 15% of patients who survive aneurysm rupture, but in up to 80%
of poor grade patients [2, 81, 107]. Mortality from
aneurysmal SAH is commonly associated with IVH.
For example, Schievink et al. [141, 142] observed IVH
in 92% of the patients who died suddenly after aneurysm rupture. Among these patients, 38% suffered a
ruptured posterior circulation aneurysm. Any aneurysm can cause IVH if the SAH is large enough or from
extension of an ICH. However, IVH is most frequent
after posterior circulation and anterior communicating
artery aneurysm rupture. Internal carotid and posterior communicating artery aneurysm may rupture into
the temporal horn of the lateral ventricle particularly if
the aneurysms are large and have grown into the temporal lobe. Intraventricular hemorrhage is associated
with acute or chronic hydrocephalus, increased intracranial pressure, decreased cerebral blood flow and the
subsequent development of vasospasm. Acute hydrocephalus generally results from obstruction of CSF
flow whereas chronic hydrocephalus results from
ependymal, subependymal and arachnoid villi damage, fibrosis and blockage of CSF absorptive surfaces
[10, 39, 107, 128, 139]. Intracranial pressure is often
normal in chronic hydrocephalus.
Cerebral infarction is common in poor grade patients, particularly those surviving greater than 1 day
[17, 40]. In addition, the amount of subarachnoid
blood seen on CT scan, but not its rate of clearance is
associated with infarction [33]. The presence of hypotension and ICH increases the risk of infarction threefold [2, 17, 40]. In some patients ICH and resultant
brain herniation can lead to strangulation of the
posterior cerebral artery and consequent occipital infarction. Delayed infarction also can result from intractable intracranial hypertension or vasospasm.
Pathophysiology

Aneurysm rupture is a complex pathophysiologic


event. There are several consistent and often severe
intracranial alterations that occur in poor grade patients. First, poor grade patients usually demonstrate
sustained elevated ICP (> 30 mm Hg) and frequent B
waves that suggest decreased intracranial compliance
[7, 51, 81, 111, 169]. The precise etiology of increased
ICP after aneurysm rupture is not fully elucidated but
may include: subarachnoid hemorrhage volume, CSF
outflow obstruction, diffuse vasoparalysis, and distal
cerebral arteriolar vasodilatation. Second, cerebral

10

blood flow (CBF) is reduced to values 30~40% of


normal after aneurysm rupture. The reduced CBF recovers in good grade but not poor grade patients and
correlates with the Hunt and Hess and Miller-Fisher
grades [30, 103, 116]. For example, using 133 Xenon
measurements, Fazl et al. [30] observed that CBF
ranged between 48.6 12.3 mlj100gjmin in grade I
and 37.3 9.6 in grade V patients. In most patients
the reduced CBF progress in severity from the day of
SAH for the next 14 days, in part due to vasospasm
[102]. In contrast to CBF, cerebral blood volume
(CBV) is often increased since the distal microcirculation may vasodilate [43, 170]. This distal vasodilatation contributes to decreased compliance and
cerebrovascular reserve [153]. Third, autoregulation
and C02 reactivity are impaired in poor grade patients
[18, 102, 103]. The autoregulatory curve is shifted to
the right, consequently even small reductions in blood
volume or blood pressure may contribute to cerebral
ischemia whereas excessive blood pressure elevation
beyond the reset autoregulatory curve may contribute
to cerebral edema or hemorrhage. Finally, SAH induced damage to cerebral vessel intima or local brain
tissue results in the release of thromboplastin and biogenic amines such as norepinephrine. These compounds predispose to platelet hyperactivity, and activation of coagulation and fibrinolytic systems resulting
in a hyperfibrinolytic, hypercoagulable state that can
impair microcirculation [36, 49, 67]. In general, the
severity of these hemostatic abnormalities correlate
with the severity of the SAH.
Aneurysm rupture results in a variety of biochemical
alterations that can be associated with ischemia and
brain energy failure. These abnormalities correspond
to the overall severity of SAH and may be important
since autopsy studies suggest brain injury after aneurysm rupture is related to ischemic damage. Animal
models, however, fail to demonstrate persistent ischemia below a critical infarction level [68]. For example,
clinical studies using intracerebral dialysis have demonstrated increased excitatory amino acid such as glutamate, particularly in poor grade patients or those
who experience a poor outcome [122, 138]. In high
concentration, these substances, are integral to cell
death and cell damage associated with cerebral ischemia. In experimental studies hemoglobin potentiates
excitotoxic cell damage [131]. Aneurysm rupture is
also associated with cytokine release [93]. Cytokines
such as IL-1 can damage neurons directly by inducing
apoptosis and edema or indirectly by inducing nitric

P. D. Le Roux and H. R. Winn

oxide synthetase in macrophages, astrocytes, and endothelial cells, a process that is augmented by hemoglobin [60,86, 161]. Together these observations suggest that the administration of cerebral protectants to
poor grade patients may ameliorate the effects of cerebral ischemia.

Clinical Features
A depressed level of consciousness is the sentinel
neurologic finding of poor grade aneurysm patients.
Other neurologic findings may include a dilated pupil
and asymmetric motor or reflex responses. However,
the most consistent clinical observation in these patients is neck stiffness [1]. In comatose patients a history is often not available, consequently the diagnosis
of SAH should be suspected in non traumatic coma
patients, particularly females in their 4th and 5th decades. Some poor grade patients may present with
cardiac abnormalities, respiratory irregularity, neurogenic pulmonary edema or cardiorespiratory arrest
[85, 129, 149]. For example, in a population based
study of all SAH grades, Ramirez and Lassepas [129]
found 14% of the patients suffered cardiorespiratory
arrest. This represented 4.9% of all cardiorespiratory
arrest patients who were successfully resuscitated before arrival at the emergency room. The patients were
all grade V at admission and generally demonstrated
thick diffuse SAH, IVH or ICH on head CT scan [129,
149]. Clinical improvement after resuscitation is a
generally favorable prognostic sign in poor grade patients particularly if there are only minor changes on
head CT scan [81, 114].

Initial Care and Evaluation


The goal of initial management is to stabilize the
patient for aneurysm obliteration and prevent systemic
complications or secondary cerebral insults, such as
hypotension, or hypoxia. We believe that the successful management of poor grade SAH begins before diagnosis and requires intensive efforts that starts with a
paramedic service, practicing in the field resuscitation
and is continued in the emergency room and intensive
care unit. Initial priorities include provision of adequate ventilation and oxygenation, normovolemia,
hemodynamic stability, normoglycemia, and ICP
control. Nimodipine, anticonvulsants, and steroids are
administered. Poor grade patients, particularly those
with a GCS ~ 10, should be intubated and mechani-

11

Intracranial Aneurysms and Subarachnoid Hemorrhage

cally ventilated. Following the initial neurologic assessment, mechanical ventilation can be maintained
using short acting drugs such as intravenous morphine,
midazolam or diprivan. These same medications also
can control severe hypertension in some patients. Each
patient should undergo a standard laboratory evaluation including electrolytes, blood glucose, complete
blood count, coagulation profile, chest xray and EKG.
Four units of blood should be crossmatched. After
initial stabilization in the emergency room a thorough
radiographic evaluation is undertaken. Some poor
grade patients particularly those demonstrating massive ICH may go directly to the operating room others,
however, should be admitted to the intensive care unit.
Intracranial pressure and invasive hemodynamic
monitoring, including an arterial line and Swan Ganz
catheter, are recommended.
Computed tomography is the investigation of choice
to diagnose aneurysm rupture. Additional information
can be obtained from infusion CT scan, or 3D spiral
CT [61, 77, 109]; these radiological tests are particularly useful in the unstable patient after aneurysmal
ICH and giant or complex aneurysms. MRI and MRA
presently playa limited role in the evaluation of poor
grade patients. Apart from moribund patients who
may go directly to the operating room for ICH evacuation, all other patients require four vessel angiography that should demonstrate: 1. the aneurysm sac
and orientation, 2. the aneurysm neck, 3. the relationship between the lesion and parent vessels, and 4. the
state of the cerebral vasculature. Angiography in poor
grade patients is best performed after intubation and
the insertion of invasive monitoring lines and with the
assistance of critical care nursing.
Management Strategies
There are several management strategies for poor
grade patients derived exclusively from clinical series:
1. no treatment, 2. treatment of select patients only,
3. delayed treatment after clinical improvement, or
4. aggressive proactive treatment including rapid resuscitation and ICP control, early aneurysm occlusion,
and prophylaxis against delayed ischemia. Without
question many patients in poor clinical grade following SAH and irreparably damaged, however, the published data suggest that an aggressive policy may provide these patients their most reasonable chance of
neurologic recovery (Table 3). Untreated greater than
90% of poor grade patients die or are severely disabled

[106, l39]. When treated according to a select delayed


policy, favorable outcomes are observed in approximately 5 to 20% of patients [15, 21, 57, 73, 106, 123,
l39], whereas, when treated aggressively between 35%
and 53% poor grade patients experience a favorable
outcome [7, 81). This aggressive policy is not associated with more survivors in poor condition; a similar
number of survivors in poor condition is observed
using either an aggressive approach or less aggressive
approach. These overall management results compare
favorably to the natural history of poor grade SAH; on
the day of hemorrhage, grade IV patients have a 35%
chance of surviving, whereas grade V patients have a
5% chance of surviving [5).
Ventricular drainage and management of patients
who improve is a common strategy to manage poor
grade patients. This approach rapidly can control increased ICP and attenuate the deleterious effects of
SAH in some patients. However, there are potential
disadvantages of ventricular drainage that may limit
its routine use in poor grade patients: 1. catheters may
be difficult to insert when edema or shift is present, or
drain poorly when there is severe IVH; 2. following
SAH ventricular drainage reduces ICP briefly and is
followed by elevated ICP when the CSF buffer becomes exhausted [111]; 3. ventricular drainage is associated with a significant increase in aneurysm rebleeding and infection [119, 127, 128, 167]; 4. an expectant
strategy using ventriculostomy alone, leaves the ruptured aneurysm unprotected, potentially limiting vasospasm treatment; and 5. clinical improvement with
ventricular drainage is not always associated with a
favorable outcome, and many patients who do not
improve undergo surgery with satisfactory results [107,
112, 127, 128, 157, 159, 165, 167). In our experience,
we have found that ICP is similar in poor grade
patients who do and do not receive ventriculostomy.
Therefore, while ventriculostomy may be effective in
some patients, it should be used as a temporary measure to stabilize the patient and should not delay definitive management. In addition, which poor grade
patients receive further care should not be based only
on the response to ventricular drainage.
Outcome Prediction in Poor Grade Patients
Aggressive management requires a large commitment of resources; is intervention justified in all poor
grade patients? Clinical series suggest that admission
clinical and radiographic findings are frequently in-

12

P. D. Le Roux and H. R. Winn

Table 3. Summary of Published Data Describing Overall Management Outcome in Hunt and Hess Grade IV or V Patients
Another

Patients"

Age (yrs)

Hunt & Hess, 1968


Adams et al., 1981
Testa et al., 1985

47(17.1%)
61 (26%)
80 (36%)

Freckmann et al., 1987

20 (6.3%)

NR
NR
mean 51.4
range 14-73
NR

Hijdra et al., 1987

42 (15.9%)

Estb 28% >60

Ohno et al., 1988


Average

32 (34.7%)

14 patients> 70

Chyatte et al., 1988


Inagawa et al., 1988
Petruk et al., 1988

80 (32.8%)
157 (24.8%)
108 (NR)

Sevrain et al., 1991

66 (24.4%)

NR
44% >60
Est 54
mean 47.2
range 20-74
mean 53.1
NR

Management

Outcome
%
favorable

poor

dead

delayed surgery until Grade I or II


delayed surgery; antifibrinolytics
delayed surgery until Grade I, II or III; limited ICU
care
delayed surgery unless ICH present; routine CCB,
HV
delayed surgery until Grade I or II; some patients
received antifibrinolytics, excluded pts > 65 yrs
delayed surgery unless ICH present

NR
18
3.8

NR
24.6
8.8

78.7
57.4
87.4

20

75

23

71

15.6
9.5

15.6
18.4

68
72.9

selective early surgery (26%)


selective early surgery; surgery deferred in 66.8% pts
multicenter randomized trial of CCB; no standard
management
early surgery except patients with large ICH and
abnormal pupils
early surgery; routine HV, no CCB
multicenter; selective early surgery (28%)

25
9.5
25

29
15.2
21.3

46
75.2
53.7

19.6

12.2

68.2

7
20.8
17.8

5
15.7
16.4

88
63.5
65.8
50
67.4
42.2
56.9
42.5

Medlock et al., 1992


Miyaoka et al., 1993
Average

41 (36%)
370 (22.8%)

Bailes et al., 1990


Seifertetal.,1991
Nowak et al., 1994
Steudel et al., 1994
Ungersbock et al., 1994

54 (23.3%)
74(17.3%)
109 (39.4%)
116 (20.2%)
48 (24.5%)

mean 56
14pts >60
NR
Est 49.5
mean 53.1
range 31-77

EVD; selective aggressive; routine HV.


EVD for hydrocephalus; selective aggressive.
EVD; selective aggressive; routine CCB
EVD for hydrocephalus; selective aggressive.
EVD; selective aggressive; routine CCB

42.6
20.2
21.1
35.3
21.3

7.4
12.2
36.7
7.8
36.2

28.1

20.1

51.8

159 (36.5%)

median 54

aggressive management of all patients

38.4

18.2

43.4

Average

Le Roux et al., 1996

Favorable independent including Glasgow Outcome Score of good and moderately disabled; Poor dependent, including Glasgow Outcome
Score of severe disability and vegetative; CCB calcium channel antagonists; EVD ventricular drainage; HVhypervolemia; ICH intracerebral
hemorrhage; selective aggressive emergency evacuation of ICH, early surgery on patients demonstrating clinical improvement or controllable
ICP after ventricular drainage; not all patients intubated and ventilated; N R not reported.
"The number of patients presenting in poor clinical grade after aneurysm rupture. This number is given in parentheses as a percentage of all
patients in all clinical grades treated at the same institution(s).
bvalue estimated from limited data.
Modifed from: Le Roux et al. [81].

sufficient to accurately predict outcome in the individual poor grade patient [7,9,12,77,81, 112, 159].
Reliable prognostic information requires additional
evaluation such as ICP monitoring, and continued
neurologic observation [7,77,81,112,147,159]. Outcome, however, is largely determined by the initial
hemorrhage and its immediate pathophysiologic consequences; a short time frame, therefore, exists in
which the deleterious effects of severe SAH may be
ameliorated [32]. In our experience, attempting to
select Grade IV and V patients for treatment based
only on admission clinical and diagnostic findings, including evidence of brainstem herniation, would result
in withholding treatment from a third of poor grade
patients who subsequently can experience a favorable

outcome [81]. Similar levels of predictive inaccuracy,


have been observed in other studies of aneurysmal
rCH, grade III-V patients, prospective studies comparing high risk and low risk patients of all grades, and
clinical series describing ventricular drainage for poor
grade patients [7, 20, 21, 159, 171]. Consequently we
believe, that aggressive management should be initiated in the vast majority of poor grade patients.

When Should Care be Withheld


Once management is initiated the failure to improve
neurologically, the development of medical complications, the failure of elevated rcp to respond to treatment and CT scan evidence of infarction are significantly associated with a poor outcome [77, 81].

13

Intracranial Aneurysms and Subarachnoid Hemorrhage


Suspected Grade IVIV SAH
Resuscitate, Intubate,

+ /- Mannitol. Head CT & Infusion CT

Neurologically Unstable .--_ _ _ _ _ _ _ _-1-_ _ _ _ _ _ _ Neurologically Stable


with ICH & Infusion CT +

...

,-----'-----,

t
IVH &/or

SAH

ICH

Hydrocephalus

Ventriculostomy

ICPM

ICP > 30
(not controlled)

ICP < 30
(controlled)

Craniotomy
Clip Aneurysm

Craniotomy
ICH Evacuation
Clip Aneurysm

< 65 yrs
No Medical Problems

> 65 yrs &/or


Medical Problems

<65 yrs
No Medical Problems

Angiography

II

Endovascular
Aneurysm Occlusion

> 65

yrs &/or Multiple


Medical Problems

Consider
Endovascular
Aneurysm Occlusion

1----

Reassess After 3-5 Days

Neurologically Improved
ICP Controlled
No Low Density on CT

Aggressive Care

No Neurologic Improvement + 1- ICP Uncontrolled


+ 1- Low Density on CT

~
Rehabilitation

L------,I

Aneurysm Remnant

Craniotomy
Clip Aneurysm

Fig. I. Algorithm illustrating management approach to poor grade aneurysm patients. CT Computed tomography; SAH subarachnoid hemorrhage; ICH intracerebral hemorrhage; IVH intraventricular hemorrhage; ICP M intracranial pressure monitor; ICP intracranial pressure

Most poor grade patients, including those who are


moribund after aneurysmal ICH who survive and experience a favorable outcome are able to follow commands within 5 days of aneurysm rupture [7, 77, 81,
159]. By contrast, those who die generally do so within
the same time period, suggesting that most neurosurgical attention is provided to those patients who
are likely to experience a favorable outcome. The
progression of neurologic abnormalities, failure to
improve following surgery, the development of intrac-

table intracranial hypertension, or follow up CT low


density changes can also be used to determine if therapy should be pursued or discontinued. This protocol
of initial aggressive management in all poor grade patients and appropriate withholding of care based on
continued neurologic evaluation, follow up CT and
ICP monitoring provides these patients their most
reasonable change of a favorable outcome [7, 81]. A
schematic of our approach to management of poor
grade SAH patients is illustrated in Fig. 1.

14

Aneurysm Rebleeding and Aneurysm Occlusion


Untreated between 20% and 30% of aneurysms rerupture within the first 30 days. Rebleeding is maximal
on day 1 (4%) and then occurs at a constant rate between 1% and 2% per day during the subsequent 4
weeks. After 6 months untreated patients rebleed at an
annual rate between 3 and 5% [135, 174]. Approximately 60%-70% of patients who rebleed die. Poor
clinical grade, is frequently associated with a greater
risk of rebleeding, particularly early rebleeding [6, 65,
135, 144). For example, in the Danish Aneurysm Study
that included 1076 patients, rebleeding during the first
two weeks was 11.6% for grade I and II and 21.6% for
grades III-V patients [135). Consequently a major
goal in treatment of poor grade SAH is aneurysm
obliteration to prevent rebleeding; this may be achieved using surgical or endovascular techniques. There
are two unanswered questions related to aneurysm occlusion in poor grade patients: 1. when is the optimum
time to perform aneurysm surgery, and 2. which technique, surgery, endovascular or a combination provides the best results?

P. D. Le Roux and H. R. Winn


Table 4. Causes ofNeurological Deterioration and Their Diagnosis in
Poor Grade Patients After Subarachnoid Hemorrhage

Etiology

Diagnosis

Neurologic

Rebleed
Vasospasm
Hydrocephalus
Cerebral edema
Arterial thromboembolism
Seizures

CT scan
TCD, angiogram, SPECT
CT scan
CTscan
angiogram
EEG

Complications of aneurysm occlusion

Intracranial hematoma
Perforator injury
Major vessel occ1uison
Inadequately occluded aneurysm
Infection

CT scan
CT scan, angiogram
angiogram
angiogram
culture wound or CSF

Systemic

Hyponatremia
Hyoglycemia or hyperglycemia
Endogenous toxins
Hypotension, hypovolemia
Infection
Hypoxia

serum electrolytes
blood glucose
hepatic and renal function
CVP,PCWP
white blood cell count, cultures
arterial blood gas, CXR

CT Computed tomography; TCD transcranial Doppler; SPECT


single photon emission computed tomography; CSF cerebrospinal
fluid; CVP central venous pressure; PCWP pulmonary capillary
wedge pressure; CXR chest xray.

Timing of Surgery

The optimum time for aneurysm obliteration in


poor grade patients is not well defined. In particular
there is limited information about surgical timing for
posterior circulation aneurysms since most information has come from specialized referral centers after
delayed referral. By contrast, epidemiological studies
demonstrate that patients with posterior circulation
aneurysms are three-fold more likely to die within the
first 48 hours of aneurysm rupture and be in worse
clinical grade than patients with anterior circulation
aneurysms [141, 142]. Neurosurgeons have generally
delayed surgery in poor grade patients to avoid technical difficulties and surgical complications. These expectations may not be entirely valid since several
studies comparing patient cohorts or historical controls demonstrate that, whereas cerebral swelling is
more frequent during early surgery, the incidence and
severity of technical difficulties, surgical complications
or surgical morbidity is similar to patients, of all
grades, undergoing delayed surgery [7, 15, 19,21, 73,
74, 104]. In addition, the incidence of surgical complications, such as intraoperative aneurysm rupture, inability to occlude the aneurysm, or postoperative
hematoma is similar in poor and good grade patients
undergoing surgery for ruptured anterior circulation

aneurysms [80). In a nonrandomized study of 184


Grade III-V patients admitted within 3 days of SAH,
Disney et al. [20] observed that management mortality
was 38% in patients undergoing surgery within 3 days
of aneurysm rupture, 69.9% when surgery was performed between 4 and 6 days after SAH, and greater
than 83% when surgery was undertaken greater than 7
days from SAH. Specific information about posterior
circulation aneurysms in poor grade patients is lacking, however, several recent studies suggest that early
surgery may reduce morbidity and mortality [54, 59,
121] after ruptured posterior fossa aneurysms among
patients of all grades.
There are several theoretical advantages of early
surgery in poor grade patients. First early rebleeding,
is more frequent in poor grade than good grade patients [6, 65, 135, 144). Second, vasospasm is more
likely in poor grade patients; vasospasm treatment
may be best performed after aneurysm obliteration
[83, 108, 155). Third, mass lesions and increased ICP
are frequent in poor grade patients; delayed surgery
may thus subject the patient to potentially reversible
insults [32, 77, 81, 85, 120, 171). Finally, CBF is decreased in poor grade patients and progresses in severity from the day of aneurysm rupture [102]; early

Intracranial Aneurysms and Subarachnoid Hemorrhage

surgery may therefore be preferable since CBF is least


reduced. We suggest that early surgery can be recommended for most poor grade patients. However, three
groups of patients may benefit from delayed surgery.
First, it is reasonable to delay surgery in patients with
multiple medical problems so that they can be effectively evaluated and stabilized to assist the patients
through anesthesia. Second, giant aneurysms (> 25
mm) pose significant technical challenges which may
be best performed in elective circumstances once the
brain has recovered. Third posterior circulation
aneurysms that pose anatomic difficulties such as posterior oriented basilar bifurcation aneurysms may be
best treated in a delayed fashion or using endovascular
techniques [84].
Endovascular Aneurysm Occlusion

Several clinical series have established that endovascular occlusion of ruptured aneurysms using GDC
coils is feasible and that in expert hands approximately
50% of aneurysms can be completely occluded [14, 41,
44, 126, 130, 168]. By contrast, routine postoperative
angiography following surgical obliteration of 637
aneurysms demonstrated complete occlusion in 94% of
the aneurysms [79]. In general adequate morphological
results using endovascular techniques are expected in
small aneurysms with small necks 4 mm) and those
at a right angle to blood flow [126, 130, 168, 177]. Endovascular procedures appear less effective in large or
wide necked aneurysms. Aneurysm location may also
influence the success of the procedure [98, 126, 130]. It
is important therefore that the surgeon and interventionist together select which patients require surgery or
coil embolization.
There are three potential limitations to the routine
use of endovascular techniques in repair of ruptured
aneurysms in poor grade patients. First, limited shortterm studies (6-12 months) suggest that aneurysm recurrence may occur after coil embolization [14, 91].
Furthermore 20% of patients undergoing endovascular aneurysm occlusion require a second procedure,
usually surgery, within 3 years [91]. By contrast, between 1 and 4% of aneurysms that are surgically occluded require a second operation [37, 79, 80]. Second,
using endovascular techniques only half the aneurysms
can be completely occluded at a primary procedure. It
is not clear whether the patient with a partially occluded aneurysm is still subject to the same risk as a
patient with an unsecured but ruptured aneurysm. It is

15

conceivable, however, that a partially coil occluded


aneurysm may be sufficient to manage the early consequences of aneurysm rupture or ameliorate the effects of rebleeding. For example, experimental models
suggest that the volume of hemorrhage may be related
to the aneurysm's initial flow rate and so partial coiling
may limit the deleterious effects of rerupture [97]. In a
clinical series of 401 ruptured aneurysms of all grades
that underwent coil occlusion, 4.5% rebleed within 6
months. Half of the aneurysms were incompletely occluded [168]. These results while worse than surgery do
represent an improvement on natural history after
SAH. In some poor grade patients it may be reasonable to achieve partial coil occlusion to facilitate vasospasm treatment and then perform definitive surgery
when the patient recovers. However, there is limited
experience with surgical treatment of coiled aneurysms
and small clinical series suggest that a coiled aneurysm
is not a simple surgical lesion particularly when there is
insufficient space between the coils and the parent vessel for clip placement [16, 44]. Third, patients undergoing endovascular procedures require heparin [168].
The impact of short-term heparin in poor grade patients has not been studied and may delay the performance of other surgical procedures such as ventricular
drainage or craniotomy or promote the development
of delayed intracranial hemorrhage. In addition, anecdotal studies suggest that the use of long-term anticoagulation doubles the risk of a poor outcome after
aneurysm rupture [132]. Finally, the only randomized
trial comparing acute surgery to acute endovascular
aneurysm occlusion found an advantage to surgery
and that only select patients were candidates for endovascular procedures because of ICH or aneurysm
anatomy [53].
Endovascular occlusion of the acutely ruptured
aneurysm may be an attractive alternative to surgery
for some poor grade patients, however, the role of endovascular therapy in poor grade patients has only
been described in limited clinical series. Malisch et al.
[91] treated 9 poor grade patients using coils; all 9 patients died or experienced a poor outcome. By contrast, Kinugasa et al. [75] used cellulose acetate polymer and cisternal tPA in 12 grade III-V patients. Eight
patients experienced a favorable outcome, however, 7
partially thrombosed aneurysms required subsequent
surgery. The potential advantage of endovascular
therapy is that it is physiologically less stressful since
brain retraction and dissection of vessels is not required. Consequently endovascular therapy may be

16

the preferable treatment of some poor grade patients


particularly if extensive cerebral swelling is seen on CT
scan or ICP is not controlled. In addition, endovascular therapy may be useful in elderly patients where
longterm coil stability may be less relevant (Fig. 1).
Surgery, however, should be the primary treatment
in young patients, when the ruptured aneurysm is
associated with an ICH, the aneurysm is associated
with mass effect, or the aneurysm is terminal or widenecked.
Intracerebral Hemorrhage
The presence of ICH significantly increases mortality after SAH [114]. In particular ICH are frequent in
patients who die within 24 hours of aneurysm rupture
Large ICH are more frequent in patients in poor clinical grade [2, 78, 80, 81, 162]. A single randomized
study has attempted to evaluate the management of
aneurysmal ICH [52]. Fifteen patients underwent
emergency surgery, 4 (27%) subsequently died and 8
(53%) experienced a favorable outcome. By contrast,
80% of the patients who received conservative therapy
died. Several non-randomized clinical series also have
observed a tendency for patients with aneurysmal ICH
to experience a more favorable outcome when emergency surgical hematoma evacuation and aneurysm
obliteration is achieved [77, 118, 120, 162, 171]. Simultaneous aneurysm obliteration and clot removal
appears to be associated with improved outcome and
permits subsequent vasospasm treatment. For example, Wheelock et al. [171] in a retrospective study of
132 patients from 11 centers found that hematoma
evacuation without aneurysm clipping was associated
with a 75% mortality. By contrast, when definitive
aneurysm clipping was achieved at the same time as
hematoma evacuation 29% of the patients died. Factors such as young age, small ICH volume 25 ml),
and absence of SAH are associated with a better outcome [152]. However many comatose patients who
demonstrate pupillary abnormalities and large ICH
can experience a favorable outcome if rapidly resuscitated and operated on within a few hours of
aneurysm rupture [12, 77, 152].
The presence of a large aneurysmal ICH in the comatose patient who continues to deteriorate poses a
surgical dilemma. Many of these patients are irreparably injured, however, some are moribund because of
intracranial hypertension and so may benefit from immediate ICH evacuation. The etiology of ICH usually

P. D. Le Roux and H. R. Winn

can be predicted from CT characteristics, however,


enough doubt often exists to warrant further investigation. We therefore obtain angiograms on patients
with suspected aneurysmal ICH provided they are
neurologically stable. In the unstable patient, however,
even single vessel angiography may cause a life
threatening delay. Infusion CT scanning [77, 109], or
CT angiography [61] obtained immediately after a
head CT scan, is useful in these patients to determine
ICH etiology. Both techniques can detect greater than
90% of aneurysms larger than 3-5 mm in size. Infusion
CT requires about 10-15 minutes to perform whereas
using helical imaging the entire CT volume can be acquired in 30-45 seconds during the arterial pass of a
rapid intravenous contrast bolus. In the neurologically
unstable patient we then proceed to craniotomy, ICH
evacuation and aneurysm obliteration based on the
CT infusion study or CT angiogram alone. Using this
technique we have observed that a third of patients
with clinical and CT evidence of significant brain stem
compression and a GCS < 5 after aneurysmal ICH
survive and are independent and follow up [77]. Empiric exploration of the Sylvian fissure, hematoma
evacuation and aneurysm clipping without angiography, is also feasible and may prove life saving [9, 12].
In the more stable patient, in whom urgent ICH evacuation is planned, limited angiography, tailored by the
CT scan may be useful. A middle cerebral artery
aneurysm requires only an ipsilateral carotid injection,
whereas anterior communicating artery aneurysms require bilateral carotid studies. Four vessel angiograms
should be performed in all other patients not going directly to the operating room. We routinely intubate
and place ICP monitors in poor grade patients with
ICH who undergo angiography.
Intraventricular Hemorrhage and Hydrocephalus
Acute hydrocephalus and IVH are often observed in
poor grade patients [48, 81, 105, 107, 128]. For example, Milhorat [105] observed acute hydrocephalus in
3% of grade I patients and 42% of grade IV patients.
There is no consensus on the management of IVH or
hydrocephalus, however, external ventricular drainage
(EVD) is recommended, particularly if the patient's
level of consciousness is depressed. Several authors,
however, have observed that EVD increases the risk of
rebleeding [48, 119, 127, 167] or may impair natural
mechanisms that arrest aneurysm rupture [111, 169].
Ventricular drainage should therefore avoid changes

17

Intracranial Aneurysms and Subarachnoid Hemorrhage

in aneurysm transmural pressure that may precipitate


rebleeding. Catheter occlusion with blood clot is a
common complication that limits the efficacy of EVD
therefore fibrinolytic therapy has been advocated by
some authors. In clinical trials recombinant tissue
plasminogen activator or urokinase, always in combination with EVD have been used to treat IVH. Rapid
clearance of IVH, more rapid normalization of ICP,
and limited catheter blockage are observed, however,
it is not known whether fibrinolytic therapy improves
outcome or reduces the need for ventriculo-peritoneal
shunting. In addition, in the published series fibrinolytic therapy has not preceded repair of the ruptured
aneurysm [31,133]. We favor large bore catheters or in
some patients pediatric feeding tubes to effectively
drain IVH and do not use fibrinolytic therapy.
Several clinical series have reported good results
using EVD in the management of hydrocephalus or
IVH following aneurysm rupture [105, 127]. Patients
who improve within 24 hours of initiating EVD are
more likely to experience a favorable outcome [128].
However, in poor grade patients, clinical improvement
after ventricular drainage is not always associated with
a favorable outcome, whereas many patients who do
not improve can undergo surgery with satisfactory
results [107, 112, 128, 159, 167]. Severe fourth ventricular hemorrhagic dilation is an ominous sign and is
generally associated with brain death despite aggressive treatment [150]. Delaying aneurysm surgery after
ventricular drainage appears to be of limited use since
the early benefits of EVD are offset by complications
such as infection or rebleeding [48, 107, 144, 167]. In
addition, hydrocephalus is frequently associated with
vasospasm [10]; EVD alone leaves the ruptured
aneurysm unprotected, potentially precluding vasospasm treatment by hyperdynamic therapy and angioplasty [83, 108, 155]. We believe therefore that ventricular drainage to treat hydrocephalus and IVH after
aneurysm rupture is most effective when used as part
of a definitive management strategy, including early
aneurysm obliteration. Most reports indicate that half
the patients with acute clinical hydrocephalus eventually require a ventriculoperitoneal shunt.

Elderly Patients
The association between advanced age and poor
outcome after SAH is well described, in part because
many elderly patients are in poor clinical grade or excluded from active treatment [29, 50, 55, 58, 66, 69, 73,

89, 110, 134, 146, 165]. Should the elderly patient in


poor clinical condition after aneurysm rupture be
treated? Many studies demonstrate that old and young
people in the same clinical condition experience a similar outcome [62,113,134,163]. Variables such as hypertension or atherosclerosis are more frequent in elderly patients; these factors may independently have
an adverse effect on outcome [29, 73, 110]. Similarly,
Stachniak et al. [158] observed that increased perioperative complications in elderly patients undergoing
repair of intracranial aneurysms resulted primarily
from comorbidity rather than advanced age. In our
series of 159 poor grade patients, an association between advanced age and poor outcome was observed
after bivariate analysis. However, when stratified according to clinical grade the association between advanced age and outcome was not observed. In addition, following multivariate analysis, advanced age
was replaced by other clinical and radiographic variables such as intraventricular hemorrhage or atherosclerosis identified on admission angiogram [81]. In a
study using historical controls, surgical treatment of
patients in their 70's and in good clinical condition
after SAH was found to be associated with better outcome than conservative therapy [35]. Whether these
results apply to patients in poor clinical condition is
not clear, however, we believe that withholding treatment solely on the grounds of advanced age may not
always be justified. Instead, the decision to treat an elderly patient after SAH should be considered in light
of the natural history of the disease and the patient's
overall physiologic condition and associated risk factors. The use of endovascular techniques to occlude
aneurysms in the elderly patient is a promising treatment but has yet to be clearly defined. The existing
literature does not support the longterm success of
endovascular aneurysm occlusion. However, this may
be less relevant in the elderly patient with a short life
expectancy.

Surgery: Technical Considerations in the Poor Grade


Patient
A relaxed brain that permits minimal retraction is
essential to repair the ruptured aneurysm in poor grade
patients. In our experience a combination of techniques, in conjunction with careful neuroanestehsia,
provides maximal brain relaxation. First, large bone
flaps are preferable to prevent brain herniation and
strangulation, and if an ICH is present provide the

18

easiest and safest access to the hemorrhage. If possible


the sphenoid bone and orbital roof should be carefully
and extensively drilled down to reduce brain retraction. In cases with a large ICH, removal of the skull
base may not be possible and thus partial clot removal,
distant from the aneurysm, may be necessary for decompression. However, aneurysm obliteration should
proceed complete hematoma evacuation. Second,
cerebrospinal fluid (CSF) volume is reduced through
appropriate lumbar subarachnoid drainage or a ventriculostomy. Rapid or excessive CSF drainage, however, should be avoided. Third, mannitol, augmented
with furosemide, is administered during positioning
and skin preparation. We do not routinely use hyperventilation since C02 reactivity is frequently deficient
in poor grade patients [18, 76]. By monitoring middle
cerebral artery blood flow velocity and jugular venous
oxygen saturation, the PaC02 can be individualized
to the patient, thus allowing maximal brain relaxation without reduction of cerebral blood flow. Drugs
such a etomidate, propofol or thiopental may be
administered if the brain remains tight. If cerebral
swelling remains, lobectomy, ventriculostomy or
dural-augmentation without bone replacement can be
used [25]. The importance of a slack brain is emphasized in a recent retrospective review of 524 patients
[37]. Twenty reoperations were required for inadequately treated aneurysms; 14 of the reoperations
were attributed to failure to obtain a slack brain or
inadequate bone exposure.
Poor grade patients may have deficient autoregulation [18, 164], therefore we utilize judicious temporary clip application, rather than systemic hypotension to decrease the risk of aneurysm rupture and to
facilitate aneurysm dissection. The primary limitation
to temporary occlusion is the risk of cerebral ischemia.
The duration of tolerable occlusion depends on many
variables including: operative and anesthetic technique, volume status and blood pressure, which vessel
is occluded, particularly if perforators are involved,
collaterals and patient condition. Clinical data suggests that in most vascular territories the duration of
tolerable normothermic occlusion is between 15 and 20
minutes. For example, Samson et al. [137] in a retrospective analysis of 100 patients who underwent deliberate elective temporary occlusion observed that occlusion for less than 14 minute was tolerated whereas
when greater than 30 minutes clinical and radiographic evidence of infarction developed. On average
patients in poor clinical condition tolerated 4 minutes

P. D. Le Raux and H. R. Winn

less occlusion time [137]. Similarly elderly patients


with limited collateral and hemodynamic reserve also
tolerated less occlusion time. To extend tolerable occlusion time, a variety of strategies used alone or in
combination can be helpful: 1. additional Mannitol
infusion acts as a free radical scavenger and improves
cerebral rheology, 2. elevated blood pressure (SBP 160
mm Hg) augments collateral flow, and 3. carefully
controlled temperature of administration of putative
neuroprotectants such as additional isoflurane, shortacting barbiturates, or etomidate attenuate the effects
of ischemia. No randomized studies exist to guide the
choice or effectiveness of cerebral protectants, however, clinical experience dictates that their effect on
both cerebral and cardiac function must be closely
monitored.

The Cause, and Impact of Surgical Complications


About 10% of SAH morbidity and mortality is related to surgical complications such as intraoperative
aneurysm rupture, major vessel occlusion, cerebral
contusion, or ICH [24, 55, 69, 73, 74, 88, 115, 139, 146,
160, 163]. For example, 1490 patients who received
treatment for ruptured cerebral aneurysms in the Cooperative Study were disabled or died; surgical complications were the cause in 141 of these patients [73,
74]. The development of an intraoperative technical
mishap or postoperative surgical complication frequently affects outcome adversely [3, 8, 37, 73, 74, 90,
94,95,134].
Why do surgical complications occur? Many variables, which may be additive, can determine whether
surgical complications occur. Factors such as inexperience or poor surgical technique may playa role [8,
94]. Some series suggest that surgical complications are
related to aneurysm location and occur most frequently when ruptured aneurysms at the basilar bifurcation or anterior communicating artery are repaired
[38, 88, 143, 160]. Other series, however, suggest that
the ruptured aneurysm's size, and not location, correlates with the development of complications [22, 74].
Similarly, when unruptured aneurysms are repaired,
size rather than location is the most important determinant of complications [156, 175]. We recently
analyzed 597 postoperative angiograms obtained in
494 patients who underwent surgery for 637 cerebral
aneurysms. Among many variables only atherosclerosis identified on preoperative angiogram, multiple clip applications during surgery, and large aneur-

19

Intracranial Aneurysms and Subarachnoid Hemorrhage

ysm size were found to be significantly associated with


aneurysm remnants or major vessel occlusion [79].
Factors such as timing of surgery or the patient's clinical condition following SAH are not associated with
surgical complications [15, 19,21, 73, 74, 80, 104]. For
example in COSTAS, technical complications were
found not to be associated with the incidence of cerebral swelling encountered during surgery or with the
timing of surgery [45, 73, 74]. Similarly, in a review of
224 good grade and 131 poor grade patients who underwent surgical repair of anterior ruptured anterior
circulation aneurysms we found that except for severe
cerebral swelling the incidence of surgical complications is similar in poor and good grade patients [80].
Together these data suggest that aneurysm anatomy,
rather than patient condition, is primarily associated
with surgical complications.
The are several unanswered questions about surgery
in poor grade patients. The longterm effects of early
surgical intervention in poor grade patients is not
known. It is relatively simple to recognize a postoperative hemiparesis, however, whether retraction of the
swollen brain results in neuropsychological or cognitive deficits that may not occur in delayed surgery
when the brain is less swollen, is not defined. Second it
is not known whether the development of surgical
complications in poor grade patients has a greater adverse impact on the patient than the development of
the same complication in a good grade patient. Third,
whether patients with anatomically complex aneurysms will be better served by delayed surgery has not
been established. Finally, the benefits or endovascular
occlusion in poor grade patients remain to be elucidated. These questions are important and need to be
carefully considered since poor grade patients are at
high risk for rebleeding and vasospasm.
Critical Care
Successful management of the poor grade SAH patient requires careful postoperative or postembolization attention to cardiorespiratory function, volume
status, intracranial hemodynamics and the prevention
of secondary cerebral insults or medical complications.
These management goals also are important to prevent
or ameliorate the consequences of vasospasm that
typically occurs several days after SAH. Secondary
cerebral insults such as hypotension, hypoxia, or hyperglycemia are common after SAH and adversely
affect outcome [28, 78, 81, 99]. We have also observed

an association between outcome and medical complications after SAH. In addition, improved management
results are associated with a decrease in the incidence
of complications and secondary insults but not our
ability to respond to them [78]. These findings suggest
that critical care monitoring in specialized neurovascular intensive care units and proactive attempts to
avoid complications may contribute to improved outcome after poor grade SAH.

leu Monitoring
Poor grade patients should be managed in the ICU
for at least the period that corresponds to the maximum risk of vasospasm approximately 10-14 days after aneurysm rupture. There are many causes of deterioration following SAH in poor grade patients (Table
4); the key to management of these problems is prevention. The clinical exam in the poor grade patient,
however, can be difficult to interpret. We therefore
recommend that poor grade patients undergo invasive
cardiopulmonary and intracranial monitoring that is
supplemented with frequent head CT scans and
SPECT scans and daily transcranial Doppler [TCD].
Cardiopulmonary monitoring is best achieved through
an intrarterial blood pressure monitor, Swan Ganz
catheter to assess pulmonary artery pressure and cardiac output, chest xray and arterial blood gas analysis.
Frequent assessment of electrolytes, osmolality, glucose, hematocrit and urine output supplement invasive
monitoring. Invasive cardiopulmonary monitoring in
necessary to safely institute and maintain hypervolemic and hypertensive therapy since up to one third
of patients receiving hypervolemic therapy may suffer
cardiopulmonary complications including myocardial
ischemia or pulmonary edema [100]. An ICP monitor
is useful in all poor grade patients. In our experience
60% experience an episode of intracranial hypertension following aneurysm occlusion. In addition we
have found that failure ofICP to respond to Mannitol
administration rather than median maximum ICP is
significantly associated with an unfavorable outcome
[81]. ICP monitoring can also be used to detect the development of cerebral edema associated with hypervolemic therapy, allowing for appropriate adjustments
in intravenous fluid and pressor management [151].
The length of ICP monitoring is determined by a variety of factors including whether the patient is intubated, clinical condition, findings on postoperative
CT, and risk factors for vasospasm. The risks of ICP

20

monitoring are very low: in over 500 aneurysm patients treated at our institution between 1983 and 1993
using routine rcp monitoring, we had no significant
complications. A retrograde jugular catheter to determine venous oxygen saturation, AVD02 and lactate
may augment rcp monitoring. In head injury, these
parameters have been found to be useful in identifying
patients with compensated hypoperfusion who are at
risk for ischemia [82].

Vasospasm
Patients in poor clinical grade after SAH are at high
risk for cerebral vasospasm and delayed ischemic neurologic deficits (DIND). Specific management of vasospasm is discussed elsewhere in this supplement,
however there are two important considerations in
poor grade patients: prevention and detection. Maintenance of an adequate intravascular volume, that is
frequently reduced after SAH, is important in preventing the development of DIND [47]. In poor grade
patients we believe this is best achieved by early hypervolemic therapy using non-glucose containing isotonic electrolyte solutions and colloids to achieve a
pulmonary capillary wedge pressure of 14-16 mm Hg
and cardiac output between 6 and 81Jmin. Mineralocorticoids such as fludrocortisone acetate may help
maintain intravascular volume and reduce the incidence of delayed ischemia [46]. If cardiac output falls
b-adrenergic agonists such as dobutamine can be administered. In some patients, hypervolemia can lead to
resolution of delayed ischemic deficits [116, 165],
however, we frequently add induced hypertension
when symptomatic vasospasm develops. In the subgroup of patients who demonstrate progressive clinical
deterioration despite maximal medical therapy, percutaneous transfemoral angioplasty or selective intrarterial papaverine, in some patients can reverse an ischemic deficit after it has developed [56, 71, 83, 108].
Transcranial Doppler studies demonstrate that balloon angioplasty is superior to papaverine infusion in
producing sustained resolution of vasospasm and is
associated with fewer treatment failures [27]. Hypervolemic therapy can be associated with potential cardiac, pulmonary and hematologic complications
therefore pulmonary artery catheter monitoring is advocated to optimize therapy.
An important factor in the management of delayed
ischemia is early and accurate diagnosis of vasospasm.
Clinical features of vasospasm are unpredictable and

P. D. Le Roux and H. R. Winn

depend on several variables including severity and location of arterial narrowing, patient age and clinical
condition, presence of complicating factors such as
raised ICP, and extent of collateral circulation. Angiography is the definitive diagnostic test for vasospasm but is invasive and can not be repeated each
time the patient develops a neurologic deficit. Instead
we have found a combination of daily TCD and frequent SPECT examinations useful in the evaluation of
poor grade patients [81, 85, 87]. Although there are
limitations in the use of TCD, elevated cerebral arterial blood velocities in the setting of SAH, are highly
correlated with angiographic vasospasm. In addition,
the ratio of middle cerebral to cervical carotid artery
velocity can differentiate vasospasm from increased
cerebral blood flow from hyperdynamic therapy or
predict the development of symptoms [42, 64, 145]. A
prominent increase or rapid rise in TCD velocities
during the first week after SAH is characteristic of
vasospasm and often precedes the onset of clinical
symptoms. Similarly return of TCD velocities to normal usually signals the remission of vasospasm and
can help determine the duration of hypervolemic therapy. In prospective studies routine TCD examinations
have been found to make a positive contribution to the
management of patients after SAH. SPECT studies
provide an assessment of regional cerebral blood flow
and provides a measure of the degree of compensation
in the microcirculation in the face of proximal vasospasm [87, 153]. In some poor grade patients alterations in TCD or SPECT may be used to institute
appropriate therapy before symptoms develop or
when an adequate neurologic assessment cannot be
performed.
Nimodipine is a lipid soluble calcium channel
blocker that was developed to selectively relax smooth
muscle of vasospastic vessels. The use ofnimodipine in
Hunt and Hess grade III - V patients has been assessed
in a multicenter randomized, placebo-controlled,
double-blind study [123]. Nimodipine treatment was
associated with a significant increase in good outcome
at 3 months: 29.2% ofnimodipine treated (n = 72) and
9.8% of placebo-treated (n = 82) patients experienced
a good outcome. In addition, the incidence of delayed
ischemic deficits were significantly lower in nimodipine
treated patients (6.9%) than patients receiving placebo
(26.8%). However, there was no difference in the incidence or severity of angiographic vasospasm. The
association between calcium influx and cell death in
cerebral ischemia is well described; it possible therefore

21

Intracranial Aneurysms and Subarachnoid Hemorrhage

that in these poor grade patients nimodipine acted as a


neuroprotective agent. The value of nimodipine in the
management of patients in good clinical grade has
been demonstrated in several other randomized trials
[4, 125]. Consequently it is recommended that nimodipine be administered to poor grade SAH patients.

Systems Approach
Prehospital and emergency department management of head trauma patients can have a profound
impact on outcome. Many individuals, including
emergency medical technicians, paramedics, emergency physicians, anesthesiologists, and ER nurses
provide important care soon after head trauma.
Several lines of evidence suggest that an organized
responsive trauma system that includes prehospital
management and triage, organization of facilities, and
immediate availability of a surgeon can prevent death
at relatively low cost [101]. Several investigators have
compared organized and non-organized trauma systems; in all comparisons better patients outcome is
observed using organized trauma systems [101, 136,
148, 154]. The improved survival is attributed to prehospital and hospital care integration and expeditious
surgery. Similarly, improved outcome results are observed after ischemic stroke when patients are treated
within 3 to 6 hours of symptom onset; this hyperacute
treatment, however, requires a systems approach
[166]. Poor grade SAH has many parallels to severe
head injury and ischemic stroke. The experience with a
systems approach in these disorders suggests that SAH
management may benefit from a multidisciplinary
systems approach. Neurosurgeons must become
actively involved in identifying, streamlining and implementing SAH treatment protocols into prehospital
and hospital care and making the care of SAH patients
an integral part of a "Brain Attack" organization. In
many instances SAH treatment may be integrated into
severe head injury or "Brain Attack" management
schemes that are already in place in many cities.

Cost
Health care is presently undergoing significant reorganization and often is driven by cost containment.
Successful management of poor grade SAH requires a
multidisciplinary approach that incorporates intensive
paramedic and hospital care and utilizes technological
advances; factors that are frequently portrayed as
responsible for a significant portion of health care

Table 5. Hunt and Hess Grade, Hospital Charges and Neurosurgical


Length a/Stay (LOS)
Hunt and
Hess grade

Median
LOS (days)

Mean LOS
(days)

Hospital charges
(1995 US dollars)

10
15
18
23
28
16

14
18
20
24
27
21

52,064
65,949
83,232
99,369
108,690
96,194

2
3
4
5

Modified from Elliott et al. [26].

expenses. We have observed a positive correlation


between Hunt and Hess grade I-IV and hospital
charges and length of stay (Table 5). The cost of
treating grade V patients, however, is reduced, in part,
because of early mortality in some of these patients.
When all poor grade and all good grade patients are
considered, however, a significant difference in median
cost and length of stay is not observed [26, 81]. Greater
than half the total costs for patients with ruptured
aneurysms is associated with surgery and intensive
care particularly in patients with vasospasm [26, 176].
However, we have found that overall improvements in
critical care techniques and advances in vasospasm
management are both associated with improved outcome and decreased length of stay in good grade
patients after SAH [78]. Similarly Pickard et al. [124] in
an analysis of cost-effectiveness found that all investigations and interventions that may avert disability
from SAH have a favorable cost-benefit ratio. It is
important therefore to identify factors that may reduce
perioperative ICU length of stay without jeopardizing
outcome in patients after SAH.

Conclusion
In this chapter we have reviewed the management of
patients in poor clinical grade after SAH. Management of these patients is controversial and challenging
but can be successful with an aggressive proactive
approach that begins with in the field resuscitation and
continues through rehabilitation. Advances such as
a systems approach, critical care techniques, neuroanesthesia, innovative neuroimaging, interventional
techniques and technical advances in surgical management can improve the outcome for patients in poor
clinical condition after SAH. The successful and costeffective use of these advances requires a dedicated,
knowledgeable, multidisciplinary team and a commitment to ongoing research.

22

P. D. Le Roux and H. R. Winn

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Correspondence: P.D. Le Roux, Department of Neurosurgery,


New York University, 550 First Avenue, New York, NY 10016,
USA.

Acta Neurochir (1999) [Suppl]72: 27-46


Springer-Verlag 1999

Etiology of Cerebral Vasospasm


B. Weir, R. Loch Macdonald, and M. Stoodley
Section of Neurosurgery, Pritzker School of Medicine, University of Chicago, Chicago, USA

Summary
Cerebral vasospasm is a gradual onset and prolonged constriction
of the cerebral arteries in the subarachnoid space after subarachnoid
hemorrhage. The principal cause is the surrounding blood clot. The
significance of vasospasm is that flow through the constricted arteries
may be reduced sufficiently to cause cerebral infarction. Subarachnoid blood clot is sufficient to cause vasospasm; it does not require additional arterial injury, intracranial hypertension or brain
infarction, although these elements are often coexistent. The blood
released at the time of aneurysmal rupture into the alien subarachnoid environment is an extraordinarily complex mix of cellular
and extracellular elements that evolves as clotting occurs; cells disintegrate; local inflammation, phagocytosis and repair take place;
severe constriction alters the metabolism and structure of the arterial
wall as well as the balance of vasoconstrictor and dilator substances
produced by its endothelium, neurogenic network and perhaps
smooth muscle cells.
Keywords: Vasospasm; hemoglobin; endothelin; nitric oxide.

Introduction
The etiology of vasospasm is subarachnoid blood
clot. There are sporadic reports of arterial narrowing
occurring in the absence of subarachnoid hemorrhage
(SAH). These usually involve hemorrhage into the
cerebrospinal fluid elsewhere such as into the ventricles, raising the possibility that the subarachnoid
arteries are bathed in blood products. In cases of
meningitis and after surgery for intracranial tumors or
unruptured aneurysms, the pathology of the arterial
narrowing may differ from vasospasm in that it may be
true vasculitis with meningitis, or there may be unrecognized SAH occurring at the time of surgery [50].
When the SAH results from rupture of an aneurysm,
there is usually little surrounding arterial injury but the
SAH will be accompanied by varying degrees of intracranial hypertension and brain ischemia. These latter
processes are not by themselves accompanied by
vasospasm with any consistency which leads to the

conclusion that vasospasm is caused by perivascular


blood. It is true, however, that the pathophysiological
consequences of these latter processes, principally
brain infarction, are influenced by and interrelated to
vasospasm clinically and are the final common pathway for neurological morbidity and mortality after
SAH. On the other hand, when considering experimental models of SAH, the key features of vasospasm
are only reproduced by clot placement models and do
not require changes in intracranial pressure or arterial
injury. They remain an important avenue of investigation since vasospasm remains a significant adverse
prognostic factor for outcome after SAH and is one of
the leading causes of morbidity and mortality [35]. It is
the authors' contention that multiple injections of
blood into the CSF or placement of clots around systemic arteries do not cause the same disease.
Clinical and Radiological Aspects of Vasospasm
Several days after a large volume SAH the conducting arteries in the subarachnoid space (especially if
surrounded by thick clot over a significant length) are
constricted enough to have this observed angiographically. The constriction often becomes maximal
around a week from SAH and gradually reverts back
to normal dimensions over another week. The onset of
symptoms from ischemia due to vasospasm alone have
a similar albeit slightly delayed time course (Fig. 1)
[11]. Thick clot on a computed tomographic (CT)
scan, widely distributed in the subarachnoid space, is
highly predictive of subsequent severe angiographic
vasospasm. The absence of such clot, or the presence
of only intracerebral or intraventricular clot, tends not
to be associated with severe angiographic spasm or
delayed ischemic deficits from vasospasm alone.

28

B. Weir et at.

peak 7 days ~
50

~----

angiographic vasospasm
symptomatic spasm

" - - peak 8 days

o
~

100

,S

'~

1l

Indma:

IEL:
Media:

nitrite/nitrate, TAT

flattened endothelial cell.


light iunctions
smooth, not
corrugated
spindle shaped
smooth muscle cells

7
Time

vacuolated endothelium
loss of tight iunctions, corrugated
fragmented
corrugated
smooth muscle cells contracted
markedly thickened, vacuoles,
some necrosis

(Days)

15

21

near nonnal caliber


necrosis, some fibrosis
corrugated

fibrotic, thickened

adventitial cellular infiltrate

foamy
regenerating smooth
muscle cell.

Fig, I, Graph of the time course of angiographic and symptomatic vasospasm and pathological changes in arteries. Angiographic vasospasm is
maximal 7 days after a single SAH whereas symptoms from vasospasm (symptomatic vasospasm) have their most frequent onset at 8 days.
Pathological changes in the cerebral arteries over time are shown at the bottom. Initially, there is contraction of the smooth muscle cells. During
the second week after SAH, there is some necrosis of smooth muscle and endothelial cells and possibly fibrosis of the arterial wall and infiltration with inflammatory cells, Weeks after SAH, there is fibrosis in the tunica media and adventitia and varying degrees of endothelial proliferation, TAT thrombin-antithrombin III complex; ET endothelins; IEL internal elastic lamina

Clinically-evident symptoms and infarction from ischemia due to vasospasm alone are more likely with
increased volume of SAH, in elderly patients, in patients with long-standing hypertension and when the
patient presents in poor neurological grade [72]. In
addition, increased intracranial pressure, low blood
oxygen or glucose, hyponatremia, hypovolemia, increased blood viscosity, hypotension, hyperthermia,
absence of favorable communicating or collateral arteries or the presence of preexisting stenoses or arterial
occlusions will tip the scales toward infarction. Since
infarction develops when a region of brain is subjected
to a critically reduced blood flow for an excessive time,
systemic physiological factors come into play. To
avoid infarction, the blood must be adequately oxygenated, the hematocrit must be sufficient and cardiac
function must provide a safe pressure and flow to the

brain. The intracranial pressure must not be so elevated that blood flow is interfered with.
If angiography is performed around a week following SAH about two-thirds of patients will show angiographic vasospasm. However, this will be sufficient
to cause symptoms in only one-third. The time course
of vasospasm is the same regardless of its severity. If a
patient does develop symptomatic vasospasm, then
recovery, permanent deficit or death can be anticipated
(in the absence of effective therapy) in about one-third
each.
Many studies have indicated that vasospasm is an
important but far from the only prognositc factor for
adverse outcome after SAH. Others include age,
neurological condition immediately after SAH, preexisting medical conditions especially hypertension,
aneurysm size and site, intraventricular/intracerebral

Etiology of Cerebral Vasospasm

hemorrhage, day of admission to hospital after the


bleed and number of hemorrhages [35]. It is likely that
in the past the tendency to an adverse outcome with
vasospasm was increased by neurosurgeons operating
preferentially around a week post-SAH, by employing
routine hypotension intraoperatively as well as at
other times, by using purposeful dehydration "therapy" and by giving anti-fibrinolytic drugs which increased the time during which the arteries would be
surrounded by blood clot.
If vasospasm is present immediately after a SAH it is
likely that there has been SAH prior to this. Severe
vasospasm in the complete absence of subarachnoid
blood (or meningitis) is extraordinarily rare - if it
occurs at all. the onset of vasospastic ischemia more
than two weeks from SAH would be extremely unusual in our experience.
While vasospasm is most commonly observed after
aneurysm rupture - because of the high pressure leak
that develops within the low pressure subarachnoid
cisterns and more blood is released - it is becoming
increasingly recognized as an adverse factor following
cerebral trauma [89]. In trauma, however, the sources
of bleeding are many, and simultaneous brain swelling
may compress the subarachnoid cisterns so large volume clots do not accumulate. Similarly, arteriovenous
malformations are not as frequently associated with
vasospasm since much of the bleeding from them
is into the brain or ventricles rather than the subarachnoid space and particularly the voluminous basal
cisterns containing the larger cerebral arteries.
Clinicians must be particularly on guard for new
onset neurological deficits during the third to fourteenth days after SAH. The neurological symptoms
and signs are myriad. A diminishing level of consciousness or new onset weakness or speech difficulty
are the most readily observed signs. The patient also
may become febrile and develop increasing headache
and blood pressure. During this phase the serum sodium may fall. Frequent observation and serial documentation of the patients' status on a neurological
vital sign sheet by the nursing staff is essential. If a turn
for the worse is noted, consideration should be given to
performing a CT scan and repeating the hematological
and biochemical tests routinely performed on admission. Measures should be taken to increase the patient's blood pressure on the way to and during the CT
exam. If the CT scan fails to show a surgical lesion
such as a clot or dilated ventricular system and the
laboratory results are unhelpful then it is increasingly

29

important to optlmize the patient's blood volume,


pressure and oxygenation. Cardiac arrhythmias
should be treated. There is no substitute for vigilant
monitoring of the patient at such times. Not all patients improve with hypertension and hypervolemia.
Some brain areas paradoxically show decreased blood
flow and may become ischemic. This has been documented by regional cerebral blood flow as measured by
xenon-enhanced CT scans [9]. In the absence of such
direct evidence clinical observation of the patient's
status can guide therapy. A serious downhill course
may call for angiography and angioplasty if severe
vasospasm is confirmed.
Transcranial Doppler studies can measure the velocity of blood flow in the larger basal arteries. If performed serially after SAH there is usually a steady rise
in velocity. Patients with the most severe vasospasm
tend to show the sharpest rate of increase and the
highest absolute velocities however both positive and
negative exceptions to the Doppler/vasospasm association occur and therapeutic decisions should not be
made on Doppler values alone [7].
We believe that the early removal of the circumarterial blood clot by suctioning and irrigation during
very early surgery is an effective way of reducing the
risk of delayed ischemia from vasospasm. In patients
with significant residual clot postoperatively who are
at high risk of severe vasospasm overall, we also instill
tissue plasminogen activator through a ventricular
catheter placed at surgery [16]. Multiple injections
may be made depending on the rapidity with which the
clot dissolves as seen on serial CT scans. In the event
that the patient develops a significant deficit thought to
be due to vasospasm, we recommend angioplasty providing the ruptured aneurysm is clipped, there is no
evidence of infarction on CT scan and a skilled neuroradiologist is available to perform it.
Magnetic resonance imaging does not playa major
role in the diagnosis and treatment of vasospasm or
delayed ischemia. The complexity and time consuming
nature of this exam, and the relative difficulty of distinguishing clot compared with the CT scan, have
limited its use in this setting. Nevertheless it can sometimes show evidence of SAH after the CT scan is uninformative and it is much more sensitive in detecting
ischemic and infarcted regions. Some neuroradiologists are reluctant to use it after aneurysm clips have been
placed although to our knowledge there have been no
untoward events with non-ferromagnetic aneurysm
clips such as the current Ya~argil or Sugita ones.

30

B. Weir et al.

OxyH,b

erythrocyte

.---

4 glo\ in chains
4 herr e moities

~!~~~~:e
membrane stroma
other cytosol
proteins

OxyHb + Deoxy Hb

PyrroJe

"'-Fe>+ -

PyrroJe
/

l'~-i' .""""00

PyrroJe

'"

0,

PyrroJe

MetHb + 02.L (superoxide radical)

02

A~

Heme

~l
~

Globin

chains

Free radical
reactions

heme
oxygenase types 1,2

biliverdin Ix.. + Fe3+ + CO


biliverdin
reductase

NADPH
NADP"

~
? vasodilation

Bilirubin IXa
Fig, 2, Diagram of the metabolic pathways for breakdown of
hemoglobin

Pathophysiology of Vasospasm
Potential Spasmogens
It is not surprising that evidence for a single, universal spasmogen has not been forthcoming. It is likely
that hemoglobin (Fig. 2, the most abundant vasoconstrictor released from decaying erythrocytes) or its
derivatives is at least one of the factors, but other
compounds such as adenosine triphosphate (ATP) also
are found in high concentrations and under some experimental conditions can lead to constriction [52,82].
An imbalance between physiological vasoconstrictors
such as endothelins (ETs) and prostaglandins and
physiological vasodilators such as nitric oxide (NO) or
prostacyclin (PGIz) could also playa part. There is
some evidence for a significant alteration in prosta-

glandin metabolism after SAH in that there is increased production of vasoconstricting prostaglandins
and thromboxanes and decreased synthesis of PGIz
(Fig. 3).
After SAH, erythrocyte hemolysis (physical disruption) begins almost immediately and continues until
all the red cells are phagocytized or lysed. In animals,
erythrocytes may cross into the bloodstream intact
after SAH but it is not known if this happens in man.
Red cells incubated in CSF in vitro at body temperature release large amounts of hemoglobin over hours
to days. The rate of hemolysis and of conversion from
ferrous (Fe2+) to ferric (Fe3+) hemoglobin depends on
the conditions of incubation such as temperature, agitation, whether incubation is in vitro or in vivo and
the presence of plasma proteins. After SAH, lumbar
puncture shows that CSF is clear of red blood cells
within a few days to a month. The rate of clearance of
SAH depends mainly on the volume of SAH and perhaps is faster in youth.
With SAH, there is influx of blood elements into the
subarachnoid space (Fig. 4). Each element is a potential spasmogen (Table 1) although the most extensively studied are hemoglobin, eicosanoids and free
radicals [17, 18,47,48]. SAH may also tip the balance
of physiological regulators of cerebrovascular tone
(Table 2) from normal towards a state of contraction.
The criteria that would be expected of any spasmogen
accounting for vasospasm are listed (Table 3). Since
vasospasm is dependent on the continuing presence of
subarachnoid blood clot (unpublished observations),
processes occur continually to produce spasm. There
could be ongoing release or formation of the same or a
series of spasmogens over time. Other potential interactions with brain and the cerebral arteries may be
postulated (Fig. 4).
Since red cells are the most numerous, since hemoglobin is their principal protein, since it is progressively
released in an appropriate time course as the cells disintegrate and since it is a vasoconstrictor in a wide variety of in vitro and in vivo model systems, it is a key
suspect as the main spasmogen [46, 47] (Table 4).
Several clot fractionation experiments have also demonstrated that erythrocytes are the blood component,
and not white blood cells, platelets, plasma, or erythrocyte ghosts alone, that cause vasospasm in vivo, although the vasospasm that was produced usually was
not as severe as that caused by whole blood [47]. We
suspect hemoglobin is not the sole factor because hemolysate of red cells, which contains numerous sub-

31

Etiology of Cerebral Vasospasm

Phospholipids

cyclo-oxygenase

PLA2, PLC

Arachidonic Acid

5-lil'H"yg,~~

15-lipo-oxygenase

PGG2
, peroxidase
PGH2

PGI2~XA2

15-HPETE

LipoxinA

LipoxinB

5-HPETE

/
LTA4

A
JI
LTB4

(prostacyclin/KmboXane)

+
~

15-HETE

glutathione
~5-transferase

LTC4
I glutamyl
transferase

LTD4

~ aminopeptidase
LTE4

+IN-acetyl
transferase
N-acetyl-LTE4

RELAXATION

CONTRACTION

I INFLAMMATION I

Fig. 3. Diagram of metabolic pathway of arachidonic acid production of eicosanoids (prostaglandins, thromboxanes, leukotrienes). PLA 2
Phospholipase A2 ; PLC phospholipase C; PG prostaglandin; HP ETE hydroperoxyeicosatetranoic acid; LT leukotriene
ICH

ICP

1 brain damage

..
?
inflammatory _ _~~rl

cells

final common
pathway of ischemia

spasm

Fig. 4. Diagram of the possible interactions between subarachnoid


blood clot, the arterial wall and the brain that may be important in
the pathogenesis of cerebral vasospasm. Most research has focused
on the clot-arterial wall interaction which is probably the most important. Other interactions have not been investigated such as the
brain and arterial wall affecting the subarachnoid clot so as to promote its breakdown or reactions in it that then cause vasospasm. The
effect of the arterial wall on the clot is also not known. ICH Intracerebral hemorrhage; SAH subarachnoid hemorrhage; ICP intracranial pressure

stances in addition to hemoglobin, usually is a more


potent vasoconstrictor than hemoglobin alone in many
model systems [2]. In addition many of the experiments using hemoglobin had unknown proportions of
oxy- and deoxyhemoglobin and may have had sub-

stantial impurities including methemoglobin, endotoxin and other substances. Ultrapure hemoglobin in
some of our recent experiments is not a very potent
constrictor in vivo. The ability of fresh erythrocyte
hemolysates to increase intracellular Ca++([Ca++U in
smooth muscle cells was more related to the ATP
content of the hemolysate than to any other compound
[99]. Aoki, et al., also noted that the contractile activity
of hemoglobin was low until a low-molecular weight
fraction of hemolysate (0.5 to 2 kD) was added to the
hemoglobin [2]. This suggests that hemoglobin alone
may not be the cause of vasospasm and that low molecular weight substances may be involved (Table 5).
Smooth Muscle Contraction

Vasospasm is for the most part a problem of smooth


muscle contraction. Understanding of the physiology
of smooth muscle contraction is incomplete and until it
has been elucidated, it is unlikely that the pathogenesis
of vasospasm will be solved. Changes in [Ca++L are a
key regulator of vascular smooth muscle tone [60].
Electrical, mechanical, or chemical stimuli may alter
[Ca++l i . An increase in [Ca++L results in binding of
Ca++ to the intracellular receptor protein calmodulin.

32

B. Weir et al.

Table 1. Potential Spasmogens Released after SAH and Their Possible Role in Vasospasm
Spasmogen or process

Possible role
Compound

1. Erythrocytes and contents


oxyhemoglobin (Deoxyhemoglobin) and
breakdown products
such as hemin, iron,
bilirubin and globin
chains
products of free radical
reactions stimulated by
hemoglobin oxidation
adenosine nucleotides
other cytosolic proteins
erythrocyte membranes

2. Platelet contents
serotonin
adenosine nucleotides

Table 2. Physiological Vasoactive Mediators of Cerebrovascular


Tone that may be Altered After SAH and Contribute to Vasospasm
(17)

vasocontriction, promote free


radical reactions, block NO
vasodilation, increase ET release,
block perivascular nerve effects,
alter eicosanoid release
may cause vasoconstriction

vasoconstriction
unknown
provide lipid for lipid peroxidation,
unknown
possible vasoconstriction early
after SAH
vasoconstriction

3. Leukocytes and inflammatory mediators


leukocytes
vasoconstriction
eicosanoids
increased vasoconstriction by prostaglandins and thromboxanes,
decreased vasodilation by decreased PGI 2
cytokines (interferons,
increase inflammation, possible
tumor necrosis factors,
vasoactive effects
interleukins, macrophage derived cytokines, growth factors,
chemokines, monokines)
4. Products of coagulation cascade
fibrin degradation
increase vasoconstriction due to
products
other spasmogens
fibrinogen
unknown
thrombin
unknown
5. Other serum proteins
unknown

Amines
norepinephrine

serotonin

histamine

dopamine
acetylcholine

Lipids
eicosanoids

leukotrienes
platelet-activating
factor

Peptides
sympathetic
other constrictors

parasympathetic

trigeminal sensory

This complex activates calmodulin-dependent myosin


light-chain kinase, phosphorylates myosin, and allows
interaction with actin to cause contraction (Fig. 5).
Sources of Ca ++ in vascular smooth muscle include the
sarcoplasmic reticulum, the extracellular space, Ca ++
bound to the plasmalemma and mitochondria. The
first two are the most important in smooth muscle. The
sarcoplasmic reticulum is an intracellular system of
membrane tubules that functions in Ca++ uptake, release, and storage and plays a role in both contraction
and relaxation of smooth muscle. Ca ++ can be released from the sarcoplasmic reticulum by inositol
1,4,5-triphosphate (IP3), which acts on the IP3 receptor or by Ca++ -induced Ca++ release, which is mediated by the ryanodine receptor. The binding of ago-

other vasodilators

Purine nucleotides
adenosine
ADP and ATP

Gases
nitric oxide

carbon monoxide

Action

perivascular sympathetic nerves originating


from cervical sympathetics, tone is balance between a and Preceptor activation,
nerves shown to degenerate after SAH,
time course lasts longer than vasospasm
innervates intrinsic vessels from brainstem
nuclei, vasoconstricts large arteries although existence of serotoninergic nerve
fibers controversial, see Table 1
acts via H2 receptors to cause vasodilation of
distal arteries and increased permeability.
H) receptor activation causes constriction
of proximal cerebral arteries.
increases cerebral blood flow probably by
indirect action on brain neurons
parasympathetic neurotransmitter, causes
endothelium-dependent relaxation
PGI 2 relaxes via increased cAMP; thromboxane A2 and prostaglandin F 2u are
vasoconstrictors, PGE2 is a vasodilator
potent vasoconstrictors of large vessels,
increase vascular permeability
no apparent direct effect

neuropeptide Y, causes vasoconstriction


angiotensin 2, also causes release of thromboxane A2 from endothelium, endothelins, vasopressin may cause direct
smooth muscle contraction and
endothelium-dependent relaxation
vasoactive intestinal peptide, peptide histidine isoleucine, pituitary adenylate
cyclase-activating peptide vasodilate
by acting directly on vascular smooth
muscle, increasing cAMP
calcitonin gene-related peptide is a vasodilator that acts via receptor to increase
cAMP, Substance P vasodilates possibly
by releasing NO and/or increasing cAMP,
neurokinin A also vasodilates
adrenomedullin is a vasodilator and may
increase vessel permeability
vasodilator, acts by receptor-mediated
increase of cAMP.
complex effects, may vasodilate by endothelium-dependent or independent
mechanisms and may vasoconstrict
by direct effect on smooth muscle
free radical, vasodilates by stimulating production of cGMP by activating guanylate
cyclase
may be vasodilator, increases cGMP

33

Etiology of Cerebral Vasospasm


Table 3. Criteria for a Spasmogen that Could Cause Vasospasm
-

present in blood clot


released in progressively increasing amounts for 5-10 days then in diminishing amounts over 7-14 days
able to penetrate to the vascular smooth muscle layer and possibly endothelium
vasoactive, causes sustained and ~ 50% reductions in arterial diameter
present in subarachnoid space or periarterial region in concentrations that are adequate to cause severe contraction
causes smooth muscle necrosis and possibly endothelial cell damage, contractions associated with decreased arterial contractility and
compliance after prolonged exposure
- contractions not readily reversed by known receptor antagonists
- not present in subarachnoid space in other conditions that alter the cerebrospinal fluid such as neoplastic or inflammatory meningitis
- vasospasm does not occur if it is removed from the subarachnoid blood clot or its action is blocked prior to vasospasm

Table 4. Evidence for and Against a Role for Oxyhemoglobin in Vasospasm


For
- thick perivascular blood clot causes severe chronic vasospasm and hemoglobin is the principal component which is progressively released as
erythrocytes lyse within CSF
- oxyhemoglobin inhibits endothelium-derived relaxing factor (NO) by binding to it and/or by producing 02' that destroys it
- oxyhemoglobin stimulates release of va so constricting ETs from endothelial cells
- qxyhemoglobin stimulates release of vasoconstricting prostaglandins from endothelial cells
- cixyhemoglobin, even from different species can constrict arterial rings and strips of both cerebral and system arteries in vitro.
- oxyhemoglobin can autooxidize to produce O 2 ' that can produce OH' by reacting with iron released from hemoglobin
- hemoglobin damages perivascular nerves of all types
- hemoglobin has synergistic effect with other vasoconstrictor substances such as K+, ATP, serotonin, fibrin degradation products and hypoxia
- hemoglobin increases rCa 2+Ji and can cause isolated vascular smooth muscle cells to contract
- hemoglobin has been shown immunohistochemically within spastic vessel walls after periadventitial blood injection
- as oxyhemoglobin is metabolized it can produce other potential vasoconstrictors such as hemin, iron and bilirubin
Against
-lllagnetic resonance imaging studies indicate oxyhemoglobin is usually gone in 1 or 2 days after intracranial bleeding (oxy changes to deoxyand methemoglobin)
- 4emoglobin usually contains trace amounts of endotoxin, stromal proteins and phospholipids which can also cause vasoconstriction and
inflammation
- most studies have been done on vessel rings or strips in vitro using impure hemoglobin
- studies show that hemoglobin is not a very potent contractile agent but that its potency can be increased by combination with low molecular
weight components of the erythrocyte
- pure human oxyhemoglobin alone did not produce severe vasospasm in monkeys

Table 5. Evidence for a low Molecular Weight Spasmogen ( LMWS), Possibly ATP, as a Cause of Vasospasm
"
- isolated rat basilar artery smooth muscle cells develop increased [Ca++]i in a dose-dependent fashion when exposed to LMWS from fresh
human erythrocyte hemolysate but the effect diminishes with time, being absent after 21 days of incubation
- effect was potentiated by a high molecular weight fraction of he moly sate and also by pure hemoglobin that did not affect [Ca++]i independently
- erythrocytes contain ATP (1.6 mmol/L) in concentrations that contract vascular smooth muscle
- rat femoral arteries contract after 7 days exposure to substances containing ATP such as dog hemolysate or ATP itself but not pure hemoglobin
- chronic vasospasm in monkeys resulted from subarachnoid placement of ATP, hemolysate or pure hemoglobin
- dog hemolysate containing ATP, 34 J.lIllol/L, produced concentration-dependent contractions of dog basilar artery that were inhibited by
suramin, a P 2 -purinoceptor antagonist
- hemolysate increases rCa ++]i in both rat basilar artery smooth muscle and bovine middle cerebral artery smooth muscle cells by releasing
Ca++ from internal stores and causing Ca++ entry by voltage-independent Ca++ influx, effects which are identical to ATP
- nucleotides such as ATP and UTP activate G-proteins coupled to P2u -purinoceptors to mobilize [Ca++]i in rat basilar artery smooth muscle
cells

nists to their cell surface receptors leads to activation


of phospholipase C by a G protein-mediated interaction, Phospholipase C cleaves phosphatidylinositol
4,5-bisphosphate to 1P3 and diacyl glycerol. IP3 can

then mediate contraction by releasing [Ca++]j and


diacyl glycerol participates in activation of protein
kinase C, which may be involved in the maintenance of
contraction or in other responses to agonist stimula-

34

B. Weir et al.
Norepinrphrin. An~iotcnsin II .
...----- Endothelin, SHT. ATP

Ca2+

d...I"';=,;oo

C+ca,.~~

Ca2+~ I_~

I Receptor.gated

Ca" channel
independent of
G'protein

Ca"

Ca" calmodulin

ATPase

myosine light
chain kinase

G protein

'.5,~;;;;,u.
Intracellular
Cal + stores
(sarcolemma)

~. ADP.

'--(

M'

---':::::====111

~_

)"T
PLC

Phosphotidylinositol

Ca" calmodulinMLCK
ATP\

-=

ft

Myosin P Actin

IP)-sensitive
1Ca" release

PKC

I alternative
contraction
regulation system

~Or:I===A=ct=in=!=~=;o=C:=I~n=,p==_===C:=:::O=N=T=RA=C=T=IO=N=/==~

Ca2+V~Na+

Na+Ca++ exchange

Fig. 5. Diagram of pathways of smooth muscle contraction. See text for discussion. PLC Phospholipase C; DA G diacyl glycerol; PKC protein
kinase C; MLCK myosin light chain kinase; ADP adenosine diphosphate; ATP adenosine triphosphate

tion. Ca++ -induced Ca++ release is Ca++ release from


sarcoplasmic reticulum that occurs when [Ca++]j increases from any cause. Refilling of the sarcoplasmic
reticulum is incompletely understood but is believed to
involve phosphorylation of phospholamban by cyclic
nucleotide (cAMP, cGMP)-dependent protein kinases
that in tum activate the Ca++ ATPase [45].
Ca++ influx from the extracellular space through
Ca++ channels is the second major source of activator
Ca ++ and is particularly important in smooth muscle
because of the limited size of the intracellular Ca++
pool. Cell membrane Ca++ channels may be activated
by depolarization, by an increase in [Ca++]j produced
by release of Ca++ from intracellular stores, or by direct opening upon binding of an agonist to its cell
membrane receptor [60]. Of the types of Ca++ channels described in smooth muscle cells, the L-type Ca++
channel plays the dominant role in mediating the influx of Ca++ in response to membrane depolarization.
L-type Ca++ channels are blocked by dihydropyridines such as nimodipine. Since nimodipine has minimal effect on vasospasm in man, other mechanisms of
contraction must be involved or inadequate concentrations of nimodipine reached the smooth muscle in
the clinical trials [72]. Ca++ influx also can be triggered
by depletion of intracellular Ca ++ stores (Fig. 5). The
mechanism of store-operated Ca++ entry is unknown

but one theory is that an intracellular second messenger signals plasma membrane channels about the state
of filling of the stores [60]. Luminal Ca++ in the sarcoplasmic reticulum activates a tyrosine phosphatase
that shifts a 130 kD protein towards a dephosphorylated state. Depletion of the Ca++ stores favors phosphorylation of the 130 kD protein, which then gates a
Ca++ -permeable membrane channel. Other theories
are that sarcoplasmic Ca ++ content is signalled to the
plasma membrane by a cytochrome P450-dependent
mechanism or by a cyclic GMP-mediated signalling
system.
Although Ca++ is an important intracellular second
messenger mediating contraction, there is only an indirect relationship between [Ca++]j and smooth muscle
contraction (Fig. 5) and contraction to agonists can
develop without any change in [Ca++Ji, Most tonic
contractions persist after [Ca++]j has returned to basal
or near-basal levels and after myosin light chain
phosphorylation also has decreased [20, 93]. Processes
postulated to explain prolonged tension development
in the absence of increased [Ca++]j and myosin light
chain phosphorylation are the latch state or another
regulatory mechanism such as one due to phosphorylation of other cytoplasmic proteins by, for example,
protein kinase C [20, 93].
Some compounds thought to cause vasospasm can

35

Etiology of Cerebral Vasospasm

increase [Ca++]j in smooth muscle cells, including hemoglobin, erythrocyte hemolysate and ATP [84, 86,
88]. Measurements of [Ca++]j in vasospastic dog basilar artery have shown either an increase [6], no change
or a decrease [78, 95]. The manipulations required to
make such measurements are extraordinarily difficult
and the significance is uncertain since there is not a
direct relation between [Ca++]j and contraction. For
example, calmodulin was reduced in vasospastic arteries and the calmodulin-inhibitor, trifluoperazine,
had minimal effect on vasospasm in vivo in dogs
suggesting that vasospasm is not due to persistently
elevated Ca++ -calmodulin complex [71]. The ability of
the smooth muscle to regulate [Ca++]j may be disrupted during vasospasm in the absence of changes in
[Ca++]j, or the contractile apparatus may be more
sensitive to [Ca++]j leading to contraction [60]. Wang
et al. reported that the plasma membrane Ca++ATPase that pumps Ca++ out of cells and lowers
[Ca++]j, was significantly decreased in basilar artery
smooth muscle after SAH in dogs and Kim, et al.,
found an increased permeability of smooth muscle to
Ca++ in the same model [41, 92].
Investigators also have examined changes in other
components of contraction during vasospasm. Most
but not all [6] studies of vasospastic arteries found
levels of myosin light chain phosphorylation were not
markedly elevated [49]. ML-9, an inhibitor of myosin
light chain phosphorylation, also had only a modest
effect on vasospasm [42]. Levels of contractile proteins
were decreased during vasospasm, perhaps reflecting
activation of proteolytic enzymes such as the calpains.
The cal pains are neutral proteases that are activated
by increased [Ca++]j. They catalyze break-down of
cytoskeletal and contractile proteins and protein kinases, leading in part to activation of these kinases,
including protein kinase C [43, 49]. Some of the pathways that are activated may lead to smooth muscle
contraction. The decrease in contractile proteins and
in caldesmon, the demonstrated activation of calpain
proteolysis, and the efficacy of inhibitors of calpeptin
against vasospasm in rats, dogs and rabbits, supports a
role for Ca++ -activated proteolysis in vasospasm [43].
Calponin is a troponin-like protein that inhibits the
actin-myosin interaction [10, 93). Its action is accentuated when it is phosphorylated by protein kinase C
or Ca++ -calmodulin-dependent protein kinase II. A
decrease in calponin that was noted in vasospastic arteries could promote vasoconstriction [10].
The activation of protein kinase C that may occur

after agonist binding to smooth muscle cells or after


activation of calpains has been investigated because it
has been postulated to be involved in tonic smooth
muscle contraction [56]. Vasospasm could be reversed
in dogs by topical application of the relatively nonspecific protein kinase C inhibitors, H-7 and staurosporine [56]. The diacyl glycerol content of the basilar
artery was elevated and correlated with vasospasm in
one study, although this finding was not replicated by
other investigators [79, 97]. Other studies of the role of
protein kinase C have been conflicting [64, 97). Involvement of IP 3 and protein kinase C in vasospasm
was also suggested by observations that oxyhemoglobin elevates [Ca++]j and IP3 in cultured smooth
muscle cells and that these responses are blocked
by neomycin, an inhibitor of phospholipase C [49].
Blockade of protein kinase C could be detrimental
because the release of endothelial vasodilatory NO
and PGI2 are dependent on protein kinase C activation
[93].
Smooth Muscle Relaxation

Smooth muscle relaxes by increasing cAMP, cGMP


or by hyperpolarization due to activation of K+ channels (Fig. 6). ~-adrenergic stimulation and PGI 2 elevate cAMP. Nitrovasodilators, endothelium-derived
relaxing factor and atriopeptins elevate cGMP. The
mechanism of cGMP relaxation is unknown but seems
to involve activation of cGMP-dependent protein kinase, which reduces [Ca++]j by activating the membrane
Ca++ -Mg++ ATPase [13). NO also hyperpolarizes
smooth muscle which will promote relaxation and
might occur by opening of K + channels. Whether NOinduced increases in cGMP mediates K+ channel activation is not known. Activation of K+ channels is the
third mechanism of relaxation [5] and may interact
with cAMP in that compounds that increase cAMP
produce vasodilation partly by opening large conductance Ca++ -activated K+ channels and ATP-sensitive
K+ channels.
There have been several investigations of the effects
of SAH and vasospasm on cerebrovascular relaxation.
The role of cGMP is reviewed under NO below. It is
known that cAMP relaxes cerebral arteries in response
to several constrictors including acute subarachnoid
blood but the effects on the true delayed phase of vasospasm have not been investigated [21,69, 76). Relaxation of human arteries to nitroglycerin was more impaired than to PGI2 8 to 19 days after SAH, suggesting

36

B. Weir et al.
Agonists Ach

Thrombin,
bradykinin.
shear stress,
5HT,ADP

- - - - - - t..~

arachidonic acid

1\

~
....,

EDHF

:: )

~_

. . . . . . /NO

} ~~~: __~--~------'--J~_~

.,

"~_O

Endothelial Cen

// t tK + ~,
/

?
"'

,,"'''''"','~,;..

"

-'~~~

'
~@

',__! _
ATP

Smooth
muscle
cell

~---''=--'--=-

cAMP

On'

RELAXATION

~--

Fig. 6. Diagram of pathways of smooth muscle relaxation. EDHF Endothelium-derived hyperpolarizing factor; AC adenylate cyclase; GC
guanylate cyclase; ATP adenosine triphosphate; cGMP cyclic guanosine monophosphate. See text for discussion

relative preservation of the cAMP pathway [66]. Two


days after SAH in rats, vasodilator responses to acetylcholine and sodium nitroprusside, agents that relax
by activation of soluble guanylate cyclase and increased cGMP, were impaired whereas vasodilation to
cGMP was preserved. There was increased relaxation
to activation of ATP-sensitive K+ channels [83].
Smooth muscle cells rely on high energy phosphate
compounds such as ATP and GTP for mediating contractions and relaxations. Deficiencies, particularly of
ATP, can result in rigor in smooth muscle, a state that
is similar to vasospasm. Vasospasm has been associated with a reduction in high-energy phosphates
and there is evidence that hemoglobin and bilirubin
decrease ATP in cultured smooth muscle cells [62,
90, 98]. The possibility of a rigor state secondary to
metabolic exhaustion in the cerebral arterial smooth
muscle as an underlying process in vasospasm remains
an attractive but infrequently investigated possibility
[93].

Endothelins
The ETs are 3 2l-amino acid peptides synthesized
by endothelium and other tissues (Fig. 7). They are
proteolytically cleaved from preproET precursors.
Once released from cells as proETs (big ETs), they are
cleaved by ET converting enzyme(s) to the active ETs.
Endothelin-l and -3 are found in brain and endothelial

cells. There is very little ET in plasma. Physiological


stimuli for synthesis include shear stress, hypoxia,
ischemia, thrombin and other receptor agonists. The
intracellular pathways involved in the transduction of
these stimuli in order to cause increased ET-l seem to
include both protein kinase C dependent and independent pathways as well as protein tyrosine kinase pathways [55]. NO and PGh also are synthesized by protein kinase C dependent pathways in endothelial cells
[94]. They increase cAMP and cGMP which inhibit ET
synthesis.
Endothelins act on at least 2 receptor types called
ETA and ETB receptors (Fig. 7). ETA receptors are
more sensitive to ET -1 and -2 and are found mainly on
smooth muscle cells were they mediate contraction
through G-protein-mediated activation of phospholipase C leading to formation of IP3 and diacylglycerol.
The former releases intracellular Ca++ and causes
contraction and the latter activates protein kinase C.
ET Breceptors are equally sensitive to all 3 ETs and
may be found on endothelial cells where they mediate
relaxation or on smooth muscle cells where they mediate contraction. The role of the ETs in regulation of
the cerebral circulation is unknown [5]. There are also
ET receptors on neurons and astrocytes.
The data on ET-1 and vasospasm do not form a coherent story at present. A theory was based initially on
the observation that SAH and vasospasm are associated with increased CSF ET levels [25, 53, 80, 85].

-i
r

Etiology of Cerebral Vasospasm


Oxyhemoglobin

Thrombin
-~~-------------~.
Vasospasm
------....
Angiotensin II
Big endothelin-l

TGFJ3

37

Bigendothelin-3

endothelin converting
enzyme(s)

Receptors
[G protein coupled)

? opens voltage-gated
Ca 2+ channels
? activates PLC

;:l

Contraction
(slow onset,
long-acting, potent)

ET-l

ET-3

ET! '\T"

:0
~

In anterior
pituitary cells only

contraction

relaxation
Fig. 7. Diagram of pathways for endothelin (ET) synthesis and actions on ETA and ET B receptors.
phospholipase C

An equal number of reports, however, found no such


correlation [30, 74]. Overall, the data probably do
support an association between increased ET -1 levels
and the post-SAH state although this association does
not prove that ET-l causes vasospasm since ET-l is
elevated in other conditions that are not associated
with vasospasm [53]. No increase in ET-l messenger
ribonucleic acid (mRNA) was found during vasospasm after SAH in monkeys although there was an
increase in ET Breceptor in vasospastic arteries and in
ETA and ETB receptors in the cerebral cortex [30].
These changes were postulated to be compensatory
changes to increase cerebral blood flow after SAH.
They were similar to changes reported in ET receptor
binding after SAH in dogs [77]. The data suggest that
alterations in ET and ET receptors occur after SAH
but that they may be secondary to other pathophysiological processes involved in SAH. Finally, a large
body of literature shows that ET receptor antagonists
prevent or decrease experimental vasospasm [53, 77].
The efficacy of these agents is at odds with the lack of
changes in ET-l mRNA during vasospasm and with
the inability to find increased ET-l during vasospasm.
Pluta et al. offered one explanation [74]. Normally
there is a balance between vasoconstricting substances
(prostanoids, ETs) and vasodilating substances (NO
and/or related NO-containing compounds, PGI2).
SAH impairs NO-mediated relaxation which leaves
ET -induced vasoconstriction unopposed and therefore

TGB~

Transforming growth factor

~;

PLC

the blockade of the ET system would decrease vasospasm. ET-l production also is normally under inhibition by NO which if lost after SAH could further
enhance the effects of the ETs, perhaps in the absence
oflarge changes in ET mRNA or protein.
Nitric Oxide

NO is a diffusible free radical gas with a half-life of


seconds. It or a related NO-containing compound is a
potent vasodilator that is synthesized from I-arginine
and oxygen by 3 types of NO synthases (Table 6,
Fig. 8) [14, 15]. NO (or a related NO-containing
compound) is the endothelium-derived relaxing factor
released from endothelial cells that relaxes smooth
muscle in response to stimulation by a variety of substances. NO causes relaxation by activation of soluble
guanylate cyclase and increasing cGMP. Sodium nitroprusside and nitroglycerin also relax smooth muscle
by increasing cGMP formation.
During vasospasm after experimental and human
SAH, numerous studies have shown that endotheliumdependent relaxation is impaired [39, 40, 49]. The human studies show decreased endothelium-dependent
relaxations occur 1 day [29] as well as 8 to 19 days
post-SAH [66]. The time course of changes in the NO
system do not always correlate with vasospasm. There
was loss of NO synthase immunoreactivity in perivascular nerves for up to 14 days after SAH in mon-

38

B. Weir et al.

Table 6. Types of Nitric Oxide Synthase


Characteristic

Endothelial

Neuronal

Inducible

Location

endothelial cells
membrane associated
calcium-calmodulin
tetrahydrobiopterin
NADPH
constitutive

neurons
cytosolic
calcium-calmodulin
tetrahydrobiopterin
NADPH
constitutive

picomolar levels of NO

picomolar levels of NO

macrophages, smooth muscle, endothelial


cells, cardiac myocytes, astrocytes
not calcium dependent
? tetrahydrobiopterin
?NADPH
induced by cytokines, lipopolysaccharides
inhibited by steroids and some cytokines
nanomolar levels of NO

Cofactors

Activity

~rg0inine~
;--

::

'4

NADPH

- acetylcholine
- serotonin

relax smooth muscle


by activation of
guanylate cyclase

acts on
cell membrane
receptor

- substance P
- adenosine nucleotides
bradykinin
histamine
A23187

arginine vasopressin

Fig. 8. Diagram of pathway for NO synthesis. Some forms of NO synthase require Ca++ and calmodulin

keys, although vasospasm had resolved at this stage


[73]. Endothelial NO synthase could not be assessed.
There is conflicting information on the mechanism
by which endothelium-dependent relaxation is inhibited after SAH. Decreased endothelial NO synthase
mRNA was found in vasospastic arteries 7 days after
SAH in monkeys, a finding that correlates with pharmacological studies that show that endotheliumdependent relaxation is impaired during vasospasm
and that the mechanism is a decrease in NO production by endothelial NO synthase [1, 31, 33, 38, 96].
Decreased endothelium-dependent relaxation could
also result from scavenging of NO by hemoglobin,
destruction of NO by reaction with superoxide anion
radical (02~) produced during hemoglobin oxidation
or impaired response of the smooth muscle to NO. Investigations of vasospastic arteries, principally from
dogs, are conflicting as to the cause of decreased relaxation. Abnormalities have been identified both in
the endothelial cell production of NO [29, 33] and
in the response of smooth muscle to NO that were
secondary to reduced soluble guanylate cyclase or

to reduced GTP that is necessary for the relaxation


response [38, 40]. In human arteries, endotheliumdependent relaxation is impaired before and during
vasospasm but endothelium-independent relaxations
were impaired only during vasospasm [29, 66]. Impairment in the smooth muscle relaxation response
would not be supported by the observation that intracarotid nitric oxide or intravenous nitroglycerin infusions partially reverse vasospasm in monkeys [1, 631Inflammatory cells infiltrating the periarterial space
also release free radicals that may destroy NO and release constricting factors from the endothelium that
may inhibit relaxation responses [29].
Another potentially important reaction is the formation of NO in perivascular nerves and brain parenchymal neurons and astrocytes. The parenchymal
neurons may influence vascular tone [14]. Some of the
same mechanisms of dysfunction noted above could
apply in that, for example, hemoglobin may bind
NO not only from endothelium but also perivascular
nerves and prevent its access to smooth muscle. The
role of inducible NO synthase in vasospasm is un-

39

Etiology of Cerebral Vasospasm

Free Fe2+/FeJ+
(Fenton catalysis)
Auto-oxidation of hemoglobin

Inftammation
leukocyte myeloperoxidase

..

Free Radicals ----+-

~ .NO,!.OH
t

Arachidonic Acid
Metabolism

- 5-Upoxygenase
- Prostaglandin Synthase

---- .. ? Apoptosis

~
~

1'--- W

ONOo-

~O;

proteins~

~~
contractile proteins
regulatory proteins
suchasmembrnne
ion channels

~\1

Cell Membrane

Disruption & loss


of ion homeostasis

NO

Cell Death

Fig. 9. Diagram of pathways for free radical generation after SAH

known. Inflammatory mediators are increased after


SAH and some of these mediators may induce it.
Induction in vascular tissue might produce favorable
effects such as vasodilation and inhibition of platelet
and leucocyte adherence whereas production in neural
tissue may be beneficial because NO can block
NMDA receptors or it may also be toxic either directly
or by forming toxic peroxynitrite anion (ONOO-) by
combination with 02~ [14].

Free Radicals
A free radical is any molecule with an unpaired
electron in its outer orbital. This renders the molecule
very reactive in that it will donate (reduce) or remove
(oxidize) electrons to or from other biological molecules. This alters that molecule's chemical properties,
may create other reactive species, and may alter the
biological function of that molecule. Most free radicals
of biological importance are oxidizing agents. There
are a number of sources of free radicals after SAH
(Fig. 9) but the principle process in vasospasm is
probably the spontaneous oxidation of oxyhemoglobin to methemoglobin in the subarachnoid space,
leading to production of 02~. The oxygen-derived
radicals include superoxide (02~), hydroxyl (OH') and
hydrogen peroxide (H202). H202 is not a free radical
but is a reactive oxygen species capable of reacting

readily to form other radicals. The iron in hemoglobin


is important because it catalyzes formation of OH'
from H202 (Fenton's reagent) and catalyzes the
Haber-Weiss reaction, the classic formulation of which
is [24]:
Fe+++

+ 02~ --+ Fe++ + O2

Fe++ + H 202

--+

Fe+++

+ OH' + OH-

Free radicals may react with and damage cell lipids,


proteins, and nucleic acids (Fig. 9). They are postulated to be involved in vasospasm but they are also
important in the pathogenesis of cerebral ischemia
and infarction, rendering the interactions complex and
conclusions on the pathogenesis of angiographic vasospasm difficult to draw from effects of antioxidant
drugs on SAH [81]. Investigations in vasospasm have
focused on damage to lipids which is by the lipid peroxidation chain reaction while damage to proteins and
nucleic acid have not been studied.
There are complex interrelationships between free
radicals and other postulated mechanisms in vasospasm. For example, inflammation produces free
radicals. NO (a free radical itself) derived from endothelial cells, perivascular nerves or NO derived from
inflammatory cells or possibly smooth muscle cells
through inducible NO synthase may participate in

40

B. Weir et al.

Table 7. Summary of Studies of Tirilazadfor Aneurysmal SAH


Study

Vasospasm
angiographic

clinical

Canadian phase 2 (n = 245)


vehicle
41%
31%
0.6 mg/kg/d
2mg/kg/d
21%
6 mg/kg/d
40%
European Australasian phase 3 (n = 1023)
vehicle
3 2 % ' 26%
0.6 mg/kg/d
30%
22%
2 mg/kg/d
32%
27%
6 mg/kg/d
28%
18%
North American phase 3 (n = 897)
vehicle
28%
2 mg/kg/d
26%
6 mg/kg/d
24%

33%
30%
33%

Outcome
good recovery or
moderate disability

dead

Comments

13%

no statistically significant differences


between groups, trend for better
outcome with 2 mg/kg/d

70%
82%
90%
71%

8%
5%
20%

66%
66%
64%
71%

21%
19%
22%
12%

significantly better outcome with 6


mg/kg/d, subgroup analysis showed
that this benefit was confined to
males

73%
66%
71%

16%
16%

no significant differences in outcome


between groups, subgroup analysis
suggested better outcome in grade 4
and 5 males

injurious frec radical reactions. Products of hemoglobin metabolism such as bilirubin may actually be antioxidants [48]. Finally, the body has natural defences
against free radicals, including the enzymes superoxide
dismutase, catalase and glutathione peroxidase and
other compounds such as vitamin E (a-tocopherol),
glucose and some serum proteins. These are not found
in very high levels in CSF, rendering the environment
susceptible to uncontrolled free radical attack. One
feature missing from the free radical story is smooth
muscle contraction. While there is evidence from study
of cardiac myocytes and the role of free radicals in
myocardial reperfusion injury, there is little to suggest
how the above noted reactions might cause contraction [48]. Although free radicals were shown to mediate changes that might cause contraction in smooth
muscle [84] and injection of large doses of lipid peroxides into the CSF caused arterial narrowing, there
also are reports of how free radicals cause vasorelaxation [4, 48]. On the other hand, lipid peroxidation theoretically damages cell membranes making
them more permeable to ions such as Ca++ which
would cause contraction.
There is abundant evidence that free radicals are
formed in the subarachnoid space after SAH in animals and man. Free radicals can be detected by direct
methods such as electron spin resonance spectroscopy,
chemiluminescence or by reaction with spin-traps
to produce stable products. All studies of vasospasm
have used indirect measurement of products of free
radical reactions, principally lipid peroxide levels

13%

[34, 75]. These methods may be more susceptible to


methodological flaws. Lipid peroxidation products are
increased during vasospasm and often to higher levels
in patients with vasospasm than in those without.
Correlation does not imply causation, however, and
interpretation of the results is complicated further because tissue injury produces free radicals and a correlation would be expected since vasospasm is more
likely in poor-grade patients with large-volume SAH
and more brain damage. Other "markers" of brain
injury which have no known vasoactive effects, such as
S-IOO and membrane bound tissue factor, are similarly
correlated with vasospasm [32, 87]. It is also needs to
be considered that lipid peroxides themselves can
cause brain damage and at least in high doses, constriction of cerebral arteries so that even if their production is an epiphenomenon, they could still contribute to vasospasm.
Additional evidence for a causal role of free radicals
in vasospasm would be demonstration that preventing
these reactions prevented vasospasm and decreased
levels of free radicals or their reaction products in
CSF. Antioxidants such as I ,2-bis(nicotinamide)propane (nicaraven or AVS) and tirilazad mesylate
(U74006F) decreased vasospasm in experimental
models and in one study of tirilazad, caused a minimal
decrease in a marker of lipid peroxidation (malondialdehyde) in the subarachnoid clots [3, 22, 23, 34, 36].
Most studies, however, were not accompanied by biochemical measurements to confirm the drug's action.
Human trials of tirilizad are summarized in Table 7

Etiology of Cerebral Vasospasm

[22, 23, 36]. Tirilazad is a steroid derivative that


inhibits iron-dependent and - independent lipid peroxidation, scavenges hydroxyl free radicals, stabilizes
cell membranes and preserves endothelium-dependent
relaxation. It has no glucocorticoid activity and no
important side effects have been identified. Each trial
included patients with aneurysmal SAH admitted
within 2 days of SAH and treated for 10 days. This
may have been too short because a substantial number
of deficits came on more than 10 days post-SAH. The
lack of significant improvement in outcome in the
North American study was postulated to be related to
greater use of anticonvulsants in North America which
may have reduced drug levels [23]. The increased
metabolism of the drug in women was supposed to
account for the more marked effects in males. Higher
dose studies have been conducted but not published.
Metaanalysis of all results including 2 high dose
studies showed no benefit overall [37]. In subgroup
analysis, there was a significant decrease in deaths
from 18% overall to 6% and improvement in favorable
outcome from 69% to 77% in males only with no benefit in women. There was no effect on angiographic
vasospasm. Reasons for the lack of striking effect of
tirilazad are that the drug is very lipid soluble. The
drug may become concentrated in the membranes of
the endothelial cells and inner layers of smooth muscle
and not attain high enough levels in the tunica media
or CSF, although there may be slightly higher CSF
penetration when the blood brain barrier is disrupted
such as after SAH. Perhaps additional studies with
longer duration of therapy and measurement of drug
levels would clarify these issues. One other free radical
scavenger (nicaraven) also showed effects on vasospasm in man [3].
Inflammation

Inflammation is reaction of the body to injury and


by definition must accompany the healing of the brain
after SAH. Inflammation is important in the pathophysiology of cerebral ischemia and processes identified in these studies could contribute to vasospasm.
There is an inflammatory response in the subarachnoid
space after SAH that is accompanied in experimental
models by upregulation of cell adhesion molecules that
are necessary for the recruitment ofleukocytes into the
area [26]. Inhibition of leukocyte recruitment decreased vasospasm in a rat femoral artery model [67].
In the authors' experience the amount of inflammation

41

seen in this model is far greater than that observed


after intracranial SAH, suggesting that the role of
inflammation may be overestimated in these studies.
Also in rat femoral arteries, it was shown that intercellular adhesion molecule-l was elevated 3 to 24
hours after blood placement and correlated with vasospasm 12 days later [67]. In our experience (unpublished observations), vasospasm is always dependent on the presence of subarachnoid blood clot.
Therefore, processes occuring early after SAH before
vasospasm are probably not important in the pathogenesis of vasospasm. It is interesting, nevertheless, to
speculate on how inflammation might cause vasospasm. It must always be kept in mind that in the
disease with the most subarachnoid inflammation,
bacterial meningitis, vasospasm is not a clinical problem. In any case, leukocytes release vasoconstricting
substances that contract arteries and they cross into
the brain, where they degranulate and release cytotoxic enzymes such as myeloperoxidase. The respiratory burst of phagocytes generates oxygen-derived free
radicals as a mechanism for killing cells. Inflammation
also may be related to vasospasm because, for example, inflammatory cells make free radicals that can react with and destroy NO and decrease a natural vasodilatory mechanism. Inflammatory mediators such as
cytokines also may increase the synthesis of vasoconstrictors such as ETs [14].
Since ischemia and infarction are the most important final common pathway for production of morbidity and mortality in patients with SAH, inflammation and therapies to prevent it might be of benefit in
these patients regardless of whether there are effects on
vasospasm per se. Thus, improvement in outcome with
an antiinflammatory agent does not necessarily imply
an effect on vasospasm itself. In the author's opinion,
however, these agents do not prevent vasospasm. In a
literature repleat with studies demonstrating the effects
of numerous agents, it is notable that studies demonstrating no effect of cyclosporine A, FK506 and glucocorticoids can be found [28,54,61,94]. Finally, the
large doses of these drugs that have sometimes been
given cause numerous effects other than inhibition of
inflammation.
Peterson and colleagues reported that lysis of aging
human erythrocytes was accelerated by activation of
the complement pathway, analogous to the mechanisms involved in lysis offoreign cells and activation of
the inflammatory response [70]. This mechanism
would suggest that inflammation and complement

42

pathways contribute to vasospasm by promoting lysis


of erythrocytes and release of their spasmogenic
contents. This could explain how systemic complement depletion decreases vasospasm [19]. Other investigations, however, report no effect of decomplementation on vasospasm [70]. Another possibility is
that complement membrane attack complexes insert
into the smooth muscle cell membranes, causing abnormal Ca ++ homeostasis and prolonged contraction
[68].
Changes in Gene Expression in Vasospasm

There may be changes in gene expression in the cerebral arteries and in the brain after SAH. The changes
in the brain may be secondary to ischemia or to subarachnoid blood. In general, the change that is ultimately important is a change in the protein product of
the gene. Thus, changes in protein levels may be
measured. Changes in levels of the mRNA, the stability of the mRNA, or in the rate of transcription of the
gene of interest might also be determined. A particular
physiological or pathological system known to mediate vascular tone might be assessed or a method to
look at changes in a variety of gene products, such as
mRNA differential display, might also be used.
In the spastic arteries, changes in gene expression
have been assessed by studying changes in genes that
are thought to modulate vascular tone. These are reviewed above under sections pertaining to the system
in question. Several investigators used mRNA differential display to examine genes whose expression is
altered during vasospasm. Seven days after SAH in the
double hemorrhage dog model, there were 16 mRNAs
that were altered compared with normal dog basilar
artery [65]. The control arteries were from dogs that
did not undergo surgery so the effect of surgical stress
cannot be excluded. Six of the 16 mRNAs corresponded to known sequences and all were increased by
SAH. There were 2 stress proteins (BiP protein, protein disulphide isomerase-related protein), 2 protease
inhibitors (inter a trypsin inhibitor family heavy chain
related protein, cystatin protein), I phosphodiesterase
(sphingosine phosphodiesterase) and serum amyloid A
protein. The significance of the findings is uncertain
but a detailed study of changes in mRNA and protein
levels over time might lead to new information on the
pathogenesis of vasospasm.
Other pathways that have been investigated are the
stress gene and hemoglobin metabolism systems (Fig.

B. Weir et al.

2). Heat shock protein 70 (HSP70) and its mRNA


were induced in focal areas of brains of rats injected
with lysed blood but not whole blood or oxyhemoglobin solution [58, 59]. These areas also showed
DNA fragmentation. The changes were hypothesized
to be ischemic foci from SAH. The rate limiting enzyme in hemoglobin breakdown, heme oxygenase, is
induced in brain after injection of lysed blood into the
CSF of rats [57]. That heme oxygenase is important in
vasospasm is suggested by the findings that hemoglobin solutions which are toxic to cells, can be rendered
less toxic by induction of heme oxygenase [51].
Cerebrovascular Nerves

The cerebral arteries have sympathetic, parasympathetic and sensory nerves arising from extrinsic
sources in their tunica adventitia and outer tunica
media [27]. These are distinct from the intrinsic system
of neurons arising in the brain parenchyma and in
some way innervating or exerting effects on mainly
intraparenchymal cerebral vessels. The sympathetic fibers release norepinephrine that acts predominately on
a receptors and neuropeptide Y, both of which cause
contraction. Parasympathetic nerves release acetylcholine and the 2 products of the preprovasoactive
intestinal polypeptide (VIP) gene, VIP and peptide
histidine methionine. The action of acetylcholine is
to cause endothelium-dependent relaxation through
release of NO and cGMP and to cause endotheliumindependent contraction probably by direct activation
of muscarinic receptors. The VIP products seem to
relax via a cAMP endothelium-independent mechanism. Sensory nerves containing substance P, neurokinin A and calcitonin gene related peptide (CGRP) the first 2 are products of ~ preprotachykinin and
cause endothelium-dependent relaxation through a
NO mediated pathway whereas CGRP causes endothelium-independent relaxation that is associated with
increased cAMP [13]. In the pial arteries, serotonin is
present but there is controversy as to whether there are
serotonergic nerve fibers or whether the serotonin is
present because of rapid uptake of exogenous serotonin from blood into catecholaminergic nerves at the
time of tissue processing [8, 27]. ATP may be released
from sympathetic nerves and causes endotheliumdependent relaxation and endothelium-independent
contraction [99]. Other neuropeptides that may modulate cerebral blood flow have been identified in the
central nervous system but they arise from brain

Etiology of Cerebral Vasospasm

neurons and tend to innervate the intraparenchymal


vessels (intrinsic system). There is evidence that NO
may mediate relaxation to perivascular sensory nerve
substance P and to transmural electric stimulation,
suggesting that it is a vasodilatory neurotransmitter
[44]. NO-containing nerves are visible around cerebral
arteries.
The extrinsic innervation of the cerebral arteries
influences cerebral pressure autoregulation and blood
flow alterations in response to changes in oxygen, carbon dioxide and possibly metabolic demand. It is
probable that major decreases in diameter of the basal
arteries do not occur in response to even the most
drastic changes in these nerves. The large arteries of
the circle of Willis that develop vasospasm are conductance vessels not resistance vessels and they do not
change substantially in diameter in response to factors
that alter cerebral blood flow. There are several reasons why SAH would be unlikely to affect these nerves
in such a way as to cause large diameter changes. The
same could be said about changes in the endothelium
(ET, NO, PGI 2). Tachyphylaxis develops to changes
in tone iduced by most of the neurotransmitters and
there are opposing regulatory mechanisms. However,
the loss of normal, potentially vasodilatory functions
could contribute to vasospasm. Unlike the data on
contractions to erythrocyte cytosol, the data in support
of neurogenic mechanisms are much more varied. For
example, denervation supersensitivity was suggested as
a cause of vasospasm but others reported that causing
it by surgical sympathectomy prevented vasospasm
and still others found no evidence for a supersensitive
state or an effect of sympathectomy after SAH [12, 91].
This may reflect a lack of understanding of neural
mechanisms but certainly indicates a need for further
investigations before conclusions can be drawn.

Acknowledgements
The authors thank Lydia Johns for preparing the figures.

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B. Weir et at.: Etiology of Cerebral Vasospasm

calmodulin levels in cerebrospinal fluid after subarachnoid


hemorrhage. J Neurosurg 63: 417-420
Takenaka K, Yamada H, Sakai N, Ando T, Nakashima T,
Nishimura Y, Okano Y, Nozawa Y (1991) Cytosolic calcium
changes in cultured rat aortic smooth-muscle cells induced by
oxyhemoglobin. J Neurosurg 74: 620-624
Taneda M, Kataoka K, Akai F, Asai T, Sakata I (1996) Traumatic subarachnoid hemorrhage as a predictable indicator of
delayed ischemic symptoms. J Neurosurg 84: 762-768
Tsukahara T, Kassell NF, Hongo K, Lehman RM, Tomer JC
(1988) Metabolic alterations in rabbit cerebral arteries caused by
subarachnoid hemorrhage. Stroke 19: 883-887
Tsukahara T, Taniguchi T, Miwa S, Shimohama S, Fujiwara M,
Nishikawa M, Handa H (1989) Presynaptic and postsynaptic
C( 2-adrenergic receptors in human cerebral arteries and their
alteration after subarachnoid hemorrhage. Stroke 19: 80-83
Wang J, Ohta S, Sakaki S, Araki N, Matsuda S, Sakanaka M
(1994) Changes in Ca++ -ATPase activity in smooth-muscle cell
membranes of the canine basilar artery with experimental subarachnoid hemorrhage. J Neurosurg 80: 269-274
Weir B (1995) The pathophysiology of cerebral vasospasm. Br J
Neurosurg 9: 375-390
Yamakawa K, Sasaki T, Tsubaki S, Nakagomi T, Saito I,
Takakura K (1991) Effect of high-dose methylprednisolone on
vasospasm after subarachnoid hemorrhage. Neurol Med Chir
(Tokyo) 31: 24-31

95. Yamada T, Tanaka Y, Fujimoto K, Nakahara N, Shinoda S,


Masuzawa T (1994) Relationship between cytosolic Ca++ level
and contractile tension in canine basilar artery of chronic vasospasm. Neurosurgery 34: 496-504
96. Yamamoto S, Nishizawa S, Yokoyama T, Ryu H, Uemura K
(1997) Subarachnoid hemorrhage impairs cerebral blood flow
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97. Yokota M, Peterson JW, Kaoutzanis MC, Yamakawa K,
Sibilia R, Zervas NT (1995) Protein kinase C and diacyl glycerol
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98. Yoshimoto Y, Kim P, Sasaki T, Takakura K (1993) Temporal
profile and significance of metabolic failure and trophic changes
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Correspondence: Bryce Weir, M.D., Section of Neurosurgery,
MC 3026, University of Chicago Medical Center, 5841 South
Maryland Avenue, Chicago, IL 60637, USA.

Acta Neurochir (1999) [Suppl]72: 47-57


Springer-Verlag 1999

Hemodynamics of Cerebrovascular Spasm


R. Aaslid
University of Washington, Department of Neurological Surgery, Harborview Medical Center, Seattle, USA

Summary
An understanding of the hemodynamics of cerebrovascular spasm
following subarachnoid hemorrhage is important for the diagnosis
and treatment of this potentially dangerous condition. An overview
model is presented which includes the main elements determining the
overall effect of vasospasm. The model included realistic pressureflow-velocity-diameter relationships encountered in a geometry resembling that of vasospasm of the middle cerebral artery. Viscosity
was adjusted to that expected of human blood. Furthermore, a realistic model the cerebral autoregulation was included. The effects of
induced hypertension as well as hypotension were studied.
It was found that the friction pressure loss in the spastic segment
was 3.5 times as high as that predicted by using the Hagen-Poiseuille
formula. The reason for this discrepancy was probably the 'inlet
length effect' considerably increasing the friction. Furthermore, including the Bernoulli kinetic pressure energy, a formula was proposed that accurately described the experimental data.
From this hemodynamic perspective, strong support was found
for the present trend to use aggressive hypertensive therapy in patients with vasospasm. The results also confirmed that TCD velocity
measurements in the spastic segment when taken alone may not be a
good index of the degree and effect of the spasm. These measurements must be combined with other techniques such as extracranial
Doppler or CBF to assess the degree of spasm.
Keywords: Cerebrovascular spasm; hemodynamics; subarachnoid
hemorrhage; transcranial Doppler.
"Hence it plainly appears, that there is a communication between the
Vessels watering the whole Head; and although every Artery is carried
to one only Region, as its peculiar Province, and provides for it apart;
yet, lest that any part should be deprived of the influence of the blood,
more ways lye open to every part by the ingraftings of those vessels; so
that if the proper vessels by chance should be wanting in their office, its
defect may perfectly be compensated by others neighbouring. "

Thomas Willis 1664 [36]

Introduction
The work of Willis [36] is remarkable not only for
the artistic and detailed anatomical drawings - but
even more so by the apt functional description of the

circle named after him. The cerebral circulation has


much built-in redundancy and in addition it is guarded
by multiple physiologic control mechanisms. It takes
quite a dramatic event to make it fail its purpose of
supplying the brain with adequate energy to function
and survive. However, subarachnoid hemorrhage
(SAH) is such an event - not only in the acute, often,
catastrophic phase - but also in the lurking dangers of
cerebrovascular spasm occurring several days after
SAH and surgery. In many patients the blood simply
does not flow where needed with permanent neurological deficits or even death as consequences. Modern
intensive care of SAH patients is increasingly able to
assist the built-in safeguards of the cerebral circulation
in maintaining perfusion above critical ischemic levels.
This chapter deals with the concepts and understanding of cerebral hemodynamics as applied to cerebral
vasospasm. Understanding of the main factors involved in this patho-hemodynamic state is vital to accurate diagnosis and effective treatment. Especially
with the newer trends towards early surgery, a much
wider range of treatment has become available since
the threat of further rupture and hemorrhage is greatly
reduced when the aneurysm is clipped. The hemodynamics of the acute phase following aneurysm rupture
has mainly academic interest, and will not be discussed
in this chapter.

Overview and Main Concepts


A schematic representation of the main systems and
concepts involved in understanding the effects of cerebral vasospasm is given in Fig. 1. The energy for perfusing the cerebral circulation as well as other organ
systems is supplied by the left ventricle. It produces an

48

R . Aaslid

Uenous
Sinus

Jugular
Uein

Fig. 1. Schematic drawing of the cerebral circulation with vasospasm affecting the middle cerebral artery (MCA). Abbreviation:
ABP arterial blood pressure; cABP cerebral arterial blood pressure;
rABP regional (post-spasm) arterial blood pressure; ICP intracranial pressure; CVP central venous pressure; ICA internal carotid
artery; ACA anterior cerebral artery. See text for description

oscillating blood pressure (ABP) in the aorta which


can be regarded as the driving force or input of potential energy for the cerebral circulation. The ABP is
controlled by a number of factors, the most important
being venous return, total peripheral resistance, heart
rate, and contractility. From the viewpoint of cerebral
circulatory physiolpgy, fortunately , we do not have to
consider all these factors individually; only their total
result in producing a certain level of blood pressure.
(While it is irrelevant to the understanding of cerebral
hemodynamics if a low ABP is caused by low cardiac
output or low total peripheral resistance, central cardiovascular factors must be dealt with in the ICU
when trying to maintain ABP at an optimal level).
Leaving the aorta, the blood passes through the carotid and vertebral arteries to the network of arteries of
the intracranial circulation. These conductance vessels
are quite large in caliber, and therefore exhibit low
flow velocities. As an example, blood flows at 37 cmls
in the extracranial internal carotid artery, accelerating
to 62 cmls in the middle cerebral artery (MCA) [3].

Slow flow combined with large caliber conduits means


low friction - thus conserving the pressure energy. In
actual measurements in patients undergoing surgery
[31] the pressure in the MCA was shown to be insignificantly different from that in the radial artery in
patients without obstructive disease of the carotid arteries. It should be noted that the same hydrostatic
reference level was used for comparing the two pressures. As will be shown later, the actual cerebral perfusion pressure is best calculated using the ABP referenced to the cerebral level - cABP in Fig. 1. In the
upright or sitting position the head is situated above
the heart by about 40 to 50 cm giving a drop in hydrostatic pressure of about 30 mm Hg. In the ICU, the
patients may assume varying degrees of tilt of the
upper body, but very seldom the strict supine position.
This variable hydrostatic effect must be accounted for
- in most typical settings the difference will amount to
about 10- 20 mm Hg. Thus the blood arrives at the
basal cerebral arteries with the potential energy supplied by the left ventricle minus the hydrostatic difference between the heart and the base of the brain.
Cerebral vasospasm typically has its main focus in
the basal cerebral arteries. Figure 1 assumes that the
MCA is affected, but narrowing might also occur in
the ICA, ACA, PCA or basilar artery. The hemodynamic effects of vasospasm are analog to those caused
by stenosis, however, since end-arteries might be
affected (MCA and segments of ACA and PCA distal
to the communicating arteries) the effects are more
serious since the only collateral flow available is that
via leptomeningeal anastomoses as indicated in Fig 1.
This network is not as efficient as the Circle of Willis in
providing collateral flow when isolated spasm occur in
the proximal segments (AI, PI, ICA).
In itself, the actual pressure-flow relation of a segmental spasm is quite complicated. Since this relationship is of prime importance for cerebral perfusion, it
will be dealt with in more detail below. The effect of
the arterial narrowing is a pressure loss AP = cABP
-rABP where rABP is the regional blood pressure
supplying the vascular territory distal to the vasospasm. This pressure loss may become significant in
patients with severe spasm and as a consequence flow
decreases to and below critical levels. It is not an uncommon occurrence that patients suffer cerebral ischemia after SAH. This shows that the leptomeningeal
anastomoses cannot be relied upon to provide flow to
the entire territory served by the artery affected by
vasospasm.

49

Hemodynamics of Cerebrovascular Spasm

The cerebral vascular bed as indicated in Fig.


consists of arteries, arterioles, precapillary sphincters,
capillaries, venules, and veins. As stated by McDonald
[22] about 60% of the pressure loss occur in the arterioles and precapillary sphincters over the last 5 mm
before the capillary. This pressure loss can be made
less by autoregulatory vasodilation. This mechanism
can compensate for the pressure loss in spasm to some
extent. The effects of the cerebral autoregulation are
well documented [33]. The importance of considering
the combined interplay of blood pressure, vasospasm
and autoregulation for the total effect of cerebral vasospasm cannot be overemphasized and will be discussed
in a separate section below.
Pressure losses also occur in cerebral and jugular
veins, although in a fundamental different manner
than in arteries. Since veins collapse and create socalled waterfall effects [27] when the transmural pressure goes negative, their actual resistance is adjusted
automatically to match the flow to the difference between the external pressure and the outflow pressure. If
the veins had been rigid tubes without the habit of
collapsing, the hydrostatic loss in the arteries from the
heart to the brain would have been regained by the
same hydrostatic gain in the jugular veins. However,
the right arterial pressure is typically just a few mm
Hg, and the pressure in the jugular vein cannot go
negative without its collapsing. Therefore, the pressure
in the cerebral venous sinuses, which are indeed more
like rigid tubes [21] will be close to zero. This is the
reason why the hydrostatic difference between the
ABP and the cerebral arteries must be subtracted when
calculating true cerebral perfusion pressure. Important
is also the first proximal waterfall which occur in the
bridging veins connecting the cerebral veins to the
sinuses [27]. Since these veins cannot sustain intraluminal pressures lower than the surrounding intracranial pressure (lCP), they do collapse if the sinus
pressures is below the ICP. The pressure immediately
proximal to the collapsed segment will for all practical
purposes be equal to the ICP. The outflow pressure of
the cerebrovascular bed will thenceforth be equal to
the ICP; and the regional cerebral perfusion pressure
(rCPP) will be given by:
rCPP = rABP - ICP.

[Equation 1]

From this overview it is clear that the actual flow to


the vascular bed will be determined by the interaction
between the cerebral perfusion pressure, the pressureflow characteristics of the spastic segment (in combi-

nation with the leptomeningeal anastomoses) and the


cerebrovascular resistance, and how it is controlled by
the autoregulatory mechanism.
Pressure-Flow Characteristics of Arterial Segments
with Vasospasm

Two main factors contribute to how pressure loss


(L1P) relates to blood flow (F) through a spastic arterial segment. T otalloss is the sum of kinetic loss (L1Pk)
and viscous or friction loss (L1Pr). The velocity of the
jet as well as the geometry of the distal vasculature is
responsible for kinetic energy losses caused by accelerating the flow to a certain velocity which is not regained because of post-stenotic flow separation and
loss in turbulent vortex formation. Such turbulence is
seen in practically all patients with high flow velocities
caused by vasospasm [5], and it is indeed a reasonable
assumption that none of the kinetic energy is regained,
as this would have required a very smooth long nozzlelike post-spastic geometry. If the velocity is V in a
lumen with radius r, and the density of the fluid is p;
the kinetic loss in terms of pressure is given by the
Bernoulli equation:
[Equation 2]
As seen from this equation, the kinetic loss is proportional to the square of the flow and inversely proportional to the square of the radius. This formula has
been found to accurately predict the pressure difference over stenotic heart valves [12].
For cerebral vessels we must also take into account
the resistance effects caused by friction within the fluid
itself. The important factors for such effects are the
diameter or radius of the channel, its length (L), and
the viscosity of the fluid ().l). In much of the hemodynamic literature one finds this friction loss expressed as
the Hagen-Poiseuille law or formula:
[Equation 3]
Since the formula expresses a linear relationship
between flow and pressure, the concept of vascular resistance (R) is frequently used. This formula is based
upon many assumptions; the two most important
being that the flow is laminar and that a steady-state
'minimum friction' flow profile has been developed.
Neither of these assumptions are guaranteed in a
vasospasm. Let us examine both assumptions with an
example of a moderate/severe spasm with a lumen
diameter of 1.5 mm and a flow of 240 ml/min = 4 ml/ s.

50

R. Aaslid

The velocity will be 230 cmls - close to the highest


values that have been observed in human patients
without clinical symptoms after SAH [2]. The index
used to predict whether flow is laminar or turbulent is
called the Reynolds number (Re) which in a circular
pipe is given by:
Re = 2r V jv

= 0.057r . Re

Bemoulli

Bemoulll l. SPoI_me

[Equation 4]

Assuming a kinematic viscosity (v) of blood at 37 C


of 0.038 Stokes [22] the Reynolds number will be about
900. Generally, turbulence requires a Reynolds number of around 2000, so within the spastic segment the
flow is likely not to be turbulent. However, the flow
still might border on being unstable [13], a condition
that might favour its breakup in vortices and turbulence in the post-spastic segment.
The condition of steady-state minimum friction flow
can only be achieved after a certain inlet length (Li)
given by [22]:
Li

Po lseume

[Equation 5]

In this example, the calculated inlet length will be


about 3.8 cm. Clearly all flow in typical vasospasm in
basal cerebral arteries is contained within the inlet
length. In such flow, the flow profile is not optimal and
the Hagen-Poiseuille formula much understates the
pressure loss and cannot be used quantitatively to estimate the resistance of the segment. A modification of
the Hagen-Poiseuille formula can be applied in nonoptimal flow profiles by introducing a constant k that
is always greater than or equal to 1:
[Equation 6]
The actual value of the constant k cannot be easily
computed without resorting to very complex fluid dynamics mathematical models. However, it is relatively
simple to measure such pressure losses. To illustrate
typical pressure-flow relations of vessels resembling
cerebral vasospasm, I conducted experiments on a
hydrodynamic model of a spasm as illustrated in the
insert in Fig. 2. The flow model was machined from
PVC, and had a 'spastic' lumen diameter of 1.5 mm
and a length of 15 mm. The pressures were measured
by hydrostatic measurements and the flow by a calibrated measuring glass and a stopwatch. Pressures
ranging from 10 mm Hg to 100 mm Hg were imposed
to simulate a wide range of flows up to 5 mIls (300 mIl
min) in the segment. A solution of sucrose in water
perfused the segment between two reservoirs. Its viscosity as measured in a tube viscosity-meter was 0.035

II1l

PRESSURE LOSS L>P

1 HgI

Fig. 2. Pressure-flow characteristics of the hydrodynamic model


of vasospasm. The model is illustrated in the insert. Theoretical
predictions by Bernoulli and Hagen-Poiseuille formula are shown.
The experimental data (open squares) are fitted by Equation 7 as
described in the text

Poise at the temperature used (20 C), approximating


that of blood at 37 C [22]. Actual blood is a nonNewtonian fluid, meaning that viscosity varies with
shear flow. However, at the very high shear rates encountered in spastic and stenotic segments, this effect is
negligible.
Figure 2 shows the measured pressure-flow characteristics (open squares) of this segment. The data are
compared to the theoretical kinetic and friction loses
using Bernoulli's and Hagen-Poiseuille's equations.
The actual loss is about twice as high as that predicted
by the unmodified equations at a flow level of 240 mIl
min. Using the sum of the kinetic loss and the modified
formula for friction loss the total pressure loss is given
by:
AP = F2 . pj(2m2)

+ F k 8I!Lj (nr4 )

[Equation 7]

An excellent prediction of the experimental data


could be achieved with k = 3.5. This is shown by the
solid line in Fig. 2. The data illustrate the results of
having non-optimal flow profile within the inlet length.
This phenomenon generates excessive losses in pressure. The findings also demonstrate that the direct use
of the unmodified Hagen-Poiseuille formula on stenosis and vasospasm severely (by a factor of 3.5) underestimates the friction losses. It is also important to
point out that the friction losses will not be proportional to the length of the spasm as the main effects of
the inlet length will be found in the very beginning of
the narrowing segment.
This experiment also indicates that the main cause
of pressure loss in vasospasm is due to friction mechanisms and not kinetic effects like in heart valves. Fric-

51

Hemodynamics of Cerebrovascular Spasm

350

150

DiaMeter:
2. DAM

1~_Ar_fon_ad

1. 5 MM

_ __

120

300

~,:'O"

.~

E:

.....
"E:

250
90

200

E
E

CI

.....

...J

....
z:

150

...J

100

::::I
CI

:::0

1. 0 MM

250,
60

200

~ E.~

150

50

J1

i L.1

~. . . . .' ' ....~.

PaCO,33

100

50

PRESSURE LOSS l>P

\'

~\AN

[MMHg]

Fig. 3. Pressure-flow characteristics of hydrodynamic models of


different degrees of vasospasm. Open squares represent the experimental data, whereas the solid curves represent the mathematical
model described by Equation 7. Note the very strong effect of the
diameter on the pressure loss

tion losses are inversely proportional to the diameter in


the 4th power. Using similar models with 2 mm and
1 mm diameter, the pressure-flow relationships were
measured and compared to the 1.S mm model. The
dramatic influence of diameter on pressure loss is illustrated in Fig 3. The solid lines in the figure are those
predicted using the modified equation [7] with k = 3.S.
This formula was found to accurately describe the
pressure losses with varying diameters and flow rates
in the range expected to be encountered in a cerebral
vasospasm. These data were obtained with a IS mm
long narrowing. For shorter and longer segments, different values of k will have to be determined.
A concept of critical stenosis was introduced to
determine at which level the stenosis has a significant
effect such as reducing flow [6]. The same concept can
also be used for cerebral vasospasm, but since cerebral
flow is typically higher than in other organs and in
addition effectively regulated, we have to consider
the joint effect of stenosis and autoregulation on the
pressure-flow relationship.

Cerebral Autoregulation
The mechanism that maintains a constant cerebral
blood flow (CBF) within a wide range of perfusion
pressures is called cerebral autoregulation. The first
studies in humans [17] documented that this mechanism was remarkably effective. Perhaps one of the
most illustrating examples of the ability of this mechanism to maintain constant flow in situations where

Fig. 4. Tracing from a patient aged 62 years with an internal carotid


artery (leA) aneurysm. Painful stimulus due to skin incision caused
marked and rapid rise in arterial blood pressure. The ICA flow
shows nearly instant autoregulation. Autoregulatory range is from
135 to 60 mm Hg. Note slight dip in ICA flow at this lower level of
blood pressure. Gap in lower tracing x - x, is due to failure of
recorder pen. From Nornes et at. [25] Fig. 1, reproduced with
permission

the ABP fluctuates wildly was published by Nornes et


al. [2S] using electromagnetic flowmetry during aneurysm surgery. In the reproduction (Fig. 4), the trace
representing flow is seen to be practically at the same
level except for a brief episode of hypotension. Even
then it does not change much. The rapidly developing
hypertensive episodes are all dealt with perfectly.
These findings contrast with concepts and results reviewed by physiologists [11] where results from both
animal experiments and humans indicated that autoregulation was slower and exhibited flow deviations
from the control value of 3.S-7% per 10 mm Hg. The
authors argued that these 'error signals' were necessary
to vary the concentration of eventual transmitter substances so as to vasoconstrictJdilate the resistance vessels. In other words their data were consistent with a
proportional control system acting by feedback via
metabolic mechanisms. This is only one of the actual
mechanisms that may be responsible for autoregulation; the other two contenders are myogenic
mechanisms (broadly seen this also includes endothelial factors) and neurogenic regulation. Possibly two or
more of these mechanisms may operate in parallel.
Moreover, it is by no means given that the control
mechanism is based upon proportional control even if
the main mechanism is metabolic.
It is also conceivable that differences exist among
species in the response of this mechanism - humans
have a much greater need of effective autoregulation
than for example cats due to significantly larger or-

52

R. Aaslid

300

"

250

"

200

.....
....

150

==
.....

100

.~

.....
"

3
C

....
:z:

50
0

50

CEREBRAL PERFUSION

100

150

PRESSURE [MMHg]

Fig. 5. Steady-state cerebral autoregulation curve used to calculate


the flow and velocity in varying degrees of vasospasm as shown in
Fig. 6 and 7. The lower level of autoregulation was 60 mm Hg

tho static stresses inducing changes in CPP. Another


explanation for the discrepancy is that the relatively
elaborate preparation in the animal experiments and
the conditions of the humans during testing may have
degraded autoregulatory effectiveness. It is well known
that some anesthetic agents profoundly influence
autoregulation [34].
Recent studies using transcranial Doppler [1, 4, 24,
34, 35] have documented that the cerebral autoregulation mechanism in normal humans indeed may
be as fast and effective as the early report of Nomes
et al. [25] suggested. The results in the first of these
studies [1] were contested on methodological grounds,
the editorial stating that: " ... the slopes that Aaslid et al.
calculated have nothing to do with the rate of autoregulation of the cerebral vascular bed" [15]. A series of
reports on the method, however, confirmed the initial
results and technique used [4, 10, 24, 34]. Further
studies found a strong correlation between the rate of
the dynamic response and the steady state 'gain' response of the cerebral autoregulation [35]. In a particularly elegant study, Larsen et al. [16] used the TCD
method in combination with SPECT to define the
lower limit of autoregulation in normal subjects.
Cerebral autoregulation also has an upper limit [32]
or breakthrough level. Since the effect of cerebral vasospasm is to reduce perfusion pressure, we do not need
to consider this phenomenon in the hemodynamic
analysis of the region affected by the spasm. For clinical treatment of patients with induced hypertension,
however, the upper level of autoregulation must be
considered for the vascular territories not affected by
the spasm.
Due to the many studies on cerebral autoregulation,

both its steady-state and dynamic responses are well


known although the mechanisms remain contested.
Since cerebral vasospasm develops over time, the dynamics of the response plays a lesser role although it
may be useful for characterizing autoregulation in
SAH patients. An early study [29] seemed to indicate
that it is preserved in patients with low to moderate
degrees of vasospasm.
Figure 5 illustrates the steady-state autoregulation
curve that will be combined with the vasospasm pressure-flow model to analyze the combined effect on
cerebral blood flow and velocity. The lower limit of
autoregulation in this model is 60 mm Hg as referred
to the cerebral perfusion pressure. Assuming an ICP of
10 mm Hg and a hydrostatic difference of 15 mm Hg,
this corresponds to an ABP of 85 mm Hg - close to the
findings of Larsen et al. [16].
Critical Vasospasm
Critical vasospasm can be defined analogous to
critical stenosis [6] as the degree of spasm that starts
to restrict flow. The study by Spencer and Reid [30]
introduced the quantitative analysis of flow, pressure
and velocity in carotid artery stenosis. The same principles can be applied to cerebral vasospasm, although
the parameters will be quite different. Instead of using
theoretical calculations, I have used the experimental
data from the realistic hydrodynamic vasospasm
models described above, combined with the autoregulation curve of Fig. 5. Arterial blood pressure levels
of 80, 100 and 140 mm Hg were analyzed. The hypotensive state reflects that of a patient not yet operated
where blood pressure is a critical factor in aneurysmal
rerupture. The hypertensive state reflects aggressive
modern postoperative therapy of SAH involving hypervolumia and possibly also induced hypertension
using catecholamines. The viscosity for the three states
were 4, 3.5 and 3 cP (centiPoise) respectively representing different degrees of hemodilution [14]. For all
calculations an ICP of 10 mm Hg and a hydrostatic
loss of 15 mm Hg as explained above were assumed.
The results were recalculated from the cgs-system into
units normally used in medical literature. The analysis
was first carried out assuming no collateral flow, then
in the next section using an assumed collateral capacity
from territories not affected by vasospasm.
The pressure-flow relationship of the spastic segment and the autoregulation were simulated on a personal computer. Segment length was 15 mm and seg-

53

Hemodynamics of Cerebrovascular Spasm

""
on

RBP: 140

200

150
~

""-'w
=>

'"
""
...-'

100

50

250

"
:::;"
.~

200

~
3

~
""
=>
'"

5:>

150

100

50

3.0

0.5

3.5

OIRMETER OF SPASTIC SEGMENT 1M.]

Fig. 6. Influence of arterial blood pressure (ABP) and diameter of


spastic segment on volume flow (lower) and flow velocity (upper) in
model of cerebral vasospasm. Note maximum velocities occurring at
diameters within a range encountered in human patients. Further
diameter decreases (reverse side of the velocity-diameter relation)
lead to decreases in flow velocity. Also note strong effect of simulated
induced hypertension on maintaining flow and increasing the maximum velocity

ment diameter was varied from 0.5 to 3.3 mm. Flow


and 'jet' velocities were calculated, and the results are
summarized in Fig. 6. The normotensive state shows
flow reduction by 10% at a lumen diameter of 2 mm.
To bring this finding into context, this represents a
stenosis degree of slightly less than 50%. Such narrowing would have been considered a hemodynamically nonsignificant stenosis in the carotid artery. The
much higher normal flow velocities in the basal cerebral arteries are responsible for this difference in
stenosis effect.
The beneficial effects of induced hypervo1umia and
hypertension are also clearly seen. At an ABP of 140
mm Hg, a further reduction of diameter down to 1.45
mm is tolerated with a flow reduction ofless than 10%.
At this level of spasm, the normotensive example has
flow reduction of almost 40%, and in the hypotensive
exam pel flow is reduced by almost 60%. In such a perfusion state, ischemia and clinical symptoms would
be expected. The results also confirm the beneficial
effects of trans1umina1 angiop1asty for treatment of

vasospasm [9]. Clearly, if the diameter is reduced to a


critical level, any increase as a consequence of this
procedure will have a dramatic effect on improving
flow.
The effect of spasm on velocity is seen in the upper
panel of Fig. 6. In the right-hand part of the curve
(no significant reduction in flow) the velocity is a
hyperbolic function, being inversely proportional to
the square of the diameter. As flow is affected, velocity
falls below this hyperbola, and reaches a maximum at
about 1.4 mm diameter in the normotensive example,
slightly lower (1.3 mm) in the hypertensive case. Further diameter reductions will cause a decrease in flow
velocity. This critical point is well within the range that
can be expected in patients. As an example, a velocity
of 130 cmls in the normotensive patient can either be
found at a diameter of 1. 7 mm corresponding to a reduction of flow of about 15%, or at a diameter of 1.0
mm causing a flow reduction of more than 60%.
From such a hemodynamic analysis, it is seen that
vasospasm quantification based on velocity within the
narrowed segment alone has limitations when used to
assess degree of narrowing. For example, using Fig. 6,
let us assume that a patient has a 1.45 mm diameter
spasm and an ABP held at 140 mm Hg. Cerebral blood
flow will be nearly normal although the velocity of
230 cmls might be interpreted as indicating severe
vasospasm. The blood pressure is then lowered to
normotensive levels. Flow falls to about 60% of
normal, and the patient becomes symptomatic. Simultaneously, the velocity drops to 140 cmls according to
the graph. Seen in isolation, the TCD finding might be
falsely interpreted as an improvement of vasospasm,
and would be contradicted by the clinical observations. Using velocity determined by TCD alone as an
index of degree of spasm is based upon the tacit assumption that flow is maintained constant by an intact
autoregulation mechanism and that perfusion pressures (after the spasm) are maintained at or above the
lower level. This is not guaranteed in SAH patients
whose autoregulation may fail andlor its capacity may
become exhausted. Recent reports have confirmed that
TCD, when used without additional information, is
not a good index of the degree of vasospasm [7, 8, 23,
28]. However, the inherent value of a velocity reading
can be increased by combining it with other measurements.
Recognizing this problem, we proposed in 1985 [2]
to perform measurements of velocities both intracranially and extracranially (in the distal ICA just

54

before it enters the skull) to get a more complete assessment of the effects of cerebral vasospasm. We also
proposed that the rate of velocity increase per day in
the first stage of vasospasm - when flow is not yet reduced - might be a better prognostic index that absolute velocities at later stages. Lindegaard et al. (19)
proposed to use the VMCA/V'CA index - i.e. the ratio
between these velocity readings - to assess the severity
of the spasm. This was found to correlate much better
than velocity alone to the degree of spasm as seen on
angiography. Other groups have used CBF measurements combined with TCD to assess both flow and
velocity [IS, 20, 2S]. In spite of these findings and
ignoring the basic hemodynamic principles, many
authors continue to evaluate cerebral vasospasm based
on the intracranial velocity measurement alone. The
addition of at least a careful measurement in the extracranial ICA - which only takes a few minutes to
perform with the same TCD equipment (3) - allows a
more accurate evaluation of the degree and the effects
of vasospasm.
It should be noted that the upper panel in Fig. 6
shows the cross-sectional mean velocity within the
lumen. TCD is normally used to measure maximum
velocity, which is somewhat higher than the mean. The
relationship between the two is complicated in a short
segmental narrowing where parabolic velocity profiles
have no chance to develop, and the complex problems
of blunt velocity profile flow are outside the scope of
this chapter.

Effects of Collateral Channels


The leptomeningeal anastomoses can potentially
supply blood to regions supplied by arteries affected
by cerebrovascular spasm and thus 'wanting in their
offices' as Willis described it. What effect does this
have on cerebral perfusion and the effect of the spasm?
These collateral pathways are usually not effective, but
for illustration purposes it was assumed that they
could supply a third of normal blood flow at normal
blood pressure if the main channel was totally blocked.
The flow and velocities as function of diameter of the
spastic segment were again simulated for the same
three levels of ABP as in the preceding section, and the
results are shown in Fig. 7. As expected, the flow-diameter curve is shifted up, particularly in the left part,
as a result of the collaterals supplying increasing flow
with the spasm becoming more severe. In particular
with induced hypertension, the flow never goes below

R. Aaslid

250

"
~

200

..,
=
.......

150

=>

'"'
=
....

RBP: 140

100

50

250

."

-.
.....

200

....=

150

=>
....

100

...

=
=>

50

0.5

1.0

1.5

2.0

2.5

3.0

3.5

OIRHETER DF SPRSTIC SEGMENT [nnl

Fig. 7. Influence of collateral circulation via leptomeningeal anastomoses as schematically illustrated in Fig. I on the total flow and
the velocity in vasospasm. Compared to Fig. 6 which shows these
relationships without such collateral circulation, the main effect is an
increase in total flow at the most severe degrees of spasm, as well as a
decrease in the maximum velocities encountered. Note strong effect
on simulated induced hypertension on maintaining flow at the most
severe degrees of spasm (diameter less than 1 mm)

levels which are typically compatible with tissue survival. Again this is hemodynamic evidence for potential beneficial effects of such therapy.
The effects on the velocity are not nearly as marked,
but the maximum velocities do drop from 240 to just
under 200 cm/s for the hypertensive example. If the
collateral circulation originates form the ACA and
the spasm is in the MCA, the VMCA/V'CA index may
underestimate the actual degree of spasm as seen on
angiography because MCA velocity will be lower and
the ICA velocity (and flow) will be higher than without
collaterals.

Turbulence and Vortex Formation in Cerebral


Vasospasm
As briefly discussed above, the kinetic energy in
high velocity stenotic jets probably gets lost in the
post-stenotic segment. The reason being the flow bordering on an unstable state because of high Reynolds

55

Hemodynamics of Cerebrovascular Spasm

..

250

E
0

200

.....

)0-

150

-1

00

SO

,.>

-'
u-

"
2000

1000

)0-

W
Z

a=>
w
a::
u-

0
1000
2000

Fig. 8. Spectral display of a musical murmur (lower) and the Doppler signal (upper) from a 54 years old male patient with an aneurysm of the anterior communicating artery. The recording was made
from the right middle cerebral artery, slightly distal of the bifurcation of the internal carotid artery. Three sound modes are recognized
in the lower tracing: A systolic bruit (1 ) , a musical murmur displayed as a narrow hand in early diastole (2) , and a silent phase in
late diastole (3). The second harmonic of the musical murmur is also
seen in the recording, this is probably an artifact from the ultrasonic
modulation/demodulation process. From Aaslid and Nornes [5] Fig.
2, reproduced with permission

numbers in combination with non-optimal 'nozzle'


geometry [13]. Figure 8 is a reproduction of a TeD
recording from a patient with vasospasm after aneurysmal SAH [5]. The high velocities (time-mean of 190
cm/s) are accompanied by low-frequency murmurs or
bruits during systole and the early part of diastole.
These phenomena were examined by high-resolution
spectrum analysis as shown in the lower panel. For this
purpose, the frequencies that make up the bruits are
not caused by Doppler shifts proper, but by phase
modulation of the ultrasound beam. The instrument
functions as a focused, highly sensitive detector of
mechanical vibrations - in other word as a microphone
(try holding a vibrating tuning fork in front of a TeD
transducer). It should be noted that such bruits have
been recorded using highly amplified audio detection
[26], but the TeD is in principle even more sensitive.
TeD also has the advantage of being focused so that

the signal can be associated with an anatomicallocation. In the case of Fig. 8 it occurred in the vicinity
of, and distal to the high-velocity jet in the spastic
segment.
This example shows no such bruits during the latter
half of the cardiac cycle with the lowest flow velocities.
This also means the lowest Reynolds numbers and the
highest stability of the flow. The complete absence of
bruits suggests laminar flow in this regime. In contrast,
during systole, the bruits are characteristic of most
vascular sounds having a broad-banded noisy character. These are indicative of random chaotic vortex
formation which is generally recognized as turbulence.
This phenomenon occurs during the highest Reynolds
numbers, indicating the flow being the least stable.
An interesting phenomenon of a musical murmur
occurs in the transition of the turbulent and the laminar flow regimes. In the spectral analysis it is seen as
a narrowing of the spectral bruit into single spectral
lines. The frequency of the sound is proportional to
the velocity, even reproducing the dicrotic notch. Vortex shedding in jets coming from nozzles are characterized by the dimensionless Strouhal number StD:
[13]
StD=2fr/V

Equation [8]

In SAH patients with musical murmurs, the frequency (f) of the first harmonic of the murmur divided
by the velocity was 2.35 [5]. The Strouhal number most
conducive to periodic vortex shedding is 0.4 according
to Hussain [13]. For this value, the diameter of the
corresponding nozzle was 1.7 mm to match the relationship between frequency and velocity observed in
our patients. This is very close to what we would expect in terms of vasospasm in this group of patients
given the increase in velocity observed. So the most
likely explanation for the relatively frequent musical
murmurs in SAH patients is the flow stability becoming neutral or borderline unstable favoring shedding of
a von Karman vortex street. These regularly spaced
vortices in turn impinge upon the wall of the postspastic segment, setting up the vibrations which can be
detected as the musical murmur. If the Strouhal number for vortex shedding can be verified for this situation, this phenomenon opens up an intriguing possibility for accurate determination of vessel diameter in
cerebral vasospasm. However, this has limited clinical
application since it can only be used in those patients
(about 40%) who exhibit such murmurs.

56

Conclusions

In this chapter, the effects of cerebrovascular spasm


have been analyzed from a hemodynamic viewpoint. It
was found that the flow velocity profile in such narrowing causes much larger friction losses than could be
assumed by using the unmodified Hagen-Poiseuille
equation directly. Modifying the equation and adding
kinetic energy losses provided a model that accurately
predicted the pressure-flow relationship of spasmlike
hydrodynamic models. This provided the opportunity
to predict flow and velocity in different degrees of vasospasm. From the hemodynamic perspective, it was
found that these quantitative results strongly support
the present trend to use aggressive hypertensive therapy in patients with vasospasm. The results also confirmed that TCD velocity measurements in the spastic
segment may not be a good index of the degree and
effect of the spasm. These measurements must to
combined with other techniques such as extracranial
Doppler or CBF to assess the degree and the overall
effect of cerebral vasospasm.
References
1. Aaslid R, Lindegaard K-F, Sorteberg W, Nomes H (1989)
Cerebral autoregulation dynamics in humans. Stroke 20: 45-52
2. Aaslid R, Huber P, Nomes H (1985) A transcranial Doppler
method in the evaluation of cerebrovascular spasm. Neuroradiology 28: 11-16
3. Aaslid R, Markwalder T-M, Nomes H (1982) Noninvasive
transcranial Doppler ultrasound recording of flow velocity in
basal cerebral arteries. 1 Neurosurg 57: 769-774
4. Aaslid R, Newell DW, Stooss R, Sorteberg W, Lindegaard K-F
(1991) Assessment of cerebral autoregulation dynamics from
simultaneous arterial and venous transcranial Doppler recordings in humans. Stroke 22: 1148-1154
5. Aaslid R, Nomes H (1984) Musical murmurs in human cerebral
arteries after subarachnoid hemorrhage. 1 Neurosurg 60: 32-36
6. Berguer R, Hwang NHC (1973) Critical Arterial Stenosis: a
theoretical and experimental solution. Ann Surg 180: 39-50
7. Clyde BL, Resnick DK, Yonas H, Smith HA, Kaufmann AM
(1996) The relationship of blood velocity as measured by transcranial Doppler ultrasonography to cerebral blood flow as determined by stable xenon computed tomographic studies after
aneurysmal subarachnoid hemorrhage. Neurosurgery 38: 896905
8. Ekelund A, Saveland H, Romner B, Brandt L (1996) Is transcranial Doppler sonography useful in detecting late cerebral
ischaemia after aneurysmal subarachnoid hemorrhage? Br 1
Neurosurg 10: 19-25
9. Eskridge 1M, Newell DW, Pendleton GA (1990) Transluminal
angioplasty for treatment of vasospasm. Neurosurg Clin N Am
1: 387-399
10. Giller CA, Bowman G, Dyer H et al (1993) Cerebral artery
diameters during changes in blood pressure and carbon dioxide
during craniotomy. Neurosurgery 32: 737-742

R. Aaslid
11. Heistad DD, Kontos HA (1983) Cerebral circulation. Handbook of physiology: the cardiovascular system III: 137-182
12. Holen 1, Aaslid R, Landmark K, Simonsen S (1976) Determination of pressure gradient in mitral stenosis with a noninvasive ultrasound Doppler technique. Acta Med Scand 199:
455-460
13. Hussain AKMF (1977) Mechanics of pulsatile flows of relevance to the cardiovascular system. In: Hwang NHC, Normann
NA (eds) Cardiovascular flow dynamics and measurements.
University Park Press, Baltimore, pp 609-614
14. Kee DB, Wood IH (1984) Rheology of the cerebral circulation.
Neurosurgery 15: 125-131
15. Kontos HA (1989) Validity of cerebral arterial blood flow calculations from velocity measurements. Stroke 20: 1-3
16. Larsen FS, Olsen KS, Hansen BA, Paulson OB, Knudsen GM
(1994) Transcranial Doppler is valid for determination of the
lower limit of cerebral blood flow autoregulation. Stroke 25:
1985-1988
17. Lassen NA (1959) Cerebral blood flow and oxygen consumption
in man. Physiol Rev 39: 183-238
18. Lewis DH, Newell DW, Winn HR (1997) Delayed ischemia due
to cerebral vasospasm occult to transcranial Doppler. An important role for cerebral perfusion SPECT. Clin Nucl Med 22:
238-240
19. Lindegaard K-F, Nomes H, Bakke SI, Sorteberg W, Nakstad P
(1989) Cerebral vasospasm diagnosis by means of angiography
and blood velocity measurements. Acta Neurochir (Wien) 100:
12-24
20. Martin NA, Patwardhan RV, Alexander MI, Africk CZ, Lee
IH, Shalmon E, Hovda DA Becker DP (1997) Characterization
of cerebral hemodynamic phases following severe head trauma:
hypoperfusion, hyperemia, and vasospasm. 1 Neurosurg 87: 919
21. Martins AN, Kobrine AI, Larsen DF (1974) Pressure in the
sagittal sinus during intracranial hypertension in man. 1 Neurosurg 40: 603-608
22. McDonald DA (1960) Blood flow in arteries. Edward Arnold,
London, pp 17-48
23. Meixensberger 1, Hamelbeck B, Dings 1, Ememann U, Roosen
K (1996) Critical increase of blood flow velocities after subarachnoid haemorrhage: vasospasm versus hyperaemia. Zentralbl Neurochir 57: 70-75
24. Newell DW, Aaslid R, Lam A, Mayberg TS, Winn HR (1994)
comparison of flow and velocity during dynamic autoregulation
testing in humans. Stroke 25: 793-797
25. Nomes H, Knutzen HB, Wikeby P (1977) Cerebral blood flow
and aneurysm surgery part 2: induced hypotension and autoregulatory capacity. 1 Neurosurg 47: 819-827
26. Olinger CP, Wassermann IF (1977) Electronic stethoscope for
detection of cerebral aneurysm, vasospasm and arterial disease.
Surg Neurol8: 298-312
27. Permutt S, Riley RL (1963) Hemodynamics of collapsible vessels with tone: the vascular waterfall. 1 Appl Physiol18: 924-932
28. Ronmer B, Bellner 1, Kongstad P, Sj6holm H (1996) Elevated
transcranial Doppler flow velocities after severe head injury:
cerebral vasospasm or hyperemia? 1 Neurosurg 85: 90-97
29. Schmieder K, Hardenack M, Harders A (1996) cerebral hemodynamics in patients with traumatic subarachnoid hemorrhagesequential studies with TCD. Acta Neurol Scand [Suppl] 166:
123-127
30. Spencer MP, Reid 1M (1979) Quantification of carotid stenosis
with continuous-wave (C-W) Doppler ultrasound. Stroke 10:
263-330
31. Spetzler RF, Roski RA, Zabramski 1 (1983) Middle cerebral

Hemodynamics of Cerebrovascular Spasm


artery perfusion pressure in cerebrovascular occlusive disease.
Stroke 14: 552-556
32. Strandgaard S, MacKenzie ET, Sengupta D, Rowan JO, Lassen
NA, Harper AM (1974) Upper limit of autoregulation of cerebral blood flow in the baboon. Circ Res 34: 435-440
33. Strandgaard S, Paulson OB (1984) Cerebral autoregulation.
Stroke 15: 413-416
34. Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell
DW (1995) Dynamic and static autoregulation during Isoflurane, desflurane and propofol anesthesia. Anesthesiology 83:
66-76

57
35. Tiecks FP, Lam AM, Aaslid R, Newell DW (1995) Comparison
of static and dynamic autoregulation measurements. Stroke 26:
1014-1019
36. Willis T (1664-1964) The anatomy of the brain and nerves. In:
Feindel W (ed) Tercentenary edition. McGill University Press,
Montreal

Correspondence: R. Aaslid, University of Washington, Department of Neurological Surgery, Harborview Medical Center, Seattle,
USA.

Acta Neurochir (1999) [Suppl]72: 59-71


Springer-Verlag 1999

The Role of Transcranial Doppler in the Management of Patients with


Subarachnoid Haemorrhage - a Review
K.-F. Lindegaard
University of Oslo, Department of Neurosurgery, Rikshospitalet, The National Hospital, Oslo, Norway

Summary
Introduced 15 years ago, transcranial Doppler (TCD) recordings
of blood velocity in patients with recent subarachnoid haemorrhage
(SAH) have two objectives: to detect elevated blood velocities suggesting cerebral vasospasm (VSP) and to identify patients at risk for
delayed cerebral ischemic deficits (DID). The pathophysiological
cascade causing DID is complex. Discrepancies between blood velocities and DID (presuming that there actually is an "ischemic
threshold" for blood velocity in absolute terms, which seems most
unlikely) have been demonstrated, particularly in patients with elevated intracranial pressure (ICP) levels. Furthermore, the vessel
showing the highest blood velocity is not always the one perfusing
the area where ischemic symptoms arise, nor does the site of the
greatest subarachnoid blood clot always relate to the ischemic brain
region. Moreover, it is probable that the complex haemodynamic
changes following SAH and the subsequent development of VSP
may be underestimated if only considering the crude intracranial
artery blood velocities. Cerebral blood flow measurements combined
with TCD to assess both flow and velocity have emphasised this
point. Despite these findings and ignoring the basic principles of cerebral haemodynamics, cerebral vasospasm is still being assessed
from the intracranial velocity measurement alone. The addition of at
least a careful measurement from the extracranial internal carotid
artery - using the same TCD equipment and taking only a few short
minutes to perform - allows a much more accurate assessment of the
degree and the effects of vasospasm.
This probably explains why the clinical value of TCD is still debated. There is still uncertainty as to the best method to prevent and to
treat VSP, and the overall outcome after SAH depends on so many
factors besides VSP. Conclusive evidence may therefore be hard to
obtain, and it appears sound to conclude that even with advanced
investigation technology available, proper selection, pre- peri- and
postoperative care and timing of surgery remain cornerstones in the
management of these patients,- equal in importance to their treatment in the operating room or in the interventional angiography suite.

Keywords: Transcranial Doppler ultrasound; cerebral vasospasm;


subarachnoid haemorrhage; cerebral aneurysm; humans; clinical;
review article.

and degree of cerebral vasospasm after subarachnoid


haemorrhage may be considered as the raison d'etre of
the transcranial Doppler technique. Previously, he had
been using miniaturised Doppler probes in the operating field during aneurysm surgery, and observed
increased blood velocities in arteries appearing as
being in spasm [76]. Velocities in the order of 150 to
200 em S-1 were found, which is between two and
four times the velocity recorded from vessels appearing
normal. A reduction in blood velocity paired with an
increase in diameter was seen following the topical
application of papaverine 3% on the spastic artery
segments.
Subarachnoid haemorrhage (SAH) is a dramatic
event,- during the first seconds after the rupture of an
arterial aneurysm the intracranial pressure approaches
systemic blood pressure levels [72] accompanied by the
transient arrest in cerebral blood flow [73]. Aside from
the direct brain damage from initial and recurrent
bleed, a substantial amount of the morbidity and
mortality from SAH is being attributed to the narrowing of cerebral arteries, so-called "vasospasm"
(VSP), occurring in the wake of the haemorrhage [34,
45, 67]. VSP is a multifactorial process, and while a
review of its pathogenesis is outside the format of this
presentation, it is generally accepted that if VSP is
severe and the compensatory vasomotor mechanisms
are depleted, VSP may be the decisive factor in the
complex equation which determines if and how the
brain will eventually recover [60, 67, 106, 107].

Introduction

Blood Flow Velocities; Threshold Values

The desire of one neurosurgeon, Helge N omes, to


assess individual patients with regard to the presence

Following the introduction of transcranial Doppler


in 1982 [4], the capabilities of the technique were di-

60

rected towards the assessment of VSP in patients with


aneurysmal SAH. Typically, the Doppler audio signal
from severely spastic arteries has a high-pitch quality,
resembling the sound of air from a jet. The centre-line
blood velocity corresponds to the outline of the velocity spectrum in transcranial Doppler recordings (V).
When VSP is very severe the reflected signal becomes
weak because blood flow is reduced. Musical murmurs
[6] may be recorded from sites near the circle of Willis.
In 1984, the first study on the diagnosis of cerebral
VSP with TCD was presented [5]. For the middle
cerebral artery (MCA) the authors demonstrated an
inverse relationship between blood velocity (YMCA)
and residual lumen diameter (DMcA) measured from
angiographic films. Grading VSP angiographically as
an absent/present phenomenon, proximal MCAs with
evidence ofVSP had blood velocities from 120 to more
than 200 cm . S-I. From these observations the authors
suggested velocities> 120 cm . S-I as indicating VSP
of the MCA mainstem. Seven other studies have supported this view [27, 35, 61, 62, 83, 84,92]. Higher and
lower cut-off limits have been proposed: 155 cm . S-I
[91], and 100 cm . S-I [14]. The limits more recently
recommended by Schaller et al. [86] were: no or mild
VSP < 120 cms- I , 120-160 cms- I moderate
VSP, and> 160 cm . S-I, severe VSP. These threshold
values have in common that they are obtained post hoc
- based on observation. They should, therefore, be
considered as being provisional.
When we discuss velocity threshold values in the
context of cerebral VSP it is prudent to remember that
by assessing MCA spasm, or rather the MCA diameter, from the absolute MCA blood velocity one implicitly presumes a predictable relationship between
MCA diameter and blood velocity. Indeed, MCA
blood flow variations do compromise this assumption
[2]. Consider the following: for a YMCA of 64 cm . S-I
in the normal situation, the YMCA becomes 115 cm . s-I
given a 25% MCA lumen diameter reduction. For a
50% MCA diameter reduction the predicted YMCA
becomes 256 cm . S-I, - exceeding the highest blood
velocity observed in our previously published clinical
series [59].
However, after SAH the cerebral perfusion, or
blood flow (CBF), may differ substantially from the
normal [32, 41, 42, 65, 66, 78]. Therefore, if we assume
a 40% blood flow reduction in all patients with severe
MCA spasm, one obtains 150 cm . S-I for a 50% calibre reduction, instead of 256 cm . S-I. The assessment
of VSP from MCA blood velocity alone may be diffi-

K.-F. Lindegaard

cult or even misleading in settings with hyperperfusion


[43,44], as well as when the perfusion is reduced due to
VSP with or without intracranial hypertension [44, 48].
Such error may be serious when TCD is used as a
clinical management tool.

The Hemispheric Index VMCAfVICA


To reduce the impact of blood flow variations in the
practice of stand-alone Doppler one may consider the
following: the ICA blood flow (QrcA), and blood velocity (V rcA ) could be expected to reflect these changes
in cerebral perfusion. In general terms, the relationship
between blood flow and blood velocity in a given vessel
segment may be written:
V = Const Q. (Dr2

[Equation la]

thus:
YMCA

= Const QMCA . (D McA)-2 [Equation 1b]

and:
VrCA

= Const QrcA . (D rcA r 2

[Equation lc]

Calculating the ratio VMCA/VICA and eliminating


the constant:
VMCA/VrCA = (QMcA/QrcA) . (DrcA )2 . (D MCA r 2
If the M CA can be regarded as an end artery from the
ICA, then variations in blood flow should not change
the ratio QMcA/QrcA. Provided an unchanging ICA
lumen diameter (D rcA ), the expression (QMcA/QrcA) .
(D rcA ) -2 should also be constant.
The ratio VMCA/VrCA then emerges as:
VMCA/VrCA

Const (DMCA)-2

[Equation 2]

The hemispheric index VMCA/V1CA therefore seems


attractive for predicting MCA lumen narrowing. Similar considerations were obviously important to Weir
et al. [103]. They assessed angiographical spasm employing the indices of Gabrielsen and Greitz [24] to
compensate for individual variation of the cerebral
artery tree. The hemispheric VMCA/V1CA index can be
considered as the application of similar principles to
the field of blood velocity measurements.
Benalcazar et al. [9] investigated the robustness of
the hemispheric VMcA/VrcA index. The CBF was
augmented by induced hypercapnia: the pC0 2 increased by about 31 torr, the YMCA increased by 80%,
and the VrcA increased by 60%. The VMcA/VrcA index
changed only by 11%, confirming its utility to correct
for blood flow variation.

61

Role ofTCD in Patients with SAH

Comparing angiograms and blood velocity recordings in 80 patients with SAH we found that compared
with the MCA blood velocity, the hemispheric index
showed less variation with age and gender [59]. This
agrees with studies in normal persons [8, 28]. With
angiographical VSP of the MCA mainstem scored as
severe, moderate, suspected, or absent, the better correlation was obtained with the hemispheric index,
suggesting an index of> 3.0 as denoting the presence
of angiographical MCA spasm, with values :2: 6.0 indicative of severe VSP [58, 59].
The advantage of the index was most evident in
patients in poor clinical condition, Grade III-IV [39].
Some of these patients had a YMCA about 120 cm . s-1
despite severe angiographical MCA spasm. In these
patients the VrcA was very low, about 20 cm . s-l,
suggesting reduced hemispheric blood flow, nonetheless the VMCA/VrCA index was about 6.0. We
interpret this as confirming that the hemispheric index
adds relevant information, and therefore maintain that
to reduce misjudgement it is essential to obtain an
insight into the blood flow in the artery system of
interest.

The First Minutes and Hours After SAH


An early phase of VSP does not occur during the
first 24 hours after the first aneurysm rupture in
humans. This conclusion follows from angiograms
obtained during and immediately after aneurysmal
rupture [104] and from recordings of blood velocity
obtained during the first minutes [31] and hours [83]
after the bleed.
During the first critical seconds after SAH the blood
velocities drop precipitously [31]. This reflects the drop
in CBF as shown by means of electromagnetic flowmetry [72, 73], which again is due to the steep increase
in intracranial pressure (ICP) occurring during this
momentous phase [74]. In a patient who ultimately had
a good recovery, Grote and Hassler [31] observed
transiently reverberating MCA blood velocities compatible with total or near-total cerebral circulatory arrest [37] for the first 100 seconds following a rebleed.
The blood velocities became normalised within the
next 2-3 minutes. Another patient showed reverberating blood velocities and total or near-total blood flow
arrest persisting for 10 minutes. This patient later died
from the resulting ischemic brain damage. Romner et
al. [83] investigated 19 patients within 12 hours after

SAH with MCA blood velocities within normal limits


in all.

Blood Velocities After Aneurysmal SAH


As seen from X-ray films, VSP rarely appears less
than three days after aneurysmal SAH. The maximum
incidence ofVSP is during the second week [10,50,98,
103]. With angiography unacceptable as a routine
method to follow the course of VSP on an individual
day to day basis, serial blood velocity measurements
by TCD can provide the information required for individualised patient management during this critical
stage, atraumatically and with no cooperation from
the patient apart from lying relatively still.
Basically, the time-course of blood velocities seems
to follow the pattern demonstrated by serial angiograms. Increased velocities are rare within the first two
days after a single bleed, while the velocities escalate
from the end of the first and well into the second week
[7, 35,40, 87, 91]. High velocities persist for days and
thereafter recede more slowly. There may be a relationship between the increase in blood velocities (in
VSP) and the extent of the subarachnoid clot [22, 35,
89]. Two recent studies have, however, challenged this
conclusion [11, 87]. Furthermore, the correlation with
clinical grade seems to be poor [14,91]: some patients
remain in good clinical condition despite blood velocities well above 200 cm . S-1 [89]. This could be due to
increased perfusion and hyperaemia [64]. Patients in
poor condition have lower CBF and lower blood velocities [63, 91]. It seems reasonable to assume that
some of these patients, possibly all, have intracranial
hypertension [48, 49].
According to Brint et al. [10], MCA blood velocities
were normalised after a median of21 days (range 1-31
days) following surgery for ruptured aneurysm. These
patients had recent SAH with Fisher Grades 1-3 [22],
however, no differentiation was made with respect to
the localisation of the aneurysm.
Similar data pertaining to the hemispheric index
VMCA/VICA have not been reported as yet. Aas1id et al.
[7] noted significantly reduced ipsilateral ICA blood
velocity in patients when the MCA velocity was> 200
cm . S-I. From this it may be inferred that the time
profile of the hemispheric index can be expected to
improve the visualisation of the rise and fall ofVSP.
With current TCD equipment the aneurysm itself
can be detected only when large and favourably situated [58].

62
Distal Cerebral Artery Spasm

Distal cerebral arteries, i.e. the pericallosal artery


and the MCA branches beyond the Sylvian fissure, are
out of reach with current TCD techniques. Thus, if
VSP is limited to these vessels it may be overlooked
with TCD. To assess the incidence and significance of
predominantly distal VSP, Newell et al. [71] reviewed
136 angiograms from 68 patients with ruptured
aneurysms of the anterior circulation. A total of 40
angiographic series showed VSP defined as ~ 25%
lumen narrowing: of these one half had VSP of the
basal arteries, 42.5% had evidence of spasm of both
basal and distal segments, and 7.5% showed VSP
involving distal segments only.
In their series of 34 patients investigated with TCD
within 24 hours of angiography, Sloan et al. [92] had
12 false negative findings. These were attributed to
distal MCA spasm (four), proximal or distal anterior
cerebral artery spasm (six) and supraclinoid ICA
spasm (two). Hutchinson and Weir [40] claimed that in
their experience, severe narrowing of distal MCA
branches in the absence of proximal spasm was "exceedingly rare". It seems that a significant proportion
of patients may have DID due to VSP limited solely to
vascular segments beyond reach of the TCD technique. To diagnose such a condition will require CBF
measurements and/or angiography.
Delayed Ischemic Dysfunction

The incidence of delayed ischemic dysfunction


(DID) is about one half of the incidence of angiographical VSP. The degree ofVSP on angiograms does
not inevitably correlate with the patient's clinical condition. TCD findings corroborate the latter observation [89, 105], however, TCD data also indicate that
VSP is more prevalent than known from angiography
studies [7]. DID has been observed with YMCA values
as low as 120 cm . S-I, while in other patients, a YMCA
twice as high may be well tolerated. High velocities
seem to precede DID by at least 1-2 days [68, 89, 101].
During this time-window the situation seems to proceed from the "prodromal" to the "symptomatic"
stage of VSP [91].
Seiler and colleagues [89] reported on 39 patients.
Ten of 11 patients with reversible DID had YMCA >
200 cm . S-I. Three of the 20 asymptomatic patients
had YMCA > 200 cm . S-I. Harders and Gilsbach [35]
observed DID in 14/50 patients treated with early
surgery and nimodipine. DID occurred between six

K.-F. Lindegaard

and 12 days after SAH and all these patients had


120 cm . s-l.
Klingelh6fer et al. [48] observed nine patients with
angiographical VSP (severity not specified). Four patients with ICP levels < 20 mm Hg had an average
YMCA of 186 cm . S-I, while five patients with ICP
levels> 20 mm Hg had YMCA < 120 cm . S-1 (average
98 cm s-I). Under such circumstances, DID may
occur despite absolute blood velocity values well below
the thresholds specified above. Although no data on
blood velocity in precerebral arteries were reported, we
suspect that the ICA blood velocities were very low in
these patients. The same group also observed that the
outline of the envelope of the blood velocity spectrum
showed augmented pulsatility with increasing ICP
levels in excess of 20 mm Hg. This valuable clinical
information may explain the unexpectedly low absolute blood velocities sometimes seen in patients in poor
clinical condition. The results also emphasise that
when intracranial hypertension and VSP concur the
risk increases significantly for DID, for brain infarction, and for death.
Laumer et al. [51] followed 100 patients treated
sugically, noting a poor correlation between blood
velocity and the clinical condition. Velocities > 200
cm . S-1 might be well tolerated while DID developed
in the presence of near normal velocity levels. In
Grades IV and V lower velocities were generally
found. They also presented a series of presumed
healthy individuals aged from 2 to 84 yerars. One of
these volunteers showed the highest blood velocity reported as normal at the time of writing; 154 cm . S-1 .
However, no comment was made on the possibility of,
for example, asymptomatic intracranial artery stenosis
[56]. From their findings the authors concluded that
longitudinal TCD investigation may be indicated only
in patients admitted more than three days after SAH,
or if the case history suggests a sentinel bleed having
occurred several days before admission.
According to several studies, steep velocity increases
(increases by > 20 cm . s-1 /day) may signal an increased risk for DID [20, 30, 32, 89, 101]. In Seiler's
series, three patients died from brain infarction, and
the mean YMCA increase exceeded 30 cm . S-1 per day
in these patients [89]. In 80 patients, Kili~ et al. [47]
noted a 56% incidence of DID in patients with increases> 35 cm . s-l/day and an 80% incidence if with
preexisting high velocities a similar increase ensued.
Out of a series of 121 patients, Grosset et al. [29]
observed DID in 47. The average of the highest MCA

YMCA ~

63

Role of TeD in Patients with SAH

or ACA blood velocity in patients with DID was 186


cm . S-I, significantly higher than in patients not developing signs of DID. The hemispheric index was also
significantly higher in patients with DID, 6.0 versus
4.5. Extremely steep velocity increases, of the order of
50 cm . S-1 jday, were observed in a substantial proportion of the patients. The average increase in the 47
patients with DID was 67 cm . S-1 jday, with an average of 47 cm . S-1 jday in the others. Twenty patients
with steep velocity increases were selected for CBF
studies with the HMPAO-SPECT technique. DID developed in 10 of 15 patients studied before the onset of
any deficit. The CBF pattern showed low perfusion
areas in 14 of these 15 patients and in a further five
patients with already manifest DID. These findings
correlated with the arteries showing elevated blood
velocity [29]. Velocity increases of > 50 cm . S-1 jday
were detected in 12 of the 109 patients of Ekelund et al.
[20], in the majority occurring between day 6 and day
10 after SAH. Seven of these patients developed DID,
with neurological deficits persisting in five.
Two studies have addressed the usefulness of TCD
recordings in the clinical routine: Ekelund et al. [20]
followed up 109 patients, 57 showed VMCA values
> 120 cm . S-1 during the course, and 23 of these developed DID. The average velocity in this group was
170 cm . S-I, compared to 155 cm . S-1 in patients not
having DID. Wardlaw et at. [101] reported on 189
consecutive patients, of whom 29 developed DID.
TCD performed by radiographers made an important
positive contribution to the diagnosis of DID in 72%
of the patients with this complication. This led to altered management strategies in 42%. Patients with
DID showed YMCA values of about 160 cm . s-l, while
the mean was 95 cm . S-1 in patients whose recovery
was uneventful.
It may be difficult to appoint an "ischemic threshold" for blood velocities, and this is not surprising. The
blood flow and blood veloctiy in a specific artery depends not only on the lumen calibre, but also on the
size of its perfusion territory [94]. Depending on the
potential of the leptomeningeal collateral system one
could expect that the perfusion territory of one spastic
artery may contract, its borders temporarily receiving
blood flow from adjacent territories [95, 96]. Thus even
a severely narrowed MCA may be well tolerated provided that autoregulation is not defective. Computer
simulations seem to confirm this assumption [2, 80].
However, this delicate balance may become decompensated if spasm afflicts the other input channels, the

anterior and posterior cerebral arteries as well. To obtain a better insight into the haemodynamics of DID it
is therefore important to consider the circle of Willis
and its inlets and outlets as a system having the potential for redistributing the blood flow to the neuronal
pool. The average hemispheric index, i.e. the average
of the ipsilateral MCA and ACA values suggested by
Sekhar et al. [91] may be useful. Jakobsen's spasm index (VMCAjCBFMCA) is very interesting, but sacrifices
the technical simplicity and the short response time,
which are important advantages with the stand-alone
TCD approach.
Indices of Pulsatility

Two studies have addressed specifically the pulsatility of the blood velocity signal in VSP. Steinmeier et
at. [97] found an inverse relationship between the
VMCA and the pulsatility index, PI or
(Vsystolic -

Vdiastolic) / V mean,

recorded from the extracranial ICA blood velocity


[26]: the higher the VMCA the lower the PI. No absolute
ICA blood velocities and no ICP data were reported.
There was no significant difference between patients
who developed DID and those who did not. It is not
unequivocally clear whether these lower PI values were
due to hyperemia, VSP or systemic haemodynamic
factors. KlingelhOfer et al. [49] investigated 44 patients, the selection criteria were not specified. Compared to patients having a favourable course, the peak
YMCA was slightly lower in patients having DID,
about 130 versus 120 cm . S-I. Even lower velocities
were observed (about 100 cm . S-I) in those with VSP
and DID developing to CT-documented brain infarction (9 patients) or who died (7 patients). In the same
patients, the more the pulsatility of the YMCA signal
increased are the worse the clinical outcome. These
authors calculated pulsatility as the index de resistance
(IR) of Pourcelot [54], or
(Vsystolic -

Vdiastolic) / Vsystolic.

These findings seem to conflict as far as pulsatility is


concerned. Some of this difference may be owing to the
fact that the site of measurement differed: Steinmeier
et al. [97] recorded from the extracranial ICA while
KlingelhOfer et al. [49] recorded intracranially: from
the presumably spastic MCA itself. Pulsatility is difficult to assess when VSP is concerned, because pulsatility changes do not only reflect changes in peripheral
brain vascular resistance. Equally decisive are: 1. the

64

compliance of the vasculature distal to the point of


measurement, 2. how the pressure waves become reflected in the distal vascular tree, and 3. the proximal
input signal (blood pressure) originating from the
aorta. It is commonly believed that increased pulsatility is a sign of increased peripheral resistance. A
similar change may in fact result from increased
peripheral compliance [3, 54].
The Effect from Surgery
To assess the effect of aneurysm surgery on cerebral
artery blood velocities, Hutchinson and Weir [40]
investigated 12 patients operated electively (no recent
bleed). After the operations they observed only very
moderate velocity increases, by up to about 60 cm . s-1 .
Very moderate MCA blood velocity increases after
surgery for non-ruptured aneurysm were also reported
by Brint et al. [lO]. In their patients the velocities had
normalised after a median of lO days postoperatively
(range 1-36 days). After surgery for ruptured aneurysm, the time for MCA blood velocity normalisation
was twice as long, 21 days (range 1-31 days). In patients operated for asymptomatic aneurysms or sellar /
parasellar tumour, MCA blood velocity increased up
to about 110 cm . s-1 [89].
Romner et al. [84] addressed the haemodynamic
consequences of the timing of aneurysm clipping. In 36
patients the preoperative MCA blood velocities were
similar in the patients operated upon at 48 hours or less
and those having surgery at 49-96 hours after SAH.
The allocation mechanism was not explained, but the
average clinical Grade was very similar in the two
groups. No signs of DID and no velocities > 120
cm . S-1 were observed in the 18 patients operated
upon within 48 hours. In the other patients, velocities
of 120 cm s-1 were seen in three at 5-7 days after
SAH, and in seven at lO-12 days after the bleed (difference statistically significant). Two patients died
from DID and brain infarction, having been operated
upon at 76 and 96 hours after SAH and showing MCA
blood velocities of at least 170 cm . S-I.
Correlation with Angiography
The term cerebral vasospasm (VSP) basically refers
to the narrowing of brain arteries observed on angiograms. Described about 50 years ago [19, 82], the diagnosis by cerebral angiography continues to be the
reference standard with regard to this condition [93].

K.-F. Lindegaard

Comparisons with angiograms are necessary to validate the TCD findings [5, 35, 91]. Three studies have
questioned the sensitivity of TCD to detect VSP, particularly following rupture of aneurysms on the anterior cerebral artery complex [15, 52, 79]. However, in
order to assess how TCD and angiographical findings
correlate (using angiography as the standard of reference) we need answers to the following questions:
1. How should angiographical VSP be defined, and
2. how accurate is the assessment of VSP from the
angiograms?
1. Standardised measurement points for basal brain
arteries have been devised [24], but these points may
not coincide precisely with the narrowest vessel segments in VSP. The calibre of cerebral arteries is individually variable, and the assessment of angiograms
obtained after an SAH is difficult since only very exceptionally will patients with recent SAH have had
angiography performed before the bleed. It therefore
seems realistic to assume that when comparing with
the corresponding vessel on the other side, only diameter differences exceeding 20% will be recognised [98].
Diffuse VSP, involving all basal cerebral arteries, will
complicate this estimation.
2. Two studies have addressed the issue of interobserver variability in reading angiograms using
Kappa statistics (the correlation of categorical data
with correction for agreement occurring by chance).
Eskesen et al. [21] confirmed that two independent
judges may read one and the same angiogram very
differently. This may explain why the reported incidence ofVSP after SAH shows considerable variation:
from 21 to 78% [12]. Even when angiographic VSP is
evident, deciding if it is moderate or severe may be intricate. Hence, Lindegaard et al. [59] found agreement
between two independent judges (neuroradiologist and
neurovascular surgeon from the same institution) in
lO5/124 hemispheres (Kappa = 0.67 or good agreement) for VSP of the MCA and in 62/124 (Kappa
= 0.43 or moderate agreement) for the ACA. There
seem to be no reports on intra-observer variability.
Since the assessment of angiograms by eye is categorical (VSP being present/absent or either severe,
moderate, mild or absent) while blood velocities and
velocity indices are reported on continuous scales,
these two methods of evaluation are difficult to reconcile. It may be suggested that at least for research purposes judgement by eye should be replaced by measurements of the contrast-filled column on angiograms
and corrected for magnification [18]. This would be

Role of TeD in Patients with SAH

very relevant if the deleterious effects of vasospasm are


due mainly to the loss of inflow pressure from viscous
drag in the narrowed vascular segments and disturbed
flow (or so-called turbulence). Indeed, reports on the
relief of DID occurring within minutes after the successful transvascular balloon dilation of severely spastic brain arteries documented angiographically and
with TCD [70] seem to support this.
Giller et al. [25] have proposed the non-invasive
assessment of vessel diameter variation by calculating
an area index (AI) from TCD recordings. This AI =
FI lv, with v the time-mean velocity derived from the
outline of the velocity spectrum envelope. The FI,
introduced to the methodology of TCD by Aaslid [1],
denotes the flow index calculated as: FI = Iv;li with Vi
the i-th velocity and Ii the acoustic intensity of the
corresponding Doppler-shifted frequency [38]. In 20
patients with recent SAH and who underwent arteriography twice, changes in the AI predicted correctly
the direction of changes (larger or smaller) in the arterial lumen area as measured from the X-ray films. The
mean difference between the two methods was - 2%
with standard deviation 17.7%. A 60% reduction
in vessel lumen area shown angiographically corresponded with reductions in AI from 15 to 50%. In
healthy individuals, where the vessel diameters could
be assumed to remain constant, the mean difference
between the first and the second calculations of the AI
was 3%.
In the future, this method could be useful in documenting the relative contributions of blood flow or
vessel area (or diameter) changes to velocity changes
in various clinical settings. It may, however, be less
robust under routine daily testing conditions due to
probe movement, variations in gain, beam angle,
depth setting, and disturbed flow conditions owing to
stenosis or VSP. Hence, technical error problems may
result in more serious and additive errors with the AI
than with raw TCD velocity measurements. Moreover, with indices to stipulate lumen area or blood
flow as well as with blood velocity and the hemispheric
index, trends over time and the clinical setting will
most likely remain important in the clinical use of
TCD after SAH.
Correlation with CBF Measurements

After SAH the CBF may be significantly reduced,


even in the absence of VSP [32, 41, 42, 43, 65, 66, 68,
78, 99]. When interpreting TCD findings a correction

65

is necessary to reduce confusion due to regional blood


flow variation. A close conceptual relation to the
hemispheric VMCA/VrCA index is the spasm index of
Jakobsen [44]. This is obtained from dividing the
YMCA by the regional CBF in the MCA perfusion territory: VMCA/CBF MCA . This index remained remarkably stable even in cases showing great day to day
variation in YMCA as well as in CBF [44].
Weir et al. [103] assessed angiographical spasm employing the indices of Gabrielsen and Greitz [24] to
compensate for individual variation of the cerebral
artery tree, using the patient as his own control.
The hemispheric VMcA/VrcA index and the VMCA /
CBF MCA index of Jakobsen can be regarded as extrapolations of the basic idea of Weir and colleagues
[103]. The CBF MCA may be estimated by means of the
initial slope algorithm with 133~Xe inhalation, by
SPECT [53, 100] or by CT scanning using stable xenon
enhancement [13, 17].
Taking advantage of the VMcA/VrcA hemispheric
index, Weber et al. [102] found signs ofVSP in 14 of 35
severely head injured patients, and VSP correlated
with the amount of blood seen from CT-scans. A high
index value was an ominous prognostic sign, the two
patients with values of >5.0 died. Martin et al. [61]
investigated 30 head injury patients, vasospasm occurred in eight. Three of these had no blood on the
CT -scans and a brief course of spasm. In patients with
CT -scans showing traumatic SAH the maximum
blood velocities occurred during the second week, resembling the course of blood velocities in vasospasm
after spontaneous SAH [7]. This may be interpreted
as reflecting that both conditions involve diffuse and
direct trauma to the brain and the collection of blood
in the basal cisterns.
Mizuno et al. [68] measured blood velocities and
CBF in 73 patients, of whom 26 (35.6%) developed
DID, reversible in all but 4 (5.5%). A direct comparison between blood velocity and CBF was not carried
out, however, the conclusions were: 1. for blood velocities there was no significant difference pertaining to
the occurrence of DID. 2. blood velocities > 200
cm . S-1 were seen without DID, while a value < 120
cm . S-1 was not incompatible with DID. 3. the authors recommended using TCD to detect VSP and
CBF to follow symptomatic patients.
In a recent study, Martin et al. [62] investigated the
extent and time-course of cerebral haemodynamic alterations following severe head trauma. In the early
phase (hypoperfusion) CBF was low, while the arte-

66

riovenous oxygen difference (AVD0 2 ), the YMCA and


the hemispheric VMCA/VICA index were normal. In the
hyperaemic phase (Days 1-3) CBF was increased, the
AVD02 decreased, the YMCA rose while the hemispheric VMCA/VICA index remained within normal
limits. On days 4-15 after the injury, there was a fall in
CBF, the YMCA increased further, and the hemispheric
VMCA/V ICA index showed a pronounced rise. These
findings may be interpreted as illustrating the importance of comparing intracranial artery blood velocity,
such as the YMCA, with either the regional CBF or with
the velocity of the blood flow in the extracranial ICA,
and to calculate the hemispheric VMCA/VICA index.

Spontaneous SAH Without Aneurysm


According to two studies cerebral VSP seems to be
relatively rare following non-aneurysmal SAH [105],
particularly with the so-called perimesencephalic pattern of SAH [81]. Schaller et al. [87] recently reported
severe VSP (> 160 cm . S-I) in six of 16 patients. Five
of these patients became obtunded during the course of
VSP, but no other focal deficit occurred and no sign of
brain infarction was seen from CT-scans.
After the rupture of an arteriovenous malformation
VSP is considered rare [77], but may have clinical importance. In two A VM patients with haemorrhage
mainly to the basal cisterns we have observed signs
typical ofVSP of the MCA opposite to the hemisphere
harbouring the malformation [57]. In these remote and
normal MCA's blood velocity increased to about 150
cm . S-1 and the VMCA/VICA index rose to about 5.
However, no signs of DID developed. According to
Hassler [36], after the rupture of an AVM even its
feeding artery may develop VSP.

Special Considerations

K.-F. Lindegaard

obtain a large body of angiographical proof in such


situations, we surmise that especially if a high priority
is given to avoid underdiagnosing severe vasospasm in
high-risk patients, a slightly lower threshold, 5.0-5.5,
could be used.
Dahl et al. [16] demonstrated the influence of MCA
dilation by sublingual nitroglycerine: regional CBF
remained constant while the YMCA decreased significantly. In the setting of VSP after SAH, some investigators have used CBF measurements combined
with TCD to assess both flow and velocity. [44, 53, 62,
85]. In spite of these findings and ignoring the basic
haemodynamic principles (Equations la-c, see above)
many authors nevertheless continue to evaluate cerebral vasospasm from the intracranial velocity measurement alone. The addition of at least one careful
measurement in the extracranial ICA - using the same
TCD equipment and taking only a few short minutes
to perform [23] - allows a much more accurate evaluation of the degree and effects of vasospasm.
Examination Technique

The MCA branches in the Sylvian fissure can often


be detected at depths between 30 and 45 mm. By
changing the probe position slightly it seems possible
to differentiate between different branches. Occasionally, unexpectedly high velocities may be found corresponding to one branch, while other branches, and the
MCA mainstem, have lower velocities. Such findings
probably indicate spasm at the Sylvian (M2) level, and
we regard this as being equal to a similar velocity
found more proximally. In such situation we calculate two index values, one proximal (M 1) and one
more distal (M2). However, finding one vasospastic
MCA branch could have less clinical consequence because of the potential for collaterals within the MCA
territory.

The Hemispheric Index

We have considered a VMCA/V ICA index of;?: 3.0 as


denoting angiographical MCA spasm, with values
;?: 6.0 indicating severe spasm [59]. The latter value
emerged through taking repeated angiography into
consideration: a slimming of the ICA (average about
7%) seemed to occur with increasing cerebral vasospasm, probably reflecting the vascular adaptation to
lower rates of flow. In patients in very poor condition,
precluding angiography, this slimming could be even
more pronounced. Although it may be difficult to

Clinical Implementation
Microsurgical Aneurysm Clipping

In patients with subarachnoid haemorrhage from


aneurysm rupture TCD blood velocity measurements
allow definition of location and severity of VSP in a
standardised way whenever needed. In our practice
we perform aneurysm clipping within 72 hours after
SAH in good-risk patients. Following operation VSP

67

Role ofTCD in Patients with SAH

remains a threat. An escalating VMCA/V1CA index then


underscores the need for intensified medical treatment.
If surgery is delayed for any reason, we determine the
timing of the operation individually with the aid of
TCD. Combining clinical data and blood velocity
measurements is of particular interest when the VMCA/
VrcA index is between 3 and 6. Serial observations are
performed because from day 3 the course and the
spread of vasospasm become important as well. We
routinely use nimodipine 2 mg/hr through a central
venous line, and agree with Seiler et al. [90] who operate upon alert patients admitted after 72 hours provided that no indication of severely escalating vasospasm appears over the preceding 12-24 hours.
During the second week, a stable index of about 5
on one side does not preclude operation if the technical
risk and the patient's clinical condition is acceptable.
Surgery is withheld if the hemispheric VMCA/VICA
index is above 6.0 unless the risk of a rebleed is considered to be extremely high and aneurysm surgery
appears to be technically straightforward. Precipitous
increases in the hemispheric VMCA/VICA index during
the first week may in our view overrule even a good
clinical grade. We operate on these patients when the
index recedes, indicating remission of VSP. Blood velocity measurements also reduce guesswork in deciding
whether or not a clinical deterioration is due to VSP.
We submit that repeated angiography for these purposes is not indicated unless, if the presence ofVSP in a
relevant vascular territory is confirmed, one is prepared to proceed with interventional therapy directed
at relieving VSP.
The role of TCD in routine clinical management
was addressed by Wardlaw et al. [101]. Twenty-nine
out of 189 consecutive SAH patients developed DID.
TCD performed by radiographers made an important
positive contribution to the diagnosis of DID in 72%
of the patients with this complication. This led to
altered management strategies in 42%. In 9% the
authors believed that the outcome might have been
better if the findings had been acted upon appropriately. No adverse effect on clinical management was
experienced. The correlation with angiographical
findings was described as being "generally accurate".
Having used TCD in the clinical routine for eight
years, Ekelund et al. [20] concluded that on an individual basis the lack of an absolute relationship
between DID and blood velocities complicates interpretation of the TCD findings and that clinical management must be based on a combination of parame-

ters, including, in selected cases, angiography and/or


CBF measurements. The incidence of DID causing
permanent morbidity and mortality had been 5-7%,
the same as before the introduction of TCD.
Endovascular Surgery Using Guglielmi Detachable
Coils (GDC)

Endovascular techniques using GDC's have


emerged as an alternative treatment for acutely ruptured aneurysm [33]. In our institution we currently use
GDC's in about one half of the patients with acutely
ruptured aneurysm. Treatment with GDC's has the
advantage of providing excellent protection against
further aneurysm rupture while avoiding brain retraction. Obviously, the blood clots from the aneurysm
rupture are not removed, and patients treated with
GDC's could therefore be more prone to VSP and
DID.
One recent study has addressed this question [69]. A
total of 69 patients in Hunt and Hess' Grades I to III
[39], the majority of whom had thick subarachnoid
clots, were followed up clinically with respect to
symptomatic VSP verified by TCD or angiography.
While the incidence of anatomical VSP was not reported, the incidence of symptomatic VSP was 16/69
(23%). The combined morbidity and mortality rate at
six months after SAH was 5.6%. In surgical series the
incidence of symptomatic VSP is between 22 and 32%
[34, 46]. Haematomas presenting as life-threatening
mass lesions require immediate surgery. It is therefore
possible that the surgical series included patients particularly prone to deterioration due to VSP. The TCD
technique is equally useful in the postoperative monitoring after GDC, and may contribute to clarify
whether or not surgical opening of the basal cisterns
prevents VSP and DID.
Conclusions

Performing TCD recordings after SAH has two


goals: to detect elevated blood velocities (VSP) and to
identify patients at risk for DID. The cause of DID is
however complex. Discrepancies between the occurrence of DID and absolute blood velocity levels have
been demonstrated (presuming that there really is a
crude blood velocity "ischemic threshold" - which
seems unlikely), particularly in patients with elevated
ICP levels. Further, the vessel showing the highest
blood velocity is not always the one perfusing the area
where ischemic symptoms seem to have their origin,

68

nor does the site of the greatest subarachnoid blood


clot relate precisely to VSP or to the ischemic brain
region. Moreover, it is conceivable that the complex
haemodynamic changes following SAH and the subsequent development ofVSP may be underestimated if
one only considers the crude blood velocities in the
basal cerebral arteries.
Several investigators have emphasised this point by
using CBF measurements combined with TCD to
assess both flow and velocity. [44, 53, 62, 85]. Despite
these findings and ignoring the basic principles of
cerebral haemodynamics; see Equations la-c above;
many authors continue to evaluate cerebral vasospasm
from the intracranial velocity measurement alone. The
addition of at least one careful measurement in the
extracranial ICA - using the same TCD equipment
and taking only a few short minutes to perform [23] allows a much more accurate assessment of the degree
and the effects of vasospasm.
Although the TCD technique was introduced about
15 years ago, its value in the management of SAH is
still debated. This may partly be because uncertainty
still exists about the best method to prevent and to
treat the enigmatic condition known as VSP. Observational studies are prone to bias, and a study where
patients are randomised to receive longitudinal followup using TCD or not may be considered as unacceptable by some clinicians, not least because the
overall outcome from a ruptured aneurysm depends
on a great many factors other than VSP. To obtain
hard evidence on this issue may therefore be difficult. It
thus appears sound to conclude that even with advanced investigational technology available, proper
selection, pre- peri- and postoperative care and timing
of surgery remain cornerstones in the management of
these patients,- equal in importance to their treatment
in the operating room [75] or in the interventional
neuroradiology suite.
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Correspondence: K.-F. Lindegaard, University of Oslo, Department of Neurosurgery, Rikshospitalet, The National Hospital, N0027 Oslo, Norway

Acta Neurochir (1999) [Suppl]72: 73-80


Springer-Verlag 1999

Neurointensive Care of Aneurysmal SAH


L. Persson and P. Enblad
Department of Neurosurgery, University Hospital, Uppsala, Sweden

Abstract
This paper briefly reviews some basic principles of neurosurgical
intensive care of patients with aneurysmal subarachnoid hemorrhage. The importance of early identification of secondary insults are
underlined. Special attention is paid to the newly introduced method
for neurochemical monitoring by means of intracerebral microdialysis. It is concluded that a well functioning neurointensive care
unit constitutes an important organisational frame for the detection,
prevention and treatment of secondary insults, after aneurysmal
subarachnoidal hemorrhage and that improved results can be expected by applying a modern neurointensive care strategy also for
patients with aneurysmal subarachnoid hemorrhage.
Keywords: Neurointensive care; subarachnoid hemorrhage; intracranial hypertension; intracerebral microdialysis.

Introduction

Neurointensive care (NIC) has emerged into a subspeciality of the clinical neurosciences and is an integrated part of neurosurgery, neurology and anaesthesia. NIC should be viewed upon as a general
concept, or an organizational frame for patient care,
rather than a specific mode of treatment. The scientific
rationale for NIC is that permanent brain damage
after a number of acute neurosurgical and neurological
disorders, to a greater or lesser extent, are caused by
secondary insults, which mainly are the result of disturbances of the intracranial dynamics (i.e. intracranial pressure, cerebral blood flow, cerebral metabolism) set in motion by the primary event. NIC is thus
devoted to the control of the intracranial dynamics
and emerged from research and clinical management
of traumatic brain injury (TBI). Registration of the
intracranial pressure (ICP) in clinical practice and the
use of artificial hyperventilation [14,15] were the basic
methods forming NIC. Clinical research on TBI also
formulated the concept of "secondary insults" and
most important was the observation that they to a

large extent are avoidable [22, 24]. It soon became


evident that many aspects of the intracranial dynamics
after TBI also could be applied to aneurysmal subarachnoid hemorrhage (aSAH).
NIC is perhaps more pertinent to the management
of an aSAH patient than in any other neurosurgical
patient, because in no other condition is a patient so
often admitted to neurosurgery in a good clinical condition, and nevertheless experiences a poor clinical
outcome from potentially avoidable complications.
NIC of aSAH is based on the idea that poor clinical
outcome is caused by the cumulative effect of all secondary ischemic insults sustained by the brain during
the acute phase of the disease, and that prevention of
these insults will have an impact on the overall clinical
outcome. Although rebleeding is a part of the natural
course of the disease, it should be considered as a potentially avoidable insult, because both the risk, and to
a certain extent the effect, of rebleeding can be influenced by therapeutic measures.
Evolution of NIC in SAH Patients

In his pioneer work on the pathology of SAH,


Crompton [3, 4] demonstrated that cerebral infarction
was the dominating cause of poor outcome. He described ischemic changes of varying degrees, from
scattered microscopic lesions to gross infarctions, and
showed that arterial hypotension during the acute
phase of the disease was associated with cerebral
infarction, thus identifying a potentially avoidable
secondary insult. Crompton also pointed out that the
amount of blood in the subarachnoid space, as well
as the degree of surgical trauma, also influenced the
propensity for the development of cerebral infarction.
The understanding of the significance of arterial vaso-

74

L. Persson and P. Enblad


Increased metabolism

Increased lep
Rebleeding
- ICH
-IVH
Hydrocephalus
Oedema
Seizures
Pyrexia

Decreased CBF

---+-

I. Increased lep

0Chaemi"'0 .....--1 .

1/

Hypoxaemia

Fig. 1. Complex interplay of insults responsible for secondary brain


damage in subarachnoid haemorrhage. The sudden increase in intracranial pressure (ICP) caused by the aneurysm rupture renders the
brain vulnerable to secondary insults. Secondary ischemic brain
damage is a result of insufficient cerebral blood flow (CBF) in relation to cerebral metabolism. Vasospasm, hypotension, and surgical
trauma may all decrease the CBF. The CBF may also decrease because of an increase in ICP, which in turn is caused by, for example,
rebleeding, intracerebral (ICH), and/or intraventricular haematoma
(IVH) and acute hydrocephalus. Cerebral metabolism is increased
by infections, pyrexia, and seizures and this will, under certain conditions, increase the ICP and thereby also decrease CBF. Furthermore, an ischemic lesion may become expansive and increase the
ICP resulting in a further decrease in CBF

spasm, in particular its delayed onset and its causative


relation to delayed ischemic deterioration and cerebral
infarction have also had a major impact on research
and management of aSAH, because the delayed onset
of the infarction process envisages a therapeutic
window.
The seminal studies of Nornes on aneurysm rupture
and ICP made important contributions to the NIC
management of aSAH and increased our knowledge
of the role of the intracranial dynamics and cerebral
ischemia in aSAH [17, 18]. Other studies on ICP,
cerebral blood flow (CBF) and cerebral metabolism
have confirmed the importance of disturbed intracranial dynamics and cerebral ischemia as the major
adverse consequences after aSAH. Experimental and
clinical research have increased our knowledge of
the pathophysiological and biochemical mechanisms
involved in cerebral ischemia after aSAH and it has
become evident that several other mechanisms than
vasospasm alone are involved in the development of
ischemia and brain damage [9, 12,26,28,29,30]. This
knowledge has further advanced NIC of this disorder.
Figure 1 summarizes the major factors involved in the
ischemic process.
SAH and Secondary Ischemic Insults
Aneurysm Rupture

Aneurysm rupture (or rebleeding) causes an instant


and dramatic increase in ICP, and at least in severe

aSAH, the ICP may reach the level of the mean arterial
blood pressure, thereby causing a brain circulatory
arrest and global cerebral ischemia [9, 17, 18]. About
15% of the aSAH population are thought to die instantly by this mechanism [13, 25]. In most cases
though, intracranial compensatory mechanisms, e.g.
CSF movement to the spinal canal allows the ICP to
decrease and the brain circulation to return. [16].
However, a global ischemic insult causing brain damage of varying degree appears to develop in most cases
and its severity is clinically reflected by the initial loss
of consciousness. Figure 2 shows two CT scans in a
patient with a severe aSAH, who survived the initial
bleed, but died a few days later as a direct consequence
of the rupture. Note the widespread cortical lesions
apparently caused by global ischemia. It has also been
hypothesized that this initial primary global insult
renders the brain susceptible to subsequent ischemic
insults. This means that the initial effects of the bleed
may increase the risk for cerebral infarction when
delayed arterial vasospasm and/or other secondary
insults emerge (Fig. 2) [12, 28, 29, 30].

Acute Hydrocephalus

The filling of the subarachnoid space with blood


may interfere with the CSF circulation/resorption and
acute hydrocephalus may follow. This is a major cause
of intracranial hypertension in the early post-rupture
phase. Today, this is best diagnosed on CT, but it is
important to note that even a slight ventricular dilatation is often associated with dramatically increased
ICP (Fig. 3).

Intracranial Hematoma

About 20% of the patients with aSAH have an expansive intracerebral hematoma (ICH) and sometimes
an aneurysm rupture also causes a subdural hematoma
(SDH). Both ICH and SDH may give raise to intracranial hypertension and global ischemia. Moreover,
an intracranial hematoma may produce focal cerebral
ischemia and it is a rather common observation that a
large infarction of the affected MCA territory follows
after a Sylvian hematoma from a ruptured ICA or
MCA aneurysm. One should also note that an expanding cerebral infarction also may lead to intracranial hypertension. Intraventricular hemorrhage,
which occurs in about 15% of aSAH patients [2], is

75

Neurointensive Care of Aneurysmal SAH

Fig. 2. CT-scans obtained immediately upon admission (upper row) and about 18 hours later (lower row) in a patient with severe aneurysmal
subarachnoid hemorrhage. Note the widespread cortical ischemic lesions on the second scan

another cause of increased ICP due to blockage of the


CSF pathways and subsequent acute hydrocephalus.
Seizures

About 20% of the aSAH patients are thought to develop seizures at the time of hemorrhage or soon after.
It is difficult to differentiate between true epilepsy and
other form of jerks, perhaps related to disturbed brain
stem function. However, epileptic seizures increase
CBF and cerebral blood volume and may cause intracranial hypertension, if compensatory mechanisms are
exhausted. Furthermore, seizures increase cerebral
metabolism and oxygen demand, and this mechanism
may also aggravate cerebral ischemia.

Delayed Arterial Vasospasm

The pathogenesis of delayed arterial vasospasm is


not fully understood, but arterial narrowing do reduce
cerebral perfusion. Vasospasm is clearly related to delayed ischemic deterioration and cerebral infarction,
but the exact relation is complex and the propensity for
infarction is apparently influenced by other factors,
e.g. other secondary insults (previous or ongoing).
Surgical Trauma

Although modem microsurgical techniques have


minimized inevitable surgical trauma, the use of retractors, temporary clips and manipulation of the ves-

76

Fig. 3. CT scans obtained immediately upon admission (left row) in


an awake patient with aneurysmal subarachnoid hemorrhage. Afew
hours later neurological deterioration to coma was noticed and a
second CT (right row) showed development of acute hydrocephalus

sels, may add to the overall ischemic impact sustained


by the brain. Surgical complications do occur and
obviously further add to the ischemic impact. We
have yet little knowledge of the impact of complications after endovascular aneurysm repair, but thrombembolism, and blockage of vessels by coils, as well as
"peroperative" aneurysm rupture are apparent risks
with this technique, and may all cause cerebral ischemia. Abundant use of anticoagulants in conjunction
with the intervention procedure may increase the risk
of intracranial hemorrhage, especially if an intracranial hematoma already is present [7].

L. Persson and P. Enblad

after aSAH, but it is well established that hypoxemia


aggravates cerebral ischemic states and therefore
should be considered as a secondary insult [5]. A major
cause of hypoxemia after aSAH is pneumonia caused
by aspiration, or as a consequence of prolonged artificial ventilation. Cardiac dysfunction and pulmonary
edema are other causes of hypoxemia in the aSAH
patient.
Pyrexia is probably an underestimated secondary
insult. Experimental research has pointed out that
even small increases in temperature aggravate cerebral
ischemia, and clinical studies on patients with ischemic
stroke or TBI have further confirmed the detrimental
effects of pyrexia [8). It is highly plausible that pyrexia
aggravates cerebral ischemia also in the aSAH patient.
Aseptic meningitis caused by subarachnoid blood, or
infections, such as meningitis, pneumonia and septicemia are common causes of pyrexia during NIC, and
may thus add to the overall ischemic impact of the
brain.
aSAH also affects the body fluids and electrolyte
balance. Hyponatremia is a common feature and may
cause tissue edema, also in the brain. Today, this is
generally not a major problem, because fluid and electrolytes are easily controlled during NIC. Increased
blood viscosity may reduce cerebral circulation and
thus contribute to cerebral ischemia. In experimental
studies severe hypoglycemia or hyperglycemia may
aggravate cerebral ischemia.
In conclusion, a number of secondary insults may
follow aSAH and aggravate the clinical condition. In a
recent pilot study of aSAH patients we found that secondary insults are indeed common and the number of
secondary insults independently predicted a poor clinical outcome [5].

Neuromonitoring
Systemic Insults

Already Crompton noticed that arterial hypotension in the acute phase after SAH was a risk factor
for cerebral infarction. There are extensive experimental and clinical evidence that hypotension aggravates cerebral ischemia. Hypovolemia is not an
uncommon finding in the aSAH patient and this
may increase the risk that sedative and narcotic drugs
elicit hypotension. Nimodipine has potent hypotensive
properties when given intravenously, and drastic hypotension may follow the institution of this therapy.
The role of hypoxemia has not been studied in detail

Delineating secondary insults as a major threat to


the aSAH patient has naturally focused the interest on
clinical monitoring of the intracranial dynamics and
vital systemic functions. The term - neuromonitoring refers to continuous or frequently repeated registration
of parameters that signals disturbances of the intracranial dynamics and impending cerebral ischemia.
The clinical situation in an individual patient is often
complex and no monitoring technique alone gives the
full picture. Thus, diagnostic information obtained by
various means must be interpreted and integrated
continuously for clinical decisions to be made. It is an

77

Neurointensive Care of Aneurysmal SAH

Fig. 4. Illustration of multimodality monitoring in the neurointensive care unit

axiom that monitoring is based on the understanding


of the role of the monitored parameter in the pathophysiological processes. The development of new
monitoring methods has therefore been closely linked
to research on the pathophysiological process leading
to cerebral infarction. Recent technical advances have
lead to the development of a number of new monitoring techniques. The term "multimodality neuromonitoring" has been coined to describe a clinical setting where a large number of parameters are registered
simultaneously (Fig. 4), and the obvious potential is
that it provides new possibilities for the identification
of impending cerebral ischemia.
There are a number of sophisticated methods available for surveillance of the brain, such as transcranial
doppler techniques for intermittent or continuous
monitoring of cerebral blood flow velocity and digital
computerized EEG-monitoring suitable for NIC. Recently, a method for continuous brain tissue P02
measurement has become available, as well as probes
allowing also brain tissue PC02 and PH to be continuously measured. Non-invasive "near infrared light
spectroscopy" may be used to continuously register the
oxygen saturation of circulating brain blood. The socalled laser doppler technique allows focal brain monitoring of the cortical microcirculation. Presently, the
major task for applied NIC research is to validate all
these new methods in terms of their ability to signal
impending ischemia and to define the indications for
their use.
However, close clinical surveillance of the neurological condition still remains the most important diagnostic measure. In this context, trained NIC nurses,
doing regular checks, which are noted in bed chart

Fig. 5. Schematic drawing of the microdialysis probe. Dialysis fluid


is pumped through the double lumen probe, where it passes the
dialysis membrane allowing substances from the extracellular fluid
to diffuse into the dialysis fluid

protocols, are still a mainstay of NIC. Continuous


registration of ICP is also a basic requirement because
intracranial hypertension is the most common secondary insult. The cerebral perfusion pressure should also
be calculated. Preferentially ICP should be monitored
via an intraventricular catheter because it allows
drainage of CSF. We use ventriculostomy essentially
in all obtunded or unconscious patients, as well as in
those who are awake with intense headaches in conjunction with dilated ventricles or large amounts of
subarachnoid blood on CT [2].
Neurochemical Monitoring

Recently, neurochemical monitoring by the use of


intracerebral microdialysis (MD) has been developed
and introduced to the NIC [19]. With this technique
bed-side monitoring of a number of neurochemical
substances can be performed in neurointensive care
patients, including those with aSAH [6, 19, 21, 27].
Briefly, MD is based on the passive diffusion of substances across a dialysis membrane built into a thin
probe which is inserted in the cortex in conjunction
with a ventricular catheter (Fig. 5). The probe is con-

78

L. Persson and P. Enblad

Table I. Some Biochemical Markers in Brain Interstitial Fluid


Energy metabolism

Excitotoxicity
Membrane degradation
Oxygen radicals

glucose
lactate/pyruvate ratio
lactate/glucose ratio
hypoxanthine
glutamate
aspartate
glycerol
hypoxanthine, xanthine
uric acid and its oxidation products
(e.g. allantoin)

Biochemical markers with potential value for clinical use in neurosurgical patients with intracerebral microdialysis. The left column
indicates the phenomena the markers are reflecting.

tinuously perfused with fluid passing the dialysis


membrane. Essentially all small molecules can be retrieved and their concentration in the dialysis fluid determined by HPLC. Bed-side equipment for clinical
use in the NIC has recently been developed and made
neurochemical monitoring feasible.
One may say that frequent chemical sampling of the
brain, at the bed-side, has brought NIC monitoring
from a "physiological level" to a "chemical level" , and
the term neurochemical monitoring has been used to
describe this development. A number of biochemical
mechanisms involved in the development of secondary
ischemic brain damage, such as lactic acidosis, excitotoxicity, and free radical reactions can be monitored by MD and yields information on the ischemic
process for management decisions and therapy. We
have used MD in severely affected aSAH patients for
up to 11 days after ictus and showed that the levels of
lactate, lactate/pyruvate ratio, glucose, hypoxanthine
and glutamate reflect impending or manifest secondary insults occurring during the clinical course, as well
as the clinical outcome [6, 21].
Table 1 gives a list of markers found to reliably
reflect secondary brain ischemia and infarction. We
believe that markers for energy metabolic disturbances
(glucose, lactate, pyruvate, hypoxanthine) and excitotoxicity (glutamate) can be regarded as validated
markers of energy failure and excitotoxicity, respectively, whereas substances such as glycerol, urea, xanthine, uric acid and allan to in need further validation.
MD is an invasive technique but the tissue injury
caused by probe implantation seems to be negligable
from a clinical point of view. Bleeding and infection
are possible adverse effects following implantation, but
according to the current experience they do not seem
to present a problem, although they need to be con-

sidered. However, a tissue reaction detected on the


biochemical level is elicited by implantation and this
may influence the measurements and the interpretation
of the data, and these are well described in experimental studies [1, 23]. There is less information from clinical studies on this issue, but the current knowledge
suggests that the implantation causes less pronounced
chemical reactions in the human brain [10, 19].
Imaging Techniques and NIC

A number of imaging techniques applicable to the


aSAH patients are also available and constitute an
important part of the brain surveillance. CT is a routine method, and serial CT scans give indirect but crucial information on the intracranial dynamics. More
sophisticated methods for CBF measurement are
available (bed-side Xenon-CBF, CT-Xenon, SPECT,
PET). PET also gives values on regional oxygen extraction, cerebral blood volume and cerebral metabolism. These methods are complicated and expensive
but may yield important information in selected patients. Serial use gives a good picture of the dynamics
of the pathophysiological process.
Registration of Systemic Vital Functions

Continuous registration of systemic parameters is


obviously important and arterial blood pressure, body
temperature, pulse-oximetry, and central venous pressure should be registered in most patients. Frequent
checks of arterial blood gases, especially in artificially
ventilated patients and newly extubated patients, are
also important. More sophisticated techniques used in
selected patients where hemodynamic control is essential, are jugular vein oximetry and pulmonary wedge
pressure measurements.

Discussion
NIC Treatment

Neuromonitoring and treatment are truly closely


linked because the main aim of treatment is to control
the intracranial dynamics and keep normal body
physiology. In this context it is important to keep in
mind that the brain of an affected aSAH patient is
extremely vulnerable to physiological aberrations. For
example, moderate arterial hypotension, hypoxemia
or pyrexia to levels that are tolerated by the normal

79

Neurointensive Care of Aneurysmal SAH

brain, may in selected cases aggravate cerebral ischemia and elicit infarction.
Increased ICP due to CSF resorption disturbance is
common and several studies have demonstrated clinical improvement after CSF drainage. An advantage of
CSF drainage appears to be that more patients become
amenable to surgery because the preoperative neurological condition may improve or deterioration is
avoided. CSF drainage of patients with untreated
aneurysm is somewhat controversial, because the risk
of rebleeding may be augmented by drainage. However, we found no association between more abundant
use of preoperative CSF drainage and rebleeding [2].
Expansive hematoma is an important cause of intracranial hypertension and swift evacuation is paramount. In some patients, ICP-registration is used to
define the surgical indication. In unconscious or severely obtunded patients, intubation and artificial
ventilation secure airway control and oxygenation.
There is no data available propagating regular hyperventilation and generally moderate hyperventilation or
normoventilation is used. In life-threatening intracranial hypertension, the use of hyperventilation,
mannitol, barbiturates, induced hypothermia, and
surgical decompression with removal of expansive
cerebral malacic tissue is warranted. Recently, hemicraniectomy has been proposed to counteract intracranial hypertension from large and expansive infarctions in the MCA-territory.
Treatment of vasospasm is a central part of NIC. It
is our general impression that vasospasm is less of a
problem today and there may be several explanations
for this. One is probably the use of nimodipine. Moreover, the NIC unit provides a better environment for
the overall care, especially in detecting and preventing
other secondary insults, such as increased ICP, hypotension, hypoxemia, pyrexia etc, which probably also
are involved in the development of delayed ischemic
deterioration. The NIC environment also enables safe
use ofhypervolemia-, hemodilution- and hypertension
therapies. Newer methods such as angioplasty and intraarterial papaverine infusions may in selected cases
also playa role in reducing the effects of vasospasm.
In conclusion, a well functioning NIC unit constitutes an organizational frame for the detection of
secondary insults and can mobilize the personal resources which is a prerequisite for successful treatment. During the last years new pharmacological
agents for neuroprotection against ischemic brain
damage have been developed and given hope that

medical therapy would become available for the aSAH


patient. Unfortunately, all tested neuroprotective
drugs have so far failed to show significant clinical
efficacy. This underlines that the main focus of aSAH
management must remain the detection and prevention of secondary ischemic insults.
Conclusion
Contemporary treatment has made aSAH a medical
emergency and patients are managed within NIC setting in increasing numbers. In a recent survey of 873
patients with aSAH treated in Uppsala during 12 years
1981-1992 we found that the introduction of the
described NIC concept was followed by a significant
reduction in mortality, despite the fact that older and
more affected patients were admitted during the later
part of the 12-year period. We also observed that the
number of patients who "talked and died" was significantly reduced. In 1981-82, 76% of the patients
who died within 6 months had talked on admission,
whereas in 1991-1992, this figure was 32%. The "talk
and die" concept originally used for TBI, can in our
opinion be applied also in aSAH and gives an overall
index of the impact of secondary insults, including rebleeding. Moreover, it provides an estimation of the
quality of the neurosurgical care and allows comparison of management results because it is largely independent of variations in patient populations [2].
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Acta Neurochir (1999) [Suppl]72: 81-88


Springer-Verlag 1999

Virtues and Drawbacks of Titanium Alloy Aneurysm Clips


H.-J. Steiger and J. J. L. van Loon
Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany

Keywords: Aneurysm clip; cerebral aneurysm; computed tomography; magnetic resonance imaging; titanium alloy.

There is little doubt that a small percentage of aneurysms is not adequately eliminated after surgery and
might rebleed sooner or later [6, 9, 11]. Routine postoperative digital subtraction angiography (DSA) is
certainly charged with a non-negligible rate of morbidity due to the fact that these exams have to be performed during the phase of vasospasm. Delaying DSA
until after vasospasm, which means for 3 to 4 weeks,
cannot be the answer since an incompletely clipped
aneurysm might already have re-ruptured within the
waiting period. Recent improvements of MRA and
CTA as well as the availability of titanium aneurysm
clips potentially render these methods non-invasive
alternatives to DSA for postoperative control [1, 3, 4,
10, 14, 15, 16, 17]. Therefore we introduced titanium
alloy aneurysm clips (Aesculap AG, Tuttlingen,
Germany) into clinical routine in 1995 [2, 5, 7, 8, 12,
13]. In the meantime over 300 patients have been
treated using titanium alloy clips. The purpose of the
actual report is to describe the CT and MR imaging
properties as studied initially and to review our clinical
expenence.

Introduction

Material Properties of Titanium Alloy Clips

CT and MRA artifacts after aneurysm surgery using


traditional cobalt alloy clips are detrimental to image
quality particularly within the vicinity of the aneurysm. Therefore these clips seriously interfere with the
interpretation of post-surgical changes at the surgical
site. Particularly identification of small lacunar infarctions is rendered virtually impossible. On the other
hand, there is an increasing demand for non-invasive
postoperative vascular imaging after aneurysm surgery, for example by means of magnetic resonance
angiography (MRA) or spiral CT angiography (CTA).

The titanium alloy used for the manufacturing of


aneurysm clips considered in this report is TiAI6V4.
Besides the principal titanium component, the alloy
contains aluminum (5.5-6.76% of weight) and vanadium (3.5-4.5%). Properties and minimum requirements are stipulated in standard ISO 5832-3.
The alloy TiAI6V4 is used for the manufacturing
of aneurysm clips since pure titanium has inferior
mechanical characteristics. Although pure titanium
would principally be sufficient for the manufacturing
of clips, the critical mechanical load capactiy of pure

Summary
This report describes the imaging characteristics of titanium alloy
aneurysm clips and our clinical experience with these clips in more
than 300 patients. Phantom and clinical investigations showed that
clip artifacts on CT and MR are minor as compared to the cobalt
alloy clips used previously. Spiral CT angiography (CTA) in combination with titanium alloy clips could be shown to be a feasible mode
of postoperative control and can be used to determine completeness
of aneurysm elimination, patency of adjacent arteries as well as vasospasm. In contrast, magnetic resonance angiography (MRA)
proved to be unfeasible as a method of postoperative vascular
imaging since the titanium clips still produce a shadow in the order of
size of the entire aneurysm. Therefore, completeness of aneurysm
elimination cannot be judged on magnetic resonance angiography.
The clinical experience in more than 300 cases showed that the titanium alloy clips essentially performed well. However, the limits of
elastic deformation appear to be somewhat inferior to cobalt alloy
clips. The standard appliers do not open the blades of the titanium
clips quite as far as with the comparable cobalt alloy clips and the
corresponding appliers. Therefore the titanium aneurysm clips are
not quite as well suited for large broad based aneurysms. Furthermore, the increased susceptibility of the new clips with regard to
abuse suggests to follow the recommendations of the manufacturer
not to recycle and re-sterilize clips that have been tried but not permanently implanted.

82
titanium would be reached. Since TiAI6V4, as far as
body compatibility, corrosion resistance and reaction
in the MR surrounding are concerned, is comparable
to pure titanium, the use of the alloy with the higher
mechanical characteristics appears preferable in order
to guarantee the required properties.
The alloy TiAI6V4 is a so-called a + ~ alloy, which
is used as basic material for the manufacturing of clips
in form of annealed, extended wire. The annealing
procedure is used to create a homogenous equiaxial
texture. Phase a shows a hexagonal crystal structure
with a grid distance of a = 0.2925 nm, and in the c-axis
a distance of 0.4670 nm which results in an axis ratio of
1.58. This axis ratio is markedly lower than that of
other hexagonal metals such as zinc and magnesium.
The cubical surface centred ~ phase has a grid constant
of approx. 0.3 nm.
According to ISO 5832-3, the material has to meet
the following characteristics:
The tensile strength has to be a minimum of 860
MPa.
The 0.2% extension stress has to be above 700 MPa.
The failure extension has to be a minimum of 8%.
The elastic modulus is in the range of 110 GPa.

CT Imaging Properties
In order to evaluate the streak artifacts on CT, titanium alloy mini clips and titanium alloy standard clips
were compared to the corresponding cobalt alloy clips.
The clips were mounted on a plastic phantom in such
a way that the clip blades were perpendicular to the
standard axial imaging plane. The material density
was compared at the level of the springs and at the
level of the blades (Fig. 1). The CT images using standard cranial window and level settings did not show
any streak artifacts with this strictly orthogonal clip
orientation, neither with titanium nor with cobalt alloy
clips. Therefore, even with cobalt alloy clips, streak
artifacts are only observed if the longitudinal axis of
the clips lies more or less within the imaging plane.
However, the contrast intensity of the titanium alloy
clips was substantially less prominent than the contrast
intensity of the cobalt alloy clips. The contrast intensity
of a standard titanium alloy clip grossly corresponds to
the contrast intensity of a cobalt alloy mini clip.
In order to assess the artifacts during practical use, a
number of patients with similar aneurysms and identical clip sizes, who had either been treated using titanium or cobalt alloy clips, were matched and po stop-

H.-J. Steiger and J. J. L. van Loon

Fig. I. Phantom CT imaging density study with standard and minititanium and cobalt alloy clips mounted perpendicular to the image
plane. Outer circle: optical image and clip designation. Inner circle:
corresponding CT image with the imaging plane through clip blades.
Titanium alloy clips are significantly less dense. Note: streak artifacts
are not noted with either alloy with this clip orientation

erative CT scans were compared (Fig. 2). With the clip


axis usually lying plus or minus within the axial imaging plane, streak artifacts were substantial with cobalt
alloy clips of mini and standard sizes, whereas titanium alloy clips created no streak artifacts neither in
standard nor mini sizes. Depending on the orientation
with regard to the clip axis, the tissue surrounding
cobalt alloy clips was not interpretable for a distance
of one to several centimeters. With titanium alloy clips
and hence no streak artifacts, the tissue in the immediate vicinity of the clips could constantly be analysed
in all directions.

Postoperative MRA and CTA


In order to compare pre- and postoperative MRA
and CTA with DSA, a prospective analysis was done
in 10 patients. All 3 studies were performed in these
patients prior to surgery and after surgical elimination
using titanium clips. MR angiography was performed
with a 1.5 Tesla Vison scanner (Siemens AG, Erlangen, Germany) using a 3D time-of-flight (TOF) technique and a 3D phase contrast (PC) technique. [18].
The spiral CT scans were performed with the Somatom plus 4 (Siemens AG, Erlangen, Germany).
After injection of 100 ml of non-ionic contrast agent

Virtues and Drawbacks of Titanium Alloy Aneurysm Clips

83

Fig. 2. Similar ruptured middle cerebral artery aneurysms (A, B) clipped with titanium or cobalt alloy mini clips. (C) Postoperative CT of A (2
titanium mini clips). (D) Postoperative CT ofB (1 cobalt mini clip). Note: streak artifacts occur only with cobalt alloy clips

84

H.-J. Steiger and J. J. L. van Loon

Fig. 3. Ruptured anterior communicating artery aneurysm as visualized with magnetic resonance (MRA) and spiral CT angiography (CTA)
prior to surgery and after clipping with a titanium alloy mini clip. (A) Preoperative MRA. (B) Preoperative CTA. (C) Postoperative MRA.
Note: clip shadow obscuring the area of interest. (D) Postoperative CTA showing aneurysm elimination and vasospasm in the right A2 segment

(Ultravist 300, Schering, Berlin, Germany) at a rate of


4,5 mIls in a peripheral vein, an axial CT scan focused
on the region of the aneurysm or clip was performed
with a delay of 14 seconds after starting the injection.
The resulting data were processed for three dimensional (3D) reconstructions. The postoperative CTA
and MRA images were compared to DSA with respect
to occlusion of the aneurysm sac, presence of residual
neck, patency of parent vessels and other major arteries, presence of vasospasm, and presence of clip

artifacts. The CTA proved to be sufficient for postoperative determination of all these parameters (Figs.
3-5). In contrast, the titanium alloy clips resulted in a
shadow on the MRA images extinguishing at least the
area of the aneurysm neck and sometimes the entire
aneurysm (Fig. 3). From these results it was concluded
that at the present stage CTA is a viable alternative to
DSA for postoperative control in patients treated with
titanium alloy aneurysm clips while these clips do not
allow adequate vascular imaging by MRA.

Virtues and Drawbacks of Titanium Alloy Aneurysm Clips

85

Fig. 4. CT A of small ruptured basilar bifurcation aneurysm and postoperative CTA control. (A, B) 3-D surface reconstructions of aneurysm.
(C, D) Two different projections of the postoperative control after clipping with titanium alloy mini clip

Experience with Titanium Alloy Clips During Clinical


Routine

As mentioned, titanium alloy clips were introduced


into clinical routine in 1995 after a period of evaluation and comparison with cobalt alloy clips. In the
meantime more than 300 patients have been treated
with these new clips (Fig. 6). The advantages consist
exclusively of the improved postoperative imaging
qualities as outlined above. Although CT A can be
used for postoperative vascular imaging, we reserve
this modality for complex situations with known or
suspected imperfect aneurysm elimination requiring
follow-up exams. The respective routine experience
has confirmed the practical usefulness of CT A as suggested by the initial study.

As far as the intraoperative handling of the titanium


appliers and clips is concerned as well as the intraoperative performance of the clips, a few interesting
observations have been made:
1. One has to get used to the much lighter titanium
appliers. In the beginning, the new appliers feel
somewhat unhandy as compared to the old ones.
With the early series mini clips, a few instances were
encountered where the aneurysm neck was not
completely occluded although the blades crossed
the entire aneurysm neck. All these cases were
thin walled small aneurysms and it appears that the
clip blades might have been somewhat divergent.
As mentioned, these problems occurred only with
clips supplied in 1994 and 1995.

86

H.-I. Steiger and I. I . L. van Loon

Fig. 5. Giant unruptured carotid bifurcation aneurysm. (A) Preoperative DSA. (B) Preoperative contrast CT. (C, D) Postoperative contrast
CT demonstrating aneurysm elimination (titanium standard clip)

2. The titanium alloy clips do not seem to be well


suited for very large aneuryms with a broad neck
since the clip blades do not open quite as far as the
corresponding cobalt alloy clips. This difference is
a concession to the slightly reduced mechanical robustness of the titanium alloy. There is little doubt
that the titanium alloy is more prone to non-elastic
deformation than cobalt alloys. We have also seen
that the temporary clips are much easier destroyed
by abuse than the old cobalt alloy clips. Another
disadvantage of the titanium alloy aneurysm clips

was the initial lack of special configurations, e.g.


there were no fenestrated clips available during
the early years after introduction. Meanwhile,
however, complex and fenestrated shapes are also
manufactured.
So far we have not seen any failure of implanted
titanium clips in the sense of slipping or breaking or
insufficient closing force. However, due to the increased vulnerability of the titanium clips it appears to
be mandatory that the recommendations of the man-

87

Virtues and Drawbacks of Titanium Alloy Aneurysm Clips

Fig. 6. Example of practical use of titanium alloy clips in a case of multiple aneurysms. (A) Vertebral DSA showing small ruptured aneurysm
at the right P I/P2 junction (arrow). (B) Right carotid DSA showing incidental middle cerebral artery aneurysm (arrow) and incidental small
carotid artery aneurysm (arrowhead). (C) Dissected neck of the ruptured right PI / P2 aneurysm through transsylvian approach and (D) application of titanium mini clip. (E) Complex right middle cerebral artery trifurcation aneurysm and (F) combined treatment by polytetrafluorethylene ( PTFE) wrap and titanium mini clip. (G) Small carotid aneurysm clipped with titanium mini clip. (H) Postoperative CT showing two
clips on this slice

88

H.-J. Steiger and J. J. L. van Loon: Virtues and Drawbacks of Titanium Alloy Aneurysm Clips

ufacturer to use only clips from the original packaging


are respected and not to recycle and resterilize clips
that have been unpacked but not permanently implanted. In our operating rooms we have only temporary clips on the table, and the required permanent
clips are only selected and unpacked after dissection of
the aneurysm.
Conclusions and Open Issues

The CT and MR imaging properties of titanium


alloy clips are much superior compared to cobalt
alloys. These results are not suprising taking into
account the experience with other titanium implants.
Our results have shown that non-invasive vascular
imaging using spriral CT angiography can be used
for non-invasive postoperative control. In contrast,
MRA does not allow appropriate imaging of the area
of interest even with titanium alloy clips.
Whether a routine postoperative spiral CT angiogram should be performed or not is a matter of debate.
Our experience with the routine application of titanium alloy clips has been positive so far. Although we
have not performed mechanical stress tests, we have
the impression that the titanium material is less resistent to abuse than cobalt alloys. The results of
mechanical stress tests on pure titanium clips have
been reported by Lawton and coworkers [8]. These
authors did not report any indications of material
fatigue during use with the normal envelopes. At the
moment it appears wise to respect the manufacturer's
recommendations and not to recycle these clips.
Therefore the introduction of titanium alloy clips
might add some costs due to the clips that have to be
discarded.
Acknowledgements
The authors are indebted to Mrs. I. Anders for preparation of the
manuscript and to Mr. Ch. Barth for the illustrations.

References
I. Dorsch NWC, Young N, Kingston RJ, Compton JS (1995)
Early experience with spiral CT in the diagnosis of intracranial
aneurysms. Neurosurgery 36: 230-238
2. Fisher RS, Ehsan T, Smith K, Lawton MT, Bichard WD,
Spetzler RF (1996) Titanium aneurysm clips, part II. Seizure
and electroencephalographic studies in implanted rabbits. Neurosurgery 38: 1165-1169

3. Harbaugh RE, Schlusselberg DS, Jeffery R, Hayden S, Cromwell LD, Pluta D, English RA (1995) Three-dimensional computed tomographic angiography in the preoperative evaluation
of cerebrovascular lesions. Neurosurgery 36: 320-327
4. Huston III J, Rufenacht DA, Ehmann RL, Wiebers DO (1991)
Intracranial aneurysms and vascular malformations: comparison of time-of-flight and phase contrast MR angiography. Radiology 181: 721-730
5. Kato Y, Sano H, Katada K, Ogura Y, Ninomiya T, Okuma I,
Kanno T (1996) Effects of new titanium cerebral aneurysm clips
on MRI and CT images. Minim Invasive Neurosurg 39: 82-85
6. Kassell NF, Torner JC, Haley EC Jr (1990) The international
cooperative study on the timing of aneurysm surgery, part I:
overall management results. J Neurosurg 73: 18-36
7. Lawton MT, Ho JC, Bichard WD, Coons SW, Zabramski JM,
Spetzler RF (1996) Titanium aneurysm clips, part I: mechanical,
radiological, and biocompatibility testing. Neurosurgery 38:
1158-1164
8. Lawton MT, Heiserman JE, Prendergast VC, Zabramski JM,
Spetzler RF (1996) Titanium aneurysm clips, part III: clinical
application in 16 patients with subarachnoid hemorrhage. Neurosurgery 38: 1170-1175
9. Macdonald RL, Wallace MC, Kestle JRW (1993) Role of
angiography following aneurysm surgery. J Neurosurg 79: 826832
10. Marchal G, Bosmans H, Van Fraeyenhoven L, Wilms G, Van
Hecke P, Plets C, Baert AL (1990) Intracranial vascular lesions:
optimization and clinical evaluation of three-dimensional timeof-flight MR angiography. Radiology 175: 443-448
11. Mayberg MR, Batjer HH, Dacey R, Diringer M, Haley EC,
Heros RC, Sternau LL, Torner J, Adams HP, Feinberg W,
Thies W (1994) Guidelines for the management of aneurysmal
subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the stroke council,
American Heart Association. Circulation 90: 2592-2505
12. Payner TD, Tew JM Jr, Steiger HJ (1995) Aneurysm clips. In:
Wilkins RH, Rengachary SS (eds) Neurosurgery, 2nd edn.
McGraw Hill, New York, pp 2271-2276
13. Piepgras A, Guckel F, Weik T, Schmiedeck P (1995) Titanium
aneurysm clips and their advantages in diagnostic imaging.
Radiologe 35: 830-833
14. Ross JS, Masaryk TJ, Modic MT (1990) Intracranial aneurysms: evaluation by MR angiography. AJNR Am J Neuroradiol II: 449-456
15. Schmid UD, Steiger HJ, Huber P (1987) Accuracy of high resolution computed tomography in direct diagnosis of cerebral
aneurysms. Neuroradiology 29: 152-159
16. Schwartz RB, Tice HM, Hooten SM, Hsu L, Stieg PE (1994)
Evaluation of cerebral aneurysms with helical CT: correlation
with conventional angiography and MR angiography. Radiology 192: 717-722
17. Tampieri D, Leblanc R, Oleszek J, Pokrupa R, Melan90n D
(1995) Three-dimensional computed tomographic angiography
of cerebral aneurysms. Neurosurgery 36: 749-755
18. van Loon JJL, Yousry TA, Fink U, Seelos KC, Reulen HJ,
Steiger HJ (1997) Postoperative spiral computed tomography
and magnetic resonance angiography after aneurysm clipping
with titanium clips. Neurosurgery 41: 851-857
Correspondence: H.-J. Steiger, M.D., Klinikum Gro13hadern,
Neurochirurgische Klinik und Poliklinik, Marchioninistr. 15, D81377 Munich, Germany.

Acta Neurochir (1999) [Suppl]72: 89-97


Springer-Verlag 1999

A Combined Transorbital-Transclinoid and Transsylvian Approach to


Carotid-Ophthalmic Aneurysms Without Retraction of the Brain
V. V. Dolenc
University Medical Centre, Department of Neurosurgery, Ljubljana, Slovenia

Summary
A series of 138 patients with 143 carotid-ophthalmic aneurysms
(COAs) have been treated by direct surgical approach over the past
15 years. In 5 cases the COAs were bilateral and in 15 cases either
one or more aneurysms were associated with a COA. Of the 143
COAs, 87 were small, 41 large and 15 were giant. Seventy-four
COAs bled, while 69 were diagnosed either incidentally or else manifested themselves through neurological deficits resulting from compression of the adjacent structures by the aneurysms. Visual deficits
were diagnosed in all the patients with large/giant COAs and in 27
patients with small COAs.
Of the whole series of patients operated on for COAs, 2 died after
surgery. Two patients had endocrinological deficits, 2 had hemiparesis, 36 had the same visual deficits as prior to surgery, whereas in
47 patients the visual function improved. Of all the 138 patients, 96
remained without neurological deficits, and the 36 patients with the
same visual deficits as preoperatively also showed no neurological
deficits after surgery and hence they were able to resume their previous way of life. Vasospasm did not occur in patients with COA(s)
only, but was observed in 6 out of 15 patients with multiple aneurysms where subarachnoid hemorrhage (SAH) had occurred due to a
rupture of an aneurysm other than the COA.
There has been a major change in the surgical approach to COAs,
from the classical pterional intradural approach to the transorbitaltransclinoid and transsylvian approach which is described in this report. The latter approach provides ample space for proximal and
distal control of the internal carotid artery (ICA) and makes it possible to deal with demanding large/giant COAs safely. In the series
presented, there was no case of premature rupture of the aneurysm.
Moreover, since we started using the described approach to COAs,
retraction of the brain has not been necessary, regardless of the size
of the aneurysm.
Keywords: Internal carotid artery; ophthalmic artery; aneurysm;
carotid-ophthalmic aneurysm.

Introduction
Drake described COAs as a specific subgroup of intracranial intradural ICA aneurysms as early as 1968
[13]. However, controversy still exists regarding the

precise definition, the clinical symptoms and the


treatment of these demanding vascular lesions. Most
authors describe COAs as aneurysms located on the
intrathecal segment of the ICA, on its supero-medial
wall, distal to the ophthalmic artery and proximal to
the posterior communicating artery (PComA) [S, 8,
10, 13, 14, 20, 2S, 39, 43, 46, 49, SO]. A subgroup of
COAs originating from the intrathecal infero-medial
wall of the ICA was termed "paraclinoid aneurysms"
[16,34,49], "carotid cave aneurysms of the ICA" [24].
According to some authors, COAs are all aneurysms
originating in the supero-medial wall of the ICA between the ophthalmic artery proximally and the bifurcation of the ICA distally [22, 2S]. In another report,
COAs were described as "aneurysms of the ophthalmic segment" [7]. As to the percentage of COAs
among intracranial aneurysms, different authors give
significantly different data, i.e. ranging from 1.S%
to 8% of all intracranial aneurysms [13, 20, 2S, 29].
Nevertheles, the authors mostly agree that this group
of aneurysms is significant because of their clinical presentation and because of the difficulties encountered in
their surgical management. In cases of rupture and
SAH, COAs manifest themselves like other aneurysms; however, the percentage of unruptured COAs
causing neurological deficits is much higher than in
any other group of intrathecal aneurysms. In cases of
unruptured COAs, the location, the projection, and,
above all, the size of the aneurysm are responsible for
the neurological symptoms and signs.
The attitude toward the treatment of COAs has
changed considerably since Drake's original report on
direct surgery for such aneurysms [13]. Due to technical difficulties in the direct surgical approach to these

90

V. V. Dolenc

Table I. Presentation of COAs and Results After Surgical Treatment


Size and presentation of COA

Small (87)

rupture (60)
incidental (27)
finding

Large (41)

rupture (10)
mass effect (31)

Giant (15)

rupture (4)

mass effect (II)


Total

143

Clipping

Aneurysm
resection and
reconstruction
of the ICA

60
27

Patency of ICA
in follow-up
angiography

New neurological
deficits

22

29

same as
preoperatively

hemiparesis 1
died I
endocrinological
disorders I
hemiparesis 1
endocrinological
disorders I
died I

better than
preoperatively

II
14

20

II

60
27

Visual function

121

22

137

36

47

aneurysms, some authors advocated indirect treatment, i.e. ligation of the common carotid artery [25,
43, 46], while others favoured a direct approach with
complete exclusion of the lesion [1,5, 7, 10,20,22,25,
38, 44, 49, 51]. The development of endovascular
interventional procedures, where the aneurysm is occluded with balloon(s) and/or coils, has challenged the
direct surgical approach [21, 28]. On the other hand,
the surgical approach was made even safer by combining it with the Dallas technique where temporary
occlusion of the ICA is obtained with a balloon proximal to the COA, thus ensuring an easier and safer exclusion of the aneurysm and reconstruction of the ICA
wall [3, 42]. This combined endovascular/surgical
method probably represents the optimum approach as
it enables complete exclusion of the lesion and immediate cure.
Clinical Presentation of COAs and the Diagnostic
Work-up

COAs are presented according to their size, symptoms and signs in Table I. Like other intracranial
aneurysms, COAs mostly manifest themselves with
SAH. When the aneurysm is large, it can produce local
signs i.e. slowly progressive visual deficits due to the
compression of the optic nerve (ON), the optic chiasm
and the optic tract. The extent of visual deterioration (visual field deficits) depends on the size and
location of the aneurysm. Sub-optochiasmatic (Figs.
I b, c) and global sub-optochiasmatic aneurysms
(Fig. Ie) affect the visual apparatus much more than

supra-optochiasmatic aneurysms (Fig. Id). Large/


giant sub-opto-chiasmatic aneurysms and global
sub-opto-chiasmatic aneurysms also compress the pituitary stalk, the hypothalamus, and even the upper
brainstem. In addition to visual deficits patients with
such large/giant COAs may also have endocrinological deficits or, as in cases of compression of the
upper brainstem, symptoms due to compression of the
pyramidal tracts.
Giant supra-optochiasmatic aneurysms projecting
posteriorly and compressing the brain tissue may,
although rarely, cause epileptic seizures. In cases
of partially thrombosed large/giant COAs (Fig. 2),
aneurysm-to-artery embolism may occur, causing
transitory ischemic attacks (TIA) or even stroke.
Another rare situation is encountered in cases of
large, bilateral COAs projecting medially causing
endocrinological deficits due to compression of the
pituitary body. A considerable number of COAs,
however, are discovered incidentally during aCT,
MRI, or angiography done for various other diagnostic purposes, like SAH from another aneurysm, intracranial tumors, or trauma.
The diagnostic work-up in small, ruptured COAs is
the same as for any other ruptured intracranial aneurysm. The initial evaluation of a large/giant COA
should carefully assess the degree of impairment of
visual function, and document symptoms and signs
due to compression of the hypothalamus and/or the
pituitary stalk, and should therefore include endocrinological studies. Pre-operative ophthalmological
assessment of the visual status is important in all cases

Ophth. A.
ON

Vz

Ophth. A.

III'IVV,
ON
ICA(AL)

- DR

- PCP

PCP

III

- III

ON

Vz
III IVV,
- PR

Ophth. A.
ON .

ICA(AL)

V2
IIIIVY,
PR
- ICA(AL)

- DR

DR

- PCP

PCP

' III

III

c
Ophth. A.

- PR
ICA(AL)

- DR

Ophth. A.

..-_ IIIIYV,

d
V2

Opnth. A.,

- IIIIVV,
- PR

V2
IIIIVV,

ON

PR

~.~~~!--- - ICA(AL)

- ICA(AL)
- DR

DR

- PCP
' III

Fig. 1. Types of COAs. (a) A small COA, located at the branching of the ICA and the ophthalmic artery, is in most cases inferolateral to the
ON. The initial position of the small COA and the direction of its further growing dictate the type of the COA. (b) A suboptochiasmatic COA,
projecting medially and inferiorly, remains located over the diaphragm sellae and underneath the ICA. This type of COA is known also as
carotid cave aneurysm. (c) A suboptochiasmatic COA projecting inferiorly and posteriorly may reach the hypothalamus and upper brainstem,
thus causing corresponding endocrinological visual, and long tract symptoms and signs. (d) Supraoptochiasmatic COA, projecting posteromedially overlays the visual apparatus and ACA I and compresses the brain when it is large and/or giant. (e) Global COA (suboptochiasmatic) usually displaces the visual apparatus medially and upward by stretching the ipsilateral ON and the optic tract around its sac.
The ACAI also may be stretched and looping around the sac of the aneurysm. The PComA and the anterior choroidal artery may be firmly
adherent to the lateral wall of the aneurysm and nerve III might be stretched and displaced laterally. (f) A suboptochiasmatic COA is clipped
with fenestrated rect-angular Sugita clip. The dural ring is cut circumferentially around the ICA. The ophthalmic artery is visualized. The peripheral part of the aneurysm is resected and excluded and the pressure against the visual apparatus and pituitary stalk is not existing anymore.
Due to the circumferential cut ofthe dural ring and the dissection ofthe AL ofthe ICA from the lateral wall of the sphenoid sinus, the coursing
of the ICA from extradural to intradural space is preserved normal.
In Figs. a- f the completed epidural approach is presented: the orbit is unroofed on the anteroposterior aspect of the sphenoid wing, the
sphenoid wing and the ACP are resected and so are the superior, lateral and inferior walls (the optic strut) of the optic canal. The anteromedial
triangle is wide opened. The dural layer of the lateral wall of the CS is peeled from its anterior part of the lateral wall of the CS so that nerves III,
IV, VI, V2 are visualized. The CS has not been opened. The dura along the Sylvian fissure is cut and the Sylvian fissure is split in its entirety
along the MCA. The bifurcation of the ICA into the ACAI and the MCA, the anterior choroidal artery, the PComA, nerve III, the ON and
different aneurysm(s) are visualized in Figs la through Ie

92

V. V. Dolenc

Fig. 2. A left carotid angiogram, AP view (a) and lateral view (b), demonstrates a giant COA with a large thrombus in it. The large mass of the
lesion caused epileptic seizures whereas aneurysm-to-artery embolisms caused several TIAs and a moderate stroke. Cross-flow studies revealed
significant displacement of the ACAI in the supero-posterior direction and borderline filling of the ipsilateral MCA (c). The postoperative
angiogram, AP view, demonstrates that the ICA after resection of the giant COA and reconstruction of the artery is occluded, but the ipsilateral
ACAI and the MCA are in a good position and are much better filled (d) from the contralateral side than preoperatively (c). The most probable
reason for the postoperatve occlusion of the ICA was that the inner diameter of the ICA was too small since the wall of the aneurysm at its neck
was very thick

where a direct surgical approach is planned, in order to


preclude optic damage during surgery.
The angiographic evaluation of patients with large/
giant CO As should include cross-studies and a balloon
occlusion test. It is also important to obtain information on the size and course of the superficial temporal artery which may be needed for an extracranialintracranial (EC-IC) by-pass. An by-pass is primarily

used in cases where exclusion of the COA cannot


be achieved without compromising the patency of the
ICA, when reconstruction of the ICA is impossible and
cross-circulation has been found inadequate.
Since the combined transorbital-transclinoid and
transsylvian approach to COAs involves complete
epidural removal of the anterior clinoid process
(ACP), good quality preoperative CT or MRI is criti-

93

Carotid-Ophthalmic Aneurysms

cal for identifying possible pneumatization of the ACP


and/or the walls of the optic canal [10, 11]. CT/MRI
also provide valuable information about the size and
variations of the ACP, which is important in cases
of large supra-optochiasmatic aneurysms projecting
anteriorly, thus overlying the ACP and the optic canal
from the intrathecal side.
In cases of multiple aneurysms one of which is a
COA - either small or large - it should be determined
which aneurysm has bled. If this cannot be ascertained, it is wise to plan a surgical procedure so that
both (all) aneurysms are excluded during the same
operation.
Relevant Surgical Anatomy and the Definition of the
COA

The distal segment of the extradural ICA, representing the anterior loop (AL) of the ICA, is situated
infero-medial to the ACP and supero-lateral to the
lateral wall of the sphenoid sinus. After the of the
ACP, the AL of the ICA is exposed from the proximal
ring (PR) to the distal ring (DR) in the antero-medial
triangle [11]. The AL of the ICA is covered with a
dural sheath which makes the PR and distally the DR
around the ICA. The ICA then courses through the
DR into the intradural space where it gives off the
ophthalmic artery on its supero-medial side, underneath the ON. In the majority of cases the ophthalmic
artery originates approximately 1-2 mm distal to
the DR. The ophthalmic artery courses upward and
anteriorly, under the ON, into the optic canal. The
Dawson arteries originate on the inferomedial side of
the wall of the intrathecal ICA. They provide vascularization of the visual apparatus and the pituitary stalk
[6]. The PComA, and more distally the anterior choroidal artery, originates from the lateral side of the
ICA.
According to the definition, COAs are aneurysms of
the intrathecal ICA, arising from the segment between
the ophthalmic artery and the PComA. This definition,
however, only holds if the aneurysm is small (Fig. 1a).
In cases where it is a large aneurysm, the segment of
the ICA involved in the orifice of the aneurysm may
extend either more proximally, i.e. into the extradural
space, or more distally, i.e. beyond the origin of the
PComA, or in both directions. In cases where a large
part of the circumference of the I CA is involved in the
orifice of the aneurysm, the lesion fills most of the
suprasellar space and is classified as a global COA [25].

In large/giant COAs, and particularly in global COAs,


the ophthalmic artery usually arises from the aneurysm wall, since most of the circumference of the ICA is
involved in the orifice of such an aneurysm (Fig. Ie).
As the name "carotid-ophthalmic aneurysm" implies,
the majority of these aneurysms originate in the ICA
wall close to the origin or at the origin of the ophthalmic artery, i.e. on the supero-medial aspect of the ICA.
Some of the aneurysms - particularly when they are
small- have no connection with the ophthalmic artery,
because they are located more medially or even inferomedially on the ICA circumference, i.e.at the point of
origin of the Dawson arteries [6]. Small COAs are
usually located inferolateral to the ON. When the
aneurysms become larger, they project either under or
above the ON (Figs. Ib-1e). The COAs are subdivided into supra-optochiasmatic, projecting either
anteriorly or posteriorly, and sub-optochiasmatic
aneurysms, projecting toward the pituitary stalk and
posteriorly toward the optic tract and/or the hypothalamus.
In rare cases the aneurysm arises from the ICA at
the point where the ophthalmic artery ought to originate. The ophthalmic artery is then either missing or
arises from the intracavernous portion of the ICA. It is
possible, though very uncommon, that the COA originates on the lateral side of the ICA, at the level of the
ophthalmic artery, and projects into the ACP.
Surgical Technique

The surgical approach to COAs, as described initially [10] and re-described later [11], proved - in cases
of large and giant COAs - a rather demanding procedure and was not generally accepted; it was even classified as hazardous [31]. Additional laboratory studies
led to the transorbital, transclinoid and transsylvian
approach to COAs which was published 10 years after
the initial report [12].
The patient and the patient's head is positioned as
in cavernous sinus (CS) surgery. The other initial surgical steps, including the type of skin incision and osteomuscular flap used, as well as the unroofing of
the orbit and the resection of the sphenoid wing, also
follow established guidelines for CS surgery and are
published elsewhere [12]. After the resection of the
medial portion of the sphenoid wing and the roof of
the orbit on the posterior aspect of the superior orbital
fissure (SOF), the dural tent covering the neural structures coursing through the SOF from the CS to the

94

orbit, is dissected free on the antero-medial and posterior side. The dural duplicature is then cut, and a
cleavage line located so that the outer layer of the
lateral wall of the CS is peeled off cranial nerves III,
IV, and VI, and from the inner layer of the lateral wall.
This maneuver provides good access to the the inferolateral aspect of the ACP. Drilling of the ACP starts on
its infero-Iateral side and proceeds in posteromedial
direction. It is performed with a diamond drill and is
carried out in short bursts. After each drilling period
the walls of the hollowed ACP is checked. Continuous
irrigation of the tip of the drill is necessary in order to
avoid over-heating of the drill as this puts cranial
nerves II, III and IV in danger. Hollowing the ACP by
short periods of drilling thus also minimizes the possibility of mechanical injury to the ON, ICA, nerves III
and IV and the aneurysm itself. The optic strut should
be removed in the same manner, care being taken not
to open the sphenoid sinus which may result in a CSF
fistula. The optic canal should be opened on the lateral
and superior aspects. After the removal of the optic
strut the optic canal is also opened on its inferior
aspect and the ICA is exposed along ~ of its lateral
circumference. Additional dissection of the ICA at the
level of the AL from the bone on its medial side (i.e.
from the wall of the sphenoid sinus on medial side of
the artery) will enable placement of a temporary
proximal clip on the AL of the ICA in cases of rupture
of the aneurysm or in cases of difficult dissection and/
or resection of the aneurysm and reconstruction of the
ICA wall.
After the removal of the ACP, exposure of the ON
on the superior, lateral and inferior aspects and dissection of the AL of the ICA from the wall of the
sphenoid sinus, the dura is opened along the Sylvian
fissure. Retraction of the frontal or temporal lobes is
not allowed since it may cause premature rupture of a
large/giant COA. The Sylvian fissure is split from its
periphery along the entire length of the MCA so that
the ICA bifurcation is fully visualized. The next step is
dissection of the anterior choroidal artery, cranial
nerve III and the PComA. The DR is cut circumferentially around the ICA first when of the AL and
the intrathecal ICA proximal to the anterior choroidal
artery has been visualized. Venous blood oozing from
the intercavernous sinuses on the inferomedial side of
the ICA can be stopped by packing the intercavernous
sinuses with Surgicel. By holding the dura propria with
a stitch in the anteromedial direction and lifting the
ON the surgeon will be able to see the ophthalmic

V. V. Dolenc

artery and its relation to the aneurysm as well as the


relation of the aneurysm to the entire visual apparatus
and the pituitary stalk. In cases of large/giant COAs,
large partially thrombosed COAs, and/or a sclerotic
ICA wall it is wise to put temporary clips on the ICA
at the level of the AL proximally and proximal to
the anterior choroidal artery intradurally. This enables
complete exclusion of the aneurysm without rupture
during dissection, prevents dislodgement of emboli
from clots in the aneurysm and counteracts laceration
of the ICA wall itself. Mobilization of the ON and
ICA (its extra- and intra-dural segments) allows good
access to the COA originating from the medial side of
the ICA, regardless of the size and projection of the
aneurysm. The ophthalmic artery can be preserved in
all cases, unless it arises from the COA itself. After a
circumferential incision of the DR it is difficult to close
the dura in a watertight manner. It is therefore advisable to put a piece of muscle around the ICA which at
the same time will protect the ON and keep the clip
away from the ON. The dura is then sutured and additionally reinforced with two-component fibrin glue
from the epidural side.

Results
The postoperative results of the whole series of
COAs treated by the direct surgical approach are presented in Table 1. One hundred and twenty-one COAs
were clipped, whereas 22 COAs were treated by resection of the aneurysm and reconstruction the ICA wall
with sutures. Postoperative angiography was performed in all the patients except in two cases, who died
after surgery. In 137 cases postoperative angiography
showed patency of the ICA. In 4 cases the ICA was
occluded after surgery. In these 4 cases the COAs were
partially thrombosed and were resected, the thrombotic material being evacuated from the aneurysms
and the ICA wall being reconstructed with sutures. In
none of these 4 cases were neurological deficits or endocrinological disturbances present postoperatively.
The ipsilateral ICA after surgical exclusion of the
COA was patent in 2 patients with postoperative contralateral hemiparesis and in 2 patients with postoperative endocrinological disturbances. In 36 cases, visual
function remained unchanged after surgery, whereas
in 47 cases visual function improved. The overall results of the whole series were considered to be excellent
in 96 patients, very good in 36 patients, and good in
4 patients.

Carotid-Ophthalmic Aneurysms

Discussion
Anatomical studies of the parasellar area [9,11, 15,
18,26,27,33,35-37,40,41,45,47,51] have brought
new knowledge and stimulated further research of
normal anatomy and pathological conditions in the
region. Despite the benefits of such studies, controversy still remains regarding the definition and treatment of CO As [1, 2, 4,5,7,10,13,16,20,22-25,29,
34,38,39,43,48-51]. There is general agreement that
aneurysms of this kind originate in the medial half of
the wall of the intrathecal ICA. Controversy thus,
centres on the segment of the ICA from which COAs
emerge, the shortest being the segment of the ICA
between the ophthalmic artery proximally and the
PComA distally and the longest being the segment
from the ophthalmic artery proximally to the bifurcation of the ICA into the MCA and the ACA distally [7,
10, 13, 14, 16, 20, 22-27, 34, 43, 46, 49-51]. In the
available literature we were not able to find reports of
COAs located proximal to the origin of the ophthalmic
artery, i.e. on the segment of the intrathecal ICA from
the DR proximally to the origin of the ophthalmic artery distally. On the other hand, several authors claim
that COAs may extend beyond the intradural space
into the extradural space, i.e. proximal to the DR. The
description of COAs as being supraclinoid or paraclinoid [16,34,49] or terming them "carotid cave ICA
aneurysms" [24] does not offer any clarification of the
anatomical relationship of the aneurysms in this area.
It is generally accepted that the DR around the ICA
represents the site where the ICA pierces the dura and
enters the intradural space, and that the DR provides
the best anatomical landmark on the ICA, at the same
time representing the most proximal point of the intrathecal ICA, and for this reason it should be included
at least in the description if not in the definition of
COAs.
The DR forms a border between the two major
portions of the intracranial ICA, i.e. the extra- and
intra-dural segments [11]. It is very important to realize that the great majority of COAs are located intradurally and only exceptionally extends into the extradural space. In such cases the DR runs around the
aneurysm which is located in both the intradural and
the epidural compartments. In such instances it is also
very likely that the ophthalmic artery arises from the
aneurysm and not from the ICA. The preoperative
study of the exact size and location of the aneurysm
and of the point of origin of the ophthalmic artery

95

provides very important information of the proximal


extension of the aneurysm. In our experience, the ACP
does not have much relevance in clarifying the intradural and/ or extradural location of the aneurysm. The
ACP varies significantly, it may be dense or pneumatized, bulky, excessively long or short. Preoperatively
it must be established whether there is any indentation
in the ipsilateral ACP, i.e. any signs of long-standing
compression and hence erosion of the bone. This information is important when planning the resection of
the ACP, the optic strut and the walls of the optic
canal in order to avoid injury to adjacent structures. In
cases where the ACP is eroded, the extradural part of
the surgical approach requires utmost caution. The
only safe approach for resection of the ACP is from the
inferolateral side, as described here. This also enables
safe resection of the walls of the optic canal and the
optic strut without any retraction of the dura.
From the neurosurgical point of view, it is generally
accepted that COAs should be treated surgically, not
only in cases of rupture and SAH, but also in cases of
visual deficits related to a COA. However, the direct
surgical approach to a COA is not just "another operation for another aneurysm" but a completely different
procedure from that for an aneurysm on the ICA distal
to the PComA. Most COAs can be appropriately dealt
with only when the bony structures have been appropriately removed from the epidural side and the Sylvian fissure completely opened. This provides a
broader access to the ICA proximal and distal to the
COA, and thereby proximal and distal control, and
protects the neighbouring neural and vascular structures from surgical injury.
In cases of bilateral COAs it is possible - after resection of the larger COA on one side - to reach and
clip a small contralateral COA. It is not, however,
possible to resect the aneurysm and reconstruct the
ICA with sutures on the contralateral side. In the author's opinion, a contralateral approach to a single
COA [17, 30, 32] does not represent a safe approach.
In our experience, intradural partial removal of the
ACP is risky and does not provide the same space as
epidural ACP extirpation combined with resection of
the optic strut and wide opening of the optic canal. It is
most important that the optic canal is opened from the
proximal, lateral and inferior side because in this way
it becomes possible to perform safe dissection of the
aneurysm away from the ON after cutting the DR circumferentially. Complete dissection of the ICA at the
level of the DR, along with the opening of the optic

96

canal and opening of the dura propria, permits good


proximal control over the ICA as well as good mobility of the ICA, which is of paramount importance for
placing a clip on the neck of the aneurysm parallel to
the longitudinal axis of the ICA, and for reconstructing the wall of the ICA with sutures after resection of
the aneurysmal sac [11, 12]. After dissection of the AL
and complete resection of the DR, it is in most cases
not necessary to explore the ICA in the petrous bone
[19] or in the neck. Proximal control of the I CA in the
petrous bone or in the neck should be used only in
COAs extending through the DR into the epidural
space.
Less than 2% mortality and very low morbidity in
the direct surgical approach to COAs leave little place
for indirect treatment techniques such as common
carotid artery ligation [25, 43, 46]. Despite controversy
regarding the management of incidentally found large/
giant aneurysms which, as is well-known, cause visual
impairment and even endocrinological disturbances,
we believe that direct surgical treatment should be
considered as the first choice treatment.
Balloon occlusion or coiling of a large/giant broadnecked COA is by no means a good alternative to surgical treatment. With the endovascular technique it is
difficult to preserve the patency of the ICA in cases of
broad-necked COAs, and even where this is possible,
the mass of the aneurysm persists and may even grow.
Further, thrombotic material may be dislodged from
the aneurysm and cause repeated embolisms in the
distal arterial tree.
Endovascular proximal control of the ICA with a
balloon is very helpful during aneurysm surgery, especially in cases where the neck and the sac of the
aneurysm are either very weak or sclerotic [31]. The
Dallas procedure - aspiration of blood proximal to a
temporary clip across the ICA and distal to an inflated
endovascular balloon - removes blood from the
aneurysm [3]. If there is a blood clot or a thrombus in
the aneurysm, it is mandatory to combine a distal
temporary clip with either external or intravascular
proximal control since it is necessary to open the
aneurysm in order to remove the blood clot or an old
thrombus, and to wash out the adjacent proximal and
distal segments of the ICA with saline solution. Following this a permanent clip can be placed or the wall
of the ICA can be reconstructed with sutures. Only by
obtaining proximal and distal control over the ICA
before any handling of a partially thrombosed aneurysm will aneurysm-to-artery embolisms be prevented.

V. V. Dolenc

In cases of large/giant sub-optochiasmatic COAs adherent to the chiasm, pituitary stalk, optic truct and/or
the hypothalamus, the sac of the aneurysm should not
be peeled off the surrounding structures since this may
cause damage to the previously compressed structures.
These aneurysms should therefore be transsected and
emptied berfore the neck is clipped or the ICA wall
reconstructed with sutures, whereas the fundus firmly
attached to surrounding structures should be left in
place.
Once extremely demanding to be dealt with by the
direct surgical approach, COAs are - if the approach
described above is used - nowadays quite an easy task
for a surgeon who is familiar with the anatomy of the
central skull base and who is ready to spend more time
in carrying out the approach than in dissecting the
aneurysm itself. With this approach it is possible to
safely exclude the COA and at the same time both
preserve the patency of the ICA and avoid damage
to surrounding structures, thereby conserving the remaining function of the visual apparatus, and provide
the conditions for its improvement. When one uses this
approach as is described, any postoperative worsening
of the visual acuity should be avoided.
Contemporary treatment of COAs reflects the
microsurgical skills and also testifies interventional
neuroradiology, offering a good opportunity for
co-operation, not only in discussion, but in actual
performance.
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Correspondence: V. V. Dolenc, University Medical Centre,
Department of Neurosurgery, Ljubljana, Slovenia.

Acta Neurochir (1999) [Suppl]72: 99-106


Springer-Verlag 1999

Extradural Approach to Intracavernous leA Aneurysms


V. V. Dolenc
University Medical Centre, Department of Neurosurgery, Ljubljana, Slovenia

Summary
A series of 115 intracavernous internal carotid artery (lCA)
aneurysms have been treated by a direct surgical approach during
the past 15 years. Sixty-eight aneurysms were small. Of these 11 were
traumatic; nine caused by severe head injury and 2 by ICA injury
during transsphenoidal surgery. Twenty-six aneurysms were large
and 21 were giant.
Thirty-eight aneurysms were clipped, 46 were treated by resection
followed by ICA wall reconstruction with interrupted sutures, 16 by
excision and proximal/distal ICA end-to-end anastomosis and 15 by
resection/grafting. Postoperative angiography was performed in 107
cases and the ICA was found to be patent in 100 of these. Three patients died after surgery, two (with traumatic aneurysms) from associated brain injury and 1 from pulmonary embolism. Oculomotor
palsy was present in the immediate postoperative period in 104 patients. However, six months after surgery only 7 patients had residual
palsy.
The direct surgical approach to intracavernous ICA aneurysms
has constantly been changed and improved. The approach in its
original version [6] was mainly intradural, whereas its contemporary
version in most cases is extradural [10, II]. The latter approach provides complete exposure of the entire parasellar region, good proximal control of the ICA [13], and good access to the cavernous sinus
through the individual "corridors" between the cranial nerves [7]. In
the author's opinion the direct surgical approach provides better results than endovascular treatment with regard to patency of the ICA

[11].
Keywords: Aneurysm; cavernous sinus; internal carotid artery;
surgical technique.

Introduction
Surgical treatment of vascular lesions in the cavernous sinus (CS) has until recently been controversial. A
direct surgical approach to the CS was considered
hazardous notably because of lack of knowledge about
the topography of the region, the risk of venous
and arterial bleeding, and the inherent danger of the
approach. Even though some preliminary descriptions
of the region were available already in the 1940's [2,
27], more detailed anatomic studies have only emerged
during the last 30 years [6-11,19-22,28-31]. Follow-

ing the revolutionary surgical procedures performed


by Parkinson [19-21] and further anatomic studies [7,
30, 31], the neurosurgical attitude to vascular pathology in the CS changed dramatically.
As intracavernous internal carotid artery (lCA)
aneurysms are rarely life-threatening and surgical
treatment was possible only with the use of extracorporeal circulation, the introduction of endovascular procedures [24] brought the surgical approach to
a temporary halt. It did, however, also stimulate neurosurgeons worldwide to improve the treatment of
these lesions, and the advent of a new direct approach
to the CS [6] brought treatment of intracavernous
aneurysms back into the surgical domain. The exclusively extradural approach to the CS is the only logical
approach as the CS is an extradural space; moreover,
the dura when preserved intact over the temporal lobe
provides natural protection to the brain. The new
principles for CS surgery provide a safe extradural
approach to the CS as well as good proximal and distal
control of the ICA [6, 7, 10, 11]. Extracorporeal circulation with cardiac arrest and hypothermia [19-22] is
therefore not necessary.
The choice between surgical or endovascular treatment of vascular intracavernous lesions is interesting
and controversial, and has generated an extensive literature [1,3-12,14-17,22,23,25,26,29-32]. Due to
a better understanding of the anatomy of the parasellar region, intra-arterial and intra-aneurysmal morphology, and the condition of the ICA and the aneurysmal wall, it has become evident that neither surgical
nor endovascular treatment alone can be the ultimate
answer in all cases. Hence, good planning and team
work are important during the diagnostic investigations in order to achieve the best outcome for the
patients.

100

V. V. Dolenc

Table I. Size and Presentation of lntracavernous leA Aneurysms


Aneurysm
size

Number

Aneurysm presentation
incidental

rupture

/.

paresis of
nerves III,
IV, VI

0/7
2/9
1/15
3/31

2/1
2/1

20
26
21
67

impaired
nerveV function
Small
Large
Giant
Total

68
26
21
115

27

9+2 3

/
/

/
/

27

14

The aim in treating aneurysms is complete exclusion


of the aneurysm from the circulation with preservation
of parent artery patency. In cases where this cannot be
achieved by the endovascular technique, surgery is required. In the direct surgical approach the aneurysm is
resected and the wall of the ICA reconstructed in one
of three ways: local, direct, or complete [9].
In the past it was generally accepted that small intracavernous aneurysms did not require treatment.
They may, however, rupture and cause a high-flow
carotico-cavernous fistula (CCF) or a large false
aneurysm. It may therefore be wise to treat them.
Large/giant aneurysms must be treated in order to remove the mass, prevent possible catastrophic rupture
through the wall of the CS into the intradural space
[14], and preclude aneurysm-to-artery embolism. The
latter is likely to occur in partially thrombosed large/
giant aneurysms. In cases of traumatic (false) aneurysms projecting into the sphenoid sinus, surgical reconstruction of the artery wall is urgently required to
prevent fatal epistaxis [7, 18].
Presentation of Intracavernous Aneurysms

The data about the size and the clinical presentation


of intracavernous ICA aneurysms are summarized in
Table 1. There were no mycotic aneurysms in this series.
There were 68 small intracavernous ICA aneurysms.
Eleven of these were traumatic in origin. Of the 11
traumatic aneurysms, 9 arised due to severe head injury. Massive epistaxis occurred in 7 of these 9 aneurysms and ipsilateral blindness in 5. Two traumatic
aneurysms resulted from surgical injury during a
transsphenoidal approach to a pituitary tumor. Of the
68 small aneurysms, 3 had ruptured, causing acute
ophthalmoplegia and large false aneurysms. In 7 patients small intracavernous ICA aneurysms caused

stroke

4/2

irritation of the trigeminal nerve (VI and/or V2).


Aneurysm-to-artery embolism from partially thrombosed aneurysms caused transient ischaemic attacks
(TIA) in 2 and a minor stroke in 1 patient. In 20 patients small aneurysms caused palsy of one or more
cranial nerves (III, IV, VI).
Large/giant aneurysms were seen in 47 cases.
Among these, 24 experienced sensory disturbances in
the ipsilateral face and 3 had trigeminal pain as the
presenting symptom. All patients with large/giant
aneurysms had a paresis of one or more of the cranial
nerves III, IV and VI. In 2 patients with a partially
thrombosed large/giant aneurysm a TIA occurred due
to an aneurysm-to-artery embolism and in 1 patient a
minor stroke occurred from the same cause.
Exophthalmos was present in 2 patients with large
aneurysms caused by the rupture of a small intracavernous aneurysms. Both patients experienced sudden retroorbital pain associated with proptosis. Visual
deterioration (without exophthalmos or sensory deficits) was the presenting symptom in 3 patients. This
was caused by erosion of osseous structures and compression of the optic nerve (Fig. 1).
Preoperative Diagnostic Investigations

Four-vessel angiography is mandatory in all patients with intracavernous ICA aneurysms in order to
identify incidental aneurysm. During the angiography
cross-flow via the anterior and posterior communicating arteries is investigated, a balloon occlusion test is
performed and venous out-flow studied. Apart from
the angiography, computed tomography (CT) and/or
magnetic resonance imaging (MRI) are also necessary
to demonstrate extension of the sphenoid sinus into the
anterior clinoid process (ACP), the presence of thrombus in the aneurysm or calcification of the wall of the

101

lntracavemous ICA Aneurysms

l .c

:t9n,~

Tnl ni.TC'

-OO~ . ' I~ AD I 0

d
'-J

lJ - (

Fig. I . Preoperative left carotid angiogram showing a large intracavemous ICA aneurysm - the antero-posterior view (a) and the lateral view
(b). The situation after resection of the aneurysm and reconstruction of the ICA with separate sutures in the anteroposterior view (c) and the
lateral view (d). The patient was right-handed and did not tolerate the balloon occlusion test. Endovascular exclusion of the aneurysm was attempted in three different centres and was not feasible due to the very broad neck of the aneurysm. The preoperative visual defect from the left
optic nerve completely disappeared during the first postoperative week. The postoperative paresis of nerves III and IV was also of short duration and one month after the operation the patient no longer had diplopia

aneurysm or the ICA. Only by carefully studying the


CT, MRI and angiographic images is it possible to get
the necessary information about the position, size,
contents and wall of aneurysm, as well as the status of
the ICA proximal and distal to the aneurysm. On the
basis of these data, occlusion of the aneurysm and reconstruction of the ICA can be planned in advance
and any necessary preparations can be made before
starting to operate on the aneurysm.

Relevant Surgical Anatomy and Types of


Intracavernous ICA Aneurysms

The length of the ICA from its point of entry into


the petrous bone to the distal dural ring (DR) where it
enters the intradural space, is approximately 6 cm. It
has two segments, each 3 cm in length; the proximal
(petrous) segment, which is covered with bone, and the
distal (CS) segment, which is bone free. In its course

102

through the skull base the ICA makes 4 loops [7]: the
posterior (PL), lateral (LL), medial (ML) and anterior
loops (AL). There are well defined anatomical points
which are of great importance for describing the configuration and the course of the ICA. The PL of the
ICA is located in the petrous bone and represents the
first tum of the ICA at the skull base, where its course
changes from vertical to a horizontal course towards
the foramen lacerum. From the LL, overlying the
foramen lacerum, the ICA passes in a supero-medial
direction towards the lateral aspect of the posterior
clinoid process (PCP). In its intracavernous part, on
the lateral aspect of the PCP, the ICA forms the ML
and courses anteriorly towards the ACP, where it
forms the AL which is situated on the inferomedial
side of the ACP. At the DR the ICA pierces the dura
and enters the intradural space.
True aneurysms are only found on the intracavernous segment, where the ML gives off two
branches: the meningohypophyseal and the inferolateral trunk. True aneurysms are not found in the
petrous segment since it is covered by bone. A false
aneurysm may, however, arise in the bone-covered
segments of the ICA. This is usually caused by a
fracture of the lateral wall of the sphenoid sinus that
lacerates the artery wall, most commonly of the AL.
The resulting false aneurysm projects into the sphenoid
sinus. Mycotic aneurysms are found on any segment of
the ICA.
The location, size and nature of an intracavernous
aneurysm dictate the extent of displacement and
stretching of cranial nerves III-VI. The corridors
between the individual nerves, i.e. the anteromedial,
paramedian and Parkinson's triangles [7], are very
important because different segments of the ICA, as
well as the aneurysm, are accessible through these triangular entry points. The distal part of the PL of the
intrapetrous ICA is covered with bone in about 80% of
cases, but it is easily accessible to the surgeon and after
being exposed it enables proximal control of the ICA
and/ or reconstruction of the artery by grafting.
Surgical Technique
The skin incision starts in front of the tragus and
continues close to the ear in an upward direction and
in a semicircular fashion. It ends 2-3 cm beyond the
midline and behind the hairline. The skin flap is reflected anteriorly until the orbital rim is exposed. The
temporal muscle is cut in the direction of the muscle

V. V. Dolenc

fibers in its posterior part. Burr holes are placed in


the parietal bone, the posterior part of the squama of
the temporal bone, and in the frontal bone close to the
coronal suture. The craniotomy is performed along the
squama of the temporal bone, the inferolateral and
anterior parts of the parietal bone and through anterior part of the frontal bone to the pterion. The bone
flap, together with the temporal muscle, is lifted as a
single flap, reflected dorsolaterally, and fixed with fish
hooks. Additional trimming of the squama of the
temporal bone toward the base of the middle fossa is
necessary in order to provide a better viewing angle
and a more direct access to the CS.
The foramen spinosum and the middle meningeal
artery, the foramen ovale and V3, and the foramen
rotundum and V2 are visualized. After the dura has
been peeled off the intracranial side of the orbital roof
and the periorbital fascia from the intraorbital side, the
orbit is unroofed as far as the lateral end of the superior orbital fissure (SOF). Unroofing of the orbit along
the posterior side of the SOF should only be performed
after exposure of the ICA in the petrous bone. When
the ICA is exposed and prepared for temporary clipping, bone removal is continued over the orbit. Care
should be taken not to exert any pressure against the
lateral wall of the CS. The orbital roof is then completely removed on the side of the SOF towards the
foramen rutundum. The duplication of the dura at the
lateral end of the SOF is then cut and the dural layer of
the lateral wall of the CS gently peeled off the inner
layer, the cranial nerves (III, IV, VI and V2) and the
aneurysm. In this way the inferolateral aspect of the
sphenoid wing and the ACP are visualized. The sphenoid wing, the ACP and the superior, lateral and inferior walls of the optic canal are resected. After complete resection of the ACP and the optic strut, the AL
of the ICA is well visualized in the anteromedial triangle and can be dissected from the lateral wall of the
sphenoid sinus and prepared for distal temporary
clipping. Additional intradural exposure of the ICA is
necessary only in cases where the AL is involved in the
aneurysm and therefore not available for temporary
clipping. The remaining outer dural layer of the lateral
wall of the CS can at this point be safely dissected from
the bulging inner layer and from the nerves over the
dome of the aneurysm. The Gasserian ganglion (GG)
is encountered on the posterior side of the lateral wall
of the CS. Although the GG is located posterior to the
CS, it should nevertheless be completely visualized by
peeling the dural layer away from it. In most cases VI

103

Intracavemous leA Aneurysms

and V2 are stretched over the aneurysm, whereas V3


and the GG are displaced in a posterior direction. If
the aneurysm is small and located on the horizontal
segment of the intracavernous ICA, the paramedian
and Parkinson's triangles are opened and cranial nerve
III dissected from the aneurysm and retracted medially, whereas cranial nerves IV and VI following
dissection from the aneurysm are retracted laterally. If,
however, the aneurysm is located on the lateral side of
the ML, cranial nerve IV should be dissected from VI
and retracted medially, in the direction of cranial nerve
III, thereby enabling exploration of the proximal part
of the ML and dissection of the aneurysm from cranial
nerve VI. Small aneurysms without thrombus may be
excluded with a simple clip. If the aneurysm contains a
thrombus, however, both proximal and distal temporary clipping is necessary so that the aneurysm can be
opened and the thrombus removed. The ICA wall is
then reconstructed by clipping or by suturing, or by a
combination of both.
A large/giant aneurysm with a relatively small neck
is excluded in the same way as a small aneurysm, i.e.
by clipping the neck and/or resecting the aneurysm
and suturing the wall of the ICA. In broad-necked
large/giant aneurysms, with or without thrombus,
proximal and distal temporary clipping is mandatory.
If local reconstruction of the ICA is not feasible, the
part of the ICA containing the aneurysms may be excised. Following additional dissection along the proximal stump with mobilization of the LL and the distal
stump with mobilization of the AL, the two loops are
straightened, and the proximal and distal stumps approximated and anastomosed (end-to-end suture).
In cases of fusiform intracavernous ICA aneurysms
it is necessary to perform grafting from the petrous
part of the ICA to the clinoidal part, i.e. the AL. If the
AL also is affected, the distal end of the graft is anastomosed to the intrathecal ICA distal to the ophthalmic artery. In such cases the ophthalmic artery is sacrificed. In fusiform large/giant aneurysms the graft
(either saphenous vein or radial artery) should be harvested prior to surgery. lflocal or direct reconstruction
of the ICA after resection of the aneurysm is not possible, the arm or leg should be prepared in advance in
order to obtain a graft. In such cases the graft is taken
only when direct (end-to end) reconstruction of the
ICA fails. At the end of the reconstruction of the ICA,
the patency of the ICA should be checked intraoperatively by a Doppler probe. To shorten the distance between the proximal and the distal stump of the

Table 2. Size of the lntracavernous ICA Aneurysms, Type of Aneurysm Exclusion. Postoperative Patency of the ICA and Outcome
Size and
Type of aneurysm exclusion leA
number of
patent
aneurysms leA reconstruction
clipping local direct graft

Small 68
Large 26
Giant 21
Total 115

32
4
2
38

30
10
6
46

6
4
6
16

8
7
15

Postop. nerve( s)
III, IV, VI
deficits after
one
week

59
63/63
24
20/24
21
17/20
100/107 104

6
months
2
2
3
7

ICA, the stumps should be placed lateral to cranial


nerves III-VI. The same principle applies when grafting is performed.
Any venous bleeding that occurs after resection of
the aneurysm is stopped by packing the intercavernous
sinuses with Surgicel. As an additional precautionary
measure to prevent postoperative bleeding, the entire
parasellar space is filled with fibrin glue.
Results
The results of surgical treatment of intracavernous
ICA aneurysms are summarized in Table 2. Of 115
intracavernous ICA aneurysms only 38 were clipped.
In 46 cases resection of the aneurysm was performed
and the artery wall was reconstructed with interrupted
sutures. End-to-end anastomosis after resection of the
aneurysm was used in 16 cases and aneurysm resection
combined with grafting in 15. Postoperative angiography was carried out in 107 patients. The ICA was
patent in 100 and occluded in 7. Immediate postoperative palsy of the oculomotor nerve(s) was present in
104 patients, but resolved within six months after surgery in all except 7 cases. In all patients with preoperative trigeminal pain the pain gradually disappeared
after surgery. Diminished sensory function in the distribution of the trigeminal nerve present before surgery, did not cause any postoperative discomfort; on
the contrary, in most cases the sensory function of
the trigeminal nerve improved after resection of the
aneurysm. Four patients had persistent, although
slight, residual contralateral hemiparesis. No patient
developed postoperative epilepsy. Three patients died,
2 of them (with traumatic aneurysms) from associated
brain injury and 1 from pulmonary embolism. The
final outcome was considered to be excellent in 101
patients. Seven patients with persistent paresis of cra-

Fig. 2. (a) MRI (coronal cut) showing a right CS lesion. (b) MRA showing right CS aneurysm. (c) Right carotid angiogram showing a large
intracavernous ICA aneurysm - preoperative anteroposterior view. (d) The lateral view ofthe right carotid angiogram shows the broad-necked
intracavernous ICA aneurysm originating from the horizontal segment ofthe intracavernous ICA. (e) Postoperative right carotid angiogramanteroposterior view. (f) Postoperative carotid angiogram, lateral view, showing narrowing of the intracavernous ICA. The arterial tree ofthe
right ICA is well visualized, hence the flow through the intracavernous ICA stenotic segment is sufficient (one month after surgery the patient
was symptom free - not even sUbjective diplopia)

105

Intracavernous ICA Aneurysms

nial nerve(s) III, IV, VI and diplopia were more


symptomatic than 4 patients having slight contralateral hemiparesis.
Discussion

The majority of small, intracavernous ICA aneurysms do not rupture, and may remain unchanged and
asymptomatic for many years. They rarely cause intrathecal hematoma or subarachnoid haemorrhage
(SAH) (14). If they rupture, they cause a CCF or, very
occasionally, a large false aneurysm which usually fills
the whole intracavernous space. Such CCFs and large
false intracavernous ICA aneurysms require an active
therapeutic approach. Small, incidentally found intracavernous ICA aneurysms should therefore be taken
seriously and - if possible - treated either by an endovascular or a direct surgical approach in a center where
sufficient experience has been accumulated from a
large number of comparable cases.
Traumatic (false) aneurysms, regardless of size, necessitate urgent treatment. Since false aneurysms are
located along the AL of the ICA and reconstruction of
the artery wall is necessary, surgical treatment is the
first choice. This applies especially to cases where endovascular treatment cannot preserve the patency of
the ICA and occlude the neck ofa false aneurysm (e.g.
in large false aneurysms projecting into the cavity of
the sphenoid sinus), the wall of the ICA should be
surgically reconstructed with separate sutures and/or
with a Sundt-Kees cuff clip. If the patient's medical
condition does not permit a direct surgical approach,
and provided the patient tolerates ICA occlusion, endovascular treatment should be considered.
As large/giant intracavernous ICA aneurysms
mostly manifest themselves with symptoms and signs
due to compression of the adjacent cranial nerves, it is
clear that a direct surgical approach is indicated to
remove the aneurysm mass. In elderly patients and
in those with medical problems the direct surgical
approach may not be appropriate and therefore endovascular treatment - either alone or in combination
with extracranial - intracranial (EC-IC) by-pass - is
the treatment of choice.
Even in patients that tolerate the balloon occlusion
test, occlusion of the ICA is not considered the treatment of choice, since postoperative neurological deficits may develop even if the patient has passed the test.
Such patients can, however, tolerate reconstruction of
the ICA after excision of the aneurysm, and hence re-

construction of the artery is strongly advisable because


it ensures the patency of the ICA. On the other hand, it
is essential to preserve the patency of the ICA in patients who do not tolerate the balloon occlusion test
and do not have an adequate collateral circulation.
Thus, a direct surgical approach is the ultimate answer
in cases where the aneurysm cannot be excluded with
preserved ICA patency by endovascular techniques.
In all surgically treated patients it is imperative to
preserve the superficial temporal artery for an EC-IC
by-pass in case the reconstruction. of the ICA in the CS
is impossible. In cases where grafting of the ICA is
necessary, and the ICA proximal and distal to the
intracavernous aneurysm is severely diseased, it is
advisable to first perform the EC-IC by-pass before
ICA grafting is started.
Mycotic intracavernous ICA aneurysms represent a
special entity among the intracavernous aneurysms
[12]. Opinions about the most appropriate treatment
are even more diverse than for other intracavernous
aneurysms. Some authors suggest treatment with antibiotics initially, since some of these aneurysms occlude
spontaneously, others favor ICA ligation combined
with EC-IC by-pass.
Based on experience gained both with the direct
surgical and with endovascular treatment of intracavernous aneurysms, it is evident that both techniques should be considered in each individual case. The
author regards these two techniques as complementary, and they may indeed be used in combination to
treat an individual patient. The future management
of these difficult aneurysms must lie in a combined
multidisciplinary approach.

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Correspondence: V. Dolenc, University Medical Centre, Department of Neurosurgery, Ljubljana, Slovenia.

Acta Neurochir (1999) [Suppl]72: 107-121


Springer-Verlag 1999

Surgical Treatment of Anterior Circulation Aneurysms


I. A. Langmoen 1 , K. Ekseth 1 , E. Hauglie-Hanssen 2 , and H. Nornes 2
1

Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden


Department of Neurosurgery, National Hospital, Oslo, Norway

Summary
The purpose of this paper is to present the results, assessed by
an independent observer, of surgical treatment of 428 consecutive
patients harbouring aneurysms of the anterior circulation, together
with a review of relevant anatomy and operative strategy.
At follow-up (mean 5.6 years) 89.3% lived at home and were independent, 5.1% lived at home but needed some kind of assistance,
2.0% lived in institution, whereas information was unavailable in
3.6% ofliving patients. Two hundred and fifty-three patients (64.5%)
had unchanged employment status, 0.3% worked in sheltered environment, whereas 30.9% went out of work due to their subarachnoid
hemorrhage (SAH). Information about employment status was unavailable in 4.3%. For aneurysms of the internal carotid, anterior
communicating and middle cerebral artery, respectively, mortality
was 3.2, 3.9 and 5.6%, whereas 92.0, 88.1 and 89.0% of surviving
patients lived at home and were independent and 67.0, 63.6 and
63.0% had unchanged employment status.
Three-months mortality of all causes was 4.2%. In the postoperative period 53 (12.4%) patients developed clinical signs of vasospasms, 6 (1.4%) had cardiac infarction, 4 (0.9%) lung oedema, 4
(0.9%) deep vein thrombosis, and 7 patients (1.6%) infection. During
the follow-up period shunt-dependent hydrocephalus developed in
4.2% and 0.2% had a subsequent SAH from the same aneurysm.
Forty-three patients were on anticonvulsive therapy.
Keywords:

Cerebral

aneurysm;

subarachnoid

hemorrhage;

surgery.

Introduction
The term aneurysm was coined by Galen and first
used to describe an intracranial aneurysm by Wiseman
in 1669 [90]. Saccular aneurysms have a predilection
for the intracranial vessels and are found in 1-8% in
autopsy studies [8, 54, 87]. The major part of the 10
subarachnoid hemorrhages occurring per 100.000 citizens per year [66,69] is caused by aneurysms, of which
about 85% are located in the anterior circulation.

Surgical treament was mainly initiated by Dandy


[14], but the benefit of this remained unclear for years
[55, 56] until introduction of the operating microscope
and microsurgical techniques [103-105].
The purpose of this paper is to present the results of
surgical treatment of 428 consecutive patients harbouring aneurysms of the anterior circulation together
with a review of relevant anatomy and operative
strategy.

Patients and Methods


The present series consists of 428 consecutive patients with anterior circulation aneurysms that underwent microsurgical treatment
at the National Hospital in Oslo during the period January 1989June 1997. All patients were followed up by an independent observer
(K.E.) after the 3 senior authors had left this institution. The patients
were checked out by questionnaires, telephone interviews, and medical reports by the patients' neurologists. Mean follow-up was 5.6
years (range 1.0-9.5 years).
There were 253 (59.1 %) females and 175 males (40.1 %). Mean age
at operation was 49 years (range 5-80 years). Ninety (21.0%) of the
patients had had more than one bleeding prior to surgery (see Table
1). Surgical treatment was delayed because the patients failed to seek
medical attendance in 60 cases, because the primary physician did
not take appropriate action in 58 cases, a combination of these in 19
cases, and due to negative angiography at peripheral hospitals in 28
cases.
One hundred and twenty-four aneuryms (29.0%) were located at
the internal carotid artery (ICA), 161 (37.6%) at the middle cerebral artery (MCA) and 143 (33.4%) belonged to the anterior cerebral
artery (ACA) complex (Table 2). Of the latter 4 were located at the
proximal ACA (AI), and 12 at the pericallosal artery.
Fifty-six patients had more than one aneurysm, including one patient operated for an MCA aneurysm following treatment of a ruptured superior cerebellar artery aneurysm. The distribution of the
asymptomatic aneurysms among patients harbouring two or more
lesions is shown in Table 3.

108

I. A. Langmoen et al.

Table I. Number of SAH Prior to Surgery Related to Location of


Aneurysm
NoofSAH

o
I

2
3
~4

Total

Location of aneurysm
ACA

MCA

6
108
20
7
2
143

17
110
28
3
3
161

ICA

Total

11
86
24
2

34
304
72
12
6
428

124

2.

3.

Table 2. Location of Aneurysms

Anterior cerebral artery (ACA)


Internal carotid artery (ICA)
Middle cerebral artery (MCA)
Total

143
124
161
428

33,4
29,0
37,6
100,0

Table 3. Location of Secondary Aneurysms*


Symptomatic aneurysm

ICA
ACA
MCA
Other**
Total

Asymptomatic aneurysm
lCA

ACA

12
10

4
2

27

MCA
5

7
10
1
23

other

total

3
1

24
20
21
I
66

4.

* Sixty-six secondary (asymptomatic) aneurysms in 56 patients.


** One patient with a symptomatic aneurysm on the superior cerebellar artery was later operated for an asymptomatic MCA aneurysm.

General Operative Technique


In order to obtain a satisfactory result for the patient
it is of primary importance to avoid brain retraction,
and injury to afferent arteries and perforating vessels.
Much of the key to successfully avoid this lies in the
first phase of the operation. Correct positioning of the
patient, adequate bone removal, dissection of the basal
cisterns, liberation of cerebrospinal fluid (CSF) and
opening of the Sylvian fissure will provide a surgical
space sufficient for dealing with most aneurysms with
little or no retraction.
1. The neck is extended in order to provide gravitational assistance in frontal lobe retraction. The

5.

head is turned 20-60 degrees to the contralateral


side depending on the location of the aneurysm.
Care is taken to avoid extreme positions that may
affect the jugular veins, carotid or vertebral arteries,
cervical spine or trachea.
A slightly curved incision is carried from the posterior part of the zygomatic arch to the hairline in the
midline (modified in bald patients). A scalp-muscle
flap [84] is employed for pterional and orbitopterional craniotomies, whereas separate reflection of
the temporal muscle [l06] is used for orbitozygomaticopterional craniotomies.
We have used an eye-brow incision combined with
a minimal craniotomy in some cases, but as this
approach requires more brain retraction in the initial dissection of the basal cisterns, especially in
acute cases, and reduces the freedom of movement
in the final dissection of the aneurysm, we prefer a
larger craniotomy. In principle, all cases can be operated by a conventional pterional approach. The
more generous space provided by including the orbital roof - or even the posterior part of the zygoma
- in the flap, however, facilitates both the initial
dissection of the basal cisterns with liberation of
cerebrospinal fluid - particularly if the brain is
swollen - and later dissection of the aneurysm with
no or only minimal brain retraction. The approach
is further improved by liberal sphenoid wing removal.
Once the dura is opened, reflected and secured, attention is directed to the carotid cistern in order to
liberate CSF and obtain proximal control of the
ICA. Three landmarks are helpful for localizing the
ICAI optic nerve: a.) The olfactory nerve at the orbital face of the frontal lobe (can be followed backwards to the optic nerve), b.) The remnant of the
sphenoid ridge, and c. The junction of the frontal
and temporal cortex.
The main goal at this stage is: a.) To release CSF in
order to obtain adequate brain relaxation. This
sometimes also requires opening of the membrane
of Liljequist and the lamina terminalis, but infrequently ventricular puncture. b.) To prepare the
ICA for temporary clipping. We do generally not
prepare the proximal ACA (AI) or MCA (MI)
for temporary occlusion before the Sylvian fissure is opened because it usually requires brain
retraction.
The next step is to open the Sylvian fissure which is
usually followed by multiple large veins draining

109

Surgical Treatment of Anterior Circulation Aneurysms

into the sphenoparietal and cavernous sinus, occasionally to the superior petrosal sinus [104]. They
are in general in associated with the temporal lobe,
although smaller frontal veins cross the fissure to
join them. The fissure is therefore almost always
entered between the frontal lobe and the superficial
middle cerebral veins. The lateral part of the anterior fissure is often compressed. Consequently the
frontal and temporal lobes are often adherent in
this area. Also, the frontal lobe/orbital gyrus frequently indents the temporal lobe, or vice versa.
The correct plane of dissection in this part of the
fissure can be easier identified if working from the
inside to the outside. Slightly further distal, however, the cortex on the two sides of the fissure is less
compressed against each other and the Sylvian cistern is closer to the surface. By following a distal
arterial branch retrogradely by sharp dissection the
deep part of the Sylvian cistern is easily reached.
Dissection proceeds retrogradely along M2 and Ml
to the ICA bifurcation. Following this the outer
part of the anterior Sylvian fissure is opened from
the inside to the outside.
6. The following steps depend on the location, size
and projection of the aneurysm. We generally
puncture, and - if necessary - remove the aneurysm
dome, in order to verify occlusion and to facilitate
the final inspection of surrounding structures. It is
of special importance to assure that the clip(s) do
not interfere with the patency of parent vessels,
arterial branches, or major perforators. If in doubt,
this may be evaluated by intraoperative microvascular doppler sonography [2, 58, 59] or in some
centers intraoperative angiography [50, 51]. If
occlusion of the aneurysm is impossible without
parent artery occlusion, special techniques like
extracranial-intracranial bypass grafting [4, 44, 83,
85, 86] and clip reinforced wrapping [5] should be
considered.

()verallltes~ts

All patients included in the present material underwent microsurgical treatment. Twenty-five patients
had more than one aneurysm ligated during the operation for the symptomatic aneurysm and 17 patients had surgery twice. In one of these the symptomatic aneurysm was located at the superior cerebellar
artery. In the postoperative period 53 (12.4%) patients

Table 4. Postoperative Complications

Infection
Cardiac infarction
Lung oedema
Mortality (all causes within 3 months of surgery)
Clinical vasospasm
Symptomatic DVT*
Shunt dependent
Rebleeding
Seizures
Anticonvulsive medication

7
6
4
18
53
4
18
I
2
43

1,6
1,4
0,9
4,2
12,4
0,9
4,2
0,2
0,5
10,0

* DVT Deep vein thrombosis.


Table 5. All Anterior Circulation Aneurysms: Employment and
Independence of Living at Follow-up. Mortality
n

Independence

living at home, independent


living at home, dependent
living in institution
alive, but information missing
total

350
20
8
14
392*

89,3
5, 1
2,0
3,6
100,0

Employment

unchanged employment status


work in sheltered environment
unemployed following SAH
alive, but information missing
total

253

64,5
0,3
30,9
4,3
100,0

Mortality

(of all causes 3 first months after


SAH)

121
17
392*
18

4,2

* Eighteen patients dead at follow-up. Sixteen patients were dead of


unrelated causes 1.5-7 years after SAH. Two patients died at after 4
and 5 months.

developed clinical signs of vasospasms, 6 (1.4%) had


cardiac infarction, 4 (0.9%) lung oedema, 4 (0.9%)
deep vein thrombosis, and 7 patients (1.6%) infection
(Table 4).
Three months mortality of all causes was 4.2%. At
follow-up 350 (89.3%) lived at home and were independent, 20 (5.1%) lived at home but needed some
kind of assistance and 8 (2.0%) lived in institutions,
whereas information was unavailable in 14 (3.6%)
living patients (Table 5). Two hundred and fifty-three
patients (64.5%) had unchanged employment status, 1
(0.3%) worked in sheltered environment, whereas 121
(30.9%) went out of work due to their SAH. Information about employment status was unavailable in 17
patients (4.3%). Grading according to the Glasgow
()utcome Scale (GOS) is shown in Table 6.
Eighteen patients (4.2%) had developed shuntdependent hydrocephalus and 1 (0.2%) had a sub-

110

I. A. Langmoen et af.

Table 6. Frequencies (%) of Outcome (Glasgow Outcome Scale (GOS)) Related to Location of Aneurysm
GOS

ICA

MCA

AComA

Other ACA*

All aneurysms

2
3
4
5
Unknown**
Total

3,2
0,8
7,3
17,7
68,6
2,4
100

5,6
0
5,6
23
62, 7
3, I
100

3,9
0
4, 7
13,4
71, 7
6, 3
100

0
0
0
18,8
68,7
12,5
100

4,2
0,2
5,6
18,5
67, 3
4,2
100

* Pericallosa and AI.


** In 4 patients that died during the follow-up period and 14 patients alive at follow-up there was insufficent information for GOS grading.

sequent SAH from the same aneurysm. Forty-three


patients were on anticonvulsive therapy (Table 4).
Internal Carotid Artery (lCA)
Surgical Anatomy

The relevant anatomy of the cavernous ICA and


ophtalmic artery, as well as aneurysms in these sites,
is discussed in separate chapters (see Dolenc this
volume).
The diameter of the intradural internal carotid
artery (lCA) is 3.5-4 mm [24, 102]. This artery gives
rise to the posterior communicating artery (PComA),
anterior choroidal artery (AChorA), and a number of
perforating arteries before its terminal bifurcation.
The PComA originates at the posterior surface of
intradural ICA and courses posteriorly above cranial
nerve III to the posterior cerebral artery (PCA). The
diameter is usually about 2 mm, but variable as it is
frequently hypoplastic or aplastic [1, 76, 104]. An important variant is the fetal PcomA where the diameter
of the PComA is equal to or larger than the PCA [99].
The PComA may then be the major afferent artery of
the PCA. Duplication and fenestrations are frequent.
Along its course the PComA gives rise to 7 (4-12)
branches [80, 104] that penetrate the posterior perforated substance, peduncle, optic tract and chiasm.
They have diameters of 0.1-0.6 mm and are evenly
distributed along the artery. The main trunk is the
anterior thalamoperforating artery. They supply the
posterior hypothalamus, anterior thalamus, subthalamus, posterior limb of the internal capsule, chiasm,
optic tract, mammillary bodies and tuber cinereum.
Although the PComA itself may be divided when
dealing with aneurysms or other pathological struc-

tures in this region - provided it is not of the fetal type


- the perforating branches must be spared since they
represent end-arteries supplying important central
structures.
The AChorA usually represents the first branch
after the PComA [6, 26, 73]. It originates from the
posterior surface of the ICA 2-5 mm distal to PcomA
and 3-6 mm proximal to the ICA bifurcation. In 3%
the AChorA branches off from the ICA bifurcation,
Ml or PcomA [65, 75]. The diameter is 0.6-1.0 mm.
The artery courses lateral to and then under the optic
tract, posteriorly in the crural cistern to the posteromedial side of the uncus, and through the choroidal
fissure. Although in some studies it has been seen to
arise exclusively as a single artery [73], it often
branches early into a group of arteries, and may also
arise from the ICA as separate vessels [l05]. Careful
exploration of the area prior to occlusion of the
aneurysm neck, and again following puncture of
the aneurysm, is therefore necessary. Occlusion of
the AChorA carries a mortality of 6% and morbidity
of 20% [10, ll].
The ICA bifurcation is the last common site of
aneurysms along the ICA. Although the bifurcation
itself generally is free from perforating arteries, such
vessels usually originate less than 0.5 mm from its
midportion [104]. In addition, anterior perforating
branches arising from the AChorA and intradural
ICA, as well as the recurrent artery of Heubner, may
be stretched around or closely associated with the
aneurysms in this location [28, 79, 104].

Operative Technique and Strategy

1. In order to bring the aneurysm, PComA and


AChorA into view lateral to the ICA wall without

111

Surgical Treatment of Anterior Circulation Aneurysms

increasing the necessity for temporal lobe retraction, the head is rotated 20 degrees towards the
contralateral side. The neck is extended to provide
gravitational retraction of the frontal lobe.
2. These aneurysms are treated through a conventional pterional craniotomy with radical sphenoid
wing removal. An orbitozygomaticopterional craniotomy with or without anterior clinoidectomy
facilitates proximal control and dissection from a
wider angle in large/complex aneurysms (see separate article by Lawton and Spetzler in this issue and
ref[18, 19, 108]).
3. Depending on the type of aneurysm different parts
of the basal cisterns are opened to deliver cerebrospinal fluid. When operating PComA, AChorA
or ICA bifurcation aneurysms, the initial approach
to the basal cisterns is made through the chiasmatic
cistern and the carotid cistern medial to the ICA.
When operating superior hypophyseal or ophtalmic
artery aneurysms, the inital opening is usually made
lateral to the ICA, into the carotid, crural and interpeduncular cisterns. This is followed by isolation
of the proximal ICA in order to secure proximal
control in the event of intraoperative rupture.
4. Some proximal ICA aneurysms may be treated
without opening the Sylvian fissure. ICA bifurcation aneurysms, however, require wide opening of
the fissure. PComA amd AChorA aneurysms may
be adherent to the temporal lobe, and ICA bifurcation aneurysms to the frontal lobe. Selective retraction of the appropriate lobe is therefore used in the
early stage of microsurgical dissection. When following MI to the ICA bifurcation it is important to
realize that one may meet the dome of the aneurysm
first. Depending on the location of the aneurysm,
the superior (PComA, AChorA) or inferior (ICA
bifurcation) wall of the MI is followed.
Results of Surgical Treatment of leA Aneurysms

In the present material 124 aneurysms were located


at the ICA. Twenty-two patients with a symptomatic
ICA aneurysm had secondary (asymptomatic) aneurysm(s), most commonly on the contralateral ICA.
Nine of these patients had more than one aneurysm
clipped during the first operation, whereas 7 patients
underwent additional surgery later. Twenty-seven ICA
aneurysms were found in patients with a symptomatic
aneurysm in another part of the anterior circulation.
Eleven aneurysms were unruptured, and 113 were

diagnosed following SAH. Of these patients 86 suffered one SAH, whereas 24 suffered 2 bleedings, 2 patients 3 bleedings and 1 patient 4 bleedings prior to
surgery (Table 1).
Three months mortality of all causes was 3.2%. One
hundred and twelve patients were alive at follow-up.
Among these 75 (92.0%) lived at home and were independent, 5 (4.4%) lived at home but needed some kind
of assistance and 2 (1.8%) lived in institutions (Table
6). Seventy-five patients (67.0%) had unchanged employment status, 1 (0.9%) worked in sheltered environment, whereas 33 (29.4%) went out of work following their SAH. Information about employment
status was unavailable in 3 (2.7%) living patients.
Eight patients were dead in the follow-up period. This
was unrelated to surgery and had occurred after 2,3,5
(2 patients), 6 (2 patients), and 7 years. Grading according to the Glasgow Outcome Scale (GOS) is
shown in Table 6.

Anterior Cerebral Artery (ACA)


Surgical Anatomy

The proximal ACA (AI) courses medially and


partly anteriorly above the optic nerve (30%) or
chiasm (70%) in the direction of the interhemispheric
fissure [74]. It is 13 (7-18) mm long. Infrequently there
is a marked difference in length between the two AI,
in which cases the anterior communicating artery
(AComA) is not located in the midline. Al has a
diameter of 1-3 mm [104], and in 3 out of 4 cases it
is thinner than the corresponding MCA. Unilateral
hypoplasia (defined as diameter < 1.5 mm) [74] is seen
in roughly 10% of non-aneurysm cases and in 50% of
aneurysm cases [39, 40, 42, 76]. Angiographically observed aplasia is almost never confirmed at surgery.
Unilateral aplasia is thus very rare. Fenestrations and
duplications are also uncommon [68]. Bilateral aplasia
has not been described.
Al gives rise to an average of 8 small perforating
branches (range 0-13) [68] with a diameter of 0.1-1.0
mm. They mainly arise from the proximal half of Al
and usually originates from the superior or posterior
wall [68, 104], not infrequently as a single stem vessel.
Most run recurrently to penetrate the anterior perforated substance, others to the dorsal chiasm, suprachiasmatic hypothalamus, optic tract/nerve, and
inferior frontal lobe.
The recurrent artery of Heubner [33] arises from the

112

ACA close to the AComA [20, 64] and runs in a retrograde fashion along its mother vessel. Perlmutter
and Rhoton [68] found it to arise from A2 in 78%, Al/
A2 junction in 8% and A 1 in 14%. The diameter is on
average about 1 mm [27, 68], but varies considerably
(0.2-2.9 mm). It is almost always the largest branch
from AI/proximal A2, and may - if the Al is hypoplastic - be almost as large [lOS]. On its retrograde
course along Al it is most frequently situated on its
anterior side. Its mean length is 22 mm [46], and at
the ICA bifurcation it usually divides into several
branches (mean number 4.2) mainly turning into the
anterior perforated substance, but also into the frontal
lobe and the Sylvian fissure [20, 46, 68]. It is double in
5-20%, absent in 1-17%, and asymmetric in about
20% [20, 46, 68, 95, 107]. It supplies the anterior parts
of the caudate nucleus, putamen and internal capsule,
as well as a small part of the lateral globus pallidus
[20,64].
The anterior communicating artery (AComA) connects the two A I in the lamina terminalis cistern. It is
2.5 mm (range 0.1-7 mm) long. The diameter is up to
3.0 mm. If < 1.0 mm, which occurs in 16%, it is considered to be hypoplastic. It runs a single channel in
60% [68, 104], but variations are common, including
duplication, triplication, fenestration(s), and reticular
patterns [68, 104, 107], whereas true aplasia may not
occur.
The AComA gives rise to 1-4, or even more, perforating arteries [20, 74, 104] that terminate in the
suprachiasmatic area, dorsal chiasm, anterior perforated substance, and frontal lobe [74]. Dye perfusion
has indicated blood flow to the fornix, corpus callosum, anterior cingulum, and septal region [20]. They
most often emerge from the superior or posterior side,
often as a single vessel. If the two Al segments are of
unequal size, the site of origin is most commonly the
side of the larger Al [104]. In the case of a third or
single A2, these arteries may arise at or within the first
15 mm of its origin.

I. A. Langmoen et al.

2.

3.

4.

Operative Technique and Strategy

1. Aneurysms of the AComA may be treated by the


pterional [105] or interhemispheric approach [22,
23, 49, 92] of which we use the former. The neck is
extended and the head rotated 60 degrees towards
the contralateral side to permit a vertical microsurgical approach. If the position is correct the
superior part of the operative field will be repre-

5.

sen ted by the maxillary eminence, the sphenoid


ridge will be oriented vertically and the force of
gravity will contribute to pull the frontal lobe away
from the floor of the frontal fossa. Some righthanded surgeons prefer to approach most of these
aneurysms from the right side [3, 105]. We prefer to
go from the left side if the left Al is dominant and
the aneurysm is pointing to the right side because it
allows early control of the dominant feeding vessel
and dissection of the neck before the dome is
reached.
In the poor grade patient with increased intracranial pressure the accessibility is improved by including the orbital roof - or even the posterior part
of the zygoma - in the bone flap. This reduces the
requirement for brain retraction and facilitates the
initial dissection of the basal cisterns with liberation
of cerebrospinal fluid under a full frontal lobe, and
increases the degree of freedom during final dissection of the aneurysm.
The initial dissection of the basal cisterns and liberation of CSF is followed by complete opening of
the Sylvian fissure. This mobilizes the lateral part of
the frontal lobe and gives access to the proximal Al
which is prepared for temporal occlusion by sharp
dissection.
If the aneurysm is projecting superiorly or posteriorly, the arachnoid fibers attaching the gyrus rectus
on both sides to the optic nerves and chiasm are
divided by sharp dissection. Both optic nerves, and
the chiasm are exposed, the lamina terminalis
cistern opened, and the proximal Al prepared
(bilaterally) for temporary occlusion. Temporary
clips are placed as close to the AI-A2 junction as
possible in order to avoid perforator ischemia.
When dealing with aneurysms projecting anterioinferiorly this technique may cause premature
rupture. In these cases the surgeon must be especially vigilant not to tear the aneurysm while elevating the frontal lobe. The ipsilateral Al is followed to the Al/A2 junction, before an initial
dissection of the neck is performed. If possible, the
contralateral Al and A2 is dissected behind the
aneurysm before the fundus is mobilized.
The ipsilateral A2 is localized through a small gyrus
rectus corticectomy, or - preferably - by opening
the interhemispheric fissure. The contralateral A2
may be covered by the aneurysm. Depending on the
projection of the aneurysm it is uncovered by following the AComA inferior to the aneurysm, or by

113

Surgical Treatment of Anterior Circulation Aneurysms

dissection in the interhemispheric fissure superior to


it. This is promoted by a retractor blade, or a sucker
(placed on a small cottenoid), in the interhemispheric fissure providing forces to lift rostrally away
from the optic chiasm and laterally to open the
fissure.
6. In the final dissection of the AComA complex there
are 14 arteries or groups of arteries to consider
(see ref [105] p 178). It is of utmost importance to
appreciate the considerable anatomical variations
in the area and to meticulously identify and preserve each vessel. In patients harbouring AComA
aneurysm the two Al segments are often of unequal size. Most commonly both the aneurysm and
the AComA perforators origin from the side of the
larger A1. When dealing with anterio-inferiorly
projecting aneurysms these perforators relatively
infrequently cause difficulties. On posteriorly directed aneurysms, however, the perforators are
usually running over the inferior belly and may be
very difficult to avoid. Generally they are best
identified and dissected by deflecting the ipsilateral
A2 and aneurysm dome superiorly during temporary occlusion of both Al segments, although dissection between the ipsilateral A2 and the aneurysm
also is an option. In superiorly projecting aneurysms hiding the contralateral A2 and Heubner, the
contralateral A2 may be identified distally and followed proximally by gently pushing the aneurysm
anteriorly until the A1JA2junction is reached. The
same technique is used to reflect the perforators.
7. Temporal occlusion of one or both Al is often very
useful. Pool stated that temporary trapping during
hypothermia is safe up to 20 minutes [70]. Crowell
and Ogilvy [12] has reported that total trapping can
safely by applied for 20 minutes without risk and
for 40 minutes with a small risk of cerebral infarction, provided adequate pharmacological brain
protection is used in combination with moderate
hypothermia and moderate hypertension.
8. Anterio-inferiorly projecting aneurysms are most
often closed by a straight or curved clip fitting flush
along the ipsilateral Al - AComA - contralateral
A1. Aneurysms projecting superiorly are also
usually clipped in the front of both A2 segments,
less frequently between them. Posteriorly directed
aneurysms are most frequently closed by a fenestrated clip encompassing the ipsilateral A2, less
frequently by a clip between the two A2 segments or
a fenestrated clip encompassing the ipsilateral AI.

Results of Surgical Treatment of ACA Aneurysms

In the present material 143 aneurysms were located


in the ACA complex; 127 at the AComA, 4 at the
proximal ACA (AI) and 12 at the pericallosal artery.
Thirteen patients with AComA, 2 with pericallosal
and 1 with Al aneurysm had additional aneurysms.
Ten of these patients had more than one aneurysm
clipped during the first operation, whereas 4 underwent additional surgery later. Seven ACA aneurysms
were found in patients with a symptomatic aneurysms
in another part of the anterior circulation.
Among the AComA aneuryms 5 were unruptured,
and 122 were diagnosed following SAH. Of these patients 100 suffered one SAH, whereas 14 suffered 2
bleedings, 6 patients 3 bleedings and 2 patients 4 or
more bleedings prior to surgery. All Al and 11 of the
pericallosa aneurysms had ruptured. Two of the Al
and 5 of the pericallosa aneurysms had multiple ruptures prior to surgery.
Among the AComA aneurysms three months mortality of all causes was 3.9%. 118 were alive at followup. Of these 104 (88.1%) lived at home and were independent, 5 (4.2%) lived at home but needed some kind
of assistance and 3 (2.6%) lived in institutions (Table
7). Seventy-five patients (63.6%) had unchanged employment status, none worked in sheltered environment, whereas 37 (31.3%) went out of work following
their SAH. Information about employment status was
unavailable in 6 (5.1%) living patients. Four patients
were dead at follow-up. In one patient who had died
after 5 months, there was a possible relation to the
SAH. Of the other patients one died after 3 years, and
two after 6 years.
Table 7. leA Aneurysms: Employment and Independence ofLiving at
Follow-up. Mortality
n

%
92,0
4.4
1.8
1, 8
100,0
67,0
0,9
29,4
2, 7
100,0
3,2

Independence

living at home, independent


living at home, needs assistance
living in institution
alive, but information missing
total

103
5
2
2
112*

Employment

unchanged employment status


work in sheltered environment
unemployed following SAH
alive, but information missing
total

75
33
3
112*

(all causes 3 months post SAH)

Mortality

* Eight patients dead at follow-up. This was unrelated to surgery


and occurred after 2, 3, 5 (2 patients), 6 (2 patients), and 7 years.

114

There was no mortality among the patients with Al


or pericallosa aneuryms. Three of the 4 patients with
A 1 aneurysms had unchanged employment status and
lived at home, whereas information was unavailable
about one. Among the patients with pericallosa
aneurysms 11 lived at home, of which one needed assistance. Eight had unchanged employment status and
two had gone out of work. Information about housing
condition was missing in one patient and employment
status in two. Grading according to the Glasgow Outcome Scale (GOS) is shown in Table 6.

Middle Cerebral Artery (MCA)


Surgical Anatomy

The main MCA trunk (Ml) - situated between the


leA and MeA bifurcations - passes laterally about
10 mm behind the sphenoid ridge [25]. It has a diameter of 2.4-4.6 mm at its origin and is usually 14-16 mm
long [25, 28, 30, 36, 97, 104].
The Ml divides into 1. the superior trunk, supplying
the inferior frontal cortex, frontal operculum, area
around central sulcus and parts of the parietal lobe,
and 2. the inferior trunk, supplying the middle and
posterior temporal convexity, temporooccipital region
and angular and posterior parietal regions [104]. The
true MeA bifurcation is always located at the high
point of the limen insulae [104]. The diameter of the
secondary trunks (M2) is 1.4-2.3 mm and the length is
12.1-14.9 mm [97]. The inferior trunk is dominant in
32%, the superior in 28%, whereas they are equal in
18% [25] (multiple trunks of various diameters in
22%). The majority of the arterial branches close to the
bifurcation are large, occasionally as large as Ml/2.
According to Rhoton and coworkers [25, 97] MI terminates in a bifurcation in 64-68%, trifurcation in 1229%, or even in multiple branches. Yasargi1, however,
does stress that careful dissection usually reveals that
these represent bifurcations of the superior or inferior
trunk (M2) [104]. From a practical point of view the
important point is that more than two branches may
surround an MeA bifurcation aneurysm.
The M 1 gives off early branches to the temporal lobe
and perforating arteries to subcortical areas [16, 25, 28,
97, 104]. Less frequently (6%) [25] an early branch to
the frontal lobe is found. The branches to the temporal
lobe are located at the superio-Iatera1 part of M 1. According to Yasargil [104] 3 temporal branches are observed in 30%, these are the uncal artery, the tempor-

I. A. Langmoen et al.

opolar artery, and the anterior temporal artery. The


uncal artery may also arise from intradural leA [28,
98, 104]. The most frequent anatomical configuration
is therefore one temporopolar and one anterior temporal branch. Either of the vessels may be hypo- or
aplastic, or arise from M1 (or M2) as a common stem.
This may have a considerable diameter, especially if it
represents a common temporal stem (i.e. including the
middle and posterior temporal arteries), and gives the
impression of an early bifurcation (i.e. false bifurcation) [104].
The lenticulostriate branches from the M1 [30, 36,
45, 97, 104] consist of2-15 arteries that enter the lateral two-thirds of the anterior perforated substance to
supply subcortical areas. They have an average diameter of 0.58 mm [97]. As they arise from the inferiomedial part of the mother artery, they are more
difficult to disclose during surgery than the temporal
branches, unless the M 1 is gently retracted. Some
authors have divided these vessels into a medial and
lateral group [45], but such a distinction is clear only in
a minority of cases [97]. The perforating arteries may
arise as one or two trunks branching after 2-10 mm, or
as a number of individual vessels. They may originate
all along the course of Ml, but more frequently from
the proximal or middle parts, or even from the MeA
bifurcation, or M2. When they arise from the bifurcation they are frequently hidden by the aneurysm [21].
The lenticulostriate branches supply the superior
part of internal capsule and corresponding corona
radiata, body and head of caudate nucleus, most of the
putamen, the lateral segment of the globus pallidus,
the substantia innominata, and the lateral half of the
anterior commissure [89].
Operative Technique and Strategy

1. The neck is extended and the head rotated 45


degrees towards the contralateral side.
2. Aneurysms located at Ml branching points or the
MeA bifurcation can be handled through a conventional pterional craniotomy, whereas more peripherally placed lesions may need an extended
craniotomy. An orbitopterional or orbitozygomatico-pterional craniotomy facilitates initial release
of cerebrospinal fluid from the basal cisterns if
the brain is full, as well as proximal control and
dissection from a wider angle in large/complex
aneurysms.
3. As superficially pointing aneurysms may be adher-

115

Surgical Treatment of Anterior Circulation Aneurysms

ent to the dura, special care must be taken when the


dura is opened, reflected and secured. If a hematoma is present, evacuation of its major part (leaving clot close to the aneurysm) will usually result
in substantial brain relaxation. Following this the
basal cisterns around the optic nerve and ICA
are opened, and clot removed. The membrane of
Liljequist and lamina terminalis are opened if required to obtain CSF liberation and adequate brain
relaxation.
4. MCA aneurysms can be aproached by a. opening
the Sylvian fissure medially and following the Ml
distally [34, 67, 103], b. opening the Sylvian fissure
peripherally and following a M3 branch proximally
[105], or c. entering the Sylvian fissure through a
small resection in the superior temporal gyrus [32,
96]. Except for some cases with temporal lobe
hematoma we do not access the fissure through the
temporal lobe as we find resection of brain tissue
undesirable. In most instances we prefer to start the
dissection of the Sylvian fissure peripherally by following one of the small temporal or frontal arterial
branches retrogradely to the insulae. Although this
- in contrast to starting the dissection at the ICA
bifurcation - does not allow early proximal control,
it is less traumatic. If the aneurysm is projecting
down into the temporal lobe, for instance, the
frontal side of superior M2 can usually be followed
safely beyond the aneurysm to the M 1 which then
can be prepared for temporal occlusion before the
dissection is completed.
5. Temporary occlusion of main MCA trunk may be
used during final dissection. Ljunggren et al. and
Suzuki et al. found that temporay clipping up to 20
minutes was safe [48, 91], although most authors
recommend occlusion time of less than 15 minutes
[7, 61, 63, 81, 94]. The safety depends upon pharmacological brain protection, together with the use
of moderate hypertension and hypothermia. Lavine
and collaborators reported that all patients (four of
four) who underwent occlusion lasting 10 minutes
or longer without pharmacological brain protection
suffered an infarction, versus five of 23 patients in a
group with brain protection [43].
6. The technical difficulties encountered in the final
preparation of MCA aneurysms are usually identification of a. the M2 trunks, b. the striate perforators, and c. lateral orbitofrontal or anteriotemporal arteries adherent to the aneurysm dome.
As mentioned above, early M2 bifurcation fre-

quently occurs. In these cases one may easily be


misled after having identified two major trunks if a
branch is hidden behind the aneurysm or under the
temporal operculum. The lenticulostriate perforators arise from the bifurcation or the proximal
M2, and usually run recurrently along the Ml
trunk. Their origin is most often close to and hidden
by the aneurysm neck. Since the anatomy is quite
variable, it is important to perform a complete dissection of the aneurysm, mobilize it, and identify
and preserve all arterial branches. Following clip
application the aneurysm is opened - and if necessary the dome removed - before a final inspection of
the area is performed.
Results of Surgical Treatment of MeA Aneurysms

There were 161 primary MCA aneurysms in the


present material. Seventeen patients with a symptomatic MCA aneurysm had altogether 21 secondary
(asymptomatic) aneurysms, most commonly on the
contralateral MCA. Six of these patients had more
than one aneurysm clipped in the first operation,
whereas 5 patients underwent additional surgery later.
Twenty-three MCA aneurysms were found in patients
with a symptomatic aneurysms in another part of the
anterior circulation (Table 3).
Seventeen aneurysms were unruptured, and 144
were diagnosed following SAH. Of these patients 110
suffered one SAH, whereas 28 suffered 2 bleedings, 3
patients 3 bleedings and 3 patients 4 or more bleedings
prior to surgery (Table 1).
Three months mortality of all causes was 5.6%.
Among the survivors 130 (89,0%) lived at home and
were independent, 9 (6,2%) lived at home but needed
some kind of assistance and 3 (2.3%) lived in institutions (Table 8). Ninety-two patients (63,0%) had
unchanged employment status, none worked in sheltered environment, whereas 49 (33,6%) went out of
work following their SAH. Information about employment status was unavailable in 5 living patients.
Grading according to the Glasgow Outcome Scale
(GOS) is shown in Table 6.
Discussion
History

The term aneurysm was coined by Galen and first


used to describe an intracranial aneurysm by Wiseman

116

I. A. Langmoen et at.

Table 8. AComA Aneurysms: Employment and Independence of


Living at Follow-up. Mortality
n

Table 10. MCA Aneurysms: Employment and Independence of


Living at Follow-up. Mortality.
n

Independence

living at home, independent


li ving at home, needs assistance
living in institution
alive, but information missing
total

104
5
3
6
118*

88, I
4,2
2,6
5, I
100,0

Independence

living at home, independent


living at home, needs assistance
living in institution
alive, but information missing
total

130
9
3
4
146*

89,0
6,2
2, 1
2, 7
100,0

Employment

unchanged employment status


work in sheltered environment
unemployed following SAH
alive, but information missing
total

75
0
37
6
118*

63,6
0
31,3
5, 1
100,0

Employment

unchanged employment status


work in sheltered environment
unemployed following SAH
alive, but information missing
total

92
0
49
5
146*

63,0
0,0
33,6
3,4
100,0

Mortality

(of all causes 3 months post SAH)

3,9

Mortality

(all causes 3 months post SAH)

5,6

* Four patients were dead at follow-up. Possible relation to SAH in


one (death occurred after 5 months), unrelated to SAH in three (one
died after 3 years, and two after 6 years).

** Six patients were dead at follow-up. Possible relation to SAH in


one (death occurred after 4 months), unrelated to surgery in the
others (dead after 1.5, 3, 5, 6 and 7 years).

Table 9. Further Branches of the MCA *

right eye, he found a pea-sized aneurysm projecting


from the internal carotid artery; "An ordinary flat silver clip was placed over the neck of the sac and tightly
compressed, obliterating it completely" [13]. During
the next years he collected the first larger series of surgically treated patients [14].
Despite numerous advances in diagnosis and operative technique, the benefit of surgery remained controversial for years, and the first controlled studies of
operative versus conservative treatment failed to
establish surgery as the treatment of choice [55, 56].
This situation was gradually changed by the introduction of the operating microscope and microsurgical
techniques. Although Adams and Witt are credited for
introducing the microscope in aneurysm surgery [90]
its use was mainly popularized by Yasargil, the father
of neurosurgical microsurgery [103-105]. Better lighting and higher magnification, with minimal brain retraction, meticulous microsurgical technique, detailed
cisternal approaches, and refined neuroanaesthesia,
greatly improved surgical results.

Orbitofrontal artery
Prefrontal artery
Precentral artery

Central arteries
Anterior and posterior
parietal artery
Angular artery
Temporo-occipital
artery
Posterior temporal
artery
Middle temporal
artery

orbital parts of middle and inferior frontal


gyrus
middle and inferior frontal gyrus, overlaps
with 1)
sulcus precentralis Supplies posterior part
of inferior and middle frontal gyrus and
inferior 2/3 of prfrontal gyrus
upper precentral and lower postcentral
gyrus
parietal 10 be
posterior part of superior temporal gyrus,
angular gyrus and part of occipital lobe
supplies the area above the posterior
temporal artery
posterior part of temporal lobe
temporal gyri anterior to the posterior
temporal artery

* Both the number of branches, branching pattern and area of


supply is variable. The table lists the commonly identified branches
and their area of supply.
in 1669 [90]. Ten years later Bonet reported a possible
relation to subarachnoid hemorrhage (SAH). The
presence of blood in the subarachnoid space following
an aneurysmal bleed was established by lumbar puncture by Quincke [72] in 1891, but a clear concept of the
clinical picture of aneurysmal SAH first developed in
the 1920ies [9, 14,93].
Treatment by cervical carotid artery ligation was
reported by Nunneley in 1865 [60]. Although intracranial ligation was attempted by Zeller in Germany
[90], Dandy was the first to successfully clip an intracranial aneurysm in 1937 when during a craniotomy
on a 43 year old man who presented with ptosis of the

Incidence
Saccular aneurysms have a predilection for the
intracranial vessels which has been attributed to their
thin walls with less elastic tissue. They are distinctly
infrequent in children and adolescents, and often
associated with atherosclerosis. Prior to formation of
the aneurysm there is mural atrophy with fragmentation of the internal elastic membrane, attenuation of
medial muscle and thinning of the adventitia. These
observations are consistent with a degenerative rather

117

Surgical Treatment of Anterior Circulation Aneurysms

than a developmental ethiology [88]. Except from a


few reported instances of berry aneurysms in chimpanzees, they do not occur in other species, a fact
that has been attributed to human longevity, and the
prevalence of atherosclerosis and hypertension among
humans.
The incidence of SAH in the Western population is
in the order of 10 per 100.000 per year [66,69] and accounts for approximately 0.5% of all deaths. According to most autopsy studies, 1-8% of the adult population harbour intracranial aneurysm(s), although the
numbers vary widely [8, 54, 87]. The annual risk of
rupture has been estimated to 1-5%, but may be substantially less in small aneurysms [15, 29, 78, 100, 101]
Yasargil estimated the life long risk to be 10-30%
[105]. Dell [15] asserted that the lifetime risk of rupture
for an asymptomatic aneurysm identified at the age of
20 to more than 16%, and less than 5% if detected at
the age of 60. Data on prevalence and risk of rupture
vary considerably according to study design, study
population, and aneurysm characteristics. Rinkel et al.
[77] reviewed 23 studies, totalling 56,304 patients. The
prevalence was 0.4% in retrospective autopsy studies,
3.6% in prospective autopsy studies, 3.7% in retrospective angiography studies, and 6.0% in prospective
angiography studies. The prevalence was higher in
patients with autosomal dominant polycystic kidney
disease, familial predisposition, or atherosclerosis.
Only 8% of the aneurysms were> 10 mm. They estimated the overall risk of bleeding to be 1.9% per year.
The risk was higher in women for symptomatic
aneurysms, aneurysms> 10 mm and posterior circulation aneurysms. All available evidence with inherent
overestimation and underestimation taken together,
they estimated that 2% of the population without risk
factors for subarachnoid hemorrhage harbour intracranial aneurysms, although the vast majority of these
are small and have an annual risk of rupture of approximately 0.7%.
Approximately 85% of the intracranial aneurysms
are located in the anterior circulation. Although ACA
and ICA aneurysms are most frequently seen in surgical series [37, 90, 105], MCA aneurysms are found
more often in autopsy studies, and especially ACA,
but also ICA aneurysms are more often symptomatic
during life [53]. Overall there is a mild female dominance of ruptured aneurysms from the fifth decade.
ICA aneurysms are more frequent in women and ACA
aneurysms in men, whereas MCA aneurysms are
equally distributed.

Timing of Surgery
In 1953 Norlen and Olivecrona published their results of delayed surgery [57]. These results compared
so favourably with earlier reports, which consisted
mainly of patients operated on in the acute phase, that
it changed the attitude of most neurosurgeons. With
the development of modern neuroanesthesia, improved surgical approaches and microsurgical techniques, however, it became possible to perform early
surgery with good results [35, 47]. Due to the high incidence of rebleeding and vasospasms, it was felt that
early surgery, which eliminated the aneurysm and
allowed more aggressive treatment of vasospasms,
would be beneficial. This hypothesis was tested in a
randomized study by Ohman and Heiskanen [62] who
found that 91.5% of patients operated early were independent at 3 months post-SAH compared to 80.0%
of the patients operated on more than 8 days postSAH, and further that management mortality was
twice as high among patients subject to delayed surgery. In a multicenter study performed between 1980
and 1983 by Kassell and coworkers it was found that
although 30% of patients admitted early would not
survive untit later surgery, the complications due to
early surgery more or less offset its advantage [37, 38].
Today it is generally agreed that most aneurysms
should be treated as early as possible.
Results of Surgery
In a series of 100 consecutive cases Post et al. [71]
observed an overall surgical mortality of 8.1 %. The
surgical mortality of patients in Grades 1,2 and 3 was
6.3%. At follow-up 60 patients had returned to their
activities, whereas activity limiting deficits were found
in 25.
Yasargil and Smith [107] reported a series of 678
anterior circulation aneurysms predominantly operated late. Postoperative results were good (returned to
normal occupation with no or minimal deficit) in 83%,
fair (returned to work in a more limited capacity because of neurological deficit) in 7%, poor (requiring
supportive care) in 4%. Operative mortality was 4%
and mortality of other causes 1.6%. Among ICA
aneurysms good results were obtained in 83%, fair in
7% poor in 4%, and operative mortality was 4.7%.
Among MCA aneurysms good results were seen in
74%, fair in 14% poor in 4.5%, and operative mortality
was 4.7%. Among ACA aneurysms good results were

118

obtained in 87%, fair in 4% poor in 4.5%, and operative mortality was 2.3%.
Sundt [90] reported a series of 1005 saccular aneurysms. Overall 73% of the patients were in normal employment without neurological deficits. Excellent
(normal employment without deficits) or good (neurological deficit with normal mentation and functional
employment) results were obtained in 94% of the patients in Botterell grade 0, 93% in grade 1, 84% in
grade 2,51% in grade 3 and 22% in grade 4. Among
ACA aneurysms, excellent results were seen in 73.6%,
ICA aneurysms 76.6% and MCA 70.7%.
In the International Cooperative Study on the
Timing of Aneurysm Surgery by Kassell et al. [38] it
was found that alert patients had a mortality rate of
10-12% when undergoing surgery prior to day 11
compared with 3-5% when surgery was performed
after day 10. Patients drowsy on admission had a 2125% mortality rate when operated on up to day 11 and
7-10% with surgery thereafter. The postoperative risk
following early surgery was equivalent to the risk of
rebleeding and vasospasm in patients waiting for delayed surgery. Good recovery was observed in 69.6%
of patients with ICA, 67.5% with MCA and 67.0%
with ACA aneurysm, whereas mortality was 12.6%,
13.0% and 16.8% respectively.
Hernesniemi et al. [31] reported a series of 1007 patients where 55% were operated on during the first
three days and 77% during the first week. Surgical
mortality at 30 days was 9%. Ninety percent of the
patients presenting in Hunt and Hess grades I-II, 68%
in grade III and 30% in grade IV- V had an independent life at follow-up. In line with the results of the
present series they found poorer management results
for MCA aneurysms compared to ICA and ACA
aneurysms.
Deruty et al. [17] followed a group of 73 patients
that had undergone either early or late surgery.
Ninety-seven per cent of the patients were available for
follow-up. The overall immediate outcome was good
or fair in 85%, poor in 4%, and death in 11%. Among
63 patients alive and available for long term follow-up,
57% had returned to their previous activities, 16% had
returned to a reduced level of activity, and 27% were
unemployed.
Siiveland et al. [82] reviewed outcome of surgery in a
prospective study where all patients with verified
aneurysmal SAH admitted between June 1, 1989 and
May 31, 1990, were enrolled. The study covered 6.93
of Sweden's 8.59 million inhabitants (81%). Among

I. A. Langmoen et al.

145 patients who preoperatively were in Hunt & Hess


grades I-III and who underwent surgery for a supratentorial aneurysm within 72 h after the bleed, 81%
(117 patients) made a good recovery. The morbidity
was 12% (17 patients) and the mortality 7% (11 patients). The most common cause of unfavorable outcome was surgical complications, which accounted for
8% of the total series (12 patients).
Although most centers today prefer early operation
followed by aggressive medical therapy, some authors
favour late surgery because they argue that the lower
surgical morbidity and mortality figures obtained by
this strategy outweighs the risk associated with delayed
operation. In a group of 131 patients where 83% underwent late operation Krupp et al. [41] had a management mortality rate of 13%. Good results (Glasgow
Outcome Scale 4 or 5) were attained in 75% of the
entire study population, in 85% of patients admitted at
grades 1 to 3, and in 53% of those patients who were
admitted at grades 4 to 5 and who underwent late surgery after their condition had improved to grades 1 to
3. In a series of patients where 93% underwent surgery
on day 8 or later and 78% on day 11 or later, MauriceWilliams and Wadley [52] found 88% to be in GOS
grade 1 at one year follow-up, while 5% had died (30day surgical mortality was 3.5%).

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106. Yasargil MG, Reichman MV, Kubik S (1987) Preservation of
the frontotemporal branch of the facial nerve using the interfascial temporalis flap for pterional craniotomy. Technical
article. J Neurosurg 67: 463-466
107. Yasargil MG, Smith RD (1982) Management of aneurysms
of the anterior circulation by intracranial procedures. In:
Youmans JR (ed) Neurological surgery. W.B. Saunders,
Philadelphia, pp 1663-1696
108. Yonekawa Y, Ogata N, Imhof HG, Olivecrona M, Strommer
K, Kwak TE, Roth P, Groscurth P (1997) Selective extradural
anterior clinoidectomy for supra- and parasellar processes.
Technical note. J Neurosurg 87: 636-642
Correspondance: Professor Iver A. Langmoen, M.D., Ph.D., Department of Neurosurgery, Karolinska Hospital, S- 171 76 Sweden.

Acta Neurochir (1999) [Suppl)72: 123-140


Springer-Verlag 1999

Posterior Circulation Aneurysms


Technical Strategies Based on Angiographic Anatomical Findings
and the Results of 60 Recent Consecutive Cases
Y. Yonekawa 1, Y. Kaku 1, H. G. Imhof1 , M. Kiss 2 , M. Curcic 2 , E. Taub 1, and P. Roth 1
1 Department
2 Department

of Neurosurgery, University Hospital Zurich, Switzerland


of Anesthesiology, University Hospital Zurich, Switzerland

Summary
Ninety-eight patients with aneurysms of the posterior circulation
were admitted to our department from 1993 to 1997. Sixty of them
underwent microsurgical treatment, mostly in the acute stage of
subarachnoid hemorrhage. Peri- and intraoperative management
were carried out according to a structured treatment strategy. Special aspects of surgical technique included extradural selective anterior clinoidectomy for basilar head aneurysms, lateral SUboccipital
craniotomy and partial condylectomy without laminectomy for
aneurysms of the vertebral artery or posterior inferior cerebellar
artery, and a trans-Sylvian approach, as used in selective amygdalohippocampectomy, for aneurysms of the posterior cerebral artery. A
careful angiographic evaluation of the aneurysms in relation to the
neighboring important arteries and bony structures was essential for
optimal surgical planning. Forty-nine patients (82%) made a good
recovery by 3 months after surgery. The mortality was 7%.
Keywords: Posterior circulation aneurysms; basilar head aneurysm; acute stage; extradural selective anterior clinoidectomy.

Introduction
Posterior circulation aneurysms remain a therapeutic challenge despite improvements in microsurgical
technique [7, 35, 40] and advances in endovascular
therapy. Promising early results have been obtained
with the latter method: about 50% of posterior circulation aneurysms can be completely occluded initially,
although coil compaction may often occur afterwards,
resulting in incomplete occlusion. [19, 22, 26] In this
paper, we report our technical strategies and the results
obtained in 60 consecutive operative cases performed
during the last 5 years (1993-1997), in accordance
with our principle that ruptured aneurysms, particu-

larly, in the acute stage should be occluded microsurgically with clipping of the neck [44]. Our structured perioperative treatment strategy for ruptured
aneurysms in the acute stage has been reported previously [24, 42, 44] and is summarized in Table 1. In
this paper, we discuss the application of this strategy to
aneurysms of the posterior circulation.
Strategies and Surgical Methods
Basilar Head Aneurysms
Angiographic and anatomical considerations. The
preoperative angiographic examination yields important information about the aneurysm: its size, shape,
and orientation, the width of its neck, the vertical and
anteroposterior distance of the neck from the posterior
clinoid process, and the distance of the neck from the
midline. Further important angiographic data include
the diameter of the posterior communicating artery
(PcomA), the distance of the internal carotid bifurcation from the midline (seen in an anteroposterior view)
and from the anterior clinoid process (lateral view), the
course of the posterior cerebral artery (PCA), the
presence of concomitant aneurysms, etc. These data
may be confirmed and extended by means of threedimensional angiographic CT (3D CT).
The location of the aneurysm in relation to the posterior clinoid process is of cardinal importance. A
plain lateral angiographic view demonstrating the

124

Y. Yonekawa et al.

Table I. Management of Patients with Ruptured Aneurysms in the Acute Stage


Perioperative management against vasospasm
nimodipine administration (2 mg/hour i.v.) for 10 days to 2 weeks
enough hydration to moderate hypervolemia
triple H therapy
interventional endovascular administration of papaverine with or without angioplasty
(barbiturate coma for refractory vasospasm)
Intraoperative management
opening of the lamina terminalis and the membrane of Liliequist
optimal neck clipping with the use of temporary clipping
topical administration of papaverine to spastic vessels
hemodynamic monitoring for checking the patency of important vessels with micro-Doppler sonography and Peltier stack
closure of craniotomy without any drainage

Trannygomati<:... __ _
Pterional,

--=

Subtempora ~ ___ _ =-.


_ __

Transpetrosal

Transcondylar

Fig. I . Selection of the surgical approach according to the location


of the aneurysm neck in relation to bony structures (modified from
Kawase [II])

bony structures, in addition to subtraction angiography, is indispensable for proper evaluation (Fig. 1).
The aneurysm neck is located above the posterior clinoid process in approximately 60% of basilar head
aneurysms [13]. The optimal distance of the aneurysm
neck above the posterior clinoid process for the pterional approach has been reported to be between 0.5
to 1 cm [37]. This approach may still be used for
aneurysm necks situated up to 1.5 cm above the
posterior clinoid process, as long as the operative field
is widened in a manner discussed below. Aneurysms
located above this level can be managed with other
approaches, including the transzygomatic subtemporal approach, the orbitozygomatic temporopolar
approach, or special approaches through the third
ventricle [11, 14,31]. On the other hand, an aneurysm
neck more than 2- 3 mm below the posterior clinoid
process can be can be reached if the operative
approach is widened by a posterior clinoidectomy.
Aneurysm necks beneath this level require the use of
the subtemporal-transtentorial approach.

When the width of the neck exceeds 7 mm it becomes


difficult to manage at one scope [11], even after the
operative field has been widened as discussed below. In
addition, the thalamoperforating arteries originating
from the PI segment of the PCA will be situated very
close to the neck. Their preservation during aneurysm
clipping will therefore be problematic.
A basilar head aneurysm pointing posteriorly is difficult to clip, as the neck is covered by the PI segment
and several tiny perforating arteries originates from
the posterior wall of the basilar artery (BA) and the
superior wall of the proximal SCA [28, 29]. With
posteriorly directed aneurysms, these perforators are
difficult to dissect and the clip blade will have to be
inserted posterior to the PI and the BA. The subtemporal approach [7, 8] may therefore be considered
in this situation.
When the exposed length of the internal carotid
artery (ICA) is less than I cm, or when it curves outwards, the usual retrocarotid approach to the basilar
head requires medial retraction of the ICA [11]. When
there is a distance of 5- 10 mm between the optic nerve
and the ICA, the basilar head may be accessed through
this space - the optic carotid triangle [39]. The size of
this triangle is roughly estimated by the product of the
length of the ICA and the distance of the ICA bifurcation from the midline (Fig. 2). The larger the area of
the triangle, the easier is the access to a basilar tip
aneurysm through this approach (provided that the
basilar head is above the posterior clinoid process)
(Fig. 3) [20]. This approach is particularly useful in
elderly patients, as the optic carotid triangle increases
with age [20].
Other important anatomical relations to study
on the preoperative angiograms includes the type
BA bifurcation - as a high-shouldered PCA (Yconfiguration) may obstruct the path to the aneurysm

125

Posterior Circulation Aneurysms

Distance of 1(, BIF


from Midline: D(mm )

]
neck [11], the length and size of the PcomA - as it may
need to be mobilized and transected to gain a wider
operative field, and the thalamoperforating arteries although difficult to see on the angiogram preoperative
detection will make them easier to identify and preserve intraoperatively.
Our routine surgical strategy for basilar tip aneurysms and basilar artery-superior cerebellar artery (BASCA) aneurysms in the acute stage is as follows:
1. Conventional pterional craniotomy, usually from
the right side.
2. Extradural selective anterior clinoidectomy [45].
3. Opening of the membrane of Liliequist and the
lamina terminalis.
4. Posterior clinoidectomy (when necessary).
5. Transection of the PcomA (when necessary).
6. Temporary clipping of the BA trunk. Mannitol
(20 g) is given routinely in advance, and a bolus of
thiopental (500 mg) if the duration of temporary
occlusion exceeds 15 minutes.
7. Dissection of the aneurysm, identification of the
thalamoperforating artery, and isolation of the
aneurysm with a rubber dam [34].

10

;f

10

if

Dx H(mm' )

200

20

20

Fig. 2. Radiometry diagram. Distance of the lCA bifurcation from


the midline ( D) and its height above the base-line between the anterior and posterior clinoid processes ( H ) (Nagasawa et al. [20D

Height of IC- BIF


from Baseline: H(mm )

'--------'

OCT RCA

100

oo~

'--------l

OCT

RCA

0;1

'------'
OCT
RCA

Fig. 3. Results of radiometry. Distance from the midline (D left),


height above the base line (H center) and D x H(right), in the optic
carotid triangle (OCT) group and the retrocarotid approach (RCA)
group, are expressed as means " SD, and as open and closed circles,
respectively (Nagasawa et al. [20D

8. Permanent clipping of the aneurysm and puncture


of its dome.
Our method of operating on ruptured aneurysms in
the acute stage without cerebrospinal fluid drainage

126

Y. Yonekawaetal.

tures, so that even relatively high-lying aneurysms


can be managed.
2. It widens the operating field anterolaterally, allowing a larger working space and better illumination.
3. Transcavernous access to the BA (if necessary).
[4, 5, 6] is facilitated.
4. As this approach preserves the greater part of the
orbital roof, the orbital contents do not bulge into
and obscure the operative field, and postoperative
enophthalmos does not occur.

Fig. 4. Selective extradural anterior clinoidectomy. After a conventional pterional craniotomy and drilling away of the lateral part of
the sphenoid ridge, the anterior clinoid process can be removed en
bloc by drilling away of the lateral cranial bony wall of the superior
orbital fissure and that of the roof of the optic canal and optic strut.
(a) This enables the access to the clinoid space (b)

procedures has been reported elsewhere [44, 45].


Opening the basal cisterns, the lamina terminalis, and
the membrane of Liliequist slackens the brain enough
for surgical management of aneurysms around the
basilar head, even in the acute stage, when they may
prove difficult to approach subtemporally.
Selective extradural anterior clinoidectomy (Fig. 4)
[45] provides the following advantages:
1. It allows extensive mobilization of the ICA and
the optic nerves without compromising these struc-

If the PcomA must be divided it should be transected at its junction with the PCA. Perforating arteries
arising from the posterior communicating artery
should be preserved as far as possible, even if the artery
is hypoplastic. Compromise of its tuberothalamic
branch can result in a small infarct and mild hemiparesis [3, 27]. With our standard technique, there is
no need to sever the anterior temporal venous drainage
into the sphenoparietal sinus, or to sacrifice a well
developed temporopolar artery, as is done in the temporopolar approach or extended lateral approach [l, 4,
30]. These approaches remain very useful, however,
for special and difficult types of aneurysms.
Case J RT. This 49-year-old man suffered a subarachnoid hemorrhage (SAH) on February 19, 1995.
He was transferred to our clinic in good clinical condition about two months later.
Angiography (April 20): An aneurysm with a diameter of approximately I cm was found at the basilar
head (Fig. 5). The neck was located 0.5 cm above the
posterior clinoid process. The left PCA was filled from
ICA.
Operative procedure and findings (Fig. 6): A conventional right pterional craniotomy was followed by
an extradural selective anterior clinoidectomy which
provided a wider operative field for the retrocarotid
approach to the aneurysm. A partial posterior clinoidectomy was performed to expose a site for temporary
clipping of the BA trunk. The PcomA was transected
at its junction with the PCA. After temporary clipping
of the BA trunk for 3 minutes, the aneurysm was isolated with a rubber dam from the thalamoperforators
arising from the PI segments on both sides, and occluded with two permanent clips.
Postoperative course and follow-up angiography:
The patient woke up after surgery with an unexpected
left hemiparesis and a CT scan revealed a small tuberothalamic infarct (Fig. 7). The hemiparesis subsided
within a few days. Follow-up angiography on April 28

127

Posterior Circulation Aneurysms

~~~~~~~------------~--M :

I :

. Os

.8:11

Fig. 6. Artist's view of the operative procedure and findings of


Case I. After extradural selective anterior c1inoi-dectomy, partial
drilling away of the posterior clinoid process was necessary to allow
temporary clipping of the basilar trunk. Transection of the posterior communicating artery also facilitated radical clipping of the
aneurysm

Fig. 5. Case I: RT, 49year-old man. (a) AP view. (b) Lateral view.
Note the height of the aneurysm neck (5 mm) above the posterior
clinoid process

documented complete occlusion of the aneurysm. The


patient was discharged in good condition on Apri130.
Comment. The typical retrocarotid approach to
a basilar head aneurysm was facilitated by an anterior clinoidectomy, which provided a more generous
working space and better illumination of the operative
field. The case demonstrates that transection of the
PcomA can give rise to a tuberotha1amic infarction
[3, 27].
Case 2 RB. This 65-year-old man was admitted to
our department on Sept. 8, 1997. Diagnostic eva1ua-

tion of a left lower quadrantanopsia had led to the


discovery of an unruptured aneurysm of the basilar
head measuring more than I cm in diameter. An attempt had been made at another institution to occlude
the aneurysm by endovascu1ar coiling. Because the
aneurysm had a broad neck this failed, and resulted in
occlusion of the left PI artery. The patient was therefore referred to us for surgical treatment.
Angiography and 3-D CT findings (Sept. 9) (Fig. 8):
The aneurysm was pointing slightly anteriorly. The
right PCA was filled from the right ICA (hypoplastic
PI). The aneurysm neck was so broad that the left
PCA originated from the aneurysm neck at the level of
the posterior clinoid process. The right ICA bifurca-

128

Y. Y onekawa et af.

Fig. 7. A tuberothalamic infarct due to transection of the posterior


communicating artery

tion was located approximately 1 em lateral to the


midline in the AP view.
Operative procedure and findings (Sept. 10) (Fig. 9):
A right pterional craniotomy with selective extradural
anterior clinoidectomy was performed. In spite of that
the anterior clinoid process was removed, adequate
mobilization of the leA for access to the aneurysm
through the retrocarotid space could not be obtained.
Initial exploration through the opticocarotid triangle
revealed neither the aneurysm neck nor the trunk of
the BA, because they were obscured by a high posterior clinoid process. Adequate exposure of these structures was, however, obtained following a posterior
clinoidectomy. The BA trunk was temporary clipped
through the retrocarotid space for 12 minutes and the
aneurysm radically occluded with three different types
of clips. The left PI, giving rise to the thalamoperforating artery, and the right hypoplastic PI, originally
attached to the aneurysm dome, were both successfully
preserved. Several small atheromatous plaques were
observed in the aneurysm dome; these may have been
the source of past embolism, resulting in the abovementioned quadrantanopsia.
Postoperative course and follow-up angiography:

Fig. 8. Case 2: RB, 65-year-old man. (a) AP view. The right PCA was opacified by carotid angiography. (b) Lateral view. (c) 3D-CT angiography reveals that the aneurysm neck is at the level of the posterior clinoid process

Posterior Circulation Aneurysms

129

Fig. 9. Artist's view of the optic carotid triangle approach in Case 2.


Note the drilling away of the posterior clinoid process; note also that
the space created is large enough for the insertion of three aneurysm
clips for complete clipping of the aneurysm

The postoperative course was uneventful until the follow-up angiography on Sept. 17, which showed complete occlusion of the aneurysm and preservation of
important neighboring vessels (Fig. 10). Just after the
angiography, a severe visual disturbance developed,
almost to the point of finger detection only. This disturbance subsided day by day with conservative therapy with dexamethsone and heparin. By the date of
discharge (Sept. 23) Goldmann perimetry revealed
approximately the same visual field defect that the
patient had preoperatively.
Comment. This is a typical case in which the neck
could be clipped through the optic carotid triangle
after posterior clinoidectomy. Wide-necked aneurysms

Fig. 10. Postoperative angiography displaying a complete occlusion


of the aneurysm. (a) AP view. Note preservation of both PI's, whose
preservation was not possible at the time of endovascular occlusion.
(b) Lateral view

like this one may need multiple clips for complete


occlusion.
Case 3 FL. This 28-year-old female suffered from
SAH on July 5,1995 and was transferred to our service
the next day. She was in Grade IV on the WFNS clinical scale for SAH, and the CT scan revealed a bleed of
Fisher Grade 3 (Fig. 11). Emergency angiography
(Fig. 12) revealed a lobulated basilar head aneurysm
with a diameter of 8 mm. The dome was directed

130

Y. Y onekawa et al.

ARt'RAR S-IX

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Fig. II. Case 3: FL, 28-year-old woman. The CT scan shows extensive SAH and hydrocephalus with dilatation of the temporal horn

posterosuperiorly, and the PCA was somewhat Yshaped in the AP view. The aneurysm neck was
located approximately I cm above the posterior clinoid process.
Operative procedure and findings: (Fig. 13) The
patient was operated upon on the day of admission,
immediately after angiography. A conventional right
pterional craniotomy with selective extradural anterior
clinoidectomy was performed. Opening of the lamina
terminalis and the membrane of Liliequist, with removal of an extensive subarachnoid clot, enabled dissection of the aneurysm. Transection of PcomA was
necessary. A considerable part of the aneurysm dome
was hidden behind the right PI, as could be expected
from the angiographic finding of a Y-shaped PCA.
After dissection of an important thalamoper-forator
originating from the left PI, the basilar trunk was
temporarily clipped for 13 minutes, and the aneurysm
was occluded with a curved Yasargil clip inserted behind the right PI. A small piece of muscle was applied
to a small remnant of the aneurysm neck and fixed in
place with Aron Alpha (Sankyo Co. Ltd. Tokyo).
The head of the permanent clip touched the oculomotor nerve.
Postoperative course and follow-up angiography:
the course was uneventful except for an oculomotor
nerve palsy, and the patient was discharged on July 22.
The oculomotor palsy subsided completely by the time
of outpatient follow-up 3 months after surgery. Fol-

NEURORADIOLOGIE USZ
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Fig. 12. Case 3: FL. 28 years old female . Preoperative angiograhpy.


(a) AP view showing lobulated aneurysm with Y-shaped PI's.
(b) Lateral view indicating aneurysm directed posteriorly. The height
of the aneurysm neck above the posterior clinoid process was approximately I cm

low-up angiography on July 20, 1996 revealed radical


occlusion ( Fig. 14).
Comment. This is a typical case of a basilar head
aneurysm directed posteriorly that could be managed
in the acute stage. Temporary clipping of the proximal basilar trunk was indispensable for dissection of
the aneurysm neck. Oculomotor palsy usually recovers completely within 3 months, as it did in this
case.

131

Posterior Circulation Aneurysms

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Fig. 13. Artist's view of the operative procedure and findings: Note
transection of the posterior communicating artery. Because of
the Y-shaped PI and the posteriorly directed aneurysm, it was necessary to insert an aneurysm clip from behind the PI and the basilar
artery. A piece of muscle was applied to the small residual aneurysm
neck.

1'05
2 . 0$

3 . 9$

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Fig. 14. Postoperative angiography. (a) AP view and (b) lateral view
showing a complete clipping of the aneurysm neck

Vertebral Artery-Posterior Inferior Cerebellar Artery


(VA-PICA) Aneurysms
Angiographic and anatomical considerations. Three
distances that can be measured on the preoperative
angiogram are important predictors of the difficulty of
operative access and the frequency of operative complications involving the lower cranial nerves (Fig. 15).
These are the distance of the aneurysm from the midline (A), from the most lateral point of the foramen
magnum (B), and from the clivus (C). For optimal
results, these distances should be more than 5~ I 0 mm,
less than 1O~21 mm, and less than 13 mm, respectively
[21,37,38]. Furthermore a smaller value ofB will ne-

cessitate dissection of the point of entry of the VA into


the intradural space, so that adequate extracranial exposure can be obtained for temporary clipping with
little or no manipulation of the lower cranial nerves.
The anatomical relation of the aneurysm to the knee of
the VA also yields clues to its relation to the lower
cranial nerves [37].
Technical considerations. A transoral approach is
not necessary even for aneurysms at or very near the
midline [2, 7]. A conventional lateral suboccipital craniotomy, performed either with or without occipital

132

y. Y onekawa et al.

condylectomy, is the procedure of choice for such lesions, as well as for midline aneurysms at the junction
of the vertebral arteries. The lateral suboccipital
approach was reported on by Drake [7] and Heros [10]
but had been in use much earlier, as Yasargil had performed such procedures micro surgically as early as the
late 1960's. The prevailing method before that time
was the extensive midline posterior fossa craniotomy
approach described by Kempe [12].
Our routine approach to the VA-PICA aneurysms is
as follows:
1. Lateral (retroauricular retromastoid) suboccipital
craniotomy in the sitting position.
2. Dissection of the extracranial VA at its horizontal
segment between the occipital bone and the atlas.
There is no need to perform even a partial resection
of the posterior arch of C 1.
3. Partial occipital condylectomy (Fig. 16) (eventually
by drilling away of the jugular tubercle).
4. Dural opening and dissection of the aneurysm
5. Temporary clipping of the proximal VA and clipping of the aneurysm neck.

Fig. 15. Distances of aneurysm from bony structures. (A) From the
midline. (B) From the most lateral part of the foramen magnum. (C)
From the clivus. These distances are related to operative accessibility
and postoperative complications involving the lower cranial nerves
(see text)

Fusiform aneurysms, dissecting aneurysms, and


aneurysms whose dome incorporates the origin of the
PICA have been managed by some with proximal
ligation, but this should be avoided as much as possible. With a combination of various types of clips, or
microsurgical reconstruction with sutures, the patency
of the VA and the PICA is preserved.
Case 4 TK This 56-year-old woman suffered from
SAH in late February 1996 and was diagnosed as
having a VA-PICA aneurysm. The patient declined an
open procedure and was, therefore, referred to our department for endovascular aneurysm occlusion with
Guglielmi detachable coils (GDC). An attempt to coil
the aneurysm failed because of its wide neck and was
complicated by occlusion of the PICA. A minor leak
from the aneurysm, confirmed by CT scan, occurred
on March 8, 1996, and hydrocephalus developed, with
clinical deterioration. An emergency operation was
performed.
Angiography (March 8) (Fig. 17): The aneurysm is
close (5mm) to the midline and far from the clivus and
foramen magnum, so that surgical access was predicted to be difficult. Furthermore, the aneurysm neck
is wide and gives rise to the PICA, thus explaining both
the failure to occlude the aneurysm with GDC and the
PICA occlusion complicating the attempt.
Operative findings: On March 8, 1996, a lateral

133

Posterior Circulation Aneurysms

Fig. 16. Operative approach for aneurysms of the vertebral artery.


Lateral suboccipital approach in combination with partial condylectomy (i) and drilling away of the tuberculum jugulare enables
access to the midline. Extradural dissection of the vertebral artery
exposes a site for temporary clipping while avoiding manipulation of
the lower cranial nerves

suboccipital craniotomy was performed in the sitting


position. The extradural VA was exposed with a partial occipital condylectomy, but the posterior arch of
C1 was left intact. The aneurysm was dissected as
illustrated, and the anatomy corresponded to the angiography. The PICA originating from the wide neck
of the aneurysm, adjacent to the cranial part of the
hypoglossal nerve. The proximal extracranial VA was
temporarily clipped for 15 minutes, and the aneurysm
neck was completely occluded with a fenestrated clip
and a small regular clip overlapping it, as illustrated in
Fig. 18. Patency of the PICA was checked and confirmed with micro-Doppler sonography. Postoperative
course and follow-up angiography: The postoperative
course was uneventful, except for dysphagia lasting
several days. Follow-up angiography revealed a complete clipping of the aneurysm neck with preservation
of the PICA circulation. The patient was discharged
on March 13, 1996. Dysphagia recovered by the time
of outpatient follow-up three months later.

Fig. 17. Case 4: TK, 56-year-old woman. (a) AP view. Note that the
aneurysm is near the midline. (b) Lateral view showing origin of the
PICA from the aneurysm neck

Basilar Trunk Aneurysms


Angiographical and anatomical considerations.
Aneurysms at the upper portion of the basilar trunk
above the level of the trigeminal nerve (i.e., the level

134

Fig. 18. Artist's drawing showing a method of preservation of the


PICA at the aneurysm neck using a combination of a fenestrated clip
and a regular clip

of the sellar floor) can be managed through a conventional subtemporal approach combined with transection of the tentorium. Aneurysms at lower levels
should be managed through either an anterior transpetrosal approach or a lateral suboccipital approach,
with or without transection of the sigmoid sinus, and
with or without condylectomy [4, 33].
The orientation of the aneurysm is an important
factor in the ease or difficulty of access [9]. Laterally
pointing aneurysms are the most difficult, as these
must be approached from the aneurysm dome. The
dissection of posteriorly directed aneurysms is made
difficult by the need to dissect out the nearby perforating arteries. When the anterior inferior cerebellar
artery (AICA) and superior cerebellar artery (SCA)
are hypoplastic, great care should be taken to preserve
the circumferential branches of the BA, as these are the
main source of the blood supply to the brain stem [18,

Y. Yonekawa et al.

28]. Anteriorly directed aneurysms, in contrast, can be


managed relatively easily.
Case 5 BJ. This 59-year-old man suffered a SAH on
March 8,1993 . He was initially comatose, but gradually recovered consciousness. On admission to our department on April 27, he was alert and had bilateral
abducens palsies, dysphagia, and a mild left hemiparesis.
Angiography (April 28) (Fig. 19): An aneurysm of
the upper basilar trunk measuring 4 mm in diameter,
directed posteriorly and slightly to the left, was demonstrated. It was embedded in the pons and gave rise to
a number of small perforating arteries at its periphery.
Operative procedure and findings (May 3): A left
temporal osteoplastic craniotomy was performed,
followed by an anterior petrosectomy. After incision
of the tentorium and the superior petrosal sinus, the
aneurysm was dissected, as shown in Fig. 20. The
proximal basilar trunk was temporarily clipped for 3
minutes, a perforating artery in the vicinity of the neck
was isolated and preserved, and the aneurysm was
occluded with a permanent clip. The patient woke up
from general anesthesia with a right hemiparesis.
Postoperative course and follow-up angiography:
The hemiparesis persisted, as did the bilateral abducens palsy and dysphagia. The postoperative CT scan
displayed an extensive infarct of the left side of the
pons (Fig. 21). Follow-up angiography revealed a
complete occlusion of the aneurysm and an absence of
opacification of the small perforating branch near the
aneurysm neck. The patient died of pneumonia 4
months later.
Comment. Aneurysms of the upper basilar trunk,
corresponding to the upper two-thirds of the clivus,
can be managed through a subtemporal approach with
anterior petrosectomy combined with transection of
the superior petrosal sinus and the tentorium. Although the perforating artery in the vicinity of the neck
was thought to be preserved at the time of clipping,
this may not have been the case, as a pontine infarction
resulted from the operation. As the AICA was not seen
on the preoperative angiogram, this small circumferential arterial branch may well have been an
important supplier of the left side of the pons at this
level.
Aneurysms of the Posterior Cerebral Artery (PCA)

Angiographic and anatomical considerations.


Aneurysms of the PI segment are usually approached

135

Posterior Circulation Aneurysms

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Fig. 19. Case 5: BJ, 59-year-old man. (a) AP view. (b) Lateral view
showing a posteriorly directed basilar trunk aneurysm at the level of
the upper third of the clivus

pterionally, and aneurysms ofP2 or P3 subtemporally.


In the latter case, the degree of brain retraction needed
to reach the peA is problematic. It makes anatomical
sense to approach the P2- P3 junction through the
trans-Sylvian, transcortical, transtemporal horn route,
as is done to perform a selective amygdalohippocampectomy [41]; we describe this further below. The
difficulty of access to the P2-P3 junction has given rise
to a number of alternative approaches, including the
occipital interhemispheric transtentorial approach
[17, 39]. Our new approach [43], a modified para-

Fig. 20. Artist's drawings of the operative procedure and findings:


anterior petrosectomy with transection of the superior petrosal sinus
and incision of the tentorium

median infratentorial supracerebellar approach (after


Yasargil), may be a further solution to this problem.
Case 6 LP. This 39-year-old woman suffered from
SAH, with severe headache and a generalized seizure,

136

Y. Yonekawa et al.

Fig. 21. Postoperative CT scan indicating an extensive pontine infarction in spite of apparent preservation of the perforating arteries
from the basilar trunk

on Sept. 23, 1997. On admission to our department the


next day, the patient was clinically in WFNS grade III.
The hemorrhage was graded to 3 on the Fisher scale.
Angiographical findings (Sept. 24) (Fig. 22): A bilobed aneurysm with a fusiform component, measuring 1.5 cm in diameter, was found at the junction ofP2
and P3 on the right side.
Operative procedure and findings (Sept. 24, 1997):
A conventional pterional craniotomy with removal of
the sphenoid ridge was performed. Brain relaxation
was obtained by opening of the lamina terminalis. The
Sylvian fissure was opened, and a cortical incision was
made in the sulcus circularis insulae parallel to the M 1
and M2 segments. The dissection was carried more
deeply, the fimbria hippocampi incised, and the P2 and
P3 dissected. This yielded a good exposure of the bilobed, partially fusiform aneurysm at the junction of
P2 and P3, as illustrated in Fig. 23. The proximal P2
was temporarily clipped for 25 minutes, and the
aneurysm occluded with application of multiple clips.
All important neighboring vessels were preserved, except for a small branch to the temporal base originating from the dome of the aneurysm.
Postoperative course and follow-up angiography:
The postoperative course was uneventful, except for an
infection of the bone plate necessitating its removal.
Follow-up angiography displayed an occlusion of the
aneurysm, with preservation of important vessels except for the right temporo-occipital artery (Fig. 24a).

Fig. 22. Case 6: LP, 39-year-old female. (a) AP view. (b) Lateral
view showing a bilobed fusiform aneurysm at the junction of the
right P2 and P3 segments

A CT scan revealed no evidence of infarction (Fig.


24b), despite the relatively prolonged temporary clipping (25 minutes) and the known occlusion of the
temp oro-occipital artery. The patient was discharged
in good condition on October 4,1997. The bone plate
will be replaced in 6 months' time.
Comment. The trans-Sylvian, transcortical, transventricular approach allows exposure of the proximal
part of the P2 for temporary clipping and may be used
profitably in the management of P2- P3 aneurysms,
even large ones, such as the one presented here. It is

137

Posterior Circulation Aneurysms

Fig. 24. (a) Postoperative angiography, AP view, showing occlusion


of the aneurysm but also no opacification of the occipitotempal artery, in spite of its apparent preservation at surgery. (b) Postoperative CT scan with no evidence of ischemia, correlating with normal
neurological status

Fig. 23. Artist's drawing showing operative procedure and findings.


After a pterional craniotomy, the aneurysm was exposed through a
transcortical transventricular transchoroidal fissure approach and
occluded with multiple clips

noteworthy that no neurologic sequelae resulted from


prolonged temporary occlusion of the peA. The risk
associated with protracted temporary clipping has
been discussed elsewhere [25, 36].

Patients and Results


From January 1993 to October 1997, 98 patients
with posterior circulation aneurysms were treated in
the Department of Neurosurgery of the University

138

Y. Yonekawa et al.

Table 2. Posterior Circulation Aneurysms Surgically Treated (1993-1997) - 60 Consecutively Operated Patients - Results (3 Months)
GR
Basilar head
ruptured
unruptured
Basilar-SCA
ruptured
unruptured
Basilar trunk
ruptured
unruptured
PCA-PI
ruptured
unruptured
PCA-P2-P3
ruptured
unruptured
VA-PICA
ruptured
VA-BA dissection
ruptured
Total

MD

SD

VS

20
16
4

15 (I: 5 @., II 4, III 2 @, IV 4 @)


3*

7(I:l,II4 @,III2)
1*

1 (II)
I

3
2

I (II)
2*

I (III)
I

17

14(I:3, 114 @,III5 @,IV2 @.)

2 (I, III)*

60

49 (82%)

I (III) @

3
I (III)

2 (III, IV) ++

17

1 (III .) +

1 (IV) @

1 (IV) +

1 (IV) @

I (IV)

3
I (IV)*
2 (3%)

2 (3%)

3 (5%)

4 (7%)

SCA Superior cerebellar artery; PCA posterior cerebral artery; VA vertebral artery; PICA posterior inferior cerebellar artery; BA basilar artery;
GR good recovery (Glasgow outcome scale); MD mildly disabled; SD severely disabled; VS vegetative state; D death; I-IV grading after
WFNS world federation of neurological surgeons; * coating; + proximal ligation or trapping; symptomatic vasospasm; @ hydrocephalus.

Hospital Zurich. There were 36 men and 62 women,


ranging in age from 18 to 76 years (mean 49). Sixty
patients underwent neurosurgical treatment, including
four patients in whom endovascular treatment had
failed. There was only one giant aneurysm (a PCA
aneurysm 2.5 cm in diameter), all others were less than
1.5 cm in diameter. Fifty-one (85%) of these 60 patients had ruptured aneurysms and were operated
upon, mostly in the acute stage, by the senior author
(YY), within three days of rupture. Complete clipping
was performed in 50 cases (83%), coating in 5 cases
(8%), and ligation of the parent artery or trapping in
5 patients (8%). Twenty-four patients underwent
endovascular treatment by an interventional neuroradiologist (Prof. A. Valavanis), including 3 cases in
which previous attempts of surgical occlusion had
failed. Fourteen patients received neither surgical nor
endovascular treatment because of poor neurological
grade (WFNS Grade V) or other medical problems.
The results of surgical treatment of 60 consecutive
cases, assessed according the Glasgow Outcome Scale
at 3 months, are presented in Table 2. Eighty-two per
cent of the patients made a good recovery, and 7%
died. Among cases of ruptured aneurysms only, 78%
made a good recovery and 8% died. Three unfavorable
results (VS, D) in grade III were due to technical in-

sufficiency, as mentioned above in Case 5. Six unfavorable results (SD, VS, D) in grade IV resulted in one
case from a combination of vasospasm and technical
insufficiency, and in five cases from direct injury of the
initial bleeding. Symptomatic vasospasm occurred in
7 cases (13.7%) and communicating hydrocephalus
necessitating a ventriculoperitoneal shunt in 10 cases
(19.6%).
Discussion

Improvements in microsurgical technique, the development of skull base surgery, and advances in the
understanding of the microsurgical anatomy of the
vertebrobasilar arterial territory have made it possible
to treat ruptured aneurysms of the posterior circulation in the acute stage, as has been done earlier with
aneurysms of the anterior circulation.
We consider surgery in the acute stage of SAH to be
necessary, as the mortality during the first 48 hours
after an aneurysmal rupture in the posterior circulation has been reported to be significantly higher than
that after an aneurysmal rupture in the anterior circulation [9, 16, 32]. Several authors have recently reported favorable results for the acute surgical management of ruptured aneurysms in the posterior

139

Posterior Circulation Aneurysms

circulation, comparable to those obtained with aneurysms in the anterior circulation. Lang and Galbraith,
in 1993 [15], reported a series of 121 patients with
posterior circulation aneurysms, of whom 97 presented
with SAH; the overall management mortality was
30%, and the operative mortality was l3%, comparable to results obtained with anterior circulation aneurysms. The larger series of Peerless et al. included 206
patients [25] who underwent early surgery, including
cases of basilar head aneurysms managed through a
subtemporal approach; 82% of patients made a good
or excellent recovery, and 9.7% died. In the 146 cases
of Nukui et al. [23] 76% made a good recovery and
12% died. These authors stressed that the results were
better in patients less than 65 years old, and aggressive surgical treatment in the acute stage in patients
over 65 years old with an impairment of consciousness
due to hydrocephalus. Our results agree with those
reports. The figures we obtained in this series for the
frequency of complicating symptomatic vasospasm,
and for the frequency of hydrocephalus, were l3.7%
and 19.6%, respectively. These are to be compared
with the 17.5% and 9% that we reported previously
[42] in our series of 150 consecutive cases of ruptured
aneurysms.
It should be emphasized that deliberate planning of
the operative procedure, based on a careful evaluation
of the angiographic findings in relation to neighboring
bony structures, is mandatory for successful surgical
management of posterior circulation aneurysms. Furthermore, it should be pointed out that results as good
as those presented may be obtainable only in a limited
number of institutions that treat many SAH patients,
as these aneurysms are rather infrequent, and trained
hands and the associated infrastructure are prerequisites for the success of surgical management.
The role of endovascular treatment in the management of aneurysms, and particularly of ruptured
aneurysms in the acute stage, seems highly promising
but still remains to be established [19, 22, 26]. We
consider this form of treatment to have a largely auxiliary role in current management.

Acknowledgments
This work could not have been accomplished without the good
cooperation of the department of neurora-diology (Prof. A. Valavanis), University Hospital, Zurich.
The authors are indebted also to Ms Frick, Mrs Schurter and
Mr. Stillhard for their assistance.

After the submission of the manuscript, we reported a new


approach to aneurysms of the P2-P3 junction, a supracerebellar
transtentorial approach in the sitting position. This is a further option for aneurysms in this difficult locatiion. We have used this
approach successfully in two cases of ruptured P2-P3 junction
aneurysm in the acute stage.

Reference
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infratentorial supracerebellar approach: technical note and summary ofresults. Kitakanto Med J (SI): 15-22

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Acta Neurochir (1999) [Suppl]72: 141-156


SpringerVerlag 1999

Surgical Strategies for Giant Intracranial Aneurysms*


M. T. Lawton! and R. F. Spetzler2
1 Department
2 Division

of Neurological Surgery, University of California, San Francisco, California


of Neurological Surgery, Barrow Neurological Institute, Mercy Healthcare Arizona, Phoenix, Arizona

Summary
Untreated giant intracranial aneurysms have a dismal natural
history as a result of hemorrhage, cerebral compression, and throm
boembolism. The poor prognosis of patients with giant aneurysms
therefore warrants aggressive treatment. A surgical approach is
chosen to maximize the operative exposure of the aneurysm and de
pends mainly on the aneurysm's location. Once exposed, vascular
control of the aneurysm is required not only to manage an intra
operative rupture, but also to collapse the aneurysm, to increase
working space, and to improve visualization of the anatomy. Hypo
thermic circulatory arrest may be indicated in select patients with
complex posterior circulation aneurysms. Direct clipping of giant
aneurysms, with meticulous preservation of parent and branch ar
teries, is the preferred method of occlusion. Unclippable aneurysms
require alternative techniques (e.g., trapping, parent artery occlu
sion, excision, and aneurysmorrhaphy) that compromise parent ar
teries and may require revascularization to restore adequate cerebral
blood flow. Giant aneurysms are complex lesions that demand thor
ough surgical planning, individualized strategies, and a multi
disciplinary effort in specialized neurovascular centers.
Keywords: Giant aneurysm; hypothermic circulatory arrest;
revascularization; subarachnoid hemorrhage.

Introduction
Although giant aneurysms are rare lesions, their inherent anatomical complexity and the technical difficulty of their surgical treatment make them a common
topic of analysis. What makes giant aneurysms so
challenging are the preoperative and intraoperative
decisions required to devise the best strategy for safe
management. Sound decisions depend on familiarity
with the spectrum of treatment options, mastery of the

* Printed with permission of Barrow Neurological Institute

techniques required in surgery, and experience. Therefore, this review presents the critical elements of the
surgical strategies for giant intracranial aneurysms,
derived from an experience with more than 250 surgical patients.

Clincal Materials and Methods


Patient Population and Presentation

By definition, giant intracranial aneurysms measure more than 2.5


cm in diameter [31]. Between 1980 and 1997, the authors treated 262
patients with giant aneurysms (mean age, 53 years; range, 4 to 78
years). As in most series [24, 36, 38], females predominated. Giant
aneurysms represent 3 to 5% of all cerebral aneurysms in most gen
eral neurosurgical populations [36, 38, 51], but in tertiary referral
centers the incidence is approximately doubled (6% in this series).
One third of patients presented with subarachnoid hemorrhage
(SAH), with HuntHess [20] grades distributed more toward lower
grades: 21% were HuntHess grade I; 31% were grade II; 27% were
grade III; 15% were grade IV; and 6% were grade V. Fisher [11]
computed tomography (CT) grades were distributed more toward
higher grades, with two thirds of the patients having thick sub
arachnoid blood (grades III and IV).
A third of the patients exhibited symptoms and signs of mass effect
and neural compression that reflected the location of the aneurysm.
In the anterior circulation, giant aneurysms produced pain and dys
function of extraocular movement and vision. Those in the posterior
circulation produced lower cranialnerve dysfunction, bulbar palsy,
and limb weakness.
The remaining third of the patients presented with incidentally
diagnosed giant aneurysms or with symptoms of distal thrombo
embolism, including transient ischemic attacks and stroke. Symp
toms leading to the diagnosis of an incidental giant aneurysm
included headaches, seizures, syncope, sinusitis, epistaxis, head
trauma, confusion, and stroke (in an unrelated vascular territory).
Screening magnetic resonance (MR) imaging in patients with a sig.
nificant family history of aneurysms led to the diagnosis in 7% of
patients.

142
Diagnostic Evaluation

High-quality, four-vessel cerebral angiography is essential in the


preoperative evaluation of patients with giant aneurysms. Angiography provides detailed information about the aneurysm's location,
anatomy, adjacent branch vessels, collateral circulation, and distal
cerebral perfusion. Angiography only shows luminal filling, which
may not represent the true size of the aneurysm. Layers of laminated
thrombus frequently make giant aneurysms much larger than they
appear on angiography alone. CT scans often demonstrate a calcified, eggshell border that defines the true diameter of the aneurysm.
MR images demonstrate a signal void within a patent lumen. Alternating high- and low-intensity signals on Tl-weighted images correspond to hemosiderin and methemoglobin within the layers of
thrombus. These preoperative studies are used to determine whether
the aneurysm is amenable to direct clipping and which surgical
approach would optimize exposure.
Two-thirds of the giant aneurysms in this patient series were located in the anterior circulation, and one-third were located in the
posterior circulation. Of the anterior circulation aneurysms, the
aneurysms of the middle cerebral artery (MCA) were the most common (25%). Aneurysms on the ophthalmic segment of the internal
carotid artery (ICA; including the ophthalmic artery, superior hypophyseal artery, and paraclinoid aneurysms) accounted for another
25%. In decreasing order of frequency, other anterior circulation locations were the cavernous ICA (15%), anterior cerebral artery
(ACA; 13%), ICA bifurcation (8%), communicating segment ofICA
(8%), and petrous ICA (3%).
In the posterior circulation, the basilar artery apex was the most
common giant aneurysm location. Seventy percent of these aneurysms were at the basilar tip, PI segment of posterior cerebral artery
(PCA), or the superior cerebellar artery (SCA). Midbasilar artery
aneurysms (18%) and vertebral artery aneurysms (including vertebrobasilar junction and posterior inferior cerebellar artery (PICA)
aneurysms; 12%) were less commonly encountered.
Preoperative Management

Patients who presented with SAH were managed using the same
principles and protocols that have been established for other patients
with SAH [4]. Blood pressure was controlled carefully to minimize
the risk of rupture. Ventriculostomy with cerebrospinal fluid drainage was used to treat patients with Hunt and Hess grades IV and V,
and measurements of intracranial pressure (ICP) were used to guide
surgical decisions [5]. ICP elevations were managed aggressively
with conventional methods. Surgery was performed within 24 hours
of presentation in suitable patients.
Surgical Treatment

With the exception of three frontal-interhemispheric approaches


for ACA aneurysms, a pterional or orbitozygomatic approach was
used in patients with anterior circulation giant aneurysms. The orbitozygomatic approach was only used in 10% of these cases, but its
use has increased in recent years.
A wider variety of approaches was used for giant aneurysms of the
posterior circulation. A pterional approach was used in a third of
patients (35%); the orbitozygomatic approach was used in a third of
patients (37%); and the remaining third underwent either a far-lateral approach or one of the transpetrosalfcombination approaches
(28%).
Overall, direct clipping was accomplished in 62;(, of patients. Alternative methods of excluding the aneurysm from the circulation
were required in the remaining patients. Aneurysm trapping was
performed in 20% of patients, many of which were on the cavernous

M. T. Lawton and R. F. Spetzler


ICA. Parent artery occlusion, either proximally or distally, was performed in 7% of patients. Aneurysm excision with primary reanastomosis was performed in 5% of patients. Four percent of patients
underwent aneurysmorrhaphy, and 2% of patients had their aneurysms wrapped in a reinforcing sling. Revascularization procedures
were performed in 30% of patients.
Hypothermic circulatory arrest [48] was used in the treatment of
43 giant aneurysms.
Postoperative Management

Postoperatively, all patients underwent angiography to confirm


complete elimination of the aneurysm and patency of bypass grafts.
Treatment cannot be considered complete until the aneurysm is
eliminated. Residual aneurysm filling is treated with direct surgical
or, occasionally, with endovascular techniques until the aneurysm is
obliterated. Graft occlusions are treated emergentIy to re-establish
patency. Patients with SAH are managed according to established
protocols with hypervolemia, hypertension, and hemodilution for 2
weeks after hemorrhage or until the symptoms resolve [22].

Results
Patient Outcome
The surgical mortality of this series was 7%. Many
of these patients presented with poor Hunt-Hess
grades after SAH. The treatment-associated neurological morbidity rate was 11 %.
Pre- and postoperative neurological function was
evaluated using Glasgow Outcome Scale (GOS) scores
[21]. At late follow-up, 85% had an excellent or
good outcome. Specifically, 66% had an excellent outcome (GOS 1), 18% had moderate disabilities (GOS
2), 7% had severe disabilities (GOS 3), and 2% were
vegetative. The mean length of follow-up was 2.2
years.
As expected, outcome for patients who presented
with SAH correlated with Hunt-Hess grade. As a
group, the SAH patients did worse than patients
with other presentations (i.e., compressive symptoms,
thromboembolic symptoms, and incidental aneurysms). Outcomes tended to be better in patients with
giant aneurysms in the anterior circulation. Eightynine percent of these patients had excellent or good
outcomes compared to 74% of the patients with posterior circulation aneurysms. The technique of aneurysm obliteration did not correlate with outcome.

Discussion
Rationale for Surgical Treatment of Giant Aneurysms
The natural history of untreated giant intracranial
aneurysms is dismal, due to a high risk of hemorrhage,

143

Surgical Strategies for Giant Intracranial Aneurysms

progressive neurological deficits from cerebral compression, and distal thromboembolism causing stroke
and death [23, 33, 34, 37, 38]. The mortality rate of
untreated giant aneurysms reported by Peerless et al.
was 68% after 2 years and 85% after 5 years [37]. All
survivors had marked neurological dysfunction. Michel [34] reported a 100% mortality rate at 2 years in
untreated patients. Seventy-five percent of Kodama
and Suzuki's [23] untreated patients died of SAH during their hospitalization. Therefore, the poor prognosis
of untreated giant aneurysms warrants aggressive
treatment.
In contrast to the natural history of giant aneurysms, surgical outcomes in large patient series have
been excellent to good, ranging from 61% to 86%.
Surgical mortality rates have ranged from 5% to 22%
(Table 1). When these surgical results are compared
with the poor outcome associated with the natural
history of untreated giant aneurysms, it is apparent
that an aggressive surgical posture is appropriate.
The objective of treatment is to eliminate the risk of
neurological impairment resulting from hemorrhage,
cerebral compression, or thromboembolism. Surgical
strategies are therefore designed to exclude the aneurysm completely from the circulation, to maintain
adequate cerebral blood flow, and to decompress vital
neural structures [29].
Elements of Surgical Strategies for Giant Aneurysms
Surgical approach: anterior circulation giant aneurysms. Selection of the approach that provides the

widest exposure and most direct access to the aneurysm is the first and most important surgical decision,
and aneurysm location is the primary factor that influences this decision.
F or anterior circulation giant aneurysms, selection
of approach amounts to deciding whether an orbitozygomatic osteotomy will enhance the routine pterional exposure enough to justify its use [1, 9, 39, 40].
The pterional craniotomy is the standard approach for
these aneurysms and requires extensive drilling of 1.
the lesser wing of the sphenoid bone medial to the superior orbital fissure, 2. the bony ridges of the orbital roof, 3. the inner table of the inferior frontal bone
over the superior orbital rim, and 4. the squamosal
portion of the temporal bone inferiorly to the floor
of the middle fossa. The removal of bone around
the pterion flattens this corridor and creates space
under the frontal and temporal lobes and Sylvian

Table 1. Comparison of Outcomes in Surgical Series of Giant


Intracranial Aneurysms

Author/reference

Sundt [49]
Peerless et al. [37]
Hosobuchi [17]
Ausman et al. [3]
Kodama and Suzuki [23]
Symon and Vajda [50]
Yasargil [52]
Heros [14]
Lawton and Spetzler [30]

Total patients

315
305
82
62
49
36
30
28
171

Outcome
excellent/
good

fair/ dead
poor

80%
67%
84%
84%
61%
86%
67%
82%
87%

6%
22%
9%
11%
16%
6%
23%
7%
8%

15%
11%
7%
5%
22%
8%
10%
5%
5%

fissure. This exposure is usually adequate for giant


aneurysms on the MCA and communicating segment
ofICA.
An orbitozygomatic approach expands the exposure
of a pterional approach by removing the orbital rim,
orbital roof and lateral wall, and zygomatic arch. Five
osteotomies are cut with a reciprocating saw: 1. across
the zygomatic root; 2. across the maxillary bone, cutting from inferior orbital fissure to the anterior-inferior
aspect of the zygomatic arch; 3. along the medial
orbital roof, just lateral to the supraorbital notch; 4.
across the posterior orbital roof; and 5. across the lateral orbital wall, connecting the previous cut with the
inferior orbital fissure. After the orbitozygomatic unit
has been removed as a single piece, additional bone is
removed over the orbital apex around the superior
orbital fissure. The orbitozygomatic approach creates
a significant amount of additional space under the
frontal and temporal lobes and Sylvian fissure. A dural
flap based over the pterion, when tented forward with
tacking sutures, gently depresses the globe to widely
expose the Sylvian region.
The extra space provided by an orbitozygomatic
osteotomy is particularly important for anterior circulation giant aneurysms in three situations: for skull
base techniques, bypass procedures, and an upward
viewing angle. First, work along the skull base typically requires additional bone removal with a drill,
which is greatly facilitated by the additional working
room of the orbitozygomatic approach. Maneuvers
such as anterior clinoidectomy, posterior clinoidectomy, and ICA exposure in Glasscock's triangle are
safer and technically easier through this approach.
Therefore, the orbitozygomatic approach is indicated

144

for proximal giant ICA aneurysms (ophthalmic artery,


superior hypophyseal artery, and paraclinoid aneurysms) that may require anterior c1inoidectomy, and
for cavernous and petrous ICA aneurysms that may
require drilling in Glasscock's triangle.
Second, deep bypass procedures typically require
the maximum space in order to facilitate the anastomosis. Anastomoses to the petrous ICA or the supraclinoid ICA are deep in the wound, and the additional
maneuvering room with the orbitozygomatic approach
enables easier bites of vessel wall and improved results
overall. Therefore, petrous and cavernous ICA giant
aneurysms will require an orbitozygomatic approach
for this reason in addition to the skull base drilling
discussed above. In addition, MCA aneurysms that
require reanastomosis of the parent artery after resection of the aneurysm also may require an orbitozygomatic approach.
Third, some giant aneurysms in the anterior circulation need an upward viewing angle for the relevant
anatomy to be visualized. For example, aneurysms of
the anterior communicating artery or the ICA bifurcation typically project upward, and dissection is performed beneath the aneurysm. Additional exposure
helps minimize the amount of brain retraction or, in
the case of anterior communicating artery aneurysms,
resection of the gyrus rectus.
The selection of an approach for giant aneurysms of
the anterior circulation, therefore, reduces to a decision about orbitozygomatic osteotomy. The additional
risks of this component of the approach include
periorbital bruising, pulsatile enophthalmos, frontal
nerve injury, orbital entrapment, diplopia from extraocular muscle or nerve injury, and blindness. The risk
of these complications is low, making the decision to
incorporate an orbitozygomatic approach an easier
one.
One additional approach is rarely indicated for
giant ACA aneurysms, namely, the interhemispheric
approach through a frontal or bifrontal craniotomy.
This approach was used for distal ACA aneurysms and
for revascularizing the ACA territory distal to the
aneurysm.
Surgical approach: posterior circulation aneurysms.
Four categories of surgical approaches are used for
giant aneurysms of the posterior circulation: 1. the
orbitozygomatic approach, 2. one of the transpetrosal
approaches, 3. the far-lateral approach, and 4. one of
the combination approaches. Selection of approach is
directly related to aneurysm location within the poste-

M. T. Lawton and R. F. Spetzler

Fig. 1. Selection of surgical approaches to posterior circulation


giant aneurysms. (a) Aneurysms of the upper two-fifths of the basilar
artery are typically exposed with an extended orbitozygomatic
approach, aneurysms of the middle one-fifth with a transpetrosal
approach, and aneurysms of the lower two-fifths of the basilar artery
and intradural vertebral arteries with a far-lateral approach. (b)
Giant aneurysms that straddle these zones or extend across multiple
zones may require one of the combination approaches [i.e., a combined supra- and infratentorial approach or a combined far-lateral
supra- and infra tentorial approach ("combined-combined
approach")]. With permission from Barrow Neurological Institute

rior circulation. If the basilar artery is divided conceptually into fifths [26], then the posterior circulation can
be considered as three distinct zones: an upper basilar
zone (upper two-fifths of the basilar artery), a midbasilar zone (middle fifth of the basilar artery), and
a lower vertebrobasilar zone (lower two-fifths of the
basilar artery and the intradural segment of the vertebral arteries). Giant aneurysms located in the upper
basilar zone may be accessed through the orbitozygomatic approach; those located in the midbasilar zone
may be accessed through a transpetrosal approach;
and those located in the lower vertebrobasilar zone
may be accessed through a far-lateral approach (Fig.
la) [26]. Giant aneurysms that straddle different zones
may require one of the combination approaches (Fig.

145

Surgical Strategies for Giant Intracranial Aneurysms

d
Fig. 2. (a)The extended orbitozygomatic approach uses a pterional craniotomy and removes the orbitozygomatic unit as a single piece. Osteotomies are made across the root of zygoma, across the malar eminence to the inferior orbital fissure, through the orbital roof lateral to the
supraorbital nerve, across the posterior orbit and pterion, and down to the inferior orbital fissure. (b) The view of the mid basilar artery is obstructed by the anterior and posterior clinoid processes and dorsum sella. (c) Drilling away these bony obstacles creates a window in the upper
clivus through which the mid basilar artery can be visualized. (d) Additional inferior exposure of the basilar artery enables the aneurysmal neck
to be dissected and defined, working along the axis of artery. With permission from Barrow Neurological Institute

Ib). For example, an aneurysm involving the upper


and middle zones can be exposed adequately through
a combined supra- and infratentorial approach. An
aneurysm involving the middle and lower zones can be
adequately exposed through a combined far-lateral
supra- and infratentorial approach ("combinedcombined approach"). This scheme is a useful guide to
selecting the optimal approach for a giant posterior
circulation aneurysm from among the list of possible
approaches.

Several modifications to the orbitozygomatic


approach extend its exposure to facilitate the surgical
management of giant posterior circulation aneurysms,
particularly those located down from the basilar artery
apex (Fig. 2) [26]. Additional inferior exposure is
gained by removing three intradural bony obstacles:
the anterior clinoid process, the posterior clinoid process, and the dorsum sella. Removal of the anterior
clinoid process does not directly increase exposure of
the basilar artery, but the viewing angle down the

146

M. T. Lawton and R. F. Spetzler

~~""""""""'~#-=Transcochlear

Translabyrinthlne
Retrolabyrinth.ne

Fig. 3. The three types of presigrnoid transpetrosal approaches are


shown. The retrolabyrinthine approach preserves the semicircular
canals and cochlea but provides limited exposure anteriorly where
the neck of a midbasilar aneurysm is located. Therefore, exposure
through a retrolabyrinthine approach is frequently inadequate for
these lesions. A translabyrinthine or transcochlear approach is
indicated, despite the sacrifice of hearing and risk to facial nerve
function. With permission from Barrow Neurological Institute

basilar artery is often obstructed by this bony process.


Removal of the structures that form the upper clivus,
namely, the ipsilateral posterior clinoid process and
dorsum sella, exposes the second fifth of the basilar
artery. The upper clivus is free of cranial nerves or
vascular structures, making its removal safe and quick.
Before entering the cavernous sinus, the third cranial
nerve, which is the cranial nerve most at risk during
drilling, runs just inferior and lateral to the posterior
clinoid process. Other cranial nerves and vascular
structures are located in the cavernous sinus lateral to
the area of clival resection. Preservation of the medial
dural wall of the cavernous sinus avoids entry into
the cavernous sinus and protects the structures within
it. Removal of the upper clivus opens a window to
the anterior surface of the basilar artery, through
which the aneurysm can be dissected. The microscope is angled to view along the axis of the basilar
artery. In contrast to the trans petrosal approaches, the
only bone removed in the extended orbitozygomatic
approach is the upper clivus; the petrous bone is left
intact.
The transpetrosal approaches are categorized into
three variations: retrolabyrinthine, translabyrinthine,
and transcochlear (Fig. 3) [16, 18, 19,25,32,45]. The
retrolabyrinthine approach removes temporal bone
between the semicircular canals anteriorly and the
posterior fossa dura on the posterior aspect of the
temporal bone. The semicircular canals are skeleton-

ized, but not violated, to maximize this working space.


The translabyrinthine approach removes the semicircular canals, which causes loss of hearing. Their removal increases the exposure anteriorly to the internal
auditory canal. The transcochlear approach requires
the facial nerve to be dissected from its bony canal and
transposed to gain access to the cochlea for its removal. This approach enables almost complete removal of the petrous bone, with maximum exposure of
the brain stem and clivus. The three types of temporal
bone dissections represent a graduated increase in the
amount of petrous bone resected with a corresponding
increase in anterior exposure. Anyone of them can be
used to access a giant aneurysm on the middle zone of
the basilar artery. The price of increased surgical exposure with more radical petrosectomy is progressively
greater sacrifice of function in the seventh and eighth
cranial nerves. Therefore, selection of the most suitable transpetrosal approach depends largely on the
patient's preoperative neurological condition and his
or her willingness to lose function in these cranial
nerves.
The far-lateral approach, utilized for giant aneurysms in the lower vertebrobasilar zone, is a lateral
suboccipital craniotomy with three important modifications: 1. the arch of C I is removed laterally to the
sulcus arteriosus of the vertebral artery; 2. the bony
rim of the foramen magnum is resected laterally to the
occipital condyle; and 3. the posterior half to twothirds of the condyle is drilled away [13, IS, 43, 46].
This extensive bone removal opens a corridor to the
anterolateral brain stem, vasculature, and cranial
nerves. Crucial to this approach is patient positioning
in a "park bench" position with the head flexed anteriorly, rotated laterally, and flexed laterally. The basilar artery is then aligned vertically (perpendicular to
the floor), enabling the surgeon to view up the axis of
the vertebral and basilar arteries.
With giant posterior circulation aneurysms that
straddle the above zones, combination approaches
provide the added exposure to visualize the lesion
adequately [25]. The combined supra- and infratentorial approach joins the subtemporal and transpetrosal
exposures, and the far-lateral combined supra- and
infratentorial approach adds to them the far-lateral
exposure [6]. There are three essential components of
the combination approaches. First, one of the temporal bone dissections described above is performed.
Second, a supra- and infratentorial craniotomy is
made that crosses the transverse sinus. Third, the

Surgical Strategies for Giant Intracranial Aneurysms

tentorium is divided to connect the supra- and infratentorial compartments. Extensive exposure of the
medial petrous and clival regions and associated neurovascular structures is obtained with minimal brain
retraction.
Vascular control of giant aneurysms. Once the surgical approach has been performed and the dura opened,
the next concern is vascular control of the aneurysm.
Vascular control is a basic tenet of aneurysm surgery
because it enables the surgeon to manage an intraoperative rupture. The fact that only a third of giant
aneurysms present with subarachnoid hemorrhage
may appear to lessen the importance of vascular control of these aneurysms, but it is equally important for
other reasons. The aneurysmal mass necessitates
maneuvers that decompress it and reduce it. This size
reduction, whether by collapsing the aneurysm or debulking it, enables visualization of the parent arteries
and aneurysm neck, which is essential to the repair.
Vascular control in the anterior circulation is usually easy to obtain; temporary clips can be placed
proximal and distal to the aneurysm to eliminate blood
flow through the parent artery. Several locations can
be difficult, however, including the clinoidal and ophthalmic segments ofICA. There are several options for
proximal control. I. The cervical ICA can be exposed
through a separate neck incision with temporary arterial ligation. 2. The petrous ICA can be exposed
through Glasscock's triangle on the middle fossa floor.
The artery can then be occluded temporarily with clips
or with temporary extraluminal balloon compression
with a Fogarty catheter inserted in the carotid canal
between the bone and the artery. 3. The clinoidal
segment of the ICA can be exposed and temporarily
occluded with a clip after the anterior clinoid process
has been removed. The final option is endovascular
balloon occlusion of the cavernous ICA with a catheter threaded into position through a femoral arterial
puncture.
Each of these four options has distinct advantages
and disadvantages. Proximal control via the cervical
ICA requires a visible incision of the neck, but it is the
quickest and easiest method. Drilling Glasscock's triangle is elegant because there are no external signs of
this exposure, but the procedure can be time-consuming. Anterior clinoidectomy is easier to perform, but
often the giant aneurysm obscures access to this region
and incising the medial portion of the distal dural ring
can be difficult. Endovascular balloon occlusion is easy
for neuro-interventionalists to perform and enables

147

suction decompression of the aneurysm. Typically,


however, it requires heparin while the catheter is in
position, with the obvious risk of hemorrhagic complications. For these reasons, cervical ICA exposure is
usually the method of choice for proximal control of
proximal ICA giant aneurysms.
Vascular control in the posterior circulation is considerably more difficult because the middle portion of
the basilar artery is so inaccessible. With basilar tip
aneurysms, proximal control is gained by exposing a
segment of basilar artery below the superior cerebellar
arteries and placing a temporary clip. Clip placement
is often a deep and difficult reach, and the coil of the
clip sometimes occupies valuable space in the region
where the permanent clip needs to be applied. Furthermore, complete distal control of these aneurysms
would require clip occlusion of the posterior cerebral
and superior cerebellar arteries, which is rarely practical. Fortunately, a temporary clip on the proximal
basilar artery often softens the aneurysm enough to
proceed with clipping.
Similar difficulties apply to distal control of vertebral and lower basilar artery giant aneurysms. While
proximal control is readily gained with a temporary
clip on the vertebral artery (or arteries) as it pierces the
dura, distal control is typically obscured by the aneurysm or simply too deep to reach. Again, one hopes
that a temporary clip placed proximally on the vertebral artery will soften the aneurysm enough to proceed
with clipping.
Other alternatives for control of upper basilar artery
aneurysms include endovascular balloon occlusion of
the basilar artery and hypothermia-induced circulatory arrest. Endovascular balloon occlusion is only
suited to proximal control of a basilar apex aneurysm.
Distal control of a lower basilar or a vertebral artery
aneurysm is usually not possible endovascularly because the upper basilar artery is poorly accessed from a
retrograde direction, and access from an anterograde
direction requires traversing the aneurysm. A concern
with endovascular balloon occlusion of the basilar artery, in the absence of deep hypothermia and its added
cerebral protection, is a brain stem infarction from
prolonged perforator occlusion.
Hypothermic circulatory arrest is the extreme
method of vascular control. For the reasons discussed
above, it is not typically indicated for anterior circulation giant aneurysms and is only indicated for complex
posterior circulation aneurysms that cannot be treated
by conventional techniques. Hypothermic circulatory

148

M. T. Lawton and R. F. Spetz\er

Surgical Strategies for Giant Intracranial Aneurysms

arrest provides complete vascular control, eliminates


the need for temporary clips, eliminates the risk of
rupture, and enhances cerebral protection. Disadvantages of the technique include femoral artery and vein
cannulation, which can injure these vessels; heparinization, which increases risk of hemorrhagic complications; trauma to red blood cells and platelets from
the bypass pump [10]; slowing of the coagulation cascade due to hypothermia [7]; hemodilution of coagulation factors [35]; risk of ischemic brain injury; and
expense. The successful use of the technique therefore
requires that the period of circulatory arrest be limited
to the final period of aneurysm dissection and clip application, and that meticulous attention be given to
intraoperative hemostasis, with close surveillance of
the patient's clotting mechanisms. Steps taken to treat
this hypocoagulable state include heparin reversal with
protamine, whole blood and platelet transfusions,
fresh frozen plasma, calcium chloride, and restoring
normothermia at a carefully controlled rate (0.20.5 DC/min).
In our experience with hypothermic circulatory
arrest in 60 patients (62 procedures), the treatmentassociated morbidity was 13% and the surgical mortality was 8% (unpublished data) [28]. Although seemingly high, the combined morbidity and mortality rate
of 21 % reflects discriminating patient selection and the
complexity of aneurysms referred to a specialized cerebrovascular center, in addition to the inherent hazards of the technique. Again, the potential morbidity
associated with circulatory arrest stipulates that it be
used only when vascular control is not possible with
routine surgical techniques.
Once achieved, vascular control not only enables the
surgeon to deal with intraoperative hemorrhage but
also permits reduction of the aneurysmal mass, which
is so critical when dealing with giant aneurysms. Reducing the aneurysm's mass increases working space
and improves visualization of the configuration of the
aneurysm in relation to the anatomy. Without the
normal arterial blood pressure and flow, aneurysms
without intraluminal thrombus can be collapsed and
maneuvered to proceed with the repair. Aneurysms
with intraluminal thrombus cannot be collapsed easily,

149

but the aneurysm can be opened, thrombus removed,


and the repair can proceed (Fig. 4). The ultrasonic
aspirator is very effective for delicate removal of the
hardened thrombus, without the traction or manipulation of the aneurysm that would be applied by
piecemeal removal using cup forceps or pituitary rongeurs. Complete vascular control also enables resection of the aneurysm. Therefore, vascular control, by
whatever means necessary, creates valuable space required for clipping the aneurysm or making repairs by
alternative methods.
Implicit in this discussion of vascular control is the
necessity of intraoperative cerebral protection. Cerebral protection with barbiturates has become standard
in the intraoperative management of aneurysm patients, reducing the metabolic demands of neural cells
and extending the brain's tolerance to a decreased nutrient supply. Consequently, barbiturates help prevent
cerebral injury from the focal ischemia associated with
temporary occlusion of the parent vessel and dissection
of giant aneurysms [41, 42, 44, 53]. Patients receive
intravenous barbiturate (thiopental) titrated to achieve
electroencephalographic (EEG) burst suppression [47].
Barbiturates are most effective when administered before the period of temporary ischemia [42]. Intraoperative blood pressure is maintained mildly hypertensive,
especially during any temporary vessel clipping, to
enhance cerebral perfusion. Patients are monitored
with SSEPs to determine tolerance to vessel occlusion.
Surgical clipping of giant aneurysms. After the surgical approach is completed and vascular control of
the aneurysm is attained, the aneurysm is ready to be
excluded from the circulation - an objective best met
with clipping. Surgical clipping of a giant aneurysm,
like any other aneurysm, requires a favorable neck.
The vessel walls that form the aneurysm neck need to
be approximated in such a way as to close the aneurysm's lumen, preserve patency of parent arteries, and
preserve perforating arteries adjacent to the neck.
Saccular aneurysms that form at bifurcations or
branch arteries typically will have parent arteries with
an obvious flow trajectory. The neck parallels this flow
trajectory and, ideally, should be clipped along this
parallel. Giant aneurysm necks are often so wide that

Fig. 4. (a) A dolichoectatic aneurysm involving the intradural vertebral artery is shown compressing the brain stem and cranial nerves. (b) This
compressive mass is eliminated by opening the aneurysm and (c) removing thrombus with an ultrasonic aspirator. (d) The thrombectomy
proceeds until the lumen of the aneurysm is encountered. (e) Bleeding is controlled with Surgicel, and (f) the aneurysm walls are brought together with clips to reconstruct the parent-artery lumen. Note that the thrombectomy eliminates mass effect and generates the redundant vessel
wall for reconstructing the artery. With permission from Barrow Neurological Institute

150

any other clip placement would kink the parent artery


and compromise its patency. In contrast, fusiform or
dolichoectatic giant aneurysms have separate afferent
and efferent arteries and no intervening neck [2]. Clip
reconstruction of these aneurysms requires a recreation of the normal anatomy from an existing vessel
wall (Fig. 4). Clips are used to fashion a lumen that
connects afferent to efferent arteries while excluding
the wall of the aneurysm that appears abnormal. Such
a reconstruction requires the ability to design the reconstruction, a thorough knowledge of the adjacent
arteries to ensure that they are kept patent, and the
ability to apply the clips to complete it. These reconstructions demand the utmost creativity and caution.
The limitations of aneurysm clips need to be remembered when clipping giant aneurysms. One large
clip is often not the best choice because such a clip does
not contour the reconstruction. In addition, the closing
force of long clips is lowest at the tip, allowing the
aneurysm to fill where visualization is most difficult.
Similarly, aneurysm tissue in the heels of the blades
may keep the blades apart at the tip, again leaving residual filling of the aneurysm through the distal neck.
Several shorter clips (usually fenestrated clips) placed
serially across the aneurysm neck are often the better
choice because the reconstruction can be contoured.
Shorter clips have higher closing pressures throughout
the length of the blades, helping to occlude the entire
neck and to minimize clip slippage. Clips placed in
tandem need to be closely approximated to prevent
filling of the aneurysm through gaps between clips.
Tandem clips are applied working from the distal to
proximal neck. The distal neck is typically deepest in
the wound and more difficult to visualize, necessitating
that it be clipped first. The easier proximal portion of
the neck is clipped last.
Sometimes the neck of a giant aneurysm is so expansive that a clip reconstruction cannot be devised
initially, or the optimal clip simply cannot close the
aneurysm neck. A large clip placed across the body of
the aneurysm well above the neck may approximate
the walls of the aneurysm and enable subsequent clips
to close the aneurysm successfully. The initial clip is
placed high on the neck, leaving space for subsequent
clips to be applied below it in permanent position. The
secured dome also can be opened to decompress
the aneurysm and improve visualization during this
process.
The vessel wall of many giant aneurysms is thickened with fibrous tissue, atherosclerotic degeneration,

M. T. Lawton and R. F. Spetzier

calcification, and organized thrombus. Therefore, in


addition to the external caliber of the parent artery
that is apparent to the surgeon, the internal caliber of
the parent artery that is not apparent also must be
considered. Many times the greater risk in treating a
giant atherosclerotic aneurysm is not residual aneurysm but compromise of the parent artery lumen and
subsequent cerebral infarction. Consequently, clips are
placed high on the neck of such aneurysms to ensure
that lumenal plaque does not compromise blood flow.
Because calcified atherosclerotic necks can sometimes
crack during clip closure, the clip is released slowly and
under complete visualization. Because these aneurysms are susceptible to slippage of clips, the aneurysm
should be observed to ensure that the clips hold.
All important branches and perforating arteries are
inspected to confirm patency after an aneurysm has
been clipped, particularly behind the aneurysm where
visualization may not have been optimal before clipping. The tips of a clip can be a site of inadvertent
occlusion of perforators. The importance of careful
inspection of perforators cannot be overstressed. In a
review of the factors affecting patient outcome in
aneurysm patients treated with hypothermic circulatory arrest, perforator infarction correlated significantly with poor outcome. If visual inspection is not
satisfactory, then Doppler ultrasonography or intraoperative angiography should be considered. If intraoperative angiography is to be performed, then a
radiolucent operating table, a radiolucent headholder,
and a sterile groin site for arterial access need to be
planned preoperatively.
Alternative techniques of giant aneurysm occlusion.
Some giant aneurysms (more than a third of this patient series) cannot be clipped directly because of their
size, the lack of a discrete neck, or the technical difficulty associated with the dissection. Alternative techniques for these unclippable aneurysms include proximal vessel occlusion, distal vessel occlusion, trapping,
aneurysmorrhaphy, and excision of the aneurysm.
These techniques are inferior to direct clipping because
they sacrifice the parent artery and sometimes branch
arteries. Consequently, cerebral blood flow may be
compromised and patients are at risk for ischemic
complications. Alternative techniques are therefore
reserved for aneurysms that have failed attempts at
direct clipping. Revascularization procedures are often
an integral component of these alternative techniques.
Proximal or distal parent-vessel occlusion is best
suited for dolichoectatic aneurysms (Fig. 5). They

Surgical Strategies for Giant Intracranial Aneurysms

151

Fig. 5. (a) Some giant midbasilar artery aneurysms are too difficult to reconstruct with clips, and treatment is limited to parent-vessel occlusion.
(b) Blood flow to the distal basilar artery territory is augmented with a superficial temporal artery-to-superior cerebellar artery bypass in an
initial surgical stage. (c) The proximal or distal basilar artery is then clip-occluded during a second surgical stage. (d) Reduction of flow through
the aneurysm promotes thrombosis of its lumen, which enables thrombectomy to be performed during a third surgical stage. The dashed line
designates the extent of the thrombectomy. Note that treatment relieves mass effect on the brain stem and preserves distal cerebral blood flow.
With permission from Barrow Neurological Institute

152

M . T.Lawton and R. F. Spetzler

Fig. 6. (a) This giant middle cerebral artery aneurysm is amenable to resection with primary reanastomosis. (b) Proximal and distal control of
the aneurysm is obtained with temporary clips and the aneurysm is resected. The ends of the artery are mobilized by cutting their arachnoid
adhesions. (c) The artery is reanastomosed to reconstitute flow to Sylvian vessels. With permission from Barrow Neurological Institute

have separate afferent and efferent arteries, and no


clippable neck [2]. Dolichoectatic aneurysms are
thought to arise from arterial dissections that injure
intima. Intimal defects progressively enlarge the artery
to form fusiform aneurysms. Over time, extreme enlargement causes a dolichoectatic aneurysm to form.
Typically, these aneurysms are filled with organized
thrombus through which a serpentine lumen carries
blood flow. These lesions are best treated by changing
the blood flow through the aneurysm; complete elimination of the aneurysm does not appear to be indicated. Altering the hemodynamics with proximal or
distal clip occlusion of the parent artery promotes
thrombosis of the aneurysm lumen yet maintains flow
to important perforating arteries that originate from

the involved artery/aneurysm. Trapping such an


aneurysm would sacrifice these perforating arteries,
and clip reconstruction would be hampered by the
large volume of intraluminal thrombus. Whenever a
proximal or distal parent-artery occlusion is planned, a
revascularization procedure should be considered beforehand, particularly when collateral anatomy is
insufficient to compensate for the sacrificed parent
artery. After the aneurysm has thrombosed, debulking
the aneurysm to decrease its compressive effects also
should be considered.
Aneurysm trapping completely eliminates the aneurysm from the circulation. The segment of vessel sacrificed is minimized by applying the clips as close to the
aneurysm as possible. However, when dealing with gi-

153

Surgical Strategies for Giant Intracranial Aneurysms

Supraclinoid

.
"

v
\

ICAv.,~__

Ophth A.

Saph .
Vein
Graft

Ophth A.

STA

Fig. 7. Surgical approaches to revascularization of the anterior circulation. Overview showing the anterior circulation and common locations
for aneurysms. (a) The internal carotid artery ( ICA ) aneurysm at the skull base is trapped and revascularized with a cervical-to-petrous carotid
bypass with saphenous vein graft. (b) The cavernous ICA aneurysm is trapped and revascularized with a petrous-to-supraclinoid (C3-C5) carotid bypass with a saphenous vein graft or, alternatively, with a cervical-to-supraclinoid carotid bypass. (c) The supraclinoid ICA is trapped
and revascularized with a superficial temporal artery to middle cerebral artery (STA-MCA) bypass or, alternatively, with an STA-MCA bypass with a saphenous vein interposition graft. (d) The MCA aneurysm is trapped and revascularized with a double-barrel STA-MCA bypass
or, alternatively, with an anterior temporal artery-to-MCA in situ bypass. (e) The anterior cerebral artery (ACA) aneurysm is trapped and
revascularized with A2-A2 in situ bypass. ECA External carotid artery; saph saphenous; supraclin. a supraclinoid artery; ophth. a ophthalmic
artery; PCoA posterior communicating artery; Ant. Temp. A anterior temporal artery; ree. a recurrent artery of Heubner, and A CoA anterior
communicating artery. With permission from Barrow Neurological Institute

ant aneurysms, this segment of trapped parent artery


can be long. When important branch vessels are located along this segment, it is advisable to only occlude
proximally. Trapping is reserved for aneurysms that
have a good collateral blood supply or that can be revascularized. Examples of aneurysms at such locations
include the MCA, ACA, PI segment of the PCA, distal
vertebral artery, and PICA.
Aneurysm excision and aneurysmorrhaphy are alternatives for aneurysms of the MCA, ACA, and
PICA (Fig. 6) [12]. The Sylvian fissure, in particular,
provides ample room for performing the suturing. In
addition, there usually is enough redundant artery at
this location to enable the proximal and distal stumps

to be mobilized and brought together without undue


tension on the anastomosis. Primary reanastomosis of
the parent artery after resection of a giant aneurysm
can be difficult because the vascular tissues around the
neck can be atherosclerotic or too friable to suture. If
the base of the aneurysm involves a long segment of
artery, the aneurysm's dome can be resected partially
and the artery reconstructed with vessel wall around
the neck [8].
Revascularization procedures are frequently a part
of these alternative techniques that compromise the
parent artery [27]. A variety of bypasses is available for
anterior circulation aneurysms (Fig. 7). Aneurysms
located on the petrous ICA that are trapped proxi-

154

M. T. Lawton and R. F. Spetzler

./

-.-~

--

Fig. 8. Surgical approaches to revascularization of the posterior circulation. Overview showing the posterior circulation and common locations
for aneurysms. (a) The midbasilar artery is occluded proximally or distally to the aneurysm and revascularized with an superficial temporal
artery-to-posterior cerebral artery (STA-PCA) bypass or superficial temporal artery-to-superior cerebellar artery (STA-SCA ) bypass. (b) The
vertebral artery aneurysm is trapped (clips on proximal vertebral artery and at origin of posterior inferior cerebral artery ( PICA ) , and endovascular coils distally in vertebral artery) and revascularized with a PICA-PICA in situ bypass. Alternatively, an occipital artery-to-PICA bypass is shown. SCA Superior cerebellar artery; AICA anterior inferior cerebellar artery; vert. a vertebral artery. With permission from Barrow
Neurological Institute

mally in the neck and distally along the petrous carotid can be revascularized with a cervical-to-petrous
carotid bypass, remaining entirely extraduraL Intracavernous aneurysms can be trapped and bypassed
with a (C5) petrous-to-supraclinoid (C3) carotid bypass. The proximal clip is placed on the petrous carotid
artery, and the distal clip is placed on the ICA proximal to the ophthalmic artery to preserve the collateral
blood flow from the external carotid system. If the
petrous ICA is friable or difficult to anastomose, a
cervical-to-supraclinoid ICA saphenous-vein bypass is
another option.
Revascularization of the supraclinoid ICA and
MCA territory is achieved with a superficial temporal
artery (STA)-MCA bypass. A saphenous-vein interposition graft increases the caliber of the bypass vessel
and delivers blood flow deeper within the Sylvian
fissure. Alternatively, a "double-barrel" STA-MCA

bypass connects two branches of the STA to two


recipient vessels and can also increase flow from the
bypass if necessary. An in situ bypass with the anterior
temporal artery anastomosed side-to-side to the MCA
distal to the aneurysm can be used when the extracranial vessels are injured or small in caliber.
The ACA can be revascularized with an in situ
bypass using distal A2 vessels. If one ACA remains
intact, a side-to-side A2-A2 anastomosis preserves
distal blood flow.
Options for revascularization of the posterior circulation are more limited (Fig. 8). Revascularization of
the upper basilar artery is accomplished with a bypass
from the STA to the SCA or the PCA. The SCA lies
lower than the PCA, just medial to the tentorial incisura, making it the easier of the two recipient vessels
to use.
Revascularization of the lower vertebrobasilar cir-

155

Surgical Strategies for Giant Intracranial Aneurysms

culation is accomplished with a bypass from the occipital artery to the PICA. In addition, the PICA vessels
run in the posterior midline in proximity to each other,
enabling a side-to-side PICA-to-PICA anastomosis to
be performed. These lower vertebrobasilar bypasses
enable the sacrifice of one vertebral artery as part of
a proximal aneurysm occlusion. The PICA origin
ipsilateral to the aneurysm is clipped proximally to
prevent retrograde filling of the aneurysm from the
bypass. It is possible to anastomose the occipital artery
to the anterior inferior cerebellar artery, but this
bypass is technically difficult.

15.
16.

17.

18.

19.
20.

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Correspondence: Robert F. Spetzler, M.D., Neuroscience Publications, Barrow Neurological Institute, 350 W. Thomas Road,
Phoenix, AZ 85013-4496.

Acta Neurochir (1999) [Suppl]72: 157-174


Springer-Verlag 1999

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage


B. O. Hutter, I. Kreitschmann-Andermahr, L. Mayfrank, V. Rohde, U. Spetzger, and J. M. Gilsbach
Department of Neurosurgery, University of Technology (RWTH) Aachen, Aachen, Germany

Summary
The introduction of the operating microscope, the principle of
early surgery, specialized intensive care units, the calcium antagonist
nimodipine, the sophisticated pre- and postoperative management
and an aggressive antiischemic pharmacological management have
substantially reduced morbidity and mortality after aneurysmal
subarachnoid hemorrhage (SAH). In spite of this progress, many
patients after rupture and surgical repair of an intracranial aneurysm
exhibit substantial cognitive deficits and emotional problems although their neurological outcome was rated as good according to
the Glasgow Outcome Scale (GOS = I). Therefore, a comprehensive
neuropsychological examination is called for in order to evaluate the
factual functional outcome after SAH. Neither focal brain damage
associated with aneurysm location nor surgery but the hemorrhage
itself and related events can be regarded as the most important causal
factors for the late result after SAH. In contrast to the mild permanent effects of aneurysm surgery, the initial bleeding itself seems to
have substantial lasting adverse neurobehavioral effects after. In
concordance with other authors our own data stress the strong predictive power of the bleeding pattern such as the presence of intraventricular and/or intracerebral blood on the functional outcome
after aneurysmal SAH.
Keywords: Aneurysm rupture; subarachnoid hemorrhage; early
surgery; cognitive deficits; quality oflife.

Introduction
Since the last 25 years the progress made in the
neurosurgical management of aneurysmal subarachnoid hemorrhage (SAH) has been associated with a
substantial reduction of morbidity and mortality. The
introduction of the operating microscope, the concept
of early surgery, specialized intensive care units, the
calcium antagonist nimodipine and a sophisticated
pre- and postoperative management including hypervolemia, hemoclilution and induced hypertension
(triple-H therapy) have increased the survival of the
catastrophic event SAH [20, 28, 29, 58, 59]. In the
meantime, 50-60% of the patients affected by the rupture of one or more intracranial aneurysms can be re-

garded as functional survivors [28, 29, 58, 59]. Taking


into account the fact that most patients are victimized
in the middle of their lives by aneurysm rupture, the
question about the quality of life of the surviving patients deserves increasing attention [43, 75, 104, 117].
In neurosurgery, the Glasgow-Outcome Scale (GOS)
[52] is widely used for outcome assessment. However,
such a simple scale is reduced only to the physical
functional level of the patients and, therefore, cannot
assess all relevant aspects of quality of life [43, 45, 52,
53]. In studies of cognitive deficits and impairments in
daily life after SAH, many patients showed prolonged
reductions of their cognitive capacity and complained
of irritability, personality change, loss of interests and
emotional disturbances although their neurological
outcome had been rated as good (GOS = I) according
to the GOS [11, 41, 43, 49, 68, 75, 86, 104, 108, 117].
There is a growing body of evidence that neither focal
brain damage associated with aneurysm location nor
surgery, but the hemorrhage itself and related events
can be regarded as the most important causal factors
for the neurobehaviorallate sequelae of SAH [18, 42,
43,49,85-87,97, 104, 105, 110, 117].
Aneurysmal SAH: Postoperative Mortality
The main causes of death among surgically treated
patients with ruptured aneurysms have changed considerably during the last three decades. Macrosurgical
approaches, trapping of parent vessels and the use of
irremovable clips in the 1960s explain why surgery
itself contributed predominantly to fatal outcomes. In
that decade, the postoperative mortality rates ranged
between 28% and 53% [76, 112]. In the 1970s, postoperative mortality was reduced significantly by the
use of operating microscopes and technical refine-

158

ments of the used clips and instruments. The policy to


delay the operation to the 11th to 14th day post-SAH
further facilitated surgery. Postoperative mortality
rates as low as 0% and 2.7% have been reported [79,
94]. The concept of early surgery in good-grade patients was re-introduced at the end of the 1970s, after
re-rupture of the aneurysm during the waiting time for
the scheduled late operation had been identified as the
leading cause of severe morbidity and mortality [79,
103]. In the 1980s, cerebral vasospasm replaced the rerupture of the aneurysm as the main cause of death,
which stimulated the introduction of active hemodynamic management (e.g. triple H-therapy) and the development of drugs for the prevention and treatment
of vasospasm (e.g. the calcium channel blocker nimodipine) [9, 22, 30, 57].
In order to elucidate the causes of postoperative
mortality, we studied our own patients who were consequently submitted to a modern neurosurgical management of aneurysmal SAH, consisting of microneurosurgical techniques, early surgery, a specialized
intensive care unit, application of the calcium antagonist nimodipine and induced hypertensive therapy or
even modified triple H-therapy. In the last 8 years, 390
patients (134 men, 256 women, aged 16-80 years)
underwent microsurgical repair of their aneurysm in
the Department of Neurosurgery, University Hospital
of the University of Technology (RWTH) Aachen,
Germany. Ninety-six patients (24.6%) were admitted
in Hunt&Hess [39] grade IV or V. Early surgery
(within 72 hours) was performed in all patients in
Hunt&Hess grades I to IV, if admitted on time. Poor
grade patients with intracerebral hematoma underwent immediate operation, some of them without angiography. Early surgery in poor grade patients was
performed if the clinical state improved after placement of a lumbar or ventricular external cerebrospinal
fluid (CSF) drainage. The remaining poor grade
patients underwent late surgery. Intraoperative microvascular Doppler sonography was used routinely to
evaluate the patency of parent vessels following clip
placement. Intravenous nimodipine was given at least
for 14 days. Transcranial Doppler sonography (TCD)
was performed daily for early detection of cerebral
vasospasm. In cases of elevated blood flow velocities,
induced hypertension, mild hypervolemia and hemodilution was initiated even in the asymptomatic state.
Patients with a significant amount of intraventricular
blood received intraventricular recombinant tissue
plasminogen activator (rt-PA) via a ventricular cathe-

B. O. Hiitter et al.

Table I. Causes of Death in a Series of 390 Microneurosurgically


Treated Patients with Ruptured Aneurysm
Cause

No.

o;()

Initial SAH
Surgical complications
Vasospasm
Medical complications
Unknown

18
6
4
4

4.6%
1.5%
1%
1%
0.3%

Post-operative mortality

33

8.4%

ter. Thirty-three of the 390 surgically treated patients


(8.4%) died during the follow-up period of six months.
Table 1 lists the different causes of mortality in our
series.
In 6 (1.5%) patients, death was related directly to
surgery, because of significant clinical deterioration
immediatly after the operation. Cerebral vasospasm
with subsequent fatal cerebral infarction led to death
in 4 patients (1.0%). Fatal medical complications occurred in 4 of the surgically treated patients (1.0%).
Twenty-five of the additional 32 patients with aneurysmal SAH who came to admission, but were excluded
from operation because of the poor clinical state, died.
Accordingly, the management mortality rate, which is
based on the sum of postoperative and the total of
nonoperative fatalities, was 13.7% in our series.
As can be seen in our contemporary series, the main
cause of death changed again in the last years. The
permanent use of the microscope, a large armamentarium of microsurgical instruments and clips, and the
routine intraoperative investigation of the basal vessels
after clip placement by Doppler sonography allowed a
reduction of the rate of fatal operative complications
to 1.5%. In our series, the rate of fatal re-rupture before the planned operation was 0.7%, which underlines
again the superiority of the concept of early surgery.
By the use of intravenous nimodipine [9, 30], daily
TCD [34], and modified triple H-therapy, only 1% of
the casualities could be attributed to cerebral vasospasm. Today, the main cause of death among surgically treated patients with aneurysms is the severity of
the inital SAH alone or in conjunction with medical
complications. Because of the rare occurrence of
fatal surgical complications and lethal vasospasm,
improvements in the treatment of vasospasm and
refinements of operative techniques would not contribute substantially to a further reduction of the postoperative mortality. For the future, we should focus
more on attempts to reduce the neurological and neu-

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

159

robehavioral morbidity after aneurysmal SAH, reaching from prevention of the deleterious event SAH to
improved recognition of warning bleeding, a reduction
of the encephalopathy resulting from the bleeding and
related events to improved rehabilitation and psychosocial counselling.

ciated with a higher increase of intracranial pressure at


ictus. In our own series (N = 251), 14-days mortality
in patients with mild SAH (defined as SAH CT score
according to Hijdra et al. [38] ranging between 0 and
10) was 11%, compared to 14% in patients with moderate SAH (SAH score 11-20) and 35% in patients
with severe SAH (SAH score 21-30). A similar relationship was found between SAH score and functional
outcome after 6 months: 21 % of patients with mild
SAH were either severely disabled, vegetative, or dead
(GOS = III, IV, or V, respectively), compared to 27%
of patients with moderate SAH and 59% of patients
with severe SAH. These results are in agreement with
several previous reports which also suggested the
prognostic relevance of the severity of SAH on initial
CT scans [3, 13, 32]. A more severe brain damage at
the time of SAH, a higher risk to develop delayed ischemic neurological deficits, and an increased rate of
chronic hydrocephalus are factors which have been
made responsible for the worse prognosis of patients
with more severe SAH [4, 13,25,26,32,35].

Effects of the Bleeding Pattern on the Neurological


Outcome

After cerebral computed tomography (CT) was introduced, SAH is diagnosed more readily and with
greater reliability. Moreover, the amount of blood and
its anatomical distribution can be determined accurately. Several clinical studies have addressed the relationship between the extent of the hemorrhage, as
assessed by means of CT scans, and the outcome,
incidence of vasospasm, and occurrence of chronic
hydrocephalus in patients with SAH. Various methods
have been used to estimate the quantity of extravasated blood following aneurysm rupture using CT.
Some authors measured the density at a single point in
the subarachnoid space in Hounsfield units [95].
Others evaluated the thickness oflayers of blood in the
basal cisterns [25, 26, 32]. While some scoring systems
quantify solely the amount of cisternal blood [32, 38],
others also consider the presence of cerebral hematomas and/or intraventricular hemorrhage [25]. Until
now, the CT score introduced by Fisher et al. in 1980
[25] is by far the most commonly applied instrument to
grade the severity of SAH based on morphological
criteria and has proved to be a valid prognostic indicator [2, 3, 25, 28, 36]. On the other hand, this grading
scale (as many others with a limited number of categories) is inadequate to reflect the variability concerning anatomical distribution as well as quantity of
intracranial blood following SAH [114]. A more sophisticated method for assessing the severity of SAH,
according to which the amounts of blood in 10 basal
cisterns and fissures are graded separately, has been
proposed by Hijdra et at. [38].
We recently performed an analysis of 251 patients
with SAH to investigate the relationship between the
initial CT findings and the clinical course which
yielded a significant correlation between the amount of
cisternal blood as determined by the grading system of
Hijdra et al. [38] and the clinical grade according to
Hunt & Hess (Spearman correlation coefficient r =
0.35; p < 0.001). A likely explanation might be that
the extravasation of a greater volume of blood is asso-

Intraventricular Hemorrhage

Intraventricular hemorrhage (IVH) is associated


with aneurysm rupture in up to 56% [66]. There are
several ways by which blood may enter the ventricles.
First, aneurysm bleeding may cause parenchymal
cerebral hematoma which may rupture into the ventricles. This seems to be most frequently the case in
aneurysms of the anterior communicating artery
(AComA), where the parenchymal layer between the
aneurysm and the anterior horn of the lateral ventricle
is thin. The second mechanism is retrograde flow of
blood from the basal cisterns through the fourth ventricle. Thirdly, aneurysms may bleed directly into
the ventricles, especially aneurysms of the posterior
inferior cerebellar artery or, very rarely, aneurysms
located within the ventricles. Intraventricular spread
of the hemorrhage has been identified as a strong predictor for a poor outcome [3, 58]. In our own series,
134 (53.4%) patients had associated IVH on the initial
CT scan. Severity of IVH was graded according to the
system proposed by Le Roux et al. [64] (Table 2).
There was a significant correlation between the
severity of IVH and the initial Hunt&Hess grade
(r = 0.31;p < 0.001). The 14-days mortality was 9%
in patients with no IVH, compared to 18% in patients
with mild IVH (defined as IVH score 1-6), and to 52%
in patients with severe IVH (IVH score 7-16). IVH

160

B. O. Hutter et al.

Table 2. System for Grading Amount of Intraventricular Blood According to Le Raux et al. [64 ]
Score*

Description

2
3
4

trace of intraventricular blood


less than half a single ventricle filled with blood
more than half a single ventricle filled with blood
entire ventricle filled and expanded with blood

Each ventricle is scored separately and a total score calculated.


Maximum score = 16.

also had a striking effect on the functional outcome


after 6 months: A poor outcome (as defined above)
was observed in 21% of patients with no IVH, compared to 33% of patients with mild IVH, and 72% of
patients with severe IVH. Although the poor prognosis
may partly be explained by the association of IVH
with more severe SAH, intraventricular spread of the
hemorrhage has been shown to be an independent
outcome predictor. The mechanisms by which IVH
causes additional brain damage may be acute hydrocephalus due to obstruction of CSF outflow pathways
[78, 80, 113, 115], and compression of periventricular
brain structures by space occupying intraventricular
clots, especially around the fourth ventricle and aquaeduct, which may impair microcirculation [101]. Since
both mechanisms may be reversed by intraventricular
application of plasminogen activators which markedly
accelerate clot clearance, fibrinolytic treatment might
improve the prognosis of SAH associated IVH in the
future [23, 72-74, 92].
Intracerebral Hematomas

Intracerebral hematomas (lCH) occur in up to 43%


of patients with ruptured aneurysms [111]. Although
aneurysms at any site may cause ICH, they are more
frequently associated with aneurysms of the middle
cerebral artery. Patients with ICH are in a worse clinical condition than those without ICH [2, 111]. In our
own series, 63 (25%) patients had an ICH. As many as
47% of patients with an ICH volume> 10 ml, and 42%
of those with an ICH volume < 10 ml were graded
Hunt&Hess IV or Von admission, compared to 15%
of patients with no ICH. ICH has been shown to have
a strong negative impact on prognosis [3, Ill]. In our
series, 14-days mortality was 12% in patients with no
ICH, 29% in those with a small ICH 10 ml), and
43% in patients with a large ICH (> 10 ml). A poor
outcome after 6 months was found in 26% of patients

with no ICH, 47% of those with an ICH < 10 ml, and


in 58% of patients with an ICH > 10 m!. Brain damage
at the site of the hematoma, increase of intracranial
pressure, and secondary brain stem lesion due to
uncal herniation are the most important mechanisms
by which ICH worsens the prognosis after aneurysm
rupture. Several studies suggest that emergency craniotomy, performed to evacuate space-occupying
hematomas and to clip the ruptured aneurysm, may
improve the prognosis, especially in cases with depressed level of consciousness and signs of uncal herniation [37]. In summary, grading the amount of subarachnoid, intraventricular, and intracerebral blood
after aneurysm rupture may provide important prognostic information and may be helpful in predicting
mortality and functional outcome. It may be useful in
identifying patients at risk for specific complications
and in the therapeutic management of these patients.

Cerebral Vasospasm - an Underscored or


Overestimated Complication After Aneurysm Rupture
Followed by Early Surgery?
The introduction and broader acceptance of the
concept of early surgery and improved intensive care
management have led to a significant reduction of
vasospasm associated morbidity and mortality within
the last two decades. Fisher et al. reported in 1977 that
50% of a series of 50 patients who survived aneurysmal
SAH developed delayed neurologic deficits due to
vasospasm [24]. In the Cooperative Study by Kassell
et al. [58, 59] vasospasm was held responsible for death
in 7.2% and disability in 6.3% of all investigated patients. In the abundant publications on this topic, the
incidences of vasospasm and the associated delayed
ischemic deficits vary considerably, depending on the
definitions and method used to assess cerebral vasospasm. Divergent opinions as to the best regimen for
the prevention and treatment of ischemic deficits due
to vasospasm further characterize its recognized role
as perhaps the major complication in the postoperative
management complex after aneurysmal SAH. Compared, however, to the still existing surgical morbidity
and mortality and the deleterious consequences of the
severity of the bleeding itself, as well as surgical misadventures, which are mostly not equally addressed in
these publications, the role of symptomatic vasospasm
as a major reason for a poor outcome is probably
overestimated. A prudent surgical and medical pre-

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

161

ventive and treatment regimen further reduces the


number of patients disabled by this complication.
An important prerequisite for an individual therapy
of cerebral vasospasm was the demonstration of its
relation to the amount of subarachoid blood [25] and
the assessment of increased blood flow velocities by
means of TCD [1]. Recognized risk factors include
amount of blood as seen on primary CCT scans, preor postoperative angiographically proven vasospasm,
timing of surgery and a history of hypertension [88].
According to our own observations, young women on
oral contraceptives, who have history of hypertension,
smoke, and exhibit a heavy bleeding are at the highest
risk of developing symptomatic vasospasm [61]. A
further indirect profit of early surgery was that it provided the prerequisite for an adequate pharmacological management of vasospasm as well as its prevention
by means of the reduction of the amount of subarachnoid blood. The initial fear, that the surgical
trauma would negate the beneficial effects of early
surgery did not hold true. If performed according to the
state-of-the-art, the risks of aneurysm rupture, occlusion of perforating or supplying vessels, direct brain
lesions or "complicated surgery" are not increased as
compared to delayed surgery [29]. Already more than
ten years ago the Cooperative Study led to the conclusion that "the postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery" [58, 59].
In the wake of the tremendous surgical, technical and
pharmacological advances within the last years, we
can safely conclude that current results must be better.
Many postoperative complications leading to socalled delayed neurological deterioration are often
falsely attributed to vasospasm [15]. They have other
causes and their treatment relies heavily on the differential diagnosis of their origin. Among these complications briefly to be mentioned range infections, electrolyte and metabolic disturbances, the SAH related
syndromes of salt and water wasting and inappropriate
secretion of antidiuretic hormone (SIADH) as well as
hydrocephalus and brain edema. A further aspect that
confounds the published numbers on vasospasm related morbidity and mortality is the fact that different
definitions are used to characterize this entity. We
must differentiate between the morphological narrowing of arterial vessels proven by means of angiography,
which may remain asymptomatic or become symptomatic in form of delayed ischemic neurological deficits. The incidence of markedly increased blood flow

velocities over a threshold of 120 cmls as a sign of


vasospasm ranges as high as 70-75% in patients after
aneurysmal SAH [34]. However, not all patients in
whom these elevated blood flow velocities are measured develop symptomatic vasospasm. Nevertheless,
TCD remains a well established, repeatable measure
which allows to identify patients at risk for severe vasospasm already in the asymptomatic stage and permits
initiation of preventive hemodynamic therapy. An
effective treatment regimen for a significant prevention
of the arterial narrowing itself still does not exist, only
its secondary complications can be prevented or
treated. Next to purely mechanical measures such as
balloon dilatation of vasospastic vessels [65], intraarterial infusion of papaverine [55] which as of now
lack verification by means of larger controlled clinical
trials, current treatment concepts center on pharmacological measures such as nimodipine prevention and
hypervolemic hemodilution and hypertension (TripleH therapy). An analysis of clinical studies performed
by our group in 1988 converged on the finding that the
lowest published incidence of delayed ischemic deficits
was observed in non-controlled open prospective trials
using the combination of early surgery and nimodipine
prophylaxis (between 1-7% severe disability or death
due to vasospasm) [31]. Triple-H therapy are used for
the amelioration of cerebral perfusion by means of the
elevation of perfusion pressure. Indications exist,
however, that aggressive over-hydration for the treatment of severe vasospasm may cause complications
that are potentially harmful. Medlock and co-workers
[77] saw 20 complications in 16 patients, one of them
fatal, and found, however, no clear reduction in mortality or morbidity attributed to prophylactic hypervolemia. In an experimental study, Handa et al. [33]
concluded that hypervolemic hemodilution therapy
for cerebral vasospasm may be beneficial in decreasing
the incidence of ischemic deficits. However, after infarction has occurred, this form of treatment may be
detrimental, because of the potential risk of increasing
vasogenic brain edema.
Our own treatment regimen for the prophylaxis and
treatment of secondary ischemia due to vasospasm
focuses on pharmacologically induced hypertension as
the most important and straightforward factor of the
Triple-H approach. To be effective, it must be begun at
the latest at the occurrence of symptomatic ischemic
deficits, but we strongly recommend initiation of preventive therapy based on TCD criteria, when patients
are still in the asymptomatic stage. In a retrospective

162

study of patients with severe and prolonged vasospasm, we found that patients who had been treated by
means of aggressive catecholamin-induced hypertension at the onset of dopplersongraphically defined
vasospasm (as compared to a historical control group)
exhibited an insignificant trend (p = 0.065) for a better
neurological result at discharge (GOS) and a significantly better self-rated quality of life in the areas
mobility (p <0.05) and free-time activities (p < 0.05).
The partner-rated overall quality of life in these
patients was significantly better (p = 0.012) than in the
conventionally treated patient group [61]. The above
mentioned pathophysiological considerations, empirical evidence from clinical studies and our positive experiences confirm our opinion that the role of vasospasm as a leading factor for a poor outcome after
aneurysmal SAH is overestimated. State-of-the-art
early surgery, postoperative medical management
based on TCD guided hypertension combined with
nimodipine prevention provides a promising concept
to further reduce the number of patients afflicted by
this complication.
Neurological Results in Poor-Grade Patients
(Hunt&Hess Grades IV or V)
Various clinical studies in poor-grade patients have
clearly demonstrated that re-bleeding and vasospasm
are the leading and most serious complications of
aneurysmal SAH [7, 19,29]. However, the attitude of
early treatment of the ruptured aneurysm is still controversial, although conservative treatment in poorgrade patients exerts a significant unfavorable influence on morbidity and mortality. Several authors
found a mortality rate of nearly 100% in their nonsurgical group, and concluded that half of these patients would, in retrospect, have profited from surgery,
because they died of vasospasm and re-bleeding [7, 99).
An often mentioned argument against early surgery in
poor-grade patients is the expectation of difficult surgical conditions in the acute stage of a severe SAH
with the awareness of possible fatal results, and a
marked rate of severely disabled patients [99, 107].
In our department, we follow the policy of early
surgery also in selected poor grade patients with
aneurysmal SAH. This aggressive surgical policy is, in
our opinion, warranted by the results of an 8-year
consecutive series of 76 prospectively evaluated poorgrade patients, who have been operated upon early
(within 72 hours) in our department. The indication

B. O. Hiitter et al.

Table 3. Early Postoperative Outcome in Poor-Grade Patients After


Early Operation (n = 76)
Early outcome

Good
Fair
Poor
Dead

Grade IV
(n= 44)
n
10

10
17
7

Grade V
(n = 32)
n

23
23
39
16

4
8
8
12

13
25
25
38

Table 4. Late Postoperative Outcome in Poor-Grade Patients After


Early Operation (n = 76)
Late outcome

Good
Fair
Poor
Dead

Grade IV
(n= 44)
n

16
13

6
9

Grade V
(n = 32)
n

36
30
14
20

8
4
8
12

25
13

25
38

for surgery was based on the subjective judgement of


the responsible neurosurgeon and generally denied in
patients with severe internal diseases, patient age over
70 years, present critical vasospasm and long lasting
coma in grade V patients. Grade V patients without
any improvement under ventriculostomy were only
operated if a space occupying intracerebral hematoma
was present. Postoperatively, the outcome was assessed according to the GOS, as early outcome at the
end of neurosurgical treatment (average 23 days) and
as late outcome in an additional re-examination
(average 8 months postoperatively). The early and late
postoperative outcome (according to the GOS) after
early surgical treatment is demonstrated in Tables 3
and 4.
Considering all poor grade-aneurysmal SAH patients, the overall late outcome after early surgery was
favorable in 41 (54%) patients with a good or a fair late
outcome and unfavorable in 35 (46%) patients with a
poor late outcome or death.
Immediate postoperative deterioration is an aspect
that must be carefully evaluated not only in poorgrade patients in order to differentiate between the
different causes that have an influence on the overall
outcome after aneurysmal SAH. Next to the morbidity
and mortality that may be explained by the severity of
the bleeding itself as one of the most important prognostic factors, we must identify other causes of postoperative deterioration for a critical assessment of the

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

surgical and medical management policy in poorgrade patients after aneurysmal SAH. In our series, ten
(13%) patients showed an immediate postoperative
deterioration and in a further 5 (6.5%), recovery was
markedly impaired, resulting in a permanent disability
in two and lethal outcome in three. In half of the patients with immediate postoperative deterioration, the
worsening of the clinical state was transient and resolved during the hospitalisation period. Immediate
postoperative deterioration was related to surgical
problems such as massive hemorrhage (1%) due to a
prematurely ruptured aneurysm, prolonged temporary
clipping (3%), major vessel occlusion (4%) and the
closure of small perforating vessels or local compression by spatula (5%). Sixteen (21%) patients presented
delayed postoperative deteriorations due to infection
(1%), rebleeding (3%), vasospasm (3%), edema (7%)
and hydrocephalus (7%). Especially in poor grade patients, the timing of surgery after aneurysmal SAH
must be decided in every individual case anew. Delayed surgery is favoured in the hope that the patient
will recover to a better clinical condition with a decreased postoperative mortality. However, if the patient dies from rebleeding or vasospasm during the
waiting period, the reproach will remain, because we
have lost this patient due to inactive treatment. The
risk of rebleeding is highest around the fourth to the
tenth day, with an additional peak within the first 24
hours after the initial SAH [19, 29, 67]. Most grade IV
and V patients have a great amount of subarachnoid
blood. Consequently, patients in Hunt&Hess grades
IV or V frequently will develop severe or even fatal
complications and should therefore be treated by early
surgery [83, 99, 107]. Furthermore, the prevention of
delayed neurological deficits by aggressive treatment
of vasospasm is only safe with a sufficiently clipped
aneurysm. In our series, only one patient showed a
postoperative deterioration and finally died due to
symptomatic vasospasm. Another problem that may
be improved by early surgery because of the possibility
to remove blood clots from the subarachnoid cisterns
and ventricles and to open the lamina terminalis is the
impairment of CSF, especially in poor-grade patients
with an increased risk for consecutive hydrocephalus.
In addition to the overall mortality rate, there is a
further aspect, the frequency of postoperatively permanently severely disabled patients. Totally, 18% of
our patients remained in a poor condition, seriously
handicapped with all medical, psychological, ethical
and financial problems of long lasting nursing and in-

163

tensive care as lifelong management for these patients.


These poor results (46% with unfavorable outcome in
our series) are generally not a consequence of surgical
misadventure, but of the natural course of the severe
bleeding. The low incidence of immediate postoperative deterioration in our series proves that generally
intraoperative conditions are not more difficult than in
good-grade patients during early surgery. We think
that the reluctancy towards early surgery may be more
a psychological problem of the surgeon, fearing a large
number of disabled patients or even a bad surgical
reputation.

The Discrepancy Between the Neurological Status and


the Factual Functional Result After SAH

The Glasgow Outcome Scale (GOS) is a widely used


instrument for the assessment of the functional result
of patients after SAH and head injury [52]. The use of
the GOS enables global predictions about the efficacy
of neurosurgical treatment in these patients [11, 28, 30,
52, 53]. Since the GOS is reduced only to the dimensions of neurological integrity and physical independence it must be doubted that it is really a suitable
instrument for measuring the full range of psychosocial functioning [41, 45, 53, 68]. It is meanwhile questionable that a good outcome (GOS = I) in patients
after aneurysmal SAH justifies the assumption that
these patients have no relevant neurobehavioral abnormalities. In the last years an increasing body of
evidence has accumulated, showing that patients after
rupture and surgical repair of an intracranial aneurysm exhibit substantial cognitive deficits and emotional problems although their neurological outcome
had been rated as good (GOS = I) [8, 11, 18,40-43,
46,68,75,87,97, 104, 110, 117]. In a retrospective
study we examined neuropsychologically a series of 31
patients one to five years after aneurysmal SAH and
early surgery with a good neurological outcome (GOS
= I) rated at 6-month follow-up [41]. The single-case
analysis revealed that only 6 (20%) patients had no
persistent cognitive deficits. A total of 54% of the early
operated SAH patients with a good neurological outcome (GOS = I) exhibited substantial reductions of
their cognitive capacity [41]. Our findings are in line
with the pattern of cognitive impairments after SAH as
reported in other studies [8, 11, 18, 62, 87, 97, 104, 105,
110, 117]. Table 5 gives an overview of the neuropsychological deficits of neurologically intact patients

164

B. O. Hutter et al.

Table 5. Frequency of Cognitive Deficits in Neurologically Intact Patients in the Chronic State After SAH in whom Comparable Tests were
Employed
Cognitive function tested

Sonesson et al. ,
1985 (N = 40)

Concentration
Figural short-term memory
Verbal long-term memory
Aphasia
Perceptual speed and accuracy

130/0-25%
53%
30%

Ogden etal.,
1993 (N = 66) #

Hutter & Gilsbach,


1993 (N = 31)

not comparable

7%-13%
53%
21%
10%
28/0-62%

47%
18%
7%
44%-76%

not examined
40%-45%

# 58 patients had a good (GOS = J) and 6 patients a fair (GOS = II) neurological result while 2 patients were dependent.

(GOS = I) in the chronic state after SAH when comparable neuropsychological tests have been employed.
The general conclusion that can be drawn from this
comparison is that impairments of short-term memory
and cognitive speed seem to be the most frequent longterm sequelae of SAH and that short-term memory
tends to be more often defective than long-term memory [62]. This pattern of neuropsychological impairments seems quite similar to the mental late sequelae of
mild to fair head injury [109]. On the other hand, the
discrepancies in the reported frequencies of substantially impaired patients can mainly be attributed to
differences between the tests employed and the criteria
used for defining a single cognitive deficit. In the study
by Hutter and Gilsbach [41] multivariate analyses
proved significant harmful effects of the severity of the
bleeding as rated according the the CT grading system
of Fisher [25] on information processing and wordfinding capacity. This could be interpreted as an indication for the detrimental effect of the subarachnoid
blood on the brain, especially on frontobasal structures. Older patients at the time of SAH were at follow-up significantly more disturbed in concentration,
short-term memory and information processing capacity [41]. Similar results have also been reported by
Bomstein et al. [11]. Neither the grade of vasospasm,
even if severe, the neurological grade on admission
(Hunt&Hess), the interval between SAH and investigation nor the gender of the patients had any significant influence on neuropsychological test performance
at follow-up [11].
The cognitive functional level of patients after SAH
and the classification of their outcome as good (GOS =
I) may diverge completely with regard to the neuropsychological and psychosocial late result. This apparent discrepancy challenges the neurological status
of SAH patients as the gold standard for the evaluation of disease sequelae and treatment outcome [41].

Therefore, a comprehensive neuropsychological examination is called for in order to evaluate the factual
outcome after SAH.
The Profile of Neuropsychological Impairments After

SAH
Beyond methodological differences, most neuropsychological studies converge in the finding that SAH
patients are particularly impaired in functions of
memory, attention, concentration and cognitive speed
and flexibility [8, 11, 18,62,68,97, 104, 105, 110, 117].
According to the studies of Hutter and coworkers [41,
43] the neuropsychological impairments in SAH patients were most prominent in the complex choice reaction time task and figural short-term memory. These
findings are in accordance with data of other research
groups [11, 68, 87, 97, 104, 105, 110, 117]. In a retrospective study 58 patients after SAH were examined
neuropsychologically one to five years after the acute
event [43]. There were 38 (65%) early (within 72 hours)
operated patients and 20 (35%) patients with spontaneous SAH of unknown origin. The neurological outcome rated according to the GOS at 6-month followup was good (GOS = I) in 48 (83%) and fair (GOS =
II) in 10 (17%) patients. Most deficits (46%) emerged
in figural short-term memory and in different parameters of a complex choice reaction time task reaching
from 31 ~65% of significantly disturbed patients. Verbal long-term memory was impaired in 28% of the
patients. The Token test revealed an aphasic language
disturbance in six (10%) patients after SAH. Only 9
(15%) patients presented with no single cognitive deficit. On the other hand, the mean scores of all neuropsychological tests were with one exception in the
normal range [43]. Vilkki et al. [117] reported similar
results in a sample of 83 SAH patients. The authors
found that deficits in memory functions and cognitive

165

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

Table 6. Cognitive Functions Tested, Neuropsychological Tests Used and Frequency of Cognitive Deficits in the Acute and Chronic Stage After
Early Aneurysm Surgery in Patients whose Neurological Result had been Rated as Good (GOS = /) at the 6-Month Follow-up
Cognitive function

Neuropsychological test

1-13 (median 5) days


after early surgery
(n= 28)
cognitive deficits #
~)
no.

1-5 (median 3) years


after early surgery
(n = 31)
cognitive deficits #
no.
%

Speed of concentration
Accuracy of concentration
Error-reduced concentration
Aphasia screening
Verbal long-term memory
Figural short-term memory

concentration test (d2)


concentration test (d2)
concentration test (d2)
Token test
1ST memory scale
Benton test

3
11
3
9
15
20

3
2
4
3
6
16

11%
39%
11%
32%
54%
71%

10%
7%
13%
10%
21%
53%

Deficits in functions of attention were not comparable because of different tests used
# A cognitive deficit was defined as a test performance two standard deviations or more below the population mean according to the test
norms; the Benton and the Token test have individual cutt-offvalues.

inflexibility were typically associated in SAH patients


with incomplete neurological recovery, inability to return to work and impaired social relations. Even in the
first days after early aneurysm surgery, patients after
SAH exhibit predominantly cognitive deficits in shortand long-term memory, language and functions of attention [46]. Moreover, the profile of deficits found in
the acute stage after SAH is identical to the persisting
cognitive impairments in the chronic stage [11, 46, 87,
97, 104, 105, 110, 117]. In close correspondence to our
own results, Maurice-Williams et al. [71] found attention and memory problems as the main areas of cognitive disturbance in the first days after aneurysm surgery. Table 6 shows the comparison of the frequency
of cognitive deficits found in our SAH patients shortly
after surgery and in the patients in the chronic state
one to five years after the acute event.
Cognitive Deficits in Surgically Treated Patients as
Compared to Those After SAH of Unknown Origin
In 15% to 22% of all cases with SAH no source of
the bleeding can be proven even by repeated angiography [5, 12, 14, 21, 84, 106]. Several studies have
shown that many of the patients without an angiographically proven source of the bleeding complain
such diffuse psychological difficulties as fatigue, memory problems, emotional changes, reduced daily functional capacity and persistent headaches comparable
to the complaints of patients after aneurysmal SAH
[12,21,42, 54, 85, 86, 102, 105]. Sonesson et al. [105]
compared the neuropsychological test performance of
20 patients after SAH of unknown origin and a good

neurological outcome (GOS = I) to the test scores of a


group of patients who had sustained a proven aneurysmal SAH. No significant differences between the two
groups emerged. This is in clear contrast to the common opinion of the more benign course and better
long-term prognosis in non-aneurysmal SAH patients.
Table 7 gives an overview of the presently available
studies where these two etiological groups of SAH
patients have been compared.
Spallone et al. [106] examined 56 patients with SAH
of unknown origin from 2.6 to 15 years after the acute
event and a neurological outcome from good to fair.
They reported that about half of their patients suffered
from frequent headache and cognitive slowing. Eskesen et al. [21] published results about a follow-up examination of 42 non-aneurysmal SAH patients with a
neurological result ranging from good to fair. Three
months to five years after the SAH the patients were
interviewed by phone or in a clinical examination
about their actual problems. Most frequent were complaints about headache and mental slowing. In a further retrospective study, 38 patients with aneurysmal
SAH and 20 patients without an angiographically
proven source of their SAH were tested neuropsychologically one to five years after the acute event
[42]. Both etiological groups exhibited roughly comparable cognitive deficits in spite of the fact that SAH
was significantly less severe in the unknown origin
group. However, an analysis with clinically homogenous subgroups revealed that in a subgroup with worse
clinical grades, the patients with aneurysmal SAH
were significantly more disturbed in focal cognitive
functions like short- and long-term memory and word-

166

B. O. Hutter et al.

Table 7. Neuropsychological Impairments in Patients After SAH of Unknown Origin and After Aneurysm Rupture

Authors

No. 1

Clinical
condition (H&H)2

GOS
(interval) 3

Non-aneurysmal
SAH

Aneurysmal
SAH

Spallone
eta!., 1986

56

I-IV

I-II
2.6-15

50% headache
50% mental alowing

not examined

Eskesen
et al., 1984

42

I-IV

I-II
0.6-5

44% headache
41 % mental slowing
29% reduced mental capacity
15% aphasia

not examined

Sones son
et al., 1989

20

I-III

55% memory problems


33% reduced perceptual speed
33% reduced abstract thinking

56% memory problems


32% reduced perceptual speed
33% reduced abstract thinking

Ogden
eta!., 1990

66% mental slowing


0% reduced mental flexibility
33% long-term memory
50% short-term memory
O'/'o aphasia

20% mental slowing


50% reduced mental flexibility
40% long-term memory
40% short-term memory
10% aphasia

Hutter
etal.,1994

20

10-35% reduced concentration


30% long-term memory
60% short-term memory
45-95% reaction time
5% aphasia

2-4% reduced concentration


15% long-term memory
26% short-term memory
15-29% reaction time
23% aphasia

0.3-7
I-IV
5

I-III

I-II
1-5

1 No. of patients with SAH of unknown origin.


2 Neurological state on admission according to the grading system of Hunt&Hess.
3 Neurological result rated according to the Glasgow Outcome Scale (GOS}/interval SAH-investigation (years).

finding capacity. The patients with SAH of unknown


origin scored lower in tasks for cognitive selectivity
and complex choice reaction time [42]. These results
can be interpreted as an indication that the hemorrhage itself is the main causal factor for the mental
impairments after SAH and that aneurysm surgery
does not additionally damage the brain. The more
pronounced diffuse deficits after non-aneurysmal SAH
could be a consequence of the bleeding itself and the
associated functional disturbances due to lacking surgical evacuation and/or later vasospasm triggered by
the blood remaining in the subarachnoid space. The
higher prevalence of focal deficits after aneurysmal
SAH possibly results from local effects of aneurysm
rupture and the related anatomical bleeding pattern
and/or the surgical procedure. However, the groups
studied as yet are rather small and therefore, the power
of statistical tests to detect substantial differences is
limited.
Emotional Adjustment in Patients After SAH
In the chronic stage after SAH patients frequently
present with increased irritability, personality change,
loss of interests, social problems and emotional disturbances [11, 12, 21, 43, 49, 68, 71, 75, 85-87, 104,

108, 117]. Several studies have shown that these emotional problems and subjective complaints are also
frequent when the neurological and/or cognitive impairment is relatively slight [11, 43, 75, 86, 104, 108,
117]. Ljunggren et al. [68] reported that 25% of their
SAH patients with a good neurological outcome complained in clinical interviews of emotional problems.
Bornstein et al. [II] found frequent emotional disturbances in SAH patients using a clinical interview
and the Minnesota Multiphasic Personality Inventory
(MMPI). In a further study Vilkki and coworkers
[117] described personality disturbances and emotional problems in 32% of their patients after SAH using standardized personality tests. Stegen and Freckmann [108] found in a collective of 87 SAH patients
with an almost good neurological recovery changes in
mood in 51 %, depression in 36% and changes in social
behavior in 98%. Ropper and Zervas [93] investigated
a series of 112 consecutive cases after aneurysmal SAH
with a good neurological recovery and saw in 25%
substantial emotional disturbances. In a study exploring the emotional adjustment of 58 patients one to five
years after SAH, emotional lability was significantly
increased in 48%, motivation was significantly reduced
in 41 % and life-satisfaction in 37% [43]. Of the 58 SAH
patients studied, 17 (30%) were identified as depres-

167

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

sive. The psychological disturbances were comparable


between patients after spontaneous SAH of unknown
origin and patients after aneurysmal SAH. There were
also no substantial differences between patients after
rupture of an aneurysm of the anterior communicating
artery (ACoA) and patients after SAH of other origin
[43].
Unfortunately, many previous studies lack an adequate control group for clarifying the specificity of the
psychological disturbances following SAH, allowing
no discrimination if SAH patients present with psychological disturbances comparable to those of chronically ill patients. In order to answer this question, we
studied a series of 45 patients one to five years (median
3 years) after SAH whose neurological outcome according to the GOS at 6-month follow-up had been
rated as good (GOS = I) in 38 (84%) and fair (GOS =
II) in 7 (16%) [49]. The SAH group consisted of 31
(69%) patients after rupture and early repair of an intracranial aneurysm and of 14 (31 %) patients with
spontaneous non-traumatic SAH of unknown origin.
The psychological adjustment of these patients was
compared to the psychological disturbances found in
36 oxygen-dependent patients with end-stage chronic
obstructive pulmonary disease (COPD). Both groups
showed a comparable frequency of psychological disturbances, except that the COPD patients presented
with significantly higher bodily complaints and bodily
concern (p < 0.05, respectively). In the SAH patients
predominantly loss of motivation (42%), abnormal introversion (40%), increased emotional lability (38%)
and strain (31%) were found. The increased emotional
lability and the loss of motivation after SAH could
possibly be explained by damage to limbic or frontobasal structures which must not necessarily be detectable even by CT or MRI scan. Those patients, who
had been in a worse clinical state (Hunt&Hess grade
IV) on admission showed a significantly higher loss of
motivation than those patients in Hunt&Hess grades
I-III (p < 0.05). In a correlational analysis, the neurological state on admission (Hunt&Hess), the severity
of the bleeding (Fisher CT score) and vasospasm as
assessed by TCD exhibited substantial associations
with a reduced self-assertiveness and increased bodily
complaints ranging between r = 0.32 and r = 0.39
(p < 0.01, respectively). The patients after SAH of
unknown origin suffered significantly more of emotionallability than the patients after aneurysmal SAH
(p = 0.04). Possibly, the uncertainty about recurrence
in the non-aneurysmal SAH patients influences their

psychological adjustment. The surgical clipping of an


aneurysm reassures the patients that the bleeding will
never recur and, therefore, reduces the emotional impact. On the other hand, the sudden catastrophic event
of SAH acts as a psychological trauma leading to
symptoms of a post-traumatic stress disorder (PTSD).
For example, in a study by Stegen and Freckmann
[108] 79 percent of their patients were anxious about a
rebleeding.

Neuropsychological Effects of Aneurysm Location


Several authors have proposed that the aneurysm
location itself is an important causal factor for the
neurobehavioral sequelae ofSAH [6, 56, 62, 69, 82, 89,
100,116,118]. On the other hand, others believe that
the SAH leads to a diffuse cerebral damage causing
mental impairments independent of aneurysm location
[17, 18,40-44,46,49,86,87,91,97, 110]. However,
the recent empirical evidence supporting the assumption of specific neuropsychological sequelae depending
on aneurysm location is rather sparse. Moreover, even
the side of the ruptured aneurysm (left- versus rightsided) does not have any specific neuropsychological
effects [8, 18, 11 0]. Since a long time, ruptured
AcoA aneurysms have been of particular interest
for neuropsychologists, motivated by the impressive
cognitive and psycho organic symptoms, similar to a
Korsakoff syndrome, frequently described in these patients. Norlen and Olivecrona [82] were among the first
to describe impressive amnestic syndromes in patients
after rupture of an AcoA aneurysm consisting of amnesia, confabulations, disorientation and neglect of
deficits. Okawa et al. [89] found in a sample of 85
AcoA patients, that 66% presented with postoperative
amnestic symptoms and marked changes in personality. These deficits remained unchanged in 16% of
them at a long-term follow up 2-3 years later [89].
Gade et al. [27] reported, that 30% of 48 AcoA patients presented with a memory deficit with or without
a Korsakoff syndrome three months after surgery and
still remained unchanged at a follow-up examination.
These psychoorganic impairments after rupture and
surgical repair of an AcoA aneurysm were related to
damage of diencephalic and/or frontal structures,
caused by the hemorrhage itself, vasospasm and/or
surgery. Volpe and Hirst [118] speculated that the
memory function of patients with a ruptured AcoA
aneurysm is especially hindered by an effect of interference suggesting fronto-cortical dysfunction. In two

168

B. O. Hutter et al.

Table 8. Studies, Where no Neuropsychological Differences Between


ACoA Patients and Patients with Ruptured Aneurysms of Other Locations Have Been Found
Author(s)

Journal

Year of
publication

Richardson
Hutter & Gilsbach
DeLuca
Odgen et al.
Hutter & Gilsbach
Satzger et al.
Tidswell et al.
Hutter & Gilsbach
Hutter

Brain and Cognition


Acta Neurochir (Wien)
J Clin Exp Neuropsychol
Neurosurgery
J Clin Exp Neuropsychol
Acta Neurochir (Wien)
Neurology
Acta Neurochir (Wien)
Neuropsychiatry Neuropsychol
Behav Neurol

1989
1992
1992
1993
1995
1995
1995
1996
in press

studies the patients after AcoA aneurysm rupture presented apart of their confabulatory memory syndrome
with additional deficits in neuropsychological tests
measuring frontal functions [6, 56]. The authors assumed, that the frontal lesions do not necessarily have
to be so extensive, that they can be recognized on CT
scans [6, 56]. In a single-case study of Vilkki [116], all
five patients with an operated AcoA aneurysm had a
postoperative Korsakoff syndrome. In three of them, a
postoperative CT scan showed frontal defects.
However, most of these studies are flawed by several
factors: 1. many have been performed before the introduction of the operating microscope; 2. many
studies are only casuistic and not based on consecutively treated patients - therefore, the cases presented may be selected and in fact not typical for AcoA
patients; 3. nearly all studies lack an adequate control
group in order to demonstrate typical neuropsychological sequelae of rupture and surgical repair of
AcoA aneurysms. An adequate control group
should be composed of patients with ruptured aneurysms of other locations and of patients after spontaneous non-traumatic SAH of unknown origin in order
to control for the effects of the bleeding itself. An increasing number of studies performed during the last
10 years have been unable to find more memory disturbances or more severe neuropsychological impairments in AcoA patients. Table 8 gives an overview of
those publications where the AcoA patients did not
differ from patients with aneurysms at other locations
in terms of neuropsychological impairment including
memory.
Richardson [91] found no statistically significant
differences in the postoperative impairment in a verbal
recall task in patients with different aneurysm loca-

tions. However, the author analyzed his data not


selectively for effects of ruptured AcoA aneurysms
and tested only functions of verbal recall. MauriceWilliams et al. [71] could not find any relationship
between cognitive postoperative performance and side
of aneurysm. In the study of Hutter and Gilsbach [40],
the neuropsychological performance of 18 patients
after rupture and early repair of an AcoA aneurysm
was compared to 21 patients after aneurysmal SAH of
other locations and to 9 patients after spontaneous
SAH of unknown origin. Both groups proved to be
comparable in terms of age, delay from SAH to
follow-up, neurological condition on admission
(Hunt&Hess) and severity of SAH (Fisher CT grading). However, there was a tendency of more frequent
intracerebral or intraventricular hemorrhages seen on
CT scan in the AcoA patients than in the control
group. The neurological result at the 6-month followup ranged between GOS = I and GOS = II. No single
patient in the AcoA group presented with a global
amnestic disturbance and/or a Korsakoff-like confabulation or disorientation. The AcoA patients did
not differ significantly from the control group, neither
in the frequency of cognitive impairments, nor in their
mean test scores in any of the neuropsychological tests
used including memory functions. Furthermore, in a
study about quality of life and cognitive deficits after
SAH, there was also no statistically significant difference neither in the frequency of neuropsychological
deficits nor in the self-and proxy rated impairments in
daily life between AcoA patients and patients with
ruptured aneurysms at other locations [43]. Even in the
acute stage, several days (median 5 days) after early
surgery, no substantial differences between the test
score means of 13 patients after rupture of an AcoA
aneurysm and 15 patients bearing aneurysms at other
locations could be revealed [46]. In a further study patients after rupture and early repair of an AcoA
aneurysm did not present with more psychological
problems than patients with spontaneous SAH of
other etiology [49]. This differs from results of earlier
studies where AcoA patients showed marked emotional disturbances [6, 56, 89, 100]. Furthermore,
Hutter and Gilsbach [44] found no relationship between impaired introspection and AcoA aneurysm
location.
These overall results can be interpreted as a consequence of the improved modern management of
aneurysmal SAH, i.e. as the introduction of the operating microscope, modern aneurysm clips, the aban-

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

donment of trapping procedures of the aneurysmbearing vessel and the principle of early surgical repair
[27-29,40, 59]. Neuroanatomical studies have shown
that there is a supply of structures near the anterior
wall of the III. ventricle by perforating arteries, which
originate from the AcoA [16, 90]. They supply the
anterior hypothalamus, septum pellucidum, anterior
parts of the cingulate gyrus, sections of the fornices
and the anterior parts of the corpus callosum [70]. Recently, neuroanatomical evidence was provided that
the perforators stemming from the AcoA primarily
supply the basal nucleus of Meynert [50]. This structure can be supposed to be of critical importance for
memory processing [48]. These findings prove a neuroanatomical basis for the neuropsychological deficits
in AcoA patients described in earlier studies. The use
of the operating microscope and of modern
aneurysm clips help the neurosurgeon to prevent
damage to the small perforators originating from the
AcoA and, therefore, to minimize the patient's risk for
a postoperative Korsakoff-syndrome [27, 40]. Evidence for the relevance of different surgical techniques
in aneurysm surgery for the neuropsychological outcome in patients with ruptured AcoA aneurysms
was presented first by Gade [27]. The author found a
close relationship between intraoperative trapping of
the AcoA and postoperative memory disturbances.
If trapping of the aneurysm was performed, 9 (81 %) of
11 patients showed a postoperative amnestic syndrome. Of the 37 patients, where the neck of the
AcoA aneurysm was operated by ligation, only 6
[16%] cases presented with an postoperative amnesia
[27].
Early and Late Effects of Surgical Procedures and
Events in Aneurysm Surgery

Studies about the neuropsychological sequelae of


surgical procedures and events in aneurysm surgery
are rare as of yet. An increasing number of authors
have been unable to demonstrate significant effects of
different aneurysm sites on neuropsychological test
performance [8,17,18,40-44,46,49,62,87,91,104,
105, 117]. Therefore, the cognitive deficits after aneurysmal SAH are probably not caused by focal damage
to structures close to the aneurysm ruptured or by the
effects of surgical procedures and events [46]. So far,
the neuropsychological consequences of different operative procedures themselves, intraoperative complications and related problems are quite unclear [27, 42,

169

46, 71, 97]. The only relevant finding is that the careful
clipping of AcoA aneurysms sparing the perforating
arteries originating from the AcoA and the Al segment seems to prevent massive memory disturbances
and/or psycho organic syndromes [27, 40]. Regarding
the overall effect of early aneurysm surgery, indirect
evidence supports the assumption of only marginal
additional adverse effects of aneurysm surgery because
in several studies patients after spontaneous nontraumtic SAH of unknown origin showed comparable
deficits to patients after aneurysmal SAH [42, 86, 105].
However, a direct attempt to explore possible neuropsychological effects of aneurysm surgery on cognition has rarely been performed. Maurice-Williams et
al. [71] examined 27 patients after aneurysmal SAH in
a prospective study with one preoperative and two
follow-up examinations on the day before discharge
and one year later. All patients were operated upon
late without any surgical complications. At the time of
postoperative assessment, 11 (41 %) patients performed
substantially worse as compared to their preoperative
level and one presented with a newly developed aphasia. Persistent deficits were explained by prolonged
intraoperative ischemia, prolonged fixed retraction of
the dominant hemisphere and inadvertent occlusion of
the right choriodeal artery [71]. The authors could not
find any relationship between cognitive postoperative
performance and the degree of induced hypotension
and intraoperative aneurysm rupture [71]. In a study
by Hutter and Gilsbach, a series of 28 patients was
examined neuropsychologically one to 13 days (median 5 days) after early (within 72 hours) aneurysm
surgery [46]. Plegias, other severe neurological impairments, fluent aphasia or acute psychosis were exclusion criteria. The neurological outcome of all patients
at 6-month follow-up was good (GOS = I). Induced
hypotension was never employed during surgery. Four
years after surgery the patients were examined in a
follow-up study for their quality oflife by means of the
Aachen Life Quality Questionnaire (ALQI) [45, 47].
No substantial effect of premature aneurysm rupture
or surgical approach (left versus right pterional), neither on the acute neuropsychological performance nor
on the later quality of life could be revealed. Temporary clipping of vessels was used in 18 (64%) operations. The mean occlusion time of one vessel was 2.8
minutes with a range between two and 13 minutes. If
temporary clipping was employed, the patients performed significantly worse in the concentration and
alertness task as compared to those patients in whom

170

temporary clipping had not been applied (p < 0.05,


respectively). Four years later, those patients in whom
temporary clipping was employed, rated themselves as
significantly more impaired in the life quality area of
mobility (p = 0.05). However, it cannot be excluded
that complicating factors like effects of blood pressure
or individual collateralisation confounded these adverse effects of temporary clipping. Tidswell et al. [110]
reported that the temporary clipping of the anterior
cerebral artery was associated with significantly higher
impairment as assessed by the relatives of the patients.
Moreover, the single patient with a posterior circulation aneurysm who required temporary clipping exhibited a severe word recall deficit postoperatively
[110]. The risk of temporary clipping is a point of controversy between neurosurgeons [lO, 51, 60, 81, 98].
However, it can be concluded that sofar there is no
mean to predict the tolerance of temporary vessel occlusion [98]. The as yet available data give some indication that inadequate aneurysm clipping, temporary
clipping, prolonged retraction and inadvertent surgical
damage to vessels and parenchyma bear the risk of
additional and sometimes persistent neurobehavioral
impairments [27, 46, 71, 110]. However, our data suggest that the effects of surgery are much weaker than
the impact of the hemorrhage itself if a skilled
neurosurgeon employs strictly microneurosurgical
techniques accompanied by adequate modern postoperative management [46, 28-30, 58, 59, 96, 104].
Quality of Life in Patients who had been in Hunt&Hess
Grades IV and V on Admission to the Neurosurgical
Unit
The progress made in the neurosurgical management of aneurysmal SAH enables the surgical treatment of patients being in Hunt&Hess grades IV or V.
Therefore, it was the aim of an own pilot study to
explore the later quality of life of these patients. Furthermore, the relevance of several clinical variables
was analysed in order to identify possible prognostic
factors for the later quality of survival. A consecutive
series of 192 patients with aneurysmal SAH treated
between 1990 and June 1992 in the Department of
Neurosurgery, University of Technology (RWTH)
Aachen was examined for their quality oflife 2-3 years
after the acute event by means of the Aachen Life
Quality Inventory (ALQI) [45, 47]. Of these, 39
(20.3%) patients were in Hunt&Hess grade IV or V on
admission, while 153 were rated as being in grade

B. O. Hutter et af.

I-III. In the Hunt&Hess grade IV or V group 33


(84.6%) patients were operated upon early (within 72
hours). In the group of patients with grade IV or V, 12
(30.7%) died during the acute stage of their illness,
while a further 5 (12.8(%) had died until the follow-up
2-3 years after discharge. In the other patient group
there were 6 (3.9%) fatalities during treatment while
10 (6.5%) had died until the follow-up examination.
Quality of life data of 119 patients were available at
the follow-up. Quality of life was significantly worse in
terms of ambulation, mobility, social contact, freetime activites, communication, autonomy and cognitive capacity (p < 0.05, respectively) in the patients
who were in Hunt&Hess grade IV or V on admission
(n = 20) as compared to those with Hunt&Hess grade
I-III (n = 99). Age, number and severity of accompanying illnesses and sociodemographic variables were
comparable between both groups. A detailed analysis
of the quality of life in the Hunt&Hess IV or V group
revealed that 6 (30%) patients enjoyed a good to acceptable quality of life while the others remained substantially impaired according to arbitrary criteria.
Statistical analyses revealed no significant differences
between these both subgroups in terms of vasospasm,
aneurysm location, number and severity of accompanying illnesses, delay SAH/surgery, incidence of
an intracrebral or intraventricular bleeding or hydrocephalus. However, the patients with an acceptable
quality of life were significantly (p = 0.006) younger
than the other patients. Correspondingly, a discriminant analysis revealed age as the most important discriminating variable. By means of this analysis the
later quality of life of 85% of the patients could be
predicted correctly. The results suggest that younger
patients after aneurysmal SAH and almost early surgical repair who were on admission in Hunt&Hess
grades IV or V have a certain chance to regain an
acceptable quality of life. On the other hand, older
patients showed a severely restricted quality oflife 2-3
years after SAH. Therefore, age seems to be an important predictor of the later life quality of patients in
Hunt&Hess grades IV or V. This is in line with findings
that the age of patients suffering from SAH has a general prognostic significance [63].
Conclusions
In spite of the essentially improved medical management of aneurysmal SAH and the routine use of
sophisticated microneurosurgical techniques, many

Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

171

patients suffer from persistent neurobehavioral impairments after aneurysm rupture. Even a good neurological result (GOS = I) does not exclude substantial
mental impairments. Therefore, we suggest a comprehensive neuropsychological assessment after SAH in
order to obtain information about the factual functionallevel of the patients. Adverse neuropsychological effects of aneurysm surgery remain relatively weak,
if performed by a skilled neurosurgeon using modern
microneurosurgical techniques. In contrast to the
weak permanent effects of aneurysm surgery, the severity of the bleeding, its anatomical pattern and the
initial neurological state have the main prognostic
impact for the neurological and neurobehavioral
functional late outcome after aneurysmal SAH.

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Correspondence: Dr. B. O. Hiitter, Department of Neurosurgery,
University of Technology (RWTH) Aachen, Pauwelsstr. 30,
D-52057 Aachen, Germany.

Author Index

Aaslid, R. 47
Curcic, M. 123
Dolenc, V. V. 89,99
Ekseth, K. 107
Enblad, P. 73
Gilsbach, J. M. 157

Kaku, Y. 123
Kiss, M. 123
Kreitschmann-Andennahr, I. 157
Langmoen, 1. A. I, 107
Lawton, M. T. 141
Le Roux, P. D. 7
Lindegaard, K.-F. 59
Loch Macdonald, R. 27
Lundar, T. I
Mayfrank, L. 157

Rohde, V. 157
Roth, P. 123
Spetzger, U. 157
Spetzler, R. F. 141
Steiger, H.-J. 81
Stoodley, M. 27
Taub, E. 123
van Loon, J. J. L. 81

Hauglie-Hanssen, E. 107
Hiitter, B. O. 157

Nomes, H. 107

Weir, B. 27
Winn, H. R. 7

Imhof, H. G. 123

Persson, L. 73

Yonekawa, Y. 123

Index of Keywords

Acute stage 123


Aneurysm 7,89,99
Aneurysm clip 81
Aneurysm rupture 157

Early surgery 157


Endothelin 27
Extradural selective anterior clinoidectomy
123

Basilar head aneurysm 123


Biography 1

Giant aneurysm 141

Quality of life 157

Hemodynamics 47
Hemoglobin 27
Humans 59
Hypothermic circulatory arrest 141

Revascularization 141
Review article 59

Carotid-ophthalmic aneurysm 89
Cavernous sinus 99
Cerebral aneurysm 1,59,81,107
Cerebral arteriovenous malformations
Cerebral pathophysiology I
Cerebral vasospasm 59
Cerebrovascular spasm 47
Clinical 59
Clinical grade 7
Cognitive deficits 157
Computed tomography 81

Internal carotid artery 89, 99


Intracerebral microdialysis 73
Intracranial hypertension 73
Magnetic resonance imaging 81
Neurointensive care 73
Neurosurgery 1

Nitric oxide 27
Ophthalmic artery 89
Posterior circulation aneurysms 123

Subarachnoid haemorrhage 1,7,47,59,


73, 107, 141, 157
Surgery 107
Surgical technique 99
Titanium alloy 81
Transcranial Doppler 1,47
Transcranial Doppler unltrasound 59
Vasospasm 27

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Intracranial Pressure
and Neuromonitoring in Brain Injury
Proceedings of the Tenth inlernationallCP Symposium,
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1998. XVI. 4JO pages. 176 figures.

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This volume contains the most re cent works on intracranial pressure and neuromoniloring in
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intens ive care as well as the c urrent stale of knowledge in neurochemical and oxygen monItoring of the injured brain. Recent advances In molecular mechanis ms of injury and the pathophYSiology of ischemia and trauma are also included.

Contents
Manageme nt of ICP and CPP
I CP Measurement Techni(IUeS
Neuromonitoring in Inte ns ive Care
Traumatic Brain Inju ry
Brain Oxyge n Monitoring
Molecular Mechanisms of Injury
Cerebral Blood Flow and Metabolism
Micro<lialysis in Brain Injury
Near Infra-He(j Spectroscopy
Biophysical Modeling of ICP
Pathophys iology of ICP

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