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Original Paper

Eur Neurol 2009;62:293–297 Received: March 2, 2009


Accepted: July 13, 2009
DOI: 10.1159/000235808
Published online: August 27, 2009

Repetitive Lumbar Punctures as Treatment


for Normal Pressure Hydrocephalus
T.S. Lim S.W. Yong S.Y. Moon
Department of Neurology, Ajou University School of Medicine, Suwon, South Korea

Key Words Introduction


Lumbar punctures ⴢ Normal pressure hydrocephalus ⴢ
Shunt operation Normal pressure hydrocephalus (NPH) is character-
ized by slowly progressive gait disturbance, cognitive de-
cline, and urinary disturbance. It can be diagnosed by
Abstract characteristic clinical features and laboratory findings,
Selected normal pressure hydrocephalus (NPH) patients especially brain imaging showing enlarged ventricles
cannot be treated by shunt operation because of the pro- with relatively less significant periventricular white mat-
cedure’s high complication rate. We have treated cases in ter changes [1]. However, in the clinical setting, making
which prolonged clinical improvement of NPH was experi- an NPH diagnosis is not straightforward. It is necessary
enced after one or two lumbar punctures (LPs). We eval- to rule out other possible causes and refer to response to
uated the predictors of prolonged improvement of NPH lumbar punctures (LP) and imaging findings to make a
symptoms by repeated LP. Thirty-one NPH patients were ret- diagnosis and plan for the treatment. Dementia from
rospectively evaluated (age 72.5 8 5.8 years). Gait distur- NPH is treatable by either a ventriculoperitoneal shunt or
bance, urinary incontinence, and cognitive impairment were ventriculoatrial shunt. The response to the shunt opera-
semiquantified. We divided the patients into three groups tion can be predicted by an LP or external cerebrospinal
(non-responders, temporary responders, and prolonged re- fluid (CSF) drainage prior to the operation [2]. However,
sponders) according to their responses after LP. We analyzed it is not simple to select candidates for the shunt operation
the characteristics of the groups. Gait disturbance (p = 0.046) due to combined pathology and poor general medical
and urinary incontinence (p = 0.040) scores and total NPH conditions in the aged population. In addition, according
symptom score (p = 0.007) after cerebrospinal fluid drainage to the long-term follow-up studies, about 6–8% of pa-
were more significantly improved in prolonged responders tients experience serious and permanent neurological
than in temporary responders. On multiple logistic regres- deficits such as hemiparesis or even death. Various com-
sion analyses, total NPH score improvement was the only plications such as subdural hematoma, intracranial hem-
predictor of the prolonged responders (p = 0.03, odds ratio orrhage, or shunt infection were reported in more than
0.148). Our study showed that some NPH patients could 30% of patients [3]. These problems underscore the need
maintain favorable courses for at least 1 year after LP without for other treatment options.
shunt operation. Repeated LP could be an alternative treat- A few studies reported that patients who underwent
ment in selected NPH patients. an LP once or twice without the shunt operation showed
Copyright © 2009 S. Karger AG, Basel prolonged symptomatic improvement [4]. However, there

© 2009 S. Karger AG, Basel So Young Moon, MD, PhD


0014–3022/09/0625–0293$26.00/0 Department of Neurology, Ajou University School of Medicine
Fax +41 61 306 12 34 San 5, Woncheon-dong, Yeongtong-gu
E-Mail karger@karger.ch Accessible online at: Suwon, Kyungki-do 443-721 (South Korea)
www.karger.com www.karger.com/ene Tel. +82 31 219 5175, Fax +82 31 219 5178, E-Mail symoon.bv@gmail.com
Fig. 1. MRI images showing dilated ventricles with various degrees of white matter changes in three represen-
tative prolonged reponders (a, b, c).

have been no studies that evaluated if repetitive LP can Evaluation of NPH Symptoms
be an alternative treatment to the shunt operation in An NPH scale modified from Larsson et al. [6] and Krauss et
al. [7] that assessed gait (1 = normal, 2 = walk without any assis-
NPH patients. In this study, we reported patients with tive device but insecure, 3 = walk with cane, 4 = walk with bi-
NPH whose symptomatic response to repetitive LP was manual support (walker), 5 = walk aided by an assistant, 6 =
maintained for more than 1 year without the need for a wheelchair-bound), urinary disturbance (0 = normal, 1 = spo-
shunt operation and analyzed what was the predictor of radic incontinence or urge phenomena, 2 = frequent incontinence
the prolonged symptomatic response to repetitive LP in or urge phenomena, and 3 = no or minimal control of bladder
function) and cognitive deficit (0 = normal, 1 = minimal attention
patients with NPH. or memory deficits, 2 = considerable attention or memory deficits
but oriented to situational context, and 3 = not or only margin-
ally oriented to situational context) was used to characterize and
Patients and Methods grade the clinical syndrome. Patients were evaluated both before
and 6 h after the LP.
Patients
Among patients who visited the Department of Neurology at Classification of Patients
the Ajou Medical Center, Suwon, South Korea, from January 2001 After 1 year of observation, patients were grouped into non-
to December 2007, we recruited 31 patients who met the criteria responders, temporary responders, and prolonged responders.
for NPH and were observed for at least 1 year after admission Non-responders were patients who showed neither improvement
treatment. All patients had brain MRIs and an LP. The clinical in any scores nor subjective improvement after the LP. Temporary
criteria for NPH included the following: (1) insidious onset, age responders were patients whose score in any category improved
of onset 1 40, disease duration 13–6 months, progressive course, by at least one point or who reported subjective improvement but
and no other neurologic, psychiatric, or medical condition apart whose improvement was not sustained up to 3 months. Prolonged
from the disease symptoms; (2) MRI showing ventricular en- responders were patients whose improvement corresponded to
largement not entirely attributable to cerebral cortical atrophy; (3) that mentioned above but whose improvement was sustained up
gait disturbance with or without cognitive deficit or urinary dis- to 3 months.
turbance, and (4) no evidence for the increased intracranial pres-
sure (70–245 mm H2O) [5]. After making a diagnosis of NPH, one MRI
or two LPs were performed to drain 30–50 ml of the CSF. All par- All MR images of patients were reviewed by three neurologists
ticipants were fully informed that there were two therapeutic op- (authors) with visual inspection (fig. 1a–c). The Evans index and
tions of repetitive LP or shunt surgery and agreed to be treated by white matter changes were assessed using MRI. The Evans index
repetitive LP at least for 1 year. The study was approved by the was defined as the maximal frontal horn ventricular width di-
Institutional Review Board of the hospital, and informed consent vided by the transverse inner diameter of the skull and signifies
was obtained in accordance with the principles of the Declaration ventriculomegaly if it is 60.3 [5]. White matter change was eval-
of Helsinki. uated by the method designed by Mantyla et al. [8]. Both peri-
ventricular (0–6) and deep (0–4) white matter changes were as-
sessed [9].

294 Eur Neurol 2009;62:293–297 Lim/Yong/Moon


Table 1. Demographic and clinical characteristics of the patient groups

Non- Transient Long-term Total


responders responders responders
(n = 6) (n = 12) (n = 13) (n = 31)

Men:women 5:1 8:4 8:5 21:10


Age, years 72.886.7 71.685.8 73.285.9 72.585.8
Duration, days 3348353 5218458 4448381 4538400
Evans index 0.3480.03 0.3480.02 0.3380.02 0.3480.02
PVWMH 2.0081.0 2.8381.8 3.6181.7 3.0081.71
DWMH 1.1681.16 2.2581.28 2.0781.18 1.9681.25
White matter changes 3.1682.13 5.0883.02 5.6982.65 4.9682.79
CSF protein, mg/dl 42.3813.2 36.5811.4 38.4810.8 38.4811.3
CSF glucose, mg/dl 68.0813.7 78.2821.6 70.1811.8 72.8816.7
Anti-parkinsonian drugs, n 3 7 6 16
Pre-gait score 2.080.00 2.8381.33 3.1581.21 2.8081.19
Pre-urinary score 1.1680.40 1.3380.77 1.5380.77 1.3880.71
Pre-cognition score 0.8380.40 1.0880.79 1.1580.80 1.0680.72
Pre-NPH score sum 4.0080.63 5.2582.34 5.8481.72 5.2581.93
Post-gait score 2.0080.00 2.2580.86 1.8480.55 2.0380.65
Post-urinary score 1.1680.40 1.0880.66 0.6980.48 0.9380.57
Post-cognition score 0.8380.40 0.9180.51 0.7680.43 0.8380.45
Post-NPH score sum 4.0080.63 4.2581.86 3.3081.10 3.8081.42

PVWMH = Periventricular white matter hyperintensity; DWMH = deep white matter hyperintensity;
CSF = cerebrospinal fluid; NPH = normal pressure hydrocephalus.

Statistical Analysis To look for predictors to be able to discriminate be-


First, using the Mann-Whitney test, we compared demo- tween temporary and prolonged responders, we used
graphic features, CSF findings, Evans index, white matter chang-
es, medications taken, total and categorized scores for the NPH multiple logistic regression analysis. We categorized sev-
before and after the LP, and the amount of the improvement in eral variables as follows: age of onset (61–70, 71–80, 181),
the scores after the LP between temporary responders and pro- disease duration (!1 year, 61 year), scores for white mat-
longed responders. We also used logistic regression analysis to ter changes (!3, 63), amount of CSF protein (!40 mg/dl,
search for independent predictors to discriminate between the 640 mg/dl), and changes in the total NPH scores (!2,
two groups. p ! 0.05 was regarded as statistically significant. The
statistical analyses were performed using commercially available 62). The analysis showed that the amount of changes in
software (SPSS, Version 12.0). the total NPH scores was the only independent predictor
to discriminate two groups (odds ratio 0.148 (95% confi-
dence interval 0.026–0.860), p = 0.03).
Results

We recruited 31 patients (21 men and 10 women). The Discussion


mean age of onset was 72.5 and the mean disease dura-
tion was 453 days. These features are summarized in ta- Although a few studies have reported that patients
ble 1. The patients consisted of 6 non-responders, 12 tem- showed prolonged response to LP, these studies have not
porary responders and 13 prolonged responders. We sta- been given full attention. In addition, good response to
tistically compared temporary and prolonged responders the LP, which is revealed to be an independent predictor
using the Mann-Whitney test. Among the variables test- of the prolonged responders in this study, is also the pre-
ed, the amount of changes in total NPH scores, gait score dictor of favorable outcome of the shunt operation [10].
changes, and urination score changes after LP were sig- Therefore, repeated LP has not been systematically stud-
nificantly different (table 2). ied since the shunt operation was introduced in 1960s.

Lumbar Punctures for Normal Pressure Eur Neurol 2009;62:293–297 295


Hydrocephalus
Table 2. Comparison of demographic and clinical characteristics pressure according to the Pascal’s law. If the ventricles are
between transient responders and long-term responders slightly shrunken by CSF removal, the elasticity of the
ventricles can recover along with symptomatic improve-
Transient Long-term p
responders responders value ment for a certain period. It seems that prolonged re-
(n = 12) (n = 13) sponders to LP did not acquire irreversible damage to the
brain although patients showed symptoms. However, if
Men:women 8:4 8:5 0.852 appropriate CSF removal is not done at the threshold,
Age, years 71.685.8 73.285.9 0.503 irreversible damage to the cerebrum occurs and can
Duration, days 5218458 4448381 0.852
Evans index 0.3480.02 0.3380.02 0.650 produce non-responders or temporary responders to
PVWMH 2.8381.8 3.6181.7 0.295 the LP.
DWMH 2.2581.28 2.0781.18 0.728 We should accept that this study has several limita-
White matter changes 5.0883.02 5.6982.65 0.611 tions. This study was retrospective and could not quan-
CSF protein, mg/dl 36.5811.4 38.4810.8 0.689 tify each symptom accurately. Each symptom was evalu-
CSF glucose, mg/dl 78.2821.6 70.1811.8 0.437
Anti-parkinsonian drugs, n 7 6 0.825 ated every 3 months at the outpatient clinic. Therefore,
Pre-gait score 2.8381.33 3.1581.21 0.437 we could not assess exactly when patients started to wors-
Pre-urinary score 1.3380.77 1.5380.77 0.470 en. In addition, some parts of the scales were somewhat
Pre-cognition score 1.0880.79 1.1580.80 0.810 subjective and vulnerable to patients’ other medical con-
Pre-NPH score sum 5.2582.34 5.8481.72 0.225 ditions including mood. Unfortunately, we did not evalu-
Post-gait score 2.2580.86 1.8480.55 0.347
Post-urinary score 1.0880.66 0.6980.48 0.247 ate mood with scales throughout the study although we
Post-cognition score 0.9180.51 0.7680.43 0.611 excluded patients with major depression. Furthermore,
Post-NPH score sum 4.2581.86 3.3081.10 0.270 many patients failed to be followed after just 1 year of ob-
Gait score improvement 0.5880.90 1.3080.94 0.046* servation. Future studies are needed to compare clinical
Urinary score improvement 0.2580.45 0.8480.68 0.040* courses according to the treatment modality (the shunt
Cognition score improvement 0.1680.38 0.3880.65 0.538
NPH score improvement 1.0080.95 2.5381.50 0.007*
operation/repeated LP) among non-responders, tempo-
rary responders, and prolonged responders.
PVWMH = Periventricular white matter hyperintensity; In conclusion, this study showed that good responders
DWMH = deep white matter hyperintensity; CSF = cerebrospinal to the LP should be observed for at least 3 months to see
fluid; NPH = normal pressure hydrocephalus. * p < 0.05. if their responses are prolonged. If they are prolonged and
patients agree, they can be observed without an immedi-
ate shunt operation, especially in cases where the patients
are not in an appropriate condition for the operation or
could have several degenerative diseases.
This study showed that prolonged responders had sig-
nificantly more improvement in the total NPH score, gait
score, and urination score. In addition, we found that the Acknowledgement
amount of the total NPH score change was an indepen-
This study was supported by a grant of the Korea Health 21
dent predictor to discriminate between temporary and
R&D Project, Ministry of Health and Welfare, and Family Af-
prolonged responders. Although it is impossible to dis- fairs, Republic of Korea (A050079).
tinguish responses to the LP from the natural course of
the NPH, the presence of patients who showed sustained
response with repeated LP could be evidence for the ther-
apeutic responses. In addition, it is difficult to exclude
any disease responsive to the anti-parkinsonian drugs.
However, there was no significant difference in the drug
history among the three groups.
At an early stage of NPH, patients can compensate for
abnormalities in CSF flow through both reduced produc-
tion and increased absorption of the CSF due to increased
intracranial pressure [11]. However, as the ventricles get
larger, they lose the elasticity with the even intracranial

296 Eur Neurol 2009;62:293–297 Lim/Yong/Moon


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