Dr.

Haseeb Hassan
 Affects > 780,000 persons per year
 3rd major cause of death & long-term
disability
 Estimated U.S. cost for 2008 = $65.5 billion

 In Trivandrum, annual incidence rates was

135/100 000
Stroke. 2009;40:1212-1218
 Pre-hospital management
 Initial assessment and emergency
management
 Thrombolysis
 Acute stroke intervention
 Medical support
 Antiplatelet agents
 Anticoagulation
 Surgery
 Golden 90 Minutes

0 10 20 30 40 50 60 70 80 90
minutes
 Penumbra

Core

CEREBRAL Normal
BLOOD 20 function
FLOW
(ml/100g/min)
Neuronal
15 dysfunction CBF
PENUMBRA 8-18
10

5 CORE Neuronal CBF

death <8

1 2 3
TIME (hours)

Time is Brain
 Diminishing Returns over Time
Favorable Outcome (mRS 0-1, BI 95-100, NIHH 0-1) at Day 90 Adjusted odds ratio with 95% confidence interval by stroke
onset to treatment time (OTT) ITT population (N=2776)

Pooled Analysis NINDS tPA, ATLANTIS, ECASS-I, ECASS-II

~4h 40min

NNT 5

NNT 20

Courtesy Brott T et al
 Penumbra damaged by:
• Hypoperfusion
• Hypoxia
• Acidosis
• Hyperglycemia
• Fever
• Seizure
 Emergency care in acute stroke depends on a
four-step chain:
 Rapid recognition of, and reaction to, stroke signs
and symptoms

 Immediate EMS contact and priority EMS dispatch

 Priority transport with notification of the receiving

hospital

Guidelines Ischaemic Stroke 2008

 Stroke vs Stroke mimikers

 Time of onset of the stroke

 Brief clinical evaluation, NIHSS score

 Vitals, Blood sugar by glucometer

 Check list for thrombolysis

 Imaging
 Is it stroke?
 Type of stroke
Ischemic Intracerebral Subarachnoid
Stroke Hemorrhage Hemorrhage
85% 10% 5%

Clot occluding Bleeding Bleeding

artery into brain around brain
 Cranial Computed Tomography (CT)
 Immediate plain CT scanning distinguishes reliably
between haemorrhagic and ischaemic stroke
 Detects signs of ischaemia as early as 2 h after
stroke onset von Kummer R et al. Radiology (2001) 219:95-100

 Helps to identify other neurological diseases (e.g.

neoplasms)
 Most cost-effective strategy for imaging acute
stroke patients
Wardlaw J et al. Stroke (2004) 35:2477-2483
HYPERACUTE STROKE ON CT
WINDOW PERIOD UPTO 6 HOURS
EARLY ISCHEMIC CHANGES (EIC)
1. HYPERDENSE MIDDLE CEREBRAL ARTERY (HDMCA)
2. ATTENUATION OF LENTIFORM NUCLEUS (ALN)
3. LOSS OF INSULAR RIBBON (LIR)
4. EFFACEMENT OF SULCI
5. LOSS OF CM DIFFERENTIATION
INSULAR RIBBON?
 Hyperdense MCA sign (HMCAS)

NCCT CTA
 MCA dot sign

NCCT
CTA
Specificty-100% : Sensitivity -38% Leary MC Stroke 2003;34:2636-40
 Hyperdense ACA

86 year old with acute onset of rt side weakness,leg more weak than arm
and difficulty in speech ,came in 1.5 hrs of onset. CT scan shows hyperdense
left ACA. CTA shows clot in left ACA
 Hyderdense ICA (HICAS)

Specificity 100% Ozdemir O et al.Stroke 2008;39:2011-16.

 Basilar artery thrombus

52 yr old with acute diplopia and ataxia and left INO .

CTA shows thrombus in the top of basilar and left P1 occluded.
 A
A
M1 M4
C

L I
M5
M2
IC

M6
M3

P
P

Fig 1a
 40
35
30
25
40
20
15
10 20

5 6.4 10.6 13.5 9.5

5 2.6 4.5
0
ASPECTS
8-10 8-10 8-10 3-7 4-7 4-7 0-2 0-3 0-3
NINDS ATLANTIS ECASS-2 NINDS ATLANTIS ECASS-2 NINDS ATLANTIS ECASS-2
n 201 424 280 89 104 119 10 21 5
 DISADVANTAGE OF CT

•Less sensitive than MRI

•Posterior fossa stroke

•Stroke mimics diagnosis is inferior to MRI

•Window period 3 to 6 hours- identification of penumbra –

not possible
 Diffusion-weighted MRI (DWI) is more sensitive
for detection of early ischaemic changes than CT
 Posterior circulation stroke
 Detects even small intracerebral haemorrhages
reliably on T2* sequences
 MRI is particularly important in acute stroke
patients with unusual presentations
 In most instances, CT will provide the
information to make decisions about emergency
management (Class I, Level of Evidence A). 

 The brain imaging study should be interpreted

by a physician with expertise in reading CT or
MRI studies of the brain (Class I, Level of
Evidence C).  
 Multimodal CT and MRI may provide additional
information that will improve diagnosis of
ischemic stroke (Class I, Level of Evidence A). 
 Class II Recommendations
 Vascular imaging is necessary as a preliminary
step for intra-arterial administration of
pharmacological agents, surgical procedures, or
endovascular interventions (Class IIa, Level of
Evidence B). 
 Class III Recommendations

 Emergency treatment of stroke should not be

delayed in order to obtain multimodal imaging
studies (Class III, Level of Evidence C). 
 Vascular imaging should not delay treatment of
patients whose symptoms started <3 hours ago
and who have acute ischemic stroke (Class III,
Level of Evidence B). 
I. Triage–10 min III. CT & Labs–45 min
 Review t-PA criteria  Obtain lab results
 Page acute stroke team  Read CT
 Draw pre t-PA labs  Return pt to ED
II. Medical Care–25 min IV. Treatment–60 min
 Place O2 , 2 NS IVs  Start IV t-PA
 Obtain BP, weight, NIHSS  Monitor for ICH sxs
 Obtain 12-lead ECG ▪ HTN, headache
 Send patient to CT ▪  neuro status
 IV thrombolysis
 NINDS, ECASS I + II, ATLANTIS
OTT Odds Ratio for normal at 3 mo. Hemorrhage

0-1.5 h 2.81 3.1%

1.5-3 h 1.55 5.6%
3-4.5 h 1.40 5.9%
4.5-6 h 1.15 6.9%

The ATLANTIS, ECASS and NINDS rt-PA

Study Group Investigators, Lancet 2004
 Infuse 0.9 mg/kg (maximum dose 90 mg) over 60
minutes
 10% of the dose given as a bolus
 Neurological assessments
 every 15 minutes during the infusion
 every 30 minutes thereafter for the next 6 hours
 hourly until 24 hours after treatment

 Discontinue the infusion if worsening, raised ICP

features
 Obtain emergency CT scan.
Measure blood pressure
 every 15 minutes for the first 2 hours
 every 30 minutes for the next 6 hours
 hourly until 24 hours after treatment.
 Delay placement of nasogastric tubes,
indwelling bladder catheters, or intra-arterial
pressure catheters.
 Follow-up CT scan at 24 h before starting
anticoagulants or antiplatelet agents.
 ECASS III
 % Normal at Symptomatic
3 mo.* ICH**
tPA 52% 2.4%

Placebo** 45% 0.2%

Hacke, N Engl J Med 2008

*OR 1.34 (1.02-1.74) P = 0.04
**p = 0.006
 < 3.0 Hours 3.0-4.5 Hours
 No upper age limit  Do NOT give if:
 No limit on stroke size  Pt > 80 yr
 Can give if taking warfarin &  NIHSS > 25
INR < 1.7  DM / previous stroke
 Taking warfarin at all
 Mismatch Concept

 Treatment need to be individualised

 Heterogeneous Disease: Infarction at different rates

1 Hr 3 Hr 6 Hr
average

slow

fast
 CT perfusion
Parameters Definition of Advantages Limitations
Penumbra

CT CBF, CBV, MTT •Combined •Limited brain coverage

Perfusion MTT, TTP threshold at with plain •Poorly sensitive to posterior
145% CT circulation
•Available •Iodonated contrast
•Fast

DWI-PWI CBF, CBV, Relative •Sensitive •Limited availability

MRI MTT, TTP, TTP (or •No •Patient cooperation
ADC MTT) delay radiation required
>45s and •Frequent contraindications
normal DWI
Muir KW et al. Lancet Neurology 2006; 5:755-768
 Lancet Neurol 2008;7:299–309.

 Diffusion and Perfusion Imaging Evaluation

for Understanding Stroke Evolution
(DEFUSE)
Ann Neurol. 2006 Nov;60(5):508-17

 Echoplanar Imaging Thrombolytic Evaluation

Trial (EPITHET)
Lancet Neurol 2008;7:299–309.
 N = 101

 RCT – Placebo controlled

 non-significantly lower rates of infarct

growth were seen in PWI/DWI mismatch
patients who received rt-PA
 Contraindication for IV thrombolysis
 Stroke onset ; anterior circulation ; 6-8 hrs
 Posterior circulation stroke (12-24 hrs)
 Concomitant vascular stenosis or dissection/
 Large vessel occlusion
 Poor NIHSS score > 20
 Large salvageable territory (>20% on perfusion
imaging)
 Hyperdense MCA sign
 Suspected hard embolus (calcified debris)
 Intra-arterial thrombolysis

 Bridging therapy
 (0.6 mg/kg IV) + (10-22 mg IA);

 Mechanical thrombolysis
 Neurosurg Clin N Am. 2009 Oct;20(4):419-29
EKOS - MicroLys infusion catheter (EKOS)
 FDA-approved for recanalizing acutely occluded
cerebral arteries.
 Multi-MERCI study - Patients who did not
improve immediately after IV rt-PA underwent
mechanical embolectomy within 8 hours of
symptom onset.
 Partial or complete recanalization occurred in 74% of
patients,
 Symptomatic intracerebral hemorrhage (sICH) rate of
6.7%.
Baseline angiogram Post treatment angiogram demonstrates
demonstrates complete occlusion complete reperfusion of the right ICA
of the right ICA terminus (black territory after 1 pass of the Merci L6
arrow). device.
Available in 3 different sizes aimed to treat different vessel diameters.
Thromboaspiration is achieved by connecting the microcatheter (black arrows) to an
aspiration pump.
The “separator” (white arrows) is then advanced in and out of the microcatheter
to“unclog” any obstructive thrombus.
 Healthy Subject Chronic Hypertensive

CBF 50 ml/min/100 gram brain tissue at Autoregulatory range is shifted upwards

MAP 50- 150 mm Hg Ishemic symptoms develop at higer SBP
than normal

 Autoregulation is impaired/abolished in stroke.

 CBF follows perfusion pressure
 Blood pressure
 >220 systolic or > 120 dystolic BP only needs
emergency treatment if no end organ damage
Guidelines for the Early Management of Adults With Ischemic Stroke,
AHA/ASA Guideline, Stroke. 2007

 Hypertensive encephalopathy
 Symptomatic ischemic heart disease
 Congestive cardiac failure
 Rapidly progressive renal dysfunction
 Before and after thrombolytic therapy
 Deterioration of patient due to h’mgic conversion of infarct.
 Aortic dissection
 Ideal Drug  Avoid Drugs –that
 Short acting dilate intracranial
 easily titrated vessels and increase
 predictable response ICT .e.g.
Drug used -nitroglycerine
 Use of nifidepine
 Labetolol

strongly discouraged
Nicardipine infusion
 sodium nitroprusside
(if refractory)
 Hypoglycemia
 Mimicker
 Can compromise penumbra

 Hyperglycemia
 Related to poor outcome in both thrombolysis
and non-thrombolysis patients
 Majority of trials addresses secondary
prevention
 2 major trials (International Stroke Trial (IST)
and Chinese Acute Stroke Trial (CAST)]
evaluated the benefit of aspirin in AIS
 associated with a significant reduction in
death or dependence (OR 0.95, 95% CI 0.91 to
0.99; p = 0.008) and recurrent ischemic strokes
(OR 0.77, 95% CI 0.68 to 0.86; p < 0.00001). 
 Asprin 150-325 mg to be given within 24-48
hrs (Class I, Level of Evidence A)
Stroke. 2007;38:1655-1711
 Fast Assessment of Stroke and Transient
Ischemic Attack to Prevent Early Recurrence
(FASTER) pilot trial –
 Trend towards better benefit with clopidogrel  +
Asprin but no statastical significance
 Cochrane Database Syst Rev 2008

 Heparin
 Controversial
 Meta-analysis of 24 trials involving 23 748
participants
 showed no benefit with regards to death and
dependency or death alone in patients with AIS
▪ Cochrane Database Syst Rev 2008
 Not recommended in acute ischemic stroke
 Low molecular weight heparin
 No benefit on stroke outcome for low molecular
heparin (nadroparin, certoparin, tinzaparin,
dalteparin)
 Heparinoid (orgaran)
 TOAST trial neutral
▪ TOAST Investigators: JAMA (1998) 279:1265-72.
 High dose statins
 SPARCL study
 recent stroke or TIA
 without known coronary heart disease,
 80 mg of atorvastatin per day reduced the
overall incidence of strokes and of
cardiovascular events,
 despite a small increase in the incidence of
hemorrhagic stroke.
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.
N Engl J Med 2006
Admission shortly after ictus
Elevated systolic BP of >160mm Hg
(Broderick J, Stroke 2007)
Irregular shape of clot
Liver dysfunction
Coagulation abnormalities
Markers of vascular injury &
inflammation (high TLC, fibrinogen levels, low
platelet count, high levels of IL-6, TNF-α, MMP-9, c-Fn)
 ICH – on Heparin
 Protamine sulphate 1 mg/100 units of heparin
 ICH - on Warfarin
 5-25 mg Vitamin K1
 FFP (10-20 ml/ kg)
 Recombinant factor VIIa
 ICH – on Thrombolytic therapy
 4 -6 units of cryoprecipitate or FFP
 The INTERACT study, 2008: showed a trend toward lower
relative and absolute growth in hematoma volumes from
baseline to 24 hours in the intensive treatment group compared
with the control group.
 In addition, there was no excess of neurological deterioration or
other adverse events related to intensive BP lowering.
 The study provides an important proof of concept for early BP
lowering in patients with ICH, but the data are insufficient to
recommend a definitive policy.
 Another study, the Antihypertensive Treatment in Acute
Cerebral Hemorrhage (ATACH) trial,also confirms the feasibility
and safety of early rapid BP lowering in ICH.
Ref: Anderson CS, Huang Y, Wang JG et al. INTERACT Investigators. Intensive blood pressure
reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol.
2008
Class II b , Level of evidence C
 Management of raised ICP
 Cerebellar hematoma > 3 cms or > 40 ml
 Vermian hematoma
 lobar clots >30 mL and within 1 cm of the
surface

 For rest of the ICH, surgery is uncertain

  SIHCPA  MISTIE
 RCT -2003  RCT , 2007
 71 pts, 36 randomised
 ongoing
to surgery  Clot reduction in
 Statistically
significant reduction 46% in surgery arm
in the volume of clot vs 4% in control arm
 No reduction in  Adverse events
mortality at 6 months within safety limits
 High risk of
rebleeding 22%
 rtPA, urokinase

 May improve survival significantly

(Cochrane Database Syst Rev 2002;(3))
 Clear IVH trial (Clot Lysis Evaluating Accelerated
Resolution of IVH)

 “Appears to have a fairly low complication rate, efficacy

and safety of this treatment is uncertain and is considered
investigational”
(Class IIb; Level of Evidence: B)
 Acute stroke treatment should be initiated as
early as possible

 IV thrombolysis to be administered at the

earliest in eligible candidates

 Medical management to be optimized to

ensure adequate perfusion of penumbra
 Adams HP et. al., Guidelines for the Early
Management of Adults With Ischemic Stroke.
AHA/ASA Guideline. Stroke. 2007;38:1655
  Novakovic R et. al. Review of current and
emerging therapies in acute ischemic stroke. J
NeuroIntervent Surg 2009
 Guidelines for Management of Ischaemic Stroke
and Transient Ischaemic Attack 2008. Available
at http://www.esostroke.org
 Indications for the Performance of Intracranial
Endovascular Neurointerventional Procedures. AHA
scientific statement. Circulation. 2009;119:2235-
2249

 Morgenstern LB et. al. Guidelines for the

Management of Spontaneous Intracerebral
Hemorrhage. AHA/ASA guideline.
Stroke. 2010;41:2108
A. ASPECTS <7
B. NIHSS >25
C. Age > 65
D. Coronary A. Disease
A. Hypertension should not be aggressively
treated unless SBP > 220
B. Short acting antihypertensive to be used
C. Nitroglycerine infusion is recommended for
BP control during IV thrombolysis
D. Aggressive reduction in BP associated with
poor outcome
 Thalamic bleed
 Intraventricular bleed
 Lobar ICH
 Brainstem bleed