Prepared By:

Vijay Kumar

 Affects > 780,000 persons

3rd major cause of death &

per year
long-term

disability
Estimated U.S. cost for 2008 = $65.5
billion
In

Trivandrum, annual incidence

rates was 135/100 000 Stroke. 2009;40:1212-121

 Pre-hospital management
Initial assessment and emergency

management
Thrombolysis
Acute stroke intervention
Medical support
Antiplatelet agents
Anticoagulation
Surgery

10

20

30

40

50

minutes

60

70

80

90

Penumbra

Core

CEREBRAL
BLOOD
FLOW

20

(ml/100g/min)

15
10

Normal
function
Neuronal
dysfunction

PENUMBRA
CORE

5
1

Neuronal
death

TIME (hours)

Time is Brain

CBF
8-18

CBF
<8

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

 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

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
Stroke
85%

Clot occluding
artery

Subarachnoid
Hemorrhage

Intracerebral
Hemorrhage
10%

Bleeding
into brain

5%

Bleeding
around brain

 Cranial

Computed Tomography (CT)

Immediate plain CT scanning

distinguishes reliably between

haemorrhagic and ischaemic stroke
Detects signs ofvonischaemia
as(2001)
early
as 2
Kummer R et al. Radiology
219:95-100
h after stroke onset
Helps to identify other neurological

diseases (e.g. neoplasms)

Most cost-effective strategy for imaging
acute stroke patientsWardlaw 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
M1

M4

C
L
IC

M5

M2

M6

M3
P
P

Fig 1a

ASPECTS

8-10 8-10

8-10

NINDS ATLANTIS ECASS-2

201 424 280

89

3-7

4-7

4-7

0-2

NINDS ATLANTIS ECASS-2

104

119

0-3

0-3

NINDS ATLANTIS ECASS-2

10

21

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 makedecisionsabout
emergency management (Class I, Level
of EvidenceA).

The

brain imaging study should be

interpreted by a physicianwith
expertise in reading CT or MRI studies of
the brain (ClassI, Level of Evidence C).

 Multimodal

CTand MRI may provide

additional information thatwill
improvediagnosis of ischemic stroke
(Class I, Level ofEvidence A).

Class II Recommendations
Vascular imagingis necessary

as a

preliminary step for intraarterialadministrationof pharmacological

agents, surgical procedures,or
endovascularinterventions (Class IIa,
Level of EvidenceB).

 Class

III Recommendations

Emergency

treatment of stroke should not

be delayed in orderto obtain multimodal
imaging studies (Class III, Level of
EvidenceC).

Vascular

imaging should not delay

treatment of patients whosesymptoms
started <3 hours ago and who have acute
ischemicstroke (Class III, Level of Evidence
B).

I. Triage10 min
Review t-PA criteria
Page acute stroke team
Draw pre t-PA labs

II. Medical Care25

min
Place O2 , 2 NS IVs
Obtain BP, weight,

NIHSS
Obtain 12-lead ECG
Send patient to CT

III. CT & Labs45

min
Obtain lab results
Read CT
Return pt to ED

IV. Treatment60
min
Start IV t-PA
Monitor for ICH sxs

HTN, headache
neuro status

 IV thrombolysis
NINDS, ECASS I
OTT

+ II, ATLANTIS

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 intraarterial pressure catheters.
Follow-up CT scan at 24 h before
starting anticoagulants or antiplatelet
agents.

 ECASS

III

% Normal at
3 mo.*

Symptomatic
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

No upper age limit
No limit on stroke size
Can give if taking
warfarin & INR < 1.7

3.0-4.5 Hours
Do NOT give if:
Pt > 80 yr
NIHSS > 25
DM / previous stroke
Taking warfarin at all

 Mismatch
Treatment

Concept
need to be individualised

Heterogeneous Disease: Infarction at different rates

average

slow

fast

1 Hr

3 Hr

6 Hr

CT perfusion
Parameters

Definition of
Penumbra

Advantages

CBF, CBV,
CT
Perfusion MTT, TTP

MTT
threshold at
145%

Combined

CBF, CBV,
MTT, TTP,
ADC

Relative
TTP (or
MTT) delay
>45s and
normal DWI

Sensitive

DWI-PWI
MRI

Muir KW et al. Lancet Neurology 2006; 5:755-768

with plain
CT
Available
Fast
No

radiation

Limitations
Limited

brain coverage
Poorly sensitive to posterior
circulation
Iodonated contrast
Limited

availability
Patient cooperation
required
Frequent contraindications

Lancet Neurol 2008;7:299309.

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 Neurol2008;7:299309.

= 101

RCT

Placebo controlled

non-significantly

lower rates of
infarct growth were seen in PWI/DWI
mismatch patients who received rtPA

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

Bridging

thrombolysis

therapy

(0.6 mg/kg IV) + (10-22 mg IA);

Mechanical

thrombolysis

Neurosurg Clin N Am.2009 Oct;20(4):

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
demonstrates complete occlusion
of the right ICA terminus (black
arrow).

Post treatment angiogram demonstrates

complete reperfusion of the right ICA
territory after 1 pass of the Merci L6
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
tounclog any obstructive thrombus.

Chronic Hypertensive

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 Ischemi

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 hmgic conversion of
infarct.
Aortic dissection

 Ideal

Drug

Short acting
easily titrated
predictable

response
Drug used
Labetolol
Nicardipine
infusion

Avoid

Drugs
that dilate
intracranial
vessels and
increase ICT .e.g.
-nitroglycerine
Use of nifidepine
strongly
discouraged

 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)

Fast

Stroke. 2007;38:1655-1711

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 Rev2008

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
80 mg of atorvastatin per day

disease,
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.

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-, 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

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 within1
cm of the surface
For

rest of the ICH, surgery is

uncertain

 MISTIE

SIHCPA
RCT -2003
71 pts, 36

randomised to
surgery
Statistically
significant reduction
in the volume of clot
No reduction in
mortality at 6 months
High risk of
rebleeding 22%

RCT

, 2007
ongoing
Clot reduction in
46% in surgery
arm vs 4% in
control arm
Adverse events
within safety limits

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 Surg2009

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.
B.
C.
D.

ASPECTS <7
NIHSS >25
Age > 65
Coronary A. Disease

A.
B.
C.

D.

Hypertension should not be

aggressively treated unless SBP > 220
Short acting antihypertensive to be
used
Nitroglycerine infusion is
recommended for BP control during IV
thrombolysis
Aggressive reduction in BP associated
with poor outcome

 Thalamic bleed
Intraventricular bleed
Lobar ICH
Brainstem bleed