Prepared By: Rohit Upadhyay

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

0 10 20 30 40 50 60 70 80 90

minutes

Penumbra

Core

CEREBRAL

BLOOD

FLOW

(ml/100g/min)

CBF < 8

CBF 8-18

TIME (hours)

1 2 3

20

15

10

5

PENUMBRA

CORE

Neuronal dysfunction

Neuronal death

Normal function

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

Courtesy Brott T et al

NNT 5

NNT 20

Penumbra damaged by:

Hypoperfusion

Hypoxia

Acidosis

Hyperglycemia

Fever

Seizure

Guidelines Ischaemic Stroke 2008

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

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

Clot occluding

artery

Intracerebral

Hemorrhage

Bleeding

into brain

Subarachnoid Hemorrhage

Bleeding

around brain

85% 10% 5%

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

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

von Kummer R et al. Radiology (2001) 219:95-100

HYPERACUTE STROKE ON CT

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

WINDOW PERIOD UPTO 6 HOURS

INSULAR RIBBON?

Hyperdense MCA sign (HMCAS)

NCCT CTA

MCA dot sign

NCCT CTA

Specificty-100% : Sensitivity -38% Leary MC Stroke 2003;34:2636-40

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

Hyperdense ACA

Hyderdense ICA (HICAS)

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

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

CTA shows thrombus in the top of basilar and left P1 occluded.

Basilar artery

thrombus

M1

C

IC

L

A

I

P

M2

M3

M4

M5

M6

A

P

Fig 1a

52.6

6.44.5

10.6 13.5

20

9.5

40

0

5

10

15

20

25

30

35

40

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

ASPECTS

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

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 + 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 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 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 Penumbra

Advantages Limitations

CT Perfusion

CBF, CBV,

MTT, TTP

MTT

threshold at

145%

Combined with plain

CT

Available

Fast

Limited brain coverage

Poorly sensitive to posterior circulation

Iodonated contrast

DWI-PWI MRI

CBF, CBV,

MTT, TTP,

ADC

Relative

TTP (or

MTT) delay

>45s and

normal DWI

Sensitive

No radiation

Limited availability

Patient cooperation required

Frequent contraindications

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

Diffusion and Perfusion Imaging Evaluation

for Understanding Stroke Evolution

(DEFUSE)

Echoplanar Imaging Thrombolytic Evaluation

Trial (EPITHET)

Lancet Neurol 2008;7:299309.

Lancet Neurol 2008;7:299309.

Ann Neurol. 2006 Nov;60(5):508-17

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

EKOS - MicroLys infusion catheter (EKOS) Neurosurg Clin N Am. 2009 Oct;20(4):419-29

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.

Autoregulation is impaired/abolished in stroke.

CBF follows perfusion pressure

Chronic Hypertensive

Blood pressure >220 systolic or > 120 dystolic BP only needs

emergency treatment if no end organ damage

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

Guidelines for the Early Management of Adults With Ischemic Stroke,

AHA/ASA Guideline, Stroke. 2007

Ideal Drug

Short acting

easily titrated

predictable response

Drug used

Labetolol

Nicardipine infusion

sodium nitroprusside (if refractory)

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

Asprin 150-325 mg to be given within 24-48

hrs (Class I, Level of Evidence A)

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

Stroke. 2007;38:1655-1711

Heparin

Controversial

Meta-analysis of 24 trials involving 23748 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

Cochrane Database Syst Rev 2008 Cochrane Database Syst Rev 2008 Cochrane Database Syst Rev 2008

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-, 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

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%

MISTIE

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 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 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