ISCHEMIC STROKE, THROMBOLYSIS & TIA

Matthias Georg Ziller

R5 Neurology

September 10th 2008

Objectives

1. Understand the clinical approach to acute stroke

2. Understand the use of thrombolysis in acute stroke

3. General management of stroke4. Approach to TIA

Why it’s important

Everyday 3rd -4th cause of death 1st cause of adult disability . 50,000 new /year in

Canada . 750,000 new/year in USA . Annual 40-44 billion (US) 30% of survivors require

daily assistance

Definition

Abrupt symptom onset

Focal neurological deficits lasting > 24 hours Definition changing towards tissue

damage

Interruption of vascular supply leads to energy failure

TYPES

ICH10%

SAH10%

Lacunar20%

Thromboembolic10%

Cardioembolic20%

Other 5%

Unknown25%

Ischemic 80%

Hemorrhagic 20%

Risk Factors

Non-modifiable Age Ethnicity: Blacks, Asians Male gender Family history

Stroke in first degree relative Genetics

Dyslipoproteinemias Vasculopathies Cardiomyopathies MELAS, CADASIL

Risk Factors

Modifiable : HTN – 3-4 x DM – 2-4 x with HTN SMOKING – 2-3 x Hyperlipidemia CAD Afib – 5-6 x Stroke , TIA , stenosis. EtOH

Risk Factors

Others: High fibrinogen APL antibody Homocysteine Recent bacterial

infection Sickle cell disease

Pathophysiology

Metabolically active tissue (15-20% CO )

Complete arrest of flow: 15 sec: suppression of electric activity 2-4 min: inhibition of synaptic excitability 4-6 min: inhibition of electric excitability

Normal CBF > 55ml/min/100 g CBF<18 ml/min/100 g: electric failure CBF < 8 ml/min/100g: membrane failure

Stroke syndromes

MCA, ACA, PCA, VBS, IC Lacunar (PM, SM, HP, CD and 200 more Brain stem syndromes

Weber, Claude, Benedikt, Wallenberg ... Various constellations of CN and long tract

findings

“53333-1”Now what?

ER evaluation

Immediate response ABC, Quick History:

ONSET , ONSET, ONSET

WHEN WAS THE PATIENT LAST SEEN NORMAL ?

Atypical features H/A, NECK PAIN, SZ Improvement

BEWARE OF MIMICS !

P/E

Vitals, BP both arms, Pulse(s) Listen for murmurs and bruits LOC , speech Inattention, neglect…etc CN (Pupils, visual fields, gaze, facial) Arm, leg drift, fine finger movements Sensory Dysmetria

Requisite

IV lines, O2 CBC SMA7, ESR, PT/PTT INR: wait for it in alcoholics, possible ATC

GLUCOSE EKG, ischemia markers CXR Selected patients: toxicology, b-HCG

Imaging in acute stroke

Goal

Exclude hemorrhage Exclude mass lesions Assess degree of brain injury Identify the vascular lesion

Next step: CTA protocol to identify occluded vessel

First step

CT scan: Plain, aim is door-to-CT 25 min

Look for subtle signs - 50% 6 hrs Grey-white matter differentiation Sulcal effacement Obscuration of lentiform nuclei, insula MCA Parenchymal hypodensity

ASPECTS: Alberta Stroke Program Early CT scoring

American Journal of Neuroradiology 22:1534-1542 (9 2001)

Normal: 10 points. Substract one point for each area of attenuation. Increased disability < 7.

• ▼stroke severity .

Time is brain!

Saver, Stroke 2006

Indications for rt-PA

Patients presenting within 3 hours of an acute ischemic stroke

To be given <3 hours after stroke symptoms onset

May be given <6 hours under the care of a stroke neurologist in IA protocol

Inclusion Criteria

Acute ischemic stroke presenting within 3 hours of onset of symptoms

No hemorrhage on CT No evidence of massive infarction or

edema involving >1/3 MCA territory No midline shift (mass effect) No evidence of tumour, aneurysm or

AVM

Exclusion Criteria

Decreased level of consciousness Symptom onset >3 hours SAH, aneurysm, AVM, ICH, mass effect,

tumour on CT, or any major hypodensity representing well-evolved infarction

Stroke or serious head injury with 3 months

More exclusion criteria

Previous CNS bleed History of GI/GU hemorrhage <21 days Major trauma/surgery <14 days Hematological abnormality or

coagulopathy, INR >1.7 Arterial puncture at a non-compressible

site in the last 7 days

Even more . . . .

HTN (BP>185/110) not responding to antihypertensive therapy

Pericarditis <3 months

NINDS: methods

National Institute of Neurological Disorders and Stroke(NEJM 1995)

RCT in 2 parts of 624 pts between January 1991 and October 1994

30 of 40 centers were community hospitals Included only patients within 3h

Half within 90 minutes Half between 90-180 minutes

Strict exclusion criteria BP criteria Bleeding risk No ischemic size criteria

NINDS: methods

2 parts were independent Part 1: early improvement

291 pts randomized to tPA or placebo Looked at NIHSS improvement > 3 pts at 24h

Part 2 : delayed improvement 333 pts randomized to tPA or placebo Looked at proportion of pts who recovered with

minimal or no deficits at 3 months Looked at both outcomes for both parts

(624 pts) Appropriate power for primary outcome

< 3 Hours from onset:NINDS TrialParts A and B

27 26 26

43 21 20 17

Disability

None Moderate Severe Death

Placebo

rt-PA

16% absolute risk reductionNNT = 7 – 8 for 1 excellent or complete recovery

21

1 symptomatic ICH for 15 treated patients …Treatment does not decrease mortality.

NINDS results: bleeding

Asymptomatic bleeds: no difference Symptomatic bleeds:

6.4%, half were fatal (occurred within first 24 hours)

Benefit of tPA occurs despite increased risk of ICH ! Later studies: Increased ICH rate associated with protocol violations.

Symptomatic

Asymptomatic

Treatment Group

20 (6.4%) 13 (4.2%)

Placebo Group

2 (0.6%) 8 (2.6%)

NINDS: Conclusion

‘‘Despite an increased incidence of intracerebral hemorrhage, an improvement in clinical outcome at three months was found in patients treated with intravenous t-PA within three hours of the onset of acute ischemic stroke’’ with decreased combined severe disability and death at 3 months and a trend towards decreased mortality.

Stroke outcome with alteplase

Cochrane Review

Community Experience

Cleveland Experience

Not very good results (JAMA 2000) Little experience with tPA 50% protocol deviation 15.7% sICH – 15.7% mortality

Results better with time (Stroke 2003) Institution of stroke quality improvement

program Less protocol deviation (19.1%) 6.4% sICH Learning curve exists and can be overcome

Community Experience

Canadian Experience

Canadian Altepase for Stroke Effectiveness Study (CASES) CMAJ 2005

Collected 2 years of Canadian experience: Post-marketing study (Phase IV) 1135 patients in 60 centres (33 community

hospitals)

CASES

Similar or better results than NINDS Symptomatic intracranial hemorrhage 4.6% (75% died) Excellent clinical outcome in 37% at 90 days (NINDS 39%) 154 protocol violations

Outside the window !

Nothing to do?

Don’t be sad! Or angry at someone ...

There are still ways to help your patient

Things to do

Admit Maintain adequate tissue oxygenation, > 92 %

Common: pneumonia, hypoventilation, atelectasis 50 % of patients requiring intubation die within 1 month NPO Avoid aspiration No supportive data for hyperbaric oxygen, may be

toxic

Avoid hyperthermia Treat fever and infections No firm recommendation for cooling in 2007 AHA

guidelines

Things to do

Cardiac monitoring MI and arrhythmia frequent after stroke, most often AFib Arrhythmia associated with right hemispheric insular strokes 24 hour monitoring recommended

Blood pressure monitoring Transiently elevated, optimal: 160-200 mm Hg SBP, 70-110

DBP Lower and higher BP associated with ↑ infarct volume at 7 days Lower it only if > 220/130

or 185/110 for tPA, use IV labetalol 10 mg q 10-20 min Avoid hypotension, < 100 SBP associated with - outcome

ASA within 48 hours reduces the risk of early recurrence without a

major risk of bleed and improves long-term outcome

Things to do

Glucose Treat hyperglycemia aggressively, frequent testing, scales and Insulin

Seizures: 5-8 % after stroke, prophylaxis not recommended

DVT prophylaxis Frequent complication 5000 U bid or LMWH, safe with ASA

Incontinence not uncommon in acute stroke Limit use of Foleys to avoid urosepsis

Pressure sores in 15 % after stroke Think of it Positioning, dressings, adequate nutrition

TRANSIENT ISCHEMIC ATTACKS

TIA

Focal neurological deficits lasting < 24 hours

New proposed definition: Rapidly resolving neurologic symptoms

typically lasting less than 1 hour with no evidence of infarction on imaging

Most last 5-20 minutes

It is a stroke that did not finish YET

TIA

Prognostic indicator of stroke 30 % of untreated patients have a stroke

within 5 yrs 10% within the next 3 months 50 % of them within the first 48 hours

Mortality 5-6 % annually, mainly by MI

Speech, motor, >10 min, age >60, diabetes

TIA Prognosis

Gladstone D et al. CMAJ. 2004 Mar 30;170(7):1099-104.

Speech, motor, >10 min, age >60, diabetes

TIA RiskGladstone D et al. CMAJ. 2004 Mar 30;170(7):1099-104.

TIA Prognosis

Timing weeks ago hours agoDuration sec – few minutes >10 minFrequency multiple one to fewSensory yes alone noMotor no yesSpeech no yesRisk factors no HTN, DM, Deficit dynamics Mild at onset Severe at

onset

Benign Malignant

High risk TIA –ABCD2 score

Age > 60 yrs =1 BP >140/90 =1 Clinical

Weakness (2 pts) Speech without weakness (1 pt)

Duration >60 min (2pts), 10-59 1 (pt) <10 (0 pts)

Diabetes = 1 pointRothwell PM et al-Lancet 2005

High risk TIA –ABCD score

Rothwell PM et al-Lancet 2005

DWI restriction common in TIA

~50% of all TIA’s associated with permanent damage. Especially if it lasts > 1 hour.

Even brief symptoms cause areas of

permanent injury

Kidwell C et al. Stroke 1999; 6:1174-1180. Couttts SB et al. Annals of Neurology 2005;57:848-854

TIA- Evaluation

Detailed history CT head/MRI brain Metabolic parameters ECG- AF Carotid doppler/MRA/CTA Echo

Management

Admission for malignant TIA Urgent evaluation Antiplatelets Statin Control risk factors CEA or stenting early

Thank you:

On the shoulders of giants: Mike Sidel, Alexandre Poppe, Adel Al-

Hazzani, Dr Minuk and Dr Cote, Charles Miller Fisher …

The Patient Study Group

and …