ischemic stroke, thrombolysis & tia matthias georg ziller r5 neurology september 10 th 2008
TRANSCRIPT
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 …