Transcript Everything you ever wanted to know about stroke (and were

ISCHEMIC STROKE,
THROMBOLYSIS & TIA
Matthias Georg Ziller
R5 Neurology
September 10th 2008
Objectives
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Understand the clinical approach to acute stroke
Understand the use of thrombolysis in acute stroke
General management of stroke
Approach to TIA
Why it’s important
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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
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Abrupt symptom onset
Focal neurological deficits
lasting > 24 hours
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Definition changing towards tissue damage
Interruption of vascular
supply leads to energy
failure
TYPES
Lacunar
20%
SAH
10%
Hemorrhagic
20%
Thromboembolic
10%
Cardioembolic
20%
Ischemic
80%
ICH
10%
Other 5%
Unknown
25%
Risk Factors
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Non-modifiable
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Age
Ethnicity: Blacks, Asians
Male gender
Family history
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Stroke in first degree relative
Genetics
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Dyslipoproteinemias
Vasculopathies
Cardiomyopathies
MELAS, CADASIL
Risk Factors
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Modifiable :
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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
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Others:
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High fibrinogen
APL antibody
Homocysteine
Recent bacterial infection
Sickle cell disease
Pathophysiology
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Metabolically active tissue
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Complete arrest of flow:
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(15-20% CO )
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
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CBF<18 ml/min/100 g: electric failure
CBF < 8 ml/min/100g: membrane failure
Stroke syndromes
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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
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Immediate response
ABC, Quick History:
 ONSET
, ONSET, ONSET
 WHEN
 Atypical
WAS THE PATIENT LAST SEEN NORMAL ?
features H/A, NECK PAIN, SZ
 Improvement
BEWARE OF MIMICS !
P/E
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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
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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
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Exclude hemorrhage
Exclude mass lesions
Assess degree of brain injury
Identify the vascular lesion
 Next
step: CTA protocol to identify occluded vessel
First step
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CT scan:
 Plain,
 Look
aim is door-to-CT 25 min
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
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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
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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
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Decreased level of consciousness
Symptom onset >3 hours
SAH, aneurysm, AVM, ICH, mass effect, tumour on
CT, or any major hypodensity representing wellevolved infarction
Stroke or serious head injury with 3 months
More exclusion criteria
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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 . . . .
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HTN (BP>185/110) not responding to
antihypertensive therapy
Pericarditis <3 months
NINDS: methods
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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
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2 parts were independent
 Part
1: early improvement
291 pts randomized to tPA or placebo
 Looked at NIHSS improvement > 3 pts at 24h
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 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
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at both outcomes for both parts (624 pts)
Appropriate power for primary outcome
< 3 Hours from onset:NINDS Trial
Parts A and B
16% absolute risk reduction
NNT = 7 – 8 for 1 excellent or complete recovery
Disability
None
27
Moderate
Severe
26
Death
26
21
Placebo
43
21
20
rt-PA
1 symptomatic ICH for 15 treated patients …
Treatment does not decrease mortality.
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NINDS results: bleeding
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Symptomatic
Asymptomatic
Treatment
Group
20 (6.4%)
13 (4.2%)
Placebo
Group
2 (0.6%)
8 (2.6%)
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.
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
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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)
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Institution of stroke quality improvement program
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Less protocol deviation (19.1%)
6.4% sICH
Learning curve exists and can be overcome
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Community Experience
Canadian Experience
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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
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Similar or better results than NINDS
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Symptomatic intracranial hemorrhage 4.6% (75% died)
Excellent clinical outcome in 37% at 90 days (NINDS 39%)
154 protocol violations
Outside the window !
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Nothing to do?
Don’t be sad! Or angry
at someone ...
There are still ways to
help your patient
Things to do
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Admit
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Maintain adequate tissue oxygenation, > 92 %
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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
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Treat fever and infections
No firm recommendation for cooling in 2007 AHA guidelines
Things to do
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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
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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
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Glucose
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Seizures:
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Frequent complication
5000 U bid or LMWH, safe with ASA
Incontinence not uncommon in acute stroke
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5-8 % after stroke, prophylaxis not recommended
DVT prophylaxis
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Treat hyperglycemia aggressively, frequent testing, scales and Insulin
Limit use of Foleys to avoid urosepsis
Pressure sores in 15 % after stroke
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Think of it
Positioning, dressings, adequate nutrition
TRANSIENT ISCHEMIC ATTACKS
TIA
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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
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It is a stroke that did not finish YET
TIA
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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
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Mortality
 5-6
% annually, mainly by MI
TIA Prognosis
Speech, motor, >10 min, age >60, diabetes
Gladstone D et al. CMAJ. 2004 Mar 30;170(7):1099-104.
TIA Risk
Gladstone D et al. CMAJ. 2004 Mar 30;170(7):1099-104.
Speech, motor, >10 min, age >60, diabetes
TIA Prognosis
Benign
Timing
weeks ago
Duration
sec – few minutes
Frequency
multiple
Sensory
yes alone
Motor
no
Speech
no
Risk factors
no
Deficit dynamics
Mild at onset
Malignant
hours ago
>10 min
one to few
no
yes
yes
HTN, DM,
Severe at onset
High risk TIA –ABCD2 score
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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 point
Rothwell 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
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Detailed history
CT head/MRI brain
Metabolic parameters
ECG- AF
Carotid doppler/MRA/CTA
Echo
Management
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Admission for malignant TIA
Urgent evaluation
Antiplatelets
Statin
Control risk factors
CEA or stenting early
Thank you:
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On the shoulders of giants:
 Mike
Sidel, Alexandre Poppe, Adel Al-Hazzani, Dr
Minuk and Dr Cote, Charles Miller Fisher …
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The Patient Study Group
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and …