Download Stroke

Clinical Aspects of Stroke
Pierre Fayad, MD
Reynolds Centennial Professor & Chairman,
Department of Neurological Sciences
University of Nebraska Medical Center, Omaha, NE
1
“Stroke”
• APOPLEXY from Greek “Apo Plexe”
meaning “a stroke”.
• Anyone seized by sudden disability was
thought to be “struck down” by the Gods.
Haubrich WS. Medical Meanings: A Glossary of Word Origins.
Publisher: American College of Physicians 2003
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Steps in Neurologic Evaluation
Gather information
– Chief complaint
– Symptoms, evolution
– Physical examination
Analysis
– Localization
– Pattern of disease
– Comparison to clinical database
Gather information
– Diagnostic tests
Diagnosis & Treatment
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Steps in Stroke Evaluation
Gather information
– Chief complaint
– Symptoms and history: risk factors, chronologic
evolution
– Physical examination: vascular and neurologic
Analysis
– Localization: CNS level, large vessel, branch, …
– Pattern of disease: tempo, risk factors
– Comparison to clinical datatbase
Gather information
– Diagnostic tests: location, size, type, mechanism
Diagnosis & Treatment
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What Is A “STROKE”?
CLINICAL DEFINITION of focal neurologic deficit,
of vascular etiology, lasting > 24 HOURS.
Diagnosis is dependent on neurologic deficit and
NOT imaging.
“Generic term for a clinical syndrome that includes
infarction, hemorrhage, and SAH.”
NINDS Classification of CVD III. Stroke 1990, 20:627-680
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Types of Stroke
• Ischemic Stroke
– Brain damage from lack of blood flow
– Occlusion of blood vessel
– Thrombosis, embolism
• Hemorrhagic stroke
– Rupture of blood vessel
– Brain damage from blood invasion
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Stroke Subtypes: Stroke Data Bank
Undetermined
32%
SAH
13%
ICH
13%
Other
3%
Atherosclerotic
6%
Lacunar
19%
Cardioembolic
14%
Stroke Data Bank, Foulkes et al, Stroke 1988;19:547
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Definition of Transient Ischemic Attack
• Classic definition
– A sudden, focal neurologic deficit lasting less than
24 hours, presumed to be of vascular origin, and
confined to an area of the brain or eye perfused by a
specific artery
• Proposed definition
– A brief episode of neurologic dysfunction caused by
focal brain or retinal ischemia, with clinical
symptoms typically lasting less than 1 hour, and
without evidence of acute infarction
Albers GW et al. N Engl J Med. 2002;347:1713-1716.
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Short-term Prognosis after
Emergency Department Diagnosis of TIA
Outcome events
15 %
Objective:
12.7%
10 %
Inclusion criteria: TIA by ED physicians
Outcome
measures:
10.5%
Within
90 days
Total events:
Short-term risk of stroke
after ED diagnosis
Risk of stroke and other
events during the 90
days
after index TIA
25.1%
5%
5.3%
0%
2.6%
2.6%
Within
48 hr
Stroke
Recurrent CV event
TIA
Death
Johnston SC, et al. JAMA 2000;284:2901-2906.
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US Stroke Facts 2003
• Incidence
– 700,000 new or recurrent stroke yearly
– One stroke every 45 seconds
• Mortality
–
–
–
–
168,000 Stroke-related death yearly (1 of 14 deaths)
Third leading cause of death after heart and cancer
One stroke-related death every 3 minutes
Of every 5 stroke deaths: 2 men, 3 women
• Costs
– $51 billion in 2003 for stroke related medical costs and
disability
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American Stroke Association
Stroke Risk Factors
Modifiable
Medical Conditions
Hypertension
Cardiac disease
Atrial fibrillation
Hyperlipidemia
Diabetes mellitus
Carotid stenosis
Prior TIA or stroke



Behaviors

Cigarette smoking

Heavy alcohol use

Physical inactivity


Non-Modifiable


Age, Gender, Race,
Heredity
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Goals For Acute Stroke Care
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Rapid triage and identification of stroke
Stroke type: Ischemic vs Hemorrhagic
Eligibility for “acute stroke therapy”
Determine size, location, & vascular territory
Establish plans for efficient Management &
discharge
Stabilization & prevention of complications
Determine etiology & mechanism
Initiate secondary stroke prevention strategies
Initiate rehabilitation assessment and therapy
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Intracerebral Hemorrhage
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Hypertensive ICH: Post-Mortem
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Clinical Features Suggestive Of ICH
• Severe headache
• Depressed consciousness
• Nausea and vomiting
• Horizontal diplopia
• Papilledema and pre-retinal hemorrhages.
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ICH
Sx
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CAUSES OF INTRACRANIAL HEMORRHAGE
HTN
Amyloid angiopathy
Anticoagulants
Tumors
Prescription and street drugs
AVMs and aneurysms
Miscellaneous
50%
12%
10%
8%
6%
5%
9%
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Charcot-Bouchard
Microaneurysms
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Intracranial Vascular
Malformations
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ICH - General Management
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Nutrition
DVT prophylaxis
Hydration and electrolytes
Acute arterial hypertension
Intracranial hypertension
Hydrocephalus
Seizure prophylaxis and treatment
Surgery and decompression
AHA Special Writing Group, Stroke 1999;30:905-915
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Dose-Ranging Study: rFVIIa in Preventing
Early Hematoma Growth in Acute ICH
• Multicenter, international, Phase II study, 400 patients, CT
< 3 hrs from Sx, Rx < 60 min CT.
• Arms: Placebo, 40, 80, 160 mcg/kg
• Significantly reduces
– 45-62% RR Dose-dependent hematoma growth
– 38% RR Mortality
• Significantly improves
– Global functional outcome (mRS and BI) at 90 days
• Small increase in the risk of acute thromboembolic events
Mayer SA et al. N Engl J Med. 2005;352:777-785.
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Subarachnoid Hemorrhage
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Subarachnoid Hemorrhage:
Schematic
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Berry Aneurysm Rupture
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Location of Berry Aneurysms
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SAH
Symptoms
& Diagnosis
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Intracranial
Aneurysms Sx
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Aneurysm Coiling or Clipping
Johnston SC, et al. Ann Neurol. 2000;48:11-19.
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SAH - Delayed Vasospasm
• Facts
– A leading cause of death and disability
– Starts 3-5 d after SAH, and maximal at 3-14 d.
– 20-30% delayed neurologic ischemic deficits.
• Diagnosis
– TCD, angiography.
• Treatment
– Nimodipine
– Hypertensive, hypervolemic, hyperosmolar Rx (HHH)
– Local IA papaverine -> transluminal angioplasty
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Ischemic Stroke
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• Metabolic
Stroke Mimics
–Hyper/hypoglycemia, Hyponatremia,
Hypo/hyperthyroidism, Hepatic encephalopathy
• Seizures
• Subdural hematoma
• Infections
–Brain abscess, encephalitis, meningitis
• Neoplasm
• Drug overdose (also a cause of stroke).
• Hypertensive encephalopathy
• Psychogenic
• Migraine
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Vascular Localization
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!!!Learn Neurology
Stroke-By-Stroke!!!
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Brain Picture
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What The Brain Does
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Cortical Functional Localization
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Homunculus
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Localizing Stroke
• Stroke affects three main areas of the brain
– Left hemisphere
– Right hemisphere
– Brainstem/cerebellum
• Neurologic deficits patterned in syndromes
according to brain part affected and location
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Cerebral
Circulation
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Cerebral Vascular Territories
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Left (Dominant) Cerebral Hemisphere Syndrome
• Aphasia.
• Left gaze preference.
• Right visual field cut.
• Right hemiparesis.
• RIght hemisensory loss.
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Right (Non-dominant) Cerebral Hemispheric Syndrome
• Neglect (left hemi-inattention)
• Right gaze preference.
• Left visual field deficit.
• Left hemiparesis.
• Left hemisensory loss.
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Syndromes of Carotid Branch Occlusions
Location
Artery
Dominant
Non-dominant
ACA
Contralat LE
weakness
Abulia
Contralat LE
weakness
Abulia
MCA:
ant division
Expressive aphasia
Contralat
hemiparesis
Ipsilat gaze deviation
Aprosodia
Contralat
hemiparesis
Ipsilat gaze deviation
Parietal
lobe
MCA:
post division
Conduction aphasia
Gerstman’s synd, HH
Contral hypoesthesia
Anosognosia,
Apraxia,
Contralateral neglect,
Hypoesthesia, HH
Temporal
lobe
MCA:
post division
Receptive aphasia,
Contralateral HH
Contralateral
Hemianopia
PCA
Alexia without
agraphia
Contralateral HH
Contralateral
Hemianopia 47
Frontal
Lobe
Occipital
lobe
Brainstem Syndrome
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Crossed signs.
Hemiparesis or quadraparesis.
Hemisensory loss or sensory loss in all four limbs.
Eye movement abnormalities.
Oropharyngeal weakness.
Decreased consciousness.
Hiccups or abnormal respirations.
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Cerebellar Syndrome
• Gait or limb ataxia
• Vertigo, tinnitus
• Nausea, vomiting.
• Decreased Consciousness.
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Acute Stroke Therapy
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Platelets in Acute Vascular Events
Plaque
Atherosclerotic
Vessel
Collagen
Plaque
Rupture
Platelets
Platelet
Adhesion,
Recruitment,
Activation,
and
Aggregation
Thrombus
Thrombus
Formation
Thrombotic
Occlusion
MI
Stroke
Acute Peripheral
Arterial Occlusion
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Cerebral Ischemia: Basic Mechanisms
•Perfusion failure
•Energy failure
•Loss of membrane function
•Edema
•Cell death
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QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
Ischemic
Cascade
Brott T et al, NEJM 2000,343:710-721
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ISCHEMIC PENUMBRA
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Acute Ischemic Stroke:
Large MCA, CT
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Time is Brain
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Supportive Acute Stroke Care
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Monitor for potential worsening
Stabilize vital signs
Maintain adequate hydration
Optimize nutrition: early, PO, NG feeds, PEG
Prevent aspiration: screen for those at risk
Treat fever aggressively: any elevations
Mobilize early: within 24 hours
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Therapies for Acute Cerebral Ischemia
• Antithrombotic therapy
– Antiplatelet medications
– Aspirin, Clopidogrel, ASA/ER-DP
– IV GP IIb IIIa antagonists (Abciximab)
– Anticoagulants
– Hypofibrinogenemic (Ancrod)
• Reperfusion and perfusion enhancement
– Thrombolytic therapy: Intravenous, intra-Arterial
– Mechanical clot dissolution/removal
• Neuroprotective Therapies
– Non-specific cellular protection
– Specific neuronal protection
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Acute Antiplatelet Therapy for
Stroke
• Aspirin 160 mg daily, started within 48
hours, decreases risk of stroke and death at
one month.
CAST Collaborative Group, Lancet 1997;349:1641-1649
• Other antiplatelet agents not tested acutely.
• As a rule early AP Rx start recommended.
• Preferable to start same AP agent as OP.
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Acute Anticoagulation For Stroke:
Conclusions
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•
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Acute anticoagulation DOES NOT…
–
Does not improve overall outcome, prevent neurologic deterioration or
prevent recurrence
Indications
–
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SQ anticoagulation for DVT prophylaxis in immobilized patients or
paralyzed leg
Sinus venous thrombosis
Risks
–
Risk of cerebral hemorrhage and systemic bleed substantially
increased.
Untested
–
Acute anticoagulation < 12 hours
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NINDS IV
tPA
Primary
Outcomes
NEJM 1995;333:1581-1587
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Acute Stroke: Intra-Arterial Lysis
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Brott T et al, NEJM 2000,343:710-721
Merci Clot Retriever
Concentric Medical Inc.
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Gobain YP. Stroke 2004;35:2848-2854
MERCI-1: Example of Clots Retrieved
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Gobain YP. Stroke 2004;35:2848-2854
Stroke Prevention Strategies
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Identify stroke subtype and mechanism
Risk Factors and Lifestyle modification
Non-Anti-thrombotic Treatments
Oral Anticoagulation
Antiplatelet Medications
Surgery and interventions
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Stroke Mechanism Determination
Specific work-up
other
Hemorrhagic Stroke
blood
TIA or Stroke
CT/MRI
normal or infarct
Duplex, TCD,
MRA,
angiogram
Ischemic Stroke
Tandem pathology, Yes
No
Large Artery Stroke
TTE/TEE, ECG
cardiac source, Yes
No
Cardioembolic Stroke
Lacunar syndrome, Yes
Risk Factors
No
Other defined etiologies, Yes
No
Adapted Fayad PB; J. Cardiovascular
Diagn & Proc 1994;12 (1):35-42.
Lacunar small vessel
stroke
Infarction Determined
Etiology
Infarct undetermined
cause 67
Carotid Bifurcation AtheroThrombo-Embolism
68
MCA Embolism
69
Common
Cardioembolic
Sources
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Intracranial
Atherothrombosis
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Lenticulostriate Arteries
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Classic Lacunar Syndromes
Lacunar Syndrome
Clinical features
Common locations
Pure motor
hemiparesis
Hemiparesis (arm, leg,
face equally)
Post limb IC, Ant limb
IC, Corona radiata
Pure sensory
stroke
Sensory loss,
dysesthesia (face,
arm, leg)
Thalamus, centrum
semiovale
Sensory-motor
stroke
Combined hemi motor
and sensory deficits
Thalamus, putamen,
corona radiata
Ataxic hemiparesis
Homolateral ataxia
with crural paresis
Corona radiata,
posterior limb IC,
thalamus
Dysarthria-clumsy
hand syndrome
Combined dysarthria,
upper limb ataxia
Anterior limb IC, genu,
pons hemorrhage
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Fayad et al. Curr. Rev CVD 1996, Current Medicine: 81-92
Carotid
Pathologies
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Non Anti-Thrombotic Treatments
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Non-Anti-Thrombotic Medical Therapies
For Stroke Prevention-1: Lipid Lowering
• Clear benefit for statins in primary stroke
prevention (20-30%) in patients with CAD
and even average level of LDL cholesterol.
• No demonstration yet of statin benefit in
secondary stroke risk reduction. (Exception
HSP, SPARCL pending).
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Non-Anti-Thrombotic Medical Therapies
For Stroke Prevention-2: Anti-HTN
• Significant stroke risk reduction (20%-30%
RRR ischemic, >50% RRR hemorrhagic) in
treating hypertension, systolic or diastolic.
(more evidence for systolic)
• Anti-HTN: Significant primary & stroke
risk reduction, even in non-hypertensives.
• Superiority of Anti-HTN drug classes in
stroke prevention undetermined yet.
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Non-Anti-Thrombotic Medical Therapies
For Stroke Prevention-3: Miscellaneous
• No benefit (but clear harm) from hormonal
replacement in post-menopausal women.
• No benefit from Vitamin B supplementation
in hyperhomocystinemia in patients with
stroke or TIA.
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Antiplatelet (AP) Therapy in
Stroke Prevention: Summary
• Aspirin (ASA) not indicated for primary stroke
prevention.
• Low-dose ASA recommended for secondary
stroke prevention.
• No single AP agent more effective than aspirin.
• To Date, ASA-ER DP only AP combination
effective and safe (> ASA) in secondary stroke
prevention
• In patients at risk for stroke, the combination of
Clopidogrel and aspirin significantly increase the
risk of ICH, life-threatening and major bleeding.
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Primary Prevention Of Ischemic Stroke
Asymptomatic but
with risk factors
Asymptomatic and healthy
without risk factors
Risk factor
modification
Women postmenopausal
Men
> 60
No other
Cardioembolic
Asymptomatic
NVAF
AMI
pathology
source/pathology
ICA/CCA stenosis
Low risk
High risk
Evaluate CAD
X
Estrogen Antiplatelet
Anti-HTN?
Statins?
Warfarin
Statins
Endarterectomy
Adapted From Fayad PB; J. Cardiovascular Diagn & Proc 1994;12 (1):35-42.
80
Secondary Prevention of Ischemic Stroke
TIA or STROKE
Large Vessel
Athero
Extracranial
carotid stenosis
Small Vessel
Lacunar
Undetermined
etiology
Intra/extra-cranial
stenosis/occlusion
Cardiogenic
embolism
Documented
source/pathology
AF
70-99% 50-69% < 50%
CEA
Antiplatelet, XXXX
Estrogen
Anti-HTN? Statins?
Warfarin
Adapted From Fayad PB; J. Cardiovascular Diagn & Proc 1994;12 (1):35-42.
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Carotid Stenting
Reimers B, et al. Circulation. 2001;104:12-15.
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ACCULINK & ACCUNET Stent System
(Guidant): ARCHER & CREST
ACCULINK
ACCUNET
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Cerebral Circulation
85
Stroke Case
72-year-old right-handed African-American woman
admitted with weakness and speech difficulty
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Stroke Case:
72-year-old woman
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•
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Presentation
Sudden onset of right arm and leg weakness
Speech difficulty
Hospital admission ~6 h after symptom onset
History
Hypertension
Dyslipidemia
Diabetes
Nonsmoker
Rarely drinks alcohol
87
Stroke Case:
72-year-old
woman
CT scan at 10 days
Should this patient have
had a follow-up scan
earlier than 10 days postadmission?
Would an MRI have been
better?
88