Diagnosis, Evaluation, and Treatment of Stroke
Fariborz Khorvash, MDAssistant Professor of Neurology
Topics
Definitions Evaluation of Suspected Stroke Evaluation of TIAs Stroke Prevention Evaluation & Treatment of Ischemic Stroke Evaluation & Treatment of Hemorrhagic
Stroke
Case #1
62 year old woman presents after a abrupt onset of blindness in her left eye while shopping today. Sx resolved en route to ER via EMS about 20 minutes after they started.
VS Afeb; BP 148/78; P 68 Exam unremarkable in ER
What’s the diagnosis?
Case #2
76 yo male, rehabbing at local NH after recent hip fx, has abrupt onset of slurred speech and left arm/leg weakness.
Sx persistent in ER. Pt has no complaints. VS Afeb; BP 188/96; P 72 Head CT is “negative”
What’s the diagnosis?
Case #3
33 yo woman presents with “worst headache of her life”, abruptly starting 1 hour ago.
On exam, she is mildly confused, has mild nuchal rigidity, but no other focal findings
VS Afeb; BP 155/82; HR 58
What’s the diagnosis?
Classification of Stroke
2 broad categories of stroke:• Ischemia
• Inadequate blood supply (oxygen & nutrients) to an area of the brain
• Hemorrhage- • Leakage of blood into the closed cranial cavity
• Direct damage to tissue by compression/edema
Incidence in US• ~700K per year (~200K are recurrent)
80-90% are ischemic Male:Female ratio 1.25:1
• Ratio reverses after age 80 Higher rates in Blacks, Hispanics, & Native
Americans
Epidemiology of Stroke
Heart disease• AFib, Valvular Dz, MI, endocarditis
Hypertension Smoking Diabetes/Metabolic Syndrome Dyslipidemia Pregnancy Drug Abuse/Meds Bleeding Disorders/Anticoagulant Use
Risk Factors
Ischemic Stroke
Thrombosis• In situ arterial obstruction
• Arteriosclerosis, dissection, FMD
• Superimposed thrombosis
Embolism• Arterial obstruction from debris from another
source Systemic Hypoperfusion
• Circulatory collapse
• Multiorgan involvement
Thrombosis
Large Vessel Disease• Common & Internal
Carotids
• Circle of Willis & proximal branches
Small Vessel Disease• Penetrating arteries
• “Lacunar Stroke”
“Stuttering” course
Embolism
Cardiac• Atrial fibrillation
• Heart valves, atrial thrombus, recent MI, dilated CM, endocarditis, recent CABG
Aortic Arterial (e.g. carotids) Other/Unknown
• DVT- “Paradoxical embolus” Abrupt onset, rapid improvement
Hypoperfusion
Shock• Cardiogenic, septic, hypovolemic
Sx are more diffuse/nonfocal “Border-zone regions”
• Cortical blindness
• Stupor
• Proximal Weakness
Hemorrhagic Stroke Intracerebral
Hemorrhage (ICH)• Bleeding within the brain
tissue
• Forms a hematoma
• Growth stopped by tamponade or leaking into the ventricles or CSF
• Headache, vomiting, delirium
• Progressive sx
Causes of ICH
HTN Trauma Bleeding Disorder
• Inherited
• Acquired, i.e. meds
Amyloid
Drug use• Cocaine
• Amphetamines
AVMs Bleeding into tumor Vasculitis
Hemorrhagic Stroke
Subarachnoid Hemorrhage (SAH)• Bleeding into CSF on
outer aspect of brain
• Quick rise in ICP
• Sudden onset headache in 97%
• Aneurysm & AVMs are most common cause
Differential Diagnosis
Seizure with Todd’s Paralysis
Syncope Migraine Head Trauma Brain tumor
Metabolic Causes• Hypoglycemia
• Hyponatremia
• Intoxication
• Uremia/ARF
• Hepatic Encephalopathy
Conversion Disorder
Initial Evaluation:Physical Exam
Vital signs• Temperature, Pulse, Blood Pressure
Pulses Carotid Bruit Cardiac Exam Funduscopic exam Skin exam Signs of trauma
Neurologic Exam• Level of consciousness/GCS
• Language/Speech
• Cranial nerves
• Vertigo, diplopia, ataxia
• Visual deficits
• Weakness/Paralysis
• Reflexes/ Babinski
Initial Evaluation:Physical Exam
Initial Evaluation: Studies
CBC with platelets Electrolytes, Bun, Cr Glucose LFTs PT/PTT O2 Sat ECG Chest XRay
ESR Blood Cultures ANA Tox screen Alcohol level Blood type & cross Urine/Serum HCG Hypercoaguability
Profile
Initial Evaluation: Imaging
CT Scan• “R/O Bleed”
• Sensitivity much better after 24 hrs for ischemic stroke
• Early signs (<6 hrs)• May indicate worse prognosis
CT Scans of Stroke
Initial Evaluation: Imaging
MRI• T1/T2 images, DWI
• Provides immediate evaluation of ischemia
• Not available for emergency use in many settings
Further Evaluation: Carotids
Carotid U/S for stenosis If ASVD, but no stenosis…
• Risk Factor Modification If stenosis, consider…
• Carotid Endarterectomy
• ?Carotid Stenting Vertigo & Syncope are not considered
symptomatic
100% occlusion• No treatment
70-99% occlusion• If good 5-yr survival & risks <6%, early CEA (within 2
weeks)
50-69%• If above criteria & male, early CEA
• If female, medical mgt
<50%• Medical management
Treatment of Carotid Stenosis with Symptoms
Further Evaluation: Echo
Echocardiography indicated for• Patients who may need anticoagulation
• Atrial fibrillation
• Risk of atrial thrombus
• Recent MI
• Risk for Endocarditis TEE is more sensitive than TTE, but will it
change management?
Further Evaluation: Intracranial
Not necessary for all patients Consider…
• Pts <50 without a clear source
• Pts with recurrent stereotyped TIAs
• Posterior circulation event without cardiac source
• Prior to CEA CTA vs. MRA vs. TCD
Transient Ischemic Attack
Sudden onset of neurologic dysfunction that lasts less than 24 hrs, brought on by presumed transient ischemia to a portion of the brain
May be better to describe as sx <1 hr with no evidence of infarction
May have infarct even with sx lasting a few hours (~50% of TIA patients have MRI evidence of ischemia)
TSI?
Transient Sx Associated with Infarction No established diagnostic criteria In one case series, 15% of TSI pts had a
recurrent stroke in-hospital vs. 0% in TIA group.
Hospitalize for TIAs?
Could consider home if able to expedite urgent outpatient work-up
AHA does not make a recommendation re: hospitalization
One study suggested cost-effective if 24-hr stroke risk is >5%
Risk of Stroke post-TIA
NASCET trial suggested 90-day stroke risk of 20% with non-retinal TIAs (higher than for true stroke)
2000 JAMA study• 5% risk w/in 2 days
• 11% risk w/in 90 days
• Higher risk with age >60, DM, sx >10 min, weakness, speech impairment
2004 Neurology study: 21% risk of stroke/MI/death within 1 year of TIA
ABCDs of TIAs
Age >60 = 1 pt Blood Pressure >140/90 = 1 Clinical Features
• Unilateral weakness = 2
• Isolated speech deficit = 1
• Other = 0
Duration• >60 minutes = 2
• 10-59 minutes = 1
• <10 minutes = 0
Risk of “early stroke”Score ≤ 3: 0%4: 1-9%5: 12%6: 24-31%
Secondary Prevention of Stroke
Risk factor modification Antithrombotic therapy Anticoagulant therapy
Stroke Prevention: Risk Factors
Hypertension• Goal <130/80
• SHEP Study, ISH in pts >60• Dropped SBP from 155 to 143
• 36% reduction in stroke over 4 years
• Pts >80 may not benefit as much & aggressive BP lowering may increase mortality
• Diuretic +/- ACEI as 1st line
Smoking• Stop it
Diabetes• Goal A1c <7, i.e. normoglycemic
• Metabolic syndrome
Stroke Prevention: Risk Factors
Dyslipidemia• Evidence not as strong as may think, but still a
good idea, especially given other vascular disease
• SPARCL Study• Atorvastatin 80 mg/day in pts 1-6 months from CVA/TIA
• Mean LDL reduction 56
• Endpoint was stroke: 16% RRR, but only 2.2% ARR (NNT ~50)
Stroke Prevention: Risk Factors
Dyslipidemia, continued• For average-risk patient, goal LDL <100
• For high-risk, goal <70• Diabetes
• Prior CAD
• Multiple RFs with continued smoking
Stroke Prevention: Risk Factors
Lifestyle Modification• Weight loss
• Exercise
• Dietary changes Reduce alcohol intake, especially heavy
drinkers ?Homocysteine
• Consider B12, B6, Folate (MVI doses OK)
Stroke Prevention: Risk Factors
Antiplatelet Therapy
Aspirin• 20-25% reduction in stroke (& MI or other
vascular death)
• Standard doses of 81-325 mg as good as higher doses
• 81 mg dose just as good and less risk of bleeding
• ASA-non-responders?
Clopidogrel (Plavix)• 8% RRR vs. ASA for stroke/MI/Vasc death
• 5.3% vs. 5.8%: NNT ~200
• All for only $100+/month
• ?2nd-line therapy or ASA-allergic patients
• No increased bleeding vs. ASA, but combo should be avoided
• No neutropenia (like ticlopidine)
Antiplatelet Therapy
Dipyridamole• Alone 50-100 mg TID
• Aggrenox (200mg ER-DP & 25mg ASA) BID
• 2 studies have shown ~3% ARR (NNT 33) over ASA alone for stroke prevention
• Some guidelines are suggesting this a 1st line therapy over ASA alone for stroke prevention
• Cost >$100/month
Antiplatelet Therapy
Anticoagulant Therapy
Warfarin has only been proven effective in primary prevention of stroke in the setting of atrial fibrillation
AF is responsible for 1/6th of all strokes in patients older than 60
Risk reduction• Warfarin about 3 times as effective as ASA
• Absolute annual risk reduction of ~3% “Low Risk” patients may consider ASA rx
Risk of AF-Related Stroke
0%
1%
2%
3%
4%
5%
6%
50-59 60-69 70-79 80-89
Age
An
nu
al
Ris
k o
f S
tro
ke
Risk Stratification for Stroke
Highest Risk: Prior Stroke or TIA High Risk: Any of the following
• Prior thromboembolism
• Female >75 yo
• SBP >160
• Heart failure/LV dysfunction Moderate Risk: None of above, but HTN Low Risk: None of the above, no HTN
Choice of Medication
Risk Category
Annual Stroke Risk
NNT Choice
Highest:
Prior CVA10% 14 Warfarin
High 6% 33 Warfarin
Moderate 3% 66 Warfarin
Low 1% >200 Aspirin
Based on SPAF-III Trial, Lancet 1996
Treatment of Ischemic Stroke
Thrombolysis Blood Pressure Management Antithrombotic Therapy Management of Medical Complications
Thrombolysis of Acute Stroke
Time-sensitive• Studies show that thrombolytics must be given
within 3 hours of symptom onset Effective
• NINDS- Complete or near-complete recovery at 3 months post-event (38% vs. 21%, NNT=6)
• No difference in mortality Harmful
• At least 6% risk of ICH
Alteplase (tPA) 0.9 mg/kg dose up to 90 mg
• 10% as IV bolus, then 60 min infusion Multiple exclusion criteria Obtain informed consent (if possible)
Thrombolysis of Acute Stroke
"There is a treatment for your stroke called alteplase that must be given within three hours after the stroke started. It is a 'clot-buster' drug that can lead to a complete or near-complete reversal of a stroke in about one of every three patients treated. However, it has a major risk, since it can cause severe bleeding in the brain in about one of every 15 patients. If bleeding occurs in the brain, it can be fatal. When used to treat large numbers of stroke patients, on average the potential benefits of this treatment outweigh the risks; however, in any individual patient it is a very personal decision."
Exclusion Criteria for tPA Stroke/head trauma <3 mos Surgery <14 days GI Bleed <21 days Any prior ICH Acute MI or MI < 3 months LP < 7 days Arterial puncture @
noncompressible site <7d Rapidly improving or minor
sx Seizure with postictal sx
Sx of SAH, even if CT (-) BP >185/110 Pregnancy Active bleeding or trauma Platelets <100K Glucose <50, >400 INR >1.7 or elev PTT Hemorrhage on CT “Major” infarct on CT
Thrombolysis of Acute Stroke
100
22
80
10
20
30
40
50
60
70
80
90
100
All Stroke Within 3 hrs No Exclusions
Thrombolytic Treatment
Guidelines for In-Hospital Evaluation• Physician Evaluation: 10 minutes
• Stroke Team Contact: 15 minutes
• Imaging: 25 minutes
• Interpretation: 45 minutes
• Thrombolysis Started: 60 minutes
• ?Coagulopathy- Don’t wait for labs unless on Coumadin, Heparin, or Dialysis
Predictors of Success with tPA
Early Treatment Less severe symptoms Younger Age Lack of systolic HTN Normoglycemia
Blood Pressure Management
Blood flow in dilated, post-obstructive blood vessels is BP-dependent
Aggressive BP lowering can increase mortality
In one study, a fall in SBP >20 in first 24 hrs was the most likely factor associated with neurologic deterioration
This does NOT apply to hemorrhagic stroke
Do not treat BP unless >220/120, unless• Given thrombolytics (goal <180/105)
• Acute coronary syndrome
• Acute heart failure/pulmonary edema
• Aortic Dissection Meds
• Labetalol
• Nitroprusside
• Avoid SA nifedipine
Blood Pressure Management
Antithrombotic Therapy
ASA – YES• IST- ASA 300 mg within 48 hrs
• Reduced 14 day recurrent stroke (NNT=100)
• Reduced nonfatal stroke & death (NNT=100)
• CAST- ASA 160 mg within 48 hrs• Reduced mortality at 4 weeks (NNT=166)
• Slight increased risk of hemorrhagic stroke• 2 per 1000 patients (11 ischemic strokes prevented)
Clopidogrel & Dipyridamole not tested
Heparin (UFH or LMWH)• 2004 review of 23 trials, >23K patients
• No clear benefit over ASA alone
• Reduced recurrent ischemic strokes by 9/1000 patients, but increased hemorrhagic strokes by same number
• ?Effective in some subsets• “Stroke-in-evolution” or “Progressive Stroke”
• Many patients show neurologic deterioration in 1st 24 hrs
• No studies effectively define this population or prove a benefit
Antithrombotic Therapy
Heparin for Atrial Fibrillation• IST
• No difference between heparin & placebo in stroke/death at 2 weeks
• Reduction in new ischemic stroke (NNT=38)
• Increase in new hemorrhagic stroke (NNH=42)
• Consider in patients with known intra-atrial clot or repetitive “showering” sx
• If used, no IV bolus
• ASA is of benefit, though (as stated before)
Antithrombotic Therapy
Anticoagulant Therapy
Warfarin for Atrial Fibrillation• Must r/o ICH
• For small infarcts, start when medically stable
• For large infarcts, consider after 2 weeks
• Goal INR 2-3
• Consider ASA as bridging therapy until INR >2
Management of Medical Complications Acute Coronary Syndromes/Heart Failure Infections
• Aspiration pneumonia• UTI
Venous thromboembolism• Consider DVT prophylaxis for all patients
• SCDs for pts with bleeds• Heparin or Lovenox SQ for others
Malnutrition/Dehydration (consider Adv Directives) Decubitus ulcers Contractures
CONSIDER EARLY MOBILIZATION IN ALL PATIENTS!
Intracerebral Hemorrhage
Accounts for ~8% of all strokes Presenting sx
• Headache (~50%)
• Seizures (7-9%)
• Delirium/Altered LOC
• Focal neuro sx (depends on area of brain)
Mortality 35-50%• Half of deaths in 1st 24 hours
Prognosis• Size & location of hemorrhage
• Age
• Glasgow Coma Score
• Comorbid conditions
• Prior antiplatelet/anticoagulant therapy
Intracerebral Hemorrhage
Treatment of ICH
Neurosurgical ICU Constant monitoring Bedrest Pain control Reverse coagulopathies
• Vitamin K, FFP, Platelets ICP control
• Mannitol, Induced Coma, Hyperventilation
Treatment of ICH
Blood pressure management Surgery
• Indicated for cerebellar bleeds >3 cm
• Supratentorial bleeds more controversial• Depends on size, location, LOC, comorbidities
rFVIIa therapy• Small studies show promise, but concern for pro-
thrombotic effects
Subarachnoid Hemorrhage
High mortality rate, ~50%• 10% pre-hospital
• 25% within 24 hrs
• 45% within 30 days Prognostic Factors
• Level of consciousness
• Age
• Amount of blood on CT
Diagnosis• Head CT
• (+) in 92% of cases w/in 24 hrs
• Most sensitive in first 12 hrs
• Lumbar Puncture• Not necessary for diagnosis but consider if clinical
suspicion & negative head CT
• Elevated pressure & RBCs
• Xanthochromia: pink/yellow tint due to RBC breakdown
Subarachnoid Hemorrhage
Neurosurgical ICU Constant monitoring Bedrest Pain control Reverse coagulopathies DVT Prophylaxis (SCDs) Blood Pressure Management Management of Aneurysms/AVMs
Treatment of SAH