Diagnosis, Evaluation, and Treatment of Stroke Fariborz Khorvash, MD Assistant Professor of Neurology.

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