SHAZIA KHAN

Assistant Prof. of Clinical Medicine. USC

Learning objectives

Review the pathophysiology , signs and symptoms of ischemic stroke.

Familiarize our selves with the signs and symptoms.

Use of ABCD , NIHSS .

Primary and Secondary Prevention.

Epidemiology

Incidence of stroke in USA is 795,000/ year in the United States of America

Stroke kills about 140,000 Americans each year –that’s 1 out of every 20 deaths

Stroke: 4th killer in USA (used to be third)

2nd killer in world

Definition

Acute brain injury caused by occlusion or rupture of a blood vessel in the brain .

Ischemic stroke: Reduced blood supply to a region of the brain resulting in brain ischemic and neuronal death (87%)

Hemorrhagic stroke: Primary brain hemorrhage resulting in compression of normal brain tissue (13%)

Anterior and Posterior Cerebral Arterial Circulation

Internal carotid arteries and their branches: supply the anterior circulation

Vertebral arteries and the basilar artery (and their branches): supply the posterior cerebral circulation

Hemorrhagic Stroke

INTRACEREBRAL HEMORRHAGE.

More common in Asian countries.

Two distinct pathologies exist

1. Basal Ganglia – Cerebellum

2. Lobar – likely secondary to Cerebral

myloid angiopathy.

Higher Mortality then Ischemic Stroke.

Sub Arachnoid Hemorrhage.

Likely from rupture of a saccular aneurysm

Rare causes are AVM , Mycotic Aneurysm.

Diagnosis : Ct head , Lumbar puncture.

LP: Erythrocytes and Xanthochromia.

Mechanism of Ischemic Stroke and Transient Ischemic Attacks

Atherosclerotic cerebrovascular disease (20%): 1. Extracranial carotid or vertebral artery disease

2. Intracranial cerbrovascular disease

Penetrating small arterial disease (25%)

Cardiogenic source (20%): 1. Atrial fibrillation & other arrythmias

2. Myocardial infarction

3. Valvular disease

4. Ventricular thrombi

5. Aortic plaque

Unusual causes (<5%): dissection, migraine, illicit drugs, vasculitis, venous strokes, hypercoagulability,…

Cryptogenic source 30 %(no mechanism identified)

Transient Ischemic attack (TIA)

Definition: duration of transient neurologic symptoms lasting less than 1 hour

Transient reduction of blood flow to a region in brain in the absence of evidence of infarction on brain imaging

Mechanisms for TIA similar as for ischemic stroke

Reconstitution of flow to the hypoperfused region hence the resolution of symptoms

Significance of TIAs is increased risk of stroke after a TIA specifically early on after a TIA

Prompt evaluation of mechanism and appropriate treatment

Transient Ischemic Stroke

ABCD2 score

Age ≥ 60 years: score 1

HTN (≥140/90): score 1

Diabetes mellitus: score 1

TIA duration: 10-59 min (score 1); ≥60min (score2)

Clinical: Hemiparesis with or without speech deficit (score 2); speech impairment without hemiparesis (score 1).

Higher ABCD2 scores are associated with greater risk of stroke during the 2, 7, 30, and 90 days

Definite admission for ABCD2 score of ≥4

Caution to work the TIA patients urgently to address underlying source and treat appropriately

STROKE

Signs and Symptoms

Acute Onset of Any of the Below Symptoms

Hemiparesis or quadriparesis ( latter in basilar occlusion)

Facial weakness

Aphasia

Dysarthria

Limb/truncal/gait ataxia +/- nausea & vomiting

Vertigo, tinnitus, hearing deficit (posterior circ.)

Impairment of vision in homonymous visual field defect

Monocular impairment of vision (amaurosis fugax)

Diplopia

Impairment or loss of consciousness or confusion

Hemineglect (visual or sensory)

Headache (non-specific symptom)

New onset seizure (3-4%) or acute new movement abnormality

Adopted from AHA

Differential Diagnosis

Space occupying lesion (tumor, infection/ abscess, Epidural, Subdural Hematomas)

Subarachnoid hemorrhage

Seizures

Hypoglycemia

Migraine

Syncope

Labyrinthine disorders

NIH Stroke Scale

Designed for acute stroke trials.

Quick (5-10 min) & reproducible.

Requires speech/language cards & safety pin.

Quantifies clinical stroke deficit:

o < 4 = mild stroke

o > 15 = poor prognosis if no treatment

o > 22 = risk for ICH

Code Stroke

Evaluation &Treatment

Initial Evaluation and Management

Urgent transport to the nearest stroke receiving hospital via 911 system

Notification of the destination ED

Alert ED of the need for urgent CT

Initial Evaluation

STAT CT brain

ABC .Pulse ox . IV

c-xray

CBC, Platelet, PT, PTT

Accucheck & blood glucose, serum electrolytes

Cardiac markers, ABG’s

Blood alcohol level, Toxicology screen, Pregnancy test

Initial Evaluation and Rx

IV line: IVF bolus/hydration

2nd IV line in anticipation of IV t-PA

Non contrast CT: rule out hemorrhage

Usually later but may need stat: Ct angiogram ,MRI perfusion MRI and MR-a, CT-a brain and cerebral vessels

Acute Therapy

NINDS Stroke Study group: randomized placebo controlled clinical trial (N Engl J Med 1995)

Intravenous recombinant tissue Plasminogen Activator (IV t-PA) given within 3 hour of symptoms onset in acute ischemic strokes

N=624 patients (IV t-PA or placebo):dose 0.9mg/kg, 10% IV bolus, then the remainder is IV drip over 1 hour

NINDS Stroke Study

Patients in the t-PA arm were at least 30% more likely to have minimal or no disability at 3 months

Symptomatic Intracranial Hemorrhage was 6.4% in the t-PA group versus 0.6% in the placebo arm

Mortality at 3 months was not statistically different between t-PA and placebo

The benefit of IV t-PA was sustained at one year follow up

The earlier the treatment the better the outcome

ECASS III Trial

ECASS 3: N Eng J Med sept 2008 This study showed persistent benefit of IV t-PA up

to 4.5 hours from onset in acute ischemic stroke Excluded patients>80 years of age Excluded patients with severe deficit NIHSS>25 Excluded patients who have combination of

previous stroke and diabetes Excluded patients who were on anticoagulation

regardless of the INR

Intravenous t-PA

Standard FDA approved therapy for acute stroke Rx

Window of treatment has been prolonged after ECASSIII to 4.5 hours

Not all patients are eligible for the 3 to 4.5 hour window

Inclusion Criteria for IV t-PA

Ischemic Stroke clinically

Persistent neurologic deficit beyond an isolated sensory deficit / ataxia

CT brain: No Blood

Initiation of Rx within 3 hours

Exclusion Criteria

Onset to treatment >3 hr (NINDS)

Rapid improvement

Blood on CT

Oral anticoagulant & PT>15 sec, INR>1.7

Heparin (last 48 hr) & increased PTT

Platelet<100,000

SBP >220 or DBP>110

Aggressive treatment of b.p.

Stroke or head trauma (3 months)

Major surgery (2 wks)

Cont’d Exclusion Criteria

Prior ICH

GI tract/ Urinary bleed (14 d)

Seizure at onset

Signs & Sx’s of SAH

Non-compressible site of arterial puncture (7d)

Additional Exclusions for the 3 to 4.5 Hour

Age≥80 years

Any use of anticoagulant regardless of the PT/PTT

NIHSS≥25

Coexistent history of stroke and diabetes mellitus

Management Post Thrombolysis

Admit to ICU

BP monitoring (Q 15 m x2 h, Q 30 m x6 h, Q 1 h x16 h)

Treat SBP for a goal <185 and DBP<110

No anticoagulants, no anti-platelet for 1st 24 hr post t-PA

Cont’d Management of Patients Post-thrombolysis

Worsening of neurologic state---CT brain

ICH---Neurosurgery consult

Possible surgical intervention

Preferably: no foley or NG for 2 hr > t-PA (t1/2-t-PA = 8-12 min)

Endovascular Rx

Mechanical thrombectomy:

Add on-Rx to the standard FDA approved stroke Rx IV t-PA in cerebral infarction with proximal large arterial occlusion within 6 hours from onset.

DAWN and DEFUSE3 Trials

Select patients LVO treated up to 24 hours based on CT perfusion selection.

What do we do given this data ?

1.All patients eligible for IV t-PA should receive it ..Quickly ! 2.Patients with in 6 hours should recieve a CTA to look for a large vessel occlusion (LVO) 3.If LVO is present , endovascular therapy should occur ,even following IV-tPA regardless of perfusion data.

4. If the patient has a LVO and presents between 6-24 hours ,CT perfusion required and selects patients who should receive endovascular therapy

Poor Outcome Predictors in Ischemic Stroke

Age

Elevated blood sugar

Initial NIHSS score which is a measure of the patient’s initial deficit

Cerebral infarction changes on CT brain

Anti platelet therapy

Aspirin after 24 hours of Iv t-PA .

160mg – 300mg .

In patients with minor stroke ,treatment for 21 days with dual therapy (aspirin and plavix ) can be beneficial for secondary stroke prevention for a period of 90 days.(CHANCE)

Oxygen : >94 % Blood pressure :< 180 /105 Temp <38 Glucose 140-180mg/dl DYSPHAGIA SCREEN Nutrition :Enteral diet should be initiated within 7

days DVT Prophylaxis Depression Screen REHAB!!

Is Stroke Preventable??

Prevention

Primary prevention

Secondary prevention

Primary Prevention

Primary prevention starts at the level of the physician playing the role of the primary care and occasionally at the level of the cardiologist and the stroke neurologist

Key is identification of underlying risk factors and modification and treatment of modifiable risk factors

Primary Prevention Elements

Establishing good medical history and family history

Identifying the patient’s vascular risks including medical illnesses, habits such as smoking and substance use and genetic predisposition through review of significant family history for cardiovascular risk factors and stroke

Exam elements which are key: pulse (rate and establishing how regular), blood pressure, carotid auscultation (bruits), cardiac auscultation (murmurs and abnormal rhythm), symmetry and detection of pulses, diabetic peripheral changes

Identification of Risk Factors for Stroke

Non-modifiable risk factors

Modifiable risk factors

Modifiable Risk Factors

Non-modifiable Risk Factors

Age: the risk of stroke doubles with every decade after the age of 55 years

Sex: lifetime risk in Male>Female but risk in F>M after age of 80 years

Race and ethnicity: Stroke incidence and subtypes: higher in African

Americans and Hispanics >Caucasians Stroke related mortality is higher in African

American population Asian population has an increased risk of

hemorrhagic stroke subtype compared to Caucasians

Non-modifiable Risk Factors Genetic Factors

Family history: inherited susceptibility, inherited predisposition to risk factors, similar culture and lifestyle

Hyperhomocysteinemia:)

Inherited coagulopathies: FV Leiden mutations, prothrombin gene mutation PC, PS deficiencies Anticardiolipin antibodies/LA are genetic in 10% cases Others

CADASIL: Cerebral autosomal dominant arterof iopathy with subcortical infarcts and leukoencephalopathy: NOTCH 3 gene mutation on chromosome 19

Others: Marfan and NF I and II, Fibromuscular dysplasia (FMD), Ehlers-Danlos syndrome IV, polycystic kidney disease

Novel genes identified which may have specific associations with large artery stroke

Well Documented Modifiable Risk Factors

Hypertension Smoking Diabetes Mellitus Carotid disease Cardiac disease: Atrial Fibrillation, Myocardial

infarction secondary to coronary artery disease Dyslipidemia or hyperlipidemia (high cholesterol,

high LDL, low HDL) Migraine with aura in women Obstructive sleep apnea

Less-Documented Potentially Modifiable Risk Factors

Obesity Lack of exercise Poor diet Alcohol abuse Hyperhomocystei-

nemia

Illicit drug abuse

Hypercoagul-opathy

Sickle cell disease

Estrogen/HR hormonal therapy

Inflammation

Infection

Hypertension

Hypertension (HTN)

Prevalence in USA is 29%- Improved control of HTN over the years 50%

More than 2/3 of patients ≥ 65 yrs of age have hypertension

Major risk factor for ischemic and hemorrhagic strokes

the higher the blood pressure the greater the risk of stroke

HTN is undertreated

It ‘s prevalence is increasing partly due to increased prevalence of patients who are overweight and obese

One of the most important modifiable risk factors for stroke

Hypertension Evaluation and Treatment Current Guidelines

Regular blood pressure screening

Behavioral life style modifications :

management of obesity/ weight loss,

diet: low salt, encourage vegetables. Reduce red meat (AHA, DASH, Mediterranean diets)

Encouragement of exercise

Treatment with antihypertensive agents to achieve BP< 140/90 mm Hg

Cigarette Smoking

Cigarette smoking doubles the risk of ischemic stroke

It also increases subarachnoid hemorrhage by 2-4 folds

Inconsistent data for parenchymal intracerebral hemorrhage

Inconsistent data with second hand smoking Contributes to increased risk of stroke by:

Increased thrombus generation in atherosclerotic arteries

Increased atherosclerosis

Diabetes Mellitus

Close to 11% of US population are estimated to have diabetes mellitus

Studies have shown that diabetes mellitus increases the risk of stroke 1.8 - 6 fold

This increase in stroke risk is related to increased risk of atherosclerosis & increased pro-atherogenic risk factors in diabetic patients

Interventions to Reduce Stroke in Diabetes Mellitus?

Diabetes Mellitus: Glycemic control?

North Manhattan Study: subjects who had diabetes and fasting blood glucose (FBG)> 126 mg/dl had 2.7 fold increase in stroke risk versus no increase in risk if FBG<126 mg/dl

3 clinical trials: ACCORD, ADVANCE, and a trial which enrolled US veterans

Failure to demonstrate reduction in stroke in the group of intensive glycemic control

ACCORD: halted earlier due to increased all-cause mortality in the intensive-glycemic control group

Diabetes mellitus: Glycemic Control

Use standard guidelines for glycemic control

Avoid lowering of HbA1c<6.5 in patients with cardiovascular disease or the presence of vascular risk factors

Diabetes Mellitus and Lipid Altering Rx

Clinical evidence of the benefit of statins in stroke risk reduction in diabetic patients

No supportive evidence for fibrates in stroke prevention in diabetic patients

Use of Aspirin in Primary Prevention of Stroke in Diabetes Mellitus

No statistically significant benefit from aspirin in prevention of stroke in diabetes mellitus has been found

Use in patients with established carotid disease or coronary artery disease

Lipids

Modest association of elevated total cholesterol or LDL with increased risk of ischemic stroke

Association between low HDL and increased risk of ischemic stroke

Relationship between low total cholesterol as well as LDL-C and a higher risk of hemorrhagic stroke

ACC/AHA Guidelines for the Treatment of Blood Cholesterol in Primary Prevention

Recommendations based on the 10 year risk for cardiovascular disease

Shifts away from specific cholesterol goals

Estimated risk dictates intensity of statin Rx: high risk mandates high intensity statin Rx

Atorvastatin 10 mg is moderate intensity statin Rx and 40 t0 80 mg is high intensity

10 year Risk calculator

Statins in Secondary Prevention of Stroke

Statin therapy with intense lipid lowering effect is recommended to reduce stroke risk in the population of ischemic stroke and TIA patients (SPARCL)

Target LDL-C<70 mg/dl or 50% lowering of baseline LDL

May use other agents if patient can not take statins (Niacin, Gemfibrozil)

No established benefit in stroke reduction

Carotid Endarterectomy

Indicated with proven benefit in severe symptomatic extracranial carotid artery disease

Symptomatic = clinical or radiologic evidence of stroke in the distribution of that carotid artery

Stenting is an alternative in patients who are not eligible for CEA

Asymptomatic Carotid Disease

Asymptomatic Carotid Artery Disease

Increased risk of stroke with carotid artery stenosis Asymptomatic Carotid Artery Study (ACAS) Asymptomatic Carotid Surgery Trial (ACST) Number needed to treat to prevent 1 stroke patient

was 40 The low benefit may not justify the risks of carotid

revascularization: individualize patients and assess risk factors

The annual rate of stroke associated with asymptomatic carotid stenosis has significantly declined with intensive medical management ≤1% (Statins and antiplatelet Rx)

May consider carotid revascularization in severe asymptomatic carotid artery stenosis but with

perioperative and surgical risk <3 %

Cardioembolic sources of Stroke

Cardiac arrhythmias with increased risk of cardiac clots and cardioembolism: atrial fibrillation

Coronary artery disease, myocardial infarction/ ischemic cardiomyopathy

Valvular heart disease (septic embolism or thromboembolism)

Aortic arch atheroma

Paradoxical embolism: presence of right to left shunt such as a PFO in the presence of a venous thrombus

Atrial Fibrillation

Both persistent and paroxysmal atrial fibrillation are potent predictors of first as well as recurrent stroke

Atrial fib >2 million Americans

Increases with age

Atrial fibrillation patients with prior strokes and TIAs have the highest risk of recurrent stroke

Other risk factors: age, HTN, CHF, diabetes mellitus

CHADS2

Age ≥ 75 years (1)

HTN (1)

DM (1)

CHF (1)

Ischemic stroke or TIA (2)

--------------------------------------------------------

Total score: ------ (maximum is 6)

Antithrombotic Rx in Atrial Fibrillation

Anticoagulation: CHADS2 >1

Antiplatelet Rx for CHADS=0

CHADS2=1 either anticoagulation or antiplatelet

ASA plus clopidogrel maybe used in patients who have contraindication to anticoagulation

If there is Stroke/TIA with atrial fibrillation then anticoagulation is the recommendation

Patient has to be cleared for the absence of fall risk

Oral Anticoagulants

Warfarin (valvular and non-valvular A.Fib.)

Apixaban((approved for non-valvular A.Fib.)

Rivaroxaban(approved for non-valvular A.Fib.)

Dabigatran (approved for non-valvular A.Fib.)

Migraine with Aura

An independent risk factor for stroke in women

It is still unknown if migraine preventive therapy will reduce the risk of stroke

A woman who has migraines with aura, who smokes tobacco and who is on oral contraceptive pills has a 7-9 fold increase in the risk of stroke

Cessation of smoking and consideration of avoiding OCPs in patients with migraines with aura

Obstructive Sleep Apnea (OSA)

Increases risk of stroke and cardiovascular disease

Screening for symptoms of OSA and appropriate referrral to sleep center for evaluation and treatment when appropriate

Hormonal Replacement Therapy and Oral Contraceptive Pills

Some increased risk of ischemic stroke

May avoid or stop using if additional risk factors for stroke

Stop/avoid use if patient is a smoker and esp. if it is a woman who has migraines with aura

Substance Use

Alcohol beyond 2 drinks/day for men and beyond

1 drink /day for women increases the risk of stroke

Illicit drug use increases the risk of intracerebral hemorrhage (ICH) and ischemic strokes esp. with Cocaine and Amphetamines/ derivatives

Substance use increases the risk of development of poorly controlled BP and its complications

Cessation should be recommended however with the help of detox and rehab programs

Antiplatelet Therapy in Primary Stroke Prevention: No Benefit

No benefit in primary prevention

Consider in diabetic patient with high risk factors and carotid artery disease

Recent FDA warning about use of aspirin in primary prevention due to increased hemorrhagic risks which are not offset by any significant benefit.

Summary

Goal should be primary prevention in stroke

Role of the primary care and sometimes the neurologist and cardiologist in assessing risk factors for stroke

Intervention with education about life style modification and treatment of risk factors for stroke

Summary

Family history: identify people who have higher risk and counseling those patients

Genetic counseling for rare genetic disorders

Non-invasive imaging/ screening for patients with specific disorders: screen for cerebral artery aneurysms in patients with ≥ 2 first degree members with SAH/cerebral aneurysms, EDS IV, polycystic kidney disease

Summary:

Physical activity is recommended:

Moderate to vigorous intensity aerobic

Suggested ≥ 40 min/ time, 3-4 days /wk 2013 AHA/ACC guidelines

Weight reduction for BMI≥ 25

Dietary restriction of salt and increased potassium in diet (HTN conrtol)

DASH, AHA, Mediterranean diets

Summary: Primary Prevention

Cessation of smoking esp. in women who have migraines with aura and who are on OCPs

Cessation of illicit drugs

Cessation of alcohol or limitation to ≤1 drink/day for women and ≤2 drinks/day for men

Summary: Primary Prevention

Control of BP<140/90 mm Hg

Control of blood sugar but avoid intensive glycemic control

Use of statins in diabetic patients maybe protective and particularly if high risk factors

Maximize medical management with statins and antiplatelets in carotid artery disease

Anticoagulation is reserved for atrial fibrillation and cardiac thrombi or potent hypercoagulable states (latter in secondary prevention)

Summary: Primary Prevention

Use of ACE Inhibitors and or an angiotensin II receptor blocker (ARB) in diabetes mellitus

No documented benefit for aspirin in primary prevention of stroke (may consider patients with high risk factors) with the exception of some possible benefit for women>65 years old