What can we learn from

celebrities who’ve had a stroke?

Thomas A. Kent, MD

Professor and Director of Stroke Research and

Education

Department of Neurology

Baylor College of Medicine

Chief of Neurology

Michael E. DeBakey VAMC

Case

Active Veterinarian in his 70’s

No major medical problems

Brief episode of right sided numbness

weakness Friday afternoon

Admitted

Suffered major CVA Monday morning

Expired several days later

Stroke and TIA

Stroke is the 4th leading cause of death in

US

795,000 new strokes a year

250,000 TIA

Risk of stroke after TIA

4-6% at 2 days, 8-11% at 7 days, and 9-15% at

90 days

The probability of stroke in the 5 years following a

TIA is reported to be 24-29%.

Prominent People who have suffered a

Stroke: Presidents (Meschia et al J Stroke Cerebrovasc Dis. 1997)

John Quincy Adams (? Risk factor; two rapid strokes, last one fatal in 1848)

John Tyler (general poor health; fatal stroke followed a TIA in 1862)

Millard Fillmore (“sedentary”; two strokes in rapid succession in 1874)

Andrew Johnson (“loved his mint juleps and whiskey”; 2 strokes in rapid succession in 1875)

Chester Alan Arthur (heart disease and more than his share of “fine living” before a fatal stroke in 1886)

Woodrow Wilson (never healthy, smoked; visual loss first sign (1906), suffered a speech loss TIA in September 1919 then permanent paralysis two weeks later—served out his term)

FDR (smoking and hypertension; possibly mini-strokes before fatal hemorrhagic stroke in 1945)

Ike (heart disease; aphasic stroke in 1957; recovered; fatal heart attack)

Richard Nixon (atrial fibrillation; stroke was fatal in 1994)

Gerald Ford (mini-stroke while talking to reporters in 2000; heart treatment 2006; died of complications from atherosclerosis later that year at age 93)

Can we refine the risk of stroke

Stroke Subtype

Lumpers and splitters

Lumpers:

ABCD2 and variant scores

age, blood pressure, clinical features, duration of TIA, and

presence of diabetes

Newer variants: Vessel imaging: carotid stenosis

!Without intervention, annual risk of stroke from

symptomatic carotid stenosis >50% 15-20%!

Brain imaging with multiple infarcts

Shower of emboli or thrombi

Splitters

Subtype based on etiology

Ischemic stroke subtypes

Large vessel atherosclerosis

Cardioembolic

Small subcortical strokes

Other causes Hypercoaguable state, stimulant abuse

Cryptic Cannot determine cause

History and physical examination a clue to stroke subtype ~ 75% correct predictor

Ischemic stroke secondary to Large vessel

atherosclerosis

Stroke subtype most similar to CAD

Plaque rupture

Platelet aggregation

Thrombosis

Occlusion/recanalization/reocclusion

Carotid artery

Basilar/vertebral

Middle cerebral artery

Intracranial large branch vessels

History

1 or more TIA’s about 30-50% of the time

Stereotyped

Equivalent to unstable angina

Stroke usually occurs upon awakening

Like MI

Can have a stuttering onset

The most likely to propagate and progress in

the initial hours/days

Acute management

tPA and endovascular intervention if within

the time window and no contraindications

Otherwise, antiplatelet agents

Other secondary management

But recall that these patients are the most

likely to progress

As a result, these are the ones most likely to

respond to anticoagulation or acute

antiplatelet loading

TOAST subtype outcomes

NASCET trial and subsequent analysis

15-20% annual stroke risk in symptomatic

carotid artery stenosis (>50%)

7% risk with intervention within 3 months

Reanalysis suggested all benefit was within the

first 2 weeks

Open question what to do until intervention

ASA, dual anti-platelet, anticoagulation?

Cardioembolic Stroke

Occurs mostly while active

Maximal deficit at onset

Less collateral circulation in distal vessel

TIA’s, but not stereotypical

Any sudden change in neurological function is

vascular until proven otherwise (seizures in

differential)

Underlying cause

Cardiac disease Most at risk is Atrial fibrillation-stable or intermittent

low thrombus yield on TTE

Risk factor profile more predictive If hx suggestive, recommend prolonged search for

atrial fibrillation

Low risk of recurrence acutely in the absence of underlying ventricular thrombus or acute MI (Coretta Scott King)

Likely much higher recurrence in those conditions and anticoagulation can be considered

Lacunar Stroke

Small subcortical strokes

Penetrating vessels without collateral Cause can be intrinsic small vessel disease, large

artery thromboembolism or embolism

Patterns suggestive (size especially)

Stroke can occur any time

TIA’s--stereotyped

Never involves a cortical function Dementia can occur after sufficient subcortical disease

(subcortical dementia)

Many are silent

Highly recurrent (FDR)

40% will have cognitive decline in 4 years

Highest mortality AA women under 70

Many will have stereotyped TIA’s

Sometimes hundreds prior to infarction

Aggressive secondary prevention (low BP

targets) does not reduce recurrence but does

reduce likelihood of hemorrhagic transformation

Not Just American Presidents

Winston Churchill

Depressed, smoker, whiskey and soda, heart

attach 1941

Strokes in 1949, 53, 56, fatal in 1965

Lenin

Stroke in May, December 1922, died stroke in

1924

Joseph Stalin

Smoker, hypertension

First stroke in 1945

Massive Hemorrhage in 1953; lost the ability to

speak

Died 3 days later

Thought to have been poisoned by warfarin

Hemorrhage everywhere

Ariel Sharon

Illustrates the difficulty in treating a prominent

person with a number of difficult medical conditions

CAD, hypertension, obesity

Suffered a minor ischemic stroke

W/u found Patent Foramen Ovale

Anticogulated for several days prior to cath/closure

Suffered massive ICH

Coma for 8 years prior to death

Why would PFO be considered as likely

cause of CVA?

In the early 2000’s PFO had a resurgence of

interest as non-invasive devices were

developed

The natural history, RCT treatment response

had not been performed.

Incidence of PFO is 20%

Likely he lived with it for his entire life while

other stroke risk factors accumulated

Other Prominent People who have

suffered a Stroke

Actors and Actresses

7.3% of Oscar Winners suffered from a stroke

Average age 67

Women: Like Lauren Bacall, died of of “massive” stroke

at 87

Sharon Stone, Grace Kelly, Elizabeth Taylor

Cary Grant, Gene Kelly, Glenn Ford

The rate is not greatly higher than expected, but

the mortality is suggested to be higher

Often extremely aggressive acute management

including pre-stent retriever thrombectomy

Are there patterns that we can learn

from

Few presidents had modern secondary

prevention

May be tempted to follow the latest fad or change

usual practice

In the case of Roosevelt, unclear whether he

received optimum BP therapy

Even in absence of modern secondary

prevention, presidents seemed overly prone

to a sedentary life

Metabolic syndrome

Metabolic Syndrome Reavan in 1988 put the intersection of high insulin levels,

hypertension, hyperlipidemia and ultimately the ravages

of diabetes was put into the context of modern medicine

This pre-diabetic syndrome plus central obesity is called

metabolic syndrome.

Diagnosis of insulin resistance is made with the

Homeostatic Model of Assessment of Insulin Resistance

(HOMA-IR) criteria (obtain Insulin and glucose levels and

calculate).

HOMA-IR > 3.0, but lower levels associated with

metabolic syndrome in certain ethnic, racial groups

Physical activity can improve insulin resistance

Ca. 30% of the population, and incidence is increasing

Insulin Resistance Intervention after

Stroke (IRIS) trial (Kernan et al, NEJM 4/2016)

Treated with pioglitazone (Actos™), a

thiazolidinedione (TZD) class of peroxisome

proliferator–activated receptor γ (PPAR-γ)

agonists

This receptor is involved in glucose uptake

and fatty acid metabolism

Subtypes present in nearly all cells

IRIS started this medication after stroke/TIA

IRIS treatment resulted in 24% fewer MI/CVA

over 5 year follow up

Increased bone fractures, weight gain and

SOB

Non-significant rise in bladder cancer

These are known sided effects of the medication

Nearly 50% reduction in development of

diabetes over the course of the trial

Improved all biochemical markers of glucose

Because of the reduction in progression to

diabetes, it is possible the benefits of IRIS will

extend beyond the study duration

?Other diabetic complications

We recommend consultation with vascular

medicine and endocrinologist before started

treatment and follow closely for development

of side effects as well as benefit on glucose

metabolism (Ntaios and Kent, Stroke 2016)

New Developments in Stroke In the Last

Few Years

Along with thrombolytics, stent retriever

thrombectomy devices improves outcome well

beyond that of medication alone

Works best when in combination with rt-PA

Can be given up to 6-8 hours, but only if meets

imaging criteria

Few meet these criteria beyond 4-6 hours

In our analysis, patients that got both tPA and the clot

removal device had a 70% chance of a good functional

outcome compared to around 40% without the treatment

Recent Developments: Treatment of

severe ischemic cerebral edema (Nixon)

For MCA stroke: Hemicraniectomy

Improves by half chance to not be totally

independent

Reduces mortality equivalent

Faster the better

Prior to frank herniation

More commonly done for cerebellar

hemisphere stroke

Less functional disability following removal

Modern Approach to Reducing Stroke

after TIA Increasing implementation of rapid

identification of TIA

TIA units; TIA protocols

Emergent/urgent workup of potential

etiologies

Ultrasound, CTA, MRA

Cardiac rhythm, echocardiogram

Laboratory, sedimentation rate

Urgent intervention

Recent natural history of TIA studies suggest

a 50% reduction in stroke compared to pre-

”TIA” unit implementation (Amerenco et al, NEJM N

Engl J Med 2016; 374:1533-1542 April 21)

Urgent workup of etiology

Bridge with anti-platelet (or begin

anticoagulation if a-fib)

Lipid, BP, glucose management

Analysis of TIA management

Most important predictor of subsequent

stroke was carotid stenosis (p<.0001)

ABCD2 score required for qualifying for

admission, but showed low relationship to

stroke, and missed nearly a quarter of

strokes at the higher score region

Case study?

Most likely symptomatic large artery plaque

Could stroke have been prevented?

If carotid artery stenosis and either surgically

or endovascular accessible, recommend

urgent intervention

If can tolerate, we use unfractionated heparin until

intervention

Try to have the intervention as soon as possible

Other alternative bridging medications, e.g.

ASA/Plavix load

If a different vessel is the symptomatic one

Medical management only

Questions?