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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?