Transcript Stroke
Dec 8th, 2014
Lama Al-Khoury, MD
Clinical Assistant Professor
Neurology
UCI Medical Center
Stroke Epidemiology
Incidence of stroke in USA is 795,000/ year in
the United States of America
Incidence of Non-fatal strokes is 15
million/year in the world
Stroke: 4rd killer in USA (used to be third)
2nd killer in world
Secondary disability is present in one third of
stroke survivors
Stroke
Stroke is Acute brain injury caused by:
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
Mechanism of Ischemic Stroke and
Transient Ischemic Attacks
Atherosclerotic cerebrovascular disease (20%):
1.
2.
Extracranial carotid or vertebral artery disease
Intracranial cerbrovascular disease
Penetrating small arterial disease (25%)
Cardiogenic source (33%):
1.
2.
3.
4.
5.
Atrial fibrillation & other arrythmias
Myocardial infarction
Valvular disease
Ventricular thrombi
Aortic plaque
Unusual causes (<5%): dissection, migraine, illicit
drugs, vasculitis, venous strokes, hypercoagulability,…
Cryptogenic source (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
Ischemic Stroke
Signs and Symptoms of Stroke
Acute Onset of Neurologic Symptoms
and Signs of Central Nervous System
Nature
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 defectAdopted from
Monocular impairment of vision (amaurosis fugax)
AHA
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
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
NIH Stroke Scale
“Traditional” order of items”
1a.
1b.
1c.
2.
3.
4.
5a.
5b.
LOC
LOC questions
LOC commands
Best gaze
Visual fields
Facial palsy
Right arm motor
Left arm motor
6a.
6b.
7.
8.
9.
10.
11.
Right leg motor
Left leg motor
Limb ataxia
Sensory
Best language
Dysarthria
Extinction/
inattention
Evaluation &Treatment
Initial Evaluation and Management
Urgent transport to the nearest stroke
receiving hospital via 911 syste
Notification of the destination ED
Alert ED of the need for urgent CT
Code Stroke
Initial Evaluation
Cardiac monitoring, pulse-ox, ECG
Stat CT brain
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: Carotid U/S,
Echocardiogram, MRI and MR-a, CT-a brain and
cerebral vessels
CT Brain
CT Patterns
MRI Brain
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
IV t-PA treatment
IV t-PA was FDA approved for acute ischemic
stroke Rx based on the NINDS study group
Inclusion and Exclusion criteria
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>185 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≥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)
Acute Interventional Treatment
Intraarterial thrombolysis or mechanical thrombectomy
Successful recanalization has been shown
Clinical benefit?
PROACT II: intra-arterial pro-Urokinase was positive
3 interventional studies published in 2013 were negative
for benefit from endovascular Rx
Implementation of stent retrieval devices (superior in
recanalization)
MR CLEAN (Multicenter Randomized Clinical trial of Endovascular
treatment for Acute ischemic stroke in the Netherlands) : positive
trial
SWIFT PRIME halted enrollment pending review of data
Endovascular Rx
At the time being and in the United States the only
FDA approved acute treatment for stroke is IV t-PA
Mechanical thrombectomy: (currently)
Add on-Rx to the standard FDA approved stroke
Rx IV t-PA in cerebral infarction with proximal
large arterial occlusion within 8 hours from onset
Or as alternative Rx in patients who do not qualify
for IV t-PA
For basilar artery occlusion the window is prolonged
to up to 24 hours for concern of locked in syndrome
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
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: C677T allele (one or more) of the
methylenetetrahydrofolate reductase gene (MTHF)
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), EhlersDanlos 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
Hyperhomocysteinemia
Illicit drug abuse
Hypercoagulopathy
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%
A patient who is normotensive at 55 years of age has a 90% life time risk
of developing hypertension
More than 2/3 of patients ≥ 65 yrs of age have hypertension
Major risk factor for ischemic and hemorrhagic strokes
Throughout usual range of blood pressure (BP) including the normal BP
ranges, 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 increases stroke risk due to the following:
It worsens atherosclerosis
It predisposes to small vessel disease
It accelerates heart disease
Antihypertensive Agents
Multiple clinical trials have established that treatment of BP
with antihypertensive medications reduces risk of stroke
Several meta-analyses evaluated and compared specific
antihypertensive agents
One meta-analysis: Thiazide diuretics, ACEI and Ca channel
blockers each reduced risk of stroke compared to placebo
Another meta-analysis: showed diuretics superior to ACEI
Subgroup analysis in one trial: benefit if diuretic is more
prominent among African Americans
A meta-analysis of 13 trials in patients with hypertension:
ACEI and ARBs reduced significantly stroke risk
Recent evidence that calcium channel blockers are better in
reducing variability in blood pressure that betablockers
Hypertension Evaluation and Treatment
Current Guidelines
Regular blood pressure screening
Behavioral life style modifications should be
recommended to hypertensive patients:
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
Intraindividual variability of blood pressure may
cause additional risk
Degree of Blood Pressure Reduction
Current AHA guidelines in chronic
hypertension < 140/90 mm Hg
Most trials did not test a goal of less intensive
therapy being less than140/90
One meta-analysis compared clinical trials
with more intensive BP reduction with those
of less intensive reduction and found a 23%
reduced risk of stroke in more intensive
therapy
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
Cessation of
Smoking
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?
Steno-2 Study
Patients with DMII and persistent
microalbuminuria
Intervention with intensive therapy with
behavioral risk factor modification and statin,
ACEI, ARB, or antiplatelet as appropriate
versus conventional Rx
Intensive therapy was associated with
significant reduction in each of death,
cardiovascular events and stroke endpoints
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
Hypertension Control in DM
New AHA guidelines
Evidence from studies and meta-analyses to
suggest that more aggressive bp control in DM
lowers further risk of stroke
There is an increased risk of adverse events
with more aggressive antihypertensive Rx
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
?? Role of Triglycerides
No consistent association between triglycerides
and risk of stroke
Statins (HMG-CoA Reductase Inhibitors)
Statins: 3-hydroxy-3methylglutaryl coenzyme A reductase
inhibitors
Statins lower LDL cholesterol by 30-50%
Treatment with statins reduces the risk of stroke in patients
with or at high risk for atherosclerosis
Meta-analysis of 26 trials: statins reduced risk of all strokes
by 21%
Risk of all strokes was reduced by 15.6% for each 10%
reduction of LDL-C
Statins reduce progression and promote regression of
atherosclerotic plaque
Beneficial effect on carotid intima media thickness (IMT)
mostly with higher intense Rx with statins
Lipid Lowering in Patients with CHD
National Cholesterol Education Program (NCEP)
NCEP recommends LDL lowering as primary
target
Lifestyle modification
Decrease saturated fat, trans fat and cholesterol
intake
weight reduction
Exercise
PMH of CHD and CHD risk equivalents (DM and
symptomatic carotid artery disease): aim at LDL
at least ≤ 100 and preferably ≤70
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.)
Carotid Disease
No role for CEA in carotid occlusion
No benefit from EC/IC bypass in carotid
occlusion
SAMPRIS: In intracranial cerebral artery
stenosis, best medical management is
superior to angioplasty and stenting
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
May have some benefit in women ≥ 65 years
old (AHA / AHS guidelines)
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
Lama Al-Khoury, MD
Clinical Assistant Professor
UCI Medical Center
Stroke Center
T:(714)456-7637
Fax: (714)456-2333