2/7/2009
Disclosure
Intracranial Atherosclerosis
None
an update
Mai N. NguyenNguyen-Huynh, MD, MAS
Assistant Professor of Neurology
UCSF Neurovascular Service
February 7, 2009
Case #1
60 y.o. ChineseChinese-speaking woman h/o
anxiety/depression, HTN, c/o HAs. PCP
obtained a MRI/MRA brain. Found
several areas of significant intracranial
atherosclerosis. Refer to Neuro
Meds: HCTZ
What to do next?
a)
b)
c)
d)
e)
f)
Start antiplatelet
Start coumadin
Start a statin
Get a diagnostic catheter angiogram
Get CTA
Refer to NIR for angioplasty/stenting
Case #2
66y.o. Filipino man h/o HTN, DM,
presented with left sided weakness.
Found on CT/CTA to have intracranial
occlusion of right M2, severe (70(70-80%)
bilateral vertebral stenoses.
Meds: lisinopril, HCTZ, glucophage, ASA
What to do next?
a)
b)
c)
d)
e)
Add Clopidogrel to ASA
switch to Clopidogrel alone
Switch to Aggrenox
Start a statin
Refer to NIR for angioplasty/stenting of
vertebral arteries
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2/7/2009
Asians in the U.S.
~4% of the U.S. population
Fastest growing ethnic group in U.S.
Estimated to make up ~10% of the
population by 2050
Many studies on racerace-ethnic
disparities in health focus on African
Americans & Hispanics.
Few stroke studies on Asians in the
U.S.
Stroke
Stroke
#3 killer in the US, #1 in China
#1 longlong-term disability in the world
Higher incidence rates in Asia
compared to U.S.:
• 39% greater in Japan
• 23% greater in Taiwan
• 81% greater in Northern China
Cerebrovascular system
~795,000 strokes per year in the US
2009 costs estimated ~ $68.9 billion
~87% ischemic
• 8-10% with intracranial atherosclerosis
(ICAD)= 47,600 to 59,500 strokes per
year
• Extracranial carotid dz 100,000 –
140,000 cases/yr
• Afib 70,000 cases/yr
www.familydoctor.co.uk/.../STROKE_specimen.html
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2/7/2009
Circle of Willis
Epidemiology of ICAD
Northern Manhattan Stroke Study
(Sacco et al., 1994)
• >39 y.o. hospitalized w/ acute ischemic
stroke
• N=483 (35% black, 46% Hispanic, 19%
white)
• 75% got TCD, 12% catheter angio
• 9% had extracranial dz, 8% had ICAD
• ICAD higher in non
non--whites (OR=4.4, CI
0.6--35; adjusted for age, education,
0.6
IDDM, hyperlipidemia)
Webanatomy.net and meddean.luc.edu
Epidemiology of ICAD
Johns Hopkins study (Wityk et al.,
1996)
• Consecutive patients admitted with
acute ischemic stroke or TIA over 2yrs
• N=274 (61% black, 39% white)
• 156 patients (57%) had evaluation of
intracranial vessels by MRA, TCD or
catheter angio
• Of all patients in study, 12% had ICAD
• Symptomatic ICAD = 8% of total
• No difference between races
Race--Ethnicity & ICAD
Race
Prevalence varies by racerace-ethnicity
ICAD responsible for ischemic stroke
is estimated to be:
• 6-29% in Blacks
• 11% in Hispanics
• 2222-26% in Asians
Very limited data on ICAD among
Asians in the US
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2/7/2009
ICAD rates in Asia
Chinese in Boston
China (asymptomatic)
Hong Kong
Korea
Taiwan
Taiwan
# subjects
24
590
705
268
108
578
ICAD rate
43%
7%
37%
52%
26%
41%
Diagnosing ICAD
Technique
Angio
TCD
TCD
Angio
MRA
TCD
Transcranial Doppler (TCD)
MR Angiogram (MRA)
CT Angiogram (CTA)
Transcranial Doppler (TCD)
Digital Subtraction Angiography (DSA)
• Gold standard
TCD
Non-invasive
NonCheap
Readily available in the community
Highly operatoroperator-dependent
Not feasible on every patient
Still no standardized velocities
• SONIA (Stroke Outcomes & Neuroimaging of
Intracranial Atherosclerosis): 407 patients 505099% stenosis. Compared to DSA: PPV=55%,
NPV=83%
http://www.hospimedicaintl.com/Products.aspx?CatID=5&SubCatID=39
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2/7/2009
Magnetic Resonance Imaging
(MRI)
MR Angiography
Minimally invasive
Better vessel image
More expensive
Not readily available in the community
Flow dependent
Tends to overcall degree of stenosis in
higher grade due to turbulence
SONIA: PPV=66%, NPV=87%
http://www.strokecenter.org/pat/diagnosis/
Computed Tomography (CT)
CT Angiogram
http://www.strokecenter.org/pat/diagnosis/
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2/7/2009
CT Angiogram
Minimally invasive; uses iodinated
contrast
Better vessel visualization
Relatively cheap
Can be readily available in the community
Potential allergy to IV contrast
Compared to DSA, for >50% stenosis:
sensitivity = 97.1%, specificity=99.5%*
*Nguyen-Huynh, MN et al., Stroke, 2008
DSA
DSA
Basilar
Carotid Siphon
Pathology -- ICAD
Considered gold standard for its high
spatial resolution
Most invasive; uses iodinated contrast
Most expensive
Most time consuming
Only available at major medical centers
Requires highly specialized expertise
Risk of stroke ~1%
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2/7/2009
Risk Factors for ICAD
Non--modifiable:
Non
Modifiable:
• Gender (female>male)
• RaceRace-ethnicity
• Age (younger in Asians)
•
•
•
•
•
•
•
HTN
DM
Smoking
Hyperlipidemia
Diet
Physical inactivity
Obesity
Stroke Risk in Symptomatic ICAD
Treatment Options for ICAD
Antiplatelets
• Still
1st
line therapy
Anticoagulants
Angioplasty
Intracranial stenting
• Bare metal stent
• Drug
Drug--eluting coronary stent
• Self
Self--expanding intracranial stent
Annual stroke rate in ICAD on medical
therapy:
• 8-10% in the carotid siphon
• About 22% over 14 mos. in vertebral or
basilar artery
Overall risk of recurrent stroke in patients
with symptomatic ICAD is as high as 151517% per year (WASID study)
WASID
Warfarin-Aspirin Symptomatic Intracranial
WarfarinDisease Study
Randomized, doubledouble-blinded, multimulti-center
TIA & nonnon-disabling stroke, enrolled
between Feb 1999 to July 2003
Warfarin (INR 2.0 – 3.0) vs. 1300mg
Aspirin
Primary endpoint: ischemic stroke, brain
hemorrhage, or death from vascular
causes other than stroke
Chimowitz, MI et al., NEJM 2005; 352:1305
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2/7/2009
WASID
Stopped after 569 enrolled
Mean f/u 1.8 years
Mean INR=2.5
63.1% achieved INR 2.0 – 3.0
Major hemorrhage 3% in ASA, 8% in
warfarin (HR 0.39 in favor of ASA, 95% CI
0.18--0.83, p<0.01)
0.18
1-yr rate of ischemic stroke in territory of
stenotic artery = 12% in ASA, 11% in
warfarin
Factors associated with increased
risk of recurrent stroke (WASID
(WASID))
Severe stenosis (≥70%); HR=2.03
Enrolled early (≤17 days); HR=1.69
Female gender; HR=1.59
HTN (sbp ≥140 mmHg); HR=1.79
Cholesterol (≥200 mg/dL); HR=1.44
Blacks with ICAD have higher risk of
recurrent stroke than whites (25%
vs. 16%). No data on Asians
WASID
Location of stenosis and type of
event were not associated with an
increased stroke risk
Failed antianti-thrombotics do not have
higher stroke risk
CoCo-existing asymptomatic
intracranial stenoses (50(50-99%) have
low risk of stroke
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2/7/2009
TOSS--2
TOSS
Trial of Cilostazol in Symptomatic
Intracranial Arterial Stenosis II
Hong Kong, Korea, Philippines,
Thailand, 480 patients >35 y.o. with
symptomatic M1 or basilar
Cilostazol + 100mg ASA vs.
Clopidogrel + 100 mg ASA
Outcome: progression rate on MRA
Angioplasty
Stenting
SSYLVIA: Neurolink bare metal stent, 95%
success rate, 32.4% inin-stent restenosis @
6 mos, 13.1% ischemic stroke @ 12 mos
Drug eluting stent: retrospective review,
90% success rate, 5% of rere-stenosis rate
intracranially at 4±
4±2 months
Wingspan self expanding intracranial stent
(FDA approved): single arm study, 97.7%
success rate, 7.5% inin-stent restenosis @ 6
mos, all asymptomatic, 7% ipsilateral
stroke or death rate @ 6 mos
Cochrane Collaboration 2006 review
No randomized trials
79 articles with openopen-label case series ≥3
cases
Perioperative stroke rate 7.9% (CI 5.55.510.4)
Periop death rate 3.4% (CI 2.02.0-4.8)
No comments could be made on
effectiveness
Insufficient data to recommend
angioplasty
SAMMPRIS
Stenting and Aggressive Medical
Management for Preventing Recurrent
stroke in Intracranial Stenosis
NIH sponsored, randomized, multimulti-center
Patients with a TIA or stroke within 30
days prior to enrollment & 7070-99%
stenosis of a major intracranial artery on
angio
Randomize to aggressive med rx vs.
intracranial stenting (Wingspan) &
aggressive medical rx
Possible patient recruitment starting at
UCSF in Spring 2009
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2/7/2009
Summary
ICAD is underunder-recognized
Higher prevalence among Asians
High recurrent stroke rate despite medical
therapy
Need:
• Fast, readily available, reliable, minimally
invasive diagnostic methods
• Better predictors of clinical outcomes
• Better predictors of progression or regression
of disease
• Better treatment options
Case #1
Case #2
66y.o. Filipino man h/o HTN, DM,
presented with left sided weakness.
Found on CT/CTA to have intracranial
occlusion of right M2, severe (70(70-80%)
bilateral vertebral stenoses.
Meds: lisinopril, HCTZ, glucophage, ASA
What to do next?
a)
b)
c)
d)
e)
Add Clopidogrel to ASA
switch to Clopidogrel alone
Switch to Aggrenox
Start a statin
Refer to NIR for angioplasty/stenting of
vertebral arteries
60 y.o. ChineseChinese-speaking woman h/o
anxiety/depression, HTN, c/o HAs. PCP
obtained a MRI/MRA brain. Found
several areas of significant intracranial
athero. Refer to Neuro
Meds: HCTZ
What to do next?
a)
b)
c)
d)
e)
f)
Start antiplatelet
Start coumadin
Start a statin
Refer to NIR for angioplasty/stenting
Get a diagnostic catheter angiogram
Get CTA
Thank you!
UCSF Neurovascular Faculty
• Wade Smith, Director of Neurovascular
• S. Claiborne Johnston, Director of Stroke
Service
• Claude Hemphill, Director of Neuro ICU @
SFGH
• Vineeta Singh
• Nerissa Ko
• Andy Josephson
• Anthony Kim
10