Transcript 20070206_intracrania..

CURRENT CONCEPTS IN THE
MANAGEMENT OF
INTRACRANIAL
ATHEROSCLEROTIC DISEASE
Robert D. Ecker, M.D.
~Neurosurgery 59:S3-210-S3-218, 2006
Feb. 06, 07
VJ
• Intracranial atherosclerosis accounts for 8
to 10% of all ischemic strokes.
• Patients with symptomatic intracranial
atherosclerotic disease
>> oral antithrombotic medications as the
first and only line of treatment till now
• The Warfarin-Aspirin Symptomatic Intracranial Disease
(WASID) investigators compared outcomes among
patients with symptomatic intracranial stenosis receiving
warfarin (INR: 2.0–3.0) and those receiving high-dose
aspirin (1300 mg daily) in a randomized, double-blinded
trial .
-- In 569 patients at a mean follow-up period of 1.8
years,
1. warfarin was associated with a higher rate of death,
major hemorrhage, myocardial infarction or sudden
death, and death from nonvascular or
2. At 1 year, the stroke risk for patients with 50 to
69% stenosis was 6%, compared with 19% for those
with 70 to 99% stenosis.
3. the ipsilateral stroke risk for patients with
symptomatic intracranial stenosis is 13 ~ 14%
Experience from CATH of the treatment of intracranial atherosclerosis:
1) coronary stents were, until recently, the only available
devices able to be navigated and deployed in the
intracranial circulation;
2) lower restenosis rates with angioplasty and stenting than
stand alone angioplasty;
3) well-defined antithrombotic regimens and evidence of
the benefits of periprocedural bolus-dose administration
and postprocedural therapy with aspirin and
clopidogrel : decreases recurrent stenosis and
postprocedural neurological events; and
4) implantation of new coated and drug-eluting stents is
proving to yield significantly lower restenosis rates
strategy
• a technique of submaximal angioplasty followed by
delayed repeat angioplasty and, if necessary, stenting
was developed for intracranial symptomatic
atherosclerotic disease.
• Repeated angiography approximately 4 to 6 weeks after
angioplasty. If in-lesion binary stenosis (50% luminaldiameter stenosis) -- stenting
• neointimal proliferation and scar formation result in a
thickened fibrous lesion -- incur a lower risk for plaque
embolization and vessel dissection during a subsequent
stenting procedure.
• mortality and permanent neurological morbidity for the
procedure dropped to less than 5%, and between 20 and
30% of patients did not require further intervention at
follow-up
PATIENT SELECTION
• CT perfusion imaging with and without
acetazolamide challenge testing is used most
often for evaluation of lesions located in the
supratentorial vasculature,
• single-photon emission computed
tomographic scanning -- posterior circulation
or for those patients who cannot tolerate a
significant load of contrast material.
72-year-old woman with a history of a 5-minute episode of unresponsiveness
at home - increased time to peak in the right posterior cerebral territory.
B, DWI MR scan - only a small area of infarction in the right posterior cerebral
territory.
C, DSA: a fetal posterior cerebral artery with more than 90% stenosis.
CLINICAL SERIES
• Humanitarian Device Exemption (HDE) program for use
in patients with symptomatic intracranial stenosis of 50%
or more in severity.
• Use of this system involves submaximal inflation of an
angioplasty balloon, followed by removal of the balloon
and subsequent deployment of the stent.
• The Wingspan is a self-expanding
intracranial stent composed of
nitinol with similar trackability
but at least twice the radial
outward strength of the
Neuroform III stent
(Boston Scientific).
• SSYLVIA was a safety and feasibility
study designed to evaluate the Neurolink
stent (Guidant Corporation, Indianapolis,
IN), a flexible, stainless steel stent
specifically designed for intracranial
placement, in 61 symptomatic patients
with intracranial stenosis
• Jiang et al. -- In a single-center series
consisting of 40 patients with 42
symptomatic M1 stenotic lesions treated
with angioplasty and balloon-mounted
coronary stenting
• Between 1993 and 2000, technical and clinical
success with stand-alone angioplasty was
documented in 11 case series consisting of 193
patients
• Good revascularization-- 67 to 100% of the
patients, with overall complication rates -- 5 to
40%.
• Technical success rates -- 64 to 100%,
major complication rates -- 0 to 36%.
• In a single-center series consisting of 40 patients with 42
symptomatic M1 stenotic lesions treated with
angioplasty and balloon-mounted coronary stenting,
Jiang et al. reported a technical success rate (20%
residual stenosis) of 97.6%, with a 10% major
complication rate -- one died of a subarachnoid
hemorrhage and three experienced no major
neurological injury.
• The results of both the SSYLVIA study and the series
reported by Jiang et al. clearly demonstrate more than
95% accuracy for deployment of a stent in the correct
intracranial location.
• Despite improved technical success, it remains uncertain
whether or not the cardiac literature, which demonstrates
that stenting in small coronary arteries leads to less
restenosis than stand-alone balloon angioplasty, is
applicable to the intracranial circulation
A comparison of the findings of the Wingspan study with
those from the SSYLVIA trial and the series reported by
Jiang et al. demonstrates lower complication and restenosis
rates for the self-expanding Wingspan stent
ANTITHROMBOTIC AGENTS
• IIb-IIIa inhibitors
• By binding the platelet GP IIb-IIIa receptor, these agents
(abciximab, eptifibatide, tirofiban) are the most potent
inhibitors of platelet aggregation.
• GP IIb-IIIa inhibitors to date -- a rescue drug when
embolic phenomena have occurred during an
endovascular procedure
• For patients with TIA or stroke medical treatment
-- no benefit for the combination of aspirin and
clopidogrel and an associated increase the risk of
bleeding
• The Clopidogrel versus Aspirin in Patients at Risk of
Ischaemic Events trial demonstrated a slight benefit for
clopidogrel compared with aspirin
FROM THE PAST TO THE
FUTURE
• Technique progressed from directly sizing the
balloon to the artery caliber with rapid balloon
inflation to undersizing the balloon with slow
inflation. The occurrence of acute vessel
occlusion and dissection dropped from 75 to
14% with this technique
• The classification scheme developed by Mori et
al. , ; based on length of stenosis, degree of
stenosis,and eccentricity of plaque, is highly
predictive of outcome, with 92, 86, and 33%
clinical success rates in patients with Types A, B,
and C lesions, respectively:
Type A, 5 mm or less in length concentric or moderately
eccentric lesions less than totally occlusive;
Type B, tubular 5 to 10 mm in length, extremely eccentric or
totally occluded lesions, less than 3 months old; and
Type C, diffuse, more than 10 mm in length, extremely
angulated (90 degrees) lesions with excessive tortuosity
of the proximal segment, or totally occluded lesions, and
3 or more months old.
• At the 1-year follow-up evaluation, restenosis rates
associated with these lesion types were 0, 33, and 100%,
respectively; the risk of major stroke or death was 8% in
Type A, 26% in Type B, and 87% in Type C
In 2002, Levy et al.
• staged stent placement after
angioplasty-- delayed stent placement
gives the artery time to heal in the acute
phase after angioplasty
• balloon angioplasty injures the intima,
upregulating inflammatory mediators and
leukocytes at the injury site
>>> neointimal proliferation and fibrosis
Drug-eluting stents
Sirolimus (rapamycin) -- antifungal agent induces
cell-cycle arrest and reduce neointimal
proliferation in animals.
Paclitaxel, a microtubule inhibitor, also has been
shown to prevent neointimal proliferation.
• An ideal stent would need to be visualized easily,
to be navigable through the intracranial
circulation, to be porous, to deploy reliably at low
atmospheres of pressure, and to be coated with
an agent to prevent restenosis and thrombosis.
CONCLUSION
• Intracranial stenosis is common and
dangerous. Symptomatic stenosis carries
a 10 to 20% 2-year risk of stroke and
should be treated.
• Patients experiencing a single TIA and
with less than 50% stenosis, no
perfusion abnormality, or poor life
expectancy -- treated medically with
antiplatelet agents.
• High-dose aspirin, clopidogrel, or dipyridamole :
used as single agents.
• Warfarin : increase the risk of death and
hemorrhage and no longer should be used
• Asymptomatic patients – medically
• Symptomatic patients: considered for treatment
with interventional techniques.
• The risk of percutaneous angioplasty and
stenting has been lowered by the staged
technique. With new self-expanding stents,
the restenosis rate has dropped, without
compromising safety
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