Prospective Study of Symptomatic Atherothrombotic Intracranial

7/30/2019 Prospective Study of Symptomatic Atherothrombotic Intracranial

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CME Prospective study of symptomatic

atherothrombotic intracranial stenoses

The GESICA Study*

M. Mazighi, MD; R. Tanasescu, MD; X. Ducrocq, MD; E. Vicaut, MD, PhD; S. Bracard, MD;

E. Houdart, MD; and F. Woimant, MD

AbstractBackground: Symptomatic intracranial atherothrombotic stenoses (ICAS) are associated with high rates of

cerebrovascular ischemic events. Objective: To conduct a prospective multicenter study to evaluate the natural history of

ICAS and, in those patients refractory to medical treatment, the outcomes associated with intracranial angioplasty.

Methods: Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of 50%. Optimal medical

therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator.

Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy. Neurologic

and ultrasonographic examinations were performed at study inclusion, 3 months after enrollment, and every 6 months of

follow-up thereafter, for 36 months. Results: One hundred two patients were included, with a mean age of 63.3 10.4

years. Intracranial artery stenoses involved the vertebral artery in 22.5%, the basilar artery in 25.5%, the middle cerebral

artery in 26.5%, and the internal carotid artery in 25.5%. In 27.4% of the patients, the stenoses had clinical hemodynamic

characteristics. During a mean follow-up of 23.4 months, 38.2% of the patients had a cerebrovascular event: ischemic

stroke in 13.7% and TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7% had a recurrent

stroke or TIA in the territory of the stenotic artery; this association was significant in univariate analysis. Twenty-eight

patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2%. The overall

vascular death rate was 8.8%. Conclusions: Despite medical treatment, the 2-year recurrence rate of ischemic events in

the territory of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6% of patients. Clinically significant

hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients.

NEUROLOGY 2006;66:11871191

The development of noninvasive vascular imagingtechniques such as transcranial color-coded duplexscanning and MR angiography (MRA) allows more

extensive noninvasive investigations of stroke pa-tients and the accurate diagnosis of intracranialatherothrombotic stenoses (ICAS). The majority ofthese stenoses are due to atherosclerosis; however,the natural history and prognosis of ICAS are poorlyunderstood, especially in Caucasian patients, inwhom cervical lesions are widely prominent. ICASare estimated to represent 5 to 10% of ischemicstrokes,1 and the annual risk of recurrent stroke var-ies from 10 to 50%.2,3 The initial retrospective Warfa-rinAspirin Symptomatic Intracranial Disease(WASID) Study suggested that warfarin was moreeffective than aspirin at preventing recurrences.4

However, the recent prospective WASID trial wasstopped early owing to safety concerns related to anexcess of adverse events in the warfarin group.5

Many unanswered questions exist regarding the op-timal management of ICAS: What is the risk of fur-

ther stroke or other vascular events? Are therecurrences due to embolic or hemodynamic mecha-nisms? What is the best medical treatment? In whom

should intracranial angioplasty be considered?From 1999 to 2003, we conducted a prospective

study called GESICA (Groupe dEtude des StenosesIntra-Craniennes Atheromateuses symptomatiques)aimed at evaluating the natural history of symptom-atic ICAS and intracranial angioplasty in those pa-tients refractory to medical treatment.

Methods. GESICA was a prospective, multicenter, nonrandom-ized study. Twenty-one neurologic centers participated in thestudy. From April 1999 to December 2003, all patients diagnosedas having a recent (6 months) TIA or minor (nondisabling) isch-emic stroke (IS) related to an ICAS were included. The maininclusion criteria are listed in table 1. This database was collectedby two of the investigators in two of the centers (F.W. and X.D.).

At inclusion, patients were investigated for history of TIA orstroke, coronary artery disease (CAD), peripheral arterial disease(PAD), vascular risk factors, and current medical treatment. A sys-tematic diagnostic workup, including cervical color-coded duplexscanning, transcranial ultrasound, MRA, EKG, transesophageal

*See the Appendix for a complete list of the GESICA Study members.

From the Departments of Neurology (F.W.) and Neuroradiology (M.M., E.H.), Hopital Lariboisiere, and Centre de Recherche Clinique (E.V.), Hopital Fernand

Widal, Paris, and Departments of Neurology (R.T., X.D.) and Neuroradiology (S.B.), Hopital Central, Nancy, France.

Disclosure: The authors report no conflicts of interest.

Received July 26, 2005. Accepted in final form January 18, 2006.

Address correspondence and reprint requests to Dr. M. Mazighi, Service de Neuroradiologie, Hopital Lariboisiere, 2 rue Ambroise Pare, 75010 Paris, France;e-mail: [email protected]

Copyright 2006 by AAN Enterprises, Inc. 1187


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echocardiography, and hypercoaguability workup, was performedto exclude other potential causes of stroke, according to theTOAST (Trial of ORG 10172 in Acute Stroke Treatment) classifi-cation.6 Optimal medical therapy for risk factors and preventiveantithrombotic therapy was at the discretion of the local investi-gator. No indication was given for the use of either oral anticoag-

ulant or antiplatelet therapy. As per prespecified protocol, allpatients were examined at 3 months and every 6 months thereaf-ter for clinical symptoms and signs; whenever possible, ultra-sonography was obtained. The study protocol was approved by theEthic Committee of the Hospital Central of Nancy (Comite Con-sultatif des Protections des Personnes se pretant a la RechercheBiomedicale de Lorraine), and all patients gave written informedconsent for participation. Supplementary visits were planned forthe occurrence of a new vascular event. If a new TIA or strokeoccurred, diagnostic workup was repeated with digital subtractionangiography (DSA), and, if clinically appropriate, intracranial an-gioplasty was offered to the patient.

Intracranial stenosis (50 to 99%) had to be demonstrated byeither DSA or ultrasonography and confirmed by one of the follow-ing methods: MRA, angiography, or CT. Stenoses were graded bythe peak systolic velocity measurement on ultrasonography.7 For

angiography, the degree of stenosis was measured at its point ofmaximal narrowing and compared with the normal section of thevessel distal to the stenosis ([normal lumen diameter residuallumen]/normal lumen diameter) or proximal to the stenosis if ec-tasia or a bifurcation was identified downstream of the stenosis.The angiograms were reviewed retrospectively and independentlyat separate reading sessions by two neuroradiologists. Stenoseseligible for the study had to be located either in the intracranialcarotid artery (ICA), the middle cerebral artery (MCA), the basilarartery (BA), or the intracranial vertebral artery (VA). The steno-ses were considered to be atherothrombotic if the patient had atleast two of the following vascular risk factors: hypertension, dia-betes, hypercholesterolemia, smoking, history of CAD, PAD, pre-existing atherosclerotic stenosis (20%) in another location, or thepresence of aortic plaques. Stenoses were classified clinically ashemodynamic, by a neurologist, if symptoms related to the steno-sis occurred during a change of position (supine to prone), an

effort, or the introduction or increase of an antihypertensivemedication.

GESICA angioplasty. A parallel study was conducted for pa-tients refractory to medical treatment, becoming mandatory formore aggressive treatment as angioplasty. They constitute a sub-group (GESICA angioplasty) of the cohort of patients of the GE-SICA Study. We assumed that some patients included in thestudy would develop recurrent events related to their ICAS, eitherTIA or IS despite receiving appropriate medical treatment. Thecriteria for the selection of these patients (table 2) were designedto include only those patients with symptoms clearly related tothe ICAS and refractory to medical treatment.

Angioplasty method. All patients gave written informed con-sent prior to the procedure. The procedure was performed undergeneral anesthesia. The patients received two antiplatelet agents(aspirin and clopidogrel) 5 days prior to the procedure and contin-ued for 1 month. Diagnostic cerebral DSA was performed in eachpatient. Each angiogram was evaluated for stenoses pre and postangioplasty. Following each procedure, patients were admitted tothe intensive care unit for postoperative observation and manage-ment. A CT scan was obtained within 24 hours in each case orimmediately after neurologic deterioration during hospitalization.

Statistical analysis. All data were entered into the Statviewsoftware for analysis and were summarized as median (interquar-

tile distance) or mean (SD). In the current study, sex, vascularrisk factors, location of stenotic arteries, and recurrent cerebro-

vascular and other vascular events were used as categorical vari-ables. Independent-sample t test and 2 test or Fisher exact testwere used for continuous or categorical variables, respectively. Alltests were two sided with a significance level fixed at 5%.

Results. A total of 102 patients with symptomatic intra-

cranial stenosis (50 to 99%) of the anterior or posterior

circulation were included in the study. All 21 centers ac-

tively enrolled patients, although the majority (59.8%) of

patients were enrolled at two centers. The clinical features

of the patients are provided in table 3. The mean age at

admission for index stroke was 63.3 10.4 years (38 to 93

years), 71.5% of the patients were men, and patients were

Table 1 Selection criteria for the GESICA Study

Age 18

TIA or IS in territory of intracranial stenosis

TIA or IS onset 6 months

Cerebral nonischemic lesion ruled out by appropriate imaging

Modified Rankin score 2 at time of inclusion

NIHSS score 15 at inclusion

Absence of handicap interfering with neurologic or functional

evaluation

Stenosis of ICA, or MCA, or VA, or BA

Presumed due to atheroma*

Stenosis 50%

Stenosis confirmed by either MRA, angio-CT, or DSA

No other severe life-threatening disease known

Follow-up presumed possible during study period

* Stenoses were considered atherothrombotic if the patient had

at least two of the following vascular risk factors: hypertension,

diabetes, hypercholesterolemia, smoking, history of coronary

artery disease, peripheral artery disease, pre-existing athero-

sclerotic stenosis (20%) in another location, or the presence ofaortic plaques.

GESICA Groupe dEtude des Stenoses Intra-Craniennes Athe-

romateuses symptomatiques; NIHSS NIH Stroke Scale; IS

ischemic stroke; ICA internal carotid artery; MCA middle

cerebral artery; VA vertebral artery; BA basilar artery;

DSA digital subtraction angiography.

Table 2 Supplementary selection criteria for patients included in

angioplasty group

Age 18 and 80

Recurrent episodes such as TIA or minor IS in territory of

intracranial stenosis under appropriate antithrombotic

treatment

Another cause than ischemia ruled out by appropriate imaging

Stenosis of either ICA, or MCA, or VA, or BA

Presumed due to atheroma*Stenosis 50%

Length of stenosis is short (length 3 diameter of artery as

measured just before or just after stenosis)

Good distal flow

No endoluminal thrombus

Modified Rankin score 2 before qualifying event

NIHSS score 15 at inclusion

* The stenoses were considered to be atherothrombotic if the pa-

tient had at least two of the following vascular risk factors: hy-

pertension, diabetes, hypercholesterolemia, smoking, history of

coronary artery disease, peripheral artery disease, pre-existing

atherosclerotic stenosis (20%) in another location, or the pres-ence of aortic plaques.

IS ischemic stroke; ICA internal carotid artery; MCA

middle cerebral artery; VA vertebral artery; BA basilar ar-

tery; NIHSS NIH Stroke Scale.

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predominantly Caucasian (97.1%). Hypertension (73.5%),

history of smoking (70.5%), and hypercholesterolemia

(50%) were the three most common vascular risk factors(table 3). The qualifying events for the patients included in

the study were a single TIA (7.9%), multiple TIAs (40.5%),

single stroke (47.7%), and multiple strokes (3.9%). The

mean time from symptomatic event to inclusion was 1.2

(1.5) months. At baseline, the functional status of the

studied population was high; 92.4% patients received a

modified Rankin Scale Score of 0 (no symptoms) or 1 (able

to perform all the previous activities despite symptoms).

The stenoses involved the following intracranial arter-

ies: the VA in 23 patients (22.5%), the BA in 26 patients

(25.5%), the MCA in 27 patients (26.5%), and the ICA in 26

patients (25.5%). The degree of stenosis was assessed by

angiography in 62.7% of patients. The stenoses had clinical

hemodynamic characteristics in 27.4% of the patients andassociated ICAS were noticed in 41%.

After inclusion, 38.2% patients were treated with a sin-

gle antiplatelet agent, 31.4% with one antiplatelet agent

and one anticoagulant, 15.7% with one anticoagulant, and

14.7% were treated with another antithrombotic combina-

tion (two antiplatelet agents: 8.8%; two antiplatelet agents

with one anticoagulant: 5.9%, table 4). During a mean

follow-up of 23.4 months, 38.2% of the patients had a

stroke or a TIA in the same territory of the stenotic intra-

cranial artery. The cerebrovascular events were a TIA in

25 patients (24.5%) and an IS in 14 patients (13.7%). In

two patients, one IS and one TIA were observed in other

territories than in the symptomatic stenotic artery. Cere-brovascular events were discovered within a median time

of 2 months (3.4 months), whereas noncerebrovascular

events arose within a median time of 20.5 months (17.5

months).

Recurrent strokes affected the anterior circulation for

19 patients (18.6%) and the posterior circulation for 20

patients (19.6%). Patients experiencing a recurrent stroke

had a symptomatic stenosis in the ICA in 29.3%, in the

MCA 22.0%, in the BA in 35.3%, and in the VA in 13.4%.

Among the 38 patients with other associated intracranial

lesions, 50% had a recurrent stroke, whereas only 35.1% of

the patients without associated intracranial stenosis had a

recurrent event. The association of recurrent strokes and

multiple intracranial stenoses was not significant in uni-

variate analysis (table 4).

Among patients with a hemodynamic stenosis, 60.7%

had a recurrent IS or TIA in the territory of the stenotic

artery, whereas only 31.7% of the patients without a hemo-

dynamic stenosis had a recurrent event. In univariate

analysis, the hemodynamic significance (see Methods) of

the stenosis appeared to be the unique element associated

with stroke recurrence (table 4).

Twenty patients underwent an endovascular procedure,

13 of whom received a stent. The mean time from the

symptomatic event to intracranial angioplasty was 1.5

(0.9) months. Cerebrovascular events resulting in angio-

plasty were TIAs in 62.9% and IS in 37.1%. An endovascu-

lar procedure was not performed in nine patients withrecurrent strokes in the territory of the stenotic artery due

to arterial occlusion (n 3), patient refusal (n 1), other

mechanism of stroke, (e.g., atrial fibrillation; n 1), sub-

therapeutic international normalized ratio (n 1), and

other causes (n 3).

Neurologic periprocedural complications were observed

in 14.2% patients including one death (one arterial rup-

ture), two fatal strokes (one hemorrhagic and one ischemic

responsible for death, respectively, 2 and 9 months after

the procedure), and one nonfatal minor IS (modified

Rankin Scale score 0 after 26 months of follow-up). In a

mean follow-up of 19.5 months, recurrent strokes were

noticed in two (7.1%) patients: one TIA (no restenosis on

Table 3 Baseline characteristics of 102 patients with intracranial

symptomatic stenoses

Age, y 63.3 10.4

Male 73 (71.6)

Race

Caucasian 99 (97.1)

Other 3 (2.9)

Hypertension 75 (73.5)

Diabetes mellitus 31 (30.4)

Ever smoker 72 (70.6)

Cholesterol 200 mg/dL 61 (59.8)

History of coronary artery disease 34 (33.3)

Peripheral arterial disease 6 (5.9)

Values (except for age) are n (%).

Table 4 Patient characteristics and frequency of stroke recurrence

Patients,

n

Recurrent

stroke, %

No

recurrent

stroke, % p

Hemodynamic stenosis 28 60.7 39.3 0.009

Male 73 47.8 52.2 NS

Female 29 28.6 71.4 NS

Diabetes 31 36.7 63.3 NS

Hypertension 75 38.9 61.1 NS

Hypercholesterolemia 61 37.9 62.1 NS

Smoking 72 43.5 56.5 NS

Anticoagulant 16 43.7 56.3 NS

One APD 39 28.2 71.8 NS

Two APDs 9 66.6 33.4 NS

Anticoagulant 1 APD 32 43.7 56.3 NS

Anticoagulant 2 APDs 6 50.0 50.0 NS

BA 26 58.3 41.7 NS

VA 23 26.3 73.7 NS

MCA 27 34.6 65.4 NSICA 26 48.0 52.0 NS

Coexistent stenoses 38 50.0 50.0 NS

Values for stroke recurrence are percentages. After univariate

analysis, an association between the parameter and the stroke

recurrence was considered significant if p 0.05.

APD antiplatelet drug; BA basilar artery; VA intracranial

artery; MCA middle cerebral artery; ICA internal carotid

artery.

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ultrasonography) and one stroke (related to the disclosure

of atrial fibrillation).

Noncerebrovascular events, that is, acute coronary syn-

dromes, occurred in 14 patients (13.7%) and symptomatic

PAD in 5 patients (4.9%), 3 of whom had a history of

previous PAD. At the end of the follow-up study, the death

rate reached 11.7% in a mean time of 21.8 (14.8) months.

Nine patients died in the group without angioplasty: five of

CAD, one of IS (other territory than the related intracra-

nial symptomatic stenosis), and three of nonvascular

causes.

Discussion. The GESICA Study demonstratesthat the patient population with symptomatic intra-cranial stenosis is at high risk of recurrent vascularevents. Despite optimal medical treatment, 38.2% ofpatients experienced a recurrent cerebrovascularevent in the territory of the stenotic artery at 2-yearfollow-up (13.7% IS and 24.5% TIAs). The impor-tance of this atherothrombotic burden is illustratedby the associated CAD or PAD present in more than30% of the patients. During the follow-up, acute cor-

onary syndromes and symptomatic PAD occurred in18.6% of the patients in a median time of 20.5months. The death rate reached 8.8% in patientswithout endovascular treatment, predominantly dueto CAD. These results illustrate the need for manda-tory screening for CAD in patients with symptomaticintracranial stenosis.

Intracranial atherosclerosis is a severe diseasewith recurrent annual strokes rates of 4% to 24% peryear.3,8-21 In patients with symptomatic ICAS failingmedical therapy, the stroke rate may be even higher,reaching 55.8% within a median time of 36 days.3 Inthe GESICA Study, recurrent cerebral ischemic

events occurred in a median time of 2 months follow-ing the first qualifying event. The short time forrecurrence argues for an aggressive frontline thera-peutic strategy. The disparity observed in the anti-thrombotic regimens likely reflects the lack ofconsensus between the investigators regarding thetherapeutic management of this disease. This studywas conducted before the results of the WASID pro-spective trial,5 which revealed a significant increaseof hemorrhagic complications in the warfarin-treatedgroup. Based on this trial, warfarin should not beused in preference to aspirin,22 but the high rate ofIS despite antithrombotic agents highlights the need

to consider endovascular treatment as a therapeuticoption.24-26 The increasing enthusiasm for intracra-nial intervention should be dampened some by theneurologic periprocedural complication rate, esti-mated at 5.3 to 28%.27-31 In accordance with theseresults, a relatively high neurologic periproceduralmorbidity/mortality rate of 14.2% was observed inour population. In GESICA, 2 of the 28 patientstreated by angioplasty had recurrent neurologicevents within a mean follow-up of 19 months: a TIAand an IS. The IS was confounded by the presence ofatrial fibrillation. In the SSYLVIA multicenter tri-al,30 a similar stroke recurrence after intracranial

stenting was reported, with a rate at 1 year of 7.3%.This raises the important issue of whether the pro-posed treatment of intracranial stenting improvesthe natural history of this disease. Defining a groupof patients at higher risk is relevant when determin-ing the benefit of an interventional approach. In ourseries, the hemodynamic characteristics of the intra-cranial stenosis predicted stroke recurrence afterunivariate analysis. These characteristics, based on

clinical criteria, are easy to assess, are not depen-dent on a specific imaging technique, and are usefulin selecting patients who will derive a benefit fromangioplasty when antithrombotic therapy remainsunsuccessful.23

Although the aim of the study was not to comparethe efficacy and tolerance of different preventivetreatments, the lack of standardized therapy for an-tithrombotic or antihypertensive medication is a lim-itation. As an example, it would be of interest toknow whether arterial blood pressure should be low-ered or not, as some patients with ICAS are at risk ofhemodynamic ischemia. In this condition, comple-

mentary ultrasonographic explorations with assess-ment of hypoperfusion or high-intensity transientsignals are required to identify the mechanism of IS.

Another limitation is that two centers enrolled themajority of patients (59.8%), which may be a resultof referral bias, explaining the clinical severity of therecruited patients. Nonetheless, ICAS are character-ized by high and early recurrences of strokes anddelayed cardiovascular events. The identification ofthe patients that may benefit from angioplasty andthe long-term vascular follow-up are main issues.Based on the postangioplasty complication rate inour series, it is premature to recommend intracra-

nial angioplasty as a primary treatment for this con-dition until more safety data are available.Therefore, this technique should be reserved for pa-tients experiencing medical treatment failure andshould be performed only by skilled operators.

Appendix

The GESICA Study investigators are as follows: F. Woimant, MD, E. Hou-dart, MD, M. Mazighi, MD, A. Checoury, MD (Services de Neurologie[F.W.], Neuroradiologie [E.H., M.M.], Exploration fonctionelle [A.C.], Hopi-tal Lariboisiere, Paris); X. Ducrocq, MD, R. Tanasescu, MD, S. Bracard,MD, J.-C. Lacour, MD (Service de Neurologie [X.D., R.T.], Service de Neu-roradiologie [S.B., J.-C.L.], Hopital Central, Nancy); M. Giroud, MD, O.Martin, MD (Service de Neurologie [M.G.], Service de Neuroradiologie[O.M.], Centre Hospitalo-Universitaire, Dijon); S. Bouly, MD, P. Labauge,

MD (Service de Neurologie, Centre Hospitalo-Universitaire, Nmes); L. Mi-landre, MD, O. Levrier, MD (Service de Neurologie [L.M.], Service de Neu-roradiologie [O.L.], Centre Hospitalo-Universitaire, LaTimone, Marseille);J.-L. Mas, MD, J.-F. Meder, MD, E. Touze, MD, C. Arquizan, MD, M. Zuber,MD (Service de Neurologie [J.-L.M., E.T., C.A., M.Z.], Service de Neuroradi-ologie [J.-F.M.], Hopital Sainte Anne, Paris); P. Bakouche, MD, A. Boucha-reine, MD, J. Moret, MD (Service de Neurologie [P.B., A.B.], Service deNeuroradiologie [J.M.], Fondation Rothschild, Paris); F. Dubas, MD, A.Pasco, MD (Service de Neurologie [F.D.], Service de Neuroradiologie [A.P.],Centre Hospitalo-Universitaire, Angers); T. Moulin, MD, J.-F. Bonneville,MD (Service de Neurologie [T.M.], Service de Neuroradiologie [J.-F.B.],Centre Hospitalo-Universitaire, Besancon); J.-M. Orgogozo, MD, J. Berge,MD (Service de Neurologie [J.-M.O.], Service de Neuroradiologie [J.B.],Centre Hospitalo-Universitaire, Bordeaux); J.-M. Blard, MD, D. Milhaud,MD, A. Bonafe, MD (Service de Neurologie [J.-M.B., D.M.], Service deNeuroradiologie [A.B.], Centre Hospitalo-Universitaire, Montpellier); F.Chollet, MD, C. Cognard, MD (Service de Neurologie [F.C.], Service deNeuroradiologie [C.G.], Centre Hospitalo-Universitaire, Toulouse-Purpan);M. Dupuy, MD, L. Pierot, MD (Service de Neurologie [M.D.], Service de

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Neuroradiologie [L.P.], Hopital Foch); B. Guillon, MD, A. de Ker Saint Gilly,MD (Service de Neurologie [B.G.], Service de Neuroradiologie [A.K.S.G.],Centre Hospitalo-Universitaire, Nantes); F. Pinel, MD, Y. Roland, MD (Ser-vice de Neurologi e [F.P.], Service de Neuroradi ologie [Y.R.], CentreHospitalo-Universitaire de Pontchaillou, Rennes); A. Legout, MD (Servicede Neurologie, Centre Hospitalier General, Le Mans); T. De Broucker, MD(Service de Neurologie, Centre Hospitalier Delafontaine, Saint Denis); P.Rondepierre, MD, A.C. Zeghoudi, MD (Service de Neurologie, Centre Hospi-talier General, Dreux); M. Maillet-Vioud, MD (Service de Neurologie, Cen-tre Hospitalier General, Montlucon); D. Saudeau, MD (Service deNeurologie, Centre Hospitalo-Universitaire, Tours); H. Hosseini, MD (Ser-vice de Neurologie, Centre Hospitalo-Universitaire Mondor, Creteil); F.G.Barral, MD (Service de Neuroradiologie, Hopital Bellevue, Saint-Etienne).

Acknowledgment

The authors thank F. Baudouin (Department of Neurology, Hopi-tal Lariboisiere) for technical assistance and data collection andM. Hook (Department of Cardiovascular Medecine, ClevelandClinic Foundation) for copyediting the manuscript.

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Prospective Study of Symptomatic Atherothrombotic Intracranial