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Case 74 year old male, recent carotid doppler following episode of dizziness 74 year old male,...

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Case Case 74 year old male, recent carotid doppler 74 year old male, recent carotid doppler following episode of dizziness following episode of dizziness 50-79% right carotid stenosis 50-79% right carotid stenosis PMH- coronary artery disease, PMH- coronary artery disease, hypertension, hyperlipidemia hypertension, hyperlipidemia Spell consisting of “fuzzy vision”, Spell consisting of “fuzzy vision”, uncertain if monocular, lasting minutes uncertain if monocular, lasting minutes up to 15 minutes, with associated up to 15 minutes, with associated “tingling left side of face” “tingling left side of face”
Transcript

CaseCase

74 year old male, recent carotid doppler 74 year old male, recent carotid doppler following episode of dizzinessfollowing episode of dizziness50-79% right carotid stenosis50-79% right carotid stenosis

PMH- coronary artery disease, PMH- coronary artery disease, hypertension, hyperlipidemiahypertension, hyperlipidemia

Spell consisting of “fuzzy vision”, uncertain if Spell consisting of “fuzzy vision”, uncertain if monocular, lasting minutes up to 15 minutes, monocular, lasting minutes up to 15 minutes, with associated “tingling left side of face”with associated “tingling left side of face”

QuestionsQuestions

Is this amaurosis fugax?Is this amaurosis fugax?What is this patient’s risk for stroke?What is this patient’s risk for stroke? Is carotid endarterectomy indicated in this Is carotid endarterectomy indicated in this

case?case?

Amaurosis FugaxAmaurosis Fugax

……and the role of and the role of

Carotid EndarterectomyCarotid Endarterectomy

COL Beverly Rice Scott MDNeurology and Neuro-ophthalmologyMadigan Army Medical Center

OutlineOutline

Definition and etiologies of transient visual lossDefinition and etiologies of transient visual loss Clinical features & pathophysiology Clinical features & pathophysiology Evaluation of transient monocular blindnessEvaluation of transient monocular blindness Amaurosis Fugax and Stroke Risk Amaurosis Fugax and Stroke Risk

North American Symptomatic Carotid North American Symptomatic Carotid Endarterectomy Trial (NASCET) Endarterectomy Trial (NASCET)

Spectrum of ocular ischemic syndromes and Spectrum of ocular ischemic syndromes and stroke riskstroke risk

DefinitionDefinition Painless unilateral transient loss of vision, Painless unilateral transient loss of vision,

partial or complete, related to retinal arterial partial or complete, related to retinal arterial microembolization or hypoperfusionmicroembolization or hypoperfusion

““fleeting darkness or blindnessfleeting darkness or blindness””Retinal transient ischemic attack (RTIA)Retinal transient ischemic attack (RTIA)transient monocular blindness (TMB)transient monocular blindness (TMB)

Accounts for 25% of anterior circulation transient Accounts for 25% of anterior circulation transient ischemic attacks (TIAs).ischemic attacks (TIAs).

Transient visual loss

AmaurosisFugax

Transient Visual Obscuration

Binocular Monocular (TMB)

RetinalMigraine

Cortical Migraine

Heart disease

Arteritis

Etiologies:Etiologies:Transient visual lossTransient visual loss

Occlusive retinal artery diseaseOcclusive retinal artery diseaseAtheroembolicAtheroembolic, cardioembolic, arteritic, , cardioembolic, arteritic,

hematological disorders, congenital, orbital tumorhematological disorders, congenital, orbital tumor

Low retinal artery pressureLow retinal artery pressure Ocular ischemia syndromeOcular ischemia syndrome, arteriovenous fistula, , arteriovenous fistula,

congestive heart failure, anemiacongestive heart failure, anemia

Optic disc disease and anomaliesOptic disc disease and anomalies Papilledema, Glaucoma, DrusenPapilledema, Glaucoma, Drusen

Vasospasm Vasospasm ((ophthalmic migraineophthalmic migraine))MiscellaneousMiscellaneous

Uhthoff’s phenomenon, classic migraineUhthoff’s phenomenon, classic migraine

Clinical Features:Clinical Features:SymptomsSymptoms

Abrupt or gradual monocular* visual loss, Abrupt or gradual monocular* visual loss, progressing from peripheral toward center of fieldprogressing from peripheral toward center of field +/- descending/ ascending shade, partial or complete+/- descending/ ascending shade, partial or complete ‘ ‘looking through fog’looking through fog’

Visual disturbance: Dark, foggy, gray, whiteVisual disturbance: Dark, foggy, gray, white Minutes (1-5 minutes, occasionally longer); Minutes (1-5 minutes, occasionally longer);

full resolution takes 10-20 minutes full resolution takes 10-20 minutes PainlessPainless StereotypedStereotyped Usually occurs in isolationUsually occurs in isolation

**may be difficult to distinguish monocular from binocular visual may be difficult to distinguish monocular from binocular visual lossloss

Clinical features: Clinical features: Retinal findingsRetinal findings

Acute infarctionAcute infarctionOpaque and gray (early)Opaque and gray (early) ““bright plaques” of cholesterol or other bright plaques” of cholesterol or other

microemboli; may persist weeks to yearsmicroemboli; may persist weeks to yearsCotton-wool spotCotton-wool spotSegmental arteriolar mural opacificationSegmental arteriolar mural opacificationOptic disc pallor, arteriolar narrowing (late)Optic disc pallor, arteriolar narrowing (late)

Hollenhorst PlaqueHollenhorst Plaque

Retina and Vitreous, Basic and Clinical Science Course, AAO 1996

Cotton-wool SpotCotton-wool Spot

Retina and Vitreous, Basic and Clinical Science Course, AAO 1996

PathophysiologyPathophysiology

Atheromatous degeneration and stenosis of the Atheromatous degeneration and stenosis of the cervical carotid arteriescervical carotid arteries Estimated 27% - 67% w/ amaurosis or retinal strokes Estimated 27% - 67% w/ amaurosis or retinal strokes

Retinal emboliRetinal emboliCholesterol crystalsCholesterol crystalsPlatelet aggregatesPlatelet aggregatesFibrin and blood cellsFibrin and blood cellsNeutral fatNeutral fat

VasospasmVasospasm

Primary thrombosis of retinal arteries does not occurPrimary thrombosis of retinal arteries does not occur

PathophysiologyPathophysiology

Microemboli occludes retinal vessels, then Microemboli occludes retinal vessels, then fragment and pass into retinal peripheryfragment and pass into retinal periphery

If disaggregation with reconstitution of If disaggregation with reconstitution of blood flow does not occur, ischemic blood flow does not occur, ischemic damage to the inner retinal layers may be damage to the inner retinal layers may be irreversible irreversible

Branch Retinal Artery Branch Retinal Artery OcclusionOcclusion

Retina and Vitreous, Basic and Clinical Science Course, AAO 1996

Evaluation: Evaluation: Transient Monocular BlindnessTransient Monocular Blindness

Consider disorders with greatest morbidity and Consider disorders with greatest morbidity and most common disordersmost common disorders Consider age, stereotypy of eventsConsider age, stereotypy of events

Physical exam Physical exam (blood pressure, carotid/cardiac exam)(blood pressure, carotid/cardiac exam) Ophthalmologic ExamOphthalmologic Exam

Visual acuity, visual fields, relative afferent pupil defectVisual acuity, visual fields, relative afferent pupil defect dilated fundus exam (emboli, anomalous discs)dilated fundus exam (emboli, anomalous discs) Visual fieldsVisual fields

Electroretinogram – diminished B-wave Electroretinogram – diminished B-wave amplitudeamplitude

Evaluation: Evaluation: Transient Monocular BlindnessTransient Monocular Blindness

Under age 40Under age 40

Migraine history, familyMigraine history, family Echocardiogram w/ Echocardiogram w/

bubblebubble CBC, ESR, ANA, CBC, ESR, ANA,

antiphospholipid antiphospholipid antibodiesantibodies

stop birth control pill stop birth control pill stop smokingstop smoking

Over age 40Over age 40

History for giant cell arteritis, History for giant cell arteritis, polymyalgia, coronary artery polymyalgia, coronary artery disease, stroke & risk disease, stroke & risk factorsfactors

ESR, Creactive Protein if older ESR, Creactive Protein if older than 50)than 50)

Carotid DopplerCarotid Doppler Echocardiogram w/ bubbleEchocardiogram w/ bubble MRA , CT angiographyMRA , CT angiography Fluorescein angiogramFluorescein angiogram Carotid angiography Carotid angiography

Cerebrovascular diseaseCerebrovascular disease

A spectrum of signs, symptoms, A spectrum of signs, symptoms, and stroke risksand stroke risks

Asymptomatic Asymptomatic w/ signsof atheroscleroticCerebrovascular disease

Symptomatic AtheroscleroticCerebrovasculardisease

Low risk High risk

Amaurosis FugaxAmaurosis Fugax and Stroke Risk and Stroke Risk

Isn’t if funny that I went blind Isn’t if funny that I went blind

in the wrong eye”in the wrong eye”

CM Fisher. Transient monocular blindness associated with CM Fisher. Transient monocular blindness associated with hemiplegia. hemiplegia. Archives OphthalmologyArchives Ophthalmology, 1952. , 1952.

What is the relationship of AF and the other What is the relationship of AF and the other ocular ischemic syndromes to the ocular ischemic syndromes to the

carotid arteries? carotid arteries?

Amaurosis Fugax (AF)Amaurosis Fugax (AF) & Stroke Risk & Stroke Risk

Early studies and reports uncontrolled Early studies and reports uncontrolled Different populationsDifferent populations Causes aggregatedCauses aggregated

Best studied ocular ischemic syndromeBest studied ocular ischemic syndrome Prognosis following AF considered more Prognosis following AF considered more

favorable than TIA, unless severe stenosisfavorable than TIA, unless severe stenosis Prognosis altered by carotid endarterectomy?Prognosis altered by carotid endarterectomy? Stroke risk estimated 2-4% prior to NASCETStroke risk estimated 2-4% prior to NASCET

Carotid Endarterectomy (CEA):Carotid Endarterectomy (CEA):Historical PerspectiveHistorical Perspective

1954: CEA introduced1954: CEA introduced1959-70: Joint Study of 1959-70: Joint Study of

Extracranial Arterial OcclusionExtracranial Arterial Occlusionsurgery: 32% stroke risk surgery: 32% stroke risk medical: 39% stroke riskmedical: 39% stroke riskoperative M&M of 11.4% operative M&M of 11.4% CEA benefit if 3% morbidity CEA benefit if 3% morbidity

1970: 15,000 operations/yr1970: 15,000 operations/yr1980s: 100,000 operations/yr 1980s: 100,000 operations/yr

Practical Neurology, Vol 4, 2005.

NASCET NASCET 1987-1996 1987-1996

North American Symptomatic Carotid North American Symptomatic Carotid Endarterectomy Trial Endarterectomy Trial (NASCET)(NASCET)

2885 patients enrolled ; TIA/stroke 120 days2885 patients enrolled ; TIA/stroke 120 days 1583 patients(54.9%) -- TIA1583 patients(54.9%) -- TIA 1302 patients (45%) – nondisabling stroke1302 patients (45%) – nondisabling stroke

carotid stenosis; angio confirmedcarotid stenosis; angio confirmed moderate (30-69%) ; severe (70-99%)moderate (30-69%) ; severe (70-99%)

Established CEA over medical RX in patients Established CEA over medical RX in patients with high grade stenosis (>70%)with high grade stenosis (>70%)

NASCET NASCET

MedicalMedical Surgical Surgical AbsoluteAbsolute

DifferenceDifference

Rel Risk Rel Risk Reduction NNTReduction NNT

70-99%70-99% 26.0%26.0% 9.0%9.0% 17%17% 65% 65% 88

50-70%50-70% 22%22% 16%16% 6%6% 39% 1539% 15

Cumulative risk for ipsilateral stroke in symptomatic Carotid Endarterectomy trials at 2 years

< 50% , CEA not better than ASA (aspirin)

NASCET:NASCET:Amaurosis & Stroke RiskAmaurosis & Stroke Risk

The Risk of Stroke in Patients With First-Ever The Risk of Stroke in Patients With First-Ever Retinal vs Hemispheric Transient Ischemic Retinal vs Hemispheric Transient Ischemic Attacks and High-grade Carotid Stenosis. Attacks and High-grade Carotid Stenosis. Archives of NeurologyArchives of Neurology. 1995.. 1995.

Prognosis after Transient Monocular Blindness Prognosis after Transient Monocular Blindness Associated with Carotid-Artery Stenosis. Associated with Carotid-Artery Stenosis. NEJMNEJM. . 2001 2001

NASCET Medical SubgroupNASCET Medical Subgroup: : High grade stenosisHigh grade stenosis

129 patients with first TIA 129 patients with first TIA 59 retinal TIAs (RTIAs)59 retinal TIAs (RTIAs)70 with hemispheric TIAs (HTIAs)70 with hemispheric TIAs (HTIAs)

Characterize the features and course of Characterize the features and course of subgroups with high grade stenosissubgroups with high grade stenosis

Compare outcomes with RTIAs to HTIAsCompare outcomes with RTIAs to HTIAsAverage follow-up: 19monthsAverage follow-up: 19months

Arch Neurol. 1995; 52

NASCET Medical SubgroupNASCET Medical Subgroup::High Grade Stenosis High Grade Stenosis

HTIAs: older, higher risk factorsHTIAs: older, higher risk factorsRTIAs: higher risk for smokingRTIAs: higher risk for smokingLonger delay for medical treatment for Longer delay for medical treatment for

RTIAs (48 days vs 15.2 days )RTIAs (48 days vs 15.2 days )Estimates for stroke risk at 2 yearsEstimates for stroke risk at 2 years

RTIAs 16.6% +/- 5.5%RTIAs 16.6% +/- 5.5%HTIAs 43.5% +/- 6.7%HTIAs 43.5% +/- 6.7%

Arch Neurol. 1995; 52

NASCET Medical Subgroup: NASCET Medical Subgroup: Risk Factors w/ High Grade StenosisRisk Factors w/ High Grade Stenosis

RTIA (n=59)RTIA (n=59) HTIA (n=70)HTIA (n=70)Mean ageMean age 61.561.5 66.966.9

Male genderMale gender 59%59% 70%70%

hypertensionhypertension 59.3%59.3% 64.3%64.3%

diabetesdiabetes 17%17% 21%21%

heart attackheart attack 6.8%6.8% 18.6%18.6%

AnginaAngina 27.1%27.1% 40%40%

ClaudicationClaudication 13.6%13.6% 15.7%15.7%

HyperlipidemiaHyperlipidemia 30.5%30.5% 40.0%40.0%

Smoking (5yrs)Smoking (5yrs) 61%61% 51.4%51.4%

Antiplatelet RxAntiplatelet Rx 20.3% 20.3% (delayed, 48d)(delayed, 48d) 25.7% (15 d)25.7% (15 d)

NASCET Medical Subgroup:NASCET Medical Subgroup: Outcomes w/ High Grade StenosisOutcomes w/ High Grade Stenosis

RTIA (n=59)RTIA (n=59) HTIA (n=70)HTIA (n=70)

Ipsilateral stroke, minorIpsilateral stroke, minor 77 1717

majormajor 00 88

retinalretinal 11 22

Contralateral strokeContralateral stroke 00 00

retinal stroke retinal stroke

00 11

Vascular deathVascular death 00 22

MIMI 11 22Arch Neurol. 1995; 52

NASCET Surgical Subgroup: NASCET Surgical Subgroup: OutcomesOutcomes

328 surgically treated patients328 surgically treated patients5.8% perioperative stroke 5.8% perioperative stroke 9% 2 year stroke rate9% 2 year stroke rate

54 surgical treated patients with RTIA54 surgical treated patients with RTIA2 minor perioperative strokes (4%)2 minor perioperative strokes (4%)One stroke (2%) 17 months post-opOne stroke (2%) 17 months post-op6.8% stroke risk at 2 years6.8% stroke risk at 2 years

NASCET:NASCET:Amaurosis & Stroke RiskAmaurosis & Stroke Risk

The Risk of Stroke in Patients With First-Ever The Risk of Stroke in Patients With First-Ever Retinal vs Hemispheric Transient Ischemic Retinal vs Hemispheric Transient Ischemic Attacks and High-grade Carotid Stenosis. Attacks and High-grade Carotid Stenosis. Archives of NeurologyArchives of Neurology. 1995.. 1995.

Prognosis after Transient Monocular Prognosis after Transient Monocular Blindness Associated with Carotid-Artery Blindness Associated with Carotid-Artery Stenosis. Stenosis. NEJMNEJM. 2001. 2001

NASCET Subgroups:NASCET Subgroups:Prognosis of TMB (transient Prognosis of TMB (transient

monocular blindness) monocular blindness) Compared 397 patients with Compared 397 patients with isolated TMBisolated TMB

(medical and surgical subgroups) to 829 (medical and surgical subgroups) to 829 patients with hemispheric TIAspatients with hemispheric TIAs

Compared stroke risk for TMB and HTIAs in Compared stroke risk for TMB and HTIAs in patients with patients with high grade stenosis with and high grade stenosis with and without collateralswithout collaterals

Identified Identified risk factorsrisk factors for ipsilateral stroke in for ipsilateral stroke in patients with patients with carotid stenosis > 50%carotid stenosis > 50%

NASCET Subgroups:NASCET Subgroups:Prognosis of TMBPrognosis of TMB

HTIAs: older, higher risk factorsHTIAs: older, higher risk factors TMB: higher risk for smoking, increased high TMB: higher risk for smoking, increased high

grade stenosis, higher incidence of collateralsgrade stenosis, higher incidence of collaterals Medically treated TMB had 3 year ipsilateral Medically treated TMB had 3 year ipsilateral

stroke risk approx ½ HTIAstroke risk approx ½ HTIA Surgically treated TMB showed 30-day stroke Surgically treated TMB showed 30-day stroke

rate ½ of HTIA (3.6% vs 7.4%)rate ½ of HTIA (3.6% vs 7.4%) Stroke risk increased with degree of carotid Stroke risk increased with degree of carotid

stenosis and specific stroke risk factorsstenosis and specific stroke risk factors

NASCET Med/Surg SubgroupsNASCET Med/Surg Subgroups::Isolated TMB vs TIAIsolated TMB vs TIA

ICA stenosisICA stenosis TMBTMB

(N=397) (N=397)

Hemispheric TIAHemispheric TIA

(N=829) (N=829)

< 50%< 50% 28.5%28.5% 50%50%

50-69% 50-69%

30.5%30.5% 29.8% 29.8%

70-94%70-94% 31.7%31.7% 16%16%

Near occlusionNear occlusion 9.3%9.3% 3.7%3.7%NEJM. Vol 345,2001

NASCET Med/Surg SubgroupsNASCET Med/Surg Subgroups::Isolated TMB vs TIAIsolated TMB vs TIA

TMBTMB

(N=397) (N=397)

Hemispheric Hemispheric TIATIA (N=829) (N=829)

Collateral Collateral Circulation *Circulation *

24.2%24.2% 6.9%6.9%

*Collateral circulation = filling of the ACA, PComA, or ophthalmic artery

NEJM. Vol 345,2001

NASCET Med/Surg SubgroupsNASCET Med/Surg Subgroups::Three year stroke risk Three year stroke risk

NASCET Medical SubgroupsNASCET Medical Subgroups::Collaterals & 3 year stroke riskCollaterals & 3 year stroke risk

TMB w/ collaterals (N=25) 2.9%TMB w/ collaterals (N=25) 2.9%HTIAs w/ collaterals (N=30) 16.7%HTIAs w/ collaterals (N=30) 16.7%

TMB w/o collaterals (N=44) 16.0%TMB w/o collaterals (N=44) 16.0%HTIAs w/o collaterals (N=69) 44.4%HTIAs w/o collaterals (N=69) 44.4%

NEJM. Vol 345,2001

NASCET Med/surg SubgroupNASCET Med/surg Subgroup: : Isolated TMB (N=397)Isolated TMB (N=397)

Median # of TMB episodes: 3 (1-7)Median # of TMB episodes: 3 (1-7)5% had >45 episodes5% had >45 episodes

Median duration : 4 minutes (1-10min)Median duration : 4 minutes (1-10min)5% had episode > 60min5% had episode > 60min

No correlation to carotid stenosisNo correlation to carotid stenosis3 year stroke risk (N= 198, medical) 3 year stroke risk (N= 198, medical)

1 episode -- 10.4 %1 episode -- 10.4 % >2 episodes-- 8.2 %>2 episodes-- 8.2 %

NEJM. Vol 345,2001

NASCET Medical SubgroupNASCET Medical Subgroup: : Stroke Risk FactorsStroke Risk Factors

TMB with > 50% stenosisTMB with > 50% stenosisAge > 75Age > 75Male sexMale sexh/o hemispheric TIA or strokeh/o hemispheric TIA or strokeh/o intermittent claudicationh/o intermittent claudication Ipsilateral stenosis 80-94%Ipsilateral stenosis 80-94%No collaterals on angiographyNo collaterals on angiography

NEJM. Vol 345,2001

Amaurosis Fugax & Stroke Risk:Amaurosis Fugax & Stroke Risk:NASCET findingsNASCET findings

TMB has high stroke risk if high grade TMB has high stroke risk if high grade carotid stenosis, though less than HTIAscarotid stenosis, though less than HTIAs

Higher collaterals improve prognosisHigher collaterals improve prognosisAge, gender, h/o stroke/TIA,& claudication Age, gender, h/o stroke/TIA,& claudication

may alter stroke risk may alter stroke risk CEA reduces stroke risk if surgeon has low CEA reduces stroke risk if surgeon has low

complication ratecomplication ratePerioperative risk for stroke and death was Perioperative risk for stroke and death was

lower in patients with TMBlower in patients with TMB

Spectrum of clinical stroke riskSpectrum of clinical stroke risk

Amaurosis Fugax (2% -?6%)

TIA(3.7%)

Minor Stroke (6.1%)

Major Stroke (9%)

Low risk High risk

Estimated Annual Stroke Rates

Asymptomatic Stenosis (2%)

AsymptomaticBruit (2%)

AION

BRAO

Asymptomatic retinal emboli Acute & Chronic Ocular

Ischemic Syndrome

ConclusionsConclusions

Amaurosis Fugax is caused by ischemia to the Amaurosis Fugax is caused by ischemia to the retina, often associated with carotid stenosis, retina, often associated with carotid stenosis, and is a risk factor for strokeand is a risk factor for stroke

Prognosis is better for patients with amaurosis Prognosis is better for patients with amaurosis fugax treated both medically and surgically fugax treated both medically and surgically compared to patients with hemispheric TIAs. compared to patients with hemispheric TIAs.

Amaurosis Fugax should be recognized, with Amaurosis Fugax should be recognized, with strong consideration for carotid endarterectomy strong consideration for carotid endarterectomy with high grade carotid stenosis, vascular risk with high grade carotid stenosis, vascular risk factors present, and low complication rate of factors present, and low complication rate of procedure in your center procedure in your center

ReferencesReferences Benavente, et al. Prognosis after Transient Benavente, et al. Prognosis after Transient

Monocular Blindness Associated with Carotid Monocular Blindness Associated with Carotid Artery Stenosis. Artery Stenosis. NEJMNEJM, Vol 345(15), 2001., Vol 345(15), 2001.

Easton and Wilterdink. Carotid Endarterectomy: Easton and Wilterdink. Carotid Endarterectomy: Trials and Tribulations. Trials and Tribulations. Ann NeurologyAnn Neurology. Vol . Vol 35.1994. 35.1994.

Glaser.Glaser. Neuro-ophthalmology. Neuro-ophthalmology. 33rdrd ed. 1999 ed. 1999 Mizener, et al. Ocular Ischemic Syndrome. Mizener, et al. Ocular Ischemic Syndrome.

OphthalmologyOphthalmology, Vol 104, 1997. , Vol 104, 1997. Rizzo. Neuroophthalmologic Disease of the Rizzo. Neuroophthalmologic Disease of the

Retina. Retina. Neuro-ophthalmology.Neuro-ophthalmology.

References References Sacco et al. Guidelines for Prevention of Stroke Sacco et al. Guidelines for Prevention of Stroke

in patients with ischemic stroke or transient in patients with ischemic stroke or transient ischemic attack. ischemic attack. StrokeStroke. Feb 2006. . Feb 2006.

Streifler, et al. The Risk of Stroke in Patients Streifler, et al. The Risk of Stroke in Patients with First-Ever Retinal vs Hemispheric Transient with First-Ever Retinal vs Hemispheric Transient Ischemic Attacks and High-grade Carotid Ischemic Attacks and High-grade Carotid Stenosis. Stenosis. Archives of Neurology, Archives of Neurology, Vol 52(3), Vol 52(3), 1995.1995.

Wilterdink and Easton. Vascular event rates in Wilterdink and Easton. Vascular event rates in patients with atherosclerotic cerebrovascular patients with atherosclerotic cerebrovascular disease. disease. Arch NeurologyArch Neurology. Vol 49. 1992. Vol 49. 1992


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