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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, hypertension, PMH- coronary artery disease, hypertension, hyperlipidemiahyperlipidemia
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 partial or complete, related to retinal arterial microembolization or hypoperfusionarterial microembolization 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 AbsoluteAbsoluteDifferenceDifference
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 HTIAs Average 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 66.966.9Male 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 22Contralateral strokeContralateral stroke 00 00 retinal stroke retinal stroke
00 11
Vascular deathVascular death 00 22MIMI 11 22
Arch 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