Neuro-Ophthalmology: Case After Case Neuro-Ophthalmology .

Neuro-Ophthalmology: Case After Case Neuro-Ophthalmology: Case After Case Nancy J. Newman, MDValérie Biousse, MDEmory University School of Medicine, Atlanta, GANancy J. Newman, MDValérie Biousse, MDEmory University School of Medicine, Atlanta, GA Disclosures:––––Consultant for Gensight, Santhera and StealthResearch support: Gensight, Santhera and NIHData Safety Committee: Quark NAION clinical trialMost illustrations are from Neuro-Ophthalmology Illustrated, Thieme 2019.3rd edition1219 yo woman with visual loss19 yo woman with visual loss Past medical history: Obese Meds: None No tobacco, no alcohol Past 2 weeks:– severe headaches– Rapidly progressive visual loss OU– Diplopia Family history: Unremarkable34Extraocular Movements:Abduction deficit / EsotropiaExaminationVisual acuityColor visionSLE/IOPPupilsLids5Right eyeLeft eye20/3013/14NormalNo RAPDNormal20/2014/14NormalNo RAPDNormal61

Visual field testing Blood pressure 118/66What next?78She needs Send her to Emergency Department In hospital with:– Neurology– Neurosurgery– Neuroradiology– Available 24/7– And Neuro-ophthalmologistNeurologic examinationGeneral examinationBlood pressureBrain MRI with GadoliniumBrain MRV with GadoliniumLumbar puncture if imaging normal Immediately9 Warn Neuro-Ophthalmologist and ED10EvaluationFulminant Idiopathic Intracranial Hypertension Normal neurologic examinationBlood pressure: 122/72Brain MRI with Gadolinium: NormalBrain MRV: Normal (signs of raised ICP)Lumbar puncture:– Opening pressure: 63 cm H2O– Normal CSF contents No anemia, no sleep apnea, no medications11 Acetazolamide 500 mg bid Dramatic improvement of headaches and diplopiaafter lumbar puncture Consult Neurosurgery122

Fulminant Idiopathic Intracranial HypertensionExamination 1 week later 12 hours later: recurrence of headaches and diplopiaVAColor visionSLE/IOPPupilsEOMs– VA: 20/400 right eye, 20/50 left eye– Lumbar drain Lumbo-peritoneal shunt next day13141516Right eyeLeft eye20/5014/14NormalNo RAPDFull20/4014/14NormalNo RAPDFullBilateral Disc Edema (headache)Idiopathic Intracranial HypertensionBrain imaging (contrast)(Normal CT MRI/MRV)-Hydrocephalus-Mass-Venous thrombosisNl CSF OPNl CSFNo RaisedICPPseudo DE17 NormalHeadachesPapilledema Diplopia (VIth) TinnitusMRI rules out intracranial process andvenous thrombosisLumbar puncture confirms high CSF OPand normal CSF contents LPPressure 25cmH2ONl CSFIsolated intracranial hypertensionAbnl CSF -Meningitis-Spinal cordAlwaysreconsider cerebral“Idiopathic”tumorvenous thrombosisintracranialhypertension (IIH) 183

Idiopathic Intracranial HypertensionIdiopathic Intracranial HypertensionEvaluationManagement Severity of headaches Diplopia Visual function Prognosis Rapid onset Patient’s characteristics Severe obesity, black race, male gender Anemia / sleep apnea syndrome / HTN Visualfunction Visual acuity, color vision Visual field (automated perimetry, Goldmannperimetry)1920Raised ICP and PapilledemaVisual Field Testing21Raised ICP and PapilledemaVisual Field Testing22Raised ICP and PapilledemaVisual Field Testing23244

Idiopathic Intracranial HypertensionIdiopathic Intracranial HypertensionFollowup/Treatment (1-2 weeks)Management Follow-up/Treatment Lumbar puncture(1st treatment) CorrectTreatment efficacyVisual function (visual field)Improvementprecipitation factors Drug, anemia, sleep apnea, Followup (1-2 mo) Weightloss (long term) Acetazolamide (1-3 grams/day)Followup (3 mos)Followup (6 mos)25No improvementWorsening-Repeat LP/drain-Surgery ?-Venous stenting?26Optic Neuritis:Is It or Isn’t It ?A 39 y/o man with visual loss right eyePast Medical History: hypertension, cigsNancy J. Newman, M.D.Medications: atenololEmory University School of MedicineAtlanta GA27Family History: Unremarkable28Examination:5 weeks ago:- progressive, painless visual loss ODover 4-5 daysVision:Color:Orbits:SLE:IOPs:Pupils:No previous visual loss or neurologicsymptomsNo rmalNormal1414Pharmacologically Dilated305

3132Optic NeuritisIs It Optic Neuritis?Typical Idiopathic Macular disease A different cause of optic neuropathy33 34Optic NeuritisMimickersSexPainFieldPupilFundus Macular disease35Inflammation of the optic nerveF:M 3:1Age: 15-45Pain on eye movementNormal or swollen discSpontaneous improvementAssociated with multiple sclerosisOptic NeuritisFemaleYesCentralRAPDNerve nl/edemaCSRMaleNoCentralNo RAPDBlister366

SexPainFieldPupilFundusOptic NeuritisFemaleYesCentralRAPDNerve nl/edemaCSRMaleNoCentralNo alNo RAPDBlister38Optic NeuropathyIs It Optic Neuritis?Causes Inflammatory Vascular Compressive/Infiltrative Hereditary Toxic/Nutritional Traumatic Elevated intracranial pressure Elevated intraocular pressure A different cause of optic neuropathy3940Optic NeuritisOptic NeuritisMimickersDDx Inflammatory Vascular Compressive/Infiltrative Hereditary Toxic/Nutritional Traumatic Elevated intracranial pressure Elevated intraocular pressure41Optic NeuritisFemaleYesCentralRAPDNerve nl/edema Anterior ischemic optic neuropathyCompressive optic neuropathyLeber hereditary optic neuropathyOther inflammatory/infectious optic neuritis427

Optic ltitudinalNerve nl/edema Nerve edemaNerve enhancesNerve nlImprovesNo changeSexAgePainFieldFundusMRICourse4344Optic Neuritis Leber HONMaleNoCentralYesSevere lossNerve nlPseudoedemaOp rseImprovesMRINerve enhancesFundusNerve nl/edema45NAIONCompressiveLeber HONAgeYoungerOlderAnyYoungerGenderF MM FM FM FFam HxNo or MSNoNoYesBilateral? 10% at 1yr 10% at 1yrNo100% at 1yrOnsetRapidSlowSubacutePain? (w EOM) RareNoNoColorPoorRapidOften spared PoorPoorVisual Field CentralAltitudinalCentral/tempCecocentralOptic Nerve N /edemaEdemaNl/edemaNl/pseudoMRIAbnl ONNormalTumorNormalPrognosisGoodPoorPoor (if no Rx) PoorSystemicMSHTN/DMNoneNone46Op Neuritis47Optic Neuritis al/TemporalNerve nl/edema Nerve nl/edemaNerve enhances Nerve rseNAIONCompressiveYoungerOlderAnyYoungerGenderF MM FM FM FFam HxNo or MSNoNoYesBilateral? 10% at 1yr 10% at 1yrNo100% at 1yrOnsetRapidSlowSubacutePain? (w EOM) RareNoNoColorPoorRapidOptic NeuritisLeber HONAgeOften spared PoorPoorVisual Field CentralAltitudinalCentral/tempCecocentralOptic Nerve N /edemaEdemaNl/edemaNl/pseudoMRIAbnl ONNormalTumorNormalPrognosisGoodPoorPoor (if no Rx) PoorSystemicMSHTN/DMNoneTypical Idiopathic NoneInflammation of the optic nerveF:M 3:1Age: 15-45Pain on eye movementNormal or swollen discSpontaneous improvementAssociated with multiple sclerosis488

Atypical Optic Neuritis BilateralIntra-ocular cellsDisc swellingHemorrhagesExudates (“star”) ypical Optic Neuritis AQP4 (NMO) Abs MOG Abs50A 39 y/o man with painless visual loss OD to20/200 over 5 days, past history of HTN,no family history of visual loss, and noimprovement over the past 5 weeks.A 39 y/o man with painless visual loss OD to20/200 over 5 days, past history of HTN,no family history of visual loss, and noimprovement over the past 5 weeks. Normal maculaRight RAPDNormal MRI orbits/brain with contrastNo vision recovery OD and no vision lossOS for 1 year51Normal maculaRight RAPDNormal MRI orbits/brain with contrastNo vision recovery OD and no vision lossOS for 1 year52 37-yo woman with visual loss OS Visual loss OS: Central shadow Progression over 5 days Pain with eye movements PMHx: 2 normal pregnancies 2 abortions No associated neurologic or systemicsymptoms Fam Hx: Unremarkable53BilateralSevereNo recoveryRecurrent549

ExaminationExamination BP: 116/74, RR 67 Neurologic examination normal VA Color Orbits Lids IOP SLE Pupils ount FingersNo controlNormalNormal15Normal RAPDFull56Visual FieldsFundus5758Diagnosis ?What next ? Optic neuropathy OS Retrobulbar Inflammatory Refer « Idiopathic optic neuritis »-59-6010

Work-upBrain MRI Negative syphilis testing Normal ACE Negative AQP4/MOG antibodies6162Management-Follow-up: 6 weeks later 3 days IV methylprednisolone (250 mgq6 hours) 10 days oral prednisone (taper)63 /14NormalNormal15Normal RAPDFull64Follow-up: 6 weeks later65VAColorOrbitsLidsIOPSLEPupilsEOMFollow-up: 6 weeks later6611

Patient’s Questions What next ? Are you sure it is an optic neuritis? Is it idiopathic demyelinating opticneuritis? Do I have MS ? What is my risk of MS ? How should I be treated ? Refer-6768HPI51 yo woman with visual loss in left eyePMHx: Breast cancer 11 years prior (lumpectomy, radiation,chemotherapy, neg lymph nodes) Hypertension, borderline diabetes Migraine headaches (no aura) Medications: Hydrochlorothiazide, aspirin 81, vitamins, ibuprofen prnFollowed by neurologist for episodes of tingling of both legsand occasionally left arm shaking Normal brain MRI Scheduled for electromyography Saw optometrist for annual visit: Decreased vision left eye Left optic nerve pallor “Left optic neuritis” 6970Neuro-Ophthalmology 71Neurologist: Cancelled electromyography Repeated brain MRI (normal) Planned LP for possible multiple sclerosis BP: 148/92. BMI 32Visual acuity Color vision Slit lamp IOP Pupils Eye movements Patient: Panicked Refused LP Second opinionRight eye20/2014/14Mild cataracts12NormalFullLeft eye20/403/1413RAPD Full7212

Humphrey Visual FieldsFundus ExaminationLeft eyeRight eye73Right eyeLeft eye74DiagnosisReview MRILeft optic neuropathy (chronic)Incidentally found No pain 7576With contrast777813

MRI Orbits with Contrastand Fat SuppressionMRI Orbits with ContrastLeft Optic Nerve Sheath Meningioma7980 20-yo WM with visual loss in both eyes Age 8: told he had « swelling OU »during routine examination Asymptomatic Observed yearly, without change PMHx Unremarkable Fam Hx: Unremarkable College student – no ETOH or drugs8182 Age 20 (8 months prior seeing us) Sudden, painless visual loss OS MRI brain/orbits: normal CBC, bartonella, toxo, RPR, FTA:normal or negative VA: 20/20 OD; 20/200 OS “Swelling” OS838414

3 months later: Repeat MRI: normal « More blood tests » : all normal Lumbar puncture: OP: 16 cm CSF contents: normal Visual loss OD VA: 20/100 OD; CF OS8586Examination 2 months later VA Col Vis Orbit Lid IOP SLE Pupils EOMODOSCFNo controlNormalNormal14NormalNormalFullCFNo controlNormalNormal15Normal1.2 RAPDFull87Goldmann Visual Fields-88FundusWork-up Leber’s hereditary optic neuropathy: 3 primary mutations: mt DNA 11778 mt DNA 14484 mt DNA 3460 Negative-899015

Leber’s Hereditary Optic NeuropathyWork-up Blood sent to lab with expertise in LHON Complete sequencing of mtDNA 10 mutations found Including, novel mtDNA mutation atnp 12848 (heteroplasmic) Alters complex 1 Subacute sequential bilateral central visual lossAge of onset typically 18-30 (range 1-87)Male predominance (80-90%)Progression in each eye over weeks to monthsRecognized interval between eyes in 50%(days to months) 97% bilateral within 1 year-9192Leber’s Hereditary Optic Neuropathy Acuity usually worse than 20/200 Color vision affected early Central or cecocentral defects9394 95Leber’s Hereditary Optic NeuropathyLeber’s Hereditary Optic NeuropathySpontaneous RecoveryAssociated FindingsMay occur years later4% - 71%Depends on the mtDNA mutationMore likely if visual loss before age 20 (esp 10) Cardiac conduction defectsMinor neurologic abnormalitiesMultiple sclerosis-like illnessMore severe neurologic syndromes9616