Neuro-Ophthalmology and Multiple Sclerosis

The Neuro-Ophthalmology The Neuro-Ophthalmology of Multiple Sclerosisof Multiple Sclerosis

Charles Maxner MD, FRCPCCharles Maxner MD, FRCPCProfessor, Departments of Medicine (Neurology) and OphthalmologyProfessor, Departments of Medicine (Neurology) and Ophthalmology

Dalhousie UniversityDalhousie UniversityConsultant, Dalhousie MS Research Unit Consultant, Dalhousie MS Research Unit

Halifax , N.S.Halifax , N.S.

Dr. C.E. Maxner: DisclosureDr. C.E. Maxner: DisclosureDr. Maxner has attended and conductedDr. Maxner has attended and conductededucational events and participated in MSeducational events and participated in MSresearch studies affiliated with the followingresearch studies affiliated with the followingfirms:firms:

Berlex Berlex Biogen IdecBiogen IdecSerono Serono TevaTeva

The Visual SystemThe Visual Systemand MSand MS

Objectives:Objectives:

Briefly review MS as a disorder Briefly review MS as a disorder Review how it affects:Review how it affects: The Afferent Visual SystemThe Afferent Visual System The Efferent Visual SystemThe Efferent Visual System

MS: Historical PerspectiveMS: Historical Perspective

Augustus d’Esté (1794-1848)

Grandson King George III

Carswell ~1836

J.M. Charcot (1825-1893)(1868 leçons: ”sclérose en plaques disseminées” from Vulpian)

Multiple SclerosisMultiple Sclerosis

Disorder of Central Myelin (Oligodendroglia)Disorder of Central Myelin (Oligodendroglia)Brain and Spinal CordBrain and Spinal CordImmune BasedImmune BasedInflammatory demyelinating disorderInflammatory demyelinating disorderAxonal injury (Disability)Axonal injury (Disability)

Demyelination Axonal Loss

Inflammation

Multiple Sclerosis:Multiple Sclerosis:3 Components3 Components

Courtesy Dr. G. Rice

Multiple Sclerosis Multiple Sclerosis PathologyPathology

Gross Pathology

Luxol Fast Blue

Multiple Sclerosis Multiple Sclerosis PathologyPathology

Optic Nerves

Chiasm

Optic Tract

Anterior Visual Pathway

Luxol Fast Blue

Action Potential Transit in MS

1. Delayed Conduction

2. Conduction Block

Concepts

Courtesy Dr. A.Bar-Or

Natural Progression of MSNatural Progression of MS

Level of disability

Accumulated MRI lesion burden

Gadolinium enhancement Cognitive dysfunction

Brain atrophyRelapses

SubclinicalMono-

symptomatic Relapsing-Remitting Secondary Progressive

Relapsing Forms

Time

Clin

ical

Wor

seni

ng

Initial demyelinating

eventClinically

definite MS Relapse

Courtesy Dr. G. Rice

MRI Dissemination in MRI Dissemination in Space and TimeSpace and Time

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Presenting Symptoms of MSPresenting Symptoms of MS

SymptomSymptom Approximate PrevalenceApproximate Prevalence

Weakness in one or more Weakness in one or more limbslimbs 40-50%40-50%

Sensory loss/paresthesiasSensory loss/paresthesias 40-45%40-45%Visual lossVisual loss 16-36%16-36%Gait disturbance/ataxiaGait disturbance/ataxia 5-15%5-15%DiplopiaDiplopia 7-15%7-15%Dizziness/vertigoDizziness/vertigo 5%5%PainPain 3%3%Sensory in faceSensory in face 3%3%

Neuro-ophthalmological Neuro-ophthalmological IssuesIssues

Loss of Vision Loss of Vision (Monocular and Binocular)(Monocular and Binocular)

DiplopiaDiplopiaOscillopsiaOscillopsia

MS and the Visual SystemMS and the Visual System

Afferent Visual SystemAfferent Visual SystemVision loss and distortionVision loss and distortion

Efferent Visual SystemEfferent Visual SystemDiplopia and OscillopsiaDiplopia and Oscillopsia

MS and The Afferent MS and The Afferent Visual SystemVisual SystemPre-chiasmalPre-chiasmalOptic NerveOptic Nerve

ChiasmalChiasmalBitemporal VF defect rareBitemporal VF defect rareJunctional Scotoma defect not uncommonJunctional Scotoma defect not uncommon

Post-ChiasmalPost-ChiasmalOptic tractOptic tractGeniculocalcarine pathwayGeniculocalcarine pathway

Case: Ms. H.B. 35 YOWFCase: Ms. H.B. 35 YOWF

MS diagnosed 12 years priorMS diagnosed 12 years priorCopaxone TherapyCopaxone TherapyDecreased vision left eyeDecreased vision left eyeProgressed over 48 hoursProgressed over 48 hoursPain on eye movementPain on eye movementImpaired depth perceptionImpaired depth perception““Can’t drive”Can’t drive”

Case: Ms. H.B. 35 YOWFCase: Ms. H.B. 35 YOWF ExaminationExamination

Va 6/6 Right, HM LeftVa 6/6 Right, HM LeftCentral scotoma left eyeCentral scotoma left eyeRAPD 1.5 log units left eyeRAPD 1.5 log units left eyeImpaired colour perception leftImpaired colour perception leftOcular motility normalOcular motility normalLeft disc slightly swollen and hyperemicLeft disc slightly swollen and hyperemic

Pupil Testing

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Goldmann Visual FieldsGoldmann Visual Fields


Va 6/6 Right, 6/9 LeftVa 6/6 Right, 6/9 LeftCentral blur left eyeCentral blur left eyeRAPD 0.6 left eyeRAPD 0.6 left eyeColour improvedColour improvedTemporal pallor left discTemporal pallor left disc

Follow Up: 3 months laterFollow Up: 3 months later

Optic NeuritisOptic NeuritisCommon SymptomsCommon Symptoms

MonocularMonocularCentral Vision lossCentral Vision lossPain (eye movement)Pain (eye movement)Altered colour visionAltered colour vision

Recovery commonRecovery commonUhthoff’s symptomUhthoff’s symptomFlashesFlashesPulfrich phenomenonPulfrich phenomenon

Uhthoff’s SymptomUhthoff’s Symptom

Uhthoff described 3 patients in whom Uhthoff described 3 patients in whom exertion and fatigue caused a desaturation exertion and fatigue caused a desaturation in colour visionin colour vision

Patient XVIII had decreased acuity after Patient XVIII had decreased acuity after walking around the roomwalking around the room

What did he describe?

Who was Uhthoff?

Uhthoff’s SymptomUhthoff’s SymptomWilhelm Uhthoff (1853-1927)Wilhelm Uhthoff (1853-1927)Born Warin , GermanyBorn Warin , GermanyStudied in Tübingen, Göttingen, BerlinStudied in Tübingen, Göttingen, BerlinConsultant at Westphal’s Clinic (With Oppenheim, Consultant at Westphal’s Clinic (With Oppenheim,

Wallenberg, Thomsen, Möbius)Wallenberg, Thomsen, Möbius)Named Professor of Ophthalmology at Breslau 1896Named Professor of Ophthalmology at Breslau 1896Eye Symptoms in Diseases of the Nervous System Eye Symptoms in Diseases of the Nervous System

(Published 1915)(Published 1915)Described by Bielschowsky as the “true originator” Described by Bielschowsky as the “true originator”

of clinical neuro-ophthalmologyof clinical neuro-ophthalmology

Wilhelm UhthoffWilhelm Uhthoff

Uhthoff’s SymptomUhthoff’s Symptom

Uhthoff’s symptom in optic Uhthoff’s symptom in optic neuritis:relationship to MRI and neuritis:relationship to MRI and development of MS.development of MS. (Scholl GB, Song HS, (Scholl GB, Song HS, Wray SH) Ann Neurol 1991; 30(2):180-4Wray SH) Ann Neurol 1991; 30(2):180-4

Uhthoff and his Symptom Uhthoff and his Symptom (Selhorst JB, (Selhorst JB, Saul RF) Journal of Neuro-ophthalmology Saul RF) Journal of Neuro-ophthalmology 1995; 15(2):63-91995; 15(2):63-9

FlashesFlashesMovement phosphenes in optic Movement phosphenes in optic neuritis: A new clinical signneuritis: A new clinical sign (Davis F, (Davis F, Bergen D, Schauf C, McDonald I, Deutsch W) Bergen D, Schauf C, McDonald I, Deutsch W) Neurology 1976; 26: 1100-1104.Neurology 1976; 26: 1100-1104.

Bright flashes in darkBright flashes in darkEye movementEye movementDifferentiate from Lightning Streaks of MooreDifferentiate from Lightning Streaks of MooreEye equivalent of Lhermittes symptomEye equivalent of Lhermittes symptom

Pulfrich PhenomenonPulfrich Phenomenon

Optic Neuritis: Physical Optic Neuritis: Physical FindingsFindings

Decreased visual acuityDecreased visual acuityVF defect VF defect (Central/Altitudinal 29% )(Central/Altitudinal 29% )

DyschromatopsiaDyschromatopsiaAfferent Pupil Defect Afferent Pupil Defect (RAPD)(RAPD)Optic disc swelling 35%Optic disc swelling 35%

Abnormal Contrast Abnormal Contrast SensitivitySensitivityAbnormal VEPAbnormal VEPAltered Flicker Altered Flicker PerceptionPerceptionAltered depth perceptionAltered depth perceptionOptic disc pallor Optic disc pallor

Optic Neuritis: Optic DiscOptic Neuritis: Optic Disc

Case: Ms. A.B. 23 YOWFCase: Ms. A.B. 23 YOWF

Two months impaired vision both eyesTwo months impaired vision both eyesProgressive courseProgressive courseBlurred centrally right eyeBlurred centrally right eyeHazy to left of fixation both eyesHazy to left of fixation both eyesOccasional migraineOccasional migraine

Case: Ms. A.B. 23 YOWFCase: Ms. A.B. 23 YOWF

Va 6/15 Right, 6/7.5 LeftVa 6/15 Right, 6/7.5 LeftConfrontation VF: Left Central HHConfrontation VF: Left Central HHNo RAPDNo RAPDAO Plates: 7/14 Rt 10/14 LtAO Plates: 7/14 Rt 10/14 LtOcular motility normalOcular motility normalAnomalous discs both eyesAnomalous discs both eyes

Case: Ms. A.B. 23 YOWFCase: Ms. A.B. 23 YOWFAutomated PerimetryAutomated Perimetry

Case: Ms. A.B. 23 YOWFCase: Ms. A.B. 23 YOWF MRI ImagingMRI Imaging

Case:Case: Ms. C.S. 41 YOWFMs. C.S. 41 YOWF

2 week hx of L sided visual blurring2 week hx of L sided visual blurringBoth eyes involvedBoth eyes involved15 years ago “poor balance”15 years ago “poor balance”MigrainesMigrainesSister with MSSister with MS

Case: Ms. C.S.Case: Ms. C.S.ExaminationExamination

Va: 6/6 Both EyesVa: 6/6 Both EyesAO Plates: 13/14 Rt, 11/14 LtAO Plates: 13/14 Rt, 11/14 LtPupils normalPupils normalOcular motility normalOcular motility normalFundi normalFundi normalDTR’s brisk, Unsteady RombergDTR’s brisk, Unsteady RombergVF’s abnormalVF’s abnormal

Ms. C.S. Visual FieldsMs. C.S. Visual Fields

Ms. C.S. MRIMs. C.S. MRI

Ms. C.S. MRI (2 mos later)Ms. C.S. MRI (2 mos later)

Optic Neuritis: Optic Neuritis: The DifferentialThe Differential

AION (Ischemic Optic Neuropathy)AION (Ischemic Optic Neuropathy) Vasculitic Disorders (i.e. SLE)Vasculitic Disorders (i.e. SLE) Hereditary (i.e. Leber’s)Hereditary (i.e. Leber’s) Toxic/Nutritional (ETOH)Toxic/Nutritional (ETOH) Infectious (i.e.Bartonella, Lyme)Infectious (i.e.Bartonella, Lyme) Inflammatory (i.e. Sarcoid)Inflammatory (i.e. Sarcoid) Neoplastic/Paraneoplastic (i.e. lymphoma)Neoplastic/Paraneoplastic (i.e. lymphoma) Compressive (i.e.Tumours, Grave’s orbitopathy)Compressive (i.e.Tumours, Grave’s orbitopathy) AmblyopiaAmblyopia

Neuro-ophthalmological Neuro-ophthalmological IssuesIssues

DiplopiaDiplopiaHorizontal, Vertical, MixedHorizontal, Vertical, MixedFluctuatingFluctuating

OscillopsiaOscillopsia

Ocular Motility DisordersOcular Motility DisordersInfranuclear or NerveInfranuclear or NerveSaccadic systemSaccadic systemPursuit systemPursuit systemInternuclear abnormalitiesInternuclear abnormalitiesVestibulo-ocular dysfunctionVestibulo-ocular dysfunctionNystagmusNystagmus

Ocular Motility DisordersOcular Motility Disorders

Nuclear Palsies: RareNuclear Palsies: RareInfranuclear or NerveInfranuclear or Nerve

VI: Most commonVI: Most commonIII: Partial or CompleteIII: Partial or CompleteIV: RareIV: Rare

Ms. H.M. 34 YOWFMs. H.M. 34 YOWF

CC: DiplopiaCC: DiplopiaHx: 6 months progressing diplopiaHx: 6 months progressing diplopiaInitially intermittent, now persistentInitially intermittent, now persistentOtherwise asymptomaticOtherwise asymptomaticSister has MSSister has MSO/E: Incomitant esotropiaO/E: Incomitant esotropiaLeft abduction deficitLeft abduction deficit

Ms. H.M. 34 YOWFMs. H.M. 34 YOWF

Ms. H.M. 34 YOWFMs. H.M. 34 YOWF6 Months Later6 Months Later

Ocular Motility DisordersOcular Motility DisordersSaccadic abnormalitiesSaccadic abnormalitiesHypometricHypometricHypermetricHypermetricDysmetriaDysmetriaSaccadic IntrusionsSaccadic Intrusions

Square wave jerksSquare wave jerksSaccadic pulsesSaccadic pulsesOcular flutterOcular flutter

Saccadic AbnormalitiesSaccadic Abnormalities

From: Leigh & Zee. The Neurology of Eye Movements, F.A. Davis Company

Saccadic OscillationsSaccadic OscillationsSaccadic Dysmetria

Macrosaccadic Oscillations

Square Wave Jerks

Macro Square Wave JerksOcular Flutter



Square Wave Jerks

Ocular Flutter


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Ocular Motility DisordersOcular Motility DisordersPursuit DysfunctionPursuit Dysfunction

Saccadic IntrusionsSaccadic Intrusions

Internuclear OphthalmoplegiaInternuclear OphthalmoplegiaMLF LesionMLF Lesion

Skew DeviationSkew DeviationVertical diplopiaVertical diplopia

Gaze PalsiesGaze PalsiesDorsal Midbrain SyndromeDorsal Midbrain Syndrome

Ocular Motility DisordersOcular Motility DisordersPursuit DysfunctionPursuit DysfunctionSaccadic IntrusionsSaccadic Intrusions



Ocular Motility DisordersOcular Motility DisordersInternuclear Ophthalmoplegia:MLF LesionInternuclear Ophthalmoplegia:MLF Lesion

From: Kline & Bajandas. Neuro-ophthalmology Board Review Manual; Slack Inc

Ms.C.P. 24 YOWFMs.C.P. 24 YOWF

CC: Blurred VisionCC: Blurred VisionHx: Hx: • 2 week history of “dizzy” feeling and 2 week history of “dizzy” feeling and

disorientation with looking downdisorientation with looking down• Difficulty focussing on rapid EOM’sDifficulty focussing on rapid EOM’s• 2003 sensory symptoms in legs and Lhermittes 2003 sensory symptoms in legs and Lhermittes

symptomsymptom

O/E: Abnormal EOM’sO/E: Abnormal EOM’s





T 2 Flair

Internuclear OphthalmoplegiaInternuclear OphthalmoplegiaMRI Detection of MLF LesionsMRI Detection of MLF Lesions Proton density>T2>FlairProton density>T2>Flair Frohman et al Neurology 2001; 57:762-768Frohman et al Neurology 2001; 57:762-768

Proton Density

T2 Flair

Internuclear OphthalmoplegiaInternuclear Ophthalmoplegia

Versional Disconjugacy IndexVersional Disconjugacy Index: Assess adduction : Assess adduction vs abduction saccade peak velocityvs abduction saccade peak velocity

Most accurate method for identification of INO is Most accurate method for identification of INO is quantitative EOM recordingquantitative EOM recording

Clinical detection accuracy vs RecordingClinical detection accuracy vs Recording93% severe INO93% severe INO75% moderate INO75% moderate INO29% mild INO29% mild INOFrohman et al. Neurology 2003;61:848-850Frohman et al. Neurology 2003;61:848-850


Vestibulo-ocular DysfunctionVestibulo-ocular Dysfunction VOR MismatchVOR Mismatch

Failure of VOR SuppressionFailure of VOR Suppression

Vestibulo-Ocular reflex


Vestibulo-Ocular reflex

From: Kline & Bajandas. Neuro-ophthalmology Board Review Manual; Slack Inc

Head Thrust TestHead Thrust TestHalmagyi ManeuverHalmagyi Maneuver

Thrust head 20-30 degrees while fixating targetThrust head 20-30 degrees while fixating targetAbnormal:Abnormal:

Refixation saccadeRefixation saccade

Headshake TestHeadshake Test

Shake head for 20 seconds at 2 hz (horizontal Shake head for 20 seconds at 2 hz (horizontal and vertical) with eyes closed, then open and vertical) with eyes closed, then open and observe for nystagmus (Frenzel lenses)and observe for nystagmus (Frenzel lenses)

Abnormal:Abnormal:Unidirectional nystagmus in plane of Unidirectional nystagmus in plane of headshake (peripheral)headshake (peripheral)Vertical nystagmus after horizontal Vertical nystagmus after horizontal headshake (central)headshake (central)

Dynamic Visual Acuity Test*Dynamic Visual Acuity Test*

Read eye chart with eyes open and with slow Read eye chart with eyes open and with slow head shakehead shake

Abnormal:Abnormal:>3 line drop in acuity>3 line drop in acuity

* VOR test

Fixation Suppression Test*Fixation Suppression Test*

Fixate own thumb while chair rotatesFixate own thumb while chair rotatesAbnormal:Abnormal:

Nystagmus in direction of rotationNystagmus in direction of rotation

* VOR suppression test

Failure of VOR SuppressionFailure of VOR Suppression

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Ophthalmoscopic TestingOphthalmoscopic Testing

Spontaneous nystagmusSpontaneous nystagmusRetinal slip: Observe fundus while patient fixates Retinal slip: Observe fundus while patient fixates

target and oscillates head at frequency greater than target and oscillates head at frequency greater than 1 cps1 cps

Abnormal: If the VOR gain is too high the disc Abnormal: If the VOR gain is too high the disc appears to move with the head , if too low, appears to move with the head , if too low, opposite the headopposite the head

Provocative TestingProvocative Testing

Caloric stimuliCaloric stimuliHyperventilationHyperventilationPressure stimulusPressure stimulusSound stimulus (Tullio’s Phenomenon )Sound stimulus (Tullio’s Phenomenon )

NystagmusNystagmus

Gaze evokedGaze evokedDirection changing Direction changing

cerebellarcerebellarDirection selectiveDirection selective

vestibularvestibularAtaxic of INOAtaxic of INOVertical (Upbeat or Vertical (Upbeat or

downbeat)downbeat)

ReboundReboundTorsionalTorsionalAcquired pendularAcquired pendularPeriodic alternatingPeriodic alternatingLid nystagmusLid nystagmusSuperior oblique Superior oblique

myokymiamyokymia**

Interesting but rarely localizing

*Not really a “nystagmus”



Nystagmus(es) in MS Patient


Congenital strabismusCongenital strabismusLatent nystagmusLatent nystagmusDVD (Dissociated Vertical Divergence)DVD (Dissociated Vertical Divergence)Convergence spasmConvergence spasmVoluntary nystagmusVoluntary nystagmusCongenital or chronic IVth (FAT scan)Congenital or chronic IVth (FAT scan)Duane’s Retraction SyndromeDuane’s Retraction Syndrome

There are some ocular motility disturbances that have nothing to do with MS.

What is this?What is this?



Jelly nystagmus: Constant Ocular Oscillation seen in association

with poor vision

Thank You !

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Neuro-Ophthalmology and Multiple Sclerosis