The Neuro-Ophthalmology of Multiple Sclerosis Charles Maxner MD, FRCPC Professor, Departments of...

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: Disclosure

Dr. 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 Cord

Immune BasedImmune Based

Inflammatory demyelinating disorderInflammatory demyelinating disorder

Axonal 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

Cli

nic

al W

ors

enin

g

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)

DiplopiaDiplopia

OscillopsiaOscillopsia

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 System

Pre-chiasmalPre-chiasmalOptic NerveOptic Nerve

ChiasmalChiasmalBitemporal VF defect rareBitemporal VF defect rare

Junctional Scotoma defect not uncommonJunctional Scotoma defect not uncommon

Post-ChiasmalPost-ChiasmalOptic tractOptic tract

Geniculocalcarine 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”


ExaminationExaminationVa 6/6 Right, HM LeftVa 6/6 Right, HM Left

Central scotoma left eyeCentral scotoma left eye

RAPD 1.5 log units left eyeRAPD 1.5 log units left eye

Impaired colour perception leftImpaired colour perception left

Ocular motility normalOcular motility normal

Left 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 Left

Central blur left eyeCentral blur left eye

RAPD 0.6 left eyeRAPD 0.6 left eye

Colour improvedColour improved

Temporal pallor left discTemporal pallor left disc

Follow Up: 3 months laterFollow Up: 3 months later

Optic NeuritisOptic NeuritisCommon SymptomsCommon Symptoms

MonocularMonocular

Central Vision lossCentral Vision loss

Pain (eye movement)Pain (eye movement)

Altered colour visionAltered colour vision

Recovery commonRecovery common

Uhthoff’s symptomUhthoff’s symptom

FlashesFlashes

Pulfrich 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?


Wilhelm 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 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

FlashesFlashes

Movement 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 dark

Eye movementEye movement

Differentiate from Lightning Streaks of MooreDifferentiate from Lightning Streaks of Moore

Eye equivalent of Lhermittes symptomEye equivalent of Lhermittes symptom

Pulfrich PhenomenonPulfrich Phenomenon

Optic Neuritis: Physical Optic Neuritis: Physical FindingsFindings

Decreased visual acuityDecreased visual acuity

VF defect VF defect (Central/Altitudinal 29% )(Central/Altitudinal 29% )

DyschromatopsiaDyschromatopsia

Afferent Pupil Defect Afferent Pupil Defect (RAPD)(RAPD)

Optic disc swelling 35%Optic disc swelling 35%

Abnormal Contrast Abnormal Contrast SensitivitySensitivity

Abnormal VEPAbnormal VEP

Altered Flicker Altered Flicker PerceptionPerception

Altered depth perceptionAltered depth perception

Optic 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 eyes

Progressive courseProgressive course

Blurred centrally right eyeBlurred centrally right eye

Hazy to left of fixation both eyesHazy to left of fixation both eyes

Occasional migraineOccasional migraine


Va 6/15 Right, 6/7.5 LeftVa 6/15 Right, 6/7.5 Left

Confrontation VF: Left Central HHConfrontation VF: Left Central HH

No RAPDNo RAPD

AO Plates: 7/14 Rt 10/14 LtAO Plates: 7/14 Rt 10/14 Lt


Anomalous discs both eyesAnomalous discs both eyes


Automated 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 blurring

Both eyes involvedBoth eyes involved

15 years ago “poor balance”15 years ago “poor balance”

MigrainesMigraines

Sister with MSSister with MS

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

ExaminationExaminationVa: 6/6 Both EyesVa: 6/6 Both Eyes

AO Plates: 13/14 Rt, 11/14 LtAO Plates: 13/14 Rt, 11/14 Lt

Pupils normalPupils normal


Fundi normalFundi normal

DTR’s brisk, Unsteady RombergDTR’s brisk, Unsteady Romberg

VF’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, Mixed

FluctuatingFluctuating

OscillopsiaOscillopsia

Ocular Motility DisordersOcular Motility Disorders

Infranuclear or NerveInfranuclear or Nerve

Saccadic systemSaccadic system

Pursuit systemPursuit system

Internuclear abnormalitiesInternuclear abnormalities

Vestibulo-ocular dysfunctionVestibulo-ocular dysfunction

NystagmusNystagmus


Nuclear Palsies: RareNuclear Palsies: Rare

Infranuclear or NerveInfranuclear or NerveVI: Most commonVI: Most common

III: Partial or CompleteIII: Partial or Complete

IV: RareIV: Rare

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

CC: DiplopiaCC: Diplopia

Hx: 6 months progressing diplopiaHx: 6 months progressing diplopia

Initially intermittent, now persistentInitially intermittent, now persistent

Otherwise asymptomaticOtherwise asymptomatic

Sister has MSSister has MS

O/E: Incomitant esotropiaO/E: Incomitant esotropia

Left 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


Saccadic 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 Oscillations

Saccadic Dysmetria

Macrosaccadic Oscillations

Square Wave Jerks

Macro Square Wave Jerks

Ocular Flutter



Square Wave Jerks

Ocular Flutter






Pursuit DysfunctionPursuit DysfunctionSaccadic IntrusionsSaccadic Intrusions

Internuclear OphthalmoplegiaInternuclear OphthalmoplegiaMLF LesionMLF Lesion

Skew DeviationSkew DeviationVertical diplopiaVertical diplopia

Gaze PalsiesGaze Palsies

Dorsal Midbrain SyndromeDorsal Midbrain Syndrome


Pursuit DysfunctionPursuit Dysfunction

Saccadic 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 Vision

Hx: 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 Ophthalmoplegia

MRI 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 target

Abnormal: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 rotates

Abnormal: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 stimuli

HyperventilationHyperventilation

Pressure stimulusPressure stimulus

Sound stimulus (Tullio’s Phenomenon )Sound stimulus (Tullio’s Phenomenon )

NystagmusNystagmus

Gaze evokedGaze evoked

Direction changing Direction changing cerebellarcerebellar

Direction selectiveDirection selective

vestibularvestibular

Ataxic of INOAtaxic of INO

Vertical (Upbeat or Vertical (Upbeat or downbeat)downbeat)

ReboundRebound

TorsionalTorsional

Acquired pendularAcquired pendular

Periodic alternatingPeriodic alternating

Lid nystagmusLid nystagmus

Superior oblique Superior oblique myokymiamyokymia**

Interesting but rarely localizing

*Not really a “nystagmus”



Nystagmus(es) in MS Patient


Congenital strabismusCongenital strabismus

Latent nystagmusLatent nystagmus

DVD (Dissociated Vertical Divergence)DVD (Dissociated Vertical Divergence)

Convergence spasmConvergence spasm

Voluntary nystagmusVoluntary nystagmus

Congenital 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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