the neuro-ophthalmology of multiple sclerosis charles maxner md, frcpc professor, departments of...
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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”
Case: Ms. H.B. 35 YOWFCase: Ms. H.B. 35 YOWF
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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Case: Ms. H.B. 35 YOWFCase: Ms. H.B. 35 YOWF
Goldmann Visual FieldsGoldmann Visual Fields
Case: Ms. H.B. 35 YOWFCase: Ms. H.B. 35 YOWF
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?
Uhthoff’s SymptomUhthoff’s Symptom
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 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
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
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 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
Ocular motility normalOcular motility normal
Anomalous discs both eyesAnomalous discs both eyes
Case: Ms. A.B. 23 YOWFCase: Ms. A.B. 23 YOWF
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
Ocular motility normalOcular motility 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
Ocular Motility DisordersOcular Motility Disorders
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
Ocular Motility DisordersOcular Motility Disorders
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
From: Leigh & Zee. The Neurology of Eye Movements, F.A. Davis Company
Ocular Motility DisordersOcular Motility Disorders
Square Wave Jerks
Ocular Flutter
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Ocular Motility DisordersOcular Motility Disorders
Pursuit DysfunctionPursuit DysfunctionSaccadic IntrusionsSaccadic Intrusions
Internuclear OphthalmoplegiaInternuclear OphthalmoplegiaMLF LesionMLF Lesion
Skew DeviationSkew DeviationVertical diplopiaVertical diplopia
Gaze PalsiesGaze Palsies
Dorsal Midbrain SyndromeDorsal Midbrain Syndrome
Ocular Motility DisordersOcular Motility Disorders
Pursuit DysfunctionPursuit Dysfunction
Saccadic IntrusionsSaccadic Intrusions
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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
Ms.C.P. 24 YOWFMs.C.P. 24 YOWF
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Ms.C.P. 24 YOWFMs.C.P. 24 YOWF
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
Ocular Motility DisordersOcular Motility Disorders
Vestibulo-ocular DysfunctionVestibulo-ocular Dysfunction VOR MismatchVOR Mismatch
Failure of VOR SuppressionFailure of VOR Suppression
Vestibulo-Ocular reflex
From: Leigh & Zee. The Neurology of Eye Movements, F.A. Davis Company
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”
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Nystagmus(es) in MS Patient
Ocular Motility DisordersOcular Motility Disorders
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?
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Jelly nystagmus: Constant Ocular Oscillation seen in association
with poor vision
Thank You !
Time for Questions