The Neuro-Ophthalmology of Multiple Sclerosis Charles Maxner MD

The Neuro-Ophthalmology of Multiple Sclerosis Charles Maxner MD, FRCPC Professor, Departments of Medicine (Neurology) and Ophthalmology Dalhousie University Consultant, Dalhousie MS Research Unit Halifax , N. S.

Dr. C. E. Maxner: Disclosure Dr. Maxner has attended and conducted educational events and participated in MS research studies affiliated with the following firms: Berlex Biogen Idec Serono Teva

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

MS: Historical Perspective Augustus d’Esté (1794 -1848) J. M. Charcot (1825 -1893) Grandson King George III (1868 leçons: ”sclérose en plaques disseminées” from Vulpian) Carswell ~1836

Multiple Sclerosis Disorder of Central Myelin (Oligodendroglia) Brain and Spinal Cord Immune Based Inflammatory demyelinating disorder Axonal injury (Disability)

Multiple Sclerosis: 3 Components Inflammation Demyelination Axonal Loss Courtesy Dr. G. Rice

Multiple Sclerosis Pathology Gross Pathology Luxol Fast Blue

Multiple Sclerosis Pathology Optic Nerves Chiasm Optic Tract Anterior Visual Pathway Luxol Fast Blue

Action Potential Transit in MS Concepts 1. Delayed Conduction 2. Conduction Block

Courtesy Dr. A. Bar-Or

Natural Progression of MS Relapsing Forms Relapsing-Remitting Clinically definite MS Secondary Progressive Relapse Clinical Worsening Mono. Subclinical symptomatic Initial demyelinating event Time Level of disability Gadolinium enhancement Cognitive dysfunction Relapses Accumulated MRI lesion burden Brain atrophy Courtesy Dr. G. Rice

MRI Dissemination in Space and Time

Presenting Symptoms of MS Symptom Weakness in one or more limbs Sensory loss/paresthesias Visual loss Gait disturbance/ataxia Diplopia Dizziness/vertigo Pain Sensory in face Approximate Prevalence 40 -50% 40 -45% 16 -36% 5 -15% 7 -15% 5% 3% 3%

Neuro-ophthalmological Issues Loss of Vision (Monocular and Binocular) Diplopia Oscillopsia

MS and the Visual System Afferent Visual System Vision loss and distortion Efferent Visual System Diplopia and Oscillopsia

MS and The Afferent Visual System Pre-chiasmal Optic Nerve Chiasmal Bitemporal VF defect rare Junctional Scotoma defect not uncommon Post-Chiasmal Optic tract Geniculocalcarine pathway

Case: Ms. H. B. 35 YOWF MS diagnosed 12 years prior Copaxone Therapy Decreased vision left eye Progressed over 48 hours Pain on eye movement Impaired depth perception “Can’t drive”

Case: Ms. H. B. 35 YOWF Examination Va 6/6 Right, HM Left Central scotoma left eye RAPD 1. 5 log units left eye Impaired colour perception left Ocular motility normal Left disc slightly swollen and hyperemic

Pupil Testing

Case: Ms. H. B. 35 YOWF Goldmann Visual Fields

Case: Ms. H. B. 35 YOWF Follow Up: 3 months later Va 6/6 Right, 6/9 Left Central blur left eye RAPD 0. 6 left eye Colour improved Temporal pallor left disc

Optic Neuritis Common Symptoms Monocular Central Vision loss Pain (eye movement) Altered colour vision Recovery common Uhthoff’s symptom Flashes Pulfrich phenomenon

Uhthoff’s Symptom What did he describe? Uhthoff described 3 patients in whom exertion and fatigue caused a desaturation in colour vision Patient XVIII had decreased acuity after walking around the room Who was Uhthoff?

Uhthoff’s Symptom Wilhelm Uhthoff (1853 -1927) Born Warin , Germany Studied in Tübingen, Göttingen, Berlin Consultant at Westphal’s Clinic (With Oppenheim, Wallenberg, Thomsen, Möbius) Named Professor of Ophthalmology at Breslau 1896 Eye Symptoms in Diseases of the Nervous System (Published 1915) Described by Bielschowsky as the “true originator” of clinical neuro-ophthalmology

Wilhelm Uhthoff

Uhthoff’s Symptom Uhthoff’s symptom in optic neuritis: relationship to MRI and development of MS. (Scholl GB, Song HS, Wray SH) Ann Neurol 1991; 30(2): 180 -4 Uhthoff and his Symptom (Selhorst JB, Saul RF) Journal of Neuro-ophthalmology 1995; 15(2): 63 -9

Flashes Movement phosphenes in optic neuritis: A new clinical sign (Davis F, Bergen D, Schauf C, Mc. Donald I, Deutsch W) Neurology 1976; 26: 1100 -1104. Bright flashes in dark Eye movement Differentiate from Lightning Streaks of Moore Eye equivalent of Lhermittes symptom

Pulfrich Phenomenon

Optic Neuritis: Physical Findings Decreased visual acuity VF defect (Central/Altitudinal 29% ) Dyschromatopsia Afferent Pupil Defect (RAPD) Optic disc swelling 35% Abnormal Contrast Sensitivity Abnormal VEP Altered Flicker Perception Altered depth perception Optic disc pallor

Optic Neuritis: Optic Disc

Case: Ms. A. B. 23 YOWF Two months impaired vision both eyes Progressive course Blurred centrally right eye Hazy to left of fixation both eyes Occasional migraine

Case: Ms. A. B. 23 YOWF Va 6/15 Right, 6/7. 5 Left Confrontation VF: Left Central HH No RAPD AO Plates: 7/14 Rt 10/14 Lt Ocular motility normal Anomalous discs both eyes

Case: Ms. A. B. 23 YOWF Automated Perimetry

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

Case: Ms. C. S. 41 YOWF 2 week hx of L sided visual blurring Both eyes involved 15 years ago “poor balance” Migraines Sister with MS

Case: Ms. C. S. Examination Va: 6/6 Both Eyes AO Plates: 13/14 Rt, 11/14 Lt Pupils normal Ocular motility normal Fundi normal DTR’s brisk, Unsteady Romberg VF’s abnormal

Ms. C. S. Visual Fields

Ms. C. S. MRI

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

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

Neuro-ophthalmological Issues Diplopia Horizontal, Vertical, Mixed Fluctuating Oscillopsia

Ocular Motility Disorders Infranuclear or Nerve Saccadic system Pursuit system Internuclear abnormalities Vestibulo-ocular dysfunction Nystagmus

Ocular Motility Disorders Nuclear Palsies: Rare Infranuclear or Nerve VI: Most common III: Partial or Complete IV: Rare

Ms. H. M. 34 YOWF CC: Diplopia Hx: 6 months progressing diplopia Initially intermittent, now persistent Otherwise asymptomatic Sister has MS O/E: Incomitant esotropia Left abduction deficit

Ms. H. M. 34 YOWF

Ms. H. M. 34 YOWF 6 Months Later

Ocular Motility Disorders Saccadic abnormalities Hypometric Hypermetric Dysmetria Saccadic Intrusions Square wave jerks Saccadic pulses Ocular flutter

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

Saccadic 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 Disorders Square Wave Jerks Ocular Flutter

Ocular Motility Disorders Pursuit Dysfunction Saccadic Intrusions Internuclear Ophthalmoplegia MLF Lesion Skew Deviation Vertical diplopia Gaze Palsies Dorsal Midbrain Syndrome

Ocular Motility Disorders Pursuit Dysfunction Saccadic Intrusions

Ocular Motility Disorders Internuclear Ophthalmoplegia: MLF Lesion From: Kline & Bajandas. Neuro-ophthalmology Board Review Manual; Slack Inc

Ms. C. P. 24 YOWF CC: Blurred Vision Hx: • 2 week history of “dizzy” feeling and disorientation with looking down • Difficulty focussing on rapid EOM’s • 2003 sensory symptoms in legs and Lhermittes symptom O/E: Abnormal EOM’s

Ms. C. P. 24 YOWF

Ms. C. P. 24 YOWF T 2 Flair

Internuclear Ophthalmoplegia MRI Detection of MLF Lesions Proton density>T 2>Flair Frohman et al Neurology 2001; 57: 762 -768 Proton Density T 2 Flair

Internuclear Ophthalmoplegia Versional Disconjugacy Index: Assess adduction vs abduction saccade peak velocity Most accurate method for identification of INO is quantitative EOM recording Clinical detection accuracy vs Recording 93% severe INO 75% moderate INO 29% mild INO Frohman et al. Neurology 2003; 61: 848 -850

Ocular Motility Disorders Vestibulo-ocular Dysfunction VOR Mismatch Failure 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 Test Halmagyi Maneuver Thrust head 20 -30 degrees while fixating target Abnormal: Refixation saccade

Headshake Test Shake head for 20 seconds at 2 hz (horizontal and vertical) with eyes closed, then open and observe for nystagmus (Frenzel lenses) Abnormal: Unidirectional nystagmus in plane of headshake (peripheral) Vertical nystagmus after horizontal headshake (central)

Dynamic Visual Acuity Test* Read eye chart with eyes open and with slow head shake Abnormal: >3 line drop in acuity * VOR test

Fixation Suppression Test* Fixate own thumb while chair rotates Abnormal: Nystagmus in direction of rotation * VOR suppression test

Failure of VOR Suppression

Ophthalmoscopic Testing Spontaneous nystagmus Retinal slip: Observe fundus while patient fixates target and oscillates head at frequency greater than 1 cps Abnormal: If the VOR gain is too high the disc appears to move with the head , if too low, opposite the head

Provocative Testing Caloric stimuli Hyperventilation Pressure stimulus Sound stimulus (Tullio’s Phenomenon )

Nystagmus Interesting but rarely localizing Gaze evoked Direction changing cerebellar Direction selective vestibular Ataxic of INO Vertical (Upbeat or downbeat) Rebound Torsional Acquired pendular Periodic alternating Lid nystagmus Superior oblique myokymia* *Not really a “nystagmus”

Nystagmus(es) in MS Patient

Ocular Motility Disorders There are some ocular motility disturbances that have nothing to do with MS. Congenital strabismus Latent nystagmus DVD (Dissociated Vertical Divergence) Convergence spasm Voluntary nystagmus Congenital or chronic IVth (FAT scan) Duane’s Retraction Syndrome

What is this? Jelly nystagmus: Constant Ocular Oscillation seen in association with poor vision

Thank You ! Time for Questions