Post on 30-Jan-2015
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Neuro-ophthalmic Complications in Multiple Sclerosis
Dwight Thibodeaux, OD
MS
Immune mediated, inflammatory disorder
Focal demyelinating plaques on axons
Episodes separated in time and space
Affects sensory and motor functions through neuronal injury within the CNS
MS Histology
Inflammation involves neutrophils, plasma cells and macrophages
Cellular responses cause the breakdown of myelin into fat globules
Macrophages ingest the fat, stimulate astrocytes and they form glial tissue (scars)visualized as plaques on MRI
Axonal damage and neuron loss follows
MS
Historically, 30% have had physical disability within 25 yrs of Dx
Wide range of disease severity
Incidence 12/10,000 per confirmed dx
Significant geographic variability
Dx by clinical signs and ancillary tests
McDonald criteria for formal dx
McDonald Criteria
Developed in 2001, last revised in 2010
Uses MRI to document dissemination of lesions in time and space
DIS – more than one T2 lesion in at least 2 of 4 specific areas of the brain or sp. cord
DIT – new T2 or gadolinium enhancing lesions on F/U MRI at a later date
MRI for MS
Optic nerve – Thin, 2-3 mm, fat suppressed, T-2 weighted images
Brain – T2 weighted images demonstrate inflammation, breakdown of b/b barrier and fluid presence in ovoid shapes in para-ventricular white matter (Dawson’s bars or claws), brainstem, cerebellum and spinal cord, Gadolinium enhancement helpful in some cases
Additional TestsCSF – oligoclonal banding and increased IgG levels
VEP’s – increased latency/reduced amplitude
OCT – Thinning of RNFL/GCL/IPL (GCC) independent of optic neuritis
PET - measuring myelin reduction (damage) in brain - independent of inflammation
Classification
RRMS Relapsing/Remitting – 75%+
SPMS Secondary Progressive
PPMS Primary Progressive
PRMS Progressive Relapsing
Subgroups: CIS, “Benign”, RIS
MS
More common in women, greater gender bias more recently points to environmental vs. sex-linked genetic factors
Family history – shared Human Leucocyte Antigen profiles
Childhood in northern latitudes
Vitamin D deficiency, increased incidence and decreased response to therapies
Questionable viral trigger, Epstein-Barr virus antibodies
Males of African decent generally have most aggressive disease
Smoking (cumulative dose), moderate/high salt diet and obesity all assoc. with both incidence and progression
Signs and Symptoms
Paresthesia, peripheral neuralgia and anesthesia, trigeminal neuralgia, L’Hermitte’s- shock or buzz on bending the neck
Ophthalmic manifestations
Muscle cramping/spasticity/myokymia/tremor/ataxia/dysarthria/”MS hug”
Urinary/sexual dysfunction
Fatigue/heat intolerance/Uhthoff phenomenon
Depression/bipolar disorder/dementia/pseudobulbar affect
Cognitive difficulties
Vertigo, balance issues
Management Immunosuppression- steroids for acute phase
Immunomodulation therapy (IMT)
Symptomatic therapies for inflammation, pain, fatigue, depression, cognition, etc
Avoidance of high salt and sugar intake, and cessation of smoking, vitamin D supplements
Re-myelination therapy in future through reduction in endogenous hyaluronidase-enzyme depresses myelin repair activities
Plasmapheresis – auto-antibody removal
Promising new therapy?
Transdermal application of Myelin Peptides – antigen specific therapy
Small referral center study - 30 patients reduced relapses, reduced Gd+ lesions in 2/3rds vs placebo
Safe, only local skin reactions in 20%
RRMS patients studied
JAMA neurology 2013
Immunomodulation Therapy
Reduced conversion from a CIS to MS in high risk patients (w/one or more brain lesions on MRI)
Improved motor function over time
Reduces relapse frequency and also the loss of function with each relapse
IMT options Interferon Beta 1a, 2a – Avonex q1wk IM, Betaseron, Rebif q2-3d SQ, interferes with immune response, blood-brain barrier protection, flu-like symptoms, hepatotoxic, blood work needed
Glatiramer – Copaxone, daily SQ, lipo-atrophy, occasional acute mild reactions, otherwise safe
Orals – 3 recently approved, some with rare heart risk, flu- like symptoms, hepatotoxic, uveitis, renal dysfunction, peripheral neuropathy, rarely PML (progressive multifocal leukoencephalpathy)
Tysabri (natalizumab) monthly infusion, monoclonal antibody blocks receptors on WBC’s that allow infiltration into axon, PML, HZO
PMLProgressive Multifocal Leukoencephalopathy
Debilitating, often deadly viral encephalopathy
Caused by JC (John Cunningham) virus, genus Polyoma
Common non-pathologic incidence (50%)
Antibodies detected in blood work prior to tx allowing virus to propagate in brain
Ophthalmic Manifestations
Other than optic neuritis, what are they?
Ophthalmic manifestations
Demyelinating Optic Neuritis - DON
EOM palsy
Internuclear ophthalmoplegia
Nystagmus
Saccadic abnormalities
Uveitis
EOM Palsy
Abducens (6th nerve) most commonly affected
Loss of abduction in ipsilateral eye
DDx: post viral in younger patients and ischemic vasculopathy in older population
Internuclear Ophthalmoplegia
Adduction deficit in ipsilateral eye combined with a pendular nystagmus in abducting contralateral eye
Lesion in medial longitudinal fasciculus
Nystagmus
Newly acquired pendular most common
Other forms can also be found
Depends on lesion location
Saccadic Abnormalities
Common in MS
Retinal slip – shift of an object off the macula
Square wave jerks – conjugate horizontal saccadic intrusions that interrupt fixation
Ocular flutter – shorter jerks
Opsoclonus - random multidirectional saccades
Uveitis
Ten times more common in MS patients
Found in 1-2% of MS population
May precede or follow Dx of MS – 12% assoc.
Pars planitis most common form, CME
Can also see anterior, posterior uveitis and periphlebitis
DONDemyelinating Optic Neuritis
Acute, inflammatory
Young adults
Monophasic (CIS) or polyphasic (recurs)
MS vs. neuromyelitis optica (NMO)
Neuromyleitis OpticaDevic’s disease
Demyelinating disease of optic nerves, spinal cord and occasionally, the brainstem
Bouts of DOM and transverse myelitis - loss of limb, bladder and bowel control separated by months to years
Female, African and Asian most common pts.
Biomarker NML-IgG in 70%, not in MS
Treated with steroids, IMT and plasma exch.
DON
Initial presenting event of MS in 20%
Occurs in 50% during course of disease
Typically unilateral, subacute vision loss
Retrobulbar pain first in most (90%)
No assoc. systemic or neuro symptoms
DON
VA from 20/20 to NLP
Progression of loss over 1-2 weeks
79% see improvement in 3 wks
93% by 5 wks
5-10% fail to recover significant function
DON
ONTT -- VA’s, Contrast Sensitivity, VF’s
Typically VA worse w/previous dx of MS
Altitudinal/centrocecal/central VF defects most common
Also spectrum of diffuse and focal defects
DONAPD
Dyschromatopsia and reduced vision in bright light
Phosphenes during, before or after onset
Reduced contrast sensitivity, stereovision
1/3rd have mild nerve head swelling
Other Optic Neuropathies
Inflammatory - sarcoid, SLE, Wegener’s
Infectious – bacterial, viral, fungal
Infiltrative – leukemia, lymphoma
Toxic – antimetabolites, Plaquenil, methanol
Nutritional - B-12, folate
Compressive – tumor, aneurysm, thyroid
Ischemic – AION, PION
Leber’s herid. optic neuropathy
NMO
Red Flags for Differentials
Lack of pain
Onset age>50
Lack of recovery
Worsening > 2 wks
Temple pain
Other acute symp.
Hemes/exudates/marked swelling
Bilateral
Treatment
ONTT –multicenter, randomized, 15yr
IV steriods followed by oral taper vs no treatment - no difference in final visual outcome, just more rapid recovery
Oral steroids alone showed 2X increased recurrence in same or fellow eye
ONTT
IV steroids for DON decreased risk of developing MS at two years, but effect not sustained after 3 yrs..
Over the short-term:
8% w/IV steroids converted to MS
18% of placebo group converted
16% of oral steroid group converted
Other Predictive Factors for Conversion to MS
Prior episode of optic neuritis
White matter lesions in spinal cord on MRI
Early recurrence
Family Hx of MS
Early age of onset
HLA DR2
DON
Although IV steroids are often recommended, no consensus on dosage or duration of treatment has been developed
ONTT - IV infusion of methylprednisolone, 250 mg every 6 hrs x 3 days with oral taper of 1mg/kg/day x 11days
Neuro consult, discussion with patient on logistics of infusion, cost/ benefit ratio
Other Treatments for DON
If steroids contraindicated or not effective
IVIG controversial, conflicting data, possible remyelination effect
Plasma exchange – recent studies show some improvement in endpoint visual function compared to placebo
DON work-up
MRI brain and orbits
OCT and VF studies
DON wo brain lesions: 25% MS in 15 yr.
75% risk w/one or more brain lesions
Spinal cord lesions very predictive of MS
DON without MRI lesions
With only one-fourth of patients converting to MS after first episode, management remains a challenge
Follow with OCT vs MRI?
Frequency? No established guidelines.
MRI if progression of NFL loss on OCT?