Neuro-ophthalmic Complications in Multiple Sclerosis


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Neuro-ophthalmic Complications in Multiple Sclerosis

  1. 1. Neuro-ophthalmic Complications in Multiple Sclerosis Dwight Thibodeaux, OD
  2. 2. 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
  3. 3. 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
  4. 4. 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
  5. 5. 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
  6. 6. 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
  7. 7. Additional Tests CSF – 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
  8. 8. Classification RRMS Relapsing/Remitting – 75%+ SPMS Secondary Progressive PPMS Primary Progressive PRMS Progressive Relapsing Subgroups: CIS, “Benign”, RIS
  9. 9. 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
  10. 10. 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
  11. 11. 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
  12. 12. 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
  13. 13. 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
  14. 14. 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
  15. 15. PML Progressive 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
  16. 16. Ophthalmic Manifestations Other than optic neuritis, what are they?
  17. 17. Ophthalmic manifestations Demyelinating Optic Neuritis - DON EOM palsy Internuclear ophthalmoplegia Nystagmus Saccadic abnormalities Uveitis
  18. 18. 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
  19. 19. Internuclear Ophthalmoplegia Adduction deficit in ipsilateral eye combined with a pendular nystagmus in abducting contralateral eye Lesion in medial longitudinal fasciculus
  20. 20. Nystagmus Newly acquired pendular most common Other forms can also be found Depends on lesion location
  21. 21. 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
  22. 22. 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
  23. 23. DON Demyelinating Optic Neuritis Acute, inflammatory Young adults Monophasic (CIS) or polyphasic (recurs) MS vs. neuromyelitis optica (NMO)
  24. 24. Neuromyleitis Optica Devic’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.
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. DON APD Dyschromatopsia and reduced vision in bright light Phosphenes during, before or after onset Reduced contrast sensitivity, stereovision 1/3rd have mild nerve head swelling
  29. 29. 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
  30. 30. Red Flags for Differentials Lack of pain Onset age>50 Lack of recovery Worsening > 2 wks Temple pain Other acute symp. Hemes/exudates/m arked swelling Bilateral
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. 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
  35. 35. 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
  36. 36. 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
  37. 37. 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?