Devic

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Devics neuromyelitis optica its distinctive
features and treatment

• Mark Morrow, MD
• Providence Multiple Sclerosis Center
• Portland, Oregon

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Conclusions

• Neuromyelitis optica is a distinct demyelinating
  disease with accurate diagnostic criteria
• Demographic and historic features predict
  relapses
• Relapse prevention requires broad-spectrum or
  B-cell-specific immunosuppression

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Age 4 Severe visual loss OU and generalized
burning sensation Age 7 Quadriparesis and
progression to no light perception OU Age 28-33
Progressive weakness, neuropathic pain Exam no
light perception, sheet-white optic atrophy OU
severe spastic quadriparesis
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NMO-IgG antibody gt160,000
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Neuromyelitis optica (NMO)

• Acute/subacute demyelination, necrosis of optic
  nerves, spinal cord
• Often preceded by viral illness, associated with
  systemic autoimmune disease
• Significant residua common
• Partial responses to steroids, other
  immunosuppressants

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Key clinical features

• Optic neuritis
• Acute/subacute neuropathic visual loss
• Typically painful
• Mild, if any, disc edema

• Myelitis
• Acute/subacute weakness, numbness
• Bowel/bladder problems
• Lhermittes sign

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The broadening spectrum of NMO

• Textbook form
• Monophasic
• Simultaneous ON and SC disease
• Bilateral ON involvement
• No disease outside SC, ONs
• No brain MRI lesions

• Current description
• gt70 recurrent
• ON and SC attacks may be years apart
• ON disease may be unilateral
• Brain disease occurs (ca. 10)
• Brain MRI changes may occasionally resemble
  multiple sclerosis

ON optic nerve SC spinal cord
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NMO disease or syndrome?

• Differential diagnosis
• Multiple sclerosis
• Acute disseminated encephalomyelitis (ADEM)
• Lupus
• Sjogrens syndrome
• Parainfectious

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How does NMO compare with MS?

• Similarities
• Female predilection
• Age of onset
• Relapse rate

• Differences
• Geography
• Brain symptoms
• Prognosis
• MRI appearance
• Cerebrospinal fluid findings
• Response to treatment

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Ancillary tests in NMO

• MRI
• Elongated, expansile, enhancing spinal cord
  lesions
• Brain MRI usually normal occasional
  multiple-sclerosis-like plaques or
  confluent/symmetrical lesions
• CSF
• gt50 white blood cells/mm3 or gt5
  polymorphonuclear leucocytes/mm3 common
• Oligoclonal bands, ?IgG synthesis less common

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The NMO antibody

• IgG autoantibody localizes to glia at
  blood-brain-barrier
• Binds to aquaporin-4, the main water channel in
  the central nervous system
• About 90 specific, 75 sensitive for NMO
• Often in brain MRI- negative relapsing
  myelitis/optic neuritis
• Available commercially

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The epidemiology of MS and NMO differs in Japan
and the West

• Lower prevalence of MS in Japan
• Higher ratio of classic, monophasic NMO to MS,
  likely true throughout Asia
• More Japanese MS patients present with
  bilateral optic neuropathy and severe ON or SC
  disease (ca. 25)
• Up to 60 of Asian optospinal MS may be for
  NMO-IgG, implying that this condition represents
  recurrent NMO

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Laotian woman Age 47-52 4 bouts unilateral optic
neuritis Age 54 transverse myelitis Exam no
light perception OD, 20/20 OS, spastic
paraparesis NMO-IgG positive
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NMO the latest criteria

• History of optic neuritis
• History of acute myelitis
• Two of three of
• MRI spinal cord lesion gt 3 segments
• NMO-IgG antibody
• Brain MRI not consistent with multiple
  sclerosis

Wingerchuk et al. Revised diagnostic criteria for
NMO. Neurology 2006661485-9 (99 sensitive,
90 specific)
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Who will relapse?

• Older patients with more common, sequential optic
  neuritis/myelopathic disease
• Less severe disease at onset
• High-titer NMO-IgG antibodies
• Step-wise progression portends worse prognosis
  than monophasic disease

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45 year old man 1.5 yrs ago subacute myelopathy
preceded by flu-like illness Since then several
mild myelopathic relapses, occasional blurring
Exams spastic paraparesis, normal optic nerves
and vision Normal CSF, - NMO-IgG
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Treatment for NMO

• Relapses/acute disease
• IV methylprednisolone 1000 mg/day, 3-5 days
• Plasmapheresis
• Prevention / stabilization
• Consensus ABCR drugs not helpful
• Azathioprine 2.5-3 mg/kg/day
• Concurrent prednisone 1 mg/kg/day, tapering
  slowly after azathioprine takes effect
• Mycophenolate mofetil, Mitoxantrone, Rituximab,
  IVIg, Plasmapheresis possible second liners

No class I or II data
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From Ransohoff R. J Clin Invest. 2006 September
1 116(9) 23132316.