Devic’s neuromyelitis optica: Devic’s neuromyelitis optica: its distinctive features and treatmentits distinctive features and treatment

Mark Morrow, MDMark Morrow, MDProvidence Multiple Sclerosis CenterProvidence Multiple Sclerosis Center

Portland, OregonPortland, Oregon

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

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

NMO-IgG antibody: >1:60,000

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

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

L’hermitte’s sign

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• >70% 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 nerveSC – spinal cord

NMO – disease or syndrome?

Differential diagnosisMultiple sclerosis

Acute disseminated encephalomyelitis (ADEM)Lupus

Sjogren’s syndromeParainfectious

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

Ancillary tests in NMOMRI• Elongated, expansile, enhancing spinal cord lesions

• Brain MRI usually normal; occasional multiple-sclerosis-like plaques or confluent/symmetrical lesions

CSF• >50 white blood cells/mm3 or >5 polymorphonuclear

leucocytes/mm3 common

• Oligoclonal bands, ↑IgG synthesis less common

‘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

The epidemiology of MS and The epidemiology of MS and NMO differs NMO differs

in Japan and the Westin 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

Laotian womanAge 47-52: 4 bouts

unilateral optic neuritis

Age 54: transverse myelitis

Exam: no light perception OD, 20/20 OS, spastic paraparesis

NMO-IgG positive

NMO: the latest criteria

Wingerchuk et al. Revised diagnostic criteria for NMO. Neurology 2006;66:1485-9(99% sensitive, 90% specific)

• History of optic neuritis

• History of acute myelitis

• Two of three of: MRI spinal cord lesion > 3 segments + NMO-IgG antibody Brain MRI not consistent with multiple sclerosis

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

45 year old man1.5 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

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

From Ransohoff R. J Clin Invest. 2006 September 1; 116(9): 2313–2316.