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.