Transcript PowerPoint Presentation - Devic’s neuromyelitis optica

Devic’s neuromyelitis optica:
its distinctive features and treatment
Mark Morrow, MD
Providence Multiple Sclerosis Center
Portland, 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 Bcell-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
Myelitis
Acute/subacute
neuropathic visual loss
Acute/subacute weakness,
numbness
Typically painful
Bowel/bladder problems
Mild, if any, disc edema
L’hermitte’s sign
The broadening spectrum of NMO
‘Textbook’ form’
• Monophasic
Current description
• >70% recurrent
• Simultaneous ON and SC
disease
• ON and SC attacks may be years
apart
• Bilateral ON involvement
• ON disease may be unilateral
• No disease outside SC, ONs
• Brain disease occurs (ca. 10%)
• No brain MRI lesions
• Brain MRI changes may
occasionally resemble multiple
sclerosis
ON – optic nerve
SC – spinal cord
NMO – disease or syndrome?
Differential diagnosis
Multiple sclerosis
Acute disseminated encephalomyelitis (ADEM)
Lupus
Sjogren’s syndrome
Parainfectious
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 NMO
MRI
• 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 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
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
NMO: the latest criteria
• 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
Wingerchuk et al. Revised diagnostic criteria for NMO. Neurology 2006;66:1485-9
(99% sensitive, 90% specific)
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 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
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.