1. Devic’s neuromyelitis optica: its distinctive features and treatment
Mark Morrow, MD
Providence Multiple Sclerosis Center
Portland, Oregon

2. 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

3. 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
Brain MRI unimpressive, suggests MS

4. NMO-IgG antibody: >1:60,000

5. 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

6. Key clinical features Optic neuritis Myelitis
Acute/subacute neuropathic visual loss
Typically painful
Mild, if any, disc edema
Myelitis
Acute/subacute weakness, numbness
Bowel/bladder problems
L’hermitte’s sign

7. 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
About 70% recurrent
Mean about 6 months between attacks
ON – optic nerve
SC – spinal cord

8. NMO – disease or syndrome?
Differential diagnosis
Multiple sclerosis
Acute disseminated encephalomyelitis (ADEM)
Lupus
Sjogren’s syndrome
Parainfectious
SLE, Sjogren’s, infx can be easily ruled out with lab work
ADEM is monophasic by definition, generally causes widespread brain changes

9. 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
Higher incidence of visual acuity less than 20/200 or persistent paraplegia, higher incidence of respiratory failure and mortality

10. 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
MS-like brain plaques ca. 10%
Characteristic bilateral thalamic lesions in some

11. ‘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
A massive paradigm shift came with the introduction of a biological marker
Aquaporin 4 is distributed throughout the CNS, not just ON and SC
Located on astrocytes at the BBB

12. 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
NMO Ab solves the puzzle!!!
NMO about 8% of demyelinating dz there, 1% here, but it seems to be shifting
Africa seems to have this story too; Japan just better studied

13. 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

14. 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
Cord MRI plus NMO-Ab are 100% specific, but 73% sensitive
Cord MRI or NMO-Ab is 100% sensitive but 79% specific
Wingerchuk et al. Revised diagnostic criteria for NMO. Neurology 2006;66:1485-9
(99% sensitive, 90% specific)

15. 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
Mean age – 29 for monophasic, 39 for relapsing ; Patient 2 fits these parameters, patient 1 doesn’t
Mortality 10%, 32%
90% of relapses occur within 5 years, 55% at 1 year
About 70% relapse
Consider to be relapsing if >a month after first attack of ON or SC disease

16. 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

17. Treatment for NMO* Relapses/acute disease
IV methylprednisolone 1000 mg/day, 3-5 days
Plasmapheresis
Prevention / stabilization
Consensus: ABCR drugs not helpful
Azathioprine mg/kg/day
Concurrent prednisone 1 mg/kg/day, tapering slowly after azathioprine takes effect
Mycophenolate mofetil, Mitoxantrone, Rituximab, IVIg, Plasmapheresis possible second liners
First line tx in bold
I like Imuran plus pulse IVMP
* No class I or II data

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