A 19-year-old African-American woman with history of neonatal meningitis with baseline mental retardation, left hemiparesis and seizure disorder presented with altered mental status, decreased responsiveness, new right hemiparesis and aphasia. Brain and spine MRI revealed demyelination representing an acute inflammatory myelopathy. MR spectroscopy revealed findings of necrosis and anoxia. Mental status change was initially thought to be secondary to carbamazepine toxicity and improved with its discontinuation. However, given these imaging findings, further work up was performed. Further history also revealed the she had falls and episodes of “going blind” for several months. Laboratory evaluation found positive anti-histone IgG and anti-NMO IgG.
She was diagnosed with NMO and drug-induced lupus from carbamazepine. She was given high dose steroids and plasmapheresis with no improvement in neurologic symptoms. Plasmapheresis was discontinued and chronic azathioprine was initiated. Symptoms did not resolve but improved minimally.
This patient’s non-specific presentation is consistent with the presentation of NMO, a rare CNS inflammatory demyelinating disease characterized by relapsing attacks of optic neuritis and/or myelitis. Prevalence ranges from <1-4.4/100,000 in Europe and North America but may actually be higher due to misdiagnosis for MS. NMO was thought to be a subtype of MS until 2004 when an auto-antibody to aquaporin-4 (NMO-IgG) was discovered. NMO-IgG is highly sensitive and specific for NMO and levels correlate with disease activity. In animal experiments, passive transfer of IgG from NMO-IgG positive patients even reproduced neuropathologic findings.
As the diagnosis is not straightforward, it is important for hospitalists to have NMO in their differential for demyelinating diseases. It is important to distinguish between the MS and NMO because treatments for MS, including interferon, exacerbate NMO. NMO attacks are more disabling than MS flares with poorer remission and faster development of irreversible neurological disability. NMO compared with MS is associated with concomitant autoimmune disorders more frequently; the mechanism of this is unknown. In our patient, it was associated with drug-induced lupus.
NMO diagnosis requires two of the following criteria: contiguous spinal cord MRI lesion extending to 3 or more vertebral segments, brain MRI not meeting diagnostic criteria for MS according to Paty and NMO-IgG seropositivity.
Imaging findings and techniques that help to distinguish NMO from MS include spinal “bright spotty lesions” and MR spectroscopy and diffusion tensor imaging confirming severe tissue injury.
There is no known cure for NMO. Treatment goals are symptom management and improvement of neurologic function in acute attacks and prevention of further attacks. Attacks are treated with high dose methylprednisolone, and if refractory, with plasma exchange, IVIg or cyclophosphamide. Patients receive rituximab, azathioprine and/or prednisone for chronic immunosuppression.
Neuromyelitis optica is a rare CNS inflammatory demyelinating disease characterized by relapsing attacks of optic neuritis and/or myelitis. Diagnosis can be made with spinal lesions on MRI and antibody testing.