Neuromyelitis optica (NMO; Devic's disease) is an aggressive inflammatory disorder characterized by recurrent attacks of optic neuritis (ON) and myelitis; the more inclusive term NMO Spectrum Disorders (NMOSD) incorporates pts with partial forms, and with involvement of additional CNS structures (Table 193-1 Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder). NMO is more frequent in women than men (>3:1), and typically begins in adulthood but can arise at any age. An important consideration is distinguishing between NMO and multiple sclerosis (MS; Chap. 192 Multiple Sclerosis). In NMO, attacks of ON can be bilateral and produce severe visual loss (uncommon in MS); myelitis can be severe and transverse (rare in MS) and is typically longitudinally extensive (Fig. 193-1. Imaging Findings in Neuromyelitis Optica: Longitudinally Extensive Transverse Myelitis, Optic Neuritis and Brainstem Involvement) involving three or more contiguous vertebral segments. Also in contrast to MS, progressive symptoms typically do not occur in NMO.
Brain MRI may be normal or show areas of nonspecific signal change as well as lesions associated with specific syndromes such as the hypothalamus causing an endocrinopathy; the lower medulla presenting as intractable hiccoughs or vomiting; or cerebral hemispheres producing focal symptoms, encephalopathy, or seizures. Large MRI lesions in the cerebral hemispheres may have a “cloud-like” appearance and, unlike MS lesions, are often not destructive and can resolve completely. Spinal cord MRI lesions typically consist of focal enhancing areas of swelling and tissue destruction, extending over three or more spinal cord segments, and on axial sequences, these are centered on the gray matter of the cord. CSF findings include pleocytosis greater than in MS, with neutrophils and eosinophils in many acute cases; oligoclonal bands are uncommon.
NMO is an autoimmune disease associated with a highly specific autoantibody directed against the water channel protein aquaporin-4 (AQP4) that is present in the sera of approximately 70% of pts with a clinical diagnosis of NMO. AQP4 is localized to the foot processes of astrocytes. Pathology reveals inflammation, loss of astrocytes, and an absence of staining of AQP4 by immunohistochemistry, plus thickened blood vessel walls, demyelination, and deposition of antibody and complement.
NMO is typically a recurrent disease; the course is monophasic in fewer than 10% of pts. Individuals who test negative for AQP-4 antibodies are somewhat more likely to have a monophasic course. Untreated NMO is usually disabling over time; in one series, respiratory failure from cervical myelitis was present in one-third of pts, and 8 years after onset, 60% of pts were blind and more than half had permanent paralysis of one or more limbs. NMO can occur in people of any ethnic background, but individuals of Asian and African origin are disproportionately affected.
Up to 40% of NMO pts have a systemic autoimmune disorder, such as systemic lupus erythematosus, Sjögren's syndrome, perinuclear antineutrophil cytoplasmic antibody (p-ANCA)-associated vasculitis, myasthenia gravis, Hashimoto's thyroiditis, or mixed connective tissue disease. In others, onset may be associated with acute infection with VZV, EBV, HIV, or tuberculosis. Rare cases appear to be paraneoplastic.
| TREATMENT | ||
Neuromyelitis OpticaAcute attacks are usually treated with high-dose glucocorticoids (e.g., methylprednisolone 1 g/d for 5-10 days followed by a prednisone taper). Plasma exchange (typically 5-7 exchanges of 1.5 plasma volumes/exchange) is used empirically for acute episodes that do not respond to glucocorticoids. Given the unfavorable natural history of untreated NMO, prophylaxis against relapses is recommended for most pts using one of the following regimens: mycophenolate mofetil (1000 mg bid); rituximab a B-cell depleting anti-CD20 monoclonal antibody (2 g IV Q 6 months); or a combination of glucocorticoids (500 mg IV methylprednisolone daily for 5 days; then oral prednisone 1 mg/kg per day for 2 months, followed by slow taper) plus azathioprine (2 mg/kg per day started on week 3). Some therapies with proven efficacy in MS do not appear to be useful for NMO. Clinical trials with the B-cell depleting anti-CD19 monoclonal antibody (inebilizumab), the terminal complement inhibitor (eculizumab), and an IL-6 receptor blocking antibody (SA-237) are ongoing. |
Demyelination Associated With Anti-Mog Antibodies 
Antibodies against myelin oligodendrocyte glycoprotein (MOG) are present in some pts with AQP4 seronegative NMO. Pts who are seropositive for anti-MOG antibodies are at risk for bilateral, synchronous ON and myelitis. A clinical feature of ON associated with anti-MOG antibodies is the presence of papillitis seen by funduscopy or orbital MRI. ON associated with anti-MOG antibodies is typically longitudinally extensive on MRI, and brain MRI can be normal or show fluffy areas of increased signal change in white or gray matter structures, similar to NMO. Spinal cord lesions can be longitudinally extensive or short. Demyelination associated with anti-MOG antibodies is sometimes monophasic, as in acute disseminated encephalomyelitis (ADEM), but can also be recurrent. Acute episodes are managed with high dose glucocorticoids followed by a prednisone taper and sometimes by PLEX, as with NMO. Brain lesions associated with anti-MOG antibodies often respond rapidly to treatment with glucocorticoids and may resolve entirely. Some pts experience disease recurrence following discontinuation of prednisone and can become glucocorticoid dependent. There is limited data on use of other immunosuppressant medications typically used in NMO.