The prevalence of NMO ranges from 0.5 to 4.4 cases per 100,000 in different populations (Pandit and colleagues). It is relatively rare in the United States and European countries, with a prevalence that is 50 to 100 times lower than that of MS (Mealy et al). In persons of Asian or African descent, however, the prevalence of NMO is only 2 to 4 times lower than the prevalence of MS, primarily because MS is less common in these populations. The disease is 3 to 7 times more common in women than men, and the typical age of onset is about 1 decade later than MS (median age 33 to 46 versus 28 to 31 in MS).
The disease formerly termed “Asian optic–spinal MS” almost certainly represents Devic disease and displays this antibody in the majority of cases. Most cases of NMO stand apart from MS by virtue of distinctive clinical and pathologic features, mainly, a predilection for involvement of the optic nerves, spinal cord, and particular areas of the brain including the area postrema and hypothalamus; the absence of oligoclonal bands in the CSF; a tendency to CSF pleocytosis more so than in MS, and the necrotizing and cavitary nature of the lesions, affecting white and gray matter alike with prominent thickening of vessels but with minimal inflammatory infiltrates. It is quite unusual for MS to involve several contiguous longitudinal segments of the spinal cord, and this is a frequent finding in Devic disease (Fig. 35-3).
As would be expected, the clinical effects associated with the severe, destructive lesions of NMO are more likely to be permanent than those of typical demyelination. The optic neuritis associated with NMO is often characterized by severe vision loss, poor visual recovery, simultaneous or rapidly sequential bilateral involvement of both eyes, chiasmal lesions, and severe retinal nerve fiber layer loss demonstrated by optical coherence tomography.
Until the diagnostic criteria were revised in 2015, the definitive diagnosis of NMO had required the presence of optic neuritis and transverse myelitis. These syndromes may occur either simultaneously or sequentially, separated by days to several years. Because of growing recognition of the specificity of the NMO-IgG assay, the concept of NMO spectrum disorders (NMOSD) was introduced by Wingerchuk and colleagues in 2007 to describe clinically limited forms of the disease with NMO-IgG seropositivity. These diagnostic criteria were updated to reflect the importance of NMO-IgG serostatus in other clinical situations, beyond the limited forms of isolated transverse myelitis or optic neuritis (Wingerchuk and colleagues, 2015).
In patients with NMO-IgG positivity, NMO can be diagnosed in the setting of any of the 6 clinical criteria of optic neuritis, transverse myelitis, area postrema syndrome (characterized by hiccoughs or vomiting), or another brainstem, diencephalic, or other large cerebral lesion. On the other hand, for patients that are not known to be seropositive, the diagnosis still requires 2 of the 3 typical features of optic neuritis, extensive transverse myelitis, or area postrema syndrome with vomiting.
Occasionally, NMO occurs in the context of a rheumatologic disease such as Sjögren syndrome or lupus, and many of these patients have this same circulating anti-aquaporin antibody. Pittock and colleagues (2008) give the frequency of these antibodies as approximately one-third in patients with systemic autoimmune disease and clinical features of Devic disease. Case reports of NMOSD coexisting with cancer suggest that the disease may also occasionally be a paraneoplastic immune phenomenon.