Neuromyelitis optica spectrum disorder (ORPHA:71211)
A rare inflammatory disease of the central nervous system characterized mainly by attacks of uni- or bilateral optic neuritis (ON) and acute myelitis.
Epidemiology
Neuromyelitis optica spectrum disorder (NMOSD) has a worldwide distribution and estimated prevalence of 1-5/100,000. The average annual incidence is 1/770,000 worldwide. Nearly 90% of affected individuals are female.
Clinical description
Patients are predominantly female with onset typically in late middle-age. Presentation is with acute, often severe, attacks of blindness and paraparesis or quadriparesis, accompanied by sensory and sphincter impairments. Most patients have relapsing attacks (more frequent in women), separated by months or years with partial recovery, typically with sequential episodes of ON and myelitis. More rarely, the disease course is monophasic, with nearly simultaneous episodes of ON and myelitis. This form may occur in younger individuals with no sex predilection. Rarely, patients experience other neurological manifestations, including intractable vomiting and nausea due to inflammation in the medulla, endocrine and sleep disorders due to involvement of the hypothalamus, and attacks of cerebral edema that may cause confusion or coma. Patients frequently have other systemic autoimmune disorders, such as systemic lupus erythematosus (SLE), Sjögren's syndrome or myasthenia gravis.
Etiology
Etiology is unknown but NMO is believed to be an autoimmune disease associated with autoantibodies to aquaporin-4 (AQP4) in 70% and autoantibodies to myelin oligodendrocyte glycoprotein (MOG) in 15% of patients. 15% of patients are double seronegative for these antibodies. Patients with autoantibodies to MOG have overlapping clinical features, but have demographic and clinical differences from patients with autoantibodies to AQP4 and patients with these antibodies are diagnosed with MOG associated disorders (MOGAD).
Diagnostic methods
Diagnosis is primarily clinical, but MRI evidence of long spinal cord lesions extending over three or more vertebral segments during an acute attack of myelitis is helpful in differentiating this disorder from multiple sclerosis (MS), as are normal brain MRI findings in the early stages of NMOSD. When aquaporin-4 antibodies are detected, their specificity permits diagnosis in circumstances when the clinical diagnosis is less straightforward, such as in patients with a first event of transverse myelitis or in patients with atypical brain lesions. Detection of MOG antibodies is generally reliable in diagnosis of MOG associated disorders, as distinct from MS and NMOSD, but the serology is less specific when antibodies are detected in low titer and a combination of clinical, radiologic and serologic data is necessary to achieve a specific diagnosis in patients with low titer MOG antibodies.
Differential diagnosis
Differential diagnoses include MS; idiopathic, viral, paraneoplastic and connective tissue disease (e.g. SLE)-associated myelitis; ischemic and connective tissue associated optic neuropathies.
Genetic counseling
Fewer than 5% of individuals report relatives with NMOSD; polygenic inheritance is thought to be responsible for the small excess of familial cases relative to expected.
Management and treatment
Acute attacks are treated with high dose intravenous corticosteroids and if this fails, with plasma exchange. For patients with AQP4 antibodies, three agents are approved (in the USA and Europe) eculizumab, inebilizumab and satralizumab, and which reduce clinical attacks by 75-95%. Alternative maintenance treatments for patients with AQP4 antibodies or MOG antibodies are immunosuppressive drugs (e.g. azathioprine or mycophenolate mofetil), often combined with corticosteroids, or rituximab.
Prognosis
The prognosis is variable: patients may recover completely from individual attacks, but residual neurological deficits are common and sometimes severe. Unrecognized or untreated, up to 30% of patients may die in the first 5 years of their illness due to an attack of severe myelitis leading to respiratory failure. A high proportion of patients will become legally blind in one or both eyes and/or have substantial residual paraparesis. The prognosis for good recovery from attacks is much better for those with MOG antibodies compared to those with AQP4 antibodies.

                            Last update: 
                            July 2021


                            - Expert reviewer(s): 
                            Pr Brian WEINSHENKER