Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica (NMO) and NMO spectrum disorders are inflammatory demyelinating diseases of the central nervous system characterized mainly by attacks of uni- or bilateral optic neuritis (ON) and acute myelitis.

Epidemiology

NMO has a worldwide distribution and estimated prevalence of 1-2/100,000.

Clinical description

Patients present with acute, often severe, attacks of blindness and paraparesis or quadriparesis, accompanied by sensory and sphincter impairments. Most patients have relapsing attacks (separated by months or years with partial recovery), with usually sequential index episodes of ON and myelitis. A relapsing course is more frequent in women, and nearly 90% of patients are female (typically late middle-aged). More rarely, the disease course is monophasic, with nearly simultaneous index 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 with NMO frequently have other systemic autoimmune disorders, such as systemic lupus erythematosus (SLE), Sjögren's syndrome or myasthenia gravis (see these terms).

Etiology

Etiology is unknown but NMO is believed to be an autoimmune disease associated with autoantibodies to aquaporin-4.

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 NMO. When aquaporin-4 antibodies are detected, their specificity allows diagnosis of NMO 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 (such patients are said to have NMO spectrum disorders). Asian opticospinal MS (OSMS) is a relapsing form of MS described in Japan that selectively targets the optic nerve and spinal cord. The presence of a long spinal cord lesion during acute attacks of myelitis is not required for diagnosis of Asian OSMS. many patients with this diagnosis have NMO and aquaporin-4 autoantibodies, but some are ultimately recognized as having prototypic MS.

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 (see these terms).

Management and treatment

Acute attacks are treated with high dose intravenous corticosteroids and if this fails, with plasma exchange. Long-term maintenance treatments are immunosuppressive drugs (azathioprine or mycophenolate mofetil), combined with corticosteroids in some patients, or rituximab therapy.

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 of 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 impact of early treatment with an effective long term agent is unknown, but current evidence suggests that the attack rate may be reduced by over 50% with effective immunosuppressive therapy.