(See also Overview of Demyelinating Disorders.)
Neuromyelitis optica spectrum disorder causes acute optic neuritis, sometimes bilateral, plus demyelination of the cervical or thoracic spinal cord. It was previously considered to be a variant of multiple sclerosis (MS) but is now recognized as a different disorder.
In neuromyelitis optica spectrum disorder, the immune system targets aquaporin 4, a protein that is present on astrocytes in the brain and particularly the spinal cord and optic nerves, and possibly other targets. Astrocytes are damaged by autoimmune-mediated inflammation as well as demyelination.
Symptoms of neuromyelitis optica spectrum disorder include visual loss, muscle spasms, paraparesis or quadriparesis, and incontinence.
Specific characteristic presentations include
Severe bilateral optic neuritis that involves the optic chiasm, causing loss of vision in the horizontal half of the visual field (altitudinal visual field defect) or loss of acuity (20/200 or worse)
A complete spinal cord syndrome, particularly with paroxysmal tonic spasms
An area postrema syndrome, causing intractable hiccups or nausea and vomiting (the area postrema is a structure that controls vomiting and is located on the floor of the 4th ventricle)
Acute transverse myelitis extending over ≥ 3 contiguous spinal cord segments
Diagnosis of neuromyelitis optica spectrum disorder usually includes brain and spinal cord MRI and visual evoked potentials (1).
The following features help distinguish neuromyelitis optica from multiple sclerosis (MS):
Neuromyelitis optica affects several (typically ≥ 3) contiguous spinal segments of the spinal cord, whereas MS typically affects a single segment.
On MRI, cerebral white matter lesions are uncommon in neuromyelitis optica, unlike in MS.
On MRI, morphology and distribution of the lesions differ from those in MS.
Visual evoked potentials can help differentiate neuromyelitis optica from other optic neuropathies. Findings in neuromyelitis optica spectrum disorder include reduced amplitudes or prolonged latencies. This test is also useful for detecting clinically inapparent damage before symptoms develop.
Blood tests to measure an IgG antibody specific for neuromyelitis optica spectrum disorder (aquaporin-4 antibody [also known as NMO-IgG]) may be done to differentiate it from MS. Anti-MOG (myelin oligodendrocyte glycoprotein) antibodies identify a subset of patients who have neuromyelitis optica spectrum disorder and who appear to have different clinical features, fewer exacerbations, and better recovery than patients with aquaporin-4 antibodies or with neither antibody.
1. Wingerchuk DM, Banwell B, Bennett JL, et al: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85 (2):177–189, 2015. doi: 10.1212/WNL.0000000000001729 Epub 2015 Jun 19
There is no cure for neuromyelitis optica. However, treatment can prevent, slow, or decrease the severity of exacerbations.
Eculizumab, a C5 complement inhibitor, is approved for the treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Adverse effects include respiratory infections, headache, and pneumonia and may be significant; thus, patients should be closely monitored (1) Because one patient developed meningococcal sepsis, vaccination for meningococcus is required before initiating therapy.
Satralizumab (a monoclonal antibody that targets the interleukin-6 receptor) and inebilizumab (a monoclonal antibody that targets CD19 on B-cells) were recently approved for the treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Patients should be closely monitored for infections such as urinary tract and respiratory infections.
Methylprednisolone and azathioprine are often used together. Plasma exchange may help people who do not respond to corticosteroids.
Rituximab, an anti–B-cell antibody, has been shown to reduce relapses in a double-blind, placebo-controlled trial (2). Other immunomodulatory and immunosuppressive therapies are sometimes used.
Natalizumab and fingolimod appear ineffective and may be harmful.
Treatment of symptoms is similar to that for MS. Baclofen or tizanidine may relieve muscle spasms.
1. Pittock SJ, Berthele A, Fujihara K, et al: Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med 381 (7):614–625, 2019. doi: 10.1056/NEJMoa1900866 Epub 2019 May 3
2. Tahara M, Oeda T, Okada K, et al: Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): A multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 19 (4):298–306, 2020. doi: https://doi.org/10.1016/S1474-4422(20)30066-1
Neuromyelitis optica spectrum disorder causes demyelination, typically with antibodies to aquaporin-4 or myelin oligodendrocyte glycoprotein.
Typical symptoms include visual loss, muscle spasms, paraparesis or quadriparesis, and incontinence.
Diagnose neuromyelitis optica spectrum disorder using brain and spinal cord MRI and visual evoked potentials.
Treatments include corticosteroids and immunomodulatory or immunosuppressive treatments (eg, eculizumab, rituximab).