Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare chronic inflammatory central nervous system (CNS) disorder that shares features of multiple sclerosis but is not the same. In 1894, Devic coined the french term “neuro-myélite optique aigu,” which can be interpreted as “neuromyelitis optica acuta.” Autoantibodies (Abs) against the astrocyte aquaporin-4 (AQP4) water channel are seen in most NMOSD cases, and patients often experience repeated episodes of severe optic neuritis and/or myelitis.1 Myelitis, severe optic neuritis, and attacks of persistent vomiting and hiccups (known as area postrema syndrome) are all characteristic symptoms of the condition that can assist doctors in diagnosis. Without treatment, almost half of NMOSD cases become blind and wheelchair-bound, and one-third die within 5 years of their initial attack.2
Incidence and Prevalence
NMOSD has a prevalence of 0.5 to 4 per 100,000, and it can be up to 10 per 100,000 in some racial groups. When compared to white individuals and other Asian races, East Asians have a greater prevalence of about 3.5 per 100,000. Other reported prevalences were 0.55 per 100,000 in New Zealand and Australia, 1.09 per 100,000 in Denmark, 0.89 per 100,000 in Catalonia, and 1.04 per 100,000 in Sweden. The annual incidence in white individuals is estimated to be between 0.5 and 0.8 per million.3
Clinically diagnosed patients with NMOSD may be grouped as having either AQP4-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, or double-seronegative disease.3 NMOSD, which includes optic neuritis, brain syndrome, and acute myelitis, is also divided into AQP4-antibody-seropositive and AQP4-antibody-seronegative disorders, allowing for early detection of patients. Seronegative NMOSD encompasses patients with MOG-antibody-seropositive disease and a clinical spectrum that is distinct from AQP4-antibody-seropositive NMOSD.4
The female-to-male ratio in AQP4-antibody-seropositive NMOSD is 9:1, and the average age of onset is 40 years. From a pathological basis, it is predominantly an astrocytopathic disorder rather than a demyelinating disorder. The female-to-male ratio in MOG-antibody disease is about 1:1, and the disease is more prevalent in children than in adults. Clinical signs resemble AQP4-antibody disease, however, there are variations as well.
In addition to optic neuritis and myelitis, other clinical phenotypes such as acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM), brainstem or cerebral cortical encephalitis, and cranial nerve involvement are also seen. Double (AQP4 and MOG antibodies)-seronegative disease remains unclear, necessitating more clinical and laboratory investigations before a definitive categorization can be made. 3
The key clinical manifestations of the disease can be identified from the sites of the CNS lesions (the optic nerves, spinal cord, area postrema, brainstem, diencephalon, and cerebrum). Bilateral optic neuritis affecting the optic chiasm with visual loss is the most common symptom of optic nerve involvement. A hallmark of spinal cord lesions is complete acute spinal cord syndrome. Area postrema syndrome is linked to severe nausea, vomiting, and hiccups. Narcolepsy, anorexia, abnormal diuresis, hypothermia, and hypersomnia are all symptoms of involvement of the diencephalon. Lastly, oculomotor problems, long tract signs, and ataxia are detected when the brainstem is involved.5
Seropositive and seronegative NMOSDs have different clinical symptoms and outcomes. Clinical attacks in patients with AQP4-immunoglobulin (Ig) G–seropositive disease are more severe, with a worse prognosis and higher relapse rate, than those in AQP4-IgG–seronegative individuals. Comorbidities in the form of autoimmune diseases are also more prevalent in seropositive disease, as is a higher female-to-male ratio.5
Serum antibody tests are the mainstay for diagnosis of NMOSD and MOG-encephalomyelitis (EM). Cell-based assays have the highest detection capability. The assays in NMOSD show a sensitivity between 80% and 100% and a specificity between 86% and 100%. On the other hand, enzyme-linked immunosorbent assay (ELISA) should not be used alone, as it can produce false-positive results. Children with ADEM show specific antibodies against MOG. CSF samples are not usually recommended for the detection of AQP4 or MOG antibodies because they do not appear to add to the diagnostic accuracy of NMOSD or MOG-EM. Around 70% of AQP4-Ab-seropositive individuals have AQP4-Abs in their CSF, while none of the AQP4-seronegative patients have any. Other laboratory investigations should be performed to rule out differential diagnoses and to diagnose concomitant autoimmune illnesses.1
An NMOSD attack is treated with high-dose steroids, usually 1 g of intravenous methylprednisolone per day for 5 days. Later, oral prednisolone (1 mg/kg) is given for weeks, gradually decreasing the dose over months.2
Mycophenolate mofetil (2–3 g/day) and azathioprine (2.5–3 mg/kg) are the most commonly prescribed first-line immunosuppressants for long-term treatment of NMOSD. Mycophenolate mofetil is found to be superior to azathioprine in terms of relapse rates as suggested by retrospective studies. Tocilizumab, methotrexate, cyclophosphamide, mitoxantrone, intravenous immunoglobulins, tacrolimus, and ciclosporin are other immunosuppressants that are rarely used. Immediate management of relapses with high-dose steroids with or without plasma exchange helps to achieve better outcomes.2
Three novel therapies, eculizumab, satralizumab, and inebilizumab, were found to be effective in preventing subsequent attacks, as observed in 4 randomized controlled studies.6
- Borisow N, Mori M, Kuwabara S, Scheel M, Paul F. Diagnosis and treatment of NMO spectrum disorder and MOG-encephalomyelitis. Front Neurol. 2018;9:888. doi:10.3389/fneur.2018.00888
- Huda S, Whittam D, Bhojak M, Chamberlain J, Noonan C, Jacob A. Neuromyelitis optica spectrum disorders. Clin Med (Lond). 2019;19(2):169-176. doi:10.7861/clinmedicine.19-2-169
- Hor JY, Asgari N, Nakashima I, et al. Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide. Front Neurol. 2020;11:501. doi:10.3389/fneur.2020.00501
- Fujihara K. Neuromyelitis optica spectrum disorders: still evolving and broadening. Curr Opin Neurol. 2019;32(3):385-394. doi:10.1097/WCO.0000000000000694
- Dutra BG, da Rocha AJ, Nunes RH, Maia ACM Jr. Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Radiographics. 2018;38(1):169-193. doi:10.1148/rg.2018170141
- Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol. 2021;20(1):60-67. doi:10.1016/S1474-4422(20)30392-6
Reviewed by Kyle Habet, MD, on 10/8/2021.