Neuromyelitis optica spectrum disorder overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Julinka Auta Fernandes
Overview
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease of the central nervous system (CNS) that mainly affects the optic nerves and spinal cord; the brainstem and other brain regions may also be involved.[1] Most patients have aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), which target a water-channel protein on astrocytes, supporting cells of the CNS.[2] It often begins in adulthood and predominantly affects women.[1] Coexisting autoimmune disorders may indicate a shared autoimmune predisposition.[3] The principal presentations are optic neuritis, acute myelitis, and area postrema syndrome, characterized by otherwise unexplained persistent nausea, vomiting, or hiccups.[4] Relapsing attacks can leave permanent visual impairment, limb weakness, sensory loss, and bowel or bladder dysfunction.[3] Diagnosis combines clinical findings, magnetic resonance imaging (MRI), and serum antibody testing.[5] Diagnostic requirements differ according to AQP4-IgG status, with stricter criteria for antibody-negative disease.[4] NMOSD is distinct from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).[6] Management focuses on prompt attack treatment and long-term immunotherapy to prevent relapses and limit disability.[5]
Historical Perspective
Discovery of a disease-specific serum autoantibody in 2004, subsequently shown to target aquaporin-4, helped distinguish NMOSD from MS. The 2015 international consensus criteria recognized a broader spectrum than combined optic nerve and spinal cord disease.[4]
Pathophysiology
In AQP4-IgG-positive NMOSD, antibody binding promotes complement-mediated inflammation and astrocyte injury. This can cause secondary demyelination, meaning loss of the protective myelin surrounding nerve fibers, and damage to neurons.[2]
Causes
AQP4-IgG is pathogenic in most patients. The underlying mechanisms in patients meeting NMOSD criteria who lack both AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G antibodies (MOG-IgG) remain uncertain.[2]
Classification
Published diagnostic criteria distinguish NMOSD with AQP4-IgG from NMOSD without AQP4-IgG or with unknown antibody status. Diagnosis in the latter groups requires more stringent clinical and imaging findings.[4]
Differential Diagnosis
MS and MOGAD are important differential diagnoses. MOGAD can also present with optic neuritis or myelitis but has distinct diagnostic criteria and should be identified separately.[6]
Epidemiology and Demographics
NMOSD is uncommon and often begins in adulthood. AQP4-IgG-positive disease predominantly affects women.[3] Children and older adults can also be affected.[3]
Risk Factors
Coexisting autoimmune disorders, including systemic lupus erythematosus and Sjögren's syndrome, suggest a shared autoimmune predisposition. Their presence does not exclude NMOSD.[3]
Screening
Antibody testing should be guided by compatible clinical presentations. Broad, unselected AQP4-IgG testing in otherwise typical MS is discouraged.[3]
Natural History, Complications and Prognosis
Recurrent attacks can leave substantial residual disability. Early recognition, prompt attack treatment, and effective relapse prevention improve outcomes.[1] AQP4-IgG-positive NMOSD usually follows a relapsing course, with disability accumulating mainly through incomplete recovery from attacks.[2] Gradual neurological progression independent of attacks is uncommon.[4]
Diagnosis
Diagnostic Study of Choice
Diagnosis integrates a compatible clinical syndrome, serum AQP4-IgG testing with a validated cell-based assay, MRI findings, and exclusion of alternative diagnoses.[5]
History and Symptoms
Optic neuritis causes visual loss; myelitis causes limb weakness, sensory changes, and bowel or bladder dysfunction. Area postrema syndrome and other brainstem, diencephalic, or cerebral presentations may also occur.[4]
Physical Examination
Assessment should include both eyes, visual acuity, pupillary responses, motor and sensory function, and bowel or bladder involvement. Findings depend on the location and severity of the attack.[3]
Laboratory Findings
Serum AQP4-IgG is the key diagnostic antibody. A negative result requires careful evaluation for alternative diagnoses.[5] Serum MOG-IgG testing helps identify MOGAD when the clinical presentation is compatible.[6]
Magnetic Resonance Imaging
MRI of the brain, optic nerves, and spinal cord supports diagnosis and helps distinguish competing disorders.[1] Spinal cord lesions extending over three or more vertebral segments are characteristic, although shorter lesions can occur.[4]
Other Diagnostic Studies
Lumbar puncture with cerebrospinal fluid (CSF) analysis helps assess inflammation and alternative diagnoses. CSF findings alone cannot establish or exclude NMOSD.[3]
Treatment
Medical Therapy
Acute attacks require prompt high-dose intravenous methylprednisolone. Plasma exchange should be used early for severe attacks or inadequate response to corticosteroids. Long-term treatment is individualized by antibody status, patient characteristics, and availability. Options for AQP4-IgG-positive disease include rituximab, inebilizumab, eculizumab, ravulizumab, and satralizumab.[5]
Secondary Prevention
Long-term immunotherapy should be offered after the first attack in AQP4-IgG-positive NMOSD to reduce further attacks and disability.[2]
References
- ↑ 1.0 1.1 1.2 1.3 dos Apóstolos-Pereira, SL; Damasceno, A; Piccolo, AC; et al. (2025). "2025 Brazilian guidelines for the management of neuromyelitis optica spectrum disorder in adults and children". Arquivos de Neuro-Psiquiatria. 83 (11): s00451812471. doi:10.1055/s-0045-1812471. PMID 41213657 Check
|pmid=value (help). - ↑ 2.0 2.1 2.2 2.3 2.4 Kümpfel, T; Giglhuber, K; Aktas, O; et al. (2024). "Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management". Journal of Neurology. 271 (1): 141–176. doi:10.1007/s00415-023-11910-z. PMID 37676297 Check
|pmid=value (help). - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Jarius, S; Aktas, O; Ayzenberg, I; et al. (2023). "Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis". Journal of Neurology. 270 (7): 3341–3368. doi:10.1007/s00415-023-11634-0. PMID 37022481 Check
|pmid=value (help). - ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Wingerchuk, DM; Banwell, B; Bennett, JL; et al. (2015). "International consensus diagnostic criteria for neuromyelitis optica spectrum disorders". Neurology. 85 (2): 177–189. doi:10.1212/WNL.0000000000001729. PMID 26092914.
- ↑ 5.0 5.1 5.2 5.3 5.4 Middle East and North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS): Yamout, B; Gouider, R; Al-Roughani, R; et al. (2026). "Consensus Recommendations for the Diagnosis and Treatment of Neuromyelitis Optica Spectrum Disorders (NMOSD): The MENACTRIMS Guidelines". CNS Drugs. 40 (3): 283–303. doi:10.1007/s40263-025-01260-x. PMID 41591715 Check
|pmid=value (help). - ↑ 6.0 6.1 6.2 Banwell, B; Bennett, JL; Marignier, R; et al. (2023). "Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria". The Lancet Neurology. 22 (3): 268–282. doi:10.1016/S1474-4422(22)00431-8. PMID 36706773 Check
|pmid=value (help).