Neuromyelitis OpticaEdit

Neuromyelitis optica (NMO), more broadly termed neuromyelitis optica spectrum disorder (NMOSD), is a rare autoimmune disease of the central nervous system that primarily targets the optic nerves and the spinal cord. Once thought to be a variant of multiple sclerosis, NMOSD is now considered a distinct clinical and immunological entity, especially in light of discoveries around aquaporin-4 (AQP4)–directed antibodies and characteristic disease patterns. The illness tends to present with discrete relapses that cause focal neurological deficits, and without effective treatment it can lead to significant residual disability from optic neuritis and transverse myelitis. The landscape of NMOSD has evolved to include antibody testing, refined imaging, and targeted therapies that reduce relapses and improve outcomes, but access to testing and modern treatments remains uneven in parts of the world.

NMOSD is not a single uniform disease but a spectrum. A substantial portion of patients test positive for antibodies against aquaporin-4 (AQP4-IgG), which helps define the disease mechanism as an autoimmune attack on water channels located on astrocytes. A proportion of patients are AQP4-IgG negative yet have other antibodies, most notably those directed against myelin oligodendrocyte glycoprotein (MOG-IgG), which may define a related but distinct immunological subset. In clinical practice, distinguishing NMOSD from related demyelinating diseases such as multiple sclerosis (MS) is important because the treatment approach and prognosis differ. See aquaporin-4 and myelin oligodendrocyte glycoprotein for related molecular targets, and see optic neuritis and transverse myelitis for the main clinical manifestations associated with NMOSD.

Pathophysiology

The core of NMOSD involves autoimmune injury to astrocytes due to antibodies that recognize aquaporin-4, a water channel densely expressed on the endfeet of astrocytes in the blood-brain barrier. When AQP4-IgG binds to these channels, complement-mediated cytotoxicity and inflammatory cascades contribute to breakdown of the blood-brain barrier and subsequent injury to surrounding neural tissue. The primary astrocyte damage disrupts nearby oligodendrocytes and myelin, leading to demyelination and loss of neural function in affected tracts. The complement system plays a central role in mediating tissue injury, and some therapies aim to interrupt this process. See complement system for background on this mechanism and astrocyte to learn more about the cell type involved.

On the spectrum, some patients have disease features driven by other immune pathways, and MOG-IgG-associated disease represents a related, but distinct, immunopathology with different clinical patterns and responses to therapy. See myelin oligodendrocyte glycoprotein for more. In addition to optic nerve and spinal cord involvement, NMOSD can produce brainstem and diencephalic symptoms in a subset of patients, reflecting the broader pattern of CNS involvement seen in some cases. See neuromyelitis optica spectrum disorder for broader context.

Clinical features

Recurrent optic neuritis: episodes of painful vision loss, often severe, which may affect one or both eyes over time.
Longitudinally extensive transverse myelitis (LETM): spinal cord inflammation spanning three or more vertebral segments, producing bilateral weakness or sensory loss, bladder dysfunction, or paralysis depending on the region affected.
Area postrema syndrome: intractable hiccups, nausea, or vomiting from lower brainstem involvement.
Other brainstem and diencephalic manifestations: clinical signs such as intractable vertigo, intractable nausea, or autonomic symptoms in some patients.

The disease pattern is typically relapsing, and relapses can accumulate disability if not promptly treated. The clinical presentation and trajectory differ from classic MS, which more often shows non-longitudinal spinal cord lesions and different MRI patterns. See optic neuritis and transverse myelitis for the characteristic features of related conditions.

Diagnosis

Serology: testing for AQP4-IgG by a cell-based assay is a foundational test; positive results strongly support NMOSD in the appropriate clinical context. A subset of patients may be AQP4-IgG negative but harbor MOG-IgG; testing for MOG-IgG helps refine the diagnosis in those cases. See aquaporin-4 and myelin oligodendrocyte glycoprotein.
Imaging: MRI of the brain, orbits, and spinal cord often shows characteristic findings. Spinal cord lesions that extend over multiple segments (LETM) are common; optic nerve involvement may accompany optic neuritis. Brain MRI can be normal or show lesions that differ from typical MS patterns.
Diagnostic criteria: contemporary criteria for NMOSD emphasize core clinical characteristics (optic neuritis, LETM, area postrema syndrome, etc.) in combination with AQP4-IgG status, while acknowledging MOG-IgG–associated disease as a related entity. See diagnostic criteria and neuromyelitis optica spectrum disorder for the broader framework.
Differential diagnosis: MS, MOG-IgG–associated disease, other inflammatory or infectious myelitis and optic neuropathies. Distinguishing these conditions is crucial because treatment strategies differ.

Treatment

Acute attacks

High-dose intravenous corticosteroids (for example, methylprednisolone) are standard initial therapy to shorten attacks and limit damage.
Plasma exchange (apheresis) is commonly used when steroids fail to halt an attack or when the attack is particularly severe.
Prompt treatment of acute relapses is important because accumulated disability is driven by repeated inflammatory events. See plasma exchange and methylprednisolone.

Long-term immunotherapy (relapse prevention)

Traditional immunosuppressants: azathioprine and mycophenolate mofetil have been used to reduce relapse rates in NMOSD.
B-cell–targeted therapy: rituximab has shown effectiveness in reducing relapses by depleting B cells that produce pathogenic antibodies. See rituximab.
Anti-complement therapy: eculizumab, a C5 inhibitor, reduces relapses in AQP4-IgG–positive NMOSD and represents a targeted approach based on disease mechanism. See eculizumab.
Anti–interleukin-6 therapy: satralizumab blocks the IL-6 receptor and has demonstrated relapse reduction in NMOSD, including in patients who are AQP4-IgG positive. See satralizumab.
Considerations for MOG-IgG–associated disease: treatment choices may differ, and management is tailored to the underlying immunopathology. See myelin oligodendrocyte glycoprotein.

The choice of therapy depends on antibody status, prior relapse history, comorbidities, and access to medications. Cost, monitoring requirements, and infection risk (for example, with potent immunosuppressants or complement inhibitors) are important practical considerations. See immunotherapy for a broader discussion of strategies in autoimmune CNS diseases.

Prognosis and disease course

NMOSD is typically more relapsing and may be more disabling than classic MS if relapses are not adequately controlled. Early initiation of effective relapse-prevention therapy substantially improves long-term outcomes by reducing the frequency and severity of attacks. However, even with modern therapies, residual deficits from optic neuritis or spinal cord injury can persist after relapses. Ongoing monitoring and adjustment of treatment plans are common as new therapies become available. See prognosis and relapse for related concepts.

Epidemiology

NMOSD is a rare condition worldwide, with a higher incidence in women and variable geographic distribution. The discovery of AQP4-IgG antibodies has helped clarify prevalence estimates and improved diagnostic accuracy. Access to testing and targeted therapies varies by region, influencing both reported incidence and outcomes. See epidemiology for broader context on demyelinating diseases.

History

The condition was historically called Devic’s syndrome in reference to the early description of simultaneous optic neuritis and myelitis. The 2000s brought recognition that a substantial subset of patients carried antibodies against aquaporin-4, leading to the umbrella term NMOSD to reflect the broader spectrum of disease. Subsequent work expanded understanding to include AQP4-IgG–negative NMOSD and MOG-IgG–associated disease, refining diagnostic criteria and treatment approaches. See history of neuromyelitis optica for a concise chronology.