Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy, usually due to antibodies against aquaporin 4 (AQP4 IgG).

• Prevalence is 1 to 10 per 100,000, more common in women (9:1) and in Asian and Black populations.

• AQP4 IgG positive in 70 to 80%; the rest are MOG positive (separate entity) or double seronegative.

• Associations: Sjögren, SLE, myasthenia, thymoma, paraneoplastic disease.

• Attacks cause cumulative disability; untreated, a majority become blind or wheelchair bound within 5 years.

• Severe optic neuritis (often bilateral), longitudinally extensive transverse myelitis (3 or more vertebral segments), area postrema syndrome (intractable hiccups, nausea, vomiting), brainstem syndrome, diencephalic syndrome, cerebral syndrome.

• Painful tonic spasms, neuropathic pain.

• Relapsing in 90%, with poor recovery from each attack.

• AQP4 IgG by cell based assay (not ELISA) in serum; test before plasma exchange or rituximab.

• Core clinical syndrome plus exclusion of alternatives. Seronegative requires two core features, including optic neuritis, longitudinal myelitis or area postrema syndrome.

• MRI spine (central cord lesion over 3 segments), MRI brain, orbit MRI (long optic nerve lesion, chiasm).

• CSF: pleocytosis (often neutrophils), oligoclonal bands in minority. OCT for retinal damage.

• Screen ANA, ENA, anti-Ro, thyroid antibodies, hepatitis B and TB before immunotherapy.

Acute attack

• Methylprednisolone 1 g IV daily for 5 days; early plasma exchange (5 to 7 exchanges) or immunoadsorption for severe attacks or poor response, ideally within days.

Prevention (start after first attack; lifelong)

• Satralizumab 120 mg SC at weeks 0, 2, 4 then every 4 weeks (IL-6 receptor).

• Eculizumab 900 mg IV weekly for 4 doses then 1200 mg every 2 weeks, or ravulizumab (complement C5). Meningococcal vaccination required.

• Inebilizumab 300 mg IV on days 1 and 15 then every 6 months (anti CD19).

• Rituximab 1 g on days 1 and 15 then every 6 months, or mycophenolate mofetil 1 to 1.5 g twice daily, azathioprine 2 to 3 mg/kg with prednisolone 10 mg to bridge.

• Avoid interferon beta, natalizumab, fingolimod, alemtuzumab (worsen NMOSD).

• Symptomatic: tonic spasms (carbamazepine 100 to 200 mg), pain, spasticity, bladder.

• Bone protection, Pneumocystis prophylaxis while on high dose immunosuppression.

• Pregnancy: rituximab or azathioprine can be continued; relapse risk rises postpartum.