Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG+ NMOSD)

AQP4-IgG+ NMOSD is a severe autoimmune disease of the CNS, distinct from multiple sclerosis, characterized by relapsing inflammation mainly of the optic nerves and spinal cord.

NMOSD is defined by the presence of serum antibodies against aquaporin-4 (AQP4-IgG) and clinical episodes of demyelination involving:

Optic neuritis
Longitudinally extensive transverse myelitis (LETM)
Area postrema syndrome
Brainstem or cerebral syndromes

AQP4 is a water channel protein expressed on astrocytes in the CNS.
AQP4-IgG is pathogenic, causing complement-mediated astrocytic damage.
This leads to secondary demyelination and neuronal loss.

Strong female predominance (≈9:1)
Onset: typically between 30–50 years
More common in non-Caucasian populations

Optic neuritis – often bilateral, severe, incomplete recovery
LETM – spinal cord lesions ≥3 vertebral segments
Area postrema syndrome – nausea, vomiting, hiccups
May include brainstem and cerebral involvement

2015 IPND diagnostic criteria (for AQP4-IgG+ patients):

≥1 core clinical characteristic (e.g., optic neuritis, LETM, area postrema)
Positive AQP4-IgG (preferably by cell-based assay)
Exclusion of alternative diagnoses (MS, MOGAD, sarcoidosis, etc.)

MRI:
- Spinal cord: LETM
- Brain: lesions in hypothalamus, area postrema, periependymal regions

Acute Management

IV methylprednisolone 1g/day for 3–5 days
Plasma exchange (PLEX) if inadequate response

Maintenance Therapy

Monoclonal antibodies:
- Rituximab (anti-CD20)
- Eculizumab (anti-C5)
- Satralizumab (anti-IL6R)
- Inebilizumab (anti-CD19)
Conventional immunosuppressants:
- Azathioprine
- Mycophenolate mofetil

Untreated: high risk of permanent disability or death
With early immunosuppression:
- Significant reduction in relapse rate
- Potential preservation of neurological function

📌 Key difference with MS: NMOSD is antibody-mediated (astrocytopathy), while MS is primarily T-cell-mediated (oligodendropathy).