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

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.

🧠 Definition

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

🧪 Pathophysiology

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.

📊 Epidemiology

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

⚠️ Clinical Features

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

🧬 Diagnosis

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

💊 Treatment

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

🔁 Prognosis

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).

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