Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG+ NMOSD) [Neurosurgery Wiki]

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



<WRAP info>
**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.
</WRAP>

==== 🧠 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 ====
<WRAP round important 60%>
**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.)
</WRAP>

  * 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

<WRAP tip>
📌 **Key difference with MS**: NMOSD is antibody-mediated (astrocytopathy), while MS is primarily T-cell-mediated (oligodendropathy).
</WRAP>