Neuromyelitis Optica (NMOSD)
[!WARNING] Medical Disclaimer: This content is for educational and informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional for diagnosis and treatment. Medical guidelines and best practices change rapidly; users should verify information with current local protocols.
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare, severe, autoimmune inflammatory disorder of the CNS. It primarily attacks the Optic Nerves and Spinal Cord.
Unlike Multiple Sclerosis (which is primarily a demyelinating disease), NMO is an Astrocytopathy caused by antibodies against the water channel Aquaporin-4 (AQP4).
Clinical Scenario: The Hiccupping Woman
A 35-year-old woman presents with 3 days of intractable hiccupping and nausea. A week later, she develops rapid onset bilateral visual loss and urinary retention.
Key Teaching Points
- **Diagnosis**: **NMOSD**.
- **Area Postrema Syndrome**: The hiccups/nausea are due to a lesion in the Area Postrema (medulla), which is rich in AQP4 channels.
- **Multi-focal**: Optic Nerve (blindness) + Spinal Cord (retention).
- **Caution**: Treating this as 'typical MS' with Interferon can worsen the disease.
Image Integration Plan
| Image Type | Source | Status |
|---|---|---|
| Management Algorithm | AI-generated | PENDING |
| MRI Spine (LETM) | Web Source | PENDING |
| Pathophysiology (AQP4) | AI-generated | PENDING |
| Fundoscopy (Optic Neuritis) | Web Source | PENDING |
[!NOTE] Image Generation Status: Diagrams illustrating the Astrocyte foot process attack are queued.
NMO vs MS
| Feature | NMOSD | Multiple Sclerosis (MS) |
|---|---|---|
| Antibody | Anti-AQP4 (70-80%) | None specific |
| MRI Spine | LETM (> segments long) | Short segments (<1 segment) |
| MRI Brain | Often Normal (or peri-ependymal) | Dawson's Fingers (Periventricular) |
| CSF | Pleocytosis (Neutrophils) | Oligoclonal Bands (>0%) |
| Course | Relapse = Severe/Permanent damage | Relapse = Often good recovery |
- Prevalence: 1-5 per 100,000 (Rarer than MS).
- Demographics: Female:Male ratio is extreme (9:1). Median age 40 (older than MS).
- Ethnicity: More common in Non-Caucasians (Asian, African, Caribbean).
- Anti-AQP4 Production: B-cells produce IgG1 autoantibodies against Aquaporin-4.
- Target: AQP4 channels are abundant on astrocyte foot processes at the Blood-Brain Barrier (BBB).
- Damage: Antibody binding -> Complement Activation (CDC) -> Astrocyte necrosis -> Secondary death of oligodendrocytes and neurons.
Image: Aquaporin-4 Pathophysiology
Image: Wingerchuk 2015 Criteria table
Attacks are usually severe and recovery is often poor.
- Eyes: Acuity (often <6/60). RAPD. Fundoscopy (Swollen disc or normal).
- Gait: Spastic paraparesis.
- Sensory: Defined sensory level on trunk.
- Serum Antibodies:
- Anti-AQP4 IgG (Cell-based assay): Highly specific (>99%). Positive in ~75% of patients.
- Anti-MOG IgG: If AQP4 negative. Suggests MOG-Antibody Disease (MOGAD).
- MRI:
- Spine: LETM (Indistinguishable signal abnormality extending over 3 or more vertebral segments).
- Brain: Usually non-specific. Lesions around 3rd/4th ventricle (high AQP4 expression).
Image: Optic Neuritis Fundus
Image: NMO vs MS MRI
- CSF:
- WCC >50 (Neutrophils/Eosinophils commonly present).
- Oligoclonal Bands usually negative (or transient).
- High protein.
The New Entity: MOG-Antibody Disease (MOGAD)
A third player has entered the game.
- Antibody: Anti-MOG (Myelin Oligodendrocyte Glycoprotein).
- Phenotype: Similar to NMO (Optic Neuritis + Myelitis).
- Differences:
- Often Bilateral optic neuritis (like NMO).
- Lower cord lesions (Conus Medullaris) are classic.
- Better Prognosis: Often monophasic (one attack only).
- Treatment: Responds well to Steroids/IVIG.
| Feature | MS | NMO | MOGAD |
|---|---|---|---|
| Ab Target | Unknown | Astrocytes (AQP4) | Oligodendrocytes (MOG) |
| Course | Relapsing-Remitting | Relapsing (Severe) | Often Monophasic |
| Recovery | Good initially | Poor | Good |
| MRI Brain | Dawson's Fingers | Normal/Postrema | ADEM-like (fluffy) |
A. Acute Relapse Protocol
Treat Aggressively - Time is function. "Time = Spine".
- IV Methylprednisolone: 1g daily for 5 consecutive days.
- Start immediately (do not wait for AQP4 results if criteria met).
- Plasma Exchange (PLEX):
- Indication: If no significant improvement after Day 3 of steroids, OR if attack is severe (blindness/paraplegia).
- Protocol: 5-7 cycles over 10-14 days.
- Effect: Removes circulating antibodies. Significantly improves recovery compared to steroids alone (Weinshenker et al).
B. Long-term Prevention (Immunosuppression)
Unlike MS, preventitive treatment is Mandatory indefinitely (relapses are too dangerous to risk).
- First Line:
- Rituximab (Anti-CD20): Depletes B-cells.
- Protocol: Induction (1g x 2) then maintenance every 6 months depending on CD19 counts.
- Azathioprine / Mycophenolate: Oral alternatives (slower onset, less effective than Rituximab).
- New Monoclonals (The "Mabs" for NMO):
- Eculizumab (Anti-C5): Blocks terminal complement (MAC). Shown to reduce relapse risk by 94% (PREVENT Trial). Requires Meningococcal Vaccine.
- Satralizumab (Anti-IL6 receptor): Reduces inflammation.
- Inebilizumab (Anti-CD19): B-cell depleter.
- Contraindicated (The "Do Not Use" List):
- Many MS drugs (Beta-Interferon, Fingolimod, Natalizumab, Alemtuzumab) can INCREASE disease activity in NMO.
- Mechanism: They typically boost antibody responses or shift T-cell balance in a way that fuels NMO.
- Permanent Blindness.
- Permanent Paraplegia: Wheelchair dependence.
- Respiratory Failure: If cervical cord lesion extends to medulla (C3/4/5).
- Worse than MS.
- Most disability comes from the attacks themselves (relapse-related stepwise accumulation) rather than secondary progression.
- 50% are blind in one eye or need a wheelchair within 5 years without treatment.
- With modern immunotherapy (Rituximab), relapse rates are reduced by >80%.
- IPND (International Panel for NMO Diagnosis) Criteria 2015.
- PREVENT Trial: Eculizumab in NMO.
What is NMO? It is an autoimmune disease where the body's immune system attacks the "water pipes" (Aquaporin channels) in the brain and spinal cord. It mainly affects the eyes (optic nerves) and the spine.
Is it MS? No. It used to be called "Optical-Spinal MS", but we now know it is a completely different disease. This is important because some MS drugs make NMO worse.
How serious is it? It is more aggressive than MS. A single attack can cause permanent blindness or paralysis if not treated immediately.
How is it treated?
- For attacks: Powerful steroids or plasma exchange (washing the blood) to stop the damage.
- For prevention: You need to take medication to suppress the immune system (like Rituximab) potentially for life, to stop the attacks coming back.
- Wingerchuk DM, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015.
- Pittock SJ, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019.
- Jacob A, et al. Neuromyelitis optica: a guide for the neurologist. Pract Neurol. 2013.