Bit · Neuro
Multiple Sclerosis vs Neuromyelitis Optica vs ADEM
Three central demyelinating diseases that all give optic neuritis, weakness, or both. The pivot is antibody status, lesion distribution, and tempo (relapsing vs monophasic).
Mechanism
All three involve immune-mediated demyelination of CNS white matter. They differ in target antigen and clinical course:
- Multiple sclerosis (MS) — chronic autoimmune demyelination; T-cell mediated, with autoantibodies. Classic pattern is relapsing-remitting, with discrete attacks separated by remission, eventually transitioning to secondary progressive. Lesions disseminated in space (multiple CNS regions) AND time (different ages of lesions). MRI: periventricular plaques perpendicular to ventricles (Dawson's fingers), juxtacortical, infratentorial, spinal cord (short segments). CSF: oligoclonal bands, ↑ IgG index. Typical onset 20–40, female predominance, more common with northern latitude.
- Neuromyelitis optica spectrum disorder (NMOSD) — antibody against aquaporin-4 (AQP4-IgG) on astrocyte foot processes. Selectively attacks the optic nerve and spinal cord. Spinal lesions are longitudinally extensive (≥ 3 vertebral segments). Severe attacks; less responsive to MS therapies (and some MS drugs make it worse). MOG-antibody disease is a related entity now distinguished from NMOSD.
- Acute disseminated encephalomyelitis (ADEM) — a monophasic, post-infectious or post-vaccination demyelinating event. Mostly children, days after viral illness or vaccination. Multifocal brain involvement, encephalopathy is typical (unlike MS). MRI shows large, ill-defined lesions all at the same age. Usually does not recur.
Differentiator Table
| Multiple sclerosis | NMO spectrum disorder | ADEM | |
| Course | Relapsing-remitting → secondary progressive | Relapsing, severe attacks | Monophasic (rare recurrence) |
| Typical age | 20–40, female predominance | Adult, female predominance | Children, post-viral or post-vaccine |
| Antibody | Often no specific antibody; some have anti-MOG | AQP4-IgG (aquaporin-4) | Sometimes anti-MOG |
| Optic nerve involvement | Yes, unilateral typical | Yes, often bilateral, severe | Yes, often bilateral |
| Spinal cord lesions | Short segment (< 2 vertebral segments) | Longitudinally extensive (≥ 3 segments) | Variable |
| Brain MRI | Periventricular plaques (Dawson's fingers), juxtacortical, infratentorial | Often relatively spared early; periependymal involvement | Multifocal large hyperintensities, ALL same age |
| CSF | Oligoclonal bands +, ↑ IgG index | Oligoclonal bands usually NEGATIVE; AQP4-IgG + | Pleocytosis common; oligoclonal bands variable / often transient |
| Encephalopathy at onset | Uncommon | Uncommon | TYPICAL (children with confusion / coma) |
| Treatment of acute attack | High-dose IV steroids | High-dose IV steroids + plasma exchange; long-term: rituximab, eculizumab, others | High-dose IV steroids; IVIG / plasma exchange if severe |
| Long-term immunotherapy | Yes — disease-modifying therapies (interferons, glatiramer, fingolimod, ocrelizumab, etc.) | Yes — and beware: some MS drugs worsen NMO | Usually not needed (monophasic) |
The Pivot
Three questions tell you which one:
- Course — relapsing or monophasic? Monophasic (and the patient is a child after a viral illness with encephalopathy) → ADEM. Relapsing → MS or NMO.
- AQP4-IgG positive? → NMOSD.
- Spinal cord lesion length? Longitudinally extensive (≥ 3 segments) → NMO. Short segment → MS.
One trap: starting an MS drug (especially a sphingosine-1-phosphate modulator or some natalizumab patients) in an undiagnosed NMOSD patient can worsen disease.
NBME-Style Stem
A 34-year-old woman presents with simultaneous bilateral visual loss and paraparesis. MRI of the spinal cord shows a longitudinally extensive lesion spanning T2 through T8. Serum aquaporin-4 IgG is positive. CSF shows no oligoclonal bands. Which of the following is the most likely diagnosis?
Concept Anchor
MS is a chronic relapsing T-cell-driven demyelination scattered through the brain and short cord segments; NMO is an AQP4-antibody attack focused on optic nerve and long cord segments; ADEM is a one-off post-infectious storm in a child with encephalopathy. Antibody and lesion length are the two best splitters.