Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: Board Exam Study Guide
Key Distinguishing Features
Multiple Sclerosis (MS) - MRI Characteristics
Periventricular Lesions:
- MS lesions directly abut the lateral ventricles without intervening white matter, oriented perpendicular to ventricles ("Dawson's fingers") 1
- Ovoid/round shape, distributed asymmetrically along deep medullary veins 1
- Best visualized on T2-FLAIR sequences 1
- Must be ≥3 mm along main axis to count 1
Juxtacortical/Cortical Lesions:
- Touch the cortex directly without intervening white matter 1
- Involve U-fibers (spared in vascular disease) 1
- Can be intracortical, visible on specialized sequences (DIR, PSIR, MPRAGE) 1
Infratentorial Lesions:
- Peripheral pons location (not central) 1
- Middle and superior cerebellar peduncles frequently involved 1
- Cerebral peduncles and periaqueductal regions in midbrain 1
- Paramedian location in medulla oblongata 1
Spinal Cord Lesions:
- Multiple, short lesions (<3 vertebral segments) 1
- Cervical cord preferentially affected 1
- Peripheral cord location 1
Neuromyelitis Optica Spectrum Disorder (NMOSD) - MRI Characteristics
Brain Lesions (Red Flags for MS):
- Periaqueductal lesions around cerebral aqueduct 1
- Area postrema lesions (paired, discrete) in dorsal medulla adjacent to fourth ventricle 1
- Long lesions parallel to corpus callosum (not perpendicular) 1
- Pencil-thin periependymal lesions surrounding lateral ventricles 1
- Cloud-like, poorly marginated corpus callosum lesions with marbled pattern 1
- Diencephalic lesions 1
Spinal Cord Lesions:
- Longitudinally extensive transverse myelitis (LETM): ≥3 contiguous vertebral segments 1
- Central cord involvement 1
- May be contiguous with medullary lesions 1
Optic Nerve Lesions:
- Longitudinally extensive (>1/2 length of pre-chiasmal nerve) 1
- Perioptic gadolinium enhancement 1
- Bilateral simultaneous involvement possible 1
- Prominent papilledema/optic disc swelling 1
Clinical Presentations
MS Clinical Features
- Asymmetric neurological deficits 1
- Relapsing-remitting most common initial course 1
- CSF: Oligoclonal bands present in 59% 2
- Lower disability scores (median EDSS 2) 2
- Rare association with autoimmune diseases (6%) 2
NMOSD Clinical Features
- Area postrema syndrome: intractable vomiting and hiccoughs 1
- Severe attacks with higher disability (median EDSS 3.5) 2
- Frequent association with autoimmune diseases (19%) 2
- CSF: Oligoclonal bands only in 20% 2
- Neutrophilic pleocytosis or WCC >50/μL possible 1
- Severe visual deficit/blindness more common 1
- Permanent sphincter/erectile dysfunction after myelitis 1
Diagnostic Serology
NMOSD Antibody Testing
- AQP4-IgG: 67% positive in NMOSD, 0% in MS 2
- Cell-based assays are gold standard for AQP4-IgG detection 3
- For AQP4-IgG positive: only one core clinical characteristic required for diagnosis 1, 3
- For AQP4-IgG negative: more stringent criteria with additional neuroimaging findings required 1, 3
MOG-IgG Testing Indications 1
- Longitudinally extensive optic nerve lesions
- Simultaneous bilateral optic neuritis
- ADEM-like presentations
- Fluffy, cloud-like brainstem lesions (especially fourth ventricle/cerebellar peduncles)
- Disease flare-ups after interferon-beta or natalizumab
- Steroid-dependent symptoms
- Must use cell-based assays with conformationally intact MOG 1
Critical Differential Diagnosis Pitfalls
Common Misdiagnosis Errors 1
- Counting paraventricular lesions (separated from ventricle by white matter) as periventricular
- Mistaking periventricular "capping" (age-related) for MS lesions
- Counting lesions <3 mm in diameter
- Including symmetric periventricular banding/halo as MS lesions
Red Flags Against MS Diagnosis 1
- Lacunar infarcts or microbleeds (vascular disease)
- Symmetric, confluent white matter abnormalities (leukodystrophy)
- Symmetric central pontine lesions (small vessel disease)
- Temporal pole predominance (CADASIL/CARASIL)
- Rounded central corpus callosum "snowball" lesions (Susac syndrome)
Treatment Principles
MS Treatment 1
- Intermediate-intensity conditioning for AHSCT: BEAM-ATG or cyclophosphamide-ATG recommended 1
- Low-intensity regimens (low-dose cyclophosphamide without serotherapy) not recommended 1
- High-intensity myeloablative protocols only in specialized centers 1
NMOSD Attack Treatment 4
- High-dose intravenous methylprednisolone as first-line
- Plasma exchange or immunoadsorption for severe/refractory attacks 1, 4
- Must initiate within hours for myelitis to prevent permanent deficit 1
- Anticoagulation if antiphospholipid antibodies present 1
NMOSD Prevention 4, 5
- Four approved therapies for AQP4-IgG positive NMOSD: eculizumab, ravulizumab, inebilizumab, satralizumab 4
- Rituximab remains mainstay for both AQP4-IgG positive and negative NMOSD 4
- Cyclophosphamide-based conditioning with rituximab for AHSCT in NMOSD 1
- Avoid interferon-beta and natalizumab (may worsen disease) 1
Critical Treatment Considerations
- NMOSD: frequent flare-ups after steroid cessation require careful tapering 1
- 50-60% relapse rate during corticosteroid dose reduction in NMOSD myelitis 1
- Delay >2 weeks in treatment initiation associated with severe neurological deficit 1
Prognosis Factors
NMOSD Poor Prognostic Indicators 1
- Extensive spinal cord MRI lesions
- Reduced muscle strength at presentation
- Sphincter dysfunction at presentation
- Antiphospholipid antibodies
- Delay in therapy initiation (>2 weeks)
Radiologically Isolated Syndrome (RIS) 1
- One-third develop symptoms within 5 years
- Gadolinium-enhancing lesions predict clinical evolution
- Asymptomatic spinal cord lesions predict clinical attacks
- Younger age, male sex, abnormal VEPs increase risk