Multiple Sclerosis: McDonald Criteria, MRI Findings & DMT

Creator: Progress Note
Published: 2026-07-22
Keywords: multiple sclerosis diagnosis treatment, multiple sclerosis McDonald criteria, MS demyelination symptoms, Dawson's fingers MS MRI, optic neuritis multiple sclerosis, MS disease modifying therapy

The 60-second version

MS: autoimmune demyelination of CNS oligodendrocytes; predominantly young women; RRMS is most common subtype
Classic presentations: optic neuritis (painful monocular vision loss), bilateral INO in young woman, Lhermitte's sign, Uhthoff's phenomenon
MRI: Dawson's fingers (periventricular plaques perpendicular to corpus callosum on FLAIR sagittal); OCBs in CSF
McDonald criteria: DIS + DIT required; gadolinium-enhancing + non-enhancing lesions simultaneously = DIT
Acute relapse: IV methylprednisolone; long-term: DMTs (interferon/glatiramer first-line; natalizumab/ocrelizumab high-efficacy)

Pathophysiology, Subtypes, and Clinical Presentation

**Pathophysiology**: T-cell mediated autoimmune attack on CNS myelin (oligodendrocytes). Plaques form in white matter (periventricular, corpus callosum, juxtacortical, infratentorial, spinal cord). Inflammatory demyelination → slowed/blocked conduction → symptoms. Remyelination during recovery (incomplete over time). Heat sensitivity (Uhthoff's phenomenon): transient worsening of symptoms with increased body temperature (exercise, hot bath) — due to heat-induced conduction block in demyelinated axons; NOT a new attack/relapse. **Subtypes**: Relapsing-Remitting MS (RRMS, 85%): episodic attacks with complete/partial recovery between relapses. Primary Progressive MS (PPMS, 10–15%): gradual neurological decline from onset without relapses. Secondary Progressive MS: RRMS → progressive decline with or without relapses. **Classic presentations**: Optic neuritis (most common first presentation) — monocular painful vision loss, reduced color saturation, central scotoma, afferent pupillary defect (RAPD/Marcus Gunn pupil); 50% of optic neuritis patients develop MS. Internuclear ophthalmoplegia (INO) — demyelination of medial longitudinal fasciculus (MLF) → ipsilateral adduction failure + contralateral nystagmus; bilateral INO in a young woman = MS until proven otherwise. Trigeminal neuralgia in a young person. Lhermitte's sign: electric shock sensation down spine with neck flexion (posterior column demyelination in cervical spinal cord). Uhthoff's phenomenon (heat sensitivity). Bladder/sexual/bowel dysfunction.

Diagnosis: McDonald Criteria and MRI

**McDonald Criteria (2017)**: requires demonstration of CNS demyelination disseminated in space (DIS) AND time (DIT). **DIS** (≥2 of 4 MS-typical locations): periventricular, cortical/juxtacortical, infratentorial, spinal cord. **DIT**: ≥2 attacks separated in time, OR gadolinium-enhancing AND non-enhancing lesions simultaneously (enhancing = active, non-enhancing = older), OR new T2 lesion on follow-up MRI. **MRI findings**: Periventricular plaques (most specific location, oval/finger-shaped perpendicular to corpus callosum = **'Dawson's fingers'** on sagittal FLAIR MRI). T2/FLAIR: demyelinated white matter appears bright. Gadolinium enhancement: active lesions (breakdown of blood-brain barrier during active inflammation). **CSF findings**: Oligoclonal bands (IgG OCBs in CSF but not serum, in 90% of MS — not pathognomonic). Increased IgG index. Myelin basic protein elevated during attacks. **VEPs (visual evoked potentials)**: prolonged P100 latency (slowed optic nerve conduction) — useful for subclinical optic neuritis. Differential: NMO spectrum disorder (NMOSD — AQP4-IgG antibody, bilateral optic neuritis, longitudinally extensive transverse myelitis >3 vertebral segments — does NOT respond to MS DMTs).

Acute Exacerbation Treatment and Disease-Modifying Therapy

**Acute relapse treatment**: IV methylprednisolone 1 g/day × 3–5 days — shortens duration of attacks but does NOT change long-term outcome. Plasma exchange for severe steroid-refractory attacks. **Disease-Modifying Therapies (DMTs) for RRMS**: Goal is reducing relapse rate, new MRI lesions, and disability progression. First-line (moderate efficacy): Interferon-beta (IFN-β1a/1b — Avonex, Betaseron, Rebif) — SQ/IM injection; glatiramer acetate (Copaxone) — daily SQ injection, no significant side effects; teriflunomide (oral, teratogenic); dimethyl fumarate (Tecfidera, oral). High-efficacy agents: Natalizumab (Tysabri) — anti-VLA-4 integrin, prevents lymphocyte entry into CNS; risk of PML (progressive multifocal leukoencephalopathy from JC virus reactivation — check JC antibody index); ocrelizumab (anti-CD20, also approved for PPMS); alemtuzumab (most potent, reserved for aggressive disease); cladribine. **PPMS treatment**: Ocrelizumab is the only approved DMT for PPMS. **Key principles**: Start DMT early after diagnosis; escalate if breakthrough disease on first-line therapy; monitor MRI 6–12 months on therapy.

Test yourself

Quick check — 3 questions

1. A 28-year-old woman develops painful monocular vision loss in her right eye over 3 days with reduced color vision and a central scotoma. Fundoscopy is normal acutely. MRI brain shows 3 periventricular T2 lesions, two of which are gadolinium-enhancing. What is the diagnosis and appropriate next step?

2. A 32-year-old woman with RRMS has breakthrough relapses (2 relapses in past year) on interferon-beta therapy. MRI shows 4 new T2 lesions. What is the most appropriate next step?

3. An MRI in sagittal FLAIR sequence shows oval white matter lesions perpendicular to the corpus callosum, appearing like fingers projecting from it. This finding is most consistent with:

Frequently asked questions

What is internuclear ophthalmoplegia (INO) and why is bilateral INO pathognomonic for MS?

INO is caused by a lesion in the medial longitudinal fasciculus (MLF), which coordinates conjugate horizontal gaze. A MLF lesion causes: ipsilateral adduction failure (the adducting eye can't cross midline on lateral gaze) + contralateral nystagmus (the abducting eye over-beats to compensate). The affected eye can still converge (convergence pathway is separate from horizontal gaze pathway). Bilateral INO in a young woman is nearly pathognomonic for MS, as vascular lesions rarely affect both MLFs simultaneously.

What is PML and which MS drug causes it?

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating CNS infection caused by JC polyomavirus reactivation in immunocompromised patients. Natalizumab (anti-VLA-4) prevents lymphocyte CNS trafficking, creating CNS immunosuppression. JC virus can reactivate and cause PML in natalizumab-treated patients, particularly with high JC antibody index (>0.9) and prior immunosuppressant use. Risk stratification: JC antibody serology every 6 months; consider switching if JC index rises. Fingolimod and dimethyl fumarate can also rarely cause PML.

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