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9 notes available
1 Last Minute Review 2 Multiple Sclerosis 3 Disease-Modifying Therapies 4 NMOSD & MOGAD 5 Systemic Diseases 6 Autoimmune Encephalitis 7 Paraneoplastic Syndromes 8 CNS Vasculitis 9 Other Neuroimmunology Topics
Clinical › Immunology

Multiple Sclerosis

Multiple Sclerosis

What You'll Learn

  • McDonald 2017 criteria (RITE/board standard): diagnosis requires dissemination in space (DIS: ≥2 of 4 CNS regions — periventricular, cortical/juxtacortical, infratentorial, spinal cord) AND dissemination in time (DIT: simultaneous Gd+ and non-enhancing lesions, new lesions on follow-up, OR CSF-specific OCBs). McDonald 2024 revisions (now the current criteria; 2017 remains common exam terminology): optic nerve added as a 5th DIS region (via MRI orbits, OCT, or VEP); supportive diagnostic biomarkers now include central vein sign, paramagnetic rim lesions, and CSF kappa free light chains; RIS may qualify as MS only when DIS is met with additional supportive evidence and no better alternative.
  • Subtypes: CIS → RRMS (85%) → SPMS; PPMS (10–15%) is primary progressive from onset; Lublin 2014 adds active/inactive and progressing/not progressing modifiers
  • Classic presentations: optic neuritis (painful vision loss, RAPD), INO (MLF lesion), partial transverse myelitis, Lhermitte sign, Uhthoff phenomenon
  • MRI hallmarks: periventricular Dawson fingers, ovoid lesions perpendicular to ventricles, open ring enhancement, central vein sign, short spinal cord lesions (<2 vertebral segments)
  • CSF: ≥2 oligoclonal bands unique to CSF (85–95%); elevated IgG index; CSF-specific OCBs can substitute for DIT in McDonald 2017
  • Acute relapses: IV methylprednisolone 1 g/day × 3–5 days; PLEX for steroid-refractory relapses; oral prednisone alone is NOT recommended for optic neuritis
  • Prognosis: favorable — young onset, female, sensory/ON presentation, RRMS; poor — male, older onset, motor/cerebellar symptoms, PPMS, high lesion burden
HighYield Pearls
  • McDonald 2017 criteria: diagnosis requires DIS (≥2 of 4 CNS regions: periventricular, cortical/juxtacortical, infratentorial, spinal cord) AND DIT (simultaneous Gd+ and non-enhancing lesions, OR new lesion on follow-up MRI). CSF-specific OCBs can substitute for DIT when DIS is met but DIT is not yet demonstrated.
  • Lhermitte sign (electric shock down spine with neck flexion → cervical dorsal column plaque) and Uhthoff phenomenon (transient worsening with heat/exercise/fever — 0.5°C drop in conduction) are classic MS pearls; both are demyelination phenomena, not relapses, and do NOT require treatment escalation.
  • Internuclear ophthalmoplegia (INO): impaired adduction of ipsilateral eye with nystagmus of contralateral abducting eye on lateral gaze — bilateral INO in a young woman is MS until proven otherwise; lesion in MLF between CN III and CN VI nuclei.
  • Optic neuritis: painful monocular vision loss with RAPD, dyschromatopsia, central scotoma. If pain is absent (“atypical optic neuritis,” AON), suspect NMOSD (AQP4) or MOGAD — check serum AQP4-IgG and MOG-IgG before calling it MS. Bilateral simultaneous ON, severe vision loss (<20/200), longitudinally extensive optic nerve enhancement, or chiasmal involvement also favor NMO/MOG.
  • 6 MRI lesion features to memorize: (1) periventricular ovoid Dawson fingers perpendicular to ventricles, (2) juxtacortical/cortical lesions (highly MS-specific), (3) infratentorial (pons/cerebellar peduncles), (4) short spinal cord lesions <2 vertebral segments, (5) T1 black holes (chronic axonal loss), (6) Gd-enhancing lesions = active inflammation. Contrast with NMO/MOG: LETM ≥3 vertebral segments, area postrema lesions, large fluffy MOG brainstem/ADEM-like lesions.
  • Highly active MS → high-efficacy DMT early: B-cell depletion (ocrelizumab, ofatumumab, rituximab) or natalizumab (anti-VLA-4). Natalizumab + JCV seropositivity → PML risk rises sharply after 2 years and with prior immunosuppression; monitor JCV antibody index every 6 months and surveillance MRI. Ocrelizumab is the only DMT approved for PPMS.
  • Pregnancy and MS: relapse rate decreases ~70% in third trimester (Th2 shift) and rebounds in the first 3 months postpartum. Safer options peri-conception: glatiramer acetate and interferon-β (compatible with pregnancy and breastfeeding); natalizumab can be continued in selected high-activity patients through early pregnancy; avoid teriflunomide (teratogenic — cholestyramine washout required), fingolimod, and cladribine.
  • PML vs PPMS — do NOT confuse: PML = progressive multifocal leukoencephalopathy (JC virus reactivation, subcortical confluent non-enhancing T2 lesions crossing U-fibers, seen with natalizumab/fingolimod/rituximab); PPMS = primary progressive MS (steady neurologic decline from onset, no relapses, often myelopathy in older male). New non-enhancing subcortical T2 lesion in a natalizumab patient → stop drug, do CSF JCV PCR.
  • Tumefactive MS and Marburg variant: tumefactive = single large (>2 cm) ring-enhancing lesion with open (incomplete) ring enhancement open toward cortex, vasogenic edema, mass effect — mimics tumor/abscess; biopsy shows demyelination with macrophages. Marburg variant = fulminant monophasic MS, rapid progression to death within weeks/months; treat aggressively with IV steroids, PLEX, and induction immunotherapy.
  • Pediatric MS: <18 years, ~3–5% of MS; higher relapse rate but slower disability accrual; large T2 lesions and posterior fossa involvement are common; must exclude ADEM (monophasic, encephalopathy, polyfocal) and MOGAD. For US boards: fingolimod is the only FDA-labeled DMT for relapsing MS in patients age 10 years and older. Teriflunomide and dimethyl fumarate are labeled for adults in the US (pediatric efficacy was not established for teriflunomide; DMF's US label is adult-only); non-US pediatric labeling and off-label use should be considered separately. Early high-efficacy therapy increasingly favored.
🔍 Quick ReferenceClinical · MRI / OCT · CSF / pathology
Clinical phenotype
  • Electric shock down spine with neck flexion → Lhermitte sign (cervical dorsal column MS plaque)
  • Transient blurred vision after hot shower or exercise → Uhthoff phenomenon
  • Bilateral impaired adduction with abducting eye nystagmus in young woman → Bilateral INO → MS (MLF lesion)
  • Painful monocular vision loss with RAPD (Marcus Gunn pupil) and dyschromatopsia → Optic neuritis (MS)
  • Painless severe bilateral simultaneous optic neuritis with chiasmal enhancement → NMOSD / MOGAD (NOT MS)
  • Brief recurrent painful tonic posturing of limb triggered by movement → Paroxysmal tonic spasms of MS
  • Loss of fine finger control / proprioception with preserved strength → Useless hand of Oppenheim (cervical dorsal column plaque)
  • Disabling fatigue out of proportion to exam, worse with heat → MS-related fatigue
MRI / OCT signs
  • Ovoid periventricular lesions perpendicular to corpus callosum on sagittal FLAIR → Dawson fingers (MS)
  • Hypointense T1 lesions in chronic plaques → T1 black holes (axonal loss / chronic MS)
  • Open (incomplete) ring enhancement on post-contrast T1 → Tumefactive MS / acute demyelinating lesion
  • Small central venule running through an ovoid T2 lesion on SWI/FLAIR* → Central vein sign (MS-specific, McDonald 2024 biomarker)
  • Paramagnetic iron rim around chronic lesion on SWI → Paramagnetic rim lesion (chronic active / smoldering MS)
  • Juxtacortical and leukocortical lesions on 7T MRI / DIR → Highly MS-specific cortical demyelination
  • Short spinal cord lesion <2 vertebral segments, dorsolateral, partial cross-section → MS myelitis
  • Longitudinally extensive transverse myelitis (LETM) ≥3 vertebral segments, central cord → NMOSD / MOGAD (NOT MS)
  • Thinning of retinal nerve fiber layer (RNFL) on OCT after optic neuritis → Post-ON axonal loss (MS biomarker)
CSF / pathology
  • ≥2 oligoclonal bands unique to CSF (not in serum) on isoelectric focusing → CSF-specific OCBs (satisfy DIT in McDonald 2017)
  • Elevated CSF kappa free light chains → Intrathecal B-cell activity (McDonald 2024 supportive biomarker)
  • Mildly elevated IgG index (>0.7) with normal cell count and protein → MS CSF profile
  • Perivenular demyelination with relative axonal sparing and reactive astrogliosis → MS demyelinating plaque
  • Subpial and pan-cortical (leukocortical) demyelinated lesions → Highly MS-specific gray matter pathology (not seen in NMO/MOG/ADEM)
  • Leptomeningeal contrast enhancement on post-contrast FLAIR with cortical lesions → Aggressive cortical / meningeal MS
  • Aquaporin-4 IgG positive serum, LETM, area postrema syndrome → NMOSD (NOT MS)
  • MOG-IgG positive serum with fluffy brainstem / ADEM-like lesions, often pediatric → MOGAD (NOT MS)
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