8 modules on multiple sclerosis: Charcot 1868 first description, demyelination biology, the modern EBV-causal hypothesis (Bjornevik 2022), HLA-DRB1*15:01 and the GWAS landscape, McDonald 2017 criteria, MRI signatures (Dawson’s fingers), and the 20+ disease-modifying therapies including BTK inhibitors in trials.
Eight Modules
- Part I — Overview & Epidemiology: ~2.8M global cases, latitude gradient, female 3:1 predominance, Charcot 1868 systematic description ("la sclérose en plaques").
- Part II — Neuroanatomy of Demyelination: Oligodendrocyte biology, myelin g-ratio, classical perivenular plaque, Dawson’s fingers, periventricular and juxtacortical predilection.
- Part III — Immunology: Th1/Th17 model, Treg dysfunction, B-cell role beyond antibody (anti-CD20 success), EBV as causal/permissive (Bjornevik 2022 Science HR 32), molecular mimicry. PDB: HLA-DR2/MBP.
- Part IV — Genetics: HLA-DRB1*15:01 (OR ~3), 233+ GWAS loci, the heritability gap, IL-7R and IL-2RA.
- Part V — Clinical Phenotypes: CIS, RRMS (~85%), SPMS, PPMS (~10%); Lublin/Reingold/Kappos 2014 framework.
- Part VI — Diagnosis: McDonald 2017 criteria walkthrough, MRI (T2, gadolinium-enhancing T1, black holes), CSF oligoclonal bands, IgG index, kappa free light chains.
- Part VII — Disease-Modifying Therapy (flagship): Injectables (IFN-β, glatiramer), oral (S1P modulators, dimethyl fumarate, teriflunomide, cladribine), monoclonals (natalizumab, ocrelizumab, alemtuzumab), BTK inhibitors in trials. PML/JCV monitoring.
- Part VIII — Symptomatic & Future: Spasticity, fatigue, neuropathic pain; remyelination strategies (clemastine, opicinumab failure); EBV vaccines; CAR-T B-cell depletion in early trials.
The DMT module is structured around the modern era of B-cell-depleting therapy (ocrelizumab, ofatumumab) and the prospective BTK-inhibitor pipeline (evobrutinib, tolebrutinib).