Multiple Sclerosis
Multiple Sclerosis — Neuroimmunology & the Era of Disease-Modifying Therapy
From Charcot’s «sclérose en plaques» and the perivenular lesion, through Epstein-Barr virus and HLA-DRB1*15:01, to twenty disease-modifying therapies and the search for remyelination — eight integrating modules.
Why a course on Multiple Sclerosis?
Multiple sclerosis (MS) is the commonest non-traumatic cause of neurological disability in young adults in the West, affecting an estimated 2.8 million people worldwide (Atlas of MS, 3rd edition, 2020). Onset is typically between ages 20 and 40, women are affected ~3 times more often than men, and the prevalence rises sharply with latitude in both hemispheres.
Few diseases have moved so far in so few decades. The 1990s opened with one therapy (interferon beta) and an unsolved cause; today the field manages more than twenty disease-modifying therapies (DMTs), has identified Epstein-Barr virus as a near-necessary cause (Bjornevik et al., Science 2022), and is testing remyelinating molecules and CAR-T B-cell depletion. The course traces the biology, the diagnostic revolution under McDonald 2017, the therapeutic landscape, and the open frontier of progressive MS. It cross-references Neuroscience, Alzheimer’s Disease, Cell Physiology, Pharmacology, and Stroke (white-matter pathology overlap).
Course Parts
Overview & Epidemiology
Definition (autoimmune-mediated demyelinating disease of the CNS), Charcot 1868 first systematic description, ~2.8M globally, latitude gradient, female predominance 3:1, Atlas of MS 2020.
Neuroanatomy of Demyelination
Oligodendrocyte biology, myelin sheath, saltatory conduction, the classical perivenular MS plaque, Dawson’s fingers, periventricular and juxtacortical predilection, cortical lesions.
Immunology of MS
T cell-driven autoimmunity with B-cell support; Th1/Th17 axis, EAE, Treg dysfunction, anti-CD20 success, Epstein-Barr virus as causal (Bjornevik 2022), molecular mimicry.
Genetics
HLA-DRB1*15:01 (OR ~3), >200 GWAS loci dominated by immune genes, the heritability gap, IL-7R, IL-2RA, TNFRSF1A.
Clinical Phenotypes
CIS, RRMS (~85%), SPMS, PPMS (~10%), McDonald 2017 criteria (DIS+DIT, OCBs), the Lublin/Reingold/Kappos 2014 framework.
Diagnosis
McDonald 2017 walkthrough, MRI (T2 lesions, gadolinium-enhancing T1, “black holes”, MAGNIMS), CSF OCBs and IgG index, evoked potentials, kappa free light chains.
Disease-Modifying Therapy
20+ DMTs by mechanism: injectables, orals (S1P modulators, DMF, teriflunomide, cladribine), monoclonals (natalizumab, ocrelizumab, alemtuzumab, ublituximab), BTK inhibitors. PML & JCV.
Symptomatic Therapy & Future
Spasticity (baclofen, cannabinoids), pain, fatigue, bladder, mobility (dalfampridine), remyelination (clemastine, opicinumab), EBV vaccine, CAR-T, cell therapy.
What you’ll learn
- Distinguish RRMS, SPMS, PPMS and CIS under the Lublin 2014 framework.
- Apply the McDonald 2017 criteria, including DIS/DIT and CSF OCBs.
- Explain saltatory conduction and why demyelination produces conduction block.
- Reason about Th1/Th17 vs B-cell mechanisms and why anti-CD20 works.
- Read MAGNIMS-style MRI reports for periventricular, juxtacortical, infratentorial, spinal lesions.
- Choose between platform, oral and high-efficacy DMTs based on activity and risk.
- Manage PML risk on natalizumab using JCV serology and stratification.
- Critically appraise the EBV-causation evidence and the remyelination pipeline.
Prerequisites
Working knowledge of CNS anatomy, basic immunology (T-cell/B-cell biology, MHC presentation), and clinical neurology fundamentals. The course cross-references Neuroscience, Cell Physiology, and Pharmacology.