On this page
Study tools
Write your answer
Saved on this device. No marking — you are the marker.
Q1: A 28-year-old woman presents with optic neuritis and a typical brain MRI. Define MS and explain "dissemination in time and space". (2 min)
Multiple sclerosis is a chronic, immune-mediated, inflammatory demyelinating disease of the central nervous system (brain, optic nerves and spinal cord) defined by lesions disseminated in time (occurring at different points in time) and space (in at least two of four typical regions — periventricular, juxtacortical/cortical, infratentorial, spinal cord). Onset is typically 20 to 40 years, female predominance 3:1, with relapsing-remitting disease in 85% at onset.
Q2: Describe the pathophysiology of an MS plaque. (2 min)
A genetically susceptible host (HLA-DRB1*15:01) triggered by EBV / low vitamin D loses self-tolerance to myelin antigens. Autoreactive CD4+ Th1/Th17 cells cross a disrupted blood-brain barrier, are re-stimulated by microglia/macrophages, and orchestrate macrophage- and antibody-mediated myelin destruction with oligodendrocyte loss. The acute plaque shows perivenular inflammation, demyelination with relative axonal preservation (gadolinium-enhancing on MRI). The chronic plaque shows gliosis and axonal loss (a permanent sclerotic scar). Demyelination causes conduction block (relapse), ectopic discharges (Lhermitte, paroxysmal symptoms), heat sensitivity (Uhthoff), and permanent axonal loss drives disability.
Q3: How is MS diagnosed? Reproduce the McDonald 2017 criteria. (2 min)
MS is diagnosed clinically, with MRI support. The McDonald 2017 criteria require dissemination in space (at least one T2 lesion in at least two of: periventricular, juxtacortical/cortical, infratentorial, spinal cord) and dissemination in time (simultaneous gadolinium-enhancing and non-enhancing lesions; OR a new lesion on follow-up MRI; OR CSF-specific oligoclonal bands). The 2017 changes: CSF oligoclonal bands can substitute for DIT in all phenotypes; symptomatic lesions now count; cortical lesions added to DIS. PPMS requires at least one year of progression plus at least two of brain DIS, spinal cord DIS, or CSF oligoclonal bands.
Q4: Outline the management ladder, with the acute relapse regimen and one high-efficacy DMT. (2 min)
Acute relapse: IV methylprednisolone 1000 mg daily for 3 to 5 days (speeds recovery; does not change long-term outcome); plasma exchange (5 to 7 exchanges) if steroid-refractory. DMT ladder: injectable interferon-beta / glatiramer (mild-to-moderate efficacy, safe); oral fingolimod (0.5 mg daily; first-dose cardiac monitoring, macular oedema, VZV), dimethyl fumarate (240 mg bd; lymphopenia), teriflunomide (teratogenic); monoclonal antibodies — natalizumab 300 mg IV monthly (PML risk stratified by JCV status), ocrelizumab 600 mg IV 6-monthly (RRMS and the only DMT for PPMS), alemtuzumab (secondary autoimmunity). Always exclude NMOSD (AQP4) and MOGAD (MOG) before starting — interferon worsens NMOSD.
Q5: Name two complications of MS and one serious adverse effect of natalizumab. (1 min)
Complications: progressive disability, osteoporosis (immobility + steroids), urinary/chest infection, depression and raised suicide risk. Natalizumab serious adverse effect: progressive multifocal leukoencephalopathy (PML) — reactivation of JC virus; risk stratified by anti-JCV antibody status and treatment duration (highest in JCV-positive patients over 24 months of therapy). Present with subacute progressive neurological deterioration; diagnose with MRI (confluent subcortical T2 lesions) and CSF JCV DNA PCR.
Q6: Briefly, what are the pregnancy considerations in MS? (1 min)
Relapse rate falls in the third trimester and rebounds in the first 3 months postpartum. Most DMTs are stopped pre-conception with an adequate washout; glatiramer is considered the safest in pregnancy if needed. Teriflunomide, fingolimod and mitoxantrone are teratogenic (cholestyramine washout for teriflunomide). IV methylprednisolone is acceptable for postpartum relapse; breastfeeding is generally encouraged and may reduce postpartum relapses; epidural anaesthesia is safe.