Barts & the london year 2 med student's lecture notes 10th jan 2014
Lecture Notes on Multiple Sclerosis - Professor Gavin Giovannoni (BB2 – 10th Jan 2014)
Pathological Definition: Inflammatory disease of the CNS characterised by demyelination and variable
degrees of axonal loss and gliosis.
Clinical Definition: Objective CNS dysfunction, i.e. involvement of two or more white matter structures
separated by time (1 months), with no other aetiology.
Gross Pathology - plaques (periventricular white matter, optic nerves, brainstem, cerebellum, spinal cord)
Histopathology - perivascular inflammation (venules) extending into the white matter parenchyma (cell
mediated (lymphocytes and macrophages, rare plasma cells), demyelination, axonal loss and gliosis.
Unknown; complex disease involving genes and environment
Possible viral aetiology (disease clusters / migration studies) and/or autoimmune (definitive evidence of it
being autoimmune is lacking; but is the current dogma accepted by most people)
Genetic risk (concordance monozygotic twins 30% / dizygotic twins 5%, increased risk in family members)
Age of onset - 3rd / 4th decade (10 - 50 years)
Prevalence - ~125/100,000 (UK); varies with latitude (probably due to vD; i.e. vD is protective)
Life Span - slightly reduced (~10 year)
Sex - F > M (2:1) ; incidence appears to be increasing in females (not known why)
Race - Caucasians (uncommon in Chinese / ? Viking ancestral genes)
Risk factors – Genes (HLA and others), EBV infection and infectious mononucleosis, smoking and vitamin D
Clinical - typical clinical course / exclusion of other diseases
MRI - abnormal white matter
Evoked Potentials - delayed conduction
CSF - immunological abnormalities (intrathecal synthesis of oligoclonal IgG bands)
6. Clinical (Symptoms and Signs – positive and negative phenomena)
Motor - spasticity, weakness, gait abnormalities, spasms (clonic, tonic and flexor)
Sensory - positive (pins & needles, pain, etc) and negative sensory phenomena (loss of sensation).
Cerebellum - inco-ordination, ataxia, nystagmus, dysarthria, etc.
Brain Stem - diplopia, vertigo, nystagmus, dysarthria
Optic Nerves - optic neuritis (blurred vision, reduced colour vision, central or paracentral scotomas, reduced
visual acuity, afferent pupillary defect, optic disc pallor)
Bladder and Bowel – incontinence, frequency, urgency, hesitancy
Higher Functions - depression, poor concentration, forgetfulness, cognitive impairment
Fatigue – complex (exercise induced, temperature-related)
Progressive (secondary or primary)
Highly variable - 30% benign disease / 10 yrs 30% wheel chair / 15 yrs 50%
Good prognosis - young, female, relapsing course, optic neuritis or sensory onset, long gap between first and
second relapses, good recovery from initial attack and low baseline lesion load on MRI.
Survival slightly reduced
Acute Relapse - high dose corticosteroids
Relapsing cases - interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab,
fingolimod, alemtuzumab and mitoxantrone
Drugs in development: Laquinimod, Ocrelizumab, Daclizumab, etc.
Progressive cases - immunosuppression (poor evidence base) there is a need for neuroprotection.
Spastcity (Baclofen, tizanidine, gabapentin, diazepam, etc.)
Bladder and bowel care, fatigue, depression, pain, infections, skin and foot care
10. Reading List:
Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17.
Ramagopalan et al. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol
2010; 9: 727–39.
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