神经病学课件：Multiple Sclerosis.pptVIP

Multiple Sclerosis Definition of Multiple SclerosisAn inflammatory demyelinating disease of the CNS where there is:Dissemination in space (DIS)Dissemination in time (DIT)No alternative neurologic diseaseMS is a clinical diagnosis Epidemiology of MSAge onset 20 – 50 years oldWomen are 2 times more likely to develop MS500,000 cases in USOver 2.5 million people around the worldMore prevalent in whites of northern European ancestryVitamin D3Genetic Influences Prodromal and potential causal pathway for MSRamagopalan S et al. Lancet Neurol 2010; 9: 727–39 PATHOPHYSIOLOGY OF MSDestruction of Myelin, oligodendrocytes, nerve axonsHypothesis of molecular mimicry: infected virus share with myelin molecules common antigensTargeted antigens mimicked by virusMyelin basic protein (MBP)Myelin oligodendrocyte glycoprotein (MOG)Proteolipid protein (PLP)Myelin associated glycoprotein (MAG) PATHOPHYSIOLOGY OF MSCellsCD4 TH1, CD4 TH2 and CD8 T cellsMacrophages and microglial cellsMast cellsB cellsCytokines, chemokines and adhesion molecules Inerleukin family (IL-4, 10,12) IFN-gamma ALCAM (Activated leukocyte cell adhesion molecule)Tumour necrosis factor receptor superfamily The immunopathogenesis of MSGole R et al. Acta Neurol Scand 2011: 124: 75–84 Multiple Sclerosis Subtypes(Lublin F, et al Neurology 1996)AsymptomaticSymptomaticRelapsing-remitting (85% at onset)Primary progressive (10%)Secondary Progressive (transitional form)Progressive Relapsing (5%) Multiple Sclerosis Subtypes SYMPTOMS OF MSVisual disturbancesBlurred vision, diplopia, intranuclear ophthalmoplegiaMarcus Gunn pupilFatigueMotorSpasticity, paresis, dysarthria, spasms, muscle weaknessSensory changesHeat intoleranceParaesthesia, neuralgia Lhermitte’s sign (dorsal column sign) induced by head flexionCerebellumAtaxia, nystagmus-tremor-dysarthria(Charcot triads)Bladder / bowel urgency and incontinenceCognitive deficits Blurred vision Diagnostic approachesCSF: non specific in cellular profileCSF IgG IndexOligoclonal b