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1、 Multiple SclerosisDefinition 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 diagnosisEpidemiology of MSAge onset 20 50 years oldWomen are 2 times more likel
2、y to develop MS500,000 cases in USOver 2.5 million people around the worldMore prevalent in whites of northern European ancestryVitamin D3Genetic InfluencesProdromal and potential causal pathway for MSRamagopalan S et al. Lancet Neurol 2010; 9: 72739PATHOPHYSIOLOGY OF MSDestruction of Myelin, oligod
3、endrocytes, 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 MSCe
4、llsCD4 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 superfamilyThe immunopathogenesis of MSGole R e
5、t al. Acta Neurol Scand 2011: 124: 7584Multiple 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 SubtypesSYMPTOMS OF MSVisual distu
6、rbancesBlurred vision, diplopia, intranuclear ophthalmoplegiaMarcus Gunn pupilFatigueMotorSpasticity, paresis, dysarthria, spasms, muscle weaknessSensory changesHeat intoleranceParaesthesia, neuralgia Lhermittes sign (dorsal column sign) induced by head flexionCerebellumAtaxia, nystagmus-tremor-dysa
7、rthria(Charcot triads)Bladder / bowel urgency and incontinenceCognitive deficitsBlurred visionDiagnostic approachesCSF: non specific in cellular profileCSF IgG IndexOligoclonal bandsElectrophysiologyVEP (visual evoked potentials ): 75% abnormalBAEP(brainstem auditory evoked response)30% abnormalSSER
8、 (somatosensory evoked response)Imaging: MRI is used routinely, most effectiveCSF IgG INDEX CSF IgG to CSF albumin ratio compared to serum IgG to serum albumin ratioCSF IgG / CSF albuminserum IgG / serum albuminReference value 24h without fever or infection. Demonstrated by (1) examination. (2) hist
9、orical events characteristic of MS but with no objective neurological findings.2. At least one attack must be supported by objective findings before diagnosis can be made3. “Four points” diagnosis process: attack+ clinical evidence3. DIS=dissemination in space, DIT=dissemination in timeDIAGNOSTIC CR
10、ITERIA-2Clinically isolated syndromes1 attack+ 1 objective clinical evidence+DIS+DITPrimary progressive:One year of disease progression2 of 3 of the followingDIS of =1 T2 lesions of MS charateristic DIS of = 2 T2 lesions in spinal cordCSF ologoband of IgGPolman GH, et al.ANN NEUROL 2011;69:292302McD
11、onald Criteria (2010 Revision)McDonald Criteria (2010 Revision)DIT=dissemination in time, DIS=dissemination in spaceNotes for McDonald Criteria (2010 revision)Differential diagnosisLacunar infarctionAcute disseminated encephalomyelitis(ADEM)Cerebral autosomal dominant ateriopathy, subcortical infacr
12、ts, and leukoencepholopathies (CADASIL)Mitochodiral encephalopathy with lactic acidosis and stroke(MELAS)VasculitisVitamin B12 deficiency (spinal cord lesions)Differential diagnosisCaution:Age 60Patients never experienced visual ,sensory, or bladder symptomsRoutine test of the following is helpfulES
13、RSerum Vit B12Antinuclear antibody(ANA)Treatment Principles Acute attacks- corticosteroidsDisease modifying agentsSymptom management agentsAcute attacks-corticosteroidsMethylprednisolone,1g/d for 3 days, reduce dosage in 4wPrednisone, 80mg/d for 1w, reduce dosage in 46wSide effects: gastric ulcer, f
14、luid retention, potassium loss, osteoporosisDisease modifying agents Beta-interferon (2yrs)Beta interferon 1a, 22-44ug, sc. twice a weekBeta interferon 1b, 250ug sc, q.o.dMolecular decoy (MBP analog)Glatiramer acetate, 20mg, sc,qd for 1 yrImmunodepressant Mitoxantrone 15mg ivgtt every 3 monthFor Pri
15、mary progressive MSMonoclonal antibody (against integrin)Natalizamab 300 ivgtt/monthUnder evaluationSide effects of MS medicationLocal injection site irritation/reactionsFlu like symptomsRise in liver enzymesDecreased white cell count and plateletsOpportunistic infectionsProgressive multifocal leuko
16、encephalopathy (PML)Symptom managementSpasm (alospasm)Baclofen 5mg tid; tizanidine 2mg tid; diazepam 10mg qn; dantrolene 10mg tidFatigue Amantadine 0.1 bid; phenytoin 0.2 qd at morning; Ritalin drugsBladder problemsUrinary retention: cholinergic drugsIncontinence: imipramine 10mg qid or catheterizationTremor: artane 2mg tid; propranolol 10mg tidQuestions in this sectionWhat is multiple sclerosis (definition)?Clinical features of multiple sclerosis?What is diagnostic criteria for general MS?Treatment principles of multiple sclerosis?ThankyouAnyquestions?
