1、 Definition of Multiple Sclerosis An inflammatory demyelinating disease of the CNS where there is:Dissemination in space(DIS)Dissemination in time(DIT)No alternative neurologic disease MS is a clinical diagnosisEpidemiology of MS Age onset 20 50 years old Women are 2 times more likely to develop MS
2、500,000 cases in US Over 2.5 million people around the world More prevalent in whites of northern European ancestry Vitamin D3 Genetic InfluencesProdromal and potential causal pathway for MSRamagopalan S et al.Lancet Neurol 2010;9:72739PATHOPHYSIOLOGY OF MS Destruction of Myelin,oligodendrocytes,ner
3、ve axons Hypothesis of molecular mimicry:infected virus share with myelin molecules common antigens Targeted antigens mimicked by virus Myelin basic protein(MBP)Myelin oligodendrocyte glycoprotein(MOG)Proteolipid protein(PLP)Myelin associated glycoprotein(MAG)PATHOPHYSIOLOGY OF MS Cells CD4 TH1,CD4
4、TH2 and CD8 T cells Macrophages and microglial cells Mast cells B cells Cytokines,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 et al.Acta Neurol
5、Scand 2011:124:7584Multiple Sclerosis Subtypes(Lublin F,et al Neurology 1996)Asymptomatic Symptomatic Relapsing-remitting(85%at onset)Primary progressive(10%)Secondary Progressive(transitional form)Progressive Relapsing(5%)Multiple Sclerosis SubtypesSYMPTOMS OF MS Visual disturbances Blurred vision,
6、diplopia,intranuclear ophthalmoplegia Marcus Gunn pupil Fatigue Motor Spasticity,paresis,dysarthria,spasms,muscle weakness Sensory changes Heat intolerance Paraesthesia,neuralgia Lhermittes sign(dorsal column sign)induced by head flexion Cerebellum Ataxia,nystagmus-tremor-dysarthria(Charcot triads)B
7、ladder/bowel urgency and incontinence Cognitive deficitsBlurred visionDiagnostic approaches CSF:non specific in cellular profile CSF IgG Index Oligoclonal bands Electrophysiology VEP(visual evoked potentials):75%abnormal BAEP(brainstem auditory evoked response)30%abnormal SSER(somatosensory evoked r
8、esponse)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 albumin Reference value 24h without fever or infection.Demonstrated by(1)examination.(2)historical events characteristic of MS
9、 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 CRITERIA-2 Clinically isolated syndromes 1
10、attack+1 objective clinical evidence+DIS+DIT Primary progressive:One year of disease progression 2 of 3 of the following DIS of=1 T2 lesions of MS charateristic DIS of=2 T2 lesions in spinal cord CSF ologoband of IgGPolman GH,et al.ANN NEUROL 2011;69:292302McDonald Criteria(2010 Revision)McDonald Cr
11、iteria(2010 Revision)DIT=dissemination in time,DIS=dissemination in spaceNotes for McDonald Criteria(2010 revision)Differential diagnosis Lacunar infarction Acute disseminated encephalomyelitis(ADEM)Cerebral autosomal dominant ateriopathy,subcortical infacrts,and leukoencepholopathies(CADASIL)Mitoch
12、odiral encephalopathy with lactic acidosis and stroke(MELAS)Vasculitis Vitamin B12 deficiency(spinal cord lesions)Differential diagnosis Caution:Age 60Patients never experienced visual,sensory,or bladder symptoms Routine test of the following is helpful ESR Serum Vit B12 Antinuclear antibody(ANA)Tre
13、atment Principles Acute attacks-corticosteroids Disease modifying agents Symptom management agentsAcute attacks-corticosteroids Methylprednisolone,1g/d for 3 days,reduce dosage in 4w Prednisone,80mg/d for 1w,reduce dosage in 46w Side effects:gastric ulcer,fluid retention,potassium loss,osteoporosisD
14、isease modifying agents Beta-interferon(2yrs)Beta interferon 1a,22-44ug,sc.twice a week Beta interferon 1b,250ug sc,q.o.d Molecular decoy(MBP analog)Glatiramer acetate,20mg,sc,qd for 1 yr Immunodepressant Mitoxantrone 15mg ivgtt every 3 month For Primary progressive MS Monoclonal antibody(against in
15、tegrin)Natalizamab 300 ivgtt/month Under evaluationSide effects of MS medication Local injection site irritation/reactions Flu like symptoms Rise in liver enzymes Decreased white cell count and platelets Opportunistic infections Progressive multifocal leukoencephalopathy(PML)Symptom management Spasm
16、(alospasm)Baclofen 5mg tid;tizanidine 2mg tid;diazepam 10mg qn;dantrolene 10mg tid Fatigue Amantadine 0.1 bid;phenytoin 0.2 qd at morning;Ritalin drugs Bladder problems Urinary retention:cholinergic drugs Incontinence:imipramine 10mg qid or catheterization Tremor:artane 2mg tid;propranolol 10mg tidQuestions in this section What is multiple sclerosis(definition)?Clinical features of multiple sclerosis?What is diagnostic criteria for general MS?Treatment principles of multiple sclerosis?Thank youAny questions?
