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1、Multiple Sclerosis,CHEN, Guo-Jun Ph. D. Department of Neurology The First Affiliated Hospital Chongqing Medical University,Definition of Multiple Sclerosis,An inflammatory demyelinating disease of the CNS where there is: Dissemination in space (DIS) Dissemination in time (DIT) No alternative neurolo
2、gic disease MS is a clinical diagnosis,Epidemiology of MS,Age onset 20 50 years old Women are 2 times more likely to develop MS 500,000 cases in US Over 2.5 million people around the world More prevalent in whites of northern European ancestry Vitamin D3 Genetic Influences,Prodromal and potential ca
3、usal pathway for MS,PATHOPHYSIOLOGY OF MS,Destruction of Myelin, oligodendrocytes, nerve 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) Proteoli
4、pid protein (PLP) Myelin associated glycoprotein (MAG),PATHOPHYSIOLOGY OF MS,Cells CD4 TH1, CD4 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 mole
5、cule) Tumour necrosis factor receptor superfamily,The immunopathogenesis of MS,Multiple 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%),Multi
6、ple Sclerosis Subtypes,SYMPTOMS OF MS,Visual disturbances Blurred vision, 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) indu
7、ced by head flexion Cerebellum Ataxia, nystagmus-tremor-dysarthria(Charcot triads) Bladder / bowel urgency and incontinence Cognitive deficits,Blurred vision,Diagnostic approaches,CSF: non specific in cellular profile CSF IgG Index Oligoclonal bands Electrophysiology VEP (visual evoked potentials ):
8、 75% abnormal BAEP(brainstem auditory evoked response)30% abnormal SSER (somatosensory evoked response) Imaging: MRI is used routinely, most effective,CSF IgG INDEX,CSF IgG to CSF albumin ratio compared to serum IgG to serum albumin ratio CSF IgG / CSF albumin serum IgG / serum albumin Reference val
9、ue 0.85 70% patients show higher value,Oligoclonal Bands,Bakers Clinical Neurology, CDROM-2003,Lhermittes sign,Visual Evoked Potentials (Bakers Clin Neurol 2003),MRI: FLAIR & T1 with Gadolinium (Noseworthy J, et al NEJM, 2000),MRI: T1 “Black Holes”,MRI: Sagittal Views,MRI: Spinal Imaging,DIAGNOSTIC
10、CRITERIA-1,2 attacks with clinical evidence of at least 2 lesions 2 attacks with clinical evidence of 1 lesion + DIS I attack + clinical evidence of 2 lesions + DIT,Notes: 1. An attack: duration of symptom should 24h without fever or infection. Demonstrated by (1) examination. (2) historical events
11、characteristic of MS but with no objective neurological findings. 2. At least one attack must be supported by objective findings before diagnosis can be made 3. “Four points” diagnosis process: attack+ clinical evidence 3. DIS=dissemination in space, DIT=dissemination in time,DIAGNOSTIC CRITERIA-2,C
12、linically isolated syndromes 1 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 IgG,McDonald Criteria (2010 Revision),McDonald Crit
13、eria (2010 Revision),DIT=dissemination in time, DIS=dissemination in space,Notes for McDonald Criteria (2010 revision),Differential diagnosis,Lacunar infarction Acute disseminated encephalomyelitis(ADEM) Cerebral autosomal dominant ateriopathy, subcortical infacrts, and leukoencepholopathies (CADASI
14、L) Mitochodiral encephalopathy with lactic acidosis and stroke(MELAS) Vasculitis Vitamin B12 deficiency,Differential diagnosis,Caution: Age 60 Patients never experienced visual ,sensory, or bladder symptoms Routine test of the following is helpful ESR Serum Vit B12 Antinuclear antibody(ANA),Treatmen
15、t Principles,Acute attacks- corticosteroids Disease modifying agents Symptom management agents,Acute 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, osteoporo
16、sis,Disease 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 integrin) Natalizamab 300 ivgtt/month Under evaluation,Side effects of MS medication,Local injection site irritation/reactions Flu like symptoms Rise in liver enzymes Decreased
