1、 MULTIPLE SCLEROSIS MULTIPLE SCLEROSIS (MS, (MS, P167-170P167-170) )Prof. YAN YONGDept.of Neurology, the 1st Hospital, Chongqing University of Medical Science PREFACEPREFACE MS is one of demyelinative diseases,with multifocal damage of the white matter of central nervous system (CNS,ie. brain and sp
2、inal cord) at different times that occurs in young adults,with a peak incidence between age 20 and 40,women are affected nearly twice as oftenas men(2:1). A. ETIOLOGYETIOLOGY OF MSOF MS The real cause of MS is unknown. 1.A role for immune-mediated or infectionsfactors has been proposed,but data to s
3、upportthese postulates are fragmentary and indirect. 2.Incidence varies widely in differentgeographical areas. It is very low in the tropicsand high in the temperate zones of both northern and southern hemispheres(betweenlatitudes 400N and 400S). 3. A genetic predisposition is suggestedby twin studi
4、es, the occasional familial incidence,and the strong association between the disease and specific HL- antigens(HLA DR2). 4.Present evidence supports the belief that the disease has an autoimmune basis. B. PATHOLOGYB. PATHOLOGYThe disorder is characterized pathologically bythe development of focal-of
5、ten periventricular scattered areas of demyelination followedby a reactive gliosis ; there may be axonal damage as well. These lesions occur in theCNS (eg.white matter of the brain , brainstem , spinal cord, cerebellum and in the optic ()nerve ).C. CLINICAL FINDINGSC. CLINICAL FINDINGS MS is a disea
6、se of young adults with a meanage of onset of 32 (ages 1055, most 2040). This disease usually presents in the form ofrecurrent attacks of focal or multifocal neurologicdysfunction,reflecting lesions within the CNS. Typical episode: Symptoms worsen gradually over a period of afew days to 2 3 weeks, a
7、nd then remit.Recoveryis usually lasting weeks or months. Remissionmay be complete, particularly after early attacks, however,remission of many patients is incompleteand as one attack follows another, a stepwise downward progression ensues with Increasing permanent deficit. The attacks occur-remit-r
8、ecur-remit, seemingly randomly over many years. A half of MS take the form of an intermittentlyprogressive illness and sometimes of a steadilyprogressive one, especially in patients more than 40 years of age. The first attack of MS may declare itself as asingle symptom or sign (45%) or as more thano
9、ne symptoms or signs (55%). SYMPTOMSSYMPTOMS The symptoms and signs are variously bylesions position and damaged structures. Paresthesia 37 Gait disorder 35 Visual loss 15 Diplopia 10 Lower extremity weakness or incoordination 17 Upper extremity weakness or incoordination 10 Swanson JW,MS:Update in
10、diagnosis.Mayo Clin 1989;64:577SIGNSSIGNSAbsent abdominal ref. 81 Impaired joint positionHyperreflexia 76 sense 33Lower extremity ataxia 57 Intention tremor(ataxia) 32Extensor plantar responses 54 Spasticity 31Impaired rapid alternating Impaired pain or temperaturemovements 49 sense 22Impaired vibra
11、tory sense 47 Dysarthria 19Optic neuropathy 38 Paraparesis 17Nystagmus 35 Internuclear ophthalmoplegia 11Swanson JW,MS:Update in diagnosis.Mayo Clin 1989;64:577 Common initial complaints focal weakness numbness tingling diplopia unsteadiness in a limb disequilibrium sudden loss or blurring of vision
12、 in one eye, bladder-function disturbance(urinary urgency orhesitancy). Other patients present with an acute or graduallyprogressive spastic paraparesis (paraplegia) or quadriplegia, and ataxia, and sensory deficit,andpsychic sym. and so on. D.D. SUBSEQUENT COURSESUBSEQUENT COURSE Based on its cours
13、e, the disease can be divided into 1.A relapsing-remitting form 缓解复发型缓解复发型 85% of cases in which progression does not occur between attacks; 2.A secondary progressive form 继发进展型继发进展型 80% of cases after 25 years, characterized by a gradually progressive course after an initial relapsing-remitting pat
14、tern ; 3.A primary progressive form 原发进展型原发进展型 10% of cases in which there is gradual progression of disability from clinical onset. 4.A progressive-relapsing form 进展进展-复发型复发型 occurs rarely,with acute relapses being superimposed on a primary progressive course. E. Special examsE. Special exams 1.CSF
15、 The oligoclonal bands(IgG) increased in CSF 2. Electrophysiological examinations Evoked potentials abnormalities VEP- visual evoked potential 视觉诱发电位视觉诱发电位 BAEP-brainstem auditory evoked potential 脑干诱发电位脑干诱发电位 SEPsomatosensory evoked potential 体感诱发电位体感诱发电位 We can find subclinical lesions by evoked p
16、otentials. 3.Myelography may be necessary to exclude the possibility of a single congenital or acquired surgically treatable lesions. 4. MRI: MRI is most sensitive means of detectinglesions of MS. MRI of brain can clearlyreveal lesions within white matter, brainstem and cerebellum, MRI of spinal cor
17、d may show the lesions also. They are better seen with T2-weightedthan T1- weighted images,but the FLAIR image压水成像压水成像 MRS and DWI are optimal. CT can be use sometimes.Multiple,primarily punctate An abnormal region of high density ,white matter high signal intensity of plaques(periventricular) the c
18、ervical spinal cordF. DIAGNOSISF. DIAGNOSIS Diagnosis may be uncertain at the onset and in the early years of the disease,when symptoms andsigns point to a lesion in only one locus of the NS.Later,as the disease recurs and disseminatesthrougout the cerebrospinal axis, diagnosticaccuracy approaches 1
19、00%. In most cases the initial manifestations improvepartially or completely, to be followed after avariable interval by the recurrence of the sameabnormalities or the appearance of new ones inthe other parts of the CNS. Examination in advanced cases commonly reveals optic atrophy, nystagmus, dythar
20、thria, and upper motor neuron, sensory, or cerebellar deficits in some or all of the limbs. Note that the diagnosis cannot be based on any single symptom or sign, but only on a total clinical picture that indicates involvement of differentparts of the CNS at different times. The diagnosis of MS requ
21、ires The diagnosis of MS requires evidence thatevidence that 1. At least two or more discrete lesionsseparated different regions of the central white matter have been affected at differenttimes, and a history of remission andrelapse.在在CNS的白质中，在不同的时间的白质中，在不同的时间(时间多发时间多发)，证实至少有两个或以上的孤立病灶证实至少有两个或以上的孤立病
22、灶(病灶多发病灶多发)。 So called “relapse” imply that the symptoms and signs lasted at least over24h and interval over a month once episode. 2.The onset must be in age range most characteristic of MS (ages1055yr, most2040). 3.MRI demonstrated multifocal lesionsin CNS(brain,brainstem,cerebellum and spinal cord
23、). 4.Evoked potentials abnormalities. - (VEP,BAEP,SEP) 5. Oligoclonal bands increased in CSF. There are two diagnostic criterion by Poser(1983) and McDonald(2001) P235,p236 1.Clinically definite MS: A relapsing-remitting course and signs of atleast two lesions involving different regions ofcentral w
24、hite matter, and conformed by MRI. 2. Clinically probable MS: be conformed multifocal white matter diseaseby MRI,but have had only one clinical attack, or have a history of at least two clinical episodesbut signs of only a single lesion.G. TREATMENTG. TREATMENT 1.1.Relapsing-remitting type:Relapsing
25、-remitting type: Aim: To reduce the relapse rate Interferon -1a 30ug im, once weekly Interferon -1b 50ug subcutaneously, qod. Intravenous immunoglobulin(IVIgIVIg) 0.4g/kg/d5ds Corticosteroids: Methylprednisolone 1000 mg, iv./d, 35ds, then followed by Prednisone tabella 60mg,oral,1mg/kg/d,for wks. 2.
26、 Progressive MS type2. Progressive MS type: : Interferon -1b (and probably Interferon -1a) are effective in reducing the progression rate asdetermined clinically and MRI in secondaryprogressive disease. Cyclophosphamide azathioprine methotrexate cyceosporin A mitoxandrone cladribine Those may help t
27、o arrest the course of secondaryprogressive disease,but studies are inconclusive.with high-dose intravenous methylprednisolone (1g/d once a month) is also sometimes effective. 3.3.Plasma exchange(PE)Plasma exchange(PE) It is indicated especially in patients with a severe or rapidly progressive defic
28、it or respiratory compromise. 4 .Intravenous immunoglobulin4 .Intravenous immunoglobulin (IVIG) IVIG (400mg / kg / d for 5 days ) appears to be equally effective and should be used in preference to plasmapheresis in adults with cardiovascular instability and in children . The two therapies are addit
29、ive. 5.Symptomatic treatment should not be neglected, but the fatigue, spasticity are a serious problem. Treatment for other aspects of advanced MS such as cognitive deficits, pain, tremor and ataxia isgenerally less successful. G. PrognosisPrognosis Symptoms and signs cease to progress by about 4 w
30、eeks into the illness.The disorder is self-limiting, and improvement occurs over the weeks or monthsfollowing onset. In the first episode of MS 70-75% of patients recover completely, 25% are left with mild neurologic deficits, 5% die of respiratory failure. The prognosis is poorer when there is evid
31、ence of preceding campylobacter jejuni infection 空肠弯曲菌感空肠弯曲菌感染染 ,protracted course and less completer recovery. Advanced age, the need for ventilatory support,or more rapid onset of symptoms may also predict a poorer prognosis.CASE REPORTCASE REPORT A woman, 32 years old. A worker, Marred. Chef comp
32、laint: weakness and numbness oflegs for 3 days with progressive . Present: She had weakness and numbness of legs 3 days ago . Then these symptoms had beengradually severs . she had numbness below lowabdomen and legs, urinary and fecal incontinence2 days ago . She had suffered from optic neuritis on
33、left eye 2 years ago and remitted with prednisone for 3 months. She had catch a cold 20 days ago. The neurologic examination : Consciousness and cognitive function normal. Visual acuity decreased and color of the optic nerve head are pale.Visual fields normal. There are nystagmus when the eyes move
34、.Other cranialnerves normal. The muscle tone,muscle strength, sense,deep tendon reflexes and coordination arenormal in the arms. There are loss of pain and temperature sensationbelow T10, and loss of reflex on the middle and low abdomen.The knee jerk and ankle reflex areincreased. The muscle tone of
35、 legs spasticityincreased. The muscle strength is 2 grad in theleft leg and 3 grad in the right leg, the bilateral pathologic reflexes (Babinski and chaddock)are positive .Questions:1. Can you give the diagnosis and show reason?2. What investigative studies you need to make the correct diagnosis? An
36、swers Answers1.MS(multiple sclerosis) She has been suffering from weakness andnumbness of legs gradually developing for3 days ; 2 days ago she had urinary and fecal incontinence; Optic neuritis on left eye 2 years ago.Visual acuitydecreased and color of the optic nerve head are pale, nystagmus, pain
37、 and temperature sensation below T10 and paraplegia. 2.To confirm the diagnosis of MS we have to take MRI of spinal cord and brain, VEP, BAEP, SEP and CSF exams.KEY POINTKEY POINT1. What is the MS? 2. Where are the common sits of the lesions of MS?3. What are the classic features of MS?4. What are t
38、he most effective investigations for MS?5. How do treat to MS? Reference: Adams and Victors ,P955-75,2001; Seventh Edition.McGraw-hillClassification of the demyelinative diseases.Multiple sclerosis A. Chronic relapsing encephalomyelopathic form B. Acute MS C. Diffuse cerebral sclerosis. Neuromyeliti
39、s optical (Devic syndrom). Acute disseminated encephalomylitis A.Following measles,chickenpox,smallpox,mumps,rubella, influenza, and other viral and soma bacterial infection B.Following rabies or smallpox and rarely other type of vaccination. Acute and subacute necrotizing hemorrhage encephalitis A. Acute encephalopathic from hemorrhagic leukoencephalitis of Hurst) B.Subacute necrotic myelopathy
