1、中枢神经系统脱髓鞘疾病Demyelinating Diseases of the Central Nervous System 掌握MS概念、病因、发病机制、临床表现、辅助检查、治疗、诊断标准及鉴别诊断。熟悉视神经脊髓炎概念、临床表现、辅助检查、诊断及治疗。了解MS病理、预后；急性播散性脑脊髓炎概念、临床表现、诊断及治疗。Key points-Demyelinating Diseases of CNS Chapter 1 Intraduction 1.Concept:A group of disease characterized by demyelinating of the brain a
2、nd spinal cord.PATHOLOGY:Demyelination 髓 鞘 构 成CNSPNS2.Pathologic Findings Destruction of the myelin sheaths of CNS;often primarily in white matter,either in multiple small disseminated foci or in larger foci;Infiltration of inflammatory cells in a perivenous distribution;A relative integrity of the
3、axis cylinders in the lesions and a lack of wallerian,the secondary degeneration of fiber tracts.临床常见脱髓鞘疾病急性播散性脑脊髓炎(acute disseminated encephalomyelitis,ADEM)多发性硬化症(multiple sclerosis,MS)亚型视神经脊髓炎(Devic diseases)急性出血性白质脑病(acute hemorrhage leukoencephalitis,AHLE)多发性硬化症(MS)多发性硬化Multiple Sclerosis,MS 1.
4、Concept:Ms is a kind of autoimmune diseases characterized by demyelination of CNS.Due to its high incidence,chronicity and tendency to attack young adults,it has become one of the most important CNS diseases.There are multiple areas of demyelination within the CNS.The episodes of demyelination are s
5、eparated in time and place,and classically the disease runs a relapsing-remitting course.(brain and spinal cord)是一种常见以中枢神经系统炎性脱髓鞘为特征的自身免疫性疾病病灶部位及时间上的多发性多数均以反复多次发作与缓解的病程具有免疫易感性、年轻人多见2.Etiology And Pathogenesis 1)病毒感染及自身免疫反应：Since the exact cause is uncertain.Immunological mechanisms undoubtedly play
6、a role,although the causation is probably multifactorial.麻疹病毒,人类噬 T 淋巴细胞病毒(HTLV-I),分子模拟,细胞免疫及体液免疫。2)遗传因素(inherited factor)3)环境因素(environment)3.EpidemiologyIncidence of MS associated with latitude.On moving from a high-prevalence area to a low-prevalence area prior to puberty,the risk of developing M
7、S is higher than in the low-prevalence area;However the move is made following puberty,the risk of the high-prevalence is retained.Heredity may be an important factor.MS associated with the HLA-DR locus on the sixth chromosome,HLA-DR2 express strongly and then-DR3,B7 and A3.Characteristic:Multiple d
8、emyelinated plaques.Position:White matter around the lateral ventricles and spinal cord,optic nerve,brain stem and cerebellar.Acute stage:hyperemia,ondema,demyelination,infiltriation of inflammatory cells distributed in perivenous.Recovery stage:Astrocyte proliferition,forming of astrocytic scab.急急
9、性性 期期:充血、水肿、炎性脱髓鞘、血管周围Lc浸润。恢恢 复复 期期:星状细胞增生、胶质斑痕形成。肉眼观：CNS内脱髓鞘斑块5.Clinical Manifestations 1)Prodrome:The symptoms evolved more slowly,over several weeks or months.2)Acute or subacute onset(Relapsing-remitting).3)Early symptoms and signs:Weakness or numbness;(1/2 patients have paresthesia on one or mo
10、re limbs)The visual loss in one or both eyes;Nystagmus;4)Common symptoms and signs:paralysis and paraplegia;The visual loss in one or both eyes;(1/2 patients have visual disorders,relapsing-remitting)Nystagmus and palsy of eye muscles;(internuclear ophthalmoplegia,PPRF one and a half syndrome)“一个半综合
11、征一个半综合征”垂直眼震垂直眼震 Sensation disorder:Rombergs sign,(1/2)Lhermittes sign;Ataxia(1/2),Charcots syndrom(later stage);Impairment of PNS;Attack syndrom;Other clinical feature.6.Laboratory and assistant Tests 1)CSF Test Number of MNC 0.7(70%);oligoclonal bands(OB)(95%);MBP,PLP,MAG,MOG Abs and Ab-secreting
12、cells;CSF-Alb/serum-Alb1.7(probability of MS)2)Evoked potentials:50%-90%abnormal.visual evoked potentials(VEP);brain stem auditory evoked potentials (BAEP);somatosensory evoked potentials(SEP).3)MRI:preiventricular plaques;regular plaques in brainstem,cerebellum and spinal cord;atrophy symptom.-Abno
13、rmal MRI scans are found in 96%with a definite diagnosis of MS 70%with a diagnosis of probable MS 30-50%with a diagnosis of possible MS-MRI Criteria for diagnosing MS At least 3 Lesions and two of the following:1 Lesions abutting the Lateral Ventricles 2 Lesions with diameters greater than 5mm 3 Les
14、ions present in the Posterior Fossa Source(Offenbacher H,Fazekas F,Schmidt R et al.Assessment Of MRI Criteria For A Diagnosis Of MS*Neurology 1993;43:905-909)Diagnostic criteria 1.Clinical definite MS(CDMS):two times of attack and two lesions;two attacks,one lesion and one subclinical evidence;2.Lab
15、oratory supported definite MS(LSDMS):Two attacks,one subclinical evidence and CSF OB/IgG;One attack,two lesions and CSF OB/IgG;One attack,one lesion,one subclinical evidence and CSF OB/IgG;3.Clinical probable MS(CPMS):two attacks,one lesion;one attack,two lesions;one attack,one lesion and other subc
16、linical evidence;4.Laboratory supported probable MS(LSPMS)Two attacks;CSF OB/IgG;Two attacks involving different part of CNS,intermission at lest one month;each attack must continue for 24hs.多发硬化的诊断标准多发硬化的诊断标准两次发作均累及两次发作均累及CNS不同部位，不同部位，间隔至少一个月，间隔至少一个月，每次持续每次持续24小时。小时。Differential Diagnosis 1.急性播散性脑脊
17、髓炎2.脑动脉炎、脑干炎、脊髓血管畸形 3.颈椎病脊髓型4.热带痉挛性截瘫5.大脑淋巴瘤 Treatment Anti-inflammatory treatment:methylprenisolone(high dose for 3d),prednison,dexamethasone;Suppression or modulationof the immune system:IFN-1 and 1b;Azathioprine；Immuneglublin(Ig):0.4g/kg.d IVIg3-5d 2.Progressive MS：Methotrexate,MTX;Cyclosphoamide
18、;Cyclosporine A;Plasma transplantation.3.Symptomatic treatment:Spasticity:baclofen,dantrolene,diazepam and tizanidine can be helpful.Bladder dysfunction:anticholinergic drugs urinary catheter may be required.预后分型 1.良性型 2.复发-缓解 3.缓慢进展型 4.慢性进展型Examples患者，女，患者，女，32岁。主诉：行走不稳岁。主诉：行走不稳1年，左耳鸣、视物双影半年。年，左耳鸣、
19、视物双影半年。走路不稳，踩棉花感走路不稳，踩棉花感 左耳鸣左耳鸣 复视复视 快速细小水平眼震向右凝视时明显快速细小水平眼震向右凝视时明显 右侧指鼻试验、轮替试验、跟膝胫试验均欠佳右侧指鼻试验、轮替试验、跟膝胫试验均欠佳 Romberg征征(+)，左左Hoffmann征征(+)四肢腱反射增高，以双下肢腱反射增高，右侧踝阵挛阳性四肢腱反射增高，以双下肢腱反射增高，右侧踝阵挛阳性 头颅头颅MRI未见未见异常异常 视神经和脊髓受累较多见，病灶中的软化、视神经和脊髓受累较多见，病灶中的软化、坏死较多见坏死较多见.视神经脊髓炎又称视神经脊髓炎又称DevicDevic病病,为为多发性硬化的一个亚型多发性硬化
20、的一个亚型.中国中国,日本日本等东方人等东方人1.IntroductionEtiology And Pathogenesis视神经脊髓炎 (Neuromyelitis optica,NMO)3.Patholgy主要侵犯视神经、视交叉、和脊髓胸颈段主要侵犯视神经、视交叉、和脊髓胸颈段Acute stage:infiltration of inflammatory cells.Astrocyte proliferitionClinical Manifestations-NMO 1.年轻居多，年轻居多，21-41岁。岁。2.特征：急性横贯性脊髓炎和双侧同时特征：急性横贯性脊髓炎和双侧同时 或相继出现
21、的或相继出现的ON。70%可在数日内有截瘫。可在数日内有截瘫。3.急性起病可在数小时或数日内单或双急性起病可在数小时或数日内单或双 眼失明，眼眶痛。眼失明，眼眶痛。4.脊髓症状可横贯、不对称、或呈播散性；脊髓症状可横贯、不对称、或呈播散性；特征为快速进展的双下肢瘫，感觉脱失特征为快速进展的双下肢瘫，感觉脱失 平面、括约肌障碍等，平面、括约肌障碍等，1/3病人有病人有Lhermitte征、征、根痛。根痛。一、一、1.CSF1.CSF细胞数增加，细胞数增加，73%73%单相、单相、82%82%复发。复发。2.2.复发病人脊髓复发病人脊髓MRI88%MRI88%出现纵向融合超出现纵向融合超 过数个节
22、段，钆强化和肿胀常见。过数个节段，钆强化和肿胀常见。1.1.单纯球后神经炎单纯球后神经炎 2.MS 2.MS表现为表现为NMONMO临床模式。临床模式。3.3.亚急性视神经病亚急性视神经病 大剂量甲强冲击疗法大剂量甲强冲击疗法颈髓脱髓鞘视神经炎感染出疹或疫苗接种感染出疹或疫苗接种)爆发型：急性出血性白质脑炎爆发型：急性出血性白质脑炎(acute necrotizing hemorrhagic encephalomyelitis,AHL)Etiology And Pathogenesis 病毒感染，脑组织病毒感染，脑组织+FAC+FAC可诱发可诱发EAEEAE，认为，认为ADEMADEM是急性是
23、急性MSMS或其变异型。或其变异型。3.3.Pathology 脑和脊髓多数脱髓鞘脑和脊髓多数脱髓鞘 病灶病灶,小静脉周围炎性小静脉周围炎性 反应，形成血管袖套。反应，形成血管袖套。Clinical Manifestations 1.Lab Teste 1)WBC,pressure of CSF or normal,Pr,IgG and OB(+);2)Abnormal of EEG;3)CT scan shows the lesions of multiple diffusion subcortex low desity;MRI shows the multiple lesions of a
24、bnormal T1,T2 in brain and whiter matter.2.Diagnosis and differential diagnosis乙脑及单疱病脑 3.Treatment大量皮质类固醇冲击疗法Other demyelinating diseases 1.Diffuse sclerosis 2.Leukodystrophy 3.Central pontine myelinolysis,CPM 4.Concentric sclerosis of Balo1.Diffuse sclerosis(Schilders)2.Leukodystrophy 3.Central pontine myelinolysis,CPM 4.Concentric sclerosis of Balo
