脫髓鞘病7年制

1、 Chapter 1 Intraduction 1. Concept: A group of disease characterized by demyelinating of the brain and spinal cord. PATHOLOGY: Demyelination 髓 鞘 構(gòu) 成 CNS PNS 2. Pathologic Findings Destruction of the myelin sheaths of CNS; often primarily in white matter, either in multiple small disseminated foci or

2、 in larger foci ; Infiltration of inflammatory cells in a perivenous distribution; A relative integrity of the axis cylinders in the lesions and a lack of wallerian, the secondary degeneration of fiber tracts. 臨床常見(jiàn)脫髓鞘疾病 急性播散性腦脊髓炎 (acute disseminated encephalomyelitis, ADEM ) 多發(fā)性硬化癥(multiple sclerosi

3、s, MS) 亞型視神經(jīng)脊髓炎( Devic diseases ) 急性出血性白質(zhì)腦病 (acute hemorrhage leukoencephalitis, AHLE) 多發(fā)性硬化癥(MS) 多發(fā)性硬化 Multiple Sclerosis,MS 1. 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 becom

4、e one of the most important CNS diseases. There are multiple areas of demyelination within the CNS.The episodes of demyelination are separated in time and place,and classically the disease runs a relapsing-remitting course. (brain and spinal cord) 是一種常見(jiàn)以中 樞神經(jīng)系統(tǒng)炎性 脫髓鞘為特征的 自身免疫性疾病 病灶部位及時(shí)間上的多發(fā)性 多數(shù)均以反復(fù)多

5、次發(fā) 作與緩解的病程 具有免疫易感性、 年輕人多見(jiàn) 2. Etiology And Pathogenesis 1) 病毒感染及自身免疫反應(yīng)：Since the exact cause is uncertain. Immunological mechanisms undoubtedly play a role,although the causation is probably multifactorial. 麻疹病毒,人類(lèi)噬 T 淋巴細(xì)胞病毒(HTLV-I) ,分子模擬, 細(xì)胞免疫及體液免疫。 2) 遺傳因素 (inherited factor) 3) 環(huán)境因素 (environment) 3

6、. Epidemiology Incidence of MS associated with latitude. On moving from a high-prevalence area to a low-prevalence area prior to puberty,the risk of developing MS is higher than in the low- prevalence area; However the move is made following puberty, the risk of the high- prevalence is retained. Her

7、edity 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 demyelinated plaques. Position: White matter around the lateral ventricles and spinal cord, optic nerve, brain stem and cerebel

8、lar. Acute stage: hyperemia,ondema,demyelination, infiltriation of inflammatory cells distributed in perivenous. Recovery stage : Astrocyte proliferition, forming of astrocytic scab. 急急 性性 期期: : 充血、水腫、炎性脫髓鞘、血管周?chē)鶯c浸潤(rùn)。 恢恢 復(fù)復(fù) 期期: : 星狀細(xì)胞增生、膠質(zhì)斑痕形成。 肉眼觀：CNS內(nèi)脫髓鞘斑塊 5. Clinical Manifestations 1) Prodrome: Th

9、e 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 more limbs) The visual loss in one or both eyes; Nystagmus; 4) Common symptoms and signs: paral

10、ysis 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) “一個(gè)半綜合征一個(gè)半綜合征” 垂直眼震垂直眼震 Sensation disorder: Rombergs sign, (1/2) Lhermittes sign; Ataxi

11、a (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 cells ; CSF-Alb/serum-Alb1.7(probability of MS) 2) Evoked pot

12、entials: 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. - Abnormal MRI scans are found in 96% with a def

13、inite 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 Lesions present in the Posterior Foss

14、a 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. Laboratory supported def

15、inite 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. 多發(fā)硬化的診斷標(biāo)準(zhǔn)多發(fā)硬化的診斷標(biāo)準(zhǔn) 兩次發(fā)作均累及兩次發(fā)作均累及 CNS不同部位，不同部位， 間隔至少一個(gè)月，間隔至少一個(gè)月， 每次持續(xù)每次持續(xù)24小時(shí)。小時(shí)。 Differential Dia

17、gnosis 1. 急性播散性腦脊髓炎 2. 腦動(dòng)脈炎、腦干炎、脊髓血管畸形 3. 頸椎病脊髓型 4. 熱帶痙攣性截癱 5. 大腦淋巴瘤 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 M

18、S： Methotrexate, MTX; Cyclosphoamide; 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. 預(yù)后分型 1.良性型 2.復(fù)發(fā)-緩解 3.緩慢進(jìn)展型 4.慢性進(jìn)展型 Examples 患者，女

19、，患者，女，32歲。主訴：行走不穩(wěn)歲。主訴：行走不穩(wěn)1年，左耳鳴、視物雙影半年。年，左耳鳴、視物雙影半年。 走路不穩(wěn)，踩棉花感走路不穩(wěn)，踩棉花感 左耳鳴左耳鳴 復(fù)視復(fù)視 快速細(xì)小水平眼震向右凝視時(shí)明顯快速細(xì)小水平眼震向右凝視時(shí)明顯 右側(cè)指鼻試驗(yàn)、輪替試驗(yàn)、跟膝脛試驗(yàn)均欠佳右側(cè)指鼻試驗(yàn)、輪替試驗(yàn)、跟膝脛試驗(yàn)均欠佳 Romberg征征(+)， 左左Hoffmann征征(+) 四肢腱反射增高，以雙下肢腱反射增高，右側(cè)踝陣攣陽(yáng)性四肢腱反射增高，以雙下肢腱反射增高，右側(cè)踝陣攣陽(yáng)性 頭顱頭顱MRI未見(jiàn)未見(jiàn)異常異常 視神經(jīng)和脊髓受累較多見(jiàn)，病灶中的軟化、視神經(jīng)和脊髓受累較多見(jiàn)，病灶中的軟化、 壞死較多見(jiàn)壞死

20、較多見(jiàn). .視神經(jīng)脊髓炎又稱(chēng)視神經(jīng)脊髓炎又稱(chēng)DevicDevic病病, ,為為 多發(fā)性硬化的一個(gè)亞型多發(fā)性硬化的一個(gè)亞型. . 中國(guó)中國(guó), ,日本日本 等東方人等東方人 1.Introduction Etiology And Pathogenesis 視神經(jīng)脊髓炎 (Neuromyelitis optica, NMO) 3.Patholgy 主要侵犯視神經(jīng)、視交叉、和脊髓胸頸段主要侵犯視神經(jīng)、視交叉、和脊髓胸頸段 Acute stage:infiltration of inflammatory cells. Astrocyte proliferition Clinical Manifestat

21、ions-NMO 1. 年輕居多，年輕居多，21-41歲。歲。 2. 特征：急性橫貫性脊髓炎和雙側(cè)同時(shí)特征：急性橫貫性脊髓炎和雙側(cè)同時(shí) 或相繼出現(xiàn)的或相繼出現(xiàn)的ON。70%可在數(shù)日內(nèi)有截癱。可在數(shù)日內(nèi)有截癱。 3. 急性起病可在數(shù)小時(shí)或數(shù)日內(nèi)單或雙急性起病可在數(shù)小時(shí)或數(shù)日內(nèi)單或雙 眼失明，眼眶痛。眼失明，眼眶痛。 4. 脊髓癥狀可橫貫、不對(duì)稱(chēng)、或呈播散性；脊髓癥狀可橫貫、不對(duì)稱(chēng)、或呈播散性； 特征為快速進(jìn)展的雙下肢癱，感覺(jué)脫失特征為快速進(jìn)展的雙下肢癱，感覺(jué)脫失 平面、括約肌障礙等，平面、括約肌障礙等，1/3病人有病人有Lhermitte征、征、 根痛。根痛。 一、一、 1. 1. CSFCSF

22、細(xì)胞數(shù)增加，細(xì)胞數(shù)增加，73%73%單相、單相、82%82%復(fù)發(fā)。復(fù)發(fā)。 2. 2. 復(fù)發(fā)病人脊髓復(fù)發(fā)病人脊髓MRI88%MRI88%出現(xiàn)縱向融合超出現(xiàn)縱向融合超 過(guò)數(shù)個(gè)節(jié)段，釓強(qiáng)化和腫脹常見(jiàn)。過(guò)數(shù)個(gè)節(jié)段，釓強(qiáng)化和腫脹常見(jiàn)。 1. 1. 單純球后神經(jīng)炎單純球后神經(jīng)炎 2. 2. MSMS表現(xiàn)為表現(xiàn)為NMONMO臨床模式。臨床模式。 3. 3. 亞急性視神經(jīng)病亞急性視神經(jīng)病 大劑量甲強(qiáng)沖擊療法大劑量甲強(qiáng)沖擊療法 頸髓脫髓鞘 視神經(jīng)炎 感染出疹或疫苗接種感染出疹或疫苗接種) ) 爆發(fā)型：急性出血性白質(zhì)腦炎爆發(fā)型：急性出血性白質(zhì)腦炎 ( (acute necrotizing hemorrhagic

23、encephalomyelitis,AHL) Etiology And Pathogenesis 病毒感染，腦組織病毒感染，腦組織+ +FACFAC可誘發(fā)可誘發(fā)EAEEAE，認(rèn)為認(rèn)為ADEMADEM 是急性是急性MSMS或其變異型?；蚱渥儺愋?。 3.3.Pathology 腦和脊髓多數(shù)脫髓鞘腦和脊髓多數(shù)脫髓鞘 病灶病灶, ,小靜脈周?chē)仔孕§o脈周?chē)仔?反應(yīng)，形成血管袖套。反應(yīng)，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;