脱髓鞘疾病湘雅医院周文斌.

脱髓鞘疾病湘雅医院周文斌

神经纤维指轴突而言，分为有髓和无髓神经纤维。
Nerve fiber or an axon, Myelinated Nerve Fiber Unmyelinated Nerve Fiber 髓鞘:紧裹在有髓鞘神经轴突外面的脂质细胞膜，由髓鞘形成细胞膜组成。Myelin is a layer that forms around nerves formed by wrapped plasma membrane of myelinization cells.

CNS的髓鞘主要有MBP、PLP等成份。
Myelin basic protein (MBP), myelin proteolipid protein are the major component of the central nervous system (CNS) myelin.

髓鞘：蛋白质22%，脂类78% 蛋白质: 碱性蛋白、脂蛋白、糖蛋白等。
Myelin： protein 22％and lipids 78％蛋白质: 碱性蛋白、脂蛋白、糖蛋白等。 Protein：Basic protein、lipoprotein、glucoprotein 脂类: 胆固醇、神经鞘磷脂、脑苷脂与神经节苷脂。Lipide：lipide、sphingomyelin、galactosyl ceramide、ganglioside

生理作用： Physiological functions
神经冲动的快速传导； Speeding the transmission of impulses 对神经轴突起绝缘、保护作用。 Insulation and protection of neuraxon 髓鞘系统：髓鞘、轴索与完整的血供 Myelin system: myelin、axon and intact blood supply

脱髓鞘脑病 Demyelinating encephalopathy 髓鞘构成缺陷性疾病（白质营养不良症）
脱髓鞘疾病： CNS白质对各种有害因素的反应 Demyelinating disease 脱髓鞘脑病 Demyelinating encephalopathy 髓鞘构成缺陷性疾病（白质营养不良症） myelin construction deficiency syndrome Leukodystrophy 周围神经系统脱髓鞘疾病 Peripheral nerveous demyelination

CNS: White matter disease
Demyelinating: mainly acquired MS PML Encephalomyelitis Anti-MAG Disease

CNS: White matter disease
Dysmyelinating: mainly inherited Leukodystrophies: ALD Alexander Canavan disease Krabbe Disease MLD Pelzaeus-Merzbacher Disease Refsum

PNS: Neuropathies Acquired: mainly autoimmune, demyelinating polyneuropathies. Acute: GBS Chronic: CIDP Anti-MAG syndrome Multiple Motor Neuropathy (MMN)

PNS: Neuropathies Hereditary: mainly dysmyelinating. HMSN/CMT
Cockayne Syndrome, Krabbe Disease MLD Refsum Disease

Myelinated Axon

Conduction in a Demyelinated Nerve Fiber-KH

多发性硬化 Multiple Sclerosis

概述overview CNS白质的慢性，炎性，斑块性脱髓鞘，CD 4+ T 细胞介导的自身免疫性疾病。全世界病人超过200万。
Chronic, progressive immune-mediated CNS disease Characterized by demyelination and axonal loss 全世界病人超过200万。 Affecting over 2 million persons worldwide

概述overview 最常损害部位是脑室周围白质、视神经、脊髓、脑干传导束及小脑白质。 white matter bordering the lateral ventricles、opticus、spinal cord、pyramidal tract and Cerebellar white matter 引起年轻成人中神经残疾的最常见疾病（美国）。 The most common disabling neurological disease of young people .

概述overview 女性多见 Women outnumber men 2:1
缓解复发病程，逐渐加重 Progressive relapsing-remitting course 可能与早期病毒感染有关 no specific causes, viral may be responsible

概述overview

第一次肯定了MS临床症状与MS尸检病理之间的关系；
第一次提出了“硬化与斑块”的概念； "sclerose en plaques" 第一个认定MS是一种独立的疾病；第一个提出MS的诊断标准--即“Chacot三联症”； Triad: nystagmus, intention tremor, scanning speech 他还对MS的病理特征进行了详细的描述，如"髓鞘脱失" demyelination,"胶质纤维增生" macrophages等。

病因、发病机制 Etiology：免疫immunity：病毒virus：
EAE Experimental allergic encephalomyelitis ，致敏（活化）的抗原特异性的CD4+T细胞。The activated antigenic specifically CD4+ cell. 病毒virus：分子模拟机制molecule mimicry mechanism 激发自身免疫反应autoimmune etiology 遗传heredity：单卵双生子、HLA

病因、发病机制 Etiology ： EAE：实验性自身免疫性脑脊髓炎Experimental allergic encephalomyelitis 使用MBP或PLP免疫Lewis 大鼠； Immunizing the Lewis rat by MBP and PLP MBP致敏的T细胞转输给正常大鼠。 transfusion the MBP activated Tc to normal rats

病理pathology CNS白质内有多发性脱髓鞘斑块，围绕小静脉分布，血管周围袖套状、淋巴细胞为主的浸润，引起髓鞘的崩解，可伴有轴索的破坏。 Peri-venule distribution of Demyelinating Plaques occur anywhere within the white matter of the CNS.cuffs of lymphocytes around small blood vessels,damage of myelin sheath and destruction of axis-cylinder.

病理pathology 脑、脊髓和视神经常有萎缩。The atrophy of brain、spinal cord and optical nerve. 晚期星状细胞增生、神经胶质形成—硬化斑。Proliferation of astrocytes, sclerosis plaques with glial scar formation in the late phase

Top: Coronal brain section showing numerous plaques of demyelination, particularly in the periventricular region. Bottom: The corresponding areas show decreased black staining for myelin and increased gliosis (dark staining).

It is a section of brain stained for myelin (blue)
It is a section of brain stained for myelin (blue). The plaques of demyelination appear as well-demarcated pale areas with a central blood vessel.

It is a longitudinal section of optic nerve from a patient with multiple sclerosis. The pale area to the left is demyelinated and there is sharp demarcation from the myelinated area to the right.

It is section of occipital lobe stained for myelin
It is section of occipital lobe stained for myelin. The central white matter is pale due to lack of myelin.

It is a cross section of pons from a case of central pontine myelinolysis, stained for myelin. The pale area in the middle is an area of demyelination.

临床表现 Clinical Presentation
发病年龄多为20-40岁general onset is common between the ages of ；多为静止性、亚急性起病，临床征象提示病灶多发，病程多波动，常有自然缓解及复发。可累及视神经optical nerve、脊髓spinal cord、脑干Brainstem 、小脑cerebellum及大脑的白质white matter of brain

可有前驱表现forerunner manifestation 首发症状为一个或多个肢体无力或麻木；单眼或双眼视力障碍，或复视. The first clinical event including the somatasthenia or the anesthesia of one or more limbs , vision disorder in simple eye or two, and ambiopia.

颅神经功能障碍：视神经、视交叉、脑干 Damage of encephalic nerves nerve:optical nerve、chiasm opticum、brainstem 视神经损害最常见：多为单侧性，球后视神经炎，可部分恢复，无视网膜脱落，视乳头出血少见。 Damage of optic nerve：Typically unilateral retrobulbar neuritis, Some recovery expected, No retinal exudates,Disc hemorrhages are infrequent.

眼球运动ocular movement：核间性眼肌麻痹internuclear ophthalmoplegia：内侧纵束fasciculus longitudinalis medialis 外展神经Ⅵ、动眼神经Ⅲ，可导致复视ambiopia、眼球震颤nystagmus、眼球运动受限limitation of ocular movement。

面部感觉障碍 disability of facial perception、面瘫facial paralysis 眩晕dizzy 吞咽困难dysphagia

脊髓损害Damage of spinal cord ：脊髓后柱或脊髓丘脑束病变，多见于颈髓。posterior column of spinal cord orposterior column of spinal cord, especially in cervical cord 不完全的感觉及运动障碍，感觉障碍更多Partial sensory or motor disfuncion,Sensory more common,

感觉障碍sensory disability：麻木、疼痛、瘙痒，浅感觉减退，深感觉障碍anaesthesia、pain、pruritus、decreased superficial sensation、deep sensation disability Lhermitte‘s征Lhermitte's sign ：屈颈时出现从背部放射至足底或双下肢的放射性疼痛，可为闪电感。大小便功能障碍常见，可有束带感。 Bowel and bladder dysfunctions are common, with band-like pressure

运动障碍：motor disorder 痉挛性瘫痪:motor disorder 小脑性共济失调:cerebellar ataxia 感觉性共济失调:sensory ataxia

小脑Cerebellum：小脑性震颤，共济失调，小脑性眼震 Cerebellar tremor 、 ataxia 、cerebellar nystagmus。

临床表现Symptoms of MS 常见：运动乏力、感觉异常、视力下降与复视 Common:debility、paresthesia and ambiopia。两个重要体征：核间性眼肌麻痹、眼球震颤。 Two important signs:internuclear ophthalmoplegia、nystaxis

临床表现Symptoms of MS 少见：认知障碍、癫痫、神志障碍。 Charcot三联征：共济失调（眼球震颤）、构音障碍及意向性震颤。
Few: cognitive dysfunction,epilepsia,confused state of mind. Charcot三联征：共济失调（眼球震颤）、构音障碍及意向性震颤。 Charcot Triad：dystaxia,dysarthria and Intention myoclonus

辅助检查 Laboratory Findings
脑脊液cerebrospinal fluid 寡克隆带oligoclonal band IgG指数 IgG exponent 髓鞘碱性蛋白myelin basic protein 电生理检测Electrophysiology detection 诱发电位evoked potential

Typical of MS Normal CSF glucose Normal or mildly elevated CSF protein
Absent red blood cells Small number of mononuclear white cells Evidence of intrathecal antibody production Increased IgG index or IgG synthesis rate Oligoclonal bands Increased free kappa light chains

MRI T1 反映了质子置于磁场中产生磁化所需的时间，即继90度RF质子从纵向磁化转为横向磁化之后恢复到纵向磁化平衡状态所需时间。 T2 弛豫时间，表示在完全均衡的外磁场中横向磁化所维持的时间。

多见于两侧脑室旁、尤以两侧前角及后角周围可见多发散在类圆形或融合性斑块状形态不规则的低信号区，与脑室壁垂直，无占位效应。 T2为高信号。

Figure 1. Unenhanced MRI scan showing the presence of MS plaques.

Figure 2. Nicknamed “black holes,” the areas of hypointensity seen on T1-weighted images are believed to indicate that MS is a disease not only of demyelination but also of axonal destruction

Figure3 This MRI scan with gadolinium enhancement shows active plaques (bright areas).

多发性硬化女性41岁，半个月前开哭笑无常，站立不稳，双眼视力下降。

MRI features that suggest MS
≥4 white matter lesions ≥ 3mm in diameter 3 white matter lesions, of which 1 is periventricular Lesions ≥ 6 mm Ovoid lesions oriented perpendicular to the ventricles Brainstem lesions Open ring appearance on gadolinium-enhanced T1-weighted images

Differential diagnosis
Infection : Lyme disease, syphilis, progressive multifocal leukoencephalopathy, HIV, HTLV-1 leukodystrophy Inflammatory : SLE、Sjogen、Behcet, vasculitis, sarcoidosis

Metabolic : Vitamin B12 deficiency, lysosomal disorders, Adrenoleukodystrophy mitochondrial disorders, other genetic disorders

Neoplastic : CNS lymphoma , Metastatic cancer, Paraneoplastic syndrome, Primary brain tumor Spinal disease :Vascular malformations, degenerative spinal disease

Vascular Antiphospholipid syndrome, CADASIL, Eale's disease, Cerebrovascular disease, Retrocochlear vasculopathy of Susa, Migraine, Vasculitis

Criteria of diagnosis and classification
诊断标准和分类标准 Criteria of diagnosis and classification 发作、复发（attack，bout，episode，exacerbation，relapse）：神经病学功能障碍表现为一种或多种临床表现（症状和体征），持续24h以上，即为一次发作，可以仅为自己主观感觉或为患者回忆。 One episode is one or more symptoms or signs of the neurological dysfunction last at least 24 hours,which can be the feeling and recollection of the patient.

诊断标准和分类标准 Criteria of diagnosis and classification
多发性硬化的定义definition：时间上多发是指有2次或2次以上发作；multiple in temporal means two or more distinct episodes of symptoms 空间是指CNS白质有2个或2个以上部位病变。硬化是指病理上CNS中，在炎症脱髓鞘基础上， multiple in spatial requires two or more lesions of the brain and spinal cord. Sclerosis means the sclerosis plaques with glial scar formation in the demyelinated inflammatory disease of CNS. 由于胶质增生等修复过程而于局部形成硬化斑块。

急性发作（an acute episode of new disease activity）指新病灶的出现或老病灶的重新活跃。亚临床病灶（subclinical or paraclnical）病理上和ＭＲＩ上发现的新、老病灶，在临床上不一定有或曾有过相应的症状和体征。

可明确亚临床病灶的方法：热水浴、诱发电位、ＣＴ和ＭＲＩ或特殊的泌尿科检查。 the method of definite subclinical or paraclinical lesion hot bath test, EP、ＣＴ,ＭＲＩor special examination of urology 缓解Remission ：２次发作必须累及中枢神经系统不同部位，１次缓解至少持续１个月。Two Episodes of symptoms must be attributable to involvement of 2 or more parts of the brain and spinal cord.One remission must last at least one month.

回忆性资料recallment data ：５０岁以下无颈椎病而有Ｌhermitte征。 person with Lhermitte sign under 50 have no cervical syndrome ５０岁以前典型的视神经炎typical optic neuritis under 50

暂时性截瘫伴感觉异常temporary paraplegia with paresthesia 振动性幻视oscillating hallucination 复视diplopia ７０岁以前起病的三叉神经痛。 Trifacial neuralgia before 70

不同部位的病变Various areas of lesion ：大脑皮层下白质、小脑、脑干、脊髓和视神经各算一个部位。 white matter,cerebellum, brainstem,optic nerve and spinal cord. 不同的症状和体征不能用单一病灶来解释，称之为不同病灶。different symptoms and signs that can’t be explained by only one lesion.

视神经炎Optic neuritis ：据英联邦统计，急性视神经炎后ＭＳ的发生率为５１％，中国为６３％。 In U.K:51％ of acute optic neuritis will be MS, in China , 63％。

脊髓型ＭＳ：ＭＳ脱髓鞘过程有时仅限于脊髓，或虽然向中枢神经系统其他部位扩展但仅有脊髓部位的斑块产生症状。 MS of spinal cord type: Demyelination in spinal cord only,sometimes it expand to other spaces of CNS,but only the lesion of spinal cord develop the symptoms.

国外，１２７１例ＭＳ中，１０９例（９％）有脊髓症状，中国２５６例中７０％有脊髓症状。 overseas，109(9%)of 1271MS have the symptoms of spinal cord;in China,70% of 256 have the symptoms 特点：女性多；起病年龄大；慢性进展病程多；工作能力保存较好。 characteristics:usually seen in female ,onset at old ages, chronic progression, and preserved more work capacity .

自然病程： Natural progress：１０％患者起病后呈进行性加重。 10％ of patients have progressive exacerbation 约２／３后期进入进行性加重。 ,about 2/3 of patients come into progressive exacerbation phase. ７９.７％为复发－缓解型。７９.７％of patients are RRMS

实验室支持诊断Supporting data of laboratory ＩｇＧ组分区带或中枢神经系统中ＩｇＧ合成率增高。 IgG fraction bands or the Synthesis of IgG in CNS increased 血清中正常normal level in serum 除外其他疾病：梅毒、亚急性硬化性全脑炎、肉芽肿病、胶原血管病等。Exclude other diseases:syphilis, subacute sclerosis panencephalitis, granulomatosis, collagen vascular disorders

临床确诊（clinically definite ）MS 2次发作, 又有2个不同病变部位的临床证据Two episodes with clinical evidence of two different lesions 2次发作，有一个部位病变的临床证据，和另一个部位病变的亚临床证据。 Two episodes with clinical evidence of one lesion and subclinical evidence of another one.

临床很可能（clinically probable）MS 2次发作和1个部位病变的临床证据。 2次发作必须累及CNS的不同部位。 two episodes with clinical evidence of one lesion must be attributable to involvement of 2 or more parts of CNS. 历史资料于此不能用作病变部位的临床证据。 History dates cant be the clinical evidence of lesion locus here.

1次发作和2个不同部位病变的临床证据。 one episode with clinical evidences of two different lesions 1次发作，1个部位病变的临床证据和一个不同部位病变的亚临床证据one episode with clinical evidence of one lesion and subclinical evidence of another lesion

实验室支持的确诊（laboratory supported definite）MS 1次发作，有2个病变部位的临床证据，脑脊液中有IgG组分区带和/或IgG合成率增高。One episode with clinical evidence of two lesion , IgG fraction bands or the Synthesis of IgG increased in CSF

2次发作，有1个临床或亚临床病变，和脑脊液中有IgG组分区带和/或IgG合成率增高。Two episodes ,one lesion with clinical or subclinical evidence of , IgG fraction bands or the Synthesis of IgG increased in CSF 1次发作，有1个部位病变的临床证据和另1个不同病变的亚临床证据，和脑脊液中有IgG组分区带和/或IgG合成率增高。One episode with clinical evidence of one lesion ,and subclinical evidence of another one. IgG fraction bands or the Synthesis of IgG increased in CSF

实验室支持很可能（laboratory supported probable）MS 2次发作，脑脊液中有IgG组分区带和/或IgG合成率增高。 Two episodes with IgG fraction bands and/ or the Synthesis of IgG increased in CSF

1次发作和1个病变部位的临床证据，脑脊液中有IgG组分区带和/或IgG合成率增高。 One episode with clinical evidence of one lesion , IgG fraction bands and /or the Synthesis of IgG increased in CSF 1次发作，1个部位病变的亚临床证据，脑脊液中有IgG组分区带和/或IgG合成率增高 .One episode with clinical evidence of one lesion , IgG fraction bands and /or the Synthesis of IgG increased in CSF

临床可能 Clinical probable MS 进行性截瘫史，CNS至少有2个不同部位病变，除外其他疾病。Progressive paraplegia ,at least two lesions in CNS,except other diseases

可疑Suspected 1次发作，伴或不伴CNS 1个病变部位的证据one episode with or without the evidence of lesion of CNS 。反复发作单或双侧视神经炎，另有1次视神经以外的CNS发作，但无CNS以外病变的证据repeated unilateral or bilateral optic neuritis,with another episode of CNS,but no evidence out of CNS

多发性硬化的治疗 The treatment of MS
Disease modifying therapies: to reduce the frequency and severity of relapses as well as to prevent or postpone the onset of the progressive phase of the disease, slow sustained progression of disability, reduce new CNS lesion development, decrease brain atrophy, and maintain neuropsychological function.

β-干扰素Interferon-β 主要为免疫调节作用而非免疫抑制。 Main action: immunoloregulation,not immunosuppression 包括：抑制淋巴细胞的增殖反应、抗原提呈，及T细胞通过BBB进入CNS，促进抗炎细胞因子的产生。 include: Suppression the proliferation of lymphocytes, capacity of antigen-presenting,infiltration of T cells into CNS through BBB, production of proflammatory cytokines Avonex Interferon-β-1a interferon-β-1b

Glatiramer acetate （Copaxone）由4种氨基酸肽段混合而成：L-glutamic、L-alanine、 L-lysine and L-tyrosine。模仿MBP的序列。抑制淋巴细胞的迁移及增殖反应。Mimic the rank of MBP Inhibits the proliferation and migration of lymphocytes 20mg/d，皮下注射。20mg/d，Subcutaneous injection

免疫球蛋白 Azathioporin A Ciclosporin A Methotrexate A Cladribine Anti-a4 integrin Campath-1HA Lenercept TNF拮抗剂

急性期的治疗Acute phase 病情恶化：各种感染、电解质失衡、发热或药物毒性。deterioration： infection、Disequilibrium of electrolyte, Fever and Drug toxicity 既往曾使用ACTH，目前较多用固醇类药物。 once used ACTH ，now using Drug toxicity

作用机理：减轻水肿、炎症及解除传导阻滞。可加快疾病的恢复（recovery）速度，但对病情恢复的最终程度（degree）影响不大。 mechanism：relieve edema,inflammation and conduction block,approve the recovery，but weak effects on the endpoint of recovery take orally or iv by drip 使用方法有口服及静脉滴注，疗程长短不一，最常见的用法是静滴甲基强的松龙。The course of treatment differed from each other.Most common usage: Methylprednisolone iv by drip

注意感染Attention of infection 副作用：不安、失眠、焦虑、抑郁、精神症状、欣快感。因为用药为间断性，故远期的副作用并不多，可能会有：骨质疏松症或无菌性坏死。Side effect：agitation、agrypnia、anxiety、depression、psychiatric symptom、euphoria， long-term of ill effects:Osteoporosis or aseptic necrosis。

口服固醇类药物steroid treatment
地塞米松aeroseb-D 血浆交换Plasma exchange

新进展：免疫耐受、各种单克隆抗体、疫苗等 New progression：immunologic tolerance、all kinds of Monoclonal antibody、vaccine

并发症的处理Treatment of complication 痉挛: MS的常见症状。病人可能主诉：行走困难，僵硬，阵挛，痉挛，疼痛或平衡失调。 Spasticity The common symptoms of MS。The probable complaints:ambulation difficulty，stiffness,clonus，spasm，pain or dysequilibrium .

Baclofen 睡前使用大剂量，一般40-80mg/天，分3-4次。最大不超过100mg/天。不能突然停药，副作用发生于开始、增加剂量太快、大剂量或老年人时，包括虚弱及镇静时。 Large dosage before sleep，with the most serious of Spasticity mg/d, divide into 3-4parts. Maximum< 100mg/d Abrupt withdraw should be avoid,or mill be epilepsy、confusion、psychiatric symptom、tachycardia and transitory worsed spasticity.Ill effects happened at the beginning, large dosage 、rapidness of dosage augmentation. , the aged,including weakness and sedation。

疼痛刺痛、撕裂样痛、枪击样痛及痛性抽搐是MS的常见症状。2%的病人有三叉神经痛，绝大部分双侧性三叉神经痛由MS引起。 Pain： pricking、1aceration、gunshot –like pain and trismus dolorificus are the common symptoms of MS2% of patients have trifacial neuralgia，most of bilateral trifacial neuralgia result in MS。

苯妥英 Phenytoin 胶体次枸橼酸铋 Misoprostol、拉莫三嗪 Lamotrigine、丙戊酸钠 Sodium valproate、 baclofen 加巴喷丁 gabapentin

排尿障碍 MS中排尿障碍非常普遍。包括尿急、尿频、排尿不尽及排尿中断。 Bladder dysfunction ：Miction disorder is frequently seen in MS。Such as Pollakiuria, precipitant urination, intermittency.

抗胆碱能药Anticholinergic agents 奥昔布宁：抗胆碱能制剂，作用于平滑肌，抑制膀胱收缩，托特罗定：选择性膀胱胆碱能受体竞争剂二者均禁用于青光眼、尿潴留、肌无力及严重结肠炎. Oxybutynin ： Anti-cholinergic drugs, act on smooth muscles repression the contraction of bladder. Tolterodine: selective competitive agents of bladder cholinergic receptors Contraindication:glaucoma,uroschesis, myasthenia and critical colitis desmopressin

便秘 Bowel dysfunctionis the most common symptom of bowel dysfunction in MS。腹泻 Diarrhoea 。进食含高纤维的食物，增加运动，适当的药物 High fiber diet，do more exercise，appropriate drug

Favorable prognostic indicators
Early age of onset. Female sex. Optic neuritis as first episode. Acute onset of symptoms. Little residual disability following recovery from exacerbations. Long periods between exacerbations.

Unfavorable prognostic indicators
Later age of onset. Progressive course from outset. Male sex. Frequent exacerbations. Poor recovery from exacerbations. Involvement of cerebellar or motor functions.

视神经脊髓炎 Neuromyelitis optica

视神经脊髓炎 Neuromyelitis optica
视神经脊髓炎又称 Devic 病，是脱髓鞘病变局限在视神经和脊髓的、具有复发缓解倾向的一种MS变异型。单眼或双眼视力障碍vision disorder in ocellanae or Binocular 横贯性或上升性脊髓损伤transection or augmenting spinal injury

病因Etiology 病理 Pathology 局限在视神经、视交叉、视束及脊髓。脊髓损害好发于胸段，颈次之，腰少见。坏死多见。

临床表现clinical manifestation 20~40岁起病，女性多见急性或亚急性起病前驱症状

先后出现双眼视力障碍，可完全失明可伴眼球胀痛或头痛眼底早期为炎性改变，晚期可出现萎缩脊髓表现为不同程度的横贯性损害

辅助检查 Laboratory Findings 常规 CSF 诱发电位 MRI

诊断diagnose 病史history CSF 改变 the change of CSF MRI 与ADEM 、MS 及球后视神经炎鉴别diffretiation

Devic's disease affects only the optic nerves and spinal cord, whereas MS affects the brain as well.
Attacks of Devic's disease tend to be more frequent and severe than in MS.. An MRI of the brain is typically normal in Devics disease.

An MRI of the spinal cord shows large extensive areas of inflammation of the spinal cord whereas in MS typically the areas are much smaller. Spinal fluid studies tend not to show the typical elevation of antibodies detected in patients with MS. CSF shows a lymphocytosis

治疗treatment

急性播散性脑脊髓炎 Acute disseminated encephalomyelitis

急性播散性脑脊髓炎ADEM 急性播散性脑脊髓炎是一种单相病程广泛影响中枢神经系统白质的脱髓鞘疾病。通常出现于病毒感染及疫苗接种后，由血管周围过敏性应答所致的脑和脊髓弥漫性炎症，急性或亚急性起病。 Acute disseminated encephalomyelitis (ADEM), is a monophasic progressive demyelination disease affecting the white matter of CNS extensively, as a complication of inoculation or vaccination.The diffuse inflammation of brain and spinal cord induced by Peri-vessel hypersensitivity response is acute or subacute.

急性播散性脑脊髓炎ADEM 患者尚可发生急性出血性白质脑炎，是ADEM的重症型。具有更为严重的临床病程，包括白质出血坏死及极高的死亡率。
AHLE，the critical type of ADEM,have more serious clinical course including hemorrhage ,necrosis of white matter and high mortality .

急性播散性脑脊髓炎ADEM 病因感染在1790年首次报道感染后脑脊髓炎。麻疹曾经是ADEM最常见的诱因。继发于细菌、支原体、病毒感染；蚊虫咬伤，注射破伤风毒素，及其他疾病。发生于播散性结核或神经系统布鲁氏病。 Infection postinfectious encephalomyelitis was first reported in 1790。Measles used to be the most usual inducement of ADEM,which occurred after infection of bacteria, mycoplasm, virus, mosquito biting Injection of tetanus toxin or other disease,sometimes after disseminated tuberculosis and Bruce disease in nervous system. The demyelination of center and peripheral nerve is rare at the same time

急性播散性脑脊髓炎ADEM 灭活病毒及减毒病毒疫苗接种，尤其是在天花和狂犬病毒疫苗接种后脑脊髓炎最常发生。
灭活病毒及减毒病毒疫苗接种，尤其是在天花和狂犬病毒疫苗接种后脑脊髓炎最常发生。 Vaccination ：Encephalomyelitis always happen after vaccinate the inactivation virus and attenuation virus,especially variola and Lyssa

急性播散性脑脊髓炎ADEM 药物服用某些食物或药物后，如左旋咪唑、驱虫净、复方磺胺甲恶唑、蚕蛹等。 Drug：
Levamisole,Sulfamethoxazole, silkworm pupa

急性播散性脑脊髓炎ADEM 其他罕见病例发生于某些特殊时期，如围生期，手术后，或并发于某些恶性疾病如恶性组织细胞增生还有部分病人称为特发性ADEM。 Others Some rare cases happen in specific periods:perinatal stage，post operation or complication with some malignancy (eg. malignant histiocytosis).Some patients have no history of infection and vaccination.In this place , we call it idiopathic ADEM。

急性播散性脑脊髓炎ADEM 发病机制过去曾认为与病毒感染有关，经实验证明，本病与病毒感染无直接关系。
Alvord提出（1985年）本病是一种细胞免疫介导的自身免疫疾病，为髓鞘与抗髓鞘抗体之间所产生的迟发过敏反应。目前认为本病是CD4+T细胞介导的自身免疫疾病，其抗原为髓鞘/少突胶质细胞成分，很可能为MBP

急性播散性脑脊髓炎ADEM pathogenesis
Used to believe the relationship with virus,now it had been proved there are no direct relation. Alvord（1985）It is a cell-mediated autoimmune disease,the delayed type hypersensitivity between the myelin and the anti-myelin antigens,. Now it is believed this disease is induced by T cells，the antigen is the component of myelin /oligodendrocyte,perhaps MBP

急性播散性脑脊髓炎ADEM 证据如下 ADEM与EAE、AHLE与超急性EAE有极强的相似性，由T细胞介导，如EAE及超急性EAE可以通过淋巴细胞（非血清）转移给动物使之发病。对ADEM患者的血及CSF淋巴细胞研究发现，T细胞对MBP的反应性增强。但MBP不是唯一的相关抗原，蛋白质蛋白（PLP）和髓磷脂-少突胶质细胞糖蛋白（MOG）也可以是抗原之一。

急性播散性脑脊髓炎ADEM 病理学Pathology of ADEM
主要是静脉周围炎性脱髓鞘改变。 The demyelination inflammation perivessels 肉眼可见脑组织肿胀，白质静脉扩张。 Brain swelling can be seen by naked eye with phlebectasia in white matter.

急性播散性脑脊髓炎ADEM 微观上，静脉周围水肿，单个核细胞浸润。 For microcosmic,perivessels edema, MNC infiltration are showed. 多数为淋巴细胞、巨噬细胞浸润，浆细胞、粒细胞则少见，有内皮细胞增生。Most of MNC are lymphocytes and macrophages.Plasmacytes and granulocytes are rare,with the proliferation of endothelium.

急性播散性脑脊髓炎ADEM 在AHLE，大体上可见大脑肿胀，点状出血，环形出血。 In AHLE， brain swelling ，annular and point shape blooding. 显微镜下，有纤维样坏死，有中性粒细胞、偶有嗜酸性粒细胞在血管旁浸润。 With microscope,there are fibroid necrosis with the infilitration of granulocyte in vessels。

急性播散性脑脊髓炎ADEM 血浆蛋白、红细胞、粒细胞分布于血管周围。 Plasma protein, erythrocyte and granulocytearoud the vessels 环状出血合并静脉血栓形成。 Annular shape blooding with venous thrombosis. 病变一般不累及灰质。 No lesion in gray matter

急性播散性脑脊髓炎ADEM 临床表现Clinical situation
ADEM的临床表现多种多样。它可以无明显症状，而由其他原因行MRI检查时发现脑白质多发病灶。 The clinical ADEM is nonspecific。 It can be just happened to find the multifocal lesions in white matter by MRI without symptoms

急性播散性脑脊髓炎ADEM 爆发性、急性进展性的疾病，出现抽搐、昏迷甚至死亡。 It can be the explosively acute progressive disease with twitch,coma ,even death. 神经症状通常在感染后1～3个星期出现。尤其是麻疹感染后ADEM发生更快，约3～7天。Symptoms of nervous system always occurred 1-3weeks after infection. For measles,3-7days.

急性播散性脑脊髓炎ADEM 头痛、恶心、呕吐、昏迷、妄想、愚钝并持续数天。 Symptoms includes: headache, nausea, vomitus, coma, delusion that will occure over days . 局灶神经系统体征，半身瘫痪，偏身感觉障碍，共济失调，视觉障碍，四肢瘫痪。And also hemiplegia,hemi-sensory disability,atxia,visual disorder，quadriplegia。

急性播散性脑脊髓炎ADEM 小脑共济失调，视神经炎及横贯性脊髓炎。 optic neuritis,transverse myelitis.
抽搐、肌肉强直和记忆丧失也有报道。 Tic,muscle rigidity,memory loss were reported. 偶尔基底节区的病变也可产生肌张力异常，舞蹈症，手足徐动症和肌强直Occasionally,there will be myodystonia, chorea, athetosis, myotonus because of basal ganglia lesions

急性播散性脑脊髓炎ADEM 复发病例的鉴别病前多有前驱症状多伴有发热有精神症状或智能改变模拟第一次症状

急性播散性脑脊髓炎ADEM 诊断和鉴别诊断Diagnosis and differentiation 诊断
急性或亚急性发热性神经系统疾病的临床表现。常见意识状态改变，发生于非特异性病毒感染后及接受免疫接种之后。 Diagnosis: clinical situation of acute or subacute febrile nervous system disease. frequently with the change of conscious state，after the infection of non-specific virus and vaccination

急性播散性脑脊髓炎ADEM 脑电图 EEG无特征性改变，脑电图通常表现为非特异性弥漫性慢波，高电压、不对称。EEG与疾病的活动程度相关.
EEG have no characteristic change，non-specific diffused slow wave,high pressure, asymmetry。It correlate with the activity of disease. 诱发电位体感诱发电位检查，刺激正中神经有异常。视觉诱发电位，脑干听觉诱发电位在横贯性脊髓炎的患者是正常的。Some patients with acute transverse myelitis ,in the exam of omatosensory evoked potential, median nerve is abnormal, VEP and auditory evoked potential have no abnormity

急性播散性脑脊髓炎ADEM 脑脊液检查 ADEM、AHLE脑脊液检查大多有异常，但无特异性。 The CSF of ADEM and AHLE always exhibits non-specific abnormity 脑脊液压力一般正常或略高，除横贯性脊髓炎脊髓急性肿胀引起椎管梗阻外，动力试验正常。 The pressure is normal or just slight high. Queckenstedt's test is normal except the acute edema inducing the obstruction of vertebral canal in transverse myelitis 糖和氯化物正常..Normal sugar and chloride.normal or gently increased protein.

急性播散性脑脊髓炎ADEM 蛋白含量正常或轻度升高，若有明显升高又排除椎管梗阻，则提示有脊神经根受累。20％至25％CSF中的IgG升高，并可有寡克隆带Significant increase without obstruction suggest the lesion of spinal nerve root ％of IgG raised , oligoclone zone may appear. 1000mg/dl,10% no abnormity. 在AHLE患者脑脊髓中，通常有中性粒细胞和红细胞，蛋白浓度也升高。25%病人大于200mg/dl，最高至1000mg/dl。10%患者CSF完全正常。 In CSF of AHLE,there is always neutrophil and erythrocyte with improved protein. 25%

急性播散性脑脊髓炎ADEM ADEM和MS
鉴别关键在于MRI表现及病程的发展。 ADEM组MRI显示皮层下白质病灶，两组无差别。ADEM组中90％患者部分或全部病灶消失，而无新病灶出现。 The key point of differentiation of ADEM and MS lies MRI and the development of the disease。The lesion of subcortex white matter in MRI shows no difference between ADEM and MDEM. The lesions of 90％ of ADEM/EDEM patients completely or partial disappeared without new lesion.

急性播散性脑脊髓炎ADEM MRI表现为脑白质内不对称的、多发片状或点状病灶，并可表现出“垂直征”（病灶垂直于脑室排列）的分布特点，病变可以同时累及脑干、基底节或皮质。MRI shows the asymmetrical, multifocal or point-like lesions in white matter ,sometimes with “vertical signs”,The lesion can be in brain stem,basal ganglia and cortex at the same time.

急性播散性脑脊髓炎ADEM 病变通常呈T1长信号T2长信号，病灶中心可有坏死灶、偶有小出血点，急性期可有病灶周围水肿及明显病灶增强。On MRI,the lesion always be increased T-1 and T-2 signals.There may be necrosis in the center, and micro-hemorrhagic spots by chance.There are peri-lesion edema and marked increased signals. 治疗后复查MRI应无新病灶出现，亦无异常增强。Review MRI after therapy should not show new lesions and no anomaly enhancement,

急性播散性脑脊髓炎ADEM 治疗方法无特异、有针对性的治疗方法。 No special treatment,and the treatment for the symptoms is very important 对症治疗是非常重要的，许多病人经治疗后度过急性期，并恢复有用的功能。 Lots of people live through the acute phase,and regain some functions.

急性播散性脑脊髓炎ADEM 降低高热，保持生命体征的稳定，水电解质的平衡，营养支持，防治褥疮和尿路感染，及治疗癫痫发作都非常重要。
Reducing the fever, stable of vital signs,equilibrating the balance of water-electrolyte,nutritional support, prevention and curing decubital ulcer and urinary tract infection and treat epileptic seizure are all important.

急性播散性脑脊髓炎ADEM 在出现脑疝，特别危及脑干中枢时，使用过度通气和渗透性物质治疗脑水肿十分重要。 When brain hernia present,especially endanger the centers of brain stem,it is very useful to superventilation and permeable material to treat the brain edema. 康复治疗、物理治疗在恢复期也很重要。Rehabilitation and physiotherapy can’t ignored in convalescence.

急性播散性脑脊髓炎ADEM 皮质类固醇：可以减轻水肿，减少炎症反应，和保护血脑屏障（从而减少血浆蛋白的扩散及活性免疫细胞进入脑干）。可用静脉皮质类固醇冲击治疗，而后渐减量至口服泼尼松。Corticosteroid ：relieve edema and Inflammation,protect BBB(reduce the diffuse of plasma protein and competent immunocyte into brain stem. Corticosteroid impact therapy can be used ,and then deduct to oral prednisone gradually。血浆置换：用常规皮质类固醇治疗无效后可改用血浆置换。plasma exchange ： used for Inefficiency of Corticosteroid

急性播散性脑脊髓炎ADEM 免疫球蛋白治疗 Immunoglobulin
对ADEM，尤其是难治性糖皮质激素治疗无效的ADEM的治疗有帮助。 It is helpful for ADEM，especially the inefficiency of Corticosteroid patients that is hard to treat. Marchioni E 等人尝试用免疫球蛋白治疗。对糖皮质激素反应差者。 Marchioni E et al tried to used it .4 of 5 responsed poorly to Corticosteroid. IVIG（0.4g/Kg/d），在开始5天就出现症状的改善，第三个星期则病情完全恢复After 5days of IVIG（0.4g/Kg/d）,the 5 people showed the amelioration,and fully recovered in the 3th week.The review of MRI of all the patients suggested the favorable turn

急性播散性脑脊髓炎ADEM 预后Prognosis
本病临床少见，预后因发病诱因及病情轻重而不同，病死率在10％至30％。幸存者多在发病2～3周后开始逐渐好转，绝大多数患者有相当大程度的恢复，不少病人可以痊愈，部分病人可遗留智能或行为障碍，亦有残留癫痫发作或运动障碍者。prognosis is different for the inducement and the patient's condition. fatality rate:10-30％,The survival will take a favorable turn after 2～3w.Most of patients have considerable reversion.some persons can be fully recovered, some people will have disturbance of intelligence an behavior,there are also seizure and motor disturbance left.

急性播散性脑脊髓炎ADEM 目前尚有三个问题需要解决： Three problems need to be solved
急性播散性脑脊髓炎的最佳治疗；The best treatment of ADEM ADEM的发病机制； Pathogenesis 单次的脱髓鞘发作与继发MS之间的关系。 The relationship of one episode of demyelination and the secondary MS

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