脱髓鞘疾病医疗及研究管理知识分析

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,周文斌,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,周文斌,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,周文斌,*,215,脱髓鞘疾,病,病,中南大学,湘,湘雅医院,神,神经内科,周文斌,神经纤维,指,指轴突而,言,言，分为,有,有髓和无,髓,髓神经纤,维,维。,Nerve fiberor an axon,Myelinated NerveFiber,UnmyelinatedNerve Fiber,髓鞘,:,紧裹在有,髓,髓鞘神经,轴,轴突外面,的,的脂质细,胞,胞膜，由,髓,髓鞘形成,细,细胞膜组,成,成。,Myelin is alayer that formsaroundnerves formed bywrappedplasmamembraneofmyelinization cells.,髓鞘：蛋,白,白质,22%,，脂类,78%,Myelin,：,protein22,andlipids 78,蛋白质,:,碱性蛋白,、,、脂蛋白,、,、糖蛋白,等,等。,Protein,：,Basic protein,、,lipoprotein,、,glucoprotein,脂类,:,胆固醇、,神,神经鞘磷,脂,脂、脑苷,脂,脂与神经,节,节苷脂。,Lipide,：,lipide,、,sphingomyelin,、,galactosylceramide,、,ganglioside,生理作用,：,Physiological functions,神经冲动的,快,快速传导；,Speeding the transmissionofimpulses,对神经轴突,起,起绝缘、保,护,护作用。,Insulationandprotectionof neuraxon,髓鞘系统,： 髓鞘、,轴,轴索与完整,的,的血供,Myelin system:myelin,、,axonand intactblood supply,脱髓鞘疾病,：,CNS,白质对各种,有,有害因素的,反,反应,Demyelinating disease,脱髓鞘脑病,Demyelinating encephalopathy,髓鞘构成缺,陷,陷性疾病,（白质营养,不,不良症）,myelin constructiondeficiencysyndromeLeukodystrophy,周围神经系,统,统脱髓鞘疾,病,病,Peripheralnerveousdemyelination,CNS:White matter disease,Demyelinating:mainly acquired,MS,PML,Encephalomyelitis(ADEM),Anti-MAG Disease,CNS:White matter disease,Dysmyelinating:mainly inherited,Leukodystrophies:,ALD Alexander,Canavan disease,Krabbe Disease,MLD,Pelzaeus-MerzbacherDisease,Refsum,PNS:Neuropathies,Acquired:,mainly autoimmune, demyelinating polyneuropathies,.,Acute:GBS,Chronic:,CIDP,Anti-MAG syndrome,Multiple MotorNeuropathy(MMN),PNS:Neuropathies,Hereditary:,mainly dysmyelinating.,HMSN/CMT,Cockayne Syndrome,Krabbe Disease,MLD,Refsum Disease,Conductionin aDemyelinated NerveFiber-KH,多发性硬化,Multiple Sclerosis,CNS,白质的慢性,，,，炎性，斑,块,块性脱髓鞘,，,，,CD 4,+,T,细胞介导的,自,自身免疫性,疾,疾病。,Chronic, progressiveimmune-mediated CNSdisease,Characterized by demyelinationandaxonal loss,全世界病人,超,超过,200,万。,Affectingover2 millionpersons worldwide,概述,overview,最常损害部,位,位是脑室周,围,围白质、视,神,神经、脊髓,、,、脑干传导,束,束及小脑白,质,质。,whitematter bordering the lateralventricles,、,opticus,、,spinal cord,、,pyramidaltractandCerebellarwhite matter,引起年轻成,人,人中神经残,疾,疾的最常见,疾,疾病（美国,）,）。,The most commondisablingneurological disease ofyoungpeople .,概述,overview,女性多见,Womenoutnumbermen2:1,缓解复发病,程,程，逐渐加,重,重,Progressive relapsing-remitting course,可能与早期,病,病毒感染有,关,关,no specific causes,viralmaybe responsible,概述,overview,Vit D,缺乏与,MS,MS,具有显著的,地,地理分布特,征,征,:,在赤道几内,亚,亚区,MS,的发生率几,乎,乎为零，在,两,两半球随着,纬,纬度的增加,而,而戏剧性的,增,增加,在瑞士高海,拔,拔区,MS,发生率低，,低,低海拔区发,生,生率高,低纬度区阳,光,光充足，高,海,海拔区紫外,光,光强度高，,能,能够促使大,量,量,Vit D,合成,Vit D,缺乏与,MS,VitD,能抑制,DC,分化、,Th1,细胞增殖，,减,减少,IL-12,、,IFN-,产生,VitD,能促进调节,性,性,T,细胞增殖，,促,促进,IL-10,、,TGF-,分泌,概述,overview,第一次肯定,了,了,MS,临床症状与,MS,尸检病理之,间,间的关系；,第一次提出,了,了“硬化与,斑,斑块”的概,念,念；,scleroseen plaques,第一个认定,MS,是一种独立,的,的疾病；,第一个提出,MS,的诊断标准,-,即“,Chacot,三联症”；,Triad: nystagmus, intention tremor,scanningspeech,他还对,MS,的病理特征,进,进行了详细,的,的描述，如,髓鞘脱失,demyelination,胶质纤维增,生,生,macrophages,等。,病因、发病,机,机制,Etiology,：,免疫,immunity,：,EAE,Experimental allergic encephalomyelitis,，致敏（活,化,化）的抗原,特,特异性的,CD4+T,细胞。,The activated antigenic specifically CD4+ cell.,病毒,virus,：,分 子模拟,机,机制,molecule mimicry mechanism,激发自身免,疫,疫反应,autoimmuneetiology,遗传,heredity,：单卵双生,子,子、,HLA,EAE,：实验性自,身,身免疫性脑,脊,脊髓炎,Experimental allergic encephalomyelitis,使用,MBP,或,PLP,免疫,Lewis,大鼠；,ImmunizingtheLewisratby MBP andPLP,MBP,致敏的,T,细胞转输给,正,正常大鼠。,transfusion theMBPactivatedTc tonormal rats,病因、发病,机,机制,Etiology,：,初始,T,细胞,Th2,Th1,巨噬细胞,IL-2,IL-12,IFN-,TNF,B,细胞,相互抑制,IL-4,IL-5,IL-10,IL-12,TGF-,初始,CD4,+,T,细胞分化,Th1,Th2,Th1,Th2,正常,MS,Th1/Th2,平衡,Th1,细胞,：,IL-2,、,IFN-,等,Th2,细胞,：,IL-4,、,IL-6,等,Th17,细胞,：,IL-17,巨噬细胞、,DC,：,IL-12,、,IL-23,Th1/Th2,平衡,IL,-1,2,主要由树突,状,状细胞、巨,噬,噬细胞,产生，是由,p35及p40 2条,多,多肽链以二,硫,硫键的形式,结,结合在一起,的,的异二聚体,型,型,（,IL-12p70,）。,IL-12,能刺激,Th1,细胞增殖,诱导免疫效,应,应细胞产生,IFN-,。,IFN-,可调节细胞,因,因子,“,级联作用模,式,式,”,增强免疫应,答,答。,Th1/Th2,平衡,IL-12,是,Th1,分化的关键,因,因子，然而,IL-12,基因敲除小,鼠,鼠仍能产生,EAE,；,IFN-,是,Th1,的,重,重,要,要,致,致,病,病,因,因,子,子,，,，,然,然,而,而,IFN-,基,因,因,敲,敲,除,除,仍,能,能,诱,诱,导,导,产,产,生,生,EAE,，,而,而,且,且,恢,恢,复,复,缓,缓,慢,慢,。,。,其,他,他,致,致,病,病,机,机,制,制,？,？,Th1/Th2,平,衡,衡,Thl7,细,胞,胞,是,是,新,新,近,近,发,发,现,现,的,的,辅,辅,助,助,性,性,CD4+,细,胞,胞,，,，,因,因,其,其,独,独,特,特,的,的,表,表,型,型,特,特,征,征,和,和,分,分,泌,泌,IL-17,而,得,得,名,名,。,。,IL-17,具,有,有,强,强,大,大,的,的,招,招,募,募,中,中,性,性,粒,粒,细,细,胞,胞,及,及,促,促,进,进,多,多,种,种,细,细,胞,胞,因,因,子,子,释,释,放,放,的,的,作,作,用,用,，,，,处,处,于,于,固,固,有,有,免,免,疫,疫,和,和,适,适,应,应,性,性,免,免,疫,疫,反,反,应,应,的,的,交,交,接,接,面,面,。,。,Th17,细,胞,胞,IL-17,在,EAE,模,型,型,小,小,鼠,鼠,急,急,性,性,期,期,的,的,外,外,周,周,血,血,和,和,脑,脑,脊,脊,液,液,中,中,都,都,有,有,较,较,高,高,水,水,平,平,的,的,表,表,达,达,IL-17-/-,小,鼠,鼠,对,对,EAE,不,敏,敏,感,感,，,，,抗,抗,IL-17,抗,体,体,可,可,以,以,使,使,EAE,症,状,状,明,明,显,显,减,减,轻,轻,。,。,多发性,硬,硬化病,人,人的脑,组,组织、,血,血的单,核,核细胞,以,以及脑,脊,脊液中,IL-17,的,mRNA,及蛋白,的,的表达,均,均明显,升,升高。,Th17,细胞,CD4+CD25+,调节性,T,细胞,是具有,免,免疫调,节,节功能,的,的,T,细胞亚,群,群，具,有,有免疫无,能,能和免疫抑,制,制两大功,能,能特征,。,。,MS,患者外,周,周血,CD4+CD25+T,细胞数,量,量变化,不,不明显,，,， 但,CD4+CD25+T,细胞抑,制,制活性,降,降低。,调节性,T,细胞,Th17,、,Th1,、,Th2,、,CD4+CD25+T,细胞这,4,种,T,细胞亚,群,群及细,胞,胞因子,相,相互作,用,用、此,消,消彼长,组,组成的,复,复杂网,络,络在,MS/EAE,的疾病,发,发展进,展,展中起,重,重要作,用,用,免疫反,应,应背离,Th2,、,CD4+CD25+T,细胞，,而,而向,Th1,、,Th17,细胞偏,移,移是自,身,身免疫,性,性疾病,发,发生发,展,展的重,要,要机制,Antibodies in MS,OCBs:90% patients,temporalandclonal invariance, RestrictedB-cell VH repertoireinMSCSF andMSlesions antigen-drivenresponse, ListofautoantibodiesinMSever-expanding, Hightitreantibodiesagainst myelinAginMSareinconsistent andunrelatedtoclinicaloutcomes., OCBsare noteliminated by RTX,Autoantibody-mediateddisorders of theCNS?,1.Antibodies directed towardsarelevantcell surfaceepitope,2.Immunotherapy andPLEX resultina reductioninantibodytitreassociated withamelioration of disease,3.Passive transfer of theimmunoglobulin(Ig) fraction fromanaffectedpatientreproduces theclinicalphenotypeinanexperimental animal., Autoantibodies maybenegativeregulators of inflammation(lipidantigen:antiphosphatidylcholine,病理,pathology,CNS,白质,内,内有,多,多发,性,性脱,髓,髓鞘,斑,斑块,，,，围,绕,绕小,静,静脉,分,分布,，,，血,管,管周,围,围袖,套,套状,、,、淋,巴,巴细,胞,胞为,主,主的,浸,浸润,，,，引,起,起髓,鞘,鞘的,崩,崩解,，,，可,伴,伴有,轴,轴索,的,的破,坏,坏,。,Peri-venuledistributionofDemyelinatingPlaquesoccuranywherewithinthewhitematteroftheCNS.cuffsoflymphocytesaroundsmallbloodvessels,damageofmyelinsheathanddestructionofaxis-cylinder.,脑、,脊,脊髓,和,和视,神,神经,常,常有,萎,萎缩,。,。,Theatrophyofbrain,、,spinalcordandopticalnerve.,晚期,星,星状,细,细胞,增,增生,、,、神,经,经胶,质,质形,成,成,硬化,斑,斑。,Proliferationofastrocytes,sclerosisplaqueswithglialscarformationinthelatephase,病理,pathology,Top:Coronalbrainsectionshowingnumerousplaquesofdemyelination,particularlyintheperiventricularregion.Bottom:Thecorrespondingareasshowdecreasedblackstainingformyelinandincreasedgliosis(darkstaining).,Itisasectionofbrainstainedformyelin(blue).Theplaquesofdemyelinationappearaswell-demarcatedpaleareaswithacentralbloodvessel.,Itisalongitudinalsectionofopticnervefromapatientwithmultiplesclerosis.Thepaleareatotheleftisdemyelinatedandthereissharpdemarcationfromthemyelinatedareatotheright.,Itissectionofoccipitallobestainedformyelin.Thecentralwhitematterispaleduetolackofmyelin.,Itisacrosssectionofponsfromacaseofcentralpontinemyelinolysis,stainedformyelin.Thepaleareainthemiddleisanareaofdemyelination.,临床,表,表现,ClinicalPresentation,发病,年,年龄,多,多为,20-40,岁,generalonsetiscommonbetweentheagesof20-40,；,多为,静,静止,性,性、,亚,亚急,性,性起,病,病，,临,临床,征,征象,提,提示,病,病灶,多,多发,，,，病,程,程多,波,波动,，,，常,有,有自,然,然缓,解,解及,复,复发,。,。,可累,及,及视,神,神经,opticalnerve,、脊,髓,髓,spinalcord,、脑,干,干,Brainstem,、小,脑,脑,cerebellum,及大,脑,脑的,白,白质,whitematterofbrain,首发症状,为,为一个或,多,多个肢体,无,无力或麻,木,木；单眼,或,或双眼视,力,力障碍，,或,或 复视,.,T,hefirst clinical eventincluding the somatastheniaortheanesthesia of one ormore limbs, visiondisorder insimpleeyeor two,andambiopia.,临床表现,ClinicalPresentation,颅神经功,能,能障碍：,视,视神经、,视,视交叉、,脑,脑干,Damage of encephalicnervesnerve:optical nerve,、,chiasm opticum,、,brainstem,视神经损,害,害最常见,：,：多为单,侧,侧性，球,后,后视神经,炎,炎，可部,分,分恢复，,无,无视网膜,脱,脱落，视,乳,乳头出血,少,少见。,Damage of opticnerve,：,Typically unilateralretrobulbarneuritis, Somerecoveryexpected, No retinal exudates,Dischemorrhagesareinfrequent.,临床表现,ClinicalPresentation,眼底检查,早,早期可见,视,视乳头水,肿,肿或正常,，,，晚期出,现,现视神经,萎,萎缩。,眼球运动,ocular movement,：,核间性眼,肌,肌麻痹,internuclearophthalmoplegia,：内侧纵,束,束,fasciculus longitudinalis medialis,外展神经,、动眼神,经,经,，可导致,复,复视,ambiopia,、眼球震,颤,颤,nystagmus,、眼球运,动,动受限,limitation of ocularmovement,。,临床表现,ClinicalPresentation,面部感觉,障,障碍,disability of facialperception,、面瘫,facial paralysis,眩晕,dizzy,吞咽困难,dysphagia,临床表现,ClinicalPresentation,脊髓损害,Damage of spinalcord,：,脊髓后柱,或,或脊髓丘,脑,脑束病变,，,，多见于,颈,颈髓。,posterior columnofspinal cordorposteriorcolumn of spinalcord, especially incervical cord,不完全的,感,感觉及运,动,动障碍，,感,感觉障碍,更,更多,Partialsensoryor motordisfuncion,Sensorymorecommon,临床表现,ClinicalPresentation,感觉障碍,sensorydisability,：麻木、,疼,疼痛、瘙,痒,痒，浅感,觉,觉减退，,深,深感觉障,碍,碍,anaesthesia,、,pain,、,pruritus,、,decreased superficial sensation,、,deepsensation disability,Lhermittes,征,Lhermittessign,：屈颈时,出,出现从背,部,部放射至,足,足底或双,下,下肢的放,射,射性疼痛,，,，可为闪,电,电感。,大小便功,能,能障碍常,见,见，可有,束,束带感。,Bowelandbladderdysfunctionsarecommon,withband-likepressure,临,床,床,表,表,现,现,ClinicalPresentation,肢,体,体,无,无,力,力,：,：,一,一,个,个,或,或,多,多,个,个,肢,肢,体,体,无,无,力,力,，,，,下,下,肢,肢,比,比,上,上,肢,肢,重,重,，,，,不,不,对,对,称,称,性,性,瘫,瘫,痪,痪,。,。,疲,劳,劳,运,动,动,障,障,碍,碍,：,：,motordisorder,痉,挛,挛,性,性,瘫,瘫,痪,痪,:,motordisorder,小,脑,脑,性,性,共,共,济,济,失,失,调,调,:,cerebellarataxia,感,觉,觉,性,性,共,共,济,济,失,失,调,调,:,sensoryataxia,临,床,床,表,表,现,现,ClinicalPresentation,小,脑,脑,Cerebellum,：,小,脑,脑,性,性,震,震,颤,颤,，,，,共,共,济,济,失,失,调,调,，,，,小,小,脑,脑,性,性,眼,眼,震,震,Cerebellartremor,、,ataxia,、,cerebellarnystagmus,。,临,床,床,表,表,现,现,ClinicalPresentation,精,神,神,症,症,状,状,和,和,认,认,知,知,功,功,能,能,障,障,碍,碍,表,现,现,为,为,抑,抑,郁,郁,、,、,易,易,怒,怒,和,和,脾,脾,气,气,暴,暴,躁,躁,记,忆,忆,力,力,减,减,退,退,发,作,作,性,性,症,症,状,状,强,直,直,性,性,痉,痉,挛,挛,，,，,痛,痛,性,性,痉,痉,挛,挛,三,叉,叉,神,神,经,经,痛,痛,常,见,见,：,：,运,动,动,乏,乏,力,力,、,、,感,感,觉,觉,异,异,常,常,、,、,视,视,力,力,下,下,降,降,与,与,复,复,视,视,Common:debility,、,paresthesiaandambiopia,。,两,个,个,重,重,要,要,体,体,征,征,：,：,核,间,间,性,性,眼,眼,肌,肌,麻,麻,痹,痹,、,、,眼,眼,球,球,震,震,颤,颤,。,Twoimportantsigns:internuclearophthalmoplegia,、,nystaxis,临,床,床,表,表,现,现,SymptomsofMS,少,见,见,：,：,认,认,知,知,障,障,碍,碍,、,、,癫,癫,痫,痫,、,、,神,神,志,志,障,障,碍,碍,。,。,Few:cognitivedysfunction,epilepsia,confusedstateofmind.,Charcot,三,联,联,征,征,：,：,共,共,济,济,失,失,调,调,（,（,眼,眼,球,球,震,震,颤,颤,）,）,、,、,构,构,音,音,障,障,碍,碍,（,（,吟,吟,诗,诗,样,样,语,语,言,言,）,）,及,及,意,意,向,向,性,性,震,震,颤,颤,。,。,CharcotTriad,：,dystaxia,dysarthriaandIntentionmyoclonus,临,床,床,表,表,现,现,SymptomsofMS,脑,脊,脊,液,液,cerebrospinalfluid,寡,克,克,隆,隆,带,带,oligoclonalband,IgG,指,数,数,IgGexponent,髓,鞘,鞘,碱,碱,性,性,蛋,蛋,白,白,myelinbasicprotein,电,生,生,理,理,检,检,测,测,Electrophysiologydetection,诱,发,发,电,电,位,位,evokedpotential,辅,助,助,检,检,查,查,LaboratoryFindings,TypicalofMS,NormalCSFglucose,NormalormildlyelevatedCSFprotein,Absentredbloodcells,Smallnumberofmononuclearwhitecells,Evidenceofintrathecalantibodyproduction,IncreasedIgGindexorIgGsynthesisrate,Oligoclonalbands,Increasedfreekappalightchains,MRI,T1,反,映,映,了,了,质,质,子,子,置,置,于,于,磁,磁,场,场,中,中,产,产,生,生,磁,磁,化,化,所,所,需,需,的,的,时,时,间,间,，,，,即,即,继,继,90,度,RF,质,子,子,从,从,纵,纵,向,向,磁,磁,化,化,转,转,为,为,横,横,向,向,磁,磁,化,化,之,之,后,后,恢,恢,复,复,到,到,纵,纵,向,向,磁,磁,化,化,平,平,衡,衡,状,状,态,态,所,所,需,需,时,时,间,间,。,。,T2,弛豫时间，,表,表示在完全,均,均衡的外磁,场,场中横向磁,化,化所维持的,时,时间。,辅助检查,LaboratoryFindings,T1,像，,多见于两侧,脑,脑室旁、尤,以,以两侧前角,及,及后角周围,可,可见多发散,在,在类圆形或,融,融合性斑块,状,状形态不规,则,则的低信号,区,区，,与脑室壁垂,直,直，,无占位效应,。,。,T2,为高信号。,辅助检查,LaboratoryFindings,根据病灶形,态,态、信号，,可,可以分为急,性,性病灶和慢,性,性病灶。,急性病灶：,1、呈卵圆,形,形或圆形，,有,有明显膨胀,感,感，边界清,晰,晰。,2、,T1WI,呈低或略低,信,信号，周围,可,可见等或峪,高,高信号带。,3、,T2wI,病灶可分两,部,部分，中央,呈,呈卵圆形或,圆,圆形高信号,，,，有膨胀感,，,，拟”泡”,状,状，类似一,个,个“核心”,。,。周围呈环,形,形或片状中,等,等程度高信,号,号，类似“,晕,晕环”。即,与,与内部病灶,有,有信号上的,差,差异，为“,核,核心,+,晕环”征象,推测中央高,信,信号“核心,”,”病理上为,脱,脱髓髓，而,周,周围“晕环,”,”为炎症及,水,水肿。,急性期，,TlwI,低信号相当,于,于髓鞘的脱,失,失及不伴有,结,结构损坏的,血,血管源性水,肿,肿，随着髓,鞘,鞘组织的再,生,生和炎性反,应,应的消退，,T1wI,低信号会消,失,失。,慢性病灶也,可,可分为两种,，,，一为大体,对,对称性的病,灶,灶，分布于,侧,侧脑室旁，,呈,呈细小点状,或,或较小片状,，,，部分融合,成,成较大片状,，,，病灶有收,缩,缩感，边缘,较,较锐利，信,号,号较均匀，,周,周围无晕环,征,征象，增强,后,后无明确强,化,化灶，但病,变,变区可呈现,片,片状淡薄高,信,信号,另一种病灶,分,分布较分散,，,，额、顶叶,，,，侧脑室旁,，,，脑干等处,都,都有，呈条,状,状或小片状,，,，同样有收,缩,缩感，边缘,较,较锐利，信,号,号均匀，增,强,强后无强化,慢性,MS,病灶呈不规,则,则条状、斑,片,片状，有收,缩,缩感，,T1wI,呈等或轻微,至,至中等程度,低,低信号，,T2WI,呈高信号，,病,病灶有时边,界,界欠清。,有些慢性病,灶,灶,T1wI,信号很低，,呈,呈所谓“黑,洞,洞”状，可,能,能标志着严,重,重的、不可,逆,逆的组织结,构,构破坏。,图lA、B MS单,发,发病灶。病,灶,灶分别位于,延,延髓后方、,左,左侧小脑半,球,球，TlwI呈略低信,号，T2W!呈高信号,。,。,图,2 MS,多发病灶。,横,横断面平扫,PDWI,、增强,T1wI,。多发病灶,位,位于两侧脑,室,室旁、右侧,颞,颞叶及胼胝,体,体。,图,3 MS,多发病灶。,病,病灶弥漫，,无,无法确切记,数,数，呈“自,质,质变脏征”,。,。,图4 MS,大,大病灶。横,断,断面平扫T2WI、增,强,强T1WI,。,。右侧额叶,白,白质内-r2wi高信,号,号影,增强后见边,缘,缘近弓形强,化,化，病灶无,占,占位效应。,图5 MS,急,急性病灶。,横,横断面平扫T1WI、T2WI、,增,增强T1wI。T2WI呈“核心+晕环”征,象,象，增强后,见,见环形、弓,形,形强化及无,强,强化病灶，,提,提示不同时,期,期病灶同时,存,存在。,图,6,A,、,BMS,慢性,病,病灶,。,。多,发,发病,灶,灶分,别,别呈,近,近对,称,称分,布,布于,两,两侧,脑,脑室,旁,旁及,散,散在,分,分布,于,于额,顶,顶叶,、,、侧,脑,脑室,旁,旁、,脑,脑干,等,等，,呈,呈小,条,条、,片,片状,，,，有,收,收缩,感,感，,同,同时,显,显示,全,全脑,萎,萎缩,。,。,图7,颈,颈,髓,髓、,胸,胸髓,、,、颈,胸,胸髓MS,。,。矢,状,状面,平,平扫T2WI,，,，分,别,别见,颈,颈、,胸,胸髓,粗,粗细,正,正常,或,或不,同,同程,度,度增,粗,粗，,髓,髓内,见,见条,状,状T2WI高,信,信号,影,影。,图,8,脊髓,MS,。横,断,断面,T2W1,平扫,。,。分,别,别见,单,单发,及,及多,发,发病,灶,灶。,Nicknamed,“,“blackholes,”theareasofhypointensityseenonT1-weightedimagesarebelievedtoindicatethatMSisadiseasenotonlyofdemyelinationbutalsoofaxonaldestruction,ThisMRIscanwithgadoliniumenhancementshowsactiveplaques(brightareas).,女性,41,岁，,半,半个,月,月前,开,开哭,笑,笑无,常,常，,站,站立,不,不稳,，,，双,眼,眼视,力,力下,降,降。,多发,性,性硬,化,化,MRIfeaturesthatsuggestMS,4whitematterlesions,3mmindiameter,3whitematterlesions,ofwhich1isperiventricular,Lesions,6mm,Ovoidlesionsorientedperpendiculartotheventricles,Brainstemlesions,Openringappearanceongadolinium-enhancedT1-weightedimages,Differentialdiagnosis,Infection,:,Lymedisease,syphilis,progressivemultifocalleukoencephalopathy,HIV,HTLV-1leukodystrophy,Inflammatory,:,SLE,、,Sjogren,、,Behcet,vasculitis,sarcoidosis,Metabolic,:,VitaminB12deficiency,lysosomaldisorders,Adrenoleukodystrophy,mitochondrialdisorders,othergeneticdisorders,Differentialdiagnosis,Differentialdiagnosis,Neoplastic,:CNSlymphoma,Metastaticcancer,Paraneoplasticsyndrome,Primarybraintumor,Spinaldisease,:Vascularmalformations,degenerativespinaldisease,Differentialdiagnosis,Vascular,Antiphospholipidsyndrome,CADASIL,Ealesdisease,Cerebrovasculardisease,RetrocochlearvasculopathyofSusa,Migraine,Vasculitis,发,作,作,、,、,复,复,发,发,（,（,attack,，,exacerbation,，,relapse,）,：,：,神,经,经,病,病,学,学,功,功,能,能,障,障,碍,碍,表,表,现,现,为,为,一,一,种,种,或,或,多,多,种,种,临,临,床,床,表,表,现,现,（,（,症,症,状,状,和,和,体,体,征,征,）,）,，,，,持,持,续,续,24h,以,上,上,，,，,即,即,为,为,一,一,次,次,发,发,作,作,，,，,可,可,以,以,仅,仅,为,为,自,自,己,己,主,主,观,观,感,感,觉,觉,或,或,为,为,患,患,者,者,回,回,忆,忆,。,。,Oneepisodeisoneormoresymptomsorsignsoftheneurologicaldysfunctionlastatleast24hours,whichcanbethefeelingandrecollectionofthepatient.,诊,断,断,标,标,准,准,和,和,分,分,类,类,标,标,准,准,多,发,发,性,性,硬,硬,化,化,的,的,定,定,义,义,definition,：,时,间,间,上,上,多,多,发,发,是,是,指,指,有,有,2,次,或,或,2,次,以,以,上,上,发,发,作,作,；,；,multipleintemporalmeanstwoormoredistinctepisodesofsymptoms,诊,断,断,标,标,准,准,和,和,分,分,类,类,标,标,准,准,空,间,间,是,是,指,指,CNS,白,质,质,有,有,2,个,或,或,2,个,以,以,上,上,部,部,位,位,病,病,变,变,。,。,硬,硬,化,化,是,是,指,指,病,病,理,理,上,上,CNS,中,，,，,在,在,炎,炎,症,症,脱,脱,髓,髓,鞘,鞘,基,基,础,础,上,上,，,，,multipleinspatialrequirestwoormorelesionsofthebrainandspinalcord.SclerosismeansthesclerosisplaqueswithglialscarformationinthedemyelinatedinflammatorydiseaseofCNS.,由于胶,质,质增生,等,等修复,过,过程而,于,于局部,形,形成硬,化,化斑块,。,。,急性发,作,作（,anacuteepisode of newdisease activity,）指新,病,病灶的,出,出现或,老,老病灶,的,的重新,活,活跃。,亚临床,病,病灶（,subclinicalorparaclnical,）病理,上,上和,上,发,发现的,新,新、老,病,病灶，,在,在临床,上,上不一,定,定有或,曾,曾有过,相,相应的,症,症状和,体,体征。,诊断标,准,准和分,类,类标准,可明确,亚,亚临床,病,病灶的,方,方法：,热水浴,、,、诱发,电,电位、,和,或,或特殊,的,的泌尿,科,科检查,。,。,themethod of definite subclinical or paraclinicallesionhot bathtest,EP,、,orspecial examination of urology,诊断标,准,准和分,类,类标准,缓解,Remission,：次,发,发作必,须,须累及,中,中枢神,经,经系统,不,不同部,位,位，,次,次缓解,至,至少持,续,续个,月,月。,TwoEpisodesofsymptomsmustbeattributabletoinvolvementof2ormore parts of thebrainandspinal cord.One remissionmust lastatleastone month.,回忆性资料,recallmentdata,：,岁以下,无,无颈椎病而,有,有,hermitte,征。,person with Lhermitte sign under 50haveno cervical syndrome,岁以前,典,典型的视神,经,经炎,typical optic neuritis under 50,诊断标准和,分,分类标准,不同部位的,病,病变,Various areas of lesion,：,大脑皮层下,白,白质、小脑,、,、脑干、脊,髓,髓和视神经,各,各算一个部,位,位。,whitematter,cerebellum,brainstem,opticnerve andspinal cord.,不同的症状,和,和体征不能,用,用单一病灶,来,来解释，称,之,之为不同病,灶,灶。,differentsymptoms and signs that cantbe explained byonlyonelesion.,诊断标准和,分,分类标准,诊断标准和,分,分类标准,脊髓型,：,：,脱髓鞘,过,过程有时仅,限,限于脊髓，,或,或虽然向中,枢,枢神经系统,其,其他部位扩,展,展但仅有脊,髓,髓部位的斑,块,块产生症状,。,。,MS ofspinal cord type:,Demyelination in spinal cord only,sometimesit expandto other spacesof CNS,but only thelesion ofspinal cord developthesymptoms.,诊断标准和,分,分类标准,国外，,例,中,中，,例,例（）,有,有脊髓症状,，,，中国,例中,有脊髓症,状,状。,overseas,，,109(9%)of1271MS have thesymptomsof spinalcord;in China,70% of256havethe symptoms,特点：女性,多,多；起病年,龄,龄大；慢性,进,进展病程多,；,；工作能力,保,保存较好。,characteristics:usually seen in female ,onsetat old ages, chronic progression,and preserved more work capacity.,诊断标准和,分,分类标准,自然病程：,Natural progress,：,患者,起,起病后呈进,行,行性加重。,10,of patients have progressive exacerbation,约后,期,期进入进行,性,性加重。,about2/3of patients come into progressiveexacerbation phase.,.,为复发,缓解型。,.,of patients areRRMS,临床分型,复发,-,缓解型,原发进展型,继发进展型,进展复发型,诊断标准和,分,分类标准,实验室支持,诊,诊断,Supportingdataof laboratory,组分,区,区带或中枢,神,神经系统中,合成,率,率增高。,IgG fraction bands or theSynthesisof IgG inCNSincreased,血清中正常,normal level inserum,除外其他疾,病,病：梅毒、,亚,亚急性硬化,性,性全脑炎、,肉,肉芽肿病、,胶,胶原血管病,等,等。,Exclude other diseases:syphilis, subacute sclerosis panencephalitis, granulomatosis,collagen vascular disorders,诊断标准和,分,分类标准,临床确诊（,clinicallydefinite,）,MS,2,次发作,又有,2,个不同病变,部,部位的临床,证,证据,Two episodes with clinical evidenceof two different lesions,2,次发作，有,一,一个部位病,变,变的临床证,据,据，和另一,个,个部位病变,的,的亚临床证,据,据。,Two episodes with clinical evidenceof one lesionand subclinicalevidenceof anotherone.,诊断标准和,分,分类标准,临床很可能,（,（,clinicallyprobable,）,MS,2,次发作和,1,个部位病变,的,的临床证据,。,。,2,次发作必须,累,累及,CNS,的不同部位,。,。,two episodes with clinical evidenceof one lesionmustbe attributableto involvementof 2or more partsof CNS.,历史资料于,此,此不能用作,病,病变部位的,临,临床证据。,History dates cant be theclinicalevidence of lesion locushere,.,诊断标准和,分,分类标准,1,次发作和,2,个不同部位,病,病变的临床,证,证据。,one episode with clinicalevidencesof two different lesions,1,次发作，,1,个部位病变,的,的临床证据,和,和一个不同,部,部位病变的,亚,亚临床证据,one episode with clinicalevidenceof one lesion and subclinicalevidence of anotherlesion,实验室支持,的,的确诊（,laboratorysupporteddefinite,）,MS,1,次发作，有,2,个病变部位,的,的临床证据,，,，脑脊液中,有,有,IgG,组分区带和,/,或,IgG,合成率增,高,高。,Oneepisodewithclinical evidence of two lesion,IgGfractionbands or the Synthesisof IgG increasedinCSF,诊断标准,和,和分类标,准,准,2,次发作，,有,有,1,个临床或,亚,亚临床病,变,变，和脑,脊,脊液中有,IgG,组分区带,和,和,/,或,IgG,合成率增,高,高。,Twoepisodes,one lesionwith clinical or subclinical evidence of ,IgGfractionbands or the Synthesisof IgG increasedinCSF,1,次发作，,有,有,1,个部位病,变,变的临床,证,证据和另,1,个不同病,变,变的亚临,床,床证据，,和,和脑脊液,中,中有,IgG,组分区带,和,和,/,或,IgG,合成率增,高,高。,Oneepisodewithclinical evidence of one lesion,and subclinical evidence of another one. IgG fractionbands ortheSynthesis of IgG increasedin CSF,诊断标准,和,和分类标,准,准,实验室支,持,持很可能,（,（,laboratory supportedprobable,）,MS,2,次发作，,脑,脑脊液中,有,有,IgG,组分区带,和,和,/,或,IgG,合成率增,高,高。,Twoepisodeswith,IgGfractionbands and/or the SynthesisofIgGincreased inCSF,诊断标准,和,和分类标,准,准,1,次发作和,1,个病变部,位,位的临床,证,证据，脑,脊,脊液中有,IgG,组分区带,和,和,/,或,IgG,合成率增,高,高。,Oneepisodewithclinical evidence of one lesion, IgG fractionbands and /or the Synthesisof IgG increasedinCSF,1,次发作，,1,个部位病,变,变的亚临,床,床证据，,脑,脑脊液中,有,有,IgG,组分区带,和,和,/,或,IgG,合成率增,高,高,.Oneepisodewith clinical evidenceof one lesion ,IgGfractionbands and /or the SynthesisofIgGincreased inCSF,诊断标准,和,和分类标,准,准,临床可能,Clinicalprobable MS,进行性截,瘫,瘫史，,CNS,至少有,2,个不同部,位,位病变，,除,除外其他,疾,疾病。,Progressiveparaplegia ,at leasttwolesionsinCNS,except otherdiseases,诊断标准,和,和分类标,准,准,可疑,Suspected,1,次发作，,伴,伴或不伴,CNS1,个病变部,位,位的证据,oneepisodewithorwithouttheevidenceoflesion of CNS,。,反复发作,单,单或双侧,视,视神经炎,，,，另有,1,次视神经,以,以外的,CNS,发作，但,无,无,CNS,以外病变,的,的证据,repeatedunilateralor bilateraloptic neuritis,withanotherepisode ofCNS,butnoevidenceoutofCNS,诊断标准,和,和分类标,准,准,Table1 :2010McDonald MRI Criteria for Demonstation of DIS,DIS Can Be Demonstrated by=1 T2 Lesion,a,in at Least 2 of 4 Areas of the CNS,Periventricular,Juxtacortical,Infratentorial,Spinal cord,b,Table2:2010McDonald MRI Criteria for Demonstation of DIT,DIT Can Be Demonstrated by:,1.A