脑白质病变专题宣讲

上海交通大学从属第六人民医院付剑亮脑白质病变CerebralWhiteMatterDisease脑白质病变专题宣讲第1页脑白质病变定义脑白质病变病因血管源性白质病变白质病变与认知损害脑白质病变专题宣讲第2页脑白质病变临床常见，各种疾病累及神经系统白质分原发、继发性两大类.病理过程：髓鞘形成延迟、髓鞘形成障碍、脱髓鞘诊疗：临床+MRI+病理脑白质病变AnnNYAcadSci.Oct;1142:266–309.脑白质病变专题宣讲第3页Genetic2Demyelinative3Infectious4Inflammatory5ToxicEtiologyofCWMDisorders617891011MetabolicVascularTraumaticNeoplasticHydrocephalicDegenerative脑白质病变专题宣讲第4页GeneticDiseasesLeukodystrophies(e.g.,adrenoleukodystrophy,metachromaticleukodystrophy,globoidcellleukodystrophy)脑白质营养不良（肾上腺、异染性、球样细胞脑营养不良）Vanishingwhitematterdisease白质消融性脑白质病Alexander’sdisease亚历山大病Adult-onsetleukodystrophywithneuroaxonalspheroids神经轴索球样细胞脑白质营养不良Mitochondrialencephalopathywithlacticacidandstroke(MELAS)线粒体脑肌病伴乳酸酸中毒和卒中样发作综合征FragileXtremor-ataxiasyndrome(FXTAS)脆性X相关震颤和(或)共济失调综合征Aminoacidurias(e.g.,phenylketonuria)氨基酸尿（如苯丙酮尿症）Phakomatoses(e.g.,neurofibromatosis)斑痣性错构瘤病Mucopolysaccharidoses粘多糖贮积病Myotonicdystrophy强直性肌营养不良Callosalagenesis新生儿胼胝体发育不良脑白质病变专题宣讲第5页MRIofX-ALD,MLD,GLD,VWMD(A)X-连锁肾上腺脑白质营养不良(X-ALD),T1image;(B)异染性脑白质营养不良(MLD),FLAIRimage;(C)球形细胞脑白质营养不良(GLD),T2-weightedimage;(D)白质消融性脑白质病(VWMD),T1-weightedimage.X-ALD:impairedpsychomotorspeed,spatialcognition,memory,andexecutivefunctions;MLD:psychosis,behavioraldisturbances,anddementia;GLD:hemiparesis,intellectualimpairment,cerebellarataxia,andvisualfailure;AnnNYAcadSci.Oct;1142:266–309.脑白质病变专题宣讲第6页神经轴索球样细胞脑白质营养不良(A)FLAIRMRIintheaxialplaneshowingconfluenthighsignalintheperiventricular,deep,andsubcorticalwhitematterofthefrontalandparietallobesextendingthroughthespleniumofthecorpuscallosum.

(B)Grosspathologyofacoronalsectionofthecerebralhemisphere,showinggliosisinthecentrumsemiovale(arrow)andinternalcapsule(arrowhead).Thedisorderusuallypresentswithexecutivesystemdysfunctionandotherneurobehavioraldeficits,progressingtodementia.脑白质病变专题宣讲第7页MRIinpatientswithMELASCriteriafordiagnosisarestrokelikeepisodesbeforeage40(notconfinedtovascularterritories);encephalopathycharacterizedbyseizures,dementia,orboth;withlacticacidosisand/orragged-redfibers.Recurrentheadacheorvomitingmaybepresent.PeriventricularanddiffuseWMhyperintensities,aswellasareasofcorticalinfarctionandcerebraledema,areseenonMRI脑白质病变专题宣讲第8页脆性X相关震颤和(或)共济失调综合征Whitematterpallorisseeninthecerebellarparenchyma(A),aswellasinthemiddlecerebellarpeduncles(B).Progressivecognitivedeclineischaracterizedbyimpairedexecutivefunction,workingmemory,intelligence,declarativelearningandmemory,informationprocessingspeed,temporalsequencing,andvisuospatialfunctioning,butlanguageisspared.脑白质病变专题宣讲第9页DemyelinativeDiseasesMultiplesclerosisAcutedisseminatedencephalomyelitis急性播散性脑脊髓炎Acutehemorrhagicencephalomyelitis急性出血性脑脊髓炎Schilder’sdisease谢耳德氏病,弥漫性轴周性脑炎Marburg’sdisease马尔堡病Balo’sconcentricsclerosis同心圆性硬化脑白质病变专题宣讲第10页FLAIRMRIinmultiplesclerosis(A)Whitematterhyperintensityperpendiculartothelateralventricle(Dawson’sfinger),shownbythearrow.(B)Inasecondcase,thefocalareaofhyperintensity(arrow)correspondedtotheinitialclinicalpresentationCognitiveimpairmentsinMSalsoincludeawiderangeoffocalneurobehavioralsyndromesandneuropsychiatricdisturbances脑白质病变专题宣讲第11页MRIfeaturesofADEM(A)CoronalT1-weightedpostgadoliniumimageshowingenhancinglesionsintherightmorethanlefthemispheres.(B)Axialzero-BMRIdemonstrationofthemultiplelesions.(C)FLAIRMRI6monthsaftermarkedclinicalrecoveryshowsmuchimprovedareasofhyperintensity.脑白质病变专题宣讲第12页InfectiousdiseaseHIVandAIDSdementiacomplex艾滋病痴呆综合征Progressivemultifocalleukoencephalopathy进行性多灶性白质脑病Subacutesclerosingpanencephalitis亚急性硬化性全脑炎Progressiverubellapanencephalitis进行性风疹全脑炎Varicellazosterencephalitis水痘-带状疱疹病毒性脑炎Cytomegalovirusencephalitis巨细胞病毒脑炎Lymeencephalopathy莱姆脑病脑白质病变专题宣讲第13页HIVFLAIRMRIshowinghyperintensitiesinprefrontalwhitematterinapatientwithHIVandcognitiveimpairmentSchmahmannJD,PandyaDN.FiberPathwaysoftheBrain.OxfordUniversityPress;NewYork:脑白质病变专题宣讲第14页PML(A)T2-WIshowsinvolvementofwhitematteroftherightoccipitalregion(arrow),accountingforthehemianopsiainthisHIV-positivepatient.(B)FLAIRMRIinapatientwithsystemiclymphomaandPML,demonstratingconfluentprefrontalwhitematterlesionspreadingacrossthegenuofthecorpuscallosum(arrow),andadditionallesionsaffectinglocalassociationfibersoftherightprefrontalandparieto-occipitalcortices(arrowheads).(C,D)AxialFLAIRimagesinanHIV-positivepatientshowingconfluentsubcorticalanddeepwhitematterinvolvementbyPML.Cognitivepresentationsincludefrontallobesyndromesandaphasia,progressingtoquadriparesis,mutism,andunresponsiveness脑白质病变专题宣讲第15页AutoimmuneInflammatoryDiseaseSystemiclupuserythematosus系统性红斑狼疮Behcet’sdisease白塞病,贝西氏病,贝赫切特病Sjögren’ssyndromeWegener’sgranulomatosiTemporalarteritis颞动脉炎Polyarteritisnodosa结节性多动脉炎Scleroderma硬皮病Isolatedangiitisofthecentralnervoussystem孤立中枢神经系统血管炎Sarcoidosis结节病脑白质病变专题宣讲第16页ToxicDiseasesCranialirradiation颅脑照射Therapeuticdrugs(e.g.,methotrexate甲氨蝶呤,BCNU卡莫司汀,cyclophosphamide环磷酰胺)Drugsofabuse(e.g.,toluene甲苯,heroin海洛因)Toluene:adramaticsyndromeofdementia,ataxia,andotherneurologicsignsAlcohol(Marchiafava–Bignamidisease又称胼胝体变性，一个慢性酒精中毒性疾病)Environmentaltoxins(e.g.,carbonmonoxide)脑白质病变专题宣讲第17页ToxicLeukoencephalopathyFLAIRMRIintheaxialplaneofapatientwithcognitivedeclineafterreceivingmethotrexateT2-WMRIappearanceintheaxialplaneoftolueneencephalopathyintwopatientsadramaticsyndromeofdementia,ataxia,andotherneurologicsigns脑白质病变专题宣讲第18页Heroin

Clinicalmanifestationsincludecerebellarmotorfindingsofataxia,dysmetriaanddysarthria,bradykinesia,rigidity,andhypophonia,andthesyndromemayprogressoverweekstopseudobulbarpalsy,akineticmutism,decorticateposturing,andspasticquadriparesis.MRIscansafterheroininhalation,knowncolloquiallyas“chasingthedragon.”FLAIRimagesintheaxialplane(A–D).Inhalationofheatedheroinvapor(colloquiallytermed“chasingthedragon”)producesadevastating,progressivespongiformleukoencephalopathy.脑白质病变专题宣讲第19页MetabolicDiseasesCobalamindeficiencyVitB12缺乏Folatedeficiency叶酸缺乏Centralpontinemyelinolysis桥脑中央髓鞘溶解症Hypoxic–ischemicinjury缺氧缺血性脑损伤Posteriorreversibleencephalopathysyndrome可逆性后部白质脑病综合征Hypertensiveencephalopathy/eclampsia高血压脑病/惊厥High-altitudecerebraledema高原脑水肿脑白质病变专题宣讲第20页HypoxicischemicencephalopathyAxialMRIindelayedleukoencephalopathyafterhypoxic–ischemicinsult.(A)FLAIRimageshowsextensive,symmetricwhitematterhyperintensitieswithrelativesparingofsubcorticalwhitematter.(B)Diffusion-weightedimagingshowsrestricteddiffusionofthewhitematterabnormalities,confirmedon(C),apparentdiffusioncoefficientmapping脑白质病变专题宣讲第21页TraumaticDiseaseTraumaticbraininjury(diffuseaxonalinjury)外伤性脑损伤（弥散性轴索损伤）Shakenbabysyndrome婴儿摇摆综合征Corpuscallosotomy胼胝体切开术FocallesionsofWMtracts(e.g.,fornixtransection,spleniumofCCtumor)白质纤维束局灶病变（海马伞切开术，胼胝体亚部肿瘤）脑白质病变专题宣讲第22页NeoplasticDiseasesGliomatosiscerebri脑胶质瘤Diffuselyinfiltrativegliomas弥漫性浸润性胶质瘤Lymphomatosiscerebri大脑淋巴瘤病Langerhanscellhistiocytosis朗格汉斯细胞组织细胞增多症Focalwhitemattertumors局灶性白质肿瘤脑白质病变专题宣讲第23页GliomatosiscerebriFIG3.55M.A,AxialT2-weightedspin-echolocalizerimage(1900/80).B,Correspondingspectrum.Stereotacticbiopsysamplewastakenfromthedenotedvoxel,withamaximumCho/NAAratioofthelesionof8.9aswellasalactatedoubletat1.35ppm.FIG4.10yearoldboywithseizure.脑白质病变专题宣讲第24页朗格汉斯细胞组织细胞增多症T2-weightedaxialMRIinapatientwithLangerhanscellhistiocytosis,showinghyperintensesignalabnormalityinthewhitematterofthecerebellum脑白质病变专题宣讲第25页VascularDiseasesHydrocephalicDiseasesBinswanger’sdiseaseEarlyhydrocephalusCADASILNormalpressurehydrocephalusLeukoaraiosisCerebralamyloidangiopathyDegenerativeDiseaseIntravascularlymphomaWhitematterchangesinAlzheimerdiseaseWhitematterdiseaseofprematurityEffectsofagingonmyelinMigraine脑白质病变专题宣讲第26页BCAWMlesionsAging脑白质病变VascularDisease脑白质病变专题宣讲第27页白质高信号（WMHyperintensities）Leukoaraiosisisvisibleas(A)whitematterhypodensityonCTand(B)whitematterhyperintensityonFLAIRMRIinthesamepatient.脑白质病变专题宣讲第28页0203040170岁以上老人，95%在MRI上能够发觉白质高信号，随年纪增加逐步增多危险原因：高血压、糖尿病、吸烟,、视网膜血管改变、肾脏血管改变；内皮功效紊乱(血清同型半胱氨酸和细胞粘附分子1),血栓形成(血栓调整蛋白和纤维蛋白原）,炎性反应(CRP),氧化应激2髓鞘脱失和胶质增生，破坏髓鞘和少突胶质细胞影像学发觉和病理学显示髓鞘脱失含有相关性WMH相关概念1.JNeurolNeurosurgPsychiatry.Jan;70(1):9-14.2.Brain.Jan;127(Pt1):212-93.Neurology.Sep12;67(5):830-3.脑白质病变专题宣讲第29页01WMH负荷与脑梗死以及卒中史相关02与脑血管病有共同危险原因，如高血压等03利用ACEI和利尿剂降压治疗能够减缓WMH进展04CSVD造成血管狭窄、阻塞,破坏血管反应性，造成白质低灌注05认知障碍病人WMH高负荷，局部脑血流量下降代谢水平降低WMH病理机制脑白质病变专题宣讲第30页脑白质病变与认知功效下降显著相关脑白质病变越严重，认知功效下降越快Stroke;36;56-61.脑白质恶化级别无1级2级及以上首次MRI随即MRI年改良后MMSE评分95949392919089888786854567891011脑白质病变专题宣讲第31页高WMH负荷与认知功效从正常转化到MCI，MCI转化到痴呆相关系脑室周围WMH与未来痴呆尤其是AD相关在MRI上见到白质高信号（WMH）同正电子发射断层扫描（PET）中使用脑淀粉样标识物一样，能够独立预测AD诊疗WMH与认知改变脑白质病变专题宣讲第32页WMHs影响信息加工速度和执行功效，影响记忆提取而不是编码1脑室周围白质区域为“远端供血区”，这种情况因为缺乏吻合更易受到中度血流降低损害2脑室周围WMHs破坏联络较远皮质区域联络性长束，执行功效受累较为突出3皮质下区域由致密短回路U纤维组成，皮质下痴呆则主要是认知过程速度减慢4WMHs相关认知改变脑白质病变专题宣讲第33页OttoBinswanger在1894年首先提出WMCs与痴呆之间可能存在关联；Alzheimer在19再次提到Binswanger病例，以后提出Binswanger脑病（BD）这一名词。1WMC是痴呆危险原因，与认知功效下降相关。头部CT检出AD患者WMCs可占30%，VaD患者可占70%。WMC与AD亲密相关，提醒血管病原因在AD病变过程中主要性。2皮质下白质缺血主要是少突胶质细胞和髓鞘破坏；皮质下U纤维密度较高WMLs主要破坏由弓状U纤维组成短皮质-皮质联络；脑室周围WMLs则破坏联络较远皮质区域联络性长束3脑白质改变（WMC）与AD脑白质病变专题宣讲第34页1234主要累及脑皮质小动脉、中动脉、微动脉及毛细血管，表现为血管壁Aβ进行性沉积5是老年人自发性颅内出血和认知损害主要原因临床表现主要包含：重复颅内出血，认知下降和痴呆等约30%脑血管淀粉样变性患者能够出现老年痴呆症状，如严重记忆障碍、注意力、定向力和计算力减退，或精神异常Ⅰ型主要病理改变是皮质微血管内Aβ异常蓄积；Ⅱ型Aβ主要沉积于脑膜血管及皮质动脉、小动脉，偶然会累及静脉。脑淀粉样血管病(CAA)脑白质病变专题宣讲第35页

CAAMRI表现

(A)GradientechoMRIdemonstratingmultiplepunctuateareasofhemorrhage(microbleeds,arrow)atthecortico–subcorticaljunctions.(B)MRIFLAIRsequenceinapatientwithlobarintraparenchymalhemorrhageintheleftoccipitallobe(doublearrows),aswellasperiventricularWMH(singlearrow)andsubcorticalWMH(arrowheads)脑白质病变专题宣讲第36页1894年Binswanger首先报道该病例，并强调本病患者两个主要特点：（1）患者脑血管有重度粥样硬化。（2）大脑半球白质损害显著，而皮质几乎不受影响01深穿支动脉供血脑室周围白质发生大面积缺血性损害，仅有皮质穿支动脉供血皮层下U型纤维未见显著受损02痴呆是最显著症状，主要表现为记忆障碍、计算力差，可伴有心情、人格改变，无欲、冷淡、精神错乱03Binswanger’s脑病脑白质病变专题宣讲第37页Binswanger’sMRIHyperintensesignalabnormalityisseenatperiventricularzones,whitematterimmediatelybeneathcortex,spleniumoftheCC,andinternalandexternal/extremecapsuleregions.MultiplehypodensitiesconsistentwithlacunarinfarctsarealsoseeninthebasalgangliaandthalamusSchmahmannJDFiberPathwaysoftheBrain.OxfordUniversityPress;NewYork:脑白质病变专题宣讲第38页19号染色体notch3基因突变，血管壁增厚并含有一个嗜伊红物质，沉积在血管中层和内弹性膜.1MRI：多发性腔隙性脑梗死，白质灶性或弥漫性疏松，颞极区域对称损害2请在此处输入您文本3CADASIL偏头痛（＜30）、脑卒中（＞30）、痴呆及精神异常、周围神经亚临床损害3脑白质病变专题宣讲第39页CADASILMRI(A,B)FLAIRMRIinanasymptomatic39-year-old,notch3genepositivewithfamilyhistoryofearlystroke,whoseimagingfindingswereincidentallynoted.Characteristictemporallobewhitematterinvolvementishighlighted(arrows).(C)FLAIRMRIinapatientwithclinicallyestablishedCADASIL.(D)T2-weightedMRIinapatientwithnotch3geneandpathologicallyprovendisease.脑白质病变专题宣讲第40页神经行为综合征神经精神综合征白质性痴呆脑白质病变与神经精神综合征脑白质病变专题宣讲第41页ABC局部白质病变造成失语,失用症(apraxia),失认症(agnosia),胼胝体分离综合征(callosaldisconnection)等主要病因是卒中，肿瘤和脱髓鞘病也能够发生病变部位：顶下小叶、颞顶交界、前额叶、基底节、丘脑、扣带回等，以非优势半球多见NeurobehavioralSyndromes脑白质病变专题宣讲第42页FocalWMlesionswithneurobehavioralmanifestations(A)Lacuneinthegenuoftherightinternalcapsule(arrow)onCTpresentingwithhemineglect.(B)DiagramoftheWMlesionresponsibleforparietalpseudothalamicpainsyndrome,thoughttodisruptthesecondsomatosensorycortexfromthalamus.(C)FLAIRMRIofposteriorreversibleencephalopathysyndromeproducingvisualloss.(D,E)FocalWMlesionconsisting