脑健黄瘤病(病例分享及文献)PPT课件.ppt

脑健黄瘤病,1,.-,2019/11/12,Case1,A44-year-oldmanpresentedwithprogressivecerebellarataxiaandspasticparaparesis.Gaitdifficultieshadstartedatage16years,andatage42yearsbilateralcataractswerediagnosed.Hiscognitivefunctionprogressivelydeclined,andseizuresrepeatedlyoccurred.,Neurology2005;64;1476,2,.-,2019/12/15,A47yearsoldwhitemanwhichsymptomsbeganat20yearsold.Hepresentedprogressivewalkingdifficulty,becomingunabletowalkfastat40yearsold.Hepresenteddelayofthepsychomotordevelopment.Hehadahistoryofchronicdiarrheaduringthechildhood.Hismotherdeniedotherfamilymemberswithsimilarsymptoms,exceptforthepatientsyoungerbrother.,Case2,ArqNeuropsiquiatr2004;62(4):1085-1089,3,.-,2019/12/15,Intheneurologicalexamination,hepresentedmildmentalretardation,mildbilateralfacialpalsywithoutotherfindingsincranialnerves.HismuscularstrengthwasIVinsuperiorlimbs(SL)andIV-ininferiorlimbs(IL).WenotedmoderatespasticityinIL,increaseddeeptendonreflexeswithbilateralBabinskisign.Thesensibilitywaspreserved.ThepatientpresentedsymmetricaldismetryanddisdiadococinesyinSL.Hehadalsogaitataxiaandwalkedwithsupport.,ArqNeuropsiquiatr2004;62(4):1085-1089,4,.-,2019/12/15,A,40yearsoldwhiteman,casetwosbrother,whichaccordingtothemothersinformation,presentedlearningdifficultysincechildhood,unabletoreadortowrite.Hedidnotfinishthebasicschool.At35yearsofagehebeganwithprogressivedifficultytowalk.Healsopresentedchronicdiarrheaandwassubmittedtoabilateralcataractssurgeryinthechildhood.,Case3,ArqNeuropsiquiatr2004;62(4):1085-1089,5,.-,2019/12/15,Intheneurologicalexamhepresentedmildmentalretardation,visualhandicapandfacialpalsywithoutotherabnormalitiesincranialnerves.ThemusclestrengthwasVinSLandIV+inIL.OtherfindingswerespasticityinIL,increaseddeeptendonreflexeswithbilateralBabinskiandHoffmansigns.Sensibilitywaspreserved.HehadwalkingdisturbancewithataxiaandspasticityinIL.,ArqNeuropsiquiatr2004;62(4):1085-1089,6,.-,2019/12/15,患者男性,52岁。以“头痛、发热、声音嘶哑1周”入院。入院前1周无明显诱因出现头痛,为后枕部跳痛,呈阵发性并持续加重,伴有发热,体温最高达38.8,咳嗽,无痰,声音嘶哑。入院后患者出现尿潴留,饮水呛咳并逐渐出现进食饮水困难。患者13岁双眼曾患白内障,25岁行白内障手术;1990年开始逐渐出现痉挛性截瘫和智能障碍。入院查体:体温37.8,血压130/70mmHg。神志清楚,声音嘶哑,反应淡漠,计算力差,左侧软腭抬举无力,咽反射消失,左侧声带麻痹,伸舌左偏,双上肢肌力级,肌腱反射对称,双下肢肌力级,双侧膝反射及跟腱反射活跃,双侧踝阵挛阳性,双侧巴宾斯基征阳性。家系调查:患者妹妹也呈痉挛性步态,无白内障和明显智能障碍,父母无类似病史。,病例4,中国神经免疫学和神经病学杂志2007年14卷2期,7,.-,2019/12/15,本病的共同特点：小脑性共济失调锥体束受损脑干受累智力障碍白内障、腹泻家族史,8,.-,2019/12/15,9,.-,2019/12/15,10,.-,2019/12/15,Case1,11,.-,2019/12/15,Case2-3,12,.-,2019/12/15,Case2-3,13,.-,2019/12/15,CerebrotendinousXanthomatosis(CTX)脑腱黄瘤病,14,.-,2019/12/15,脑腱黄瘤病（）是一种常染色体隐性遗传的脂肪代谢障碍性疾病，致病基因位于常染色体，导致固醇羟化酶缺乏，使胆固醇合成胆酸受阻，引起不同组织胆固醇代谢障碍。,15,.-,2019/12/15,多系统损害：肌腱黄瘤(71%)青少年白内障(92%)早发的动脉硬化神经系统损害(100%)小脑性共济失调进行性智能减退(81%)进行性下肢痉挛性瘫痪延髓麻痹周围神经病,16,.-,2019/12/15,诊断线索1）infantile-onsetdiarrheaChronicdiarrheafrominfancymaybetheearliestclinicalmanifestation.,17,.-,2019/12/15,2）childhood-onsetcataractInabout75%ofaffectedindividuals,cataractsarethefirstfinding,oftenappearinginthefirstdecadeoflife.,18,.-,2019/12/15,3）adolescent-toyoungadult-onsettendonxanthomasXanthomasappearinthesecondorthirddecade;theyoccurontheAchillestendon.,19,.-,2019/12/15,4）adult-onsetprogressiveneurologicdysfunctiondementiawithslowdeteriorationinintellectualabilitiesoccursinthe20sinover50%ofindividuals.Neuropsychiatricsymptomssuchasbehavioralchanges,hallucinations,agitation,aggression,depression,andsuicideattemptsmaybeprominent.Pyramidalsigns(i.e.,spasticity)and/orcerebellarsignsarealmostinvariablypresentbetween20and30yearsofage.Otherfindingsincludeextrapyramidalmanifestations(dystoniaandatypicalparkinsonism),seizures,andperipheralneuropathy.,20,.-,2019/12/15,肌腱黄瘤,21,.-,2019/12/15,肌腱黄瘤,22,.-,2019/12/15,肌腱黄瘤,23,.-,2019/12/15,肌腱黄瘤,24,.-,2019/12/15,肌腱黄瘤,25,.-,2019/12/15,肌腱黄瘤,26,.-,2019/12/15,肌腱黄瘤,27,.-,2019/12/15,脑腱黄瘤病的MRI表现,ConventionalMRIstudieshaveshownfocal/diffusewhitematterabnormalitiesanddifferentdegreesofcerebralandcerebellaratrophyinthebrainofpatientswithCTX.Thebilateralnonhomogenous,hyperintensemagneticresonancesignalindentatenucleiandsurroundingcerebellarwhitematter,canbeconsideredasaneuroradiologicalfeaturesuggestiveofCTXandcouldbecomeanimportantdiagnosticmarker.,28,.-,2019/12/15,脑腱黄瘤病的MRI表现,29,.-,2019/12/15,脑腱黄瘤病的MRI表现,30,.-,2019/12/15,脑腱黄瘤病的MRI表现,31,.-,2019/12/15,脑腱黄瘤病的MRI表现,32,.-,2019/12/15,脑腱黄瘤病的MRI表现,33,.-,2019/12/15,脑腱黄瘤病的MRI表现,34,.-,2019/12/15,脑腱黄瘤病的MRI表现,35,.-,2019/12/15,脑腱黄瘤病的诊断,临床表现家族史MRI血浆胆甾烷醇升高、固醇27-羟化酶活性下降基因检查:mutationsinthesterol27-hydroxylasegene(CYP27gene)病理检查:肌腱内发现腱黄瘤细胞或胆固醇结晶,36,.-,2019/12/15,脑腱黄瘤病的治疗,SeveralmodesoftreatmenthavebeentriedforCTX.Since1975,chenodeoxycholicacid(CDCA)(鹅脱氢胆酸)750mgdailyhasbeencommonlyusedasthestandardtherapy,Thereisaconsiderabledecreaseintheserumcholestanolandasharpdeclineintheexcretionofurinebilealcohols.ButacombinationofCDCAwith3-hydroxy3-methylglutarylcoenzymeA(HMGCOA)reductaseinhib