肌无力综合症翻译

Abstract.Lambert-Eatonmyasthenicsyndrome(LEMS)istypicallycharacterizedasaparaneoplasticsyndromeassoci-atedwithsmallcelllungcarcinoma.ThepresenceofLEMSinassociationwithotherneuroendocrinelungtumors,includingcarcinoidsorlargecelllungcarcinoma,ishighlyunusual.ThepresentcasestudyreportstheveryrarecaseofapatientwithmediastinalsmallcellcancercombinedwithLEMS.A53-year-oldmanwasadmittedtotheBethuneFirstHospitalwitha3-monthhistoryofweaknessinthelowerextremitiesthathadbecomeaggravatedduringtheprevious20days.Apositronemissiontomography-computedtomography(CT)examinationdemonstratedmultipleenlarged,hypermetaboliclymphnodesbetweenthevenacavaandtrachea,indicatingthepresenceofinflammation.Nootherabnormalitieswereidentified.Amediastinallymphnodebiopsyrevealedahighprevalenceofsmallcellneuroendocrinecarcinoma.Theimmunohistochemistryresultswereasfollows:Ki-67(+50,meaningthat50%ofthecellsexhibitedKi-67expression),cytokeratin(CK;+),clusterofdifferentiation(CD)56(+),synaptophysin(+),thyroidtranscriptionalfactor-1(+),epithelialmembraneantigen(+),neuron-specificenolase(+),P63(weakly+),leukocytecommonantigen(-),CD99(-),vimentin(-)andCK5/6(-).FollowingadiagnosisofLEMS,thepatientunder-wentonecourseofcisplatin+etoposidechemotherapy,whichwasineffective.Subsequently,thepatientunderwentadifferentchemotherapyregimen(cisplatin+etoposide+ifosfamide),whichsignificantlyimprovedthesymptomsofmyasthenia.Followingcompletionofthistreatmentregimen,theprimarylesionwasnotobservedonalungCTscan,andthemediastinallymphnodeshadclearlydiminished.Subsequently,thepatientunderwenttwocoursesofradiotherapy(40Gy/22f/6W).DiscussionLEMSisanautoimmunediseaseinvolvingthedysregulationofacetylcholinereleaseatthepresynapticmembraneoftheneuromuscularjunction(3).Thesymptomsoftheconditionresemblethoseofmyastheniagravis.LEMSisoftenassoci-atedwithtumors,and50-60%ofpatientswithLEMShaveanunderlyingtumor(T-LEMS).SCLChasbeenobservedin90%ofT-LEMScases.Bycontrast,NT-LEMSisoftenassociatedwiththehumanleukocyteantigen-B8-DR3haplotypeandavarietyofotherautoimmunediseases,suchasrheumatoidarthritis,perniciousanemia,thyroiddisordersandSjögren'ssyndrome(7).Inthemajorityofcases,LEMSinvolvesmusclefatigueandweaknessofthelimbsandtrunk.Lowerlimbweaknessismorecommoncomparedwithupperlimbweakness;similarly,theproximalaspectsofthelimbsaremorecommonlyaffectedthanthedistalaspects.Dominantcranialnervemusclesarenotgenerallyinvolved.Asmallnumberofpatientshavesymp-tomsofdroopingeyelids,doublevision,difficultyswallowinganddysarthria.Muscleweaknessisfeltintherestingstate,andstrengthincreasesafterafewsecondsduetothevigorouscontractingofmuscles.EvidencesuggeststhathalfofpatientswithLEMSalsoexhibitdisruptionoftheautonomicnervoussystem.Theseindividualsmayexperienceadrymouth,impotenceandimpairedtearsecretionandsweating(8).Furthermore,inasmallnumberofpatients,animpairedperformanceofcertainregionsofthecentralnervoussystem,suchasthecerebellum,canbeobserved(4).InthemajorityofpatientswithLEMS,muscleweaknessappearspriortosymptomsofcancer.TherehaveonlybeenafewcaseswheretumorshavebeendiagnosedearlierthanLEMS(9).Therefore,carefulscreeningtodetectanypossibleassociatedcancersatanearlystageisacrucialstepinoptimaldiseasemanagement(7).AtimelydiagnosisofLEMSiscrucialnotonlytoensurepropertreatmentoftheneurologicaldisease,butalsotodetectanyunderlyingtumorsearlyinthecourseofthedisease.However,earlydiagnosisisoftenhamperedbytherarityofLEMSanditsfluctuatingsymptoms(4).Evenwhenthepatient'ssymptomshavebeenproperlyassociatedwithaneuromusculartransmissiondisorder,LEMSisoftenmisdi-agnosedasmyastheniagravis.ClinicalsuspicionofLEMSshouldbeconfirmedwithanEMG.Althoughweaknessismoreevidentintheproximallimbs,electrophysiologicalabnormalitiesaremoreeasilydetectedinthedistalmuscles.Therefore,thediagnosisofLEMSisbasedonthepresenceofthetypicaltriad,comprisingalowCMAPamplitudeatrest(0.1-6.0mV),afurtherdecreaseintheCMAPamplitudeduringlow-frequencyRNS(2-5Hz),andanincreaseintheCMAPamplitudeduringhigh-frequencyRNS(20-50Hz)orimmediatelyafterabriefmaximalvoluntarycontraction(15-20sec).Thelatter(anincreaseintheCMAPamplitudeduringhigh-frequencyRNSorimmediatelyafterabriefmaximalvoluntarycontraction)isthetechniqueofchoiceduetothehigherleveloftolerance(7).A≥100%increaseintheCMAPamplitude/area(post-tetanic/postexercisefacilitation)inatleasttwotestedmusclesisfairlytypicalofLEMS,withasensitivityrangingbetween84and96%(4).Low-frequencyRNSduringmaximalcontractionmayincreasethesensitivityoftheEMG.Inaddition,single-fiberEMGmaybemoresensitivecomparedwithRNS;however,thetechniquedoesnotdistinguishbetweenmyastheniagravisandLEMS(5).Inthepresentcase,theEMGresultsrevealedthattheCMAPamplitudewithlow-frequencyRNSdiminishedby15%,whilethatwithhigh-frequencyRNSincreasedby100%.AntibodiestargetingtheP/Q-typevoltage-gatedcalciumchannel(VGCC)arepresentin75-90%ofpatientswithLEMS.InpatientswithT-LEMS,thisratecanfurtherincreaseto100%,andtheconditionisgenerallyassociatedwithhighantibodytiters(4).Researchhasindicatedthatmonitoringtheanti-P/Q-typeVGCCserumantibodytitermaybeimportantfo