双侧苍白球切开术治疗原发性帕金森病
中华外科杂志2000年第3期第38卷英文原著
作者：李勇杰石常青邵明
单位：首都医科大学宣武医院；北京功能神经外科研究所，北京100053，中国
关键词：帕金森病；立体定位技术
bilateralpallidotomyfortreatmentofidiopathic
parkinson′sdisease
liyongjie(李勇杰),shichangqing(石长青),shaoming(邵明),dingyuji(丁育基)
abstract：objectivetoclarifythebenefitsandrisksofpatientsundergoingbilateralposteroventralpallidotomy(bpvp)forpatientswithidiopathicparkinson′sdisease(pd)andthedifferencesbetweencontemporaneousbpvp(cbpvp)andstagedbpvp(sbpvp).
methodstwentypatientsunderwentmicroelectrode-guidedcbpvpand26sbpvpforbilateralpdsymptoms.thedatawereretrospectivelyreviewed.unifiedparkinson′sdiseaseratingscale(updrs)wasusedtoevaluatetheeffectsoftheseoperations.
resultsbpvp,eithercbpvporsbpvp,significantlyimprovedpatients′bilateralpdsymptoms(p＜0.001).theimprovementwasconsistentlyhigherin“off”statethanin“on”state.nostatisticaldifferencewasobservedintheimprovementpercentagesofcbpvp,sbpvp1andsbpvp2.cbpvpcontributedgreatlytol-dopainducedsideeffects(partiv).bpvp,sbpvp1,andsbpvp2significantlyimprovedcardinalparkinsoniansignsbutnodifferencewasfoundamongthem.onepatientaftercbpvpdevelopedhypophniaandswallowingproblem,while2patientsaftersbpvpsustainedhypophnia.theseconditionswereimproved3monthslater.
conclusionsbpvpmaysignificantlyimprovebilateralsignsofpd.itissaferthanbilateralthalamotomy.cbpvpisapplicabletosomepatients.bpvpmaynotcausementalimpairmentbutshowsahigherincidencerateofhypophnia.thepracticeofbpvprequiresarefinedsurgicaltechniqueandabetterunderstandingofpathophysiologyofthebasalganglia.
keywords：parkinsondisease；stereotactechniques
摘要：目的客观评估双侧苍白球腹后部切开术（bpvp）治疗原发性帕金森病（pd）的疗效，探讨其必要性和利弊。方法46例具双侧pd症状的患者接受了微电极导向的双侧苍白球手术。其中，20例cbpvp，26例sbpvp。sbpvp又分为首次手术sbpvp1和第二次手术sbpvp2，二者间隔3～12个月，平均6.5±2.4个月。患者的hohn和yahr评分均在2.0以上。采用pd病情评估的updrs方法，对手术前后和“开、关”4种状态进行评分。统计分析bpvp手术前后症状改善情况的组内差异，cbpvp、sbpvp1和sbpvp2之间的组间差异，以及并发症的发生类型和高低情况。结果cbpvp、sbpvp1以及sbpvp2均明显改善患者的整体病情和典型症状（震颤、僵直和行动迟缓，p＜0.001），它们对“关”状态的改善总是高于对“开”状态的改善。与sbpvp1或sbpvp2相比，cbpvp有着较高的改善率，但未达到统计学差异。分期手术对updrs的第4部分即左旋多巴类药物治疗副作用的改善明显低于同期手术（p＜0.05）。手术未发生脑出血、视野缺损和肢体力弱等苍白球手术较常见的并发症，也未发现与双侧手术相关的认知障碍。cbpvp组1例患者术后明显语音低下、吞咽困难，sbpvp组2例患者出现语音低下。3个月后随访，以上并发症有所缓解但未完全恢复。结论对于存在明显的双侧症状的苍白球手术适应症范围内的原发性pd患者，bpvp是必要的手术方法，也是相当一部分患者必然的选择。
parkinsoniansymptomsmostlyappearatonesideofbodyandthendeveloptotheothersideseveralyearslater.manyneurosurgeonsassumedthatunilateraloperationforbilateralsymptomswas“halfthejob”.however,bilateralthalamotomyhasnotbeenadvisablesincethelastdecadebecauseofarelativelyroughsurgicaltechniquesatearlystageandcomplicationsfollowingasecondsidethalamotomyinparticularsuchaspermanentdysarthriaandseverementalimpairments.［1-3］similarly,theadvisabilityofbilateralpallidotomyisdoubtedbymanyclinicianseventhoughnooneatthistimequestionstheeffectivenessofleksell′stargetpallidotomyrecurredbylaitinen.［4，5］reportsontheresultsofbilateralpallidotomyhavebeenrareintherecentliterature.asurveyonthepracticeofpallidotomyinnorthamericain1996showedthat20%of1015patientswhounderwentpallidotomyhadbilateralprocedureseitherstaged(7%)orcontemporaneous(13%),buttheclinicalresultswerenotreported.［6］mixed“feeling”abouttheresultsofbilateralpallidotomyhasbeenevidentinpeer-reviewedmedicaljournalsandatinternationalmeetings.toclarifythebenefitsandrisksofbilateralpallidotomyforpatientswithidiopathicpd,weretrospectivelyreviewedourexperienceswithstagedbilateralposteroventralpallidotomy(sbpvp)andcontemporaneousbilateralposteroventralpallidotomy(cbpvp).itisexpectedthatevaluatingpatientswithupdrspre-andpostoperativelywillprovidescientificevidencesforclinicalapplicationofbilateralpallidotomy.
methods
patients
fromjuly1998todecember1999,atotalof46patientswithidiopathicpdweresubjectedtocbpvp(n=20)orsbpvp(n=26)atthebeijinginstituteoffunctionalneurosurgery,xuanwuhospital.theyaccountedfor8.8%of520patientswhoreceivedpallidotomyatthesameperiod.twoexperiencedneurologistsalsoscreenedthepatientsreferredforpallidotomy.inclusioncriteriaincludedahistorycompatiblewithidiopathicpd,twoofthefourcardinalsymptoms(resttremor,rigidity,akinesia/bradykinesiaandaxialsymptoms),andaclearhistoryofsignificantresponsivenesstolevodopa.allofthepatientsweregivensystematictherapyofmadoparandsomedopaminereceptoragonisttherapyaswell.exclusioncriteriawereneurologicalsignssuggestiveofsecondaryformsofparkinsonismandparkinsonplus.
inthecbpvpgroup,themeanageofthe20patientswas52.5±9.6years(range,35-66)andthemeandurationofpdwas10.2±4.1years(range,5-24)atthetimeofsurgery.ahoehn%26yahrscorewhileoffmedicationwas2.0(n=12),2.5(n=7)and5.0(n=1)respectively.l-dopatherapylastedfor5.5±2.4years(range2-12years).allofthepatientshadtremoreitheratonesideorbothsides.sixpatientsdevelopedsignificant“on/off”fluctuationor/anddyskinesias.ofthecbpvppatients,9(45%)wereof“juvenile-type”withearly-onsetpd(symptomsbefore40yearsage).
inthesbpvpgroup,themeanageofthe26patientswas58.3±7.7years(range,32-72)andthemeandurationofpdwas8.3±5.0years(range,2-20).ahoehnlyahrscorewhileoffmedicationwas2.0(n=14),2.5(n=9),3.0(n=2)and4.0(n=1)atthetimeoffirstsidesurgery(sbpvp1).thesamedosageoflevodopawasmaintainedforallpatientsafteroperation.theintervalofthetwooperationswas6.5±2.4months(range,3-12).
surgery
acosman-roberts-wellframewassecuredtopatient′sskullunderlocallidocaineanesthesiaandmri(seimens,tesla1.0)wasperformedforinitialstereotacticdeterminationsofthetarget,usingthelocationsoftheanteriorandposteriorcommissures(ac-pcline).ourtargetforpvpliedwithintheglobuspallidusinterna(gpi),whichwas2-3mmanteriortothemidpointofacpcline,4-7mmbelowacpclineand19-23mmlateraltothemidline.aftertheinitialtargetwasdetermined,a10-mmburrholewasmadeonthecoronalsuture.atungstenmicroelectrode(impedance,300-600kω)wasintroducedintothebrain.extracellularrecordingstarted10mmabovetheinitialtarget.amplifiedandfilteredspontaneousactionpotentialsweredisplayedonanoscilloscopeandplayedoveranaudiomonitor.themicroelectrodewasadvancedoutofaguidetubetowardthetargetwithanelectronicmicrodrive.accordingtothecharacteristicsofneuronaldischargefrequenciesandpatternsofgpie,intralaminarbordercells,gpii,ansalenticularis,andoptictract,thefinaltargetwasidentified.onlyafteranelectrophysiologicalconfirmationwasdone,theinitialanatomictargetcouldbethefinaltargettomakelesions.a1.1by2mmradionicthermocoupleradiofrequencylesionprobewasthenusedtoreplacemicroelectrodeandmacrostimulationwasperformedrightbeforelesioningtoavoidpossibledamagetothetargetadjacentimportantstructures(internalcapsuleandoptictract).thelesionwasmadeattemperaturesof60-85℃for60-90seconds.
evaluations
twoexperiencedneurologistswhowerenotamongthesurgicalteamconductedpatientevaluationsindependently.theupdrswasusedtoevaluateneurologicallypreoperativebaselineandpostoperativechangewithinoneweekbeforeandaftersurgery.follow-upassessmentsofcbpvpweremadeon3patients1yearaftersurgery.theyweretestedin“on”state(maximaltherapeuticbenefit)and“on”state(noantiparkinsonianmedicationsovernightforatleast12hours)respectively.theimprovementpercentageswerecalculated:
(updrspre-op－updrspost-op)/updrspre-op×100%
statisticalanalysis
thepairedttestwasusedforcomparisonofimprovementsamongthesamegroups,andttestforthoseamongdifferentgroupsofcbpvp,sbpvp1andsbpvp2.
results
intraoperativechangeswerenoticedimmediatelyafterthelesionprobewasintroducedattheelectrophysiologicallyconfirmedtarget.themechanicallyaffectedimprovementsoftremor,rigidityandakinesialastedseveralminutesandseemedtooccuratrightsidesurgerymoreoften.aftersurgery,mostpatientswalkedoutoperationroomwithoutassistance.allofthepatientswerebenefitedfromeithercbpvporsbpvp.
totalupdrsscoresandtheircomparisons
cbpvpgroup
updrsvaluesbeforeandafteroperationwere41.1%±15.8%and21.7%±12.3%respectivelyinthe“on”state,whichcontributedtoanimprovementof48.6%±18.7%(p＜0.001),and88.1%±18.2%and35.0%±13.3%inthe“off”state,withanyimprovementof61.1%±10.9%(p＜0.001).
sbpvp1group
updrsvaluesbeforeandafteroperationwere45.3%±20.9%and28.8%±16.5%respectivelyinthe“on”state,whichcontributedtoanimprovementof35.0%±14.6%(p＜0.001),and87.2%±25.1%and48.1%±21.9%inthe“off”state,withanimprovementof46.3%±15.9%(p＜0.001).
sbpvp2group
updrsvaluesbeforeandafteroperationwere32.7%±16.0%and19.3%±11.2%respectivelyinthe“on”statewithanimprovementof44.6%±20.1%(p＜0.001),and54.9%±23.6%and29.5%±15.1%inthe“off”statewithanimprovementof47.1%±17.6%(p＜0.001).
theimprovementsorchangesofupdrsvaluesaredemonstratedinfigs.1and2a,b.comparedtosbpvp1orsbpvp2respectively,cbpvphadamarkedimprovementbutdidnotreachasignificantchange.infig2b,aslightreturningofupdrsvalueswasnoticedbetweenpost-sbpvp1andpre-sbpvp2inboth“on”and“off”states.eventhoughthechangedidnothaveasignificantmeaning,itismostlikelytobeasignoftheprogressingdiseaseattheotherside.
threecasesofcbpvpwerefollowedupforoneyear.thepreliminarydataofupdrsarealsoshowedinfig.2a.amoredetailedfollow-upstudyisunderwayandwillbereportedlater.
fig.1comparisonsofsurgicalimprovementsoftotalupdrsscoresfollowingcbpvp,sbpvp1andsbpvp2inboth“on”and“off”state.
fig.2atrenddemonstrationofupdrsvaluesaftercbpvpandatanone-uearone-yearfollow-up(fig.2a),updrsvaluesaftersbpvp1andsbpvp2(fig.2b).
subscaleupdrsscores
tocomparehowbpvpimprovesthe4partsofupdrsrespectivelyamongthegroupsofcbpvp,sbpvp1andsbpvp2,wefurtheranalyzedthesubscaleupdrsscores(fig.3).therewerenosignificantdifferencesamongthe3groupsexceptforpartiv(p＜0.05).
cardinalparkinsoniansigns
akinesia,rigidity,andtremorfromitems23-27plus31,item20anditem22ofupdrswerequantitativelyevaluated(fig.4).bpvpsignificantlyimprovedthesecardinalparkinsoniansigns,butnosignificantdifferenceswereobservedamongthegroupsofcbpvp,sbpvp1andsbpvp2.
fig3.comparisonsofsurgicalimprovementsofsubscaleupdrsscoresfollowingcbpvp,sbpvp1andsbpvp2.asignificantdifferenceexistedamongpartiv(p＜0.05).
fig4.improvementpercentagesofthreecardinalparkinsoniansignsfollowingbpvp.akinesiawasrepresentedwitha.akinesiain“off”statewithaofftwithtremorandrwithrigidityrespectively.
adverseeffects
amongthe46patients,severalsurgicalcomplicationswereobserved.inthecbpvpgroup,onepatientdevelopedhypophniaandswallowingproblem.theseconditionswereimproved,butdidnotshowafullrecoveryat3months'follow-up.inthesbpvpgroup,2patientsdevelopedhypophonia.nohemorrhage,hemiparalysis,andvisualfielddeficitwereobserved.transientsleepinessexistedinseveralelderpatients,butnomarkedmentalimpairmentswerefound.sixpatientshadtransientcontralateralfacialweakness.
discussion
thebetterunderstandingofpathophysiologyoftheglobuspallidus(gp)andtheadvancesinstereotactictechnologyhavemadetheposteroventralpartofthegpbecomethebesttargetforthetreatmentofidiopathicpdinthepastyears.thesafenessandeffectivenessofsurgeryhavebeengreatlyenhancedbecauseoftheapplicationofintraoperativemicroelectroderecording,whichcanlocalizethetargetwithin1mm.bpvpisrequiredtoimprovebilateralsymptomsofpdpatients.however,controversyexistsaboutthebenefitsandrisksofcbpvpcomparedtosbpvp.thegeneralconceptisthatifthesecondsidesurgeryhastobedone,theintervalofthetwooperationsshouldbemorethan6months.
ourresultsshowedthatbothcbpvpandsbpvphavesignificantimprovementinpdpatients.therewasnostatisticaldifferenceintheimprovementofcbpvpandsbpvpgroup,indicatingthatcbpvpimprovesbilateralparkinsoniansymptomsaseffectivelyassbpvp.theimprovementinthe“off”statewashigherthanthatinthe“on”state,whichisconsistentwithotherreports.［7］cbpvpcontributedgreatlytothetreatmentofl-dopasideeffects(partiv,p＜0.05).
regardlessofregularcomplicationsofstereotacticneurosurgerysuchasintracranialhemorrhageandextremityweakness,bilateralbrainsurgeryincludingthalamotomyandpallidotomymakesneurosurgeonsnervousandcautious.therehavebeenmanyevidencesdemonstratingthatbilateralthalamotomymaycausehighincidenceofdysarthriaandcognitiveimpairment.however,bilateralpallidotomyisdifferentfrombilateralthalamotomyandseemstobeamuchsaferprocedure.ourresultsshowedthatthereisnoincreasedcognitiveimpairmentafterbpvp.comparedwithunilateralpallidotomy,bpvphasanincreasedriskofhypophonia.theseresultsweresupportedbytahaandscott′sreports.［8，9］however,thecomplicationrateofcbpvpwasnothigherthanthatofsbpvp.itismeantthatifbilateralpallidotomyhastobedone,thereisnosignificantcomplicationdifferencebetweencbpvpandsbpvp.itisnoteworthnotingthat3ofourearliestseriesof16patientshadhypophonia.thismaybecontributedtotheimprovementofoursurgicaltechnique,thatisamorelateraltargetselectionrecommended.iaconoandhiscolleagues［10］reported68casesofcbpvp(n=49)andsbpvp(n=19).comparedwithunilateralpallidotomy,bpvpwasnotassociatedwithanincreasedriskofseverecomplication.
inconclusion,bpvpcansignificantlyimprovebila-teralsignsofpd.bpvpvismuchsaferthanbilateralthalamotomy.sbpvpisnotnecessarilyforallpatients.ifthepatientisyoungerandinagoodgeneralconditiontotoleratealongerdurationofoperation,cbpvpisadvi-sable.cbpvpmayrelievebothsides'symptomsatonceandsavepatient'smedicalcost.bpvpmaynotcausecognitivedeficit,butdoeshaveahighercomplicationrateofhypophonia.thepracticeofbpvprequiresmeticuloussurgicaltechniquethatisbasedonsurgeon'sexperience,intraoperativeconfirmationoflesionprobeposition,patient'scooperation,andmoreimportantlyabetterunderstandingofpathophysiologyofthebasalganglia.
基金项目：国家科委资助项目（96-920-06-05-17）；北京市科委资助项目（953304001）
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收稿日期：1999-12-29
（责任编辑：jbwq）
