Biobehavioral sources of variance in presurgical neuropsychological performance among patients with temporal lobe epilepsy

138 Pages·1997·5.4 MB·English

by  Moser, David J

BIOBEHAVIORALSOURCESOFVARIANCEINPRESURGICAL
NEUROPSYCHOLOGICALPERFORMANCEAMONGPATIENTSWITHTEMPORAL
LOBEEPILEPSY
By
DAVIDJ.MOSER
ADISSERTATIONPRESENTEDTOTHEGRADUATESCHOOL
OFTHEUNIVERSITYOFFLORIDAINPARTIALFULFILLMENT
OFTHEREQUIREMENTSFORTHEDEGREEOFDOCTOROFPHILOSOPHY
UNIVERSITYOFFLORIDA
1997
ACKNOWLEDGEMENTS
Completionofthisstudywouldnothavebeenpossiblewereitnotfortheimportant
contributionsofmanyindividualswhodeservemyrecognitionandgratitude. Firstandforemost,
Iwouldliketoextendmysincerethankstomydissertationchairperson.Dr.RussellBauer,for
theenormousamountofknowledge,time,effort,patienceandhumorthathebroughttothis
project. IwouldalsoliketothankDr.EileenFennellandDr.DuaneDedefortheirinsightful
comments,supportandvaluableinputduringallphasesofthestudy. Theassistanceand
guidanceofDr.RobinGilmoreisgreatlyappreciated,asshewasverygivingofherknowledge
andexpertiseregardingepilepsyandalsoallowedmeaccesstoEpilepsyMonitoringUnit
resources. IwouldalsoliketoextendmysinceregratitudetoDr.JamesAlgina,whowentto
greatlengthstoprovidevaluableandtimelystatisticalguidance.
Dr.ChristianaLeonardalsodeservesrecognitionandthanksforherassistanceand
generosityinallowingmeaccesstotheImageProcessingLaboratory. Iwouldalsoliketothank
Dr.TaraSpevackforhervaluableandthoughtfiilinputthroughoutthestudy. Dr.StevenRoper,
Mr.TimothyLucas,Ms.ArleneFrank,Ms.CandaceLariz,Dr.RitaJakus,Ms.DonnaLilly,Ms.
ChristieSnively,thegraduatestudentsinDr.RussellBauer'sNeuropsychologyLaboratory,and
theEpilepsyMonitoringUnittechniciansalsoplayedimportantrolesintheformationand
completionofthestudy.
FinallyIwouldliketothankmywife,Becky,andourdaughter,Ameliafortheirconstant
andunwaveringlove,supportandgoodhumor.
ii
TABLEOFCONTENTS
page
ACKNOWLEDGEMENTS ii
ABSTRACT v
CHAPTERS
1 OVERVIEWOFRELEVANTLITERATURE I
Epilepsy:Description,Incidence,andClassification 1
NeuropsychologicalAssessmentofEpilepsyPatients 4
HippocampalPathologyandNeuropsychologicalPerformance 25
QuantitativeMRIVolumetricStudiesinEpilepsy 29
HippocampalVolumes,Pathology,andNeuropsychologicalPerformance 34
EEGLocalizationofSeizureFoci 37
NeuropsychologicalTesting,MRI,andEEG 50
EpilepsySurgeryattheUniversityofFlorida 52
PurposeofthePresentStudy 54
2 METHODS 56
Subjects 56
Measures 56
MissingNeuropsychologicalData 58
MRIVariables 59
EEGVariables 59
DataCollectionProcedures 62
ExperimentalHypotheses 68
3 RESULTS 78
DemographicandIllness-RelatedVariables 78
NeuropsychologicalVariables 78
HippocampalVolumetrics 84
EEGVariables 84
4 DISCUSSION 100
DiscussionofExperimentalandExploratoryHypotheses 100
GeneralDiscussion 113
iii
DirectionsforFutureResearch 117
APPENDIX 120
REFERENCES 124
BIOGRAPHICALSKETCH 131
iv
AbstractofDissertationPresentedtotheGraduateSchool
oftheUniversityofFloridainPartialFulfillmentofthe
RequirementsfortheDegreeofDoctorofPhilosophy
BIOBEHAVIORALSOURCESOFVARIANCEINPRESURGICAL
NEUROPSYCHOLOGICALPERFORMANCEAMONGPATIENTSWITHTEMPORAL
LOBEEPILEPSY
By
DavidJ.Moser
December,1997
Chairman: RussellM.Bauer,Ph.D.
MajorDepartment: ClinicalandHealthPsychology
Mostepilepsycentersuseelectroencephalographic(EEG),structural-anatomic(MRI),
andneuropsychological(NP)datatoidentifypotentiallyresectableregionsofepileptogenictissue
inepilepsysurgerycandidates. Inidealcases,thesedataareconvergentandidentifyadiscrete
regiontoberesected. Sometimes,however,NPdataarelessspecificthanEEGandMRIdatain
lateralizingandlocalizingseizureonset. Inthecurrentstudy,discriminantfunctionanalyses
(DFA)wereusedtoevaluatethestatisticalefficacyofEEG,MRI,andNPinpredictingsideof
seizurefocusandeventualsurgeryinagroupofcomplexpartialseizurepatientsundergoing
unilateralanteriortemporallobectomy(ATL). Subjectswerethendividedintotwogroups
dependinguponwhethertheirNPdatawereconvergentordivergentwithEEGandMRI
regardingpredictionofeventualsurgicalhemisphere. Thesegroupswerethencompared
regardingdemographicandillness-relatedvariables.
Subjectswere61surgicalcandidateswithcomplexpartialseizureswhoeventually
underwenteitherright(n=26)orleft(n=35)ATL. Foreachsubject,scalpEEGonsetwas
v
codedandtransformedtoproduceasinglevaluereflectingdegreeofseizureonsetlaterality
(SLI). Likewise,quantitativeMRIdatawereusedtoproduceavaluereflectingamountof
volumetricasymmetrybetweenthetwohippocampi(DHF). Neuropsychologicalperformance
wascharacterizedbycalculatingaveragez-scoresinlanguage,verbalmemory,nonverbal
memory,motorandvisuoconstructivedomains. Then,SLI,DHF,andthefiveNPdomainscores
wereenteredaspredictorsofsideofsurgeryandofsideofepileptogenicfocususingDFA.
ResultsindicatedthatSLIwasaslightlybetterpredictorofsideofsurgeryandsideof
seizurefocusthanDHF,andthatbothweresignificantlysuperiortoNPdomainscoresinthis
regard. CorrectpredictionratesgenerallyimprovedwhentheseSLI,DHF,andNPdomainscores
wereusedincombinationwithoneanotherratherthaninisolation. Groupcomparisonsmade
betweenthosesubjectsforwhomNPdatawereconvergentwithEEGandMRIandthosefor
whomthesedataweredivergentyieldednosignificantdifferencesondemographicorillness-
relatedvariables. Implicationsformakingtreatmentdecisionsinepilepsyprograms,and
directionsforfutureresearch,werediscussed.
vi
CHAPTER1
OVERVIEWOFRELEVANTLITERATURE
Epilepsy:Description.Incidence,andClassification
Epilepsyisaneurologicaldisordercharacterizedbyrecurrentseizures(Locharemkul,
Primrose,Pilcher,Ojemann,&Ojemann,1992). Aseizureoccurswhenagroupofneurons
becomes"irritable"andfiresinrepeatedbursts(Engel,1989),andmayleadtoclinically
observablechangesinbehaviorifsufficientnumbersofneuronsareinvolved. Epilepsyisthe
mostcommonchronicneurologicaldisorderintheUnitedStates,affectingmorethan2million
adultsandchildren(Mcintosh,1992).
Althoughwidelyused,theterm"epilepsy"isnotadiagnosisinitself,butisageneral
term,whichsubsumesmanydifferentsyndromes(Kuzniecky&Jackson,1995). In1964,the
CommissiononClassificationandTerminology(CCT)oftheInternationalLeagueagainst
Epilepsy(ILAE)soughttocategorizethesevariousseizuretypesinsuchawaythatprofessionals
worldwidecouldtreat,research,anddiscusstheseeventsusingconsistentcriteriaand
terminology. Priortothattime,manyseparateclassificationsystemshadbeendevelopedfor
differentpurposes,asituationwhichgaverisetovaryingandconfusingterminology(Wyllie&
Luders,1993).TheeffortsoftheCCTweresuccessful,andtheclassificationsystemthatwas
developedremainedinuseuntil1981,whenitwasrevisedintothesystemwhichiscurrentlyin
use. Abriefdescriptionofthecurrentsystemfollows.
Currently,allseizuresareinitiallyplacedinoneoftwolargecategories. Aseizureis
definedas"generalized"ifitsonsetinvolvesactivationofalargenumberofneuronsinboth
hemispheres. "Partial"or"focal"seizures,ontheotherhand,arethosethatbeginwithactivation
1
2
ofneuronsinalimitedpartofonehemisphere. Asecondmajorclassificationconcernsthe
presenceorabsenceofalterationsofconsciousnessduringtheseizure. Thoseaccompaniedbyno
suchalterationsaretermed"simple",whilethosethatproducechangesinconsciousnessare
definedas"complex." Forthepurposesofthepresentstudy,thefollowingwillconcernonly
partialseizures.
Accordingtothe1981classificationsystem,partialseizuresarefiirthersubdividedinto
threecategories. Ascanbeinferredfi-omtheabove,"simplepartialseizures"arethosethatbegin
focallyandinvolvenoalterationofconsciousness,while"complexpartialseizures"(CPS)begin
focallyanddoinvolvesuchchangeseitherimmediatelyorshortlyafteronset. Finally,thereare
seizureswhicharedescribedas"secondarilygeneralized",whichbeginassimpleorcomplex
partialeventsandpropagateuntillargeareasofbothhemispheresareinvolved. Simpleand
complexpartialseizuresarethendescribedmorespecificallyaccordingtothepresenceor
absenceofconcomitanteventssuchasmotorinvolvement,somatosensoryexperiences,
autonomicsigns,andcognitiveandemotionaldisturbances(CommissiononClassificationand
TerminologyoftheInternationalLeagueAgainstEpilepsy,1981). Approximately40percentof
allepilepticindividualssufferfromCPS(Gastautetal.,1975),andapproximately60percentof
thesepatientshaveseizuredisorderswhicharerefractorytomedication(Rodin,1968). Thus,
findinganalternativetreatmentforpatientswithCPSisessential.
Anincreasinglyavailableandeffectivetreatmentforpatientswhoseepilepsycannotbe
controlledwithmedicationissurgicalresectionofanidentified"epileptogenicfocus",whichhas
beendefinedasthatbrainlocationfromwhichapatient'shabitualseizuresarise,andremovalof
whichwilltheoreticallyresultincompletecessationofseizures(Risinger,1991). Ithasrecently
beenestimatedthatapproximately1,000oftheseresectiveseizuresurgeriesareperformedeach
year(Pilcher,Locharemkul,Primrose,Ojemann,&Ojemann,1992),andthat80to90percentof
thesepatientsbenefitsignificantlyfi-omthisintervention.
Inordertoprovidehealthcareprofessionalswithausefiilandconsistentindicatorof
surgicaloutcome,Engel(1987)developedaclassificationsystemwherebyeachpostsurgical
patientreceivesascoreofIthroughIV. Criteriaforeachclassificationareasfollows: ClassI
(Seizure-free):A)Completelyseizure-freesincesurgery,excludinganyseizureswhichmayhave
occurredduringthefirstfewpostoperativedays;B)Aurasonlysincesurgery;C)Someseizures
aftersurgery,butseizure-freeforatleasttwoyears;orD)Atypicalgeneralizedconvulsionswith
antiepilepticdrugwithdrawalonly.ClassII(RareSeizuresor"ahnostseizure-free"):A)Initially
seizure-freefollowingsurgerybuthasrareseizuresnow;B)Rareseizuressincesurgery;C)More
thanrareseizuresaftersurgery,butrareseizuresforatleasttwoyears;orD)Nocturnalseizures
only,whichcausenodisability. ClassIII(WorthwhileImprovement):A)Worthwhileseizure
reduction;orB)Prolongedseizure-freeintervalsamountingtogreaterthanhalfthefollow-up
period,butnotlessthantwoyears. ClassFV(NoWorthwhileImprovement):Significantseizure
reduction;B)Noappreciablechange;orC)Seizuresworse. Ascanbeinferredfromthese
criteria,agivenpatient'sEngelClassificationmaychangeacrossthecourseoftimefollowing
surgery.
Resectivesurgeryhasbeenshowntobeparticularlysuccessfiilwhentheseizurefocus
andsubsequenttargetofresectionisinthetemporallobe(Chelune,1981;Engel,VanNess,
Rasmussen,&Ojemann,1993). Althoughtheaforementionedratesofsurgicalsuccessare
impressive,itisimportanttonotethattheeffectivenessofsurgeryreliesheavilyontheselection
ofappropriatesurgerycandidates,andmustbejudgedinthecontextofseveralfactorsinaddition
toagivenpatient'sdegreeofpotentialpostoperativeseizurerelief
4
Whenevaluatinganindividualforseizuresurgery,thepotentialforseizurecontroland
confidencewithwhichagivenseizurefocusisidentifiedmustbeestimatedandcomparedwith
thepotentialfortheseriouscognitiveandpsychosocialimpairmentsthatmayresultfrom
temporalloberesection. Thistypeof"risk-benefit"assessmentallowsboththephysicianand
patienttomakewell-informeddecisionsregardingthelikelyeffectsofsurgery(Ivnik,
Sharbrough,&Laws,1988). Becausesuchadeterminationiscomplexandmultifactorial,datain
severaldomainsisusuallycollectedtoassistinmakingsurgerydecisions. Thosetobediscussed
inthisstudyincludeneuropsychologicalevaluation,magneticresonanceimaging(MRI),and
electroencephalographic(EEG)investigation.
NeuropsychologicalAssessmentofEpilepsyPatients
Neuropsychologicaltestingplaysauniqueroleintheassessmentoftheepilepticpatient,
asitprovidesinformationwhichiscomplementarytophysiologicalandanatomicalmeasures
suchasEEGandMRI. AlthoughEEGandMRIprovidevaluableinformationaboutthestateof
thebrain,onlyneuropsychologicaltestingcanrevealthebrain'sactualbehavioralcapacities. In
fact,properlyadministeredandinterpretedneuropsychologicaltestingmayrevealbrain
dysfunctionbeforestructuralabnormalitiesareevidentusingothermeasures(Jones-Gotman,
1991).
Onegoalofneuropsychologicalassessmentinthestudyofepilepsyistoidentify
impairmentsthatmaysuggestthatseizureonsetislateralizedtoaparticularhemisphere,oreven
morespecifically,localizedwithinthathemisphere. Suchinformation,whencombinedwithdata
obtainedthroughMRI,EEG,andclinicalinterview,mayrevealanepileptogeniczone(Pilcheret
al.,1992). Inadditiontoidentificationofthisareaofseizureonset,neuropsychologicaldataalso
playsanimportantroleindetermininghowlikelyitisthatremovalofbraintissuewillresultina