Detecting interictal discharges in first seizure patients: ambulatory EEG or EEG after sleep deprivation?

Detecting

interictal

discharges

in

first

seizure

patients:

ambulatory

EEG

or

EEG

after

sleep

deprivation?

I.

Geut

,

S.

Weenink

,

I.L.H.

Knottnerus

,

M.J.A.M.

van

Putten

*

a

DeptofNeurologyandClinicalNeurophysiology,MedischSpectrumTwente,Enschede,TheNetherlands

b

ClinicalNeurophysiology(CNPH),MIRA-InstituteforBiomedicalTechnologyandTechnicalMedicine,UniversityofTwente,Enschede,TheNetherlands

ARTICLE INFO Articlehistory: Received10July2017

Receivedinrevisedform29July2017 Accepted31July2017

Keywords: Epilepsy AmbulatoryEEG SleepdeprivedEEG Diagnostics Interictaldischarges

ABSTRACT

Purpose:Uncertaintyaboutrecurrenceafterafirstunprovokedseizureisasignificantpsychological burdenforpatients,andmotivatestheneedfordiagnostictoolswithhighsensitivityandspecificityto assessrecurrencerisk.AsthesensitivityofaroutineEEGafterafirstunprovokedseizureislimited, patientsoftenrequirefurtherdiagnostics.Here,westudyifambulatoryEEG(aEEG)hassimilardiagnostic accuracyassleepdeprivedEEG(sdEEG).

Methods:Inthisretrospectivecohort,weincludedpatientswithanunprovokedfirstseizureandanormal routineEEGwhosubsequentlyunderwentansdEEGoraEEG.AllEEGswerereviewedforthepresenceof interictalepileptiformdischarges(IEDs).WecalculatedspecificityandsensitivityofsdEEGandaEEG, usingtheclinicaldiagnosisofepilepsyasgoldenstandard.Allpatientshadafollow-upofoneyear. Results:Weincluded104patients.SensitivitiesforsdEEGandaEEGwere45%(specificity91%)and63% (specificity95%),respectively.IndependentriskfactorforrecurrentseizurewereIEDsontheadditional EEG,witharelativeriskof1.5ofhavingarecurrentseizurewithinayear.

Conclusion: Diagnostic accuracies of sdEEG and aEEG are similar and dependingon patients’and clinicians’preferencebothcanbeconsideredinpatientswithafirstseizureandanormalroutineEEGto determinerecurrencerisk.

©2017BritishEpilepsyAssociation.PublishedbyElsevierLtd.Allrightsreserved.

1.Introduction

Afirstseizurehasasignificantpsychologicalimpactonpatients

[1]wheretheclinician'sroleincludesfindingapotentialcauseand estimatingtherecurrencerisk.Mainpredictorsforrecurrenceare symptomaticetiologyandthepresenceofinterictalepileptiform discharges(IEDs)ontheEEG.Whilehighlyspecific,thesensitivity ofaroutineEEGafterafirstunprovokedseizureislimited,ranging from25to50%[2].Longerregistrationsorrecordingsduringsleep increasestheyieldto50–75%[3,4].

Noconsensusexistsaboutthenextdiagnosticstepifaroutine (20–30min)EEGrecordingafterafirstseizuredoesnotcontain interictal epileptiform discharges (IEDs). In the Netherlands, approximately 48% of the clinicians order a sleep deprivation EEG(sdEEG),45%asecondroutineEEGand3%anambulatoryEEG (aEEG)[5].AlthoughaEEGisrecommendedbytheILAEforspecific indications like classification of epilepsy syndromes and for differentiation between seizures and pseudo-seizures, there is

no literature about the diagnostic yield of aEEG after a first unprovokedseizurewithanormalroutineEEG[3,6].Westudythe detection rate of IEDs in aEEGs in comparison with sdEEGs in patientswith a first unprovoked seizure and a normal routine recording.

2.Methods 2.1.Patientinclusion

WesearchedourEEGdatabaseforpatientswithunprovoked focalor generalizedseizureswhowereadmittedtoourClinical NeurophysiologydepartmentbetweenJanuary2011and Novem-ber 2015. Unprovoked seizures were defined as convulsive episodes occurringin the absenceof precipitating factors. This included seizures of unknown etiology as well as seizures in relation to a demonstrated pre-existing brain lesion (remote symptomaticseizure)[7].Weexcludedpatientsyoungerthan6 years,patientswithknownepilepsyandpatientswithprovoked seizures.Wesubsequentlyselectedpatientsinwhomtheroutine EEG (including hyperventilation and photic simulation) was normalordidnotshowconvincing IEDs,andeithera sdEEGor aaEEGwasrequested.Finally,wematchedbothgroupsforageand

*Corresponding authorat: DeptofNeurology andClinicalNeurophysiology, MedischSpectrumTwente,Enschede,TheNetherlands.

E-mailaddress:m.j.a.m.vanputten@utwente.nl(M.J.A.M. vanPutten).

http://dx.doi.org/10.1016/j.seizure.2017.07.019

1059-1311/©2017BritishEpilepsyAssociation.PublishedbyElsevierLtd.Allrightsreserved.

Seizure51(2017)52–54

ContentslistsavailableatScienceDirect

Seizure

gender.aEEGhadadurationof16–24h,includingsleep.sdEEGhad a duration of 1.5–3h, including sleep, and was recorded after completesleepdeprivationduringthepreviousnight.

2.2.EEGrecording

EEGswererecordedwith21electrodespositionedaccordingto theinternational10–20systemusingaBrainlabEEGsystem(OSG, Belgium) or Mobita mobile amplifiers (TMS-i international, Oldenzaal,theNetherlands),sampledat512Hz.

2.3.EEGassessmentandclinicalevaluation

AllEEGswerere-reviewedforepileptiformdischarges(spikes, polyspikes,sharpwaves,sharp-slowwavesorspike-slowwaves) byeitheraresidentinneurology(IG)orexperiencedlabtechnician (SW),bothsupervisedbyaclinicalneurophysiologist(MvPorIK). Thepatients’clinicalrecordwasevaluatedforage,sex,firstseizure, startofanti-epilepticdrugs,MRIorCTresultsandwhetherornot diagnosisofepilepsywasmadewithafollowupofoneyear.The diagnosisofepilepsywasbasedonthenewILAEcriteriapublished in 2014 [8]. Sensitivity and specificity were determined using diagnosisofepilepsyafteroneyearoffollowupasgoldenstandard. Resultsarepresentedassensitivity,speci_ficityand95%con_fidence intervals (CI). Statistical significance was evaluated using Chi-squared-tests,withsignificancethresholdofp<0.05.

3.Results

Weincluded104patients.Themajorityofpatientspresented witheitheraprimaryorsecondarygeneralizedseizure,46%inthe aEEG group, 62% in the sdEEG group. Eleven patients showed pathologyonCTorMRI.Patientcharacteristicsaresummarizedin

Table1.

ThedifferenttypesofIEDsdetectedarepresentedinTable2. InthesdEEGgroup16patients(31%)showedIEDs,intheaEEG group21patients(40%).Inbothgroups,one(aEEG)ortwo(sdEEG) patients showed IEDs, but were not diagnosed with epilepsy. DiagnosticfindingsaresummarizedinTables3AandB.Thisresults inasensitivityofsdEEGof45%(CI:27–64%),withaspecificityof 91%(CI:70–99%)andapositive(PPV)andnegativepredictivevalue (NPV)of88%and53%,respectively.ForaEEG,thesensitivitywas 63% (CI: 44–79%) with specificity 95% (CI: 75–100%), with

PPV=95% and NPV=61%. All differences were not statistically significant.

In both groups, epileptiform discharges were most often presentduringsleepstageII,withameantimetooccurrenceof 14minintheaEEGand20mininthesdEEG,respectively(p=0.98). Of the sixteen patients with non-convincing abnormalities on routine EEG,12 showed IEDs inthe follow uprecording (75%). Elevenofthesepatientswerediagnosedwithepilepsyafterone yearoffollow up.Fiftyonepercentofpatientshada recurrent seizurewithinoneyear,50% intheaEEGgroupand 52%inthe sdEEGgroup.Independentriskfactorforrecurrentseizurewere IEDsontheadditionalEEG,witharelativeriskof1.5ofhavinga recurrentseizurewithinayear.

4.Discussion

Toourknowledge,thisisthefirststudytocomparesdEEGwith aEEG inpatients withafirst unprovokedseizure and a normal routineEEG.OurdatashowthatthediagnosticaccuracyofsdEEG and aEEG are similar.The sensitivity fordetection of IEDs ina sdEEGwas 45%(specificity91%),similartowhat isreportedby others[9,10],andthesensitivityfordetectionofIEDsinaEEGwas 63% (specificity95%).Further,inabout75% ofpatientswithan initialEEGshowing‘non-convincingabnormalities’,sdEEGoraEEG showed interictal epileptiform discharges. Only a few studies contrastedambulatoryEEGwithsdEEG,butallinpatientswithan existing diagnosis of epilepsy. In a cohort of 42 patients, both sdEEGandaEEGimproveddetectionofepileptiformdischargesby asimilaramount(24%versus33%)[11].

AlthoughthetotalregistrationdurationofaEEGislonger(18– 20h) than sdEEG (2h), in most patients the epileptiform discharges were observed during sleep stage II, without a difference in mean time to first occurrence. While SD-induced sleepseemstobemorelikelytoevokeIEDsthannaturalsleep[12], this(additional)effectmaybemodest.Wearguethereforethatitis sleepratherthansleepdeprivationthatincreasesthelikelihoodof detectinginterictaldischarges.Potentialexplanationsfortheeffect ofsleepontheoccurrenceofIEDsarediscussedinarecentreview

[12].WhilesdEEGmayinduceseizures,thisdidnotoccurinour patients.Howlargethispresumedincreaseis,isstillamatterof debate[10,12],butonecouldspeculatethataEEGisperhapssafer thanasdEEG.

Inourcohort,recurrenceratewas53%,whichseemsrelatively largeas in untreatedpatients, 40–50%can expecta recurrence within2yearsoftheinitialseizure[13,14].However,weincluded patientswithafirstunprovokedseizurewhowerealsoreferredfor additional diagnostics, and in many EEGs showed IEDs. This apparentlyresultedinalargerfractionofpatientswithepilepsy.A limitationofourstudyisthatit isasinglecenter,retrospective study, witha restrictedfollow-upperiod ofone year.However, recurrenceriskafteroneunprovokedseizureislargestwithinthe first year, and didnot differ betweenthetwo groups.Another limitation of aEEG is the lack of video recording, especially in patientswithparoxysmalevents.However,weincludedpatients withafirstseizure,wheredetectionofIEDsistheprimarygoal,in

Table1

Clinicalcharacteristics.

sdEEG(n=52) aEEG(n=52) Age(years,median) 46 48 Malesex,n(%) 36(69%) 31(60%) Typeseizure Primary/secondarygeneralized 32(62%) 24(46%) Focal 11(21%) 21(40%) Nocturnal 8(15%) 5(10%) AbnormalMRI 6(12%) 5(10%) Table2

Overviewofdetectedinterictaldischarges.

Epileptiformdischarges sdEEG aEEG

Numberofpatients percentage Numberofpatients percentage

Sharp-slowwave 7 43.8% 8 38.1%

Sharpwave 1 6.2% 4 19%

Generalizedspike-wavedischarges 2 12.5% 1 4.8%

Isolatedspikewavedischarges 6 37.5% 8 38.1%

Isolatedspike 0 0% 0 0%

contrasttostudieswhereaEEGisusedforthedifferentialdiagnosis ofparoxysmalevents.

Atpresent,mostcliniciansuseaEEGtodifferentiateepileptic andnon-epilepticeventsortoquantifyIEDsindifferentstagesof pharmacologicalinterventions[15–17].IntheNetherlands,aEEGis orderedbyonly3%ofneurologistsinpatientswithaseizureand normalinitialEEG[5].However,inourhospitalaEEGhasbecome anavailable alternativeforsdEEGsinceabout2012,andseveral neurologistshavesincethenusedthisforfollow-upEEG.Ourdata showthataEEGhassimilarefficacyassdEEGfordetectionofIEDs infirst unprovokedseizure patientswithnormal routine EEGs. Ambulatory EEG was well tolerated. As no significant macro-economicdisadvantagesofaEEGoversdEEGexist[18],aEEGmay beconsideredinsteadofsdEEGinthediagnosticwork-upaftera firstseizurewithnormalroutineEEG,accordingtothepreference ofthepatientandclinician.

Conflictofinterest

Noneoftheauthorshasanyconflictofinterest,norhasthework been published before or is being considered for publication elsewhere.

References

[1]VelissarisSL,WilsonSJ,SalingMM,NewtonMR,BerkovicSF,AndreskiP.The psychologicalimpactofa newlydiagnosedseizure: losing andrestoring perceivedcontrol.EpilepsyBehav2007;10:223–33.

[2]KrumholzA,WiebeS,GronsethG,ShinnarS,LevisohnP,TingT,etal.Practice parameter:evaluatinganapparentunprovokedfirstseizureinadults(an evidence-basedreview):ReportoftheQualityStandardsSubcommitteeofthe American Academy of Neurology and the American Epilepsy Society. Neurology2007;69:1996–2007.

[3]FaulknerHJ,ArimaH,MohamedA.Latencytofirstinterictalepileptiform dischargeinepilepsywithoutpatientambulatoryEEG.ClinNeurophysiol 2012;9:1732–5.

[4]AskampJ,vanPuttenMJAM.24hin-homeEEGafterafirstseizureinadults. NeurophysiolClinNeurophysiol2013;43:73.

[5]Askamp J, van Putten AM. Diagnostic decision-making aftera first and recurrentseizureinadults.Seizure2013;22:507–11.

[6]Velis D, Plouin P, Gotman J, da Silva FL, ILAE DMC Subcommittee on Neurophysiology.Recommendationsregardingtherequirementsand appli-cationsforlong-termrecordingsinepilepsy.Epilepsia2007;48:379–84. [7]Guidelinesforepidemiologicstudiesonepilepsy.commissionon

epidemiol-ogy and prognosis, international league against epilepsy. Epilepsia 1993;34:592–6.

[8]FisherRS,AcevedoC,ArzimanoglouA,BogaczA,CrossJH,ElgerCE,etal.ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55:475–82.

[9]LeoneMA,VallaltaR,SolariA,BeghiE,FIRSTGroup.Treatmentoffirst tonic-clonicseizuredoesnotaffectmortality:long-termfollow-upofarandomised clinicaltrial.JNeurolNeurosurgPsychiatry2011;82:924–7.

[10]GiorgiFS,PeriniD,MaestriM,GuidaM,PizzanelliC,CasertaA,etal.Usefulness ofasimplesleep-deprivedEEGprotocolforepilepsydiagnosisindenovo subjects.ClinNeurophysiol2013;124:2101–7.

[11]LiporaceJ,TatumW,MorrisGL,FrenchJ.Clinicalutilityofsleep-deprived versuscomputer-assistedambulatory16-channelEEGinepilepsypatients:a multi-centerstudy.EpilepsyRes1998;32:357–62.

[12]GiorgiFS,GuidaM,CaciagliL,MaestriM,CarnicelliL,BonanniE,etal.Whatis theroleforEEGaftersleepdeprivationinthediagnosisofepilepsy?Issues, controversies,andfuturedirections.NeurosciBiobehavRev2014;47:533–48. [13]Berg AT. Risk of recurrence after a first unprovoked seizure. Epilepsia

2008;49:13–8.

[14]Randomizedclinicaltrialontheefficacyofantiepilepticdrugsinreducingthe riskofrelapseafterafirstunprovokedtonic-clonicseizure.FirstSeizureTrial Group(FIRSTGroup).Neurology1993;43:478–83.

[15]MichelV,MazzolaL,LemesleM,VercueilL.Long-termEEGinadults: sleep-deprivedEEG(SDE),ambulatoryEEG(Amb-EEG)andlong-termvideo-EEG recording(LTVER).NeurophysiolClin/ClinNeurophysiol2015;45:47–64. [16]KoeppMJ,FarrellF,CollinsJ,SmithS.Theprognosticvalueoflong-term

ambulatoryelectroencephalographyinantiepilepticdrugreductioninadults withlearningdisabilityandepilepsyinlong-termremission.EpilepsyBehav 2008;13:474–7.

[17]FaulknerHJ, Arima H, Mohamed A. The utilityof prolonged outpatient ambulatoryEEG.Seizure2012;21:491–5.

[18]AskampJ,vanPuttenMJAM.MobileEEGinepilepsy.IntJPsychophysiol 2014;91:30–5.

Table3A

Diagnosticfindingsinpatients(n=52)withasdEEG.Abnormalimpliespresenceof interictalepileptiformdischarges.

Epilepsy(n=31) Noepilepsy(21) AbnormalsdEEG 14 2

NormalsdEEG 17 19

Table3B

Diagnosticfindingsinpatients(n=52)withanaEEG.Abnormalimpliespresenceof interictalepileptiformdischarges.

Epilepsy(n=32) Noepilepsy(20)

AbnormalaEEG 20 1

NormalaEEG 12 19