strengthmarcoblaze

RESEARCHOpenAccessEffectivenessofupperlimbfunctionalelectricalstimulationafterstrokefortheimprovementofactivitiesofdailylivingandmotorfunction:asystematicreviewandmeta-analysisJohnEraifej1*,WilliamClark1,BenjaminFrance1,SebastianDesando1andDavidMoore2AbstractBackground:Strokecanleadtosignificantimpairmentofupperlimbfunctionwhichaffectsperformanceofactivitiesofdailyliving(ADL).
Functionalelectricalstimulation(FES)involveselectricalstimulationofmotorneuronssuchthatmusclegroupscontractandcreateoraugmentamomentaboutajoint.
WhilstlowerlimbFESwasestablishedinpost-strokerehabilitation,thereisalackofclarityontheeffectivenessofupperlimbFES.
Thissystematicreviewaimstoevaluatetheeffectivenessofpost-strokeupperlimbFESonADLandmotoroutcomes.
Methods:SystematicreviewofrandomisedcontrolledtrialsfromMEDLINE,PsychINFO,EMBASE,CENTRAL,ISRCTN,ICTRPandClinicalTrials.
gov.
Citationcheckingofincludedstudiesandsystematicreviews.
Eligibilitycriteria:participants>18yearswithhaemorrhagic/ischaemicstroke,interventiongroupreceivedupperlimbFESplusstandardcare,controlgroupreceivedstandardcare.
OutcomeswereADL(primary),functionalmotorability(secondary)andothermotoroutcomes(tertiary).
QualityassessmentusingGRADE(GradingofRecommendationsAssessment,DevelopmentandEvaluation)criteria.
Results:Twentystudieswereincluded.
NosignificantbenefitofFESwasfoundforobjectiveADLmeasuresreportedinsixstudies(standardisedmeandifference(SMD)0.
64;95%ConfidenceInterval(CI)[0.
02,1.
30];totalparticipantsinFESgroup(n)=67);combinationofallADLmeasureswasnotpossible.
AnalysisofthreestudieswhereFESwasinitiatedonaveragewithin2monthspost-strokeshowedasignificantbenefitofFESonADL(SMD1.
24;CI[0.
46,2.
03];n=32).
InthreestudieswhereFESwasinitiatedmorethan1yearafterstroke,nosignificantADLimprovementswereseen(SMD0.
10;CI[0.
59,0.
38],n=35).
QualityassessmentusingGRADEfoundverylowqualityevidenceinallanalysesduetoheterogeneity,lowparticipantnumbersandlackofblinding.
Conclusions:FESisapromisingtherapywhichcouldplayapartinfuturestrokerehabilitation.
ThisreviewfoundastatisticallysignificantbenefitfromFESappliedwithin2monthsofstrokeontheprimaryoutcomeofADL.
However,duetotheverylow(GRADE)qualityevidenceoftheseanalyses,firmconclusionscannotbedrawnabouttheeffectivenessofFESoritsoptimumtherapeuticwindow.
Hence,thereisaneedforhighqualitylarge-scalerandomisedcontrolledtrialsofupperlimbFESafterstroke.
(Continuedonnextpage)*Correspondence:jxe117@student.
bham.
ac.
ukEqualcontributors1SchoolofMedicine,CollegeofMedicalandDentalSciences,UniversityofBirmingham,Edgbaston,BirminghamB152TT,UKFulllistofauthorinformationisavailableattheendofthearticleTheAuthor(s).
2017OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.
0InternationalLicense(http://creativecommons.
org/licenses/by/4.
0/),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinktotheCreativeCommonslicense,andindicateifchangesweremade.
TheCreativeCommonsPublicDomainDedicationwaiver(http://creativecommons.
org/publicdomain/zero/1.
0/)appliestothedatamadeavailableinthisarticle,unlessotherwisestated.
Eraifejetal.
SystematicReviews(2017)6:40DOI10.
1186/s13643-017-0435-5(Continuedfrompreviouspage)TrialRegistration:PROSPERO:CRD42015025162,Date:11/08/2015Keywords:Functionalelectricalstimulation,Upperlimb,Stroke,Systematicreview,Meta-analysis,neurorehabilitationBackgroundStrokeisdefinedasaclinicalsyndromecharacterisedbyrapidlydevelopingfocalorglobaldisturbanceincerebralfunctionlastingmorethan24horleadingtodeathduetoapresumedvascularcause[1].
Globally,approxi-mately16millionpeoplehaveastrokeeachyear[2]andintheUK,first-everstrokeaffectsabout230peopleper100,000populationeachyear[3].
StrokerepresentsacosttotheUKeconomyofapproximately9billionan-nually,ofwhich1.
33billionresultsfromproductivitylosses[4].
Strokeoftenleadstosignificantimpairmentofupperlimbfunctionandisassociatedwithdecreasedqualityoflifeinalldomainsexceptformobility[5].
Fewpatientsattaincompletefunctionalrecovery[6];thisdeficitimpairsperformanceofactivitiesofdailyliving(ADL),includingself-careandsocialactivities[7,8].
ADLreflecttheleveloffunctionalimpairmentindailylifeandarethereforethemostclinicallyrelevantoutcomemeasuresinassessingrecoveryafterstroke[9].
Functionalelectricalstimulation(FES)waswellestablishedasaninterventionformotorrehabilita-tion.
FESistheelectricalstimulationofmotorneuronssuchthatmusclegroupsarestimulatedtocontractandcreate/augmentamomentaboutajoint[2].
Transcutaneouselectrodesofferthemostimmediateandclinicallyviabletreatmentoptionastheyarenon-invasiveandmaypermithome-basedtreatment.
Therearevarioustermsusedintheliteraturetodescribedifferentformsofelectricalstimulation,ofteninconsistently.
SomeauthorsdefineFESaselectricalstimulationappliedtoasubjectwhichcausesmusclecontraction.
Thispassivemodalityisalsoreferredtoasneuromuscularelectricalstimula-tion[10].
OthersdefineFESaselectricalstimulationappliedduringavoluntarymovement[4].
Thisdefin-itionacknowledgesthevolitionalcomponentofphysicalrehabilitationandwasusedinthissystem-aticreview.
Thedistinctionisimportantbecauseneuroimagingstudieshaveidentifieddifferentcor-ticalmechanismsaccordingtostimulationtype[11–13].
Indeed,perfusiontotheipsilesionalsensory-motorcortexandcorticalexcitabilitywereincreasedwithFESwhencomparedtopassivemodalitiesofelectricalstimulation[12–14].
ThesefindingscouldindicategreaterpotentialforvolitionalFEStoinduceneuroplasticity.
Thisisbelievedtoplayanimportantroleinneurorehabilitation[15]andisakeyobjectiveofpost-strokefunctionalrecovery[16].
FEShasbeenwidelyresearchedforpost-strokelowerlimbrehabilitation;severalsystematicreviews[17–19]andnationalguidelines[20,21]exist.
Im-provementinupperlimbfunctioniscentraltopost-strokerehabilitationasitpositivelyaffectsADLandqualityoflife[22].
Yet,thereisstillalackofclarityontheeffectivenessofFESinpost-strokeupperlimbrehabilitation[23]despitesystematicreviewshavingbeenundertaken[24–28].
Inpart,thisisduetomethodologicallimitations[27,28]ortheoutdatednatureofsomeexistingreviews[24–26].
ThelatterwashighlightedbyarecentCochraneoverviewofreviewscallingforanup-to-datereviewandmeta-analysisofrandomisedcontrolledtrials(RCTs)re-latedtoelectricalstimulation[29].
AmorerecentsystematicreviewfoundasignificantimprovementinmotoroutcomeswithupperlimbFES[27].
However,thiswasbasedonasinglemeta-analysisthatcom-binedADLswithupperlimb-specificmeasuresoffunctionalmotorability,includingstudieswherere-sultswereatriskofperformancebias(interventiongroupsreceivinggreaterdurationoftreatmentthancontrolgroups)[27].
AnotherfoundnoimprovementinmotorfunctionwhenFESwasappliedwithin6monthsofstroke[28].
However,thispredomin-antlyincludedstudiesthatappliedelectricalstimula-tionintheabsenceofvolitionalmusclecontraction,confoundinginterpretationoftheresults.
Thisin-consistencyisreflectedinthe2016guidelinessetbytheRoyalCollegeofPhysicianswhichrecommendsFESonlyinthecontextofclinicaltrialsasanad-juncttoconventionaltherapy[21].
Thissystematicreviewaimstoelucidatetheeffect-ivenessofupperlimbFEScomparedtostandardtherapyinimprovingADL,inadditiontomotorout-comes,post-stroke.
ItrepresentsanimportantadditiontotheliteraturethatfocusesontheuseofvolitionalFESand,forthefirsttime,distinguishesitseffectonclinicallyrelevantpatientoutcomesfromsurrogatemarkersofpatientrehabilitation.
Thisincludesanalysesbasedonpatientsub-groupsdefinedbythetimeafterstrokeatwhichFESwasinitiated.
Eraifejetal.
SystematicReviews(2017)6:40Page2of21MethodsThissystematicreviewwasregisteredapriorionPROS-PERO(CRD42015025162)[30]andwasreportedinaccordancewiththePreferredReportingItemsforSys-tematicReviewsandMeta-analysis(PRISMA)statement(seeAdditionalfile1)[31].
SearchstrategyAsystematicsearchofMEDLINE(Ovid),PsychINFO(Ovid),EMBASE(Ovid)andCochraneCentralRegisterofControlledTrialsdatabasesfromincep-tionto06/09/2015wasundertakenusingacombin-ationoffreetextandindextermsforstroke,FESandupperlimb.
AnexamplestrategyisinAppendix1.
Thefollowingongoingtrialdatabaseswerealsosearched:InternationalStandardRandomisedCon-trolledTrialsNumberRegistry,WHOInternationalClinicalTrialsRegistryPlatformandClinicalTrials.
-gov.
Citationcheckingwascarriedoutonstudiesin-cludedinthisreviewandexistingsystematicreviewstoidentifyanyfurtherstudies.
Authorswerecon-tactedtwicebyemailfororiginaldatawherepub-lishedstudydatawasinsufficientastoallowdataanalysis.
Non-Englishlanguagearticlesweretrans-latedwherepossible.
StudyselectionInclusioncriteria:population:patients>18yearsdiag-nosedwithischaemicorhaemorrhagicstroke.
Inter-vention:interventiongroupreceivetranscutaneousFESappliedtotheperipheralnervoussystemoftheupperlimbdefinedas(a)appliedtotheskinexter-nallyand(b)duringvoluntarymovementinadditiontostandardpost-strokerehabilitativetherapy.
Com-parator:controlgroupsreceivestandardpost-strokerehabilitativetherapyalone,nobetweengroupdiffer-encesotherthanthestimulation.
Outcomes:ADL/motoroutcomesrecorded.
Studydesign:RCTsandcross-overstudies(onlyifrandomisedandcontrolled,suchthatfirstphaseisequivalenttoanRCT).
Exclusioncriteria:(1)previousFEStherapyininter-ventionorcontrolgroup.
(2)Othertypeofelectricalstimulationusedininterventionorcontrolgroup.
Nootherrestrictionswereplacedonpatientage,sex,ethnicity,timesincestroke,baselinefunctionalability,publicationdateorlanguage.
Tworeviewersindependentlyscreenedeachtitleandabstractforrelevance.
Fulltextsofrelevantarti-cleswereretrievedandassessedindependentlybytworeviewersagainsttheselectioncriteria.
Disagreementsbetweenreviewerswerediscussed,andathirdre-viewerconsultedifrequired.
OutcomeclassificationPrimaryoutcomeswerethosemeasureswhichdirectlyassessedADL.
Secondaryoutcomeswerethosemeasureswhichassessedperformanceofataskthatisnotclassifiedasanactivityofdailylivingsuchasgraspingandmovingacube.
ThesewereregardedasgoodsurrogateoutcomesofADLandassuchtheyweretermed'functionalmotorability'.
Tertiaryoutcomeswereanyothermeasureofmotoroutcome:muscletone,forcegeneration,distancereachedandrangeofactivemovement.
Tertiaryout-comesareregardedaspoorsurrogateoutcomeswhichmaynotcorrelatewithADL.
SeeTableS1(Additionalfile2)forfulldefinitionsofindividualmeasurementinstruments.
Dataextraction,riskofbiasandqualityassessmentParticipantbaselinecharacteristics,FESparametersandrelevantoutcomedataatallreportedtimepointswereextracted;forcross-overstudies,datafromthefirstphaseonlywereextracted.
DatawereextractedandtheCochraneCollaboration'sToolforAssessingRiskofBiaswasappliedtoallincludedstudiesbytworeviewersindependently;overallriskofbiasjudgementmadebasedonmostfrequentlycitedriskacrossthesevencategories.
QualityassessmentwasperformedusingGRADE(GradingofRecommenda-tionsAssessment,DevelopmentandEvaluation)cri-teria.
Riskofbiasandqualityassessmentinformationwasconsideredininterpretationoffindings.
AnalysisForeachoutcome,datawerecollatedandassessedforsuitabilityformeta-analysis.
Carewastakentoavoiddouble-countingofcontrolgroupparticipantsinmeta-analyses.
Meta-analysiswasundertakenusingarandomeffectsmodelduetoanunderlyingassump-tionthat,althoughstudiesweresimilar,theywouldberepresentativeofadistributionofeffectsontheoutcomeratherthanrepresentasingleunderlyingef-fect.
Wherethesameoutcomewasmeasuredusingdifferentbutcomparabletoolsonacontinuousscale,standardisedmeandifferencewasused.
Meandiffer-encewasusedelsewhere.
TheI2wasreportedasameasureofheterogeneity,aswellasthe95%confi-denceinterval.
Comparabletoolswereregardedtobethoseclassifiedasprimaryoutcomesandseparatelythoseclassifiedassecondaryoutcomes.
Tertiaryout-comeclassificationincludesseveraltypesofmeasureswhicharenotallcomparable.
Studyresultsreportedasmedian,andinterquartileranges(IQR)werenotincludedinmeta-analyses.
Theshortestfollow-uptimepost-strokewasusedforanalysis,forthepurposesofconsistency,asthiswasEraifejetal.
SystematicReviews(2017)6:40Page3of21themostfrequentlyreportedtimepoint.
Wheredatawereonlyrepresentedgraphicallyinpapers,esti-matesweretaken.
Datathatcouldnotbeincorpo-ratedintometa-analysesarereportednarratively.
Meta-analysesandforestplotswereproducedwithRevman(version5.
35,CochraneCollaboration).
Separateanalyseswereundertakenformeantimepost-strokeatwhichFESwasinitiated(lessthan2months;greaterthan1year).
ResultsIncludedstudiesThesearchstrategyidentified603recordsforscreen-ing;135studiesproceededtoselection,ofwhichtwonon-Englishlanguagestudiesweretranslated.
TwentyRCTsmettheinclusioncriteria.
Sixstudiescouldnotbeassessed(Fig.
1).
DetailsofexcludedstudiesareinAppendix2.
Fivepossiblyrelevantongoingclinicaltrialswereidentified(Appendix3).
Detailsofthe20includedRCTsA1-A20arepresentedinTableS2(Additionalfile2).
PopulationTheincludedstudiescontainedatotalof431partici-pantsintherelevantinterventionandcontrolgroups.
Maximumgroupsizewas28participantsandninestu-diesA2-A5,A8,A12,A14,A15,A18includedfewerthantenpartic-ipantsineithergroup.
Forstudieswhichreportedthesemeasures,meanparticipantagewas60(range:45.
5–66.
4)andmeangenderdistributionwas68.
8%male(range:44.
4–88.
2).
Themeantimesincestroke(across15studies)was2.
87yearswithconsiderablevariation:fivestudiesA12,A13,A16,A19,A20reportingmeantimeslessthan2months,fiveA4,A9,A15,A17,A18reportingmeantimesbetween1and3yearsandsixA1,A2,A5-A7,A14reportingmeantimesover3years.
NoteonestudyA16reportedthatallpatientsweretreatedwithin60daysofstrokeonset,hencemeantimesincestrokewaslessthan2months,butitdidnotreportaspecificmeantime.
Ofthe13studiesA2,A4-A8,A10,A12-A16,A20whichreportedstrokesite,49.
0%ofparticipants(range:9.
1–75.
0)hadalefthemispherestroke(allmeansareweightedbypar-ticipantnumberinstudies).
Therewasalsovariationwithinandbetweenstudiesintheseverityofpost-strokeimpairment.
InterventionsandcomparatorsTwohundredthirty-eightparticipantsreceivedFES.
ForstudieswhichreportedFESparametersfrequencyFig.
1FlowdiagramforincludedstudiesEraifejetal.
SystematicReviews(2017)6:40Page4of21ranged20–50Hz,peakcurrent≤70mAanddurationofstimulationfrom3to10s.
Musclesstimulatedin-cludeddeltoid,tricepsandthewristandfingerexten-sors/flexors.
Onehundredninety-threeparticipantsreceivedacontroltreatment.
Bothinterventionandcontrolgroupsreceivedstandardcare,whichvariedbetweenstudiesbuttypicallyincludedphysiotherapy,occupa-tionaltherapy,task-basedactivitiesorotherexercise-basedinterventions.
Inaddition,threestudiesutilisedorthosesA1,A6,A16,oneutilisedbotulinumtoxinA7andoneutilisedmirrortherapyA20.
ThreecontrolgroupsalsoreceivedshamFES,whereastimulationdevicedeliveredeithernocurrentatallorasub-thresholdcurrentA6,A7,A18.
Withinallin-cludedstudiescontrolandinterventiongroupsre-ceivedequivalenttotaltherapydurations,mediansessiondurationis45min,minimisingtheriskofperformancebias.
RiskofbiasandqualityassessmentTableS3(Additionalfile2)detailsthefullcriticalap-praisalinformation.
Includedstudiesspanarangeofmethodologicalquality.
NinestudieswereconsideredlowriskofbiasA5,A7,A9,A13,A14,A16-A19.
OnestudywasconsideredhighriskA8.
TheremainingtenstudiesA1-A5,A10-A12,A15,A20wereconsideredatanoverallunclearriskofbias.
OnlytheshamcontrolledstudiesA6,A7,A18wereconsideredtohaveadequateparticipantblinding.
QualityassessmentusingGRADEcriteriafoundverylowqualityevidenceinallanalysesperformedasaresultoftheheterogeneity,lowparticipantnumbersandlackofblindinginmoststudies.
ActivitiesofdailylivingAtleastonemeasureofADL(e.
g.
dressingandgrooming)wasreportedbyninestudiesA6-A8,A10-A13,A16,A19.
Sevenstudiesprovideddatasuitableformeta-analysis;oftheothertwo,oneprovidedinsuffi-cientdataA8andtheothermediansandinterquartilerangesA10.
Meta-analysisofresultsobtainedthroughobjectivelyassessedmeasuresofADLA6,A7,A11-A13,A19wascarriedoutseparatelyfromthosethatreliedonpatientrecall,whichmaybeatriskofrecallbias.
NodifferencewasfoundbetweenFESandcontrolgroupsfortheobjectivelyobtainedmeasures(SMD0.
64;CI[0.
02,1.
30];I2=66%)(Fig.
2a).
Sensitivityanalysisdemonstratedthatthiseffectwasconservedwhenonlysham-controlledstudieswereincludedinmeta-analysis(Additionalfile3:FigureS1).
AnanalysisofstudieswhereFESwasinitiatedintheacutephaseA12,A13,A19(meantimepost-strokelessthan2months)showedasignificantbenefitofFES(SMD1.
24;CI[0.
46,2.
03];I2=43%)andmoderatestatisticalheterogeneity(Fig.
2b).
Incontrast,whereFESwasiniti-atedmorethan1year(meantime)afterstrokeA6,A7,A11,nosignificantimprovementswereseen(SMD0.
10;CI[0.
59,0.
38];I2=0%)(Fig.
2c).
Franciscoetal.
(1998)A8,whichcouldnotbein-cludedinthismeta-analysisforreasonsoutlinedabove,alsoinitiatedFESwithin2monthsandre-portedastatisticallysignificantimprovementinfunctionalindependencemeasure(FIM).
Similarly,Mangoldetal.
(2009)A10reportedasignificantim-provementinextendedBarthelindexhandfunctionsubscore;patientswerealsotreatedonaveragewithin2monthspost-ictus.
VisualrepresentationofalloftheADLdataformeta-analysisisshowninFig.
2d.
Nosummaryesti-mateisgivenduetoinclusionofmultipleADLscaleswithinseveraloftheincludedstudies.
Tocombinethesedatainameta-analysis,anarbitrarychoicewouldhavebeenmadeonwhichADLscalestousefromstudiesthatusemorethanonemeasureofADL.
ThefigureindicatesvariableeffectofFESal-thoughthereseemstobeapreponderanceofdatafavouringapositiveornooverallbenefit.
FunctionalimprovementMeasuresoffunctionalimprovementwhichdonotin-corporateADL,werereportedby17studiesA1-11,A14-A20(ofwhich4presenteddatagraphicallyA2,A3,A5,A19,2onlyreportednarrativeresultsA2,A17and2reportedmediansandIQRA5,A10).
Manytoolswereusedinthesestudiestomeasurefunctionalimprovements.
Thefindingsaredisplayedinaforestplotforvisualcomparison(Fig.
3c)identifyingnoconsistenttrendacrosssecondaryoutcomes.
Somestudiesshowedin-dividualimprovementA6,A9,A15,A19,A20.
Again,similarlytoADLanalyses,secondaryoutcomedatawerenotpooledbecausewherestudiesutilisedmorethanonescaleinthiscategory,anarbitrarychoicewouldhavetobemadeonwhichtoincludetoavoiddoublecountingofparticipants.
Separateanalysiswithpooledtotalswasperformedfortwoofthetools:Fugl-MeyerAssessment(FMA)andBoxandBlockTest(BBT).
Meta-analysisofsevenstudiesreportingFMAA6,A7,A11,A14,A16,A19,A20(Fig.
3a)showedastatisticallysignificantimprove-mentinupperlimbmotorfunctionwithFEScorre-spondingtoaclinicallyimportantdifference(MD6.
72;CI[1.
76,11.
68],I2=62%).
Onestudy,Francisco1998,couldnotbeincludedinthismeta-analysisandindividuallyreportedsignificantFMAimprovementwithFESA8.
FurtheranalysisbasedonmeantimesincestrokedemonstratedasignificantimprovementEraifejetal.
SystematicReviews(2017)6:40Page5of21inFMAwhereFESwasinitiatedwithin2monthsafterstroke(MD11.
11;CI[5.
07,17.
16];I2=37%)A16,A19,A20.
InstudieswhereFESwasinitiatedover1year(meantime)therewasnosignificantim-provement(MD2.
75;CI[2.
46,7.
95];I2=32%)(Additionalfile4:FigureS2)A6,A7,A11,A14.
Sensitivityanalysisundertakendemonstratedthatmeta-analysisofsham-controlledstudiesdidnotfavourFES;itshouldbenotedthatthesestudiesinitiatedtherapyafter1yearfromstroke(mean)(Additionalfile5:FigureS3).
Meta-analysisofBBTresultsshowednosignificantimprovementwithFESA5,A7,A15(MD5.
34;CI[0.
06,10.
75];I2=54%)(Fig.
3b).
FESwasinitiatedonaveragemorethan1yearafterthestrokeinthesestudies.
Theresultsofthestudiesthatcouldnotbeincludedinthismeta-analysisA2-A4showedmixedresults.
OthermotoroutcomesTheseoutcomesareassessedusingteststhatdonotdirectlymeasureparticipantfunctionbutmaycon-tributetowardsparticipantfunctionindailylife,e.
g.
Fig.
2SMD(95%CI)offunctionalelectricalstimulation(FES)vscontrolonactivitiesofdailyliving.
aNon-patientrecallbasedmeasuresofADL.
bFESinitiatedwithin2monthsofstroke.
cFESinitiatedafter1yearofstroke.
dVisualrepresentationofallADLmeasures.
AMATArmMotorAbilityTest,CAHAIChedokeArmandHandActivityInventory,FIMFunctionalIndependenceMeasure,UEFTUpperExtremityFunctionTest,HFGhigherfunctioninggroup,LFGlowerfunctioninggroupEraifejetal.
SystematicReviews(2017)6:40Page6of21muscletoneorstrength.
Thesewerereportedin14studiesA1-A7,A9,A10,A13-A15,A19,A20,ofwhich2reportedmedianandIQRA5,A10,andafurthertwopresentednoSDA2,A3.
FiveofthesevenstudiesthatmeasuredModifiedAshworthScale(ameasureofmuscletone)providedsufficientinformationforanalysi-sA6,A7,A10,A13,A14(Fig.
4a).
Manyofthesereportedmuscle-specifictone,henceaquantitativemeta-analysiscouldnotbeperformed.
Sevenoftheninestudiesthatreportedforcegenerationprovidedsuffi-cientinformationforanalysisA1,A4,A6,A7,A15,A19,A20.
However,duetofrequentreportinginmuscleormovement-specificsubscales,thiscouldonlybedis-playedasavisualrepresentation(Fig.
4b).
Therewasnocleartrendobserved.
Therewasinsufficientdatatoanalysedistancereachedorrangeofactivemovement.
DiscussionTheaimofthissystematicreviewwastoevaluatetheeffectofpost-strokeupperlimbFESonactivitiesofdailyliving(ADL)andmotoroutcomes.
TheresultsbringnewunderstandingoftheeffectivenessofFESonupperlimbrehabilitationafterstroke.
Fig.
3SMD(95%CI)offunctionalelectricalstimulation(FES)vscontrolonsecondaryoutcomes(functionalmotorrecovery).
aFMA.
bBBT.
cVisualrepresentationofallsecondaryoutcomemeasures.
MASHMMotorAssessmentScaleHandMovements,MASUAFMotorAssessmentScaleUpperArmFunction,FMAFugl-MeyerAssessment,BBTBoxandBlockTest,ARATActionResearchArmTest,FTHUEFunctionalTestfortheHemipareticUpperExtremity,RELHTRehabilitationEngineeringLaboratoryHandTest(Blocksubscoreshownhere),CMSAChedokeMcMastersStrokeAssessment,9HPTNineHolePegTest,10CMTTenCupMovingTest,5s5-secondstimulationpulseduration,10s10-secondstimulationpulsedurationEraifejetal.
SystematicReviews(2017)6:40Page7of21WhenFESwasinitiatedwithin2months(meantime)ofstroke,therewasasignificantimprovementinADLcomparedtothecontrolgroup.
NobenefitwasfoundwhenFESwasinitiatedover1yearsincestroke.
Althoughtherewassubstantialheterogeneityintheanalysisofthe1yearpost-strokesubgroup,thesefindingsfitwithstudieswhichhavefoundthatthemajorityofmotorrecoveryafterstrokeoc-cursintheinitialfewmonths[32–34].
However,onemustalsointerpretthesefindingsinlightoftheriskofbiasofincludedstudies.
Allstudiesinlessthantwomonthgrouplackadequateparticipantblinding,whilsttwooutofthethreein-cludedstudiesintheoneyeargroupusedshamtreatment.
Furthermore,theoverallevidencequality,assessedusingGRADEcriteria,wasverylowasaresultofthesubstantialheterogeneity,lowparticipantnumbersandlackofblindinginmoststudies.
Meta-analysisperformedonobjectiveADLmea-sures,whichareconsideredmorereliablethanself-reportedmeasures,foundnosignificantbenefitofFES.
Patientrecall-basedADLmeasuresmaynotreli-ablycorrelatewithobjectivemeasuresofpatientac-tivityandclinicalimprovement[35–38].
Humanperceptionisinfluencedbymanyfactorsandcogni-tivebiases[38],recallbiasisonesuchfactorthathasbeenshowntoresultinlargeerrorsinpatientre-portedoutcomes[36].
Meta-analysisofFMA,themostcommonlyreportedmeasurementinstrument,showedastatisticallysig-nificantbenefitofFEScorrespondingtoamoderateeffectsize.
AdditionalanalysisofFMAfoundasig-nificantbenefitforFESappliedwithin2monthsofstrokebutnotforFESapplied1yearormoreafterstroke.
Mostincludedstudiesintheseanalyseswerenotadequatelyblindedandoverallevidencequalitywasverylow.
Meta-analysisofBBTresultsfoundnobenefitfromFES,butthiscouldhavebeenmaskedbythelowgroupnumbers:only30patientsintotalfortheinter-ventiongroupsand24incontrolgroups.
Indeedallstudiesincludedinthisreviewhadsmallgroupsizes,thusitislikelythatthesestudieswouldlackthepowernecessarytodemonstrateasmallincreaseinupperlimbmotorfunction.
Evenasmallimprovementinfunctionmaybeclinicallysignificant,sinceupperlimbfunctionissoimportantfordailyactivities[39].
Analterna-tiveexplanationisthatallstudieswhichreportedBBTap-pliedFES1yearormoreafterstroke,sothelackofimprovementinBBTwithFEScouldalsoreflectthefactthatFESwasnotappliedduringtheoptimumtherapeuticwindow.
However,cautionisneededwhendrawingconclusionsabouttheoptimumtimewindowforFESpost-strokegiventheverylowqualityofevi-denceintheaboveanalyses.
ItispossiblethatFESisbeneficialonlywhenap-pliedusingcertainstimulationparametersorwhenFig.
4VisualrepresentationofSMD(95%CI)offunctionalelectricalstimulation(FES)vscontrolontertiaryoutcomes.
aModifiedAshworthScale,upperlimbcomponentpresented.
bForcegeneration,musclegroup/movementpresentedEraifejetal.
SystematicReviews(2017)6:40Page8of21appliedtoaspecificpatientpopulation.
Indeed,vari-ationinFESparametersincludingcurrent,frequency,durationofstimulationandalsoinbaselinefunctionofparticipantsbothbetweenandwithinstudieswerenoted.
Itappearsthattherearenoagreedstimulationparameters,anditislikelythatnoneoftheincludedstudiesemployedexactlythesamestimulationproto-col.
Potentialbenefitscouldthusbehiddenamongtheinter-studyvariabilitybetweenstudiesinthissys-tematicreview.
ThisvariabilityinFESparameterscouldinfluenceresultsinthisreviewandmaybeacontributingfactortotheheterogeneityintheanalyses.
Toourknowledge,foursystematicreviewshavepreviouslyattemptedtoevaluatetheeffectivenessofFESforupperlimbrehabilitationafterstroke[24–27].
VanPeppenetal.
[25]foundnoimprovementwithFESintertiaryoutcomes,specificallystrengthordexterity.
Boltonetal.
[26]carriedoutameta-analysisonfiveelectromyography(EMG)-triggeredneuromuscularstimulationstudiesandfoundanim-provementacrosssecondaryoutcomesasdefinedbythepresentsystematicreview.
Meta-analysisbyMeilinketal.
[24]foundnosignificantimprovementinBBT.
However,whilstthecurrentreviewfoundasignificantimprovementinFMA,Meilinketal.
didnot.
Thisdiscrepancycouldbeexplainedbythesmallmeta-analysisgroupsizeofthreestudiesinMeilinketal.
comparedtotheeightstudieshere.
Howlettetal.
[24]conductedthemostrecentrele-vantsystematicreview.
Whilsttheyfoundasignifi-cantimprovementwithupperlimbFEScomparedtocontrol,thisfindingwasbasedonasinglemeta-analysiswhichcombinedprimaryandsecondaryoutcomesasdefinedabove.
Theseoutcomesarear-guablynotcomparable.
Moreover,suchanapproachpreventsprimary,secondaryandtertiaryoutcomesfrombeingindependentlyassessed.
Todate,nosys-tematicreviewhasassessedthetherapeuticwindowofupperlimbFESapplicationpost-stroke.
StrengthsandlimitationsThissystematicreviewisthemostcomprehensiveandprovidesamuchneededevaluationofupperlimb-specificFESafterstroke,whichwasmissingfromtheliterature.
Analyseswereperformed,inac-cordancewiththeaprioriprotocol,enablingimport-antconclusionsabouttheuseofFESinclinicalpracticetobedrawn.
99%ofthearticlesidentifiedbyoursearchstrategywereassessed.
However,itwasnotpossibletotranslatefourstudiesthatwerenotintheEnglishlanguageandtwoarticlescouldnotbefoundafterextensiveattemptstolocatethem(seeAppendix2).
Meta-analysesgaverisetocertainlimitations.
Firstly,includedstudiesutilisedmanydifferentmeas-urementinstrumentsandonlyaminoritywereemployedbymorethanafewstudies.
Secondly,manystudiesusedmultiplemeasurementinstrumentsforeachoutcome,e.
g.
severalscaleswhichmeasureADLinasinglestudy.
Assuch,itwasnotappropriatetocombinedatainsinglemeta-analyses.
Thirdly,onestudycontainedmultiplerelevantinterventiongroupsbutonlyasinglecontrolgroupforcomparisonA4;theinterventiongroupmostsimilartotheotherincludedstudieswasselected.
Thesmallnumberanddistributionofstudieslim-itedpotentialforformalbetweengroupcomparisonsinformofsubgroupanalyses.
Inaddition,analysesonseverityofstrokeandstimulationparameters,whichwehadintendedinourprotocol,werenotpossibleduetomethodologicalvariability.
Allincludedstudies,withtheexceptionofoneA8whichcouldnotbeincludedinquantitativeanalysis,wereconsideredatloworunclearriskofbias.
Inad-equateparticipantblindingwasanissueinmoststudies.
RecommendationsforclinicalpracticeandresearchThissystematicreviewfoundinsufficientevidenceofclinicalbenefittosupportroutineuseofFESinclinicalpractice;however,thismayreflectalackofhighqualitytrialsinthefieldwhichstronglysupportstheneedforFESuseinclinicaltrials.
ThissystematicreviewhighlightstheneedforlargeRCTsinordertoensurehomogeneityamonggroupsandtohavesufficientpowertoidentifysmallfunctionalimprovements.
Randomisedtriple-blindedcontrolledtrials,wherecomparatorgroupsreceiveshamtreatment(subthresholdstimulation),arerec-ommendedastheoptimalstudydesign.
AnRCTthatincludestwointerventiongroupswithFESap-pliedattwodifferenttimepointsafterstroke(e.
g.
2monthsand1year)couldhelpclarifytheoptimaltherapeuticwindowforFES.
FutureresearchshouldalsoattempttoidentifytheoptimalFESparametersinordertostandardiseFEStreatmentforfuturestudies.
ItisadvisablethatprospectiveRCTsinthisfielduseanagreedcoreoutcomesetunlessthereisaclearjustificationtousealternativemeasures[40]becausetheuseofdifferentbutcomparablemeasurementinstrumentslimitsthesuitabilityofdataformeta-analysis.
Millaretal.
arecurrentlyworkingonacoreoutcomesetforupperlimbEraifejetal.
SystematicReviews(2017)6:40Page9of21rehabilitationafterstroketoaidevidence-basedclin-icalpractice[41].
ConclusionsFESisapromisingtherapywhichcouldplayapartinfuturestrokerehabilitationstrategies.
ThisreviewfoundastatisticallysignificantbenefitfromFESappliedwithin2monthsofstrokeonourprimaryoutcomeofADL.
However,duetotheverylow(GRADE)qualityevidenceoftheseanalyses,firmconclusionsabouttheeffectivenessofFESoritsoptimumtherapeuticwindowcannotbedrawn.
Hence,thereisaneedforhighqualitylarge-scalerandomisedcontrolledtrialsofupperlimbFESafterstroke.
Appendix1SearchStrategyThefollowingisthesearchstrategyusedtosearchdatabasesonOvid.
ThesearchterminologywasadaptedtomeetCochranesearchrequirementsbutremainedotherwiseunchanged.
Thesamesearchstrategywasusedtoidentifybothprimarystudiesandsystematicreviews,butthedatabasessearcheddifferedasoutlinedintheMethodssection.
1.
electrostimulat*2.
electric*stimulat*3.
electrotherap*4.
transcutaneousadj5stimulat*5.
neurostimulat*6.
Electricstimulation/7.
1OR2OR3OR4OR5OR68.
Stroke/9.
stroke*10.
CVA11.
cerebrovasc*12.
brain*orcerebr*13.
ischem*orthromb*orembol*orinfarct*14.
12AND1315.
hemorrhageorhematomaorbleed16.
12AND1517.
8OR9OR10OR11OR14OR1618.
upperlimb*19.
shoulder*20.
arm*21.
forearm*22.
wrist*23.
hand*24.
UpperExtremity/25.
finger*26.
digit*27.
18OR19OR20OR21OR22OR23OR24OR25OR2628.
7AND17AND2729.
RandomizedControlledTrialsasTopic/30.
randomallocation/31.
ControlledClinicalTrialsasTopic/32.
controlgroups/33.
clinicaltrialsastopic/34.
double-blindmethod/35.
single-blindmethod/36.
Placebos/37.
placeboeffect/38.
ResearchDesign/39.
ProgramEvaluation/40.
randomizedcontrolledtrial.
pt.
41.
controlledclinicaltrial.
pt.
42.
clinicaltrial.
pt.
43.
(random*orRCTorRCTs).
tw.
44.
(controlledadj5(trial*orstud*)).
tw.
45.
(clinical*adj5trial*).
tw.
46.
((controlortreatmentorexperiment*orintervention)adj5(group*orsubject*orpatient*)).
tw.
47.
(quasi-random*orquasirandom*orpseudo-random*orpseudorandom*).
tw.
48.
((controlorexperiment*orconservative)adj5(treatmentortherapyorprocedureormanage*)).
tw.
49.
((singl*ordoubl*ortripl*ortrebl*)adj5(blind*ormask*)).
tw.
50.
placebo*.
tw.
51.
sham.
tw.
52.
(assign*orallocat*).
tw.
53.
controls.
tw.
54.
or/29-5355.
28and5456.
expanimals/nothumans.
sh.
57.
55not56Eraifejetal.
SystematicReviews(2017)6:40Page10of21Appendix2ExcludedstudieslistTable1StudyNotanRCTNotstrokePreviousstimulationNotupperlimbFESInadequatecontrolNorelevantoutcomesDuplicatedatasetNotpublishedinfullinpeerreviewedjournal(1)Ottawapanelevidence-basedclinicalpracticeguide-linesforpost-strokerehabilitation.
TopicsinStrokeRe-habilitationSpr2006;13(2):1–269.
x(2)AlonG,LevittAF,McCarthyPA.
Functionalelectricalstimulation(FES)maymodifythepoorprognosisofstrokesurvivorswithseveremotorlossoftheupperextremity:apreliminarystudy.
AmericanJournalofPhysicalMedicine&Rehabilitation2008Aug;87(8):627–636.
x(3)AlonG,LevittAF,McCarthyPA.
Functionalelectricalstimulationenhancementofupperextremityfunctionalrecoveryduringstrokerehabilitation:apilotstudy.
NeurorehabilitationandNeuralRepair2007May–Jun;21(3):207–215.
x(4)AlonG.
Definingandmeasuringresidualdeficitsoftheupperextremityfollowingstroke:anewperspective.
TopicsinStrokeRehabilitation2009May–Jun;16(3):167–176.
x(5)AlonG,RingH.
Gaitandhandfunctionenhancementfollowingtrainingwithamulti-segmenthybrid-orthosisstimulationsysteminstrokepatients.
JStrokeCerebro-vascDis2003;12(5):209–216.
x(6)ArmaganO,TasciogluF,OnerC.
Electromyographicbiofeedbackinthetreatmentofthehemiplegichand:aplacebo-controlledstudy.
AmJPhysMedRehabil2003Nov;82(11):856–861.
x(7)Au-YeungSS,Hui-ChanCW.
Electricalacupointstimu-lationoftheaffectedarminacutestroke:aplacebo-controlledrandomizedclinicaltrial.
ClinRehabil2014Feb;28(2):149–158.
x(8)BarkerRN,BrauerSG,CarsonRG.
Trainingofreachinginstrokesurvivorswithsevereandchronicupperlimbparesisusinganovelnonroboticdevice:arandomizedclinicaltrial.
Stroke2008Jun;39(6):1800–1807.
x(9)BasmajianJV,GowlandC,BrandstaterME,SwansonL,TrotterJ.
EMGfeedbacktreatmentofupperlimbinhemiplegicstrokepatients:apilotstudy.
ArchPhysMedRehabil1982Dec;63(12):613–616.
x(10)BhattE,NagpalA,GreerKH,GrunewaldTK,SteeleJL,WiemillerJW,etal.
Effectoffingertrackingcombinedwithelectricalstimulationonbrainreorganizationandhandfunctioninsubjectswithstroke.
ExperimentalBrainResearch2007Oct;182(4):435–447.
x(11)BoespflugEL,StorrsJM,AllendorferJB,LamyM,EliassenJC,PageS.
Meandiffusivityasapotentialdiffusiontensorbiomarkerofmotorrehabilitationafterelectricalstimulationincorporatingtaskspecificexerciseinstroke:apilotstudy.
Brainimagingbehav2014Sep;8(3):359–369.
x(12)BowmanBR,BakerLL,WatersRL.
Positionalfeedbackandelectricalstimulation:anautomatedtreatmentforthehemiplegicwrist.
ArchivesofPhysicalMedicineandRehabilitation1979Nov;60(11):497–502.
xxEraifejetal.
SystematicReviews(2017)6:40Page11of21Table1(Continued)(13)BoyaciA,TopuzO,AlkanH,OzgenM,SarsanA,YildizN,etal.
Comparisonoftheeffectivenessofactiveandpassiveneuromuscularelectricalstimulationofhemiplegicupperextremities:arandomized,controlledtrial.
InternationalJournalofRehabilitationResearch2013Dec;36(4):315–322.
(14)CauraughJH,CoombesSA,LodhaN,NaikSK,SummersJJ.
Upperextremityimprovementsinchronicstroke:coupledbilateralloadtraining.
RestorativeNeurologyandNeuroscience2009;27(1):17–25.
x(15)CauraughJH,KimSB,DuleyA.
Coupledbilateralmovementsandactiveneuromuscularstimulation:intralimbtransferevidenceduringbimanualaiming.
NeurosciLett2005Jul1–8;382(1–2):39–44.
x(16)CauraughJH,KimSB,SummersJJ.
Chronicstrokelongitudinalmotorimprovements:cumulativelearningevidencefoundintheupperextremity.
CerebrovascularDiseases2008;25(1–2):115–121.
x(17)CelnikP,HummelF,Harris-LoveM,WolkR,CohenLG.
Somatosensorystimulationenhancestheeffectsoftrainingfunctionalhandtasksinpatientswithchronicstroke.
ArchivesofPhysicalMedicineandRehabilitation2007Nov;88(11):1369–1376.
x(18)CelnikP,PaikNJ,VandermeerenY,DimyanM,CohenLG.
Effectsofcombinedperipheralnervestimulationandbrainpolarizationonperformanceofamotorsequencetaskafterchronicstroke.
Stroke2009May;40(5):1764–1771.
x(19)ChaeJ,BethouxF,BohineT,DobosL,DavisT,FriedlA.
Neuromuscularstimulationforupperextremitymotorandfunctionalrecoveryinacutehemiplegia.
Stroke1998May;29(5):975–979.
x(20)ChaeJ,PageS,DelahantyM.
Surfaceelectricalstimulationdoesnotimprovehandfunctioninsubacutestroke.
Stroke2012;43(2MeetingAbstracts).
x(21)ChantraineA,BaribeaultA,UebelhartD,GremionG.
Shoulderpainanddysfunctioninhemiplegia:effectsoffunctionalelectricalstimulation.
ArchivesofPhysicalMedicineandRehabilitation1999Mar;80(3):328–331.
x(22)ChurchC,PriceC,PandyanAD,HuntleyS,CurlessR,RodgersH.
Randomizedcontrolledtrialtoevaluatetheeffectofsurfaceneuromuscularelectricalstimulationtotheshoulderafteracutestroke.
Stroke2006Dec;37(12):2995–3001.
x(23)ChurchC,CurlessR,HuntleyS,PriceC,PandyanD,RodgersH.
Doessurfaceneuromuscularelectricalstimulation(sNMES)totheupperlimbfollowingacutestrokeimproveoutcome12thEuropeanStrokeConference2003.
x(24)ConfortoAB,CohenLG,dosSantosRL,ScaffM,MarieSK.
Effectsofsomatosensorystimulationonmotorfunctioninchroniccortico-subcorticalstrokes.
JNeurol2007Mar;254(3):333–339.
x(25)ConfortoAB,FerreiroKN,TomasiC,dosSantosRL,MoreiraVL,MarieSK,etal.
Effectsofsomatosensorystimulationonmotorfunctionaftersubacutestroke.
NeurorehabilitationandNeuralRepair2010Mar–Apr;24(3):263–272.
x(26)ConfortoAB,Kaelin-LangA,CohenLG.
Increaseinhandmusclestrengthofstrokepatientsaftersomato-sensorystimulation.
AnnNeurol2002Jan;51(1):122–125.
xEraifejetal.
SystematicReviews(2017)6:40Page12of21Table1(Continued)(27)ConfortoAB,FontesRLS,FerreiroKN,CorreiaCER,ScaffM.
Home-basedperipheralnervestimulationen-hanceseffectsofmotortraininginpatientsinthechronicphaseafterstroke.
CerebrovascularDiseases2010May2010;29:251.
x(28)DalyJJ,RogersJ,McCabeJ,MonkiewiczM,BurdsallR,PundikS.
Recoveryofactualfunctionaltasksinresponsetomotorlearning,robotics,andfunctionalelectricalstimulation.
Stroke201001Apr2010;41(4):e355–e356.
x(29)DorschS,AdaL,CanningCG.
EMG-triggeredelec-tricalstimulationisafeasibleinterventiontoapplytomultiplearmmusclesinpeopleearlyafterstroke,butdoesnotimprovestrengthandactivitymorethanusualtherapy:arandomizedfeasibilitytrial.
ClinRehabil2014May;28(5):482–490.
x(30)DosSantos-FontesRL,FerreirodeAndradeKN,SterrA,ConfortoAB.
Home-basednervestimulationtoen-hanceeffectsofmotortraininginpatientsinthechronicphaseafterstroke:aproof-of-principlestudy.
Neuroreh-abilitationandNeuralRepair2013Jul–Aug;27(6):483–490.
x(31)FaghriPD,RodgersMM,GlaserRM,BorsJG,HoC,AkuthotaP.
Theeffectsoffunctionalelectricalstimulationonshouldersubluxation,armfunctionrecovery,andshoulderpaininhemiplegicstrokepatients.
ArchivesofPhysicalMedicineandRehabilitation1994Jan;75(1):73–79.
x(32)FieldsRW.
Electromyographicallytriggeredelectricmusclestimulationforchronichemiplegia.
ArchivesofPhysicalMedicineandRehabilitation1987Jul;68(7):407–414.
x(33)FilA,ArmutluK,AtayAO,KerimogluU,ElibolB.
TheeffectofelectricalstimulationincombinationwithBobathtechniquesinthepreventionofshouldersubluxationinacutestrokepatients.
ClinRehabil2011Jan;25(1):51–59.
x(34)FlemingMK,NewhamDJ,Roberts-LewisSF,SorinolaIO.
Self-perceivedutilizationofthepareticarminchronicstrokerequireshighupperlimbfunctionalability.
Ar-chivesofPhysicalMedicineandRehabilitation2014May;95(5):918–924.
x(35)FlemingMK,SorinolaIO,RobertsLewisSF,WolfeCD,WellwoodI,NewhamDJ.
Theeffectofcombinedsomatosensorystimulationandtask-specifictrainingonupperlimbfunctioninchronicstroke:Adouble-blindrandomizedcontrolledtrial.
NeurorehabilNeuralRepairFeb2015;29(2):143–152.
x(36)FujiwaraT.
Effectofhybridassistiveneuromusculardynamicstimulation(HANDS)therapyforfunctionalrecoveryafterstroke.
ClinicalNeurophysiology2010October2010;121:S49.
x(37)GabrU,LevineP,PageSJ.
Home-basedelectromyography-triggeredstimulationinchronicstroke.
ClinRehabil2005Oct;19(7):737–745.
x(38)GharibNMM,AboumousaAM,ElowishyAA,RezkAllahSS,YousefFS.
Efficacyofelectricalstimulationasanadjuncttorepetitivetaskpracticetherapyonskilledhandperformanceinhemipareticstrokepatients:arandomizedcontrolledtrial.
ClinRehabilApr2015;29(4):355–364.
xEraifejetal.
SystematicReviews(2017)6:40Page13of21Table1(Continued)(39)HaraY,OgawaS,MuraokaY.
Hybridpower-assistedfunctionalelectricalstimulationtoimprovehemipareticupper-extremityfunction.
AmericanJournalofPhysicalMedicine&Rehabilitation2006Dec;85(12):977–985.
x(40)HaywardKS,BarkerRN,BrauerSG,LloydD,HorsleySA,CarsonRG.
SMARTArmwithoutcome-triggeredelec-tricalstimulation:apilotrandomizedclinicaltrial.
TopicsinStrokeRehabilitation2013Jul–Aug;20(4):289–298.
x(41)HeckmannJ,MokruschT,KrockelA,WarnkeS,VonST,NeundorferB.
EMG-triggeredelectricalmusclestimu-lationinthetreatmentofcentralhemiparesisafterastroke.
EurJPhysMedRehabil1997;7(5):138–141.
x(42)HesseS,ReiterF,KonradM,JahnkeMT.
BotulinumtoxintypeAandshort-termelectricalstimulationinthetreatmentofupperlimbflexorspasticityafterstroke:arandomized,double-blind,placebo-controlledtrial.
ClinRehabil1998Oct;12(5):381–388.
x(43)HesseS,SchmidtH,WernerC.
Machinestosupportmotorrehabilitationafterstroke:10yearsofexperienceinBerlin.
JournalofRehabilitationResearchandDevelopment2006Aug–Sep;43(5):671–678.
x(44)HsuSS,HuMH,WangYH,YipPK,ChiuJW,HsiehCL.
Dose-responserelationbetweenneuromuscularelec-tricalstimulationandupper-extremityfunctioninpa-tientswithstroke.
Stroke2010Apr;41(4):821–824.
x(45)IkunoK,KawaguchiS,KitabeppuS,KitauraM,TokuhisaK,MorimotoS,etal.
Effectsofperipheralsensorynervestimulationplustask-orientedtrainingonupperextremityfunctioninpatientswithsubacutestroke:apilotrandomizedcrossovertrial.
ClinRehabil2012Nov;26(11):999–1009.
x(46)InobeJ-,KatoT.
Effectivenessoffingerequippedelectrode(FEE)-triggeredelectricalstimulationinchronicstrokepatientswithseverehemiplegia.
InternationalJournalofStroke2010October2010;5:290.
x(47)InobeJ,KatoT.
Effectivenessoffinger-equippedelectrode(FEE)-triggeredelectricalstimulationimprovingchronicstrokepatientswithseverehemiplegia.
BrainIn-juryJan2013;27(1):114–119.
x(48)JoaKL,KimWH,MinJH.
Thesynergisticeffectsofmirrortherapyandfunctionalelectricalstimulationonhandfunctioninseverestrokepatients.
CerebrovascDis2013;35Suppl3:588–589.
x(49)JohanssonBB,HakerE,vonArbinM,BrittonM,LangstromG,TerentA,etal.
Acupunctureandtranscutaneousnervestimulationinstrokerehabilitation:arandomized,controlledtrial.
Stroke2001Mar;32(3):707–713.
x(50)KarakusD,ErsoZM,KoyuncuG,TurkD,SasmazFM,AkyuZM.
Effectsoffunctionalelectricalstimulationonwristfunctionandspasticityinstroke:arandomizedcontrolledstudy.
TurkiyeFizikselTipveRehabilitasyonDergisi2013;59(2):97–102.
x(51)KawahiraK,ShimodozonoM,EtohS,KamadaK,NomaT,TanakaN.
Effectsofintensiverepetitionofanewfacilitationtechniqueonmotorfunctionalrecoveryofthehemiplegicupperlimbandhand.
BrainInj2010;24(10):1202–1213.
x(52)KimTH,InTS,ChoHY.
Task-relatedtrainingcom-binedwithtranscutaneouselectricalnervestimulationxEraifejetal.
SystematicReviews(2017)6:40Page14of21Table1(Continued)promotesupperlimbfunctionsinpatientswithchronicstroke.
TohokuJExpMed2013;231(2):93–100.
(53)KimJH,LeeB.
Mirrortherapycombinedwithbiofeedbackfunctionalelectricalstimulationformotorrecoveryofupperextremitiesafterstroke:apilotrandomizedcontrolledtrial.
OccupationalTherapyInternationalJun2015;22(2):51–60.
x(54)KimberleyTJ,LewisSM,AuerbachEJ,DorseyLL,LojovichJM,CareyJR.
Electricalstimulationdrivingfunctionalimprovementsandcorticalchangesinsubjectswithstroke.
ExperimentalBrainResearch2004Feb;154(4):450–460.
x(55)KingTI.
Theeffectofneuromuscularelectricalstimulationinreducingtone.
AmJOccupTher1996;50(1):62–64.
x(56)KnutsonJS,HiselTZ,HarleyMY,ChaeJ.
Anovelfunctionalelectricalstimulationtreatmentforrecoveryofhandfunctioninhemiplegia:12-weekpilotstudy.
Neu-rorehabilNeuralRepair2009Jan;23(1):17–25.
x(57)KobayashiH,OnishiH,IhashiK,YagiR,HandaY.
Reductioninsubluxationandimprovedmusclefunctionofthehemiplegicshoulderjointaftertherapeuticelectricalstimulation.
JournalofElectromyographyandKinesiology1999Oct;9(5):327–336.
x(58)KoyuncuE,Nakipoglu-YuzerGF,DoganA,OzgirginN.
Theeffectivenessoffunctionalelectricalstimulationforthetreatmentofshouldersubluxationandshoulderpaininhemiplegicpatients:arandomizedcontrolledtrial.
DisabilityandRehabilitation2010;32(7):560–566.
x(59)KraftGH,FittsSS,HammondMC.
Techniquestoimprovefunctionofthearmandhandinchronichemiplegia.
ArchivesofPhysicalMedicineandRehabilitation1992Mar;73(3):220–227.
x(60)LaiCJ,WangCP,TsaiPY,ChanRC,LinSH,LinFG,etal.
Corticospinalintegrityandmotorimpairmentpredictoutcomesafterexcitatoryrepetitivetranscranialmagneticstimulation:apreliminarystudy.
ArchPhysMedRehabil2015Jan;96(1):69–75.
x(61)LeandriM,ParodiCI,CorrieriN,RigardoS.
ComparisonofTENStreatmentsinhemiplegicshoulderpain.
ScandJRehabilMed1990;22(2):69–71.
x(62)LeungJ,HarveyLA,MoseleyAM,TseC,BryantJ,WyndhamS,etal.
Electricalstimulationandsplintingwerenotclearlymoreeffectivethansplintingaloneforcontracturemanagementafteracquiredbraininjury:arandomisedtrial.
JournalofPhysiotherapy2012;58(4):231–240.
x(63)LiL,YuanJ,ZhangC.
Clinicalobservationonhemiplegicpatientswithfunctionalelectricstimulationandintensivetrainingontheirlowerextremities.
ChineseJournalofPhysicalMedicineandRehabilitation2000;22(1):18–19.
x(64)LiN,TianFW,WangCW,YuPM,ZhouX,WenQ,etal.
Double-centerrandomizedcontrolledtrialonpost-strokeshoulderpaintreatedbyelectroacupuncturecom-binedwithTuina.
Zhongguozhenjiu[Chineseacupunc-tureandmoxibustion]2012;32(2):101–105.
x(65)LiepertJ,RestemeyerC,MunchauA,WeillerC.
Motorcortexexcitabilityafterthalamicinfarction.
ClinicalNeurophysiology2005Jul;116(7):1621–1627.
xEraifejetal.
SystematicReviews(2017)6:40Page15of21Table1(Continued)(66)LinKC,HuangPC,ChenYT,WuCY,HuangWL.
Combiningafferentstimulationandmirrortherapyforrehabilitatingmotorfunction,motorcontrol,ambulation,anddailyfunctionsafterstroke.
NeurorehabilitationandNeuralRepair2014Feb;28(2):153–162.
x(67)LinZ,YanT.
Long-termeffectivenessofneuromus-cularelectricalstimulationforpromotingmotorrecoveryoftheupperextremityafterstroke.
JRehabilMed2011May;43(6):506–510.
x(68)LinK,ChenY,HuangP,WuC,HuangW,YangH,etal.
Effectofmirrortherapycombinedwithsomatosensorystimulationonmotorrecoveryanddailyfunctioninstrokepatients:apilotstudy.
JFormosMedAssoc2014Jul;113(7):422–428.
x(69)LinnSL,GranatMH,LeesKR.
Preventionofshouldersubluxationafterstrokewithelectricalstimulation.
Stroke1999May;30(5):963–968.
x(70)LinnSL,GrantMH,CrossanJS,LeesKR.
Theuseofelectricalstimulationforthepreventionofshouldersubluxationpoststroke.
Physiotherapy1995;81(12):742.
x(71)LisinskiP,HuberJ,SamborskiW,WitkowskaA.
Neurophysiologicalassessmentoftheelectrostimulationproceduresusedinstrokepatientsduringrehabilitation.
IntJArtifOrgans2008Jan;31(1):76–86.
x(72)LiuJ,YouWX,SunD.
[Effectsoffunctionalelectricstimulationonshouldersubluxationandupperlimbmotorfunctionrecoveryofpatientswithhemiplegiaresultingfromstroke].
DiYiJunyiDaxueXuebao2005Aug;25(8):1054–1055.
x(73)LoonedR,WebbJ,XiaoZG,MenonC.
AssistingdrinkingwithanaffordableBCI-controlledwearablerobotandelectricalstimulation:apreliminaryinvestiga-tion.
JournalofNeuroengineeringandRehabilitation2014;11:51.
x(74)LumPS,BurgarCG,VanderLoosM,ShorPC,MajmundarM,YapR.
MIMEroboticdeviceforupper-limbneurorehabilitationinsubacutestrokesubjects:afollow-upstudy.
JRehabilResDev2006Aug–Sep;43(5):631–642.
x(75)MakowskiNS,KnutsonJS,ChaeJ,CragoP.
Variationsinneuromuscularelectricalstimulation'sabilitytoincreasereachandhandopeningduringvoluntaryeffortafterstroke.
ConferenceProceedings:…AnnualInternationalConferenceoftheIEEEEngineeringinMedicineandBiologySociety2012;2012:318–321.
x(76)MalhotraS,RosewilliamS,HermensH,RoffeC,JonesP,PandyanAD.
Arandomizedcontrolledtrialofsurfaceneuromuscularelectricalstimulationappliedearlyafteracutestroke:effectsonwristpain,spasticityandcontractures.
ClinRehabil2013Jul;27(7):579–590.
x(77)MannG,TaylorP,LaneR.
Accelerometer-triggeredelectricalstimulationforreachandgraspinchronicstrokepatients:apilotstudy.
NeurorehabilitationandNeuralRepair2011Oct;25(8):774–780.
x(78)MannGE,BurridgeJH,MaloneLJ,StrikePW.
Apilotstudytoinvestigatetheeffectsofelectricalstimulationonrecoveryofhandfunctionandsensationinsubacutestrokepatients.
Neuromodulation2005;8(3):193–202.
x(79)MannGE,MaloneLJ,TaylorPN,BurridgeJH.
ArandomisedcontrolledpilotstudytoinvestigatetheeffectofneuromuscularelectricalstimulationonupperxEraifejetal.
SystematicReviews(2017)6:40Page16of21Table1(Continued)limbfunctionandhandsensationfollowingstroke.
1stAnnualConferenceofFesnet20022002.
(80)ManoTS,TerradezJRS,TomasJM,MoralJCM,FuenteFT,JoseCC.
Electricalstimulationinthetreatmentofthespastichemiplegichandafterstroke:arandomizedstudy.
Spanish.
MedClin2011;137(7):297–301.
x(81)McDonnellMN,HillierSL,MilesTS,ThompsonPD,RiddingMC.
Influenceofcombinedafferentstimulationandtask-specifictrainingfollowingstroke:apilotran-domizedcontrolledtrial.
NeurorehabilitationandNeuralRepair2007Sep-Oct;21(5):435–443.
x(82)MeadmoreK,ExellT,FreemanC,KutluM,RogersE,HughesAM,etal.
Electricalstimulationanditerativelearningcontrolforfunctionalrecoveryintheupperlimbpost-stroke.
IEEEInternationalConferenceonRe-habilitationRobotics2013Jun;2013:6650359.
x(83)MeadmoreKL,ExellTA,HallewellE,HughesAM,FreemanCT,KutluM,etal.
Theapplicationofpreciselycontrolledfunctionalelectricalstimulationtotheshoulder,elbowandwristforupperlimbstrokerehabilitation:afeasibilitystudy.
JournalofNeuroengineeringandRehabilitation2014;11:105.
x(84)MerlettiR,AcimovicR,GrobelnikS,CvilakG.
Electrophysiologicalorthosisfortheupperextremityinhemiplegia:feasibilitystudy.
ArchPhysMedRehabil19751975;56(12):507–513.
x(85)MohamedFCK,PrakashPNO,AjithS.
Efficacyoffunctionalneuromuscularelectricalstimulation(FNMES)intheimprovementofhandfunctionsinacutestrokesurvivals.
NitteUniversityJournalofHealthScience2012;2(4):16–21.
x(86)MokruschT.
Treatmentofstroke-inducedspastichemoparesiswithEMG-triggeredelectrostimulation.
Ger-man.
NeurologieandRehabilitation1997;3(2):82–86.
x(87)MoniruzzamanM,SalekKM,ShakoorMA,MiaBA,MoyeenuzzamanM.
Effectsoftherapeuticmodalitiesonpatientswithpoststrokeshoulderpain.
MymensinghMedicalJournal:MMJ2010Jan;19(1):48–53.
x(88)Nakipoglu-YuzerGF,KoyuncuE,OzgirginN.
Effect-ivenessoffunctionalelectricalstimulationonupperex-tremityrehabilitationoutcomesinpatientswithhemiplegiaduetocerebrovascularaccident.
Turkish.
Tur-kiyeFizikselTipveRehabilitasyonDergisi2010;56(4):177–181.
x(89)NomaT,MatsumotoS,ShimodozonoM,KawahiraK.
Novelneuromuscularelectricalstimulationsystemfortheupperlimbsinsub-acutestrokepatients:apilotran-domizedcontrolledtrial.
Braininjury2014;28(5–6):725.
x(90)Packman-BraunR.
Relationshipbetweenfunctionalelectricalstimulationdutycycleandfatigueinwristex-tensormusclesofpatientswithhemiparesis.
PhysTher1988Jan;68(1):51–56.
x(91)PageSJ,LevinL,HermannV,DunningK,LevineP.
Longerversusshorterdailydurationsofelectricalstimulationduringtask-specificpracticeinmoderatelyimpairedstroke.
ArchivesofPhysicalMedicineandRe-habilitation2012Feb;93(2):200–206.
x(92)PandyanAD,GranatMH,StottDJ.
Effectsofelectricalstimulationonflexioncontracturesinthehemiplegicwrist.
ClinRehabil1997May;11(2):123–130.
xEraifejetal.
SystematicReviews(2017)6:40Page17of21Table1(Continued)(93)PandyanAD,GranatMH.
Canneuro-muscularelec-tricalstimulationofthewristextensorsfacilitatethere-coveryofarmfunctionintheseverelydisabledacutestrokepatientAgeAgeing2004;33(Suppl2):ii43.
x(94)PandyanAD,GranatMH.
Cantreatmentwithupperlimbelectricalstimulationbejustifiedintheseverelydisabledacutestrokepatient9thAnnualConferenceoftheInternationalFESSociety20042004.
x(95)PeuralaSH,PitkanenK,SiveniusJ,TarkkaIM.
Cutaneouselectricalstimulationmayenhancesensorimotorrecoveryinchronicstroke.
ClinRehabil2002Nov;16(7):709–716.
x(96)PopovicDB,PopovicMB,SinkjaerT,StefanovicA,SchwirtlichL.
Therapyofpareticarminhemiplegicsubjectsaugmentedwithaneuralprosthesis:across-overstudy.
CanadianJournalofPhysiologyandPharma-cology2004Aug–Sep;82(8–9):749–756.
x(97)PowellJ,PandyanAD,GranatM,CameronM,StottDJ.
Electricalstimulationofwristextensorsinpoststrokehemiplegia.
Stroke1999Jul;30(7):1384–1389.
x(98)RingH,RosenthalN.
Controlledstudyofneuroprostheticfunctionalelectricalstimulationinsub-acutepost-strokerehabilitation.
JRehabilMed2005Jan;37(1):32–36.
x(99)RosewilliamS,MalhotraS,RoffeC,JonesP,PandyanAD.
Cansurfaceneuromuscularelectricalstimulationofthewristandhandcombinedwithroutinetherapyfacilitaterecoveryofarmfunctioninpatientswithstroke.
ArchivesofPhysicalMedicineandRehabilitation2012Oct;93(10):1715–21.
e1.
x(100)SahinN,UgurluH,AlbayrakI.
Theefficacyofelectricalstimulationinreducingthepost-strokespasti-city:arandomizedcontrolledstudy.
DisabilityandRe-habilitation2012;34(2):151–156.
x(101)SentandreuManoT,SalomTerradezJR,TomasJM,MelendezMoralJC,delaFuenteFernandezT,CompanyJoseC.
[Electricalstimulationinthetreatmentofthespastichemiplegichandafterstroke:arandomizedstudy].
MedClin2011Sep17;137(7):297–301.
x(102)ShengB,Hui-ChanCW.
Treatmentofupper-limbparesisbytranscutaneouselectricnervestimulationandtask-relatedtrainingduringchronicstroke:arandomizedplacebo-controlledtrial.
ArchPhysMedRehabil2007;88:E2.
x(103)SondeL,GipC,FernaeusSE,NilssonCG,ViitanenM.
Stimulationwithlowfrequency(1.
7Hz)transcutaneouselectricnervestimulation(low-tens)increasesmotorfunctionofthepost-strokepareticarm.
ScandJRehabilMed1998Jun;30(2):95–99.
x(104)SondeL,KalimoH,FernaeusSE,ViitanenM.
LowTENStreatmentonpost-strokepareticarm:athree-yearfollow-up.
ClinRehabil2000Feb;14(1):14–19.
x(105)SullivanJE,HurleyD,HedmanLD.
Afferentstimulationprovidedbygloveelectrodeduringtask-specificarmexercisefollowingstroke.
ClinRehabil2012Nov;26(11):1010–1020.
x(106)TarkkaIM,KononenM.
Methodstoimproveconstraint-inducedmovementtherapy.
NeuroRehabilita-tion2009;25(1):59–68.
xxEraifejetal.
SystematicReviews(2017)6:40Page18of21Appendix3OngoingstudieslistTable1(Continued)(107)TekeogluY,AdakB,GoksoyT.
Effectoftranscutaneouselectricalnervestimulation(TENS)onBarthelActivitiesofDailyLiving(ADL)indexscorefollowingstroke.
ClinRehabil1998Aug;12(4):277–280.
(108)VodovnikL,KraljA,StanicU.
RecentapplicationsoffunctionalelectricalstimulationtostrokepatientsinLjubljana.
ClinOrthop19781978;NO.
131:64–70.
x(109)WangRY,ChanRC,TsaiMW.
Functionalelectricalstimulationonchronicandacutehemiplegicshouldersubluxation.
AmericanJournalofPhysicalMedicine&Rehabilitation2000;79(4):385–90;quiz391–4.
x(110)WangRY,YangYR,TsaiMW,WangWT,ChanRC.
Effectsoffunctionalelectricstimulationonupperlimbmotorfunctionandshoulderrangeofmotioninhemiplegicpatients.
AmericanJournalofPhysicalMedicine&Rehabilitation2002;81(4):283–290.
x(111)WeberDJ,SkidmoreER,NiyonkuruC,ChangCL,HuberLM,MuninMC.
CyclicfunctionalelectricalstimulationdoesnotenhancegainsinhandgraspfunctionwhenusedasanadjuncttoonabotulinumtoxinAandtaskpracticetherapy:asingle-blind,randomizedcontrolledpilotstudy.
ArchPhysMedRehabil2010;91(5):679–686.
x(112)WongAM,SuTY,TangFT,ChengPT,LiawMY.
Clinicaltrialofelectricalacupunctureonhemiplegicstrokepatients.
AmericanJournalofPhysicalMedicine&Rehabilitation1999Mar–Apr;78(2):117–122.
x(113)WuCW,SeoHJ,CohenLG.
Influenceofelectricsomatosensorystimulationonparetic-handfunctioninchronicstroke.
ArchivesofPhysicalMedicineandRe-habilitation2006Mar;87(3):351–357.
x(114)WuFC,LinYT,KuoTS,LuhJJ,LaiJS.
Clinicaleffectsofcombinedbilateralarmtrainingwithfunctionalelectricalstimulationinpatientswithstroke.
IEEEInternationalConferenceonRehabilitationRobotics2011;2011:5975367.
x(115)YozbatiranN,DonmezB,KayakN,BozanO.
Electricalstimulationofwristandfingersforsensoryandfunctionalrecoveryinacutehemiplegia.
ClinRehabil2006Jan;20(1):4–11.
xTable2TitleTrialregistrationnumberAuthorRepetitivearmtrainingcombinedwithfunctionalelectricalstimulationonupperextremitymotorrecoveryinsub-acutestrokesurvivorsNCT02267798Straudi,S.
TreatmentofhanddysfunctionafterstrokeNCT00508521Daly,J.
Poststrokehandfunctions:bilateralmovementsandelectricalstimulationtreatmentsNCT00369668Cauraugh,JH.
BrainandcoordinationchangesinducedbyroboticsandfestreatmentfollowingstrokeNCT00237744Daly,J.
MyndMovetherapyforseverehemiparesisoftheupperlimbfollowingstrokeNCT02266836Hebert,DA;Bayley,M.
Tableofpossiblyrelevantongoingtrials(searched31/10/2015)Eraifejetal.
SystematicReviews(2017)6:40Page19of21AdditionalfilesAdditionalfile1:PreferredReportingItemsforSystematicReviewsandMeta-Analyses(PRISMA)statement.
(DOC60kb)Additionalfile2:TableS1.
OutcomeMeasureDefinitionsTableandReferences.
TableS2.
IncludedStudyCharacteristicsTableandReferences.
TableS3.
CriticalAppraisalTable.
(DOC171kb)Additionalfile3:FigureS1.
SMD(95%CI)ofFunctionalElectricalStimulation(FES)vscontrolonActivitiesofDailyLivingforsham-controlledtrialsonly.
AMATArmMotorAbilityTest;CAHAIChedokeArmandHandActivityInventory;FIMFunctionalIndependenceMeasure;UEFTUpperExtremityFunctionTest;HFGHigherFunctioningGroup;LFGLowerFunctioningGroup.
(JPG85kb)Additionalfile4:FigureS2.
SMD(95%CI)ofFunctionalElectricalStimulation(FES)vscontrolonsecondaryoutcomes(functionalmotorrecovery)measuredbyFMA.
aFESinitiatedwithintwomonthsofstrokebFESinitiatiedafteroneyearofstroke.
(JPG96kb)Additionalfile5:FigureS3.
SMD(95%CI)ofFunctionalElectricalStimulation(FES)vscontrolonsecondaryoutcomes(functionalmotorrecovery)forsham-controlledtrialsonlymeasuredbyFMA.
(JPG74kb)AbbreviationsADL:Activitiesofdailyliving;BBT:Boxandblocktest;CI:Confidenceinterval;FES:Functionalelectricalstimulation;FIM:Functionalindependencemeasure;FMA:Fugl-Meyerassessment;IQR:Interquartilerange;PRISMA:PreferedReportingItemsforSystematicReviewandMeta-Analysis;RCT:Randomisedcontrolledtrial;SD:Standarddeviation;SMD:StandardisedmeandifferenceAcknowledgementsWewouldliketothankProfessorSteveSturman,ConsultantNeurologistspecialisinginNeurologyandRehabilitation(QueenElizabethHospitalBirmingham,UK),forhisclinicalperspectiveandhelpinrevisingthemanuscript.
FundingNofundingwassourcedforthissystematicreview.
AvailabilityofdataandmaterialsAvailableonrequest.
Authors'contributionsAuthorsJE,WC,BF,SDandDM.
OthercontributorSS.
JE,WC,BF,SDandDMcontributedtotheconceptionanddesignoftheworkandpreparationoftheaprioriprotocol.
JE,WC,BF,SDwereinvolvedinthesearch,screening,selection,criticalappraisal,dataextractionandwritingofthedraftmanuscript.
JEandWCperformedallstatisticalanalysesandproducedtheforestplots.
SDandBFproducedthetables.
JE,WC,BF,SDandDMcontributedtorevisionofthedraftmanuscriptandapprovalofthefinalversiontobepublished.
SScontributedtocriticalrevisionofthedraftpaper.
JEisthecorrespondingauthorandguarantor.
CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.
ConsentforpublicationNotapplicable.
EthicsapprovalandconsenttoparticipateNotapplicable.
Authordetails1SchoolofMedicine,CollegeofMedicalandDentalSciences,UniversityofBirmingham,Edgbaston,BirminghamB152TT,UK.
2InstituteofAppliedHealthResearch,CollegeofMedicalandDentalSciences,UniversityofBirmingham,Edgbaston,BirminghamB152TT,UK.
Received:19September2016Accepted:15February2017References1.
HatanoS.
Experiencefromamulticentrestrokeregister:apreliminaryreport.
BullWorldHealthOrgan.
1976;54(5):541–53.
2.
LynchCL,PopovicMR.
Functionalelectricalstimulation.
IEEEControlSystMag.
2008;28(2):40–50.
3.
RothwellPM,CoullAJ,SilverLE,etal.
Population-basedstudyofevent-rate,incidence,casefatality,andmortalityforallacutevasculareventsinallarterialterritories(OxfordVascularStudy).
Lancet.
2005;366:1773–83.
4.
DoucetBM,LamA,GriffinL.
Neuromuscularelectricalstimulationforskeletalmusclefunction.
YaleJBiolMed.
2012;85(2):201–15.
5.
FranceschiniM,LaPortaF,AgostiM,etal.
Ishealth-related-qualityoflifeofstrokepatientsinfluencedbyneurologicalimpairmentsatoneyearafterstrokeEurJPhysRehabilMed.
2010;46(3):389–99.
6.
KwakkelG,KollenBJ,vanderGrondJ,etal.
Probabilityofregainingdexterityintheflaccidupperlimb:impactofseverityofparesisandtimesinceonsetinacutestroke.
Stroke.
2003;34(9):2181–6.
7.
LaiSM,StudenskiS,DuncanPW,etal.
Persistingconsequencesofstrokemeasuredbythestrokeimpactscale.
Stroke.
2002;33(7):1840–4.
8.
SveenU,Bautz-HolterE,SodringKM,etal.
Associationbetweenimpairments,self-careabilityandsocialactivities1yearafterstroke.
DisabilRehabil.
1999;21(8):372–7.
9.
ClinicalKnowledgeSummary:StrokeandTIA.
NationalInstituteforHealthandCareExcellence.
http://cks.
nice.
org.
uk/stroke-and-tia.
PublishedFebruary,2009.
UpdatedDecember,2013.
Accessed1Jan2016.
10.
ChaeJ,ShefflerL,KnutsonJ.
Neuromuscularelectricalstimulationformotorrestorationinhemiplegia.
TopStrokeRehabil.
2008;15(5):412–26.
11.
HaraY.
Rehabilitationwithfunctionalelectricalstimulationinstrokepatients.
IntJPhysMedRehabil.
2013;1(6):147.
12.
HaraY,ObayashiS,TsujiuchiK,etal.
Theeffectsofelectromyography-controlledfunctionalelectricalstimulationonupperextremityfunctionandcorticalperfusioninstrokepatients.
ClinNeurophysiol.
2013;124(10):2008–15.
13.
JoaKL,HanYH,MunCW,etal.
Evaluationofthebrainactivationinducedbyfunctionalelectricalstimulationandvoluntarycontractionusingfunctionalmagneticresonanceimaging.
JNeuroengRehabil.
2012;9:48.
14.
BarsiGI,PopovicDB,TarkkaIM,etal.
Corticalexcitabilitychangesfollowinggraspingexerciseaugmentedwithelectricalstimulation.
ExpBrainRes.
2008;191(1):57–66.
15.
NahumM,LeeH,MerzenichMM.
Principlesofneuroplasticity-basedrehabilitation.
ProgBrainRes.
2013;207:141–71.
16.
TakeuchiN,IzumiS.
Rehabilitationwithpoststrokemotorrecovery:areviewwithafocusonneuralplasticity.
StrokeResTreat.
2013;2013:128641.
17.
PereiraS,MehtaS,McIntyreA,etal.
Functionalelectricalstimulationforimprovinggaitinpersonswithchronicstroke.
TopStrokeRehabil.
2012;19(6):491–8.
18.
RobbinsSM,HoughtonPE,WoodburyMG,etal.
Thetherapeuticeffectoffunctionalandtranscutaneouselectricstimulationonimprovinggaitspeedinstrokepatients:Ameta-analysis.
ArchPhysMedRehabil.
2006;87(6):853–9.
19.
RocheA,LaighinG,CooteS.
Surface-appliedfunctionalelectricalstimulationfororthoticandtherapeutictreatmentofdrop-footafterstroke-asystematicreview.
PhysTherRev.
2009;14(2):63–80.
20.
Functionalelectricalstimulationfordropfootofcentralneurologicalorigin.
NationalInstituteforHealthandCareExcellence.
https://www.
nice.
org.
uk/guidance/ipg278.
PublishedJanuary,2009.
UpdatedJanuary9th,2012.
Accessed1Jan2016.
21.
Nationalclinicalguidelineforstroke.
RoyalCollegeofPhysicians.
https://www.
rcplondon.
ac.
uk/guidelines-policy/stroke-guidelines.
PublishedFifthEditionOctober,2016.
Accessed13Oct2016.
22.
VeerbeekJM,KwakkelG,vanWegenEE,etal.
Earlypredictionofoutcomeofactivitiesofdailylivingafterstroke:asystematicreview.
Stroke.
2011;42(5):1482–8.
23.
Strokerehabilitationinadults.
NationalInstituteforHealthandCareExcellence.
https://www.
nice.
org.
uk/guidance/cg162.
PublishedJune2013.
Accessed1Jan2016.
24.
MeilinkA,HemmenB,SeelenHA,etal.
ImpactofEMG-triggeredneuromuscularstimulationofthewristandfingerextensorsoftheparetichandafterstroke:Asystematicreviewoftheliterature.
ClinRehabil.
2008;22(4):291–305.
Eraifejetal.
SystematicReviews(2017)6:40Page20of2125.
VanPeppenRP,KwakkelG,Wood-DauphineeS,etal.
Theimpactofphysicaltherapyonfunctionaloutcomesafterstroke:What'stheevidenceClinRehabil.
2004;18(8):833–62.
26.
BoltonDA,CauraughJH,HausenblasHA.
Electromyogram-triggeredneuromuscularstimulationandstrokemotorrecoveryofarm/handfunctions:Ameta-analysis.
JNeurolSci.
2004;223(2):121–7.
27.
HowlettOA,LanninNA,AdaL,etal.
Functionalelectricalstimulationimprovesactivityafterstroke:asystematicreviewwithmeta-analysis.
ArchPhysMedRehabil.
2015;96(5):934–43.
28.
VafadarAK,CtéJN,ArchambaultPS,etal.
Effectivenessoffunctionalelectricalstimulationinimprovingclinicaloutcomesintheupperarmfollowingstroke:asystematicreviewandmeta-analysis.
BioMedResInt.
2014;2015.
29.
PollockA,FarmerSE,BradyMC,etal.
Interventionsforimprovingupperlimbfunctionafterstroke.
CochraneDatabaseSystRev.
2014;12(11)30.
EraifejJ,ClarkW,FranceB,etal.
Doesupperlimbtranscutaneousfunctionalelectricalstimulationafterstrokeimprovemotoroutcomeshttp://www.
crd.
york.
ac.
uk/PROSPERO/display_record.
aspID=CRD42015025162.
PublishedAugust11th,2015.
UpdatedJanuary11th,2016.
Accessed23June2016.
31.
MoherD,LiberatiA,TetzlaffJ,etal.
PreferredReportingItemsforSystematicReviewsandMeta-Analyses:ThePRISMAStatement.
BMJ.
2009;339:b2535.
32.
JorgensenHS,NakayamaH,RaaschouHO,etal.
Outcomeandtimecourseofrecoveryinstroke,partII:timecourseofrecovery,theCopenhagenstrokestudy.
ArchPhysMedRehabil.
1995;76(5):406–12.
33.
LeeKB,LimSH,KimKH,etal.
Six-monthfunctionalrecoveryofstrokepatients:amulti-time-pointstudy.
IntJRehabilRes.
2015;38(2):173–80.
34.
KuptniratsaikulV,KovindhaA,SuethanapornkulS,MassakulpanP,PermsirivanichW,KuptniratsaikulPS.
Motorrecoveryofstrokepatientsafterrehabilitation:one-yearfollow-upstudy.
IntJNeurosci.
2016;29:1–7.
35.
BitzerEM,PetrucciM,LorenzC,etal.
Acomparisonofconventionalandretrospectivemeasuresofchangeinsymptomsafterelectivesurgery.
HealthQualLifeOutcomes.
2011;9:23.
36.
McPhailS,HainesT.
Responseshift,recallbiasandtheireffectonmeasuringchangeinhealth-relatedqualityoflifeamongstolderhospitalpatients.
HealthQualLifeOutcomes.
2010;8:65.
37.
PrinceSA,AdamoKB,HamelME,etal.
Acomparisonofdirectversusself-reportmeasuresforassessingphysicalactivityinadults:Asystematicreview.
IntJBehavNutrPhysAct.
2008;5:56.
38.
RedelmeierDA,DickinsonVM.
Determiningwhetherapatientisfeelingbetter:pitfallsfromthescienceofhumanperception.
JGenInternMed.
2011;26(8):900–6.
39.
Reyes-GuzmanADL,Perez-NombelaS,Dimbwadyo-TerrerI,etal.
Functionalupperlimbevaluationofactivitiesofdailylivinginpeoplewithneurologicaldisorders.
In:GirouxJ,ValleeG,editors.
Activitiesofdailyliving:performance,impactonlifequalityandassistance.
Hauppauge,NewYork:NovaSciencePublishers;2013.
p.
55–76.
40.
WilliamsonPR,AltmanDG,BlazebyJM,etal.
Developingcoreoutcomesetsforclinicaltrials:Issuestoconsider.
Trials.
2012;13:132.
41.
MillarJ,AliM,PollockA,etal.
Standardisationofoutcomemeasuresintrialsofupperlimbrehabilitationafterstroke.
http://www.
comet-initiative.
org/studies/details/653result=true.
PublishedOctober,2014.
Accessed10Jan2016.
IncludedStudies:A1.
BarkerRN,BrauerS,CarsonR.
Training-inducedchangesinthepatternoftricepstobicepsactivationduringreachingtasksafterchronicandseverestroke.
ExpBrainRes2009;196(4):483–96.
A2.
CauraughJ,LightK,KimS,etal.
Chronicmotordysfunctionafterstroke:Recoveringwristandfingerextensionbyelectromyography-triggeredneuromuscularstimulation.
Stroke2000;31(6):1360–64.
A3.
CauraughJH,KimS.
Twocoupledmotorrecoveryprotocolsarebetterthanone:Electromyogram-triggeredneuromuscularstimulationandbilateralmovements.
Stroke2002;33(6):1589–94.
A4.
CauraughJH,KimSB.
Chronicstrokemotorrecovery:durationofactiveneuromuscularstimulation.
JNeurolSci2003;215(1-2):13–19.
A5.
CauraughJH,KimSB.
Strokemotorrecovery:activeneuromuscularstimulationandrepetitivepracticeschedules.
JNeurolNeurosurgPsychiatry.
2003;74(11):1562–66.
A6.
ChanMK,TongRK,ChungKY.
Bilateralupperlimbtrainingwithfunctionalelectricstimulationinpatientswithchronicstroke.
NeurorehabilNeuralRepair2009;23(4):357–65.
A7.
DuarteE,MarcoE,CervantesC,DazD,ChiarellaSC,EscaladaF.
EfectosdelatoxinabotulínicatipoAyelectroestimulaciónenlaespasticidadflexoradistaldelaextremidadsuperiorenelictus.
ensayoclínicoaleatorizado.
Rehabilitacion(Madr).
2011;45(3):194–201.
A8.
FranciscoG,ChaeJ,ChawlaH,etal.
Electromyogram-triggeredneuromuscularstimulationforimprovingthearmfunctionofacutestrokesurvivors:Arandomizedpilotstudy.
ArchPhysMedRehabil1998;79(5):570–75.
A9.
HaraY,OgawaS,TsujiuchiK,MuraokaY.
Ahome-basedrehabilitationprogramforthehemiplegicupperextremitybypower-assistedfunctionalelectricalstimulation.
DisabilRehabil.
2008;30(4):296–304.
A10.
MangoldS,SchusterC,KellerT,etal.
Motortrainingofupperextremitywithfunctionalelectricalstimulationinearlystrokerehabilitation.
NeurorehabilNeuralRepair2009;23(2):184–90.
A11.
McCabeJ,MonkiewiczM,HolcombJ,PundikS,DalyJJ.
Comparisonofrobotics,functionalelectricalstimulation,andmotorlearningmethodsfortreatmentofpersistentupperextremitydysfunctionafterstroke:Arandomizedcontrolledtrial.
ArchPhysMedRehabil.
2015;96(6):981–90.
A12.
PopovicMB,PopovicDB,SinkjaerT,etal.
Restitutionofreachingandgraspingpromotedbyfunctionalelectricaltherapy.
ArtifOrgans2002;26(3):271–75.
A13.
PopovicMB,PopovicDB,SinkjaerT,etal.
Clinicalevaluationoffunctionalelectricaltherapyinacutehemiplegicsubjects.
JRehabilResDev2003;40(5):443–53.
A14.
ShimodozonoM,NomaT,MatsumotoS,etal.
Repetitivefacilitativeexerciseundercontinuouselectricalstimulationforseverearmimpairmentaftersub-acutestroke:Arandomizedcontrolledpilotstudy.
BrainInj2014;28(2):203–10.
A15.
ShinHK,ChoSH,JeonHS,etal.
Corticaleffectandfunctionalrecoverybytheelectromyography-triggeredneuromuscularstimulationinchronicstrokepatients.
NeurosciLett2008;442(3):174–79.
A16.
ShindoK,FujiwaraT,HaraJ,etal.
Effectivenessofhybridassistiveneuromusculardynamicstimulationtherapyinpatientswithsubacutestroke:Arandomizedcontrolledpilottrial.
NeurorehabilNeuralRepair2011;25(9):830–37.
A17.
TarkkaIM,PitkanenK,PopovicDB,etal.
Functionalelectricaltherapyforhemiparesisalleviatesdisabilityandenhancesneuroplasticity.
TohokuJExpMed2011;225(1):71–6.
A18.
ThorsenR,CortesiM,JonsdottirJ,etal.
Myoelectricallydrivenfunctionalelectricalstimulationmayincreasemotorrecoveryofupperlimbinpoststrokesubjects:Arandomizedcontrolledpilotstudy.
JRehabilResDev2013;50(6):785–94.
A19.
ThrasherTA,ZivanovicV,McIlroyW,etal.
Rehabilitationofreachingandgraspingfunctioninseverehemiplegicpatientsusingfunctionalelectricalstimulationtherapy.
NeurorehabilNeuralRepair2008;22(6):706–14.
A20.
YunGJ,ChunM,ParlJY,etal.
Thesynergiceffectsofmirrortherapyandneuromuscularelectricalstimulationforhandfunctioninstrokepatients.
AnnRehabilMed2011;35:316–21.
Weacceptpre-submissioninquiriesOurselectortoolhelpsyoutondthemostrelevantjournalWeprovideroundtheclockcustomersupportConvenientonlinesubmissionThoroughpeerreviewInclusioninPubMedandallmajorindexingservicesMaximumvisibilityforyourresearchSubmityourmanuscriptatwww.
biomedcentral.
com/submitSubmityournextmanuscripttoBioMedCentralandwewillhelpyouateverystep:Eraifejetal.
SystematicReviews(2017)6:40Page21of21