BrazJOtorhinolaryngol.2019;85(6):788---798
www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
REVIEW
ARTICLE
Vestibular
implant:
does
it
really
work?
A
systematic
review
夽
Yaná
Jinkings
de
Azevedo
a,
Alleluia
Lima
Losno
Ledesma
b,c,d,
Larissa
Vilela
Pereira
e,f,
Carlos
Augusto
Oliveira
a,d,g,h,
Fayez
Bahmad
Junior
a,d,g,∗aUniversidadedeBrasília(UnB),FaculdadedeCiênciasdeSaúde,ProgramadePós-Graduac¸ãoemCiênciasdaSaúde,Brasília,DF,
Brazil
bUniversidadedeBrasília(UnB),ProgramadeCiênciasdaSaúde,Brasília,DF,Brazil
cCentroUniversitárioPlanaltodoDistritoFederal(UNIPLAN),CursodeFonoaudiologia,Brasília,DF,Brazil dFaculdadedeCiênciasdeSaúde---AsaNorte,Brasília,DF,Brazil
eUniversidadedeSãoPaulo(USP),HospitaldasClínicas,SãoPaulo,SP,Brazil fHospitalAnchieta,Brasília,DF,Brazil
gHospitalUniversitáriodeBrasília,Brasília,DF,Brazil hUniversidadedeBrasília(UnB),Brasília,DF,Brazil
Received7March2019;accepted29July2019 Availableonline20September2019
KEYWORDS Vestibularloss; Vestibularimplant; Vestibularfunction
Abstract
Introduction:Peoplewithvestibularlosspresentadeficitinthevestibularsystem,whichis primarilyresponsibleforpromotingposturalcontrol,gazestabilization,andspatialorientation whiletheheadmoves.Thereisnoeffectivetreatmentforabilaterallossofvestibularfunction. Recently,avestibularimplantwasdevelopedforpeoplewithbilaterallossofvestibularfunction toimprovethisfunctionand,consequently,thequalityoflifeofthesepatients.
Objective:Toidentifyinthescientificliteratureevidencethatvestibularimplantsinpeople withvestibulardeficitimprovesvestibularfunction.
Methods:Onehundredandfortysixarticleswerefoundfromfivedatabasesand323articles fromthegrayliteraturementioningtherelationshipbetweenvestibularimplantandvestibular functioninhumans.ThePICOSstrategy(Population,Intervention,ComparisonandOutcome) wasusedtodefinetheeligibilitycriteria.Thestudiesthatmettheinclusioncriteriaforthis second stepwere includedinaqualitativesynthesis, andeachtype ofstudy was analyzed accordingtothebiasriskassessmentoftheJoannaBriggsInstitutethroughthecritical assess-ment checklistJoannaBriggsinstitute forquasi-experimentalstudiesandtheJoannaBriggs institutecriticalassessmentchecklistforcasereports.
夽 Pleasecitethisarticleas:AzevedoYJ,LedesmaAL,PereiraLV,OliveiraCA,BahmadJuniorF.Vestibularimplant:doesitreallywork?A
systematicreview.BrazJOtorhinolaryngol.2019;85:788---98.
∗Correspondingauthor.
E-mail:fayezbjr@gmail.com(F.BahmadJunior). https://doi.org/10.1016/j.bjorl.2019.07.011
1808-8694/©2019Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
Vestibularimplant:doesitreallywork?Asystematicreview 789 Results:Ofthe21articlesincludedinreadingthefulltext,10studieswereselectedforthe qualitative analysisin thepresent systematicreview. All ten articles analyzed throughthe criticalassessmentchecklistJoannaBriggsinstituteshowedalowriskofbias.Thetotalnumber ofsamplesintheevaluatedarticleswas18patientswithvestibularimplants.
Conclusions: Takentogether, thesefindings support thefeasibility of vestibular implantfor restorationofthevestibulo-ocularreflexinabroadfrequencyrangeandillustratenew chal-lengesforthedevelopmentofthistechnology.
© 2019 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
PALAVRAS-CHAVE Perdavestibular; Implantevestibular; Func¸ãovestibular
Implantevestibular:elerealmentefunciona?Umarevisãosistemática Resumo
Introduc¸ão: Pessoascomperdavestibularapresentamumdéficitnosistemavestibular,oqual éoprincipalresponsávelpelocontrolepostural,pelaestabilizac¸ãodoolhareorientac¸ão espa-cialenquantoacabec¸asemovimenta.Nãohátratamentoefetivoparaumaperdavestibular bilateral. Recentemente, foi desenvolvidoum implantevestibular para pessoas com perda vestibularbilateralparamelhoraressafunc¸ãoe,consequentemente,aqualidadedevidadesses pacientes.
Objetivo: Identificarnaliteraturacientíficaevidênciasdequeoimplantevestibularmelhoraa func¸ãovestibulardepessoascomdéficitvestibular.
Método: Centoequarentaeseisartigosforamencontradosemcincobasesdedadose323 arti-gosdaliteraturacinzenta,mencionandoarelac¸ãoentreimplantevestibularefunc¸ãovestibular em humanos.Aestratégia PICOS(Populac¸ão,Intervenc¸ão,Comparac¸ão eDesfechos)foi uti-lizadaparadefiniroscritériosdeelegibilidade.Osestudosquepreencheramoscritériosde inclusãoparaestasegundaetapaforamincluídosemumasíntesequalitativa,ecadatipode estudo foianalisado de acordocomaavaliac¸ãode riscode viésdoJoanna BriggsInstitute atravésdacriticalappraisalchecklist forquasi-experimentalstudies edacriticalappraisal checklistforcasereports.
Resultados: Dos21artigosincluídoscujostextoscompletosforamlidos,10foram seleciona-dosparaaanálisequalitativanapresenterevisãosistemática.Todososdezartigosanalisados atravésdacriticalappraisalchecklistmostraramum baixoriscodeviés.Onúmerototalde amostrasnosartigosavaliadosfoide18pacientescomimplantesvestibulares.
Conclusões: Emconjunto,essesachadosapoiamaviabilidade doimplantevestibularpara a restaurac¸ãodoreflexovestíbulo-ocularemumaamplafaixadefrequênciaseilustramnovos desafiosparaodesenvolvimentodestatecnologia.
© 2019 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Everydayweareconfrontedwithavarietyofdynamic situa-tionsinwhichpreciseinformationonheadandbodymotion andonthespatialpositionsoftheheadandbodyisrequired to guarantee adequate function of the vestibular system and,consequently, safetyand well being.1 The vestibular
system is one of the main systems responsible for ensur-ingposturalcontrol,stabilizationofthegazeandaspatial orientation,contributingtothemaintenanceofbalance.2
This system consistsof a setof sensoryorgans located intheinnerear,whereitiscomposedofthreesemicircular canalsandtwootolithicorgans(sacculeandutricle), respon-sibleforprovidingthecortexwithsimultaneousinformation aboutthepositionoftheheadinrelationtothebodyand
producingtheVestibulo-OcularReflex(VOR),whichhasthe functionofgeneratingcompensatoryocular movementsin relationtothe directionof thehead tomaintaina stable fieldofviewintheretina.1
Ifthesystemisdamagedbydisease,agingorinjury,the person willexperience a loss of vestibular function. As a result,an inefficient or absent VOR and, consequently, a reductionof visual acuity will occur during movement.3,4
These vestibular deficits can cause symptoms such as oscillopsia,imbalance,vertigo, spatialdisorientation,and cognitive alterations, among others,5 compromising the
patient’s ability to perform basic daily activities such as walking.6
Despite scientific advances, the existing therapeutic options are limited and of low effectiveness in certain
790 AzevedoYJetal. cases.7 Studiesshowthat,despite intensivebalance
train-ing, some patients do not show significant improvement, maintainingdisabling symptomswithinterference indaily and work activities.1,3,6,8 In this context, some research
groupssuggestaVestibularImplant(VI)toreplacethe func-tionofthevestibularorgans.8---11
Vestibularimplants
Currently, the use of VI in humans has been studied by research groups in Europe (Geneva University Hospitals andMaastricht University Medical Center)andthe United States (University of Washington) as a therapeutic alter-native for people with definitive vestibular loss without improvementwithclinicaltreatment.12,13Researchonboth
animals10,11,14,15 andhumans8,10,12hasshownthatelectrical
stimulationisapotentiallyeffectivemeansofactivatingthe vestibularsystem.
TheVIconsistsofamodificationoftheCochlearImplant (CI),containingonetothree‘‘vestibular’’electrodestaken outofthecochlearelectrodearray,eachconstructedwith anarrangementof2.5mmfineelectrodeswithadiameter of150m,implantedin theperilymphaticspaceadjacent tothemembranouslabyrinthofeach semicircularcanal.13
Thus,ratherthandetectingsoundinformationastheCI,it capturetheinformationonmovementusinghead-fixed sen-sorsandfedtoaspecialprocessorwhereitisconvertedinto anappropriateneuralpattern.2Thisneuralpatternsof
pro-cessedmotioninformationarethentransmittedintheform ofelectricalcurrentsdeliveredviathevestibularelectrodes totheimplantedstimulatorandtransferstheinformationto theCentralNervousSystem(CNS).2,8Inthisconcept,theVI
aimsattransmitting‘‘artificial’’neuralpatternstotheCNS similartothosecodedbythenormallyfunctioningvestibular system.2
To date, two surgical strategies have been described for VI: the intralabyrinthine surgical approach1,8,12,16 and
the extralabyrinthine approach.15,17,18 With the
intral-abyrinthineapproach, each semicircularcanal is opened, and the electrodes are inserted until they contact the ampullary ciliary cells.12 Using an extralabyrinthine
approach,thelabyrinthisnotopen,andtheelectrodesare placeddirectlyonthenerves.13
Theevolutionofknowledge aboutathemeinmedicine requiresSystematicReviews(SR)tocapture,recognizeand synthesizethescientificevidencetosupporttheproposals ofqualifiedclinicalpracticesinhealth.19Thepurposeofthis
SRistoidentifyevidenceinthescientificliteraturethatVIin peoplewithvestibulardeficitimprovesvestibularfunction.
Methods
In this study, a Systematic Review (SR) was performed, sinceitisarecognizedmethodologyforhigh-levelscientific researchinthehealtharea.ThefirststepinstartinganSRis toformulateaspecificresearchquestionthatcontainsthe targetpopulation,theinterventionorexposure,a compar-ison(ifapplicable),theexpectedoutcomesandthetypes ofstudythatmayanswerthequestion(PICOS).19InthisSR,
thefollowing questionwasposed:Dopeoplewith
vestibu-larlosswhouseVIexperienceanimprovementinvestibular function?
Searchstrategy
The search strategy that was performed in this SR fol-lowedthecriteriarecommendedbythePreferredReporting ItemsforSystematicReviewsandMeta-Analyses----PRISMA19
and for which the protocol was registered on June 6, 2018 at the International Prospective Register of Sys-tematic Reviews----PROSPERO20 under registration number
CRD42018093469.
ThesearchwasperformedinthePubMed,Scopus,Lilacs, LivivoandSpeechbite databases.The grayliteraturewas consultedthroughtheGoogleScholardatabase.Therewas norestrictionontheperiodorlanguageofpublication.
The keywords of the search strategy were described as follows: ‘‘vestibular loss’’ OR ‘‘vestibular deficit’’ OR ‘‘vestibulopathy’’ OR ‘‘vestibular dysfunction’’ OR ‘‘vestibular deficiency’’ AND ‘‘vestibular implant’’ OR ‘‘vestibular prosthesis’’ OR ‘‘neural prosthesis’’ AND ‘‘vestibular function.’’ This search strategy was adapted to the other databases, where the correspondents were appliedin PortugueseandSpanishin Lilacs.Then,a man-ual search of the references of the selected articles was performed.
After the search, the references of each database were exported to the EndNote X8 program (https://endnote.com/) and then these same references were exported fromEndNote X8tothe RayyanQCRI pro-gram(https://rayyan.qcri.org/).Thepurposeofthesetwo programs was to record all duplicate articles that have been found in thescientific literature, promoting greater reliabilityintheselectionofarticlesandproceedingtothe eligibilitystage.
Eligibilitycriteria
The PICOSstrategy(Population,Intervention,Comparison, Outcomes) wasusedto definethe eligibilitycriteria.19 As
inclusion criteria, we selectedpeoplewith vestibularloss whouseda VI,havingastheirintervention thevestibular prosthesisandasacomparisontheperiodbeforeandafter surgeryoftheVIineachindividual.Theresultshadto con-tainanevaluationofvestibularfunction,andthetypes of studiesshouldbeprospectiveclinicalstudies,clinicalcases andcase reports.Exclusioncriteriaincluded patientswho werenotcandidatesforvestibularimplantation,animaland invitrostudiesandstudieswithabstentionfrom postoper-ativedata.
Allstudieswereanalyzedforeligibilityinthescreening phasesbasedontheinclusionandexclusioncriteria.Inthe firstphase,allthestudieswereselectedbasedonthetitle andabstractbytworeviewersindependently.Therewasno disagreementamongthereviewers,ruling outtheneedto consultthethirdreviewer.Inthecaseofsummary absten-tion,butwithanapplicabletitle,thestudywasincludedin thesecondphase.
Inthe secondphase, thesametworeviewers read the full textofeach selectedarticle usingthesame inclusion andexclusioncriteria,butaddingtheexclusionjustification
Vestibularimplant:doesitreallywork?Asystematicreview 791 foreachdiscardedstudy.Thestudiesthatmettheinclusion
criteriain thissecond stepwereincluded in aqualitative synthesis, andeach typeof study wasanalyzedaccording to the bias risk assessment of the Joanna Briggs Insti-tute(JBI)21 throughtheJBICriticalAppraisalChecklistfor
Quasi-ExperimentalStudies(non-randomizedexperimental studies) and the JBI Critical Appraisal Checklist for Case Reports.
In the JBI Critical Appraisal Checklist, each question shouldbeansweredthroughfouroptions:Yes (Y),No(N), Unclear(U)andNotApplicable(NA).Thebiasrisk percent-agecalculationisdonebytheamountof‘‘Y’’thathasbeen selected in the checklist. When ‘‘NA’’ was selected, this question wasnotconsidered in thecalculation, according totheguidelinesoftheJoannaBriggsInstitute.21Upto49%
isconsideredahighriskofbias.From50%to70%ismoderate andabove70%islowriskofbias.
Aftertheseevaluations,theselectedstudiesunderwent a statisticalanalysis toverifythepossibilityof construct-ingameta-analysis.Thisanalysiscombinesandsummarizes resultsfrommultiplestudies,thusincreasingtheaccuracy andthepowerofevidenceoftheresults.
Results
InthefirstphaseofthisSR,146articleswerefoundinfive databasesand323articlesinthegrayliterature.After elim-inationof212duplicatestudies,294wereselectedtoread titles and abstracts. Of these, 273 were excluded by the establishedexclusioncriteria.Ofthe21articlesincludedin thesecondstage,whichconsistedofreadingthefulltextof eachstudy,11wereexcludedforthefollowingreasons:in sixarticles,12,18,22---25theydidnotintervenewithVI;two2,26
werenotclinicalstudies;two27,28 didnotassessvestibular
functionandinone29study,theexperimentwasconducted
usingcadavers.Intheend,10studieswereselectedforthe qualitativeanalysisinthepresentSR(Table1).Nostudies werefoundbyperformingamanualsearchofthereferences of the articles. The whole process of article selection is describedin Fig.1,whichshows theflow PRISMAdiagram forinclusion.
Regarding the general characteristics of the included articles,thefirstpublishedtoperformVIinahumanpatient wasin2011;30sevenarticles1,3,8,16,30,32,33wereauthoredby
theGeneva-Maastrichtgroupandthree10,13,31wereauthored
by the Washington group. Overall, these two groups per-formedtheVIsurgeryin18people,ranginginagefrom34to 76years(Table2).TheGeneva-Maastrichtgroupperformed its first vestibular implant in 2007 in a 68-year-old man. ThisgroupperformedtwotypesofVIsurgeryin14patients withvestibularlossofdifferentetiologies,withsixpatients implantedthroughtheextralabyrinthineapproachandeight withanintralabyrinthineapproach.The Washington group performeditsfirstVIina56-year-oldman.Accordingtothe publications,thisgroupusedtheintralabyrinthineapproach forimplantationinfourpatientsdiagnosedwithunilateral Meniere’sdisease.
Sincethereisanon-negligibleriskofinducingprofound hearinglosswithimplantationsurgery,inthecasesof sub-jectswithunilateraldeafness,theVIwasimplantedinthe sameaffectedear.
All ten articles were analyzed using the JBI Critical AppraisalChecklistforQuasi-ExperimentalStudies(Table3) and the JBI Critical Appraisal Checklist for Case Reports (Table 4) according to each type of study, and nine articles3,8,10,13,16,30---33showedlowriskofbiasandonearticle1
showedmoderatedriskofbias.21
Itwasnotpossible toelaborate ameta-analysisinthis SRbecause thearticles included presented verydifferent methodologiesandmeasuresresultingfromthetests.
Guyot et al.30 conducted a case study assessing a
patient with idiopathic bilateral deafness and vestibular losswhowasalreadyscheduled for cochlear implantation andreceivedaVI.Theyassessedwhetherthepatientcould adapttocontinuouselectricalstimulationofthevestibular systemand whetherit waspossible toelicit artificialeye movementsvia modulation of the stimulation. Successive ‘‘on-off’’cyclesofcontinuouselectricalstimulationinthe vestibularelectrodesresultedinnystagmicresponsewitha progressivelyshorterduration.Oncetheadaptedstatewas reacheduponconstantstimulation,amplitudeorfrequency modulationsofelectricalstimulationproducedsmooth oscil-latoryconjugatedeyemovements.
Phillips et al.31 performed VI in four patients with
intractableunilateralMeniere’sdiseaseintherightear.All subjectswere implanted withthe VI (UW/Nucleus)based ontheNucleusFreedomcochlearimplant(Cochlear,Ltd.). Duringsurgery,anelectrodearraywasinsertedintothe per-ilymphatic space adjacent to the ampulla of each of the three semicircular canals via a small fenestration in the bonylabyrinthadjacenttotheampullae.Thefenestrations were closed with fascia while trying not to occlude the canallumens,andthe leads externaltothe fenestrations weresecuredwithsuture.Duringarrayplacement, electri-callyEvokedCompoundActionPotential(vECAP)recordings wereobtainedtooptimizeelectrodeplacementfor affer-entactivation.IflargeamplitudevECAPswerenotobtained at low current levels, the fenestration was widened and theelectrodearraymovedclosertotheampulla.Aremote groundballelectrodewasplacedunderthetemporalis mus-cle. In three subjects, the surgery was performed with stimulating electrode arrays in three semicircular canals of theaffected right ear,and onesubject wasimplanted witharraysinthelateralandposteriorcanalsonly.Priorto theelectricalstimulationstudies,beforeandafterdevice implantation, the patients received a battery of clinical vestibularteststoevaluatetheirunderlyingvestibular func-tion,includingcalorics,rotarychair,dynamicvisualacuity, subjectivevisualverticaltestingandposturography.Testing wasconductedovertwosessions,17---136weeksafter surgi-calimplantation.Dataanalysisperformedwiththesystem offlineshowedthatallsubjectshadsignificantdecreasein caloricresponsesintheimplantedearpostoperativelyand showedareductionfrompreoperativelevelsinrotarychair gain,an advancein phaseand an asymmetry toward the implantedearpostoperatively.
Golub et al.10 described the case of a patient with
uncontrolledMénière’sdiseasesubmittedtoVI.At6weeks post-implantation, theprosthesis wasprogrammed witha take-homemap.Ninelevelsettingswereprovidedin incre-mentsof25A,rangingfrom150Ato350A.Thepatient wasinstructed to progress through the mapsettings dur-ing an acute attack until the symptoms were minimized
792 AzevedoYJetal.
Table1 Selectedstudiesfollowingtheinclusionandexclusioncriteriaestablishedinthesystematicreview.
Title Author Location Studydesign N
1 Adaptationtosteady-state electricalstimulationofthe vestibularsysteminhumans
Guyotetal.30 Geneva (Switzerland)
Casereport 1
2 Posturalresponsestoelectrical stimulationofthevestibular endorgansinhumansubjects
Phillipsetal.31 Washington(EUA) Quasi-experimental studies
4
3 Prostheticimplantationofthe humanvestibularsystem
Golubetal.10 Washington(EUA) Casereport 1
4 Artificialbalance-restorationof thevestibulo-ocularreflexin humanswithaprototype vestibularneuroprosthesis
Fornosetal.8 Geneva (Switzerland)e Maastricht (Netherlands) Quasi-experimental studies 3
5 Firstfunctionalrehabilitation viavestibularimplants
Pelizzoneetal.3 Geneva (Switzerland)
Quasi-experimental studies
3 6 Vestibularimplants----Hopefor
improvingthequalityoflifeof patientswithbilateral vestibularloss
Guinandetal.32 Geneva (Switzerland)
Quasi-experimental studies
11
7 Vestibularimplants----8yearsof experiencewithelectrical stimulationofthevestibular nervein11patientswith bilateralvestibularloss
Guinandetal.1 Geneva (Switzerland)e Maastricht (Netherlands) Quasi-experimental studies 11 8 Thevestibular
implant----frequency-dependencyoftheelectrically evokedvestibulo-ocularreflex inhumans
VandeBergetal.16 Geneva (Switzerland)
Quasi-experimental studies
7
9 Vestibularimplantationand longitudinalelectrical
stimulationofthesemicircular canalafferentsinhuman subjects
Phillipsetal.13 Washington(EUA) Quasi-experimental studies
4
10 Thevideoheadimpulsetestto assesstheefficacyof
vestibularimplantsinhumans
Guinandetal.33 Geneva (Switzerland)
Quasi-experimental studies
3
or eliminated. At about the time his take-home proces-sor was provided, his attacks ceased. He had only one subsequent attack, which occurred 6 months postopera-tively. Turning off the implant also resulted in increased symptoms.Comparativetopreoperativelyvalues,rotational chair velocity step testing revealed decreased gain at 6 weeks post-implantation. At 63 weeks post-implantation, thegainrecovered,buttherewasapersistentasymmetry. Calorictestingindicateda26%unilateralweakness preoper-atively,whichincreasedto95%at 6weekspostoperatively andrecoveredslightlyto71%at87weeks.Electrical stim-ulationresultedincanal-specificeyemovements,although thethresholdsincreasedovertime.
Fornos etal.8 investigatedwhether VI waspossible to
artificially restore the VOR in three patients with Bilat-eralVestibular Loss (BVL). The etiology of these patients wasmeningitis(F-58), DFNA9(M-66) and traumatic(F-67) and they were recruited at the Service of Otorhino-laryngology and Head and Neck Surgery at the Geneva
University Hospitalsand at the Division of Balance Disor-ders at the Maastricht University Medical Center. These subjects received a vestibular neuroprosthesis prototype consisting of a modified cochlear implant (MED-EL, Inns-bruck, Austria)and theimplantationwasperformed using anintralabyrinthinesurgicalapproach.Thisdevice,in addi-tiontothecochlearelectrodearray,providedextracochlear electrodes, which were implanted in the vicinity of the ampullarybranchesof thevestibularnerve.Patientswere submittedtohorizontalwhole-bodyrotations(i.e.,around thevertical axis)incomplete darkness(without head sta-bilization).Rotationvelocitieshadasinusoidalprofilewith a30◦/speakamplitudebasedonthetypicalmotionprofile of human locomotion. Five different rotationfrequencies (0.1, 0.25, 0.5, 1 and 2Hz) were tested. Rotations were achievedwithacustom-modified,velocitycontrolled rota-tory chair. Tests were performed without any electrical stimulation(systemOFF)anduponelectricalstimulationof the lateral semicircularcanal (system ON). In thesystem
V estibular implant: does it really work? A systematic review 793
Table2 Demographicsandimplantdetailsforeachpatientwithbilateralvestibularhypofunction.
Patient nofarticle Sex Age BLVetiology Deafness Implantedear Year Surgicalapproach Testedvestibular
electrodes(nof
article)
Location
S1 6;7;8 M 68 Idiopathic B Left 2007 EL PAN--- 6;7;8 Geneva
S2 5;6;7;8;10 M 46 Idiopathic B Left 2008 EL PAN--- 5;6;7;8;10 Geneva
S3 6;7 M 34 Idiopathic B Right 2008 EL PAN--- 6;7 Geneva
S4 6;7 M 71 Menière B Left 2011 EL PAN--- 6;7 Geneva
S5 6;7 M 63 Trauma U Right 2012 EL PAN/LAN--- 6;7 Geneva
S6 6;7;8 F 48 Meningitis U Right 2012 IL PAN/LAN/SAN--- 6;7 Geneva
PAN--- 8
S7 6;7;8 M 67 DFNA9 B Left 2012 IL PAN/LAN/SAN--- 6;7 Geneva
SAN/LAN--- 8 S8 4;6;5; 7;8 M 66 DFNA9 B Left 2013 IL LAN---4 Maastricht PAN/LAN/SAN--- 6;5;7;8 S9 4;6;7; 8;10 F 67 Trauma B Left 2013 IL LAN---4;10 Geneva SAN/LAN-8 PAN/LAN/SAN---6;7
S10 6;7 M 64 DFNA9 B Left 2013 IL PAN/LAN/SAN---6;7 Geneva
S11 6;7;8 F 68 DFNA9 B Left 2013 IL PAN/LAN/SAN---6;7 Geneva
SAN/PAN---8
S12 4;5 F 58 Meningitis U Right --- IL LAN---4 Maastricht
PAN/LAN/SAN---5
S13 10 M 53 Trauma --- Right 2015 IL SAN---10 Geneva
S14 1 M 69 Idiopathic B Left --- EL PAN---4 Geneva
S15 2;3;9 M 56 Menière U Right --- IL PAN/LAN/SAN---2;3;9 Washington
S16 2;9 M 76 Menière U Right --- IL PAN/LAN---2;9 Washington
S17 2;9 F 65 Menière U Right --- IL PAN/LAN/SAN---2;9 Washington
S18 2;9 F 72 Menière U Right --- IL PAN/LAN/SAN---2;9 Washington
Age,Ageatimplantation;Year,Yearofimplantation;B,Bilateral;U,Unilateral;EL,Extralabyrinthine;IL,Intralabyrinthine;PAN,PosteriorAmpullaryNerve;SAN,SuperiorAmpullary Nerve;LAN,LateralAmpullaryNerve.
794
Azevedo
YJ
et
al.
Table3 JBICriticalappraisalchecklistforquasi-experimentalstudies. Phillips etal.31 Fornos etal.8 Pelizzone etal.3 Guinand etal.32 Guinand etal.1 Vande Berg etal.16 Phillips etal.13 Guinand etal.33 Isitclearinthestudywhatisthe
‘‘cause’’andwhatisthe‘‘effect’’ (i.e.thereisnoconfusionabout whichvariablecomesfirst)?
Y Y Y Y Y Y Y Y
Weretheparticipantsincludedinany comparisonssimilar?
Y Y Y Y Y Y Y Y
Weretheparticipantsincludedinany comparisonsreceivingsimilar treatment/care,otherthanthe exposureorinterventionof interest?
Y Y NA N N Y Y N
Wasthereacontrolgroup? Y Y Y Y N Y Y Y
Weretheremultiplemeasurements oftheoutcomebothpreandpost theintervention/exposure?
Y Y Y N N N Y Y
Wasfollowupcompleteandifnot, weredifferencesbetweengroups intermsoftheirfollowup adequatelydescribedand analyzed?
Y Y Y Y Y Y Y Y
Weretheoutcomesofparticipants includedinanycomparisons measuredinthesameway?
Y Y Y Y NA Y Y Y
Wereoutcomesmeasuredina reliableway?
Y Y U Y Y Y Y Y
Wasappropriatestatisticalanalysis used?
Y Y Y Y Y Y Y Y
Biasrisk(%) 100% 100% 87.5% 77.77% 62.5% 88.88% 100% 88.8%
Vestibularimplant:doesitreallywork?Asystematicreview 795
Fig.1 DiagramoftheidentificationandselectionofarticlesadaptedfromPRISMA.
Table4 JBICriticalappraisalchecklistforcasereports.
Guyotetal.30 Golubetal.10
Werepatient’sdemographiccharacteristicsclearlydescribed? Y Y
Wasthepatient’shistoryclearlydescribedandpresentedasatimeline? N Y Wasthecurrentclinicalconditionofthepatientonpresentationclearlydescribed? Y Y Werediagnostictestsorassessmentmethodsandtheresultsclearlydescribed? Y Y
Wastheintervention(s)ortreatmentprocedure(s)clearlydescribed? Y Y
Wasthepost-interventionclinicalconditionclearlydescribed? Y Y
Wereadverseevents(harms)orunanticipatedeventsidentifiedanddescribed? Y Y
Doesthecasereportprovidetakeawaylessons? Y Y
Biasrisk(%) 87.5% 100%
Y,Yes;N,No.
ON condition, the amplitudeof theelectrical stimulation wasmodulatedviathemotionsignalcapturedbyaninertial sensor(gyroscope).SignificantlyhigherVORresponseswere observedwhentheprototypewasturnedON.Furthermore, VORresponsesincreasedsignificantlyastheintensityofthe stimulation increased, reaching on average 79% of those measured in healthyvolunteers inthe sameexperimental conditions.
Pelizzone et al.3 performed VI in three patients with
profound bilateral deafness and vestibularloss. First, the patient received steady state electrical stimulation to restorean artificial‘‘spontaneous’’ firingrateinhis
deaf-ferented vestibular nerve until the nystagmic responses vanished. Once the patient wasin this ‘‘adapted state’’, a gyroscope, to coderotational movements, was used to up-anddown-modulatetheamplitudeofthetrainofpulses delivered to the vestibular electrode. The patient’s eye movementswererecordedwhilethepatientwassubmitted towholebodyrotationsinthehorizontalplaneincomplete darkness.Theresultsshowedthatinpeakangularvelocity at1Hz,theVORgainofthe3testedpatientswasverylow inthesystemoffline(gains <0.2).Inthesystem on condi-tion,thegains inthe3patientsimprovedsignificantlyand reachedup to75---98% ofthe median VORgainof healthy
796 AzevedoYJetal. volunteers.Furthermore,thegainincreasedsignificantlyas
weincreasedtheintensityofstimulation.TheVORgainin thesystemofflinewasverylow,whileitincreased signifi-cantlyinthesystemoncondition,reaching51---69%ofthat observedinhealthyvolunteers.
Guinand et al.32 described eleven BVL patients with
bilateral or unilateral severe deafness, all of whomwere implantedwithaVIdevelopedthroughmodifiedaCI provid-ingonetothreeextracochlear electrodes.Duringsurgery, the cochlear array was inserted, and each extracochlear branch was placed in proximity to the Posterior (PAN), Lateral (LAN), and Superior (SAN) ampullary branches of the vestibular nerve. In total, 24 vestibular electrodes were implanted in these patients. An extralabyrinthine surgical approach was performed in five patients and an intralabyrinthineapproachwasusedinsixpatients.Device activationtookplacenoearlierthanfourweeks postoper-atively, when healingof the surgery site wasassumed to becomplete. Videonystagmography(VNG) and Electronys-tagmography (ENG) were used for vestibular tests. HIT was performed with the Ulmer system (Synapsis©; Mar-seille,France),theEyeSeeCam(EyeSeeCamVOG©;Munich, Germany)and/or the ICS Impulse (Otometrics, Denmark). Cochlear electrodes were always switched off during the experimentalprocedure.Thetwo-dimensionaleye-in-head angular position was recorded using a fast monocular 2D video oculographysystem (EyeSeeCamVOG; Munich, Ger-many). All eye movement recordings were performed in the dark with the patients sitting in an upright position. Nocomplicationsrelatedtosurgeryortotheexperimental procedurewerereported.Despitedifferentetiologies (Idio-pathic, Menière’s, Traumatic, Meningitis and DFNA9) and different disease durations, it was possible to elicit con-trolledeyemovementsofvariableamplitudesanddirections inallelevenBVLpatientsuptoalmost8yearsafter implan-tation.Theseresultsindicatethatelectricalstimulationof thevestibularnervehasasignificantfunctionalimpact;eye movementsgeneratedthiswaycouldbesufficienttorestore gazestabilization during essential everyday tasks such as walking.However,the resultsalsodemonstrate that elec-tricallyevokedeyemovementsresultinasignificantlossof visualacuity.Importantly,thegoalofthevestibularimplant isnottoimpairvisualacuity,buttheopposite.Fromthetime afine-tunedandanappropriatematchbetweenpacingand patientmovementwere made,thepossibilityof improve-ment in visual acuity is real and this would improve the stabilizationoftheimagesintheretina.
In a posterior study of the same 11 patients, Guinand etal.1didnotassessvisualacuityaswasdone inGuinand
etal.32Guinandetal.1hadatotalof24vestibularelectrodes
availableforelectricalstimulationinthese11patients.Of these,threeelectrodeswereunresponsive,soavestibular thresholdwasdeterminedinonly21ofthe24available elec-trodes. In 19 of these electrodes, the upper comfortable level corresponded tofacial nerve stimulation.In 2 elec-trodes, noupper comfortable level was determined even atthehighestcurrentamplitudetested(550mA).The two-dimensionaleye-in-headpositionwasrecordedusingafast monocular2Dvideooculographysystem(EyeSeeCamVOG) toassesstheeffects ofthe electrical stimulation.Alleye movementrecordingsweredone indarknesswithpatients sittinginan uprightpositionwithelectricalstimulationin
thelabyrinthtocapturetheeVOR.Consistentwiththevery variabledynamicrangesmeasured,therangeofeye veloc-itieswasalsoveryvariable.Themeanpeakvelocitiesper electrodeacrosspatientswere8.7---7.6◦/s forPAN(n=11), 13---12.5◦/sforLAN(n=6),and11.9---6.6◦/sforSAN(n=5). The patients diagnosed with DFNA9 showed the smallest responses.Oneoftheresultsofthisstudyisthateye move-ments could be successfully evoked in a heterogeneous group of patients regarding the etiology of the deficit or thedurationofthedisease.
VandeBergetal.16investigatedhowthecharacteristics
of theeVORchangedasafunction ofthemodulation fre-quency inpatients witha VI,and comparedthese results tothe ‘‘natural’’VOR responses obtainedin healthy age-matchedvolunteerswhoweresubjectedtohorizontalwhole body rotations withequivalentsinusoidal velocityprofiles atthesamefrequencies.SevenpatientswithBVLreceived a VI prototype consisting of a modified cochlear implant (MED-EL, Innsbruck, Austria) with extracochlear branches for vestibular stimulation. Twelve vestibular electrodes implanted at different anatomical locations were tested: four electrodes implanted in the vicinity of the superior ampullarynerve,threeelectrodesimplantedinthevicinity ofthelateralampullarynerveandfiveelectrodesimplanted inthevicinityoftheposteriorampullarynerve.Theintensity ofmodulationwaskeptconstantthroughoutthe experimen-tal trials and 3 modulation frequencies (0.5, 1 and 2Hz) weretested.TheeVORexperimentswereconductedunder stationary conditions and the electrical stimulation was deliveredexclusivelytoonevestibularelectrodeatatime. Individual and pooled results revealed a clear frequency-dependent behavior for the threestimulation sites. They observed a strong and significant effect of frequency in the total peak eye velocity of the eVOR: the total peak eye velocityincreased withincreasingfrequency for both groups,withoutanysignificanteffectbetweenthegroups. OthercharacteristicsoftheeVOR(angle,habituation-index andasymmetry)showednosignificantfrequency-dependent effect. This effect was similar to that observed in the ‘‘natural’’ VOR. The eVOR angle was markedly variable acrosstheBVLGroupforthewholetestedfrequencyrange. These results demonstrated that, at least in the specific (limited)frequencyrangetested,theVIcloselymimicsthe naturalfrequency-dependencyofthevestibularsystem.
Phillipsetal.13 implantedfoursubjectswithintractable
unilateral Meniere’s disease. Although the subjects had limitedvestibularfunctionandrelativelypoorhearing pre-surgically,followingimplantationoftheVI,thesubjectslost hearingandvestibularfunctionintheimplantedearrelative to their preoperative levels with no recovery of vestibu-lar function. Additionally, the electrical stimulation of VI appearedtobewelltoleratedbythepatients,withno signif-icantpain,nauseaorelectricallyevokedauditorypercepts inassociation withtheelectrical stimulation.Overall, the vECAPrecordingresultsshowedanincreaseinthe horizon-talslowphasevelocitywithanincreasingstimulusrate.The authorsalsoobservedageneraldecreaseovertimeinthe slowphasevelocityelicitedbyelectricalstimulationinmost canalsinthesefoursubjectswithMeniere’sdisease.
Guinandetal.33evaluatedthreepatientssufferingfrom
severe BVL and implanted with a VI. The high-frequency VORwasassessedusingthevHIT,whilemotion-modulated
Vestibularimplant:doesitreallywork?Asystematicreview 797 electricalstimulationwasdeliveredviaoneoftheimplanted
vestibular electrodes at a time. In three out of the five tested electrodes, the VOR gain increased monotonically with increased stimulation strength when head impulses weredeliveredintheplaneoftheimplantedcanal.Inthe threecasespresented,theVORresponsesmeasuredwithout activationoftheVIweredeficientinbothdirectionsofthe testedplane.
Discussion
The present SR was designed to identify evidence in the scientific literature that VI in people with BVL improves vestibularfunction.
We observed that the intralabyrinthine approach was most frequently used, probably because the extral-abyrinthine approach is surgically more challenging with regard to the extent of the exact site of stimulation. However, the main disadvantage of the intralabyrinthine approach is the risk of hearing compromise when the labyrinthisopenedandtheelectrodesareinsertedintothe semicircularcanals.1Forthisreason,theGeneva-Maastricht
groupchosetoperformsurgeryonlyindeafpatientsinthe implanted ear. The Washington group underwent surgical implantation10,13,31 in four Menière’s patients with
resid-ualhearing:allofthemlosttheirhearing.However,these negativeresultsdonotnecessarilyimply thathearingwill always be affected by the implantation of electrodes in the semicircular canals. Research on rhesus monkeys has shownthathearingpreservationispossiblewiththe intral-abyrinthineapproach.9,14,34,35Therefore,themainchallenge
offuturestudiesistooptimizethesurgicaltechniqueandto developelectrodesthatcaneliciteffectivestimulationfor the activation of vestibular function and, simultaneously, thepreservationofhearinginpatients.
The Geneva/Maastricht team showed that, by using a virtual motion profile to modulate the baselineelectrical stimulation of the ampullary branches of the vestibular nerve,itwaspossibletoartificiallygenerateeyemovements inallBVLpatientsoftheirgroup,independentlyofthe dis-ease etiology,durationof implantation,andmodel of the vestibularimplantprototypeused.Theirresultsalso demon-stratethatelectricallyevokedeyemovementsresultedina significantlossofvisualacuity.
The groupatthe UniversityofWashington showedthat implantationof thedevice infourMeniere’s patients pro-ducedhearingandvestibularlossintheimplantedear.These resultssuggestthatelectricalstimulationofthevestibular endorganinhumansubjectsprovidedcontrolledvestibular inputsovertime,butin Meniere’spatientsthisresultwas apparently obtainedat the costof hearingand vestibular functionintheimplantedear.
WealsoobservedbetterartificialVORresponsesathigher rotation frequencies. At rotation frequencies of 0.1 and 0.25Hz,theartificiallyevokedVORwaspracticallyabsent. TheVORresponsestartedtogrowat0.5Hz,reachinga max-imumperformance at rotation frequencies of 1 and2Hz. This phenomenon resembles well-known and documented dynamiccharacteristicsofthenormalVOR.Important every-day activities such as walking induce head movements predominantlyinthe1---2Hzfrequencyrange.Thisartificial
restorationoftheVORintheseimplantedpatientscanbe thereforeconsideredassubstantialfunctionalrecovery. Fur-thermore,thisachievement waspossiblefor patientswith substantiallydifferentdeficit durationsand withdifferent BVLetiologies.
This SR showed that humans can adapt to electrical stimulation of the vestibular system without too much discomfortandthat77%ofthe18implantedpatients expe-riencedanimprovementinvestibularfunction.
Conclusion
Severalstudies have demonstrated these findings support thefeasibilityofaVItorestoretheVORinabroadfrequency rangeandillustratednewchallengesforthedevelopmentof thistechnologytoguaranteeanimprovementinthe vestibu-larfunctionwithoutlosinghearing.
Taken together, this evidence holds good promise for achievingthefirstrealalternativeforrehabilitatingpatients with a BVL and warrants further research efforts and increasedinterestinthefield.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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