BrazJOtorhinolaryngol.2020;86(5):534---544
www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Cervical
vestibular
evoked
myogenic
potentials
and
video
head
impulse
test
in
Ménière
disease
夽
Thaís
Alvares
de
Abreu
e
Silva
Grigol
∗,
Karen
de
Carvalho
Lopes,
Fernando
Freitas
Gananc
¸a
UniversidadeFederaldeSãoPaulo(Unifesp),EscolaPaulistadeMedicina(EPM),DisciplinadeOtologiaeOtoneurologia,São Paulo,SP,Brazil
Received4October2018;accepted11February2019 Availableonline16March2019
KEYWORDS
Headimpulsetest; Ménièredisease; Vestibularevoked myogenicpotentials; Vestibularfunction tests Abstract
Introduction:Ménière’s disease is among the mostfrequent causes of vestibular disorders.
Althoughitisaclinicaldiagnosis,abetterunderstandingofthepathophysiologyandclinical courseofthediseasethroughtestswouldallowimprovementintheprognosisandmoreeffective treatments.
Objectives:Todescribetheresultsofthecervicalvestibularevokedmyogenicandvideohead
impulsetestinpatients withadefineddiagnosisofMénière’sdiseaseandtocorrelate them withdiseaseduration.
Methods:Thesampleconsistedof50participants,ofwhom29comprisedthestudygroupand
21thecontrolgroup.Theindividualsweresubmittedtoaquestionnaire,otoscopy,audiometry andvestibularfunctionassessmentthroughthecervicalvestibularevokedmyogenicpotential andvideoheadimpulsetest.
Results:Forthevideoheadimpulsetest,lateralcanalgainvaluesbelow0.77wereconsidered
abnormalandfortheverticalchannels,below0.61.Thepercentagesofnormalitywere82.76% for lateral, 89.65%for posterior and91.37% for anteriorcanals. For thecervical vestibular evokedmyogenicpotential,theupperlimitsofnormalforlatenciesweredefinedas18.07ms forp13and28.47msforn23;andintheSG,19.57%showedprolongationoflatencyofp13and 4.35%ofwaven23,whereas18.96%didnotshowbiphasicpotential.
夽 Pleasecitethisarticleas:GrigolTA,LopesKC,Gananc¸aFF.Cervicalvestibularevokedmyogenicpotentialsandvideoheadimpulsetest inMénièredisease.BrazJOtorhinolaryngol.2020;86:534---44.
∗Correspondingauthor.
E-mail:thais.grigol@hotmail.com(T.A.Grigol).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.
https://doi.org/10.1016/j.bjorl.2019.02.002
1808-8694/©2019PublishedbyElsevierEditoraLtda.onbehalfofAssociac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial. ThisisanopenaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
CervicalvestibularevokedmyogenicpotentialsandvHITinMénièredisease 535
Conclusions: Forthevideoheadimpulsetest,adecreasedgainofthevestibulo-ocularreflex
forthelateralcanalwasobserved,withahigherincidenceofoverttypecorrectivesaccades comparedtothecontrolgroup.Forthecervicalvestibularevokedmyogenicpotential,there wasasignificantdifferencebetweenthegroupsfortheinter-amplitudeparameter,including forasymptomaticears.Therewasnocorrelationbetweentheresultsofthetestsanddisease duration.
© 2019 Publishedby Elsevier Editora Ltda. onbehalf of Associac¸˜ao Brasileira de Otorrino-laringologiaeCirurgiaC´ervico-Facial.ThisisanopenaccessarticleundertheCCBYlicense (http://creativecommons.org/licenses/by/4.0/).
PALAVRAS-CHAVE
Testedoimpulsode cabec¸a;
Doenc¸adeMénière; Potenciaisevocados miogênicos
vestibulares; Testesdefunc¸ão vestibular
Potencialevocadomiogênicovestibularcervicaletestedeimpulsocefálicoporvídeo
nadoenc¸adeMénière
Resumo
Introduc¸ão: A doenc¸a deMénière estáentre ascausas mais frequentesde vestibulopatias.
Apesardeodiagnósticoserclínico,compreendermelhorafisiopatologiaeocursoclínicoda doenc¸apormeiodosexamesvestibularespermitemelhoresprognósticosetratamentos.
Objetivos: Descrever resultados dopotencial evocadomiogênico vestibular cervicaleteste
deimpulsocefálicoporvídeoempacientescomdiagnósticodedoenc¸adeMénièredefinidae correlacionarcomotempodedoenc¸a.
Método: A amostra foi constituída por50 participantes, dos quais 29 compuseram ogrupo
deestudoe21formaramogrupocontrole.Osindivíduosforamsubmetidosaumquestionário clínico,otoscopia,avaliac¸ãoaudiológicaeavaliac¸ãodafunc¸ãovestibularpormeiodopotencial evocadomiogênicovestibularcervicaletestedeimpulsocefálicoporvídeo.
Resultados: Paratestedeimpulsocefálicoporvídeoforamconsideradosalteradososvalores
de ganhopara canal lateralabaixo de0,77e para oscanais verticais abaixo de0,61; eos percentuais denormalidadeparaogrupode estudoforam82,76%para lateral;89,65%para posterior e 91,37% anterior.No potencial evocadomiogênico vestibular cervical, os limites superioresdaslatênciasforamdefinidos18,07msparap13e28,47msparan23;nogrupode estudo19,57%apresentaramprolongamentodalatênciadap13e4,35%daondan23e18,96% nãoapresentaramopotencialbifásico.
Conclusões: Noteste de impulsocefálico por vídeoobservou-seganho do reflexovestíbulo
oculardiminuídoparaoscanaislaterais,commaiorocorrênciadesacadascorretivasdotipo
overt.Paraopotencialevocadomiogênicovestibularcervicalobservou-sediferenc¸asignificante
entreosgruposparaoparâmetrointeramplitude,inclusiveparaorelhasassintomáticas.Não foievidenciadacorrelac¸ãodosresultadosdosexamescomotempodedoenc¸a.
© 2019Publicadopor ElsevierEditora Ltda.em nomede Associac¸˜ao Brasileira de Otorrino-laringologia eCirurgiaC´ervico-Facial.Este ´eumartigo Open Accesssob umalicenc¸a CCBY (http://creativecommons.org/licenses/by/4.0/).
Introduction
Ménière’s disease (MD),initiallydescribed in 1861, is one of the most frequent vestibular disorders. It is consid-eredamultifactorialdisease,characterizedbysymptomsof episodicvertigo,fluctuatinghearingloss,tinnitusandaural fullness.1,2
Endolymphatichydrops,thedistention ofthe endolym-phatic space, was discovered by Hallpike and Cairns3 in thetemporal bonesof patientswiththis condition.It has longbeenbelievedthatendolymphatichydropsaloneisthe histopathological substrate of MD,but this finding cannot explainthecomplexityoftheclinicalpicture.
ThediagnosisofMDisclinicalandbasedonthepresence ofcharacteristicsymptoms.Accordingtothecurrent classi-fication,publishedin2015,releasedbytheBáránySociety,
TheJapan Societyfor EquilibriumResearch,theEuropean AcademyofOtologyandNeurotology(EAONO),theAmerican Academy of Otolaryngology-Head andNeck Surgery (AAO-HNS)and theKoreanBalance Societycommittees,MDcan beclassifiedasDefinite or Probable.MDis categorizedas Definite when there aretwo or more episodes of vertigo lastingbetween20minand12h,documentedsensorineural lossatlow or mediumfrequency (below2kHz)and symp-toms of hearing fluctuation (hearing loss, tinnitus and/or auralfullness).TheProbableMDischaracterizedbytwoor moreepisodesof vertigo lasting between 20min and24h andsymptoms of hearingfluctuation(hypoacusis, tinnitus and/orauralfullness).1
Accordingtotemporalbonestudies, hydropsformation occurs in the cochlea, sacculus, utricle and semicircular canals,inadecreasingorderoffrequency.4,5Althoughthe
536 GrigolTAetal. diagnosis is a clinical one, a better understanding of the
pathophysiology and clinical course of the disease could resultina moreaccurateand timelydiagnosis andlessen the impairment of the quality of life of patients with MD.Therefore,the examsthat assessthe function ofthe auditory and vestibular system could assist in the treat-ment, especially in the early stages.6 Currently, because of thehigh prevalence of hydropsin thesaccular region, oneof the morefrequently utilizedexamsis the cervical VestibularEvokedMyogenic Potential(cVEMP).cVEMP isa short-latency,biphasicmusclepotentialthatevaluatesthe inferiorportionofthevestibularsystem,specificallythe sac-cule, inferiorvestibular nerve,vestibular-spinal pathways andneuromuscularplaque.Afterauditorystimulation,the vestibular-spinalmusclereflexismanifestbyacontraction ofthecervicalmusculature.7,8
ItwasobservedthatcVEMPinMDisveryuseful,asithelps todetectanddocumentchangesinthesevestibularregions andtoidentifythediseasestage.Theliteraturefindingsare diverse, andan absenceof biphasic potentials, increased latency,decreased inter-amplitude intervaland increased asymmetryindexhaveallbeendescribedinMD.9---11Another interestingfindingisthatofthepresenceofabnormalitiesin theasymptomaticear,suchasabsenceofcertainwavesor increasedlatency,whichmayrevealthepossibleevolution ofthediseaseasoccultbilateralMD.12,13
Anotherverycurrentexamthatallowsthedetectionof alterationsintheOculovestibularReflex(OVR)inthethree semicircularcanalsistheVideoHeadImpulseTest(vHIT).It identifyiesandquantifiestheHeadImpulse Test(HIT)test commonlyperformedinneurotologicalevaluation.
During the evaluation, rapid and unpredictable head movementsareappliedinthehorizontalandverticalplanes andtheeyesmustremainatafixedpoint.Whenthereisan abnormalOVR,theeyesdonotremainfixedandthereare ocularcompensatorymovements,calledsaccades.The sac-cadescanbetriggeredduringthecephalicimpulse(covert), notvisibletothenakedeye,oraftertheimpulse(overt).14 SeveralparameterssuchasOVRgain,andsaccade charac-teristics(latency,velocity,andrateofoccurrence)gavethe vHITincreasedsensitivityandspecificitywhencomparedto theHIT.15
TheliteraturefindingsontheuseofvHITinMDare vari-able.Moststudiesshow normalgainor smallreductionin OVRgain.16---18Somestudiescorrelatetheresultsobtainedat thisexamwiththeevaluatedperiod(crisisorinter-crisis), timeofdiseaseanddegreeofhearingloss.19,20
ThecVEMPandvHITareeasytoperform,non-invasive, andwelltoleratedbythepatient.Theybothallowa func-tionalevaluationofthevestibularsystem,whichfavorsthe earlyinvestigationandmonitoringoftheclinicalevolution ofMD.Therefore,objectiveandreliabletestssuchasthese canhelpinthedifferentialdiagnosis.
Thisstudywasproposedafternotingthehighprevalence ofMD in thepopulation and theneed for complementary tests that investigate and help in the disease monitoring andevolution.FewstudieshaveevaluatedMDaccordingto thecurrentclassificationof2015.Thus,weseektoincrease knowledge by exploring and identifying the structures involved in MD and the effects on body balance, which may contribute to the choice of the best therapeutic strategy.
Theobjectivesofthisstudyweretoevaluatetheresults ofthecVEMPandvHITinpatientsdiagnosedwithdefiniteMD inthesymptomaticandasymptomaticearsandtocorrelate testresultswiththetimeofdisease.
Methods
This is an observational,cross-sectional study carried out at the Department of Otorhinolaryngology and Head and Neck Surgery of Escola Paulistade Medicina/Universidade FederaldeSãoPaulo,afterapprovalbytheResearchEthics Committee,number706.875/2014.
Thesampleconsistedof50participants,ofwhom29 con-stitutedtheStudyGroup(SG)and21theControlGroup(CG). Patients of both genders aged between 18 and 70 years, with a medical diagnosis of definitive unilateral or bilat-eralMénière’sdiseaseaccordingtotheclassificationofthe currentCommittees(2015),wereincludedintheSG.1This clinicaldiagnosiswasconsideredasthegoldstandardinthis study.
TheCGconsistedofvolunteerswithoutcomplaintsor his-toryofdizziness,hearingloss,otologicsurgeryormiddleear abnormalities.
All study participants received explanations and infor-mationonthe studyand wereaskedtosign the Freeand InformedConsentForm.Thefollowingwereexcludedfrom the study: patients with probable MD, patients who had undergonesomeinvasiveprocedure,historyofheadtrauma, otologic surgery, middle ear and retrocochlear diseases, neurologicalandpsychiatricdiseases,cervicalrotation lim-itationsandvisualimpairment.
After the clinical evaluation, performed by the same otorhinolaryngologist, all subjects were submitted to a clinical-demographic questionnaire,otoscopy,audiological andvestibularfunctionevaluationwithcVEMPandvHIT.
ThediseasewasstageedaccordingtotheAAO-HNS Audi-toryandBalanceCommittee(1995)classification,basedon themeanofthetonalthresholdsof500Hz,1kHz,2kHzand 3kHz,inthesymptomaticear,attheworstaudiometry.This meansubdividesthediseasestageintoStagesI(≤25dB),II (26---40dB),III(41---70dB)andIV(>70dB).
The ICS Charp EP200 (GN-Otometrics) equipmentwas usedtoperformthe cVEMP,Disposablesurfaceelectrodes were used,afterskin dermabrasion,to capture responses andcontroltheElectromyographic(EMG)activity.The max-imumimpedanceallowedfortheelectrodeswas5ohms(). Theplacementofthesurfaceelectrodesfollowedthisorder: activeelectrodeplacedintheupperhalfofthe sternoclei-domastoidmuscle,ipsilateraltothesoundstimulationand below the electrode that controls the electromyographic activity; the reference electrode, on the manubrium of thesternum boneandthe groundelectrodein thefrontal midline. The patientremainedseated, withmaximal cer-vical rotationof thehead tothe sidecontralateraltothe stimulus.21
The rarefaction tone burst stimuli, presented through insertionphones,withatotalof150 stimuli,wasusedfor cVEMP recording. The tested frequency was500Hz, with a 97dBHL intensity,10Hz high-passand1000Hz lowpass filters,and60msrecordingwindow.
CervicalvestibularevokedmyogenicpotentialsandvHITinMénièredisease 537 R195(500) [9.2] R195(500) [10.2] ADD N1 P1 ADD P1 N1 L195(500) [1.1] L195(500) [2.1] -5.00 0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 -5.00 0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00
Figure1 ExampleofCervicalVestibularEvokedMyogenicPotentialevokedbilaterally.
Theacquiredresponsesconsistedofabiphasicpotential withthefirstpositivewaveexhibitingalatencyof approxi-mately13ms,knownasp13,andthesecondnegativewave havingalatencyofapproximately23ms,knownasn23.Each earwastesteduntilreproducibleresponseswereobtained, andthetwobestwaveswerechosen,withtheweightedsum ofboth beingperformed andathirdrecordwasobtained, which was used for analysis (Fig. 1). Electromyographic responseswereaccepted between50and200V,inorder tomaintainadequate andconstantcontraction level.The cVEMPparametersconsidered inthisstudywerethe pres-ence of biphasic potential, absolute latencies of p13 and n23,p13---n23 inter-amplitudeintervalandtheAsymmetry Index(AI).
The interpretation of the cVEMP results was based on thereferencevaluesdeterminedbytheCG.Thereference valuesfortheinterpretation ofnormalityforp13andn23 latencies, p13 and n23 inter-amplitude and AI were cal-culated by the mean±2 standard deviations (SD).22 This methodwasselectedtoallowthequalitativeclassification oftheresultsofcVEMPasnormaloraltered,unilateralor bilateral.Theabsenceofthebiphasicpotential,anincrease inthelatencyofp13orn23,adecreaseinthep13---n23 inter-amplitudeandtheAIabovetheupperlimitwereinterpreted asabnormalresponses.
TheICSImpulse(GN-Otometrics)equipmentwasusedto performthevHIT.The vHITsystem consistsofglasses and integratedvideo-oculographycamerawithsensorsthatare connectedtotheheadbyanelasticband.Thecamera ana-lyzesthe movement of the eyesat a samplingrate of up to250Hzand hasa mirror thatreflects the image of the patient’seyeintothecamera.Asmallsensorintheglasses measures the headmovement. The test wasappliedwith theindividual sittingin achair approximately1.0m away fromthetarget,duringwhich thesubjectisinstructed to keeptheeyesonafixedpoint.19,23
The researcher applied unpredictable frequency and direction movements in the planes of the semicircular canals, withlowamplitude (near10◦ to20◦),high veloci-ties(above100◦s) andaccelerations(2000---6000s2).First, movementswereperformedinthehorizontalplaneto eval-uatethelateralcanals. Soonafter,thepatient’sheadwas turned 30◦ to the right, and head movements were per-formed back and forth in the vertical plane to test the synergicpairsoftheleftanteriorandrightposterior(LARP ---LeftanteriorandRightPosterior)semicircularcanals. Sub-sequently,theinstructionwasrepeatedwiththeheadat30◦ totheleftandtherightanteriorandleftposterior(RALP
---RightAnteriorandLeftPosterior)canalswereevaluated.In allevaluations, the individual wasinstructed tokeep the eyes on a fixed point. During the test, at least 10 head impulseswereperformedineachevaluatedplane.14,19,24
Basedontherecordingofthecephalicandocular veloc-ity,thecalculationof theOVRgainwasperformed bythe equipment. The OVR gain was represented by the mean ratioof thesevelocities (Fig.2). The corrective saccades weredetectedbytheequipmentandqualitativelyclassified accordingtotheirlatencies.Thecovertsaccadesoccurred beforetheend of theimpulse, approximately100msand theovertsaccades100msaftertheheadmovement.14,25
TheinterpretationofthevHITresultswasbasedonthe referencevalues determinedby the CG. The vHIT results werecalculated by the mean±2 SD. Abnormal responses weredecreased OVR gain andthe presence of corrective saccades(covertorovert).
The data were tabulated and analyzed in order to describe the clinical and demographic characteristics of patientsandtoestablishapatternofdistributionbetween thegroups.TheShapiro---Wilkstestwasusedtoevaluatethe normaldistribution between the groups. Parametrictests wereusedwhentherewasanormaldistribution,and non-parametriconeswhentherewasanon-normaldistribution. Theeffectsizeofthedifferencebetweenthegroupsfor eachvaluewasmeasuredbycalculatingthecoefficientdor thecoefficientr.Inthecorrelationanalysis,thecorrelation coefficient (r) wascalculated, which couldvary from −1 to+1. Thestatistical significancewassetat 5%(p<0.05). The95%ConfidenceIntervals(95%CI)werecalculatedusing thebias-correctedandacceleratedmethod,basedon2000 bootstrapsamples.
Results
The study sample consisted of 50 individuals, distributed into two groups. The Study Group (SG) consisted of 18 womenand11men,withameanageof52.24yearsandthe ControlGroup(CG)of 15womenand6men,withamean ageof39.67years.
Asforthesamplehomogeneitystudy,nostatistically sig-nificantdifferences wereobserved between thegroups in relationtogender(p=0.557).Regardingage,thegroupsdid notshow anormal distribution.The results showed there wasastatisticallysignificantdifferencebetweenthegroups, withthepatientsfromtheSGbeingolderthanthosefrom theCG.
538 GrigolTAetal.
Left
Right Right mean Left mean 1.2 300 200 100 0 -100 300 200 100 0 -100 -140 0 140 280 420 560 -140 0 140 280 420 560 1.0 0.8 0.6 0.4 0.2 0.0 40 80 120 160 200 240 280 Gain
Peak velocity (deg/s)
Left lateral (LL) ms RIght lateral (RL) ms Mean gains 0.96 Mean gains 1.07
Head & e y e v elocity Head & e y e v elocity
Figure2 Exampleofthevideoheadimpulsetestrecordinginthelateralcanals.
Table1 ClinicalcharacteristicsofpatientswithMénière’s disease.
Initialsymptoms Stageofdisease Headache Dizziness:21 (72.41%) I:7(18.92%) Non-migraine: 9 (31.03%) Tinnitus:18 (62.07%) II:11(29.73%) Hearingloss:14 (48.28%) III:17(45.95%) Migraine: 5 (17.24%) Auralfullness:8 (27.59) IV:2(5.40%)
Regardingdiseaselaterality,22(75.9%)patientshad uni-lateral MD and 7 (24.1%) had bilateral MD, totaling 36 affectedearsinthesample.Asforthedistributionof unilat-eralMD,12(41.4%)hadMDintherightearand10(34.5%) inthe leftear. Of thepatients withbilateral MD, allhad theinitialsymptomsinonlyoneearand,subsequently,the diseaseprogressedtotheoppositeear.
Thetimeofdiseaseevolutionuntilthecontralateralear wasaffectedrangedfrom2monthsto15years.Themedian durationofthediseasewas6years,withamean8.57years, rangingfrom4monthsto25years.
Theinitialsymptoms,diseasestage(hearinglossinthe earwith MD)and the presence of headache(migraine or non-migraine)areshowninTable1.
TocalculatethethenormalitypatternforvHIT,2DPwere subtractedfromthemeangainvalues.Therefore,gain val-ues for lateral canal <0.77 and gain values for vertical channels <0.61were consideredabnormal. In theanalysis ofthe gainvalues forOVR inthe SG, withrespecttothe symptomaticandasymptomatic ears(58ears),82.76%(48 ears)had normalresults for thelateral canal,89.65% (52 ears)for the posteriorcanal and91.37% (53 ears)for the anteriorcanal.
Elevenearsin theSG(18.96%)didnotshow abiphasic potentialresponsenordid3ears(7.14%)intheCG.Forthe analysis of cVEMP parameters, subjects with noresponse wereexcluded,sotheSGconsistedof25earsandtheCGof 39ears.
Theasymmetryindex(AI),aparametercalculatedonly inthe presence of bilateral response,was obtainedin 19 individualsfromtheSGand19fromtheCG.Theupperlimits ofnormalforthelatenciesweredefinedbythemeanplus2 SD:18.07msforp13and28.47msforn23.Itwasobserved that19.57%oftheearsintheSGshowedprolongationofthe p13latencyand4.35%ofthen23wave.
AccordingtotheearaffectedbyMD,theSGwas subdi-videdinto symptomatic(n=36) andasymptomatic (n=22) ears.
There was a statistically significant difference among the three groups regarding lateral canal gain (p=0.002), andpost hocanalysisshowedadifferencebetween symp-tomaticearsandtheCG,butnotbetweenthesymptomatic andasymptomaticears(p=0.718)andbetweenthe asymp-tomaticearsandtheCG(p=0.093).Thesymptomaticears showedlessgaininthelateralcanalinthevHITcompared totheearsoftheCG. Regardingthegainoftheposterior andanteriorcanals, therewasnodifferencebetween the ears(Table2).
When considering the presence of corrective saccades in vHIT, there were no corrective saccades in the poste-riorandanteriorcanalsinbothgroups.Whencomparingthe ears in relation tothe occurrence of saccades in the lat-eralcanal, asignificant differencewasobserved between thegroupsofears.Saccadeswereabsentmoreofteninthe asymptomatic ears of theb SGthan in the CG. Regarding thesaccadesubtypes(overtandcovert),therewasno sta-tisticalsignificance,despitethemorefrequentpresenceof overtlateralsaccades.
Regarding the presence of the biphasic potential of cVEMP, there was a statistically significant difference between the groups. Failure to record the potential in the symptomatic ears was more common than such a failure to record it in the asymptomatic ears and the CG. Regarding the asymptomatic ears and controls, there was no difference in relation to the presence of cVEMP.
FortheanalysisofcVEMPresults,thevaluesofeachear wereconsideredindividually,soitwasnotpossibleto estab-lishthiscomparativeanalysisforAI.The resultsofTable3 show that there was a statistically significant difference among the threegroups regarding cVEMP inter-amplitude (p<0.002),andtheposthocanalysisshowedthattherewas a statisticallysignificant difference betweenthe group of symptomaticearsandtheCG(p<0.001),andbetweenthe group ofasymptomatic ears andthe CG(p=0.001). Thus, bothsymptomaticandasymptomaticearsofindividualswith MDshowedlowercVEMPinter-amplitudewhencomparedto theCG.Therewasnostatisticallysignificantdifferencein thelatencyvaluesofwavesp13andn23betweentheears (Table3).
Attemptingtoascertainwhethertherewasacorrelation between timeof the disease and the performed tests, p
valuewascalculatedusingSpearman’s(non-parametric)or Pearson’s(parametric)tests,andthecorrelationcoefficient
Cervical vestibular evoked myogenic potentials and vHIT in Ménière disease 539
Table2 Descriptivevaluesandcomparativeanalysisoftheearsinrelationtothevestibulo-ocularreflexgainvalues,accordingtotheevaluatedcanal,atthevideohead impulsetest.
Gain Ear Mean SD Median Min Max p Posthoc p d
Lateral canal Symptomatic 0.89[0.84/0.95] 0.17 0.93[0.89/0.95] 0.59 1.26 0.002a S×A 0.718 0.303 Asymptomatic 0.93[0.88/0.86] 0.12 0.92[0.85/1.01] 0.73 1.13 S×C 0.001a 0.935 Control 1.01[0.97/1.05] 0.12 1.02[0.96/1.06] 0.76 1.24 A×C 0.093 0.645 Posterior canal Symptomatic 0.82[0.76/0.87] 1.81 0.82[0.76/0.88] 0.27 1.31 0.653 Does not apply --- ---Asymptomatic 0.79[0.73/0.86] 0.18 0.82[0.75/0.86] 0.37 1.18 Control 0.83[0.80/0.86] 0.11 0.85[0.85/0.85] 0.52 1.08 Anterior canal Symptomatic 0.80[0.74/0.86] 0.18 0.76[0.72/0.86] 0.41 1.17 0.286 Does not apply --- ---Asymptomatic 0.84[0.77/0.92] 0.18 0.83[0.74/0.92] 0.48 1.20 Control 0.86[0.82/0.90] 0.13 0.87[0.83/0.91] 0.60 1.16
Note:One-wayANOVAwithposthocanalysisusingtheGabrieltest. SD,standarddeviation;Min,minimum;Max,maximum;d,effectsize.
Thevaluesinbracketsindicatetheupperandlowerlimitsofthe95%ConfidenceIntervals.
540
Grigol
TA
et
al.
Table3 DescriptivevaluesandcomparativeanalysisoftheearsinrelationtotheparametersevaluatedbytheCervicalVestibularEvokedMyogenicPotentialinthegroups ofsymptomatic,asymptomaticandcontrolears.
cVEMP Ear Mean SD Median Min Max p posthoc p d
Latency p13 (ms) S 15.40[14.37/16.56] 2.80 14.33[13.95/15.83] 12.25 21.50 0.134a Does not apply --- ---A 14.34[13.37/15.43] 2.41 13.93[12.75/14.67] 11.83 19.83 C 14.99[14.51/15.46] 1.54 15.00[14.75/15.33] 11.50 18.67 Latency n23 (ms) S 23.70[22.19/25.25] 3.27 23.30[21.50/24.67] 19.00 30.60 0.074b Does not apply --- ---A 22.52[21.40/23.67] 2.86 22.00[20.42/23.08] 18.33 27.67 C 24.22[23.53/24.91] 2.13 24.67[23.67/25.00] 19.42 28.50 Inter-amplitude (V) S 86.80[68.57/105.62] 51.90 72.05[68.48/81.62] 18.68 213.47 <0.001a,cS×A >0.999 0.132 A 119.31[84.45.160.52] 102.22 79.51[63.08/114.58] 17.72 445.86 S×C <0.001a 0.602 C 215.05[176.20/258.90] 135.82 174.56[135.03/208.10] 56.38 640.70 A×C 0.001a 0.462
Note:Kruskal---Wallistest(a)withposthocanalysisusingtheDunn---Bonferronitestandone-wayANOVA(b).
cVEMP,CervicalVestibularEvokedMyogenicPotential;S,symptomatic;A,asymptomatic;C,control;SD,standarddeviation;Min,minimum;max,maximum;d,effectsize. Thevaluesinbracketsindicatetheupperandlowerlimitsofthe95%confidenceintervals.
CervicalvestibularevokedmyogenicpotentialsandvHITinMénièredisease 541 Table 4 Correlation analysis between time of disease
andexamparameters:CervicalVestibularEvokedMyogenic Potentialsandvideoheadimpulsetestforthesymptomatic ears.
Variable Timeofdisease
cVEMP---Latency P13 r −0.059[−0.423/0.409] p 0.780a cVEMP--- Latency N23 r −0.048[−0.406/0.422] p 0.821a cVEMP ---Amplitude r 0.084[−0.190/0.403] p 0.690a cVEMP ---AsymmetryIndex r 0.054[−0.358/0.542] p 0.826 VHIT---Lateral Gain r −0.007[−0.368/0.331] p 0.968a VHIT---Posterior Gain r −0.049[−0.367/0.234] p 0.778a VHIT---Anterior Gain r 0.127[−0.295/0.545] p 0.462a
Note:Pearson’scorrelationtest(a)andSpearman’scorrelation test(b).
(r).ThevHITparametersshowednostatisticallysignificant correlationwithtimeofthedisease(Table4).
Discussion
Withrespecttothedemographiccharacteristicsofpatients with MD,the sample had a higher prevalence of females (62.02%).InastudyevaluatingtheprevalenceofMDinthe population,itwasobservedthatwomenaremoreaffected thanmen,ataratioof1.89:1.26Themeanageofthe sub-jectswas52years,withanagerangevaryingfrom19to69 years.Asimilarmeanagewasobservedinanotherstudy,27 andasimilaragerangehasalsobeenreported.4,28---30Asfor themeanage ofdiseaseonset,the currentstudy found a meanof44.1years,aresultsimilartothatobservedinother studies.31,32
Inthepresentstudysample,mostpatientshadunilateral disease22(75.90%)andofthese,therightearwasaffected in12subjects(54.50%).Moststudiesincludedpatientswith unilateral MD12,18,19,27 and the predilection for oneof the earswasnotaconsensus.
Considering the prevalence of bilateral MD (24.10%), another study also obtained a similar prevalence, with 20.00%ofthepatientsdiagnosedwithinvolvementinboth ears.33Patientswithbilateralinvolvementinthisstudy ini-tiallyhaddefiniteMDinoneoftheearsandthenthedisease progressedbilaterally,withtimeofdiseaseevolution vary-ingfrom2monthsto15years.InthestudybyPerezetal.,34 thetimeintervalbetweentheinitialdiagnosisandthe dis-easeonsetinthe oppositeearrangedfrom3to26years. The occurrenceofbilateral involvementmayindicate dis-ease progression and depends on factors such as timeof evolution anddiagnosticcriteriaused.Bilateral MDrarely presentswithsimultaneousonsetinboth ears,butis usu-allysequentialwiththecontralateralearbecominginvolved onlyaftersomeyears.35
Thepresentstudyshowedgreatvariationregardingthe durationofdisease(4monthsto25years).Thiswide vari-ationwasalso reportedin other studies.18,27,36 As for the initial symptoms to appear in this study, dizziness and tinnituswerethemostcommon.Inagreementwiththe lit-erature,the prevalence of dizziness wasfound to bethe initialsymptom,followedbytinnitus.29,37Whatmayexplain thehigh occurrenceof dizzinessastheinitial symptom is thepossibilitythatvestibularMDistheinitialformof dis-easedevelopment, which is corroboratedby a study that evaluatedtheonsetofvertigo,hearinglossandtinnitusin MD and associated with endolymphatic hydrops, assessed throughmagneticresonanceimaging.29
Thepresenceofheadachewithmigrainecharacteristics wasalsoobservedinthisstudy.Theoccurrenceofmigraine in MD can vary from 22% to 56%, being more prevalent than in the general population.38,39 A study suggests that theremaybethesamepathophysiologyandsome genetic componentbetween MD andmigraine.39 Although not yet proven,onehypothesisisthatvasospasticeventsassociated withmigraineresultindamagetotheinnerear, predispos-ingtheeartoauditoryandvestibularsymptoms,35 aswell asthe presenceof mutations ingenes relatedto voltage-dependentneuronalchannels.40
Asforthedegreeofhearingloss,therewasaprevalence indescendingorderofStagesIII,II,IandIV.Kimetal.37when studyingMD, found the same proportionof prevalence of StagesIIandIII.Leeetal.20whenevaluatingpatientsduring thecrisisfoundahigheroccurrenceofStageI,thenIIIandII. ThestudybyRubinetal.,18whichanalyzedadvanced unilat-eralMDwithaprogression>1yearandmorethanonecrisis permonth,foundahigherproportionofStageIII,followed byIV,IIandI.
MDisamultifactorialcondition witha variabledisease courseandduration.Someauthorsperceiveitasa contin-uumofaninitialdiseasethatevolvesintoafullydeveloped diseaseentity.29 However,itisaconditionthatisstillwell studied,andthetestsbecomealliesforthefunctional eval-uationofthesepatientsandthedifferentialdiagnosisofthe disease.5Theprevalenceofhydropsis100%inthecochlea, 86.3%in the saccule, 50% in the utricle and36.4% in the semicircularcanals.41
Currently, vHIT has become a useful clinical tool to quantitativelydetectthefunctionofthethreepairsof semi-circularcanals,throughtheevaluationofangularOVR.42
There are studies that have reported different results thanthoseofthepresentstudy.Theonlystudythat evalu-atedvHITindefiniteMDsubjectsusingthesamediagnostic criteria found vHIT gain to be 100% of the normal, and the established standard of normality was 0.78 for the lateralcanalsand0.64forverticalcanalsHowever,the sam-pleincluded only advanced MD.18 Other studies usingthe previousAAO-HNScriteriafound differentresults.17,20 The discrepanciesinresultsbetweenthestudiesmayberelated tothe differences in the methods and diagnostic criteria used,periodevaluated(crisisor inter-crisis) andstandard ofnormalityforOVRgain.
Following theorderof MD involvement,the semicircu-larcanalsarethelastsitestobeaffectedintheinnerear, whichcouldexplaintheusuallynormalresultsinvHIT.5The semicircularcanalsaremore resistant tohydropic expan-sionandhavethickerandmorerigidwallsthanthesaccule,
542 GrigolTAetal. forinstance.43 Additionally, it issuggested thatthe
disso-ciationbetweennormal vHITandalteredcalorictestmay beanindicatorthatthepatienthasMD,sincehydropshas littleeffectontheresponsesofthecupulainthecephalic impulse.44
Anexplanationforfindingmoreabnormalresultsinthe lateralcanal,comparedtoverticalcanalscouldreflectthe vestibularanatomyanddiseasepathophysiology.The verti-calcanalshavegreatermarginal spaceincomparisonwith the horizontal ones, favoring an additional resistance to thevolumecausedbythehydrops.Thus,thepressurethat impairs the endolymphatic flow would be proportionally smallerintheverticalcanals.19
As for the presence of saccades, the study by Blödow et al.25 showed a higher prevalence of the overt com-pared to the covert subtypes, as did the present study. Thissamestudyindicatedthattheoccurrenceofsaccades investibulardysfunctionsis common,withovertsaccades appearing more frequently, alone or in combination with covertsaccades,mainlyinacutevestibularinjury.14 There isa decreasein the OVRgainin vestibularloss and refix-ationsaccadesareattempttocompensateforthisfailure. Whenthepatientcannotkeephiseyesonthetarget,covert saccadesoccuraspartof adynamiccompensation, which aim to stabilize the gaze. However, when the eyes can-not reach the target, the secondary overt saccades may appear,aclearsignof vestibulardysfunction.25,45As overt saccades occur later, theyare related toa central visual firingmechanism; the mechanism for thecovert saccades remainsuncertain.25 Itwasalsoobservedthat,ascephalic impulseaccelerations increased, covert saccades became more common.45 This finding confirms the importance of vHITat highaccelerations. Moreover,saccadesare impor-tantfortheunderstandingofplasticityduringtherecovery fromunilateral vestibularloss,sincetheyarerelatedtoa compensationmechanismorsubstitution withinthe oculo-motorsystem.46
Supportingtheresults ofthepresent study,most stud-iesdidnotfindvHITtobeanexamthatdetectschangesin asymptomaticearsasapredictorofbilateralMD.Inastudy in which OVR was evaluated in patients after parenteral antibiotictherapywithgentamicin,areductioningainwas alsoobservedontheasymptomaticside,butthiseffectwas onlypresentforlowergainvalues,ofaround0.38.47
The cVEMP, in turn, is also a broadly used clinical examinationtoinvestigatedifferentneurologicaland neu-rotological disorders.21 The lastsystematic reviewcarried outbytheAmericanAcademyofNeurology8indicatedthat animalstudies suggest thatcVEMPis moreclosely related tosacculefunction;however,theaccuracyofbothcervical andocularVEMPtoaccuratelyidentifythevestibular func-tionofthesaccule andutricleis stillunknown.According tothisreview,studiesindicatethepossibilitythatVEMPcan helpevaluatethedisease,butitisnotconclusivethatVEMP canbeusedtodiagnoseMD.But,thistestmaybeusefulin theclinicalmonitoringofpatientswithMD.
Intheliterature,moststudiesusedthediagnosticcriteria ofAAO-HNS(1995)forthediagnosisofMD,buthadvariable anddivergentresults.4,9,12
Theonlystudywefoundthatusedthecurrentcriteriaof 2015,observeddifferencesbetweenthegroups(definiteMD andcontrols)forallcVEMPparameters,andtheabnormal
responses were 3.00%absence of potentialand 33.00% of abnormallatenciesofthep13andn23waves.21
RegardingthemeansandlimitsofnormalityofthecVEMP parameters,thereis greatvariability betweenthe results (equipment,typeofstimulus,adoptedparameters). There-fore,itisimportantthateachresearchcenterstandardize thereferencevaluesbasedonexamsperformedinhealthy individualsandindifferentagegroups.7,10
StudiessuggestthattheabsenceofcVEMPcanberelated to decreased sensitivity in the saccular region, occult vestibular alteration or insufficient muscle contraction.9 Thislastfactorwasruledoutinthisstudy,since electromyo-graphy recordings to monitor the sternocleidomastoid muscle contraction were obtained. Other authors also inferred that,depending on theevolution of the disease, patients may show irreversible degeneration of the sen-soryepitheliumofthesaccularmacula,culminatinginthe absenceofthebiphasicpotential.6,12,48
Latencyprolongation,especiallyofthefirstpeak(p13), can be related to changes in the saccule such as high endolymphatic pressure, impairing sound transmission.12 Otherinvestigatorssuggestothercauses,suchas vestibular-spinal tract lesions, such as multiple sclerosis, and a retrolabyrinthineabnormalitya.36,48Theasymptomaticears alsoshowedincreasedwavelatency,buttoalesserdegree, indicatingapossiblebilateraloccultalteration.12,21
Inter-amplitudeinterval,aparameterthatwasreduced inthe earwithMDinthepresent study,reflects the mag-nitudeofthevestibular-spinalreflex.10Manystudiesdonot considerthisparameterwhenitis assessedalone,sinceit hasgreatintersubjectvariability,duetodifferencesin mus-clemassandtoneofeachindividual.9,12Forbettercontrol, theinter-amplitudeintervalinthepresentstudywas stan-dardized by the electromyographic activity control. Some studiesalsofoundadecreaseinpeak-to-peakamplitudein patientswithMD.6,37
In turn, the AI in the current study did not exhibit a significant differencebetween the groups, and thisresult was attributed to the large standard deviation found in the CG, which translated into a high upper normative limit. A study by Silva et al.21 corroborates the find-ings of the present study and also found no difference in relation to AIbetween patients with MDand controls. However, several studies have reported abnormalities of this parameter in MD.10,11 The increase in the asymme-try index can lead to two interpretations, one of which may be the amplitude increase in the affected ear, sug-gesting a high sensitivity of the saccular macula as the hydrops approaches the stapes footplate. However, most of the time,it reflects the decrease in the amplitude of the affected side compared to the healthy side, culmi-natingin an elevated AI.22 Other studieshave shown that the AI can help in the clinical monitoring of MD progres-sion, ashigherindexeswere observedfor more advanced diseasestages, reflectinggreater asymmetrybetween the labyrinths.22,36
Studies in the literature suggest the possibility that cVEMP can predict involvement of the asymptomatic ear, either incasesofoccultsaccularhydropsor inalterations in the binaural interactions of the otolith-cervical reflex arc;12,21theseareinharmonywiththefindingsofthepresent study.cVEMPalterationsintheasymptomaticearareinline
CervicalvestibularevokedmyogenicpotentialsandvHITinMénièredisease 543 withthehigh prevalenceofsaccular hydropsandthehigh
proportionofMDinvolvementinthecontralateralears.5,29 Thepresentstudydidnotshowacorrelationofthetest parameterswiththedurationofthedisease.Thisresultmay berelatedtothesmallsamplesizeandthelargevariation inthedurationofthedisease.AsforthecVEMP,some stud-iesdidnotfindthiscorrelation,either.AstudybyOsei-Lah et al.36 found no evidence between MD duration and the absenceorpresence ofcVEMP.Katayamaetal.,49 inturn, didnotobserveanassociation betweenthe cVEMPresults andthestageofthedisease.Asfor thevHIT,thestudyby Cerchiaietal.,50comparedtwogroupsofunilateralMD sub-jects,withonegrouptreatedwithintratympanicgentamicin andtheother groupundergoingconservativetherapy,and didnotshowacorrelationwithdurationofthediseasefor eithergroup.However,thestudybyZulueta-Santosetal.,19 assessed 36 patients with definite MD, without a control group,andobservedthatasthediseaseprogresses,the num-berofabnormalitiesinthesixsemicircularcanalsincreased, moreintheipsilateralsideand,particularly,intheposterior canals.
Conclusion
The vHIT examination in MD showed decreased OVR gain for the lateral canals, corrective saccades in the lateral canalonly,predominantlyoftheoverttypeanddidnotfind any significant differences between the symptomatic and asymptomaticears.
For cVEMP, the patients with MD showed absence of biphasic potential and latency prolongation, and a sig-nificant difference was observed between groups for the inter-amplitude parameter, both for symptomatic and asymptomaticears.Therewasnocorrelation betweenthe testresultsandthedurationofdisease.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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