7th international symposium on ... - acufeni, che fare · meniere’s disease and inner ear...

Meniere’s DiseaseInner Ear Disordersand

7th International Symposium on

ROME ITALY October, 17th-20th, 2015Auditorium Antonianum

ABSTRACT BOOK

ORAL COMMUNICATIONS p. 1 POSTERS p. 96



ROME ITALY October, 17th-20th, 2015




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OCTOBER 17th

ANTISECRETORYFACTOR–ACLINICALINNOVATIONINMENIERE’SDIEASE? p.3

BPPV-CANWEMANAGEALLWITHREPOSITIONINGMANEUVERS? p.5

OCTOBER 18th

KEYNOTELECTURE1 p.7

HUMANPATHOLOGICALFINDINGS p.7

KEYNOTELECTURE2 p.9

PATHWAYSTOTHEINNEREAR p.10

KEYNOTELECTURE3 p.12

BLOODPERILYMPHBARRIER p.13

THEFUNCTIONOFTHEENDOLYMPHATICSAC p.14

REGENERATION,PROTEOMICSANDGENETICS p.17

SYMPOSIUMONELECTRICALVESTIBULARSTIMULATION p.21

KEYNOTELECTURE4 p.23

AUDIOLOGICALDIAGNOSTICS p.23

VESTIBULARDIAGNOSTICS p.26

IMAGING p.29

SYMPOSIUM“INTRATYMPANICDEXAMETHASONEASATREATMENT FORMENIERE’SDISEASE” p. 33

DIAGNOSTICS p. 35 ENDOLYMPHATIC HYDROPS p. 38

INDEXORAL COMMUNICATIONS

OCTOBER 19th

KEYNOTE LECTURE 5 p. 41

IMMUNE SYSTEM AND MENIERE’S DISEASE p. 41

BARANY SYMPOSIUM: FROM MOUSE MODELS TO CLASSIFICATION OF MB MENIERE p. 44

KEYNOTE LECTURE 6 p. 45

VENOUS CONGESTION IN MENIERE’S DISEASE p. 45

VESTIBULAR MIGRAINE p. 47 JAPANESE SOCIETY OF EQUILIBRIUM RESEARCH (JSER) SYMPOSIUM p. 48

VESTIBULAR REHABILITATION p. 51

SUDDEN HEARING LOSS & PERILYMPHATIC FISTULA & OTOTOXICITY p. 53 DEHISCENCE SYNDROME p. 57

CONTROVERSIAL ASPECTS OF THE CLINICAL STUDIES ON THE USE OF BETAHISTINE IN MENIERE’S DISEASE p. 61

IT GENTAMYCIN TREATMENT p. 63

BPPV p. 66

IT STEROID TREATMENT p. 69

CLINICAL ISSUES 1 p. 71



OCTOBER 20th

SAC SURGERY p. 84


VESTIBULAR FUNCTION AFTER CI p. 89 KEYNOTE LECTURE 7 p. 91

EFFECT OF CI ON MENIERE DISEASE p. 91







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ANTISECTORY FACTOR - A CLINICAL INNOVATION IN MENIERE’S DIEASE?

ANTISECRETORY FACTOR AND MEDICAL FOOD - NOVEL THERAPY CONCEPTS

J. G. Bruhn

PhD(Pharm),AdjProfessor,ScientificAdvisorLantmännenAS-FaktorAB,Stockholm, Sweden

The antisecretory factor (AF) is a protein secreted in plasma and other tissue fluids in mammals. This 41-kDa protein providesprotectionagainstdiarrhealdiseasesandintestinalinflammation.TheendogenousplasmalevelofAFisincreasedbyenterotoxinsandalsobycertainfoodconstituents.Basedonthesefindings,AF-inducingmedicalandfunctionalfoodandfeedproductshavebeendeveloped.OneoftheseproductsisnamedSPC,SpeciallyProcessedCereals.Testswiththisproductshowedittobeeffectiveinreducingdiarrheainvariousanimalspecies.InhumanclinicaltrialsSPCstimulatestheproductionoftheAFproteininpatientssufferingfromIBD,reducestheirsymptomsandimprovestheirqualityoflife.InfurtherclinicaltrialsinCrohn´sdisease,secretorydiarrheaandshortbowelsyndrome,SPChasbeenshowntoexertbothantisecretoryeffects(byinducingAF)andanti-inflammatoryeffects.Becauseoftheeffectsonhyper-secretionintheGItract,itwashypothesizedthatantisecretorytreatmentwithSPCcouldbevaluableinotherinstanceswherefluidimbalanceisthoughttoplayarole,suchasMD.Inanopenpilotstudy,24MDpatientsreceivedSPCfor14-30days,andAFlevelsinplasmaincreasedby83%in20ofthe24patients.Theattacksofrotatoryvertigowerereducedin12patientsandinthreeofthemhearingwasnormalized(Hanneretal,2004).Inafollow-upstudy,51adultpatientswithMDwereincludedinadouble-blind,placebo-controlledtrial.27subjectsweretreatedwithSPCand24withcontrolcerealsfor3months.TheseverityofMDwasclassifiedaccordingtotheAAO-HNSgradingsystem.14ofthe27patientsintheSPCgroupreporteddecreasedvertigo,comparedwith2of24 in thecontrolgroup (Hanneretal,2010).SPC isnotacommondietary supplement.AccordingtotheEUCommissionDirective1999/21/EGofMarch25,1999,SPCisclassifiedasa“Foodforspecialmedicalpurposes”,i.e.fooddevelopedforspecificpatientGroups.SPChasbeenapprovedbytheNationalFoodAdministrationinSweden,andthehealthclaimthathasbeenacceptedis“Forthenutritionaltreatmentofdisordersinconnectionwithincreasedintestinalsecretions”.

ANTISECRETORY FACTOR-INDUCING THERAPY IMPROVES PATIENT-REPORTED FUNCTIONAL LEVELS IN MENIERE’S DISEASE

S. C. Leong, T. H. Lesser

SkullBaseUnit,Liverpool,U.K.DepartmentofOtorhinolaryngology-HeadandNeckSurgeryAintreeUniversityHospitalLiverpool, U.K.

OBJECTIVES:Theaimofthisstudywastoevaluatetheeffectivenessofspeciallyprocessedcereal (SPC)asasuitableadjunctivetreatmentforMeniere’sDisease.METHODS:Weperformedarandomizeddouble-blinded,placebo-controlled,crossoverstudyinatertiaryreferralcenterofpatientswhohadadiagnosisofMeniere’sDiseasebasedontheguidelinesoftheCommitteeonHearingandEquilibriumoftheAmericanAcademyofOtolaryngology-HeadandNeckSurgery(AAO-HNS).ThemainoutcomemeasurewastheAAO-HNSFunctionalLevelScale(FLS).RESULTS:Thirty-ninepatientscompletedthestudywithoutanyreportedcomplications.ThemeanpretreatmentFLSscorefortheentirestudycohortwas3.8(median,4;range,1to6).TheoverallFLSscore improvedsignificantly(p<0.001),to2.8(median,3),afterSPCtreatment.NopatientsshowedworseningontheFLSduringSPCorplacebotreatment.Ofthe39patients,23showedimprovementontheFLS,andnochangewasobservedintheremaining16.Themedianimprovementon theFLS in these23patientswas2points (mean,1.7; range,1 to4). ThemeanFLS scoreafterplacebocerealtreatmentwasnot significantlydifferent frombaseline (p=0.452),butwas significantlyhigher thanthatafterSPCtreatment(mean,3.7;p<0.001).ThemarginaldifferenceobservedbetweenthebaselineFLSscoreandtheplaceboFLSscorewasduetothefactthat5patientsreported1-pointimprovementsontheFLSafterplacebotreatment.Nevertheless,significantlyfewerpatientsimprovedonplacebothanonSPC(p<0.001).CONCLUSIONS:TreatmentwithSPCappearstobewelltoleratedbymostpatients(91%)withoutanycomplications.Morethanhalf(59%)ofthestudycohortreportedsubjectiveimprovementinfunctionallevel.

SPC FLAKES IN PROPHYLAXIS OF MENIERE’S DISEASE

R. Teggi 1, V. Marcelli 21SanRaffaeleScientificInstitute

2CentroOspedaliero“SanGiovanniBosco”

Introduction:Araisedendolymphaticpressure(hydrops)isthecommonlyacceptedpathophysiologicalmechanismleadingtoMD.Adisorderoffluidandionichomeostasishasbeenpostulatedasacausalfactorleadingtohydrops,andamongprophylacticmeasuresinMDdiureticsarewidelysuggested.AntisecretoryFactor(AF)isa41kDaendogenousprotein;indifferentstudiesdemonstratedtheconstitutivecapacityofmodulatingfluidandionictransportthroughmembranes.SPC-Flakeshavebeenclinicallyshowntosupportcellularfluidbalancestimulatingthebody’sownproductionofproteinAF.PurposeofourworkwastoassessapossibleeffectofSPCFlakesinprophylaxisofMD.MaterialandMethods:TwentyfivepatientswithdefiniteMDhavebeenincludedinthestudy,consecutivelyrecruitedin2Universitycentresamongthosepoorlyresponsivetobetahistine48mg/dayintheprevious3months.Duringthenext3monthstheyunderwentacombinedtherapywithbetahistineandSPCFlakes(1gr/Kgday).Exclusioncriteriawereongoingtherapieswithcalciumchannelblockers,diureticsanddrugsactiveonCentralNervousSystem(SSRIsandbenzodiazepinesamongthem).Mainoutcomewasthenumberofvertigospells(permonth)inthe6monthsbeforeandinthe3monthsofcombinedtherapy.AnEfficacyIndex(EI)wascalculatedwiththeformulay/xper100,whereyisthenumberofvertigospells(permonth)duringcombinedtherapyandxthenumberofvertigospells(permonth)inthe6previousmonths.Betterresultsareexpressedbylowerrates.Results:vertigospellsreducedfrom1.8±0.7to0.6±0.3permonth(p≤0.001).Particularly,8subjectspresentedanEIlowerthan25%(32%),8(32%)intherangebetween25%and50%,5(20%)intherangebetween50%and75%and4(16%)higherthan75%.Audiometricexamdidn’tdemonstratesignificantchangesaftercombinedtherapy.Moreover,4subjects(16%)reportedanoverallreductionofthedurationofvertigospells.Conclusions:ourdataconfirmthoseofpreviousworksreportingasignificativereductionofvertigospellsduringtherapywithSPCFlakes.Aboveall,inoursample16outof25patientsdemonstratedasignificativeresponsetoSPCFlakes.







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BPPV – CAN WE MANAGE ALL WITH REPOSITIONING MANEUVERS?

PATHOPHYSIOLOGY OF BPPV. WHAT HAPPENS TO OUTLETS IN THE SSC IN LONG TERM IF NOT REPOSITIONED

M. Kameswaran

India

IS THERE ANY PLACE FOR MEDICAL TREATMENT IN BPPV? HOW MUCH DO VITAMIN D LEVELS AFFECT?

E. A. GuneriIzmir, Turkey

TheoptimalconcentrationofserumvitaminDisdefinedbythe25-hydroxyvitaminDlevelandtheprevalenceofvitaminDdeficiency/insufficiencywasreportedtobearound60%inthenormalpopulation.VitaminDinsufficiencyandserum25-hydroxyvitaminDlevel<30ng/mlincreasestheriskofosteoporosis.RecentstudiespointedtoanassociationbetweenvitaminDdeficiency,osteoporosisandbenignparoxysmalpositionalvertigo(BPPV),suggestingthatanabnormalcalciummetabolismmaybeanunderlyingcondition.SincethelevelofvitaminDwasfoundtobelowinBPPVpatients,itwasspeculatedthatanincreaseincalciumresorptionmayreducethecapacityoftheotoconiabeingdissolvedinendolymphleadingtoanincreasedconcentrationoffreecalcium.ItwasalsoreportedthatBPPVrecurrencesmaybetreatedwithvitaminDsupplementation.EstablishmentadefinitepathogeneticlinkbetweenlowserumvitaminDlevelandBPPVrequiresanimalexperiments;inaddition,prospectiverandomizedcontrolledclinicaltrialsevaluatingthepreventiveeffectsofvitaminDsupplementationonBPPVrecurrencesarenecessarybeforemakingaparadigmshiftinthetreatmentofBPPV.

POSTERIOR CANAL INVOLVEMENT. HOW IS IT DIAGNOSED AND TREATED. WHY DOES IT OCCUR SO OFTEN?

M. Mandalá

Siena, Italy

Benign paroxysmal positional vertigo (BPPV) is certainly the most common cause of vertigo in adults. The lifetime cumulativeincidenceinthegeneralpopulationamountstoabout10%.TheposteriorsemicircularcanalisbyfarthemostcommonlyresponsibleforBPPV,asitisthemostgravity-dependent.Theincreasinginterestofotolaryngologistsandneurologistshasledtoaprogressiveadvanceintheknowledgeofthislabyrinthinedisorderwithregardtoitsepidemiologic,pathophysiological,clinical,andtherapeuticaspects. Despite the often-effective diagnosis and treatment of most cases of BPPV, the pathophysiological explanations ofthediseasearemainly speculative. Theposterior canal isby far themost frequentlyaffectedcanal inpatientswithBPPV,andcanalolithiasisisbyfarthemechanismmostusuallyresponsible.TheDix-Hallpiketestisthetechniquemostusedtodetectit.Thismaneuverbringstheampullatoahigherpositionwithrespecttothecanalandthecanalisalignedwiththeplaneofmovement,sofavoringactionofthegravityvectoronanydebrisinsidethecanal.Itisadvisabletotesttheleftsidefirst,sincerightposteriorcanal-BPPVismoreprobable,andalwaystoperformthetestbilaterally,soasnottomissabilateralBPPV,especiallyafteratrauma.Posteriorcanal-BPPVistreatedbyEpley’scanalithrepositioningprocedureorSemont’sliberatorymaneuver.Bothproceduresaresafeandeffectivein80–90%ofcases,despitethattheEpley’smaneuverisaclassArecommendedtreatmentforposteriorcanalBPPVwhiletheSemont’smaneuverisaclassBrecommendationdotothelackofonemoreclassIstudy.Atypicalandrarevariantsofposteriorcanalinvolvementsuchascupololithiasisorpositionaldown-beatingnystagmuswillbediscussedwithspecialemphasisonpathophysiology,clinicalpicturesandpossibletreatments.

LATERAL SSC APOGEOTROPIC NYSTAGMUS. WHAT IS THE DIFFICULTY IN IT? WHY DO NEW MANEUVERS COME OUT. WHAT IS THE BEST TREATMENT

D. Nuti

Siena, Italy

It iswellknownthatLC-BPPVcanbedivided intotwovariants, themorecommononewithgeotropicnystagmusandthe lesscommonwithapogeotropicnystagmus.Direction-changinggeotropicpositionalnystagmus(PN)isalways,oralmostalways,duetocanalolithiasisoftheLateralCanalandnodifferentialdiagnosisisrequired.Thepathophysyologyof theapogeotropicvariant ismoredebated. Themostpopular theory is thatofcupulolithiasis,whereamassonthecupulaoftheLCdeterminesitsdeflectionbygravity.Analternativetheoryproposesthatcanalolithiasisisalsoabletodetermineapogeotropicnystagmus,ifdebrisarelocatedneartheampullaofthelateralcanal,onitsanteriorpart,andmovingintheoppositedirectionwithrespecttothegeotropicvariant.Moreover,horizontalapogeotropicPNmaybeoccasionallyduetoacentralvestibularlesion.ThemostcommonmimicsofperipheralPNarethedemyelinatingandsmallischemiclesionsinthecerebellumorinthestructuresaroundthefourthventricle.DifferentiatingperipheralfromcentralcausesofapogeotropicPNisusuallyeasy:symptomsandsignsarerelativelystereotypedandsymptomsandsignspointingtowardscentrallesionsareabsent.Moreover,therearesomenystagmusbehaviorsandfeaturesthatprovideusefulinformationfordifferentialdiagnosis.ThenystagmuscharacteristicscanalsobehelpfulintryingtofigureoutifotoconialdebrisarefreetomoveintheendolymphoftheLCoriftheyareattachedtoitscupula.ApogeotropicPNistreatedwiththesamephysicalmaneuvers/positionsusedtotreatthegeotropicform:Barbecuerotation,Gufoni’smaneuverandForcedProlongedPosition.Oneoption is toconvert thepositionalnystagmus into themore treatablegeotropicvariant,bychangingthepositionofdebrisinthecanal(twostepstreatment).Thereisalsothepossibilityofaone-steptreatmentwithamodifiedGufoni’smaneuver.

ARE THE CANALITH REPOSITIONING MANEUVERS EFFECTIVELY TREAT BPPV ONCE? WHAT TO DO FOLLOWING THE MANEUVER? ARE THERE ANY PRECAUTIONS TO BE INSTRUCTED THE PATIENT? WHEN SHOULD WE CONSIDER SURGERY?

V. Darrouzet

Bordeaux, France

Theefficiencyofcanalithrepositioningmaneuversisdependingontheinvolvedcanal.InposteriorcanalBPPVwedoconsiderusingtheSemont’smaneuverasthefirst-linetreatment,exceptedinelderlypatientinwhomwepreferusingEpleymaneuver.Patientsarecuredinahighpercentageofcase(80%).Incaseofincompleteresultsorrecidivismwetryanothermaneuveragain.Ifnoteffective,weperformacompleteneurotologicalwork-upleadingtoanMRI,sincein1or2%ofcasesaffectedpatientshaveeitheratumorofthecerebello-pontineangleand/orinternalacousticmeatus,mostlyvestibularschwannomaoranischemicorinflammatoryprocessinthevicinityofvestibularnuclei...In typical geotropic lateral canal BPPV, we use the barbecue maneuver, which seems to us the most effective. When facingapogeotropicBPPVwepreferperforminganMRI,sinceahighpercentageofpatientsmaysufferfromcentraldiseases.InthequiterareanddifficultproblemofanteriorcanalBPPV,difficulttodiagnoseandtotreat,thereisnoconsensusonhowtomanagethem.Mostly,thenaturalevolutionofthediseasehelpstocurethepatient.Inthispattern,wesystematicallyuseacompletework-up.Thepatientcounselingisofparamountimportancefollowingmaneuver.Wewillexplainourhandling.SurgicaltreatmentisrarelynecessaryinourexperienceintypicalBPPV.Itmustbeconsideredwhenitisduetoanteriorcanaldehiscence,Chiarimalformationorcerebello-pontinetumor.

THE HISTORY OF MENIERE’S SYMPOSIUM

David J. Lim

ProfessorsinResidence,Dept.ofHead&NeckSurgery,UCLAGeffenSchoolofMedicine

The antisecretory factor (AF) is a protein secreted in plasma and other tissue fluids in mammals. This 41-kDa protein providesprotectionagainstdiarrhealdiseasesandintestinalinflammation.TheendogenousplasmalevelofAFisincreasedbyenterotoxinsandalsobycertainfoodconstituents.Basedonthesefindings,AF-inducingmedicalandfunctionalfoodandfeedproductshavebeendeveloped.OneoftheseproductsisnamedSPC,SpeciallyProcessedCereals.Testswiththisproductshowedittobeeffectiveinreducingdiarrheainvariousanimalspecies.InhumanclinicaltrialsSPCstimulatestheproductionoftheAFproteininpatientssufferingfromIBD,reducestheirsymptomsandimprovestheirqualityoflife.InfurtherclinicaltrialsinCrohn´sdisease,secretorydiarrheaandshortbowelsyndrome,SPChasbeenshowntoexertbothantisecretoryeffects(byinducingAF)andanti-inflammatoryeffects.Becauseoftheeffectsonhyper-secretionintheGItract,itwashypothesizedthatantisecretorytreatmentwithSPCcouldbevaluableinotherinstanceswherefluidimbalanceisthoughttoplayarole,suchasMD.Inanopenpilotstudy,24MDpatientsreceivedSPCfor14-30days,andAFlevelsinplasmaincreasedby83%in20ofthe24patients.Theattacksofrotatoryvertigowerereducedin12patientsandinthreeofthemhearingwasnormalized(Hanneretal,2004).Inafollow-upstudy,51adultpatientswithMDwereincludedinadouble-blind,placebo-controlledtrial.27subjectsweretreatedwithSPCand24withcontrolcerealsfor3months.TheseverityofMDwasclassifiedaccordingtotheAAO-HNSgradingsystem.14ofthe27patientsintheSPCgroupreporteddecreasedvertigo,comparedwith2of24 in thecontrolgroup (Hanneretal,2010).SPC isnotacommondietary supplement.AccordingtotheEUCommissionDirective1999/21/EGofMarch25,1999,SPCisclassifiedasa“Foodforspecialmedicalpurposes”,i.e.fooddevelopedforspecificpatientGroups.SPChasbeenapprovedbytheNationalFoodAdministrationinSweden,andthehealthclaimthathasbeenacceptedis“Forthenutritionaltreatmentofdisordersinconnectionwithincreasedintestinalsecretions”.

THE HISTOPATHOLOGY OF MENIERE’S DISEASE: OBSERVATIONS FROM THE TEMPORAL BONE COLLECTION AT THE MASSACHUSSETS EYE AND EAR INFIRMARY

M. J. McKenna, MD, J. B. Nadol Jr., MD

DepartmentofOtologyandLaryngology,HarvardMedicalSchool,MassachusettsEyeandEarInfirmary,Boston, MA, USA

ThehistopathologyofMeniere’sDiseasewasfirstdescribedbyHallpikeandCairnsandindependentlybyYamakawain1938.Thehistopathologic findings of hydrops has been subsequently confirmed in numerous studies since that time. The OtopathologyLaboratoryattheMassachusettsEyeandEarInfirmaryhasprocessedandexamined83earsfrompatientswithadiagnosisofMeniere’ssyndrome. Observations from these studies have revealed that early in the development of Meniere’s Disease, endolymphatichydrops primarily involves the cochlear duct and saccule. However, in later stages the entire endolymphatic system becomesinvolved.Inadditiontoendolymphatichydrops,otherpathologicfindingsincluderupturesofthemembranouslabyrinth,fistulaeofthemembranouslabyrinth,collapseofthemembranouslabyrinthandvestibularfibrosis.Thesefindingsarereviewed.Thesefindingsprovidethebasisforspeculationregardingtheunderlyingpathophysiologyincludingthepotentialroleoftheendolymphaticductandsacandthepotentialexplanationforthesymptomsofhearinglossandvertigo.Recentdevelopmentsinimmunohistochemistryof archival human temporal bones are beginning to shed new light on some aspects of the disease process which cannot beappreciatedbystandardH&Eprocessing.







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KEYNOTE LECTURE 1

HUMAN PATHOLOGICAL FINDINGS

ULTRASTRUCTURE AND IMMUNOHISTOCHEMISTRY OF THE HUMAN INNER EAR RELEVANT FOR MENIÈRES DISEASE

A. Schrott-Fischer 1, W. Liu 2, R. Glueckert 3, H. Rask-Andersen 4

1DepartmentofOtolaryngology,MedicalUniversityofInnsbruck, Anichstr, Austria2DepartmentofSurgicalSciences,SectionofOtolaryngology,DepartmentofOtolaryngology,UppsalaUniversityHospital,Sweden3DepartmentofOtolaryngology,MedicalUniversityofInnsbruck, Austria4DepartmentofSurgicalSciences,HeadandNeckSurgery,sectionofOtolaryngology,DepartmentofOtolaryngology,UppsalaUniversityHospital,Sweden

Duringhis last yearProfessorHeinrichSpoendlin, at theResearchDepartment at InnsbruckUniversityHospital coordinatedaninternationalstudyofahumantemporalboneobtainedfromadiseasedpatientwhosufferedfromunilateralMenièresdisease(MD).Severalexpertsgatheredtounearththerootofthisintriguingdisease.OrganofCorti,lateralwall,includingthestriavascularis,vestibularepithelia,neuralportionsandendolymphaticsacwerethoroughlyandblindlyscrutinized.Severalmorphologicalchangeswerecharacterizedbothatthelightandfinestructurallevel.Thestudyendedwithapublicationofthejointefforts.Thispresentationwilldisplayandsummarizesomeoftheresultsthatwereobtained.Itwillalsogivesomeresultsobtainedfromhumaninnerearstudies using super-resolution immunohistochemistry with particular reference to the normal human cochlea. Obviously muchremains toaccomplish tobetterunderstand the fascinatingmicrostructureandmolecular composition. Fromthese studies it isobviousthattranslationalanimalstudiesmustbeinterpretedwithcareduetodistinctvariationsinhumanandanimalmodels.Human inner ear tissuewasobtainedat surgeryandalsoat autopsyafterperilymphaticperfusion. The study conforms to TheDeclarationofHelsinkiandwasapprovedbythemedicalethicalcommitteeattheUppsalaUniversityHospital(2013)andInnsbruck.Patientsconsentwasobtained.

CLINICAL SIGNIFICANCE OF BAST’S VALVE

A. BelalAlexandria, Egypt

The utriculo-endolymphatic valve was first described by Bast in 1928. It allows the controlled egress of endolymph from thepars superiorof the labyrinth (utricleandsemicircularcanals) to thepars inferior (sacculeandcochlea) tobeprocessed in theendolymphaticsac.Itspresumedfunctionistoprotecttheparssuperiorfromsuddenchangesofpressureintheparsinferior.Areversedfunctionmayoccurifsuddenchangesoccurinthepressureofendolymphintheparssuperior.Clinicalandoperativeconditionsoftheinnereararereviewedinlightofthesefunctions.







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ROLE OF HUMAN ES IN THE PATHOGENESIS OF MENIERE’S DISEASE: HUMAN TEMPORAL BONE STUDY

F. Linthicum, MD, D. J. Lim, MD

ProfessorsinResidence,Dept.ofHead&NeckSurgery,UCLAGeffenSchoolofMedicine

NumberofhumantemporalbonestudiesofMeniere’spatientsreportedthesmallendolymphaticductandsac(ES)isariskfactorforMD.Basedonthemeasurementofendolymphaticsac(ES)of21temporalbones(TBs)from14patientswithhistoryofMeniere’sDisease(MD)andthoseof21(14subjects)age-matchedTBsascontrolgroup,Linthicum(unpublisheddata)observedthesmallESisassociatedwiththeMDincomparisontonon-MDES.VolumeofthehumanESinMDpatientsvariedfrom0.0385mm3to0.871563(Mean=0.336803+/-0.669267mm3)andSurfaceAreavariedfrom5.281421mm2to108.9476mm2(Mean=37.2182+/-2.167451mm2).Thevolumeof theES innon-MDvariedfrom0.265551mm3to1.451164mm3(Mean=0.685684+/-0.687603mm3)andSurfaceAreavariedfrom21.83769mm2to122.5041mm2(Mean=69.7182+/-2.056707mm2).ItissuggestedthattheremaybevaryingdegreeESdysfunctionornumberofdysfunctionalESepithelialcellsintheMDpatients.IthasbeenreportedthatHSVantibodyintheperilymphaticfluidoftheMDwasfoundintheESofMeniere’spatients(Arnold&Niedermeyer,1997)andalsointheEStissueoftheMDpatients(Wellingetal.,1994).However,theubiquitousnatureoftheHSVraisedtheskepticismforthespecificityoftheroleoftheHSVforthepathogenesisofMD.LimandGlasscockearlierexaminedtheESfromthe6MDpatientswhoundergonefortheESsurgeryandfoundevidenceoffocaldamageoftheESandHSV-likeviralparticlesintheneighboringcellsthatundergodegeneration.Furthermore,theESareinnervatedbynumberneuronssuchasparasympathetic(pterygopalatineggl.), sympathetic (superiorcervicalggl.), and somatosensory (trigeminalggl.)neurons. Thus, it ispossible thatlatentHSVintheseneuroncouldbereactivatedbythestressandinfecttheESepithelialcellscausingitsdegeneration.WhenstressisappliedtotheseES,theydevelophydrops.Exactnatureofthedysfunctionisnotyetunderstood.However,ithasbeenshownthatexcessivevasopressin type-2receptorexpression inES isassociatedwithMeniere’sDisease (KitaharaTetal, JEndocrinology,2008).Inconclusion,theendolymphaticsacplayscriticalroleinthepathogenesisoftheMeniere’sDisease.

COCHLEAR PROTEOMICS OF FLUID AND ION TRANSPORT

A. F. Ryan 1, A. Wong 1,2, K. Pak 1, J. N. Savas 31 Department of Surgery/Otolaryngology, UCSD School of Medicine and San Diego VA Medical Center, La Jolla, CA2 Department of Physiology, UNSW Australia, Sydney, Australia3 Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Thedeterminantsofinnerearfluidcompositionhavebeenextensivelyevaluated,butfewerstudieshavebeenperformedattheprotein level. To address this, we assessed cochlear proteins known or suspected to be involved in endolymph and perilymphhomeostasis,includingtheeffectsofnormalandexcessivecochlearactivation,usingisotopicshotgunproteomics.WholecochleaewereharvestedfromFVBmiceraisedonanormaldiet,aswellasfrommicerearedonadietcontainingonlynitrogen15(15N).14Nmicewerekeptinsilence,orexposedto70,100or105dBSPLnoisefor30minutespriortosacrifice.Proteinwasextracted,andindividual14Nsampleswerespikedwithapooled15Nsample.Thesamplesweretrypsindigestedandanalyzedbymassspectroscopytoidentifyproteinfragments.14N/15Nisotopicratioswereusedtoquantifyproteinlevelsacrossgroups.Morethan8,000proteintraceswereidentifiedinthescreen.Themajorityofproteinsthathavebeenimplicatedincochlearfluidcompositionandvolumeregulationwererepresented.ThisincludedNa+/K+-,K+-andCa2+-ATPases,Na+/H+andNa±/HCO3-exchangers,K±channels,gap junctionproteins,purinergicreceptorsandaquaporins. Changes inprotein levelsassociatedwithcochlearactivationwereinterpretedasevidenceofactivationfollowedbyrecycling(increases)ordegradation(decreases).Oftheproteinsnotedabove,cochlearstimulationsignificantlyalteredtheexpressiononlyofiontransportproteins.IsoformsofNa+/K+-ATPase,aswellasNa+/H+,Na+/CO3-andCl-/CO3-exchangerswereincreased,whileaK+/Cl-transporterwasdecreased.Theresultssuggestthationtransportproteinsinthecochleaareparticularlysensitivetocochlearactivationandstress.(Wordcount:260)SupportedbyVAgrantRX000977(AFR),GarnettPasseandRodneyWilliamsMemorialFoundationResearchFellowship(AW)andNIHgrantDC013505(JNS).

GENTAMICIN DISTRIBUTION IN THE EAR FOLLOWING LOCAL APPLICATIONS

A. N. Salt 1, F. B. Kraus 2, E. B. King 3, S. K. Plontke 41 Washington University School of Medicine, St Louis, MO, USA2 Universitätsklinikum Halle (Saale), Germany3 Bionics Institute, Melbourne, VIC, Australia4 University of Halle-Wittenberg, Halle (Saale), Germany

Ithasgenerallybeenassumedthatintratympanicgentamicinentersperilymphoftheearthroughtheroundwindow(RW)membrane.Inthisstudy,perilymphkineticsofgentamicinwasquantifiedbydirectmeasurementsfollowinglocalgentamicinapplicationstotheear.Solutionsofgentamicinwereapplied to theguineapigearby twomethods. Thefirst, toestablisheliminationkinetics,wasbyinjectionfromapipettesealedintothelateralsemi-circularcanal(LSCC).Asthecochlearaqueductprovidestheoutletforflow,thisloadstheentireperilymphaticspacewithdrug.Inthesecondmethod,gentamicinsolutionwasappliedtotheRWnichearea.Inbothcases,10x2μLsamplesofperilymphweresubsequentlycollectedfromtheLSCCandanalyzedbyspectrophotometricmmunoassay(Coulter)toquantifygentamicindistributionintheear.FollowingLSCCinjectionofgentamicin,perilymphwassampledeitherimmediatelyorafterdelaysof1,2or4hours.Thedeclineofgentamicinwithtimewasdominatedbyconcentrationdecreaseinthebasalpartofscalatympani(ST),consistentwithCSF-perilymphinteractions (dilutionby slowentryofCSF intoSTandpressure-inducedoscillationsacross thecochlearaqueduct). In separateexperiments,perilymphwassampled1,2or4hoursafterapplicationofgentamicintotheRWniche.Gentamicinconcentrationswerehighestininitialsamples(originatinginthevestibuleandscalavestibuli(SV))andlowerinsamplesoriginatingfromST.ThesedataconfirmthatgentamicinentersthevestibuledirectlyinthevicinityofthestapesaswellasthroughtheRW.GentamicinentrywassimulatedinacomputermodelincorporatingtherapiddeclineinSTduetoCSFinteractions.ThisanalysisconfirmedthatmoregentamicinenteredtheRWcomparedtothestapes,butevenwithhigherentry,lowerconcentrationsweregeneratedinSTduetoCSFinteractionsinfluencingthekinetics.ThesestudiesshowthatgentamicinlevelsinthevestibulearesubstantiallyhigherthanthoseinthecochleafollowingRWnicheapplications,contributingtothepreferentialvestibulotoxicityofthedrug.Nevertheless,thedifferentphysicalprocessesaffectingdrugconcentrationsinSVandSTneedtobeconsideredinaccountingforthedistribution.

KEYNOTE LECTURE 2

PATHWAYS TO THE INNER EAR







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DRUG DELIVERY VIA THE OVAL WINDOW

S. O’Leary 1, E. King 2, J. Fallon 2, D. Brown 3, A. Salt 4

1 University of Melbourne, Australia2 Bionics Institute, Australia3 University of Sydney, Australia4 Washington University, USA

It has been thoughtuntil recently that the roundwindow (RW)was themain routeof entry into the inner ear following theapplicationoftherapeuticagentstothemiddleear.Morerecentlyithasemergedthattheovalwindow(OW)/stapesfootplateisalsoanimportantpathwayfordrugdeliverytotheinnerear.MRIscanninghasdemonstratedthatgadoliniumderivedcontrastagents(GDCA)canbeseenwithinboththevestibularandthecochleawithinonehourwhenappliedtotheroundwindow/stapesnicheofexperimentalanimals.ThisraisedthepossibilitythatGDCAenteredthe innerearviathestapes, inadditiontotheroundwindow. Wewentontotestthisdirectlybyassessingtheconcentrationofthesolutetrimethylphenylammonium(TMPA)withinthefluidsoftheinnerearafteritsselectiveapplicationtoeithertheRWortheOW.PerilymphTMPAlevelsweremeasuredusingion-selectivemicroelectrodessealedintotheoticcapsuleorinperilymphsamplescollectedfromthelateralsemicircularcanal.AnalysisofthesedataindicatedthatlargeportionsofGDCA(upto90%)andTMPA(30-40%)enteredtheinnerearviatheOW.SimilarrecentstudieswithgentamicinindicatehighergentamicinlevelsinthevestibuleandentrycharacteristicscomparabletothoseofTMPA(seepresentationbySaltetal.)Wehaveturnedourattentiontopotentialtherapeuticramificationsofthesefindings.WehavereasonedthatitmightbepossibletopreferentiallytargeteitherthevestibularsystemorthecochleabytargetingdrugtoeithertheOWortheRW,respectively.InthetreatmentofMeniere’sDiseasethismightmeanthatanoptimaldosageofgentamicincouldbedeliveredtothevestibule,potentiallyreducingtheconcentrationinthecochleathusreducingtheriskofinadvertentototoxicity.Inearlyexperiments,weappliedahighconcentrationofgentamicinontotheOWorRW.GentamicinappliedtotheOWinducedsignificantlyhigherlevelsofototoxicity.NewdatanowshowthattargetedapplicationofalowerdosageofgentamicinontheOWcanresultinareductionofvestibularfunctionwhileavoidingelevationsinhearingthreshold.Next,gentamicin (1uLof5mg/mL)wasapplieddirectlyonto theOW inadultguineapigs.Oneand twoweeks following thisprocedure,shortlatencyvestibularevokedpotentials(VsEP)inresponsetolinearheadaccelerationwererecordedwithanelectrodelocatedinthefacialnervecanal.Auditoryfunctionwasassessedbyrecordingauditoryevokedpotentials(AEP)inresponsetopuretonepips(2-32kHz)usingthesameelectrode.Twoweeksaftertreatment,therewasa64%reductioninVsEPamplitudewithoutelevationsinAEPthresholdingentamicin-treatedanimals.ThesefindingssuggestthattheriskofototoxicityduringlocalgentamicintherapyforMeniere’sDiseasecouldpotentiallybereducedbytargetingalowdosageofgentamicinontotheOW.ThiscouldbeachievedbyinjectionofgentamicintotheOWunderdirectvisionwithanendoscope,orpotentiallywithself-gellingpolymersinjectedthroughthetympanicmembrane.Areliableclinicalimplementationwouldneedtocontrolforthepossibilitythatmucosalfoldscouldobstructthepassageofdrugtotheovalwindowniche,andthislatterconsiderationmightinfluencewhetherliquidorgel-likepreparationswereemployed.

HUMAN ENDOLYMPHATIC DUCT SYSTEM, TRANSEPITHELIAL WATER CHANNELS AND COCHLEAR ULTRASTRUCTURE

H. Rask-Andersen, W. LiuDept of ORL, Uppsala University Hospital, Uppsala, Sweden

Meniere´sdisease (MD)continuestodefyandconfoundtheclinical/scientificcommunitymorethan150yearsafter itsoriginaldescription.AlreadyGuild(1927),Portman(1927),HallpikeandCairns(1938),Yamakawa(1938)andKimuraandSchuknecht(1965)suggestedthatMDiscausedbyadysregulationofendolymph.Yet,themechanismsbywhichendolymphquantityandcompositionareregulatedandthemolecularmechanismsgoverningwaterpermeationacross theductepitheliumremainelusive.Thefinelytunedhaircellsandciliamechanotransductionwouldseemtoimposeextraordinaryhomeostaticdemandsforregulationofwaterand ionbalance (osmoticpressure),metabolicexchangeand theextra-cellularDCpotential. The restricted longitudinalflowofendolymphtowardsthesac(Saltetal.1986)isambiguousandhowendolymphaticductobstructionproduceshydropsneedsfurtherexplanation.AVP/V2Rcomplexmayplayasignificantroleinlocalfluidhomeostasisbycontrollingtheelimination/reabsorptionoffluidintheinnerearthroughstimulationofV2receptorstomobilizeAQPwaterchannels,similartothekidney.Thiscouldspotlightanovel therapeutic strategy.Human immunohistochemistry and in silico simulations suggest exceptionally highosmoticwaterpermeabilitycoefficientsfortheepithelialregionofoutersulcuscellsinthecochlearapexco-expressingAQP4andAQP5.Itcouldpin-pointanaqueouspore-facilitated“watershunt”locatedinthehumancochlearapex(Eckhardetal.2014).ExperimentalfindingsandresultsfromrecentstudiesofthehumaninnerearinourlaboratorywillbepresentedrelevantforwaterdynamicsrelatedtoendolymphatichydropsandMeniere´sdisease.Humaninnereartissuewasobtainedatsurgery.ThestudyconformstoTheDeclarationofHelsinkiandwasapprovedbythemedicalethicalcommitteeattheUppsalaUniversityHospital(2013).Patientsconsentwasobtained

KEYNOTE LECTURE 3







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A NEW MURINE MODEL FOR MENIERE’S DISEASE - VASOPRESSIN INDUCED ENDOLYMPHATIC HYDROPS

M. Takumida 1, Y. Katagiri 1, M. Anniko 21 Department of Otolaryngology, Hiroshima University Hospital, Hiroshima, Japan2 Department of Otorhinolaryngology and Head and Neck Surgery, Uppsala University, Uppsala, Sweden

Thepurposeofthis studywastodevelopamoresuitableanimalmodel,havingacloser resemblancetothepathophysiologicalprocessinMeniere’sDisease.AdultCBA/JorICRmiceweretreatedbysubcutaneousinjectionof50μg/100g/dayvasopressinfor5daysupto8weeks.Morphologicalanalyseswereperformedofthecochlea,vestibularendorgansandendolymphaticsac.Results. All experimental animals showed mild to moderate endolymphatic hydrops, increasing in severity as the vasopressintreatmentwasprolonged.Animalstreatedwithvasopressinfor8weeksshowedsevereendolymphatichydropswithpartiallossofouterhaircellsandspiralganglioncells.Theseanimalsalsohadareversiblevestibulardysfunctionfollowingintratympanicinjectionofepinephrine.WehavealsodemonstratedthatEHcausedbyVPrecoveredfollowingthecessationofVPadministration.TheEHgraduallyincreasedastheVPadministrationwaslengthened,butgraduallyrecoveredafterthecessationofVP.Incontrast,therewasnorecoveryfromthedegenerationofcochlearhaircellsandlossofspiralganglioncells.AnewmurinemodelofMeniere’sDiseasehasbeendeveloped,basedon long-termadministrationofvasopressin. Inductionofvestibulardysfunctioninthepresentanimalmodelcancauseadditionalstress,byreducinginnerearbloodflow.Ournewmicemodelis,nonsurgical,moresuitableanimalmodel,havingacloserresemblancetothepathophysiologicalprocessinMD,whichcanbewidelyusedfortheMDresearch.hemedicalethicalcommitteeattheUppsalaUniversityHospital(2013).Patientsconsentwasobtained.

ULTRASTRUCTURE AND GENE EXPRESSION IN THE HUMAN ENDOLYMPHATIC SAC – NOVEL EVIDENCE OF MULTIPLE FUNCTIONS

M. N. Møller, S. Kirkeby, K. Qvortrup, J. Vikeså, F. C. Nielsen, P. Cayé-ThomasenDepartment of Oto-Rhino-Laryngology, Head and Neck Surgery, Rigshospitalet, Copenhagen DenmarkDepartment of Oral Medicine, Dental School, Panum Institute, University of Copenhagen, Copenhagen, DenmarkCenter for Genomic Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, DenmarkFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Thefunction(s)oftheendolymphaticsacandits involvementininnereardiseaseremainenigmatic.Toexploretheseissues,weappliedtransmissionelectronmicroscopy,cDNAmicroarrayandimmunohistochemistrytofreshhumanendolymphaticsactissuesamples. Electron microscopy revealed novel ultrastructural features indicative of function and the gene expression analysisshowed anupregulation of genes of several functional annotations, including immune systemand solute carrier family genes.Immunohistochemistryverifiedtranslationofselectedgenes,aswellaslocalizationofthespecificproteinwithinthesac.Theuniquedataonhumantissuesupporttheendolymphaticsacasapluripotentorganinvolvedinimmunedefenseandpressureregulationwithintheinnerear.

THE FUNCTION OF THE ENDOLYMPHATIC SAC

THE BLOOD PERILYMPH BARRIER IS VULNERABLE TO SYSTEMIC INFLAMMATION BUT IS MINIMALLY AFFECTED BY COCHLEAR MACROPHAGES

K. Hirose, SZ. Li, J. Hartsock, A. Salt

Department of Otolaryngology, Washington University School of Medicine

Thebloodperilymphbarrier(BPB)playsanimportantroleinseparatingthecontentsofthebloodstreamfromtheinnereartissuesandfluids.Duringperiodsofacuteinflammation,solutesandfreewaterfromthebloodcanleakintotheinnerearfluids.Vascularbarrierleakinesshastraditionallybeenviewedasanimportantsourceofcochleardysfunctionandpathology.SomehaveproposedthatmacrophagesintheperivascularspaceplayafunctionalroletomaintaintheBPB.However,whatcellscontributetothisbarrierwithintheinnerearandwhatcellsparticipateinbarrierdysfunctioniscurrentlynotthoroughlycharacterized.PermeabilityoftheBPBwasevaluatedinmicebyapplyingfluoresceinsystemicallyandcollectingperilymphfromtheposteriorcanaloftheinnerearwithaninvivosequentialsamplingtechnique.Entryratesoffluoresceinfrombloodintoperilymphwerecomparedforcontrol(saline-treated)miceandendotoxemicmice(lipopolysaccharide-treated,1mg/kgIPx2days).Wild-typeandmacrophage-depletedmice(CX3CR1-DTRmiceafterdiphtheriatoxin)wereusedastheanimalsubjects.Wefoundthatbreachesinthevascularcompartmentoccurwhenexperimentalmicearetreatedwithsystemiclipopolysaccharide(LPS).However,inmostcases,whenthereismarkedextravasationofsolutefromthevascularcompartmentintotheperilymph,thereisremarkablylittleassociatedchangeinendocochlearpotentialorhearingthreshold. Wealsofoundthateliminationofmacrophages does not render the barrier leaky, and normal barrier function and normal hearing thresholds are maintained asmeasuredbydirectperilymphsamplingandABR.Inexperimentally-inducedendotoxemia,therewasamarkedincreaseinvascularpermeabilitythatwasminimallyaffectedbymacrophagedepletiondespitewidespreadentryofcochlearmacrophagesintothespiralligamentandlimbusinmacrophage-repleteanimals.Whiletheinteractionbetweenvascularpermeabilityandinnerearfluidsislikelytobeimportantincertaincasesofacquiredhearingloss,thetraditionalbeliefthatbarrierleakinessandinflammatorycellentryalonewouldinduceimmediatelossoffunctionrequiresreevaluation.Inaddition,whatrolesinflammatorycellsplayinthemaintenanceandcompromiseofthevascularbarrierincochleardiseasewillbeimportanttoourunderstandingofhowtoimprovetreatmentfortheseconditions.

BLOOD PERILYMPH BARRIER







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MENIERE’S DISEASE HISTOPATHOLOGICAL ANALYSIS: NOVEL ULTRASTRUCTURAL, MOLECULAR AND MRI FINDINGS

G. Ishiyama, I. Lopez, A. IshiyamaDepartment of Head and Neck Surgery, UCLA School of Medicine, Los Angeles, CA, USA

ThepathophysiologyofMeniere’sDisease(MD)suggestaninvolvementofabnormalitiesaffectingendolymphresorption,vascularabnormalities,postviralautoimmune,and factors related towaterhomeostasis.Histopathologicalanalysis is thegold standardtodeterminewhichcellsareaffectedinMD.Inthisstudyweperformedasystematichistologicalandaultrastructuralanalysis,complemented with molecular and immunohistochemical analysis in vestibular end organs acquired from labyrinthectomy inMeniere’sDisease.Weperformthisstudyin20subjectswithintractableMDandipsilateralnon-serviceablehearingpresentedinourNeurotologicclinic(averageage62,range29-83yearsold)atUCLA.Theaveragedurationofsymptomspriortosurgerywas7years(range1-20years).Histologicalanalysisofthinplasticsectionsdemonstratedvaryingdegreesofdegeneration,beingthecristaemoreaffectedthanthemaculautricle.Amonolayerofepithelialcellsinthecristae,wasconsistentlyobserved,incontrastthemaculautricleisbetterpreserved.Wealsodetectedapronouncedbasementmembranethickeninginthecristaascomparedto themaculautricle.Additionalfindings includehair cell and supportingcell vacuolization, stereocilia loss, andedema in thestroma.Transmissionelectronmicroscopic(TEM)analysisofthesespecimensshoweddisorganizationofthebasementmembraneunderneaththeepithelia,normalmorphologyofnerveterminalsandmyelinatedfibers.Furtheranalysisofthevasculatureshowednovelultrastructuralchangesinthebloodlabyrinthinebarrier(BLB)notpreviouslyreportedintheotologyliterature.IntheBLBofcapillariesinthevestibularendorgansstromawefoundincreasedtranscellularvesiculartransportacrossvascularendothelialcells,pericytedetachmentandperivascularbasementmembranedisruption inthestromawasobserved. SevereMDcasesshowed inaddition,vacuolizationofendothelialcellsand/orcompleteatrophy.UltrastructuralalterationsintheBLBfromMeniere’sspecimen’scorrelateswiththepresenceofedemaintheperilymphaticspace.Utriclesfromnormal individualsobtainedatautopsyshowednopathologicalalterationsintheBLB,stromaltissueorsensoryepithelia.TheseresultssuggestthatalterationsoftheBLBmaybeacontributingfactorintheunderlyingphysiopathologyofMD.RecentstudiesusingCellularandultrastructuralchangesmatchwellwithourmolecularbiological studies in similar typeof specimens.Wehavedetectedchanges in theexpressionof severalspecific innerearproteins:Specificallydownandupregulationofaquaporin4and6respectively (bothexpressed insupportingcells),upregulationofcochlin(expressedinthestroma)anddecreaseincollagenIVandlaminin-1btwobasementandperivascularmembrane proteins. Recently, objective quantitative criteria for EH using delayed intravenous gadolinium 3D fluid attenuationinversionrecovery(3D-FLAIR)MRIhavebeendeveloped,andthedegreeofEHwassignificantlycorrelatedwiththedegreeofhearingloss.UsingthistechniquewefoundthatthedegreeofEHstronglycorrelatedwithauditoryhearinglossbasedonthepuretoneaverageinthesettingofMD.InconclusionMDisacomplexsyndromethatinvolveshistologicalandmolecularsubtractedthatneedtobefurtherinvestigatedtoprovidenoveltreatmentsforthisdebilitatingdisease.

ION TRANSPORT IN ENDOLYMPHATIC SAC EPITHELIAL CELLS ON THE BASIS OF EXPERIMENTAL ANIMAL RESEARCHES

N. Mori 1,2, T. Miyashita 2 1 Osaka Minato Central Hospital, Osaka, Japan 2 Department of Otolaryngology, Faculty of medicine, Kagawa University, Kagawa, Japan

The endolymphatic sac (ES) is believed to play important roles in the homeostasis of the endolymphatic system. However, iontransportsystemoftheESremainstobeclarified.Basedonrecentresearchresultsinexperimentalanimals,iontransportsystemintheESepithelialcellsisoutlined.Unlikecochlearandvestibularendolymph,ESendolymphhashigherNa+andlowerK+concentrations.Na+andCl−aredominantionsintheES.ESendolymphhasapositiveDCpotentialof+15-20mV.TherestingmembranepotentialintheESepithelialcellsisapproximately-60mV.Theelectrochemicalgradientacrosstheapicalmembraneofepithelialcellsiscalculatedtobealargevalueof+140mVforNa+,indicatingaverystrongNa+inflowfromtheESlumeninsidethecell.Severalionchannels(outwarddelayedrectifierK+channel,amiloride-sensitiveepithelialNa+channel(ENaC),Ca++sensitivenonselectivecationchannel),andseveraliontransporters(Na+–K+–2Cl−cotransporter(NKCC),thiazide-sensitiveNa+–Cl−cotransporter(TSC),Na+–H+exchanger,Cl--HCO3-exchanger(SLC4A2),pendrin)havebeenreportedinESepitheliacells.TheESintermediateportionhasastrongeractivityofNa+,K+-ATPaseandahigherNa+permeabilityinmitochondria-richcells,stronglysuggestingahigherpotentialofNa+absorptionfromendolymphintheES.Several molecules relating to mineralocorticoid action such as ENaC, TSC, 11β-hydroxysteroid dehydrogenase (11βHSD),mineralocorticoidreceptorhavebeenreportedlyexpressedinESepithelialcells,suggestingthatESepithelialcellsmaybeatargettissueformineralocorticoidhormone,whichincreasesendolymphabsorptionintheES.TheESepithelialcells(mainlymitochondria-richcells),whichareinvolvedinESendolymphabsorptionviaactivesodiumtransport,maycrucialrolesinmaintainingthehomeostasisintheendolymphaticsystem.

POTASSIUM SECRETION VIA APICAL MULTIPLE POTASSIUM CHANNELS IN HUMAN ENDOLYMPHATIC SAC EPITHELIUM

S. Kim, B. G. Kim, J. Y. Kim, J. S. Jung, J. Y. ChoiYonsei University College of Medicine, Sooncheonhyan University College of Medicine

Theendolymphaticsac(ES)hasbeenthoughttobeinvolvedintheregulationofinnerearhomeostasis.Sofar,manyionchannels,transporters,andexchangerswereidentifiedinendolymphaticsac,theexactlocationandtheroleofK+channelshavenotbeenfullyidentified.TheroleofK+channelsontheESmustbeimportantinregulatingrelativelyhighK+concentrationinESluminalfluidbywhichESpotentialismaintained.Inthisstudy,wetriedtoinvestigateK+channelsandexchangerswhichcontributetothe regulation of K+ concentration in human endolymphatic sac. Human ES was harvested during acoustic tumor surgery viatranslabyrinthineapproach . ThecandidateK+channelswere investigatedbyproteomicanalysis (LC-MS/MS)andbymeasuringtransepithelialcurrentwithscanningvibratingelectrodetechnique(SVET).ToverifyK+transportingionchannelsandexchangersidentifiedbySVETandLC-MS/MS,RT-PCR,andimmunohistochemistrywereperformed.ThetransepithelialcurrentfromhumanESepitheliumwasblockedby4-AP,Ba,andapamin.Thecurrentchangeafterapplicationofthepharmacologicagentwassignificantfromtheconcentrationof10mM4-AP,1mMBa,and100nMapamin.Thecurrentwasalsosignificantlyinhibitedbybumatanide(10uM)andouabain(1mM).K+channelswiththispharmacologicpropertieswereKCNJ13,KCNJ14,KCNK2,andKCNK6.AdditionalK+channelssuchasKCNB1,KCNC4,andKCNH1wereidentifiedbyLC-MS/MS.FinallyverifiedK+channelsexistinginhumanESepitheliumbyfunctionalstudy,RT-PCR,andimmunohistochemistrywereKCNB1,KCNN2,KCNJ14,KCNK2,andKCNK6.ThisisthefirstreportofapicalK+secretioninthehumanESepithelium.MutipleK+channelsincludinginwardlyrectifying,voltage-dependent,andCa-activatedK+channelswereinvolvedintheapicalK+secretioninhumanESepithelium.NKCCandNa+,K+-ATPaseprovidedrivingforcesfortheK+secretion.ThisapicalK+secretioninhumanESepitheliumislikelytoplayanimportantroleinregulatingrelativelyhighK+concentrationofESluminalfluidandendolymphaticsacpotential.







-17- -18-

AcknowledgementsThisstudywasfundedbyPI13/1242Grant.SoniaCabreraissupportedbyMeniere’sSocietyUK,WES-MDGrant.ReferencesRequenaT,CabreraS,Martín-SierraC,PriceSD,LysakowskiA,Lopez-EscamezJA.IdentificationoftwonovelmutationsinFAM136Aand DTNA genes in autosomal dominant familial Meniere’s Disease. Hum. Mol. Genet. (2015). 24(4):1119-26.doi: 10.1093/hmg/ddu524.oplayanimportantroleinregulatingrelativelyhighK+concentrationofESluminalfluidandendolymphaticsacpotential.

CONFOCAL IMAGING OF STIMULUS-INDEPENDENT ACTION POTENTIAL ACTIVITY IN THE DEVELOPING COCHLEA

F. Ceriani 1,2,3, S. Johnson 3, W. Marcotti 3, F. Mammano 1,3,41 Venetian Institute of Molecular Medicine (VIMM), Padua, Italy2 Department of Physics, University of Padua, Italy3 Department of Biomedical Science, University of Sheffield, UK4 CNR Cellular Biology and Neurobiology Institute, Monterotondo Scalo, Rome, Italy

Spontaneousactionpotential(AP)activityoccursduringcriticalperiodsofmammaliansensorysystemdevelopment.Inthemammaliancochlea,itislikelythatsuchactivityisdrivenbyAPfiringincochlearinnerhaircells(IHCs).Inthiswork,wecomplementedsingle-cellelectrophysiologywithlargescaleopticalimagingusingconfocalmicroscopysystemsdevelopedinourlaboratorytoinvestigatethe relationshipbetween spontaneous APactivity in sensory IHCsandconnexin-mediatedcalcium transients in cochlearnon-sensorycells.WefoundthatIHCsfireactionpotentialsevenintheabsenceofdetectablecalciumwavesinnearbynon-sensorycells,thereforeconfirmingthatspontaneousactivityisintrinsicallygeneratedinIHCsduringdevelopment.Moreover,weshowthatcalciumwavesexertsamodulatoryeffectonIHCsfiringandsynchronizethesimultaneousresponseofseveralnearbyIHCs.WehypothesizethatthesynchronizedresponseofnearbyIHCsrefinestonotopicmapsalongtheauditorypathwaybeforetheonsetofsensoryexperience.

HES-1 AND COUP-TFI SHRNA KNOCKING DOWN GIVE RISES TO NEW HAIR CELLS AND SUPPORTING CELLS IN ORGAN OF CORTI ORGANOTYPIC CULTURE

J. Oiticica, A. C. Batissoco, K. Lezirovitz, M. Massucci Bissoli, D. Zanatta, B. Strauss, R. C. Mingroni-Neto, L. Haddad, R. F. BentoUniversity of São Paulo

Notchpathwayproteins, includingHes-1, play a role in keeping supporting cells phenotype andprevent them frombecominghaircellsbylateralinhibitionmechanism.COUP-TFIisexpressedduringearlyoticvesicledevelopmentandiscorrelatedwiththedifferentiationofhairandsupportcellsintheorganofCorti.TheaimofthisstudyweretocomparedtheexpressionofhairandsupportingcellsandquantifythemRNAlevelsafterknockingdownHes-1andCOUP-TFItranscriptsinorganofCortiorganotypicculturesofpostnatalday3mouse.48hafterlentiviraltransfection,RNAfromtheorganofCortiwasextractedfromsixconditions:control,scrambled,shRNAforHes1,shRNAforCOUP-TF1.RealTimePCRassesstheamountofHes-1andCOUP-TFIsilencing,aswellasMyo7a,Pax2,Sox2andp27.AmongtheconditionswillingtosilenceHes1gene,theonewiththelowestlevelofsilencing(Hes1.210%)showedinterestingresultssuchasincreasedlevelsofexpressionofMyo7a(200%),Sox2(150%)andp27(10%).ThesefindingssuggestminorsilencingofHes1geneleadstocellproliferation,bothhairandsupportingcells.OntheotherhandamongtheconditionswillingtosilenceCoup-Tf1gene,theonewithhighest levelofsilencing(COUP1030%)revealedincreasedlevelsofexpressionofMyo7a(70%),Sox2(60%),Pax2(130%)andp27(40%).ThesefindingssuggestmajorsilencingofCoup-Tf1geneleadstocellproliferation,bothhairandsupportingcells,andwassupportedbyimmunofluorescenceanalysisoftheorganofCorticryostatsections.

HISTOLOGICAL AND FUNCTIONAL ANALYSIS OF XENOGRAFT STEM CELLS OF THE INNER EAR OF MICE IN THE GUINEA PIG COCHLEA-INDUCED HEARING LOSS

L. C. M. Barboza Jr 1, K. Lezirovitz 1, D. B. Zanatta 2, B. E. Strauss 2, A. C. Batissoco 3,R. Mingroni-Netto 3, J. Oiticica 1, L. A. Haddad 3, R. F. Bento 11 Otorhinolaryngology Department. University of São Paulo, School of Medicine2 Viral Vector Laboratory, Translational Research Center for Oncology, Cancer Institute of São Paulo State3 Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo

Inmammals,damagetothesensoryreceptorcells(haircells)oftheinnerearresultsinpermanentsensorineuralhearingloss.Here,weinvestigatewhetherpostnatalmouseinnerearprogenitor/stemcells(mIESCs)areviableaftertransplantationintothebasalturnsofneomycin-injuredguineapigcochleas.Wealsostudiedthepotentialeffectsofthecelltransplantationonauditoryfunction.Eightadultguineapigsweredeafenedby intratympanicneomycindelivery.After7days, theanimalswererandomlydivided intwogroups.Thestudygroup (n=4)receivedtransplantationofLacZ-positivemIESCs inculturemediatothescalatympani.Thecontrol group (n=4) received culture media only. Fourteen days after the transplantation, functional analyses were performedbyauditorybrainstemresponse (ABR)measurement,andtheanimalsweresacrificed.ThepresenceofmIESCswasevaluatedbyimmunohistochemistryofsectionsofthecochleafromthestudygroup.Non-parametrictestswereusedforstatisticalanalysisofthedata.Intratympanicneomycindeliverydamagedhaircellsandincreasedauditorythresholdspriortocelltransplantation.Therewerenosignificantdifferencesbetweenauditorybrainstemthresholdsbeforeandaftertransplantationinindividualguineapigs.SomemIESCswereobservedinallscalaeofthebasalturnsoftheinjuredcochleas,andaproportionofthosecellsexpressedthehaircellmarkermyosinVIIa.SometransplantedmIESCsengraftedinthecochlearbasilarmembrane.OurexperimentsdemonstratedthattransplantedcellssurviveandengraftintheorganofCortiaftercochleostomy.

CHARACTERIZATION AND GENE EXPRESSION PROFILE OF AN INDUCED PLURIPOTENT STEM CELL MODEL FOR FAMILIAL MENIERE’S DISEASE

S. Cabrera 1, AR. Ji 1,2, V. Ramos-Mejia 3, T. Romero 3, L. Frejo 1, P. Real 3, J. A. Lopez-Escamez 1,4 1 Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research Pfizer/University of Granada/ Junta de Andalucía, PTS, Spain2 Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Republic of Korea.3 Gene regulation, Stem Cells and Development Group, Department of Genomic Oncology, GENYO - Centre for Genomics and Oncological Research – Pfizer/University of Granada/ Junta de Andalucía, PTS, Granada, Spain.4 Department of Otolaryngology, Hospital de Poniente, El Ejido, Spain.

Meniere’sDisease(MD)isaninnereardisordercharacterizedbysensorineuralhearingloss,episodicvertigoandtinnitus.Usingwholeexomesequencing,wehaveidentifiedforthefirsttimetwomutationsintheFAM136andDTNAgeneswhichcanbecandidatedisease-causinggenes(1).TheaimofthisstudyistogenerateacellularmodelofMDusinghumaninducedpluripotentstemcells(iPSCs)willhelptodeterminethefunctionalroleofthesegenesinfamilialMD.WehavegeneratediPSCsfromaMDpatientandahealthyrelativefromperipheralbloodmononuclearcells(PBMCs)usingnon-integrativeSendaivirusescontainingSox2,Oct3/4,c-MycandKlf4reprogrammingfactors(CytoTune®-iPS2.0SendaiReprogrammingKit-LifeTechnologies).Twoclones,MD-iPSCs(W7)andcontrol-iPSCs(A2),wereestablishedandcharacterizedinvitroandinvivo,includinggeneexpressionstudies.First,wedeterminedthatexogenousreprogrammingfactorswerenotexpressedinA2atpassage7(p7)andW7passage18(p10).Initial characterization included alkaline phosphatase staining and expression of pluripotency markers hOCT4, hSOX2, hKLF4,hMYCandhNANOGbyquantitativePCR.W7andA2clonesalsoexpressedOCT4,SSEA4andTRA-1-60proteinsasassessedbyimmunocytochemistry. Furthermore, both cell lines demonstrated pluripotency in vitro by embryoid bodies formation whichdifferentiatedintothreegermlayers(ectoderm,mesodermandendoderm)andbydetectionofdifferentiationmarkersininvivo–generatedteratomasbyimmunohistochemistry.Ofnotice,bothcelllinesshoweddifferentproliferationrates,asMD-iPSCsW7haveadoublingtimeof48-53hours,whileWTA2cellsdivideevery36-39hours.Futurestudieswiththiscellularmodelwill includeinvitrodifferentiationtowardsoticprecursorstorepairFAM136AandDTNAmutationsindifferentiatedcells-derivedfromiPSCsfromFMDpatientsusingtheRNA-guideCRISPR-Cas9systemtorestorethephenotype.

REGENERATION, PROTEOMICS AND GENETICS

pippo

Evidenziato







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ROLE OF OXIDATIVE STRESS IN THE COCHLEAR DAMAGE IN ACQUIRED SENSORINEURAL HEARING LOSS: ANIMAL MODEL LESSON

A. R. Fetoni 1, F. Paciello 1, R. Rolesi 1, S. Eramo 2, D. Troiani 2, G. Paludetti 11 Institutes Of Otolaryngology - Catholic University of Rome, Rome, Italy2 Institutes Of Physiology - Catholic University of Rome, Rome, Italy

Sensorineuralhearinglossrecognizesseveralcausesrangingfromdirectandprolongedacoustictraumatoadministrationofdrugssuchasstreptomycinandcisplatin.Themechanismsthroughwhichtheseagentsinducehearinglossarewellunderstoodandtheroleplayedbyexcessiveproductionoffreeradicals,namelyreactiveoxygenspecies,andtheconsequentoxidativestressarenolongermatterofdebate.Throughtheadaptivestressresponse,cells,inparticularneuralcells,trytocounteractfreeradical-induceddamageand increase lifespan.Thehemeoxygenase-1/biliverdinreductasesystem(HO-1/BVR) isamainplayer inthecellstressresponsebecauseitcatabolyzesheme,toxicifproducedinexcessorunderconditionofredoximbalance,andgeneratesbilirubin,astrongfree radical scavenger.Severalapproacheshavebeenproposed toactivate theHO-1/BVRsystemandprevent/contrastneuronaldamage,oneofthemorereliableconsistsinthesupplementationwithnaturalantioxidantssuchasferulicacid(FA),curcumin(CUR),CoenzymeQ(CoQ),rosmarinicacid(RA)etc.Ourstudiesdemonstratedthatthesub-chronicsystemicadministrationofbothFAandCURandCoQandRAimprovedauditoryfunctioninrodentsexposedtonoiseorcisplatinwithacompositemechanismofactionwhichincludeanefficientfreeradicalscavengingactivityandreducedoxidativestress,particularlyevidentatearliertimepoints.Furthermore,asustainedinductionofHO-1,throughthenucleartranslocationofthetranscriptionfactorNrf2,isanadjunctivemechanismof neuroprotectionwhich becomes significant at later time points. In conclusion, systemic administration of (poly)phenolsandothernaturalantioxidantsisanovelstrategytoimproveauditoryfunctioninsubjectsexposedtoacoustictraumaorototoxicdrugs.

ALTERED CHROMOGRANIN-A CIRCULATING LEVELS IN MENIERE’S DISEASE

R. Teggi 1, B. Colombo 2, M. Trimarchi 1, M. Bianco 2, A. Manfredi 3, M. Bussi 1, A. Corti 21 ENT Division San Raffaele Scientific Institute, Milan2 Division of Experimental-Oncology, San Raffaele Scientific Institute, Milan3 Department of Internal Medicine & Division of Regenerative Medicine, Stem Cells & Gene Therapy, San Raffaele Scientific Institute, Milan and Università Vita-Salute San Raffaele, Milan

Objectives:Menière’sDisease(MD)isaninnereardisordercharacterizedbyepisodicvertigo,earfullnessandhearingloss;usuallyvertigoattacksclusterinspecificperiods,followedbyasymptomaticperiods.WestudiedinMDpatientsthecirculatinglevelsofimmunoreactive chromograninA (CgA) and its fragment vasostatin-1 (VS-1), twopolypeptides secretedby theneuroendocrinesysteminvolvedintheregulationoftheendothelialbarrierfunctionandvascularhomeostasis.Methods:SerumlevelsofimmunoreactiveCgA(full-lengthCgAandfragmentslackingtheC-terminalregion)andofVS-1wereassessedin37consecutiveMDpatientsand36controls.TheratiobetweenVS-1andCgAwascalculated.Results:CgAlevelsweresignificantly increased inpatientscomparedtocontrols (1.46±1.78vs0.67±0.27nM,p=0.01),whilenodifferencewasdetectedforVS-1(0.41±0.19vs0.39±0.18nM,respectively).TheCgAlevelsinpatientspositivelycorrelatedwiththefrequencyofvertigospellsinthepreviousfourweeks(p=0.008)andnegativelywiththetimeindaysfromthelastvertigoattack(p=0.018). Furthermore, the VS-1/CgA ratio negatively correlated with the frequency of vertigo spells (p=0.029) and positivelycorrelatedwiththetimefromthelastattack(p=0.003).Conclusion: The results indicate that variations inCgA levels, butnot of VS-1, occur in thebloodof patientswith activeMD,dependingonthefrequencyofvertigospellsandthetimefromthelastcrisis.ConsideringtheknowneffectsofCgAandfragmentsontheregulationofvascularhomeostasis,thisfindingmayhavepathophysiologicalimplicationsthatmeritfurtherinvestigation.

HETEROZYGOUS MUTATIONS IN DTNA AND FAM136A GENES IN FAMILIAL MENIERE’S DISEASE

T. Requena 1, S. Cabrera 1, C. Martín-Sierra 1, L. Frejo 1, S. D. Price 3, A. Lysakowski 3, J. A. Lopez-Escamez 1,21 Otology & Neurotology Group CTS495, GENYO, - Centro de Genómica e Investigación Oncológica – Pfizer/Universidad de Granada/ Junta de Andalucía, PTS, Granada, Spain2 Department of Otolaryngology, Hospital de Poniente, El Ejido, Almería, Spain 3 Department of Anatomy and Cell Biology, University of Illinois, Chicago, IL, USA

FamilialMeniere’sDisease(MD)isfoundin9%ofcasesinEuropeanpopulation.Althoughgeneticheterogeneityisobserved,mostofthefamilieshaveanautosomaldominantpatternofinheritancewithincompletepenetrance(1).Weinvestigatedafamilywith3affectedwomeninconsecutivegenerations.DNAwasisolatedfromhumanperipheralbloodandwholeexomesequencing(WES)wascarriedoutinaSOLiD5500xlplatform.Abioinformaticspipelinewithvariant-prioritizationalgorithms, includingphenotypeontologywereusedtofilterandprioritizetheresultingvariants(2),obtainingsevencandidatevariantsthatwerevalidatedbySangersequencing.Morphologicalandfunctionalstudiesincludingimmunohistochemistry,geneexpression,andimmunoblottingwerecarriedouttoconfirmthepathologicaleffectofthetwofinalcandidatevariants.Wehaveidentifiedtwonovelvariants:aheterozygousnonsensemutationintheFAM136Agenechr2:70527974C>Twhichtruncatestheproteinby62AAandasecondheterozygousmissensemutationinDTNAchr18:32462094G>Tgeneratinganovelsplice-site.ItseffectwasevaluatedinlymphoblastsandanewmRNAisoform,missing49nucleotidesinexon21,wasconfirmed.TwoFAM136AmRNAtranscriptsand theirproteinproductswereconfirmed inpatient lymphoblasts.CarriersofFAM136Amutation showedasignificantdecreaseintheexpressionlevelsofbothtranscriptsinlymphoblastoidcelllines(p=0.002).FAM136Aencodesamembraneproteinofunknownfunctionassociatedwithmitochondria.Inratcristaampullaris,wehavefoundthatFAM136Aproteinco-localizeswiththemitochondrialmarkerCOXIVinthebasalpoleofvestibularhaircells.DTNAencodesalpha-dystrobrevin,amembraneproteininvolvedintheformationandstabilityofsynapsesandthepreservationofbrain-bloodbarrier(3).Intheinnerear,alpha-dystrobrevinwaslocatedinsupportingcells,closetothestromalregion.Preliminaryresultsshowthatbothproteinsarepresentedincochlea.Novelmutations in FAM136AandDTNAgenes areprobable causal variants in familialMD.Adecrease in expressionof codingtranscriptsinpatientlymphoblasts,leadingtohaploinsufficiencyofFAM136A,andthegenerationofanovelsplice-siteinDTNAgene,skippingexon21,suggestafunctionalroleforbothgenesinfamilialMD.AcknowledgementsFundedbyGrantsfromCSBS-2012-0242(TR),EF-0374-2013(TR),Meniere’sSocietyUK(JALE),andNIHR21-DC013181(AL).

A PROTEOMICS BASED APPROACH IN MENIERE DISEASE

E. Cassandro 1, C. Petrolo 2, G. Cuda 3, A. Scarpa 1, G. Sequino 1, G. Chiarella 21 Department of Medicine, University of Salerno, Italy2 Department of Experimental and Clinical Medicine, Audiology and Phoniatrics Unit, “Magna Graecia” University, Catanzaro, Italy3 Department of Experimental and Clinical Medicine, “Magna Graecia” University, Catanzaro, Italy

DiagnosisofMeniere’sDisease(MD)isstillwidelyonclinicalbasis.ThisiscausedfromthefactthatthepathophysiologyofMDisstilllargelyunknown,withoutspecificsignsorsymptoms.Consequencesareoninaccuracyintermsofepidemiology,diagnosisandtreatment.Wehaveusedaproteomics-drivenapproachtoidentifypotentialbiomarkersofMD.Tothisend,plasmawasobtainedfromwholebloodof20individualspreviouslydiagnosedassufferingfromMDandcomparedtoplasmafromhealthydonors.Adepletionofthehighlyabundantproteins(i.e.albumin, IgG,transferrin,etc.)wasperformedinordertoenhancethechanceofdetectionof the less representedones, therefore reducing thenoise-background. Two-dimensionalgelelectrophoresis, followedbyin-geltrypticdigestionoftheselectedspotsandLC-MS/MSanalysis,allowedustoidentifyasetofproteinswhoseexpressionappears tobedifferentiallymodulated inpatientsvs. controls. Inparticular: complement factorHandB,fibrinogenalphaandgamma chains, beta-actin and pigment epithelium derived factor are over expressed; on the other hand, the levels of beta-2glycoprotein-1,vitaminDbindingproteinandapolipoprotein-1aresignificantlydecreasedintheplasmaofMD-affectedindividuals.Even thoughpreliminaryandnotnecessarily linkeddirectly to themolecularpathogenesisof thedisease,ouroriginalfindingssuggestthatamolecularsignature,representedbytheplasmaproteinprofilepreviouslydescribed,mightrepresentapotentiallypowerful, innovativeandnot invasive tool for earlydiagnosis andclinicalmanagementofMDpatients.Moreoverourfindingsuncoverapotentiallystarringroleforsomeproteinsinthedevelopmentandfateofthisfrustratingdisease,whosepathogenesisstillremainsunclear.







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alsoreportsignificantlyreducedqualityoflife,increasedhealthcareexpenses,anddecreasedproductivityduetodizziness-relatedworkplaceabsenteeism.Animplantableprosthesisthatcontinuouslyandaccuratelyemulatesnormalsensorytransductionofheadrotationcouldsignificantlyandcost-effectivelyimprovequalityoflifefortheseindividuals.Thistalkwilldiscussvestibularimplantcandidacy,cost-effectivenessandcharacteristicsofthepopulationofpatientswhostandtobenefitmostfromthistechnology.

THE VESTIBULAR IMPLANT: TOWARDS A CLINICALLY USEFUL DEVICE

R. Van de Berg 1,3, N. Guinand 2, JP. Guyot 2, R. Stokroos 1, H. Kingma 1,3, A. Perez-Fornos 21 Division of Balance Disorders, Department of Otorhinolaryngology and Head and Neck Surgery, Faculty of Health Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands2 Service of Otorhinolaryngology and Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland3 Faculty of physics, Tomsk State University, Tomsk, Russia

Objective:Tofurtherassessthefeasibilityofamultichannelvestibularimplant(VI)inpatientswithabilateralvestibularloss(BVL).Methods:MultiplecharacteristicsoftheVIwereinvestigatedin12BVLpatientsfittedwithamodifiedcochlearimplant(MED-EL)providingvestibularelectrodesinadditiontothe“standard”cochleararray:1)InteractionofpredominantlyhorizontalandverticalVI-inputwithhorizontalresidualvestibularfunction.2)Dynamicvisualacuity(DVA).3)PerceptionofVI-input.Results:1)VI-inputcombinedwithresidualfunctionproducedaVORthatwastheresultofbothinputsandinwhichcharacteristicsofthestrongestcomponentdominatedintheacutephaseofstimulation.2)TheVIwasabletosignificantlyimprovetheDVA.3)PerceptualthresholdsweregenerallylowerthanVOR-thresholds,implyingactivationofdifferentneuralpathways.Conclusion:TheserecentinvestigationsprovidemoreevidenceforthefeasibilityofaclinicallyusefulVIinthenearfuture.Sincedifferentneuralpathwaysarestimulated,theeffectoftheVIshouldnotonlybeobjectifiedbyevaluationofthevestibulo-ocularreflex.

VESTIBULAR IMPLANT: 12 YEARS OF DEVELOPMENT IN THE HUMAN

JP. Guyot 1, A. Perez-Fornos 1, N. Guinand 1, M. Miffon 1, R. Van de Berg 2, R. Stokroos 2, H. Kingma 21 Department of Clinical Neurosciences Service of Otorhinolaryngology, Head and neck Surgery University Hospital and Faculty of Medicine, University of Geneva, Switzerland2 Division of Balance Disorders, Department of ENT Maastricht University Medical Center, Maastricht, The Netherlands

Thedescriptionofsymptomsresultingfromabilateralvestibulardeficitisdifficultforpatientsandoftenmisinterpretedbydoctors.Patientsdonotknowaboutthevestibularsystemthatworksunconsciously.Moreover,thevocabularywhichwouldbeneededislacking.Thereforethediagnosisismadeonlyaftermanyyearsofwandering(morethan2.5yearsinaseriesof23patients,upto9inonecase)andnumerousvisitstoallkindsofspecialists(7inaverage,upto20).Since 12 years we are testing a vestibular prosthesis in the human. It is made of motion sensors, an electronic processor andelectrodesimplantedclosetotheampullaryorgans.Atthetimeofwritingthissummary,12patientsareequippedwithourartificialinnerearprototype.Wehavebeenthefirststoshowthatitispossibletorestorethevestibulo-ocularreflexeswithagainclosetonormal,allowingtocorrectoneofthemajorsymptomsofwhichthepatientsarecomplaining,ablurredvisionwhilewalking.The resultsobtained in the laboratoryareveryencouragingand suggest that itwill bepossible tooffera solution topatientssufferingfromabilateralvestibulardeficitwithinafewyears.

HIGH RESOLUTION MICRO CT SCANNING OF THE HUMAN LABYRINTH TO ASSESS ANATOMICAL VARIABILITY FOR A VESTIBULAR ELECTRODE DESIGN

R. Glueckert 1, L. Johnson Chacko 2, M. Gloesmann 2, S. Handschuh 2, A. Schrott-Fischer 11 Innsbruck, Austria2 VetCore Facility for Research, Imaging Unit, University of Veterinary Medicine, Vienna, Austria

Peoplewhosufferfromseverelossofvestibularsensationmaybehelpedinthefuturewithelectricalstimulationbyavestibularimplant.Likeinthecochleathereareinter-subjectmorphologicaldeviationsinthevestibularsystemthatmayberelevantforthedesignofvestibularelectrodes.Toassessdimensionsandvariationsofsensorystructures,fluidspacesandnervefibrepathwayswedevelopedmethodstonon-destructivelyimagewholehumantemporalboneswithmicrocomputertomography(µCT)athighresolution.ThisallowsustoacquireaccuratequantitativemorphologyofthecomplexinnerearstructuresdowntofewmicrometerresolutionatreasonablecostswithcommerciallyavailableµCTs.Establishedforvisualizationofmineralizedtissuetheuseofbroadbandx-raysrequirescontrastenhancementofsofttissue.Theinnerearisachallengeforthistechniquesinceitissituatedwithinthehardestbone(highabsorption)andcontainsdelicatemembranousstructures(verylowx-rayabsorption).Wetestedseveralcontrastenhancementagentstoselectivelydisplaynervefibersandsofttissueinhumanandanimalinnerearsbeforeandafterdecalcificationofmineralcomponents.Obtaineddataserveinafurthersteptoevaluatedeviationsofwithstatisticalshapemodelsandfiniteelementmodelingofcurrentspread.35humanspecimenswereimagedwithaSCANCOµCT40andCarlZeissXradia400at70KeVforossifiedand45KeVfordecalcifiedbones.DatasetswerevisualizedandprocessedwithAmira®5.5.Initialtestsforcontrastenhancementweredonewithmice,catandhumantemporalbonesandimagedatvoxelresolutionsbetween3,5µmand15µmusingphosphotungsticacid(PTA),Lugol`s10%iodinepotassiumiodine(IKI),1%iodineinabsoluteethanol,osmiumtetroxide,TannicacidandaMegluminamidotrizoat-Natriumamidotrizoatmixture.IKIandPTAprovidethehighestcontrastofsofttissueinossifiedinnerearssothatboneaswellassofttissuecanbedisplayedwithinthesamespecimenacquiredinonescanat70KeV.Thisprocedureisidealforscreeningpurposesofsmalleranimals(mice,rats,cats,guineapigs,etc.)todetectanomaliesofgrossanatomy,boneandmembranouslabyrinth.Substantiallossofnervefibersandneuronsaswellasdegenerationofspiralligamentandstriavasculariscanbedetectedandvolumesquantifiedacrossthewholeinnerear.Forhumantemporalbonesthistechniquedidnotprovideequalresultswiththeequipmentandsettingsused.Theextremelydenseboneandbiggerspecimensize(henceincreasedvoxelsize)impedesvisualizationofdelicatemembranousstructureswithintheossifiedtemporalbonewhichmaybean issueofdynamicrange in imageacquisition.OsO4 incombinationwithdecalcificationofmineralcomponentsseemstobethemethodofchoicetoselectivelypresentmyelinatednervefibersandmembranousstructurestogetherwithsometissuesthatgivehighercontrast(sensoryepitheliumofthevestibularsystemandstriavascularis).Isotropicnon-destructiveµCTimagingisaversatiletooltoassessdimensionsofrelevantstructuresfornewtypesofvestibularelectrodesandidentifyvariabilityforoptimalandsafeelectrodepositioning.

VESTIBULAR IMPLANT FOR SENSORY RESTORATION – CANDIDACY AND EPIDEMIOLOGY

B. K. Ward, D. Q. Sun, Y. R. Semenov, C. C. Della SantinaResident and Post-doctoral Research FellowDepartment of Otolaryngology - Head and Neck SurgeryJohns Hopkins Hospital

Profoundbilateralvestibulardeficiency(BVD)causesdisablingoscillopsia,chronicdisequilibrium,andposturalinstability,anddespitemedicaltherapyandrehabilitation,thereisnoadequatetreatmentforindividualsdisabledbythisloss.Affectedindividualssufferillusorydriftofvisualfieldsduringheadmovement,chronicdisequilibriumandposturalinstabilitycausedbyfailureofvestibulo-ocularandvestibulo-spinalreflexes.RecentepidemiologicdatafromanationalsurveyofUnitedStatesadultsrevealthatmorethan64KUSadults(28/100K)sufferaconstellationofsymptomsconsistentwithchronic,profoundbilaterallossofvestibularsensation.Affectedindividualsreportreductionorcessationofdrivingduetotheirsymptoms(44%),ahighincidenceofreducedparticipationinsocialactivity(56%),a>24-foldincreaseinfallriskincomparisontothenationwideaverage(Wardetal.,2013).BVDindividuals

SYMPOSIUM ON ELECTRICAL VESTIBULAR STIMULATION







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SENSITIVITY OF ELECTROCOCHLEOGRAPHY VS. OTOACOUSTIC EMISSIONS TO DISRUPTED COCHLEAR HOMEOSTASIS IN MENIERE PATIENTS

P. Avan, Y. Pavier, T. Mom, F. GiraudetLaboratory of Neurosensory Biophysics, INSERM UMR 1107, School of Medicine, University of Auvergne, Clermont-Ferrand, France

Theresponsesofcochlearhaircellstosoundstimuliarehighlysensitivetotherestingenvironmentandoperatingpointoftheirstereociliabundles,adjustedforoptimaloperation.Cochlearhydrops,ahallmarkofMenière’sdisease(MD),likelydisruptsstereociliaoperation,withfluctuatinghearingsensitivityasanexpectedresult.Forseveraldecades, itsobjectivediagnosishasresteduponelectrocochleography.TheincreasedsizeofthesummatingpotentialSPrelativetothecompoundactionpotentialofthecochlearnerveAPhasbeenthoughttoreflectanexaggerateddepolarizationofhaircellsinrelationtoadeformed,inflatedscalamedia.Recently,otoacousticemission(OAE)changeswithbodytilthaveshownanabnormalbehaviorinthepresenceofMDsymptoms(Avanetal,HearRes.2011,277,88-95).Here,theoutcomesofSPandOAEtestsperformedconcomitantlywerecomparedintypicalMDpatients.

USE OF MULTIFREQUENCY ADMITTANCEMETRY ASSOCIATED TO GLYCEROL TEST TO ASSESS HYDROPS – NORMATIVE VALUES IN HEALTHY SUBJECTS

V. Franco-Vidal, D. Bonnard, J. Nodimar, V. DarrouzetBordeaux University, Pellegrin ENT and Skullbase surgery department, France

HydropsandabnormalitiesofinnerearfluidpressureareinvolvedinsomeotologicaldiseasesuchasMeniere’sDisease.However,demonstratingpresenceofhydrops is challenging. It is alsodifficult topredict theefficiencyofosmotic treatments.Using theadmittancemetrytestsat2kHz(conductanceandresonancefrequency)associatedwithglyceroltest,weaimedtoanswerthesetwoquestions.Moreover,evenifitisusedsincemanyyears,glyceroltesthasneverbeenassessedwithnormativedatainhealthysubjects.Thefirstpartofthisstudyaimedtocollectnormativedatafrom17healthysubjects (34ears).Weobtainedforallofthemacompleteaudiometry,measurementofconductanceà2kHz,beforeand1hourandhalfafteranoraldoseofglycerol(1,5g/kgbodyweight)(concentration:63g/100ml).Weassessedtheeffectonaudiometry,widthofconductancetympanogramsat2kHz,resonancefrequency,andthepresenceofclinicalsymptoms.Themeanageofthehealthysubjectswas 33+/-12yearsold.Sexratio :3males /14females.Thesymptomsduetoglycerolingestionwere:unsteadiness(47%),nausea(71%),headaches(88%),asthenia(35%).Audiometrywasunchangedafterglycerolingestion.Widthofconductancetympanogramsweredecreasedbyglycerolingestionfrom126,4+/-107daPato121,2+/-113daPabutwithoutanysignificantstatisticaldifference.Theresonancefrequencywasincreasedbyglycerolingestionfrom905,88+/-145to954+/-130Hzwithasignificantstatisticaldifference(p<0,005).Glyceroltestinhealthysubjects,withoutanyhydropsseemstohavefeweffectsonhearing.However,theinnerearfluidpressurecanbedecreasedbyglyceroleveninhealthysubjectsasdemonstratedbytheresonancefrequencyincrease.ThenextstepofthisstudywillbetoassesstheglyceroltestassociatedtomultifrequencyadmittancemetryinMeniere’sDiseasepatientsinordertopredictthetherapeuticeffectofglycerol.

REGENERATIVE MEDICINE FOR THE INNER EAR

J. Ito MD., PhD, Kyoto, Japan

Innereardisorderssuchassensorineuralhearingloss,vertigoanddizzinessandtinnitusareincurableinsomeoccasionbyconventionaltherapeuticstrategies.Newtherapeuticstrategiesforprotectionorrecoverofinnerearfunctionarethereforetobeinvestigated.Latestfindingsonregenerativetherapyfortheinnereardiseaseswillbepresented.Intheearlyphaseofinnereardamage,weshouldtrytorescueinnerearcellsfromcelldeathandpromoteself-repairactivity.Togetherwiththeexperimentalresults,resultofclinicaltrialoflocaldrugapplicationusingnewdrugdeliverysystem(DDS)intotheinnerearusingneurotrophicfactorsorsomeotherdrugswillbepresented.Inductionofcelltransdifferentiationisapossiblestrategy.However,ifnocellsourcesremainintheinnerear,celltransplantationthenbecomes another choice to restore cell growth through regeneration. Thepotential of several kindsof stemcells suchasembryonicstemcells(EScells),bonemarrowstromalcells(BMSCs)andinducedpluripotentstemcells(iPScells)wereexaminedasdonorcellsoftransplantationforreplacinginnerearhaircells,spiralorScarpaganglionneurons(cochlearandvestibularnerve)andothercellsintheinnerear.Transplantationofthosecellswillimproveauditoryandvestibularfunction.Socelltransplantationtherapyisausefulmethodfortreatmentofinnereardiseases.Thenasanoveltherapeuticmethodforsensorineuralhearingloss,implantationofanArtificialAuditoryEpitheliumwillbeexplained.

ON THE ROLE ON DEPLETIVE TESTS: A REVIEW ANALYSIS

E. Covelli, S. Monini, V. Marrone, S. Tarentini, M. BarbaraRome, Italy

Thestate-of-artofthe“glyceroltest”showsthateveniftheinterestintheclassicglyceroltestofKlockhoffandLindblomintherecentyearsisreduced,tosomeextentthetestisstillamongthemostused,forthediagnosis,theidentificationofthediseasestageand,eventually,forspecifictherapeuticalmodalities.Theauthorsevaluatetheevolutionofthedepletivetestsinthelastfifteenyears,intermsof:thecharacteristicofthedifferentdrugsusedfordiagnosticandtherapeuticpurposesintheclinicalmanagementof the endolymphatic hydrops; the administration method; and the method of evaluation of the outcome. During this period,maximumefforthasbeendevotedtotheimprovementofthesensitivityandspecificityofthe“glyceroltest”thattodayseemstobethemostuseddrugthatallowsanobjectivecorrelationwithMenière’sdisease.Apartfromtheosmoticaction,othereffectshavebeenidentifiedandproposedondifferentinnereardistricts.Theauthorsconcludethatitwouldbenecessaryamoreappropriateselectionofthecandidatesforadepletiontestinordertoincreaseitssensitivityrateaswellastousealsoobjectiveprocedures(ECochG,MRI)tovalidateit.

KEYNOTE LECTURE 4

AUDIOLOGICAL DIAGNOSTICS







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RETROSPECTIVE EVALUATION OF HYDROPS DIAGNOSTIC ON MENIERE’S DISEASE

T. LenarzHannover Medical University, Hannover, Germany

ToevaluatethevalueofbothelectrocochleographyandtheglyceroltestforthediagnosisofMenière’sdiseaseandthedecisionmakingfortreatment.128patientswithMenière’sdiseaseasdiagnosedbymedicalhistoryandclinicalpicturewereexaminedwithelectrocochleographyandtheglyceroltest.Resultswereclassifiedisbeinghydropspositiveorhydropsnegativewithrespecttostandardcriteria.Thedecisionforhydropsspecifictherapy(Acetazolamidetherapy,sacdecompression,nervesection)wasbasedontheresultsoftheexaminations.Thesuccessofthetherapywasratedascompleteremission,partialremissionornosuccessoveraperiodof3months,1yearandmorethan1year.TheresultswerecomparedtothatofagroupwithnegativecriteriaforMenière’sdisease.Theremissionrateofanyofthesetreatmentswashigherinthehydropspositivegroupcomparedtothehydropsnegativegroup.Thecalculatedsensitivityofthetestis0.71fortheelectrocochleographyand0.65fortheglyceroltest.ThehydropstestsgivesomehelpinthedecisionmakingfortherapyinMenière’sdisease.However,thelowsensitivityratemightmisssomepatientswithMenière’sdisease.Thereasonsforthelowsensitivityandspecificityarediscussed.

OCULAR AND CERVICAL VESTIBULAR-EVOKED MYOGENIC POTENTIALS TO AIR CONDUCTED SOUND AND BONE CONDUCTED VIBRATION IN MENIERE’S DISEASE

L. Manzari 1, A. M. Burgess 2, H. G. MacDougall 2, I. S. Curthoys 21 MSA ENT Academy Center – Cassino, Italy2 Vestibular Research Laboratory, School of Psychology, University of Sydney, NSW, Australia

Introduction.ThechangeswhichoccurinthelabyrinthduringMeniere’sDisease(MD),arestillpoorlyunderstood.InthisstudywesoughttotestotolithfunctionbyusingarelativelynewtechniqueinMDpatientsevenduringtheacuteMDattack.AirConductedSound(ACS)andBoneConductedVibration(BCV)deliveredatthemidlineoftheforeheadatthehairline(Fz)(causingsimultaneousandapproximatelyequalamplitudelinearaccelerationstimulationatbothmastoids)resultsincervicalevokedmyogenicpotentials(cVEMPs)recordedovercontractedSCMandocularevokedmyogenicpotentials(oVEMPs)recordedbeneathbotheyeswhilethesubjectsislookingup.Methods.30patientswithdefiniteMeniere’sDiseaseduringquiescence,meetingguidelinessetbytheAAO-HNScriteria,weretestedatMSAENTclinicinCassino(Italy)withACS(500,750and1000Hz)andFzBCV500HzoVEMPsandcVEMPsontwooccasion.13subjectswithdefiniteMeniere’sDiseaseweretestedduringquiescenceandatthetimeofattack.16healthycontrolsubjectsweretestedatcomparableintervalsinthesameparadigm.Results.ResponsestoFzBCVshorttoneburststimuliconfirmedresultsobtainedbyManzarietal.2010,showingsignificantasymmetryofn10oftheoVEMPtoFzBCV500HzSTBduringtheattackcomparedtoquiescencebutwithnodetectablechangeinthesymmetryoftheBCVcVEMPduringtheattackcomparedtoquiescence.HealthycontrolsubjectstestedontwooccasionsshowednodetectablechangeinthesymmetryofoVEMPsorcVEMPstoFzBCV500HzSTB.ResponsestoACSshoweddifferentresults.InpatientsduringquiescenceACScVEMPsandoVEMPsrevealeddifferenttuningorsometimesACScVEMPspotentialsarepresentandACSoVEMPsabsentandviceversa.AtthetimeofattackACScVEMPsinMDsubjectsshowquitesameresultsobtainedwithBCVwhilen10toACSoVEMPsinattackisenhanced.Whenapplyingtoneburstsinnormal,thereisafrequencytuningwithlowestthresholdsat500–1000Hzandbestresponsesat500HzforcVEMPsinnormalsconfirmingRauchetal.2006.Air-conductedsoundoVEMPexhibitedadominantpeaklocatedat750or1000confirmingLewisetal2010.Conclusion.InMeniere’sDiseasepatientsairconductedsoundshorttoneburststimulishowednotreliableresults.TheseresultsaretosignifythatthisstimulusinMDpatientsisnotsymmetricallydeliveredtotheotolithicregions(utricularmaculaandsaccularmacula),probablyduetotheendolymphatichydropsthathindersthearrivalofthestimulustotheseinnerearregions.Inotherwords,amechanicalprocessratherthananionicchangeinendolymphmayberesponsibleforthisvestibularpotentialsbehaviorinMDpatients.

A COMPARISON OF ECOCHG, VEMP, VNG AND ROTARY CHAIR RESULTS IN PATIENTS DIAGNOSED WITH MENIERE’S DISEASE

J. A. Ferraro, PhD, P. Svitak, AuDUniversity of Kansas Medical Center, Kansas City, Kansas, USA

Thisstudycomparestheresultsof4testscommonlyusedinthediagnosisofMeniere’sDisease/endolymphatichydrops(MD)fromagroupofpatientswithaconfirmeddiagnosisofthisdisordertodeterminewhichtest(orcombinationoftests)isthemostsensitiveandspecificforthisapplication.Dataweregatheredfromthechartsof30adults(16maleand14female)whohadundergoneElectrocochleography(ECochG),VideoNystagmography(VNG),VestibularEvokedMyogenicPotential(VEMP)andRotaryChair(RC)testing to help diagnose MD. Fisher exact test and chi-square analysis were used to examine the correlation between tests indeterminingthediagnosisofMD.Sensitivityandspecificitywerealsocalculatedforeachdiagnostictest.Post-hocanalysisusingBonferronicorrectionchi-squareoneachpairofdiagnostictestsrevealedastatisticallysignificant (p<0.01)differencebetweenECochGandRC,ECochGandVEMP,VNGandVEMPandVNGandRC.Theoverallsensitivityandspecificityofeachtestwerealsocalculated.Althoughthesamplesizewasrelativelysmall,theresultsareconsistentwithpreviousstudiesinthatECochGwasthemostsensitiveandspecifictestforMDfollowedbyVNG.ThecombinationofECochGandVNGshowedastatisticallysignificantdifferencebetweenVEMPandRCinthediagnosisofMD.

ELECTROCOCHLEOGRAPHY AND VESTIBULAR EVOKED MYOGENIC POTENTIAL IN MENIERE’S DISEASE

S. Dabiri Satri, N. Yazdani, P. Abolhasani, B. Amirzargar, N. RezazadehOtorhinolaryngology Research Center - Tehran University of Medical Sciences, Tehran, Iran

Introduction:asMeniere’sDiseaseisachronicinnereardysfunctionwithoutanydefinitediagnostictools,thegoalofstudywasevaluationtheresultsofelectrocochleography(ECoG)andcervicalvestibularevokedpotential(cVEMP)testsinadultpatientswithdefiniteMeniere’sDiseaseandcorrelationofthesebothtestswitheachother.PatientsandMethods:62patientsafterexcludingoneswithprevioushistoryofotologicsurgeryorinjectionsorneurologicdisorderswereenrolled.ClicksoundstimulationforECoGandtoneburstsoundstimulation(500Hz)forcVEMPtestwereused.Summationpotential (SP) to action potential (AP) ratio more than 0.4 was accepted as elevated ECoG. In addition, absent wave, elevatedthreshold,orabnormalmorphologywasconsiderednegativecVEMPtest.Alltestsweredoneinnon-activephaseofdiseaseaccordingtoclinicalfindings.Results:58%ofpatientswerefemaleandmeanageofpatientswere43.66yearsold.Meanfollowupinthemwere46.8months.75%ofpatientshadelevatedECoGandinwhomthatdiseasewereonrightsideaccordingtoAAO-HNSguideline(29patients),79.3%hadelevatedresultswhileinpatientswithleftsideclinicaldisease(27patients),elevatedratiowas66.8%.TheresultsforcVEMPtestareasthefollowing:71%hadnegativecVEMPoverall,whilein58.6%ofpatientswithrightsideddiseaseand77.3%ofthosewithleftsideddisease,testresultswerenegative.Pearsoncorrelationcoefficientofbothtestswerenotstatisticallysignificant.Nocorrelationbetweenageordurationofdiseaseandtestresultswereseen.Conclusion:asbothtestshadsomebeneficialhelpsfordiagnosingMeniere’sDisease,noneofthemcannotbeusedasadiagnosticmodality.Combinationofbothtestsfordiagnosismaybehelpful,astheydidnothadsignificantcorrelation.

VESTIBULAR DIAGNOSTICS







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NORMAL VIDEO HEAD IMPULSE TEST WITH ABNORMAL CALORIC IRRIGATION TEST IN DEFINITE MENIERE’S DISEASE: A POTENTIAL NEW CRITERIA FOR DIAGNOSIS?

F. Rubin, MD, R. Kania, MD, PhD, B. Verillaud, MD, C. Hautefort, MD, P. Herman, MD, PhDLariboisière University Hospital, Paris, FranceParis Diderot University, University Paris Sorbonne Cité

Menière’sDisease(MD)iscurrentlydiagnosedaccordingtoAmericanAcademyofOtolaryngology–HeadandNeckSurgery(AAO-HNS)criteria.ThediagnosisofMDstillremainsdifficultatearlystageofthedisease(possible lackofcriteriaashearinglossortinnitus). Using VHIT allows exploring the vestibule-ocular reflex (VOR) gain of the three semi-circular canals at physiologicalfrequencies,offeringmoredistinctdatathancalorictest.ThisworkaimedatstudyingVideoHeadImpulseTest(VHIT)onpatientsaffectedbyMD.StudyDesign:prospectivestudyinatertiaryreferralcenter,ofconsecutivelyincludedpatientswithMD.DefiniteMDpatientswereincluded,accordingtoAAO-HNScriteria.AllpatientshadnormalMRIexcludingothersinnereardiseasesandsensorineuralhearinglosshadtoinvolvelow-andmedium-frequencies.VHITwasperformedaswellascalorictestingsundervideonystagmoscopy(Synapsys®).Abnormalityofcalorictestwasdefinedbyunilateraldeficitabove20%,whileVHITabnormalitywasdefinedbyVORgainvalueunder0.68orpresenceofsaccades.ThemainoutcomemeasurementwasthepercentageofnormalVHITcomparedwiththatofnormalcalorictestingsusingStudentt-test.Results:37patientswereincluded,withameanageof56years±12.7.Meanhearinglosswas59dBHL±18.3.TwelvepatientsexperiencedTumarkin’sattacks.AllpatientshadnormalVHIT.Fourpatients(11%)hadnormalcalorictestsand33(89%)patientshadabnormalcalorictestswithameanunilateraldeficitof45%.ThepercentageofnormalVHITwassignificantlyhigherthanthatofnormalcalorictests(p<0,05).Conclusion:thisstudysuggeststhatVHITcouldbenormalinpatientswithdefiniteMDwhenapplyingaVORgainvalueunder0.68.Furtherstudiesarerequiredinordertoconfirmtheseresultswithalargergroupofpatients.

INSTRUMENTAL ASSESSMENT IN MENIERE’S DISEASE: WHICH ROLE FOR VIDEO HEAD IMPULSE TEST?

A.P. Casani, N. Cerchiai, E. NavariPisa University Medical School Dipartimento di Patologia Chirurgica, Medica, Molecolare e Area Critica Cisanello Hospital

InpatientsaffectedbyMenière’sDisease (MD)acompleteassessmentoftheperipheralvestibularfunction ismandatory, inordertoprovideastagingofthedisease,toplananykindoftherapyandtogetusefulinformationsabouttheprognosis.Bothcalorictest(CT)andVideoHeadImpulseTest(vHIT)representavalidatedmethodtoassessthefunctionoftheperipheralvestibularsystembyinvestigatingthefunctionofhorizontalsemicircularcanal(HSC):sincetheytestHSCresponsesrespectivelywithlowandhighfrequenciesofstimulus,CTandvHITareconsideredascomplementaryTheaimofthestudywastoanalyzeandcomparevestibule-oculomotorreflex(VOR)featuresin2populationsofMDpatients,respectivelytreatedornottreatedwithintratympanicgentamicin(ITG),employingCTandvHIT.Clinical and instrumentalfindingsof59MDpatients seenwithinaoneyearperiod ina tertiary referral centerwere retrospectivelyanalyzed.Thewholeserieswasdividedintotwogroups:group1wasrepresentedbypatientstreatedwithintratympanicgentamicin(ITG),whilegroup2wasmadebypatientstreatedwithconservativemedicaltherapy.VideoHeadImpulseTestfindingwereputinrelationshipwithcanalparesis(CP),hearingloss(puretoneaverage–PTA)anddurationofMD.Astatisticalanalysiswasmadeinordertoshowanysignificancy(setatp=.050).Thehigh-frequencyVORgainwassignificantlyreducedontheaffectedsideinthegrouptreatedwithITG,wherethisasymmetrycorrelatewiththedegreeofCPaswell.Nocorrelationwasfoundinbothgroupsbetweenhigh-frequencyVORgainandthefollowing:PTAanddurationofMD.Thestudyshowedthathigh-frequencyVORispreservedeveninthelatestageofMD;thedissociationbetweenCPandvHITfindingscouldrepresentanimportantinstrumentalhallmarkofMD.

VESTIBULAR EVOKED MYOGENIC POTENTIALS IN MENIERE’S DISEASE

O. Çelik 1, B. Şerbetçioğlu 2, G. Eskiizmir 11 Celal Bayar University, School of Medicine, Department of Otorhinolaryngology, Turkey2 Istanbul Medipol University, School of Health, Department of Audiology, Turkey

Thisstudywasdesignedinordertoclarifythechangesinvestibularevokedmyogenicpotentials(VEMP)inMeniere’sDisease.Inaddition,itsroleandfeasibilityasatestbatteryindiagnosisandfollow-upofMeniere’sDiseasewasalsoevaluated.ThestudypopulationincludednineteenpatientswithMeniere’sDisease(7male,12female;meanage46.15years)andeighteenhealthyvolunteers(7male,11female;meanage32.44years).P1andN1wavelatency,P1-N1latencydifference,P1andN1waveamplitudeandP1-N1amplitudedifferencewereobtainedfromtwogroupsusing500Hz,1000Hzand2000Hztoneburststimuli.StatisticalanalysiswasperformedusingtheMann-WhitneyUtest.InthediseasedearsofpatientswithMeniere’sDisease,theP1andN1latencywaselongatedwhencomparedtothoseobtainedfromhealthyvolunteers.TheamplitudeofP1andN1wavesandtheamplitudedifferencealsodecreasedinalltestedfrequencies.However,thisdifferencewasstatisticallysignificantonlyinN1amplitudeandP1latencyofallfrequenciestested.TheincreaseofP1andN1wavelatencyanddecreaseofbothamplitudesarethetwomainchangesintheVEMPofpatientswithMeniere’sDisease.Vestibularevokedmyogenicpotentialisaneasy,fastandrelativelyinexpensivetestfortheevaluationofpatientswithMeniere’sDisease.

OCULAR (O-VEMP) AND CERVICAL (C-VEMP) VEMPS IN PATIENTS WITH “CLINICALLY CERTAIN” MENIERE’S DISEASE

S. McIlhinney 2, G. O’Beirne 2, J. Gourley 1, J. Hornibrook 1,21 Department of Otolaryngology-Head and Neck Surgery, Christchurch Hospital, Christchurch, New Zealand2 Department of Communication Disorders at the University of Canterbury, Christchurch, New Zealand

Tocomparec-VEMPSando-VEMPSinpatientswithacertaindiagnosisofMeniere’sDiseaseandincontrolstoseeiftheycoulddetectsaccularhydrops.Ethicalapprovalwasobtained.22control subjectsand17 subjectswith “ClinicallyCertain”Meniere’sDisease (AAOHNScriteriapluselectrocochleographicconfirmationofcochlearhydrops)were tested.Custom-writtenevokedpotentialaveraging softwareonalaptopwasusedtoevokec-VEMPsandO-VEMPS.Interleavingstimuliatdifferentintensitiesaidedtheaccuracyofthresholddetection.c-VEMPP1,N1andP2peaksando-VEMPN1,P1,N2,P2,N3andP3peakswereanalyzedwithrespecttoamplitude,latencyandthreshold.Subjectswereaskedtoindicateonalinearscale(difficult→easy)thedegreeofdifficultytheyexperiencedflexingtheneckforc-VEMPSorgazingupwardforo-VEMPS.Threshold:TherewasnosignificantdifferencebetweenMeniere’searsandcontrolsforc-VEMPsoro-VEMPS.Amplitude:asignificantreductioninc-VEMPP1N1andN1P2andino-VEMPN2P2amplitudesinMeniere’searscomparedtocontrols.Latency:Thec-VEMPN1peakwas significantlyprolonged inMeniere’s ears. Foro-VEMPSno latencydifferenceswere found. Themajority (67%)ofparticipantswouldpreferhavingtheo-VEMPtestratherthanthec-VEMPtest.This small studyofVEMPS in“ClinicallyCertain”Meniere’sDiseasehasproducedsomenegativefindingsatvariancewithotherstudiesinregardtothreshold,butbyamplitudemeasuresbothc-VEMPsando-VEMPScanreliablydetectsaccularhydrops.Patientsprefertheo-VEMPtest.

OCULAR VEMP FINDINGS IN PATIENTS WITH MENIERE’S DISEASE

F. Kocyigit 1, B. Mutlu 1, Y. Olgun 2, S. Mungan Durankaya 1, E. A. Guneri 2, G. Kirkim 11 Dokuz Eylul University School of Medicine, Department of Otorhinolaryngology, Unit of Hearing, Speech and Balance, Izmir/TURKEY2 Dokuz Eylul University School of Medicine Department of Otorhinolaryngology, Izmir/Turkey

Vestibular-evokedmyogenicpotentials(VEMP)recordedfromextra-ocularmuscles,theso-calledocularVEMP(oVEMP),isbecomingcommonlyusedtoevaluatetheutricularvestibulo-ocularreflex(VOR)andsuperiorvestibularnervefunction.ThisstudywasdesignedtocollectandevaluatenormativedataforoVEMPfindingsinducedbyairconductedsoundstimuliinnormalhealthysubjectsandcomparethisdatawiththoseobtainedfrompatientswithdefiniteMeniere’sDisease(MD).Thirteenmaleand18femalepatients,agedbetween35-70years (mean:51.9±10.6) and30agematchedhealthy controlswere enrolled in this study. Latencies andamplitudesofN1andP1,peak-to-peakN1-P1amplitudeandasymmetryratios(AR)at95dBnHL,500HzairconductedtoneburststimulationlevelandwavethresholdsofrightandleftsideswererecordedinallnormalparticipantsandMDpatients.TheeffectsofgenderonoVEMPresultswerealsoinvestigated.ItwasfoundthatoVEMPwavethresholdsandamplitudesweresignificantlydifferentbetweenhealthyadultsandpatientswithdefiniteMD.However,therewerenosignificantgenderdifferencesintermsofoVEMPparameters.oVEMPmaybeavaluablepartofthediagnostictestbatteryforMenière’sdisease.

A REAPPRAISAL OF MENIERE’S DISEASE SUPPORTED BY VARIABLE LATENCY OF SYMPTOMS AND MRI VISUALIZATION OF THE ENDOLYMPHATIC HYDROPS

I. Pyykkö 1, T. Nakashima 2, T. Yoshida 2, J. Zou 1, S. Naganawa 31 Department of Otolaryngology, University of Tampere, Tampere, Finland2 Department of Otolaryngology, Nagoya University School of Medicine, Nagoya, Japan3 Department of Radiology, Nagoya University School of Medicine, Nagoya, Japan

Menière’s disorder is a symptom complex comprising attacks of vertigo, hearing loss and tinnitus which are associated withendolymphatichydrops(EH)oftheinnerear.Medicalpractitionersoftenhavedifficultymakingthediagnosisduetotheheterogeneityofthesymptoms.WithmodernimagingtechniquesthevisualizationoftheEHhasbecomepossiblein,andthedisorderseemstobemorecommonandcomplexthanhithertobelieved.Weassessedthesymptomentityof340patientsenteringatertiaryhospitalandtheoccurrenceoftheclinicalsymptomsamong740patientsbelongingtoaMenièreassociation.Weused3TMRItoimageEHintheinnerearwithgadoliniumcontrastagent(eithertranstympanicorintravenouslyadministeredGdC)among224patients.Inonsetofthefirstsymptomsonly38%ofthepatientshadthesymptomtriadatclinicalentry,permittingaclinicaldiagnosisofadefiniteMenière’sdisorder.Themeanageofonsetoffirstsymptomwas43.8years,withabout10%ofthepatientsbeingolderthan65years.Thetimedelaybetweenhearing lossandvertigowasmorethanfiveyears in20%ofthepatients. GadoliniumcontrastedMRIdemonstratedEHinEHwaspresentin190outof205ears(93%)withsymptomsattributabletoMenière’sdisorder(bothtranstympanicandintravenouslyadministeredGdC).ThevestibuleshowedEHmorefrequentlythandidthecochlea(p<0.004).Inpatientswithunilateralsymptoms75%theEHwasbilateral.Patientswithasingleinnerearsymptomsuchasvertigo,fluctuanthearingloss,ortinnituscomprisedaheterogeneousgrouponMRIfindings.53%ofpatientswithsuddenhearinglossshowedEH.69to95%oftheotherpatientgroupshadEH.TheEHwasmorefrequentlyobservedinthevestibulethaninthecochlea(p=0.025).Menière’sdiseaseshowsoftenbilateralEHandcomprisesacontinuumfromamono-symptomaticdiseasetothetypicalsymptomcomplexofMenière’sdisorder.Wesuggestthata3T-MRImeasurementshouldbecarriedoutinpatientswithsensorineuralhearingloss,vertigo,andtinnituseithertranstympanically24hafterinjectionor4hafterintravenousinjectionofGdCtoverifytheinnerearpathology.ThetermsvestibularMenière’sdisorderorcochlearMenière’sdisordershouldbeusedinmono-symptomaticpatients.Thiscanleadtobettermanagementofthecondition.







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ENDOLYMPHATIC HYDROPS IN PATIENTS WITH UNILATERAL AND BILATERAL MENIERE’S DISEASE

K. Morimoto1, T. Yoshida 1, M. Sone 1, M. Teranishi 1, S. Naganawa 3, M. Kato 1, S. Sugiura 2, K. Kato 1, T. Nakashima 1,21 Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan2 Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu, Japan3 Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Toevaluatetheendolymphatic spacesizeonbothsides inpatientswithunilateralandbilateralMeniere’sDisease (MD),andtoinvestigatethefactorscontributingtoprogressiontobilateralMDwithrespecttothedevelopmentofendolymphatichydrops(EH).Retrospectivereviewofmedicalrecordsatanacademicuniversityhospital.The subjects for this investigation included29patientswithdefiniteunilateralMD,and12patientswithdefinitebilateralMD,accordingtothecriteriaestablishedbytheAmericanAcademyofOtolaryngology—HeadandNeckSurgeryin1995.Theendolymphaticspace sizewas visualized4hours after intravenousgadoliniumadministration and/or 24hours after intratympanic gadoliniuminjectionusing3-Teslamagneticresonanceimaging.Aradiologistblindedtothepatient’sclinicaldataclassifiedthedegreeofEHinthevestibuleandthecochleainto3groups:none,mild,orsignificant.Inthe29earswithunilateralMD,somedegreeofEHwasobservedineitherthecochleaorthevestibule.SignificantEHwasobservedinthecochleaandinthevestibulein24and20ears,respectively.Onthenon-affectedside,significantEHwasobservedinthecochleaandthevestibulein4and6ears,respectively.NeitherthecochleanorthevestibuleshowedEHin8ofthe29earsonthenon-affectedside.Inthe12patientswithbilateralMD,significantEHwasobservedinallthepatientseitherinthecochleaorinthevestibule.Inall53earswithdefiniteMD,somedegreeofEHwasobservedeitherinthecochleaorinthevestibule.TheuseofMRImayprovideusefulinformationregardingprogressionfromunilateralMDtobilateralMD.

MRI EVALUATION OF ENDOLYMPHATIC HYDROPS AND CLINICAL APPLICATION FOR SURGICAL MANAGEMENT

M. Sone 1, T. Yoshida 1, T. Mukaida 2, M. Teranishi 1, T. Nakashima 1, S. Naganawa 31 Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan2 Department of Otorhinolaryngology, Toyota Memorial Hospital, Toyota, Japan3 Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Visualizationofendolymphatichydrops(EH)hasrecentlybecomepossibleusingMRIwithcontrastagents.TherelationshipbetweenEHonMRIandotologicalexaminationsinpatientswithMeniere’sDiseasehasbeeninvestigated,anditwasfoundthatphysiologicalfunctionwasrelatednotonlytothedegreeofEH,butalsotothepersistenceofEH.EHcouldbefoundincasesofcandidatesformiddleearsurgery,suchasotosclerosis,andpreoperativeEHcouldbeariskfactorforinnereardisturbancesfollowingsurgery.WeinvestigatedthepresenceofEHonMRIinearswithclinicalotosclerosis,andfurtherstudiedtocomparepreoperativeMRIfindingsandpostoperativesymptomsfollowingstapessurgerytoevaluatetheefficacyofsuchMRIevaluationforthemanagementofearswithotosclerosis.SubjectsdiagnosedashavingotosclerosisandagreedtoMRIexaminationwererandomlyrecruitedinthestudy.EarswereevaluatedbyMRIperformed4hafterintravenousinjectionofgadolinium.ThedegreeofEHinthevestibuleandcochleawasclassifiedintothreegrades(none,mild,andsignificant).Imagingdatawerecomparedwithclinicalfindings.Inearsoperated,imagingdataconcerningthedegreeofEHwerecomparedwithpostoperativeclinicalfindings.VaryingdegreesofcochlearEHandvestibularEHwereobserved.EpisodesofacutesensorineuralhearinglosswithrotatoryvertigooccurredinsomeearsthatshowedsevereEHinthecochleaeandvestibules.SevereEH,however,wasalsoobservedinearswithoutsuchsymptoms.ThepostoperativecourseinallearswithnoEHinthevestibulewasuneventful,withsuccessfulimprovementofhearinglevels,butacasewithsevereEHinthevestibulehadpostoperativenystagmusandlongperiodofdizziness.ThepresenceofEHinearswithotosclerosiswasclearlyvisualizedinthepresentpatientseries.Moreover,thepresenceofEHinthevestibuleonMRImightbeahighriskfactorinearsthatarecandidatesforstapessurgery.SuchMRIevaluationcouldprovideusefulinformationformanagingsymptomsrelatedtoEH.

IMAGING

MRI IMAGING OF INNER EAR ENDO-PERILYMPHATIC SPACES AT 3 TESLA AFTER INTRATYMPANIC CONTRAST AGENT ADMINISTRATION IN DEFINITE MENIERE’S DISEASE

S. Salice, A. Tartaro, G. Filograna Pignatelli, A. Pacella, F. Cazzato, G.NeriNeurosciences, Imaging and Clinical Sciences Dept. Gabriele d’Annunzio University Chieti-Pescara, Italy

MRIfindings inMeniere’sDiseasearenotyetdefined. Thepurposeof this studywas todetermine themainfindingsof endo-perilymphaticspacesinpatientsaffectedbyDefiniteMeniere’sDiseaseusingMagneticResonanceImaging(MRI)withintratympanicadministrationofcontrastagent.Twenty-twopatientswithDefiniteMeniere’sDiseaseunderwent3TeslaMRI.3DFLAIRand3DT2SEsequenceswereacquired24hoursafterintratympanicadministrationof0.4-0.5mlofgadobutroldilutedeightfoldwithsaline.Contrastagentwasinjectedthroughthe tympanicmembranewitha25Gneedle.Multi PlanarReconstructed (MPR) imageswereanalyzed.According to literature,vestibularendolymphatichydropswasgradedconsideringtheratiooftheareaoftheendolymphaticspacetothevestibularfluidspace(sumoftheendolymphaticspaceandperilymphaticspace).Patientswithnohydropshadaratioofonethirdorless,thosewithmildhydropshadbetweenone-thirdandahalfandthosewithseverehydropshadaratioofmorethan50%.CochlearandsemicircularcanalsendolymphatichydropswasdefinedaspositivewhenaMRIsignalvoidwasdetected.No adverse events due to contrast agent administration were observed. Four patients didn’t show perilymphatic enhancementtherebytheywerenotconsideredfordataanalysis.Vestibularendolymphatichydropswasobservedin89%ofpatientsanditwasseverein10outof16patients.Whereasposteriorsemicircularcanalendolymphatichydropswasobservedonlyin5outof18patients(28%);lateralandsuperiorsemicircularcanalsendolymphatichydropswasobservedonlyin7outof18patients(39%);cochlearendolymphatichydropswasobservedonlyin9outof18patients(50%).Ourstudyconfirmsthatendolymphatichydropscanbedetectedat3TMRimagesafterintratympaniccontrastagentadministrationandisthemainfindinginpatientswithDefiniteMeniere’sDisease.Moreover,ourpreliminaryresultsseemtosuggestthatendolymphatichydropsmayaffectmoreoftenthevestibulethancochleaorsemicircularcanals.

MRI INNER EAR IMAGING AND TONE BURST ELECTROCOCHLEOGRAPHY IN THE DIAGNOSIS OF MENIERE’S DISEASE

J. Hornibrook 1,3, E. Flook 1, S. Greig 1, M. Babbage 3, T. Goh 2, M. Coates 2, R. Care 1, P. Bird 1,31 Department of Otolaryngology-Head and Neck Surgery, Christchurch Hospital, Christchurch, New Zealand2 Department of Radiology, Christchurch Hospital, Christchurch, New Zealand3 University of Canterbury, Christchurch, New Zealand

To compare the sensitivity of Gadolinium MRI inner imaging with tone burst electrocochleography (EcochG) for diagnosingendolymphatichydrops.StudyDesign:AprospectivestudyonpatientswhoweretohaveanMRIscantoexcluderetrocochlearpathology.Setting:Tertiarycarecentre.Patients:102:57patientswithPossible,ProbableorDefiniteMeniere’sDisease,25withasymmetricalhearingloss,18withsuddensensorineuralhearinglossand2withunilateraltinnitushadadditionalMRIinnerearimagingandclickandtoneburststimulusEcochGtesting.Intervention:Diagnostic.MainOutcomeMeasure:Tocomparethesensitivityofthetwotechniques.In30patientswithsymptom-basedDefiniteMeniere’sDiseasetoneburstEcochGwaspositivein25(83%)andtheclickEcochGwaspositivein9/30(30%),andGadoliniumMRIimagingdiagnosedhydropsin14(47%).ApositiveresultforeitherMRIimagingortoneburstEcochGwasseenin26patients(87%).In14subjectswithsymptom-basedProbableMeniere’sDisease10(71%)hadeitherapositiveEcochGorMRI.In13withPossibleMeniere’sDisease,4(31%)hadapositiveEcochGorMRI.ThisstudyconfirmsthegreatlyenhanceddiagnosticsensitivityoftoneburstEcochGoverclickresponseindiagnosingendolymphatichydropsinMeniere’sDisease.EventhoughadequateMRIimagingwasachievedin90%,toneburstEcochGwasamoresensitivetest.







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IMAGING OF ENDOLYMPHATIC SPACE IN PATIENTS WITH MENIERE’S DISEASE AND NON-OTOLOGICAL DISEASES

T. Yoshida 1, M. Sone 1, K. Morimoto 1, S. Naganawa 2, T. Nakashima 11 Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan2 Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Toexploretheendolymphatichydrops(EH)withmagneticresonanceimaging(MRI)inMeniere’sDisease(MD)andhealthyears.Westudied307Patients(412ears)withMeniere’sDiseasepatientsand18(36ears)patientswithhealthyearpatientswhohaveotherbenigndiseasenon-associatedwithhearingorvestibularfunctioninourhospital.Themeanagesofthesubjectswere52.9years(range13to86years)inMDgroupand55.9years(range24to79years)inthehealthygroup.MRIwasperformed24hoursafterintratympanicinjectionofgadoliniumor4hoursafterintravenousgadoliniumadministration.EHincochleawerepresentin302outof407MDears(74.2%)and14outof34healthyears(41.2%).Significantcochlearhydropswaspresent217outof407MDears(53.3%)and4outof34healthyears(11.8%).EHinthevestibulewaspresentin345outof406MDears(85.0%)and3outof34healthyears(9.0%).Significantvestibularhydropswaspresent235outof406MDears(57.9%)andnoneof34healthyears(0%),respectively.AllofdefiniteMDpatientshadEHinthecochleaorvestibuleinourstudy.TherewerelittlebilateraldifferencesofcochlearEH.ThemaincauseofthehighrateofcochlearEHwasthatourcriteriaassessedthelargestEHinthecochlea.FurtherstudyisneededforsilentcochlearEHmaycontributetothepathogenesisofMDornot.Ontheotherhand,vestibularEHswithhealthyearswereobviouslylesserthanwithdiseaseears,thisshowedstrongassociationwithinnerearsymptomsordisease.

UNDERSTANDING MENIERE’S DISEASE: THE CONTRIBUTION OF HYDROPS- MRI

K. Orimoto, S. O’ LearySydney, Australia

Meniere’sDisease(MD)isanintractable,debilitatingdiseasewhichhasnotbeenfullyunderstoodintermsofitscausesandpathophysiology.Thoughendolymphatichydrops(EH)hasbeenthoughttobethepathologicalexplanationofMD,thereisnotestfordefinitediagnosisoraccurateprognosis.WehavereviewedthelatestresearchfindingsonhowEHMagneticimaging(MRI)hascontributedtomoreaccuratediagnosisandimprovedpathophysiologicalunderstandingandmayhaveanimpactonthechoiceofappropriatetreatmentofMD.Afterinnerear3T-MRImadeitpossibletodelineateEHinpatientswithMDfollowingintratympanicgadolinium-basedcontrastmedia(GBCM)administration(IT-Gd)in2007,numerousstudieshavetriedtovisualizeEHbyusingdifferentroutesofGBCM.SubsequentlyIT-GdandintravenousGBCMadministration(IV-Gd)havebeenvariedwithdifferentsequences,suchasthreedimensionalfluidattenuatedinversionrecovery(3D-FLAIR),heavilyT2-weighted3D-FLAIR,and3D-IRsequencestoaccuratelyvisualizeEH.Morerecently,therehavebeenrigorousinvestigationsintheareaincludingassessmentofthesizeandlocationofEH,andtherelationofthedegreeofEHtoclinicalsymptomsandaudiovestibularfunctiontests,suchaspuretoneaudiometry,Electrocochleography,Vestibular-evokedmyogenicpotential(VEMP)andCalorictests.TheseanalysesoftherelationbetweenEHandclinicalfindingscontributetodifferentiateMDfromotherdiseaseswithsimilarpresentations,suchasvestibularmigraineandperipheralrecurrentvertigo.TheaccurateidentificationofMDwithMRIwillleadtobettermanagementofthecondition.

ENDOLYMPHATIC SPACE SIZE IN PATIENTS WITH VESTIBULAR MIGRAINE AND MENIERE’S DISEASE

T. Nakada 1,2, T. Yoshida 1, K. Suga 1, M. Kato 1, H. Otake 1, K. Kato 1, M. Teranishi 1, M. Sone 1, S. Sugiura 3, K. Kuno 4, I. Pyykko 5, S. Naganawa 1,H. Watanabe 1, G. Sobue 1, T. Nakashima 1,31 Nagoya University Graduate School of Medicine2 Gifu Prefectural Tajimi Hospital3 National Center for Geriatrics and Gerontology4 Kamiida Daiich General Hospital5 University of Tampere

Meniere’sDisease (MD) is characterizedby episodic vertigo,fluctuatinghearing loss and tinnitus. Vestibularmigraine (VM) is arelativelynewdisorderthatischaracterizedbyepisodicvertigoordizziness,coexistingmigraineandshortageofhearingloss.Itisoccasionallydifficult todistinguishbetweenVMandvestibularMDwithheadache.Becauseendolymphatichydrops (EH) isacharacteristicsignofMD,weattemptedtoevaluateendolymphaticspacesizeinbothdiseases.Endolymphaticspacesizeinthevestibule and the cochleawas evaluated in sevenpatientswithVMandage- and sex-matched7patientswith vestibularMD.Forvisualizationofendolymphaticspace,three-teslamagneticresonanceimaging(3TMRI)wastaken4hoursafterintravenousinjection of gadolinium contrast agents using three-dimensional fluid attenuated inversion recovery (3D FLAIR) and HYDROPS(HYbriDofReversedimageOfPositiveendolymphsignalandnativeimageofpositiveperilymphSignal)techniques.InthevestibuleofVMpatients,EHwasnotobservedexceptfortwopatientswithunilateralorbilateralEH.Onthecontrary,inthevestibuleofpatientswithvestibularMD,allpatientshadsignificantEHbilaterallyorunilaterally.TheseresultsindicatedthatendolymphaticspacesizeissignificantlydifferentbetweenVMandvestibularMD.

INTRATYMPANIC DEXAMETHASONE AS A TREATMENT FOR MENIERE’S DISEASE

J. PhillipsNorfolk & Norwich University Hospitals NHS Foundation Trust

TheuseofintratympanicsteroidsforthemanagementofpatientswithMeniere’sDiseasehasgainedpopularityoverthelastdecadeasasafeandeffective,non-destructivemethodtoaddressthesepatients’symptoms.Inviewoftheincreasingevidenceavailablefromclinicaltrials,thispresentationwillpresentanupdateofthecurrentlyavailableevidencefromhighqualityrandomizedclinicaltrials.







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PERILYMPH PHARMACOKINETICS OF GLUCOCORTICOSTEROIDS AFTER INTRATYMPANIC, INTRACOCHLEAR, AND INTRALABYRINTHINE DELIVERY

S. K. Plontke 1, A. N. Salt 21 Dept. of Otorhinolaryngology, Head and Neck Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany2 Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, USA

Glucocorticosteroidsarethemostcommonlyapplieddrugsforthetreatmentof innereardisease.RationalpharmacotherapyoftheinnerearrequiresanunderstandingofpharmacokineticsaccordingtheLADMEprinciples:liberation,adsorption,distribution,metabolismandelimination.Anumberofstudieshaveinvestigatedthepharmacokineticsofglucocorticosteroidsintheinnerearusingdifferentdrugdeliverystrategiesandsystems.Theknowledgegainedfromthesestudiesisreviewedinthispresentation,andincludesthefollowingfindings:Intratympanic(extracochlear)applicationsleadtohigherintracochlearperilymphconcentrationsthanwithsystemicapplication.Theintracochlearconcentrationsafterroundwindowapplication,arehighlyvariable,andarerelatedtothetimethedrugisincontactwiththeroundwindow.Thus,perilymphdrugconcentrationsdependonthedeliverysystemused.Inaddition,afasteliminationfromthecochlearfluidsandtheverylowperilymphflowrateresultinsubstantialbasal-apicalconcentrationgradients.Eliminationoccursmorerapidlyfromscalatympani(ST)thanfromscalavestibuli(SV).Eliminationhalf-timesfordexamethasonehavebeenestimatedwith22.5minforSTand111minforSV,respectively.Ifthevariabilityinpeakconcentrationandgradientisalsopresentunderclinicalconditions,thismaycontributetotheheterogeneityofoutcomethatisobservedafterintratympanicapplicationofglucocorticoidsforvariousinnereardiseases.Animalstudiesshowthatintracochlearapplicationshaveadvantagesoverintratympanicinjectionswithsignificantlyhigher,lessvariabledruglevelsandsmallerbase-to-apexconcentrationgradients.Forfurtherdevelopmentofthistechnique,however,itisofimportancetocontrolleaksofperilymphanddrugfromtheinjectionsiteandtoevaluateitsclinicalfeasibilityandassociatedrisks.Initialresultsofsealingtechniqueshavebeensuccessfullytestedforothersubstances.Theprodrugdexamethasonephosphateismetabolizedtotheactivemoietydexamethasonebase.Themetabolicpathways,however,thatdegradedexamethasoneintheliver(byhydroxalasesCYP3A4andCYP17)donotcontributetotherapideliminationofDexfromperilymph.RecentexperimentsfoundthatdexamethasonemaydecreaseendolymphvolumeorslowtherateofCSFinfluxthatoccursinthenormalcochlea,andthusinfluencefluidphysiologyintheintactear.

RESULTS FROM A PHASE 2B CLINICAL TRIAL TO ASSESS THE SAFETY AND EFFICACY OF EXTENDED-RELEASE DEXAMETHASONE THERMOSENSITIVE GEL FOR INTRATYMPANIC ADMINISTRATION IN SUBJECTS WITH MENIERE’S DISEASE

P. Lambert 1, C. LeBel 2 on behalf of the OTO-104 P2 Ménière’s Study TeamMedical University of South Carolina; Charleston, SC, USA and 2Otonomy, Inc., San Diego, CA, USA

IVsteroidsolutionsareroutinelyinjectedintratympanically(IT)asoff-labeltreatmentforMeniere’sDisease(MD),howevertheyprovidelimitedcochlearexposurenecessitatingrepeatinjections.OTO-104isanovelformulationof6%dexamethasoneinthermosensitivegelthathasbeendevelopedtoovercometheselimitations.WethereforeinvestigatedthesafetyandefficacyofasingleITinjectionofOTO-104inMDsubjects.ApreviousPhase1bstudydemonstratedthatOTO-104reducedvertigofrequencyandtinnitushandicapafterasingleITinjectioncomparedtoplacebo.Prospective,randomized,double-blind,placebo-controlled,Phase2bclinicaltrialevaluating140unilateralMDsubjects,ages18to85years.Subjectsentereda1-monthbaselineperiodtocharacterizediseasestatus,followedbya1:1randomizationtoOTO-104(12mg)orplacebo.Subjectsweremonitoredfor4monthsfollowinginjection.TheprimaryendpointofthetrialwasthereductioninvertigofrequencyduringMonth3comparedtobaseline.Safetywasassessedwithotoscopy,audiometryandtympanometry.Atotalof154subjectswereenrolled inthestudy.Baselinedatashowthatthestudypatientpopulation inthisPhase2bstudywascomparabletotheMDpopulationassessedinthepreviousPhase1bstudy.OTO-104demonstrateda61%reductionfrombaselineinvertigofrequencyinMonth3vs.43%forplacebo(p=0.067),whichnarrowlymissedachievingstatisticalsignificance.Statisticalsignificancewasachievedonseveralprospectivelydefinedsecondaryvertigoendpoints.Theclearefficacytrends invertigoobserved inthis trialprovideabasis toadvanceOTO-104toPhase3testingasapotentialnoveltherapeutictotreatMeniere’sDisease.

SYMPOSIUM “INTRATYMPANIC DEXAMETHASONE AS A TREATMENT FOR MENIERE’S DISEASE”







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CLINICAL APPLICATION OF THE THRESHOLD EQUALIZING NOISE TEST IN PATIENTS WITH MENIERE’S DISEASE: A PRELIMINARY STUDY

J. E. Choi, S. H. Hong, YS. Cho, l. J. Moon, WH. ChungDepartment of Otorhinolaryngology-Otology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Cochleardeadregions(DRs)aredefinedasareasofinnerhaircellsand/orrelatedneurons,whichmaynotfunctionnormallyinhearinglossatagivenfrequency.Thethreshold-equalizingnoise(TEN)testisdesignedtodetectconvenientlythepresenceofDRsinclinicalsettings.WeaimedtomakeapreliminaryassessmentoftheprevalenceofcochleardeadregionsinMeniere’sDiseaseandrelationbetweencochleardeadregionsandhearingrecovery.Between November 2010 and May 2015, 61 patients (65 ears) with Meniere’s Disease who visited our outpatient clinic wereprospectively enrolled.Pure toneaudiometryand TEN (HL) testwereperformed for all thepatients.DRat each frequencywasindicatedbymaskedthresholdsof≥10dBabovetheTENleveland10≥dBabovetheabsolutethreshold.DRwaspresentin14%(n=9)ofthe65ears.Accordingtoaudiometricconfigurations,DRwasmostcommoninmoderatelysevere,flathearingloss.TheprevalenceofDRwaslowerthanthatofSSNHL(suddensensorineuralhearingloss)inthepreviousstudy(theprevalenceofDRinSSNHL:26.5%).MeanhearinglevelwasworseinthepresenceofDR(61.2±9.7dB)comparedwiththatintheabsenceofDR(56.7±11.0dB).WordrecognitionscorealsoworseinthepresenceofDR(47.6±31.6)comparedwiththatintheabsenceofDR(67.9±25.3).DRsinMeniere’sDiseaseweremainlydistributedinthefrequenciesof1kand1.5kHz.AmongthepresenceofDRgroup,threepatientshadhearingrecovery,twopatientshadhearingaggravation,andthreepatientshadnochanceofhearing.MostpatientsparticipatedTENtestmorethanoneyearaftersuddenhearingloss,itwasdifficulttoshowtherelationbetweenhearingoutcomeandthepresenceofDR.AlthoughperformanceoftheTENtestwaslimitedtoshowtherelationwithhearingprognosisinthisstudy,thepresenceofDRshowedpoorresultofhearingcomparedwiththeabsenceofDR.TheprevalenceofDRwasdifferentaccordingtocausesandTENtestmayhavethepotentialtobeusedasaprognostictoolforhearingloss.

USE OF MULTIFREQUENCY ADMITTANCEMETRY ASSOCIATED TO GLYCEROL TEST TO ASSESS HYDROPS – NORMATIVE VALUES IN HEALTHY SUBJECTS

V. Franco-Vidal, D. Bonnard, J. Nodimar, V. DarrouzetBordeaux University, Pellegrin ENT and Skullbase surgery department, France

Hypothesis:administrationofapulsatilepressuretotheinnerearviaaventilationtube(basisofMenietttherapy)isabletoeffectivelychangethesymptomsinpatientswithMeniere’sDiseaseandthiscanbeobjectivelyevaluatedmeasuringtheendolymphatichydrops(EH)throughanelectrochocleography(ECochG).Background:MenietttherapyhasbeenadvocatedbymanyasaneffectivetoolinthestaircaseoftreatmentsavailableforpatientsaffectedbyMeniere’sDisease,afterthepharmacologicaltherapyandbeforedestructivetreatments.OurstudyaimstoevaluatetheeffectsthatmicropressuretreatmenthasonendolymphatichydropsviatheSP/APratioobtainedthroughatranstympanicECochG.Furthermore,wecomparedtheresultswiththeeffectsthatthetreatmentshadonthesubjectivesymptomsofeachpatient.Methods:Atotalof11definiteMDpatientsunderwentmicropressuretreatmentinourdepartmentfromSeptember2014toAugust2015,followingtheinclusioncriteriaof:1.UnilateraldefiniteMDaccordingtotheAAO-HNSguidelines(2015),2.Recurrentandinvalidatingvertigoattacksnotrespondingtodietmodificationsorpharmacologicaltherapyforatleast1year,3.NoCNSsymptoms.ECochGandDHIwereobtainedfromeachpatient1monthbeforeand1,3and6monthsafteradministrationofmicropressuretreatment.ValuesofSP/APratiogreaterthan0.48wereconsideredhydropic.Results: Allselectedpatientswerefoundtobehydropic(SP/APratio>0.48)beforethetreatmentstarted.EcochGafter1monthrevealedEHin72.7%,after3monthsin18.2%andafter6monthsin18.2%ofpatients.MeanDHIwas83.36atbaseline,47.18at1month,28.27at3monthsand26.27at6months.Conclusion:Althoughpatientshadanimmediaterelieffromtheirsymptomsafteradministrationofmicropressuretreatment,mostofthemwerestillhydropicat1month.However,Menietttherapynotonlysucceededineliminatingpatients’symptomsat3months,butitwasalsoeffectiveonEHonmorethan80%ofthem;theseresultsremainedstableaftersixmonths.Patientswhoaftersixmonthsstillsufferedfromhydrops,withoutimprovementofsymptoms,wereaddressedtovestibularneurectomy.MicropressuretreatmentisarefinedtherapyforMDandcanobviatetheneedforsurgery.

EFFECTS OF BODY TILT ON MULTIFREQUENCY ADMITTANCE TYMPANOMETRY

V. Franco-Vidal, D. Bonnard, J. Nodimar, V. Darrouzet Bordeaux University, ENT and skull base surgery Department, France

HydropsandabnormalitiesofinnerfluidpressureareinvolvedinsomeotologicdiseasessuchasMeniere’sDisease(MD).However,demonstrating abnormal perilymphatic or endolymphatic pressure is challenging. Multifrequency tympanometry studies in MDpatientsdemonstratedan increaseof thewidthof conductance tympanograms (outsideanattack) comparedwith controls. Toconfirmthattheincreaseinconductancewidthiscausedbyhyperpressureandnothypopressureinthesepatientstestedoutsidean attack, we assessed the effect of changes in inner ear fluid pressure caused by body tilt on the results of multifrequencyadmittancemetrytympanograms.Amultifrequencytympanometryincludingconductance(G)tympanogramat2kHzandresonancefrequencymeasurementswereperformedin20volunteers(40ears)freeofotologicorneurologicdisease.Themeasureswerecollectedinthreedifferentpositions:vertical,supine,andTrendelenburgpositions.Changes in inner ear fluid pressure caused by body tilt induced an increase in the width of G tympanograms. In the verticalposition,themeanvaluewas141.7±56.5daPa;inthesupineposition,itincreasedto158±58.3daPa;andincreasedevenmoreintheTrendelenburgposition(20degrees),withameanof184±69.6daPa(p<0.01).ResonancefrequencyalsoincreasedintheTrendelenburgposition.WeconcludethattheincreasedwidthofGtympanogramsinMDpatientsoutsideanattackmaybecausedbyanincreaseininnerearfluidpressure.

PREDICTIVE VALUE OF ECOCHG IN OFFSPRING/SIBLINGS OF INDIVIDUALS WITH MENIERE’S DISEASE

J. A. Ferraro, J. R. WilsonUniversity of Kansas Medical Center, Kansas City, Kansas, USA

TheuseofElectrocochleography(ECochG)intheidentification,assessmentandmanagementofMeniere’sDisease/endolymphatichydrops(MD)iswelldocumentedintheliterature.ThecurrentstudywasdesignedtoassesswhetherECochGmightalsobevaluableasascreeningtooltohelppredictthisdisorderinindividualswhomaybegeneticallypredisposedtodevelopingit.Todate,ECochGhasbeenrecordedfromasmallsample(9)ofsubjectswithnohistory/symptomsofMD,butwhoareeithertheoffspringorsiblingsofindividualswithaconfirmeddiagnosis.SevenofthesesubjectshadpositiveelectrocochleogramsforMD,apercentagethatisconsiderablyhigherthantheincidenceoffalsepositiveresultswehavefoundinthegeneral,non-MDpopulation.Theseresultshavemotivatedustocontinuethislineofresearchwiththefollowingquestionsinmind:istheretimepriortotheonsetofsymptomsthattheinitiationofMDmaybedetectedand,ifso,caninterventionalapproaches(e.g.,lifestyle/dietarychanges,pharmaceuticalintervention,allergycontrol)beimplementedtohelpprevent/delaytheonsetofsymptoms.

DIAGNOSTICS







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THE INTERACTIVE GPS SYSTEM FOR DIAGNOSIS OF VERTIGO

A. BelalAlexandria, Egypt

Tosavephysician’stimeandpatient’smoney,aroadmapfordiagnosisofvertigobasedonpatient’shistorywasintroducedin2005.Fivequestionsleadsto10destinations,4withantevertigoand6withchronicdizziness.Eachdestinationhasananatomicalandetiologicaldiagnosisthatrequiresaspecificsetoftestsandinvestigations.TheroadmapwasputintoaninteractiveGP5softwareprogramthatputsthephysicianorpatientinthedriverseat,diagnosingvertigowhiledrivingalongthedizzinesshighway.Eachexitleadshimintothediagnosticbuildingtodoaspecificsetoftests,thatwilleventuallytakehimtohisfinaldestination(diagnosis).

PREVALENCE AND FEATURES OF INFERIOR VESTIBULAR NEURITIS

R. Glatre, MD, R. Kania, MD, PhD, B. Verillaud, MD, PhD, C. Domange, MD, P. Herman, MD, PhD, C. Hautefort, MDLariboisière University Hospital, Paris, FranceParis Diderot University, University Paris Sorbonne Cité

Vestibularneuritis(VN)isanacuteunilateralvestibulopathythatcommonlyaffectsthesuperiorvestibularnerve.Thevideoheadimpulsetest(VHIT)canhelptodiagnoseinferiorvestibularneuritis(IVN)byshowinganisolateddeficitontheposteriorsemicircularcanal(SCC).TheaimofthisstudywastoevaluatetheprevalenceofIVNwhenmanagingacutevertigo,whichcouldbehigherwhenusingVHITinemergency.From2010to2013,aprospectivestudywasconductedinatertiaryreferralcenterforallconsecutiveadultpatientsadmittedforafirstvestibularsyndromemimickingVNwithabnormalVHIT.IVNwasdiagnosedbyisolatedposteriorSCCdeficitonVHIT,normalcalorictestsandtorsionaldown-beatingnystagmus.Amongthe46patients,VNwasconsideredtobeIVNfor14patients(30%),superiorVNfor24(52%)patientsandbothfor8patients(18%).CalorictestswerenormalforallpatientswithIVNwhereastheywerealwaysabnormalwheninvolvingthesuperiorvestibularnerve.NoneofthemhadneurologicalorcochleardisorderandMRIwasnormalforallpatients.ThisstudyconfirmedtheimportanceofVHITwhenmanagingacutevertigoinordertodifferentiatecentralandperipheraldisorderandtodiagnoseinferiorVN.

THE SHORT FORM OF THE DIZZINESS HANDICAP INVENTORY: IS IT COMPARABLE WITH THE ORIGINAL ONE?

F. N. Ardıç, F. TümkayaDepartment of Otolaryngology, Pamukkale University, Denizli, Turkey

Thedizzinesshandicapinventory(DHI)isausefultoolforreportingthepatients’situationbeforeandaftertheinterventions.Buttherearesomanyquestionaries’usedinclinicalpracticelikeVertigoSymptomScale,SymptomChecklist-90,etc.Thenumberofthequestionsisbecomingmoreimportantforefficientworkinginthedepartments.OriginalDHIthatproposedbyJacobsonetal.in1990has25questions,whiletheshortform(sDHI)proposedbyTesioetal.hasonly13questions.OuraimistomeasurethecorrelationbetweentwoformsofDHI.Theformsfilledby2111dizzinesspatientswereevaluatedforthispurpose.TheDHIhas3subscales.Patientsanswerthequestionsasno(0),sometimes(2)andyes(4).ThesDHIhas2subscalesandpatientsrepliesonlyasno(0)oryes(1).Bothofthemshowthedegreeofhandicapaccordingthetotalpoints.Althoughtheyhavesomecorrelationinsubscalesbuttheyshowthedifferentaspectsofthepatient.Onemustbecarefulwhilecomparingtheresultsofthetwoscales.

HORMONAL REGULATION OF POTASSIUM IN INNER EAR, A NEW EXPLANATION IN MENIÈRE’S CRISIS

F. Manach 1,2, S. Viengchareun 1,2, I. Lema 1,2, E. Ferrary 3, M. Lombès 1,2, J. Nevoux 1,2,3,41 Inserm, U1185, Le Kremlin-Bicêtre, F-94276, France2 Université Paris-Sud, Faculté de Médecine Paris-Sud, UMR-S1185, Le Kremlin-Bicêtre, F-94276, France3 Inserm, U867, Université Paris Diderot, France4 Service d’ORL, Assistance Publique-Hôpitaux de Paris, CHU de Bicêtre, Le Kremlin-Bicêtre, F-94275, France

Menière’s disease is an invalidating disease evolving by crisis, frequently triggered by stress and associating vertigo, deafness andtinnitus.HorneretalhavereportedthattheplasmaticconcentrationofepinephrinehigherinpatientwithaMenière’sdisease.Intheinnerear,beta-adrenergicreceptorsarepresentintheendolymphsecretorystructures,asinthedarkcellsinvestibule.FerraryetalhavereportedalsothatpotassiumconcentrationisdecreasedintheendolymphinananimalmodelofMenière’sdisease.ThesedatasuggestthatcatecholaminecouldbeimplicatedinthepotassiumdysregulationininnerearthatconducttoMenière’sdiseasecrisis.TheaimofthisworkistostudytheroleofcatecholamineinpotassiumregulationandtheroleGJA1inpotassiumtransportininnerear.Wedevelopedanimmortalizedvestibulardarkcellline,EC5v,inthelaboratory.Thiscelllineallowsustostudyendolymphsecretionunderdifferenttypeofstimuli,especiallyhormonalstimuli.ThecellswereculturedonfiltertostudythepotassiumtransportusingRubidium.WeusedtherealtimePCRtoexploretheregulationofexpressionofGJA1genes.Thenwecharacterizedproteinsexpressionandlocalizationusingwesternblotandimmunohistochemistry.InEC5v,potassiumsecretion,frombasolateraltoapicalcompartments,wasclearlyincreasedby2-folduponisoproterenolstimulation.TheGJA1geneexpressionwasdownregulateinEC5vby2-folduponisoproterenolstimulation.Thiseffectisinhibitedbythebeat-receptorantagonism,propranolol.Theconnexin43(GJA1gene)isdownregulatinguponisoproterenolandislocalizedinsecretoryregionoftheinnerear.Cardiacmuscleandblodd-brainbarrierepitheliumstudiesreportedaroleinepithelialbarrieroftheconnexin43.Thecatecholamineincreasedduringmenière’scrisisthatcouldconducttoleakageintheperi-endolymphaticbarrierandthemovementofpotassiumthroughendolymphtoperilymphalongtheionicgradient.

IMAGING FLUID DYNAMICS IN THE HYDROPIC EAR WITH LIGHT SHEET FLUORESCENCE MICROSCOPY

D. J. Brown 1, L. Van Roon 2, C. L. Southwell 1, C. S. Pastras 1, I. S. Curthoys 31 Brain & Mind Research Inst., The University of Sydney2 Inst. for Life Sciences & Chemistry, Hogeschool Utrecht3 Department of Psychology, The University of Sydney

Aim:TovisualizedynamicendolymphflowinexperimentalhydropsinguineapigsusingLightSheetFluorescenceMicroscopy(LSFM).AclearunderstandingoffluiddynamicsintheinnerearisvitaltoourunderstandingofMeniere’sDisease,andmayenhanceourknowledgeofinnerearpharmacokinetics.Techniquesforinvestigatinginnerearfluiddynamicsincludeinvivomicropipetterecordingsofbiomarkers,orimagingtheirdistributioninhistologicalslicesorMRIscans.However,westilllackaclearunderstandingofthetransportofendolymph,antigen,ordrugswithintheinnerear.Wecombinedtheuseof200kDfluoresceinisothiocyanate(FITC)-dextranperfusionswithLSFM,toprovide3Dimagesthatprovideinsightintoinnerearfluiddynamics.Viaaglassmicropipette,FITC-dextraninartificialendolymphwasinjectedintoscalamediainanaesthetizedguineapigs.Measurementsofcochlearandvestibularevoked-responsethresholdswereobtainedcontinuouslythroughouttheinjection.Temporalboneswereharvested,fixedin4%PFA,decalcified,dehydratedingradedtetrahydrofuran,andimmersedindibenzylethertoopticallyclearthetissue.Temporalboneswerethenimagedonourcustom-builtLSFM.AsubstantialamountoftheFITC-dextranappearstobetransportedintotheendolymphaticsacshortlyafter ithasbeeninjectedintoscalamedia.Moderate levelsofFITC-dextranappear intheutricleandsemicircularcanals,butnot intheperilymphaticcompartments, suggestingthatthemembranouslabyrinthremainsintact,andthattheFITC-dextranisabletopassthroughtheutriculo-saccularduct.Whilstthistechniquerequirestermination,fixation,andopticalclearing,andcanthusonlyprovidea‘snap-shot’offluiddynamics,itprovideshigh-resolution3Dimagesofbiomarkerdistribution,andofferstheabilitytomodifythefluorescentbiomarkertoexamineeitherintra-orinter-compartmentalfluiddynamicsorpharmacokinetics.TheremarkableuptakeofFITC-dextranintotheendolymphaticsacwithin20minutessupportsthetheorythatthesacactivelyabsorbsendolymphduringhydrops.ThepresenceofFITC-dextranintheparssuperior,butnottheperilymph,followingsufficientendolymphinjectiontoinduceasuddenreliefofacochlearsensitivityloss,supportstheoriesthattheutriculo-saccularductmayopensuddenlyinthepresenceofsevereendolymphatichydrops.

ENDOLYMPHATIC HYDROPS







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MENIERE`S SYMPTOMS AND ENDOLYMPHATIC HYDROPS

C. A. Oliveira, MD, PhDBrasília University Medical School

Since the description of endolymphatic hydrops by Hallpike and Cairns all the physiopathology of Menière`s symptoms wasbasedontheassumptionthatthepathologicllesionwasthecauseofthesymptoms.SchuknechtcameoutwiththetheoryofmembranousrupturecausingthemixingupofendoandperilymphleadingtotheappearenceofMenière`ssymptoms.Lawrencehadprovedthatthiseventcauseddestructionofhaircellsandhearinglossinexperimentalanimals.In1989Istudied89temporalbonesfromtheMassachusettsEyeandEarInfirmarycollectionwhowerecollectedfrompatientswithsignificanttinnitusduringlife.Thegoalwastofindapathologiccorrelatefortinnitus.Mostoftheseboneshadnofindingsinthetemporalbonebutthenextmostfrequentanomalyamongthemwasendolymphatichydrops.Thethirdwasotosclerosis.Furthermoreonethirdoftheboneswithnormnalhistopathologycamefrompatientswhoalsohadvertigoduringlife.Theideaofacontinuumfromnormalbonestoendolymphatichydropswasattractive.ButthatwouldmeanthatMenière`ssymptomsprecededendolymphatichydropsinthesepatients.LaterRauchandMerchantpublishedpapersshowingclearlythatindeedthesymptomscouldexistwithouthydropsandvice-versa.Atthispointendolymphatichydropsmustbethoughtofasanepiphenomenonthathasacommonprecedingcausewiththesymptoms.TheclearassociationofMenière`ssyndromeandmigrainemakesitpossiblethatacentralphenomenonstartsthewholeprocess.Certainlyatleastanattractivedirectionforfutureresearch.

ARE THERE NO NEWS ABOUT THE COCHLEAR HYDROPS?

O. Michel, A. Hess, J. Su, D. Labbé, W. BlochUniversity Hospital Brussel UZB, Vrije Universiteit Brussel, UVB,Brussel, Belgium

Theendolymphatichydrops(ELH)wasfirstdescribedbyYamakawain19386monthsbeforeHallpikeandCairnsbroughtouttheirobservation.Today,immunohistochemicalinvestigationsoftheguineapigcochlea,usingspecificantibodiestoall3knownNOSisoforms,particularlytheinducibleisoformofNO-synthase(iNOS/NOSII),thetargetenzymesolubleguanylylcyclase(sGC)andthesecondmessengercGMPhavebeenperformed1-4weeksafterclosureoftherightendolymphaticductinguineapigs.AcontinuousthresholdshiftwasmeasuredbyBERAwithamaximumof30dBinthe4thweek.Endolymphatichydrops,themorphologicalsubstrateofMenière’sdisease,becamehistomorphologicallyevidentbyexcavationoftheReissner’smembraneintheparaffinsectionsofthecochlea.NOSII-expressioncouldbenotedinendothelium,spiralganglioncells, innervefibers, in supportingcellsof theCorti-organandcellsof the spiral ligament slightlyoneweekafter the surgicalprocedure.Astrongincreasewasnotedinthesecondand3rdweek,whileimmunoreactivity(NOSII)seemedtobedeclined4weekafterthesurgicalprocedure.NOSIwasexpressedinthesamepatternasintheuntreatedcontrols,whereasNOSIII,sGCandcGMPshowedamarkedreductioninthesecondweekandlatercomparedtothecontrolanimals.Activecaspase-3couldregularlybedetectedinSGCandwasalsofrequentlyfoundinlateralwall.WeconcludethatNOSII-generatedNOcouldbeinvolvedinthepathophysiologyofcochleardysfunctioninMenière’sdiseaseorotherinnereardisorderswithhydrops.ThereducedexpressionofNOSIII,sGCandcGMPcouldbeseenasdepletionbutalsoasacounter-regulation.Theactivationofcaspase-3inSGCgivesfurtherevidencethatradicalssuchasRNSorROScouldbeinvolvedintheearlystagesofELH.RNSandROSmightinduceapoptosisandcausetheirreversiblehearinglossinlaterstagesofMenière’sdisease.

ANTERIOR MEMBRANOUS LABIRYNTH HYDROPS

S. Ferrara, F. Martines, P. Ferrara

Hydropsistheincreaseoffluidsintheinnerear.Aretrospectivestudyincluded12patients(8Femalesand4Maless)fromMarch2013toMarch2015.Thestudygrouphadamedianageof47,5(range38-57yr.).Thepatientsweresubmittedtofullotorhinolaryngologicalexamandaudiometricevaluation.Patientsshowedanunilateralmoderateconductivehearinglossforlowfrequenciesormixedhearinglosswithoutvertigo.Transientunilateralfullness, tinnitus, recruitmentandnormalotoscopy.Theaimofthisstudywastofindoutpathogenesisofthisdisease.Differentialdiagnosiswasputwithotosclerosis,otitismedia,Meniere’sDisease,transitoryhearinglossandLermoyezsyndrome.Moreetiopathogeneticfactorssupporthydrops:hydricmetabolismtheory,hormonaltheory,hystaminetheoryandneurovegetativetheory.Pathogenesisofanteriormembranouslabirynthhydropsisdouble:1)increasedproductionofendolymphaticfluids becauseofNa/K-ATPase enzymatic system interveningon stria vascularis and involvingomeostasis of endolymphaticfluids;2)obstructionofendolymphaticductordisfunctionofendolymphaticsac.Thepatientsweretreatedwithdiuretic,betamethasone,citicoline,cinnarizine,dietwithoutsalt,greasyandallergicfoods.Therightdiagnosisassociatedwiththerapyaresuccessfullindoingtodisappearsymptomatologyinonemonth.

OXIDATIVE STRESS, REDOX HOMEOSTASIS AND CELLULAR STRESS

A. Serra, V. Calabrese, S. Cocuzza, P. Di Mauro, L. MaiolinoENT Department - University of Catania, Italy

Menière’sdisease(MD)ischaracterizedbythetriadoffluctuatinghearingloss,episodicvertigoandtinnitus,andbyendolymphatichydropsfoundonpostmortemexaminations.IncreasingevidencesuggeststhatoxidativestressisinvolvedinthedevelopmentofendolymphatichydropsandthatcellulardamageandapoptoticcelldeathmightcontributetothesensorineuralhearinglossfoundinlaterstagesofMD.Whileexcessreactiveoxygenspecies(ROS)aretoxic,regulatedROS,however,playanimportantroleincellularsignaling.Theabilityofacelltocounteractstressfulconditions,knownascellularstressresponse,requirestheactivationofpro-survivalpathwaysandtheproductionofmoleculeswithanti-oxidant,anti-apoptoticorpro-apoptoticactivities.Amongthecellularpathwaysconferringprotectionagainstoxidativestress,akeyroleisplayedbyvitagenes,whichincludeheatshockproteins(Hsps)aswellasthethioredoxin/thioredoxinreductasesystem.InthisstudywetestedthehypothesisthatinMDpatientsmeasurableincreasesinmarkersofcellularstressresponseandoxidativestressinperipheralbloodarepresent.Thisstudyalsoexploresthehypothesisthatchangesintheredoxstatusofglutathione,themajorendogenousantioxidant,associatedwithabnormalexpressionandactivityofcarbonicanhydrasecancontributeto increaseoxidativestressandtodisruptionofsystemicredoxhomeostasiswhichcanbeassociatedtopossiblealterationsonvulnerableneuronssuchasspiralganglionneuronsandconsequentcellulardegeneration.Wethereforeevaluatedsystemicoxidativestressandcellularstressresponse inpatientssufferingfromMeniere’sDisease (MD)and inage-matchedhealthysubjects.Systemicoxidativestresswasestimatedbymeasuringproteinoxidation,suchasproteincarbonyls(PC)and4-hydroxynonenal(HNE)inlymphocytesofMDpatients,aswellasultraweakluminescence(UCL)asend-stableproductsoflipidoxidationinMDplasmaandlymphocytes,ascomparedtoage-matchedcontrols,whereasheatshockproteinsHsp70andthioredoxin(Trx)expressionweremeasured in lymphocytestoevaluatethesystemiccellularstressresponse. Increased levelsofPC(P\0.01)andHNE(P\0.05)havebeenfoundinlymphocytesfromMDpatientswithrespecttocontrolgroup.ThiswasparalleledbyasignificantinductionofHsp70,andadecreasedexpressionofTrx(P\0.01),whereasasignificantdecreaseinbothplasmaandlymphocyteratioreducedglutathioneGSH)vs.oxidizedglutathione(GSSG)(P\0.05)werealsoobserved.Inconclusion,patientsaffectedbyMDareunderconditionofsystemicoxidativestressand the inductionofvitagenesHsp70 is amaintained response in counteracting the intracellularpro-oxidant statusgeneratedbydecreasedcontentofGSHaswellasexpressionofTrx.Thesearchfornovelandmorepotentinducersofvitageneswillfacilitatethedevelopmentofpharmacologicalstrategiestoincreasetheintrinsiccapacityofvulnerableganglioncellstomaximizeanti-degenerativemechanisms,suchasstressresponseandthuscytoprotection

FIFTEEN YEARS OF INTRATYMPANIC PRESSURE TREATMENT FOR DISABILITATING MENIERE’S DISEASE

Maurizio Barbara, Edoardo Covelli, Anna Teresa Benincasa, Luigi Volpini, Simonetta MoniniSapienza Rome, ENT Clinic, NESMOS Department, University Hospital Sant’Andrea, Italy

ThelocalpressuretreatmentwiththeMeniettdevicehasbeenadoptedsince1999inselectedcasesofdefiniteMeniere’sDiseaseforwhom,duetothefailureofmedicaltreatment,vestibularneurectomy-asgoldstandardsurgicalprocedure-hadbeenplanned.Althoughnoclearexplanationstillexistsonthemechanismofaction,ithasbeenproposedthatalocalpressuretreatmentcouldinfluencetheendolymphatichydropsbyfavoringtheflowofendolymphtowardstheendolymphaticsac,thussolicitingitforanenhancedreabsorptivefunction.TheRomeprotocolconsisted in1-month long, self-administeredtreatment, startingfromthedaywhenaventilationtubewasinserted.Asmentionedbefore,onlythosemeniericpatientswithrecalcitrantdiseaseasdisplayedbyanintenserecurrenceofcrises-suchas2/3perweeksor5permonthduringthelastthreemonths-,thereforeidentifiedasClassD(AAO-HNS,1995),wereselectedforaMenietttreatment.Morethan90subjectswerethereforetreatedbetween1999andSeptember2015.Eachpatientwastestedwithpuretoneaudiometry,aswellaswithothereventualMeniere-relatedtests(depletiontest,electrocochleography),beforeandafterthetreatment,andtheywerealsoaskedtofilladiaryduringthemonth-therapy,signalinganydisturbancerelatedtoMénière’ssymptomatology.Inalimitednumberofsubjects,further1-monthlongtreatmentswereneeded,duetoarelapseofsymptomatologyafterafirstperiodofreliefafterMenietttreatment.Inalastseriesofsubjects,ECochGwasusedtofollow-uptheeffectofMenietttreatmentsoonaftertheendoftreatment,aswellasat1,3and6monthsafter.TheoutcomefromMenietttreatmentwasevaluatedinthesubjectswithaleast2-yearsfollow-up(AAO-HNS,1995)bycomparingthepre-versus thepost-opdiseaseclass (AAO-HNS,1995).Nearly65%ofthetreatedsubjectshadrelief fromthediseaseandneverneededadditionaltreatment.Theelectrophysiologicaldatahaveallowedtohypothesizethatsuchapressuretreatmentcouldactuallypositivelyinfluencethehydropiccondition,withaprolongedaction.Menietttreatmenthasprovedtobeeffective,onlymildlyinvasive(insertionofventilationtubeneeded),andworthtobeproposedincaseoffailurefrommedicaltreatment,andbeforeamoreinvasivesurgicalprocedureistakenintoconsideration.

LOCAL TREATMENT OF IMMUNE-MEDIATED HEARING LOSS BY ANTI-TNF ALPHA DRUGS

P. P. Lefebvre, S. Barriat, F. Van WijckDept. of Otorhinolaryngology, University of Liège, Belgium

Objective:Toevaluatethelocaladministrationofanti-TNFalphaantibodiestotheinnerearofpatientssufferingfromautoimmunesensoryhearingloss.Background:LocaladministrationofTNFalphablockerinananimalmodelofautoimmunediseasepreventsinflammationinthecochleaanditsassociatedhearingloss.Methods:9patientspresentingwithautoimmunesensoryhearinglosswhorespondedtooralsteroidtreatmentwereimplantedwithaSilversteinmicrowick°localdeliverysystemtotheroundwindowmembranefor3to4weeks.Results:7patientsoutof9exhibitedastabilisationoftheirpuretoneaudiometry(PTA)foraperiodoftimerangingfrom3to15month.5of9patientsshowedanimprovementoftheirhearingthreshold.Amongthe7respondingpatients,2ofthemneededasecondtreatmentwhichinducedasecondrecoveryofthePTA.Notoxiceffectduetothelocaladministrationoftheanti-TNFalpha(Remicaid°)treatmentwereobserved.Conclusion:LocaladministrationofTNFalphablockerstotheinnerearofpatientspresentinganautoimmunehearinglossallowsstabilizationorimprovementoftheirhearingfunction.







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A LOCUS IN CHROMOSOME 6P21.33 ASSOCIATED WITH BILATERAL SENSORINEURAL HEARING LOSS MAY DEFINE IMMUNOMEDIATED VARIANT IN MENIERE’S DISEASE

S. Cabrera 1, T. Requena 1, C. Martín-Sierra 1, L. Frejo 1, A. Batuecas 2, J. M. Espinosa-Sanchez 3, J. A. Lopez-Escamez 1,41 Otology & Neurotology Group CTS495, GENYO, - Centro de Genómica e Investigación Oncológica –Pfizer/Universidad de Granada/ Junta de Andalucía, PTS, Granada, Spain.2 Department of Otolaryngology, Hospital Universitario Salamanca, Spain3 Department of Otolaryngology, Hospital San Agustinl Linares, Jaen, Spain4 Department of Otolaryngology, Hospital de Poniente, El Ejido, Almería, Spain

PatientswithMeniere’sDisease(MD)haveanelevatedprevalenceofseveralautoimmunediseasessuggestingasharedautoimmunebackground(1).Thegenotypingoflargecohortsofpatientswithseveralautoimmunediseaseshasshownthatmostofthesediseasessharesusceptibilityloci(2).However,noconsistentlociorgeneticmarkerhavebeenassociatedwithMDandmostofthegeneticstudieswerenotreplicatedinanindependentcohortofpatients.Wehaveusedahighdensitygenotypingarray,containing195805singlenucleotidepolymorphismand718smallindels,targeting186locipreviouslyassociatedwith12autoimmunedisorders(Immunochip,Illumina)toexploretheassociationwithMD.AfterQC,99765markersand1587samples(689cases/898controls)remainedforfurtherstudies.Althoughnomarkerreachedagenome-widesignificantassociation(p<10-8),twogenomicregionsinchromosomes2and6showedahighnumberofnon-codingSNVswithp0.05,Regulomedatabaseinformationandlinkagedisequilibriumdata.Meta-analysisofbothcohortshasidentifiedasmalllocuswith30Kbinchromosome6p21.33withseveralassociatedSNPs(rs9380217withp-value1x10-6andrs4947296withp-value4x10-6).ThelocusincludesregulatoryelementsbindingsitesandtheclosergenesareDPCR1,MUC21,MUC22,HCG27,CDSNandPSORS1C1.OngoingworkistryingtoidentifythefunctionalSNPsinthelocus.AcknowledgementsThisstudywasfundedbyPI13/1242Grant.SoniaCabreraissupportedbyMeniere’sSocietyUK,WES-MDGrant.References1.GazquezIetal.HighPrevalenceofSystemicAutoimmuneDiseasesinPatientswithMenière’sDisease.PLoSONE.2011;6(10):e26759.

NEUTROPHIL-TO-LYMPHOCYTE RATIO AND PLATELET TO LYMPHOCYTE RATIO IN PATIENTS WITH ACUTE MENIERE’S DISEASE

V. Squeo, P. T. D’Ambruoso, N. QuarantaOtolaryngology, Department of BMS, Neuroscience and sensory Organs, University of Bari

WeaimedtoinvestigatetherelationshipbetweenacutevertigoandinflammationinpatientsaffectedbyMeniere’sDisease(MD)byusingtheneutrophil-to-lymphocyteratio(NLR)andplatelet-to-lymphocyteratio(PLR)asaninflammatorymarker.Werecruited40patientswithMD(meanage,49±15years)whopresentedtotheOtolaryngologyDepartmentofUniversityofBari.Wealsoenrolled38age-andsex-matchedhealthysubjects(meanage,45±10years)whounderwentroutinecheckupsinourhospital.TheMDpatientswereclassifiedasdefiniteMDaccordingottheAAO-HNSguidelines.NLRandPLRwerecalculatedinallsubjectsandwascomparedbetweenthepatientandcontrolgroups.MDpatientspresentedhighertotalcholestearol,ESR,NLRandPLRcomparedtothecontrolgroup.Inconclusion,thisstudy,whichisthefirsttoinvestigatetherelationshipbetweentheNLR-PLRandMD,demonstratesthatthattheNLRandPLRaresignificantlyhigheramongMDpatientsthanamonghealthycontrols.ThisresultsuggeststhattheNLRandPLRarenovelpotentialmarkerofinflammationinperipheralvertigopatients.

KEYNOTE LECTURE 5

IMMUNE SYSTEM AND MENIERE’S DISEASE

AUTOIMMUNITY AS A CANDIDATE FOR THE ETIOPATHOGENESIS OF MENIERE’S DISEASE: DETECTION OF AUTOIMMUNE REACTIONS AND DIAGNOSTIC BIOMARKER CANDIDATE

J. Jung, J. Y. Kim, H. J. Lee, M. Gi, B. G. Kim, J. Y. Choi, S. H. KimDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea

Meniere’sDiseaseisaninnereardisorderthatcanmanifestasfluctuatingvertigo,sensorineuralhearingloss,tinnitus,andauralfullness.However,thepathologicmechanismofMeniere’sDiseaseisstillunclear. Inthisstudy,weevaluatedautoimmunityasapotentialcauseofMeniere’sDisease.Inadditionwetriedtofindusefulbiomarkercandidatesfordiagnosis.Weinvestigatedtheproteincompositionofhumaninnerearfluidusingliquidcolumnmassspectrometry,theautoimmunereactionbetweencirculatingautoantibodiesinpatientserumandmultipleantigensusingtheProtoarraysystem,theimmunereactionbetweenpatientserumandmouseinnereartissuesusingwesternblotanalysis.Nineproteins,includingimmunoglobulinanditsvariantsandinterferonregulatoryfactor7,werefoundonlyintheinnerearfluidofpatientswithMeniere’sDisease.Enhancedimmunereactionswith18candidateantigensweredetectedinpatientswithMeniere’sDiseaseinProtoarrayanalysis;levelsof8oftheseantigensweremorethan10-foldhigher inpatients than incontrols.Antigen-antibody reactionsbetweenmouse innerearproteinswithmolecularweightsof23–48kDaand63–75kDaandpatient seraweredetected in8patients. Thesefindings suggest thatautoimmunitycouldbeoneofthepathologicmechanismsbehindMeniere’sDisease.Multipleautoantibodiesandantigensmaybeinvolvedintheautoimmunereaction.Specificantigensthatcausedimmunereactionswithpatient’sseruminProtoarrayanalysiscanbecandidatesforthediagnosticbiomarkersofMeniere’sDisease.

EXPERIENCE OF IMMUNOLOGICAL ASPECTS OF MENIERE’S DISEASE

A. Nacci, J. Matteucci, B. Fattori, S. O. Romeo, S. BerrettiniENT Audiology Phoniatric Unit, University of Pisa

Thecorrelationbetweenautoimmunedisordersandpathologyoflabyrinthinestructures,hasbeenparticularlystudiedinMenière’sdisease (MD). In spite of the well-known histopathological lesion of MD, an endolymphatic hydrop involving the membranouslabyrinthine, its aetiopathogenesis remains anunresolved issue.Vascular alterations, geneticpredisposition,hormonaldisorders,nutritionalandpsychologicalfactorsmightcontributetothegenesisofhydrop.Foratleasttwodecades,ourattentionhasbeenfocusedontheroleoftheimmunesysteminmediatingidiopathicendolymphatichydrop.Intheearly’90s,weshowedanabnormalimmunologicalpatterninsamecasesofMDprobablyduetoanaspecificresponseofimmunesystem,asconsequenceofanalterationofthenormalinnerearhomeostasis.Subsequentlyourstudiesfocusedonserumlevelsofantibodiestolaminin,collagenII(CII),collagenI(CI),collagenIV(CIV),andcollagenV(CV).Theresultsofthisstudydonotindicateaclearroleforthisauto-antibodies;theycould,however,contributetotheperpetuationofthediseaseorplayaroleasacofactorinassociationwithothermechanisms.InanotherresearchweexaminedthereactivitytobovineinnerearantigensofserafromaseriesofMDpatients.Reactivitytoinnerearantigensofmolecularweight44and53kDwasfoundinapproximately40%ofthepatients.Antibodiesto44and53kDproteinscouldplayaroleinthepathogenesisofMD,contributetoperpetuationofthediseaseand/orplayaroleascofactorinassociationwithothermechanisms.Afterwards,intwoarticles,weevaluatedthepossibleassociationbetweenMDandthepresenceofseveralautoantibodies.WeevaluatedtheassociationbetweenthyroidautoimmunityandMD,andthepossibleconcomitantpresenceofthyroidautoantibodies(organspecificautoimmunity)andnon-organspecificautoantibodiesinalargeseriesofnon-selectedMDpatients.ThepresenceofpositiveserumautoantibodytitreswassignificantlyhigherinMDpatientsascomparedtocontrolgroups.A statistically significantdifferencewasalsoobservedbetweenMDpatientsandcontrolgroupseither regardingorgan specificautoimmunityandnon-organspecificautoimmunity.Amongsubjectswithpositiveautoantibody titres, the frequencyoforganandnon-organautoimmunity (“mixed”autoimmunity)wasalmostdouble, inMDpatientsascomparedtocontrols.Thesestudydemonstratedasignificantly increasedprevalenceofbothorganandnon-organspecificautoimmunitemarkers inMD.Recentlywestudiedthevestibulardisorders ineuthyroidpatientswithHashimoto’s thyroiditis (HT);our studyprovedthat52•2%ofHTpatientsshowedanalterationofVEMPsand44•7%ofcalorictest.AcorrelationwasfoundbetweenvestibularalterationsofHTpatientsandthedegreeofserumTPOAblevel.Thisfindingsuggeststhatcirculatingantithyroidautoantibodiesmayrepresentariskfactorfordevelopingvestibulardysfunctionlikehydrop.Probably,insomecasesofMD,theprecipitationoforganornon-organspecificautoantibodyimmune-complexes intheinnerearortheautoimmunemicroangioitisofthelabyrinth,couldexplainthedysregulationof innerearfluidhomeostasisandthereforethepathogenesisofendolymphatichydrops. Inthispresentation,wepresentareviewofourtwentyfiveyearsresearchabouttheroleofimmunesysteminMenière’sdisease.







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THE REGENERATING INNER EAR

Helge Rask-Andersen 1, Hubert Löwenheim 2, Rudolf Glueckert 3,Annelies Schrott-Fischer 31 Department of Surgical Sciences, Head and Neck Surgery, section of Otolaryngology, Uppsala University and Department of Otolaryngology, Uppsala University Hospital, SE-751 85, Uppsala, Sweden2 Department of Otorhinolaryngology - Head & Neck Surgery, European Medical School, University of Oldenburg, Steinweg 13-17, 26122 Oldenburg, Germany3 Department of Otolaryngology, Medical University of Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria

Thehumaninnerearhasgenerallybeenregardedasanorganwithlimitedregenerativecapacity.Unlikemammals,manyvertebrates´(reptiles,birds,amphibians,andfish)haircellscanbereplaced,apparentlyfromsurroundingnon-sensorysupportingcells(CorwinandCotanche,1988;Cotanche,1987;RyalsandRubel,1988;StoneandCotanche,2007;TaylorandForge,2005).Furthermore,studiesshowthatevenmammalianvestibularhaircells,includinghumanmayregenerate(Forgeetal.1993,Warcholetal.1993,1998;Kawamotoetal.,2009);aphenomenonalsoeminentinclinicalpractice.Recently,usingtissueobtainedfromtrans-labyrinthineneuromaremoval,acapacityforhaircellregenerationwasfoundinhumanvestibularsensoryepitheliumfrom“older”individuals(ForgeandTayloretal.2015)suggestingpossiblemeasurestoenhancehaircell regeneration inman.Regenerationhasnotyetbeenproveninhumancochlearsensoryepitheliumwherehaircellsappeartohavelittleregenerativecapacity.Thehumancochleais inaccessibleandcontentdelicate. InUppsala,humancochleaewerecollectedduringremovalof large, life-threateningpetro-clivalmeningioma.ItmadeitpossibletoanalyzefreshhumantissueandcellsusingSEM,TEM,cellandorganotypicculturesandimmunohistochemistryandcellphysiology.ProliferativepotentialwasanalyzedusingmarkerssuchasKi67,PCNA,Sox2andp27kip1.AtthemolecularlevelorganofCorticellsexpressedhighlevelsofcyclin-dependantkinaseinhibitorsp27(Kip1)(Löwenheimetal.1999).Wefound“supernumeraryhaircells“andKi67/Sox2positivesupportingcells(1.8%-unpublisheddata).Itwasunforeseentodiscoverneurospheresanddifferentiatingneuronsfromfreshlyobtainedadultcochleaeharvestedatsurgery.Findingsmaysuggestalow-gradecellturnoverinthehumancochlearsensoryepitheliumandcansupportstrategiestoinduceregenerationtotreatdeafnessinman.Acknowledgements:ThisstudywassupportedbyALFgrantsfromUppsalaUniversityHospitalandUppsalaUniversityandbytheFoundation of “Tysta Skolan”, Swedish Deafness Foundation (HRF). Our research is part of the European Community Research;Humanstemcellapplicationsforthetreatmentofhearingloss.GrantAgreementNo.603029.Projectacronym:OTOSTEM,andkindprivatefundsfromBörjeRunögård,Sweden.*informedconsentandapprovalbyethicscommitteeofUppsalaUniversityHospital(no.99398,22/91999,29/122003)

EXPERIMENTAL INDUCED HYDROPS - IN VIVO STUDIES IN MICE

M. Magnusson

Lund, Sweden

CLASSIFICATION OF MB MENIERE, A PROGRESS REPORT

J. A. Lopez Escamez

Otology & Neurotology Group CTS495, Centre for Genomic and Oncology Research (Genyo), Granada, Spain

IT THERAPY FOR MD

M. MagnussonLund, Sweden

BARANY SYMPOSIUM: FROM MOUSE MODELS TO CLASSIFICATION OF MB MENIERE

CEREBRAL VENOUS INSUFFICIENCY IN MENIERE’S DISEASE

R. FilipoRome, Italy

Toanalyzethepresenceofchroniccerebrospinalvenousinsufficiencyparameterandvascularabnormalities,intheinternaljugularveins (IJVs)and/orvertebralveins insittingandsupineposture, inpatientswithMeniere’sDiseasecomparedtohealthygeneralpopulation.Aprospectivestudyon32patientsaffectedbydefiniteMénièrewasperformedfromFebruary2012toJanuary2013.Allsubjectsunderwentanecho-colorDopplerexaminationofthecerebrospinalvenousflow.21ofthe32Meniericpatientsshowedastatisticallysignificantrefluxintheintracranialveinsversushealthy(65.6vs25%;P<0.001).AhighprevalenceofIJVsstenosiswithhemodynamicchanges(increasedvelocityorabsenceofflow)wasobserved(66.7vs33.3%;P<0.05).Theotherparametersconsidereddidnotshowstatisticallysignificantdifferencesamongthetwogroups.Theresultsobtainedshowedavascularpatternof cerebrospinal venous system present in patients affected by definite Meniere. This vascular impairment significantly affectsthevascularareasmoredirectlyinvolvedinthevenousdrainageoftheinnerear.ThusvenousstasismaybeconsideredafurtherpathogeneticmechanismfordevelopmentofMeniere’sDisease.

CHRONIC CEREBRO-SPINAL VENOUS INSUFFICIENCY IN MENIERE’S DISEASE: DIAGNOSIS AND ENDOVASCULAR TREATMENT AFTER 24-MONTH FOLLOW-UP

L. Califano MD 4, A. Bruno MD 3, G. Attanasio MD, PhD 1, F. Ciciariello MD 2, M. Viccaro MD, PhD 1, E. Covelli MD, PhD, E. Masci MD 1, L. Cagnoni MD, D. Mastrangelo MD 3, F. Salafia 4, V. Giugliano 5, B. Bernardo MD 31 Department of Sensory Organs, Sapienza University of Rome, Italy2 Department of Cardiovascular, Respiratory, Geriatric and Morphologic Sciences, Sapienza University of Rome, Italy3 Vascular Surgery Department CLINICA GEPOS Telese Terme, Benevento, Italy4 SSD Audiology and Phoniatrics, “G. Rummo” Hospital, Benevento, Italy 5 Radiology Departement Gepos Clinic Telese Terme, Benevento, Italy

Introduction:ToevaluatebythemeansofDopplerultrasound,MRIandphlebographytherelationshipbetweenMeniere’sDiseaseand chronic cerebrospinal venous insufficiency (CCSVI) and to test whether angioplasty is an effective procedure in improvingsymptoms.MaterialsandMethods:1)Phase1:172patientsdiagnosedwithdefiniteMeniere’sDisease(AAO1995)whohadgainednobenefitbymedicaltherapy,underwentecho-enhancedcolorDopplersonographyusingtheZamboniprotocoltocheckforCCSVI.100healthysubjectsmatchedforageandgenderactedascontrols.2)Phase2.In60ofECDpositiveMeniere’casesweperformeda venogram and the diagnosis of associated CCSVI was confirmed. These patients were treated by angioplasty of the InternalJugularVein,thenre-testedrespectthebaselinescalesofMeniere’sDiseases.Twentyofthemhada24-monthfollow.up.Results:Outofatotalof172patientswithMeniere’sDisease,anultrasounddiagnosisofCCSVIwasmadein150/172patients(87.2%).Inthehealthypopulation,wasfoundinonly10%ofcases.In60patientsvenographyconfirmedtheCCSVIdiagnosisandPTAprovedtobeeffectivein80%ofpatients,withsignificantimprovementofaudiologicalandvestibularfunctionat24monthfollow-up.Conclusions:TheprevalenceofCCSVIinpatientswithMeniere’sDiseaseishigherthaninhealthysubjects;PTAseemsusefulbecauseofanimprovementinsymptomswithaudiologicalandvestibularfunctionsbetterinthemajorityofpatients.







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IDIOPATHIC SUDDEN SENSORINEURAL HEARING LOSS AND MENIERE SYNDROME: THE ROLE OF CEREBRAL VENOUS DRAINAGE

N. Quaranta, V. De Ceglie, M. Damiani, M. M. CicconeUniversity of Bari

Background:theetiologyandthepathogenesisofidiopathicsuddensensorineuralhearingloss(ISSHL)andMénièresyndrome(MD)stillremainunclear.Manyhypotheses(viral,immunologic,vascular,etc)havetriedtodisclaimtheproblemoftheirorigins.Aim:toevaluatetheinfluenceofcerebralvenousdrainageonthepathogenesisofthesetwoclinicalentities.Weenrolled59consecutivepatients(32males,meanage53.05+15.37years):40sufferingfromISSHL(22males,meanage53.27+17.28years)and19fromMD(10males,meanage52.28+10.68years).30healthycontrols(15males,meanage52.63+14.83years)werealsoenrolled.Allunderwentphysicalandclinicalexamination,biochemicalevaluation(glycemicandlipidprofile,viralserology,Creactiveprotein,etc),audiometric(tonal,vocal,vestibularevokedmyogenicpotentials[VEMPs]auditorybrainstemresponse[ABR]test)andimpedanceaudiometryexamination.Thepuretoneaverage(PTA)wascalculatedforthefollowingfrequencies:250,500,1000,2000,3000,4000,8000.AnechocolorDopplerevaluationofthevenouscerebralveins,internaljugular(IJV)andvertebralveins(VV)atsupineand90°positionwasperformed.Themean,maximumandminimumveinsvelocitiesoftheextracranialveinswerecalculatedandcomparedamonggroups.Cerebralandextracranialveinsmorphologyandfunctionswereassessed.Nomorphologicalalterationswerefoundbothinpatientsandcontrols.Therewerenosignsofstenosis,blockedflow,membranes,etc.Wefoundlowerminimum,meanandmaximumvelocitiesindistalIJVs(p=0.019;p=0.013;p=0.022;respectively)andleftVVs(p=0.027;p=0.008;p=0.001;respectively)insupine(0°)positioninbothMDandISSHLpatientsascomparedtocontrols.Thesamewasfororthostaticposition(90°).Furthermore,wefoundnegativecorrelationsbetweenthevelocitiesinextracranialveinsandPTAvalues:therefore,theworsttheaudiometricperformanceofthesubjects,thelowerthevelocitiesinthevenouscerebraldrainage.ISSHLandMDpatients showedalteredvenousflow in IJVsandVVsas compared to controls, independently fromposture. Thisdifferentbehaviorofvenous tonecontrolcan influencetheearperformanceandmayhavea role in thepathogenesisofbothdiseases.

ENDOVASCULAR TREATMENT OF VERTIGO CAUSED BY JUGULAR BULB ABNORMALITIES

M. Hitier 1,2,3,4, L. M. Roussel 1, M. Humbert 1, S. Moreau 1, P. Courtheoux 5, V. Patron 11 CHU de Caen, Department of Otolaryngology- Head and Neck Surgery, Caen, France2 Normandie Univ, France 3 UCBN, COMETE, Caen, France4 INSERM, U 1075 COMETE, Caen, France5 CHU de Caen, Department of Neuroradiology, Caen, France

Jugular bulb abnormalities can induce tinnitus, hearing loss, or vertigo. Vertigo can be very disabling and may need surgicaltreatmentswithriskofhearingloss,majorbleedingorfacialpalsy.Hence,wehavedevelopedanewtreatmentforvertigocausedbyjugularbulbanomalies,usinganendovasculartechnique.Four patients presented with severe vertigo mostly induced by high venous pressure. One patient showed downbeat verticalnystagmusduringtheValsalvamaneuver;anotherexhibitedVEMPatlowthreshold.Thetemporal-boneCTscanshowedahighrisingjugularbulborajugularbulbdiverticulumwithdehiscenceandcompressionofthevestibularaqueductinallcases.Ineachcase,wepluggedtheupperpartofthebulbwithcoils,andweusedastenttomaintainthecoilsandpreservingthevenouspermeability.After1to5yearsoffollow-up,thosepatientsexperiencednomorevertigo,allowingreturntowork.The3-montharteriogramshowedgoodpermeabilityofthesigmoidsinusandjugularbulbthroughthestent,withcompleteobstructionoftheupperpartofthebulbinallcases.Disablingvertigoinducedbyjugularbulbabnormalitiescanbeeffectivelytreatedbyanendovasculartechnique.Thistechniqueisminimallyinvasivewithaprobablegreaterbenefit/riskratioascomparedtosurgery.

KEYNOTE LECTURE 6

VENOUS CONGESTION IN MENIERE’S DISEASE

VERTIGINOUS MIGRAINE AND MENIERE’S DISEASE

C. A. Oliveira MD, PhD, R. L. Bezerra MD Doc Med, C. Messias MD MSc, F. Bahmad Jr MD DDoc MedBrasília University Medical School

Beginningin1992ourgrouphaspublishedongeneticsofMenière`sdisease.WehaveobservedinthefirstfamilywepublishedtheassociationofheadachewiththesymptomsofMenière`sdisease.ThisassociatedheadachewascarefullystudiedandclassifiedasmigraineaccordingtotheInternationalHeadacheclassificationinoursecondfamilypublishedin1997.FromthenonallthefamilieswepublishedwithseveralsiblingsaffectedbyMenière`ssymptomsalsohadmigraine.In2002wepublished6familieswithseveralsiblingsaffectedbyMenière`ssymptomsandmigraine.SomehadfullblownclassicMenière`ssyndromeandmigraine.SomehadonlyMenière`ssymptoms,somehadmainlymigraine.TheindexpatientsinallthesefamilieshadfullblownMenière`syndromeandmigraine.Wefollowedthe1997familyfortwelveyearsandwefoundthatpatientswithonlymigrainein1997laterhadtheMenière`ssymptomsandthereforetherewasanevolutionfrommigrainealonetoclassicMenière`ssyndromeinsomesiblings.Basedonthesefindingswepostulatethatmigraine,vertiginousmigraineandMenière`sdiseasemaybepartofacontinuumcausedbygeneticpredispositionalliedwithlifestyleandenvironmentalfactors.Wearecurrentlystudyingthemoleculargeneticsofthe1997familyincooperationwiththeSeidmanlaboratoryofmoleculargeneticsofHarvardMedicalSchool.Problablyasinglegenemutationispresentinaffectedpatients.

VESTIBULAR MIGRAINE IN AN OTOLARYNGOLOGY CLINIC: PREVALENCE, ASSOCIATED SYMPTOMS, AND PROPHYLACTIC MEDICATION EFFECTIVENESS

A. Van Ombergen 1, V. Van Rompaey 2, P. H. Van de Heyning 1,2, F. L. Wuyts 11 Antwerp University Research centre for Equilibrium and Aerospace, University of Antwerp, Antwerp, Belgium2 Department of Otolaryngology, Antwerp University Hospital & University of Antwerp, Antwerp, Belgium

Toassesstheprevalenceofvestibularmigraine(VM)inpatientsconsultingtoanotolaryngologyclinic,theneurootologicalassociatedsymptoms,andtheeffectofprophylacticantimigrainousmedicationonVMsymptomimprovement.StudyDesign:Retrospectivechartreview.Setting:Tertiaryreferralotolaryngologyclinic.WeusedthediagnosticcriteriafromtheBáránySocietyandtheInternationalHeadacheSocietytoallocatepatientstoasubgroup:VM,possibleVM,andatypicalVM.The prevalence of VM, percentages of associated neurotological symptoms, and percentages of effectiveness of prophylacticmedication.Sixty-five(16%)patientswereselectedfromthetotalpatientpopulation(n=407)fromwhich4.2%wereassignedtothedefiniteVMgroup,5.7%totheprobableVMgroup,and6.1%totheatypicalVMgroup.Wefoundasignificantlydifferentdistributionbetweenthegroupsforphotophobia(p=0.035),earpressure(p=0.023),andscotoma(p=0.015).Thirtypatientswereadministeredwithflunarizineand68%respondedwithanimprovementinVMsymptoms(pG0.001).Forpropranolol,31patientsweretreatedandtherewasanimprovementofsymptomsin73%(p<0.001).Remarkablewasthefactthatthesepercentageswerenotsignificantlydifferentbetweenthesubgroups.VMisacommondisorderpresentinginadizzinessclinic,anddetailedhistorytakingisimportanttoassessVM-associatedsymptomsandthustopreventunderdiagnosis.Thelatterisveryimportantbecauseourstudyshowsthatthemajorityofpatients,regardlessofVMsubtype,canbenefitfromaprophylactictreatment,butfurtherprospectivestudiesarenecessary.







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VESTIBULAR ASSESSMENT IN MENIERE’S DISEASE AND MIGRAINE

B. Cakir, MD 1, O. Yilmaz, MD, PhD 2, H. Dizdar PhD 2, Y. A. Bayazıt MD 31 Associate Professor, Medipol University, Istanbul, Turkey2 Clinical Audiologist, Medipol University, Istanbul, Turkey3 Professor and Head, Department of Otolaryngology, Faculty of Medicine, Medipol University, Istanbul, Turkey

Meniere’s Disease is still one of the most important vertiginous disorders. Introduction of new vestibular assessment methodshas influenced our understanding of peripheral vertiginous diseases and their differential diagnoses. Migraine and Meniere’sDiseaseare the two importantdisorderswhichneedsdifferentialdiagnosis.VNG (videonystagmography), caloric testing,cVEMP(cervical vestibular evokedmyogenicpotentials), oVEMP (ocular vestibularmyogenicpotentials), vHIT (videohead impulse test)andposturographyhasbeenusedintheassessmentofvestibulardisorders,oneofwhichisMeniere’sDisease.Inthiscohort,thevestibularassessmentoutcomeofthepatientswithMeniere’sDiseasewhowereseeninanoutpatientsettingwerepresented.

INTRODUCTION

Mamoru Suzuki Tokyo Medical University, Tokyo, Japan

Meniere’sDisease isawell-knownvestibulardisordercomprisingapproximately10%ofdizzypatients inJapan.Thenationwidestudygrouphadbeenorganizedin1974underthesupportoftheHealthandLaborScienceResearchGrantforResearchonSpecificDisease(VestibularDisorders)fromtheinistryofHealth,LaborandWelfare,Japan.Throughthisstudy,epidemiologicaltrend,animalmodel,diagnosticcriteria,andtreatmentmeasureswereestablished.Itisourgreatpleasuretopresentsomeofourresultsthatthestudygrouphadbeenengagedinforsuchalongperiod.Wehave4topics,epidemiology,diagnosticguideline,diagnosisusingRIandtreatmentmodalitywhicharepresentedbytheexpertsineachfield.ThissessionwillhopefullydeepenourunderstandingofMeniere’sDiseaseofwhichetiologyisnotfullyknown.

EPIDEMIOLOGICAL CHARACTERISTICS OF MENIERE’S DISEASE IN JAPAN

H. Shojaku 1, Y. Watanabe 1, H. Takakura 1, M. Tsubota 1, M. Fujisaka 1, M. Suzuki 2, N. Takeda 31 Department of Otolaryngology, University of Toyama2 Department of Otolaryngology, Tokyo Medical University 3 Department of Otolaryngology, University of Tokushima

From1975to2014,nationwide,multi-centersurveysonMeniere’sDiseasewereperformedbytheResearchCommitteeofMeniere’sDiseaseandtheResearchCommitteeofthePeripheralVestibularDisorders.DenovodefiniteMeniere’sDiseasecasesweresampledbythemembersoftheCommittees. ThetransitionoftheepidemiologiccharacteristicsoftheMeniere’sDiseasewereanalyzedandcomparedover times. In theMeniere’sDisease, themale tofemale ratiohaschangedfromeventofemalepredominance.Withrespecttoonsetageatdisease,theincidenceinelderlypatients(age≥60years)wasincreasedwhenwecorrectedforagedistributionintheoverallpopulation.

VESTIBULAR MIGRAINE

JAPANESE SOCIETY OF EQUILIBRIUM RESEARCH (JSER) SYMPOSIUM

DIAGNOSIS 1: DIAGNOSTIC STANDARD FOR MENIERE’S DISEASE BASED ON THE CLINICAL GUIDELINE OF THE DISEASE IN JAPAN

Y. WatanabeToyama University

TheclinicalguidelineforMeniere’sDiseaseinJapanwaspublishedin2011byTheVestibularDisorderResearchCommitteeofJapanwiththesupportoftheMinistryofHealthLaborandWelfareofJapan.Intheguideline,thediagnosticcriteriaofMeniere’sDiseaseareclassifiedintothreecategories,definiteMeniere’sDisease,atypicalMeniere’sDiseaseofthecochleartypeandatypicalMeniere’sDiseaseofthevestibulartype.Inthecriteria,theconceptofMeniere’sDiseaseisdescribedasavestibularandcochleardisorderwiththeprimaryetiologyofendolymphatichydrops.1.DefiniteMeniere’sDisease:Repeatedattacksofvertigoaccompaniedwithauralsymptoms,suchashearingloss,tinnitusand/orearfullness.2.AtypicalMeniere’sDiseaseofthecochleartype:Repeatedauralsymptoms,suchashearingloss,tinnitusand/orearfullness,withoutvertigo.3.AtypicalMeniere’sDiseaseofthevestibulartype:RepeatedattacksofvertigosimilartodefiniteMeniere’sDisease,withoutthefluctuatingauralsymptomsassociatedwiththevertigo.Becausetherearemanycasesofvertigoduetoanunknowncause,diagnosisofthistypeshouldbelimitedonlytocaseswithahighpossibilityofendolymphatichydropsbasedupontheclinicalhistoryandneurotologicalexamination.Diagnosis1.BecauseitisverydifficulttodifferentiatethefirstattackofMeniere’sDiseasefromsuddendeafnesswithvertigo,confirmationofthesecondattackorrepeatedattacksbyfollow-upisnecessaryforthediagnosisofMeniere’sDisease.2.DiseasesindicatingsymptomssimilartoMeniere’sDiseaseforwhichthecauseisclear,suchasperilymphfistula,innerearsyphilis,vestibularschwannoma,neurovascularcompressionsyndrome,cerebellarandbrainstemdiseases,etc.,shouldbeexcludedfromthediagnosisofMeniere’sDiseaseineachofthecategories.3.Forthepurpose,neurologicalandneurotologicalexaminations,includingbalancetest,auditorybrainstemresponse,andimagediagnosis,suchasCTandMRI,arenecessarywhenrequired.4.Fortheevaluationofendolymphatichydrops,itisrecommendedtoperformglyceroltest,furosemidetestorelectrocochleogram(ECochG).Vertigo1.Althoughthedurationofvertiginousepisodevariesbetweenindividuals,itgenerallylastsfromabout10minutestoseveralhours.Caseswithtransientepisodes,i.e.,<oneminute,shouldbeexcludedfromthediagnosisofMeniere’sDisease.2.Inmanycases,horizontal-rotarynystagmusisobservedduringtheattacks.3.Casesaccompaniedbycentralnervousdisorders,suchasunconsciousness,doublevision,speechdisorder,etc.,areexcludedfromthediagnosisofMeniere’sDisease.4.Thefrequencyofvertigoattacksvariesbetweenindividuals,fromseveraltimesperweek,inthemostfrequentcases,toseveraltimespermonthoryear.Auralsymptoms1.InmanycasesofMeniere’sDisease,auralsymptomsoccurjustbeforeorsimultaneouswiththevertigoattack,andworsenaccordingtotheattackandimproveaftertheendoftheattack.2.Althoughthemainauralsymptomsarehearinglossandtinnitus,somepatientscomplainofsensitivitytosound.3.Thesensorineuralhearinglossfluctuateswiththediseasestage.4.Althoughthehearinglossisunilateralintheprimarystage,bilateralhearinglossoccursintwentytothirtypercentofthecasesdependinguponprotractionofthedisease(bilateralMeniere’sDisease).IwouldliketodescribethediagnosticcriteriaofMeniere’sDiseaseinJapan,fromthebasicconcept(s).







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DIAGNOSIS 2: DIAGNOSIS OF ENDOLYMPHATIC HYDROPS USING 3T MRI IN PATIENTS WITH MENIERE’S DISEASE

S. Usami, H. Yoshimura, H. Fukuoka, K. TsukadaDepartment of Otorhinolaryngology, Shinshu University School of Medicine

Meniere’sDisease (MD)hasbeen thought tobeattributable toendolymphatichydrops (ELH),but thishasonlybeenconfirmedhistopathologically after death. Therefore, along with clinical symptoms, clinical tests suggestive for ELH are usually used fordiagnosis.However,eveniffunctionaltestingisperformed,theresultsarestillindirectproof.Meanwhile,recentadvancesinimagingby three-dimensional,fluid-attenuated inversion recovery (3D-FLAIR)ofmagnetic resonance imaging (MRI), inassociationwithenhancementbygadolinium-basedcontrastagents(GBCAs),enablesvisualizationofELHinpatientswithMD.WehavesucceededinvisualizingELHsemi-quantitativelyinpatientswithMD,byusingbilateralintratympanicGBCAadministrationwithMRI.TovisualizeendolymphatichydropsinpatientswithMD,includingthepatientswhomettheAmericanAcademyofOtolaryngology-Head and Neck Surgery criteria for “definite” MD, “possible” MD, atypical MD patients (who had fluctuating low frequencysensorineuralhearinglosswithoutvertigo),andacutelow-tonesensorineuralhearinglosspatients,wereevaluated.3D-FLAIRMRIclearlyshowedthattheGBCAsuccessfullypenetratedtheroundwindowmembrane,enteringtheperilymphaticspaceanddelineatingtheGBCA-enhancedperilymphaticandGBCA-negativeendolymphaticspacesoftheinnerear.Almostall“definite”MDpatientsshowedELH.Furthermore,ELHwasalsodemonstratedinsomeof“possible”MD,“atypical”MD,andacutelow-tonesensorineuralhearinglosspatients.Suchimage-baseddiagnosiswill leadtore-revaluationandreclassificationofthediagnosticcriteriaforMD.

OVERVIEW OF THE TREATMENT OF MENIERE’S DISEASE IN JAPAN

I. KoizukaDepartment of Otolaryngology, St. Marianna University School of Medicine, Kawasaki, Japan

Meniere’sDisease(MD)isadisorderoftheinnerearaffectinghearingandbalancetoavaryingdegree.Itischaracterizedbyepisodesofvertigoattackslastingmorethan20minutes(10minutesinJapan),low-pitchedtinnitus,hearingloss,andafeelingoffullnessintheear.ThereiscurrentlynogoldstandardtreatmentforMD.Endolymphatichydropsmayrepresentthehistologicalinnerearfindingsinmostpatients.A variety of medical and surgical treatments have been developed to treat or control the symptoms. No cure exists for MD.Treatmentcanbedividedintonon-destructiveanddestructiveprocedures.Non-destructiveproceduresaimtoreducethesymptomsofMDthroughdietaryrestrictionsaswellasthroughtheuseofdiuretics.Isosorbideisusuallyusedasadiureticmainlytotreathydrocephalus and glaucoma. In Japan, isosorbide is also used for MD to improve endolymphatic hydrops. As for destructiveprocedures,surgicaldecompressionoftheendolymphaticsac,surgicalorchemicallabyrinthectomy,andvestibularnervesectionareappliedforintractablecases.Duringthe1970s,Inglestadtetal.observedthatsomepatientsreportedimprovementwithpressurechanges in a pressure chamber (Acta Otolaryngol 1976; 82: 368–378). Densert et al. showed that manipulation of middle earpressureinfluencesinnerearpressure(ActaOtolaryngol1975;80:93–100).Later,improvementinvertigoandhearinginpatientswithMDwasdescribedafterapplicationofpositivepressuretothemiddleear.ThesereportseventuallyledtothedevelopmentoftheMeniett®device.However,inJapan,medicalpractitionershavebeenrequiredtoimportMeniett®devicesthemselvestoprovidethismiddleearpressuretreatmentbecausetheyhavenotbeenclearedbytheMinistryofHealth,LabourandWelfareofJapan.Atympanicmembranemassage(TMM)deviceisanintermittentpressuretreatmentdeviceinitiallyusedinwesternEuropeancountriesinthelate19thcenturyforpatientswithotitismediawitheffusion(OME)andwithouttympanotomy.InJapan,theTMMdevicehasbeencleared foruse inpatientswithOMEby theMinistryofHealth, LabourandWelfareof Japan,andcurrently,medicalpractitionerscanbuythispressurepulsegeneratordevice(TympanicMassageUnit)fromadomesticsupplier.Inthissymposium,thecurrentstatusoftreatmentproceduresforpatientswithMDinJapanwillbepresented.

PRINCIPLES OF LONG-TERM VESTIBULAR REHABILITATION

M.LacourMarseille, France

Thelecturequestionstherelationshipsbetweentheplasticeventsresponsiblefortherecoveryofvestibularfunctionafteraunilateralvestibularloss,thatis,thevestibularcompensationprocesswhichhasbeenwelldescribedinanimalmodelsinthelastdecades,andthevestibularrehabilitationtherapyelaboratedonamoreempiricalbasisforvestibularlosspatients.ThemainobjectiveistoprovideclinicianswithanunderstandableviewonWhenandHowtoperformvestibularrehabilitation,andtoexplainWhyvestibularrehabilitationmaybenefitfrombasicknowledgeandmayinfluencetherecoveryprocess.Withthisperspective,10majorrecommendationsareproposedaswaystoidentifyanoptimalfunctionalrecoveryratherthantogiveacatalogofresults.Amongthemarethecrucialroleofactiveandearlyvestibularrehabilitationtherapy,coincidentalwithapost-lesionsensitiveperiodforneuronalnetworkreorganization,andtheinstructiverolethatvestibularrehabilitationtherapymayplayinthisfunctionalreorganizationwhenitisperformedduringthisopportunitytimewindow.Theneedforprogressioninthevestibularrehabilitationtherapyprotocols,andthenecessitytobasetheseprotocolsmainlyonadaptationprocessesratherthanonhabituationexercisesareunderlined.Whyitisimportanttotakeintoaccountthesensorimotorandcognitiveprofileofthepatient,andwhycustomizedor“àlacarte”vestibularrehabilitationshouldbepreferredtostandardizedprotocolsarealsoemphasized.Lastbutnottheleast,vestibularrehabilitationtherapyprotocolsshouldbeaimedatreducinganxietyandstress,andmotivatingthevestibularlosspatients.Ecologiccontextscanbeusedasawaytoachievetheselattergoals.Morethantengeneralprinciplesarelikely,buttheseprinciplesseemcrucialforthefastrecoveryofvestibularlosspatientstoensuregoodqualityoflife.

ROLE OF PERINEURONAL NETS IN VESTIBULAR COMPENSATION

F. Dagna, A. Albera, D. Carulli, A. Faralli, F. Rossi, P. Giordano, R. AlberaUniversità degli Studi di Torino, Città della Salute e della Scienza di Torino;NICO - Neuroscience Institute Cavalieri Ottolenghi, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO)

PerineuronalnetsareaggregatesofextracellularmatrixmoleculessurroundingseveraltypesofneuronsintheadultCNS,whichcontributetostabilisingneuronalconnections.Interestingly,inconditionsassociatedwithplasticityintheadultbrain,areductionofPNNshasbeenobserved.However,itisnotknownwhetherPNNchangesarefunctionaltoplasticityandrepairafterinjury.ToaddressthisissueweinvestigatedPNNexpressionandanatomicalremodellinginthevestibularnucleioftheadultmouseduringvestibularcompensation.Vestibular compensation refers to the resolutionofposturalandoculomotordeficits resulting fromaperipheralvestibularlesion.Wefoundthatfollowingunilaterallabyrinthectomy,staticposturalfunctionsofthemouserecuperatein2weeks,whiledynamic reflexes in4weeks.Remarkable structuralplasticityofglutamatergicandGABAergicfibreswasobserved in thelateralvestibularnucleusonbothsidesatdifferenttimepointsafterunilaterallabyrinthectomy,whichmaycontributetofunctionalrecovery.Moreover,PNNsappearedstronglyattenuatedduringthecourseofvestibularsymptomsamelioration,whiletheywerecompletelyrestoredoncevestibulardeficitshadfullyrecovered.Interestingly, inmicewithgeneticallydefectivePNNsvestibularcompensationwasaccelerated.Overall,theseresultsindicatethatplasticitymechanismsunderlyingvestibularcompensationdependcruciallyonPNNmodulation.







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DEVELOPMENT OF VESTIBULAR REHABILITATION PLATFORM USING IMMERSIVE VIRTUAL REALITY SYSTEM

S. K. Hong, CG. Song, HJ. JeonDepartment of Otolaryngology, College of Medicine, Hallym University, Chuncheon, Korea, College of Information and Electronic Engineering, Hallym University, Chuncheon, Korea, College of Information and Electronic Engineering, Hallym University, Chuncheon, Korea

Virtualreality (VR)systemhasbeenrapidly incorporated intoseveralnovelplatforminthefieldsofmedicaleducation,surgicalsimulation,psychiatricdisabilityorphysicalrehabilitation.TheuseofVRtoenhancevestibularrehabilitationisalsonotemergingconcept.However,VR-basedvestibular rehabilitationmostlyhasbeenadaptedatmultiscreenenvironmentwith the largecave,whichrequireshighcostandlargespace.Incontrast,headmountdisplay(HMD)basedVRsystemcouldprovidemoreimmersionascomparedtomultiscreenbasedVRandallowtheusertheabilitytomovemorefreely.WedevelopedthevestibularrehabilitationplatformusingimmersiveHMD-VRsystemconnectedwitheyeandheadinertial-tracker,whichmaybringabout innovationforvestibularrehabilitationwithitsinteractivesystemandsenseofreality.EyetrackingHMD(upgradepackagemodelforoculusriftDK2,SMI,Teltow,Germany)wereusedforinnovativevestibularrehabilitationplatform.Eachconditionforvestibularrehabilitation-1)Activeeye-headmovementwithvisualtarget,2)habituationexercisetopathologicresponse,3)balancegaitexerciseand4)generalconditioningexercise-wascreatedasvirtualreality,whichwasmadebytheUnity3Dprogram(Unitytechnologies,CA,USA).StreamofeyeandgazemovementofuserduringvestibularrehabilitationwasanalyzedbyVisualC++programinrealtime,whichwasusedasinterfaceforsensoryfeedbackbasedonuseraction.OurinnovatedVR-basedvestibularrehabilitationplatformprovides1)sensoryfeedbackusingeyeandheadinertialtrackingsystemwithoutconstraintslikespacelimitationorhighcostand2)excitingconditionwithimmersivevirtualsystem,whichmayenhancetheeffectivenessofvestibularrehabilitationascomparedtoconventionalmethods.

REDUCTION OF TIME CONSTANT BY A NOVEL VESTIBULAR HABITUATION: POSSIBILITY AS A POTENT COUNTERMEASURE FOR TREATMENT OF PATIENTS WITH MOTION SICKNESS

S. K. Hong, H. J. Lee, H. J. KimDepartment of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine

WeschemedoutanovelhabituationmethodusingopposingvisualandvestibularstimuliforreductioninTimeConstant(TC).Theaimofthisstudy isto investigatewhetherournovelvestibularhabituation(VH)methodcouldeffectivelyreduceTC inhealthysubjectspriortoclinicalimplicationforpatientswithmotionsickness(MS).Experimentswereperformedwithanearthverticalaxisrotationsystem.Wedesigned2paradigmsforreductioninTCusingout-of-phaseoptokinetic(OK)stimuli.12healthysubjects(M:5,F:7;meanage:26yrs)participatedinthestudy.ForVH,7patients(M:3,F:4)wererotatedwithrotationalvelocityof20°/sec.Habituationprotocolwasunidirectional(clockwise)2paradigmsincludingaseriesof(1)perrotatoryaVORcancellationusingOKdrummovingat25°/sectothesamedirectionaschair,(2)postrotatoryaVORcancellationusingstationaryOKdrum,followedbychairstop.Eachserieswasconductedonceperdayfor3consecutivedays.5patients(M:3,F:2)wereexposedtotherotationvelocityat20°/secascontrolgroupinthesamemannerasthatofexperimentalgroup(shamhabituation).TCs(TCcwandTCccw)ofallsubjectswereobtainedfromstepvelocitytestbeforeandafterhabituationsession.BeforeandafterVH,TCcwwere16.73±0.62sand11.74±1.2s,andTCccwwere17.44±1.03sand11.95±1.02srespectively,whichshowedstatisticallysignificantreduction(p<0.005).Incontrast,therewerenotstatisticallysignificantdifferencesofTCsbetweenbeforeandaftershamhabituationincontrolgroup.ReductionofVORgainwasnotobservedinbothgroups.OurnovelVHcouldsuggestthepossibilityasapotentcountermeasurefortreatmentinpatientswithMS.Inparticular,TCafterVHwasshorterforbothdirectioneventhoughunidirectionalstimulationwasgiven,whichcouldgivehelpfulbasisfordesigningtheVHprotocolforclinicalimplication.Ontheotherhand,VORgainwasnotaffectedbyvestibularhabituationandmustbesubstantiatedbyfurtherstudiesonalargescale.

VESTIBULAR REHABILITATION

OTOACOUSTIC EMISSIONS IN SUDDEN SENSORINEURAL HEARING LOSS

A. Shupak, R. Zeidan, R. ShemeshUnit of Otoneurology, Lin Medical Center, Haifa, Israel; Department of Otolaryngology Head and NeckSurgery, Carmel Medical Center, Haifa, Israel; The Bruce Rappaport Faculty of Medicine, The Technion,Haifa, Israel; Department of Communication Science and Disorders, University of Haifa, Haifa, Israel

Objective:Toevaluatetheroleofotoacousticemissions(OAEs) inthepredictionof idiopathicsuddensensorineuralhearingloss(ISSNHL)outcome.StudyDesign:Open-labelprospectivestudy.Setting:Tertiaryreferralmedicalcenter.Patients:FifteenISSNHLpatients(age:57.6T16.2years)wereprospectivelyfollowed7days,14days,and3monthspostpresentationandthecommencementoftreatment.Intervention:Pure-toneaudiometry,TEOAEs(TransientEvokedOAEs),andDPOAEs(DistortionProductOAEs)testing.MainOutcomeMeasures:Thepure-tonethresholdaveragesofthethreemostaffectedfrequencies,detectability,andthesignalto-noise ratios (SNRs) valuesof the TEOAEsandDPOAEswere calculated. Themainoutcomemeasureswerepure-tonehearingimprovement,sensitivity,andspecificityoftheOAEsmeasurestowardsISSNHLoutcome.PatientshavingdetectableTEOAEsonthefirstfollow-upevaluationhadaveragehearingimprovementof62+41%whereasthosewithnoresponseimprovedonlyby11+15%(p<0.001).FortheDPOAEshearingimprovement,resultswere71+37%and10+14%,respectively(p<0.001).ThesensitivityofrecordableTEOAEsontheseventhdayoffollow-uptowardsthepredictionofsignificanthearingimprovementreached71%andthespecificity100%.FortheDPOAEs,thecorrespondingvalueswere83%and100%.UnivariateanalysisshowedsignificantcontributionforthevarianceinhearingimprovementbybothTEOAEsandDPOAEsandtheirinteraction(pvaluesof0.043,0.005,and0.009,respectively).TheresultssuggestpotentialroleofTEOAEsandDPOAEsevaluationintheearlystageoftreatmentinthepredictionofISSNHLoutcome.

MRI FINDINGS AND COMPLIANCE TO PERFORM MRI IN PATIENTS WITH SSNHL

R. Khniefes, N. Yehudai, S. Masud, M. LuntzEar and Hearing Program, Department of Otolaryngology—Head & Neck Surgery, Bnai-Zion Medical Center, Technion—Bruce Rappaport Faculty of Medicine, Haifa, Israel

Duetotherelativelyhighprevalenceofvestibularschwannomaamongpatientswithsuddensensoryneuralhearingloss(SSNHL)MRIisrecommendedinthesepatients.NeverthelessMRIisstillnotalwaysperformedandthecorrectdiagnosisisdoneyearslaterinsomecases.Aimsofstudy:ToevaluateMRIperformanceinpatientswhosufferedaneventofSSNHLandtherateofpathologicfindingsinthesepatients.150consecutivepatientswhosufferedaneventofSSNHLare included in the study.UponthediagnosisofSSNHLappropriateexplanationwasgiventothepatientandaletterwassenttothefamilyphysicianandENTspecialistinthecommunity.Patientswerescheduletotheoutpatientclinic,andtheirchartswerereviewedseveralmonthslatertoexaminewhetherMRIwasperformed.Thosewhodidnotundergotheexaminationwerere-askedtodoitOf150patients18 (12.6%)were lost forfollowupduringthestudyperiodwhereas132patientswereavailableforfollowup.ComplianceforMRIperformanceinpatientswithSSNHLwas85.6%.Anabsolutecontraindication(metalimplant)justifieditinonlyoneofthesepatients.PrevalenceofsignificantMRIfindingsinpatientswithSSNHLwas8.4%.Prevalenceofvestibularschwannomawas3.0%.TheneedtoperformMRIinpatientswithaneventofSSNHLshouldbeclearlyexplainedtopatients,familyphysiciansandinsuranceauthoritiesinordertomeetcriteriaforstandardmedicalcareandtoavoidunjustifiedlatediagnosisofvestibularschwannoma.







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EFFECT OF THE HEARING LEVEL OF NON AFFECTED EAR AND SEVERITY OF ACUTE HEARING LOSS IN PATIENT WITH UNILATERAL SUDDEN DEAFNESS FROM THE PERSPECTIVE OF TINNITUS

L. Čvorović, D. Djerić, A. JotićClinic of Otorhinolaryngology and Maxillofacial Surgery, Clinical Centre Serbia, Faculty of Medicine, University of Belgrade, Serbia

Objective:Weaimedtoevaluatetheinfluenceofhearinglevelofnonaffectedearandseverityofhearinglossforacute-onsettinnitusinpatientswithunilateralidiopathicsuddensensorineuralhearingloss(ISSNHL).Methods:Atotal478patientswithISSNHLwereenrolledretrospectivelyandthemedicalrecordsreviewed.Patientswereclassifiedintotwogroupsaccordingtothepresenceofacute-onsettinnitusattheinitialexamination.Puretoneaverage(PTA)infourfrequencies(0.5,1,2,4KHz)werecalculatedforthebothear,thelevelofhearinglossclassifiedintofivegroup(mild,moderate,severe,profoundordeaf)andcorrelatedwithonsetoftinnitus.Also,patientsclassifiedintotwogroupaccordinghearinglevelofnoneffectedear(withorwithoutloss)andcorrelatedwithonsetoftinnitus.Results:Atotal68%(n=314)ofpatientswithsuddendeafnesshadtinnitusinitially.Therewerecorrelationsofonsetoftinnitusandseverityofhearinglossandhearinglevelofoppositeear(Spearmancorrelationcoefficient:-0.97,0.02respectively,significancy0.05,0.01respectively).Conclusion:Worsecontralateralhearingandseverityofhearinglosswereassociatedwithanincreasedincidenceofconcurrenttinnitus.

LONG TERM TRANSTYMPANIC STEROID TREATMENT RESULTS IN PATIENTS WITH ACUTE COCHLEAR HEARING LOSS

M. Durmusoglu, Y. Olgun, E. Dogan, M. A. Kozen, E. A. GuneriDokuz Eylül University, School of Medicine, Department of Otorhinolaryngology, Izmir, Turkey

Systemicsteroidtherapyisthestandardtreatmentforacutecochlearhearinglosses.Intratympanicsteroidinjectionsaregenerallypreferredasamaintenancetreatmentorsometimesasthefirstoptionforcases inwhichthesideeffects limitsystemicsteroidadministration. Inthisstudy,hearingresultsofpatientswithacutecochlearhearinglosswhoshowedlimitedornoresponsetosystemicandintratympanicsteroidtreatmentsandreceivedsalvagetranstympanicsteroidtreatment(TTST)throughaventilationtube(VT)wereevaluated.Therecordsof43patientswithacutecochlear(sensorial)hearingloss,whoreceivedlong-termTTSTthroughVTwiththediagnosesofsuddensensorineuralhearingloss(SSHL),Meniere’sDisease(MD)andacutelowtonesensorineuralhearingloss(ALTSNHL)wereexaminedretrospectively.Allcasesreceivedstandardsystemicsteroidtreatmentatfirstwithadoseof1mg/kgafteraudiologicaltestingandconfirmationofnoretrocochlearpathologywithMRI.TheyweredecidedtoreceiveTTSTduetotheongoinghearinglosseswhichshowedlimitedornoresponsetosystemicsteroidtreatment.VTwasplacedintheposteriorinferiorquadrantofthetympanicmembraneand5dropsofdexamethasone(0.25mg/cc)onceinadaywereadministeredintotheexternalauditorycanalofthepatients.Thepatientswereadvisedtolayontheirsideswiththetreatedearupfor20minuteswhileputtingtheeardropsintotheirears.ToynbeemaneuverwastaughtinordertofacilitatepassageofthedropsintotothemiddleearthroughtheVT.Inthiswaytheapplicationswerecontinuedfor3months.Theaverageboneconductionthresholdsin500,1000,2000and4000Hzfrequenciesofbeforeandattheendof3rdmonthwerecalculatedandcompared,animprovementofmorethan10dBwasconsideredassignificant..Thecaseswhohada≤30dBspeechreceptionthresholddifferenceand≤15%speechdiscriminationscorebetweentheaffectedandthehealthyearswereconsideredashavingserviceablehearing.HearingimprovementswerealsoclassifiedaccordingtoSiegel’scriteria.Therewassignificantimprovementinthehearingof9of15(60%)patientswithSSHL.Significantimprovementalsooccurredinthehearingof12of22(54.5%)patientswithMD.Significanthearingimprovementwasobservedin4of6patients(66.7%)withALTSNHL.Asaresult,hearingwassignificantlyimprovedin25of43patients(%58.1)whoreceivedTTSTthroughVTfor3months;in16ofthesepatients(%64)thefinalhearinglevelswereserviceable.Completeimprovementoccurredinthehearingof13patients(%52)accordingtoSiegel’scriteria.Intratympanic injections,applicationsthroughVTor lasermyringotomyandcontinuousminipumpdeliverymaybeusedforthepurposeofavoidingsystemicsideeffectsoflongtermsystemicsteroidtreatment.Long-termandhighdosesofperilymphsteroidconcentrationmaybeprovidedbythesemethodsandtreatmentcanbecontinuedaslongasitisrequired.Itisrevealedinthisstudythat,significantandserviceablehearingimprovementcanbeprovidedbylong-termTTSTadministrationthroughVT in acute cochlear hearing losses.However, comparing the results of treatment of a similar groupwho receivednotreatmentsmayprovidefurtherinformation.

SUDDEN HEARING LOSS & PERILYMPHATIC FISTULA & OTOTOXICITY

THE SPONTANEOUS PERILYMPH FISTULA CONUNDRUM- DO WE FINALLY HAVE AN EXPLANATION?

A. Gadre, MD, MS, DORL, FACS 1, I. Edwards AUD, CCC-A, F/AAA 2, C. Rutledge-Roof AUD, CCC-A, F/AAA 11 Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders, University of Louisville2 Heuser Hearing Institute, Louisville

Spontaneous perilymph fistula (PLF) is uncommon. An improvement in symptoms and signs following patching of the roundandovalwindowregion,isfelttodemonstratepresenceoffistulae.Opponentsstressthatexplorationofthemiddleearfailstodemonstrateleakageofperilymphfromtheroundorovalwindows.Histologicaltemporalbonestudieshavefailedtorevealopendefectsinoticcapsulebone.TheoccurrenceofspontaneousPLFthereforeiscurrentlyindoubt.Therearehoweverpatientswhohavesymptomsof incapacitatingvertigo,fullness,fluctuatinghearingloss,Tulliophenomenon,disequilibrium,intolerancetosounds,andwhoareexquisitelysensitivetochangesinbarometricpressure.Severalhaveahistoryofheadinjury.Thefistulasignispositiveinsomecases.CTscans(HRCT)inthesecasesconsistentlyfailtorevealthepresenceofasuperior(SSCD),orposteriorsemicircularcanaldehiscence(PSCD)syndrome.Between2009and2013,tenpatients(n=10)underwentmiddleearexplorationfortheabove-mentionedsymptoms.AllpatientsunderwentdetailedobjectivetestingatthevestibularandbalancelaboratoriesattheUniversityofLouisville,ortheHeuserHearingInstitute. All patients alsounderwentHRCT, andmagnetic resonance imaging (MRI) to ruleoutother etiologies. Surgerywasperformedundergeneralanesthesia.Theroundandovalwindowswereobservedathighmagnificationalongwithstapespalpationforperilymphleakage.AValsalvamaneuverwasthencarriedout.AftergentlydenudingthemucosaaroundtheOWandRW,lobulefatwaspackedinthetwoniches.Ofthetenpatientsexplored,onlyonehadtrueperilymphleakage.Perilymphleakagewasnotdemonstratedintheninepatients(n=9).Howevercloseobservationinthesedemonstratedamembranousfootplateinsteadofbone.Onecasefailedbutwashelpedatrevisionsurgery.Noneofthecasesdemonstratedanappreciabledropinhearing.OnreviewingtheHRCTandusingthe“invert”function,onemaybeabletodemonstratethesedeficienciesinthefootplatepreoperatively.Wereportforthefirsttimefindingsofadefect instapesfootplatewhich iscoveredbyamembraneasapossibleetiologyforsymptoms.Thisfindingmayexplaincausationofsymptomsintheabsenceoftrueperilymphleakage.Curativesurgeryinvolvespatchingdefectandprovidessubjectiveandobjectiverelief.

CHRONIC DISEQUILIBRIUM AS MAIN SYMPTOM OF BILATERAL PERILYMPH FISTULA - CASE PRESENTATION

N. Arsovic, D. PavlovicFaculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Centre of Serbia, Belgrade

IntroductionPerilymphfistulaisdiagnosticchallengebecauseofdiverseclinicalpresentationandnospecifictests.MethodsandResults We present a patient with history of chronic disequilibrium, difficulties in concentration, depression with no ability toworkandobviouslyruinedqualityoflife.Hehadhistoryoffewheadtraumas.RecurrentBPPVcould’texplainhisclinicalpicture.PositiveStepSideTest(SST)wasindicationforexploratorytympanotomy.Aftersealingtheovalwindow,patientimprovedrapidly.ConclusionHistoryofchronicdisequilibrium,headtraumaandpositiveSSTshouldrisesuspiciontoperilymphfistula.







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INTRATYMPANIC DEXAMETHASONE: POTENTIAL IN THE PREVENTION OF CISPLATIN OTOTOXICITY

A. Shupak, T. Marshak, L. Levi, M. SteinerUnit of Otoneurology Lin Medical Center, Department of Otolaryngology – Head & Neck Surgery Carmel Medical Center, Department of Oncology, Lin Medical Center, The Bruce Rappaort Faculty of Medicine, The Technion, Haifa, Israel

Objective:ToexaminetheroleofintratympanicDexamethasone(ITD)inthepreventionofCisplatin-inducedhearingloss.StudyDesign:Prospectiverandomizedcontrolledclinicaltrial.Setting:Tertiaryreferralcenter.Twenty-sixpatientssufferingfromaneoplasticdiseaseforwhichthetreatmentprotocolincludedCisplatinwererecruited.PriortoeachCisplatintreatmentsessionITDwasinjectedtothebaselinerandomlyassignedearwhiletheotherearofthesamepatientservedasthecontrol.AudiometryandDistortionProductOtoacousticEmissions(DPOAEs)testresultsofthebaselineandfollow-upexaminationswerecomparedwithinandbetweenthestudyandcontrolears.ThecumulativedoseofCisplatinwasgreaterthan400mgforthefifteensubjectsthatcompletedthestudy.Thepuretonethresholdat8000Hzandpuretoneaveragethresholdat4000-8000Hzsignificantlyincreasedinboththestudy(p<0.005,p<0.03respectively)andcontrolears(p<0.01,p<0.005respectively).Significantincreaseinthepuretonethresholdfor6000Hzwasobservedinthecontrol(p<0.02)butnotinthestudygroup.WithinthegroupscomparisonalsorevealedsignificantdecreaseintheDPOAEaveragesignal-to-noiseratio(SNR)forthef2frequencies7031(p<0.04)and8391Hz(p<0.04)andSNRaveragefor4000-8000Hzinthecontrol(p<0.04)butnotinthestudyears.ITDsignificantlyattenuatedhearinglossat6000HzanddecreasedtheouterhairdysfunctionintheDPOAEf2rangeof4000-8000Hz.ITDmighthavepotentialinthereductionofCisplatin-inducedhearingloss.

ANALYSIS OF GENETIC AND NON GENETIC RISK FACTORS FOR CISPLATIN OTOTOXICITY IN PEDIATRIC PATIENTS

Y. Olgun 1, S. Aktaş 2, G. Kırkım 3, D. Çakır Kızmazoğlu 4, A. Pınar Erçetin 2, B. Demir 2, D. İnce 4, K. Mutafoğlu 4, B. Demirağ 5, H. Ellidokuz 6, N. Olgun 4,E. A. Güneri 11 Dokuz Eylül University School of Medicine Department of Otorhinolaryngology, Izmir, Turkey2 Dokuz Eylül University School Insitute of Oncology Department of Basic Oncology, Izmir, Turkey3 Dokuz Eylül University School of Medicine Department of Audiology, Izmir, Turkey4 Dokuz Eylül University School of Medicine Department of Pediatric Oncology, Izmir, Turkey5 Behçet Uz Children’s Hospital Department of Pediatric Oncology, Izmir, Turkey6 Dokuz Eylül University School of Medicine Department of Biostatistics, Izmir, Turkey

Cisplatinisaneoplasticagentwhichiswidelyusedforthetreatmentofvariouspediatricmalignancies.Unfortunately,somesideeffectslikeototoxicityandnephrotoxicityhindersitsusageathigherdoses.Uptodatevariousriskfactorshavebeenaccusedforcisplatinototoxicity.Theaimofthisstudyistoanalyzegeneticandnongeneticriskfactorscontributingtocisplatinototoxicity.SeventytwochildrenwhoreceivedcisplatinchemotherapyinpediatriconcologydepartmentofDokuzEylulUniversitySchoolofMedicineandBehcetUzChildren’sHospitalwereincludedinthisstudy.Audiologicalexaminationofallchildrenweredonebeforeandafter their treatmentsbypure toneaudiometry, tympanometryandABR,.BrockandMuenster classificationswereusedasototoxicityscales.SixsinglenucleotidpolymorphismsincludingERCC1,GSTP1Ala114Val,GSTP1IIe105Val,Megalin,TPMT,COMTwereevaluatedbyrealtimePCR.Nongeneticfactorssuchascranial irradiation,highandbolusdosesofcisplatin,age,gender,administrationofotherototoxicdrugssuchasfurosemide,carboplatinoraminoglycosideswerealsoanalysed.ByusingChi-squaretest,alloftheriskfactorswerematchedwiththetwoototoxicityclassifications.Riskfactorswhichwerefoundtobesignificantforototoxicitybyunivariateanalyseswerereevaluatedusinglogisticregressionmodelling.Of72patients,ototoxicitywasobservedin24patientsaccordingtoBrockandin30patientsaccordingtoMuensterclassifications.Inunivariateanalyses,malegender,concurrentuseofaminoglycosidesandGSTP1IIe105Valmutantgenotypewerefoundtobesignificantlyrelatedwithcisplatinototoxicity(p<0,05).Logisticregressionmodellinganalysesshowedthat,malegender(p=0,03)andconcurrentuseofaminoglycosides(p=0,023)werefoundtobesignificantlyrelatedwithcisplatinototoxicity.Ontheotherhand,GSTP1IIe105Valmutantgenotypewasnotfoundtobesignificant,butveryclosetothelevelofstatisticalsignificance(p=0,057).Ourfindingssuggestthat,malegenderandtheconcurrentuseofaminoglycosidesaresignificantriskfactorsforcisplatinototoxicityinpediatricpatients.GSTP1IIe105Valmutantgenotypemayalsoseemtobeageneticriskfactorinunivariateanalyses,althoughnotconfirmedbymultivariateanalyses.TheimportanceofGSTP1IIe105Valgeneticpolymorphismneedstobeevaluatedinlargerpatientsseries.

OTIC CAPSULE DEHISCENCE SYNDROME: LONGITUDINAL COGNITIVE AND NEUROBEHAVIORAL FUNCTIONAL OUTCOMES BEFORE AND AFTER REPAIR

P. A. Wackym, MD, C. D. Balaban, PhD, H. T. Mackay, PsyDEar and Skull Base Center, Portland, Oregon and the Department of Otolaryngology, University of Pittsburg, Pittsburg, Pennsylvania

Patientswithperipheralvestibulardysfunctionduetogravitationalreceptorasymmetrieshavecognitivedysfunctionandassumedneurobehavioralsequelae.Pre-andpostoperativelyquantitativelymeasurementinacohortofpatientswithsuperiorsemicircularcanaldehiscencesyndrome(SSCDS)symptomswith:superiorcanaldehiscence(SCD);andoticcapsuledefectsnotvisualizedwithimagingandrepairedwithroundwindowreinforcement(RWR);orbothwascompleted.Studydesign:Prospectivepatientseries.Setting:Tertiaryreferralcenter.Patients: Therewere13 adult and4pediatric patientswith superior semicircular canal dehiscence syndrome (SSCDS)whohadcompletion of neuropsychology test batteries pre- and every 3 months postoperatively. Eight had RWR exclusively, 5 had SCDpluggingexclusively,and4hadboth.Completionofaneuropsychologytestbatterypreoperativelyandat3,6,9and12monthspostoperatively that included:BeckDepressionInventory-II(BDI);WideRangeIntelligenceTest(WRITFSIQ)includingaverageverbal(crystallizedintelligence)andvisual(fluidintelligence);WideRangeAssessmentofMemoryandLearning(WRAML),includingthefourdomainsofverbalmemory,visualmemory,attention/concentrationandworkingmemory;andDelis-KaplanExecutiveFunctionSystem(D-KEFS).Mainoutcomemeasures:Quantitativeandstatisticalanalysisoftheircognitiveandneurobehavioralfunction.TherewasasignificantdecreaseintheBDIforallgroups.FortheWRAML,therewasastatisticallysignificantimprovementforvisualmemoryandverbalmemoryfortheRWRonlyandBothgroups,butnomeanimprovementfortheSCDonlygroup.Allthreegroupshadimprovementintheattention/concentrationdomain.Therewasnochangeinworkingmemoryforallgroups.TheIQscoreswereunchanged.Overall therewasamarked improvement incognitiveandneurobehavioralfunctionpostoperatively.Variabilitymayresultfromduration of underlying disease before intervention. The initial decrement or delay in performance improvement measured inseveralpatientsmayrepresentbrainreorganization.Greaterlongitudinaldataandgreatersubjectnumbersarenecessarytobetterunderstandandoptimizecognitiverecovery.

TRANS-MASTOID REPAIR OF SUPERIOR SEMICIRCULAR CANAL DEHISCENCE

T. Somers 1, Y. C. Zhao 2, J. Husseman 2, J. van Dinther 1, R. Vanspauwen 1, R. Briggs 21 Antwerp, Belgium2 Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia

Superiorsemicircularcanal(SupSC)dehiscencesyndromeisararecondition,causingavarietyofauditoryandvestibularsymptoms.Thetraditionalsurgicalmanagementisamiddlecranialfossa,extraduralapproachtoresurfaceorplugthesuperiorsemicircularcanal.Pluggingofthecanalhasbeenshowntoprovidebettersymptomcontrolandthishasledtodevelopmentofatransmastoidapproachforpluggingofthesuperiorsemicircularcanal.Wepresentfurtherdatasupportingtheuseofthetransmastoidapproachinpreferencetothemiddlefossaapproach.Studydesign:Retrospectivemulti-institutionalcaseseriesTenpatientswithelevenprocedureswereincludedinthiscaseseriesfromtwotertiaryotologyinstitutions.SupSCdehiscencewasconfirmedbycorrelationofclinicalsymptomswithpositiveaudiometric,VEMPandCTfindings.AtransmastoidapproachwasusedforpluggingoftheSupSCcanal.Eitherasinglefenestrationwascreatedatthesiteofdehiscence,orseparatefenestrationssitedampullopetalandampullofugaltothedehiscence.Allpatientswhounderwentthisprocedurehadgoodsymptomcontrolandhearingpreservationpostoperatively.Inpatientswithadequatetemporalbonepneumatization,thetransmastoidapproachprovidesasafeandeffectivealternativetothemiddlecranialfossaapproach.Thisserieshasdemonstratedexcellentsymptomcontrolandpreservationofhearingwiththetransmastoidapproach.







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SUPERIOR CANAL DEHISCENCE AND “NEAR DEHISCENCE” SYNDROME: CLINICAL AND INSTRUMENTAL ASPECTS

A. Castellucci, G. Piras, C. Brandolini, A. PiroddaDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), ENT Unit, S.Orsola-Malpighi University Hospital, Bologna, Italy

Even though superior canaldehiscence syndrome (SCDS)hasalreadybeenwidely studied fromaclinical, etiopathogeneticandtherapeuticpointofview,somediagnosticaspectshaveyettobeclarified.ItiswellknownthathighresolutionCT(HRCT)scantendstooverestimatetheprevalenceofthebonydefectrequiringthedetectionofloweredthresholdsofair-conducted(AC)VEMPstoconfirmthediagnosticsuspect.Themostrecentdefinitionofthesocalled“neardehiscencesyndrome”(NDS),inwhichanextremelythinnedbonyroofofthesuperiorcanalresults intheonsetofasymptomatologicalscenariooverlappingSCDS,hasallowedtoexplainmostcasesof incongruencebetweenimaginganalysesandelectrophysiologicaldata.Moreover,nounivocalexplanationtothewidesymptomatologicalandsemeiologicalvariabilityofSCDShasbeenofferedyet.Theaimofthispaper istofacethediagnosticdilemmaofferedbythecomplexityofthistwo-foldsyndrome(SCDSvsNDS)reviewingtheclinicalandinstrumentaldataandsubmittingtostatisticalanalysesasubsampleof100patients(193ears)selectedfromagroupof242patients(114M,128F,meanage56.8y,range8–88y)showingadehiscenceoraanextremethinningofthesuperiorcanalatleastfromonesideatHRCTscans.Firstly,weverifiedtheeffectivenessandthediagnosticaccuracyofimaginginconfirmingelectrophysiologicaldata,consideringthethresholdloweringofAC-cervicalVEMPsasthegoldstandardindiagnosinganincreasedinner-earadmittanceduetoSCDandofferingpathophysiologicalexplanationforthosecasesofincongruencebetweenresults.Secondly,wesoughtamonginstrumentalset(ACandBCcervicalandocularVEMPs,videoheadimpulsetest,audiometricair-bonegap)thetestallowingthebestdiagnosticcriteriafor“neardehiscence”andthetestcorrelatingmostsignificantlywiththesizeofdehiscenceincaseofSCDS.WhilemostlyalltestscanreliablydifferentiateSCDSfromNDS,fromthisstudyemergesthatocularVEMPsrepresentaneffectivemethodtodetectthe“near-dehiscent”conditionfromthenormalcases.

OCULAR VESTIBULAR EVOKED MYOGENIC POTENTIALS TO HIGH FREQUENCIES SHOW SEMICIRCULAR CANAL DEHISCENCE

L. Manzari 1, A. M. Burgess 2, H. G. MacDougall 2, I. S. Curthoys 21 MSA Academy ENT Center – Cassino – Italy2 Vestibular Research Laboratory, School of Psychology, the University of Sydney, NSW, Australia

In26patientswithCT-verifiedSSCDandin30patientswithdefiniteMeniere’sDisease(MD),toinvestigatetheeffectoffrequencyonthen10componentoftheocularvestibular-evokedmyogenicpotential(oVEMPn10)evokedbyairconductedsound(ACS)andboneconductedvibration(BCV)atthemidlineforeheadatthehairline(Fz).Ahand-heldBruel&Kjaer4810minishakerprovidedBCVstimulationwasused,usingsurfaceEMGelectrodesbeneathbotheyes,torecordoVEMPn10.ThestimulusACSandBCVateitherFzoratthevertexoftheskull(Cz)weretoneburstsrangingfrom125Hzto8000Hz.27healthysubjectsweretestedinthesameparadigm.InresponsetoACSandFzBCVfrom125Hzuntil8000HzinSSCDpatientstheoVEMPn10amplitudebeneaththecontraSSCDeyewassubstantiallyandsignificantlylargerthantheoVEMPn10beneaththeipsiSSCDeye.InnormalsACSoVEMPsn10ispresentandreproducibleuntil1000HzwhileinSSCDACSoVEMPsn10ispresentuptofarhigherfrequencies(8000Hz).ToFzBCVoVEMPsn10ispresentuntil8000Hzin23patientsbutonlyto1000HzinnormalsandMeniere’sDiseasepatients.TestingOVEMPfrequencytuningwithACSandBCVallowsverysimple,veryfastidentificationofaprobableunilateralSSCDinamannerwhichisveryeasyevenforseniorpatients.

DEHISCENCE SYNDROME

HEARING OUTCOME AFTER TRANSMASTOID SEMICIRCULAR CANAL PLUGGING

V. Van Rompaey, G. Van Haesendonck, P. Van de HeyningDepartment of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, Edegem, BelgiumFaculty of Medicine and Health Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium

Transmastoidpluggingofthesuperiorsemicircularcanalinsuperiorsemicircularcanaldehiscence(SSCD)syndromeandtheposteriorsemicircularcanalinintractablebenignparoxysmalpositionalvertigo(BPPV)willproduceresolutionofpreoperativesymptoms.Ouraimwastogaininsightintheeffectofpluggingonsymptomresolutionandpostoperativeboneandairconductionthresholds.Weperformedaretrospectivereviewonhearingoutcomesandpostoperativesymptomsof13patientswhounderwenttransmastoidsemicircularcanalpluggingbytwosurgeonsinatertiaryreferralcenterbetweenOctober2008andDecember2014.Allpatientsreceivedsystemiccorticosteroidsduringandaftersurgery.Weevaluatedairconduction(AC)enboneconduction(BC)pure-toneaverages (PTA)of0.5 kHz,1 kHzand2kHZbeforeandafter surgery inninepatientswithSSCD syndrome, threepatientswithintractableBPPVand1patientwithamajorcholesteatomaandcomplicatingmastoidabscess.Wealsocomparedsymptomsof9SSCDpatientsbeforeandaftersurgery.Hearingwaspreservedinallpatientsandevenimprovedin62%.MeanACPTAimprovedfrom26dBatbaselineto20dBpostoperativeinpatientswithSSCDsyndrome.Meanboneconductionhearinglevelsremainedthesameorworsenedslightly,thisresultedinameanreductioninairbonegap(ABG)inallfrequencies.ThemostcommonsymptomsinpatientswithSSCDsyndromewereautophony(9/9),pulsatiletinnitus(7/9),hyperacusisofboneconductedsounds(6/9),Tulliophenomenon(4/9)andpressure-inducedvertigo(3/9).Resolutionofautophonywasachievedin8outof9patientsSSCDpatients,resolutionofothersymptomswasvarying.Openingandpluggingofthesemicircularcanalthroughatransmastoidapproachprovestobesafeandeffectiveinpreservingorimprovinghearing.ThisstudyalsodemonstratedsymptomreliefachievedaftersurgeryinmostpatientssufferingfromSSCD.

CHRONIC DISEQUILIBRIUM AS MAIN SYMPTOM OF BILATERAL PERILYMPH FISTULA - CASE PRESENTATION

N. Arsovic, D. PavlovicFaculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Centre of Serbia, Belgrade

IntroductionPerilymphfistulaisdiagnosticchallengebecauseofdiverseclinicalpresentationandnospecifictests.MethodsandResults We present a patient with history of chronic disequilibrium, difficulties in concentration, depression with no ability toworkandobviouslyruinedqualityoflife.Hehadhistoryoffewheadtraumas.RecurrentBPPVcould’texplainhisclinicalpicture.PositiveStepSideTest(SST)wasindicationforexploratorytympanotomy.Aftersealingtheovalwindow,patientimprovedrapidly.ConclusionHistoryofchronicdisequilibrium,headtraumaandpositiveSSTshouldrisesuspiciontoperilymphfistula.







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INTRATYMPANIC DEXAMETHASONE: POTENTIAL IN THE PREVENTION OF CISPLATIN OTOTOXICITY

A. Shupak, T. Marshak, L. Levi, M. SteinerUnit of Otoneurology Lin Medical Center, Department of Otolaryngology – Head & Neck Surgery Carmel Medical Center, Department of Oncology, Lin Medical Center, The Bruce Rappaort Faculty of Medicine, The Technion, Haifa, Israel

Objective:ToexaminetheroleofintratympanicDexamethasone(ITD)inthepreventionofCisplatin-inducedhearingloss.StudyDesign:Prospectiverandomizedcontrolledclinicaltrial.Setting:Tertiaryreferralcenter.Twenty-sixpatientssufferingfromaneoplasticdiseaseforwhichthetreatmentprotocolincludedCisplatinwererecruited.PriortoeachCisplatintreatmentsessionITDwasinjectedtothebaselinerandomlyassignedearwhiletheotherearofthesamepatientservedasthecontrol.AudiometryandDistortionProductOtoacousticEmissions(DPOAEs)testresultsofthebaselineandfollow-upexaminationswerecomparedwithinandbetweenthestudyandcontrolears.ThecumulativedoseofCisplatinwasgreaterthan400mgforthefifteensubjectsthatcompletedthestudy.Thepuretonethresholdat8000Hzandpuretoneaveragethresholdat4000-8000Hzsignificantlyincreasedinboththestudy(p<0.005,p<0.03respectively)andcontrolears(p<0.01,p<0.005respectively).Significantincreaseinthepuretonethresholdfor6000Hzwasobservedinthecontrol(p<0.02)butnotinthestudygroup.WithinthegroupscomparisonalsorevealedsignificantdecreaseintheDPOAEaveragesignal-to-noiseratio(SNR)forthef2frequencies7031(p<0.04)and8391Hz(p<0.04)andSNRaveragefor4000-8000Hzinthecontrol(p<0.04)butnotinthestudyears.ITDsignificantlyattenuatedhearinglossat6000HzanddecreasedtheouterhairdysfunctionintheDPOAEf2rangeof4000-8000Hz.ITDmighthavepotentialinthereductionofCisplatin-inducedhearingloss.

ANALYSIS OF GENETIC AND NON GENETIC RISK FACTORS FOR CISPLATIN OTOTOXICITY IN PEDIATRIC PATIENTS

Y. Olgun 1, S. Aktaş 2, G. Kırkım 3, D. Çakır Kızmazoğlu 4, A. Pınar Erçetin 2, B. Demir 2, D. İnce 4, K. Mutafoğlu 4, B. Demirağ 5, H. Ellidokuz 6, N. Olgun 4,E. A. Güneri 11 Dokuz Eylül University School of Medicine Department of Otorhinolaryngology, Izmir, Turkey2 Dokuz Eylül University School Insitute of Oncology Department of Basic Oncology, Izmir, Turkey3 Dokuz Eylül University School of Medicine Department of Audiology, Izmir, Turkey4 Dokuz Eylül University School of Medicine Department of Pediatric Oncology, Izmir, Turkey5 Behçet Uz Children’s Hospital Department of Pediatric Oncology, Izmir, Turkey6 Dokuz Eylül University School of Medicine Department of Biostatistics, Izmir, Turkey

Cisplatinisaneoplasticagentwhichiswidelyusedforthetreatmentofvariouspediatricmalignancies.Unfortunately,somesideeffectslikeototoxicityandnephrotoxicityhindersitsusageathigherdoses.Uptodatevariousriskfactorshavebeenaccusedforcisplatinototoxicity.Theaimofthisstudyistoanalyzegeneticandnongeneticriskfactorscontributingtocisplatinototoxicity.SeventytwochildrenwhoreceivedcisplatinchemotherapyinpediatriconcologydepartmentofDokuzEylulUniversitySchoolofMedicineandBehcetUzChildren’sHospitalwereincludedinthisstudy.Audiologicalexaminationofallchildrenweredonebeforeandafter their treatmentsbypure toneaudiometry, tympanometryandABR,.BrockandMuenster classificationswereusedasototoxicityscales.SixsinglenucleotidpolymorphismsincludingERCC1,GSTP1Ala114Val,GSTP1IIe105Val,Megalin,TPMT,COMTwereevaluatedbyrealtimePCR.Nongeneticfactorssuchascranial irradiation,highandbolusdosesofcisplatin,age,gender,administrationofotherototoxicdrugssuchasfurosemide,carboplatinoraminoglycosideswerealsoanalysed.ByusingChi-squaretest,alloftheriskfactorswerematchedwiththetwoototoxicityclassifications.Riskfactorswhichwerefoundtobesignificantforototoxicitybyunivariateanalyseswerereevaluatedusinglogisticregressionmodelling.Of72patients,ototoxicitywasobservedin24patientsaccordingtoBrockandin30patientsaccordingtoMuensterclassifications.Inunivariateanalyses,malegender,concurrentuseofaminoglycosidesandGSTP1IIe105Valmutantgenotypewerefoundtobesignificantlyrelatedwithcisplatinototoxicity(p<0,05).Logisticregressionmodellinganalysesshowedthat,malegender(p=0,03)andconcurrentuseofaminoglycosides(p=0,023)werefoundtobesignificantlyrelatedwithcisplatinototoxicity.Ontheotherhand,GSTP1IIe105Valmutantgenotypewasnotfoundtobesignificant,butveryclosetothelevelofstatisticalsignificance(p=0,057).Ourfindingssuggestthat,malegenderandtheconcurrentuseofaminoglycosidesaresignificantriskfactorsforcisplatinototoxicityinpediatricpatients.GSTP1IIe105Valmutantgenotypemayalsoseemtobeageneticriskfactorinunivariateanalyses,althoughnotconfirmedbymultivariateanalyses.TheimportanceofGSTP1IIe105Valgeneticpolymorphismneedstobeevaluatedinlargerpatientsseries.

EPIDEMIOLOGY, STATISTICS AND RESEARCH DESIGN

R. Shoenhuber

Bozen, Italy

MD PATIENTS IN THE ACUTE STAGE

A. CasaniPisa, Italy

Meniere’sDisease(MD)isanidiopathicinnereardisordercharacterizedbyspinningdizziness(lastingfrom20’to24h),fluctuatinghearingloss(HL),earfullnessandtinnitus.Thenaturalhistoryofthediseaseischaracterizedbyvariableperiodsofexacerbationandremissionofsymptoms,althoughcochlearsymptomscanalsobeobservedamongepisodes.Thehallmarkofanacuteattackisprolongedvertigo.Eachepisodeofvertigoischaracterizedbyasuddenunheraldedintensesensationofmovement,mostcommonlyrotationorspinning,lasting20minutesto12hours.BecauseofthebriefdurationofeachattacktheclinicalexaminationofapatientwithMDisoftenperformedduringtheinter-criticperiodandfindsnoabnormalities.Inthefewcaseswherepatientshavebeenobservedduringacrisisappearquiteunwellbecauseoftheunpleasantsensationofvertigo.Theymaybesweatyandpale,unabletostandupsafely,nauseatedandvomiting.Theymayhaveanhorizontalnystagmusthatchangesdirectionastheattackprogresses(beatingtowardthesideofthediseaseatthebeginningandaftertowardthesafehear).Followinganattack,patientsareleftwithasenseof“hangover”foradayortwobeforerecoveringtoanormalfunction.Eachcrisiscanbecontrolbytheuseofvestibularsuppressantandantiemeticmedication,inassociationwithelectrolyteadjustmentandrehydration.Becauseofthenauseaandvomitcomplainedbythepatient,themoreadaptdrugandformavailableshouldbechoiceineverysinglecase.Medicationscanbedividedintodifferentclasses,includingbenzodiazepines,antihistamines,anticholinergicsandanti-dopaminergics;alsocalciumchannelblockersmaybeusedasvestibularsuppressant,althoughtheirroleinthiscontexthasn’tbeenyetcleared.Moreover,becauseofthepossibleautoimmuneoriginofMD,theuseoforalorintratympaniccorticosteroidshasbeenalsoproposedbothtoreducetheacuityofthecrisisandtopromotetheaudio-vestibularrecovery.Lastbutnotleastisdescribedtheuseofosmoticdiuretics(mannitol,glyceroletc.)administeredintravenously.Therationalefortheiruseisbasedonthesuppositionthatthesedrugscanalterthefluidbalanceofinnerear,leadingtoadepletionofendolymphandacorrectionofhydrops.Allthesemolecules,administeredaloneorincombination,constituteapossibletreatmentduringacrisisofMD,althoughtodatethereisnotconsensusandarenotavailablestrongevidenceabouttherecommendationofanyofthesedrugs.Themethodofadministrationdependsonthedevelopmentofvegetativesymptomsandtheavailabilityintheformulationofeachmolecule,soitcouldbeorally,intramuscularly,intravenouslyorrectally.Weunderlinethat,becauseoftheactioninhibitingthevestibularcompensationofthemostofthesedrugs,theiruseshouldbelimitedtotheacutephaseandstoppedassoonaspossible.Inthisphaseamoleculeasbetahistine,thatisdescribedtofavorvestibularcompensationbecauseofhisactionagainstH3receptors,mayplayanimportantroleandhelpthepatienttorecoveryassoonaspossibleaftereachepisodeandcomebacktohisusualactivity.







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MD PATIENTS IN THE INTERCRITIC STAGE

N. OzgirginAnkara, Turkey

Principally we believe that more than seventy percent of patients with Meniere’s Disease are treated, and their symptoms arecontrolledbymedicaltreatment.Today’streatmentmodalitiesforMeniere’sDiseasearesubjectedtotheinnerearmechanismsthatarebeingaccusedforthedevelopmentofthedisease.Amongtheconservativeandmedicaltreatmentmodalities,thepreferredmeasuresalsochangeduetothegeographicallocationsovertheworld.InUS,duringtheintercriticstage,re-arrangementofdietbyespeciallyrestrictingsaltconsumptionandcoffeeaswell,andmanyothermeasurestoregulatethelivingconditionsaswellasprescribingdiureticshavebeentheprimaryconcern.Formanyothercountriesuseofbetahistinehasbeentheprimarytooltocontrolthesymptomsandtreat.Currentlythedoseanddurationofuseforbetahistineforbettercontrollingthediseaseisinfocusbymanyscientificstudies.Autoimmunedisordersarespeculatedtobeoneofthemainfactorsontheethiopathogenesisofthedisease.Theonlylocationwheretheautoimmuneresponsestakeplaceintheinnerearistheendolymphaticsac.Sotheendolymphaticsacwillremainasafocusofattentiononplanningthetreatmentmodalities.Theendolymphcirculationisalsooneofthemainfactorsbeingresponsibleofthehydropsandsotherecentlytreatmentattemptsalsolimitedthemselvesonthecellularmechanismsbeingresponsibleofendolymphproduction.ThemanagementofMeniere’sDiseaseresistanttomedicaltreatmenthasshowngreatdifferenceduringthelasttenyears.Thestrongproponentsofvestibularneurectomybeganchangingthetendenciesonthemanagementpoliciesofthedisease.Theintratympanicinjectionstookplaceofvestibularneurectomiesandevensacoperationsinmostinstances.Inthislectureashorthistoryofcontroversiesonthetreatmentpolicieswillbementionedfollowedbytoday’smanagementprinciplesandtheevidencesthattheyarebasedwillbecriticized.

MD PATIENTS IN THE REHABILITATIVE STAGE

M. LacourMarseille, France

TheaetiologyofMenière’sdisease(MD)isnotfullyunderstoodeventhoughgeneticsandenvironmentalfactorsverylikelydeterminetheonsetofthedisease.MDisaclinicalsyndromecharacterizedbyepisodesofspontaneousvertigoassociatedwithfluctuatinghearingloss,tinnitusandauralfullness.Vertigoanddizziness,andtheirassociatedneuro-vegetativesymptomsandsocio-professionalconsequences,areextremelydisablingforMDpatientswhoshowincreasedanxietyanddepression.Itseemsthereforeimportanttostopvertigoquicklyintherehabilitativestage,andtoreducethereafterthefrequencyofthevertigoattacksandtheanxietylevelaswell.Neuropharmacologicaltreatments,changesinlivingconditions,andvestibularrehabilitationtherapyprotocolsarethemainwaystoachievethisgoal.Consideringthatvertigoisadirectconsequenceoftheasymmetricaldischargeofthevestibularnuclei(VN)onbothsides,drugsrebalancingtheVNactivityconstituteafirstchoice.Amongthesemedicationsare thecalciumchannelblockersandthedrugsinterferingwiththehistaminergicsystem.Antihistaminicsprescribedforfewdaysduringtheacutestagecansubstantiallyreducetheneuro-vegetativesignsandvertigo,whereashistaminergicdrugs(betahistine)acceleratetherecoveryprocessandreducethefrequencyof thevertigoattacks.Assuming thatendolymphatichydrops is responsible forMDonset, salt restrictionanduseofdiureticscanberecommended.Finally,vestibularrehabilitationtherapymaybeusefultopreventanxietyanddepressionandtohelpthepatientstoregainagoodqualityoflife.ThemiraculousmanagementofMDpatients,whichwouldalleviatedefinitivelyvertigoandthefluctuatingsensorineuralhearingloss,remainstobefound.AbetterunderstandingoftheMDmechanismsshouldguidetherehabilitationofthesepatients.

CONTROVERSIAL ASPECTS OF THE CLINICAL STUDIES ON THE USE OF BETAHISTINE IN MENIERE’S DISEASE

INTRATYMPANIC GENTAMICIN FOR DEFINITIVE TREATMENT OF MENIERE’S DISEASE: A SERIES OF 105 PATIENTS

G. Russo, R. Grassia, F. Mosca, C. A. LeoneOtolaryngology Department, Monaldi Hospital - Naples, Italy

Meniere’sDiseaseischaracterizedbythreemajorsymptoms:vertigo,hearinglossandtinnitus,whichmaybeaccompaniedbyauralfullness.Allsymptomsarediscontinuous,whilesynchronous,andvariableinintensity.Intratympanicapplicationofgentamicin,anototoxicaminoglycoside,isarelativelynewablativetreatmentforvertigoinMeniere’sDisease.Wetreated105patientsaffectedbyMenière’sDiseasewithonetothreedosesof16mgofintratympanicgentamicin(ITG)distancetoaweek.InclusioncriteriawereunilateralMD,lackofresponsetohyposodical/hyperhydricdietanddiuretics,morethan3attacksofvertigo/month,absenceofneurologicaldisordersandage<70years.Vestibularevaluation includeda)functional levelscale (FLS), thatreflectshowMenière’sdiseaseaffectsapatient’sactivities;b)controlofvertigoattacks;c)bedsideexamination,rotatorychairtestingandcalorictest.Hearingevaluationwasperformedwithpuretoneaverage(PTA).After2years,thedifferenceofFLSvaluesshowedafullrecoveryin75patients(70%),substantialrecoveryin30patients(30%)andnolimitedorinsignificantrecovery.After4yearsthevalueswere80%,11%,3%and6%respectively.Aboutthecontrolofvertigo,after2yearsallthepatients(100%)reachedacompleterecovery,whileafter4years95patients(91%)reachedacompleterecovery,and10patients(9%)alimitedcontrol.Rotatorychairtestingshowedsymmetry(<2°)in70%ofpatients,mildasymmetry(2-4°)in20%,moderateasymmetry(5°-6°)in10%andnocasesofsevereasymmetryafter2years.Thevaluesafter4yearswere80%,17%,3%and0%respectively.PTAshowedafter2yearsimprovementof15ormoredBHLin21patients(20%),worseningin21patients(20%)(13%anacusis),andnoeffectsin63patients(60%).Afterfouryearsthevalueswere13%,68%and19%respectively(13%anacusis).OurITGprotocollaysbetweentheclassichigh-doseandmoreeffectiveITGandthemorerecentandsafelow-doseIGT.Thefirstvariantworksmoreoften(90%ofthetime),butalsoisaccompaniedbyfarmorerisk.Injectionsaregenerallygiveneveryweek,uptoatotalof4-6;thetreatmentisstoppedwhenvertigoensues,indicatingthatthegentamicinisaffectingtheinnerear.Thelowdosemethodinvolvesusing1-2injectionsofgentamicin,waitingamonthbetweeninjections.Thisvariantstopsvertigo66-80%ofthetime,withnosignificantsideeffectsatall.ITGachievedsatisfyingoutcomeinthecontrolofvertigoattacksinpatientssufferingfromunilateralMD,withaverylowincidenceofhearingdeterioration.

HEARING LOSS FOLLOWING INTRATYMPANIC GENTAMICIN

D. M. KaplanDepartment of Otolaryngology- Head and Neck Surgery, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University in the Negev, Beer Sheva, Israel

Hearinglossisaawellknowncomplicationofintratympnicgentamicin.Dozensofstudies,usingdifferentprotocolsforinstillingthedrugintothemiddleearsincethe1970’havereported,withtheincidenceofhearinglossrangingfromalmostnonetoover40%.Severalreviewshaveconcludedthattheexactprotocolofdeliveringthedrugisthemostimportantfactor,favoringtheusetitrationofdelivery,asopposedtofixedprotocols,however,patentseriesareratherlimitedinsizeandmanyofthemdonotadheretothereportingcriteriaaccordingtotheAAOL-HNSguidelines.Thispresentationwillinclude1.Reviewthemainprotocolsforinstillinggentamicinintotheinnerearandtheireffectonhearing.2.AnalyzethedataIcollectedfromoneofthelargestseriesonthesubjectfromToronto(2000,2003)withreferencetohearinglossanditsriskfactors.







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INTRATYMPANIC GENTAMYCIN TREATMENT. HOW TO CONTROL THE THERAPEUTIC EFFECT? HOW TO RESPECT OTOLITH AND COCHLEAR FUNCTIONS?

P. Lorin, M. DonnardVertigo and Vestibular rehabilitation center, Le Mans, France

Objectives:DescribethemethodofControlledIntra-tympanicGentamycinTreatment(CIGT).Assessandpreventiatrogeniceffects.MATERIALandMETHODS:Retrospectivestudyabout297casesofmenieredisease(MD)«DefiniteMD»(AAO/HNS)fromjanuary2005todecember2014.Duringthistimeperiod24(8.08%)casesgotaCIGTbecausetheyshowedahighsymptomaticgrade(4or5AAO/HNS)andalongdurationcrisis(2monthsormore).Beforeeverysession,weevaluatedSubjectiveVisualVertical(SVV),PureToneAudiogram(PTA),AirBicaloric(30/44°Celsius)Reflectivity(ABR).Intratympanicgentamycinadministration(1ccand40mg)wasdonefor20minuteseverysession.TreatmentwasstoppedwhentheABRdecreasedbelow5%orPTAdecreasedbelow15%.Afterwards,weperformedABR,PTA,VideoHeadImpulseTest(VHIT),VestibularEvokedMyogenicPotentials(VEMP)Results:BeforetheCIGT :Meanage 61.37years,Sex ratio16w/8m,meansymptomaticmeangrade AAO/HNS4.7/5, VertigoSymptomScale(VSS)63.91%,AveragePTA60.45dbHL,ABR71,29%DuringtheCIGT:4.33injectionsonaveragewerenecessarytoobtaincaloricvestibularareflexia(15%)thehearing(function)wassurprisinglystable(4patients/16.5%)orevenbetter(17patients/71%)aftertheCIGTwithanaveragePTAof56.04dBHL(p>0.01).ThemeanresidualABRattheendofthetreatment(after4.33injections)was2.33%AftertheCIGT(61.62monthsonaverage):meansymptomaticgradeAAO/HNS1.57/5(p<0.01),VSS23.61%(p<0.01),PTA64.04dBHL,ABR8.38%,VHITgainMDside0.54(averagevalueforthe3canals)and0.825healthyside(p<0.001),otolithicreflectivitywithVEMPc86%Conclusion:Itwascommontoproposeavestibularneurotomy(VN)toarefractoryMDwithhighsymptomaticgradeandlongdurationcrisis.Our studyshowstheefficiencyof thetherapeuticactionof theCIGT (canalarareflexia)andthat the iatrogeniceffectsof theintratympanicgentamycincanbecontrolled.ThedeviationofVVSisapredictiveparameterofoverdosage,WeshowaconservationofthecochlearfunctionandcomparativelytotheVN,theCIGTdidn’taffecttheotolithfunction.

IT GENTAMYCIN TREATMENT

LONG TERM VESTIBULAR FUNCTION EVOLUTION AFTER GENTAMYCIN INTRA TYMPANIC INJECTION

M. J. Esteve Fraysse, S. Nicolas, A. Weckel, B. Lepage, M. Marx, B. FraysseToulouse, France

TheototoxiceffectofGentamicin isusedasatreatmentfor intractableMénièrediseasewiththeaimtodestroythevestibularfunction.Over the time, the protocol evolved to low doses with objective of hearing preservation and has greatly reduced the dose ofGentamicininjectedwithapparentlyagoodcontrolofvertigo.Theaimofthestudyistoevaluatethelongtermresults,afterGentamicinTTIof:-Vestibularfunctionbycalorictest.-Controlofvertigo.-Correlationsbetweenthetwo.3/ Materialandmethods3.1. Retrospectivestudyofaconsecutiveseriesofpatientsbetween2007and2012withintractableMénièredisease(AAOHN criteria).40patientsincludedamong49selected.3.2. Weperformalowdoseprotocol,withoneinjectionofGentamicin40mg/ml(0,3and0,6ml),repeatedifnecessarybetween 1and12months,dependingonclinicalvertigo.3.3. Vestibularfunctionwadassessedbycalorictestwithbicaloricinvestigation,andVNGregistration.3.4. Theanalysiscriteriawere: -Thevestibulardeficit(0to100),bythreemeasures:“Defpre”beforeTTI;“Defmax,”maximalvalueofvestibulardeficit duringthefirstcourseoftreatmentand“DefLT”,deficitlongtermaslastvalueattheendoffollow-up. -Thevariationsofvestibulardeficit(0%to100%)betweenDefLTandDefmax;andbetweenDefLTandDefpre.4.1. Themeanfollow-upis4,65years(2to8years).Thecontrolofvertigoattheendoffollow-up:77%classAand23%class B.Nevertheless,differentpostTTIdiseasehistoryhasbeenseen:4.1.1. Group1:1TTIwithcompletecontrol(N=15;37,5%).4.1.2. Group2:2to4TTI,duringonecourseoftreatmentwithnorecurrence(N=13;32,5%).4.1.3. Group3:recurrencewithnewTTI,aftermorethanoneyearofvertigocontrol(N=10;25%).4.2. Globalresultsofvestibularfunctionforthemeanvestibulardeficit:Defpre=50,3(SD=17);Defmax=87,8(SD=13); DefLT=85,1(SD=15).4.3. Themeanvariationofvestibulardeficitis2,8%betweenDefLTandDefmaxand84%betweenDefLTandDefpre,traducing thatvestibulardeficitisincreasedafterGentamicin,andseemstoremainstableafterlongtermfollow-up.4.4. Weanalyzealsotheintra-individualstabilityofvestibularfunction,consideringthevariationsbetweenDefLTandDefmax classifiedon3situations:nochange(<15%),recoveryoraggravation,morethan15%ofvariations.Whenthevestibular functionrecuperates(N=5;mean31,9%)thefrequencyofrecurrencesincreases(60%ofcases),whereaswhenitremains stableN=26,thefrequencyisonlyof26%,andthereisnorecurrencewhenthereisanaggravationofvestibularfunction.4.5. Therecurrencecasesanalysiswasdonein10cases/37,andcomparedtoothercaseswithoutrecurrence.Nodifference,in meanDefpre,orinmeanDefmax(86,3/89),butavestibularrecuperationtendencywasnotedinrecurrencegrouporDefLT (78/87)orDefLT/Defmax=11%/0,2%respectivelyonrecurrencegroupversusnorecurrencegroup.Attheendofthefollow-upstudy,thisgroupofpatientshasacompleteorsubstantialcontrolofvertigo,butwithdifferentprofilesofvertigoevolution.Thisseemstobelinkedwithvestibularfunctionandcanpushustobemoreaggressive,intermofnumberandfrequencyofTTI,whenthevestibularfunctionshowedalikelyrecoveryvestibularfunction.







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MONITORING OF CHEMICAL LABYRINTHECTOMY BY GENTAMICIN INJECTION ASSESSED BY VIDEO HEAD IMPULSE TEST AND VEMPS IN PATIENTS SUFFERING FROM MENIERE DISEASE RESISTANT TO MEDICAL THERAPIES

C. de Waele 1,2, E. Chiarovano 2,3, G. Lamas 2, C. Magnani 1, H. MacDougall 4, I. Curthoys 41 Cognition and Action Group, CNRS UMR8257, Paris, France2 Pitié Salpêtrière Hospital, ENT department, Paris, France3 University of Paris Descartes, Paris, France4 University of Sydney, Sydney, Australia

Chemical labyrinthectomy by intratympanic injection of Gentamicin is an interesting alternative treatment of the vestibularneurotomyforpatientssufferingfromMenierediseaseresistanttomedicaltreatment.Buthowmanyinjectionsareneeded?WesoughttoanswerthisbyusingassessmentofvestibularfunctionusingbothhorizontalandverticalvideoHeadImpulseTest(vHIT)ofsemicircularcanalfunctionandcervicalandocularVEMPstestsofsaccularandutricularfunctionofpatientstestedbeforeandaftergentamicininjections.20patientssufferingfromMenierediseasehadweeklygentamicininjections(80mg/2ml,1to3injections).TheyweretestedbeforeinjectionsbyvHIT,calorictest,cervicalandocularVEMPs,andhearingtest.BalancewasassessedusingEquitestandWiiplusfoam.Justbeforeanewinjection,canalfunctionwasassessedbyvHITinordertofollowtheVORdecreaseandocularnystagmuswasmeasuredusingvideo-nystagmography.Patientswerefollowedlongitudinallyat1,3and6monthsafterthelastinjection.Thenecessarynumberof injectionsto induceeffectiveunilateralvestibular lossvariedbetweenpatients: somepatientsneededonlyoneinjection;othersneededtwoorthreeinjections.Themeasurementofocularnystagmuswithfastphaseorientedtowardtheintactsidewasnotsufficienttodecidetostoptheinjection.Ourfunctionaltestdatagaveclearindicationabouttheeffectofgentamycininjectionswithtime.VHITshowedadecreasedvestibulo-ocularreflexgaininhorizontalandverticalcanalplanes.OcularVEMPswerealsocrucialindicatorstoassessthegentamicin-inducedutriculo-oculardysfunction.Inconclusion,monitoringvestibular functionusingvHITandVEMPsbeforeeach injectionallowedus todefine specificcriteriatodetectsignsofeffectivevestibularlossanddeterminethenecessarynumberofintratympanicinjections.Noneofourpatientsexhibitedacutevertigoduringthefirstoneyearoffollow-up.Nohearinglosscouldbeobservedevenathighfrequencies(6000and8000Hz).Therefore,usingtheseteststomonitortheefficacyofchemicallabyrinthectomywasaverysafe,efficientandnon-invasivemethodtosuppressacutevertigoinpatientssufferingfromacochleo-vestibularhydrops.

SPONTANEOUS INVERSION OF NYSTAGMUS WITHOUT A POSITIONAL CHANGE IN THE HORIZONTAL CANAL VARIANT OF BENIGN PAROXYSMAL POSITIONAL VERTIGO

Y. Ogawa, A. Ichimura, K. Otsuka, A. Hagiwara, T. Inagaki, S. Shimizu, N. Nagai, S. Itani, A. Kawano, M. SuzukiDepartment of otolaryngology, Tokyo Medical University Hachioji Medial CenterDepartment of otolaryngology, Tokyo Medical University

Weinvestigatedtheneuro-otologicalfindings,includingnystagmus,andtheclinicalcourseofpatientswiththehorizontalcanalvariantofbenignparoxysmalpositionalvertigo(HC-BPPV),whoshowedspontaneousinversionofnystagmuswithoutapositionalchange.SomepatientswithHC-BPPVpresentwithspontaneousinversionofnystagmuswithoutapositionalchange;inotherwords,biphasicnystagmus sometimesoccurs in the sameheadpositionduring thepositional test. In this study,we speculatedon thepossiblemechanismofspontaneousinversionofnystagmuswithoutapositionalchange.Thecharacteristicsofspontaneousinversionofpositionalnystagmuswithoutapositionalchangewereanalyzedin7patientswithHC-BPPV.AllpatientswerediagnosedashavingHC-BPPV.Duringthepositionaltest,thespontaneousinversionofnystagmuswasobservedinthesameheadpositioninallpatients.Spontaneousinversionwasobservedonbothsidesin5patients,andonlyon1sidein2patients.Allpatientspresentedwithgeotropicnystagmusinthefirstphase,andageotropicnystagmusinthesecondphase.Thecoexistenceofcupulolithiasisandcanalolithiasisappearstobeapossiblemechanismofthespontaneousinversionofpositionalnystagmus.

BPPV

EFFECTS OF HEARING DYSFUNCTION IN BPPV PATIENTS

T. Inagaki, Y. Ogawa, K. Otsuka, N. Nagai, S. Itani, M. SuzukiDepartment of Otolaryngology, Tokyo Medical University

BPPV is knownas thevertigodiseasewithouthearingdysfunction. However,we see somepatientswithworsehearing in theaffectedsideofBPPV.BPPVisalsoknowntooccurintheelderlypeople.Theelderlypeoplemayhaveinnereardysfunction,becausetheyalsohavehightonelossonbothsideswithoutlaterality.ToinvestigatetheeffectofhearingdysfunctioninthepatientswithBPPV.Weretrospectivelyanalyzed258patientswithidiopathicBPPV(i-BPPV)whohadnothadinnereardysfunctionbeforetheBPPVattack,and35patientswithsecondaryBPPV(s-BPPV)whohadtheBPPVattackafterinnereardysfunction,betweenJanuary2011andDecember2013attheDepartmentofOtolaryngology,TokyoMedicalUniversityhospital.ThehearingbetweentheaffectedsideofBPPVandtheotherwasstudied.The i-BPPVpatientsweredivided into2groups,onewiththehearingwithhightone loss (H+)andtheotherwiththehearingwithouthightoneloss(H-).Whenthesumtotalofthehearingthresholdofhighfrequency(2,4and8kHz)was100ormore,thepatientwasclassifiedintogroupH+.Weinvestigated1.Ageandgender,2.Averagedhearinglevel,3.Lateralityofthehearing,4.CanaltypeofBPPV,5.CuringperiodofBPPVand6.RecurrencerateofBPPVini-BPPVands-BPPVpatients.1. Ageandgender Therewere31maleand56female,andtheaveragedageswas71.9yearsold(y.o)inthegroupH+.Therewere53male,118 female,and53.2y.o.inthegroupH-.Therewere10male,25female,and62.4y.o.inthegroups-BPPV.2. Averagedhearinglevel Averagedhearinglevelintheaffectedsideandtheothersidewere32.5dBand30.8dBinthegroupH+,15.7dBand16.1dB inthegroupH-,and42.7dBand32.3dBinthegroups-BPPV.3. Lateralityofthehearing Thehearingwasworsebymorethan5dBintheaffectedsideofBPPVinthe44.8%ofgroupH+,33.1%ofgroupH-,and 68.2%ofgroups-BPPV.Then,thehearingwasbetterbymorethan5dBintheaffectedsideofBPPVinthe30.2%ofgroup H+,33.8%ofgroupH-,and29.4%ofgroups-BPPV.Theseratesweresimilarineachfrequency.4. CanaltypeofBPPV Posteriorsemicircularcanaltype(PSC)was62.1%inthegroupH+,60.9%inthegroupH-,and65.7%inthegroups-BPPV. Lateralsemicircularcanaltype(LSC)was29.9%,35.1%and22.9%.5. CuringperiodofBPPV Theaveragedcuringperiodwas15.9daysinthegroupH+,12.7daysinthegroupH-,and51.6daysinthegroups-BPPV.6. RecurrencerateofBPPV TherecurrencerateofBPPVwas19.5%inthegroupH+,16.4%inthegroupH-,and14.3%inthegroups-BPPV.Thehightonelossini-BPPVpatientsisduetotheagingandnottoBPPV.Thelateralityofthehearingcanbeassociatedwiththeaffectedsideini-BPPVpatients,butthehearingisnotassociatedwiththeprognosisofi-BPPV.ThehearingdysfunctionduetotheinnereardiseaseisassociatedwiththeprognosisofBPPV.Thehearingdysfunction,includingthehightoneloss,inBPPVisnotassociatedwiththecanaltypeorthecuringperiodofBPPV.







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IMPACT OF CUPULOLITHIASIS ON PATIENTS’ WELL BEING

A. Abid 1, R. Yousef 1, T. Tomanovic 1,21 Department of Clinical Sciences, Intervention and Technology, Division of Ear, Nose and Throat Diseases incl. Audiology Karolinska Institutet, Stockholm, Sweden2 Department of Hearing and Balance Disorders, Karolinska University Hospital, Solna, Sweden

Thereareonlyasmallnumberofstudiesaboutbenignpositionalvertigo(BPV)typecupulolithiasis.Thestudyaimstoinvestigatetheself-perceivedsenseofdisabilityinpeoplewithBPVtypecupulolithiasisandinvestigatethevestibularsymptomsthataffectpatientsandtowhatextent.Method:Thestudyconsistedof22respondentswhoansweredthequestionnairesTheDizzinessHandicapInventory(DHI)andTheVertigoSymptomScale(VSS).TheDHIwasdividedintothreecomponents;physical,functionalandemotionalimpactofvertigo.TheVSSexaminedhowfrequentvertigorelatedsymptomsoccurredoneyearafterthediagnosisofBPVtypecupulolithiasis.Therespondents’pointswerepresented in the formofaverageswhere thebiggest troublesand themost frequent symptomswerehighlightedandwhichhealthproblemswerethehardesttolivewith.Results:Thestudydemonstratedamoderateself-perceivedsenseofdisabilitycausedbycupulolithiasis.Patientsexperiencedmainlyphysicalcomplaintswherethegreatestphysicaltroublewasthatthesymptomsincreasedduringrapidheadmovements.Themostfrequent symptomwasheadacheorpressure in thehead,whichoccurredmore thanoncepermonth. Instabilitywas themostdifficultsymptomtolivewith.Conclusion:ThestudyshowsamoderatenegativeoutcomeinpatientswithBPVtypecupulolithiasis,whichwasprimarilyphysical.

NEW THEORY OF BPPV PATHOLOGY “CRISTOLITHIASIS” - OTOCONIA ATTACHED TO THE CRISTA AMPULLARIS

K. Otsuka, M. Shiromori, M. Suzuki, U. Konomi, T. Inagaki, S. Simizu, N. Nagai, Y. OgawaDepartment of Otolaryngology, Tokyo Medical University, Tokyo, Japan

Nystagmus of BPPV canalolithiasis gradually decreases by repeating positional change (fatigability). On occasion, the nystagmusdisappearssuddenlybypositionalchangeandappearsagain.Itsmechanismseemstobedifferentfromthefatigability.Wesuspectthisphenomenonbeinginducedbytheotoconiaattachedtoanddetachedfromthebaseofthecrista.Wearbitrarilycallthis“cristolithiasis”.Thevalidityofthistheorywasinvestigated.Thelabyrinthsofthebullfrogwereused.Themembranouslabyrinthwascutatthecruscommunetocreateatiny,0.5mmopening.Asmallpieceofotoconia,removedfromthesacculusoftheotherear,wasintroducedthroughthisopeningintothecanallumen.Experiment1:Thepositionofthepreparationwaschangedsothattheotoconiamovebackandforthwithincanaltocanalandcanaltoampulla.Weobservedthemovementoftheotoconiaformaximumtotentimes.Theratesofotoconiaattachmenttothecanalwallandthecristawereinvestigated.Experiment2:Themodeloftheotoconiaattachedtothecupula(cupulolithiasis)orthecrista(cristolithiasis)wasused.Thesemodelsweregiventwokindsofstimuli,a.gravityandb.vibration.Experiment2a(Gravity):Thelabyrinthpreparationwasplacedsothatthecupula-to-cristaaxiswasinthehorizontalplanewiththecanalsideindownwardpositionfor30minutes.Theratesoftheotoconiadetachmentfromthecristaorthecupulawereinvestigated.Experiment2b(Vibration):Mechanicalvibrationwasappliedtothebonylabyrinthinecapsuleofthesemodelsusingasurgicaldrill.Thetimerequiredforotoconialdetachmentwasmeasured.AllexperimentswereconductedaccordingtotheethicalrulesforanimalexperimentsatTokyoMedicalUniversity.Experiment1:Nootoconialmasswasattachedtothecanalwallin6labyrinthpreparations.Theotoconialmasswasattachedtothecristain5outof6(83.3%)labyrinthpreparations.Theotoconiawereattachedmoreeasilytothecristathanthecanalwall.Experiment2a(Gravity):Incupulolithiasismodels,theotoconialmasswasdetachedwithin30minutesin2outof10(20%)labyrinthpreparations.Incristolithiasismodels,theotoconialmasswasdetachedwithin30minutesin11outof14(78.6%)labyrinthpreparations,whichwassignificantlyhigherthaninthecupulolithiasismodels(p=0.015).Experiment2b(Vibration):Inthecupulolithiasismodels(n=14),theaveragedetachmenttimewas140.3seconds.Inthecristolithiasismodels(n=11),theaveragedetachmenttimewas25.5seconds,whichwassignificantlyshorterthaninthecupulolithiasismodels(p=0.0010).Theotoconiaofcristolithiasisweredetachedmoreeasilythancupulolithiasis.Theinnerwallofthesemicircularcanaliscoveredbywallcellswithsmoothsurface.Theotoconiaofcanalolithiasismovealongthecanalsmoothly.Ontheotherhand,thebasalportionnearthecristahastransitionalcells,planumsemilunatum,anddarkcells.Theepitheliahavemicrovilliandsecretoryactivitytowhichtheotoconiaeasilybecomeattached.Theattachmentisweakerthancupulolithiasis.Itisassumedthatthisattachmentanddetachmentoftheotoconialeadtodisappearanceandreturnofthenystagmus.

BENIGN PAROXYSMAL POSITIONAL VERTIGO PREVALENCE IN MENIERE’S DISEASE: IS Meniere’s Disease A PREDISPOSING FACTOR?

S. Nemati, MD 1, A. S. Alia, MD 2, M. Motasaddi-Zarandi, MD 3, R. Panahi, PhD stu 4, M. Akbari, MD 51 Otorhinolaryngology- Head & Neck Surgery Department, and Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran2 Neurology Department, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran3 Otolaryngology- Head & Neck Surgery Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran4 Shahid Beheshty University of Medical Sciences, Tehran, Iran5 Otorhinolaryngology- Head & Neck Surgery Department, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Background: Meniere’s Disease (MD) is a chronic illness defined as the idiopathic syndrome of endolymphatic hydrops. Benignparoxysmalpositionalvertigo(BPPV)isabalancedisorderandcanbethesequelaofdiverseinnerearimpairments.Objectives:ThepurposeofthisstudywastoinvestigatetheincidenceofBPPVinMDpatients.MaterialsandMethods:Atotalof39patients(43ears)withdefiniteorprobableMD(23female,13male;meanage:46.4±9.2years)wereenrolledinourstudy.WeusedtheAmericanAcademyofOtolaryngology–HeadandNeckSurgery(AAO-HNS)criteriapluselectrocochleography(ECochG)testresultstodefinethepresenceofMDandpositionalandpositioningteststodeterminethepresenceofBPPV.Results:Twentyeightofthe43ears(65.1%)hadabnormalECochGtestresults.Sixoutof39cases(15.4%)hadBPPVintheposteriorsemicircularcanal.TherewerenocasesofBPPVinthelateralorsuperiorsemicircularcanals.ThemeandurationofMDwas28.5monthsinBPPVgroupand13.2monthsinthenon-BPPVgroup.Regardlessoftheageofthepatients,therewasasignificantdifference(p=0.02)betweenthedurationofMDinthetwogroups.Conclusions:Basedonourfindings,alongerdurationofMDmayresultinagreaterriskofdevelopingBPPV.ThesefindingsalsosuggestthattheincidenceofBPPVismoreaffectedbythedurationofthediseaseandtheconditionofthelabyrinththanitisbyaging.Keywords:Meniere’sDisease;BenignParoxysmalPositionalVertigo;Electrocochleography.

DEPENDENCE OF HEARING IMPROVEMENT ON THE DOSE OF INTRATYMPANICALLY APPLIED GLUCOCORTICOIDS:A META-ANALYSIS USING MATHEMATICAL SIMULATIONS OF CLINICAL DRUG DELIVERY PROTOCOLS

S. K. Plontke 1, A. Liebau 1, O. Pogorzelski 1, A. N. Salt 21 Dept. of Otorhinolaryngology, Head and Neck Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany2 Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, 63110, USA

Toestablishoptimallocaldrugdeliveryprotocolsforthetreatmentofpatientswithidiopathicsuddensensorineuralhearingloss(ISSHL).ControlledanduncontrolledstudieswithintratympanicapplicationofglucocorticoidsforISSHL.Atotalof51studieswith61treatmentgroupsbetweenJanuary2000andJune2014wereselectedbasedondescriptionofprotocolswith respect todrug concentration, dosing regimen (i.e. start, number and time intervals of treatment), andoutcomeparameterssufficientlydetailedforanalysiswiththecomputermodel.Cochleardruglevelswerecalculatedbasedontheconcentrationandvolumeofglucocorticoidsapplied,thetimethedrugremainedinthemiddleear,andonthespecifictimingofinjections.Avalidatedcomputermodelofdrugdispersionintheinnerearfluidswasusedtocalculatecochlearglucocorticoiddruglevelsresultingfromspecificclinicaldeliveryprotocols.Dosinginthecochleaandparametersofthedeliveryprotocolwerecomparedwithchangesofhearingsensitivityandfinaloutcome.Timecourseswerequantifiedintermsofthemaximumconcentration(Cmax)andtheareaunderthecurve(AUC)ofthedrugatspecificcochlearlocations.Therewasnoinfluenceofapplieddrugconcentration,applicationtime,numberofinjections,intervalbetweeninjections,durationoftreatment,totallocaldose(quantifiedasAUCorCmax)onoutcome.For“rescuetherapy”situationsthereappearedtobenoneedtostartwithintwomonthfromonsetofISSHL.Thiscallsintoquestiontheimportanceofthechoiceofdrugandapplicationprotocol,andperhapstheeffectivenessonintratympanicglucocorticoidtherapyforISSHLingeneral.Changeinpuretoneaverage(PTA)mightnotbeanadequateoutcomeparametertoassesseffectivenessoftheintervention,sinceitappearstodependoninitialhearingloss.FinalPTAmightbeusedasanalternativeparameterwhencomparingdifferentclinicalreports.Furthereffortsshouldbemadetowardsstandardizationofoutcomeparametersandpublicationofoutcomesinindividualpatientsinclinicalstudieswithinterventionstoimprovehearing.







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GLUCOCORTICOIDS STIMULATE ENDOLYMPHATIC WATER REABSORPTION IN INNER EAR

J. Nevoux 1,2,3,4, S. Viengchareun 1,2, I. Lema 1,2, AL. Lecoq 1,2, M. Lombès 1,2, F. Ferrary 41 Inserm, U1185, Le Kremlin-Bicêtre, F-94276, France2 Université Paris-Sud, Faculté de Médecine Paris-Sud, UMR-S1185, Le Kremlin-Bicêtre, France3 Service d’ORL, Assistance Publique-Hôpitaux de Paris, CHU de Bicêtre, Le Kremlin-Bicêtre, France4 Inserm, U867, Université Paris Diderot, France

Meniere’sDisease,clinicallycharacterizedbyfluctuating,recurrent,andinvalidatingvertigo,hearingloss,andtinnitus,islinkedtoanincreaseinendolymphvolume,theso-calledendolymphatichydrops.Sincedysregulationofwatertransportcouldaccountforthegenerationofthishydrops,weinvestigatedtheroleofaquaporin3(AQP3)inwatertransportintoendolymph,theK-rich,hyperosmoticfluidthatbathestheapicalciliatedmembraneofsensorycells,andwestudiedtheregulatoryeffectofdexamethasoneuponAQP3expressionandwaterfluxes.ThedifferentAQPsubtypeswereidentifiedininnerearbyRT-PCR.AQP3waslocalizedinhumanutricleandmouseinnerearbyimmunohistochemistry,andconfocalmicroscopy.Unidirectionaltransepithelialwaterfluxeswerestudiedbymeansof3H2OtransportinmurineEC5vvestibularcellsculturedonfilters,treatedornotwithdexamethasone(10-7M).ThestimulatoryeffectofdexamethasoneuponAQP3expressionwasassessedinEC5vcellsandinvivoinmice.AQP3wasunambiguouslydetectedinhumanutricle,andwashighlyexpressedinbothendolymphsecretorystructuresofthemouseinnerear,andEC5vcells.Wedemonstratedthatwaterreabsorption,fromtheapical(endolymphatic)tothebasolateral(perilymphatic)compartments,wasstimulatedbydexamethasoneinEC5vcells.Thiswasaccompaniedbyaglucocorticoid-dependentincreaseinAQP3expressionatbothmRNAandproteinlevel,presumablythroughglucocorticoidreceptor-mediatedAQP3transcriptionalactivation.WeshowforthefirsttimethatglucocorticoidsenhanceAQP3expressioninhumaninnerear,andstimulateendolymphaticwaterreabsorption.ThesefindingsshouldencouragefurtherclinicaltrialsevaluatingglucocorticoidsefficacyinMeniere’sDisease.

COMPARISON OF INTRA-TYMPANIC STEROID THERAPY PROTOCOLS FOR MENIERE’S DISEASE BETWEEN CENTERS IN THREE MEDITERRANEAN COUNTRIES

R. Perez 1, S. Battelino 2, A. Incesulu 31 Department of Otolaryngology-Head and Neck Surgery, Shaare Zedek Medical Center affiliated with the Hebrew University Medical School, Jerusalem, Israel2 Department of Otorhinolaryngology, University Medical Center Ljubljana, Slovenia3 Department of Otolaryngology-Head&Neck Surgery, Faculty of Medicine, Eskisehir Osmangazi University, Meselik-Eskisehir, Turkey

Intra-tympanicsteroidshavebecomethetreatmentofchoiceforMeniere’spatientswhodonotrespondtoconservativetherapy,whichincludeslowsaltdiet,betahistineanddiuretics.TherationalofthetreatmentisbasedonthetheorythatMeniere’sisanimmunemediateddisorder.Thetreatmentisaimedtoreducethenumberandseverityofthevertiginousattacksandamelioratetheassociatedhearinglossandtinnitus.Studieshaveshowntheefficacyofthistreatmentbutdonotrefertoaspecificuniformprotocol.Therearenumerousprotocolsinuseamongcentersaroundtheworld.WeaimtodescribethedifferentprotocolsusedinthreetertiarycentersinthreeMediterraneancountries(Slovenia,TurkeyandIsrael)intermsofthemodeofdelivery,dosageandfrequencyofapplications.ThedeliverymethodinLjubljana,Slovenia(SB)isviaamyringotomyconductedovertheroundwindowwithacircleknife.Inaddition,asmallanteriorholeismadeforpressurerelief.InEskisehir,Turkey(AI)theholeismadebya27gaugedentalneedleandinJerusalem,Israel(RP)usingalasermyringotomy.Thediameterofthemyringotomyis2.0mm,showntostaypatentforapproximatelyoneweek.Withrespecttodosage,inSlovenia1.5mlsolutionof24mg/1mldexamethasoneisusedandinTurkeyandIsrael,4mg/mlat1and0.5mlrespectively.InEskisehirandLjubljanainjectionsaregiveneveryotherday.WhileinEskisehironly3-5injectionsaregiven,inLjubljanainjectionsaregivenuntilsymptomsimprove.InJerusalemdailyinjectionsaregivenandincaseimprovementisseeninthelaterinjections,treatmentsarecontinuedonceaday.InIsraelthepatientstaysonthebedwiththeheadoppositelytiltedfor15minutes,inTurkeyfor30-45minutesandinSloveniafor2-3hours.Thewidevariability intreatmentprotocolsof intra-tympanicsteroids forMeniere’sDisease isdemonstrated.Werecommendthatthetreatmentresultsshouldbecomparedandauniformprotocoldetermined.

IT STEROID TREATMENT

EVALUATION OF LONG TERM EFFECT OF INTRATYMPANIC DEXAMETHOSONE THERAPY (ITD) IN MENIERE’S DISEASE (MD)

C. Candreia, MD (first author), A. Lehner, MD, M. Gärtner, MD, T. Linder, MDDepartment of ENT, Kantonsspital Luzern, Luzern, Switzerland

Intratympanicdexamethasontherapie(ITD)isdocumentedtoreducevertigoattacksinpatientswithMDby80-90%intheliterature.Between 2006 and 2011 we treated 48 patients with definite MD (AAO-HNS) with 1 to 3 series of intratympanic dexamethasoninjections.Thesuccessrateofreductionofvertigoattacksbyatleast60%followingITDwas94%after1yearand80%after5years.TheaimofthisstudywastoassessthecourseofMDinthepatientstreatedwithITDin2006fouryearsaftertheendofourformerstudy.Retrospectivechartreviewofthepatients(n=48)thatparticipatedintheformerstudy(2006-2011)andassessmentthecurrentactivityofMDandthequalityoflifebystructuredquestionnaires.Weobtaintwogroupsofpatients:ThefirstgrouprevealslowactivityofMDwithoutfurtherinterventionsnecessary(“cure”).Thesecondgroup (“palliation”) showshighactivityofMDwith two subsequent subgroups according to their further interventions(A:ITD;B:intratympanicgentamycin(ITG)).ITNallowLong-termcureinthemajorityofpatients,providestheoptionforfurtherinjections“asneeded”orallowsasubsequentchangetomoredestructivetreatment.

INTRA-TYMPANIC DEXAMETHASONE IN THE TREATMENT OF DISABLING VERTIGO IN MENIERE DISEASE

J. J. Wazen, MDSilverstein Institute, Ear Research Foundation

ThepurposeofthisstudyistodetermineifintratympanicdexamethasoneiseffectiveincontrollingvertigoinMeniereDisease.PatientswhounderwentintratympanicdexamethasonetherapyusingtheMicrowicktechniquebetweenMay2011andMay2013wereevaluated.Theeffectoftherapyontheincidenceofvertigo,fluctuatinghearingloss,fullnessandpressureintheear,andtinnituswasanalysed.Thenumberandpercentageofpatientswhohadtoundergointratympanicgentamicintherapyduetofailureofthesteroidtherapywillbepresented.Thetechnique,results,andstatisticalanalysiswillbepresented.Intratympanicdexamethasonedoesnotappeartobesuccessful incontrollingtherecurrentvertigoattacksinourMeniereDiseasepopulation.

IDIOPATHIC ACUTE LABYRINTHINE DISEASES AND MENIERE DISEASE: THE NECESSITY OF A MULTIDISCIPLINARY APPROACH

A. Pirodda 1, C. Brandolini 1, C. Borghi 21 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy2 Department of Medical and Surgical Sciences, University of Bologna, Italy

Inthepastyears,ourgrouphasoutlinedtheimportanceofhemodynamicimbalancesofbothorganicandfunctionaloriginasacausalfactoroflabyrinthineaffectionswithacuteonset.Actually,aseriesofobservationshaswitnessedtheinfluenceofatemporarylackofperfusion,possiblyduetoanabruptloweringofbloodpressurefollowedbyanabnormalvasoconstriction,inthegenesisofsuchdamages.Thispathogenicmodelfitswiththeanatomicandfunctionalcharacteristicoftheinnerearthatisfedbyaterminaltypecirculation,andthereforeismoreeasilypronetotransientischemia;inouropinion,itcouldbeconsideredasapossiblepathogenicfactorinanumberofunexplainedlabyrinthineaffectionsincludingMenieredisease.Startingfromthealterationsproducedinaterminalandhighlyenergyrequiringorganastheinnerearbyamoreorlesslong-lastingischemia,thedamagecouldresultinanimpairmentrelatedtothedurationofthelackofperfusion:hencetinnitus,vertigoepisodes,reversiblesuddenhearingloss,hydropsandseverenon–reversiblesuddenhearinglosscouldbeimaginedasderivingfromacommoncausalfactor.Duetothevariabilityoffactorsabletointerferewithinnerearperfusion,especiallyconcerningautonomicregulationandcardiocirculatoryconditions,adiagnosticandtherapeuticapproachseemsmandatory:whentakingintoaccountthesefactorsamoreaccurateoverallclinicalpicturecanbedisposable,thuspermittingtoavoidinappropriatetherapeuticchoices.







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MENIERES’ DISEASE SYMPTOMATOLOGY IN RELATION TO THE 1995 AAO-HNS

R. Albera, I. Bin, C. Cassandro, A. Albera, A. Canale, J. Colombini, F. C. GervasiUniversità di Torino, Città della Salute e della Scienza di Torino

Meniere’sDisease(MD)isacomplexprogressivedisorderoftheinnerearcharacterizedbysensorineuralhearingloss,episodicvertigo,tinnitusandauralfullness.MDdiagnosisisessentiallybasedonclinicalhistoryandspecifictestsareusuallynotrequired.In1995theCommitteeonHearingandEquilibriumoftheAmericanAcademyofOtolaryngology-HeadandneckSurgerypublishedtheguidelinesforMDdiagnosisandclassifieditincertain,definite,probableandpossible.Thestudygroupconsistedof384consecutivesubjectsaffectedbyMDaccordingtotheAAO-HNS1995guidelines.Ineachcasewecollectedanexhaustiveanamnesisregardingalltheaspectsofthediseaseandwemeasuredthepure-toneaudiometricthreshold.Oftheoverallsample,228subjects(59%)wereaffectedbydefiniteMD,30(8%)byprobableMDand126(33%)bypossibleMD.Inthelattergroupof126subjects,90(73%)hadonlyhearinglossand36(27%)onlyvertigo.Ageatthebeginningofthediseasewasnotdifferentbetweenprobableandpossiblegroups,whilesubjectswithdefiniteMDwereolderwithlongerdurationofthedisease.Disabilitylevelwaslesserinthepossibleforms.Amongthe228definiteforms,MDappearedwithbothvertigoandhearinglosstogether(temporaldelaylessthan24hours)in79cases(35%),withhearinglossalonein96cases(42%)andwithvertigoalonein53cases(23%).PTAmeanthresholdat0.5-1-2-3kHzatthefirstcontrolinthe228casesofdefiniteMDwasworsethaninthe90subjectsaffectedbypossibleMDwithjustcochlearinvolvement.InconclusiondefiniteformrepresentsthemostcommonformofMDatdiagnosisandcomprisesthemostdisablingcases.However,inthemajorityofcases,thediseasestartseitherwithcochlearorvestibularsymptoms(possibleMD)andevolvesindefiniteusuallywithin5years.

GLUTEN SENSITIVITY AND MENIERE’S DISEASE

F. Di Berardino, D. Soi, D. Alpini, E. Filipponi, A. CesaraniU.O.C. Audiologia. Fondazione Policlinico, Mangiagalli e Regina Elena. Dipartimento di Scienze cliniche e di comunità, Università degli studi di Milano, Milano, Italy

Apossiblerelationshipbetweenglutensensitivity(GS)andMeniere’sDisease(MD)hasalreadybeenreportedinliterature.Manyauthorsarecurrentlystudyingthehumoralimmuneresponses(biomarkers)toallwheatantigensandpeptidesinpatientswithdiseasesthatarerelatedtowheatingestion.Theaimofthisstudywastoassessthehumoralimmuneresponsestowheatantigens,andinparticular,IgGandIgAantibodyproductionagainstalloftheantigensandpeptidesassociatedwithgliadininpatientswithMDwithorwithoutGS(MD-GS+andMD-GS-).Weusedtheseraof28patientswithMD,14ofwhomprovedtobesensitivetogliadinatskinpricktestingand14whoseresultswerenegative.Theserumof100healthypatientswasusedasthecontrolinordertoestablishthenormalrangeforthebiomarkerstested.TherewerenosignificantdifferencesbetweenMD-GS+andMD-GS-forallofthebiomarkerswiththeexceptionofIgGanti-transglutaminase3.(p<0.005)OurresultsconfirmtheimportanceofthedelayedresponsetoskinpricktestinginidentifyingpatientswithGSinMD,aspreviouslyreportedinliterature.TheincreaseofIgGantiTransglutaminase3antibodiesrequiresfurtherstudyinordertodefinewhetheritispurelyincidental.

CLINICAL ISSUES 1

THE SOCIAL IMPACT OF MENIERE’S DISEASE: THE ROLE OF DIFFERENT TREATMENT STRATEGIES

D. Nuti, M. MandalàAzienda Ospedaliera-Universitaria Senese

ThesocialandworklifeimpactofdizzinessonpatientssufferingfromunilateraldefiniteMenière’sdiseasewasassessedbythevalidated‘Sociallife&WorkImpactofDizzinessquestionnaire’(SWID),whichhasbeenalreadyadoptedtoevaluatethesocialimpactofdizzinessintwodifferentcountries(1).SWIDrepresentedthemainoutcomemeasureassociatedwiththenumberofvertigoattacksandtheperceiveddeteriorationofhearinginthelastsixmonths.Thequestionnairewasadministeredtoeachpatientbye-mail.Allsubjectsreportedalso their lastpure toneaveragescoreandthetreatmenttheyunderwent in the last6months.Morethan200patientscompletedthequestionnaire.Themeannumberofdaysoffworkattributedtothedizzinessintheprevious6monthswasmorethan7days.Sociallifewasdisruptedinmorethan50%ofallpatients.Statisticallysignificantdifferencesinthesocialandworkimpactofthediseasewereobservedamonggroupstreatedwithdifferentstrategies(betahistine,diuretics,steroids,intratympanicgentamicin,etc).ThesocialandworklifeimpactofMenière’sdiseaseisveryhigh.

THE NATURAL HISTORY OF MENIERE’S DISEASE: A SYSTEMATIC REVIEW

J. Bewick 1, D. Hoare 2, J. Phillips 31 Norfolk and Norwich University Hospital2 National Institute for Health Research (NIHR) Nottingham Hearing Biomedical Research Unit/Otology and Hearing group, Division of Clinical Neuroscience, School of Medicine, University of Nottingham3 Norfolk and Norwich University Hospital

Meniere’sisacommonlyencounteredconditioninotologicalmedicineandwhilemanyhavesorteffectivetreatmentstrategiestheunderlyingpathophysiologicalbasisispoorlyunderstood.Thenaturalhistoryofthediseasevariesgreatlyandwhilesomepatientswilldeveloptheclassictriadofhearingloss,tinnitus,vertigootherswillhavealessreliablecourse.Weaimtoreportonthecourseofthediseaseinuntreatedpatientsbymeansofaepidemiologicalsystematicreview.Eight literatureplatforms includingPubMed,ScienceDirectandEBSCOHostunderwenta systematic search (ofEnglish language,peer-reviewjournals)usingtheterms:Meniere’sANDnaturalhistoryORwaitingORwait*ORwaiting-listORwatchfulORobservationORcontrolgroup.ThereviewwasregisteredonthePROSPOROreviewdatabase.Primaryoutcomes(withrespecttovertigoseverity/frequency,hearinglos,tinnitusandqualityoflife)ofpatientswithMeniere’sdisease(GradeIAAO-HNSdiagnosis)undergoingeithernoactivetreatment,watchfulwaitingoronawaitinglistfortreatmentarereported.2256paperswereidentifiedandthroughinitialinclusioncriteria,244paperswerereviewedwithreportinginlinewiththePRISMAstatement.TheresultsofthereviewwillbereportedaccordingtotheclassictriadofMeniere’ssymptomsandassuchameta-analysisforeachmeasurewillbeconsidered.ThisstudywillgeneratethelargestbodyofresearchregardingthenaturalhistoryofMeniere’s.ThevolumeofresearchlocatedinthesystematicsearchisconsiderableandtheresultswillbeofinteresttofellowresearchersandthosewhocounselandtreatpatientswithMeniere’sdisease.COI:MrJohnPhillipsistheChiefInvestigatorfortheUKOTO-104clinicaltrial.JohnPhillips’attendancetothissymposiumhasbeensupportedbyOtonomy.







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HIGH FREQUENCY DEAFNESS WITH VESTIBULAR EPISODIC SYNDROME

E. Martin-Sanz, J. Esteban, R. SanzUniversity Hospital of Getafe, Madrid, Spain

Aims and Introduction: ThepathophysiologicalbasisofMeniere’sdisease(MD)isendolymphatichydrops,whichissupposedlyprogressiveandsectorial.Itsetiologyisstillnotfullyunderstood,buttheendolymphatichydropsisconsideredasthemorphologicalcorrelateforthesymptoms,suchashearinglossfluctuation,tinnitus,auralfullnessandvertigoepisodes.However,manyauthorshavepointedoutthatthenaturalhistoryofthediseaseisnotalwayshomogeneous,beingrelativelycommon,anon-classicalevolutionofthesyndrome.InvolvementofthehighfrequenciesassociatedwithrecurrentvertigoisanotcharacteristicfindingofMD.Weaimtostudyangroupofpatientswithhighfrequencydeafnesswithvestibularepisodicsyndrome(HIVES)Methods:Wepresentapopulationof16patientswithrecurrentspontaneousvertigoassociatedwithtinnitus,auralfullnessandhighfrequencyhearingloss.andcomparewithacohortof30patientswithDefiniteMDandlowfrequencyauditoryimpairment.Bothcohortshavebeenfullystudiedbycompleteneuro-otologicalexamination,calorictests,cervicalandocularVEMPs,andextratympanicelectrocochleography.Results:Wefoundnosignificantdifferencesbetweentheresultsofdifferentvestibulartestsinbothcohorts.TheElectrocochleographySP/APratioorarearesults,didn’tshowanysignificantdifferencebetweenMDandHIVESgroup.Bothgroupshaveasimilarclinicalandvestibularpresentation.Basedontheresultsoftheelectrocochleography,bothgroupsofpatientssharethesamepathophysiologicalbasis,theendolymphatichydrops.

VESTIBULAR IMPLANT, A NEW APPROACH TO BILATERAL VESTIBULAR DISFUNCTION

A. Ramos, A. Kral, M. Barbara, E. Offeciers, M. Manrique, N. Pérez, A. Zarowski, C. Van Himbeeck, J. Benítez, M. T. Pérez Zaballos, A. Ramos de MiguelEuropean Multicenter Consortium

Vertigoofvestibularoriginhasaprevalenceof5%andrespondspoorlytocurrenttreatments.thisvaluerisesto38%intheelderlyandincreasestheriskoffallsandtheconsequentpermanentdisability,healthcostsandevendeath.12-14millionpeopleworldwidewouldrequireavestibularimplant.Currentdevicesdetectcephalicangularvelocitiesandstimulatethesemicircularcanals.Howevertheydonotcodeverticalandhorizontalaccelerations,usedtosensegravitationalforces,keepastanduppositionandrestoreasenseofself-positionbythesacculeandutricle.Wepresentaprojectthatwillelectricallyemulatelinearaccelerationsreproducedintheseorgans.Thus,theobjectivesare:1)tostudyvestibularpathways,2)toanalizevestibularneuralresponsetoelectricalstimulationand3)torestorethesenseoflinearaccelerations.Finally,theprojectwillofferatwo-wayexchangewithinertialsystemtechnology,usingwhathasalreadybeendiscoveredandreturninginnovativebioinspiredsolutions.

CLINICAL ISSUES 2

MENIERE’S DISEASE: WHAT CAN WE LEARN FROM VESTIBULAR IMPLANTS?

J. T. Rubinstein, J. O. Phillips, L. Ling, K. NieVirginia Merrill Bloedel Hearing Research CenterNational Primate Research CenterDepartments of Otolaryngology and BioengineeringUniversity of Washington, Seattle, USA

WehaveplacedaprototypevestibularimplantinfourhumansubjectswithuncontrolledMeniere’sDiseasewhowerecandidatesforlabyrinthectomy.Thesemicircularcanalswereimplantedwitha150microndiameterarrayusinga“soft-surgical”approachviaa~200micronlabyrinthotomy.Despitepreservinghearingandvestibularfunctioninnumerousnormalrhesusmonkeyswiththesamesurgeryanddevice,hearingandvestibularfunctionwaslostinallfourMeniere’spatients.Theybehavedclinicallyasiftheyhadundergonealabyrinthectomyexcepttherewasfarlesspostoperativevertigothanistypicalinasurgicallabyrinthectomy.CTinonesubjectconfirmselectrodesnearallthreeampullae.ThesecasesstronglysuggestthattheMeniere’searismoresusceptibletosurgicaltraumathanahealthyearconsistentwithpriorobservationsafterstapessurgery,andapublishedseriesofaccidentalposteriorcanalfenestrationsinretrolabyrnthinevestibularnervesection.WehavealsoobservedfluctuatingresponsivenessofthevestibularnervetoelectricalstimulationconsistentwithpriorobservationsoffluctuatingspeechdiscriminationincochlearimplantpatientswithMeniere’sDisease.Lastly,oneofoursubjectswasabletomodulatetheintensityofaMeniere’sattackusinghistake-homestimulator.Whenstimulatingatacurrentlevelthatevokedvertigocomparabletoanattackwhennoattackwaspresent,hewasabletocompletelysuppressthevertigoduringanattack.Thissuggeststhatatleastforthisindividual,thisattackwasduetoasuddendeclineinvestibularnervefiringconsistentwithonetheoryofMeniere’spathophysiology.

SUBJECTIVE VISUAL VERTICAL IN BILATERAL VESTIBULAR LOSS ROLE OF PROPRIOCEPTION

M. Toupet 1,2,3,5, C. Van Nechel 2,4, U. Duquesne 2,4, C. Hautefort 2,5, S. Heuschen 1, A. Bozorg Grayeli 3,61 Centre d’Explorations Fonctionnelles Otoneurologiques, Paris, France2 Institut de Recherche Oto-Neurologique (IRON), Paris, France3 Otolaryngology department, Dijon University Hospital, and Burgundy University, Dijon, France 4 Neurological Rehabilitation Department, Brugmann University Hospital, Brussels, Belgium5 Otolaryngology department, Lariboisière Hospital, APHP, Paris 6 CNRS, UMR-6306, Electronic, Image and Computer Research Laboratory, Dijon, France

Subjective Visual Vertical is a routine test assessing the otolithic function. The participation of proprioceptive input in SVV isprobablysignificantbutunclear.Inordertoevaluatethisparticipation,weaimedtostudyVVSinpatientswithbilateralvestibularlossanddifferentbodyandnecktilts.Thisprospectivestudyincluded22patientswithidiopathicbilateralvestibular loss(meanage:58,sexratio:1.2)and30adultcontrols(meanage:51,sexratio:1.3).SVVwasmeasuredbyaskingthepatienttoplaceverticallyaredlineonascreenusingaremotecontrol.Deviationfromverticalwasmeasuredindegrees(negativevaluestotheleftandpositivetotheright).Thepatientwasseatedonatiltableseat(TRVseat,Apt,France).SVVwasmeasuredin7bodypositions:vertical,headandbodytilted12°toright,then24°,andthenbodytiltedat24°withtheheadupright,subsequentlysamepositionsweretestedontheleft.Ineachposition,SVVwasmeasured6times.At vertical position, no difference in SVV was observed between vestibular loss and controls (-0.2° ± 1.05 versus -0.1° ± 1.98respectively,unpairedt-test).However,patientswithvestibularlossweremoresensitivetobodytilt(-8.5°±4.64forvestibularlossversus0±3.26forcontrolat24°bodyandheadtilttotheleft,p<0.01,unpairedt-test).PlacingtheheaduprightwhilethebodywasstilltiltedsignificantlyreducedthisdifferencesuggestingthatcervicalentriesparticipateinSVV.Similarresultswereobservedontheright.NotonlyotolithicfunctionbutalsoproprioceptiveentriesespeciallycervicalsensorsparticipateinSVV.







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SUBJECTIVE VISUAL VERTICAL AND HORIZONTAL IN THE INDIAN POPULATION

G. A. Amit, K. Tyagi, A. M. Augustine, A. Lepcha, A. BalrajDepartment of ENT, Christian Medical College, Vellore 632004 Tamil Nadu, India

Todeterminethenormativevaluesforstaticanddynamicsubjectivevisualverticalandhorizontal(SVV&SVH)inagroupofIndianvolunteers.Theperceptionofgravitationalvertical/horizontal,whichisalsocalledtruevertical/horizontal,canbeassessedbyaskinganindividualeithertoadjusthis/herbodypositiontothevertical/horizontal(posturalvertical/horizontal)ortoadjustacomputersimulatedlightbartohorizontalorvertical.Thiscanbedoneunderstaticanddynamicconditions.SVV/SVHisavalidvestibulartestthatcanbeusedtoidentifydysfunctionintheotolithicpathwaywhichconsistsofbothcentralandperipheralvestibularsystem.Thetestmeasuresthedeviationsoftheperceivedverticalfromthetrueverticalwhichismeasuredindegreesandthiscapacitydependsontheintegrityofvisualandvestibularpathway(inspecifictheutricularpathway)inthebrainstem.HospitalbasedprospectivecrosssectionalstudyofagroupofnormaladultsAfterclearance fromthe institutional researchboardeighty twovolunteers stratified into twogroups (20-40,41-60years)wererecruitedforthestudy.Anypersonwithhistoryofvertigo, imbalance,otologicalcomplaints(hearingloss/tinnitus/eardischarge/earache/eartrauma),persistentheadache,historyofhead-trauma,useofototoxicdrugs,priorENTsurgeries,co-morbidillnesseswereexcludedfromthestudy.The SVV and SVH angles were measured under static and dynamic conditions. This was done by using software from the SVVequipment (MUS_VS-V1.3.2.RevB)SynapsisCompany-France).SixreadingseachweretakenforSVVandSVHinbothstaticanddynamicsituations.Meanvaluesof(1.4+/-0.68)degreesstaticSVVforfemales,(1.58+/-0.71)degreesstaticSVVformales,(1.82+/-0.64)degreesdynamicSVVforfemales,(2.04+/-0.65)degreesdynamicSVVformales,(1.63+/-0.76)degreesstaticSVHforfemales,(1.65+/-0.84)degreesstaticSVHformales,(1.80+/-0.60)degreesdynamicSVHforfemalesand(2.1+/-0.86)degreesSVHformaleswereobtained.Therewasnosignificantdifferencebetweenthesexesandthetwoagegroups.ThisistheonlystudyintheIndianpopulationandthenormativedataobtainedinthisstudycanserveasreferenceforfuturestudiesandvestibulartestingespeciallyinthosesufferingfromchronicvertigoandsuspectedtohaveotolithicpathwayabnormalities.

SELECTIVE WINDOW APPLICATION OF GENTAMYCIN IN MENIERE’S DISEASE

F. N. Ardıç, F. Tümkaya, K. Aykal, B. ÇabukPamukkale University

ThepurposeofthestudyistopreventhearinglosswhenusingITgentamycinforintractableMeniere’sDisease.TenpatientswhohaddefiniteMeniere’sDiseaseanddidnotbenefitfrommedicaltreatmentwereselectedforthestudy.AllhadcompletedvestibulartestsandMRIfordifferentialdiagnosis.Exploratorytympanotomywereconductedunderlocalanesthesia.Thedexamethasonesoakedgelatinspongeswereappliedtotheroundwindowandgentamycinsoakedgelatinspongeswereappliedtoovalwindow.Theaveragehearinglevelinlowtones(250,500,1000,2000Hz)was50.5±7.7dBbeforetreatmentand51.2±6.8dBaftertreatment.Theaveragehearinglevelinhightones(4000,6000,8000Hz)was42.2±19.2dBbeforetreatmentand47.4±19.1dBaftertreatment.Theaveragecaloricweaknesswas34.3±24.3beforeand45.3±32.7aftertheapplication.Twopatientshaverecurrenceofvertigoattackinoneyearoffollowup.TheycontinuedwithIntratympanicgentamycininjection.Theuseofdexamethasoneandgentamycinfordifferentwindows in themiddleear is safeandeffectivemethod forMeniere’sDisease in the short term.Applicationofdexamethasoneprotectsnotonlythehearingcellsbutvestibularcellsalso.

IMPROVING DIAGNOSTICS IN PATIENTS WITH VESTIBULAR PAROXYSMIA TO TREAT THEM IN AN EARLIER PHASE OF ILLNESS

B. Ihtijarevic 1,2, V. Van Rompaey 1,2, P. Van de Heyning 1,2, F. Wuyts 11 Department of Antwerp University Research centre for Equilibrium and Aerospace, Antwerp University Hospital, Belgium 2 Department of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, Belgium

Vestibularparoxysmia(VP)isdefinedasshortvertiginousspellsfrequentlydependentonheadpositionwithanunderlyinghypothesisthatthereisaneurovascularconflict(NVC)withtheVIIIcranialnerve.Althoughthesyndromewasfirstdescribedmorethan30yearsagobyJannetta,thereisstillaneedformorespecificdiagnosticcriteriatomakeanearlydiagnosisandtreatpatientsinanearlystageofillness.Astudywasperformedon18patientswithcomplaintsofvertigo,aNVConMRIandimprovementofsymptomsbytreatmentwithcarbamazepineoroxcarbazepine.Anamnesticandclinicalresultswereexaminedretrospectivelytodeterminesignificantsimilaritiesamongthesepatients.Inthisstudy55%oftheVPpatientscomplainedoflightheadedness,while44%experienceddizzinessand39%wereunstable.Asmallergroupof33%experiencedrotationalsensationsaswellasadrunkenfeeling.Themostcommonaccompanyingsymptomswerecervicalpain(78%),hearingloss(55%),tinnitus(61%),headache(55%)andauralfullness(38%).Thesymptomsoccurreddailyin81%ofthepatientslastingsecondsorminutes(71%)oftendescribedbythepatientasacontinuousburdenwithshortepisodesofvertiginousspells.Thesymptomsweretriggeredbypositionalchanges(78%),specificallybyheadmovementin50%andonly27%byrollingoverinbed.Clinicalexaminationshowedapersistentnon-BPPVtypenystagmus(71%).TheChavdaclassificationwasusedtospecifytheanatomyoftheNVC.Therewasnocorrelationfoundbetweenaudiometry,ENGandthetypeofloop.Severalotherdiagnosesweremadewhichledtoameandurationof16monthsandamaximumof60monthsbeforeefficienttreatmentforVP.A combination of anamnestic criteria, clinical examination and imaging is necessary to diagnose VP and more importantly todifferentiateiteasilyfromothervestibularpathologiesasMeniere’sDisease,BPPVandvestibularmigraine.

UNILATERAL MENIERE DISEASE WITH BILATERAL HEARING LOSS

H. Lindahl 1, C. Strömberg 1, T. Tomanovic 1,21 Department of Clinical Sciences, Intervention and Technology, Division of Ear, Nose and Throat Diseases incl. Audiology Karolinska Institutet, Stockholm, Sweden2 Department of Hearing and Balance Disorders, Karolinska University Hospital, Solna, Sweden

When conventional treatment for Meniere’s Disease fails, intratympanic gentamicin is considered to be an effective treatmentinvertigocontrol.Gentamicinisanaminoglycosidewithototoxiceffect.Toourknowledgenopreviousstudyhasconsideredtheototoxiceffectintheuntreatedear,whichisoneofthequestionsaskedinthisstudy.Ourmethodwastoevaluatehearinglevelgatheredfrompatientspre-treatment,onemonthandtwoyearspost-treatment.Tinnitusrelatedquestionnaireswereanalyzedfrompatientspretreatmentandatthelongtimefollowup.Atotalof36patientswereincludedinthisstudy.Medianpuretoneaverage(PTA)was57,5dBHLpre-treatmentonwiththeMeniereaffectedside.One-monthposttreatmentPTAwas65,6dBHLandtwoyearsafterPTAwas64,7dBHL.Thedifferencewasnotsignificant.MoreinstillationsseemtorelatetohigherPTA´s.Theototoxiceffecthadasignificantimpactonthefrequencies3,4,6,8kHz.Thehighestimpactison6kHzwithamediandecreasein-10dBHL.Threepatientsexperiencedsignificanthearingimprovement;fivepatientsbecamedeafposttreatment,sevenpatientsgotsignificantlyworsenedhearingandfifteenpatientshadnosignificantchangeinPTAposttreatment.Gentamicinhadnoimpactontheuntreatedearafteronemonth.Afterthefollowupperiodoftwoyears,medianforchangeinhearinglevelbeforeandaftertreatmentshowsdecreasein5dBonthefrequencies4and6KHZ.AccordingtoVAS-results,41%ofthepatientsexperiencedanimprovementontheirtinnitus.Conclusion: ITG is an effective treatment method for intractable unilateral Meniere with unpredictable hearing outcomes. Theototoxiceffectissignificantinhighfrequenciesontreatedearafteronemonth.Untreatedearshowsatendencyforworseningininhighfrequencyhearinglevelsduringthefollowingupperiodoftwoyears.







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THE RELATIONSHIP BETWEEN THE CEREBROSPINAL FLUIDS AND PERILYMPH. NEW FINDINGS IN MRI AFTER INTRATIMPANIC ADMINISTRATION OF GADOLINIUM

G. Neri, F. Cazzato, A. Di Tano, A. Pacella, G. Filograna Pignatelli, S. Salice, A. TartaroNeurosciences, Imaging and Clinical Sciences Dept., Gabriele d’Annunzio University Chieti-Pescara Italy

InMenierediseasehydropsisthenecessaryconditionbutitdoesnotexplainallclinicalfeatures,includingtheprogressionofthehearinglossandtherecurrenceofvertigo.Theperilymphandendolymph,thetwoliquidsintheinnerear,andtheirexchangesarestillbeingstudiedandifweknowalotoftheirphysicalandchemicalpropertiesweknowlittleoftheirdynamicsinsidetheear.Inliterature,allpapersabouttheinnerearliquids,wereconductedonmiceinwhichtheinternalearpropertiesarenotoriouslydifferentthaninhuman.Inparticular,theproductionandresorptionofperilymphandendolymph,aswellastheirendocochlearflowandtheroleofthecochlearaqueductarestillunderstudy.RecentlytheradiologicalinvestigationswithMRI3TeslabeforeandafteradministrationofendotympanicGadoliniumshowedanewandcompletelyunexpectedfeatureofperilymph.In100%ofpatientswithMenieredisease(MdM)thecontrastiseliminatedinthecerebrospinalfluid(CSF)notthroughofthecochlearaqueductbutthroughtheinternalauditorycanal(IAC).ThisfindingleadstonewpathogenetichypothesesinwhichtheroleoftheCSFcouldassumegreaterimportance.Wereportedourexperienceof23patientswithdefinedMdM,accordingtothecriteriaoftheAmericanAcademy,evaluatedwith3teslaMRIwithadministrationofgadodiamidebytrans-tympanicinjection.InallthesepatientsthegadodiamidewasnotobservedinthecochlearaqueductandwaseliminatedthroughthebottomofIAC.ThisfindingsdemonstratedtherelationshipbetweenCSFandperilymphinMenieredisease.ThepossibilitythatchangesinpressureoftheCSFcouldbetransmittedtotheperilymph,alreadyhighlightedintheliterature,arediscussed.

A COMPARISON OF NEUROTOLOGICAL AND PSYCHOMETRIC TEST RESULTS IN MÉNIÈRE’S DISEASE AND PHOBIC POSTURAL VERTIGOL. Nimroda 1, L. Kise 2, M. Nimroda 3 1 Paul Stradins Clinical University Hospital, Riga, Latvia 2 Riga Stradins University, Riga, Latvia3 Ministry of Welfare of the Republic of Latvia, clinical psychologist, Riga, LatviaTheaimofthisstudywastoanalyzerelationshipbetweenneurotologicalandpsychometrictestresultsinpatientswithMeniere’sDisease(MD),phobicposturalvertigo(PPV)andcontrolgroupinaninterdisciplinaryprospectivestudy.MDisadiagnosisrequiringexpertclinicaljudgement.Thereisnospecificdiagnostictest,andmanypatientsmeetsomebutnotallofthediagnosticcriteria.SeveralreportssuggestapsychosomaticbasisforMD.Patientsweredividedintotwostudygroups:organicdisorderscausedbyMDandpsychogenicvertigocausedbyPPV(n=31and31;agerange23-77and26-76years;meanage47.48and49.26years;mediandurationofthedisease3.9and3.9yearsrespectively).Controlgroup(n=31;agerange20-65years;meanage38.58years)presentednoENTdisordersoranyseverecomorbidity.Neurotologicaldiagnosticproceduresincludedvideonystagmography(VNG)withcalorictestingandpuretoneaudiometry(PTA)wereperformed.Patientswereaskedtofilloutself-ratedscales:theDizzinessHandicapInventory(DHI),theHospitalAnxietyandDepressionScale(HADS)andtheBeckDepressionInventory(BDI). Results:PatientswithMD (45.16%)hadpathological testvaluesoncaloric irrigation.PatientswithPPVandcontrolgroupshowednormalparametersforvestibulartesting.Bothstudygroupsandcontrolgrouphadpathologicalvaluesforpsychometricmeasures.OfMDpatients,therewasweakcorrelationbetweenthecaloricresponsesandanxietysymptoms(p<0.05).OfPPVandcontrolgroup,therewasweakcorrelationbetweenthecaloricresponsesanddepressionsymptoms(p<0.05).MDpatients’medianPTAthresholdwas45dBonaffectedear.PatientswithPPVandcontrolgroupPTAwasinthenormalrangeofhearing.CorrelationbetweenthePTAandotherneurotologicalandpsychometrictestresultswasmediumcloseorweakinPPVandcontrolgroupwhileinMDgroupnocorrelationwithanyoftestresultsobserved(p<0.05).MostofpatientshadmoderateandseverevertigoinducedhandicapinbothMDandPPVstudygroups77.42%and74.19%respectively.Therewasmediumclosecorrelationbetweenthevertigoinducedhandicapanddepressioninbothstudygroupsandweakcorrelationincontrolgroup(p<0.05).Thecorrelationbetweenthevertigoinducedhandicapandanxietywasweakinbothstudygroups(p<0.05).Thecorrelationbetweenthevertigoinducedhandicapandcaloricresponseswasweakincontrolgroup(p<0.05).PatientsofMD,PPVandcontrolgroupshowedonscales67.74%,64.52%and32.26%anxiety,74.19%,70.97%and16.13%depressionrespectively.Thecorrelationbetweentheanxietyanddepressionsubscaleswasmediumcloseinallgroups(p<0.05).Conclusions:ResultsofneurotologicaldiagnosticproceduresincludedVNGwithcalorictestingandPTAshowedweakornocorrelationwithothermeasurementsinbothstudygroupsandcontrolgroup.Mildtosevereanxietyanddepressionshowedabout2/3ofMDandPPVpatients.ThecorrelationbetweenthedepressionandanxietysubscalesoftheHADSwasmediumclose,whichillustratesthefrequentcoincidenceofsymptomsofanxietyanddepressioninbothstudygroupsandcontrolgroup.Thus,comparisonamongthestudygroupswithanyoftheabovementioneddiagnosticmethodswerenotdifferentiatedpatientswithMD.Thepossibledifferenceoforganicandpsychogenicvertigosyndromescouldbevaluableinthepersonalitymultifactorialevaluation.

EHEALTH IN MENIERE’S DISORDER IMPROVES QUALITY OF LIFE WHEN MEDICAL THERAPY IS NOT ENOUGH

I. Pyykkő, MD 1, H. Levo, MD 2, J. Rasku, PhD 1, V. Manchaiah, PhD 3, E. Kentala, MD 31 Department of Otolaryngology, Hearing and Balance Research Unit, University of Tampere, Tampere, Finland2 Department of Otolaryngology, University of Helsinki, Helsinki, Finland 3 Department of Speech and Hearing, Lamar State University, Texas, USA

MedicaltherapytriestohealMeniere’sdisorderbyresolvingvertigo,gaitproblemsandhearingloss,butveryoftenthepatientshaveproblemsandrestrictionsthatreducethequalityoflife.Web-basedpeersupportcanchallengetheseproblemsbybeingperson-focusedandavailable.WehavecreatedapeersupportprogramforMenière’sdisorder(MD)thatusesdatabaseresources,appliesartificialintelligenceindecisionmaking,andhasauser-centeredapproachindeterminingtheimpactofthedisorderandinthepatientempoweringprocess.Methods:Datawasretrievedfrom740casesofMDtodeveloptheprogram.TheprogramusespatternrecognitioninthediagnosisofMD.TheimpactofMDisassessedbyICF-basedstructuredquestions.Personaldataonqualityoflife,personaltraits,complaints,andattitudearecollectedinteractively.TheNorton-Kaplanmodelisappliedtoconstructastrategicperson-focused approach. By working on critical success factors, short term goals are then pursued.Results: The peer-supportprogramcomprisesthefollowingelements:Itfirstassessesthediagnosisandindividualparticipant’sdisorderprofile.ThereafteritinteractivelydeterminestheimpactcausedbythedisorderusingICFclassification,evaluatespersonaltraitsandattitudestowardsthedisorder,andidentifiespositiveaspects.Theeligibilityofthesubjecttoentertheprogramisbasedontheirdiagnosisandqualityoflifescore.Theinferenceengineusesadatabasetocomparetheimpactofthecomplaints,personaltraitsandattitudeswith50referents.Inthetherapeuticcomponent,theparticipantdefinesvision,timeframe,inspectsconfoundingfactors,determinesgoals,establishesastrategyandstartstoworkonthethreemostimportantICF-basedproblemscausedbythedisorder.Interactivelywiththeperson, theprogramguides them tofind solutions thatminimize their restrictions. Theprogramutilizes collaborationwithsignificantothersandenhancespositivethinking.Toassistthepersontocope,referencedataoncopingstrategyareretrievedfromthedatabase.Intheoutcomeanalysis,severalmeasuresincludingqualityoflife,posttraumaticgrowthfactorindexandpersonalsatisfactionareused.Theprogramprovidesahardcopyofpersonalcomplaints,problems,strategy,attitude,goalsandoutcomemeasures.Theinformationpackagecontainspdf-filesofmajorcomplaints,240animatedslidesand12videocasehistories.Among235personsparticipatinginthedatacollection75%foundtheprogramquestionusefulorveryusefulinsupportingtheirlifewithMeniere’sdisorder.Thosewithacutediseaseregainedmoreinformationthanthosewithchronicdisorder.Among31participantspassingthewholeprogramthegeneralhealthrelatedqualityoflife(EQ-5D)improvedby14%.Wehavecreatedaweb-basedpeer-support systemthat isuser-centered,able toclassify thecharacteristics,profile the impactofthedisorder,assistindecisionmaking,andinteractwiththeindividualparticipant.TheprogramcontainsalargedatabaseonthecomplaintsandimpactofMD.ThemodifiedKaplan-Nortonmodelisusedtoestablishapersonalstrategythatempowerstheparticipantandimprovescopingwiththedisorde.







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ALTERNATIVE MEDICINE AND NON-INVASIVE THERAPIES FOR THE TREATMENT OF MENIERE’S DISEASE

M. Lauriello, I. Salvi, L. Crosta, M. FusettiDepartment of Applied Clinical Sciences, University of L’Aquila, Italy

Characterizedbyrecurrentepisodesof tinnitus,acutevertigo, sensorineuralhearing lossandaural fullness,Meniere’sDisease isknownforitsdebilitatingimpactonqualityoflife.Althoughtheetiologyandpathogenesisremainlargelyunclear,themostplausiblehypothesisascribestoendolymphatichydropsabnormalfluctuationsinthepressureofinnerear,whichwouldberesponsibleforalterationsinreceptorelements.ThemanagementofMeniere’sDiseaseiscontroversial,consequentlyitstreatmentiscurrentlyempiricalandthetherapiesareaimedatcontrollingthesymptoms.Thepurposeofthispaperwasareviewoftheliteratureoncomplementaryandalternative(CAM)methodscurrentlyavailabletocopewiththisdisease.Thecontrolofwaterintakemaybethesimplerandmoreconvenientprocedureforpatients.Eventheadaptationofthelifestyleandthetreatmentofanxietyappeartobehelpful.Nutritioneducationcanimprovetheresultsofmedicaltreatment:dietaryprotocolsoftenincludelow-sodiumdietandreductionofcaffeine,nicotine,andcarbohydratesintake.Somestudieshaveassessedtheimpactoftheingestionofspeciallyprocessedcereals(SPC)optimizedtoenhancethesynthesisofendogenusantisecretoryfactor(AF).TheAFactsasamodulatorofwaterandiontransportbyregulatingthehomeostasisofchlorides.TheintakeofOmega-3seemstosatisfyallnecessaryrequirementstoobtainacorrecthomeostasisoftheinnerear.Finally,therepetitiveapplicationofexcesspressureinthemiddleear(Meniettdevice),virtualrealityandacupuncturehavebeenshowntoinduceimprovementsinpatientswithMeniere’sDisease.

REDUCTION OF VERTIGO SYMPTOMATOLOGY WITH CHRONIC USE OF WEAK ASYMMETRIC BASE-IN PRISM SPECTACLES (WABIPS) IN VESTIBULAR MIGRAINE PATIENTS

E. Vente, MD 1, D. Zambrano, MD, PhD 21 Alphen a/d Rijn, Netherlands2 Lekkerkerk, Netherlands

Reductionofvertigosymptomatologywithchronicuseofweakasymmetricbase-inprismspectacles(WABIPS)inVestibularMigrainepatients.

CERVICAL SPECIFIC PROTOCOL AND RESULTS FOR 300 MENIERE’S DISEASE PATIENTS FOLLOWED FOR A MINIMUM OF FIVE YEARS

M. T. BurconMeniere’s Research Institute

Testingefficacyofcervicalspecificcaretocontrolvertigoin300Meniere’spatients.PatternestablishedutilizingTytronthermography,ThompsoncervicalsyndromeandmodifiedPrillleglengthinequalitytests,determiningwhenandwheretoadjust.AdjustmentlistingsobtainedbyBlairx-rayanalysis.Therearefouratlaslistingsunderthissystem.Ninetypercentofpatientshadatlaslistingsofposteriorandinferiorontheoppositesideoftheinvolvedear.Whenpatientswereinpattern,Palmertogglerecoiland/orPierceResultsknife-edgeadjustmentswereperformed.Vertigointensityratedby300patientsonascaleof0to10,with10beingtheworstimaginable.Priortotreatmentmeanscorewas8.5,sixweeksposttreatmentaveragewasdownto3.0,afteroneyear2.0,twoyears1.4,threeyears0.9,fourandfiveyears0.8,animprovementofover90%.Ninetysevenpercentclaimedadramaticimprovementinvertigo.Threepercenthadsideeffectofheadache.UppercervicalsubluxationcomplexresultingfromwhiplashcancausechronicEustachiantubedysfunctionfromacombinationoftorquingCNV,whichsuppliesthetensorvelipalatinemuscle,andswellingfromfacetfrictionimposingpressureontheauditorytubeinthenasopharynx.Thisedemacanoverstimulatethesympatheticinnervationofendolymphaticsacviathesuperiorcervicalganglion,creatingendolymphatichydrops.ThemisalignmentcantractionCNVIII,disruptinghearingandbalance,kinkingthevertebralartery,whichsuppliesbloodtoinnerearviathebasilarartery.Sincethecranialvaultisaclosedhydraulicsystem,loweredbloodpressurewillincreasecraniosacralfluidpressureviathecochlearaqueduct.Meniere’sDiseasecanbecausedbyastructuralproblemresultingfromwhiplash.Thecorrelationwasnotpreviouslymadebecauseittakesanaverageoffifteenyearsfromthetimeofthetraumatotheonsetofsymptoms.

CLINICAL ISSUES 3

INTRATYMPANIC GENTAMINC/DEXAMETASONE VERSUS GENTAMICIN ALONE IN MENIERE’S DISEASE

D. Nuti, M. MandalàAzienda Ospedaliera-Universitaria Senese

Toevaluatethevertigocontrolrateandhearingoutcomeofintratympanicgentamicin/dexamethasoneversusgentamicinaloneinsubjectssufferingfromunilateraldefiniteMeniere’sDisease.103patientsmetthe1995AmericanAcademyofOtolaryngology-HeadandNeckSurgeryCommitteeonHearingandEquilibriumGuidelinesforthediagnosisofunilateraldefiniteMeniere’sDisease.All thesesubjectscometoourtertiaryreferralcenterafterunsuccessful treatment (no adequate vertigo control) with various medications (low dosage betahistine, diuretics, steroids). Allsubjectsweretreatedforatleast6monthswithhighdosagebetahistine(48mgtwice/daily).64patientsacceptedtobetreatedeitherwithgentamicin/dexamethasonemixtureorgentamicinalonewiththetitrationtechniqueduetoincompletevertigospellscontrolorthewilltostoporalmedications.Patientswererandomlyassignedinthetwogroups.Themeanfollow-upwas1.2±11years.Substantialvertigocontrol (classA-B)wasachieved in93.1%,94.7%and71.2%respectively inthegentamicin/dexamethasone,gentamicinandbetahistinegroups.Significanthearingdeterioration(>15dBHL)wasobservedin6.4%,10.2%and5.7%respectivelyinthegentamicin/dexamethasone,gentamicinandbetahistinegroups.No statistically significant differences were observed between the betahistine and gentamicin/dexamethasone groups (p>0.05).Gentamicin/dexamethasoneinnerearperfusionmaybethesafestprotocoltreatmentforvestibularablationindisablingunilateraldefiniteMeniere’sDisease.

MANAGEMENT OF MENIERE’S DISEASE: OUR EXPERIENCE

O.Zemirli,A.Mouzali,M.Z.Sadi,K.Ouennoughi,M.S.HaraoubiaDepartment of Otorhinolaryngology Head and Neck Surgery, University Hospital Beni Messous Algiers, Algeria

Meniere’s Disease is characterized by spontaneous attacks of vertigo, fluctuating sensorineural hearing loss, aural fullness, andtinnitus.Inthepresentstudyweanalyzepatient’scharacteristics,theclinicalaspects,aswellasthetreatmentstrategyofMeniere’sDisease.Wealsoreviewtheliteratureonthesubject.Weconductedaretrospectivestudythatincluded215patientsdiagnosedinourdepartmentwithMeniére’sdisease.Thediagnosiswasmadebaseduponthe1995AAO-HNScriteriabythe“CommitteeonHearingandEquilibriumGuidelinesfortheDiagnosisandEvaluationofTherapyinMenière’sDisease”,aswellasaudiologicalandvestibularfunctiontestsresults.RadiologicalevaluationincludedCTscanandMRI.Severityofvertigo,hearinglevel,andlifestylemodificationwereevaluatedaftertreatmentinthesepatients.Inour series themajorityofpatients 182 /215 (84,6%)were controlledwithmedical treatment.Thosewhowere refractory tomedicaltherapyunderwentsurgerywhichconsistedon:endolymphaticsacdecompressionin24patients,intratympanicinjectionofgentamicinin7patients,vestibularneurotomyin2patients.Forthesepatients,thevertigocontrolratewas75%,57,1%and100%,respectively.InitialmanagementofMeniere’sDiseaseconsistsonmedicaltherapyforthemajorityofpatients,aswellaslifestylemodification.Surgicalindicationsarerare,thechoiceofsurgicalproceduredependsonthedegreeofserviceablehearing,severityofvertigoandconditionofthecontralateralear.Theresultsofsurgeryaregenerallysatisfying.







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USAGE OF VASOACTIVE THERAPY IN CASES OF MODERATE TO SEVERE HEARING DISORDERS

D. Rancic, MD, PhD, Associat. Prof. Nis, Serbia

UsageofvasoactivetherapyincasesofmoderatetoseverehearingdisordersDuringthethreeyearperiod(2013-2015),51patientsofbothgender(33femaleand18male)withmoderatetoseverehearingdisorderswasfollowedup.Fortherapyitwasusedintreatment:pentoxiphilinum,betahistinum,cinerizinumandpolyvitamintherapy.Aim:ToseeefficiencyoftherapyMaterialandMethod:51patientduringthreeyearsperiodtreatedasoutdoorpatientswithpermanentcontroloneachthreeweeks.Lengthoftreatmentwasfromtwotofourmonthsforeachpatient.Puretoneaudiometrywasperformedbeforetreatmentandoneverythreeweeksduringadmissionoftherapy.AlldatawasprocessedbyKruskal-Wallistest.Results:Betterhearinginalmost90%patientswithbetterhearingforhighfrequencies.(significanceofp>0.001)

COMPARATIVE EVALUATION OF THE EFFECT OF THE MENIETT™ DEVICE IN PATIENTS WITH MENIERE’S DISEASE

D. Bernardeschi, E. Ferrary, D. Bouccara, O. SterkersAP-HP, Groupe Hospitalier Pitié-Salpêtrière, Unité Otologie, Implants auditifs et Chirurgie de la base du crâne, Paris, France et UMR-S 1159 Inserm / Université Paris 6 Pierre et Marie Curie, France

ToevaluatetheefficacyoflowpressuretreatmentwiththeMeniettdevice, incaseofMenière’sdiseasenotcontrolledbymedicaltreatmentandvestibularrehabilitation.Arandomized,placebo-controlled,double-blind,multicenterclinicaltrialof6weeksduration.Seventeenstudysitesallfrenchspeakingacademicmedicalcenters.Follow-upwasperformedbyusingdiariesandquestionnairesateachstageoftheclinicalstudy.Inclusioncriteria:AdultspresentingwithMenière’sdiseasecharacterizedaccordingtotheAAO-HNSclassificationcriteria.Inclusioncriteriawasatleast2vertigoepisodeslastingmorethan20minutesandseveredby12hoursFirststepwasa8weekspre-selectionphasethatstartswithplacingatympanostomytube.Evaluationduring3stages: i)Run in:duringthe8weekspre-selectionphaseevaluationoftympanostomytubeeffect: incaseofresolutionofsymptomsnoninclusiontothesecondstagewithdevice,ii)incaseofactivediseaseinclusionfora6-weekperiod,withactivedeviceorplacebodeviceandiii)a6-weekperiodofrunoutafterthetreatmentstop.Criteriawastheevolutionofvertigoepisodesnumberlastingatleast20minutesandwithafreeintervalof12hours(20mn-12h)andtheirimpactondailylifemeasuredbyselfquestionnaire.129patientswereenrolledinthisstudy.29werenotincludedbecauseoftheabsenceofvertigoafterthetympanostomytubeinsertion.So97patientsweredefinitivelyincludedinthisstudy,49usingtheMeniettdevice,and48theplaceboone.Thenumberofvertigoin3weeksdecreasedfrom4.3±0.64duringtheruninperiod,to2.6±0.50after6weeksoftreatment,andto1.8±0.82after6weeksoftheremovalofthedevice,intheplacebogroup.SameresultswereobservedintheMeniettgroup:3.2±0.46duringtheruninperiod,2.5±after6weeksofMenietttreatment,and1.5±0.29afterremovalofthedevice.thisstudyfailstodemonstrateefficacyofMeniettdevicecomparedtoplaceboone.Thedecreaseofthenumberofvertigoshouldbeexplainedbyaneffectofthetympanostomytube.

INTRATYMPANIC GENTAMICIN FOR MENIERE’S DISEASE: SHORT- AND LONG-TERM FOLLOW-UP OF TWO REGIMENS OF TREATMENT

A.P. Casani, N. Cerchiai, E. NavariPisa University Medical School, Dipartimento di Patologia Chirurgica, Medica, Molecolare e Area Critica, Cisanello Hospital, Pisa, Italy

Theadventofintratympanicgentamicin(ITG)hasreducedthenumberofmoreinvasiveproceduressuchasvestibularneurectomy.AlthoughdifferenttreatmentprotocolsofITGinjectionsarecurrentlyemployed,overtheyearstherehasbeenatrendtowardtheuseofloweramountsofgentamicin,inordertominimizethesideeffects,mainlyrepresentedbyhearinglossandpost-treatmentimbalance.Theobjectivesofthisstudywerethefollowing:(1)tocomparetheresultsoftworegimensoftreatmentwithITGat2-yearfollow-up;(2)toevaluatetheneedandtheefficacyofaretreatmentaftertherecurrenceofvertigoattacksinalongerperiodoffollow-up(usingtheKaplan-Meiermethodofanalysis).ThestudywasdesignedasaretrospectivechartreviewandcarriedoninaTertiaryreferralcenter.Thestudyinvestigated77patientstreatedwithintratympanicgentamicin(ITG).Thirty-fivepatientsweretreatedwithhigh-dose(HD)ITG(intotal6injections,twiceaday,repeatedeverythreedays)and42withlow-dose(LD)ITG(1-2injections).Theresultsoftreatmentwereevaluatedintermsoffunctionallevelscale,controlofvertigo,andhearingimpairment.At 2-year follow-up, a similar percentage of vertigo control was obtained in the 2 groups; the incidence of hearing loss andposttreatmentdisequilibriumwassignificantlyhigherinpatientstreatedwithHD-ITG.Thelong-termfollow-upshowedacontrolofvertigoattackswithasingleroundoftreatmentin71.4%ofpatientstreatedwithHD-ITGandin55%ofthosetreatedwithLD-ITG.Withrepeatedrounds,aneffectivecontrolofvertigocouldbeachievedin88.5%usingaHD-ITGprotocoland97.7%usingaLD-ITGprotocol.LD-ITGallowsobtaininggoodresultsintermofvertigoattacksassociatedwithalimitedoccurrenceofsideeffects.Thelong-termfollow-up showed that LD-ITGneeded repeated roundsmore frequently than theHD-protocol.HD-ITG ran less riskofneedingrepeatedrounds,butretreatmentwasineffectivein40%ofthecasesrequiringsurgicaltherapy.

LONG-TERM RESULTS OF INTRATYMPANIC GENTAMICIN IN THE TREATMENT OF MENIERE DISEASE

J.J.Wazen,MDSilverstein Institute, Ear Research Foundation

Thepurposeofthisstudyistodeterminethelong-termsuccessrateofintratympanicgentamicinincontrollingthevertigoattacksinpatientswithdisablingvertigofromMeniereDisease.PatientstreatedwithintratympanicgentamicinbetweenMay2011andMay2013werefollowed,allowingaminimumof2yearsposttreatmentfollowup,complyingwiththeAmericanAcademyofOtolaryngologyHeadandNeckSurgeryreportingguidelines.Patientsweredividedinto2groups:thosewhoreceived40mg/mlgentamicinbyintratympanicinjections,andthosewhoweretreatedwiththeMicrowicktechniqueusing10mg/mlgentamicindaily.Thelengthofthetreatmentinbothgroupswasdeterminedbyrepeatedaudiogramsandvideonystagmographyincludingicecaloricsonthetreatedside.Theincidenceofrecurrenceofvertigoaftersuccessfulcontrolisreportedwithadescriptionofsubsequentnecessarytreatments:moregentamicin,destructivelabyrinthectomy,orvestibularneurectomy.Thedifferencesinresponsetotreatmentandhearingpreservationbetweenthetwogroupswillbepresentedaswellasthedifferencesintheneedforfurthertreatmentsaftervertigorecurrence.IntratympanicGentamicinisahighlyeffectiveminimallyinvasiveinofficemethodofcontrollingvertigoinMeniereDiseasethathasalmosteliminatedtheneedforthetraditionalhospitalbasedproceduresinourpractice.







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SAC SURGERY FOR TREATMENT OF MENIERE DISEASE

R. BentoUniversity of Sao Paulo – Brazil

IncasesofpersistentsymptomsofvertigoinpatientswithMeniere’sDisease,systematicallyusedinendolymphaticsacsurgerybythetechniquedescribedbyPaparella.Inthispresentationwewillshowthetechniqueanditsresults.147patientspreviouslytreatedwithvariousdrugsandsomewithintratympanicinjectionofgentamicinandinwhichthesymptomofvertigoremainedunderwentmastoidectomywithopeningoftheendolymphaticsacandplacinga“Silastic”draintothemastoidcavity.Consistentimprovementoreliminationofvertigowasobservedin94%ofcases.In32%ofpatientstinnitusimprovementand89%improvementofearfullness.

OSTEOPLASTIC REFINEMENT IN ENDOLYMPHATIC SAC SURGERY

R. A. Bly, MD, L. G. Duckert MD, PhDDepartment of Otolaryngology Head and Neck Surgery, University of Washington, School of Medicine, Seattle, Washington, USA

Thesurgicalapproachtotheendolymphaticsacrequiresacorticalmastoidectomy.Inanormallydevelopedmastoidaircellsystemremoval of the mastoid cortex enbloc may be standard practice. This approach can be modified to maintain the preoperativepostauricularcontourbypreservingthemusculo-periostealattachmenttothecortex.Thecortexandmusculoperiostiumcanbeelevatedasanosteoplasticunitand“hinged”anteriorlyalongthe lateralmarginoftheexternalcanal.Uponcompletionofthemastoiddissectionthecortexisrestoredtoitsanatomicalpositionandthemastoidotomyclosed.Theapplicationoftheosteoplasticapproachisnotlimitedtosacsurgery.Itisespeciallywellsuitedasanadjuncttothetranslabyrinthineremovalofacousticneuromaswheretheboneflapmaintainscompressiononthefatgraftandbuttressestherepair.Thisdemonstrationisconsistentwiththeosteoplasticprincipleappliedelsewhereintheheadandneck.

SAC SURGERY

ENDOLYMPHATIC DUCT BLOCKAGE: A NEW ERA IN THE TREATMENT OF MENIERE DISEASE

I. Saliba, N. Gabra, MH. Asmar, D. BerbicheUniversity of Montreal - Division of Otolaryngology Head & Neck Surgery

Endolymphaticsacsurgeryhasbeenafavorableoptionforpatientsasitisahearingpreservationsurgeryandhasalowsurgicalmorbidity.Theeffectivenessofthissurgeryhasbeendebated.InourInstitution,wehave,overthepastfewyears,establishedanovelsurgicaltechniqueforthetreatmentofMeniere’sDisease:TheEndolymphaticDuctBlockage(EDB).ouraimistocomparetheeffectivenessoftheEDBandtheEndolymphaticsacdecompression(ESD)tocontrolMeniere’sDiseasesymptomsandtoevaluatetheireffectonhearinglevel.weperformedaprospectivenon-blindedrandomizedstudy inourtertiarymedicalcenter. 57patientsaffectedbya refractoryMeniere’sDiseasewere includedoutofwhich22underwentanESDand35underwentanEDB.Fiveperiodsoffollow-upwereconsidered:0to1week,1weekto6months,6to12months12to18monthsand18to24months.Meanoutcomemeasurementsconsisted of vertigo control, tinnitus, aural fullness, instability and hearing level. Hearing level was evaluated using pure-toneaverage(PTA)andspeechdiscriminationscore(SDS)Therewasnosignificantdifferencebetweenthetwogroupsinthenumberofvertigospellspermonthspreoperatively(p=0.153).Twentyfourmonthspostoperatively,96.5%oftheEDBgrouphadachievedacompletecontrolofvertigospellsagainst37.5%oftheESDgroupwithastatisticallysignificantdifference(p=0.002).Therewasabettercontrolof tinnitusandaural fullnesswithEDB(p=0.021andp=0.014respectively).Therewasnostatisticallysignificantdifferenceinhearinglevelpreoperatively(p=0.976)and24monthspostoperatively(p=0.287)betweenthetwogroups.Hearinglevelwaspreservedineachgroupwithnosignificantdifferencebetweenthepreoperativeandthepostoperativelevels(p>0.05).EDBismoreeffectivethanthetraditionalESDincontrollingthesymptomsofMeniere’sDisease.ItisanovelsurgicaltechniquewithpromisingresultsforacompletetreatmentofMeniere’sDisease.Thereisnosignificantcomplicationsoradverseeffect.Aftertheseresults,westoppeddoinganESD.Weoperateduntilfebruary2015,113patientswiththeEDBtechnique.Thesuccessratecontinuetomaintainthesamepercentagepresentedintheaforementioneddata.Inourpresentation,wewillshowtheparticipantsavideoofthetechniqueetwewilldiscusstheresults,thedifficulties,andthecomplicationsaswell.

ENDOLYMPHATIC SAC REVISION SURGERY

M.M.PaparellaMinneapolis, USA

Conservatism in Menieres’s Disease precedes more radical or destructive therapy such as physical or chemical labyrinthectomyorvestibularneurectomy.ESR(8-10%ofcases)asperformedinhundredsofcaseshasnotonlybeensuccessful inamelioratingdisablingsymptomsofMenieres’diseaseusuallyforthepatient’slifetimebutitprovidesapowerfullessoninunderstandingthepathogenesisofMeniere’sDisease.Findingsinclude,fibrousandosseousinvasionintothemastoid,Trautmann’striangleandextrinsicduracontainingtheendolymphaticsacrenderingtheduraveryridged.Alloplasticsiliconet-strutsandspacersareremovedandarebrightyellowunlikethousandsofpatientswithtympanoplastywiththemiddleearsilasticimplantspacersuggestingpowerfulosmoticandhydrostaticinfluences.Afterrevisionthesepatientshavebetterresultsthanthosewhohaveaprimarysurgicalprocedure.Herepathogenesisisvisibleinalivingpatient.DuetothenaturalhistoryofthediseasethepatientdevelopsincapacitatingMenieres’sdisease.Afterendolymphaticsacenhancementthepatienthasagoodresultandoftenformanyyears.Thepathogenesisisvisibleandconsistsofendolymphaticmalabsorptionandobstructionoftheendolymphaticsacanddura.







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DID PROSPER MENIÈRE DISCOVER MENIERE’S DISEASE?

O. MichelUniversity Hospital Brussels UZB, Vrije Universiteit Brussel VUB, Brussel, Belgium

ProsperMenièrehadalastingimpactonotologyinthewholeworld,sincehebuiltupafirstinternationalbindingtoforeigncountriesbytranslatingtheGermantextbookofWilhelmKramerintotheFrenchlanguagefromtheEnglishedition.AdamPolitzerwasthefirstforeignotologisttorecognizetheguidingsignificanceofMenière’sobservationandwasoneoffirstnexttoVoltolinitousetheterm“Menière’sdisease”.UptonowthereisstilldoubtaboutwhatMenièrehimselforiginallydescribedandthepathologicalconditionwhichcarrieshisname.Sincethan,otologistsinGermanyandallovertheworldputtheireffortsinexplainingthepathophysiologyofthisdiseaseandinfindinganadequatetreatment.Duringdecades,theacademicdiscussionkeptonandwasnotwithoutcontroversies.SomeevendoubtedthesignificanceofMenière’sdiseaseasownentity.Thehistoryaboutthescientificlandmarkswasnotwithouttragedy.Thefirsttodepicttheendolymphatichydrops-Prof.Yamakawa-becamemostlyunknowntothescientificworld,becausehedidnotpublishinEnglish,latersufferedhimselffromMenièrediseaseandhistemporalboneboreevidenceofhydropsasdissectedpost-mortem.Even the correct spelling of Menière’s name became subject of discussion during years. A search in the French National ArchiveunambiguouslydepictedthatProsperMenièrehimselfsignedwithonlyoneaccentgraveonthesecond„e“,whichwasundoubtedlytestifiedbyseveralhandwrittenlettersofProsperMenière.

RE-EVALUATION OF QOL IN RELATION WITH SYMPTOMS OF MENIERE’S DISEASE

M. Manfrin, S. Quaglieri, E. Rebecchi, G. Locatelli, M. BenazzoIRCCS Policlinico San Matteo, Pavia, Dipartimento Area Chirurgica Specialistica, S.C. Otorinolaringoiatria, Direttore Prof. M. Benazzo

Meniere’sDisease(MD)isachronicinnereardiseasewithattacksofdisablingvertigo,progressivehearingloss,tinnitusandfullness.Thesesymptoms,separatelyorincombination,causegreatdistressandhaveaconsiderableimpactonthepatients’qualityoflife.Thepurposeof this study is todeterminethecorrelationbetweenfunctionalandaudiologicalaspectsofMDandpsychologicalimplication.MDpatientsweresubmittedtotheDizzinessHandicapInventory(DHI)andtheZungSelf-RatingAnxietyandDepressionScale.Thetestscoreswerecorrelatedtoage,sex,diseaseduration,unilateral/bilaterallabyrinthinvolvement,duration/frequencyofvertigoattacks,vestibularandauditoryfunction,auralfullness,tinnitus,imbalanceandfunctionaldisabilities.

CLINICAL ISSUES 4

AUDIOLOGICAL CHARACTERISTICS, IMMUNOLOGICAL MARKERS AND CYTOKINES EXPRESSIONS IN COCHLEAR IMPLANT PATIENTS AFFECTED BY AUTOIMMUNE DISORDERS

P. Mancini 1, A. Di Mario 1, D. Ballantyne 1, E. De Seta 1, C. Alessandri 2, H. Dincer 11 Department of Sense Organs, University Sapienza of Rome, Italy2 Department of Internal Medicine and Medical Specialities, University Sapienza of Rome, Italy

Aim:toinvestigatelong-termaudiologicalandelectro-physiologicaloutcomes,andserologicalcharacteristicsofadultcochlearimplantees(CI)affectedbyautoimmune/dysimmunediseases,incomparisontomatchedgroupofnon-autoimmuneCIsubjects.30Cochlear Implantees,withbilateral severe/profoundSNHL,averageage58 (±8.7)yearswereassessed.15subjectswereaffectedbyautoimmune/dysimmune diseases (IC-AD): Relapsing Polychondritis (RP) (2), Cogan disease (3), autoimmune thyroiditis (2), aspecificsystemicvasculitis(4),arthritis(3)andpsoriasis(1).ControlGroup:15subjects,affectedbyotosclerosis(12)andchronicotitis(3)(IC-C).Immunologicalevaluationwascarriedouttoidentify:cytokinesinflammatoryserummarkers(ICy)(IL-1β,IL-1RA,IL-10,PDGF,IL-2,IL-4,IL-8,IL-12,IL-17,INF-γ,MIP-1β,VEGF)(semiquantitativeRT-PCR,Bio-Rad,Berkeley,California);serumautoantibodies(ANA,ANCA,LAC,ENA,Anticardiolipina)(Elisatest);antiHSP-70autoantibodies(Otoblotassay,Immco).AudiologicalevaluationwascarriedoutunderFreeFieldconditionsbothinQuietandinNoise(primarysignalpresentedat65dB,0azimut;NoisecompetitionpresentedatSpeechNoiseRatios,SNR,+10and+5dB,0azimut).ElectricImpedancevalues(kOhm)andM-Levels(CU)wereobtainedinallpatientsandanalyzedbymeansofnon-parametricstatistics.AlowpositivityforserumautoantibodiesandHSP-70wasfoundinallCIsubjects,notsignificantlydifferentbetweenIC-ADandIC-C.Pro-inflammatorycytokinesIL-1β,INF-γandVEGFweresignificantlyhigherinIC-ADsubjects.Bothgroupsperformedverywellforspeechperceptioninquietforbothword(mean=88%versus90%forIC-ADandIC-Crespectively)andsentencerecognitiontests(mean=88%versus85%forIC-ADandIC-Crespectively).BothgroupsperformancedeterioratedwhenlisteninginthepresenceofnoiseespeciallywiththemoreadverseSNR.Statisticalanalysisdidnotshowanysignificantdifferencesbetweenthetwogroups(p>0.05).ImpedancesshowedhigherandmoreunstablevaluesinIC-ADpatients.AD-CI patients showed good long-term audiological results, comparable with CI-C subjects. Serological autoimmune Ab and HSP-70confirmedlowsensitivityandspecificity(Matsuoka,2013)whilehigherI-Cymightunderliesachronicinflammatoryprocess(Pathak,2011)whichcouldbestillactiveinsomeoftheCI-ADpatients.Chronicinflammationmightberesponsibleforintra-cochlearfibrosis,higherandmoreunstableelectricalimpedancesandmorefrequentprograms’adjustments.

ENDOLYMPHATIC SAC REVISION SURGERY

M.M.PaparellaMinneapolis, USA

Acute vertigowith spontaneousnystagmus(acute vestibular syndrome,AVS) is generallyofperipheral origin.But recently, itwasproventhatwhenapatientwithAVShasanegativecatchupsaccadeontheheadimpulsetest(HIT),acentrallesionisstronglyindicated.However,someAVSpatientsfinallydiagnosedasperipheralvertigocanshowanegativeHIT.Thepurposeofourstudywastoanalyzetheclinicalmanifestationsofthisgroupofpatients.FromMarch2013toJuly2014,155patientswithAVSunderwentthevideoheadimpulsetest(vHIT)inKangbukSamsungHospital.Ofthese155,31(20%)hadanegativelateralcanalvHIT,andaretrospectiveanalysiswasdoneontherecordsofthe31patients.Dataonthediagnosis,resultsofvideonystagmography(VNG),gainoflateralcanalvHIT,calorictestandcervicalvestibularevokedmyogenicpotential(cVEMP)wereanalyzed.Ofthe31patients,themostcommondiagnosiswasMeniere’sDisease,with17(54.5%)cases.Thenextmostcommondiagnosiswassuddensensorineuralhearinglosswith6(19.3%)patients,andacentrallesionwasthethirdmostprevalentdiagnosis,with3(9.7%)cases.Ofthe17patientswithMeniere’sDisease,9(52.9%)hadaspontaneousnystagmusbeatingtowardtheipsilesionalside,andtheremaining8(47.1%)patientshadacontralesionalbeatingnystagmus.5(29.4%)ofthe17patientswithMeniere’sDiseasehadcaloricparesis.TheaverageJonkee’sindexofthe5patientswas37.4,andtheiraveragegainonlateralcanalvHITwas1.05.Ofthe6patientsdiagnosedwithsuddensensorineuralhearingloss,nonehadcanalparesis,but5(83.3%)patientshadasymmetryoncVEMP.All3patientsdiagnosedwithcentralvertigohadvascularlesionsassociatedwiththecerebellum.AnalysisofthespontaneousnystagmusonVNGofthe31patientsrevealedthat29(93.5%)patientshadamaximalslowphasevelocityof5degreesorlower.Clinically,anegativeHIThasimportancetodiagnosestrokeinpatientsofAVS.But,asignificantnumberofcaseswithnegativeHITwerefinallydiagnosedasperipheralorigin.Therefore,anegativeHITmaynotalwaysindicateacentrallesion,especiallyinacuteisolatedvertigopatients.







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POSSIBLE ROLE OF HERPESVIRIDAE FAMILY VIRUSES IN THE PATHOGENESIS AND EVOLUTION OF SENSORINEURAL HEARING LOSS

W. Di Nardo, R. Anzivino, E. De Corso, P. Cattani, R. Santangelo, G. PaludettiInsitutes of Otolaringology and Microbiology, Catholic University of Rome, Rome, Italy

Theviraletiologyhasbeenthebeststudiedhypothesisforidiopathicsensorineuralhearinglossandhasbeensofarsupportedindirectlybymedical,clinicalandserologicalhistory.Thediscoveryof theviruswithinthe innerearcanadd informationaboutthepossibleetiologyandallowtoinvestigatethepathophysiologicalbasisofhearingloss.ThepurposeofthisstudywastoidentifythegenomeofHerpesviridaefamilyvirusesintheendolymphaticfluidofhearingimpairedpatientsundergoingcochlearimplantsurgery.31patients,agedbetween1and69years,sufferingfromsensorineuralhearingloss,weresubjected,duringthecochlearimplantplacement,toawithdrawalofinnerearfluid.Ineachsamplewelookedforseveralviruses(HSV-1,HSV-2,CMV,VZV,EBV,Enteroviruses,Adenoviruses)throughtheuseoftwomolecularmethodsandspecificprimersets.Radiologicalexams,serology(specificIgGandIgMantibodies)andPCRofperipheralbloodwerealsoperformedonthepatients.Whilethesearchoftheviralgenomeinperipheralbloodwasnegativeinallpatients,in3patientsitwasfoundinthecochlea:2patientswerepositiveforCMVand1forHSV-1DNA.ThedetectionoftheviralgenomeofCMVandHSV-1intheendolabyrinthinefluid,collectedfrompatientswithhearingloss,intheabsenceofacuteviralinfectionorcongenitalone,seemstoshowtheabilityofthesevirusestoremaininlatentphaseinthespiralganglionandcauseapersistentinfection.ThisstudysupportsthehypothesisthatHerpesvirus(HSV-1andCMV)mayhaveareactivationofapastandlatentinfection,suggestingapossibleetiologicalroleofvirus(whenacquiredinpost-natalage)inthegenesisofidiopathichearingloss.

SUPER PARAMAGNETIC NANOPARTICLES DRIVEN BY EXTERNAL MAGNETIC FIELD FOR TARGETED DRUG ADMINISTRATION TO INNER EAR: FEASIBILITY AND TOXICITY

G. Leterme 1,2, C. Guigou 1,2, A. Oudot 3, B. Collin 3, J. Boudon 4, A. Geissler 5, K. Belharet 6, A. Ferreira 6, A. Bozorg Grayeli 1,21 Otolaryngology department, Dijon University Hospital, Dijon, France2 Le2i, CNRS UMR-6306, Burgundy University, France3 Preclinical imaging center, Centre François Georges Leclerc, Dijon, France4 Laboratoire Interdisciplinaire Carnot de Bourgogne, CNRS UMR-6303, Dijon, France5 Celllmap, Burgundy University, France6 PRISM research laboratory, INSA, Orleans University, Bourges, France

Superparamagneticnanoparticle(SPMN)canvehicleinanactiveandtargetedmannerseveraltypesoftherapeuticmoleculesincludingsteroids and peptides. Theoretically, they can access the cochlear apex from the round window without generating hydrostaticpressureandavoidbloodperilymphbarrier.Theaimofthisstudywastodevelopaninsitudrugadministrationmethodwiththeseparticlestostudytheirmobilityandtoxicity.FiveadultWistarratswereincluded.Thelefttympanicbullawasopenedundergeneralanesthesia.Theroundwindowmembranewasperforatedwithamicro-needleand5µlofSPMN(ironoxide)at5mg/mlsuspendedinhyaluronicacidgel(Healon®)wasappliedonthemembrane.Amusclefragmentwasplacedonthemembranetosealtheperforation.Thewoundwasclosed.Therightearservedascontrol.SPMNweremobilizedbyarare-earthmagnet(542mT)in4differentpositionsaroundtheheadfor10mineachinordertoattractSPMNtowardtheapex.Hearingwasmonitoredat2,8,16and32kHzwithABRandtoneburstsbeforeandimmediatelyaftersurgery,7daysandonemonthsafteradministration.Histologicalstudyofthecochleaewasconducted1monthaftersurgery.Theprocedure took56minutes in average.Hearingwas completely preserved in all cases. Thresholds at 2 and8 kHz remainedunchanged.Immediatelyaftersurgery,thresholdsincreasedat16kHz(46±18,2dBSPLversus32±4.5dBforcontrol)and32kHz(58±17.9dBSPLversus46±5.5dBforcontrol,p<0.01,Friedmantest),butreturnedtonormalat7days.MicroscopicexaminationshowedSPMNinthebasalturnin3casesandinthesecondturnin2animals.SPMNcouldalsobeobservedinstriavascularisinonecase.WeshowedthatSPMNcanbedriveninsidecochleawithoutaffectingthehearinguptoonemonthafteradministration.Penetrationinthestriavascularissuggestsapossiblerouteofeliminationoftheseparticles.

A STUDY FOR LOCAL TREATMENT OF THREE DIFFERENT POLYMERS AIMED FOR MIDDLE EAR ADMINISTRATION

C. Engmér Berglin1,2, P. Videhult-Pierre1,3, A. Ekborn1,2, T. Bramer 4, K. Edsman 4, M. Hultcrantz 1,2, G. Laurell 31 Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden2 Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden3 Department of Surgical Sciences 4 Department of Pharmacy, Uppsala University, Uppsala, Sweden

Recentadvancesininnerearresearchsupporttheideaofusingthemiddleearcavityfordrugadministrationtotargettheinnerear.Rheologicalandsafetyassessmentsofthreecandidatepolymerformulationsforintra-tympanicdrugadministrationistested.Theformulationswerebasedonsodiumcarboxymethylcellulose(NaCMC),sodiumhyaluronate(NaHYA),andpoloxamer407(POL).Rheologicalstudieswereperformedwithacontrolledrateinstrumentofthecouettetype.Safetystudieswereperformedinguineapigssubjectedtoanintra-tympanicinjectionoftheformulations.HearingfunctionwasexploredwithABRbeforeand1,2,and3weeksaftertheinjection.Eliminationoftheformulationsmarkedwithcoalwasexploredwithanendoscopicdigitalcamera1,2,and3weeksafterinjection.Middleandinnerearmorphologywasexaminedwithlightmicroscopy6daysafterinjection.NaHYAdidnotcauseprolongedhearingthresholdelevations.TheresultsoftheeliminationandmorphologicalinvestigationssupporttheconclusionofNaHYAbeingmostpromising.A formulation based on sodium hyaluronate (NaHYA) was the best candidate vehicle for intra-tympanic drug administrationregardingconductivehearingloss,inflammatoryreactions,andelimination.

COMPARISON OF THE RESULT OF CALORIC TEST VS VIDEO HEAD IMPULSE TEST IN COCHLEAR IMPLANT USERS

S.A.IncesuluEskisehir Osmangazi University, Faculty of Medicine, Department of Otolaryngology-Head&Neck Surgery, Meselik-Eskisehir/Turkey

Cochlearimplantation(CI)iswidelyacceptedprocedureforthepatientswithbilateralseveretoprofoundhearingloss.Ingeneral,itisasafemethodwithlowcomplicationrate.Oneofthecomplicationisvestibulardisturbanceandithasbeenreportedbetween31-75%intheliterature.Incidenceofbalanceproblemisalsohigherinhearingimpairedpatient.VestibulardisturbanceafterCImayduetochangesinfluidhomestasisoftheinnerear,inflammationduetosurgicaltraumaorlossofhaircellsEvaluation of vestibular system may require several different kinds of tests besides detailed history and physical examinationincludingoculomotorandvestibulooculerreflexevaluation,positioningtests,evaluationofcerebellarfunction.Laboratorytestsconsists of videonistagmography including caloric test, evoked vestibular myogenic potentials, rotational chair, computerizeddynamicposturographyandrecentlyvideoheadimpulsetest(vHIT)CalorictestandvHITevaluatethevestibuloocularreflex.Calorictestisatestofthelateralsemicircular,itdoesnotevaluateverticalcanalsorotolithfunction.Itgivesinformationaboutthesymmetricorasymmetricfunctionofthecanal.Lowfrequencystimulationisusedincalorictest.vHITisatestofthreesemisircularcanalsandhighfrequencystimulationisused.In this study, twenty patients who underwent unilateral cochlear implant in Otolaryngology Head&Neck Surgery Department,EskisehirOsmangaziUniversity FacultyofMedicinewereevaluated. Lateral semicircular canal functionswereassessedbyusingcaloricandvideoheadimpulsetests.Moreover,verticalcanalfunctionwhichwasobtainedfromthevHITwasalsonoted.Threepatientswerereimplantedbecauseofthedevicefailure.Resultswerecomparedwithetiology,durationofcochlearimplantuseandsubjectivevertiginoussymptomswhichwasevaluatedbydizzinesshandicapinventory.







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VESTIBULAR FUNCTION BEFORE AND AFTER COCHLEAR IMPLANTATION IN PATIENTS WITH POSTLINGUAL DEAFNESS: A PROSPECTIVE OBSERVATIONAL STUDY

P. A. Abramides, MD, PhD, R. S. M. Bittar, MD, PhD, R. K. Tsuji, MD, PhD, R. F. Bento, MD, PhDMedical School University of Sao Paulo, Brazil

Assessvestibularfunctionbeforeandaftercochlearimplantation(CI)inadultpatientswithpostlingualdeafness.Vestibular assessments: questionnaire assessing vertigo, caloric tests (CTs), rotary chair testing, and computerized dynamicposturography(CDP),weresequentiallyperformedfor24patientsbeforeand60,120,180,and365daysafterCI.Dizzinessremainedunchangedin7.7%,improvedin84.6%,andworsenedin7.7%ofthecases.BaselineCTsidentified29.2%patientswithnormal reflexes, 33.3%withunilateral areflexiaorhyporeflexia, 12.5%withbilateral hyporeflexia, and25%withbilateralvestibularloss(BVL).Mostpatientsexhibitedobjectiveimprovementsinposturalstability,asevidencedbytheCDP.Balanceimprovedat365daysafterCIinallpatients.PatientswithBVLusedvisualinformationforposturalstabilization.Preoperativevestibularassessmentfindingsshouldbedocumentedbecauseposturalrecoveryovertimedependsonthisinformation.

VESTIBULAR FUNCTION AFTER COCHLEAR IMPLANTATION IN PARTIAL DEAFNESS TREATMENT

M. Sosna 1, K. Pietrasik 1, G. Tacikowska 1, J. Listwon 1, H. Skarzynski 1, P. H. Skarzynski 1,2,31 World Hearing Center, Institute of Physiology and Pathology of Hearing, Kajetany/ Warsaw, Poland2 Medical University of Warsaw, Warsaw, Poland3 Institute of Sensory Organs, Kajetany, Poland

Cochlearimplantationisworldwidefullyacceptedmethoddedicatedtopatientswithtotalorpartialbilateraldeafness.Nevertheless,vestibularandbalancedisordersarestilloneofthecommoncomplaintsamongthepatientsaftertheoperationandwhileusingtheimplant.Accordingtotheliteraturedata,thepercentageofvestibularsymptomsrangesfrom5,9%to80%andthatofvestibularexamination abnormalities from 20-60%. Hearing preserving methods, that are proven to be successful in protecting cochlearfunction, are supposed to diminish vestibular disorders after operation. The aim of the study is to assess vestibular status andvestibularsymptomsaftercochlearimplantationinpatientswithpartialdeafness,usinghearingpreservingmethods,emphasizingonthesacculusandutriclefunction.Allthepatients(43patients;24male,19female,middleage41y.o.)includedinthestudyweredividedintothreegroupsaccordingtothetypeofimplantationthatwasapplied.Thesegroupswereasfollowed:PDT-EC(PartialDeafnessTreatment-electricalcomplement),PDT-EAS(PartialDeafnessTreatment–electro-acousticstimulation),PDT-ES(PartialDeafnessTreatment–electricstimulation).Ineachcase,theimplantwasinsertedbyroundwindowapproach(RWA).ThepatientsunderwentcVEMPandoVEMPexaminationbefore,1-3monthsand6-9monthsaftertheoperation.Theassessmentwascompletedbyfulfillingthequestionnairedescribingvestibularsymptoms.InVEMPresponsesthelatencies,correctedamplitudeandratioofpost-topreoperativeamplitudeweremeasured.AfterintroducingRWA(roundwindowapproach)andsoftelectrodeinsertiontherateofvestibularcomplicationshassignificantlydecreased.Vestibularsymptomswererare,mostlytransientandinearlypostoperativeperiod.Onlyonepatientinourstudygroup,withcoexistingEVAS,lostVEMPresponsepostoperatively.However,ineverysinglecasethecorrectedamplitudemeasuredpostoperativelywasdecreased.TherewasnocorrelationbetweenchangesinVEMPresponseandthefrequencyofvestibularsymptoms.Hearingpreservingmethods(roundwindowapproach,softelectrodeinsertion)areprotectingforvestibularorgan.

VESTIBULAR FUNCTION AFTER CI SURGERY

PERSONALIZED MEDICINE FOR COCHLEAR IMPLANTS

Zenner HP, Friese NDept. of Otolaryngology, The University of Tübingen

PersonalizedmedicineusingmoleculargeneticsoffunctionalproteinslikeOtoferlin,Connexin26,KCNQ4,orofUshergensplayagrowingrolefortheindicationofcochlearimplants.Itservesforthestratificationofpatients.Thisisthoughttowidenspecificindicationspredominantlyforpediatriccochlear.

STRATEGY FOR END-STAGE MENIERE’S DISEASE: LABYRINTHECTOMY WITH CI

B. J. Gantz, M. R. Hansen, C. Dunn, R. TylerDept of Otolaryngology-Head and Neck Surgery, University of Iowa, USA

Objective: Compare the pre and postoperative performance in patients undergoing cochlear implantation (CI) for recalcitrantMeniere’sDisease.Studydesign:ProspectiveSetting:Tertiarycenter,UniversityofIowaCochlearImplantCenterPatients:Forty-sixpatientshaveundergoneCIforsinglesideddeafness(SSD)atourinstitution.SSDwasduetoend-stageMeniere’sDisease(MD)in18subjects.InthesepatientstheCIwasplacedsimultaneouswithalabyrinthectomy.Intervention(s):CIwithlabyrinthectomy.Mainoutcomemeasure(s):Speechperceptionandlocalizationdatawascollectedpre-andpost-operativelyat3,6,12,andannually.CNCwordandAzBiosentencesinquiettestswereadministeredpost-operativelyviaDirectConnecttothesoundprocessor.Multiple-loudspeakersoundlocalizationandadaptiveHINTspeechperceptioninnoisetestswerecollectedinthebilateralandbetterear-onlylisteningconditions.Additionally,theTinnitusPrimaryFunctionQuestionnairewasadministeredpre-andat12monthspost-operatively.CNCwordandAZBiosentencescoressignificantlyimprovedintheimplantedear.Soundlocalizationwasbetterformostsubjectsinthebilateralconditionverseswhentestedinthebetterear-onlycondition.Binauralbenefitsinnoiseweredemonstratedthroughsignificant head shadow and binaural summation effects. Most patients reported diminished tinnitus in the subcategories ofEmotions,Hearing,SleepandConcentration.AllpatientsundergoinglabyrinthectomyexperiencedresolutionofvertigoattacksandweresatisfiedwiththeCI.ACI restoresbinauralauditoryfunction individualswithaunilaterallydeafenedear.Additionally, thebinaural inputappearstoimprovesoundlocalizationandspeechperceptioninnoiseformostpatientswithnormalhearinginthecontralateralear.Mostpatients experience a reduction in their tinnitus handicap after receiving a CI. These functions cannot be restored using boneconductionhearingdevicesorcrosshearingaids.InpatientswithseverehearinglossandrecalcitrantvertigoattacksduetoMD,simultaneouslabyrinthectomyandCIeffectivelyrelievesvertigoattacksandimprovesauditoryfunction.







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TRANSLABYRINTHINE VESTIBULAR NERVE SECTION AND SIMULTANEOUS COCHLEAR IMPLANTATION IN PATIENTS WITH RECALCITRANT MENIÈRE’S DISEASE: PRELIMINARY REPORT

P. Canzi 1, M. Manfrin 1, M. Perotti 2, F. Aprile 1, S. Quaglieri 1, G. Locatelli 1, D. Fresa 1, M. Benazzo 11 Department of Otorhinolaryngology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy2 Otorhinolaryngology Unit, Ospedale Civile “SS Antonio Biagio and C. Arrigo”, Alessandria, Italy

SurgicalmanagementofMenière’sdisease(MD)isrecommendedincaseofmedicalandintratympanictreatmentfailures.Surgicaloptionsaimtocontrolvestibularsymptomsandimprovecochlearimpairment.GeorgePortmannintroducedtheconceptofconservativesurgerywiththeendolymphaticsacapproach.However,itseffectsarequitecontroversialandmanyAuthorshavequestionedwhichtechniqueleadstothebestresults.OnlywellselectedcaseswithintractableunilateraldefiniteMDmaybeproperlyaddressedtoablativesurgery,whereitseffectivenessonvestibularsymptomsisassessedbyinternationalliterature.Destructiveproceduresontheinnereararereservedtopatientswithunusablehearingandinparticular,translabyrinthinevestibularnervesection(TLVNS)seemstoleadtothebestcontrolforvestibularsymptoms.Cochlearimplantation(CI)hasbeenprovedtobesafeandeffectiveinpatientswithMDalsoafterdestructiveproceduresontheinnerear.In1975,BrackmannfirstpublishedtheresultsofCIafterTLVNS:sincethennomoreexperienceshavebeenreported.Wecarriedoutabi-centricprospectivestudytoevaluatetheeffectivenessofTLVNSandsimultaneousCIinpatientswithrecalcitrantMD.Ourpreliminaryresultswereanalyzedanddiscussed.ThestudywascarriedoutattheDepartmentofOtorhinolaryngology,UniversityofPavia,FoundationIRCCSPoliclinicoS.MatteoandattheOtorhinolaryngologyUnit,OspedaleCivile“SSAntonioBiagioandC.Arrigo”,Alessandria,(Italy).Alladultpatients(over18yearsofage)withadiagnosisofintractableunilateraldefiniteMDandunusablehearingwereenrolledaftermedicalandintratympanictreatmentfailures.Pre-andpostoperativeotoneurologicalevaluationconcerned:pure-toneandspeechaudiometry,tinnitushandicapinventorytest,frequencyofvertigoattacks,functionallevelscaleandrateofvertigocontrolaccordingtothe1995AAOHNSguidelines,dizzinesshandicapinventorytest,MDpatient-orientedseverityindex,headimpulsetestandcalorictesting.Sixpatientsmetthespecificinclusioncriteria,butonly5subjectsweresubmittedtoTLVNSwithsimultaneousCI:onecaserefusedtheablativeprocedureandwasaddressedtotheendolymphaticsacsurgery.Onepatientwas losttofollow-upduetogeographicreasons.Despitethefewnumbersoftheexaminedpopulation,inallcaseswerecordedaclearimprovementofvestibularandcochlearsymptoms.Inparticular,weobservedacompletecontrolofvertigo(classAaccordingtothe1995AAOHNSguidelines)withbeneficialresultsofqualityoflife.Hearingimprovementwasoverallreported,butthelevelofsubjectivesatisfactionwaslinkedtothedegreeofhearingimpairmentofthenon-operatedear.Follow-uprangedfrom1to40months.Inconclusion,TVLNSwithsimultaneousCIshowspromisingfindings,eventhoughagreaternumberofpatientswithahomogeneouslong-termfollow-upareneededtofullyevaluatetherealbenefitsofthisprocedure.

REHABILITATION OF FLUCTUATING HEARING LOSS BY COCHLEAR IMPLANT

D. Bernardeschi, I. Mosnier, D. Bouccara, E. Ferrary, O. SterkersAP-HP, Groupe Hospitalier Pitié-Salpêtrière, Unité Otologie, Implants auditifs et Chirurgie de la base du crâne, Paris, France et UMR-S 1159 Inserm / Université Paris 6 Pierre et Marie Curie, France

Thisretrospectivestudyevaluatedtheperformancesofthecochlearimplantation(CI)inadultswithfluctuatinghearingloss,duetoautoimmunediseaseorMenière’sdisease.Thirteenpatients(age:22to73),withuni-(n=6)orbilateral(n=8)severetoprofoundfluctuatinghearingloss,underwentaCIonone(n=12)ortwoears(n=1).Incasesofunilateralsevere/profoundhearingloss,thefluctuatinghearinglossonthecontralateralsideinducedveryhighdifficultiestofitthehearingaid(HA).Menière’sdiseasewasevidencedin8cases,Cogan’ssyndromein1case,andautoimmunediseasein2cases.Theaetiologywasunknownin3cases.Performancesweretestedinfreefield,withoutlipreading,withdisyllabicwordsrecognitioninquiet,andsentencesinquietornoise(SNR10dB).Themeanfollowupwas19monthsaftertheimplantation.Comparedtopreoperativedata,CIclearlyimprovedtheperformancesinthepatientswithbilateralprofoundhearinglossinquiet(disyllabicwords:80%versus67%;sentences:94%versus70%),andespeciallyinnoise(75%versus27%).Forpatientswhostillhadbenefitoftheircontralateralhearingaid,theperformanceswerealsoincreased(disyllabicwords:98%versus87%;sentences:98%versus91%;sentencesinnoise:75%versus48%).Itshouldbenoticedthattheirhearingaidclearlybroughtqualitativebenefitondailycommunication.Inuni-orbilateralfluctuatinghearingloss,CIisagoodopportunitytorestorehighlevelofcommunicationonquietandnoisysituations.Duetodifficultiestotreatthesepatientsbymedicaltreatment(steroids,immunosuppressor...),andtofitHA,CIshouldbediscussedasearlyaspossible.Learningoutcomes:Strategyofhearingrehabilitationinpatientswithuniorbilateralfluctuatinghearingloss.

KEYNOTE LECTURE 7

EFFECT OF CI ON MENIERE DISEASE

COCHLEAR IMPLANTATION AS THERAPY OPTION IN SINGLE-SIDED DEAFNESS AND VERTIGO CAUSED BY M. MENIERE

R. Laszig, S. Arndt, A. Aschendorff, C. Hantsch, R. BeckFreiburg, Germany

M.Menièreleadstoadeafnessontheaffectedsideinmanycases.Theintensityofthevertigousuallydecreasesovertime,afterinitiallybeingquitestrong,however,thevertigoispersistinginmostpatients.Thevertigocombinedwiththedeafnessresultinseveresuffering.Thecochlear implanthasbeenestablishedasaverysuccessfultherapyoptionforsingle-sidedpatients, sotheextensionoftheindicationforpatientswithM.Menièrehastobeevaluated.5patients(2SSD,3AHL)wereexaminedinaretrospectiveanalysis,havingbeenprovidedwithacochlearimplantbetween2009and2014withdeafnessinM.Menière.ExtensiveaudiologicaltestsweredoneduringCIpreopevaluationandafter6and12monthsaftersurgery.SubjectiveevaluationwasdonewiththeSSQquestionnaire.All5patientshadasuccessfulsurgery.TheresultsofthetestswerecomparabletothoseofotherSSDandAHLpatientswithotherunderlyingdiseases.2outof5patientssufferedfromvertigoaftersurgery;thiscouldbetreatedwithCortisoninfusionssuccessfully.TheresultsconfirmthebinauralhearinggainwiththeCI.CochlearimplantationshouldbeevaluatedasatherapyoptionwhenthereisnosufficientbenefitbyconventionalhearingaidsinpatientswithdeafnessduetoM.Menièreincombinationwithseverehearinglossandfrequentvertigo.

SPATIAL HEARING IMPROVEMENT AND LONG-TERM SUPPRESSIVE EFFECT ON TINNITUS AFTER COCHLEAR IMPLANTATION IN SINGLE-SIDED-DEAF PATIENTS WITH AND WITHOUT MENIERE’S DISEASE

V.VanRompaey,G.Mertens,P.VandeHeyning1 Department of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, Edegem, Belgium2 Faculty of Medicine and Health Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium

Cochlear implantation (CI) has the potential to significantly reduce tinnitus in single-sided-deaf (SSD) patients and to restorebinauralhearing.Thecurrentstudypresentsthelong-termevaluationoftheauditoryandtinnitusoutcomesupto10yearswithspecificinteresttoMeniere’sDisease(MD).Long-term evaluation was derived from 4 MD and 19 non-MD patients suffering from SSD and accompanying incapacitatingtinnitus.Thelatterwasdefinedastinnitusloudnessvisualanaloguescale(VAS)scoreexceeding6/10.Patientshadnormalhearingormildtomoderatehearinglossonthecontralateralear.TheywerereceivedtheCIatamedianageof55years(ranging22-71years)andhad8years(ranging3-10years)ofexperiencewiththeirCI.AllpatientsworetheirCIsevendaysaweek.Itappearedthatinallbutone,CIswitch-onisthefirstactwhenrisingandCIswitch-offisthelastactbeforebedtime.Inthemajorityofthepatients(i.e.70%)thetinnitusreductionstartedwithinoneminuteandtheresidualinhibitionafterCIswitch-offwaslessthanaminute(in65%ofthecases).Thelong-termtinnitusVASscoresindicateasignificantimprovementbetweentheCIOFFcondition(7.95/10)andtheCIONcondition(2.85/10).TheTQalsoshowedasignificanttinnitusreliefthatremainedstableover8years.Speechperception innoiseandsound localization improvedsignificantlyaftercochlearimplantation.NostatisticallysignificantdifferenceswereobservedbetweenMDpatientsandtheotherpatients.CIcansignificantlyimprovespeechperceptioninnoiseandrestorebinauralhearinginSSDpatients.SeveralyearsofCIusearenecessarytofullytakeadvantageofbinauralcuesavailablefromtheCI.Theaccompaniedtinnitusreliefappearstobestableover10yearsoffollow-up,eveninMDpatients.







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OUTCOMES OF COCHLEAR IMPLANTATION IN END STAGE MENIERE’S DISEASE: A MULTICENTER STUDY

D. Zanetti 1, F. Di Berardino 1, E. Filipponi 1, L. O. Redaelli De Zinis 3, T. Sorrentino 3, S. Costanzo 2, A. Cesarani 11 Audiology Dept. University of Milano2 ENT Dept University of Milano Bicocca, Monza3 ENT Dept University of BresciaItaly

ThebeneficialeffectofCochlearimplantation(CI)inMeniere’sDisease(MD)patientshasbeenreportedonlyinfewworksaddressingsmallgroupsofheterogeneouspatients.We performed a retrospective study on the series of MD patients admitted to three tertiary care academic medical centers inItaly,from2005through2013.Theaimofthisstudywastoevaluatetheeffectivenessandpost-operativeoutcomesofCIinMDandtorelatethemwiththedurationandthestageofthedisease,withthedegreeofpre-operativeresidualhearingandspeechdiscriminationscores,withthecontralateralhearinglevelandwiththepatients’age.Twenty-one CIs were performed in 20 patients with bilateral definite MD. Age, symptoms at admission and previous ablativeprocedureswererecorded.Puretoneandspeechaudiometry,vestibulartestingandQOLquestionnaireswereobtained.Mainoutcomemeasures:postoperativespeechperception(wordrecognitionscores–WRS-),curerateforvertigoattacks(AAOO1995)andsubjectivesatisfaction(VAS)scores.Thehearingandvestibularresultswerecontrastedwiththedurationofdisease,pre-operativehearinglevelandpatients’age.Meanlong-termfollow-upwas37months(24-78).Themeanageat implantationwas57years. AtthetimeofCI,5outof20patientspresentedactiveMD.Twelvepatientshadpreviouslyundergoneunilateralchemicalablationofthelabyrinthandwereimplantedonthesameside;onepatientsimultaneouslyunderwentatrans-labyrinthineremovalofavestibularschwannomawithsparingofthecochlearnerveandaCI.Anotherreceivedasequentialbilateralimplant.Differentbrandsandimplantsmodelswereused;thelimitednumbersdidnotallowanadequatestatisticalanalysisonthisvariable.Postoperative speech perception significantly improved in all cases (average WRS in quiet= 85%, p< 0.05). Fluctuations in CIperformancewereobservedin6MDpatients.TheperceivedhearinghandicapshowedasignificantimprovementafterCI.(62%,p<0.05).Amongthe5patientswithrecurrentvertigobeforeCI,4hadcompleteremissionand1hadsubstantialimprovement.AllothersdidnotcomplainofvestibulardisturbanceaftertheCI.SpeechperceptionoutcomesinMeniere’sCIrecipientsdonotdifferfromthoseinadultswithotheracquiredhearinglosses.CIintheend-stageofMDisavalidtreatmentoption.Asacollateralbenefit,itcanprovecurativeforvertigospells,iftheearwiththeactiveMDisimplanted.

COCHLEAR IMPLANT IN ASYMMETRIC MENIERIC HEARING LOSS

D. Cuda, A. Murri Department of Otorhinolaryngology, “Guglielmo da Saliceto” Hospital- Piacenza (Italy)

Background:Bilateralseveretoprofoundhearingloss isastandardcriterionforcochlear implantation(CI).Patientswithseveretoprofoundhearinglossinoneearandamoremoderatehearinglossintheotherear(i.e.asymmetrichearing)arenottypicallyconsideredcandidatesforcochlearimplantation.AsignificantnumberofsubjectssufferingfromMenière’sdisease(MD)hassevere-to-profoundhearinglossintheaffectedear.Whenthisoccursbilaterallyorwhenapatienthasamoremoderatehearinglossinthecontralateralear,inwhichtheamplificationareoftenunsuccessfulbecauseoflimitedbenefit,thesepatientsmaymeetcriteriaforcochlearimplantation.Object:thepurposeofthisstudywastoanalysethepost-operativeresultsinpatientssufferingfromMenierediseaseandasymmetrichearingloss.Studydesign:observationalretrospectivechart.Materialsandmethods:fifteensubjects(10malesand5females)witheitherbilateralMDorunilateralMDwhounderwentCIintheirearaffectedwithMD.ThemeanageatCIwas58,8years(SD11,5,range:41-74).NinesubjectswereimplantedwithaNucleusmultichannel device (Cochlear LTD, Sydney,Australia), three patientswith anAdvancedBionicsmultichannel device (AdvancedBionicsAG,Stäfa,Switzerland)andtheremainingthreewithaMed-Eldevice(Med-ElGmbh,Innsbruck,Austria).NinesubjectsworeaCIononeearandahearingaidontheoppositeside(“bimodalstimulation”).TheremainingsixrecipientsworeaunilateralCI.ThePTA(500-4000Hz)was121,6dBHL(SD+/-0.8)ontheCIearand78.4dBHL(SD+/-3.9)onthecontralateralear.Attimeofstudy,theCIexperienceattestingwas31.4months(SD+/-29.4),rangingfrom1to84months.Theaudiometricmeasuresincludeddisyllabicwordlistsinnoiseat+5dBSNR.TheSpeech,SpatialandQualitiesofhearingscale(SSQ)wasassessedpreandpost-operativelysuchastheTinnitusHandicapInventory(THI).Results:All patients use the device all the daywith ameanof 13hours.No intra-operative complications occurred.Only onesubjectspresentedvertigointhepost-operativeperiodwitharesolutionafter3weeks.AfterCI,thehearingofallsubjectsimprovedsignificantlyasdidtheirspeechrecognitioninnoise.Speechrecognitioninnoiseshowedameanimprovementof45%.Theresultswere less clear for the treatmentof vertigo associatedwithMenière’s, as somepatients continued tohave vertigo spells afterimplantation.Tinnitusscale(THI)showedapositiveeffectofCIstimulationandtheSSQresultsrevealedanoverallbenefitofCIuse.Somepatientsexperiencedalterationsintheirimplantperformanceinassociationwithfluctuationsinvestibularsymptoms.Conclusion:ThisstudydemonstratesthatCIisanadequatetreatmentofspeechperceptionforsubjectswithMenière’sdiseasewhogoontodevelopasymmetrichearingloss.







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AUDIOLOGICALTESTING p.97

CANALDEHISCENCE p.100

CLINICALISSUES p.101

COCHLEARIMPLANT p.111

COMBINEDTREATMENT p.117

ENDOLYMPHATICSAC p.118

GENETICS p.121 GENTAMYCIN p.124

HEARINGAIDS p.127

IMAGING p.127

IMMUNE-MEDIATEDDISEASE p.128

INNEREARFLUIDSDYNAMICS p.130

MEDICALTREATMENT p.132

OTOTOXICITY p.134

PRESSURETREATMENT p.135

STEROIDTREATMENT p.136

SUDDENDEAFNESS p.137 SURGERY p.138

TREATMENT p.141

VESTIBULARTESTING p.143

INDEXPOSTERS

AUDIOLOGICAL SCREENING IN CHILDREN WITH CEREBRAL PALSY

Khaydarova G., Shaykhova Kh.Tashkent medical academy

Theproblemofcerebralparalysisremainsoneofthemostpressingproblemsinmodernmedicine.Itsimportanceisdeterminedbytheincreasingprevalenceofthediseaseandthesocialsignificanceandoccupiesoneoftheavant-gardepositionofdisablingdiseasesofchildrenandadolescents.Currently,thereisasteadyincreaseinthenumberofpatientswithcerebralpalsy.Thefrequencyofcerebralpalsyinforeigncountriesisabout2-3per1,000newbornsinUzbekistan-8.9casesper1,000newborns.Themostsignificantintheclinicalpictureofcerebralpalsyisnotonlythedefeatofthepropulsionsystemandtheintellectualandpsychicsphere,butalsoaviolationoftheauditoryanalyzer,whichinturnaffectsthesecondarylanguagedelayandmentaldevelopment.Accordingtoforeigndatainchildrenwithcerebralparalysisofspeechis65-85%,andhearinglossisseenin10-15%[FreemanM,2006].Theaimofthisstudyis-tostudythestateoftheauditoryanalyzerinchildrenwithvariousformsofcerebralpalsybyscreening.Materialsandmethods.Thematerialofthisstudyincludes67(134ears)childrenwithvariousformsofcerebralpalsy(Table№1,№2),werehospitalizedinaspecializedNeurologicalhospital,inTashkent.Screeninggroupconsistedofchildrenfrom6to16yearsold,boys-36(53.7%)andgirlswith31(46.3%).Thelargestnumberof47(71%)childrenwerewithcommonformsofcerebralpalsy(spasticdiplegia,hemiparetic,atonic-astaticform).Withthemostsevere (hyperkineticanddoublehemiplegia)were-20(29%)children.Results.Thestudyofauditoryfunctionwasexaminedonthedevice“Neuro-Audio-Screen”CompanyNeurosoft(Russia)TEOAEtwoclasses:transientevokedotoacousticemission(TEOAE)andemissionatthefrequencydistortionproduct(DPOAE).Allstudieswereconductedinsoundproofchamberinthewakingstate.Toexcluderesultspseudo-deafness,allchildrenheldotorhinolaryngologicalexaminationtodetectinflammationinthenasalcavity,oropharynx,externalandmiddleear,estimatedthenumberofcerumenintheearcanal,andatthesametimedefinethepersonalityofthesizeoftheinsertforeachchild.ConductingDPOAErevealedthefollowingresults:67ofthechildtestispassedinbothearsin39children(78ears),inoneear-in18children(36ears),thetestfailedonbothearsin10children(20ears).ConductedsimultaneouslystudyofauditoryfunctionbyTEOAEgavesomewhatdifferentresults:67ofthechildtestispassedinbothearsin48children(96ears),inoneear-in5children(10ears),thetestfailsonbothearsin14children(28ears).Thehighprevalenceof latentoccurringdiseasesof themiddleand innerear inearlychildhood inpatientswithcerebralpalsy,accompaniedbyhearingloss,causestheneedformandatoryaudiologicalexaminations.Investigationhearingatanearlyagewiththehelpofscreeningmethodscontributestothetimelydetectionofhearingimpairment.







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CHARACTERISTICS OF HEARING ANALYZER MASKER IMMUNITY WHILE MENIERE’S DISEASE

Tadevosyan G., Lusinyan N., Mirakyan G., Balbabyan A., Martirosyan A., PkhrikyanT., Shukuryan A.ENT departmeny of Yerevan State Medical University, Erebouni MC

IntroductionHearingstatusofsocalledhealthyearhasadistinctiveimportanceinspecifyingpathogenesisofearlyandparticularlyfordifferentialdiagnosisofunilateralMeiner’shearingloss,forinvestigationofwhichmethodofspeechaudometryisusedagainstthebackgroundofnoise(masker)Absolutesilenceinhumanlifeisextremelyararething.Indailylife,manperceivesthespeechsignalsnotinisolation,butindifferentacousticenvironmentsinwhichabigstressfallsonhearingsystemidentificationandisolationofthedesiredinformationsignal,whichdependsonthenoiseimmunityacousticanalyzer.Methods21patientsaged26-58yearswithtypicalcomplaintsandwiththediagnosisofunilateralhearinglosswereexamined.Noise-immunityoftheacousticanalyzerwasdeterminedbyspeechaudiometryinthefreesoundfieldconditionswithoutinterference,atthebackgroundofwhitenoiseandextraneousspeech,separatelyfortheillandthehealthyear.ResultsThedefinitionsofspeechdiscriminationofillearonthebackgroundofnoiseandspeechMaskerareconsistentwiththoseexistingintheliterature.Duringthestudyofthehealthyear,althoughupto100%intelligibility,aphenomenonofphonemicregressionwasobservesupto93.6+-2.2%,onthecontrastwiththecontrolgroup,evenwithoutanyinterference.Atthebackgroundofthenoise60dBintelligibilityremainedthesameasinthesilence.Thedegreeofphonemicregressiononthebackgroundofspeechmaskerwasexpressedinsomewhathigherextentthanonthebackgroundofnoise-respectively87+-2.8%and93.5+-2.5%.ConclusionsThus,asaresultofourinvestigationstheintelligibilitydeterioratedwiththephenomenonofphonemicregressionorphonemicviolationofnoiseimmunityonthebackgroundofnoiseandspeechMaskeramongthepatientswithMeniere’sDiseaseofboththepatientandthehealthyearwiththeprevalenceofthemaskingeffectofthespeechMaskerwasrevealed.Takingintoconsiderationtheabsenceofhearinglossaccordingtoroutine(tonal)audiometryofthehealthyear,thedataireceivedindicatebilateraldiseaseandcanbeusedfordifferentialdiagnosisofunilateralhearingloss.

ECOG FINDINGS IN PATIENTS WITH MENIERE’S DISEASE

Basak Mutlu 1, Gunay Kirkim 1, Hande Evin 1, Yuksel Olgun 2, Enis Alpin Guneri 21 Dokuz Eylul University School of Medicine, Department of Otorhinolaryngology, Unit of Hearing, Speech and Balance, Izmir/TURKEY2 Dokuz Eylul University School of Medicine Department of Otorhinolaryngology,Izmir/TURKEY

Meniere’sDisease (MD) is an innereardisorder characterizedby suddenepisodesof vertigoassociatedwith tinnitusandpressure in theaffectedear.Fluctuatinghearinglossintheearlierstagestypicallyleadstoapermanenthearingdeficitwithamoderate-to-severedisability.Theaimofthisstudywastoanalyzetheelectrocochleography(EcoG)findingsandtheircorrelationwithotheraudiologicaltestsinpatientswithdefiniteMD.ENTexamination,clinicalhistory,pure toneaudiometry (PTA), speechaudiometryandextratympanicECoGevaluationswereperformedin33patientswithunilateraldefiniteMD.Thirteenpatientsweremale,20werefemaleandthemeanagewas45.9±13.5years.Therelationshipbetweenthesummatingpotentialtoactionpotential(SP/AP)ratiosandotheraudiometricparameterswereevaluated.MeanPTAairconductionhearingthresholdswere48.2±24.8dBHLatthepathologicalears,and19.1±13.9dBHLatthehealthyearsofthepatients.64.8%ofpatientshadabnormallyelevatedSP/APratios.CorrelationcoefficientsbetweenSP/APratiosandmeanPTAthresholdsweresignificant(p<0.05).EcoGisavaluablepartofthediagnostictoolinthediagnosisofhydrops,asitisanon-invasive,easytohandleprocedure.

AUDIOLOGICAL TESTING

AUDIOMETRIC CONFIGURATION FOLLOWING EXCESSIVE NOISE EXPOSURE

Atanasova N. 1, Ristovska L. 21. MD , ORL specialist, Division of Audiology, Department of Otorhinolaryngology City General Hospital “8 September”- Skopje, Republic of Macedonia;2. Defectolog MA,Division of Audiology, Department of Otorhinolaryngology City General Hospital “8 September”- Skopje, Republic of Macedonia;

Aim:To determine the configuration of pathologic audiograms in patients with excessive noise exposure, and to calculate thefrequencyofaudiometricnotchinpatientswithandwithoutexcessivenoiseexposurebyavoidingtheeffectofage-relatedhearingloss.Methods:Weanalyzed514audiogramsof257patientsaged20to50years.Atotalof240patients(meanageof38.7years)hadpositivenoisehistoryand17patients (meanageof41.2years)withaudiometricnotch,butwithouthistoryofexcessivenoiseexposure. All patients were civilian examined at the Department of Otorhinolaryngology, City General Hospital “8-September”,Skopje,RepublicofMacedonia.ForstatisticaldataanalysisweusedChi-squaretestandFisherexacttestwithlevelofsignificancep<0.05.Results:Pathologicaudiogramswereclassifiedin5types:0.8%wereTypeI(slopeat4000Hz);15.1%wereTypeII(slopeat2000Hz);67.4%wereTypeIII(notchat4000Hz);0.8%wereTypeIV(notchat2000Hz),8.9%wereTypeV(flat)and7%wereoutofthisclassification.Inpatientswithpositivenoisehistory79.2%hadaudiometricnotch.Unilateralnotchesattheleftearwerethemostfrequent;91.8%ofthepatientswithnotchedaudiogramwerewithand8.2%withoutpositivenoisehistory.Conclusion:AudiometricnotchisnotapathognomonicsignofNIHL.Itcanoccurinabsenceofpositivenoisehistory.Thereisaneedofuniquedefinitionofaudiometricnotch.Furtherstudiescouldfocusonhearingconservationprograms.

AUDIOMETRIC FINDINGS IN PATIENTS WITH SUBJECTIVE TINNITUS

AtanasovaN.,RistovskaL.MD ORL specialist MA defectolog

Aim:Todeterminetheprevalence,typeanddegreeofhearinglossinpatientswithsubjectivetinnitusandtoanalyzethequalityfeaturesandsometinnituscharacteristicsrelatedtoassociatedhearingloss.Methods:Weanalyzedaudiometric,otoscopicfindingsandcasehistoryof702patients,376males(53.6%)and326females(46.4%),aged19to89years.ThepatientswereexaminedattheDepartmentofOtorhinolaryngology,CityGeneralHospital“8-September”,Skopje,RepublicofMacedonia,duringtheperiodofJanuary2014toDecember2014.ForstatisticaldataanalysisweusedChi-squaretestwithlevelofsignificancep<0.05.Results:Mostofthepatientsweremalesattheage60to69years(12.8%),buttherewasnosignificantdifferenceinageandgenderdistribution(p=0.448).Bilateraltinnituswasmostcommon(59.3%).Unilateraltinnituswasmorecommonintheleftear(59.1%).Prevalenceofhearinglossamongtinnituspatientswas92.7%;7.3%hadnormalhearing.Hearinglossathighfrequencieswasmostcommon(p<0.00001).Mostcommonotologicconditionswereacoustictraumaandnoiseinducedhearingloss.Mostofthepatientsdescribedtheirtinnitusashigh-pitchwhistling,hadbilateraltinnitusandbilateralsensorineuralhearingloss.Conclusion:Mostofthepatientswithsubjectivetinnitushavesomedegreeofhearingloss.Thereisaneedofperformingextendedhigh-frequencyaudiometryintinnituspatientswithnormalhearingatstandardpuretoneaudiometry.Keywords:tinnitus,hearingloss,normalhearing.







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SEMICIRCULAR CANAL MALFORMATIONS: CLINICAL AND INSTRUMENTAL FINDINGS

Cristina Brandolini, Andrea Castellucci, Gianluca Piras, Antonio PiroddaDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy

Anomaliesinvolvingonlythesemicircularcanal(SCC)areclassifiedasamildinnerearmalformation.AmongthesethelateralSCCdysplasia(shorteningandwidening)isthemostfrequent..TheresultsofseveralstudieshavenotshownanyconsistentrelationshipbetweenSCCmalformationsandhearingloss.Asforcochlearfunction,fewreportshaveexaminedthevestibularsymptomsandanycorrelationbetweentheseverityofthecanalandthevestibulemalformationsandvestibularimpairingexists.Thepurposeofourstudywastodescribethecochleo-vestibularassessmentinpatientswithsporadicsemicircularcanalmalformationsandtosuggestpossibleexplanationsforthevariabilityofsymptomsandsignsinducedbySCCanomalies.Thestudywasperformedin22adultspatientsaffectedbylateralsemicircularcanaldysplasiaidentifiedintheENTandAudiologyUnitoftheUniversityofBolognafromJanuary2010toDecember2014.Allpatientswereexaminedbymeansofappropriatetemporalbonehighresolutioncomputedtomography(HRCT)studywithmultiplanarreconstructionandwerescreenedtoexcludecentralnervoussystemandeighthcranialnerveenhancinglesionsusingcontrast-enhancedbrainmagneticresonanceimaging(MRI).Acarefulanamnesticevaluationandafullaudio-vestibulartestbatterywereattemptedforeachpatient(puretoneaudiometry,infra-redvideonystagmoscopy(headpitchtest,Hallpikemaneuver,bilateralmastoid100Hz-vibration,headshakingtestandValsalvamaneuverwithpinchednostrils),bithermalcalorictest,cervicalandocularvestibularevokedmyogenicpotentialsstudy(airandboneconductedstimuli),headimpulsetestusingvideo-HITintheplanesofall6semicircularcanals).AllthepatientsbilaterallyhadtheSCCmalformation:15of22patientshadbilaterallateralSCCdysplasia;3patientshadleftLSCCdysplasiaandrightLSCCaplasia;1patienthadaplasiaLSCCbilaterally;1patienthadSCCdysplasiaofall6SCC;1patienthadposteriorSCCaplasiaandcontralateralposteriorSCCdysplasia;1patienthadLSCCdysplasiaandanteriorarmsuperiorSCCaplasia.Noneof thepatientshadcochlearmalformationsorenlargedvestibularaqueduct.Noexternalear,middleearorossicularabnormalitieswerenotedonimaging.6of22patientshadMeniere-likeclinicalhistory.Wewilldescribeindetailthecochlea-vestibularinstrumentalfindings.

SUPERIOR CANAL DEHISCENCE MAY INDUCE ENDOLYMPHATIC HYDROPS: PHYSIOPATHOGENETICCONSIDERATIONS ABOUT THE “SPONTANEOUS PLUGGING PROCESS” THEORY

Cristina Brandolini, Andrea Castellucci, Gianluca Piras, Antonio PiroddaDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy

Besidestypicalsymptomsandsigns(includingpulsatiletinnitus,hyperacusis,pressure/soundinducedtorsionalnystagmus,conductivehearinglossandloweredthresholdsofair-conductedVEMPs)ananalysisoftheliteraturerevealsacertainclinicalpolymorphisminducedbysuperiorcanaldehiscence(SCD).Inadditiontoasymptomaticpersonsorsubjectspresentingwithcochleardisordersastheonlysymptoms(partlyexplainedaftertheintroductionofthe“near-dehiscencesyndrome”),caseswhereatypicalMénière-likecrisesrepresentthemostprominentclinicalfeatureshavebeenrecentlydescribed.Despiteofall,nounanimousinterpretationforallthesedifferentphenotypicpatternshasyetbeenoffered.Additionally,ifsurgicalocclusionofthesuperiorcanal(SC)hasdemonstratedtoresultinSCDsymptomscontrolinducingaselectiveSCdysfunction,itiscommonfindingforpractitionerstodetectareducedSCangular-VORgaininasymptomaticpatientswithwide-sizeddehiscence.ThesefindingsledauthorstoproposetheoccurrenceofanaturalSCpluggingrealizedbymiddlefossaduraprolapsingintothecanallumen.Thecompressionofthemembranouscanalwouldresultinaprogressiveendolymphaticblockage,selectivelyinactivatingSCreflexesandexcludingthedehiscentcanalfromlabyrinthinemicromechanics.Wehypothesizethat,inparticularconditionsuchasduringsuddensmallintracranialpressurechanges,atransientandpartialherniationofdurathroughthedehiscentcanalcouldinduceatransitoryhydropicconditionoftheinnerear,leadingresultinginrecurrentvertigospellsvariablyassociatedwithcochlearsymptoms.AnalogousMénière-likeclinicalpictureshavealreadybeenregisteredinthefirstpostoperativeperiodinaconsiderableamountofpatientswithSCDwhoweresubmittedtocanalocclusion.Weconductedaretrospectivereviewoftheclinicalrecordsof242patients(114M,128F,meanage56.8y,range8–88y)diagnosedatourinstitutionashavingadehiscentoraanextremelythinnedsuperiorcanalatleastfromonesideatHRCTscans,andweselected22patientsinwhomaMénière-likesymptomatology(i.e.recurrentspontaneousvertigoattackswith“irritative”nystagmusandauditorysymptoms)wasdetected.Asubsampleofpatientswithacompleteotoneurologicassessment(audiometry,VOGeyerecording,air/bone-conductedcervical/ocularVEMPs,calorictest,videoheadimpulsetest)wasselectedforsupportingthisemergingphysiopathogenetichypothesis.

CANAL DEHISCENCE

A NEW MENIERE’S DISEASE-SPECIFIC QUALITY OF LIFE SURVEY: DOKUZ EYLUL UNIVERSITY MENIERE’S DISABILITY SCALE

Basak Mutlu1, Serpil Mungan Durankaya1, Selhan Gurkan1, Enis Alpin Guneri2,Gunay Kirkim11 Dokuz Eylul University School of Medicine, Department of Otorhinolaryngology, Unit of Hearing, Speech and Balance, Izmir/Turkey2 Dokuz Eylul University School of Medicine Department of Otorhinolaryngology, Izmir/Turkey

Meniere’sDiseaseisachronic,non–life-threateninginner-eardisease,withattacksofdisablingvertigo,progressivehearingloss,andtinnitusasmajorsymptoms.Allthreesymptoms,separatelyorincombination,causegreatdistressandhaveaconsiderableimpactonthequalityoflifeofpatients.TheaimofthisstudywastoanalyzethepsychometricpropertiesofDokuzEylulUniversityMeniere’s Disability Scale developed originally. 93 patients with definite Meniere’s Disease included in this study. Dokuz EylulUniversityMeniere’sDisabilityScaleandDizzinessHandicapInventorywereadministered.45ofpatientsweremale,48werefemaleandthemeanagewas48.9±12.1years.Cronbach’salphacoefficient,pvaluesofTukey’sadditivityandHotelling’schi-squaretests,intra-class correlations coefficients, item-total correlations coefficients, Cronbach’s if item deleted values were calculated. AndexploratoryfactoranalysesbyVarimaxrotationwithKaisernormalizationandGoodnessoffitconfirmatoryfactoranalyseswereperformed.Cronbach’salphawas0.92,intra-classcorrelationvaluewassignificant(p<0.001).BothTukey’sandHotelling’stestsshowedsignificancy(p<0.001).Resultsofthegoodnessoffitstatisticsshowedthattheexpressionlevelsoftheitemstothescalewashigh,andtherelationshipsofitem-scaleweresufficient.Asaresultofthisstudy,DokuzEylulUniversityMeniere’sDisabilityScaleisavalidandreliablescale.

ANALYSIS OF THE MOST COMMON CAUSES OF DIZZINESS.POSSIBILITY TREATMENT OF PATIENTS

Z. Pusara, Z. PejicHospital Gradiska, Reupublika of Srpska, Bosnia and Herzegovina

Introduction: AlargenumberofpatientsinENTclinicscomplainofdizzinessasmainsymptom.Objective:Theobjectiveofthisstudywastoshowtherelationshipswhicharemostcommonlydiagnosedinadults(childrenarenotcoveredinthispaper)thatissolelyorprimarilycomplainofdizziness,andtoanalyzetheperformanceofstandardtherapeuticmodalities.Substances and Methods:Aprospectiveclinicalstudyof60patients,whichtheauthorexaminedandmonitoredinthesix-monthperiod.Allpatientsgavetheirsignedconsenttoparticipationinthepreparationofthispaper.Adiagnosisofvertigohavesetuponthebasisof:audiological-vestibulatoryhistory;otorhynolaryngologycalclinicalexaminationandaudiological-vestibulologicaltests.Thestatisticalanalysisoftheresultsobtainedwereusednonparametricmethodsfortestingthedifferences.Results:ThemostcommoncauseofvertigoisBPPV(50.8%),neuronitisn.vestibularis(16.9%),Meniere’sDisease(15.3%),vertigoofcentralorigin.BPPVismorecommoninwomen,inpatientswithahistoryofheadinjury,AUPV,migraine,surgicalintervention(stapedotomy).In80%ofcasestheaffectedsemicircularcanal,in20%ofcasesaffectedbyhorizontalsemicircularcanal(geotropicvarianthBPPV,morefrequent),anextremelyrareuppersemicircularcanal.Ofreductionmaneuver(CRP)successfulin87.5%,Gufonimaneuversuccessful71%ofthecases.Patientswithacuteunilateralperipheralvestibulardeficitrecoveringanaverageof3to4weeksdependingonthelocalizationofdamage,thenatureofthepathologicalprocess,changesintheCNS,vascularandgeneraldiseases.Conclusion:Damagetotheperipheralvestibularapparatusarebyfarthemorecommon,andmostofthemBPPV.ThemostcommonformofBPPVisacanalolithiasisofsemicircularcanals,accountingforabout30%ofalldizziness.ThesuccessoftheCRPwithouttransitiontoanotherformofBPPV’s87.5%.Key wordsdizziness,classification,treatment.







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ANXIETY AND THE SEVERITY OF THE SYMPTOMS IN PATIENTS WITH MENIERE’S DISEASE

Jotic Ana, Mikic Branka, Cvorovic LjiljanaClinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Centre of Serbia, Belgrade, SerbiaMedical Faculty Belgrade, University of Belgrade, Serbia

Meniere’sDiseasesymptomsincludevertigo,hearingloss,tinnitusandauralfullnesswhichcanbeextremelystressfulandlimitingineverydaylife.Meniere’spatientsalsoreportedsymptomsofanxietyanddepression,worsesocialfunctioningandphysicalpain.TheaimofthestudyistodetermineistheseverityoftheMeniere’sDiseasesymptomscorrelatedwithanxietyinpatients,dependingontheageofthepatient,durationofthediseaseanddailydosesofbetahistine.Thestudyincluded37patientsdiagnosedwithMeniere’sDisease(28femalesand9males)ofanaverageageof46.2years.Durationofthediseasevariedfrom6monthsto5years.34patientswereontherapywithbetahistine(dailydosesfrom48to144mg)and3werewithoutanytherapy.During12weeks(fromJanuarytoMarch2014)patientsfilledoutMeniere’sDiseaseFunctionalLevelScaleandZungSelf-RatingAnxietyScaleeveryweek.Therewassignificantpositivecorrelation inscoresvariationofMeniere’sDiseaseFunctionalLevelScaleandZungSelf-RatingAnxietyScalethoughthedurationofthestudy(Pearson’scorrelation,p˂0.05).Scoresweresignificantlyhigherinolderpatientswithlongerdurationofthedisease,andtheyweren’tinfluencedbydailydosesofbetahistine.

AUDIOVESTIBULAR FINDINGS IN CEREBELLOPONTINE ANGLE TUMOR

Noriko Nagai, Yasuo Ogawa, Akira Hagiwara, Kouji Otsuka, Taro Inagaki, Shigetaka Shimizu, Shigeto Itani, Mamoru SuzukiDepartment of Otorhinolaryngology, Tokyo Medical University

Acoustictumorsarebenignschwannomasoftheeighthcranialnerve.Acoustictumorsmostfrequentlyariseinthecerebellopontineangle.Sofarthereareanumberofstudiesbeingpublishedabouttheaudiometricfindingsinthepatientswithacoustictumor.However,fewstudieshavebeendoneabouttheothercerebellopontineangletumors.Thisstudyretrospectivelyevaluatedthedifferencebetweenaudiovestibularfindingsofacoustictumorsandtheothertumors.Eightytwopatientswithunilateralcerebellopontineangletumorwereinvolvedinthisstudy.Fiftypatientshadtheacoustictumor(AT)and32patientshadtheothertumors(non-AT).Thirtypatientsweremaleand52werefemale.Fortythreecaseswererightsideand39caseswereleftside.Themean±SDagewas43.7±12.1yearsatthetimeofinitialexamination.Forallpatients,diagnosiswasmadebypreoperativeMRIandconfirmedpathologicallyaftersurgery.Beforesurgery,thepatientsunderwentpure-toneaudiometry(PTA),speechaudiometry,distortionproductotoacousticemissiontests(DPOAE)tests,caloricENG,andvestibularevokedmyogenicpotential(VEMP).PTAwasevaluatedasthemeanofthresholdsatthefourfrequencies(250,500,1000,and2000Hz).Wedividedthepatientsintotwogroupsaccordingtospeechdiscriminationscores(SDS),greaterthan80%andlessthan80%.DPOAEwasmeasuredusingILO292-USB(Otodynamicsmodel).Wedefinedtheamplitudeof5dBSPLabovethelevelofthecorrespondingnoisefloorasDPOAEpositive.Thepreoperativeandpostoperativefindingswerecompared.Tumorsizewasmeasuredasthelargestdiameteronaxial,coronal,orsagittalMRIviews.TheFischertestwasemployedtotestthecorrelationofPTA,SDSandDPOAEabnormalitybetweenATandnon-AT.Themann-whitneyUtestwasusedtoidentifytherelationshipsbetweentumorsizeandPTA,SDS,DPOAE.AP-valueoflessthan0.05wasconsideredtobestatisticallysignificant.ThepreoperativePTAwasnormalin39cases(47.6%),SDSwasmorethan80%in44cases(55.7%),DPOAEwasnormalin42(51.9%).Thetumorssizewerefrom7mmto58mm.Themean±SDtumorsizewas29.3±10.9mm.PTAandDPOAEweresignificantlybetterinnon-ATthanthoseofAT.SDSwasnotsignificantlydifferentbetweenATandnon-AT.ThepreoperativePTAandSDSinATweresignificantlyworsewhenthetumorwashuge.TherewerenostatisticallydifferentfindingsbetweentumorsizeandDPOAEinAT.TherewasnocorrelationbetweenthepreoperativePTAandtumorsizeinnon-AT.However,thestatisticaldifferencewasnotedbetweenSDS,DPOAEandtumorsizeinnon-AT.TheresultsofPTA,SDSandDPOAEwerenormalwithhalfofnon-ATItisimportanttodifferentiateATornon-ATbeforesurgeryforthepredictionofthehearingaftersurgery.ThecerebellopontineangletumorwiththeDPOAEnegativityandseverehearinglossmightindicateAT.Thetumorwhichsizeislargeandnormalhearingmightbenon-AT.PTA,SDSandDPOAEhaveanimportantroleforpredictionoftumorlocation.Thelocationofnon-ATmayaffecttheaudiovestibularfindings.

CLINICAL ISSUES

BENIGN PAROXYSMAL POSITIONAL VERTIGO FOLLOWING STAPEDOTOMY

Arsovic NenadFaculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Centre of Serbia, Belgrade

Introduction.Itiswelldocumentedinliteraturethatcertainpercentofpost-stapedotomypatientsexperienceboutsofvertigoinpostoperativeperiod.InsomeofthesepatientsDix-Hallpikemaneuverispositive,andthediagnosisofbenignparoxysmalpositionalvertigocanbemade.Whileexactincidenceofthisphenomenonstillremainsunknown,thepathophysiologyseemstobeclearer,asitisregardedtobetheconsequenceofutriculartraumaduringtheoperation.PatientsandmethodsCaseseries.Theauthorpresentscaseseriesofthepatientswithbenignparoxysmalpositionalvertigo,whichoccurredduringthefollowingyearafterstapedotomyoperation.Theyallrespondedwelltotreatmentwithrepositionmaneuvers,andremainedwellduringthefollow-upperiodofthreeyears.Conclusion.Severalauthorsreportedstapedotomy,aswellasstapedectomyoperations,asetiologicalfactorsforbenignparoxysmalpositionalvertigo.Reportedincidenceinonestudyishigh,8.5%.Itisalsostressedthatcorrectmeasurementofdistancebetweenincusandstapesisessentialforavoidingthisphenomenon.Nonetheless, itremainsofutmostimportancetowarnthepatientsaboutthiscondition,andtodifferentiateitintimelymannerfromothercausesofpost-stapedotomyvertigo.

CONSERVATIVELY MANAGED SPORADIC VESTIBULAR SCHWANNOMA: AUDIOVESTIBULAR FACTORS INFLUENCING QUALITY OF LIFE

S.Hansen1,J.Yde1,S.Stangerup1,M.Møller1,C.Workman2,P.Cayé-Thomasen1,31 Department of Otorhinolaryngology Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark.2 Center for Biological Sequence Analysis, Technical University of Denmark, Denmark.3 Faculty of Health Sciences, University of Copenhagen, Denmark

Introduction:Theobjectivewastoevaluatethequalityoflife(QoL)ofpatientswithconservativelymanagedVestibularSchwanommas(VS)anddescribetheirsociodemographiccharacteristics.Methods:Thequestionnaireswereansweredbypatientsviaanewlydevelopedwebsiteusingauniquetoken.Thosewhodidnotacceptorunderstoodansweringviatheinternethadasecondpossibilityofapaperversion,whichweresendtothembypost.Theywereaskedtoreturntheircompletedquestionnairesinaprepaidenvelope.Results:87.7%responserate(994/1133).ThequestionnairesincludedShortForm12HealthSurveyVersion2(SF-12v2),theHearingHandicap Inventory (HHI), Tinnitus Handicap Inventory (THI), Dizziness Handicap Inventory (DHI), The Penn Acoustic NeuromaQuality-of-LifeScale(PANQOLscale),andquestionsonsociodemographiccharacteristics.898patientsreportedhearingloss(95.8%).Sixhundredeightyfourreportedtinnitus(72.9%)and463reportedimbalance(49.4%).RegressionanalysisshowedthatDHIscoreandagewerestrongpredictorsofphysicalcomponentsummary.DHIandTHIscoresweresignificantpredictorsofmentalcomponentsummary.Conclusion: Dizziness is the most significant audiovestibular predictor of QoL in patients with VS. Tinnitus also has an impactonmentalQoL.Hearing lossdoesnotseemto influenceQoLsignificantly.Other factorsmayhavean important role toplay indeterminingQoL.







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EVALUATION OF URINARY DEOXYPYRIDINOLINE LEVELS AND THEIR CORRELATION WITH TEMPORAL BONE HRCT AND DENSITOMETRIC DATA IN OTOSCLEROSIS

Pınar TUNCBILEK OZMANEVRA 1, Nuri KARABAY 2, Selhan GURKAN 3, Günay KIRKIM 3, Enis Alpin GUNERI 11 Dokuz Eylul University Faculty of Medicine Department of Otorhinolaryngology, Izmir, Turkey2 Dokuz Eylul University Faculty of Medicine Department of Radiology, Izmir, Turkey3 Dokuz Eylul University Faculty of Medicine Department of Audiology, Izmir, Turkey

Otosclerosis is a disease characterized by progressive hearing loss in one or two ears. Potential causes include genetic, endocrine, immune,viralfactorsandconnectivetissuediseases.It’ssuggestedthatinpatientswithoutadiseaseassociatedwithboneresorptionorincreasedbonemetabolism(osteoporosis,osteogenesisimperfecta,Paget’sdiseaseetc.),supportingthediagnosisofotosclerosiswithanon-invasiveurinetestmaycontributetomonitoringandrehabilitationofthepatient,planningofthetimingofsurgeryandmaybeusedasascreeningtestforotherfamilymembers.High-resolutioncomputerizedtomography(HRCT)iswidelyusedtovisualizechangesintheoticcapsuleduetodemineralization.However,patientswhowerediagnosedorhadclinicalotosclerosismaynothaveanyhypodenseregionsevenbydensitometricmeasurements.Deoxypyridinoline (DPD) isamarkerwhich isexcretedbyurinewithoutmetabolizationand increaseswithboneresorptionandosteoclasticactivity.TheurinaryDPDlevel,aproductofbonebreakdown,isn’taffectedbythedegradationofnewlysynthesizedcollagenanddiet.Ithasbeendemonstratedthattohaveahighspecificitytobonetissuesandisvirtuallybonebased.It’ssuggestedthaturinaryDPDlevelmaybeadiagnosticmarkerinformingtheprogressofthediseaseinpatientswithotosclerosis.Method:Inourstudy,whenevaluatingdatarelatedtotheurinaryDPD,twogroupswereformed,includingapatientgroupandacontrolgroup.Twelvepatientssurgicalconfirmedashavingotosclerosisconstitutedthepatientgroup.Thepatientgroupwasfurthercategorizedintobilateral(n:7)andunilateral(n:5)afterradiological,audiologicalandsurgicalassessments.Audiologicaldataof18earsbelongingto12patientswereexamined.Stapedectomysurgerywasperformedunilaterallyin11earsof12patients,andinbothearsof1patient.PatientsweregroupedaccordingtopositiveornegativeradiologicalfocusdetectedbyHRCTanddensitometricmeasurements.Results:Inpatientswithbilateralinvolvement,DPDvalueswereseentobesignificantlyhighalthoughnoradiologicalfociwereobserved.Inthenormalgroup,themeanvalueofurinalDPDratiosofpatientswithbilateralinvolvementwashigherthanthepatientswithunilateralinvolvement.bWhen,inthepatientgroup,thecorrelationsbetweenthefirstandsecondurinalDPDratiosandotosclerosiswereexamined,amoderatecorrelationbetweenthemeanvalueofsecondurineDPDratiosandotoscleroticinvolvement(R=0,61)werefoundsignificant(p:0.03).AllthepatientswhowerediagnosedorhavingotosclerosiswiththecombinedofurineDPDratiosandHRCTweresurgicallyproventohavethedisease.ItwasdiscoveredthatbyaddingurineDPDratiostoHRCT,sensitivityoftheHRCTincreasedfrom50%to100%.Duetothelownumberofpatientsinourstudy,thevalueofDPDratiosinunilateralandcochlearotosclerosiscasescouldn’tbeevaluated.Inconclusion,diagnosisoftheotosclerosisneedssurgicalconfirmationandcurrentlytherearenoothermethodstoevaluatethemetabolicactivityofotoscleroticfociexceptHRCTdensitometry.However,ourstudyshowedthaturineDPDratiogivesusanopportunitytosupportthediagnosisofotosclerosisinanon-invasive,lowcostandquickway.UrinaryDPDratiocanbeadiagnosticmarkerandcaninformaboutthediseaseprogressandresponsetomedicaltreatmentinpatientswithotosclerosis.

FORMS OF VERTIGO IN ENCLOSED TYMPANUM CHRONIC MASTOIDITIS

Simona Serban, Marian Radulescu, Andreea Rusescu, Carmen-Cristina DraghiciInstitute of Phonoaudiology and ENT Functional Surgery “Prof. Dr. Dorin Hociota”

Theaimofthispaperistounderlinetwotypesofvertigowhichcanbetheclinicalmanifestationsofenclosedtympanumchronicmastoiditis:prolongedvertigo,accompaniedsometimesbyhearingsymptomssuchasauralfullnessortinnitusandrecurrentvertigo,lastingfromseveralhourstoaday,alwaysaccompaniedbyauditorymanifestations(cloggedearorworseninghearinglossortinnitus).Thestudywasperformedonanumberof13patientswhopresentedtotheEmergencyRoomwithacutevertigo. Incrisis,clinicalexaminationincluded:otoscopicexam,audiometrictests,vestibularexamination;afterovercomingtheacutephase,theinvestigationprotocolincludedpuretoneaudiometry,BERA(brainstemevokedresponseaudiometry)acousticimmitance,VEMPtesting,CTscan.8patientshadprolongedrecurrentvertigolastingmorethan24hours;accompaniedbyotalgia,tinnitus,hearingwithinnormallimits;5ofthemhadvariousdegreesoftubaldysfunction,frommildtosevere;3ofthemhadnormalmiddleearpressure.5patientshadMeniere-likeparoxysmalvertigo,lastingonlyafewhours,accompaniedbytinnitusandhearingloss.Allpatientshadtubaldysfunctionintheaffectedear.ChronicmastoiditisvertigocansometimessimulateotherclinicalvertigosuchasvestibularneuronitisorMenieredisease.MiddleearCTscanorX-rayinSchullerincidencecanindicatethepneumatizationofthemastoidaircells.Inthesecases,thesurgicaltreatmentrepresentsthecurativesolutionforhearingpreservationandvertigodisappearance.

INTRAVESTIBULAR SCHWANNOMA: SYMPTOMATIC TREATMENT WITH INTRATYMPANIC GENTAMYCIN

Luigi Volpini, Edoardo Covelli, Chiara Filippi, Simonetta Monini, Maurizio BarbaraSapienza University, NESMOS Department, Rome, Italy

Objective-Intralabyrinthineschwannomaisararebenigntumorthataffectstheendsofthecochlearandvestibularnerves.Inthemajorityofcasesitoccurswithunilateralprogressivesensorineuralhearingloss.Lessfrequentsymptomsincludetinnitus,imbalance,vertigoorfullness.Theadventofmagneticresonance imagingallowsearlydiagnosis,whichpermitsanappropriatetherapeuticprotocol.Thisreportdescribesauniquecaseofintravestibularschwannoma,withfluctuatinghearinglossandintractablevertigotreatedwithintratympanicgentamicin.Patient/Intervention- A 28-year-old woman with intractable vertigo and fluctuating left- side hearing loss caused by left-sideintravestibularschwannoma.Sheunderwentspontaneousvestibulartests,puretoneaudiometry,electrocochleographyandHeadImpulseTest.Sincesurgerywastemporarilyexcludedtoavoidhearingloss,asingledoseofintratympanicgentamicinwasthereforeadministered.MainOutcomeMeasures-Effectivenessoftreatmentwithintratympanicgentamicininreducingsymptomsofdizzinesswithhearingpreservation.Results-After intratympanicgentamicintreatment, thepatientshowedasignificant improvementofhersymptomatologywithbilateralnormoreflexiaandmoderatetoflatsensorineuralhearingloss.Conclusion- Intratympanicgentamicin infiltration is a valid therapeuticoption forpatientswith intralabyrinthine schwannomaaffectedbyintractablevertigo,whenhearingisstillsociallyuseful.Itmayprovideexcellentresultsonthevestibularsymptoms,althoughanoxiouseffectonhearingispossible,withoutthepossibilitytostopthetumorgrowth.Thereforepatientssuitableforthistreatmentneedaccuratemagneticresonanceimagingfollow-uptomonitorthedevelopmentoftumorgrowth.

MANIFESTATION OF LERMOYEZ’S SYNDROME IN MENIERE’S DISEASE PATIENT

ŠpelaKordiš1,NinaBožanićUrbančič1,ManjaHribar1andSabaBattelino11 ENT and CFS Clinic Ljubljana, University Medical Centre Ljubljana, Slovenia

AlthoughLermoyez’ssyndromehasbeendescribedalreadyatthebeginningofthe20thcenturytherearenotmanycasesfoundintheliteratureandnotmuchiswrittenaboutitsetiology,diagnosisandtreatment.Istherereallysuchalowincidenceoristhesyndromesimplyunrecognized?SomeauthorsconsideritasavariantofMeniere’sDiseaseandsomeasasoleentity.A 34-year old male with a history of a sudden hearing loss, tinnitus and feeling of pressure in the left ear was admitted toourhospital.Onadmissionhehadnovertigoandno spontaneousnystagmuswas seen.Hishearingon the rightearhasbeendamagedforyears.Audiogramrevealeddeteriorationofhearingthresholdinhisleftear,asensorineuralhearinglossespeciallyinthelowfrequencies.TympanometryshowedcurveAonbothsides.Hewastreatedwithoralcorticosteroidsandbetahistine.Duringhospitalizationpatientnoticedimprovementofhearinginhisleftearbutatthesametimevertigowithspontaneousnystagmustowardtheaffectedearhadappeared.Onexaminationhehadnosignsofearinfection.Check-uppuretoneaudiometryconfirmedimprovementofthehearinginthelowfrequenciesfrom125Hz-500Hz.MRIexcludedpathologicchangesinthebrain,cerebello-pontineangleand inthecourseofthevestibulocochlearnerve.SerologyforBorreliaBurgdorferiandrheumatologictestswerenegative.Onfollowuphecomplainedoffrequentdaytodayfluctuationsofhearingthresholdintheleftear.Usuallybeforethevertigoattackhishearing improvedand laterspontaneousnystagmustowardstheaffectedsidewasdetected.Astroubleswithvertigoattacks,tinnitus,earfullnessandfluctuationofhearinghadrepeatedseveraltimeswesuspectedofavariantofMeniere’sDisease–Lermoyez’ssyndrome.Hereceivedanintratympanicinjectionofdexamethasonebutitdidnotrelievehissymptoms.







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MENIERE’S DISEASE PRESENTED WITH MICRO VASCULAR COMPRESSION OF THE VESTIBULOCOCHLEAR NERVE

Kh. Ouennoughi 1 M.S. Haraoubia 1A. Mouzali 1, K.Kanoun 1, L. Boublata 2, D. Ioualalène 2, O. Zemirli 11 Department of Otorhinolaryngology Head & Neck Surgery, Algiers university-1.2 Department of Neurosurgery, Algiers university-1

Objective:TheAimofthepresentationistoreportthecontroversyonmanagementoftheneurologicdiseaseofneurovascularcompressionoftheeighthcranialnerve.Casepresentation:A41year-old-womanwhoisateacherattheUniversityandacandidatefordoctoralthesis,documentedfor4yearswithMeniere’sDisease,havingsymptomsofdisablingvertigo,tinnitus,auralfullnessandhearinglossontheleftside.Afterfailureofmedicaltreatment,surgerywassuggested.Thepatientdecidedtogoaheadwiththeoperation,duetothenegativeinfluenceofthevertigoandtinnitusonherqualityoflife.MRIofthebraindidn’tshowanyabnormalitybutMRIangiographyshowedaleftloopcompressionoftheanteriorinferiorcerebellarartery(AICA).Results:ARetrosigmoidapproachwasperformed.Intraoperativefindingsprovedtheradiologicfindings.TheAICAloopwasmobilizedandTeflonpadwasinterposedandseparatedfromthevestibularnerve.Neurotomyofthevestibularnervewascarriedout.Thepatient’ssymptomsresolvedaftersurgerywithafollow-upof5years.Conclusion:InthemanagementofMeniere’sDisease,MRIshouldincludesequencesthatarecapableofdemonstratingvascularanomaliesinpatientswithpersistenttinnitusandvertigo.Therateofsuccessofsurgicaldecompressionissatisfactory.However,itisstilldifficulttoconsiderneurovascularcompressionoftheeighthcranialnerveasamajorcauseofdisablingvertigoandtinnitus.

OTITIS MEDIA AND MENIERE’ S DISEASE

Dragoslava DjericMedical Faculty University of Belgrade, Clinic for Otorhynolaryngology, Clinical center of Serbia, Belgrade, Serbia

Meniere’sdiseaseisavestibulardisturbancewithaincidenceof12/1000peopleallovertheworld,characterizedbyvertiginousattacks,sensorineuralhearingloss,tinnitusandearfullness.Thesesymptoms,vertigobeingthemostdistressing,arecausedbythe presence of endolymphatic hydrops.Etiopathogenesis of disease include a various factors as: congenital, trauma, infection/inflammation,immunological,biochemical,geneticsandothers.However,natureofallmechanismsofendolymphatichydropsisstillunclear.Histopathologicaltemporalbonestudieshaveshownadifferentchangesonthestructuralelementsofinnerear.Becauseofthat,definitivecurativetreatmentforMeniersdiseasedoesnotcurrentlyexistandthetherapeuticprocedureismainlyaimedatreliefofvertigo,thatinthemajorityismostdistressingsymptoms.Frequently,wehaveseenthepatientswithsymptomsofMeniere’sDiseasewhohad previously some form chronicotitismedia (activeor inactive),withor without complications.AssociationofotitismediaandMeniersdiseaseisinterestingfordifferentiationofnaturediseaseascause-sequence.ThepurposeofourpaperistopresenttheresultourclinicalstudiedonconsequentlytreatingthepatientswithotitismediaandassociatedMeniere’sdisease.WeanalysedaninfluenceofpotentialfactorofchronicinflammationofthemiddleeartooccurrenceofMeniersdisease,butalso,forclinicalmanifestation,diagnosisandtreatment.WebelievedthatlongstandingmiddleearinflammationmayinfluenceonpathogenesisofMeniere’sDiseasewithimportancefordiagnosisandtreatmentofdiseases.

PSYCHOLOGICAL EVALUATION OF THE PATIENTS WITH VERTIGO DUE TO OTOLITH ORGANTakaakiKobayashi,ToruSeo,ShiraishiKo,MutsukazuKitano,KatsumiDoiDepartment of Otolaryngology, Kiniki University Faculty of Medicine

Introduction:Theotolithfunctionhasbeenabletobeevaluatedbyvestibularevokedmyogenicpotential(VEMP),thenanewclinicalentityasdisequilibriumduetotheotolithdysfunctionhasbeenestablished.Somecasesofthemcomplainedofseverepsychologicalproblems.Westudiedthepsychologicalexaminationsforthepatientswithotolithvertigo.Subjects and a Method:Subjectswere19patientswhowerediagnosedasvertigoduetootolithorgans.Thetentativediagnosticcriteriaforotolithvertigoisfollowing;1)thecomplaintwasofnon-rotatorydisequilibrium.2)AbnormalresultswereshownoncVEMPand/oroVEMP.3)Therewerenoabnormalresultsfromroutineexaminations.4)TherewerenocerebellarsignsorintracraniallesionsdetectedbybrainMRI.TheirpsychologicalconditionswereevaluatedusingCornelMedicalIndex(CMI),State-TraitAnxietyInventory(STAI)andaself-evaluationdejectionstandard(SDS).Inaddition,13patientswithbenignparoxysmalpositionalvertigo(BPPV)and27patientswithMeniere’sDiseasewerealsoevaluated.Result:AbnormalresultsonCMI(category3and4onFukamachi’sclassification)wereshownin58%,15%and37%ofthesubjectwithotolithvertigo,BPPVandMeniere’sDiseaserespectively.ThesubjectswithotolithvertigoresultedinhigherstateanxietythantraitanxietyinSTAI.Depressivetendency(>48inSDS)wasshownin20%,38%and33%ofsubjectswithotolithvertigo,BPPVandMeniere’sDiseaserespectively.Consideration:Thehighanxietyinthesubjectswithotolithvertigomayoriginatefromtherecurrenceofsymptomswithouttriggeranddiagnoseastheunknownorigininanotherclinic.Theirdailylivingswerenotlimitedthusthetendencyofdepressionwaslessinthesubjectwithotolithvertigo.

RELATIONSHIP BETWEEN CLINICAL PROPERTIES AND AUDIOVESTIBULAR FINDINGS IN PATIENTS WITH MENIERE’S DISEASE

BasakMutlu1,GunayKirkim1,FulyaKocyigit1,SerpilMunganDurankaya1,SelhanGurkan1,YukselOlgun2,EnisAlpinGuneri21 Dokuz Eylul University School of Medicine, Department of Otorhinolaryngology, Unit of Hearing, Speech and Balance, Izmir/Turkey2 Dokuz Eylul University School of Medicine Department of Otorhinolaryngology,Izmir/Turkey

Meniere’sDisease(MD)ischaracterizedbyendolymphatichydrops.TheaimofthisstudywastoanalyzetherelationshipbetweenaudiovestibularfindingsandhistoryofpatientswithMD.ENTexamination,clinicalhistoryandaudiovestibularevaluationswereperformedin93patientswithdefiniteMD.Fortyfivepatientsweremale,48werefemaleandthemeanagewas48.9±12.1years.ThemeandurationofMDwas5.6years.Themean0.5-2kHzand0.5-3kHzairconductionhearingthresholdswere46.8±21.4dBHLand47.4±22.3dBHL,respectivelyatthepathologicalsideofunilateralMDpatients(n:87).Inbilateralcases(n:6),thesevalueswere58±14.4dBHLand54.8±19dBHL,respectivelyattherightside;46±14.7dBHLand49.5±21.4dBHLrespectivelyattheleftside.Vestibularfunctiontestfindingsincludingeyesclosedtandemgait,sharpenedRombergandUnterbergertestswereencounteredabnormalover50%ofthepatients.Invideonystagmography,saccadicandtrackingeyemovementswerefoundasabnormalin5%ofthem.Spontaneousnystagmuswasdetected15%andbi-thermalcalorictestshowed50%canalparesisoftheinvolvedearofthecases.Patientagewasfoundtobesignificantlypositivelycorrelatedwithaudiologicalfindingsandtheattackseverity;olderpatientshadsignificantlyworsehearingthresholdsandmoreseverevertigoattacks.Therewasalsoastrongpositivecorrelationbetweenthecaloricresponsesandaudiologicalfindingsoftheinvolvedears.Thehearingstatusofthenoninvolvedsidewassignificantlycorrelatedwith theattackdurationandpresenceofheadache. Itwas concluded that audiovestibularfindings in addition to adetailedhistoryisnecessarytoobtainthesufficientinformationabouttheclinicalfeaturesofMDineachpatient.







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REVERSIBLE INNER EAR SYMPTOMS IN DESTRUCTIVE TEMPORAL BONE LESIONS

Yehudai Noam, Luntz MichalThe Ear and Hearing Program, Department of Otolaryngology—Head & Neck Surgery, Bnai-Zion Medical Center, Technion—Bruce Rappaport Faculty of Medicine, Haifa, Israel; and School of Education, Department of Communication Disorders, Tel Aviv University, Tel Aviv, Israel

Temporalbonelesionsareclassifiedasmalignantornon-malignant.Theyusuallypresentasdestructivelesions,mimickingchronicotitismedia.Innerearsymptoms,bothMeniere-likevertigoandsensorineuralhearinglossareinfrequentinitialmanifestationsoftheselesions.Twocasestudiesofpatientswith infectedtemporalbonelesionswhichdevelopedgradually,diagnosedinitiallyasa ‘Menière’s-like’attacksarepresented.Eventually,thesetwopatientswerediagnosedhistologicallywithPagetoidlesionandLangerhanscellhistiocytosis.Thepatientspresentedwithnewlyonsetacutedebilitatingvertigoandsensorineuralhearingloss.Imagingrevealedanextensivemastoidinvolvementwithdestructionofthesemicircularcanals.Bothpatientsunderwentsurgicalmanagementfordiagnosis and infectiondisease control, in faceof theunusualpresentationand inorder toprevent further inner eardamage.Postoperatively,theinfectionwascontrolledtogetherwithgradualresolutionofthevertiginoussymptoms,andanunexpectedsignificantimprovementofthesensorineuralhearingloss.Followupimagingrevealedradiologicalresolutionwithre-mineralizationoftheoticcapsuledestructionandnearnormalradiologicappearanceofthesemicircularcanals

SLEEP AND DIZZINESS HANDICAP INVENTORY PROFILES IN MENIERE’S DISEASE AND VESTIBULAR NEURONITIS

Dragoslava DjericMedical Faculty University of Belgrade, Clinic for Otorhynolaryngology, Clinical center of Serbia, Belgrade, Serbia

Introduction:Meniere’sDiseasehasbeenassociatedwithahighincidenceofsleepdisorder.GivenlifestyledifferencesbetweenpatientswithMeniere’sDiseaseinmetropolises,suchasTokyo,andthoseinlocalcities,suchasKochi,itisnecessarytoexaminethesleepprofileofMeniere’sDiseasepatientsinlocalcities.ThisreportprovidestheresultsofasleepsurveyconductedonpatientswithMeniere’sDiseaseinKochiCity.Patients:Thesurveywascarriedfor44patientswithMeniere’sDiseaseand11patientswithvestibularneuronitistreatedatourhospitalonanoutpatientbasiswhocompletedthefollowing:1)asleepquestionnaire,and2)theDizzinessHandicapInventory(DHI)betweenFebruaryandApril2015.Survey items:1)Sleepquestionnaire:sleeptime,sleepregularity,andtheuseofregularlyusedsleepingpills2)DHI:themeannumberofquestionsanswered“yes”perpatientandquestionscommonlyanswered“yes”bypatientsResults:1)Sleepquestionnaire:Therewerenosignificantdifferencesbetweendiseasegroupsintermsofsleeptime,sleepregularityandstatusofuseofsleepingpills.2)DHI:Therewasnosignificantdifferenceinthemeannumberofquestionsanswered“yes”betweendiseasegroups.Thequestionsmostcommonlyanswered“yes”wereNos.2,11,12and18bypatientsofbothdiseasegroups;Nos.3,6,9and24bypatientswithMeniere’sDisease;andNos.4and21bypatientswithvestibularneuronitis.Discussion:WechosevestibularneuronitisasacomparatorofMeniere’sDisease.DHI:PatientswithMeniere’sDiseasecommonlyanswered“yes”toquestionsNo.3,6and9,suggestingthattheywereanxiousaboutunexpectedonsetofdizziness.Thisanswerpatternalsoindicatestheirfeelingof“lackingthesenseofresponsibility”duetodizziness,whichisconsistentwithacommoncharactertraitofpatientswithMeniere’sDisease.Sleepquestionnaire:KochiCityisacitywithapopulationof300,000inKochiPrefecture,whichhasatotalpopulationof800,000.Themajorityofthepopulationconsistsofthoseengagedinprimaryindustry,suchasagricultureandfishery,suggestingadifferentlifestylecomparedtometropolises.Wethusspeculatethatthislifestyledifferenceaffectssleepprofiles.Conclusion:DHIresultsrevealedacommoncharactertraitofpatientswithMeniere’sDiseaseasreportedpreviously.TheresultsofthesleepquestionnairesuggestdifferentsleepdisorderprofilesbetweenpatientswithMeniere’sDiseaseinmetropolisesandthoseinlocalcitieslikeKochiCity.

THE MANY FACES OF MIGRAINE – AUDITORY AND VESTIBULAR PRESENTATION: A CASE STUDY

BorkaCeranic1,PaulRadomskij21 MD ENTspec PhD FRCP Consultant in Audiovestibular Medicine - Department of Audiology & Audiovestibular Medicine, St. George’s Hospital, London, UK2 Senior Clinical Scientist in Medical Physics- Department of Audiology & Audiovestibular Medicine, St. George’s Hospital, London, UK

Migraine is characterized by diversity in clinical presentations, which sometimes represent a significant clinical dilemma.This isacasestudyofa48yearoldman(MN)whopriortotheaudio-vestibularassessmenthadbeenextensively investigatedbytheneurologyandcardiologyteamsforunexplained“blackouts”-suddenlossofconsciousness(LOC).Healsohad2episodesofrighthemiparesis.NeurologicalinvestigationsincludedEEG,carotiddoppler,tilttabletestandCT/MRIbrainandcardiologicinvestigations24hrECG,transthoracicechoandarevealimplant,withnoabnormalityidentified.Audiovestibularpresentation.MNwasreferredtoAudiovestibular clinic forhearing loss4yearsafter initial LOC.MNhadhearingdifficulty, intermittent tinnitusandmarkedloudnessdiscomfort,greaterontheleft.AdetaileddescriptionofLOCwasobtained:LOCoccurredsuddenly,onaverageonceamonth,sometimeswhilesitting,usuallyincrowdedandnoisyplaces,precededbyabrieffeelingofeverythingbeing“brightandloud”,followedbyLOCforafewminutesandafeelingofnauseaanddizzinessupto2days.Healsohadepisodesofnauseaanddizzinessatnightandonwakinginthemorning,aswellasdizzinessanddisorientationinvisuallychallengingsituations.Inaddition,hehadintermittentleft“stabbing”headache.Familyhistorywaspositive:2of3hisbrotherswereaffectedbymigraine.Theclinicalexaminationrevealedastrongvisualdependency.Thepuretoneaudiometry(PTA)showedabilateralsensorineuralhearinglossofflatconfiguration:right30-40dBHL, left45-55dBHL.Strongtransientevokedotoacousticemissions (TEOAE)wererecordedontheright,whileonlythehigh-frequencyresponseswererecordedontheleft.Thecalorictestshowedasignificantleftdirectionalpreponderance(41%)andnon-significantrightcanalparesis(13%).Sinusoidalandrotationaltestsapplyingvideonystagmographyshowedleftdirectionalpreponderance.Visualenhancementofthevestibulo-ocularreflex(VVOR)wassignificantlyhigh;theVORsuppressionwasnormal.Vestibularevokedmyogenicpotentialswereabsentontheleft,whiletherewasalowVEMPthresholdontheright.Resultsinterpretation.TheelevatedPTAthresholdsinthepresenceofTEOAEweresuggestiveofasignificantauditorydysfunction,greaterontheleftandatthelowerfrequencies.Thevestibularfindingsweresuggestiveofadysfunctionwithasignificantasymmetryandincreasedvestibularsensitivity.Avestibulardysfunctionhasledtovisualdependency.Diagnosisandtreatment.Migraine-relatedauditoryandvestibulardysfunction,greaterontheleft,wassuspected.MNreceivedmigraineprophylactictreatment,followingwhichhishearingontherightreturnedtonormalandthelefttonearlynormal(25dBHL).ThefrequencyofdizzinesshassignificantlydecreasedandhehadnofurtherLOC.Discussion.Itappearsthatthesemicircularandotolithsystemswereaffectedindifferentwaysontheleft(worse)side:whiletheotolith systemappeareddepressed, the sensitivityof the semicircular systemseemed increased. Theauditory functionappearedaffected in a similar way as the otolith system, by depression. These findings reflect the complexity of the inner ear controlmechanisms,particularlyofthevestibularsystem.Theinterfacebetweenmechanismofmigraineandthecontrolmechanismsofauditoryandvestibularsystemswillbefurtherdiscussed.







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THE RISK OF MISDIAGNOSIS BETWEEN CHRONIC SUBJECTIVE DIZZINESS (CSD) AND MENIERE DISEASE (MD): A PSYCHOMETRICS ANALYSIS

G.Chiarella 1, C.Petrolo 1, R. Riccelli 3, E.Cassandro 21 Department of Experimental and Clinical Medicine, Audiology and Phoniatrics Unit, “Magna Graecia” University, Catanzaro, Italy2 Department of Medicine, University of Salerno, Italy 3 Department of Medical and Surgical Sciences, “Magna Graecia” University, Catanzaro, Italy

Chronicsubjectivedizziness(CSD)isaneurotologicdisorderofpersistentnon-vertiginousdizzinessorunsteadinessthatispresentthroughoutthedayfor3monthsormoreanditmaypersistforyears.Symptomsmaybeexacerbatedbyuprightposture,patients’ownmovements,exposuretofullfieldvisualstimuli,orperformanceofprecisionvisualtasks.CSDisusuallytriggeredbyneurotologicorothereventsthatcauseacuteattacksofvertigo,unsteadiness,ordizziness,suchasvestibularneuritisorpanicattacks.ThepathophysiologicprocessesunderlyingCSDareunknown,butmayrelatetopatients’failuretoreturntonormalposturalcontrolafteradaptingtothedemandsofacutevestibularcrises.CSDwasrarelyseenwithMénièreDisease(MD).OurstudystartsfromseveralexperiencesonpsychologicalfactorsinpatientswithCSDthatsuggestedthatpre-existinganxietyoralsoanxietydiathesismaypredictdevelopmentofCSDsymptomsafteracuteneurotologicillnesses.Incontrast,patientswithgreaterresilience,lifesatisfaction,andsenseofcoherencewerelesslikelytodevelopCSD-typesymptomsafteracuteneurotologicillnessesthanindividualswithlowerscoreonthesepositivecharacteristics.OuraimwastocompareMDandCSDpatientsandhealthycontrols(HCs)searchingforpsychometricselementsthatcanimproveourdiagnosticability,reducingtheriskofmisdiagnosisandconfusionbetweenCSDandMDpatients,especiallyinMD’sintercriticalphase.ParticipantswererecruitedfromtheAudiologyandPhoniatricsUnitofMagnaGraeciaUniversity,Catanzaro.Werecruited59subjects:19CSD,15definiteMDand25healthycontrols.Allpatientsunderwentaclinicalandinstrumentalevaluationincluding:1)detailedhistoryrelatedtodizziness/vertigo;2)self-reportsofimpairmentontheDizzinessHandicapInventory(DHI);3)vestibularlaboratorytesting; 4) imagingwith cerebral gadoliniumenhancedMRI, if indicated; 5) psychometric evaluationwith somequestionnairesGeneralizedAnxietyDisorderSeven-Item(GAD7),Nine-itemPatientHealthQuestionnaire (PHQ9),RevisedNEOPersonality Inventory, (NEO-PI-R).Groupswerecomparablefordemographic(ageandsex)variablesandstateanxiety.Atrendofdifferencewasfoundinstatedepression(p=0.06)anditwasdrivenbyahigherscoresintheCSDandMDgroupsrelativetoHCs.Thetwogroupsofpatientswerecomparablefordizzinessseverity(p=0.71).Significantdifferencesemergedin3groupsinpersonalityscoresinNeuroticism,OpenessandConscientiousness(p’s0.004,0.01and0.03respectively).MostofthesedifferencesweredrivenbythecomparisonsbetweenHCsandCSDgroupsand/orbetweenHCsandMDgroups,withlowdifferencesbetweenCSDandMDgroups.Thisallowsustosuggestapossiblecommonpsychologicalgroundinthetwogroups.inlocalcitieslikeKochiCity.

TINNITUS AND SPONDYLOARTHROSIS: A STRONG CONJUCTION BETWEEN ENT AND REUMATOLOGY

KuciAnjeza,ENT,MainPoliclinicoftheSpecialities,Nr.3,TiranaAlbaniaKollcakuJulia,Reumatologist,MainPoliclinicoftheSpecialities,Nr.3,TiranaAlbaniaBalaJKuci Anjeze, Kollcaku Julia, Bala JonidaTirana, Albania

Aim: evaluatetheroleofacoexistingspondyloarthrosisandabilateralhearingloss,duetoageorotherrelatedsystemicpathologiesinacommoncomplaintastinnitus2.agoodconjunctionbetweenanENTandareumatologistwouldimprovethecomplainoftinnitusalthoughweknowthatitwillneverdisappear completely.Wehave takenunder consideration30patientsbetween65-70yearsold complainingof: bilateraltinnitus,bilateralhearingloss,dizziness,cephalalgiaanddifficultyinmovingtheposteriorpartoftheneck.Afteranormalotoscopicexam,weperformedanaudiometryshowingamiddletoseverebilateralhearinglossduetoageothersistemicdisorders,orwork,normaltimpanometry.Thanweperformedaconsultwiththeneurologist,shedidnotfindanyneurologicalproblems.Thepatientscomplain,thattheirtinnitusbecameworstwhilemovingtheneck,bending,orwhileatmosphericpressureduetobadweatherchanged.Weperformedaconsultwiththerheumatologist,afterthexraysoftheneckexaminationhefound:cervicalspondyloarthrosisoftheposteriorpartofthespinewithdegenerativeprocessesandosteophytosis.Medication:AINSD,analgesics,physiotherapy,aswellasvasodilatatorsandvitamintherapytoimprovetinnitus.Boththesetherapiesforallofourpatientsimprovethetinnitusandtheycomplainedlessalthoughtinnitusdidnotdisappearcompletely.Conclusion:knowingthattinnitusisthemostcommoncomplainofthethirdagedpatientsthatsometimescausesneurosisaswellwehavetodoourbesttoimproveitandinourstudyagoodconjunctionbetweenENTandrheumatologistmadeitreal.

COCHLEAR IMPLANTATION AS A METHOD OF REHABILITATION OF TINNITUS

LevinaE1,LevinS1,2,KuzovkovV1,VoronovV2.1 Saint-Petersburg Institute of Ear, Nose, Throat, and Speech2 North-Western State Medical University named after I.I. Mechnikov

Introduction:About86%ofpatientswithprofoundhearing loss tinnitus bothers. Cochlear implantation is themost effectivemethodofrehabilitationofdeafnessinthemodernworld.Aim:Toevaluatetinnituspatientsaftercochlearimplantation,dependingonage,durationandetiologyofdeafness.Methods:Weexamined384patientsaged14-72(years)(237womenand145men)withprofoundsensorineuralhearinglossandtinnitus complaints. Cochlear implantation was performed in all cases. Unilateral implantation was performed in 376 patients,bilateralin8patients.Theseverityinpatientsexperiencingearswasassessedusingavisualanaloguescalebeforeimplantation,thefirstfittingsoundprocessor,and6monthsaftertheinitialfitting.Weanalyzedthedependenceofseverityoftinnituspatientsage,durationandetiologydependingcochleardeafnesspriortoimplantation.Results:At6monthsafterthefirstfitting2%oftinnitusdisappeared,81%ofpatientswithtinnituspatientshasdecreased,butnotdisappear,and16%oftinnituspatientsremainedunchanged,and1%ofpatientstinnitushasincreased.Tinnitussignificantlydecreasedinthemajorityofpatientsofallages,etiologyanddurationofdeafnessbeforethecochlearimplant.Conclusions:Thus,Cochlearimplantationreducestheseverityoftinnitusinpatientswithprofoundsensorineuralhearingloss.Inadditiontotheeffectofhabituation,reducingtinnitusmaybeduetoacousticmaskinganddirectstimulationoftheauditorynerve.Thisobservationwasconfirmedbythecochlearimplantasaneffectivetreatmentforpatientswithsingle-sideddeafnessandseveretinnitus.







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COCHLEAR IMPLANTATION IN A PATIENT WITH PAGET’S DISEASE

Noam Yehudai, Amit Wolfovitz, Talma Shpak, Rabia Shihada, Michal LuntzThe Ear and Hearing Program, Department of Otolaryngology—Head & Neck Surgery, Bnai-Zion Medical Center, Technion—Bruce Rappaport Faculty of Medicine, Haifa, Israel

Paget’sdisease(alsoknownas:osteitisdeformans)isthesecondmostcommonmetabolicbonedisease,characterizedbyincreasedbone turnover with osteoclastic phase, followed by mixed phase and exaggerated osteoblastic (sclerotic) phase. This results inpainfulbonylesions,aswellashyperuricemia,hypercalcemia,cardiovascular,neurologicandneoplasticfindings.Developmentofasignificanthearingloss,asaresultofchangesinthemineraldensityoftheOticcapsule,isoftenseenaswell.Wereporta59-year-oldmalewithPaget’sdiseasewhosufferedsevere-to-profoundhearingloss.Thepatientgainedminimalbenefitfromconventionalhearingaidsandwasreferredtoourcenterforcochlearimplantation.Preoperativeevaluationshowedverypoorcommunicationskills,evenrelativelytohisaidedpuretonethresholdandraisedconcernsregardingpost-implantationoutcomes.Nevertheless,thepatientunderwentcochlearimplantationsuccessfully.Followupforninemonthsshowedsignificantimprovement.However,objectivemeasurementsusingtheNeuralResponseTelemetry(NRT)havenotrecordedanyElectricalcompoundActionPotential(EAP)yet.SinceveryfewpublicationsoncochlearimplantationinPaget’sdiseasewerefoundintheliterature,wewishtoshareourlongterm(6years)clinicalexperienceandhearingrehabilitationdilemmasinvolvedinsuchacaseinordertobetterpredicttheoutcomeinpatientswithPaget’sdiseasefollowingcochlearimplantation.

FEATURES SOUND PROCESSOR SETTINGS IN PATIENTS AFTER ABI

Levin S. 1,2 , Koroleva I. 1 , Kuzovkov V. 1 , Levina E.1, Voronov V. 21 Saint-Petersburg Institute of Ear, Nose, Throat, and Speech2 North-Western State Medical University named after I.I. Mechnikov

Introduction:Insomecases,patientswithbilateraldeafnessisimpossibleorinappropriateconductcochlearimplantation(incaseofdamageorauditorynerveaplasia,aplasiaorsignificantossificationofthecochlea).Forthesepatients,theauditorybrainstemimplantiscreated(ABI),whichallowstostimulatethecochlearnucleusofthebrainstem.InRussiathefirst3operationsauditorybrainstemimplantationtookplaceinDecember2014incooperationwiththeResearchInstituteofSt.PetersburgENT,RNHIthem.prof.ALPolenova,neurosurgicalClinicFulda.Aim:TostudythefittingABI,differencessoundprocessorfittingcochlearimplantandABI.Results: Duringtheoperation,determinedbythelocalizationoftheelectrodearrayintheventralcochlearnucleusbyregisteringbrainstempotentialstoelectricalstimulation(eABR)thathavebeenregisteredinonlyoneadultpatientwithneurofibromatosis2.Thesecondpatientwithneurofibromatosis2andachildwithacochlearaplasiaeABRregisterfailed.ConnectingtheprocessorABIconductedin1.5monthsafteroperation.Inadultpatients,settingtheparametersofelectricalstimulationwascarriedoutontheirsubjectivefeelingsusingscalesassessthestrengthoftheauditoryandauditorysensations,aswellasthepatient’sreactionstosoundsandobservationsSpeech-LanguagePathologists.FirstconnecttheprocessorABIthechildwasheldinintensivecare.Inthefuture,thecorrectionsettingsfromthestimulationofthechildconductedbybehavioralreactionsandobservationsSpeech-LanguagePathologists.During stimulationof individualelectrodes,patientshavenoauditory sensations-vestibular,andothervegetative reactions. Electrodes, causing persistent side feeling increasing level of incentives were subsequently disabled. As aresult,onepatient8wereactivatedelectrodesinthe2nd-6electrodeschild-7electrodes.Oneoftheadultsobservedinvertedperceptionofpitchinthestimulationofthelow-andhigh-frequencyelectrode,whichisalsotakenintoaccountwhenconfiguringtheprocessor.Conclusion:Thedevelopmentofauditorybrainstemimplantwillallowfortherehabilitationofpatientswithhearinglosscausedbynotonlythepathologyoftheinnerearandoverlyingpartoftheauditorypathway(aplasiaoftheauditorynerve,neurofibromatosistype2,traumaoftheinnerearandauditorynerve).

COCHLEAR IMPLANT

INNER EAR ABNORMALITIES IN COCHLEAR IMPLANT CANDIDATES

AminaMOUZALI-MohamedSalahHARAOUBIA-KheireddineOUENNOUGHI-MohamedZakariaSADI-OmarZEMIRLIDepartment of Otorhinolaryngology Head and Neck Surgery University Hospital Beni Messous Algiers Algeria

Objectives: The purpose of this study is to analyze the inner ear abnormalities diagnosed in

PERSISTENT VESTIBULAR SYMPTOMS AFTER COCHLEAR IMPLANTATION – CLINICAL OVERVIEW

M.Sosna1,K.Pietrasik1,G.Tacikowska1,P.H.Skarżyński1,2,3,H.Skarzynski11. World Hearing Center, Institute of Physiology and Pathology of Hearing, Kajetany/ Warsaw, Poland2. Medical University of Warsaw, Warsaw, Poland3. Institute of Sensory Organs, Kajetany, Poland

Aim: Cochlear implantation is worldwide fully accepted method dedicated to patients with total or partial bilateral deafness.Nevertheless,vestibularandbalancedisordersarestilloneofthecommoncomplaintsamongthepatientsaftertheoperationandwhileusingtheimplant.Accordingtotheliteraturedata,thepercentageofvestibularsymptomsrangesfrom5,9%to80%andthatofvestibularexaminationabnormalitiesfrom20-60%.Mostly,thesymptomsaretransientandinearlypostoperativeperiod.Thestudyaimsatassessingtheclinicalreasonsforpersisting(lastingmorethan2months)vestibulardisordersafteroperationthatappeareddirectlyorwithdelayaftertheoperation.Materials and Methodology:Theretrospectivestudyofpatientsaftercochlearimplantation,boththroughcochleostomyorroundwindowapproach(PDT-EC,PDT-EAS,PDT-ES).Results: Persistentsymptomsaftercochlearimplantationarerare.ThemostfrequentreasonforvestibulardisordersisBPPV(benignparoxysmalpositionalvertigo)fromtheposteriorsemicircularcanal,followedbyvestibularhypo-orareflexiaonimplantedside.Otherpotential reasons likeperilymphfistula,endolymphatichydropsseemstobecasuistic.ThepatientswithBPPVshowgoodresponse for repositioning maneuvers. Those with hyporeactiveness of vestibulum on implanted side were proposed vestibularrehabilitation.Conclusions:Cochlearimplantationmayinfluencevestibularfunctionandgivepersistentsymptomsinrarecases.However,thereareeffectivetreatmentoptionsthatmaybeofferedforthesepatients.

RESIDUAL HEARING IN CANDIDATES FOR COCHLEAR IMPLANTATION

YaelGarti,NoamYehudai,TalmaShpak,MichalLuntzThe Ear and Hearing Program, Department of Otolaryngology - Head and Neck Surgery, Bnai Zion Medical Center, Technion-Bruce Rappaport Faculty of Medicine, Haifa, Israel

Introduction:Duringthepasttwodecadescochlearimplant(CI)technologyimprovedsignificantly,otologicsurgeonsworldwidehaveacquiredthesurgicalskillsneededandbothsurgeonsandcliniciansgainedtheconfidenceinthelongtermhearingresults.ThecriteriaforCIhavebeenwidentoincludeindividualswithlowfrequencyresidualacoustichearingwhosespeechunderstandingwithhearingaidsisinsufficientandexpectedtoimprovewithCI.Hearingoutcomeofelectro-acousticstimulationhasbeenprovedtobebetterthanCIaloneduetolowfrequenciescuesprovidedbytheacoustichearing.However,asoftoday,itisnotpossibletoguaranteeacoustichearingpreservationduringCIsurgery.Objectives:Todeterminetheamountofresidualacoustichearingintoday’sCIcandidatesinordertoestablishtheeffectivenessoftheeffortsinvestedinhearingpreservationincochlearimplantation.Material and Methods: Pre-implantation pure tone thresholds were assessed in 102CI candidates who underwent CI surgerybetween2011and2013.Allcandidateswereatleast11yearsofageatsurgery.Results: At250Hzthresholdwere80dBorbetterin41%ofCIcandidatesandin15%thresholdswere65dBorbetter;At500Hz,thresholdwere80dBorbetterin18%ofCIcandidatesolderthan11yearsandin7%,65dBorbetter;At1000Hz,2000Hzand3000Hzthresholdwas≤80Bin7%;At4000Hzthresholdwas≤80dBin5%.Conclusions:AsignificantpercentageofCIcandidatesareimplantedwhilestillhavingresidualacoustichearingintheearplannedforimplantation.ItisimperativetofurtherrefinethetechnologyandsurgicalmethodsforhearingpreservationduringCIsurgery.







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SETTING EXPECTATIONS FOR SPEECH UNDERSTANDING IN QUIET AND IN NOISE IN STRAIGHTFORWARD ADULTS COCHLEAR IMPLANT CANDIDATES

Michal Luntz, Talma Shpak, Dana Egra-Dagan, Ranin Khayr, Noam Yehudai, Tova MostThe Ear and Hearing Program, Department of Otolaryngology – Head and Neck Surgery, Bnai Zion Medical Center, Haifa; Technion – The Bruce Rappaport Faculty of Medicine, Haifa, Israel

Introduction: Thehugeamountsofcochlearimplantation(CI)outcomesdatacollectedoverthelastdecadesclearlyshowthatinmostCIrecipientsexpectationaremet.NeverthelesscandidacyevaluationforCIremainedsomewhatcumbersome(andthereforeexpensive),evenforthestraightforwardadultCIcandidates.Objective:Todeterminemonosyllabicwordrecognitionscoresinagroupofcochlearimplanteeswhowereconsideredstraightforwardcandidatespriortoimplantation(normallanguage,fullyinvolvedinthehearingsociety,normalcochleaonimaging,noorminimalauditorydeprivationprior to implantation), inanattempttodeterminebase-linevalues thatcanbeusedfor futurecandidacyevaluationinsimilarcandidates.Patients: 30 experienced adult users of the type mentioned in the ‘objectives’ (defined as straightforward candidates prior toimplantationbyhavingnormallanguage,fullinvolvementinthehearingsociety,normalcochleaonimagingandnoorminimalauditorydeprivationpriortoimplantation).Intervention:Patientswereevaluatedwiththemonosyllabicwordrecognition(AB)testatpresentationlevelof50dBHLwithandwithoutcompetingspeechnoiseSNR+5dB(boththespeechandthenoisewerepresentedat0˚azimuth).Results:Theimprovementonmonosyllabicwordrecognition(HAB)afterCIwasprominent.Priortoimplantationthemeanscoreonmonosyllabicwordsaveraged25%inquietandwasmuchlowerwithbackgroundnoise.Afterimplantationitwas75%inquietand44%inbackgroundnoise.Whenusingalsotheircontra-lateralHA,asignificantfurtherimprovementwasnoted.Conclusions:BaselinevaluesforthemonosyllabicwordsscoresinstraightforwardCIuserswereestablished.ThesevaluescanbeusedforpredictingCIoutcomeinsimilarstraightforwardadultsCIcandidatesbycomparingtheirperformanceinthebestaidedconditiontothescoresachievedbytherepresentinggroupofimplanteesassessedinthepresentstudy.

COCHLEAR AND VESTIBULAR EFFECTS OF COMBINED INTRATYMPANIC DEXAMETHASONE AND GENTAMYCINE

Enis Alpin Güneri 1, Yüksel Olgun 1, Mustafa Aslıer 1, Daniele Nuti 2, Günay Kırkım 3, Serpil Mungan Durankaya 3, Efsun Kolatan 4, Safiye Aktaş 5, Franco Trabalzini 2, Hülya Ellidokuz 6, Osman Yılmaz 4, Marco Mandala 21 Dokuz Eylül University School of Medicine Department of Otorhinolaryngology, Izmir, Turkey2 Azienda Ospedaliera Universitaria Senese, Otology and Skull Base Department, Siena, Italy3 Dokuz Eylül University School of Medicine Department of Audiology, Izmir, Turkey4 Dokuz Eylül University School of Medicine Department of Laboratory of Animal Science, Izmir, Turkey5 Dokuz Eylül University Institute of Oncology Basic Oncology Department, Izmir, Turkey6 Dokuz Eylül University School of Medicine Department of Biostatistics, Izmir, Turkey

IntratympanicgentamycineisaneffectivetreatmentmethodforMeniere’sDisease(MD).UnfortunatelyototoxicityisabigdrawbackforgentamycineandithindersitsusageespeciallyinpatientswithserviceablehearingthresoldsorbilateralMD.Theaimofthisstudyistoevaluatecochlearandvestibulareffectsofintratympanic(IT)applicationsofgentamycineandcombineddexamethasone+gentamycinetreatments.TwentysixfemaleWistaralbinoratsweredividedintofourgroupsasfollows;groupI(Control,n:6),groupII(Dexametasone,n:5),groupIII(Gentamycine,n:7),groupIV(Gentamycine+Dexametasone,n:8).OnthefirstdayofthestudybasalABR(4kHz,8kHz,16kHz,32kHz)measurementsweredone.Then0,02mlintratympanicgentamycine(26.7mg/ml)wasappliedintheanterosuperiorportionofrighttympanicmembraneofthegroupIIIrats.Acombinationsolutionwaspreparedwiththedilutionofgentamycineindexamethasone(withafinalconcentrationof13,35mg/mlgentamycineand2mg/mldexamethasone)then0,04mlofthissolutionwasappliedintratympanicallyingroupIVand0,02mlofserumphysiologicanddexametasone(4mg/ml)wasappliedrespectivelyingroupsIandII.Onthe7thdayofthestudyABRmeasurementswererepeatedandvestibularfunctionswereevaluatedbyairtightreflex,swimmingandtailhangingtests.Ablindobserverratedthesetestsas0(normal),1(mildlyaffected)and2(severelyaffected).Onthe21stdayofthestudy,ABRandsamevestibulartestswererepatedandanimalsweresacrificedtoevaluatetheirinnerearstructures at three levels( cochlea, vestibule and spiral ganglion) by lightmicroscopy for histopathological changes and TUNELstainingforapoptosis.Ingentamycinegroup,hearingthresholdsweredeterioratedinallfrequenciesforbothinearlyandlateaudiologicalmeasurements.IngroupIVat7thdayhearingthresholdsweresignificantlybetterthangroupIIIexceptfor8kHz.At21stdaygroupIVhearingthresholdsweresignificantlybetterthangroupIIIinallfrequencies.IngroupIandIIhearingthresholdswerenotdeterioratedinanyofthemeasurements.Accordingtoobserver,groupIIIandIVvestibularfunctionscoreswerehigherthancontrolgroupsbothin7thand21stdaymeasurementsandtherewerenostatisticallysignificantdifferencebetweenthesetwogroups.Histopathologicalinvestigationsrevealedsevereapoptosisinspiralganglions,mildapoptoticchangesinthecochleasandvestibulesofgroupIIII.IngroupIVapoptoticchangesinthespiralganglion,cochleaandthevestibulewereclosetocontrolgroup.Weobservedthatapplicationofdexametasonewithgentamycinledtoasignificantimprovementinthehearingthresholdsofrats.Althoughbysubjectivevestibulartestsinbothgentamycinandcombinationgroupsvestibulotoxicicitywaspresenthistopathologicalresultsshowednovestibulotoxicityinthecombinationgroup.Thereforewethinkthatintratympanicapplicationofdexametasoneandgentamycincombinationprovidesprotectionagainstototoxicitybyloweringthevestibulotoxiceffectofgentamycine.

TRANSTYMYPANIC INNER EAR DRUG THERAPY

Aziz BelalAlexandria, Egypt

WestartedintratympanicdrugtherapyofMeniere’sDiseaseinAlexandria,Egyptin1993.Inlightoftheresultsofintratympanictherapyandtheanatomicalandoperativeobservationsofthepresenceoffalseroundwindowmembraneinalmost50%ofthecases,westartedtranstympanicdrugtherapy:microscopic(2003)andendoscopic(2013).Inthispresentation,wedescribetheindications,equipment,rationale,technique,personalseriesandfuturedirections.

CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IN THE ENDOLYMPHATIC SAC OF THE RAT

A. Matsubara, T. Miyashita, R. Inamoto, H. Hoshikawa, N. Mori1 Department of Otolaryngology, Faculty of Medicine, Kagawa University2 Osaka Minato Central Hospital

Aims and Introduction:Intheendolymphaticfluidintheendolymphaticsac(ES),Na+andCl–aredominantions,andbotharethoughttobeimportantforvolumeregulation.Na+,K+–ATPaseatthebasolateralmembraneofESepithelialcellsprovidesthedrivingforceforNa+absorption.TheNa+flowisgenerallycoupledwithCl–flowtoneutralizethechargemovement,therebyguaranteeingionicneutrality.However,nochloridechannelshavebeenidentifiedintheES.Cysticfibrosistransmembraneconductanceregulator(CFTR)isaplasmamembranecAMP-regulatedCl–channel.TheCFTRalsoactsasaregulatorbyexertingmodulatoryinfluenceovertheepithelialsodiumchannel(ENaC).IntheES,ENaCwasidentifiedinhumanandguineapigsandshowntobelocalizedattheapicalmembrane.TheaimofthisstudywastoexaminetheexpressionofCFTRinESepithelia,whichmayplayrolesintheregulationofendolymphintheES.Methods: Four-week-oldfemaleSprague–Dawleyratswereused.SpecificmRNAfromESepitheliawaspreparedusinglasercapturemicrodissection(LCM)andexaminedusingRT-PCR.LocalizationofCFTRandENaCintheendolymphaticsacwasexaminedusingimmunohistochemistry.Results and Conclusions:RT-PCRformtheESsamplesdetectedtheexpressionofmRNAoftheCFTR.ImmunohistochemicalanalysisshowedtheexpressionoftheCFTRonapicalsideoftheESepitheliaandco-localizationwiththeENaC.TheseresultssuggestapathwayforCl–,possiblythroughinteractionwiththeENaC,whichmayregulatetheendolymphintheES.

HUMAN ENDOLYMPHATIC SAC AND COCHLEAR WATER CHANNELS- IMPLICATION TO INNER EAR FLUID HOMEOSTASIS AND MECHANISM OF MENIERE´S DISEASE

Wei Liu, Helge Rask-AndersenDept of ORL, Uppsala University Hospital, Uppsala, S-751 85, Sweden

Menièresdisease (MD)continues todefyandconfound theclinical/scientificcommunitymore than150yearsafter itsoriginaldescription.AlreadyGuild(1927),Portman(1927),HallpikeandCairns(1938),Yamakawa(1938)andKimuraandSchuknecht(1965)suggestedthatMDiscausedbyadysregulationofendolymph.Yet,themechanismsbywhichendolymphquantityandcompositionare regulated and the molecular mechanisms governing water permeation across the duct epithelium remain elusive. AVP/V2Rcomplexmayplayasignificantroleinlocalfluidhomeostasis.Immunohistochemistrysuggestsco-expressingAQP4andAQP5inhumancochlea. AQPswerealso found inhumanendolymphatic sac (ES)epithelia.However, results fromhumanspecimenarestill rarecomparingtoanimalstudyresults.Humaninnereartissuewasobtainedatsurgery inUppsalaUniversityHospitalandsubjectedtoimmunohistochemicalstudy.ThestudyconformstoTheDeclarationofHelsinkiandwasapprovedbythemedicalethicalcommitteeattheUppsalaUniversityHospital(2013).Patientsconsentwasobtained.AQP4and5werefoundinhumancochleaaswellasintheendolymphaticsacepithelia.V2RisalsoseenintheepitheliaofhumanES.Theexpressionpatternofwaterchannelsinhumancochleaisalsopresented.







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COMBINED TREATMENT ENDOLYMPHATIC SAC

PROX1 EXPRESSION IN THE ENDOLYMPHATIC SAC REVEALED BY WHOLE-MOUNT FLUORESCENT IMAGING OF PROX1-GFP TRANSGENIC MICE

T. Miyashita 1, J. L. Burford 2, Y. K. Hong 3, H. Gevorgyan 2, L. Lam 2, H. Hoshikawa 1, N. Mori 1,4, J. Peti-Peterdi 21 Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa, Japan2 Departments of Physiology and Biophysics and Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A.3 Department of Surgery and Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A.4 Osaka Minato Central Hospital, Osaka, Japan

ThetranscriptionfactorProx1belongstothefamilyofhomeoboxtranscriptionfactors.Prox1iscriticalfororgandevelopmentduringembryogenesisandisinvolvedinneurogenesis.Prox1regulatesdifferentiationofprogenitorcellsandinitiationofneurogenesis.Intheinnerear,Prox1isexpressedinvestibularhaircells,endolymphaticduct,andsupportingcellsintheembryonicstagebutnolongerdetectableintheadultstageexceptinthespiralganglion.ThefunctionofProx1inthecochleaandvestibuleisthoughttorelatetothestateofdifferentiationofthestem/progenitorcells.Intheendolymphaticsac,theexpressionofProx1hasnotbeenreported.OurrecentstudysuggeststhatendolymphaticsacepithelialcellsintheintermediateportionhavesufficientNa+,K+-ATPaseactivitytoprovidethedrivingforcefortheNa+transportrequiredtoabsorbtheendolymph.Thisactiveiontransportneedssufficientbloodsupply.Infact,severalearlierreportshavefoundmanyvesselsintheendolymphaticsac.Tofurtherinvestigatetheendolymphaticsacandassociatedbloodvesselsinmoredetail,threedimensionalimagingofendolymphaticsacepithelialcellsandvesselsusingconfocallaserscanningmicroscopyormultiphotonfluorescencemicroscopymaybefeasible,however,technicaldifficultiessofarhavepreventedtheopticalsectioningthroughthetemporalboneandthethreedimensionimagingoftheendolymphaticsac.Inthisstudy,weestablishedawhole-mountimagingapproachtodirectlyvisualizetheendolymphaticsac,andexaminedProx1expressionintheendolymphaticsacepitheliainadultmice.Prox1-GFPBACtransgenicmiceweredeeplyanesthetized,andwereinjectedwith10μLoftetramethylrhodaminelabeleddextranintravenously.After20min,themousewasperfusedviatheleftventriclewith4%PFA.Thesampleswerefixedin4%paraformaldehydeinPBSanddecalcifiedin0.12MEDTAat4°Cfor7days.Thetemporalboneandthecochleawereexaminedusinga2-photonlaserscanningfluorescencemicroscope.Thedecalcifiedtemporalbonesandbrainwereembedded inOCTtissuecompound.Sections werecutonacryostatat−20°C.Immunostainingwasperformed.Results and Conclusions: Whole-mount imaging techniques through the decalcified temporal bone and three-dimensionalobservationsofProx1-GFPmousetissuerevealedthepositivelabelingoftheendolymphaticsacinadultstage,andallowed,forthefirsttime,theGFP-basedidentificationofendolymphaticsacepithelialcells. Prox1expressionwasobservedinallpartsoftheendolymphatic sac epithelia. In intermediate portion of the endolymphatic sac, mitochondria-rich cells did not express Prox1,although ribosome-rich cells showed strongGFP labeling. Theanatomical relationshipbetween the endolymphatic sac and thesurrounding vasculature was directly observed. In the endolymphatic sac, expression of Prox1 may suggest progenitor cell-likepluripotencyordevelopmentalsimilaritytosystemiclymphaticvesselsinotherorgans.Thiswhole-mountimagingtechniqueoftheendolymphaticsaccanbecombinedwithotherconventionalhistological,sectioning,andlabelingtechniquesandwillbeveryusefulforfutureendolymphaticsacresearch.

THE HUMAN ENDOLYMPHATIC SAC IS AN INTRACRANIAL ENDOCRINE GLAND

Martin Nue Møller 1 M.D, Svend Kirkeby 2 DMSc, Jonas Vikeså3 Ph.D, Finn Cilius Nielsen3 M.D. DMSc, Per Cayé-Thomasen1,4 M.D, DMSc1 Dept. Of Oto-rhino-laryngology, head and neck surgery, Rigshospitalet DK – 2100 Copenhagen Denmark2 Department of Oral Medicine, Dental School, Panum Institute, University of Copenhagen, Copenhagen, Denmark3 Center for Genomic Medicine, University of Copenhagen, Rigshospitalet, DK - 2100 Copenhagen, Denmark4 The Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

Thefunctionofthehumanendolymphaticsachasbeenenigmaticfordecades.Severalhypotheseshaveemergedhowever,includingcontrollingendolymphaticfluidhomeostasisaswellas immunologicaldefenseofthe innerear. Inaddition,severalstudiesgiveindicationsofapossibleendocrinecapacityandayetundefinedroleinintracranialpressurehomeostasis.However,asofyet,nodirectevidenceofsuchcapacityexists.Accordingly,thisstudyaimstoexploreandidentifythehypothesizedendocrinecapacityofthehumanendolymphaticsac.DNAmicro-arraysandimmuno-histochemistrywereusedforanalysesoffreshhumanendolymphaticsactissuesamples.Twelvetissuesamplesfromthehumanendolymphaticsacwereobtainedduringtranslabyrinthinesurgeryforvestibularschwannoma.Microarraytechnologywasusedtoinvestigatetissuesamplegeneexpression,usingadjacentduramaterascontrol.Theexpressionofgenesspecificforanendocrinefunctionwasdeterminedandresultsforselectedkeymoleculesverifiedbyimmuno-histochemistry.SeveralpotentnatriureticpeptideswasfoundexpressedsignificantlyintheESsuchasUroguanylinandBNP,aswellaspeptidesregulatingvasculartone,includingAdrenomedullin2.InadditionbothNeurophysinandOxytocinwasfoundsignificantlyexpressed.Allpeptideswereverifiedbyimmuno-histochemistry.The present data support the human endolymphatic sac as an intracranial endocrine/paracrine gland with potent natriureticcapacity.Furthermore,theendolymphaticsacmayinfluencethehypothalamo-pituitary-adrenalaxisandmayregulatevasopressinreceptorsandAQP-2channelsintheinnerearviaOxytocinexpression.Thus,theendolymphaticsacislikelytoregulateinnerearendolymphatichomeostasis throughparacrinesecretionofseveralpeptides,butmayalso influencesystemicand/or intracranialbloodpressurethroughdirectandindirectactiononthevascularsystemandthekidney.

THE HUMAN VESTIBULAR AQUEDUCT AND LVAS – ANATOMICAL AND RADIOLOGICAL ASESSMENTS

C. K. Nordström, H. Rask-AndersenDept. of Surgical Sciences, section for Otolaryngology and Head and Neck Surgery, Uppsala University Hospital

Thehumanendolymphaticduct(ED)andsac(ES)runsinabonychannelnamedthevestibularaqueduct(VA).Itextendsfromtheinternalapertureatthemedialwallofthevestibuletotheexternalapertureattheposteriorsurfaceofthepetrouspyramid.TheEDisaminisculeepithelialextensionofthemembranouslabyrinthwithadiameteraround0.1-0.2mmwhiletheESformsatriangulardilationintheVAandduranearthesigmoidsinus.Theirfunctionalrolesarestilluncertain.WhilepathologicalchangesoftheEDandEShavebeenassociatedwithMeniere´sdiseaseabnormaldilationoftheVAisobservedinlargevestibularaqueductsyndrome(LVAS).Itisassociatedwithprogressivesensorineuralhearinglossandalsootherinnerearmalformations.VAopercularsizehasshownadirect correlationwithaudiometricoutcomeandborderlineenlargedvestibular aqueductmeasurementsappear tobeassociatedwithsensorineuralhearingloss.MutationsofSLC26A4geneorPendrin,evenintheheterozygousstate,wereassociatedwithenlargementofthevestibularaqueductandabnormalvestibule.SurgicalobliterationoftheVAwassuggestedtoarresthearingloss(Wilsonetal.1997).MorphologicalreferencedataandradiologicalassessmentoftheVAinLVASisstillsomewhatelusive.Here,weanalyzednormalsizevariationsandmorphologicalcharacteristicsin31specimensselectedforthestudyharvestedfromautopsy.324plasticcorrosioncastsbelongingtothehumantemporalbonecollectionoftheUppsalaUniversitywereanalyzedtoobtainstatisticsforassessingnormalsizevariationsandradiologicalprojections.







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EXOME SEQUENCING DATA INVOLVE MULTIPLE GENES AND PATHWAYS IN FAMILIAL Meniere’s Disease

Lidia Frejo 1, Teresa Requena 1, Carmen Martin-Sierra 1, Sonia Cabrera 1, Jose A. Lopez-Escamez 1, 21Otology & Neurotology Group CTS495, Centre for Genomics and Oncology Research (GENYO), Granada2Department of Otolaryngology, Hospital de Poniente, El Ejido, Almeria

Meniere’sDisease(MD)hasaprevalenceabout0.5-1/1000individuals.MostofMDpatientsareconsideredsporadic,evenifaround8to10%arefamilialcasesinEuropeandescendentpopulation.TheaimofthisstudyistoidentifycommongenesandpathwaysinvolvedinFMDbyusingexomesequencingdataandgenenetworksanalyses.FiveSpanishAD families, fourof themwithat least twopatientswithdefiniteMDandafifth familywithmonozygotic twinswithMD,accordingtothediagnosticcriteriaoftheAAO-HNS(1995),wereselectedforthisstudy.AfterDNAisolationandexomeenrichmentandcapture,whole-exomesequencingwasperformed in21casesandcontrols inaSOLiD5500xlplatform.All themutationsfoundinthehealthyrelativeswereconsideredasprivateSNVs,andexcludedforfurtheranalyses.FourdifferentstrategiesweredesignedtofilterandprioritizeSNVs:a)calculationofapathogenicvariantrisk(PAVAR)compositescore;b)Exomiserv2software;c)VAASTannotationtoolandd)acombinationofVAASTandPhevortools.Finally,ageneontologyandpathwayanalysisofgenesharboringdeleteriousvariantswasachievedbytheIngenuityPathwayAnalysis(IPA)softwareforeachpedigree(IPA®;IngenuitySystems,RedwoodCity,CA,USA).Withineachfamily,thetop10,20and50genescontainingrarevariantswereselectedfortheanalysestodefinecandidatecanonicalpathwaysandtofindoutconnectionsbetweengenesbymeansofnetworks.Agene listwasgenerated includingthecommongenes that remained in the top10,20or50genes fromeachfamilydatasetaccordingtothefourprioritizingtools.SeventeencandidatecanonicalpathwayswereobtainedforfamilialMD.Themostsignificantcanonicalpathwayswere:toll-likereceptorsignaling,NRF2-mediatedoxidativestressresponseandaldosteronesignalinginepithelialcells.Whenwemergedalldatasets,threecanonicalpathwayswereidentified:FcepsilonRIsignaling,naturalkillercellsignalingandCCR3signalingineosinophils.ThesenewfindingsaddnewevidencetogenomicandproteomicstudiessupportinganautoimmunehypothesisforMD.Thesefindingssuggestacriticalroleininflammatoryresponses,includingtheinnateimmuneresponseandallergicreactionsinthepathophysiologyofMD.FundingsFundedbyTheMeniereSociety,UKandEU-FEDERFundsforR+D+ibytheGrant2013-1242fromInstitutodeSaludCarlosIII,Spain.

EXTREME TINNITUS PHENOTYPE IN MENIERE´S DISEASE

Espinosa-Sanchez J.M. 1,2, Batuecas-Caletrio A. 3, Sanchez-Gomez H. 3, Lopez-Escamez J.A. 1,4.1 Otology and Neurotology Group CTS495, Department of Genomic Medicine, Centre for Genomics and Oncology Research, Pfizer/Universidad de Granada/Junta de Andalucía (GENyO), Granada, Spain.2 Department of Otolaryngology, Hospital San Agustin, Linares, Jaen, Spain3 Department of Otolaryngology, Hospital Universitario, Salamanca, Spain4 Department of Otolaryngology, Hospital de Poniente, El Ejido, Almería, Spain

Introduction:Tinnitusisasymptomthatcanappearinmanydifferentetiologicalconditionsandthatvarieswidelyinitsperceptualcharacteristics.Thisclinicalheterogeneitymakesdifficultnotonlytoassessdifferenttreatmentapproaches,butalsotoinvestigatetheunderlyingcauses.So,thedelineationoftinnitussubtypeshasbeenproposedasanimperativeneedintinnitusresearch. Inthissense,Meniere´sdisease(MD)isawell-defineddisorderthatcanbeusedasamodeltostudytinnitus.Onestepfurtherinthisstrategyistoselectindividualswithastrongdisablingtinnitustodefineahomogeneousendophenotypeforgeneticstudies.Aims:Toanalysetheclinicalcharacteristicsofextremetinnitusphenotype(ETP)inMDpatients.Patients and Methods: Patients with definite MD according to 1995 criteria of the AAO-HNSwere prospectively recruited atthreehospitalsbetweenDecember2014andMarch2015.Pure-tonehearingthresholdsfrom250to8000HzwereobtainedandpatientsfilledouttheTinnitusHandicapInventory(THI),a25-itemself-reportvalidatedquestionnaireusedtoquantifytinnitusseverity. We defined ETP as those patients with a THI score greater than 90th percentile. Acufenometrywas not performed aspsychoacousticmeasuresdonotrelatedwithtinnitusdistress.ClinicalfeatureswerecomparedbetweenpatientswithandwithoutETP.Therelationshipsbetweenallvariableswereexaminedbyuseofregressionanalysis.Results:Atotalof134MDpatientswereincluded(48males,86females;meanage57±27years).MeanageofonsetofMDwas47±13yearsandmeandurationwas11±9years.MediumTHIscorewas38.40±26.63andTHI90thpercentilewas80,thus14patientswereclassifiedasETP.Wecomparedcurrentage,sex,ageofonset,uni/bilateralinvolvement,hearingstage,antecedentofheadache,typeofheadache,existence of hypertensionor history of autoimmunity betweenpatientswith andwithout ETP, but nodifferenceswere found.ETPwasmostcommonlyfoundinfamilialMD6/45(13%)vssporadiccases3/70(4%),althoughwithoutstatisticalsignificance[OR=1.896(0.69-4.831),p=0.08].THIscorewasrelatedwithhearingthresholdsatallfrequencies,withstrongcorrelationat500Hz(r=0.238,p=0.003)and4000KHz(r=0.232,p=0.008)inthewholecohort.ThiseffectwasincreasedinpatientswithoutETPat250Hz(r=0.262,p=0.003)and4000Hz(r=0.254,p=0.006).Nevertheless,patientswithMDandETPdidnotshowcorrelationwithhearingthresholdatanyfrequencyintheaudiogram(p>0.5).Conclusions:1.THIscoreinETPisnotrelatedwithhearingthresholdsinMDpatients.2.ExtremetinnitusphenotypeseemstobemorecommoninfamilialMD.







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GENETICS

GENETIC ASPECTS AND CLINICAL CHARACTERISTICS OF FAMILIAL MENIERE’S DISEASE IN A SOUTH KOREAN POPULATION

Jin Woong Kim, Ji Hyuk Han, Jeon Mi Lee, Sung Huhn KimYonsei University College of Medicine

Objectives:Thisstudywasundertakentoinvestigatetheprevalence,inheritancepatterns,andclinicalcharacteristicsoffamilialMeniere’sDisease(MD)inaSouthKoreanpopulation.Methods: Direct and telephone interviews were performed for 286 definite MD patients and their family members who weresuspected of having MD. The diagnosis of MD in family members was made by obtaining a detailed history, performing basicneurotologicalexaminationsandreviewinghearingtestresults.TheclinicalcharacteristicsaswellastheprevalenceandinheritancepatternsoffamilialMDwereanalyzed.Results: The prevalence of familial Meniere-like syndrome (at least one family member with definite MD and other memberswithprobableMD)anddefinitefamilialMD(twoormorefamilymemberswithdefiniteMeniere’sDisease)were9.8%and6.3%,respectively,andthemostcommoninheritancepatternwasautosomaldominantwithincompletepenetrance.Thesignificantclinicalcharacteristicsoffamilialcaseswereanearlydiseaseonsetandahigherprevalenceofmigraines.Conclusions: This is thefirst reportdescribing thegeneticaspectsofMD ina single largeAsianpopulation. TheprevalenceofdefinitefamilialMDwas6.3%withanincompleteautosomaldominantinheritancepatterninmostcases.Early-onsetageandahighprevalenceofmigrainesweresignificantclinicalfeaturesoffamilialMDinthisSouthKoreanpopulation.ThesedatacouldprovideabasisfortheanalysisofthegeneticmechanismoffamilialMDinAsianpopulations.

IDENTIFICATION AND FUNCTIONAL ANALYSIS OF THAP1 GENE SEGREGATING VESTIBULAR PHENOTYPE IN MONOGYZOTIC TWINS WITH MENIERE’S DISEASE

Carmen Martin-Sierra, Teresa Requena, Lidia Frejo, AeRi Ji, Jose A. Lopez-EscamezOtology & Neurotology Group CTS495, Centre for Genomic and Oncology Research (Genyo), Granada, Spain

FamilialMeniere’sDiseasehasaprevalenceof8-10%offamilialcases.Wehaveperformedwhole-exomesequencing(WES)analysisinafamilywithtwomonozygotictwinsaffectedbyMD.Theageofonsetwas38yearsinbothpatientsandthefollow-upis13years.Bothpatientspresentedepisodicvestibularsymptoms,including vertigo and Tumarkin crises; both showed sensorineural hearing loss (SNHL) in the left ear and ipsilateral vestibularhypofunction,butoneofthemhasdevelopedalowtoneSNHLintherightearandhehasabilateraldiachronicMD.DNAwas enriched for coding regionsusingAll Exon50MBcapture kit (Agilent) and sequenced in SOLiD5500xl platform. theAfterdataprocessIng,weobtained~50.000singlenucleotidevariants (SNVs)and indelsperexome.Wefilteredthevariantsbyin-housecontrolsand theexomedbSNP138database. Toprioritizepathogenicvariantsweannotateda scoreaccording to:a)theeffectinproteinstructureandphylogeneticconservationbyusingasevenpointsscoringsystem(SIFT(SortIntolerantfromTolerant), PolyPhen2 (PolymorphismPhenotyping v2),Graham’sMatrix,GERP+ (Genomic EvolutionaryRateProfiling),Mutationtaster,PhastConsandPhyloP);b)crossspeciesphenotypecomparisonaccordingtotheinheritancepatternandmouseasmodelorganismphenotypebytheExomizersoftware[3];c)minorallelicfrequency(MAF)<0.01.FiveSNVsremainedafterprioritizationandfiltering.Fourofthem,werediscardedbecauseofitslowlevelofexpressionintheinnerearandbytheirbiologicalfunction.ThecandidategeneTHAP1isassociatedwithtype6dystonia,andencodesaTHAPdomain-containingproteininvolvedinendothelialcellproliferationandproapoptoticprocesses.THAP1proteinisconsideredatranscriptionfactorregulatingapoptosis.IthasnormallevelofexpressionintheinnerearandmutationsinthisgenecauselossofDNAbindingandtranscriptionaldysregulationofdownstreamtargets.ThefunctionalimpactofthisnovelvariantisbeinganalysedbytargetmutagenesisofTHAP1andcellulartransfectionsinJurkatcellstooverexpressthegeneandinduceapoptosis.Theeffectofwild-typeandmutantTHAP1geneswasevaluatedbyusingananexxinVIIapoptoticassay.FundingThisstudywasfundedbyMeniere’sSociety,UK







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INTRATYMPANIC GENTAMICIN IN A GRADE 1 VESTIBULAR SCHWANNOMA

Vincent Van Rompaey (1,2), Tomas Menovsky (2,3), Paul Van de Heyning (1,2)1 Department of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, Edegem, Belgium2 Faculty of Medicine and Health Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium3 Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium

Theeffectivenessofintratympanicadministrationofgentamicin(ITG)iswell-knowninpatientswithintractableMeniere’sDisease.Its toxicitytothe labyrinth leadstovestibularhypofunctionorareflexia,whichresults insymptomaticcontrolofvertigospellsanddropattacks.In1996,BrantbergreportedtheuseofITGinanelderlypatientwithagrade2vestibularschwannoma(VS)whorefusedmicrosurgicaltumorresection.In2007,MansMagnussonsuggestedtheuseofpreoperativevestibularablationwithITGand vestibular ‘prehab’ to enhance postoperative recovery in VS caseswithout preoperative vestibular areflexia (irrespective ofpreoperativevertigo).Thistreatmentresultsinvestibularcompensationbeforesurgeryandnopatientcomplainingofvertigoaftersurgery.In2013,Gianuzzi et al. reported their experiencewith ITG in4 elderly patientswith small non-growingVSbut incapacitatingvertigo.Inall4casesincapacitatingvertigodisappeared,but1patientexperiencedpersistingunsteadiness.TherationaleofITGinthispopulationistoacceleratetheprogressivedeclineoflabyrinthinefunctionsecondarytotheVS.Sincethese(ancient)VSarenotgrowingandonawait-and-scanpolicy,vertigosymptomsarenotexpectedtobecausedbyprogressivedeclineofretrolabyrinthinevestibularnervefunction.However,ephapticstimulationofaxonsisstillpossible.TheaimofthepresentstudyistoreportourexperiencewithITGinagrade1VSpatientwithincapacitatingvertigo.A54-year-oldmalepatientreportedtoourtertiaryreferralneurotologyclinicbecauseofincapacitatingvertigospellsandinstability.Video-oculoscopyexaminationcouldrevealapositionalnystagmusinleft-sidedroll-testandright-sidedDix-Hallpikemanoeuvre.Audiometrydemonstratedbilateralnormalhearing.Electronystagmographydemonstratedaleft-sidedvestibularhypofunction.ThetotalscoreoftheDizzinessHandicapInventory(DHI)atbaselinewas70.AnMRIrevealedasmallVSof1cminthecerebellopontineangle.Await-and-scanpolicywasadvisedandnogrowthcouldbeobservedat6-monthfollow-up.Becauseofpersistingvertigo ITGwasperformed.Hearingtemporarilyworsenedfroman0.5-1-2kHzpure-toneaverageof27dBHLto38dBHLandrecoveredto27dBHL.Thepatientreportedsubjectiveimprovementbutsymptomsrecurredafter2months.Microsurgicalresectionwasadvisedbymeansoftheretrosigmoidapproachtoenablehearingpreservation.Theposteriorwalloftheinternalauditorycanalwasdrilledtoexpose the fundus, total resectionwasperformedwhile sparing the facialandcochlearnerveanatomically. Thepatienthadanuneventful inpatient stay: facial functionwasnormal (House-Brackmanngrade I), no vertigowas experienced,hearingwasfunctionallypreserved(pure-toneaverageof48dBHL).ThetotalscoreoftheDHIimproved1weekaftersurgeryto50.Agradualimprovementofinstabilitywasreportedbythepatient.InVSpatientswithvertigo,ITGcanbeofferedtoreducesymptoms,butperipheralstimulationremainspossiblebecauseofincompletedeafferentiation.Moreover,afferentsignallingduetoephapticaxonalstimulationbythevestibularnerveisnotaffectedatallbythistreatment.Microsurgicalresection,whichinevitablyresultsinvestibularnervesection,remainsamoreeffectivetreatmentifvertigoiscauseddirectlyorindirectlybytheVS.

GENTAMYCIN

LONG-TERM HEARING OUTCOME AFTER INTRATYMPANIC GENTAMICIN INSTILLATION FOR MENIERE’S DISEASE

Sarah Verhoeven, Vincent Van Rompaey, Olivier Vanderveken, Paul Van de Heyning1. Department of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, Edegem, Belgium2. Faculty of Medicine and Health Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium

In1957,SchuknechtreportedthefirstcasewithsuccessfulchemicalvestibularablationtherapyinthemanagementofMeniere’sDiseasebyadministeringstreptomycinintothemiddleear.Overtheyears,intratympanicgentamicin(ITG)hasbeenincreasinglyusedbecauseofitspreferentiallyvestibulotoxiceffect.Howeveritsapplicationcanresultiniatrogenicsensorineuralhearinglossaswell.TheaimofthisstudywastoinvestigatehearingoutcomeafterITGapplication.TheITGprotocolinourhospitalinvolves1-hourroundwindowapplicationof40mg/mlgentamicinsolutionthroughtympanostomy.Thisprocedureisperformedundergeneralanesthesia.Weperformedaretrospectivestudyon81ITGcasesforunilateralMeniere’sDiseasebecauseofintractablevertigospellsdespiteoptimalmedicaltreatment.Availablepure-toneaudiometricdataweregroupedbyfollow-upperiods:baselinebeforeITG,week0-2(N=39),week3-4(N=27),month2(N=30),month3-4-5(N=51),month6-12(N=64),year2(N=60),year3(N=30),year4(N=22),year5andlater(N=28).Meanthresholdlevelsatthesefollow-upperiodswerecomparedwithmeanthresholdlevelsbeforetreatmentateachfrequency(pairedttests).Pure-toneaverage(PTA)wascalculatedasthemeanthresholdat500,1000,2000and3000Hz.Long-term(>2years)hearingoutcomewasevaluatedbasedontheclassificationproposedbytheAmericanAcademyofOtolaryngology-HeadandNeckSurgeryin1995.HearingimprovedifPTAdecreasedby10dBHLormore;hearingwasconsideredworseifPTAincreasedby10dBHLormore.Comparisonofnumbersofpatientsindifferenthearingoutcomegroupswasperformed(PearsonChi-squaretest).Meanagewas54±13years.Meanfollow-uptimewas53±78weeks.PTA(mean±SD)beforetreatmentwas58±17dB.PTAatweek1-2was61±22dB,whichwassignificantlyhigherthanbeforetreatment(p=0,047).Forallotherfollow-upperiods,therewasnostatisticallysignificantdifference(SSD)inPTA.Meanhearingthresholdat8000Hzbeforetreatmentwas69±18dB.Astatisticallysignificantdifferencewasfoundformeanhearingthresholdat8000Hzatweek1-2(77±12dB;p=0),week3-4(77±16dB;p=0,046),month2(71±13dB;p=0,025),month6-12(73±19dB;p=0,032)andyear3(81±18dB;p=0,011).Concerninglong-termaudiometricfollow-up,hearingoutcomewasworsein11(37%),unchangedin9(30%)andimprovedin10(33%)casesduring3thyearaftertreatment.During4thyearaftertreatment,hearingwasworsein8(36%),unchangedin8(36%)andimprovedin6(28%)cases.During5thyearorlater,hearingwasworsein5(18%),unchangedin15(54%)andimprovedin8(29%)cases.TherewasnoSSDbetweenhearingoutcomeandlong-termfollow-uptime.Intratympanicapplicationof40mg/mlgentamicinduring1hourcanresultinsignificantPTAhearinglossduringthefirst2weeksaftertreatment.High-frequency8000Hzismostpronetogentamicin-inducedcochleotoxicity.Long-termPTAdeteriorationisnotnotablyhigherthanthenaturalcourseofMeniere’sDiseaseandpresbyacousis.Thesehearingresultsareinaccordancewithpreviousreports.Overall,ourtreatmentprotocolhasalowriskofhearingloss.However,thedecisiontoproceedtoITGremainspreferablyreservedforpatientswithyetmoderatetoseverehearingloss(Meniere’sDiseasestageIIIandIV).







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SEMICIRCULAR CANALS’ FUNCTION IN PATIENTS WITH MENIERE’S DISEASE TREATED WITH LOW – DOSE INTRATYMPANIC GENTAMICIN

G.Tacikokwska, K. Pietrasik, H. SkarzynskiWorld Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw/ Kajetany, Poland

Introduction: Intratympanic gentamicin treatment is an evidence-based therapeutic option for recurrent vertigo attacks inMeniere’sDisease.Eitherapartialdeficitoracompletelossofvestibularreceptorfunctionmayoccurcausingvaryingdegreesofseverityofimbalanceandoscillopsiaaswellascontrolofvertigo.Inthiscontexttheobjectiveandquantitativeassessmentofthesemicircularcanalsfunctions,includingverticalonesseemstobevaluable.Objectives:Theobjectiveofourstudywastodeterminethedeficitsofhorizontalandverticalsemicircularcanalsafterintratympaniclow-dosegentamicintreatmentforMeniere’sDiseaseusingvideoheadimpulstest.Methods:Weconductedaprospectivestudyof15subjectswithunilateralMeniere’sDiseasetreatedwithintratympanicgentamicininjectionusinglow-doseprotocol(concentrationsof20mg/ml,1-2injections,waitingamonthbetweeninjections)andfollowedallsubjectsfor1.5year.Wemeasuredthegainoftheangularvestibulo-ocularreflexineachofthecanalplanesbefore,4-6and12-18monthsaftertreatmentwithintratympanicgentamicinbyusingvideoheadimpulsetest,additionallylowfrequencychangesofhorizontalvestibulo-ocularreflexweremonitoredusingthebithermalcaloricirrigation.Results: Beforetreatment10patientspresentedVORgainofallsemicircularcanalsinthenormalrangeontheaffectedside(0.92+/-0.20,0.83+/-0.30and0.79+/-0.25forthehorizontal,anteriorandposteriorcanalrespectively).Theremaining5subjectshaddecreasedgainofhorizontaland/orposteriorcanal(0.67+/-0.13,0.63+/-0.15). Aftergentamicinadministrationthevestibule-oculargainmeasured4-6monthsaftertreatmentwassignificantlyreducedin4subjectsineachcanalonthetreatedside(0.33+/-0.12,0.35+/-0.15,0.31+/-0.17forthehorizontal,anteriorandposteriorcanalrespectively),while3ofthesesubjectshadnormalgainineachcanalbeforetreatment.In11subjectsgentamicinadministrationresultedinamoderatedecreaseingainofhorizontalcanalsbutin5ofthemdidnotcauseasignificantreductioningainofverticalcanals:bothinanteriorandposteriororonlyinanterior.Measurementsmadeduring12-18monthsaftergentamicinadministrationshowedareturntonormalgainvalueinsinglecanalsin4patients.Abnormalcaloricasymmetriesbetweennormalandaffectedside(averaged47%+/-33%)werefoundin10subjectsbeforetreatmentanddeterioratedto69%+/-31%whenmeasured4-6weeksaftertreatment.Nosignificantchangesincaloricasymmetrieswerefoundintestsperformedafter12-18months.Conclusions:Ourresultssuggestthatverticalcanalsarelessaffectedthenhorizontalonesandpartialrestorationofthesemicircularcanalfunctionispossibleinintratympaniclow-dosegentamicin.







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QUALITY OF LIFE BEFORE AND AFTER HEARING AIDS

Chew HS, Heng YM, A LeongDepartment of Otorhinolaryngology, Khoo Teck Puat Hospital, Singapore

Introduction:Hearinglossisthe3rdmostprevalentchronicconditioninolderadults.Ithasafarreachingeffectonthephysical,mentalandvocationalaspectsoflifeofanuntreatedindividual.Thisisthefirststudylocally,whichallowsustoascertaintheimpactofhearinglossonqualityoflife.Objectives:Thisstudyaimstoachievethefollowing:1.Determinethequalityoflife(QOL)beforeandafterhearingaidintervention.2.AscertainanysignificantfactorsthataffectQOLafterhearingaidintervention3.EvaluateforanydifferenceinQOLbetweenunilateralversusbilateralhearingaidsuse.4.Determinethecompliancetohearingaiduseandreasonsfornon-compliance.Methods:Patientwithuntreatedhearingloss,above21yearsofageinclusive,wereapproachedbytheattendingaudiologistinasequentialmanner.FacetofaceinterviewwereconductedbasedonHHIE(HearingHandicapInventoryforElderly)forpatientsabove65yearofageandinclusiveandHHIA(HearinghandicapInventoryforAdult)forpatientsbefore65yearsofage.Thequestionnaireswereadministeredagainonfollowupin3months.Theaveragehearinglossofthebetterhearingearwasusedforanalysis.TheseverityofhearinglosswasclassifiedusingAmericanSpeechLanguageHearingAssociationclassificationofhearingloss.Defaulterswerecontactedviaphoneandtheirreasonsfordropout/non-compliancerecorded.Results:Totalof63patientswererecruitedover3monthsduration.Thiscomprisedof29malesand32femaleswithmeanageof70years±10years.SignificantimprovementinQOLscoreswereevidentafterhearingaidinterventionwithaveragescoresof25.13±24.74 prior to intervention and 7.13±12.44 post intervention (p<0.001). Patients who are widowed have 40% (p=0.016,95%CI:8.0%,72.1%)lowerinpercentagechangeinQOLpostfittingcomparedtopatientswhoaresingle.Thebenefitofhearingaidsisindependentfromthedegreeofhearingimpairment(p=0.4358).Eighty-twopercentarecomplianttotheuseofhearingaids.Malayshave98%(p=0.003,95%CI:76%,100%)loweroddsofcompliancecomparedwithChinese.Severityofhearinglossdoesnotsignificantlyimpactonthecompliance(p=0.2998).Reasonsfornon-complianceincludecosmesis,discomfortandocclusaleffect.BilateralhearingaidsdonotconferanyadditionalimprovementinQOLscorescomparedtounilateralaidinourstudy(p=0.2497).Conclusion:Unaidedhearingdisabilityismorepronouncedingroupswithmoreseverehearinglosswhilebenefitofhearingaidsisindependentfromtheseverityofhearingimpairment.SocialsupportegmaritalstatusdoesimpactontheimprovementinQOLpostfitting.Lowercompliancerateincertainethnicgroupcouldberelatedtoculturalperceptionofhearingaids.HearingrehabilitationwithhearingaidsresultsinsignificantimprovementinQOLandshouldbeadvocated.

HIGH SIGNAL ON 3D FLAIR, A PREDICTABLE FACTOR FOR PROGRESSION TO MENIERE’S DISEASE IN SUDDEN HEARING LOSS

Sang Hun Lee1, Chan Joo Yang1, Jeong Hyun Lee2 , Joong Ho Ahn1Department of Otolaryngology1, Radiology2, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Objective:Three-dimensionalfluid-attenuatedinversionrecovery(3D-FLAIR)imageinMRIhasrecentlybeendevelopedtodetecthighconcentrationsofproteinorhemorrhage.Otherarticleshavepreviouslyreportedthat50%ofpatientswithsuddenhearinglossshowhighsignalsintheaffectedinnerearon3D-FLAIRMRI.However,therelationshipbetween3D-FLAIRfindingsandhearingprognosisisunclear.Theaimofstudywastoevaluatetherelationshipbetweentheresultsof3D-FLAIRMRIandprognosis(especiallyprogressiontoMeniere’sDisease)insuddenhearingloss.Materials and Methods:RetrospectivechartreviewofaclinicaldatafromAugust2011toDecember2014,450patientsdiagnosedasunilateralsuddenhearinglossandperformedtemporalboneMRwithin2weeksfromtheonsetofhearingloss.Hearinglosstypewasdividedto4group:Lowtoneloss,hightoneloss,flat,profound.Thelow-tonelosstypemeetsthefollowingcriteria:theaveragehearinglevelat250,500and1kHzisatleast10dBworsethanthatat2,4,and8kHz.8patientswerecategorizedaslowtoneloss.Profoundtypewasdefinedastheaveragehearinglevelat500Hz,1kHzand2kHxwasworsethan90dB.Whirlingtypevertigowascheckedbychartreviewed.Meniere’sDiseasewasevaluatedaccordingtothe1995AAO-HNScriteria.AndhighsignalintensityonFLAIRimagewascheckedbyradiologist.Result:Amongthe450patients,highsignalintensityon3D-FLAIRimagewasobservedin75patients.Age,sex,affectedearwasnodifferencebetweenhighsignalgroupandnosignalgroup.Inaudiogram,highsignalgroupshowedworseresult.(p=0.047)Butfinalaudiogramandrecoverywasnostatisticaldifference.Highsignalintensitywasmorefrequentlyobservedinprofoundhearingloss.(p=0.000)IncasesofHighsignalonFLAIRimage,themorepatientshadexperiencedvertigoattack.(p=0.010)AndhighincidenceofpositiveonFLAIRimagewasobservedinMenieregroup.(p=0.026)Conclusion: If apatienthadhigh signal intensityonFLAIR, it tend tohaveworsehearingand the likelihoodofvertigoattackcouldincrease.IncasesofHighsignalonFLAIRimage,themorepatientshadexperiencedvertigoattackandhadtendencyofhighincidenceonpatientsofMeniere’sDisease.PositivefindingsonFLAIRimagemightbeconsideredaspredictablefactorforMeniere’sDiseaseinsuddenhearinglosspatients.

COST EFFECTIVENESS OF USING CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING FOR SCREENING UNILATERAL HEARING LOSS

F.N.Ardıç(1), F.Tümkaya(1), K.Ağladıoğlu(2), M.Şentürk(1), C.O.Kara(1),Y.Kıroğlu(2)1. Department of Otolaryngology, Pamukkale University, Denizli, Turkey2. Department of Radiology, Pamukkale University, Denizli, Turkey

ThepurposeofthestudyistocalculatethecostofcontrastmaterialusedforenhancementinMRIforscreeningunilateralhearingloss.Thepatientsattendedourdepartmentbetween2007and2014wereevaluated.695patientshadcontrast-enhancedMRIforunilateralhearing loss.The24ofthemwerediagnosedashavingacousticneuroma.Allsequenceswereevaluatedagainbythesameradiologist.Thedeterminingpowerofthepulsesequencesandthecostdifferencewerecalculated.Onlyverysmallacousticneuromasneedcontrastenhancementfordifferentiatingfromtheartifacts.

MICROGLIA IN MENIERE’S SYNDROME

Felipe Santos, M.D., Andreas Eckhard, M.D., Arianna Di Stadio, M.D., Jennifer O’MalleyMichael J. McKenna, M.D.Massachusetts Eye and Ear Infirmary, Harvard Medical School

TheetiologyofMeniere’s syndrome remainsunknown.An immune-mediatedetiology is supportedby several linesof evidenceincluding:1.elevatedlevelsofantiviralimmnoglobulinsinendolymph,2.identificationofviralparticlesinvestibularganglioncells3. increasedvaluesofcirculating immunecomplexes inpatientswithMeniere’ssyndromeand4. thefavorableclinical responseobservedinsomepatientswiththeadministrationofsteroidsandorantiviraltherapy.Ourlabhasrecentlyidentifiedavastarrayofmicroglia-likecellsinthehumaninnerear.Usingimmunohistochemistry,wedescribethedistributionandactivationstateofmicroglia-likecellsindocumentedcasesofdefiniteMeniere’ssyndromeinhumantemporalbonespecimenswithhistoriesofactiveandinactivediseaseatthetimeofdeath.Age-matchedcontrolsandcasesofpriorvirallabyrinthitiswerealsoexamined.Ineachconditionwecorrelatethedistributionandactivationofmicroglia-likecellstotheclinicalhistory.

HEARING AIDS

IMAGING

IMMUNE-MEDIATED DISEASE







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UNILATERAL NEUROSENSORIAL HEARING LOSS AND MULTIPLE SCLEROSIS

Kuci Anjeze 1, Bala Jonida 21 ENT, Main Policlinic of the Specialities Nr.3,Tirana, Albania2 Neurologist, Main Policlinic of the Specialities Nr.3,Tirana, Albania

Aim:DiscoverandrecognizefromacasereportonestrongpointbetweenENTandneurology:unilateralsensorineuralhearinglossandmultiplesclerosis2.evaluatetheroleofaMRIexaminationindiscoveringthisstrongconjunction3.neverthelessunderestimateaunilateralhearinglossinayoungperson,alwaysperformaMRItogetafirmerdiagnoseJ.R,female,21yearsoldcomestoourcliniccomplainingofagraveunilateralhearinglossfromherrightearfromonemonthandahalf.AfteranormalotoscopyweperformedanaudiometryshowingasevereunilateralneurosensorialhearinglossAudx,herleftearnormal,timpanometrynormal. Than froma consultwith theneurologistwedidnot discover anyneurologic sign, herneurologic testswerenormal.WeperformedanMRIandtheradiologistfoundaperiventricularleftlesionofthewhitesubstance.Forthehearinglossalthoughafterwardsonemonthandahalf-hourIgavehervasodilatators,corticosteroidsandvitaminotherapyforamonthbutIfoundaverylittleimprovement.Afteronemonthwhenshecamebackshehadalsobegantohaveamotordifficultyintheextremitiesandsometimesaroboticspeechwhentalking.Shealsohasbegantakingthetherapyformultiplesclerosis.Conclusion:ItisveryrarebutoneoftheclinicalsignsdiscoveringtheMSisasuddengraveunilateralneurosensorialhearinglossinayoungpatientandwediscovereditfromagoodconsultwiththeneurologistandofcoursewiththegoalstandardexamination:MRIofthehead.

UNILATERAL SENSORINEURAL HEARING LOSS AS IMMUNE-MEDIATED INNER EAR DISEASE

Francesca Atturo, Maurizio Barbara, Roberta Colangeli, Simonetta MoniniSapienza University, NESMOS Department, Rome, Italy

Objective: The aim of the present study was to show that the positivity of aspecific immunological tests could be found notonlyinbilateralAIEDbutalsoinsuddenandprogressiveunilateralSNHL.Methods:Tothispurpose,thepositivityofnon-specificimmunological tests was assessed in patients who came to the observation for progressive or sudden, bilateral or unilateralsensorineural hearing loss. Patients suffering from unilateral sensorineural hearing loss (SNLH), sudden or bilateral progressivesymmetric or asymmetric SNHL All the patients underwent a battery of blood exams to evaluate the immunological response,consistinginANA,ENAscreening,anti-thyroperoxidase(anti-TPO),anti-thyroglobulinandantibodyagainstsmoothmuscle(ASMA).Thepatientswereclinicallydividedintotwogroups:thefirstone,GroupA(39patients),wereaffectedbybilateralhearinglossandtheotherone,GroupB(33patients),wasformedbypatientspresentingwithunilateralhearingloss.Results:Overall,inbothgroupsasignificantpositivityofnearly70%ofaspecificimmunologicaltesthasbeenshown.Themostfrequently positive antibodies were ASMA and ANA in both groups, without statistical differences. Considering the correlationbetweenpositivity/negativityandsystemicautoimmunepathologies,inthepositiveGroupBahighincidenceofthyroidpathologieshas been found and in positiveGroupA ahighpercentageof systemic autoimmunediseases, not comparablewith the valuesreportedingeneralpopulation.Conclusions:TheauthorssuggesttoaddtotheclinicalsuspicionofautoimmuneinnerearsyndromethepossibilityandprobabilityoanAIEDaetiologyalsoinmonolateralSNHL,mostlyintheprogressivetipology.

ADRENERGIC STIMULATION-MEDIATED TRANSEPITHELIAL CURRENT FROM HUMAN ENDOLYMPHATIC SAC EPITHELIUM

Bo Gyung Kim1, Sera Park2,3, Jee Eun Yoo4, Jae Young Choi4,5, Sung Huhn Kim4,51 Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea2 Department of Otorhinolaryngology-Head and Neck Surgery, BundangJesaeng General Hospital, DaejinMedical Center, Seongnam, Korea3 Department of Otorhinolaryngology, Yonsei graduate school, Seoul, Korea4 The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea5 Department of Otorhinolaryngology, Yonsei University, College of Medicine, Seoul, Korea

Objective:Thisstudywasperformedtoinvestigatethemodulationoftransepithelialcurrentfromhumanendolymphaticsac(ES)epitheliumbyadrenergicandcholinergicstimulationandthedifferenceoftheionchannelactivitymodulatedbyadrenergicandcholinergicstimulationbetweenhealthysubjectsandMeniere’sDiseasepatients.Methods: Normal human ESs were harvested during acoustic tumor surgery using the translabyrinthine approach. The ESs ofMeniere’sDiseasepatientswasobtainedduringESdecompression.TheluminalsideofESwasexposedandfoldedfortransepithelialcurrentmeasurement. Thevibrating-probe techniquewasused tomeasure transepithelial currentsof apical sideof ES. Specificion-dependentcurrentunderadrenergicandcholinergicstimulationwasmeasuredusingelectrophysiologicalandpharmacologicalmethods. Adrenergic and cholinergic stimulators [isoproterenol (10 μM)and epinephrine (100 μM) for adrenergic stimulation;substanceP(10μM),carbachol(10μM)forcholinergicstimulation)wereusedforevaluationofeachresponse.Specificionchannelblockers for Na+ channels, K+ channels, Cl- channels were applied for identification of ion channels dependent on adrenergicor cholinergic stimulation. Theadrenergic receptorantagonists ICI-118551andCGP-20712A (specificantagonistsofβ1-orβ2-adrenergicreceptors,respectively)wereappliedforidentificationofsubtypeofadrenergicreceptor.Results:ChangesoftransepithelialcurrentbyadrenergicstimulationinhumanESepitheliumwerevarious.Adrenergicstimulationinducedcationabsorption/anionsecretioncurrentorcationsecretion/anionabsorptioncurrentdependingontheareaofES.Theisoproterenol-dependentcationabsorptioncurrent,cationsecretioncurrent,andanionsecretioncurrentwasblockedbybumetanide(10μM),Ba2+(1mM),andDIDS(10μM)innormalhumanESs,respectively.Therewasnoeffectofadrenergicstimulation(isoproterenolandepinephrine)inESsofMeniere’sDiseasepatients.Conclusions:TheseresultssuggestthattransepithelialcurrentfromhumanESepitheliumwasmodulatedbyadrenergicstimulationandcholinergicstimulations.TheinvolvedionchannelsandtransportersforeachstimulationareNKCC,K+channelsandCl-channels.However,transepithelialcurrentintheESofMeniere’sDiseasepatientswasnotlikelytobechangedbyadrenergicstimulation.Theseresultsreflectthatexcessivestress-mediatedadrenergicorcholinergicstimulationintheinnerearcaninfluenceontheionchannelfunctionsofinnerearepithelium,whichcanaggravatethesymptomsofMeniere’sDiseasebydisturbinginnerearhomeostasis.

INNER EAR FLUIDS DYNAMICS







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BAROTRAUMATIC PERILYMPHATIC FISTULA: PROPOSED APPROACH TO DIAGNOSIS AND MANAGEMENT

Ji Eun Choi, Il Joon Moon, Won-Ho Chung, Yang-Sun Cho, Sung Hwa HongDepartment of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center,Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea

Objectives:Thediagnosisofbarotraumaticperilymphfistula(PLF)iscontroversialduetothevariabilityinpatientpresentationanddifficultyinpre-operativeevaluation.Symptomslikehearingloss,earfullnessanddizzinesscandevelopfollowingminorbarotraumasuchasValsalva,noseblowingandstraining.TheaimsofthisstudyaretopresenttheclinicalmanifestationsofbarotraumaticPLFforprovidingappropriatediagnosisandmanagement.Methods:WereviewedmedicalrecordsofthepatientswhounderwentsurgicalexplorationundertheimpressionofbarotraumaticPLF.19patientswereenrolledandthecauses,symptomandsigns,andoperativefindingsandoutcomeswereanalyzed.Results:Amongthe19patients,9patientswereclassifiedastheexternaltrauma(caraccident,slapinjury)and10patientshadinternaltrauma(lifting,nasalblowing,straining,etc).RWfistulawasmainlyobservedininternaltype(5casesamong8RWfistula)whileeveryOWcaseswerecausedbyexternaltype(4casesofOWfistula).Mostsymptomsarepresentinserialorderregardlessoforigin.HoweverdizzinesstendstocomefirstinOWandhearinglossusuallyprecededinRW.Totalsixpatientshadpositionalnystagmusandallofthemhadhearinglossbeforedizziness.TheyhadRWfistula(n=3)exceptthecaseswithunknownorigin(n=3).ThecharacterofnystagmuswasampullofugalnystagmuswhichisdifferentfromtypicalBPPV(benignparoxysmalpositionalvertigo).Itusuallyinvolvedbilaterallyandlacksfatigabilityandreversibilitywithlongerduration.Hearingoutcomewasbetterafterearlyexploration.Whenwecomparedthehearingoutcomeaccordingtothefrequency,andhearinggainwassmallerinhighfrequency.Conclusions:Theclinicalpresentationofbarotraumaticperilymphfistulacouldbevariabledependingonlocationoffistula(OWorRW)anddegreeofdamage.FistulamainlyoccurredinRWintheinternaltypewhileOWfistulawasonlyfoundintheexternaltype.Regardingfistulasite,dizzinesscomesfirstwhenitoccursinOWandhearinglossisprecededwhenitoccursinRW.BecauseRWfistulacaninducepositionalnystagmus,itisimportanttodifferentiatefromBPPV.What’sdifferentfromtypicalBPPVisthatPLFdoesn’tshowreversibilityorfatigabilityandithaslongerduration.Itformsanampullofugalflowwithinthesemicircularcanal.Inaddition,earlysurgicalinterventioninclinicallysuspectedPLFseemstobeveryessentialforimprovementofsymptoms.

THE INNER EAR-A NOVEL TARGET FOR INSULIN ACTION AND RESISTANCE-IMPLICATIONS FOR DIABETES

Eva Degerman, Rene’ in ‘Zandt, Måns MagnussonSection of Diabetes, Metabolism and Endocrinology, Lund University, Sweden, Lund University Bioimaging Center (LBIC), Lund University, Sweden, Department of Otorhinolaryngology, Skåne University Hospital/Lund University, Sweden

Background:Anumberof studieshavedemonstrated an associationbetweendiabetes and inner earmorphological aswell asfunctionalalterationsaswellasanassociationbetweendysregulatedvasopressin/cAMPsignalingandMenieresdisease.However,whether the inner ear is a direct target for insulin signaling and/or insulin resistance or whether insulin can impact on cAMPsignalingintheinnerearisnotknown.Intwopreviousstudieswehavestartedtomapinsulin-andcAMPsignalingnetworksinhumaninnerear;forexample,theinsulinreceptor,theinsulinreceptorsubstrate1,theinsulinsensitiveglucosetransporter4andseveralcAMPdegradingenzymes(PDEs)wereshowntobeexpressedinthesensoryepitheliumofthehumansaccule.Inon-goingstudieswecontinuethemappingworkandwehavealsostartedtoinvestigatethefunctionalroleforselectedinsulin/cAMPsignalingproteinsinvivousingMRincombinationwithgadoliniumasread-outforendolymphatichydrops(EH).Method:HumansacculesusedforIHCareobtainedduringtheremovalofvestibularschwannoma.AmodelforfunctionalstudiesofidentifiedtargetproteinshasrecentlybeensetupandinvolvesthetreatmentofCBA/JorC57BL6micewithcontinuousadministrationofvasopressinviaosmoticpumpsusingMRincombinationwithgadoliniumasread-outforinnerearfluidhomeostasis.Results: IHC stainingdemonstrates theexpressionofPDE3B-amembraneassociated targetprotein for insulinaction inenergystoringcells-in theapicalpartof thehumansaccule sensoryepithelium.PDE4Dwasshowntobeexpressed in thehaircellsofthesensoryepitheliumtogetherwithaquaporin2.Interestingly,othershaveshownafunctionalinteractionbetweenPDE4Dandaquaporin2inkidneycells.Inaddition,preliminaryresultsshowtheexpressionoftheIGF1receptorandtheinsulintargetNaK-ATPaseinsupportingcellsandthekinasemTORandtheexocytoticproteinSYT7inhaircells.AdministrationofvasopressintowasshowntoinduceEHinmiceasshownbyMR.Inon-goingstudieswehavestartedtotesttheabilityofinhibitorsforPDE3andPDE4toinfluencevasopressin-inducedEH.Tothisend,theresultsindicatethatPDE3inhibitionpotentiatesvasopressininducedEHindicatinganimportantroleforthisenzymeintheregulationoffluidhomeostasis.Significance:Althoughtheintegratedinsulin/cAMPnetworksarewellestablishedregulatorsofenergymetabolism, intheinnerearotherprocessesrelatedtowaterandionichomeostasiscouldbetargetedaswell.ForexampletheNaK-ATPaseisknowntoberegulatedbyinsulininkidneycells.Thus,theongoingstudiesaimingatevaluatingtheroleforinsulinsignaling/actionintheinnerearandtheroleofcross-talkbetweeninsulinandcAMPsystemsforexampleviaPDEswillcontributewithnewknowledgeontheregulationofinnerearfunctionsandgeneratenewstrategiesforpreventionandtreatmentofinnereardisorders.

OPTIMAL MANAGEMENT OF MENIERE’S DISEASE

Sung Il Nam1 ; Soon Hyung Park1 ; Jae Hyun Cho1 ; Min Ju Park1 ; Seung Gon Jung1 ; Ye Won Lee1 ; Chang Hoon Bae 21 Department of Otorhinolaryngology, School of Medicine, Keimyung University, Daegu, Korea2 Department of Otorhinolaryngology, College of Medicine, Yeungnam University, Daegu, Korea

SeveraltreatmentoptionshavebeenintroducedtocontrolMeniere’sDisease(MD).ThereiscurrentlynogoldstandardtreatmentforMD.ThepurposeofthisstudywastoanalyzetheclinicalcourseandtreatmentflowinpatientswithMDAretrospectivestudywasperformedon168patientswhowerediagnosedasdefiniteMDfromMay2010toMay2014andwerefollowedupatleast1year.Theauthorsinvestigatedthecourseofdiseaseandtheresultsinourpatientsaccordingtothetreatmentoptions.Severalclinicalparametersincludingfrequencyofvertigo,audiometry,caloricandrotationtestwerereviewedandanalyzedaccordingtotheguidelineoftheAAO-HNS(1995),ifnecessary.Among168patients,vertigowasresolvedorimprovedin149patients(88.6%)withmedicalmanagement.Threepatientsneededfurthertreatment(endolymphaticsacdecompression:3,ITGM:7ITSI:9).Among7patientswhogotITGM,6patientswerefollowedupformorethan1yearafterinjection.Fivepatients(83.3%)showedsuccessfulcontrolofvertigo..Vertigowascontrolledbysupportivetreatmentsormedicationin88%ofdefiniteMDpatients.AndITGMcouldeffectivelycontrolvertigoforintractableMDpatients.

MEDICAL TREATMENT







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TREATMENT OF PERIPHERAL VESTIBULAR VERTIGO

Shaykhova Khalida, Khaydarova GavkharTashkent medical academy

Vertigoisoneofthemostfrequentsymptomsencounteredinmedicalpractice.Amongthereasonsforresortingtothedoctorsofdifferentspecialtiesdizzinessis3-4%.AboutathirdofpatientsseekingtoENTdoctors,markthedifferenttypesofdizziness.Aimsandobjectives:ToevaluatetheefficacyandtolerabilityofArlevertuseasmonotherapyforthetreatmentofsymptomsofperipheralvestibularvertigo.Themain interestposition-changetheseverityof symptomsofperipheralvestibularvertigoandautonomicdisorders.Methods.Thestudyincluded20patientswithperipheralvertigoinagefrom20to70years.Theaverageageofthesubjectswas53,3±13,9years.Inclusioncriteriainthestudywerepatientswithsymptomsofperipheralvertigoover18years,aswellasobtaininginformedconsent.ContraindicationstousingArlevert,mentaldisorders,affectinganobjectiveassessmentofthepatient’scondition,benignparoxysmalpositionalvertigowereexclusioncriteriaofthestudy.Patientstakingthedrug1tablet3timesaday.EfficiencyArlevertassessedbythedynamicsofindicatorsofseverityandintensityofvertigosymptomsofautonomicVAS(visualanaloguescale).Thesurveywasconductedpriortotheappointmentofthedrug,aswellas7and28daysoftherapy.Results.IntheprimarytreatmentfortheseverityofvertigoVASaveraged2,2±0,9points.Onthe7thdayoftherapyontheseverityofvertigoVASaveraged0,3±0,5.Onday28theseverityofvertigoVASaveraged0,1±0,2points.Thustherewasasignificantreductionintheseverityofvertigo(P<0,001).IntensityofvegetativesymptomsofVASwastheprimarytreatmentaveraged1,3±1,2points.Onday7oftherapyontheseverityofsymptomsofautonomicVASaveraged0,3±0,6points.Onday28theseverityofsymptomsofautonomicVASaveraged0,1±0,2points.Thustherewasasignificantreductionintheseverityofautonomicsymptoms(P<0,001).Ingeneral,thedrugwaswelltolerated,duringtreatmentin3(15%)patientsreportedsomnolence.Thiseffectwasobservedduringthefirstweekof treatment.Starting fromthe secondweekof thedrug inpatientswasobserveddrowsiness. Thus,allpatientscompletedthestudy.Theincidenceofprematurediscontinuationoftreatmentwasnot.Efficacyevaluatedas“excellent”in19(95%)subjects,as“good”-in1(5%).Portabilityratedas“excellent”in17(85%)subjects,as“good”in3(15%).Conclusions.Ourexperienceintreatmentofperipheralvestibularvertigodrug“Arlevert”showeditsufficientclinicalefficacyandtolerability.Thus,thedrug“Arlevert”iseffectiveintreatingsymptomsofperipheralvestibularvertigo.

PLATINUM-INDUCED OTOTOXICITY IN CHILDREN: COMPARISON OF DIFFERENT OTOTOXICITY CLASSIFICATION

Gunay Kirkim 1, Yuksel Olgun 2, Serpil Mungan Durankaya 1, Deniz Kızmaz Cakır 3, Dilek Ince 3, Kamer Mutafoglu 3, Nur Olgun 3, Enis Alpin Guneri 21 Dokuz Eylul University School of Medicine Department of Otorhinolaryngology, Unit of Hearing Speech and Balance İzmir- Turkey 2 Dokuz Eylül University School of Medicine Department of Otorhinolaryngology İzmir- Turkey 3 Dokuz Eylül University School of Medicine Department of Pediatric Oncology İzmir- Turkey

Introduction:Cisplatinandcarboplatinare importantantineoplasticagentswhichareused for treatmentofvariouspaediatricmalignancies.Unfortunatelysomesideeffectslikeototoxicityandnephrotoxicityhinderstheirusageofhigherdoses.Hearinglossrelatedtotheseagentsisirreversibleandoccursatcumulativedoses.Moreoverthesechildrenwhohavebeenexposedtohigherdosescanbecandidateforcochlearimplantation.ThefirstclassificationtodescribeototoxicitywasBrock’sclassification.OtherototoxicityclassificationshavebeenestablishedtoovercomesomeweakpointsofBrock’sclassificationafterwards.Aim:Toevaluatefrequencyandintensityofhearingimpairmentinchildrenwhoreceivedcisplatin/carboplatintreatmentaccordingtosixdifferentototoxicityclassificationsandtoaudiologicallyexaminethese6differentototoxicityclassificationandtodiscusstheirsuitability.Material Methods:Dataof87childrenwhoreceivedcisplatin/carboplatintherapywererespectivelyanalysed.Allpatientswereevaluated by otoscopic examination, pure tone audiometry, otoacoustic emission and acoustic immitansmeter before and aftertreatment.OtotoxicityseeninthesepatientswasevaluatedbyNCI,Brock,Muenster,ASHA,Chang,andSIOPBostonclassifications.Results:Themeanagewas11,2(3-17years)yearsold.Ototoxicitywasobservedin33,31,35,34,30and33patientsaccordingtofollowingNCI,Brock,Muenster,ASHA,ChangandSIOPBostonclassificationsrespectively.Consistencyoftheseclassificationswasanalyzedbyintraclasscorrelationtestanditwasfoundthatthesetestswerehighlyconsistentwitheachother(ICC:0,834).Conclusion:While treatingpediatriconcologypatients toxicity related to therapyand lifequalityare important factors tonotunderestimate.Forthispurposevariousototoxicityclassificationshasbeendescribed.Itseemsthatalltheseclassificationwereinhighconsistencieswitheachother.

OTOTOXICITY OF PARENTERALY ADMINISTRED GENTAMYCIN- CASE REPORT

Atanasova N, Stojceska V, Mihajlovska Shulevska I, Stoimenov DMD ,ORL specialis

Aim:TopresentacasereportofbilateralsensorineuralhearinglostafterparenterallyadministeredGentamycinasatherapyforacuteBronchopneumoniaMethod: Casereportof36yearsoldwomanwhichhasbeentreatedparenterallywithGentamycintwiceadayindose120mg(240mgdaily)foraperiodof12days,asatherapyforacuteBronchopneumoniaatClinicforinfectiousdiseases.Atfirst6daysofhospitalizationshewashighfebrile(39,5-40,5Cbodytemperature).After3daysoftherapyshehadfeltbilateralhearinglostandtinnitus,andthetherapywasstillthesameinthefollowing10days,withoutORLexaminationandwithoutaudiologytesting.After2monthsthepatienthadfirstORLexaminationandaudiologytestingwasprovided-Tonalliminaraudiometry,tympanometry,OAE-DpOAE,Evokedpotentials.Results:TLAshowedbilateralsensorineuralhearinglostwithslopeconfigurationofAudiogram(inrange125Hz-8kHz),bilateralhearinglostof68%,tympanometrybilaterallynormalresulttypeA,DpOAEwithbilateralhearingimpairment,EPwithnormalconfiguration.Thepatientwastreatedwithhighdosevitamintherapy,vasodilatationdrugsinaperiodofa2monthswithoutanyhearingimprovement.Hearingaidswereprovided.Conclusion:AminoglycosideantibioticssuchasGentamycinshouldnotbeincludedintreatmentofacuteinfectiousdiseasesbecauseofitsototoxicity.Highpercentageofbilateralhearinglost,tinnitusandqualityoflifeimpairmentareveryhighpricefortreatmentwithototoxicdrugs.

OTOTOXICITY







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EFFECT OF TRANSTYMPANIC VENTILATION TUBE INSERTION IN INTRACTABLE MENIERE’S DISEASE

Tessei Kuruma, Toru Tanigawa,Mayuko kishimoto, Ikue Uchida,Ogawa Tetsuya,Hiromi UedaDepartment of otorhinolaryngology, Aichi Medical University

Objectives:TranstympanicventilationtubeasatreatmentoptionforMeniere’sDiseasehasbeenreported,buttheresultshavebeencontroversial.AsatreatmentforpatientswithintractableMeniere’sDisease,insertionofaventilationtubeintothetympanicmembranewascarriedout,andtheeffectoftherapywasanalyzed.Methods:Fivepatients(2males,3females;agerange,51-79years)withactiveMeniere’sDiseasereceivedventilatingtubesintheaffectedearandpostoperativechangesinsymptoms(i.e.,incapacitatingvertigoandhearingloss)wereinvestigated.TheefficacyoftreatmentonvertigoattacksandhearinglosswiththisdiseasewasevaluatedaccordingtoAAO-HNS(1985)criteria.Results:At42monthsoftreatment,oneofthe5patientsshowedcompletecontrolofvertigo,twoachievedsubstantialcontrolandtwoachievedinsignificantcontrol.Ontheotherhand,hearinglevelwasunaffectedbytreatment.Conclusions:Thistreatmentmighthaveshort-termeffectsinreducingpersistentvertigoinsomepatientswithMeniere’sDisease,andsomightofferanadditionaltreatmentoptionbecauseofthesimple,less-invasiveprocedure.

EVALUATING EFFECTIVENESS OF INTRA-TYMPANIC DEXAMETHASONE INJECTION OF MENIERE PATIENTS WITH ALTERATION OF ELECTROCOCHLEOGRAPHY

NasrinYazdani1,SasanDabiri1, Reza Gharibi2, NimaRezazadehOtorhinolaryngology research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

Meniere’sDiseaseisachronicdisorderofinnerear..Mechanismofdiseaseisincompleteresorptionofendolymphaticfluid.CochleaespeciallyScalamediaisthemostcommonsiteofinvolvement.ECOGisnon-invasivemethodforrecordsofcochlearactionpotentials.andappliedtodiagnosisofthisdisease.Theuseofintra-tympanicdexamethasone(IT-Dex)toreducetheseverityofthesesymptomshasbeengainingpopularityinrecentyears.Corticosteroidspromotebloodflowofinnerearto26%,asmentionedbysomestudies.Evaluatingtheeffectivenessofintra-tympanicdexamethasoneinjectioninimprovementofsymptomsofunilateraldefiniteMenierepatientswithalterationofelectrocochleography.Abeforeandafterstudyincluding36adultpatientsofatertiaryreferralENTclinicwhomdefinite,unilateralMeniere’spatientswhomnonrespondertomedicaltreatmentwasselected...BaselineECOGandaudiometryobtained,treatmentstartedwith4mg(IT-Dex)inpostero-superiorquadrantoftympanicmembraneeveryweek(3dosestotally&withaweekinterval)wascarriedout.WerecordedPosttreatmentECOGandaudiometry,onemonthafter3rd(IT-Dex)injection,andEvaluatedclinicalsignofvertigoandtinnitus1to6monthsaftertreatment.36 patients included in this study. Mean age of patients was 39/89. 21 (58/3% ) of patients was male and 15(47/3%) wasfemale.22(61/9%)ofpatientshadrightearand14(38/1%)ofpatientshadleftearinvolvement.Meanaveragetimeofinvolvementwas4/06year.positivefamilialhistorywasobtainedin7(19/4%)ofpatients.4(11%)patientshadimprovementinhearingstatusbasedonAAO-HNScriteriaandothers(88%)hadnotthis.Worseningofhearingoccurredinnoneofparticipants.PTAlevelafterofinjectionnotcorrelatedwithIT-DEX(Pvalue=0.492)insteadofSDSafterofinjectioncoordinatedwithIT-DEX(Pvalue=0.008).TherelationshipbetweentinnitusandIT-DEXwasnotsignificant(Pvalue=0.334).Evaluationofvertigo inthisstudybasedonnumeric valuescaleofvertigo indexaccordingtoAAO-HNS,relationshipbetweenvertigobeforeinterventionandvertigo1monthafterinterventionandbetween1monthafterinterventionand6monthslaterwassignificant(inboth<0.001).Butthisrelationshipwasnotsignificantbetweenvertigobeforeinterventionandvertigoscalein6monthslaterafterthat.(Pvalue=0.2).Accordingtothisstudy,onemonthafterintervention,atleast75%ofpatientshadoneclassimprovementintheirformerclass,althoughthisvaluediminishedto19.5%attheendof6monthsdramatically.ImprovementinECOGoutcomewasnotsignificantbeforeandafterofintervention(Pvalue=0.052).TheresultsofasingletrialprovidelimitedevidencetosupporttheeffectivenessoftreatmentinpatientswithMenierediseaseAlsowehavenotcontrolgroupfor this research.This trialdemonstratedastatisticallyandclinically significant improvementof thefrequencyandseverityofvertigomeasured1monthafterthetreatmentwasadministered.Withoutadditionaltreatmentthiseffectdiminishedsignificantlyduringother6months.Intra-tympanicSteroidscanbeusedtoshortactingtreatmentoptionfortreatmentofvestibularsymptominMenieredisease.ECOGnotcorrelatewiththistreatmentandnottobeusedforevaluationofthismodality.

PRESSURE TREATMENT STEROID TREATMENT







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PROGNOSIS OF SEVERE TO PROFOUND IDIOPATHIC SUDDEN SENSORINEURAL HEARING LOSS

Changjoon Lee, Siyoung Jo, Yongbeom ChoDepartment of Otolaryngology-Head & Neck Surgery, Chonnam National University Hospital

Whileaseveretoprofoundsuddensensorineuralhearingloss(SSNHL)maycauseseriousdisabilityinverbalcommunication,therehavebeen little studies focusingon thishighdegreeSSNHL. Thepresent studywasaimed to investigate the characteristicsofhearingrecoveryinahighdegreeSSNHL(>70dB).ThreehundredandtwoSSNHLpatientswereenrolled.Foralong-termfollow-up,46patientswereevaluated.Hearinglevelwasexaminedbypuretoneaudiometryonday1,week3,month3,month6,andyear1orafter.Accordingtothedegreeoftheinitialhearingloss,thepatientsweredividedinto4groupsfrom70dBto≥100dB.After3weeks,therecoveryrateandmeanhearinggainwas61%,23.85dBinthe70dBgroup,whereas10%,6.61dBinthe≥100dBgroup.Therewasasignificantcorrelationbetween3week-recoveryandfinalhearingoutcome,indicatingthatanearlyrecoverycanbeaprognosticfactorforthefinalrecoveryinseveretoprofoundSSNHL.Sincerecoveryafter3monthsisrare,anearlyhearinginterventionlikehearingaidorcochlearimplantationshouldbeconsideredinthehighdegreeSSNHLtorestorethepatient’sverbalcommunication.

RELATIONSHIP BETWEEN HEARING THRESHOLD AT THE AFFECTED AND UNAFFECTD EAR IN UNILATERAL MENIERE’S DISEASE

Albera R, Canale A, Cassandro C, Albera A, Sammartano A, Boggio V, Cerutti M, Dagna FUniversità degli Studi di Torino, Città della Salute e della Scienza di Torino

Hearing loss inMenière’sdiseasehasbeendescribedtoaffectaboveallthe lowfrequencies (upwardcurve)withatendencytobecomeirreversibleandnonfluctuatingatthehigherfrequencies(peakedcurve)overtime.TheaimofthestudywastodeterminetheeffectsofMDonhearingfunctiononthebasisofdifferencesexistingbetweentheaffectedandtheunaffectedearinagroupofpatientsaffectedbydefiniteunilateralMDandwhosecontralateralearwasnotaffectedbyanydiseaseotherthanagerelatedhearingloss(ARHL).FollowingthisprocedurewehavealsoevaluatedthepossibleeffectsofageanddiseasedurationonhearinglossinMD.Thestudygroupconsistedof86subjectsaffectedbydefiniteunilateralMD.ThesecondinclusioncriterionwastheabsenceofpathologiesattheunaffectedearotherthanARHL.Inoursamplehearingthresholdattheaffectedearischaracterizedbyapeakedcurvebutdetractingthresholdofthenormaleartheresultingcurvebecomesanupwardslopingcurveduetoahigherdegreeofsufferingatthelowerfrequencies.Onthebasisofdifferencesexistingbetweenaffectedandunaffectedearourdatasuggestthatthresholdevolutionismorerelatedtodiseasedurationratherthanage.

VESTIBULAR SCHWANNOMA IN SUDDEN SENSORINEURAL HEARING LOSS PATIENTS

Yong-Soo Park, Il-Whan Lee, In-Chul Nam, Dong-Hyun Kim, Eun-Ju Jeon.Dept. of Otolaryngology-H&N Surgery, Incheon St. Mary’s Hospital, The Catholic University of Korea Incheon, Korea

Introduction:Suddensensorineuralhearingloss(SSNHL)hasseveraletiologies.ItmaybeapresentingsymptomofretrocochlearlesionsandotherCNSproblems.Highsensitivityandspecificityratesdefinemagneticresonanceimaging(MRI)ofthebrainasthegoldstandardforthediagnosisofretrocochlearpathologies.ThisstudyaimedtoestablishtheincidenceofCNSlesionsinpatientswithSSNHL,andwereportseveralunusualcasesamongthesepatients.Methods:WereviewedretrospectivelythechartsandMRIfindingsofalladultpatientswhopresentedwithSSNHLbetweenJanuary2012andMay2015.WeutilizedgadoliniumenhancedtemporalboneMRIasa screeningmethod inSSNHLpatients. Thestudyincluded252patients,137femalesand115males,withanaverageageof51years(range8-82years).Results:Ofthe252patientswithSSNHL,vestibularschwannoma(VS)wasfoundin18(7.1%)cases.thepatientshaveseveralotherCNSdiseases,asRathke’scleftcyst,meningioma,vascularanomaly,pituitaryadenoma,etc.weusedglucocorticoidtreatmentandtimelyandshort-termmedication.Conclusion:SomevestibularschwannomashaveSSNHLasinitialsymptomsandCNSlesionsweresometimesfoundedincidentallyinSSNHLpatients.Recently,asaresultoftheincreasingwidespreaduseofMRI,morepatientswithvestibularschwannoma(VS)thanexpectedhavebeendetectedamongthosewithSSNHL.MRIwouldseemtobemandatoryinallcasesofSSNHL.

ENDOSCOPIC INLAY BUTTERFLY (CARTILAGE) TYMPANOPLASTY

K.Aykal, F.Tümkaya, C.O.Kara, F.N.ArdıçPamukkale University, Department of Otolaryngology, Turkey

In this study, preoperative and postoperative anatomic and audiological results of endoscopic and inlay butterfly cartilagetympanoplastytechniquewaspresented.Sixteenpatients(8males,8females)withcentraltympanicmembraneperforationduetochronicotitismediaandnoactiveearinfectionforatleasttwomonthswereincludedinthisstudy.Allsurgicalprocedureswereperformedwiththehelpof0°/4mmdiameterrigidendoscope.Perforationdimensionsweremeasuredafter perforation edges were refreshed. Perforation diameters ranged from 2 to 6 mm. Tragal cartilage graft was prepared likebutterflywingasinEaveytechniqueanditwasinsertedthroughtheperforationlikegrommetventilationtube.Twopatientswithlargeperforationsmorethantwo-thirdsofthetympanicmembranehadminimalperforationsattheedgeofthecartilagewhichwasclosedwithfattygrafttakenfromearlobe.Attheendofthefollow-upperiod,tympanicmembraneperforationclosurewasfoundas(15/16)%93.7.Thepreop/postopdifferenceinair-bonegapdecreasedfrom18.5dBto8.25dBinaverage.Theendoscopehasadvantagesespeciallyinclearvisionofanteriortympanicmembraneperforations.Theremainingsmallperforationsarealsodetectedeasily.Thistechniquecanbeusedsafelyinthesituationswithminimalhearingloss,clearmiddleear,smallandmediumcentraltympanicmembraneperforations.

SUDDEN DEAFNESS

SURGERY







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OTONEUROLOGICAL ASSESSMENT IN LONG TERM FOLLOW UP AFTER VESTIBULAR NEURECTOMY FOR MENIERE’S DISEASE

Canale A, Caranzano F, Lanotte M, Calamo F, Dagna F, Salonia L, Lacilla M, Boldreghini M, Albera RUniversità di Torino, Città della Salute e della Scienza, Torino, Italia

Background:Vestibularneurectomyisnowregardedasthemosteffectivemethodfortreatingseverecasesofperipheralvestibulardisease.Thereisalackofdataaboutlongterminstrumentalresults.Aim:Toinvestigateotoneurologicassessmentin12patientsthatunderwentvestibularneurectomyforMenière’sdisease.Methods:Theinstrumentalassessmentconsistedofvisuo–ocularreflexes,calorictests,vestibularocularreflexes(VOR),cervicalandocularmyogenicpotentialsandtonalandspeechaudiometry.Subjectivestatuswas investigatedbytheDizzinessHandicapInventory(DHI).Themeantimebetweensurgeryandtheotoneurologicalassessmentwas7years(SD:3.16).Results:AllpatientshadgoodsubjectiveoutcomesasmeasuredbyDHI(meanvalue32.73;SD:24.74).Twopatients(16.7%)hadaspontaneousnystagmus.Amildresponseatthecalorictestontheoperatedsidewaspresent in2patients (16.7%),withsideprevalencegreater than25%. Threepatientshadcervical vestibular evokedmyogenicpotentialswith lowamplitudesandhighthresholds.Oneofthembelongedtothosewithcaloricresponses.Only1patienthadweakocularvestibularmyogenicpotentialsontheoperatedside.Thevideoheadimpulsetestshowedagaingreaterthan0.5fortheposteriorsemicircularcanalin4patients(33.3%),fortheanteriorsemicircularcanalin2patients(16.7%)andforthelateralcanalin5patients(41.7%).In1patientthepresenceofcervicalevokedmyogenicpotentialswasassociatedwithnormalposteriorsemicircularcanalVORgain(0.86).ThiswasasymptomaticpatientwithDHI=74.Conclusions:Wedonothavedefiniteexplanationsforthepresenceofmildcaloricresponsesin2casesandthepresenceofcervicalandocularmyogenicpotentialsassociatedwithlowDHIscores;webelievethatinstrumentaldatamayhighlightanomaliesthatdonotrelatetosubjectiveoutcome.Incontrast,thepresenceofcervicalpotentialsassociatedwithnormalVORintheposteriorsemicircularcanalcouldconfirmtherecenthypothesisthattheinferiorpartofvestibularfibersmightmergewithcochlearfibers.Inconclusionevenifneurectomymightnotalwaysdeterminecompletevestibularareflexia,itsurelycontrolssymptomsincaseofsevereperipheralvestibulardisease.

OUTCOME OF ATTIC RECONSTRUCTION AFTER MINIMAL INCISION ATTICOANTROSTOMY APPROACH LASER SURGERY FOR CONGENITAL CHOLESTEATOMA (MILC) - SURGICAL EXPERIENCE FROM 400 CASES

Chang Ho Lee, MD.PhDHyung-Mi Kim, MDDepartment of Otolaryngology-Head & Neck Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea

Congenitalcholesteatoma(CC)isanossicleoriginmiddleeartumorthatshowsearlyossicledestructionratherthanatticdestructionofacquiredcholesteatoma.Atticoantrostomyapproach(AA)isausefulsurgicaltechniquetovisualizeossicleswidelybycombiningotosclerosis drilling (anterior tympanotomy) and transcanal atticotomy, which provides better exposure of anterior attic andtympanicsinuscomparedtoCWUmastoidectomywithposteriortympanotomy.Methods.OursurgicaltechniqueisminimalincisionatticoantrostomyapproachLasersurgeryforCongenitalcholesteatoma(MILC),andwehaveover400CCcases.WereviewedtheoutcomeofendauralAAregardingfeasibilitytocompleteCCsurgeryandtheoutcomeofatticretractionpocket.Results.Averageageofthechildrenwas3yr1monthold(36.7+-12months).AAwasnotnecessaryin42.5%thatwereearlystageCCmanagedwith canaloplasty plus extended tympanomeatal flap elevationwithout atticotomy,AAwas required in theother57.5%;17.1%ofstageIICCtovisualizemedialsideofmalleus,andallcasesofstageIII,IVCCthatinvolvedincudostapedialjoint.MastoidinvasionoverantrumthatrequiredCWDconversionwasonlyin4cases.Secondlookoperationwasrequiredin10%,andresidualcholesteatomawasfoundin8.5%.Atticventilationwasmaintainedin99.5%,andpersistentatticretractionpocketdevelopedonlyin2children,whichcouldbemanagedwithventilationtubeinsertion.Conclusion.AAinourMILCaccomplishedaexcellentrecidivismwithouttheconcernofretractionpocketorcavityproblemincongenitalcholesteatomasurgery.

TEMPORARY CANAL WALL REMOVAL IN PRIMARY INNER EAR SCHWANNOMAS AND B2 GLOMUS TYMPANICUM TUMORS

Vincent Van Rompaey, Paul Van de HeyningDepartment of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, Edegem, Belgium.Faculty of Medicine and Health Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium

The primary inner ear schwannoma (PIES) is a group of benign tumors which are defined by their location (modified Kennedyclassification): intracochlear, intravestibular, intravestibulocochlear, transmodiolar, transmacular, tympanolabyrinthine andtranslabyrinthinetumorswhichgrowtowardsthecerebellopontineangle.MostPIEScanbemanagedwithawait-and-scanpolicy,butwhendeafness,incapacitatingvertigoortumorgrowthoccurs,microsurgicalresectioncanbeofferedtothepatient.Differentapproachesarepossibleanddependonthetumorlocation,rangingfromthetranscanalapproachtothetransoticapproach.TheglomustympanicumisabenignmiddleeartumororiginatingfromtheglomusbodiesthatliealongtheJacobson’sandArnold’snerve.TheglomustympanicumcanbestagedbyusingthemodifiedFischandMattoxclassification.ByusingthesurgicalalgorithmproposedbyMarioSannaeachtumorstageisassociatedwithadifferentsurgicalapproach.InB2glomustympanicumtumors,thedefaultstrategyisacanal-wallupmastoidectomywithextendedfacialrecessopeningcombinedwithsubfacialrecesstympanotomywithoutembolization.However,thistypeoftumorishighlyvascularizedandcanproduceexcessivebleedingduringsurgeryleadingtosubtotalresectionorpotentialcomplicationsduetolowvisibility.Ontheotherhand,thesubfacialrecesstympanotomyrequiresextensiveretrofacialdrillingwhichcanbetime-consuminganddoesnotprovideexcellentexposureofthehypotympanum.Ourdepartmentalreadyreportedfeasibilityandsafetyofthetemporarycanalwallremovaltechniqueincholesteatomacases.Thetechniqueinvolvescreatingawidefacialrecessapproachandcuttingthecanalwallwithanoscillatingsawinferiorlyatthelevelofthetympanicboneandanterosuperiorlyattowardsthezygomaticroot.Aftertumorresectionthecanalwallcanberepositionedandfixatedusinghydroxyapatitebonecement.TheaimofthepresentstudyistoreportourexperiencewithtemporarycanalwallremovalinintracochlearschwannomasandB2glomustympanicumtumors.Material and Methods:Weperformeda retrospective reviewon7consecutivecaseswithan intracochlear schwannoma (n=1)andB2glomustympanicum(n=6)whounderwentcanalwallupmastoidectomywithtemporarycanalwallremoval.Wereviewedcomplciationssuchascholesteatoma,recurrence,facialnervepalsy,etc.Totalresectionwasachievedinallcases.IntheB2glomustympanicumcasesminimalbleedingwasobservedduringsurgery,whichwaseasilycontrolledbybipolarcautery.Noneofthepatientshadanytemporaryorpermanentfacialparesisorpalsy.Nocomplicationswereobservedsuchasgranulationformation,extrusionofthecanalwallorformationofcholesteatoma.Thetemporarycanalwallremovaltechniqueisaversatileandsafestrategytoeasilyapproachthehypotympanumandpromontory.Itavoidstheneedfortheretrofacialapproachwhenaccessingthehypotympanumandavoidstheneedforthetransoticapproach(andthustheneedforblindsacclosureandabdominalfatharvesting)inselectedprimaryinnerschwannomas.Incaseofintactcochlearfunction(especiallyinB2glomustympanicumcases)itenablespreservationoftheossicularchain.







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VESTIBULAR NEURECTOMY: RETROSIGMOID OR RETROLABYRINTHINE APPROACH?

Jun YANG; Huan JIA; Yupeng LIU; Zhihua ZHANG; Zhaoyan WANG; Qi HUANG;Hao WUDepartment of Otolaryngology -Head & Neck Surgery, Xinhua Hospital, Shanghai, China

Objective:Theretrosigmoid(RS)approachandtheretrolabyrinthine(RL)approacharetwomainclassicalsurgicalapproachsforvestibularneurectomy.However,theiradvantagesanddisadvantageshavenotbeenwelldocumented.Theaimofthisstudyistocompareinseveralaspects.Methods:From2009to2014,aretrospectiveanalysisof63Meniere`sdiseasepatientswhounderwentvestibularneurectomywaspresented.RSapproachwasperformedin40cases,andRLapproachin23cases.Theoperationtime,distancebetweentheduraandthefacial-acousticnervebundle,operativevisualfieldexposed,cerebellumcompression,andtherateofpostoperativecomplicationwerecompared.Results:TheresultsshowedthattheaverageoperationtimeforRSapproachwassimilartothatforRLapproach.InRLapproach,theaveragedistancebetween theduraand the facial-acousticnervebundlewas significant shorter than thatofRSapproach.Moreover,lesscerebellumcompressionwasneededinRLapproachforvestibularneurectomy.However,RSapproachprovidedbettervisualizationofthecerebellopontineangleforvestibularneurectomy.Therewasnotstatisticallysignificantdifferencebetweenthetwoapproachsintherateofpostoperativecomplication.Conclusions:RLapproachforvestibularneurectomycouldneedsimilaroperationtime,andoffershorterdistancetothefacial-acousticnervebundle,sufficientoperationfield,lesscerebellumcompressionandequaloutcomesinthetreatmentofMDwhencomparedwithRSapproach.

DIFFICULTIES OF PSYCHOLOGICAL THERAPY IN PATIENTS WITH MENIERE’S DISEASE

Haraoubia Linda 1, Ouennoughi Kheireddine 2 Beridja Lyes 1, Haraoubia Mohamed salah 2, Zemirli Omar 21 Faculty of human and social science, algiers university-2 2 Department of Otorhinolaryngology Head & Neck Surgery, algiers university-1

Objective:TheAimofthisstudyistoreportthedifficultiesofpsychologicaltherapyandtheeffectivenessinthereductionofstressanddepressionamongpatientswithMeniere’sDisease.Material and Method:Thirty-eightpatientswithsymptomsofMeniere’sDiseasewerefollowedinourclinicalinterview;fiveofthesepatientsunderwentpsychologicalassessmentwithcognitivebehaviouraltherapy(C.B.T).WehaveusedTheQuestionnaireofStressedSurvivalSituationspreparedbyZenabMahmoudShuqair,beforeandafterthetreatmentbyC.B.T.Thefollowingactivitieswereperformedinthetherapy:BehaviouralExperiments,ThoughtRecordsandrelaxation.Results:TherearestatisticallysignificantdifferencesbetweentheaveragelevelofstressbeforeandafterthetreatmentbyC.B.T.Difficulties are:- Thepatientsdonotperceivetheunderlyingpsychologythatthetherapistsdo.- Theymakedefencetyperationalizationwithhyperactivity,whichcanmakeitdifficulttosupporttherapeuticsetting.- Absencefrompsychotherapysessionsduetothehighfrequencyofepisodesoftheillness.- PositivetransfertowardstheirENTdoctorratherthantowardstheirpsychologist.Conclusion:TheMedicaltreatmentofMeniere’sDiseaseisoftenineffective,researchpresentedevidencethatpsychologicalfactorsplayedasignificantroleinthemanagementofthisdisease.Psychologicalassessment,consultation,andCBTmayprovebeneficialtotheoverallwellbeingofthepatientanddecreasestress,duetothenegativeinfluenceofthevertigoandtinnitusonhisqualityoflife.Key-words:Meniere’sDisease–stress–cognitivebehaviouraltherapy-qualityoflife.

INTRACOCHLEAR DRUG DELIVERY BY INJECTIONS THROUGH THE ROUND WINDOW MEMBRANE: MEASURES TO IMPROVE DRUG RETENTION

Stefan K. Plontke 1, Jared J. Hartsock 2, Ruth M. Gill 2, Alec N. Salt 21 Dept. of Otorhinolaryngology, Head and Neck Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany2Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, 63110, USA

Objective:Todevelopmethodologytoapplydrugsquantitativelytoperilymphoftheear. Intratympanicapplicationofdrugstotheinnerearoftenresultinvariabledruglevelsinperilymphandcanonlybeusedformoleculesthatreadilypermeatetheroundwindow(RW)membrane.Directintracochlearandintralabyrinthineapplicationproceduresfordrugs,genesorcell-basedtherapiesby-passthetightboundariesattheroundwindow,ovalwindow,oticcapsuleandtheblood-labyrinthbarrier.However,theinnerearofanimalsisheldunderapositivehydrostaticpressuremaintainedbycommunicationwithcerebrospinalfluid(CSF).PerforationsthatreleaseinnerearpressureallowinfluxofCSFthroughthecochlearaqueductcausingvolumeflowtowardstheperforationsite.Theresultingflowdisplacesinjecteddrugsolutions,washingthemoutintothemiddleear.Methods: Twomarkers,fluoresceinorfluorescein isothiocyanate (FITC)-labeleddextran,wereusedtoquantifyhowmuchofaninjected substance is retained in cochlear perilymph following an intracochlear injection. We evaluated whether procedures tomitigatefluidleaksimprovedmarkerretentioninperilymph.Results:Almostallprocedurestoreducevolumeefflux,includingtheuseofgelsforinternalsealingandgluesforexternalsealingoftheinjectionsite,resultedinimprovedretentionofthemarkerinperilymph.AdhesiveontheRWmembraneeffectivelypreventedleaksbutalsoinfluencedfluidexchangebetweenCSFandperilymph.Conclusion:Drugscanbedeliveredtotheearinaconsistent,quantitativemannerusingintracochlearinjectionsifcareistakentocontrolthefluidleaksthatresultfromcochlearperforation.

TREATMENT







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ABNORMALITY OF DOLLS’ EYES RESPONSE TO HEAD TILT IN ROLL IN PATIENTS WITH MENIERE’S DISEASE

Tomoyuki Okada 1,2, Yasuhiko Tanaka 1,2, Kojiro Ido 2, Masahiko Fukasawa 1, Yasuhiro Miyamoto 1, Manabu Nakamura 1, Izumi Koizuka 11 Department of Otolaryngology, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki City 216-8511, Japan2 Department of Otolaryngology, St Marianna University Yokohama City Seibu Hospital, 1197-1 Yasashi-cho, Asahi-ku, Yokohama City 241-0811, Japan

Introduction:ThemostnotablehistopathologicalfeatureofMeniere’sDisease(MD)is,bydefinitionastheendolymphatichydrops(EH).DespiteinitiallytheEHinvolvesthewholeinnerearsystem,therearefewreportsofotolithdysfunctionduetotheEHinMDpatients[1,2].TodetecttheEHintheotolithorgans,weinvestigatedtheotolithicnaturebasedondolls’eyesresponsetoheadtiltinroll(dolls’eye)inMDpatients.Patients and Methods:Dolls’eyewasinvestigatedin16MDpatientsinagefrom16to67year-old,visitingourclinic.Thedolls’eyesmaneuverinheadtiltinroll(dM)wasappliedinMDpatients.Allpatientswereinstructedtositonthecouchintheuprightposition,tofixateexaminer’snosebythedominanteye,duringdM.Theheadwassmoothlytiltedfromtheuprightpositiontotherightshoulderabout10-15degreesfirstlyandafterthat,theheadrecoveredtotheupright,passively.Totheoppositesidetiltwasdoneinthesameway.AlldMswereperformedinthelight.PatientswereaskednottoblinkduringdMasfewaspossible.Eitherrightorlefteye,whichisnotdominanteye,anditseyemovementsweremonitoredbyusingamodifiedFrenzelglasseswithaninfraredcamera.Eachsideoftheglasseswasabletoopentheeyecoversothatthedominanteyecanfixatetheexaminer’snose.Recordedeyemovements(6outof16patients)wereanalyzedusingcustommadesoftwarerunningontheNIHImageProgram[3]thatiswidelyusedintheworld.AndweaskedhowtheyfeelduringdM.Results:Thesmoothdolls’eye,socalledocularcounter-rollingresponse (OCR),wasobserved in6normalsubjects, though,MDpatientsshowedquitestrangeeyemovements.TherecanbeclassifiedthemintothreemaintypesinMDpatients,asfollows:1)similartoOCRbutsomethingdifferent2)torsionalnystagmustothetiltedside3)almoststandingstill.MD patients all declared that it was difficult to fixate examiner’s nose despite the instruction, since they all felt strange eyemovementsand/orsick.Discussion and Conclusion: We could not realise which the vestibular organs actually play a main role of these strange eyemovementsinMDpatients.ItisreportedthatsomeofMDpatientsshowedabnormaloculartorsion(AOT)intheuprightpositionthat canbecontributedotolithdysfunctionbecauseof theEH [1].Andalso some reportaurguenowadaysocular tilt reaction(OTR)inpatientswithperipheralvestibulrardisoreder,MD[4],aswell.AOTand/orOTRmaydriveanincompleteresponsetodMandproducestrangeeyemovements.Accordingtothis,incasesofMD,dMcanbeusefultodetectstrangeeyemovementsnon-invasively.Therefore,weemphasisethatdMmaybeabletodetecttheEHinMDpatients.

COMPARATIVE EVALUATION BETWEEN CALORIC TEST, VEMP AND DDPAOE IN DIAGNOSING MENIERE’S DESEASE

M.Z. SADI- A. MOUZALI- Kh. Ouennoughi- M.S. Haraoubia- O.ZemirliUniversity hospital of Beni messous - Algiers - Algeria

Objective:ToestimatethesensitivityandspecificityofDDPAOEandVestibularEvokedMyogenicPotentialsincomparisonwithcalorictestindiagnosingMeniereDiseaseMD.Method: Data were retrospectively collected from 850 consecutive patients who underwent vestibular tests. Among them, 78patientswerediagnosedashavingunilateraldefiniteMD.Thesensitivityandspecificityofeachtestwereevaluated.TheresultsofeachtestwerecomparedwithhearinglevelandstagingofMD.Results:ThesensitivityandspecificityofDDPAOEwere65%.ButVEMPandcalorictestarerespectively52%and47%.Conclusion:ThesensivityandspecifityofDDPAOEindiagnosingofMDarehigherthanVEMPandcalorictest

FUROSEMIDE LOADING VESTIBULAR EVOKED MYOGENIC POTENTIALS CAN DETECT HAVING ENDOLYMPHATIC HYDROPOS –UP-TO-DATE EXPERIENCE-

Toru Seo, Ko Shiraishi, Takaaki Kobayashi, Mutsukazu Kitano, Katsumi DoiDepartment of Otolaryngology, Kinki Unversity Faculty of Medicine, Osakasayama, Japan

Objective: We previously reported that the p13-n23 peak-to-peak amplitude in vestibular evoked myogenic potential (VEMP)increasedafterfurosemideadministrationinthepatientswithMeniere’sDisease.Thepositiveratiois40%,therefore,theclinicalusageisdifficulttodetecttheendolymphatichydrops.TheprocedurestorecordingVEMPhavebeendevelopedsincethen.Thefirstistone-burststimulationwereusedtorecordVEMPinsteadofclicksound.Thesecondistoneglectvariabilityofmusculartonus,amplitudewereevaluatedafternormalizationbyintegratedEMGorRMSvalueofEMG.Weadjusttheexaminationtoapplyup-to-dateclinicalsetting.Methods:Thesubjectswere10patientswithMeniere’sDiseaseand2patientswithendolymphatichydrops (theendolymphatichydropsgroup).Theyconsistedof4malesand8femalesandtheiragesrangedfrom24to59years.Forthecontrolgroup,10earsof6normalhealthyvolunteerswereused.Theyconsistedof3malesand3femalesandtheiragesrangedfrom28to42years.Thepeak-to-peakamplitudesofVEMPwererecordedbefore(AB)andafter(AA)20mgoffurosemideadministration.Theimprovedratioiscalculatedbythefollowingformula:IR=100x(AA-AB)/AB.Inthisstudy,theamplitudewasnormalizedastherawamplitudesdividedbytheintegralEMGvalueduring20msecbeforesoundstimuli.Toneburstsoundstimuliof105dBSPLand500Hzweredeliveredfromanipsilateralheadphone.Results:Themeanamplitudebeforeandafteradministrationwere0.091±0.032and0.070±0.021respectivelyinthecontrolgroup.Therewasnotsignificantdifference(p>0.05:Wilcoxonsinned-rankstest).Themeanimprovedratiowas-15.3±25.6%inthecontrolgroup.Intheendolymphatichydropsgroup,themeanamplitudebeforeandafteradministrationwere0.079±0.047and0.096±0.052respectively.Theamplitudewassignificantlyimprovedafterfurosemideadministration(p=0.034:Wilcoxonsinned-rankstest).Themeanimprovedratiowas23.2±50.6%intheendolymphatichydropsgroup.Conclusion:Whencutoffvaluewasdefinednormalupperlimit(35.9%),sensitivitywas41.7%andspecificitywas100%.Whenthevaluewasdefined22.0%,sensitivitywas63.6%andspecificitywas90%,thusitwasthoughtthatthefurosemideloadingVEMPisusefulintheclinicaldiagnosisofendolymphatichydrops.

VESTIBULAR TESTING







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IS THE CAUSE OF A VERTIGO ATTACK MENIERE’S DISEASE OR VESTIBULAR NEURITIS ? OBJECTIVE MEASUREMENTS GIVE THE ANSWER

Manzari L. 1 , Burgess A. M. 2, MacDougall H.G. 2, Curthoys I.S. 21 MSA ENT Academy Center – Cassino, Italy2 Vestibular Research Laboratory, School of Psychology, University of Sydney, NSW, Australia

Aim and Introduction: Whenapatientarrivesataclinicwithanacuteattackofvertigo,amajorquestionfacingtheclinicianis;whatisthecauseofthisattack?IsitduetoMeniere’sDisease(MD)orduetovestibularneuritis(VN)?Bothcausesevereattackswithvertigoandnystagmus.butthetreatmentandtherapeuticprogressionandtheoutcomesforthesetwocausesareverydifferent.Howthenisitpossibletodistinguishbetweenthem?Calorictestingcangiveevidenceaboutthelevelofhorizontalcanalfunctionbutthevariabilityofthecalorictestishighandgivingacalorictesttoapatientinthemidstofamajorattackofvertigoisdifficult,unpleasantanddistressingforboththepatientandtheclinicianandmanypatientsrefusetoundergosuchdistressingtesting.Patients and Methods: HerewereporttwopatientsasexamplesofpatientsdiagnosedwithMDandtwopatientswithVNwhoarrivedattheMSAClinicinCassinowithverysimilarvertigoattacks,inordertoshowhow,byapplyingnewvalidatedclinicaltestsitispossibletosimplyandquicklydistinguishbetweenMDasopposedtoVNinawaywhichwasfastandwhichwasnotdistressingforthepatientortheclinician.Thefirsttestisthevideoheadimpulsetest(vHIT–MacDougalletal2009),thesecondnewtestistheocularvestibular-evokedmyogenicpotential(oVEMP)ofmainlyutricular.TheresultsofthesetestsisdifferentforanMDattackasopposedtoaVNattack.Results: Onthebasisofphysiology,pathophysiology,previouspublicationsofpatientresults,weknowthatvestibularneuritiscausesreducedorabsentresponseofsemicircularcanalneurons,resultinginreducedVORgain.IncontrastinMDatattack,horizontalcanaldynamicfunctionisnormalorevenenhanced(Manzarietal.2011).SoifinapatientatattackvHITindicatesreducedVORgainforheadrotationstowardstheaffectedear,thenitislikelythatitisVNnotMD.ItisestablishedthatinvestibularneuritistheoVEMPn10responseisreducedorabsentbeneaththeeyeoppositetheaffectedear(Iwasakietal.2009.,Manzarietal.2010).InMDattacktheoVEMPn10isusuallyenhanced(Manzarietal.2010).SoifinresponsetoFzBCV,thetwon10potentialsareasymmetricwiththecontralateraln10smallerorabsent,thenitislikelythattobeVN.CoulditbethattheprobableMDpatienthadastroke?sincethenewHINTsprotocoldescribesthepresenceofnormalheadimpulsetest,togetherwithnystagmus(andskewdeviation),isasensitiveandspecificindicatorofcentralstroke(NewmanTokeretal2008;Kattahetal2009)andtheprobableMDpatientsherehastwoofthoseindicators.Itisunlikelybecausetheotherusualotologicaltests-suppressionofnystagmusbyvisualfixation,absenceofgazeevokedordirectionchangingnystagmus,onlymoderateposturalinstability–allpointtoaperipheralcauseratherthanacentralone.Conclusion:Theresultsfromthesenewtwotestsarecomplementarysinceoneisinvestigatingsemicircularcanalfunctioninthesuperiorvestibularnerveandtheotherisinvestigatingotolithfunctioninsuperiorvestibularnerve.Theyanswerthequestionastothecauseoftheattack.

ISOLATED AND COMBINED SEMICIRCULAR CANAL DYSFUNCTION IN PATIENTS WITH UNILATERAL VESTIBULAR SCHWANNOMA

Andy J. BeynonVestibular & Auditory Evoked Potential Lab, Radboud University Medical CentreDonders Institute for Brain, Cognition and Behaviour, Centre for NeuroscienceDept of Otorhinolaryngology, Head and Neck Surgery, Nijmegen, The Netherlands

Introduction and Aim:Toexaminetheimpactofvestibularschwannoma(VS)onthevestibularsystem,itsfunctionisnormallyassessedusingelectronystagmography(ENG)that includesoculomotor, rotarychairandcalorictesting.Recently, supplementaryvestibulo-ocularreflexes(VOR)ofall3individualsemicircularcanals(SCC)canbeassessedbyacquiringfasteyemovementsresponsesduringaheadimpulse.Byvideorecordingofeyefixation/saccadeswith100imagespersecond(videoHeadImpulseTesting,vHIT),itispossibletoobtainnotjustovert,butalsocovertcorrectionsaccadestoassessanabsenceoftheVOR.SincestandardcaloricandrotarychairtestsarespecificallyfocusedonthehorizontalSCC,theaimofthepresentstudywastoinvestigatetheclinicalimpactofvestibularschwannomasonthevertical,i.e.posteriorandanterior,SCCsfunctionality,inparticular.Resultswillelucidateits’surplusvalue,andrevealpossibleclinicaldiagnosticimplicationsandmightimprovepatientcounseling.Patients and Methods:Patients(n=86)withaunilateralvestibularschwannomawereincludedinaretrospectivestudy.Multi-channelENGrecordingswereperformedtoassessthehorizontalcanalsusingconventionalbithermalcaloricwaterirrigationtesting.Additionally,VORswereobtainedbyvideoHeadImpulseTesting(vHIT)toindividuallyassessisolatedhorizontal,butalsobothvertical(superiorandanterior)SCCs.Results and Conclusions: StandardENG revealeda significantasymmetry in68%of thepatients, i.e. severehyporeflexiaor a completeunilateralvestibularloss.WithvHIT,itwaspossibletoevokeresponsesinall6semicircularcanalsin78%ofthepatients.In61%ofthepatients,onlyoneSCCwasaffected:lateralcanalonly:25%;posteriorcanalonly:36%.NoneofthepatientswithVSrevealasingleanteriorSCClesion,norincombinationwiththeposteriorcanal.Inallotherpatients,twoormorecanalswereaffected,inwhichthelateralcanalwasalwaysinvolved(lateral+anterior:7%,lateral+posterior:11%,lateral+anterior+posterior:21%).Thepresentresultsshowthatonlycaloricassessment,didnotprovidesufficientinformationaboutthevestibularfunction.Onlyin64%,thelateralcanalispartofacompletevestibularloss.Dataanalysisalsoshowedthatnormalorasymmetricalcalorictestoutcomesshowfalsenegativeresultsinabout11%ofallpatients,whohaveaposteriorcanallesion.Inconclusion,vHIThasasurplusvalueintheassessmentofpatientswithvestibularschwannomaandiscomplementarytocalorictesting,sinceitprovidesadditiveandusefulinformationaboutthefunctionalityofallthreeSCCs,especiallyregardingtheposteriorSCC.Followingfromthis,itsimplicationsareobviousandwillbefurtheraddressedregardingtopracticalcounselingandclinicalmanagement.

MATURATIONOFSUBJECTIVEVISUALVERTICALINCHILDREN

Michel Toupet 1,2,3, Christian Van Nechel 2,4, Alexis Bozorg Grayeli 3,51 Centre d’Explorations Fonctionnelles Otoneurologiques, Paris, France2 Institut de Recherche Oto-Neurologique (IRON), Paris, France3 Otolaryngology department, Dijon University Hospital, and Burgundy University, Dijon, France 4 Neurological Rehabilitation Department, Brugmann University Hospital, Brussels, Belgium5 CNRS, UMR-6306, Electronic, Image and Computer Research Laboratory, Dijon, France

Introduction:TheattractionoftheSubjectiveVisualVertical(SVV)tothesideofrodpresentationhasalreadybeendescribedinadultsandispotentiallyrelatedtovisualdependency.Theaimofthisstudytoevaluatethisphenomenoninchildrenandtoanalyzetheeffectofsexandage.Materials and Methods:Thisretrospectivestudyincluded601childrenandteenagersagedbetween4and19years.AllsubjectsunderwentaSVVevaluationincludedinacompletebalanceworkup.SVVwasmeasuredbypresentingaphosphorescentrod12timesintotaldarknesswitha45°deviationfromtheverticalalternativelyontheleftandtheright.Thepatientwasaskedtoreplacethebarverticallywitharemotecontrol.Results:Onaverage,SVVateachiterationwastiltedtothesideoftherodpresentation.Thecumulativetilttothesideofpresentationafter12measureswashigherinthe4-7yearsagegroupanddecreasedprogressivelywithage(25±2.2°in4-7yearsgroup,mean±SEM,n=109versus5±1.4in15-19years,n=204,p<0.001,ANOVA).Thecumulativetiltwashigheringirlsthaninboysinthe15-19yearsgroup(8±2.5,n=104ingirlsversus2±1.2°n=100inboys,p<0.001,ANOVA).Thisphenomenonappearedtobeindependentfromthetypeofvestibulardisorder.Conclusion: Young children are highly attracted to the side of rod presentation during SVV measurements. This phenomenon graduallydisappearswithagebutasignificantdifferenceappearsbetweengenderssuggestingahormonalrole.







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THE PATIENTS WITH MENIERE’S DISEASE RESULTS IN THE DISCREPANCY BETWEEN VIDEO HEAD IMPULSE TEST AND CALORIC TESTING

Mutsukzu Kitano, Toru Seo, Ko Shiraishi, Takaaki Kobayashi, Katsumi DoiDept. of Otolaryngology, Kinki University Faculty of Medicine

Introduction: Videoheadimpulsetest(vHIT)wasestablishedin2009andhasbeenwidelyperformedforclinicalexamination.ItwasreportedthattheresultsofvHITweredifferentfromthoseofthecalorictestinginsomecaseswithMeniere’sDisease.Theaimofthisstudywastoclarifywhetherthediscrepancyexists.Subjects and Method:Thesubjectsconsistedof6casesofunilateralMeniere’sDisease,5casesofvestibularneuritisandacaseofRamsayHuntsyndrome.ThevHITwereexaminedusingICSImpulse.WhenVORgainwaslowerthan0.8,wedefinedtheresultasabnormal.CP%wascalculatedfrommonothermalcalorictesting.WhenCP%exceeded25%,wedefinedaresulttobeabnormal.Result:Whileabnormalresultsincalorictestingwereshownin5casesofvestibularneuritis,vHITshowedabnormalityexceptonecaseofthem.OnecaseofRamsayHuntsyndromeshowedanabnormalityonbothcalorictestingandvHIT.Ontheotherhand,abnormalresultsoncalorictestingwereshownin4casesofMeniere’sDiseaseandvHITshowedtheabnormalresulton1caseamongthem.Conclusion: ThediscrepancybetweentheresultsonvHITandthoseoncalorictestingwasconfirmed.Wesuggestedthefollowingmechanism: endolymphatic hydrops causes the enlarged ampulla portion, and then convection flow during caloric stimulationdecrease.Whensensorycellorcupulaarenotdamaged,vHITshowsnormaleveninenlargedampullarportion.

VESTIBULAR FUNCTION IN PARTIAL AND TOTAL DEAFNESS

M. Sosna1, K. Pietrasik1, G. Tacikowska1, J. Listwon1, M. Matuszewska1, H. Skarzynski1, P.H. Skarzynski1,2,31 World Hearing Center, Institute of Physiology and Pathology of Hearing, Kajetany/ Warsaw, Poland2 Medical University of Warsaw, Warsaw, Poland3 Institute of Sensory Organs, Kajetany, Poland

Aim: Thestudyaimsatassessingandcomparingthevestibularfunction inpatientswith lowfrequencyresidualhearingversuspatientswithtotaldeafness.Thequestionthatisraisedisifandtowhatextenthearingpreservationatlowfrequencycoexistswithbettervestibularstatusandbetterresponsesinvestibulartests.Materials:Allthepatientswithbilateralprofounddeafness,between20-50yearsold,beforebeingimplantedwithcochlearimplant,weredividedintofourgroupsaccordingtothepreservationofresidualhearing:Group1–patientswithpartialdeafnessdedicatedto PDT-EC (partial deafness treatment – electrical complement), Group 2 – patients with partial deafness for PDT-EAS (partialdeafnesstreatment–electro-acousticstimulation),Group3–patientwithpartialdeafnessforPDT-ES(partialdeafnesstreatment–electricstimulation),Group4–patientswithtotaldeafness.Methodology:ThepatientsunderwentcVEMP,oVEMP,vHITexaminationandfulfilledthequestionnairetoassessthevestibularsymptoms.Results and Conclusions:PatientswithpartialdeafnessachievedbetterresponsesinVEMPtests.However,thepreliminarystudyandresultsshowednosignificantdifferencebetweenPDT-EASandPDT-ECgroupandthattheintensityofvestibularsymptomswasindependentonthetypeofhearingloss.

VESTIBULAR NEURITIS ACCORDING TO VHIT TESTINGS. CLINICAL ENTITIES AND PROGNOSTIC FACTORS

Glatre Romain, Hautefort Charlotte, Verillaud Benjamin, Domange Christelle, Herman Philippe, Kania Romain Tenured Professor in Otorhinolaryngology, Head & Neck Surgery, Lariboisière Hospital, 2 rue Ambroise Paré, 75010 Paris, France, Paris Diderot University, University Paris Sorbonne Cité, EA 7334 REMES Patient-Reported Outcomes

Introduction:Vestibularneuritis(VN)usuallyinvolvesthesuperiorvestibularnervethusdefiningsuperiorvestibularneuritis(SVN).Conversely, inferior vestibular neuritis (IVN) has also been reported. Because the video head impulse test (VHIT) is able to testvestibulo-ocularreflex(VOR)fromeachsemi-circularcanal,VHITcanbeaninterestingtoolindifferentiatingIVNshowingadeficitoftheposteriorsemi-circularcanal(SCC)fromSVNshowingadeficitonboththesuperiorandlateralSCC.TheaimofthisstudywastoevaluatetheuseofVHITindifferentiatingIVNfromSVNintheirinitialclinicalpresentationandtoidentifyclinicalentitiesaccordingtooutcomes.Patients:From2010to2013,aprospectivestudywasconductedinatertiaryreferralcenterincludingallconsecutiveadultpatientsadmittedwithafirstvestibularorcochleovestibularsyndromemimickingVN,associatedwithSCCdeficit(s)onVHIT.Cardiovascularriskfactors(CVRF)wererecorded.InitialclinicalpresentationwascomparedwithrecoveryonVHITbetweengroups.Results:Sixty-twopatientswereincludedinthisstudyandweresplitinthreegroups.PatientsingroupI(n=28)hadaVHITdeficitontheposteriorSCC(IVN)whereaspatientsingroupII(n=24)andIII(n=10)hadaVHITdeficitonbothsuperiorandlateralSCC,SVN(groupII)andonthe3SCCs(groupIII)respectively.Initialclinicalpresentationwasdifferentamongthethreegroups.InGroupI(IVN)patientshadposturalimbalance,nausea/vomitingandatorsionalanddown-beatingnystagmus.HalfofpatientsingroupIhaddeafnessandtheotherhalfhadnocochlearsymptoms.Ingroup II (SVN),allpatientshadacontroversive torsionalnystagmusassociatedwithsegmentarydeviationonthesideof thepathologicvestibuleandwithoutauditorysymptoms.GroupIIIpatientshadaclinicalpresentationsimilartothatofgroupIIexceptthattwentypercent(2/10)ofpatientsexperiencedhearingloss.39%ofpatientswithoutcochlearsymptomshadnoneCVRFwhereasallpatientswithauditorysymptomshadatleastoneCVRF(p<0.05).Outcomesat3monthsshoweddifferenttypesofrecoveryaccordingtothethreegroups.IngroupI(IVN),patientswithoutcochlearsymptomsexperienced100%recoveryonVHITwhereasdeafpatientshada46%recoveryonVHIT (p<0,05). InGroup IIand III,patientsneverexperiencedatotalrecoveryonVHIT(74%and44%respectively).RecoveryratesonVHITweresignificantlyinferiorforpatientswithcochlearassociatedsymptoms(p<0.05).Conclusion:AmongpatientswithIVN,twodifferentclinicalpresentationswithorwithoutauditorysymptomswereobservedandexhibitedtwodifferentpatternofrecovery.PatientswithoutauditorysymptomshadallgoodoutcomeswithcompleterecoveryofVHITwhereas,patientswithauditorysymptomshadworstoutcomesonVHITanddeafness.ConcerningSVN,theoutcomeonVHITissignificantlyworstthatthatofisolatedIVNwithoutcochlearsymptoms.AsforSVNwhichinvolvessuperiorandlateralSCCdeficits,amicrovascularetiologymaybesuggested.







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WHITE & GRAY MATTER DIFFERENCES BETWEEN VISUAL VERTIGO PATIENTS AND HEALTHY CONTROLS: PRELIMINARY RESULTS.

A. Van Ombergen1, B. Jeurissen2, V. Van Rompaey3, S. Vanhecke3, F. Vanhevel4, J. Sidhu1, S. Sunaert5, P.H. Van de Heyning1,4, P.M. Parizel4 & F.L. Wuyts11 Antwerp University Research centre for Equilibrium and Aerospace (AUREA), University of Antwerp, Antwerp, Belgium2 iMinds/Vision Lab, University of Antwerp, Antwerp, Belgium3 Department of Otorhinolaryngology, Antwerp University Hospital, Edegem, Belgium4 Department of Radiology, Antwerp University Hospital, Edegem, Belgium5 Translational MRI, Department of Radiology, Leuven University Hospital, Leuven, Belgium

Introduction and Aim:Visualvertigo(VV)isacomplexsyndromewherepatientsexperienceseveredizzinessduetodisorientingvisual environments (e.g. supermarket aisles, crossroads). This could be due to a mismatch at specific brain regions where theintegrationofvisual,vestibularandproprioceptivesignalstakesplace.TheaimofthispilotstudywastogaininsightintheprocessofmismatchorhamperedneuroplasticityinVVpatients.Wecomparedpatientswithahealthygroupandinvestigateddifferencesinthecerebellarandvisualpathwaysinthebrain.Materials and Methods:Forthispilotstudy,fiveVVpatients(1male,meanage:48.4years)andfivehealthycontrolsubject(1male,meanage:51.1years)wereincluded.Multi-shellhighangularresolutiondiffusionweighted(DW)datawereacquiredona3TMRIscannerusinga32-channelheadcoilforallparticipants.Diffusiontensorimaging(DTI)datawereanalyzedbymeansoftractography.Inthispilotstudy,wefocusedoncerebellarandvisuospatialpathwayssuchascerebellarpeduncles,inferiorfronto-orbitalfasciculus(IFOF)andinferiorlongitudinalfasciculus(ILF).Voxel-basedmorphometry(VBM)wasalsoperformedtoanalyzewhole-braingraymatter.Results: We found statistically significant lower values in diffusion measures for the VV patients in the visuospatial network,butstatisticallysignificanthighervaluesforthecerebellarnetwork.Furthermore,VBManalysisshowedasignificantgraymatterdecreaseintheleftinferioroccipitallobe(p<0.001,uncorrected)andtherightangulargyrus(p<0.001,uncorrected).Conclusions: Toourknowledge, this is thefirst study tousediffusion imagingmethods in this specific subgroupof vestibularpatients.Furthermore,weshowarelationbetweenparametersrepresentingbrainconnectivityandclinicalsymptomsofvertigo,definingconsequentlybiomarkersinthebrainforvisualvertigo,adiseasethatishardtoobjectify







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7th international symposium on ... - acufeni, che fare · meniere’s disease and inner ear...

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