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Chronicsymptomsaftervestibularneuritisandthehigh

velocityvestibulo‐ocularreflex

MiteshPatel1,2,QadeerArshad1,REdwardRoberts1,HenaAhmad1,AdolfoM.Bronstein1*

1DepartmentofNeuro‐otology,DivisionofBrainSciences,ImperialCollegeLondon,Charing

CrossHospitalCampus,FulhamPalaceRoad,LondonW68RF,UK.Tel:+44(0)2033135525,

Fax:+44(0)2033117577

2SchoolofHealth,Sports&Biosciences,UniversityofEastLondon,StratfordCampus,Water

Lane,London.E154LZ.

*Correspondence:a.bronstein@imperial.ac.uk

Shortrunninghead:ChronicsymptomsandtheVOR

WordCount:1867

ConflictsofInterestandSourcesofFunding

Theauthorsreportnoconflictsofinterest.TheresearchwassupportedbytheUKMedical

ResearchCouncil(MR/J004685/1). 

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provided by UEL Research Repository at University of East London

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Abstract

Hypothesis:Astheanteriorandposteriorsemicircularcanalsarevitaltotheregulationofgaze

stability,particularlyduringlocomotionorvehiculartravel,wetestedwhetherthehighvelocity

vestibulo‐ocularreflex(VOR)ofthethreeipsilesionalsemicircularcanalselicitedbythe

modifiedHeadImpulseTestwouldcorrelatewithsubjectivedizzinessorvertigoscoresafter

vestibularneuritis(VN).

Background:RecoveryfollowingacuteVNvarieswitharoundhalfreportingpersistent

symptomslongaftertheacuteepisode.However,anunansweredquestioniswhetherchronic

symptomsareassociatedwithimpairmentofthehighvelocityVORoftheanteriororposterior

canals.

Methods:TwentypatientswhohadexperiencedanacuteepisodeofVNatleastthreemonths

earlierwereincludedinthisstudy.Participantswereassessedwiththevideoheadimpulsetest

(vHIT)ofallsixcanals,bithermalcaloricirrigation,theDizzinessHandicapInventory(DHI)and

theVertigoSymptomsScaleshort‐form(VSS).

Results:Ofthese20patients,12feltthattheyhadrecoveredfromtheinitialepisodewhereas8

didnotandreportedelevatedDHIandVSSscores.However,wefoundnocorrelationbetween

DHIorVSSscoresandtheipsilesionalsingleorcombinedvHITgain,vHITgainasymmetryor

caloricparesis.ThehighvelocityVORwasnotdifferentbetweenpatientswhofelttheyhad

recoveredandpatientswhofelttheyhadnot.

Conclusions:OurfindingssuggestthatchronicsymptomsofdizzinessfollowingVNarenot

associatedwiththehighvelocityVORofthesingleorcombinedipsilesionalhorizontal,anterior

orposteriorsemicircularcanals.

Keywords:Vestibular;vestibularneuritis;dizziness;vertigo,head‐impulsetest

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Introduction

Vestibularneuritis(VN)isanacutedisordercharacterisedbyvertigo,nausea,vomitingand

imbalancefollowingsuddenunilaterallossofperipheralvestibularfunction(1).Recoveryis

throughperipheralandcentralvestibularcompensation(2).Typically,symptomslastdaysor

weeksbutaround50%ofpatientsexperiencechronicdizziness,unsteadinessandspatial

disorientation(3,4).

Ithasbeenpostulatedthatpersistentperipheralvestibularlosscouldaccountforthesechronic

symptoms(5).Thestandardmeasureofperipheralvestibularlossisthegainofthevestibulo‐

ocularreflex(VOR)whichistheratioofthesizeofslowphasecorrectiveeyemovementtothe

sizeofheadmovement(peakslowphaseeyevelocity/peakheadvelocity).TheVORmaintains

gazestabilityandpreservesvisualacuityduringheadmovements.Impairmentcancausevisual

blurringduringheadmotion(6),whichcouldbeinterpretedbythepatientasdizziness,

unsteadinessorspatialdisorientation.Thus,acentralquestionregardingtheprocessof

symptomrecoveryiswhetherthisisrelatedtoadysfunctionalVOR.

PreviousstudieshaveshownthatthelowvelocityVORresponsefromthecalorictestdoesnot

predictchronicsymptomsofdizzinessorvertigo(3,7,8).However,recentadvanceshaveledto

thedevelopmentofabedsideclinicalheadthrustorimpulsetest(HIT)measuringthehigh

velocityVORofallsixsemicircularcanals(9).ThehighvelocityVORelicitedbytheHITrecovers

moreslowlyfollowingacuteVNcomparedtothelowvelocityVORelicitedbycaloricirrigation

(10‐12),andmaythusbetterreflectclinicaloutcome.

Interestingly,Pallaandcolleagues(13)haveshownthatthereisnorelationshipbetweenthe

highvelocityhorizontalcanalVORgainandchronicsymptomsfollowingVN.However,asthe

anteriorandposteriorsemicircularcanalsarevitaltotheregulationofgazestability(14),

particularlyduringlocomotionorvehiculartravel,weposedthequestionofwhetherthehigh

velocityVORgainofthethreeipsilesionalsemicircularcanals(elicitedbythemodifiedHIT(9))

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wouldpredictsubjectivedizzinessorvertigoscoresafterVN.ThelowvelocityVORofthe

horizontalcanal(elicitedbycaloricirrigation)wasmeasuredforcomparison.

MaterialsandMethods

Twentypatients(7male,31‐87years(mean57.3+/‐18)withclinicalhistories,physical

examinationsandfunctionteststypicalofacuteVNwererecruitedi.e,horizontalnystagmus,

clinicallyabnormalhead‐impulsetestandasignificantcanalparesis.Ofourpatients,nonehad

inferiorvestibularneuritis.Theexclusioncriteriawerepatientswithnocurrentindicationsof

overlappingvestibularmigraine.Forthisstudy,allpatientsweretestedinthechronicstageof

VN(3‐36monthsafteracuteVNonset;mean9.8+/‐7.5),includingarepeatcalorictest.

Informedconsentwasobtainedfromallsubjects.

Vestibularassessment

Six‐canalvHIT:EyeandheadmovementsweresimultaneouslyrecordedusingtheICSvideo

HeadImpulsesystem(vHIT,GNOtometrics,Denmark).Thesystemconsistsofapairoflight‐

weightgogglescontaining3‐Dgyroscopestomeasureheadvelocity,andasmallmountedvideo

cameratorecordeyeposition.Thevideocameraismountedwithintherighteye‐frameofthe

goggles,whichweresecuredfirmlytothesubject’sheadwithanadjustableelasticstrap.

Thepatientwasinstructedtofixateonatargetpositionedapproximately1.5metresinfrontof

them.Theexaminer,whileholdingthepatient’sheadfrombehind,thenmadeaseriesofbrisk

headmovements(10–20°amplitude)correspondingtothehorizontal,leftanterior‐right

posterior(LARP)andrightanterior‐leftposterior(RALP)canalplanes(15).Incontrasttoearly

papersmeasuringVORresponsesalongtheLARPandRALPplanes(16),withthevHIT

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techniquetheheadmustbeturnedinyawbyapproximately40‐45osothattheheadimpulse

deliveredonly(ormostly)elicitsverticalVORmovements.

Eyeandheadvelocitiesweresampledat250Hzandtheratioofeye‐to‐headpeakvelocity(VOR

gain)wascalculatedforeachsemicircularcanalfromanaverageof20headimpulses

performedoverarangeofvelocities(50–300°/s)(17).Asymmetrybetweentheipsilesionaland

contralesionalcanalswasalsocalculatedandexpressedasapercentage(18).

Inadditiontothesinglecanalgainvaluesandasymmetryvaluesgeneratedautomaticallybythe

vHITprogram,wecalculatedatotalgainforeachside:

3⁄ ,andtotal

right/leftasymmetry(%).Aspreviousstudieshavereportednocorrelationbetweenhorizontal

canalvHITgainorasymmetrywithlong‐termrecovery,wealsofocussedontheverticalcanals

andcalculatedaverticalcanalgain 2⁄ ,and

verticalcanalright/leftasymmetry(%).Theseformulaeprovideoverallvaluesforthe

contributionsfromeachcanal.

Calorictest:Bithermalcaloricirrigations(30&44°C)wereperformed(ICSCHARTR,GN

Otometrics,Denmark)andthedegreeofcanalparesiswascalculatedusingJongkeesformula

andexpressedasapercentageaspreviousstudies(18).

Symptomsquestionnaires

Inparallel,symptomsduringthepastmonthwerescoredwiththeDizzinessHandicap

Inventory(DHI)(19)andtheVertigoSymptomsScaleshortform(VSS)(20).Wealsoaskedeach

patientwhethertheyfelttheyhadrecoveredfromtheacuteepisodeornot.

‐Table1abouthere‐

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PearsonCorrelationCoefficientanalyseswereemployedbetweenallmeasures.Independent

samplest‐testswereusedasconfirmation.LinearregressionwasusedtotestwhethervHIT

gainspredictDHIorVSSscores.P‐valueswerecorrectedformultiplecomparisons.

Results

AsshowninTable1,eightpatientsfeltthattheyhadnotfullyrecoveredfromtheacuteepisode.

ThesepatientsalsohadthehighestDHIandVSSscores(pairedt‐testP<0.002).Therewasa

strongsignificantcorrelationbetweenDHIandVSSacrossthegroupof20VNpatients

(P<0.001,PearsonCorrelationCoefficient=0.857).Therewasnocorrelationbetweencaloric

paresisandDHIscore(Pearsoncorrelationcoefficient=‐0.134,P=0.57)orbetweencaloric

paresisandVSSscore(Pearsoncorrelationcoefficient=‐0.076,P=0.572).Therewasalsono

correlationbetweencaloricparesisandhorizontalcanalvHITgainasymmetry(Pearson

correlationcoefficient=0.176,P=0.458).

Withlinearregression,theadjustedR‐squarewas0.02forDHIscoresand0.084forVSSscores.

TheregressionwasnotsignificantforeitherDHIscores(F[0.47],P=0.82)orVSSscores

(F[1.29],P=0.327).Similarly,stepwiselinearregressionidentifiednopredictingindependent

variablesintheanalysis(novariableswereenteredintotheanalysisforeitherDHIorVSS).

AsshowninFigure1A‐F,therewasnocorrelationbetweentheipsilesionalvHITgainsforthe

horizontal,anteriorandposteriorcanalsandvHITgainasymmetryforthehorizontal,anterior

andposteriorcanalsversusDHIscore.

AsshowninFigure2A‐F,therewasalsonocorrelationbetweentheipsilesionalvHITgainsfor

thehorizontal,anteriorandposteriorcanalsandvHITgainasymmetryforthehorizontal,

anteriorandposteriorcanalsversusVSSscore.

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WealsocomparedvHITgainsandvHITgainasymmetriesforthehorizontal,anteriorand

posteriorcanalsbetweenthe8patientswhofelttheyhadnotrecoveredandthe12patients

whofelttheyhadrecovered.Independentsamplest‐testsshowednodifferencebetweenthese

groups(P=0.26‐0.92).

‐Figure1abouthere‐

‐Figure2abouthere‐

WealsoinvestigatedtherelationshipbetweenvHITresponseandrecoverybygroupingthe

vHITsinglecanalgainsintothemeansumofthecanalvectorstogiveasinglegainvalueforthe

ipsilesionalandcontralesionalsides.Wealsogroupedtheipsilesionalsemicircularcanalsintoa

singlevaluefortheanteriorandposterior(vertical)canalsgainandasymmetry,asdescribedin

Methods.

Wefoundnosignificantcorrelationbetweenthevectorsumofthethreeipsilesionalcanalgains

(horizontal+anterior+posterior)andDHIscores(Pearsoncorrelationcoefficient=‐0.124,

P=0.60)orVSSscores(Pearsoncorrelationcoefficient=‐0.302,P=0.196).Asymmetrydidnot

correlatetoDHI(P=0.55)orVSSscores(P=0.13)asshowninFigures3Aand3B.

Inaddition,therewasnosignificantcorrelationbetweenthevectorsumoftheverticalcanals

(anterior+posterior)andDHIscores(Pearsoncorrelationcoefficient=‐0.125,P=0.60)orVSS

scores(Pearsoncorrelationcoefficient=‐0.152,P=0.15).AsymmetrydidnotcorrelatewithDHI

(P=0.77)orVSSscores(P=0.10)asshowninFigures3Cand3D.

NeithertotalnorverticalcanalgainandasymmetryvaluesweresignificantpredictorsofDHIor

VSSscoreswithmultipleregressionanalysis,i.e.,novalueswereenteredintotheanalysis

duringstepwiseregression.

‐Figure3abouthere‐

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Discussion

Here,wefindnoevidencetosupportthehypothesisthatchronicsymptomsofdizzinessor

vertigofollowingacuteVNareassociatedwiththehighvelocityVORofthethreeipsilesional

semicircularcanals.TherewasnocorrelationbetweenipsilesionalhighvelocityVORgainor

gainasymmetryofthesingleorcombinedhorizontal,anteriorandposteriorcanalsmeasured

withthevHITandDHIorVSSscores.Patient4isarepresentativeexample:thisindividualwas

asymptomatic(DHI=0)buthadanipsilesionalposteriorcanalgainof0.33.Incontrast,patient

20whowasthemostsymptomaticindividual(DHI=70)hadnormalvHITgainsforeachofthe

canals(above0.78).

Also,asinpreviousstudies,therewasnocorrelationbetweencaloricparesisandchronic

symptomsafterVN(21,22)orbetweencaloricparesisandhorizontalcanalHITasymmetry(11)

probablyreflectingthedifferentfrequencyrangesofthesetests.

ThereislittledoubtthatacuteVNtriggeredthepatients’chronicsymptoms,howeverresidual

semicircularcanaldeficitsmightnotbeacrucialfactor.Astheotolithsareinvolvedinthe

translationalVOR(tVOR)(23),itispossiblethatimpairedotolithfunctioncouldexplainchronic

symptomsinsomepatients.UtricularfunctionistypicallyaffectedinVNasmeasuredwith

ocularVEMP(oVEMP)(24).Inaone‐yearfollow‐upstudyinVNpatients,Magliuloand

colleagues(25)foundthatfouroutoffivepatientswithchronicsymptoms,hadabsent

ipsilesionaloVEMPresponses.Saccularfunctionisimpairedwhentheinferiorbranchofthe

vestibularnerveisaffected.However,itisunlikelythatotolithdamagewouldbethecritical

variablepredictinglongtermoutcomeinVNgiventhatevenpatientswithvestibular

neurectomyrecoverwell(26).

Anotherexplanationisthattherelativeweightingsofvestibular,visualandsomatosensory

signalschangefollowingunilateralvestibularloss.Indeed,wehavefoundthatchronic

symptomsafterVNmayrelatetoincreasedvisualdependence(3).Psychological(22,27)and

spatialorientationfactors(28),alsohaveastronginfluenceonlongtermoutcome.

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Thesamplesizeusedinthisstudy(n=20)isalsoapotentiallimitation,butifthiswerethecase

itwouldimplythattherelationshipbetweenclinicaloutcomeandvHITgainsisveryweakand

thereforeunlikelytobesensitiveenoughtobeofpracticaluseinaclinicalenvironment.Using

meanandstandarddeviationdatafromourstrongestcorrelationcoefficient(Figure2E,

anteriorcanalgainvsVSS)wecalculatedthatsubjectsrecruitedwouldneedtoequaln=58to

achieveP<0.05(Power=0.8)beforecorrectionformultiplecomparisons.

Toconclude,chronicsymptomsofdizzinessorvertigofollowingacuteVNwerenotrelatedto

thehighvelocityVORofthehorizontal,anteriororposteriorsemicircularcanals.Itislikelythat

clinicalrecoveryandoutcomedependsmostlyoncentralcompensation,includinghigherlevel

processinginthebrain.

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Figure1.vHITVORgainsfortheipsilesionalA).Horizontal,B).AnteriorandC).Posterior

canalsandvHITgainasymmetryfortheA).Horizontal,B).AnteriorandC).Posterior

canalsversusDHIscore.vHITassessmentdidnotcorrelatewithDHIscore.

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Figure2.vHITVORgainsfortheipsilesionalA).Horizontal,B).AnteriorandC).Posterior

canalsandvHITgainasymmetryfortheA).Horizontal,B).AnteriorandC).Posterior

canalsversusVSSscore.vHITassessmentdidnotcorrelatewithVSSscore.

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Figure3:vHITVORgainforthetotalresponseversusDHIscore(A)andVSSscore(B)&

vHITVORgainfortheverticalcanal(anterior+posteriorcanals)responseversusDHI

score(C)andVSSscore(D).

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Tables

Table1.Vestibulartestingdataandsymptomscoresfromthepatientswhoparticipated

inthisstudy(n=20).