Vestibular Disorders in Children WithCongenital Cytomegalovirus InfectionSophie Bernard, MDa, Sylvette Wiener-Vacher, MD, PhDa,b,c, Thierry Van Den Abbeele, MD, PhDa,b,c, Natacha Teissier, MD, PhDa,b,c

abstractBACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause ofneurologic disabilities and sensorineural hearing loss in children. Sensorineural hearing lossprevalence in CMV suggests a viral tropism for the inner ear. Vestibular disorders induced by CMVinfection are underestimated. This is the largest and most thorough study to assess the incidenceof vestibular disorders and their correlation with hearing thresholds in children with CMV.

METHODS: This retrospective study assessed a cohort of 52 children with congenital CMVinfection and sensorineural impairment who received a complete hearing and vestibularassessment. Vestibular evaluation included clinical examination, caloric bithermal test, earthvertical axis rotation, off-vertical axis rotation, and vestibular evoked myogenic potential. Theprevalence, progression, and clinical impact of vestibular disorders were studied andcorrelated with hearing thresholds and the severity of congenital CMV infection.

RESULTS: Forty-eight children (92.3%) had hearing loss and vestibular disorders. Of those,vestibular disorders were complete and bilateral in 33.3%, partial and bilateral in 43.7%, andpartial and unilateral in 22.9%. Serial testing in 14 children showed stable vestibular functionin 50% and deterioration in 50%. Congenital CMV infection has a negative impact on posturaldevelopment that is correlated with neurologic and vestibular impairment. Vestibulardisorders were significantly associated with hearing disorders, but their respective severitiesshowed no concordance.

CONCLUSIONS: Vestibular disorders are frequent and severe in CMV-infected children. Routinescreening and appropriate management of vestibular lesions is essential to initiate adapted care.

WHAT’S KNOWN ON THIS SUBJECT: Congenitalcytomegalovirus infection is the leadinginfectious cause of neurologic disabilities andsensorineural hearing loss in children. Little isknown concerning the frequency and impact ofvestibular disorders induced by cytomegalovirusinfection.

WHAT THIS STUDY ADDS: This study reports onthe largest cohort of vestibular assessment ofchildren congenitally infected withcytomegalovirus, demonstrating vestibulardamages, and analyzes the correlations betweenvestibular dysfunction and hearing impairmentor severity of infection. Cytomegalovirus infectionaffects postural development in children.

aPediatric Otorhinolaryngology Department and bInstitut National de la Santé et de la Recherche Médicale(INSERM), cUniversité Paris Diderot, Paris, France

Dr Bernard carried out the data collection and the initial analyses and conceptualized and draftedthe initial manuscript; Dr Wiener-Vacher conceptualized and designed the study, oversaw all thevestibular assessment, and reviewed and revised the manuscript; Drs Teissier and Van Den Abbeeledesigned the data collection instruments, coordinated and supervised data collection, and criticallyreviewed the manuscript; and all authors approved the final manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2015-0908

DOI: 10.1542/peds.2015-0908

Accepted for publication Jul 21, 2015

Address correspondence to Dr Natacha Teissier, Pediatric Otorhinolaryngology Department, RobertDebré Hospital, 48 Bd Sérurier, 75019 Paris, France. E-mail: natacha.teissier@rdb.aphp.fr

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2015 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant tothis article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts ofinterest to disclose

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Congenital cytomegalovirus (CMV)infection is the leading infectiouscause of developmental andneurologic disabilities andsensorineural hearing loss (SNHL) inchildren.1–5 In France, congenitalCMV infection currently affects 0.5%of all newborns.6

Clinical signs in neonates are variable:5% to 10% are symptomatic at birth,with a mortality rate of up to 10%.7

Sixty percent may develop cerebrallesions with neurologic sequelae, suchas microcephaly, seizures, hypotonia,and feeding disorders, as well assensorineural sequelae includingchorioretinitis and hearing loss.Patients may also have growthretardation, jaundice, organomegaly,and low platelet count. Furthermore,8% to 15% of asymptomatic neonateswill develop neurologic sequelae.3,8

SNHL is the main sequela of thiscongenital infection, and also themain cause of nonhereditarycongenital deafness in humans.9

Foulon et al10 performeda prospective study of children withcongenital CMV infection and foundSNHL in 21% of asymptomaticchildren and 33% of symptomatic

children. They concluded that 22% ofall infected children, irrespectiveof neonatal signs, had some degree ofSNHL. A recent review confirmed theincidence of SNHL in 32.8% ofsymptomatic cases.11 Other studiesshowed unilateral SNHL in 33% to52% of the cases, with all degreesof severity of hearing loss.12

The high prevalence of SNHL inchildren congenitally infected by CMVsuggests a viral tropism for the innerear. Autopsied pediatric CMV casesconfirmed that cytomegalic cells werepresent in the inner ear; lesionswere mainly observed in theendolymphatic compartment of theinner ear, particularly in thevestibular structures.13–20

Little research has been carried out onvestibular disorders induced bycongenital CMV, and only 2 studiesare available.21,22 Zagólski21 suggeststhat the prevalence of vestibulardisorders is probably underestimatedand could be higher than that ofhearing loss. To date, routine inner earinvestigations of these infants includeclassic audiometric follow-up butnot vestibular testing despite strongevidence of vestibular infection.13,16

In addition, congenital and early-onset complete vestibular loss areknown to induce severe delays in theacquisition of the first posturomotormilestones, such as the ability to holdthe head stably and to sit and walkindependently.23,24

The main objective of this study wasto determine the prevalence, severity,and changes over time of vestibulardeficits in pediatric CMV cases andtheir correlation with othersensorineural disorders inducedby CMV infection.

METHODS

Subjects

A retrospective study was carried outin the otolaryngology department ofRobert Debré University Hospitalfrom 2000 to 2013. All includedpatients were diagnosed withcongenital CMV infection andunderwent vestibular functionevaluation. Data concerning hearingand CMV status was also collected(institutional review board approval951008).

Some patients had several vestibularassessments during their follow-up to

FIGURE 1Global vestibular assessment.

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estimate changes in vestibularimpairment over time and beforecochlear implantation, which itselfcan lead to vestibular impairmentindependently of CMV.25

Data Concerning Congenital CMVInfection

Diagnostic Confirmation

All 52 children had a positive urine orsaliva culture in the first 2 weeksafter birth, positive dried blood spot,or neonatal immunoglobulinM–positive serology.

Clinical and Radiologic Symptoms

Neonatal symptoms of CMVintrauterine infection and the dateof vestibular testing were noted.Moreover, cerebral and inner earabnormalities were investigated byusing MRI and computed tomographyscans of the brain and temporal bone.

Hearing Evaluation

Hearing assessment was performedin all patients. Transient evokedotoacoustic emissions (TEOAEs) wererecorded; if appropriate responseswere absent, hearing evaluation wascompleted with an auditory brainstemresponse and/or behavioralaudiometry tests. Some childrenunderwent several hearing tests.Hearing thresholds were categorizedas follows: normal, ,20 dB; mildSNHL, 21 to 40 dB; moderate SNHL,41 to 70 dB; severe SNHL, 71 to 90 dB;and profound SNHL, .90 dB.

Clinical Evaluation of PosturalDevelopment and Behavior

The ages of posturomotor controlmilestone acquisition (head holding,sitting without support, standing with

support, and independent walking)were carefully recorded for each childfrom pediatric medical records(systematically recorded bypediatricians). Data were comparedwith an age-matched non–CMV-infected pediatric population (n = 58)(data previously published23–28 anddetermined from our database).

Vestibular and Neurologic Evaluation

Vestibular evaluation includedseveral tests investigating canal andotolith function (SupplementalInformation). Our protocol includedcomplete vestibular and neurologicclinical evaluations (includingcerebellar, sensitivity, and musculartesting)25,29 followed by instrumentaltesting of vestibular function. Canalfunction was evaluated at variousfrequencies with (1) bithermic calorictest (33°C and 44°C) for lowfrequencies, (2) earth vertical axisrotation (EVAR) with 40°/s2

acceleration and deceleration alonga vertical axis for mediumfrequencies,25 and (3) head impulsetest (HIT) to test the 6 semicircularcanals at high frequencies.25 Otolithicfunction was assessed by using 2techniques: (1) off-vertical axisrotation (OVAR) with 60°/s constantrotation velocity and 13° axis rotationtilt30 and (2) cervical vestibularevoked myogenic potential (c-VEMP)with short tone bursts (750 Hz, 4.1/sand 6-ms duration) delivered by airand bone conduction with a control ofthe electromyogram level for eachstimulation.31 The c-VEMP test wasperformed by using modifiedbrainstem evoked responseaudiometry equipment (Centor C+,Deltamed, France). The EVAR-OVARtests were performed usinga computer-driven rotatory chair(SAMO, La Roche sur Foron, France),and the vestibulo-ocular responses(VORs) were recorded byelectronystagmography more adaptedto young children than videorecordings.

For the bicaloric tests, the Jongkeesformula was applied, in which normal

values for relative valence anddirectional preponderance forchildren are #15%. The bicaloric testresponses could be normal, absentbilateral, partial symmetric (bilateralsymmetric hyporeflexia), or partialasymmetric (one side being orareflexic or hyporeflexic comparedwith the other side). The HIT test waseither normal (no catch-up saccade)or abnormal (presence of a catch-upsaccade) for all 6 canals if completedeficit or for some canals in case ofpartial deficit.

For the c-VEMP, we studied thelatencies (ms), thresholds (dB), andamplitude (mV) at 100 dB of P and Nwaves. The VEMP results could benormal (presence of bilateral P andN with a symmetric amplitude at100 dB), absent bilateral (absence ofP and N), partial symmetric (positiveresponses only at thresholds .100 dB),or partial asymmetric (difference ofthresholds .10 dB and of PNamplitude exceeding 100 µV betweenthe 2 ears).

For the EVAR test, we measured thetime constant and maximal initialslow phase velocity of the VOR. ForOVAR (otolith stimulation), theparameters analyzed were the biasand the modulation amplitude ofhorizontal and vertical components ofthe VOR.27,30

Normal values of EVAR and OVARwere established from a group of 58age-matched control children withnormal clinical vestibular function.The EVAR and OVAR responses couldbe normal, absent bilateral, partialsymmetric (positive response butdecreased for the age), or partialasymmetric (significant asymmetry

TABLE 1 Population Characteristics(n = 52) (SD)

Age at first vestibularassessment, months

34.7 (28.5)

Girls (n = 31) 60Boys (n = 21) 40Vestibular assessments per child 1.5 (1.2)Follow-up of multiple vestibular

assessments, months26.3 (23)

Values are expressed as mean (SD) or %.

TABLE 2 Hearing Thresholds for Each Ear(n = 104) at the Time of VestibularAssessment

Hearing Threshold, dB n %

,20 18 17.321 to 40 5 4.841 to 70 13 12.571 to 90 14 13.591 to 119 48 46.1.120 6 5.8

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between the 2 sides or only unilateralresponse).

For a global vestibular evaluation, wecollected all results and defined 8categories of modifications (Fig 1):areflexia when no response wasobserved with HIT, caloric, EVAR, andc-VEMP tests; partial and bilateralcanal or otolith disorders; partial andunilateral canal or otolith disorders;and normal vestibular function.

Statistics

Descriptive statistics and statisticalanalyses were performed with Epi-info 7 and Excel software. Data areshown as mean (SD). Student t testwas used for comparisons betweengroups. Fisher test was used toassess any correlation betweenparameters such as severity orlaterality of vestibular impairment,hearing loss, or severity ofcongenital CMV infection andvestibular impairment. Cohen’s k

coefficient was used to evaluateconcordance between theparameters analyzed for correlation.

A P value ,.05 was consideredstatistically significant.

RESULTS

Population Characteristics

Fifty-two children with congenitalCMV infection, 31 females and 21males, were included in this studyand tested for vestibular function.Age at first vestibular examinationwas 34.7 (28.5) months (range5 months to 11 years) (Table 1).Fourteen children performed .1complete vestibular assessment (witha maximum of 7 tests). The averagefollow-up was 26.3 (23) months(range 1 to 64 months).

Congenital CMV Infection

Clinical and Radiologic Symptoms

At birth, 22 infants (42.3%)presented with clinical symptomsrelated to intrauterine CMV infection.These neonatal symptoms includedhearing loss (14/22), intrauterinegrowth retardation (7/22),organomegaly (6/22),

thrombocytopenia (8/22), hepatitis(3/22), neurologic disorders (6/22),and hypotonia (3/22).

Neurologic sequelae affected 9children: 5 with hemiparesis (2 ofwhom also had seizures), 1 withpyramidal syndrome, 1 withencephalopathy, 1 with finemovement disorder, and 1 withperipheral facial palsy. Nine childrenhad visual disorders.

Cerebral and inner-ear computedtomography and MRI scans showedintracerebral calcifications (8/52),hyperintense signals in the whitematter (19/52), ventricular dilations(3/52), and ischemic lesions (1/52).

Hearing Evaluation

Hearing loss was diagnosed in 48 of52 children (92.3%) (4 children hadnormal hearing). At birth, 26.9% ofchildren (14/52) had hearingimpairment, but only 55.8% (29/52)underwent neonatal hearingscreening.

Hearing thresholds are presented andclassified in Table 2. All degrees ofSNHL were observed. Hearing losswas bilateral in 38 children (27symmetric and 11 asymmetric) andunilateral in 10 children. There wasa majority of profound hearing loss(52%) and bilateral symmetric(56.3%) impairment. The hearingimpairment was progressive (37.5%),stable (39.6%), or fluctuating (8.3%);for the others (14.6%), the evolutionwas unknown.

Forty-five patients underwentmultiple hearing tests. Hearingthresholds were stable in 19 cases,progressive in 18 cases, andfluctuating in 4 cases.

Posturomotor Development

Congenital CMV infection hada significant impact on all stages ofposturomotor development (Table 3).

Vestibular Function Assessment

Analysis of the various vestibulartests is described in Table 4. In thisstudy, 90.4% of the children (47/52)

TABLE 3 Age at Each Stage of Posturomotor Milestones for CMV-Infected Children and NoninfectedChildren

Stages of Posturomotor Milestones CMV-Infected (n = 52) Noninfected (n = 58) Pa

Head control .0002Minimum/maximum 2/12 1/6Median (interquartile range) 4.0 (3.0–7.0) 3.0 (2.0–3.0)Mean (SD) 5.1 (2.6) 2.8 (1.0)

Unsupported sitting ,.0001Minimum/maximum 4/24 4/9Median (interquartile range) 10.0 (8.0–12.0) 6.0 (6.0–7.0)Mean (SD) 10.2 (3.5) 6.4 (1.2)

Unaided walking ,.0001Minimum/maximum 14/75 7/18Median (interquartile range) 21.0 (18.0–27.0) 13.5 (12.0–15.0)Mean (SD) 24.0 (10.8) 13.6 (2.2)

a Student t-test.

TABLE 4 Results of the Vestibular Tests

Value Frequency Tract

Low:Bicaloric

Medium:EVAR

High:HIT

Vestibulo-ocular:OVAR

Vestibulospinal:VEMP

Tests, n 51 49 52 45 51Abnormal responses, n 38 43 30 35 40Abnormal responses, % 74.5 87.8 57.7 71.1 78.4Abnormal responses in

combined tests, %90.4 (47/52) 86.5 (45/52)

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had canal dysfunction, and 86.5%(45/52) had otolithic dysfunction.The severity of the vestibularimpairment evaluated by each test issummarized in Figs 2 and 3.

The global vestibular assessment forthe 52 patients was abnormal in92.3% of cases (Table 5). Completebilateral vestibular loss (absence ofresponses to all tests) was found in16 of 52 patients (30.8%), partialbilateral dysfunction in 21 patients(40.4%), and partial unilateraldysfunction in 11 patients (21.1%).Among the 21 patients with partial

bilateral disorder, an asymmetrybetween the 2 vestibules was notedin 12 patients.

Of the 14 patients with serial tests, 7(50%) had stable vestibular functionand 7 (50%) had progressivevestibular deterioration over time.

Correlation Between HearingImpairment and VestibularDisorders

A statistically significant associationwas found between the laterality ofvestibular disorders and hearingimpairment (P = .03). However, no

concordance could be demonstratedin the laterality of these disorders(k = 0.05) (Table 6).

A statistically significant associationwas found between the severity ofvestibular disorders and hearingimpairment (P = .02), but the gravityof these disorders showed noconcordance (k = 0.01) (Table 7).

Correlation Between Severity ofCongenital CMV Infection andVestibular Disorders

There was no significant relationshipbetween the initial severity ofcongenital CMV infection and thegravity of subsequent vestibulardisorders (P = .09) (Table 8).

DISCUSSION

To our knowledge, this study reportson the largest cohort of congenitallyinfected CMV children (n = 52),demonstrating vestibular damages(canalar and otolithic function), withcomplete detailed case histories.Moreover, the analysis of thecorrelations between vestibulardysfunction and hearing impairmentor severity of congenital CMVinfection is unique. Our work alsodemonstrates the impact ofcongenital CMV infection on posturaldevelopment in children.

Characteristics of the Population

At birth, 22 of the 52 children(42.3%) were asymptomatic, 17 werediagnosed neonatally by serology orurinary test, and 5 were diagnosedretrospectively on dried blood spot.However, at time of vestibular testing,98.1% presented with $1 symptomcorresponding to a sequela ofcongenital CMV infection.

All children underwent a completeassessment of hearing and vestibularfunction. We found a very highprevalence of vestibular impairment(92.3%); however, our populationmay not reflect the generalpopulation of CMV-infectedchildren,32,33 because some childrenare referred to our center for

FIGURE 2Results of canal testing according to test type (bicaloric, EVAR, and HIT). Data are expressed as thenumber of tests performed.

FIGURE 3Results of otolith testing (VEMP in bone conduction and OVAR). Data are expressed as the number oftests performed.

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profound hearing loss requiringcochlear implantation and mayrepresent severe cases of CMV.Asymptomatic congenitally CMV-infected children were less frequentlyaddressed to our center. Thisselection bias may explain the highfrequency of vestibular disorders inour study. A prospective studyincluding all children with congenitalCMV infection (symptomatic or not)would more accurately determine theprevalence of vestibular damagesinduced by congenital CMV infection.However, such a study would behindered by difficulties in diagnosis ofcongenital CMV infection, especiallywhen children are asymptomatic.Systematic screening for this infectionduring pregnancy and in neonates isnot yet recommended in France.34

Diagnosis is therefore mostlyretrospective and based on clinicaland radiologic findings.

Audiologic Characteristics

In our population, hearing loss wasthe main clinical sequelar

manifestation of congenital CMV.These data are consistent withthose described in the literature,particularly in a prospective studyinvestigating the incidence of CMVhearing loss over a 10-year period.10

Some published studies have foundunilateral deafness, of all degrees ofseverity, in 33% to 52% of cases.12,35

Progressive deterioration of hearingwas observed in 11% to 50% ofcases, hearing fluctuations in 16% to23%, and late-onset deafness in 5%to 50%.10,12,35

In our study, hearing loss wasdiagnosed at a mean age of 15.4 months(SD 20.4 months) (1 child was 7 yearsold). This is earlier than the mean age of22 months reported by Fowler inchildren symptomatic at birth.36 Thisdifference may be due to better hearingscreening in recent years.

Vestibular Assessment

In our study, vestibular assessmentswere performed in the same manner,by the same examiner, for all children.However, patient age at the time ofvestibular examination was variable(mean 26 months, range 5 months to11 years). Responses to the differenttests were interpreted according tochild age.25 We found that vestibularimpairment as well as SNHL due toCMV infection can show progressiveaggravation over time (50% of the 14tested children), and we thereforesuggest regular follow-up, sinceprogressive vestibular impairmentcan be asymptomatic.

Vestibular dysfunctions, which wereidentified in nearly all patients

included in our study, were mostlysevere and bilateral and concernedboth canal and otolith function. Only7.7% of children (4/52) had normalvestibular function.

Our results are consistent with thosefirst reported by Zagólski in 200821

and Karltorp et al.22 In Zagólski’sstudy, 16 of 26 children had noresponse to caloric testing, 12 had noevoked myogenic potentials, and only8 had normal auditory brainstemresponse. However, the battery oftests was incomplete, since canalfunction was assessed only withcaloric tests and not evaluated formiddle and high frequencies. In thestudies of Zagólski and Karltorp et al,otolith function was assessed only forsaccular function using air conductionc-VEMP; responses can be absent inyoung children in cases of middle eareffusion (frequently found), as well asin cases of otolith impairment.

Our study demonstrates theimportance of evaluating canalfunction at medium and highfrequencies: 87.8% of children(43/49) had a dysfunction detectedwith EVAR and 57.7% (30/52) withHIT. Similarly, bone conductionVEMP allowed evaluation of bothsaccular and utricular function37 evenin cases of middle ear effusion: 78.4%(40/51) had abnormal responses.We defined the severity and lateralityof canal and otolith dysfunctionprecisely and performed a globalvestibular function assessment. Thevestibular loss was complete andbilateral in 30.8% of cases (16patients) and partial in 61.5%(32 patients).

As previously published,posturomotor development ishighly dependent on vestibularfunction.23,38 Complete bilateralvestibular loss (CBVL) induces severedelay in posturomotor controlacquisition, whereas residualvestibular function or unilateraldisorders have almost no impact onposturomotor development in youngchildren.23,38

TABLE 5 Distribution of the DifferentVestibular Disorders

Global Vestibular Function n %

Complete and bilateral disorders(areflexia)

16 30.8

Partial and bilateralCanal disorders 2 3.8Otolith disorders 1 1.9Canal and otolith disorders 18 34.6

Partial and unilateralCanal disorders 2 3.8Otolith disorders 0 0Canal and otolith disorders 9 17.3

Normal 4 7.7

Percentages are calculated relative to the total pop-ulation (n = 52).

TABLE 6 Correlation Between Laterality of Hearing Impairment and Laterality of VestibularDisorders

Hearing Deficits Vestibular Deficits

Bilateral Symmetric Right Left Normal Total

Bilateral symmetric 13 9 4 2 28Right 3 3 4 0 10Left 8 0 2 0 10Normal 1 0 1 2 4Total 25 12 11 4 52

Data are expressed as number of children. There is a significant relationship between the laterality of the disorders(P = .03), but these are not correlated (k = 0.05).

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Correlation Between Hearing Lossand Vestibular Dysfunction

Vestibular impairment had the samecharacteristics as hearing disorders interms of severity and laterality (P ,.05). However, vestibular and hearingimpairments were not alwaysconcordant with each other: severedeafness could be associated withmoderate vestibular deficit, andhearing loss in 1 side may beassociated with a contralateralvestibular impairment.

Zagólski21 reported a statisticalcorrelation between vestibular lossand hearing loss: children withouthearing impairment showedstatistically less vestibulardysfunction. We could not confirmthis result because of our smallcohort of children with normalhearing (n = 4). In Karltorp et al, nocorrelation between hearing loss andthe severity or the laterality ofvestibular impairment could be foundfor the 26 candidates for cochlearimplant, since all patients hadprofound SNHL.22

Our results suggest that congenitalCMV infections induce lesions ofcochlear and vestibular parts of theinner ear. This conclusion issupported by histologic studies that

show cytomegalic lesions in thecochlea as well as the vestibule.13–20

These lesions seem particularlyconcentrated in the stria vascularis inthe cochlea and the dark cells in thevestibule, inducing inner-ear fluiddisorders that could explainprogressive or delayed inner-eardysfunction.13

Impact on PosturomotorDevelopment

All children were screened forvestibular impairment: 16 hada complete bilateral vestibular lossthat required early physical therapyto overcome posturomotordevelopment difficulties; 32presented with partial vestibular loss.Physical therapy was prescribed onlyfor those who had associatedneurologic impairment (14/32).

Based on our results, CMV infectioncould induce complete bilateralvestibular loss and therefore delayposturomotor development in youngchildren. However, neurologicimpairment can also induce delayin posturomotor development.In comparison with normaldevelopment, CMV-infected childrenhave significant delays at eachposturomotor milestone. The average

age of walking acquisition in CMV-infected children was 18.4 months,28 months for children with completeareflexia. As the age of walkingacquisition has been stronglycorrelated with the severity ofvestibular dysfunction, it has beenshown that the earlier CBVL occurs,the stronger the impact on posturalmotor development.23

Once walking is acquired, childrenwith CBVL might fall frequently.Recent studies have shown that CBVLimpact may not be limited toposturomotor delays and could alsoinduce cognitive dysfunctions,resulting in attention deficitdisorders;39,40 learning, readingand writing difficulties;41 spatialdisorientation;42 or memoryretention disorders.43 These sequelaemay also be the consequence ofneurologic and oculomotor disordersin CMV-infected children.

The patients included in the studywere assessed at a mean age of 3,long after acquisition of the differentposturomotor milestones.Appropriate rehabilitation shouldideally be given early, in the first2 years of life, to favor properdevelopment.23 Bilateral vestibulardeficit affects not only posturomotormilestones but also fine movementsand gravity perception. These deficitscan be undetected or misdiagnosedfor neurologic central sequelae. Theobject of this study is to underline theimportance of severe vestibularlesions in CMV patients and thenecessity to diagnose completebilateral vestibular loss as early aspossible to recommend earlyrehabilitation and reducedevelopmental impact.44,45 Childrenwith CMV often cumulate mild tosevere neurologic impairment andvestibular impairment. Compensationof vestibular impairment depends oncentral nervous plasticity but also onits severity and the age it occurred.23

Long-term sequelae with learningdisabilities have been reported byseveral authors in children with

TABLE 7 Correlation Between Severity of Hearing Impairment and Severity of Vestibular Disorders

Severity of Hearing Deficits Severity of Vestibular Deficits

Bilateral Areflexia Partial Normal Total

Bilateral profound 5 14 2 21Partial 11 16 0 27Normal 0 2 2 4Total 16 32 4 52

Data are expressed as the number of children. There is a significant relationship between the laterality of the disorders(P = .023), but these are not correlated (k = 0.01).

TABLE 8 Correlation Between the Severity of Congenital CMV Infection and the Severity ofVestibular Disorders

Severity of Vestibular Deficits Severity of Congenital CMV Infection

Symptomatic at Birth Asymptomatic at Birth Total

Bilateral areflexia 7 9 16Partial 22 10 32Normal 1 3 4Total 30 22 52

There is no significant relationship (P = .09).

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vestibular disorders and noneurologic impairment.45 In ourexperience, most children withcomplete congenital bilateralvestibular loss do not catch up withtheir peers (S. Wiener-Vacher,unpublished data).

Among the 52 children infected withCMV, 21% showed obvious signs ofneurologic impairment, but this doesnot exclude subliminal neurologicdisorders that may be revealed laterduring development. In CMV-infectedchildren with axial hypotonia, delayedwalking, and frequent falls, CBVLalone can explain such a clinicalpattern, suggesting that neurologicimpairment is not severe. In contrast,diagnosing a partial vestibularimpairment suggests theparticipation of severe neurologicimpairment because vestibulardysfunction cannot explain sucha clinical pattern.

CONCLUSIONS

Vestibular disorders are frequent andsevere in children congenitallyinfected with CMV. Both canal andotolith functions are affected.Considering the impact of completebilateral vestibular loss onposturomotor development,screening and monitoring forvestibular disorders should beincluded in standard assessment andfollow-up of CMV-infected children.Practitioners must screen forvestibular disorders that are frequentin CMV. This is particularly importantin cases of posturomotordevelopment delay that can be due toeither neurologic impairment orcomplete bilateral vestibular loss,both of which require early andadapted physical therapy to avoidlong-term consequences. Completebilateral vestibular loss induces lowdynamic visual acuity,46 loss ofgravity perception, and spatialdisorientation that can lead inabsence of intervention to learningdisabilities and perturbed fine motorcontrol (misdiagnosed for dyspraxia).

ABBREVIATIONS

CBVL: complete bilateralvestibular loss

CMV: cytomegalovirusc-VEMP: cervical vestibular evoked

myogenic potentialEVAR: earth vertical axis rotationHIT: head impulse testHST: head-shaking testOVAR: off-vertical axis rotationSNHL: sensorineural hearing lossTEOAE: transient evoked

otoacoustic emissionUVL: unilateral vestibular lossVOR: vestibulo-ocular response

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