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\begin{document}

\title{Otolith and balance function evolution related to cochlear implantation
in hearing loss with inner ear malformations}



\author[1]{Mengya Shen}%
\author[1]{Shujin Xue}%
\author[1]{Xingmei Wei}%
\author[1]{Biao Chen}%
\author[1]{Ying Kong}%
\author[1]{Yongxin Li}%
\affil[1]{Beijing Tongren Hospital}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
\textbf{Objectives:} In recent years, with the incidence of bilateral
cochlear implantation (CI) increasing, understanding the impact of CI on
otolith function is of greater necessity. This study aims to investigate
the development of gross motor and otolith function in patients with
inner ear malformations (IEMs) by vestibular evoked myogenic potentials
(VEMP). \textbf{Materials and Methods:} A total of 78 patients with
sensorineural hearing loss (SNHL) (age 5.7\selectlanguage{ngerman}±4.1 years) were divided into
two groups based on the presence (IEM group, n=39) or absence (control
group, n=39) of IEMs. VEMP was conducted before and 1--3 months after
CI, and gross motor development assessed. \textbf{Results:} The mean
ages of head control and independent walking were delayed in the IEM
group compared with control group ( \emph{p}=0.02). The preoperative
cVEMP and oVEMP response rates were higher in the control groups (60\%
and 86.95\%) than in the IEM group (57.69\% and 74.35\%) (
\emph{p}\textless{}0.05). Additionally, abnormal cVEMP was associated
with delayed acquisition of independent walking ( \emph{p}=0.017).
Saccular and utricular functions after CI were lost by 40\% and 31.75\%,
respectively, in group of patients present preoperatively VEMPs waveform
(n=25). \textbf{Conclusions:} Balance development is more reduced in
patients with SNHL and IEMs than in patients without IEMs. The
otolith-vestibular nerve conduction pathway can be affected by CI and
lead to otolith function impairment. As such, evaluating the otolith and
balance functions before CI is necessary and should be considered in
clinical practice.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


Otolith and balance function evolution related to cochlear implantation
in hearing loss with inner ear malformations

\textbf{ABSTRACT}

\textbf{Objectives:} In recent years, with the incidence of bilateral
cochlear implantation (CI) increasing, understanding the impact of CI on
otolith function is of greater necessity. This study aims to investigate
the development of gross motor and otolith function in patients with
inner ear malformations (IEMs) by vestibular evoked myogenic potentials
(VEMP).

\textbf{Materials and Methods:} A total of 78 patients with
sensorineural hearing loss (SNHL) (age 5.7\selectlanguage{ngerman}±4.1 years) were divided into
two groups based on the presence (IEM group, n=39) or absence (control
group, n=39) of IEMs. VEMP was conducted before and 1--3 months after
CI, and gross motor development assessed.

\textbf{Results:} The mean ages of head control and independent walking
were delayed in the IEM group compared with control group (\emph{p}
=0.02). The preoperative cVEMP and oVEMP response rates were higher in
the control groups (60\% and 86.95\%) than in the IEM group (57.69\% and
74.35\%) (\emph{p} \textless{}0.05). Additionally, abnormal cVEMP was
associated with delayed acquisition of independent walking (\emph{p}
=0.017). Saccular and utricular functions after CI were lost by 40\% and
31.75\%, respectively, in group of patients present preoperatively VEMPs
waveform (n=25).

\textbf{Conclusions:} Balance development is more reduced in patients
with SNHL and IEMs than in patients without IEMs. The otolith-vestibular
nerve conduction pathway can be affected by CI and lead to otolith
function impairment. As such, evaluating the otolith and balance
functions before CI is necessary and should be considered in clinical
practice.

\textbf{Keywords:} Otolith function, Cochlear implantation, Inner ear
malformation, Pediatric, Balance function

Key Points

There is limited studies on otolith function in patients with IEMs
before and after cochlear implants (CI).

We conducted a prospective study of otolith function with IEMs using
vestibular evoked myogenic potentials (VEMP).

We included 78 children (41 females and 37 males) who underwent CI, all
patients were divided into two groups based on the presence (IEM group)
or absence of IEMs (control group)

The IEM group had a lower response rate of cVEMP
(\emph{X\textsuperscript{2}} =4.768, \emph{p} =0.003) and oVEMP
(\emph{X\textsuperscript{2}} =4.408, \emph{p} =0.003) compared to the
control group. The abnormal cVEMP and oVEMP rate after surgery was
increased in the control group (\emph{p\textless{}} 0.001) but decreased
in the IEM group.

Evaluating the otolith and balance functions before CI is necessary and
should be considered in clinical practice. \emph{}

\textbf{INTRODUCTION}

Cochlear implantation (CI) is an important treatment for severe or
profound sensorineural hearing loss (SNHL), and pediatric candidates
with inner ear malformations (IEMs) can obtain long-term positive
auditory and speech outcomes with CI. Some children with SNHL may also
present congenital vestibular dysfunction because of the anatomical and
embryological relationship between the cochlea and vestibule. The
prevalence of vestibular dysfunction in children with SNHL ranges from
20\% to 85\%. Moreover, a recent review confirms that electrode
insertion can induce various vestibular damages in 50\%--85\% of
patients, and in the pediatric population, this figure is approximately
18--85\%\textsuperscript{{[}1{]}}. Children with vestibular dysfunction
and SNHL generally present with profound hearing loss, and their gross
motor functions, such as head control or independent walking, are
usually delayed\textsuperscript{{[}2, 3{]}}. Cochlear and vestibular
dysfunctions can exist alone or coexist, but patients with IEMs are also
susceptible to semicircular canal and saccular
dysfunctions\textsuperscript{{[}4{]}}. Jin et
al.\textsuperscript{{[}5{]}} performed the vestibular evoked myogenic
potential (VEMP) test on seven patients with different degrees of IEMs,
of which only two patients elicited VEMP on the malformed side. Notably,
studies on vestibular function in patients with IEMs are limited.

Vestibular damage after CI is more severe if it is presented before 1
year of age, because during this time, infants have not yet developed
their walking and balance abilities\textsuperscript{{[}6{]}}. Hence,
vestibular function should be evaluated before CI, and surgeons must
avoid inducing vestibular injury during surgery.

Currently, VEMP is the most commonly used vestibular function test in
children, which can reflect the neurophysiological function of the
otolith organ and vestibular nerve\textsuperscript{{[}7, 8{]}}. VEMP
test includes cervical VEMP (cVEMP) and ocular VEMP
(oVEMP)\textsuperscript{{[}9{]}}.

Considering that the number of SNHL children undergoing CI has
increased, especially bilateral surgery\textsuperscript{{[}10{]}}, there
is an urgent need to evaluate the effects of CI on the vestibular
system. This study used VEMPs to investigate gross motor and vestibular
function changes after CI in pediatric patients, especially in patients
with IEMs.

\textbf{MATERIALS AND METHODS}

\textbf{Patients}

This study included 78 children (41 females and 37 males) who underwent
CI at the Department of Otorhinolaryngology Head and Neck Surgery at
Beijing Tongren Hospital between January 2021 and February 2022. The
children's mean age at implantation was 5.7±4.1 years (range, 0.7--17.8
years). All participants met the dignosis criterion for bilateral
profound or severe hearing loss and met the CI implanted criterion. In
order to eliminate residual hearing or impact of crossover from the
normal ear ,single-sided deafness was excluded here. Besides, patients
aged \textgreater{}18 years, with cognitive and psychological
impairments, and unable to participate in follow-up examinations were
excluded from this study.

The type and degree of IEMs were classified according to the work of
Sennaroglu et al. in 2017\textsuperscript{{[}11{]}}. The IEM group
classification is listed in Table 1. All patients were divided into two
groups based on the presence (IEM group) or absence of IEMs (control
group). Each group had 39 patients.

Before surgery, inner ear computed tomography (CT) and magnetic
resonance imaging (MRI) scans, audiological assessments (including
standard pure tone audiometry, auditory brainstem response evaluation,
auditory steady-state response assessment, distortion product
otoacoustic emission, cochlear microphonics evaluation), and cVEMP test,
were performed. Electronic ear endoscope or tympanograms performs prior
to VEMP testing to ensure there was no middle ear fluid or an ongoing
hemotympanum. The O-VEMP was performed on patients who were able to
cooperate. This study was approved by the Institutional Review Board of
Beijing Tongren Hospital.

\textbf{Gross motor development}

We interviewed the children's parents regarding the age at which
patients started to acquire gross motor abilities, including head
control and independent sitting, crawling, and walking. If the age of
acquiring head control was \textgreater{}4 months and the age of
independent walking was \textgreater{}12 months, the development of
gross motor function was considered to be
delayed\textsuperscript{{[}12{]}}.

\textbf{Vestibular evoked myogenic potential (VEMP) test}

Patients underwent cVEMP and oVEMP tests 1 week prior to CI and then
again 1--3 months after. The electromyography signal from the stimulated
side was amplified using the Neuro-audio Auditory evoked potentiometer
system (version 2010, Neurosoft Ltd., Ivanov, Russia) in a soundproof
examination room. The cVEMP test was performed with the electromyogram
auto-correction mode. The children were tested in a natural awake state.
Older children with the ability to cooperate were asked to obtain a
sitting position, and younger children were placed in a 30° forward head
tilt position with their parents holding them. The sound was emitted
through a calibrated earphone, with an air-conducted 500 Hz short pure
tone (tone burst) and a stimulation intensity of 105 dB nHL. The active
electrode was placed in the middle of the sternocleidomastoid muscle
(SCM), the reference electrode was placed above the sternoclavicular
joint, and a ground electrode was placed on the midline of the forehead.
The inter-electrode resistance should be \textless{}5 k\selectlanguage{greek}Ω. \selectlanguage{english}The head of
the children was turned to the opposite side during the cVEMP test. The
SCM force in the test ear was maintained between 30 and 70 \selectlanguage{greek}μ\selectlanguage{english}V. The
signal was recorded ipsilaterally by monitoring electromyography.

oVEMP testing was performed in the sitting position. An active electrode
was placed 0.5 cm below the lower lid of each eye in line with the
pupil, a reference electrode was placed below the active electrode, and
a ground electrode was placed on the midline of the forehead. The
inter-electrode resistance was also \textless{}5 k\selectlanguage{greek}Ω. \selectlanguage{english}Each child was
instructed to gaze upward, focus on one specific place, and avoid
blinking. The stimulation sound was similar to that of the cVEMP and
administered bilaterally. The signal was recorded on the opposite side.
If the test ear had CI, the test was performed with the CI device turned
off.

\textbf{Definition of parameters}

We defined a reproducible middle-latency biphasic wave as the effective
wave type. The waveforms with missing amplitude and unreproduced waves
were rejected. P1 and N1 were the first positive and negative peaks,
respectively. The P1 and N1 latencies (the interval between 0 ms and the
corresponding maximal peak) were calculated by the interval between P1
and N1, and the rectified amplitude (the vertical distance between the
P1 and N1 peaks) was recorded. The results were reviewed before and 1--3
months after CI. No significant change in VEMP was defined as no change;
disappeared VEMP was defined as clear waveform before CI but waveform
disappeared after the implantation.

\textbf{Statistical analyses}

Data were analyzed using IBM SPSS Statistics software version 26.0
(Armonk, New York, USA). Categorical variables (response rates) were
compared by Fisher's exact test; Pearson's correlation analysis was
performed to analyze the correlation of VEMP parameters between the IEM
and control groups. Continuous variables (VEMP parameters) were
evaluated by Student's T-test. A significance level of 0.05 was applied
to all analyses.

\textbf{RESULTS}

\textbf{Demographic analysis}

Of the 78 patients included in this study, 5 and 73 underwent bilateral
and unilateral CI, respectively. The children's average implantation age
was 5.7\selectlanguage{ngerman}±4.1 years (range, 0.7--17.8 years). The mean age of the IEM
group and control group was 5.54±4.31 years and 5.92±3.96 years. The
difference in age was not statistically significant between the two
groups. All the patients underwent full CI insertion, without any
complications.

\textbf{Gross motor development}

Fig. 1 shows the comparison of the mean gross motor development timing
between the IEM and control groups. The mean ages of head control and
independent walking in the IEM group were 3.73±0.86 months and 15.39±4.5
months, respectively. The independent-samples T-test showed that the
balance development of children with IEMs was delayed when compared to
the control group (\emph{p} =0.02).

Additionally, two children in the IEM group presented with vertigo and
slight unsteadiness postoperatively, but all symptoms resolved within 48
h. The impaired otolith function did not correlate with vertigo symptoms
(logistic regression analysis, \emph{p} \textgreater{}0.05).

To estimate the effect of otolith dysfunction on the development of
gross motor function, we compared the age of acquiring gross motor
skills with the results of both the cVEMP and oVEMP test (Table 2). In
terms of acquiring independent walking, children who showed abnormal
cVEMP responses were significantly more delayed compared with those who
showed normal responses (\emph{p} =0.017). There were no significant
differences in the age of acquiring gross motor abilities between
children with abnormal oVEMP and normal response (\emph{p}
\textgreater{}0.05).

All patients and a total of 156 ears were tested for cVEMP, whilst 96
ears from 48 patients underwent oVEMP testing before surgery. The
chi-squared test showed significant differences in the response rates of
cVEMP (\emph{X\textsuperscript{2}} =4.768, \emph{p} =0.003) and oVEMP
(\emph{X\textsuperscript{2}} =4.408, \emph{p} =0.003) between the IEM
and control groups. There was no statistical difference in each
parameter between the two groups by the independent samples t-test
(Tables 3 and 4).

\textbf{Effects of cochlear implantation on VEMPs}

VEMP changes before and after surgery were recorded, but only the CI ear
was analyzed. The postoperative VEMP test was performed 25--39 days
after surgery, and 64 CI ears were retested under the condition of
CI-off. 50\% of the implanted ear cVEMP waveform and 39.1\% of the oVEMP
waveforms disappeared after CI, the difference in the lost rate was not
statistically significant between the implanted ear cVEMP and oVEMP.
Moreover, we compare the p13 and n23 latency ,peak amplitude and
corrected amplitude, there was no statistically significant difference
in above the parameters before and after surgery. In the group of 25
patients with preoperatively present VEMPs, 40\% and 31.75\% lost their
cVEMP and oVEMP, respectively, after implantation. The variation between
cVEMP and oVEMP results before and after surgery of the IEM and control
groups are shown in Fig. 2. The independent sample T-test showed that
the abnormal cVEMP rate after surgery was increased in the control group
(\emph{p\textless{}} 0.001). The abnormal oVEMP rate after surgery of
all patients together and the control group significantly increased, but
decreased in the IEM group (Fig. 2).

\textbf{DISCUSSION}

With the increasing rate of bilateral CI implementation in children with
IEMs, vestibular function development has received significant
attention. However, studies on this subject remain limited. Due to the
close anatomical and developmental relationship between otolith
end-organs and the cochlear, hearing impairment may lead to vestibular
disorder\textsuperscript{{[}13{]}}, but vestibular assessment is not
routinely performed\textsuperscript{{[}14, 15{]}}. One of the reasons
for this is the lack of clinically appropriate and effective assessment
methods in the pediatric group and a gold standard test for the
assessment of balance and postural control in
children\textsuperscript{{[}16{]}}. Another reason is that vestibular
dysfunction can be compensated by other systems, and notably,
abnormality in gait and motor coordination is not observed in children
with IEMs\textsuperscript{{[}17{]}}. The current study aimed to describe
the difference in gross motor development in patients with SNHL, and to
investigate the otolith functional modifications after CI between
children with and without IEMs.

Otoliths are important receptors of the vestibulospinal reflex pathway,
which helps to maintain balance and is significantly important for the
human body to control the erect head and the spatial orientation of the
body\textsuperscript{{[}18{]}}. Balance and motor development in early
childhood are delayed in patients with IEMs, as observed in children
with severe congenital hearing loss\textsuperscript{{[}19{]}}. In
patients with IEMs, otolith function may be significantly compromised,
and these patients often present with impairments in balance control,
such as delays in head control and independent walking, because such
functions are related to abnormal inner ear
structures\textsuperscript{{[}20, 21{]}}. Consistent with previous
studies\textsuperscript{{[}22, 23{]}}, we reported that children with
IEMs performed worse than those in the control group with regards to
gross motor development. The mean ages of head control and independent
walking in the IEM group were 3.73±0.86 months and 15.39±4.5 months,
respectively. While follow-up research continues,, even when these
children were able to walk, their balance ability, such as performance
on the single-leg standing test, remained tardive. Moreover, they also
had a higher risk of falling during advanced balance activities, such as
bicycle riding, than the normal children.

Farideh et al.\textsuperscript{{[}24{]}} reported that 68.2\% and 14.3\%
of children with IEMs and SNHL (normal cochlear anatomy), respectively,
presented with vestibular dysfunction after CI. Hosseinzadeh et
al.\textsuperscript{{[}6{]}} used the Bruininks--Oseretsky motor ability
test (BOT) and sensory organization test for postures to test the
standing/walking stability of four patients with common cavity deformity
(CCD) under open and closed eyes conditions. Their results indicated
that the balance function of the patients with CCD was more delayed than
that of other patients with SNHL. We evaluated the gross motor
development preliminarily because in our study, most of the CI
candidates had not reached the standard BOT-2 assessment age
(\textgreater{}4 years). In our study, the gross motor development of
children with IEMs was significantly more delayed compared with that of
the control group. Specifically, the mean age of independent walking in
the IEM group was 15.39 months. This result is similar to those of
previous studies, which indicate that the otolith end-organ plays an
essential role in obtaining gross motor abilities before the age of 2
years. If any postoperative balance damage is identified, such as
instability after surgery, the solution of early rehabilitation should
be recommended for the best and most rapid balance recovery.

The VEMP test is a noninvasive test that can sensitively identify
otolith function variation in younger children. Some studies have shown
that VEMP plays an important role in evaluating the otolith function and
vestibular nerve integrity of patients before and after
CI\textsuperscript{{[}25, 26{]}}. However, assessment of otolith
function in children with SNHL, especially in IEMs, remains limited. In
this study, we aimed to analyze the difference in VEMP between children
with IEMs and children with SNHL with normal cochlear anatomy.

Previous findings have revealed that the function of the saccular and
utricle may receive certain damage by CI, and this damage can last for a
long period of time and the cVEMP response rate is more likely
influenced by CI than oVEMP, because the saccule is anatomically closer
to the cochlea and has a major risk of CI\textsuperscript{{[}27{]}}. To
determine the real variation of otolith function in relation to CI, we
analyzed the VEMP variation only in the ears that had a present response
for cVEMP and oVEMP preoperatively. In the present study, 40\% of
patients lost the cVEMP response and this variation may suggest the risk
of injury during CI, specifically during intracochlear port electrode
insertion, which may seriously affect the saccular neuroepithelium.

The higher postoperative cVEMP loss rate in our study might be related
to the patients' age. The youngest children assessed for waveform were 9
and 12 months old in the normal cochlear group and IEM group,
respectively. It was not easy for children to maintain an adequate SCM
tone during the whole test process. The second factor is that the
electrical stimulation of the CI device can have an effect on VEMP
responses\textsuperscript{{[}28-30{]}}. However, the VEMP tests in our
study were performed in CI-off conditions to prevent the electrical
stimulation from having an effect on the responses to evaluate the
actual residual otolith function only. Another factor is different
surgical techniques. Studies on this matter, that is whether the
surgical approach can induce VEMP loss, remain inconclusive. Some
studies have indicated that cochleostomy might be more likely traumatic
for the otolith end-organ than the round window
approach\textsuperscript{{[}31{]}}. In this study, the approach used for
most patients was the round window approach, except for children with
CCD, who underwent the slotted labyrinthotomy approach. The latter can
significantly shorten the surgery duration and effectively reduce the
rate of postoperative cerebrospinal fluid leakage and vertigo
probability\textsuperscript{{[}32{]}}. Similarly, Cozma et
al.\textsuperscript{{[}33{]}} reported normal saccular function in
73.3\% of the CI ears using the round window approach and in 68.42\% of
ears using the cochleostomy approach, which suggests that the round
window port electrode insertion is the recommended strategy to avoid
saccular impairment. In this study, all children underwent AC-cVEMP
tests, and previous studies have revealed that CI can induce peripheral
mechanical changes, leading to air--bone gaps, which can lead to absent
AC-cVEMP responses without underlying vestibular
deficit\textsuperscript{{[}34, 35{]}}. Moreover, inaccuracies in
measurement methods can also lead to a higher rate of VEMP loss.

In our study, the rate of VEMP response was significantly different
between the two groups, but there were no significant differences in
changes within various P1-N1 parameters (Tables 2--4). It is possible
that patients with IEMs in this study had a more severe degree of
deformity and that they presented little difference in waveforms after
CI. Additionally, because the test is performed in young children who do
not have typical amplitudes, the differences between the two groups are
subtle. Currently, there is no consensus protocol for the quantitative
assessment of the P1-N1 parameters wave complex in children. However,
the type of change in VEMPs can indicate severity of IEMs affecting the
utricle and saccule. Xu et al.\textsuperscript{{[}30{]}} reported that
cVEMP disappearance occurred more frequently on the CI-implanted ear and
that waveform parameter showed abnormal changes, such as decreased
amplitude, forward movement of P1 and N1, and shortened interpeak
latency at 1 month after CI, suggesting that cVEMP waveforms can reflect
the degree of damage to the saccule caused by CI.

The present study consisted of 11 children with CCD, all of which showed
no VEMP response before surgery on either cVEMP or oVEMP. In contrast,
most patients with IEMs presented with concomitant symptoms with
cochleovestibular nerve deficiency and abnormal development of
vestibular sensory cells. Hence, patients with IEMs are more likely to
have abnormal VEMP response rate and waveform than those without IEMs.
In 2006, Jin et al.\textsuperscript{{[}28{]}} tested 12 patients with
IEMs using VEMP and found that saccule function was more likely damaged
after CI, as reflected in the absence of cVEMP waveform in short pure
tone stimulation. Our results are consistent with those of previous
studies. In the current study, the otolith function in the IEM group was
significantly more compromised than that of the control group, which
suggests that the VEMPs of IEMs might be more susceptible to influence
by CI.

Vestibular sensory cells of the semicircular canals and otolith organs
or primary vestibular afferent neurons are possibly present in patients
with IEMs to maintain a basic balance function, particularly CCD. These
patients do not have difficulty in general activities that require
dynamic balance and mobility\textsuperscript{{[}36{]}}. In an
embryological study, in the human fetal developmental stage, the
vestibular system develops earlier than the cochlear
system\textsuperscript{{[}37{]}{[}38{]}}. Children with hearing loss who
are at high risk for vestibular dysfunction can develop a new sensory
distribution process in which visual and somatosensory information
becomes essential for postural control when vestibular input is
impaired\textsuperscript{{[}3, 39{]}}. The above can explain why VEMP
can still be present in patients with severe IEMs and how they can
acquire balance function at 3--4 years of age. In the present study, one
patient with CCD presented with cVEMP waveform 6 months after CI.
Considering the small sample size, long-term changes in cVEMP parameters
should be analyzed through follow-up.

Additionally, six patients with large vestibular aqueduct syndrome
(LVAs) presented with normal VEMP waveform before surgery and normal
performance of balance function. These results are similar to those of
preceding studies. Patients with LVAs often complain of subjective
symptoms of balance disorders, such as dizziness and unsteady walking,
but may have normal waveform on VEMP tests\textsuperscript{{[}40,
41{]}}. Due to the small differences between the different types of
malformations and the small sample size, there were no statistical
differences between different types of malformations.

\par\null

This study also observed that, IEM group has two children presented with
vertigo and slight unsteadiness. all symptoms resolved within 48 h. We
analyzed that this may be due to otolith function. In these patients,
the balloon and utricle are not fully developed, with strong plasticity,
and the otoconia injury has a strong compensatory mechanism and central
system adaptability. Another reason is that the operation is gentle,
which greatly avoids damage to the vestibular system. Therefore, it is
still necessary to understand the otolith function of postoperative
patients. Long-term follow-up is needed to determine whether such
patients are at risk for vestibular decline along with age growth.

Our study has some limitations. First, recall bias exsist due to the
retrospective methodology of determining gross motor delays. Second,the
mean follow-up time was 1--3 months after CI. Patients develop or
compensate their vestibular function from the visual and central nervous
systems rapidly during the age of 1--5 years, which would affect the
results of the VEMP tests. Moreover, the otolith function test method
was primarily performed; thus, a further vestibular function test
battery is required.

\textbf{CONCLUSIONS}

The functional balance performance and otolith function of children with
IEMs are more delayed than those of children with SNHL with normal
cochlear anatomy. The otolith-vestibular nerve conduction pathway may be
affected in CI, which may lead to otolith function impairment. It is
necessary to adequately evaluate the children's vestibular and balance
functions before CI. Additionally, VEMPs, which are noninvasive and
rapid tests, can be used to reflect the status and degree of otolith
functional involvement in young children with SNHL.

\textbf{References:}

{[}1{]}. West, N., L. Tian, L.K. Vang Petersen, M. Bille, M. KlokkerP.
Cayé-Thomasen, Objective Vestibular Test Battery and Patient Reported
Outcomes in Cochlear Implant Recipients. Otology \& Neurotology, 2021.
42(4): p. e416-e424.DOI:10.1097/MAO.0000000000002959

{[}2{]}. Kaga, K., Vestibular compensation in infants and children with
congenital and acquired vestibular loss in both ears. Int J Pediatr
Otorhinolaryngol, 1999. 49(3): p.
215-24.DOI:10.1016/s0165-5876(99)00206-2

{[}3{]}. Suarez, H., S. Angeli, A. Suarez, B. Rosales, X. CarreraR.
Alonso, Balance sensory organization in children with profound hearing
loss and cochlear implants. Int J Pediatr Otorhinolaryngol, 2007. 71(4):
p. 629-37.DOI:10.1016/j.ijporl.2006.12.014

{[}4{]}. Cushing, S.L., K.A. Gordon, J.A. Rutka, A.L. JamesB.C. Papsin,
Vestibular end-organ dysfunction in children with sensorineural hearing
loss and cochlear implants: an expanded cohort and etiologic assessment.
Otol Neurotol, 2013. 34(3): p. 422-8.DOI:10.1097/MAO.0b013e31827b4ba0

{[}5{]}. Jin, Y., Y. Shinjo, Y. Akamatsu, T. YamasobaK. Kaga, Vestibular
evoked myogenic potentials of children with inner ear malformations
before and after cochlear implantation. Acta Oto-Laryngologica, 2009.
129(11): p. 1198-1205.DOI:10.3109/00016480802579041

{[}6{]}. Hosseinzadeh, F., A. Asghari, M. Moradi-Lakeh, M. Farhadi, A.
DaneshiM. Mohseni, et al., Balance function after cochlear implant and
inner ear anomaly: Comparison of dynamic posturography. Laryngoscope
Investig Otolaryngol, 2020. 5(3): p. 529-535.DOI:10.1002/lio2.394

{[}7{]}. Paillard, A.C., K. Kluk and N.P. Todd, Thresholds for
vestibular-evoked myogenic potentials (VEMPs) produced by impulsive
transmastoid acceleration. Int J Audiol, 2014. 53(2): p.
138-41.DOI:10.3109/14992027.2013.853134

{[}8{]}. Govender, S., S.M. Rosengren, N.P. ToddJ.G. Colebatch, Ocular
vestibular evoked myogenic potentials produced by impulsive lateral
acceleration in unilateral vestibular dysfunction. Clin Neurophysiol,
2011. 122(12): p. 2498-504.DOI:10.1016/j.clinph.2011.04.024

{[}9{]}. Rosengren, S.M., T.N. McAngus and J.G. Colebatch,
Vestibular-evoked extraocular potentials produced by stimulation with
bone-conducted sound. Clin Neurophysiol, 2005. 116(8): p.
1938-48.DOI:10.1016/j.clinph.2005.03.019

{[}10{]}. Masuda, T. and K. Kaga, Relationship between acquisition of
motor function and vestibular function in children with bilateral severe
hearing loss. Acta Otolaryngol, 2014. 134(7): p.
672-8.DOI:10.3109/00016489.2014.890290

{[}11{]}. Sennaroglu, L. and M.D. Bajin, Classification and Current
Management of Inner Ear Malformations. Balkan Med J, 2017. 34(5): p.
397-411.DOI:10.4274/balkanmedj.2017.0367

{[}12{]}. Bellman, M., O. Byrne and R. Sege, Developmental assessment of
children. BMJ, 2013. 346: p. e8687.DOI:10.1136/bmj.e8687

{[}13{]}. Angeli, S., Value of vestibular testing in young children with
sensorineural hearing loss. Arch Otolaryngol Head Neck Surg, 2003.
129(4): p. 478-82.DOI:10.1001/archotol.129.4.478

{[}14{]}. Verbecque, E., T. Marijnissen, N. De Belder, V. Van Rompaey,
A. BoudewynsP. Van de Heyning, et al., Vestibular (dys)function in
children with sensorineural hearing loss: a systematic review. Int J
Audiol, 2017. 56(6): p. 361-381.DOI:10.1080/14992027.2017.1281444

{[}15{]}. Telian, S.A., Comments about the value of vestibular testing
in young children with sensorineural hearing loss. Arch Otolaryngol Head
Neck Surg, 2003. 129(4): p. 483-4.DOI:10.1001/archotol.129.4.483

{[}16{]}. Karakoc, K. and B. Mujdeci, Evaluation of balance in children
with sensorineural hearing loss according to age. Am J Otolaryngol,
2021. 42(1): p. 102830.DOI:10.1016/j.amjoto.2020.102830

{[}17{]}. Rine, R.M., G. Cornwall, K. Can, C. Locascio, T. O HareE.
Robinson, et al., Evidence of progressive delay of motor development in
children with sensorineural hearing loss and concurrent vestibular
dysfunction. Perceptual and Motor Skills, 2000. 90(3c): p. 1101-1112

{[}18{]}. Bent, L.R., J.T. Inglis and B.J. McFadyen, When is vestibular
information important during walking? J Neurophysiol, 2004. 92(3): p.
1269-75.DOI:10.1152/jn.01260.2003

{[}19{]}. Kaga, K., Vestibular compensation in infants and children with
congenital and acquired vestibular loss in both ears. Int J Pediatr
Otorhinolaryngol, 1999. 49(3): p.
215-24.DOI:10.1016/s0165-5876(99)00206-2

{[}20{]}. Robert, K, Jackler, William, M.Luxfor, et al., Congenital
malformations of the inner ear: A classification based on embryogenesis.
The Laryngoscope, 2009

{[}21{]}. Kaga, K., J.I. Suzuki, R.R. MarshY. Tanaka, Influence of
labyrinthine hypoactivity on gross motor development of infants. Ann N Y
Acad Sci, 1981. 374: p. 412-20.DOI:10.1111/j.1749-6632.1981.tb30887.x

{[}22{]}. Kaga, K., Y. Shinjo, Y. JinH. Takegoshi, Vestibular failure in
children with congenital deafness. Int J Audiol, 2008. 47(9): p.
590-9.DOI:10.1080/14992020802331222

{[}23{]}. Kaga and Kimitaka, Vertigo and Balance Disorders in Children.
2014: Springer Japan

{[}24{]}. Hosseinzadeh, F., A. Asghari, M.M. Lakeh, M. Farhadi, A.
DaneshiM. Mohseni, et al., Balance function after cochlear implant and
inner ear anomaly: Comparison of dynamic posturography. Laryngoscope
Investigative Otolaryngology, 2020. 5(3)

{[}25{]}. West, N., M. Klokker and P. Caye-Thomasen, Video head impulse
test saccades and loss of cervical vestibular evoked myogenic potentials
are late vestibular footprints of cochlear implantation. J Vestib Res,
2021. 31(1): p. 61-67.DOI:10.3233/VES-190760

{[}26{]}. Apeksha, K., S. Singh, M. Rathnamala, S. Varalakshmi, D.J.
PreethuV. Kavya, et al., Balance Assessment of Children with
Sensorineural Hearing Loss. Indian J Otolaryngol Head Neck Surg, 2021.
73(1): p. 12-17.DOI:10.1007/s12070-020-01797-x

{[}27{]}. Handzel, O., B.J. Burgess and J.J. Nadol, Histopathology of
the peripheral vestibular system after cochlear implantation in the
human. Otol Neurotol, 2006. 27(1): p.
57-64.DOI:10.1097/01.mao.0000188658.36327.8f

{[}28{]}. Jin, Y., M. Nakamura, Y. ShinjoK. Kaga, Vestibular-evoked
myogenic potentials in cochlear implant children. Acta Otolaryngol,
2006. 126(2): p. 164-9.DOI:10.1080/00016480500312562

{[}29{]}. Fuemmeler, E., A.I. Rodriguez, M. Thomas, T. Creutz, D.
FitzpatrickK.L. Janky, Vestibular Evoked Myogenic Potential (VEMP)
Test-retest Reliability in Children. Otol Neurotol, 2020. 41(8): p.
e1052-e1059.DOI:10.1097/MAO.0000000000002703

{[}30{]}. Xu, X.D., X.T. Zhang, Q. Zhang, J. Hu, Y.F. ChenM. Xu, Ocular
and cervical vestibular-evoked myogenic potentials in children with
cochlear implant. Clin Neurophysiol, 2015. 126(8): p.
1624-31.DOI:10.1016/j.clinph.2014.10.216

{[}31{]}. Handzel, O., B.J. Burgess and J.J. Nadol, Histopathology of
the peripheral vestibular system after cochlear implantation in the
human. Otol Neurotol, 2006. 27(1): p.
57-64.DOI:10.1097/01.mao.0000188658.36327.8f

{[}32{]}. Wei, Xingmei, Yongxin, Qian-jie, GongYue, et al., Slotted
Labyrinthotomy Approach With Customized Electrode for Patients With
Common Cavity Deformity. The Laryngoscope: A Medical Journal for
Clinical and Research Contributions in Otolaryngology, Head and Neck
Medicine and Surgery, Facial Plastic and Reconstructive Surgery .., 2018

{[}33{]}. Cozma, R.S., M.C. Cristina, M.D. Cobzeanu, R. Olariu, O.R.
BitereC. Martu, et al., Saccular function evolution related to cochlear
implantation in hearing impaired children. Rom J Morphol Embryol, 2020.
61(1): p. 113-119.DOI:10.47162/RJME.61.1.12

{[}34{]}. Mattingly, J.K., K.M. Uhler and S.P. Cass, Air-Bone Gaps
Contribute to Functional Hearing Preservation in Cochlear Implantation.
Otol Neurotol, 2016. 37(9): p. 1255-62.DOI:10.1097/MAO.0000000000001171

{[}35{]}. Merchant, G.R., K.M. Schulz, J.N. Patterson, D.
FitzpatrickK.L. Janky, Effect of Cochlear Implantation on Vestibular
Evoked Myogenic Potentials and Wideband Acoustic Immittance. Ear Hear,
2020. 41(5): p. 1111-1124.DOI:10.1097/AUD.0000000000000831

{[}36{]}. Karakoc, K. and B. Mujdeci, Evaluation of balance in children
with sensorineural hearing loss according to age. Am J Otolaryngol,
2021. 42(1): p. 102830.DOI:10.1016/j.amjoto.2020.102830

{[}37{]}. Jin, Y., Y. Shinjo, Y. Akamatsu, E. Ogata, M. NakamuraS.
Kianoush, et al., Vestibular evoked myogenic potentials evoked by
multichannel cochlear implant - influence of C levels. Acta
oto-laryngologica, 2008. 128(3): p. 284-90

{[}38{]}. Saito and Haruo, Surgical Anatomy of the Temporal Bone.
Pract.otol, 1978. 71(2): p. 205-208

{[}39{]}. Rine, R.M. and S. Wiener-Vacher, Evaluation and treatment of
vestibular dysfunction in children. NeuroRehabilitation, 2013. 32(3): p.
507-18.DOI:10.3233/NRE-130873

{[}40{]}. Oyewumi, M., N.E. Wolter, E. Heon, K.A. Gordon, B.C.
PapsinS.L. Cushing, Using Balance Function to Screen for Vestibular
Impairment in Children With Sensorineural Hearing Loss and Cochlear
Implants. Otol Neurotol, 2016. 37(7): p.
926-32.DOI:10.1097/MAO.0000000000001046

{[}41{]}. Cushing, S.L. and B.C. Papsin, Cochlear Implants and Children
with Vestibular Impairments. Semin Hear, 2018. 39(3): p.
305-320.DOI:10.1055/s-0038-1666820

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