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Postoperative objective detecting techniques for cochlear implant children with inner ear malformation
International Journal of Pediatric Otorhinolaryngology 102 (2017) 1e6
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International Journal of Pediatric Otorhinolaryngology journal homepage: http://www.ijporlonline.com/
Postoperative objective detecting techniques for cochlear implant children with inner ear malformation Xiao-Feng Qiao a, *, Xin Li b, Qiang-Wei Zhang a, Tong-Li Li a, Dong Wang a a b
Department of Otorhinolaryngology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan 030001, China Department of Surgery, Children's Hospital of Shanxi Province, Taiyuan 030001, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 June 2017 Received in revised form 18 August 2017 Accepted 22 August 2017 Available online 25 August 2017
Objectives: This study aims to investigate the changing characteristics and rules of electrically-evoked auditory brainstem response (EABR), electrically-evoked stapedius reflex threshold (ESRT) and neural response telemetry (NRT) after cochlear implant in children with inner ear malformation, and guide postoperative equipment debug. Methods: A total of 88 children with either normal cochlea (control group) or inner ear malformation (test group) received Australian 24 multi-channel cochlear implants. The EABR, ESRT and NRT thresholds at different time points within one year postoperatively and behavioral responses (T-level and C-level) after one year were detected. Furthermore, the changing characteristics and rules of these thresholds were analyzed. Results: The EABR, ESRT and NRT thresholds were all significantly higher at all time points in the test group than in the control group, but the general changing trends were similar. Particularly, these thresholds worsened at low frequencies and improved at high frequencies. Furthermore, EABR, ESRT and NRT thresholds gradually increased during the one year postoperative period. In addition, an extremely significant correlation was found between EABR and T-level and between ESRT and C-level, but a less significant correlation was found between NRT threshold and T-level in both groups. Conclusions: The postoperative changes in characteristics and rules of EABR, ESRT and NRT thresholds among cochlear implant children with inner ear malformation were all the same as those with normal cochlea. Thus, these thresholds can be used to guide the postoperative equipment debug for cochlear implants into patients with inner ear malformation. © 2017 Elsevier B.V. All rights reserved.
Keywords: Cochlear implant Sound processor debugging Neural response telemetry Electrically-evoked auditory brainstem response Electrically-evoked stapedius reflex threshold
1. Introduction In China, as the technology and knowledge of cochlear implants have been improved in recent years, more and more children with severe or extremely severe sensorineural hearing loss have been operated with cochlear implants. The successful operation is the first step for children to recover their hearing, and mapping at regular time after the operation is very important [1e4]. However, the big problem with postoperative machine debug is how to determine the subjective threshold (T-level) and most comfortable level (C-level). For children, due to their small age, it is difficult to
* Corresponding author. Department of Otorhinolaryngology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, No.29 of Twin Towers Temple Street, Taiyuan 030001, China. E-mail address: [email protected] (X.-F. Qiao). http://dx.doi.org/10.1016/j.ijporl.2017.08.026 0165-5876/© 2017 Elsevier B.V. All rights reserved.
obtain the accurate T-level and C-level by behavioral audiometry. To date, T-level and C-level are commonly evaluated by neural response telemetry (NRT) in clinic [5,6]. For children with normal cochlea, changes in the rules and characteristics of NRT after cochlear implant and its correlations with T-level and C-level have been extensively reported and recognized [7,8]. In recent years, more and more children with inner ear malformations have been operated with cochlear implants. Due to inner ear malformations, residual hearing is less, the rate of NRT extraction is low, and the regularity and characteristics of NRT are not mastered. In this case, we hope to find other objective hearing detection indexes instead of NRT inspection, in order to accurately estimate the inner ear malformation of cochlear implantation in children with T-level and C-level, guide postoperative mapping, and ensure the hearing rehabilitation of children. In addition to NRT, the current clinical detection methods for the objective evaluation of hearing include: electrically-evoked auditory brainstem response (EABR) and
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electrically-evoked stapedius reflex threshold (ESRT). For children with cochlear implants and normal inner ear structure, a number of studies have shown that EABR and ESRT are correlated with T-level and C-level, and that these can be used to guide postoperative mapping [9e12]. Hence, there is a need to explore these values and determine whether EABR and ESRT are equally useful for cochlear implants in children with inner ear malformations. Thus, the present study aims to investigate the changes in the rules and characteristics of EABR, ESRT and NRT in children with inner ear malformations and cochlear implants, as well as its correlations with behavioral response thresholds. We have summarized these changes in rules and characteristics with the aim to guide the programming and debugging in clinic.
stimulus intensity when the NRT waveforms disappeared. 2.2.3. Detection of ESRT threshold Nucleus software 3.0, a portable programming system and acoustic-immittance device (MADSEN OTO flex 100) was used. Stimulation parameters: waviness width, 20e50 us; stimulation rate, 200 Hz; duration of stimulation, 0.5e1.0 s; stimulation interval, 1.0e1.5 s. The test probe was placed into the lateral path of the non-artificial cochlear implant. ESR was measured at the acoustic attenuation mode. The electrical stimulation and sound reflection buttons were simultaneously pressed, and the baseline drift was recorded. A baseline drift >0.05 mmho was considered as the presence of stapedius reflex, and the minimum stimulus intensity was regarded as the ESRT threshold.
2. Data and methods 2.1. Clinical data A total of 88 cochlear implant children, who were treated in Shanxi People's Hospital between August 2001 and February 2016, were included into this study. All participants were patients with severe and extremely severe sensorineural hearing loss. The control group (52 children with normal cochlea) involved 28 boys and 24 girls, who were 1e13 years old. The test group (36 children with inner ear malformations) involved 21 boys and 15 girls, who were 1e7 years old. These 36 cases of inner ear malformation included 21 cases of large vestibular aqueduct syndrome, five cases of common cavity deformity, nine cases of vestibular semicircular canal malformation, and one case of internal auditory canal stenosis. All children were implanted with Australian Cochlear Nucleus 24 cochleae, and all of them were unilateral cochlear implants. 2.2. Methods Since switch-on at postoperative one month, EABR, ESRT and NRT thresholds were detected at switch-on day, and at 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months and 1 year after switch-on. The behavioral responses were detected at one year after the surgery. The high, medium and low frequencies of the cochleae were represented by No. 3, 11 and 22 electrodes, respectively, which were used to stimulate the base, middle and cupula of the cochleae. 2.2.1. Detection of EABR threshold In the present study, an evoked potential instrument (Otometrics Chartr EP® 200), portable programming system and Nucleus software 3.0 were used, and the parameters were set as follows: alternate stimulus mode, pulse width ¼ 50 us, and frequency at 48 Hz. The EABR threshold was counted as stimulus intensity when the V-waves disappeared. The result was confirmed by at least two similar measured data. Several methods were used to eliminate interference, with the aim of obtaining clear waveforms: (1) electrical stimulation and evoked potential were synchronously recorded; (2) electric and magnetic shielding devices were used; (3) children were kept at the quiet state, and anesthesia was applied when necessary; (4) alternating polarity pulse stimulation was used; (5) appropriate stimulus was used and parameters were recorded; (6) the stimulus frequency should not be an integral multiple or fraction of the alternating current frequency from the power supply; (7) contralateral recording was used. 2.2.2. Detection of NRT threshold Test parameters on NRT 3.0: stimulus pulse width ¼ 25 us, stimulus frequency ¼ 900 HZ, stimulus mode ¼ common ground (CG), and duration ¼ 500 us. The NRT threshold was counted as
2.2.4. Detection of behavioral response thresholds The subjective threshold (T-level) and maximum comfort threshold (C-level) were measured by pediatric behavioral audiometry. 2.3. Statistical methods The mean EABR, ESRT and NRT thresholds at different time points were examined by paired t-test between groups using SPSS version 22.0. The EABR, ESRT and NRT thresholds and behavioral response thresholds at one year after surgery were tested by linear regression and correlation analyses. 3. Results 3.1 The mean NRT thresholds were significantly different between groups at each time point, and at high, medium and low frequencies (Table 1). The response rates of NRT in the control group and test group were 88.04% and 77.98%, respectively. 3.2 The mean EABR thresholds were significantly different between groups at each time point, and at high, medium and low frequencies (Table 2). The response rates of EABR in the control group and test group were 99.87% and 90.74%, respectively. 3.3 The mean ESRT thresholds were significantly different between groups at each time point, and at high, medium and low frequencies (Table 3). The response rates of ESRT in the control group and test group were 78.99% and 70.95%, respectively. 3.4 Within one year after switch-on, the NRT, EABR and ESRT thresholds between groups all changed in similar trends under these three frequency ranges. Generally, these thresholds worsened at low frequencies and improved at high frequencies. The EABR, ESRT and NRT thresholds all slowly increased from the start of surgery up to one year after surgery (Figs. 1e3). 3.5 A significant correlation was found between the EABR threshold and T-level (P < 0.01), between the ESRT threshold and Clevel (P < 0.01), and between the NRT threshold and T-level (P < 0.05) in both groups at each frequency range within the oneyear postoperative period. The correlation analysis between the EABR threshold (or NRT, or ESRT) and the behavioral audiometry Tlevel (or C-level) is illustrated in Tables 4e6. The regression equations between the ESRT and C-level of patients with inner ear malformation in the high, medium and low frequency bands were as follows: ESRT ¼ 53.072 þ 0.688 C (F ¼ 308.345, t ¼ 0.000, P < 0.01), ESRT ¼ 50.163 þ 0.690 C (F ¼ 274.11, t ¼ 0.000, P < 0.01), ESRT ¼ 23.525 þ 0.845 C (F ¼ 228.968, t ¼ 0.000, P < 0.01). 4. Discussion As the technology and knowledge of cochlear implants have been improved in recent years, this has been applied into more and
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Table 1 NRT thresholds at different times points and at high, medium and low frequency ranges compared between groups. Time
High frequency Control
Boot-up 1 week 2 weeks 1 month 2 months 3 months 6 months 9 months 1 year
171 175 173 178 177 179 181 180 185
± ± ± ± ± ± ± ± ±
11 12 14 11 14 12 11 14 12
Medium frequency Test group 183 184 186 190 189 192 195 197 198
± ± ± ± ± ± ± ± ±
11 12 14 13 14 12 13 11 13
t
Control
5.031 3.459 4.283 4.529 3.953 4.997 5.283 6.366 4.758
165 165 167 169 172 176 178 181 183
± ± ± ± ± ± ± ± ±
12 14 11 13 12 13 14 13 11
Low frequency
Test group 176 176 178 181 183 187 186 190 195
± ± ± ± ± ± ± ± ±
13 11 15 14 14 13 15 11 12
t
Control
4.026 4.119 3.756 4.070 3.838 3.903 2.528 3.500 4.771
154 153 156 159 158 161 165 167 172
± ± ± ± ± ± ± ± ±
12 15 11 12 14 15 13 14 15
Test group 170 171 169 175 176 177 180 188 190
± ± ± ± ± ± ± ± ±
11 15 13 15 12 14 12 11 14
t 6.462 5.535 4.906 5.333 6.458 5.118 5.571 7.865 5.758
Table 2 EABR thresholds at different times points and at high, medium and low frequency ranges compared between groups. Time
High frequency
Boot-up 1 week 2 weeks 1 month 2 months 3 months 6 months 9 months 1 year
152 150 159 159 158 158 157 157 157
Control ± ± ± ± ± ± ± ± ±
11 13 14 12 13 12 11 15 12
Medium frequency Test group 161 165 169 168 168 167 167 168 169
± ± ± ± ± ± ± ± ±
12 11 13 12 13 14 11 12 11
t
Control
3.466 6.111 3.644 2.982 3.073 2.998 3.628 4.034 4.357
140 150 147 146 146 150 149 151 152
± ± ± ± ± ± ± ± ±
12 11 11 13 14 12 15 11 11
Low frequency
Test group 152 160 159 158 158 159 161 153 164
± ± ± ± ± ± ± ± ±
13 14 12 12 15 11 14 12 14
t
Control
4.172 3.949 4.148 4.663 4.965 4.079 4.953 4.661 4.534
130 130 129 128 135 139 138 140 141
± ± ± ± ± ± ± ± ±
12 12 15 13 14 16 14 11 13
Test group 142 140 148 146 148 147 147 149 156
± ± ± ± ± ± ± ± ±
13 12 11 15 12 12 11 15 12
t 4.364 4.066 7.335 6.295 5.652 3.512 3.405 4.171 5.596
Table 3 ESRT thresholds at different times points and at high, medium and low frequency ranges compared between groups. Time
High frequency Control
Boot-up 1 week 2 weeks 1 month 2 months 3 months 6 months 9 months 1 year
198 190 197 199 200 200 202 203 204
± ± ± ± ± ± ± ± ±
11 13 14 11 13 12 14 15 15
Medium frequency Test group 208 202 209 208 208 209 211 212 217
± ± ± ± ± ± ± ± ±
11 12 15 12 14 12 14 15 11
t
Control
3.867 4.112 4.647 3.985 3.074 3.815 3.229 3.333 5.056
192 190 190 192 192 192 197 197 201
± ± ± ± ± ± ± ± ±
11 12 15 15 14 11 12 14 13
Low frequency
Test group 202 200 199 201 202 207 207 206 214
± ± ± ± ± ± ± ± ±
12 11 14 14 12 15 11 13 12
t
Control
4.071 4.148 3.249 3.253 4.256 5.081 4.258 4.645 5.635
179 180 181 183 185 186 186 188 190
± ± ± ± ± ± ± ± ±
11 14 11 12 13 14 15 14 11
Fig. 1. Changes of NRT thresholds at three frequency ranges in the control group and the test group.
Test group 192 190 189 193 199 197 197 200 207
± ± ± ± ± ± ± ± ±
12 11 10 15 13 15 11 14 12
t 5.364 4.646 3.005 3.785 4.263 4.012 4.005 4.582 6.591
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Fig. 2. Changes of EABR thresholds at three frequency ranges the control group and the test group.
Fig. 3. Changes of ESRT thresholds at three frequency ranges in the control group and the test group.
Table 6 Correlation analysis between ESRT threshold and M-level at three frequency ranges in the two groups.
Table 4 Correlation analysis between NRT threshold and T-level at three frequency ranges in the two groups. Electrode
H M L
Control group
Electrode Control group
Test group
NRT threshold
T level
rt
NRT threshold
T level
rt
185 ± 12 183 ± 11 172 ± 15
164 ± 14 167 ± 13 156 ± 11
0.47 0.55 0.46
198 ± 13 195 ± 12 190 ± 14
183 ± 12 179 ± 15 171 ± 11
0.53 0.44 0.59
Test group
ESRT threshold M level H M L
204 ± 15 201 ± 13 190 ± 11
rM
ESRT threshold
193 ± 11 0.72 217 ± 11 183 ± 16 0.79 214 ± 12 179 ± 13 0.83 207 ± 12
M level
rM
206 ± 12 0.75 196 ± 12 0.69 189 ± 13 0.78
Note: H, M and L indicate high, medium and low frequency, respectively (the same below).
Table 5 Correlation analysis between EABR threshold and T-level at three frequency ranges in the two groups. Electrode
H M L
Control group
Test group
EABR threshold
T level
rt
EABR threshold
T level
rt
157 ± 12 152 ± 11 141 ± 13
164 ± 14 167 ± 13 156 ± 11
0.67 0.66 0.73
169 ± 11 164 ± 14 156 ± 12
183 ± 12 179 ± 15 171 ± 11
0.71 0.64 0.67
more children with inner ear malformations. As for cochlear implant patients, the accurate determination of T-level and C-level is critically important for postoperative mapping. However, for
child patients with inner ear malformations, in addition to their reluctance to cooperate due to their age, cochlear vestibular malformations result in low residual hearing, making it difficult to
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accurately determine the subjective T-level and M-level. Objective techniques including EABR, ESRT and NRT are not influenced by subjective factors, which contribute to the accurate measurement of objective thresholds and guidance of postoperative debugging. Thus, there is an urgent need to investigate the changes in the rules and characteristics of EABR, ESRT and NRT thresholds in cochlear implant children with inner ear malformations, and analyze their correlations with T-level and C-level. In the present study, we analyzed the changes in the characteristics and rules of EABR, ESRT and NRT at high, medium and low frequencies between cochlear implant children with normal cochlea and inner ear malformations. These results revealed that EABR, ESRT and NRT thresholds were significantly different between these two groups at different time points (all, P < 0.05), and changed at the same trends. Each threshold of patients with inner ear malformation was obviously higher than that of the normal group, showing the same tendency to change. There is a general tendency of low thresholds at low frequencies and high thresholds at high frequencies, and these thresholds during operation gradually increases until one year after the operation, which is consistent with the results of previous studies. In the present study, child patients with inner ear malformations included those with common cavity malformations, internal auditory canal stenosis and other severe inner ear malformations. The histopathological result of Graham et al. confirmed that patients with common cavity malformations suffered from partial or complete loss of modiolus cochleae, and the residual spiral ganglion cells lost normal distribution, characterized by the organ of Corti and its auditory nerve components located in the side wall of the modiolus cochleae. Internal auditory canal straitness deformity is often accompanied by the maldevelopment of the eighth cranial nerve, slender cochlear nerve, less residual nerve cells and poor synchronization of neural activity. On this basis, we could explain why each threshold of patients with inner ear malformation was obviously higher than that of the normal group. These two groups exhibited the same variation trends in EABR, ESRT and NRT, suggesting that factors affecting the variation trend of each measure are irrelevant to cochlear malformation in shape and structure. In other words, cochlear malformation in shape and structure will affect the thresholds of EABR, ESRT and NRT, but is not correlated with its variation trends. We consider that factors affecting the variation trend of each measure are associated with the following: (1) rejection reaction of the human body after electrode implantation; (2) hyperplasia of the inflammatory fibrous tissue of the cochlea; (3) labyrinth fibrosis, new bone formation, and the formation of reactive neuroma; (4) the amount of cochlear lymphatic fluid around the stimulation electrode; (5) the design of the implanted electrode product. Furthermore, the high resistance of the cranked electrode has been recently proven. A significant correlation was found between the EABR threshold and T-level (P < 0.01), between the ESRT threshold and C-level (P < 0.01), and between the NRT threshold and T-level (P < 0.05) in both groups within the one-year postoperative period. Knowledge of the changes in these rules and characteristics is significant for guiding postoperative mapping in cochlear implant children with inner ear malformations. NRT detection is a near-field method that has been widely applied in clinic, owing to its convenience, rapidness and low requirement on test environments. However, as reported, failure to induce waveforms occurred in some patients due to the step-bystep state and local electrode state of the residual nerve fibers, as well as the complex regulation of parameters such as NRT record gain delay [13e15]. In the present study, the response rate of NRT in the test group was 77.98%, and the NRT threshold was less significantly correlated with T-level, which both limit the judgment of auditory functions. EABR, which basically has the same wave
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sources as ABR, theoretically reflects the functional status of the auditory conduction pathway of auditory nerve brain stems [16e18]. Furthermore, the response rate of EABR in the test group was 90.74%, and the EABR threshold was significantly correlated with T-level. This indicates that the T-level can be evaluated from the EABR threshold and set close to the EABR threshold. Stapedius reflex is a protective process, and theoretically, its threshold is close to C-level [19]. Furthermore, the ESRT threshold is significantly correlated with C-level, which indicates that C-level can be predicted from the ESRT threshold. We consider that no ideal T-level or C-level can be measured by subjective behavioral audiometry in cochlear implant children with inner ear malformations, owing to their small age and low residual hearing. In this case, objective hearing detection techniques including EABR, ESRT and NRT are good options. In the present study, the EABR thresholds were all close and significantly correlated with T-level, indicating that T-level can be set close to the EABR threshold. Since the EABR threshold is theoretically close to C-level, according to the regression equations between ERST and Clevel obtained in the present study and the total effect of multiple electrodes after switch-on [20e22], we recommend that the Clevel be set at 10e15 CL below the ESRT threshold. For some cochlear implant children with inner ear malformations, a part of the electrodes may fail to induce EABR, ESRT and NRT. In this case, based on the number of electrodes that can induce thresholds, and referring to the changes in the rules and characteristics of thresholds at different time points recorded in the present study, we can apply the EABR and ESRT thresholds of these electrodes into other electrodes, and thereby experimentally debug the equipment. Overall, objective hearing detection techniques including EABR, ESRT and NRT can be used to guide in mapping, postoperatively, among cochlear implant children with inner ear malformations, especially the setting of T and C values. However, it should be stressed that EABR, ESRT, NRT and other objective auditory detection techniques should not be recommended as routine examinations, and should be considered only when a satisfactory T-level or C-level is hard to be obtained after a patient receives postoperative subjective behavioral audiometry. Ethics approval and consent to participate I confirm that I have read the Editorial Policy pages. This study was conducted with approval from the Ethics Committee of our hospital. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants. Consent for publication All participants signed a document of informed consent. Acknowledgements We are particularly grateful to all the people who have given us help on our article. Fund project Shanxi Science and Technology Key Program (20150313010-5). Competing interests The authors declare that they have no competing interests.
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International Journal of Pediatric Otorhinolaryngology journal homepage: http://www.ijporlonline.com/
Postoperative objective detecting techniques for cochlear implant children with inner ear malformation Xiao-Feng Qiao a, *, Xin Li b, Qiang-Wei Zhang a, Tong-Li Li a, Dong Wang a a b
Department of Otorhinolaryngology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan 030001, China Department of Surgery, Children's Hospital of Shanxi Province, Taiyuan 030001, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 June 2017 Received in revised form 18 August 2017 Accepted 22 August 2017 Available online 25 August 2017
Objectives: This study aims to investigate the changing characteristics and rules of electrically-evoked auditory brainstem response (EABR), electrically-evoked stapedius reflex threshold (ESRT) and neural response telemetry (NRT) after cochlear implant in children with inner ear malformation, and guide postoperative equipment debug. Methods: A total of 88 children with either normal cochlea (control group) or inner ear malformation (test group) received Australian 24 multi-channel cochlear implants. The EABR, ESRT and NRT thresholds at different time points within one year postoperatively and behavioral responses (T-level and C-level) after one year were detected. Furthermore, the changing characteristics and rules of these thresholds were analyzed. Results: The EABR, ESRT and NRT thresholds were all significantly higher at all time points in the test group than in the control group, but the general changing trends were similar. Particularly, these thresholds worsened at low frequencies and improved at high frequencies. Furthermore, EABR, ESRT and NRT thresholds gradually increased during the one year postoperative period. In addition, an extremely significant correlation was found between EABR and T-level and between ESRT and C-level, but a less significant correlation was found between NRT threshold and T-level in both groups. Conclusions: The postoperative changes in characteristics and rules of EABR, ESRT and NRT thresholds among cochlear implant children with inner ear malformation were all the same as those with normal cochlea. Thus, these thresholds can be used to guide the postoperative equipment debug for cochlear implants into patients with inner ear malformation. © 2017 Elsevier B.V. All rights reserved.
Keywords: Cochlear implant Sound processor debugging Neural response telemetry Electrically-evoked auditory brainstem response Electrically-evoked stapedius reflex threshold
1. Introduction In China, as the technology and knowledge of cochlear implants have been improved in recent years, more and more children with severe or extremely severe sensorineural hearing loss have been operated with cochlear implants. The successful operation is the first step for children to recover their hearing, and mapping at regular time after the operation is very important [1e4]. However, the big problem with postoperative machine debug is how to determine the subjective threshold (T-level) and most comfortable level (C-level). For children, due to their small age, it is difficult to
* Corresponding author. Department of Otorhinolaryngology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, No.29 of Twin Towers Temple Street, Taiyuan 030001, China. E-mail address: [email protected] (X.-F. Qiao). http://dx.doi.org/10.1016/j.ijporl.2017.08.026 0165-5876/© 2017 Elsevier B.V. All rights reserved.
obtain the accurate T-level and C-level by behavioral audiometry. To date, T-level and C-level are commonly evaluated by neural response telemetry (NRT) in clinic [5,6]. For children with normal cochlea, changes in the rules and characteristics of NRT after cochlear implant and its correlations with T-level and C-level have been extensively reported and recognized [7,8]. In recent years, more and more children with inner ear malformations have been operated with cochlear implants. Due to inner ear malformations, residual hearing is less, the rate of NRT extraction is low, and the regularity and characteristics of NRT are not mastered. In this case, we hope to find other objective hearing detection indexes instead of NRT inspection, in order to accurately estimate the inner ear malformation of cochlear implantation in children with T-level and C-level, guide postoperative mapping, and ensure the hearing rehabilitation of children. In addition to NRT, the current clinical detection methods for the objective evaluation of hearing include: electrically-evoked auditory brainstem response (EABR) and
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electrically-evoked stapedius reflex threshold (ESRT). For children with cochlear implants and normal inner ear structure, a number of studies have shown that EABR and ESRT are correlated with T-level and C-level, and that these can be used to guide postoperative mapping [9e12]. Hence, there is a need to explore these values and determine whether EABR and ESRT are equally useful for cochlear implants in children with inner ear malformations. Thus, the present study aims to investigate the changes in the rules and characteristics of EABR, ESRT and NRT in children with inner ear malformations and cochlear implants, as well as its correlations with behavioral response thresholds. We have summarized these changes in rules and characteristics with the aim to guide the programming and debugging in clinic.
stimulus intensity when the NRT waveforms disappeared. 2.2.3. Detection of ESRT threshold Nucleus software 3.0, a portable programming system and acoustic-immittance device (MADSEN OTO flex 100) was used. Stimulation parameters: waviness width, 20e50 us; stimulation rate, 200 Hz; duration of stimulation, 0.5e1.0 s; stimulation interval, 1.0e1.5 s. The test probe was placed into the lateral path of the non-artificial cochlear implant. ESR was measured at the acoustic attenuation mode. The electrical stimulation and sound reflection buttons were simultaneously pressed, and the baseline drift was recorded. A baseline drift >0.05 mmho was considered as the presence of stapedius reflex, and the minimum stimulus intensity was regarded as the ESRT threshold.
2. Data and methods 2.1. Clinical data A total of 88 cochlear implant children, who were treated in Shanxi People's Hospital between August 2001 and February 2016, were included into this study. All participants were patients with severe and extremely severe sensorineural hearing loss. The control group (52 children with normal cochlea) involved 28 boys and 24 girls, who were 1e13 years old. The test group (36 children with inner ear malformations) involved 21 boys and 15 girls, who were 1e7 years old. These 36 cases of inner ear malformation included 21 cases of large vestibular aqueduct syndrome, five cases of common cavity deformity, nine cases of vestibular semicircular canal malformation, and one case of internal auditory canal stenosis. All children were implanted with Australian Cochlear Nucleus 24 cochleae, and all of them were unilateral cochlear implants. 2.2. Methods Since switch-on at postoperative one month, EABR, ESRT and NRT thresholds were detected at switch-on day, and at 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months and 1 year after switch-on. The behavioral responses were detected at one year after the surgery. The high, medium and low frequencies of the cochleae were represented by No. 3, 11 and 22 electrodes, respectively, which were used to stimulate the base, middle and cupula of the cochleae. 2.2.1. Detection of EABR threshold In the present study, an evoked potential instrument (Otometrics Chartr EP® 200), portable programming system and Nucleus software 3.0 were used, and the parameters were set as follows: alternate stimulus mode, pulse width ¼ 50 us, and frequency at 48 Hz. The EABR threshold was counted as stimulus intensity when the V-waves disappeared. The result was confirmed by at least two similar measured data. Several methods were used to eliminate interference, with the aim of obtaining clear waveforms: (1) electrical stimulation and evoked potential were synchronously recorded; (2) electric and magnetic shielding devices were used; (3) children were kept at the quiet state, and anesthesia was applied when necessary; (4) alternating polarity pulse stimulation was used; (5) appropriate stimulus was used and parameters were recorded; (6) the stimulus frequency should not be an integral multiple or fraction of the alternating current frequency from the power supply; (7) contralateral recording was used. 2.2.2. Detection of NRT threshold Test parameters on NRT 3.0: stimulus pulse width ¼ 25 us, stimulus frequency ¼ 900 HZ, stimulus mode ¼ common ground (CG), and duration ¼ 500 us. The NRT threshold was counted as
2.2.4. Detection of behavioral response thresholds The subjective threshold (T-level) and maximum comfort threshold (C-level) were measured by pediatric behavioral audiometry. 2.3. Statistical methods The mean EABR, ESRT and NRT thresholds at different time points were examined by paired t-test between groups using SPSS version 22.0. The EABR, ESRT and NRT thresholds and behavioral response thresholds at one year after surgery were tested by linear regression and correlation analyses. 3. Results 3.1 The mean NRT thresholds were significantly different between groups at each time point, and at high, medium and low frequencies (Table 1). The response rates of NRT in the control group and test group were 88.04% and 77.98%, respectively. 3.2 The mean EABR thresholds were significantly different between groups at each time point, and at high, medium and low frequencies (Table 2). The response rates of EABR in the control group and test group were 99.87% and 90.74%, respectively. 3.3 The mean ESRT thresholds were significantly different between groups at each time point, and at high, medium and low frequencies (Table 3). The response rates of ESRT in the control group and test group were 78.99% and 70.95%, respectively. 3.4 Within one year after switch-on, the NRT, EABR and ESRT thresholds between groups all changed in similar trends under these three frequency ranges. Generally, these thresholds worsened at low frequencies and improved at high frequencies. The EABR, ESRT and NRT thresholds all slowly increased from the start of surgery up to one year after surgery (Figs. 1e3). 3.5 A significant correlation was found between the EABR threshold and T-level (P < 0.01), between the ESRT threshold and Clevel (P < 0.01), and between the NRT threshold and T-level (P < 0.05) in both groups at each frequency range within the oneyear postoperative period. The correlation analysis between the EABR threshold (or NRT, or ESRT) and the behavioral audiometry Tlevel (or C-level) is illustrated in Tables 4e6. The regression equations between the ESRT and C-level of patients with inner ear malformation in the high, medium and low frequency bands were as follows: ESRT ¼ 53.072 þ 0.688 C (F ¼ 308.345, t ¼ 0.000, P < 0.01), ESRT ¼ 50.163 þ 0.690 C (F ¼ 274.11, t ¼ 0.000, P < 0.01), ESRT ¼ 23.525 þ 0.845 C (F ¼ 228.968, t ¼ 0.000, P < 0.01). 4. Discussion As the technology and knowledge of cochlear implants have been improved in recent years, this has been applied into more and
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Table 1 NRT thresholds at different times points and at high, medium and low frequency ranges compared between groups. Time
High frequency Control
Boot-up 1 week 2 weeks 1 month 2 months 3 months 6 months 9 months 1 year
171 175 173 178 177 179 181 180 185
± ± ± ± ± ± ± ± ±
11 12 14 11 14 12 11 14 12
Medium frequency Test group 183 184 186 190 189 192 195 197 198
± ± ± ± ± ± ± ± ±
11 12 14 13 14 12 13 11 13
t
Control
5.031 3.459 4.283 4.529 3.953 4.997 5.283 6.366 4.758
165 165 167 169 172 176 178 181 183
± ± ± ± ± ± ± ± ±
12 14 11 13 12 13 14 13 11
Low frequency
Test group 176 176 178 181 183 187 186 190 195
± ± ± ± ± ± ± ± ±
13 11 15 14 14 13 15 11 12
t
Control
4.026 4.119 3.756 4.070 3.838 3.903 2.528 3.500 4.771
154 153 156 159 158 161 165 167 172
± ± ± ± ± ± ± ± ±
12 15 11 12 14 15 13 14 15
Test group 170 171 169 175 176 177 180 188 190
± ± ± ± ± ± ± ± ±
11 15 13 15 12 14 12 11 14
t 6.462 5.535 4.906 5.333 6.458 5.118 5.571 7.865 5.758
Table 2 EABR thresholds at different times points and at high, medium and low frequency ranges compared between groups. Time
High frequency
Boot-up 1 week 2 weeks 1 month 2 months 3 months 6 months 9 months 1 year
152 150 159 159 158 158 157 157 157
Control ± ± ± ± ± ± ± ± ±
11 13 14 12 13 12 11 15 12
Medium frequency Test group 161 165 169 168 168 167 167 168 169
± ± ± ± ± ± ± ± ±
12 11 13 12 13 14 11 12 11
t
Control
3.466 6.111 3.644 2.982 3.073 2.998 3.628 4.034 4.357
140 150 147 146 146 150 149 151 152
± ± ± ± ± ± ± ± ±
12 11 11 13 14 12 15 11 11
Low frequency
Test group 152 160 159 158 158 159 161 153 164
± ± ± ± ± ± ± ± ±
13 14 12 12 15 11 14 12 14
t
Control
4.172 3.949 4.148 4.663 4.965 4.079 4.953 4.661 4.534
130 130 129 128 135 139 138 140 141
± ± ± ± ± ± ± ± ±
12 12 15 13 14 16 14 11 13
Test group 142 140 148 146 148 147 147 149 156
± ± ± ± ± ± ± ± ±
13 12 11 15 12 12 11 15 12
t 4.364 4.066 7.335 6.295 5.652 3.512 3.405 4.171 5.596
Table 3 ESRT thresholds at different times points and at high, medium and low frequency ranges compared between groups. Time
High frequency Control
Boot-up 1 week 2 weeks 1 month 2 months 3 months 6 months 9 months 1 year
198 190 197 199 200 200 202 203 204
± ± ± ± ± ± ± ± ±
11 13 14 11 13 12 14 15 15
Medium frequency Test group 208 202 209 208 208 209 211 212 217
± ± ± ± ± ± ± ± ±
11 12 15 12 14 12 14 15 11
t
Control
3.867 4.112 4.647 3.985 3.074 3.815 3.229 3.333 5.056
192 190 190 192 192 192 197 197 201
± ± ± ± ± ± ± ± ±
11 12 15 15 14 11 12 14 13
Low frequency
Test group 202 200 199 201 202 207 207 206 214
± ± ± ± ± ± ± ± ±
12 11 14 14 12 15 11 13 12
t
Control
4.071 4.148 3.249 3.253 4.256 5.081 4.258 4.645 5.635
179 180 181 183 185 186 186 188 190
± ± ± ± ± ± ± ± ±
11 14 11 12 13 14 15 14 11
Fig. 1. Changes of NRT thresholds at three frequency ranges in the control group and the test group.
Test group 192 190 189 193 199 197 197 200 207
± ± ± ± ± ± ± ± ±
12 11 10 15 13 15 11 14 12
t 5.364 4.646 3.005 3.785 4.263 4.012 4.005 4.582 6.591
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Fig. 2. Changes of EABR thresholds at three frequency ranges the control group and the test group.
Fig. 3. Changes of ESRT thresholds at three frequency ranges in the control group and the test group.
Table 6 Correlation analysis between ESRT threshold and M-level at three frequency ranges in the two groups.
Table 4 Correlation analysis between NRT threshold and T-level at three frequency ranges in the two groups. Electrode
H M L
Control group
Electrode Control group
Test group
NRT threshold
T level
rt
NRT threshold
T level
rt
185 ± 12 183 ± 11 172 ± 15
164 ± 14 167 ± 13 156 ± 11
0.47 0.55 0.46
198 ± 13 195 ± 12 190 ± 14
183 ± 12 179 ± 15 171 ± 11
0.53 0.44 0.59
Test group
ESRT threshold M level H M L
204 ± 15 201 ± 13 190 ± 11
rM
ESRT threshold
193 ± 11 0.72 217 ± 11 183 ± 16 0.79 214 ± 12 179 ± 13 0.83 207 ± 12
M level
rM
206 ± 12 0.75 196 ± 12 0.69 189 ± 13 0.78
Note: H, M and L indicate high, medium and low frequency, respectively (the same below).
Table 5 Correlation analysis between EABR threshold and T-level at three frequency ranges in the two groups. Electrode
H M L
Control group
Test group
EABR threshold
T level
rt
EABR threshold
T level
rt
157 ± 12 152 ± 11 141 ± 13
164 ± 14 167 ± 13 156 ± 11
0.67 0.66 0.73
169 ± 11 164 ± 14 156 ± 12
183 ± 12 179 ± 15 171 ± 11
0.71 0.64 0.67
more children with inner ear malformations. As for cochlear implant patients, the accurate determination of T-level and C-level is critically important for postoperative mapping. However, for
child patients with inner ear malformations, in addition to their reluctance to cooperate due to their age, cochlear vestibular malformations result in low residual hearing, making it difficult to
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accurately determine the subjective T-level and M-level. Objective techniques including EABR, ESRT and NRT are not influenced by subjective factors, which contribute to the accurate measurement of objective thresholds and guidance of postoperative debugging. Thus, there is an urgent need to investigate the changes in the rules and characteristics of EABR, ESRT and NRT thresholds in cochlear implant children with inner ear malformations, and analyze their correlations with T-level and C-level. In the present study, we analyzed the changes in the characteristics and rules of EABR, ESRT and NRT at high, medium and low frequencies between cochlear implant children with normal cochlea and inner ear malformations. These results revealed that EABR, ESRT and NRT thresholds were significantly different between these two groups at different time points (all, P < 0.05), and changed at the same trends. Each threshold of patients with inner ear malformation was obviously higher than that of the normal group, showing the same tendency to change. There is a general tendency of low thresholds at low frequencies and high thresholds at high frequencies, and these thresholds during operation gradually increases until one year after the operation, which is consistent with the results of previous studies. In the present study, child patients with inner ear malformations included those with common cavity malformations, internal auditory canal stenosis and other severe inner ear malformations. The histopathological result of Graham et al. confirmed that patients with common cavity malformations suffered from partial or complete loss of modiolus cochleae, and the residual spiral ganglion cells lost normal distribution, characterized by the organ of Corti and its auditory nerve components located in the side wall of the modiolus cochleae. Internal auditory canal straitness deformity is often accompanied by the maldevelopment of the eighth cranial nerve, slender cochlear nerve, less residual nerve cells and poor synchronization of neural activity. On this basis, we could explain why each threshold of patients with inner ear malformation was obviously higher than that of the normal group. These two groups exhibited the same variation trends in EABR, ESRT and NRT, suggesting that factors affecting the variation trend of each measure are irrelevant to cochlear malformation in shape and structure. In other words, cochlear malformation in shape and structure will affect the thresholds of EABR, ESRT and NRT, but is not correlated with its variation trends. We consider that factors affecting the variation trend of each measure are associated with the following: (1) rejection reaction of the human body after electrode implantation; (2) hyperplasia of the inflammatory fibrous tissue of the cochlea; (3) labyrinth fibrosis, new bone formation, and the formation of reactive neuroma; (4) the amount of cochlear lymphatic fluid around the stimulation electrode; (5) the design of the implanted electrode product. Furthermore, the high resistance of the cranked electrode has been recently proven. A significant correlation was found between the EABR threshold and T-level (P < 0.01), between the ESRT threshold and C-level (P < 0.01), and between the NRT threshold and T-level (P < 0.05) in both groups within the one-year postoperative period. Knowledge of the changes in these rules and characteristics is significant for guiding postoperative mapping in cochlear implant children with inner ear malformations. NRT detection is a near-field method that has been widely applied in clinic, owing to its convenience, rapidness and low requirement on test environments. However, as reported, failure to induce waveforms occurred in some patients due to the step-bystep state and local electrode state of the residual nerve fibers, as well as the complex regulation of parameters such as NRT record gain delay [13e15]. In the present study, the response rate of NRT in the test group was 77.98%, and the NRT threshold was less significantly correlated with T-level, which both limit the judgment of auditory functions. EABR, which basically has the same wave
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sources as ABR, theoretically reflects the functional status of the auditory conduction pathway of auditory nerve brain stems [16e18]. Furthermore, the response rate of EABR in the test group was 90.74%, and the EABR threshold was significantly correlated with T-level. This indicates that the T-level can be evaluated from the EABR threshold and set close to the EABR threshold. Stapedius reflex is a protective process, and theoretically, its threshold is close to C-level [19]. Furthermore, the ESRT threshold is significantly correlated with C-level, which indicates that C-level can be predicted from the ESRT threshold. We consider that no ideal T-level or C-level can be measured by subjective behavioral audiometry in cochlear implant children with inner ear malformations, owing to their small age and low residual hearing. In this case, objective hearing detection techniques including EABR, ESRT and NRT are good options. In the present study, the EABR thresholds were all close and significantly correlated with T-level, indicating that T-level can be set close to the EABR threshold. Since the EABR threshold is theoretically close to C-level, according to the regression equations between ERST and Clevel obtained in the present study and the total effect of multiple electrodes after switch-on [20e22], we recommend that the Clevel be set at 10e15 CL below the ESRT threshold. For some cochlear implant children with inner ear malformations, a part of the electrodes may fail to induce EABR, ESRT and NRT. In this case, based on the number of electrodes that can induce thresholds, and referring to the changes in the rules and characteristics of thresholds at different time points recorded in the present study, we can apply the EABR and ESRT thresholds of these electrodes into other electrodes, and thereby experimentally debug the equipment. Overall, objective hearing detection techniques including EABR, ESRT and NRT can be used to guide in mapping, postoperatively, among cochlear implant children with inner ear malformations, especially the setting of T and C values. However, it should be stressed that EABR, ESRT, NRT and other objective auditory detection techniques should not be recommended as routine examinations, and should be considered only when a satisfactory T-level or C-level is hard to be obtained after a patient receives postoperative subjective behavioral audiometry. Ethics approval and consent to participate I confirm that I have read the Editorial Policy pages. This study was conducted with approval from the Ethics Committee of our hospital. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants. Consent for publication All participants signed a document of informed consent. Acknowledgements We are particularly grateful to all the people who have given us help on our article. Fund project Shanxi Science and Technology Key Program (20150313010-5). Competing interests The authors declare that they have no competing interests.
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