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Auditory neuropathy spectrum disorder: Its prevalence and audiological characteristics in an Indian tertiary care hospital
International Journal of Pediatric Otorhinolaryngology 76 (2012) 1351–1354
Contents lists available at SciVerse ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Auditory neuropathy spectrum disorder: Its prevalence and audiological characteristics in an Indian tertiary care hospital Ruchika Mittal a,*, A.V. Ramesh a,1, S.S. Panwar b,2, Ajith Nilkanthan a,3, Satish Nair a,4, Poonam Raj Mehra a,5 a b
Army Hospital (R&R), Delhi Cantt 110010, India Command Hospital (SC), Poona 411040, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 April 2012 Received in revised form 14 June 2012 Accepted 16 June 2012 Available online 12 July 2012
Objective: Auditory neuropathy spectrum disorder (ANSD) has become a well accepted clinical entity. ANSD has now become easy to recognize with advent of test battery approach for hearing loss evaluation. However, little is known about its epidemiology and aetiology, especially its prevalence and incidence in India. This study was conducted to determine the prevalence and audiological characteristics of ANSD in our tertiary care hospital at New Delhi, India. Methods: We prospectively enrolled all the paediatric cases i.e. less than 12 years of age referred to our outpatient department for hearing evaluation. All the cases were evaluated using complete audiological test battery consisting of pure tone audiometry (PTA), impedance audiometry, acoustic reflexes, otoacoustic emissions (OAE), and brain stem evoked response audiometry (BERA). The instrument used was GSI Audera. BERA with both condensation and rarefaction polarity was performed in cases with absent wave V even at highest intensity levels. The criteria used for diagnosis of ANSD was normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). A repeat test battery was performed after 3 months on the diagnosed cases of auditory neuropathy. Based on their behavioural findings the appropriate management programme was formulated. Results: A total of 487 paediatric cases were referred for hearing evaluation. 183 (37.6%) cases showed absent BERA and 26(5.3%) cases fulfilled the diagnostic criteria for ANSD. Repeat examination after 3 months revealed presence of OAE’s in 57.6% (15/26) cases while cochlear microphonics were present in all the 26 cases. Conclusion: The prevalence of ANSD in our study is 5.3% and in children diagnosed with severe to profound hearing loss is 14%. Presence of cochlear microphonics with absent BERA seems to be reliable criteria for diagnosing ANSD. ß 2012 Elsevier Ireland Ltd. All rights reserved.
Keywords: Auditory neuropathy spectrum disorder (ANSD) Cochlear microphonics Otoacoustic emissions (OAE) Brainstem evoked response audiometry
1. Introduction Hearing loss in infancy or early childhood has been recognized as a potentially disabling condition. It leads to
* Corresponding author at: M-37C Rajouri Garden, New Delhi 110027, India. Tel.: +91 9810961266. E-mail addresses: [email protected] (R. Mittal), [email protected] (A.V. Ramesh), [email protected] (S.S. Panwar), [email protected] (A. Nilkanthan), [email protected] (S. Nair), [email protected] (P.R. Mehra). 1 Tel.: +91 9910044184. 2 Tel.: +91 9764761044. 3 Tel.: +91 8527229938. 4 Tel.: +91 9312614114. 5 Tel.: +91 9958414385. 0165-5876/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2012.06.005
serious deleterious effects on speech and language development. If a spoken or sign language is not introduced early in life, cognitive, emotional and social development are delayed. Thus early detection and early intervention for congenital or acquired hearing loss in infancy has been an overriding goal of paediatric audiology [1]. Due to efficient hearing screening programmes, an entity known as auditory neuropathy spectrum disorder (ANSD) has been recognized. Auditory neuropathy is a pattern of hearing loss characterized by preservation of outer hair cell function despite absent brainstem auditory evoked responses. Intact outer hair cell function is demonstrated by the presence of otoacoustic emissions (OAEs) and/or measurable cochlear microphonics (CM) whereas no synchronous neural activity is seen on acoustically evoked auditory evoked brainstem response testing [2]. The prevalence
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of the disorder has been estimated to range from 0.5% to 15% of all patients evaluated with hearing loss [3]. The site of the lesion of ANSD is still unknown. Proposed sites include selected outer hair cells, inner hair cells, the synapse between hair cells and the auditory nerve, neural dendrite or axon, myelin sheath or spiral ganglion fibers [4,5]. The otoacoustic emissions (OAEs) change from pass to refer over a period of time. This creates a precarious situation for both the audiologist and neuro-otologist. Isabelle Rapin also pointed out the confusion in the audiological literature regarding physiological and behavioural test results in patients with auditory neuropathy [6]. The present study was conducted in a tertiary care hospital in New Delhi, India to study the prevalence and audiological characteristics of paediatric cases with ANSD.
2. Materials and methods We prospectively enrolled all the pediatric cases i.e. less than 12 years of age referred to our tertiary care hospital’s outpatient department of ENT for hearing evaluation from March 2008 to December 2010. All the cases were evaluated using complete audiological test battery consisting of pure tone audiometry (PTA), impedance audiometry, acoustic reflexes, distortion product otoacoustic emissions (DPOAE’s), click evoked brain stem evoked response audiometry (BERA). All the audiological testing was performed in sound treated room and the uncooperative or young children were sedated with appropriate dosage of Syrup Triclofos oral solution BP (0.5 ml/kg) prior to objective testing. BERA with both condensation and rarefaction polarity was performed in cases where wave V was absent at highest intensity levels. All the cases diagnosed with hearing loss were also referred for high resolution CT scan, paediatric neurologist evaluation and child psychologist assessment and opinion. The criteria used for diagnosis of ANSD was normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). A repeat test battery was performed after 3 months on the cases diagnosed as auditory neuropathy. Based on the findings, appropriate management programme was formulated.
2.2.1. Impedance audiometry and acoustic reflex testing Age appropriate size probe was placed in the child’s ear canal. The sound at 220 Hz was presented with air pressure changing from +200 daPa (Pascal) to 400 daPa. Acoustic reflex was checked at 500, 1000, 2000 and 4000 Hz and between 70 and 100 dB. Both ipsilateral and contra lateral reflexes were observed. The instrument used was Grason Stadler Tympstar Version 2. 2.2.2. Click evoked brainstem evoked response audiometry (BERA) The electrodes were placed at mastoid of both the ears (noninverting), lower (inverting) and upper (common ground) forehead and the instrument used was GSI Audera version 2.6.7. The click stimulus was presented at alternate polarity with insert earphones ER3A at 70 dB. If wave V was not traced, the intensity was increased in 10 dB steps till the highest intensity of the instrument. Otherwise, lowest intensity was traced at which wave V could be recorded. Two waveforms were traced at each intensity level to check the reproducibility of the waveforms. The lowest level at which wave V was recorded was marked as threshold of the child. BERA with both condensation and rarefaction polarity was carried out in all the cases with absent wave V at highest intensity levels to check for cochlear microphonics (CM). The CM was considered to be present if the response waveform showed a 1808 phase shift with the change in stimulus polarity from rarefaction to condensation. The authenticity of the CM response was confirmed through test runs in which the stimulus tube was clamped to prevent the acoustic signal from reaching the ear canal. Under these circumstances, genuine cochlear potentials were abolished while the stimulus artifact remained unaltered. 2.2.3. Definitions used
1. Criteria used to diagnose auditory neuropathy spectrum disorder (ANSD): normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/ or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). 2. Classification of hearing loss on pure tone/play audiometry: Goodman [7] recommended classification was used for classification of hearing loss.
2.1. Pure tone/play audiometry (PTA) 3. Results The child was instructed to put the block (toy) down or raise the finger whenever he or she hears the sound (whichever was applicable as per the age of the child). The audiometry was done at each octave between 500 Hz and 4000 Hz for air conduction and for bone conduction testing. The tone was first presented at 2000 Hz and at 50–60 dB. Three or four trials were done before starting the test procedure. If the child hears the sound, the intensity was lowered by 10–15 dB steps. The lowest level at which the child responds 50% of the time was marked as threshold of the patient. The instrument used was Hortmann Neuro-otometric Audiomaster CA 540/2 calibrated as per American National Standards Institute S.6 2004.
A total of 487 paediatric cases from 6 months to 12 years of age were referred for hearing evaluation. 183 (37.6%) cases showed absent BERA and 26 (5.3%) cases fulfilled the diagnostic criteria for ANSD. The children diagnosed with ANSD were in the age range of 3–5 years. The mean age of patients who fulfilled the diagnostic criteria for auditory neuropathy spectrum disorder was 4.17 1.4 years. There were five males to twenty one females. All were bilateral cases of ANSD. Of the 26 children diagnosed to have ANSD, 73% (n = 19) were found to have a history of neonatal hyperbilirubinemia. 7.6% (n = 2) had birth asphyxia. No specific perinatal cause was found in 19.4% (n = 5). None of the patient was given hearing aid after initial evaluation.
2.2. Distortion product otoacoustic emissions (DPOAEs) 3.1. Pure tone/play audiometry (PTA) (Table 1) A probe according to the size of the ear canal was placed in child’s ear and DPOAE’s were recorded with settings F2/F1 = 1.2, frequency range 597–7277 Hz, intensity of F2 = 65 dB and F1 = 55 dB, noise rejection = 40. DPOAE’s were considered pass if signal to noise ratio was above 3 dB at three consecutive frequencies. The instrument used was GSI Audera version 2.6.7.
3.1.1. Impedance audiometry and acoustic reflex testing All the children diagnosed with ANSD showed Type A tympanogram which reveals normal middle ear function and absent acoustic reflexes bilaterally at both initial and after 3 month follow up testing ().
R. Mittal et al. / International Journal of Pediatric Otorhinolaryngology 76 (2012) 1351–1354
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Table 1 Showing the results of play/pure tone audiometry, pure tone/play audiometry (PTA). Degree of hearing lossa
Initial evaluation (n = 183b)
ANSD children (n = 26)
ANSD children (after 3 months) (n = 26)
Mild Moderate Moderately severe Severe Profound
1 12 11 119 5
1 12 11 2 0
1 12 11 2 0
a b
(0.55%) (6.55%) (6.01%) (65.02%) (2.73%)
(3.84%) (46.15%) (42.3%) (7.69%)
(3.84%) (46.15%) (42.3%) (7.69%)
Sensori-neural hearing loss in all the cases. During initial evaluation PTA could not be performed on 35 uncooperative children.
Table 2 Showing the results of otoacoustic emissions. OAE’s
Initial evaluation (n = 183)
ANSD children (n = 26)
ANSD children (after 3 months) (n = 26)
Absent Present
163 (89.07%) 20 (10.93%)
6 (23.07%) 20 (76.93%)
11 (42.31%) 15 (57.69%)
3.2. Distortion product otoacoustic emissions (DPOAE’s) At initial visit, OAEs were present in 20 out of 26 cases, which were diagnosed as ANSD. After three months OAE’s were present in only 15 cases. OAE’s became absent in 5 subjects after 3 months (Table 2). 3.2.1. Click evoked brain stem evoked response audiometry (BERA) Of 487 cases that were referred for hearing evaluation, 183 cases showed absent BERA. 26 children showed presence of cochlear microphonics with rarefaction and condensation polarity. CM was recordable in all the 26 cases after 3 months of initial evaluation also. A sample waveform to depict CM is shown in Fig. 1. 4. Discussion The prevalence of ANSD in our study is found to be 14% in children diagnosed with severe to profound hearing loss. Walton et al. [2] also reported prevalence of 10–14% in children diagnosed with severe to profound sensori-neural hearing loss. The prevalence of ANSD calculated in our study is 5.3% of all patients referred/evaluated for hearing loss. Similar prevalence in the range of 0.5–15% had been reported in the literature of all the patients evaluated with hearing loss [5]. In our study, the mean age of ANSD was 4.17 5.4 years. ANSD is a relatively newly described and poorly understood disorder. There is much to be learned, including incidence, prevalence, natural course, and a clearer definition of treatment
options. In the year 2007 Position Statement, the Joint Committee on Infant Hearing has recommended population based studies to determine prevalence and natural history of ANSD [8]. All the cases diagnosed in our study showed bilateral involvement of ANSD. Sininger and Oba also reported that ANSD is usually bilaterally [9]. During initial evaluation OAE’s were absent in six cases out of twenty six (23%) cases who were diagnosed with ANSD. Cochlear microphonics with abnormal BERA was the criteria for diagnosis of ANSD and hence was present in all cases at initial evaluation. Cochlear microphonics persisted at re evaluation after three months. Repeat evaluation after three months showed that OAE’s were absent in 11 cases out of 26 (42%) i.e. five patients who had OAEs present at initial evaluation converted to OAE absent. Deltenre et al. [10] and Rance et al. [11] also reported similar findings as in our study, some patients with ANSD may lose their OAE over the period of time but there was no associated change in pure tone thresholds. They also reported that some patients with ANSD do not have OAE’s but rather, evidence of hair cell function was evident from cochlear microphonics. The patients who lose OAE’s but maintain cochlear micro phonics do not appear to differ from those who maintain their OAE’s in terms of degree of pure tone hearing loss or speech perception abilities [10,11]. Rance et al. has also found that OAEs may not be adequate to identify all the cases of ANSD. Almost 50% of the subjects in his study had no OAEs but had CM response [11]. Despite the fact that CM potentials and OAEs appear to have a common generator, there are number of circumstances/situation cited in the literature in which an ear might show a microphonic
Fig. 1. Showing the cochlear microphonics. Uppermost recoding is with stimulus tube clamped. Middle recording is with condensation and lowermost recording is with rarefraction polarity.
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and yet have no OAE. Firstly, an emission may be produced by the outer hair cells but get impeded in its propagation through the middle ear system [12]. Normal tympanograms were obtained from all of our subjects, making this condition unlikely. Second condition could be that the OHCs in these children were damaged to the extent that they could produce neither the CM nor OAE responses and the observed CM were in fact IHC generated. Although it is well accepted that the CM, when recorded from extra-tympanic sites, is dominated by activity from OHCs [13], there is some suggestion that IHCs also may be able to generate a cochlear microphonics (albeit of lower amplitude). Dallos and Cheatham suggested that CM produced by inner hair cells are 19 dB less than that generated by the outer hair cells [14]. That being the case, we consider it unlikely that the CM recorded in our patients were produced by inner hair cells. Finally, it is possible that the OHCs of these had undergone sufficient insult to disrupt the active process i.e. OAEs but had not been damaged to the point where the CM was abolished. Numerous studies have found that OAEs are sensitive to even minor cochlear insults. The studies on children with sensori-neural hearing loss also suggest that CM response is more robust [11,15,16]. Moreover, Withnell [17] suggested that the production of CM is mainly dependant on the basal turn of the cochlea and it is absence do indicates abnormal OHCs function. This could be an explanation for the persistence of CM after disappearance of OAE’s.
5. Conclusion ANSD is not a rare disorder. The prevalence of ANSD is 14% in children diagnosed with severe to profound hearing loss and about 5.3% in paediatric population of our study. Absent or no waveform in click evoked BERA should be strictly followed by both condensation and rarefaction polarity to check for cochlear microphonics. Presence of cochlear microphonics with absent BERA seems to be more reliable criteria for diagnosing ANSD.
Neonatal screening should include both OAE and BERA and not just OAE as ANSD may be missed. References [1] B. Cone-Wesson, Auditory neuropathy evaluation and habilitation of a hearing disability, Infant. Young 17 (1) (2004) 69–81. [2] J. Walton, W.P.R. Gibson, H. Sanli, K. Prelog, Predicting cochlear implant outcomes in children with auditory neuropathy, Otol. Neurol. 29 (2008) 302–309. [3] C.M. John, D.M. Anne, S. Christopher, A. Ruth Roger, T.H. George, Cochlear implantation in patients with auditory neuropathy of varied etiologies, Laryngoscope 113 (1) (2003) 45–49. [4] A. Starr, Y.S. Sininger, H. Pratt, The varieties of auditory neuropathy, J. Basic Clin. Physiol. Pharmacol. 11 (2000) 215–230. [5] J.C. Mason, A. De Michele, C. Stevens, et al., Cochlear implantation in patients with auditory neuropathy of varied etiologies, Laryngoscope 113 (2003) 45–49. [6] Isabelle Rapin, Judith Gravel, Auditory neuropathy: physiologic and pathologic evidence calls for more diagnostic specificity, Int. J. Paediatr. Otolaryngol. 67 (7) (2003) 707–728. [7] Goodman, Reference zero levels for pure-tone audiometers, ASHA 7 (1965) 262–263. [8] Joint Committee on Infant Hearing. Year 2007 Position Statement: Principles and Guidelines for Early Hearing Detection and Intervention Programs. [9] Y.S. Sininger, S. Oba, Patients with auditory neuropathy: who are they and what they hear? in: Y. Sininger, A. Starr (Eds.), Auditory Neuropathy: A New Perspective on Hearing Disorders, Singular Thompson Learning, San Diego, 2001, pp. 15–36. [10] P. Deltenre, A.L. Mansbach, C. Bozet, F. Christiaens, P. Barthelmy, D. Paulissen, et al., Auditory neuropathy with preserved cochlear microphonics and secondary loss of otoacoustic emissions, Audiology 38 (1999) 187–195. [11] G. Rance, D.E. Beer, B. Cone-Wesson, R.K. Shepherd, R.C. Dowell, A.M. King, et al., Clinical findings for a group of infants and young children with auditory neuropathy, Ear Hear. 20 (1999) 238–252. [12] B.L. Lonsbury Martin, M.L. Whitehead, G.K. Martin, Clinical application of otoacoustic emissions, J. Speech Hear. Res. 34 (1991) 964–981. [13] S.J. Norton, R. Ferguson, K. Mascher, Evoked otoacoustic emissions and extratympanic cochlear microphonics recorded from human ears, in: Abstract of the Twelfth Midwinter Research Meeting of the Association for Research in Otolaryngology, 1989, p. 227 (A). [14] P. Dallos, M.A. Cheatham, Production of cochlear potentials by inner and outer hair cells, J. Acoust. Soc. Am. 60 (1976) 510–512. [15] D.A. Nelson, Kimberley, Distortion product emissions and auditory sensitivity in human ears with normal hearing and cochlear loss, J. Speech Hear. Res. 35 (1992) 1142–1159. [16] F.P. Harris, Distortion product otoacoustic emissions in humans with high frequency hearing loss, J. Speech Hear. Res. 33 (1990) 594–600. [17] R.H. Withnell, Brief report: the cochlear microphonic as an indication of outer hair cell function, Ear Hear. 22 (1) (2001) 75–77.
Contents lists available at SciVerse ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Auditory neuropathy spectrum disorder: Its prevalence and audiological characteristics in an Indian tertiary care hospital Ruchika Mittal a,*, A.V. Ramesh a,1, S.S. Panwar b,2, Ajith Nilkanthan a,3, Satish Nair a,4, Poonam Raj Mehra a,5 a b
Army Hospital (R&R), Delhi Cantt 110010, India Command Hospital (SC), Poona 411040, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 April 2012 Received in revised form 14 June 2012 Accepted 16 June 2012 Available online 12 July 2012
Objective: Auditory neuropathy spectrum disorder (ANSD) has become a well accepted clinical entity. ANSD has now become easy to recognize with advent of test battery approach for hearing loss evaluation. However, little is known about its epidemiology and aetiology, especially its prevalence and incidence in India. This study was conducted to determine the prevalence and audiological characteristics of ANSD in our tertiary care hospital at New Delhi, India. Methods: We prospectively enrolled all the paediatric cases i.e. less than 12 years of age referred to our outpatient department for hearing evaluation. All the cases were evaluated using complete audiological test battery consisting of pure tone audiometry (PTA), impedance audiometry, acoustic reflexes, otoacoustic emissions (OAE), and brain stem evoked response audiometry (BERA). The instrument used was GSI Audera. BERA with both condensation and rarefaction polarity was performed in cases with absent wave V even at highest intensity levels. The criteria used for diagnosis of ANSD was normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). A repeat test battery was performed after 3 months on the diagnosed cases of auditory neuropathy. Based on their behavioural findings the appropriate management programme was formulated. Results: A total of 487 paediatric cases were referred for hearing evaluation. 183 (37.6%) cases showed absent BERA and 26(5.3%) cases fulfilled the diagnostic criteria for ANSD. Repeat examination after 3 months revealed presence of OAE’s in 57.6% (15/26) cases while cochlear microphonics were present in all the 26 cases. Conclusion: The prevalence of ANSD in our study is 5.3% and in children diagnosed with severe to profound hearing loss is 14%. Presence of cochlear microphonics with absent BERA seems to be reliable criteria for diagnosing ANSD. ß 2012 Elsevier Ireland Ltd. All rights reserved.
Keywords: Auditory neuropathy spectrum disorder (ANSD) Cochlear microphonics Otoacoustic emissions (OAE) Brainstem evoked response audiometry
1. Introduction Hearing loss in infancy or early childhood has been recognized as a potentially disabling condition. It leads to
* Corresponding author at: M-37C Rajouri Garden, New Delhi 110027, India. Tel.: +91 9810961266. E-mail addresses: [email protected] (R. Mittal), [email protected] (A.V. Ramesh), [email protected] (S.S. Panwar), [email protected] (A. Nilkanthan), [email protected] (S. Nair), [email protected] (P.R. Mehra). 1 Tel.: +91 9910044184. 2 Tel.: +91 9764761044. 3 Tel.: +91 8527229938. 4 Tel.: +91 9312614114. 5 Tel.: +91 9958414385. 0165-5876/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2012.06.005
serious deleterious effects on speech and language development. If a spoken or sign language is not introduced early in life, cognitive, emotional and social development are delayed. Thus early detection and early intervention for congenital or acquired hearing loss in infancy has been an overriding goal of paediatric audiology [1]. Due to efficient hearing screening programmes, an entity known as auditory neuropathy spectrum disorder (ANSD) has been recognized. Auditory neuropathy is a pattern of hearing loss characterized by preservation of outer hair cell function despite absent brainstem auditory evoked responses. Intact outer hair cell function is demonstrated by the presence of otoacoustic emissions (OAEs) and/or measurable cochlear microphonics (CM) whereas no synchronous neural activity is seen on acoustically evoked auditory evoked brainstem response testing [2]. The prevalence
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of the disorder has been estimated to range from 0.5% to 15% of all patients evaluated with hearing loss [3]. The site of the lesion of ANSD is still unknown. Proposed sites include selected outer hair cells, inner hair cells, the synapse between hair cells and the auditory nerve, neural dendrite or axon, myelin sheath or spiral ganglion fibers [4,5]. The otoacoustic emissions (OAEs) change from pass to refer over a period of time. This creates a precarious situation for both the audiologist and neuro-otologist. Isabelle Rapin also pointed out the confusion in the audiological literature regarding physiological and behavioural test results in patients with auditory neuropathy [6]. The present study was conducted in a tertiary care hospital in New Delhi, India to study the prevalence and audiological characteristics of paediatric cases with ANSD.
2. Materials and methods We prospectively enrolled all the pediatric cases i.e. less than 12 years of age referred to our tertiary care hospital’s outpatient department of ENT for hearing evaluation from March 2008 to December 2010. All the cases were evaluated using complete audiological test battery consisting of pure tone audiometry (PTA), impedance audiometry, acoustic reflexes, distortion product otoacoustic emissions (DPOAE’s), click evoked brain stem evoked response audiometry (BERA). All the audiological testing was performed in sound treated room and the uncooperative or young children were sedated with appropriate dosage of Syrup Triclofos oral solution BP (0.5 ml/kg) prior to objective testing. BERA with both condensation and rarefaction polarity was performed in cases where wave V was absent at highest intensity levels. All the cases diagnosed with hearing loss were also referred for high resolution CT scan, paediatric neurologist evaluation and child psychologist assessment and opinion. The criteria used for diagnosis of ANSD was normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). A repeat test battery was performed after 3 months on the cases diagnosed as auditory neuropathy. Based on the findings, appropriate management programme was formulated.
2.2.1. Impedance audiometry and acoustic reflex testing Age appropriate size probe was placed in the child’s ear canal. The sound at 220 Hz was presented with air pressure changing from +200 daPa (Pascal) to 400 daPa. Acoustic reflex was checked at 500, 1000, 2000 and 4000 Hz and between 70 and 100 dB. Both ipsilateral and contra lateral reflexes were observed. The instrument used was Grason Stadler Tympstar Version 2. 2.2.2. Click evoked brainstem evoked response audiometry (BERA) The electrodes were placed at mastoid of both the ears (noninverting), lower (inverting) and upper (common ground) forehead and the instrument used was GSI Audera version 2.6.7. The click stimulus was presented at alternate polarity with insert earphones ER3A at 70 dB. If wave V was not traced, the intensity was increased in 10 dB steps till the highest intensity of the instrument. Otherwise, lowest intensity was traced at which wave V could be recorded. Two waveforms were traced at each intensity level to check the reproducibility of the waveforms. The lowest level at which wave V was recorded was marked as threshold of the child. BERA with both condensation and rarefaction polarity was carried out in all the cases with absent wave V at highest intensity levels to check for cochlear microphonics (CM). The CM was considered to be present if the response waveform showed a 1808 phase shift with the change in stimulus polarity from rarefaction to condensation. The authenticity of the CM response was confirmed through test runs in which the stimulus tube was clamped to prevent the acoustic signal from reaching the ear canal. Under these circumstances, genuine cochlear potentials were abolished while the stimulus artifact remained unaltered. 2.2.3. Definitions used
1. Criteria used to diagnose auditory neuropathy spectrum disorder (ANSD): normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/ or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). 2. Classification of hearing loss on pure tone/play audiometry: Goodman [7] recommended classification was used for classification of hearing loss.
2.1. Pure tone/play audiometry (PTA) 3. Results The child was instructed to put the block (toy) down or raise the finger whenever he or she hears the sound (whichever was applicable as per the age of the child). The audiometry was done at each octave between 500 Hz and 4000 Hz for air conduction and for bone conduction testing. The tone was first presented at 2000 Hz and at 50–60 dB. Three or four trials were done before starting the test procedure. If the child hears the sound, the intensity was lowered by 10–15 dB steps. The lowest level at which the child responds 50% of the time was marked as threshold of the patient. The instrument used was Hortmann Neuro-otometric Audiomaster CA 540/2 calibrated as per American National Standards Institute S.6 2004.
A total of 487 paediatric cases from 6 months to 12 years of age were referred for hearing evaluation. 183 (37.6%) cases showed absent BERA and 26 (5.3%) cases fulfilled the diagnostic criteria for ANSD. The children diagnosed with ANSD were in the age range of 3–5 years. The mean age of patients who fulfilled the diagnostic criteria for auditory neuropathy spectrum disorder was 4.17 1.4 years. There were five males to twenty one females. All were bilateral cases of ANSD. Of the 26 children diagnosed to have ANSD, 73% (n = 19) were found to have a history of neonatal hyperbilirubinemia. 7.6% (n = 2) had birth asphyxia. No specific perinatal cause was found in 19.4% (n = 5). None of the patient was given hearing aid after initial evaluation.
2.2. Distortion product otoacoustic emissions (DPOAEs) 3.1. Pure tone/play audiometry (PTA) (Table 1) A probe according to the size of the ear canal was placed in child’s ear and DPOAE’s were recorded with settings F2/F1 = 1.2, frequency range 597–7277 Hz, intensity of F2 = 65 dB and F1 = 55 dB, noise rejection = 40. DPOAE’s were considered pass if signal to noise ratio was above 3 dB at three consecutive frequencies. The instrument used was GSI Audera version 2.6.7.
3.1.1. Impedance audiometry and acoustic reflex testing All the children diagnosed with ANSD showed Type A tympanogram which reveals normal middle ear function and absent acoustic reflexes bilaterally at both initial and after 3 month follow up testing ().
R. Mittal et al. / International Journal of Pediatric Otorhinolaryngology 76 (2012) 1351–1354
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Table 1 Showing the results of play/pure tone audiometry, pure tone/play audiometry (PTA). Degree of hearing lossa
Initial evaluation (n = 183b)
ANSD children (n = 26)
ANSD children (after 3 months) (n = 26)
Mild Moderate Moderately severe Severe Profound
1 12 11 119 5
1 12 11 2 0
1 12 11 2 0
a b
(0.55%) (6.55%) (6.01%) (65.02%) (2.73%)
(3.84%) (46.15%) (42.3%) (7.69%)
(3.84%) (46.15%) (42.3%) (7.69%)
Sensori-neural hearing loss in all the cases. During initial evaluation PTA could not be performed on 35 uncooperative children.
Table 2 Showing the results of otoacoustic emissions. OAE’s
Initial evaluation (n = 183)
ANSD children (n = 26)
ANSD children (after 3 months) (n = 26)
Absent Present
163 (89.07%) 20 (10.93%)
6 (23.07%) 20 (76.93%)
11 (42.31%) 15 (57.69%)
3.2. Distortion product otoacoustic emissions (DPOAE’s) At initial visit, OAEs were present in 20 out of 26 cases, which were diagnosed as ANSD. After three months OAE’s were present in only 15 cases. OAE’s became absent in 5 subjects after 3 months (Table 2). 3.2.1. Click evoked brain stem evoked response audiometry (BERA) Of 487 cases that were referred for hearing evaluation, 183 cases showed absent BERA. 26 children showed presence of cochlear microphonics with rarefaction and condensation polarity. CM was recordable in all the 26 cases after 3 months of initial evaluation also. A sample waveform to depict CM is shown in Fig. 1. 4. Discussion The prevalence of ANSD in our study is found to be 14% in children diagnosed with severe to profound hearing loss. Walton et al. [2] also reported prevalence of 10–14% in children diagnosed with severe to profound sensori-neural hearing loss. The prevalence of ANSD calculated in our study is 5.3% of all patients referred/evaluated for hearing loss. Similar prevalence in the range of 0.5–15% had been reported in the literature of all the patients evaluated with hearing loss [5]. In our study, the mean age of ANSD was 4.17 5.4 years. ANSD is a relatively newly described and poorly understood disorder. There is much to be learned, including incidence, prevalence, natural course, and a clearer definition of treatment
options. In the year 2007 Position Statement, the Joint Committee on Infant Hearing has recommended population based studies to determine prevalence and natural history of ANSD [8]. All the cases diagnosed in our study showed bilateral involvement of ANSD. Sininger and Oba also reported that ANSD is usually bilaterally [9]. During initial evaluation OAE’s were absent in six cases out of twenty six (23%) cases who were diagnosed with ANSD. Cochlear microphonics with abnormal BERA was the criteria for diagnosis of ANSD and hence was present in all cases at initial evaluation. Cochlear microphonics persisted at re evaluation after three months. Repeat evaluation after three months showed that OAE’s were absent in 11 cases out of 26 (42%) i.e. five patients who had OAEs present at initial evaluation converted to OAE absent. Deltenre et al. [10] and Rance et al. [11] also reported similar findings as in our study, some patients with ANSD may lose their OAE over the period of time but there was no associated change in pure tone thresholds. They also reported that some patients with ANSD do not have OAE’s but rather, evidence of hair cell function was evident from cochlear microphonics. The patients who lose OAE’s but maintain cochlear micro phonics do not appear to differ from those who maintain their OAE’s in terms of degree of pure tone hearing loss or speech perception abilities [10,11]. Rance et al. has also found that OAEs may not be adequate to identify all the cases of ANSD. Almost 50% of the subjects in his study had no OAEs but had CM response [11]. Despite the fact that CM potentials and OAEs appear to have a common generator, there are number of circumstances/situation cited in the literature in which an ear might show a microphonic
Fig. 1. Showing the cochlear microphonics. Uppermost recoding is with stimulus tube clamped. Middle recording is with condensation and lowermost recording is with rarefraction polarity.
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and yet have no OAE. Firstly, an emission may be produced by the outer hair cells but get impeded in its propagation through the middle ear system [12]. Normal tympanograms were obtained from all of our subjects, making this condition unlikely. Second condition could be that the OHCs in these children were damaged to the extent that they could produce neither the CM nor OAE responses and the observed CM were in fact IHC generated. Although it is well accepted that the CM, when recorded from extra-tympanic sites, is dominated by activity from OHCs [13], there is some suggestion that IHCs also may be able to generate a cochlear microphonics (albeit of lower amplitude). Dallos and Cheatham suggested that CM produced by inner hair cells are 19 dB less than that generated by the outer hair cells [14]. That being the case, we consider it unlikely that the CM recorded in our patients were produced by inner hair cells. Finally, it is possible that the OHCs of these had undergone sufficient insult to disrupt the active process i.e. OAEs but had not been damaged to the point where the CM was abolished. Numerous studies have found that OAEs are sensitive to even minor cochlear insults. The studies on children with sensori-neural hearing loss also suggest that CM response is more robust [11,15,16]. Moreover, Withnell [17] suggested that the production of CM is mainly dependant on the basal turn of the cochlea and it is absence do indicates abnormal OHCs function. This could be an explanation for the persistence of CM after disappearance of OAE’s.
5. Conclusion ANSD is not a rare disorder. The prevalence of ANSD is 14% in children diagnosed with severe to profound hearing loss and about 5.3% in paediatric population of our study. Absent or no waveform in click evoked BERA should be strictly followed by both condensation and rarefaction polarity to check for cochlear microphonics. Presence of cochlear microphonics with absent BERA seems to be more reliable criteria for diagnosing ANSD.
Neonatal screening should include both OAE and BERA and not just OAE as ANSD may be missed. References [1] B. Cone-Wesson, Auditory neuropathy evaluation and habilitation of a hearing disability, Infant. Young 17 (1) (2004) 69–81. [2] J. Walton, W.P.R. Gibson, H. Sanli, K. Prelog, Predicting cochlear implant outcomes in children with auditory neuropathy, Otol. Neurol. 29 (2008) 302–309. [3] C.M. John, D.M. Anne, S. Christopher, A. Ruth Roger, T.H. George, Cochlear implantation in patients with auditory neuropathy of varied etiologies, Laryngoscope 113 (1) (2003) 45–49. [4] A. Starr, Y.S. Sininger, H. Pratt, The varieties of auditory neuropathy, J. Basic Clin. Physiol. Pharmacol. 11 (2000) 215–230. [5] J.C. Mason, A. De Michele, C. Stevens, et al., Cochlear implantation in patients with auditory neuropathy of varied etiologies, Laryngoscope 113 (2003) 45–49. [6] Isabelle Rapin, Judith Gravel, Auditory neuropathy: physiologic and pathologic evidence calls for more diagnostic specificity, Int. J. Paediatr. Otolaryngol. 67 (7) (2003) 707–728. [7] Goodman, Reference zero levels for pure-tone audiometers, ASHA 7 (1965) 262–263. [8] Joint Committee on Infant Hearing. Year 2007 Position Statement: Principles and Guidelines for Early Hearing Detection and Intervention Programs. [9] Y.S. Sininger, S. Oba, Patients with auditory neuropathy: who are they and what they hear? in: Y. Sininger, A. Starr (Eds.), Auditory Neuropathy: A New Perspective on Hearing Disorders, Singular Thompson Learning, San Diego, 2001, pp. 15–36. [10] P. Deltenre, A.L. Mansbach, C. Bozet, F. Christiaens, P. Barthelmy, D. Paulissen, et al., Auditory neuropathy with preserved cochlear microphonics and secondary loss of otoacoustic emissions, Audiology 38 (1999) 187–195. [11] G. Rance, D.E. Beer, B. Cone-Wesson, R.K. Shepherd, R.C. Dowell, A.M. King, et al., Clinical findings for a group of infants and young children with auditory neuropathy, Ear Hear. 20 (1999) 238–252. [12] B.L. Lonsbury Martin, M.L. Whitehead, G.K. Martin, Clinical application of otoacoustic emissions, J. Speech Hear. Res. 34 (1991) 964–981. [13] S.J. Norton, R. Ferguson, K. Mascher, Evoked otoacoustic emissions and extratympanic cochlear microphonics recorded from human ears, in: Abstract of the Twelfth Midwinter Research Meeting of the Association for Research in Otolaryngology, 1989, p. 227 (A). [14] P. Dallos, M.A. Cheatham, Production of cochlear potentials by inner and outer hair cells, J. Acoust. Soc. Am. 60 (1976) 510–512. [15] D.A. Nelson, Kimberley, Distortion product emissions and auditory sensitivity in human ears with normal hearing and cochlear loss, J. Speech Hear. Res. 35 (1992) 1142–1159. [16] F.P. Harris, Distortion product otoacoustic emissions in humans with high frequency hearing loss, J. Speech Hear. Res. 33 (1990) 594–600. [17] R.H. Withnell, Brief report: the cochlear microphonic as an indication of outer hair cell function, Ear Hear. 22 (1) (2001) 75–77.