Auditory Neuropathy with Preserved Cochlear ...

Original Article Audiology 1999; 38:187-195

P. Deltenre * A. L. Alansbach C Bozett F. Christiaens * P. Barthelemyt D. Pau/issen t T. Renglett

*

*Université Libre de Bruxelles, Brugmann & Huderf Campus, Brussels, Belgium tCentre Comprendre et Parler, Brussels,Belgium '

KeyWords Auditory neuropathy Auditory brainstem responses Cochlear microphonic potential Hearing loss Physiopathology Otoacoustic emissions

Auditory Neuropathy

with Preserved

Cochlear Microphonics and Secondary Loss of Otoacoustic Emissions

Abstract Auditory neuropathy is defined as absent or severely distorted auditory brainstem responses with preserved otoacoustic emissions and cochlear microphonics. This entity can be found in various circumstances induding pre-lingual children. An almost universal characteristic reported from adult patients is the ineffectiveness of tradition al hearing aids. Adequate management of pre-lingual cases therefore remains an open problem. This paper describes two pre-lingual children who se follow-up data demonstrated a selective loss of the otoacoustic emissions, whereas the cochlear microphonics remained preserved. ln one of the patients, hearing aid fitting as soon as she lost her otoacoustic emissions proved successful. These findings have important implications for the operational definition of the condition, since one must be prepared to encounter cases with absent otoacoustic emissions. The present data also demonstrate that conventional amplification can benefit pre-lingual auditory neuropathy cases, at least once they have lost their otoacoustic emissions.

Introduction Auditory neuropathy is a diagnostic label recently coined by Stan et aI.l It is operationally defined 1 by absent or severely distorted auditory brainstem responses (ABRs) beginning at wave 1 in the presence of preserved otoacoustic emisiions (OAEs). This peculiar combination of preserved mechanical OAE outer hair cells (OHC) response contrasting with absent neural potentials induding ABR wave 1, suggests the presence of a defect impinging upon the functional complex formed by the inner hair cells, the primary afferents (spiral ganglion neurones) and the first order synapse between hair cells and the cochlear nerve.2 A physiopathological mode! postulating a defect in the temporal synchrony of the first afferent discharges has been proposed.2 One of the values of the auditory neuropathy concept is to indicate a pathophysiological process impinging at a functional level downstream to the OHC micromechanical function, Î.e. after the stage of the cochlear amplifier which is subserved by the OHC fast contractile properties.3.4 Consistèi'1t with the preserved OAEs, the cochlear microphonic (CM) which, in surface recordings, is known to be dominated by OHC electrical activity5,6 is also preserved in auditory neuropathy and often stands out as the sole electrical response evoked by the stimulus in ABR recordings.1,2.7-9 ln the most extensive series published to date, a peripheral neuropathy is found in about 80 per cent of the patients,1 hence the name of the entity. From this latter series, it appears that the typical patient with auditory neuropathy presents as a child or Received: October 13, 1998 Accepted: November 18, 1998

young adult with mild or moderate hearing loss accompanied by disproportionate difficulties in speech understanding. The past medical history is unremarkable, and the appearance of peripheral neuropathy lags several years behind the audit ory complaints and findings. Complementing the original publications in recognizing and defining the entity,I,2 several independent reports widen the spectrum of the circumstances in which the physiological pattern operationally defining an auditory neuropathy can be found. It is also increasingly apparent that numerous variations can occur to the basic auditory neuropathy pattern. Katona et al.10 reported absent ABRs and preserved OAEs in a three-monthold child born prematurely with a history of hyperbilirubinaemia and exposure to aminoglycosides. Stein et al.7 reported four children diagnosed in the first few months of their lives who had in common a history of neonatal hyperbilirubinaemia. Deltenre et al. 8 also described three cases with such early onsets and stormy neonatal periods, one of them with a history of hyperbilirubinaemia and another with metabolic acidosis due to a mitochondrial enzymatic defect. Although they did not record the ABRs, Marangos and Mausolfll described two brothers with mitochondrial cytopathy and hearing loss characterized by preserved OAEs and isolated CMs without eighth nerve action potentials in electrocochleographic recordings. Norton12 reported 'eight children, in whom ABR is either absent or present only at 80 or 90 dB nHL, who have good OAEs.' At least one of the se children complied with the operation al definition of audit ory neuropathy. He had a history of prematurity, respiratory distress syndrome, hyponatraemia and P. Deltenre Hôpital Brugmann, Evoked Potentials Unit, Place Van Gehuchten 4, B-1020 Bruxelles, Belgium

hyperbilirubinaemia. Vohr et al.13 also briefly mentioned the existence of an unspecified number of neonatal cases who in retrospect satisfy the operational definition of auditory neuropathy. Konradsson14 described four healthy children with a unilateral pattern of audit ory neuropathy and a profound hearing loss on the affected side, and Welzl-Müller et al.15 described a unilateral case with total deafness of the involved ear. Laccourreye et al.16reported the case of a three-year-old girl with a bilateral pattern of audit ory neuropathy and profound hearing loss, thus confirming that the amount of loss can be quite severe in sorne patients. Kaga et alY reported two adult patients who had had the condition over 30 years. Familial cases of audit ory neuropathy have been reported by Robinette and Durrant.18 Quite recently, Starr et al.19 have reported instances of intermittent, temperature-sensitive (fever-induced) audit ory neuropathy. Berlin et apo initialIy emphasized the fact that amplification was of no benefit to their patients and explicitly advised21against providing amplification for patients with normal micromechanical responses of the cochlea. Very recently, however, the same laboratory reported cautious trials with hearing aids in sorne children with autlitory hfùropathy.9 The aim of the present paper is to report two cases whose physiological and behavioural follow-up data provide new information contributing to a better knowledge of the natural history which can be found in patients with audit ory neuropathy. The two patients initially presented with isolated OEAs and CMs, thus complying with the operational definition of audit ory neuropathy but selectively lost their OEAs in the course of their disease. Patients and Methods Case Reports Patient 1 (partially described as patient one in Deltenre et a1.8) was first seen at two months of life. She was the second born twin at an estimated post-conception al age of 28 weeks. She experienced severe respiratory distress syndrome complicated by persistent pulmonary hypertension and bronchodysplasia. At day Il, a haemolytic hyperbilirubinaemia (maximum blood level 20.8 mg/dl) followed a blood transfusion and prompted an exchange transfusion. Her neurological status was abnormal (generalized hypotonia accompanying stereotyped repetitive movements). Although she gradually improved, a mild psychomotor retardation, predominantly affecting fine motor skilIs, was still present when she was last seen at seven years of age. Two cerebral MRI scans performed at three months and one year of age were normal. Her dizygotic twin sister developed normally in all respects. Patient 2 was born at an estimated post-conceptional age of 30 weeks, weighing 1280 g. At day two, he developed a hyperbilirubinaemia which peaked at 21.5 mg/dl at day eleven. ln the meantime he developed a necrotizing erilerocolitis and had to be ventilated when he went into septic shock with metabolic acidosis. He received exchange transfusions and numerous antibiotics (ampiciIlin, gentamicin, amikacin, vancomycin, metronidazole, amphotericin B, cefazidim and cloxacillin). He was discharged three months later with a diagnosis of spastic diplegia and kernicterus. He was referred to our laboratory at 27 months of age, showing neither any language capability nor interest for communication. He was clearly aware of environmental sounds and exhibited several 188

definite autistic traits. At that time, his brain MRI revealed a periventricular leukomalacia and a cystic cavity in the right frontal lobe. The brainstem appeared normal. None of the two patients had familial histories of neurological or audiological problems. None had clinical signs of peripheral neuropathy when last seen. Audiological Assessment

Middle Ear Function Behavioural and physiological data from the two patients were gathered after normal middle ear status had been ascertained by otomicroscopic and tympanometric examinations. Because middle ear pressure imbalance is known to affect OAE amplitude adversely,22the definition of normal middle ear function was based on stricter th an usual tympanometric criteria and required a well-defined peak of compliance (at least 0.3 ml of equivalent volume) within ± 100 daPa of the atmospheric pressure.

Behavioural Thresholds and Language Assessment Each child was repeatedly assessed by a te am of child audiologists using Suzuki's Conditioned Orientation Reflex Audiometry,23 conditioned play audiometry or standard audiometric procedures, selecting for each child the most appropriate method for their age and capability in order to provide reliable data. Speech identification performance was measured twice for patient 1. When she was six years old, biand tri-syllabic words and phonemes produced by a human female speaker were delivered from zero azimuth at 3 metres from the patient. No lip-reading cues were available to the subject. Identification scores were obtained by defining the percentage of items which the patient correctly repeated. Three conditions were tested: low (55 dB) level without hearing aid, the same level with her binaural hearing aids and high (70 dB) level without hearing aid. When she was seven years old, bisylIabic word identification scores were compared between four conditions: binaurally without hearing aid, monaurally (right and left ears separately) with hearing aid and binaurally with both hearing aids. A male speaker produced the words with a normal voice level at 3 metres in front of the patient. No lipreading was available to the subject. At five and seven years, her comprehension of spoken language was assessed by the Khomsi test. 24,25The Khomsi test is designed for French-speaking subjects, on the same principles as the Northwestern Syntax Screening Test.26.27It assesses spoken language comprehension by requesting the subject to select which picture among the four presented best illustrates a situation that has been described oraIly. It has been calibrated for the French-speaking Belgian population and scores performances in terms of equivalent ages in the normal population. Sedation AlI evoked potential recordings were performed under sedation. The sedation regime consisted of rectal pentobarbital and oral promazine: Patients were monitored for apnoeas using continuous intranasal capnography (Datex Normocap). ABR Recordings and Analysis AlI recordings were performed in an electromagnetically and acousticalIy shielded booth, using a Nicolet Pathfinder. Further technical details about otherwise standard ABR recording Audiology,

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conditions can be found ici a previous report from our laboratory.28 It must be emphasized that our standard recording protocol uses clicks of single polarities (rarefaction and condensation separately) and that alternating polarities are not used. This strategy ensures that polarity-sensitive evoked components, of which the CM is a typical example, are not cancelled OUt.8•9For the patients reported here, ABRs were also obtained using the Nicolet Tubal Insert Phone which introduces an acoustic delay of 0.9 ms between the stimulus electrical pulse and the actual sound delivery at the entrance of the ear canal, as a means of temporally separating the electromagnetic artefact from cochlear potentials. ln order to ensure discrimination between genuine auditory neurophysiological rêsponses and artifactual signais, two control recording conditions were systematically applied. First, the click was applied at high intensity, with the sound delivery tube occluded by clamping in order to prevent the acoustic stimulus from reaching the ear canal with all other stimulating and recording conditions unchanged. Occlusion of the tube attenuated the stimulus by 80 dB as measured by a sound level meter (Larson-Davis 800B operated in,the peak and ho Id mode) in a 2 cc coupler. Secondly, distinctioh between neural and presynaptic potentials was established by 100king for an adaptation effect when the stimulation rate was raised from a standard 21.7 Hz to 99.9 Hz. Patient l's CM frequency content was computed and displayed as an amplitude spectrum (frequency resolution:8 Hz) by the Nicolet SPECTM Fortran routine which is part of the Pathfinder software package. Otoacoustic Emissions Click evoked OAEs were recorded according to the method described by Bray and Kemp,29 using an IL088 system for stimulation, emission recording, averaging, reproducibility assessment and spectral analysis. The clicks (80 ilS duration) were delivered in the non-linear mode at an intensity of 81 dB SPL±4 dB. An emission was considered to be present if the test-retest reproducibility ('whole repro' parameter on the IL088 system) was better than 50 per cent, and if the comparison between the spectra of the averaged signal and of the residual noise demonstrated a signal to noise ratio of over 3 dB in at least three frequency bands. Results Initial Findings Patients 1 and 2 both complied with the operational definition of auditory neuropathy when first seen: their ABRs did not con tain any neural component and were limited to CMs showing complete phase reversai between rarefaction and condensation clicks. The pre-synaptic nature of these''Potentials was demonstrated by the absence of any adaptation when the click rate was raised to 99.9 Hz and their dependence on the acoustical stimulation was proven by their disappeltrance when the sound delivering tube was occluded (see Deltenre et al.8 for an illustration of these control measurements). Figures la and 2a illustrate the respective ABR recordings obtained from patients 1 and 2 when the y were three and two years of age respectively. Addition of the waveforms evoked by rare faction and condensation clicks resulted in an incomplete cancellation of the CM yielding an early potential which is much more conspicuous for patient 1 than for patient 2. This early potential could be a surface-recorded summating potential (SP), but its Auditory Neuropathy with Preserved Cochlear Microphonics and Secondary Loss of Otoacoustic Emissions

exact nature has not yet been proven19 (see discussion). Figures 1band 2b illustrate their concomitant respective OAEs. Patient 2's OAEs were characterized by incomplete spectra (significant emissions above 2 kHz only). One year earlier his click evoked OAEs had been described as normal in another hospital; the tracings were unfortunately not available to us. This physiological pattern defining auditory neuropathy was found in both ears in each patient. Figures lc and 2c illustrate their behavioural thresholds to pure tones at the time of the physiological recordings. Follow-up Data Patient 1 was physiologically and behaviourally assessed once a year. Because of her preserved OAEs, amplification was withheld despite a growing concern that she was suffering because of her elevated thresholds since her language was not developing. The dilemma about the indication versus contraindication of amplification was rendered even more acute by the fact that she was still very young and probably within the critical or age-sensitive period of plasticity during which optimal exposure to language sounds is required for normal language development.3o When she was four years old, although her CMs were still definitely present (Figure 3a), her OEAs were found to be absent from both ears (Figure 3b) whereas her middle ear function was normal. Her OAEs were tested on three separate occasions at weekly intervals, once under sedation immediately before ABR recording and twice while she was awake and quiet. From the age of two onwards, her medical history had been unremarkable and no reason for the loss of her OAEs could be identified. Since she lost her OAEs when aged four, they were tested at least twice each summer. They were never again recorded. Although her CM threshold and amplitude did not change before and after the loss of her OAEs, the waveforms appeared somewhat different. Figure 4 illustrates, in the temporal and frequency domains, the fluctuation of the CM at three stimulus levels and at three recording times, when she was aged three, four and six years. She still exhibited normal OAEs when the first recording was performed but had lost them at the time of the last two. Although the response morphology c1early varies between the three recording dates, no c1ear-cut evolution can be seen before and after the time she lost her OAEs, the first and last recordings being more similar to each other than to the second. When she was aged four years, and had lost her OAEs we decided to fit her with hearing aids. A binaural gain of 25 dB (left) and 20 dB (right) at 1 kHz was provided with the maximal compression available from the device in order to limit the output to 99 dB SPL for frequencies between 250 and 2000 Hz. The absolute maximal output was 107 dB SPL at 2400 Hz. Maximal output reached 99 dB SPL at 3000 Hz and dropped sharply at higher frequencies. Amplification was linear for output levels up to 95 dB SPL. Figure 3c illustrates her unaided and aided thresholds. Her language subsequently started to develop rapidly. Since then, she has given clear evidence that she benefits from her hearing aid. Now âged seven, she wears it all day long and spontaneously asks for replacement batteries when they become weak. She now lives abroad where she is exposed to French (mother and school language), English and Italian. The advantage she draws from the amplification provided by her hearing aid was demonstrable for the first time when she was six years old by comparing her word and phonemes identification Deltenre/Mans bach/Bozet/Christiaensl Barthelemy IPa ulissen/Renglet

189

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Figure 1. Data from the left ear of patient 1 when she was aged three years. (a) The ABRs evoked by single polarity clicks are restricted to an early oscillation which exhibits phase reversai with click polarity. This microphonic activity is enhanced by subtraction of the condensation from the rarefaction response and incompletely cancelled by addition. The residual waveform seen in R +C traces may correspond to a surface-recorded SP. Note the absence of latency reduction when stimulus intensity increases, as shown by the vertical dotted line drawn through the major peak of the waveforms. ln this and subsequent diagrams the black triangle at the bottom of the traces indicates the time of actual stimulus delivery at the entrance of the external ear canal due to the use of an acoustical delay. (h) Preserved click evoked otoacoustic emissions with a fairly wide frequency spectrum (the black spectrum is computed from the residual noise of the measurement, the white spectrum describes the energy distribution of the emission). (c) The free field audiogram.

scores at high (70 dB) and low (55 dB) levels, the latter condition being tested with and without hearing aids (see Table 1). The benefit she derives from her hearing aids was demonstrated on a second occasion when last seen in the summer of 1998. Her word recognition scores were again measured with and without hearing aids, this time adding a comparison between her aided monaural and binaural performances (see Table 2). When she was five, i.e. after one year of daily hearing aid use, she totally failed the Khomsi test24,25 giving no score. When last seen at seven, her spoken language comprehenslon was judged to correspond to that of a five-year-old child on the same test. She talked spontaneously and freely fluent French and English marred by variable dysarthric errors which are attribut able to her residual motor impairment. She presently attends kindergarten and has been judged ready to enter primary school this autumn. She will be seven years and three months old at that time. Patient 2 was seen for the second time when he was aged seven years. Although his CMs were still remarkably preserved

(Figure 5a), his OAEs had completely disappeared from both ears (Figure 5b) despite normal middle ear function. His OAEs could be tested only once as his abnormal behaviour prec1uded any reliable recording without sedation. As with patient 1, no known cause for his loss of OAEs could be found in his medical history. His free field audiogram appeared similar to what it was four years earlier. His neurological deficits and autistic behaviour prevented further behavioural testing and disco uraged amplification, although he also demonstrated the anticipated level of threshold enhancement in hearing aid trials.

190

Audiology,

Discussion The two auditory neuropathy patients reported here appear to be in marked contrast with the data from the older children described by Starr et aU and Kaga et al.,17 who ail retained their OAEs even after many years of follow-up. Robinette and Durrant18 reported a case of congenital bilateral sensorineural hearing loss whose OAEs disappeared in one ear and were greatly reduced in the other over several years of follow-up. Volume 38 Number

4

(a) dB nHL

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Figure 2. Data from the right ear of patient 2 when he was two years old. (a) The ABRs are also restricted' to an isolated microphonic response. Note the absence of acoustical delay due to the use of a supra-aurai TDH-49 transducer for this recording. Aiso note that the R +C residual waveform is much smaller than for patient 1. (h) Partially preserved click-evoked otoacoustic emissions with signal:noise ratios above 3 dB (respectively 4, 12 and 9) in the three upper frequency bands (3, 4 and 5 kHz). (c) The free field audiogram.

Since amplification had been provided for this subject before his OAEs started to regress, there remains the theoretical possibility that acoustical overstimulation of the normal OHCs contributed to the OAE deterioration. ln a recent report, Berlin et aJ.9 described five children, among whom one lost his OAEs over time. They attributed this loss to either middle ear problems, mentioning an abnormal tympanogram without further details, or to sorne yet unknown retro grade degenerative process. It therefore appears that the present results are similar to a few other independent observations which indicate that sorne patients with audit ory neuropathy lose their OAEs but retain their CMs over the course of their development. This suggests that dysfunction of the cochlear amplifier3 adds to the initial synchronization deficit in these patients. This finding has a major implication for the diagnosis of auditory neuropathy. Since sorne cases may evolve to lose their OAI;:s, it seems appropriate to recommend the latest formulation of the operational definition of auditory neuropathy by Starr et al.,19 i.e. absent or abnormal ABRs beginning at wave 1 in the presence of preserved OAEs and/or CMs. Although the preservation of OAEs in the absence of ABRs is highly diagnostic of the condition, one must be prepared to encounter cases with preserved CMs only.31 ln children who are prone to middle ear dysfunction, this will probably be a frequent presentation, as suggested by the data of

Stein et aJ.7,32These authors reported following up five infants with an initial pattern of auditory neuropathy inc1uding OAEs. During the follow-up, OAEs could not be properly assessed in three of them due to middle ear/upper respiratory tract problems, although their ABRs continued to be characterized by isolated CMs. ln pre-lingual children too young to provide reliable audiometric data, demonstration of a paradoxical preservation of the CM can therefore constitute the sole remaining cue to the correct diagnosis of auditory neuropathy when OAEs have already disappeared or cannot be assessed because of middle ear problems. This implies a very careful recording methodology. On one hand, the CM is easily overlooked when alternating polarity clicks are used, and it may be confused with ABR early waves when only rarefaction or condensation clicks are used. On the other hand, since its waveform reproduces that of the stimulus, it must be distinguished from an artefact. U sing an acoustical delay, running adaptation studies and occluding the sound delivery tube by clamping are mandatory control measurements which should be systematically performed. The appropriate therapeutic approach is clearly an open question in auditory neuropathy. On one hand, the published data from the older, mostly post-lingual cases, suggest that amplification is of no benefit1,2.21 and there is a real concern about causing acoustical trauma by using amplification with

Auditory Neuropathy with Preserved Cochlear Microphonics and Secondary Loss of Otoacoustic Emissions

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Figure 3. Data from the left ear of patient 1 when she was aged four years. (a) The ABRs are always restricted to a microphonic response and a putative SP. (b) Despite the preserved CM, the click evoked otoacoustic emissions have disappeared. (c) The comparison between the behavioural aided (squares) and unaided (crosses) thresholds demonstrates the gain expected from the amplification parameters.

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Figure 4. Data from the left ear of patient 1 at three click levels. Comparison of the temporal (left tracings) and frequency (right tracings) domain representations of the isolated CM over a four-year period. OEA status (presence or absence) and patient's age (in years) at the time of recording is indicated at the right of each pair of tracings. The first recording was performed when the OAEs were still normal. The two latest recordings were obtained after she had lost her OAEs. Although the overall amplitude remains stable over time, there are morphological and spectral fluctuations without any clear-cut trend over time. The spectral evolution favouring lower frequencies on the second examination is reversed two years later. 192

Audiology,

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Table 1. Word and phoneme identification scores (IS) for patient 1 when she was six years old. Three conditions are compared: low level without hearing aid, the same level with hearing aid and higher level without hearing aid. Phoneme 1S Word1S Condition 80%

96%

55 dB without hearing aid

0%

0%

70 dB without hearing aid

80%

88%

55 dB+hearing aid

Table 2. Word IS for patient 1 when she was seven years old. Four word presentation conditions are compared: binaural without hearing aid, monaural right with hearing aid, monaural left with hearing aid and binaural hearing aids. Condition

Words 1S

(a) dB nHL

100

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Figure 5. Data from the right ear of patient 2 when he was seven years old. (a) The ABRs are again restricted to an isolated microphonic response and a small putative SP. Note the use of a tubal insert phone. (b) Despite the preservation of a prominent CM, the click evoked otoacoustic emissions have completely vanished.

cochleas with normal micromechanical responses.2 This concern seems to be reinforced by the reports of absent stapedial reflexes and efferent suppression in most cases of auditory neuropathy.I,2,20These two mechanisms are supposed to protect the cochlea against potentially harmful acoustical overstimulation.33-36On the other hand, the younger, pre-lingual children are likely to be in an age-sensitive period of plasticity for language acquisition.30 Their elevated thresholds deprive them of a normal exposure to the sounds of speech at a Fime when such an exposure is critical for normal speech acquisition. The first case reported in the present paper compellingly demonstrates that a child diagnosed as auditory neU[opathy may benefit significantly from amplification. Whether pre-lingual children with auditory neuropathy, preserved OAEs and elevated thresholds should be amplified is still a matter of debate. Robinette and Durrantl8 reported a failure of amplification applied in the first year of life in a profoundly deaf child with no ABR and preserved OAEs. Katona et al.IOaided his patient with preserved OAEs within the first year of life and reported good tolerance of the hearing aid and good performance with high level stimuli in subjective hearing tests at eight months of age.

The benefit gained from amplification by our first patient may appear paradoxical since this suggests that added cochlear amplifier dysfunction improves the response of auditory neuropathy to conventional amplification. Such an apparent paradox can be solved by the hypothesis that the genuine factor underlying successful amplification is its timing with respect to the sensitive period for language development. It may be that when auditory neuropathy is acquired post-lingually, improving detection thresholds cannot compensate for the distortion of the neural code imposed by po or synchronization. On the contrary, when auditory neuropathy is already present in the first months of life, the improvement of detection thresholds provided by amplification may contribute to better language development by a more versatile brain still in the favourable phase of the sensitive period. This would mimic the dependency upon age of surgery which is seen in deaf children treated by cochlear implantation.37 Should this reasoning be true, amplification could have been successful in our first patient had it been used before the loss of her OAEs. The observation of preserved pro minent CMs in subjects who have lost their OAEs is somewhat puzzling. Whereas OAEs

Auditory Neuropathy with Preserved Cochlear Microphonics and Secondary Loss of Otoacoustic Emissions

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reflect OHC mechanical activity,38it is generally recognized that the surface recorded CM is largely dominated by OHCs,5,6 Dallos and Wang6 demonstrated experimentally that the selective destruction of OH Cs reduces the CM to less than one tenth of its normal amplitude and elevates its threshold by 30-40 dB. It therefore seems logical to expect that if the disappearance of OAEs reflected OHC loss, it would have been coupled with a measurable amplitude reduction and threshold elevation of the CM, which was not the case in the two patients reported here. One must remain cautious, however, about such a reasoning because the respective dynamic ranges of OEAs and surface-recorded CMs are quite different. Whereas the input-output function of click evoked OAEs is characterized by an initial linear relationship followed by a compressive nonlinearity starting from around 30 dB SPL and rapidly saturating at higher levels,39,40the surface-recorded CM has its threshold around 50-60 dB nHL (85-95 dB SPL for a click),9,4!so that the respective dynamic ranges from the two physiological measurements do not overlap. It is therefore uncertain whether a partial OHC loss sufficient to obliterate OAEs would necessarily reveal itself in CM surface recordings. Although it does not show any clear trend, ,the fluctu;:ltion of the CM morphology and spectral content over time Illay reflect sorne evolution of the OHC receptor potential, but additional investigations are clearly needed in order to unravel the meaning of the morphology and frequency content of the surface-recorded CM. Another possibility is that the dissociation observed between OAEs and CMs in sorne patients with auditory neuropathy corresponds to a decoupling of the electro-mechanical transduction process that links the receptor potential of the OHCs to their fast contractile response.42 Although it is purely speculative in the present context, such a decoupling mechanism appears quite possible since it can be pharmacologically induced.43 Another theoretical possibility underlying the secondary OAE loss

observed in the present two cases has already been suggested by Berlin et al.9 and Starr et al.! The latter authors observed several frequency regions at which distortion product OAEs were abnormal in one of their adult patients.1 They hypothesized that such focal patches of altered OHC mechanical function could be a consequence of the cochlear nerve disorder exerted on the hair cells through a lack of trophic factors. This hypothesis is particularly interesting in the context of recent progress towards the clinical application of protective, trophic or growth factors targeted at both hair cells44and spiral ganglion neurones.45 Finally, the exact nature of the SP-like potential revealed by the addition of the waveforms evoked by clicks of opposite polarities remains to be identified.19 Should future investigations confirm it to be an SP, this could significantly enrich our physiological armamentarium available to study the pathophysiology of auditory neuropathy, since there is sorne evidence that the surface-recorded SP could be more dependent on the inner hair cells than the CM.46 ln this respect, it may be significant that one of our patients had a much smaller SP-like potential than the other one and that Starr et al.19found it in only two of their three temperature-sensitive cases.

Acknowledgments We gratefully acknowledge financial support from the 'ANAH-NVSG', a branch of the Belgian Rotary Club. We are grateful to Mr C. Labarre for his help in revising the English text. Parts of the data contained in the present paper have been presented as an oral communication entitled 'Auditory Neuropathy: Variations on a Brand New Theme' at the Congrès de l'Institut G. Portmann, Knokke-Lé-Zoute, Belgium, 22-24 May 1997 as weil as at the XVth IERASG Symposium held at Memphis, Tennessee, 8-12 June 1997.

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