**5. TEOAEs and MD**

Neuroimaging, such as laboratory exams, are recommended during the differential diagnosis in order to exclude other diseases causing Ménière's-like symptoms or congenital malformation/anatomic variations of the inner ear or metabolic, electrolytic, endocrine, vitaminic,

It has been suggested that OAEs and, in particular, distortion product otoacoustic emissions (DPOAEs), may determine the important information about which cochlear regions have been involved in the first phase of MD characterized by recurrent hydropic crisis [25, 26]. Considering that the acoustic energy has to cross the middle ear structures twice, OAE response may be reduced or even suppressed due to imperfections of the middle ear transmission mechanism. In this context, inner ear disorders can influence the OAE response characteristics [27]. The endolymphatic hydrops (confined primarily in the cochlear duct and in the saccule [15]), increase the impedance at the level of the stapes, attenuating any forward or backward acoustic energy

De Kleine et al. [29] found that, in patients affected by MD, DPOAEs have smaller amplitude than the unaffected ears in relation to the mechanical alterations which were hydropsinduced. An early report on MD by Eggermont and Schmidt [30] stated that in the early phase of MD, a minimal variation on the outer hairy cells function, caused by hydrops, can determine the typical auditory threshold fluctuation; this phenomenon can be indirectly observed as a reduction in the DPOAE amplitude particularly in the low DPOAE frequencies. In cases of advanced MD, the severe damage or the loss of inner ear, outer hair cells, is responsible for DPOAEs absence. Unfortunately, these claims have not been verified in subsequent reports and one of the criticisms Eggermont received [31] was that DPOAEs have very low signal-to-

DPOAEs have also been considered as an objective monitor system, for any middle ear functional changes induced by the administration of the glycerol test [32], during the hydrops phase of MD. The osmotic effect and its influence on the intracranial pressure determine a reduction of the labyrinth hypertension, because of the movements of fluids outside the inner ear. This effect can be monitored through: (i) a tonal/vocal audiometry. Effects include a hearing threshold improvement of 10 dB HL in least two frequencies between 500 Hz and 2000 Hz, or an improvement of the verbal intelligibility score of at least 10%; (ii) through electrocochleography (EchoG). Effects include a decrease of the summating potential amplitude [33]; (iii) through OAEs, in particular with an improvement of the DPOAEs amplitude [19]. Overall, the data in the literature [19, 20, 29, 32] suggest that DPOAEs can monitor successfully how glycerol recovers the hearing threshold, compromised by the presence of hydrops.

noise ratios (S/N) at the lower frequencies (i.e., 0.5 kHz and 0.75 kHz).

immunologic disorders potentially implicated in MD [24].

**3. OAEs and MD**

140 Up to Date on Meniere's Disease

transmissions [28].

**4. DPOAEs and MD**

One of the first publications relating MD with TEOAEs was a German study by Nubel et al [38]. Their data supported the hypothesis that a combination of TEOAEs and a masker tone at 30 Hz (in an adjustable relation to one another) could discriminate well cases of endolymphatic hydrops. Their protocol examines TEOAE suppression at 0° and 270°. For the latter, normal subjects showed a complete suppression, whereas MD cases showed partial or no suppression. The same protocol was reevaluated in a subsequent study by Hof-Duin and Wit [39], who reported that the Nubel et al. model was correct but their interpretation of the data was erroneous. According to Hof-Duin and Wit, the observed changes were not directly caused by the endolymphatic hydrops but by other alterations in inner ear structures, for example, in the gain of the cochlear amplifier (i.e., induced hearing loss).

The search for a particular TEOAE pattern in MD patients has not been very successful. TEOAEs detect alterations in the middle ear stimulus transmission or in the stimulus decodification and amplification (cochlea). From a TEOAE point of view, MD cases presenting hearing losses are identical to cases presenting a sensorineural deficit. **Figures 1** and **2** present TEOAE data obtained from the two subjects presenting an initial phase MD. The characteristics of these cases were similar: no use of drugs and prolonged exposure to noise, a low frequency humming feeling (tinnitus), and dizziness. Pure tone audiometry revealed a moderate hearing loss in the low frequencies up to 1.0 kHz. Acoustic Immitance and stapedial reflexes were found normal. Subject 1 was a female of 46 years old. Subject 2 was a male of 37 years old. The TEOAE responses indicate a sensorineural deficit and are **indistinguishable** from other responses originating from patients with sensorineural deficits.

**Figure 1.** Subject 1: female 46 years, with a typical MD hearing loss profile. Pure tone audiometry revealed a moderate hearing loss, in low frequencies. The TEOAE S/N ratios indicate responses up to 4 kHz, an indication of a normally functioning (although partially compromised) cochlea.

Hatzopoulos et al. [40] used advanced time-frequency (TF) spectral methods to examine the frequency content of TEOAE responses from patients presenting sensorineural deficits. Forty subjects presenting moderate hearing losses (in the range of 1.0 kHz to 8.0 kHz) were enrolled in the study. Five of these subjects were MD cases (two of them are presented in **Figures 1** and **2**). The TF patterns from these subjects followed the TF profiles of the other sensorineural cases and no particular TF-markers were observed for the MD subgroup.

TEOAEs have been employed in the detection of the hearing impairment component of MD. A French group, coordinated by Paul Avan, has made considerable contributions to the influence of intralabyrinthine pressure and endolymphatic hydrops on evoked emissions [25, 28, 41–43]. One way to understand this influence is to assess the alterations of the TEOAE phase shift (the latter is a component provided by the FFT decomposition of the TEOAE response). According to Mom et al. [41], "Acoustic phase shift highlights a variation in intra-cochlear functioning that is worth understanding. By analogy to what is observed in intracranial pressure variation as described by Büki et al. [42], it is logical to expect a marked disturbance in intralabyrinthine pressure. There may be a change in the rigidity of the annular ligament of the footplate under pressure from the perilymphatic compartment that is pushed back by the endolymphatic compartment containing the hydrops; or there may be some more subtle endocochlear modification. The endocochlear pressure resulting from change of posture would be the equivalent for the "hydropic" cochlea of a considerable rise in intracranial pressure. In Büki et al.'s experiment, the functioning of a normal cochlea reflected change in intracranial pressure [42]. In MD, however, cochlear functioning is not normal, by definition. As the model does not distinguish which part of the inner ear is being measured but considers it as a single whole, it can reasonably be considered applicable even in a pathological ear. TEOAE phase change in a test performed in an ear affected by MD during the acute phase may be attributed to the hair bundle of the outer hair cells (OHCs). OHC hair bundle inclination,

**Figure 2.** Subject 2: male 37 years, with a typical MD hearing loss profile. Pure tone audiometry revealed a mild to moderate hearing loss, in the low frequencies. The majority of the TEOAE energy is concentrated around 1–1.5 kHz. The TEOAE S/N ratios above 3.0 kHz indicate lack of responses. How this response can be possible, when the pure tone audiometry shows a low frequency deficit? Most probably the strong TEOAE response (from the first 6–10 ms in the TEOAE trace) is generated by cochlear regions above 1.0 kHz, where the subject presents better hearing thresholds.

Hatzopoulos et al. [40] used advanced time-frequency (TF) spectral methods to examine the frequency content of TEOAE responses from patients presenting sensorineural deficits. Forty subjects presenting moderate hearing losses (in the range of 1.0 kHz to 8.0 kHz) were enrolled in the study. Five of these subjects were MD cases (two of them are presented in **Figures 1** and **2**). The TF patterns from these subjects followed the TF profiles of the other sensorineural

**Figure 1.** Subject 1: female 46 years, with a typical MD hearing loss profile. Pure tone audiometry revealed a moderate hearing loss, in low frequencies. The TEOAE S/N ratios indicate responses up to 4 kHz, an indication of a normally

TEOAEs have been employed in the detection of the hearing impairment component of MD. A French group, coordinated by Paul Avan, has made considerable contributions to the influence of intralabyrinthine pressure and endolymphatic hydrops on evoked emissions [25, 28, 41–43]. One way to understand this influence is to assess the alterations of the TEOAE phase shift (the latter is a component provided by the FFT decomposition of the TEOAE response). According to Mom et al. [41], "Acoustic phase shift highlights a variation in intra-cochlear functioning that is worth understanding. By analogy to what is observed in intracranial pressure variation as described by Büki et al. [42], it is logical to expect a marked disturbance in intralabyrinthine pressure. There may be a change in the rigidity of the annular ligament of the footplate under pressure from the perilymphatic compartment that is pushed back by the endolymphatic compartment containing the hydrops; or there may be some more subtle endocochlear modification. The endocochlear pressure resulting from change of posture would be the equivalent for the "hydropic" cochlea of a considerable rise in intracranial pressure. In Büki et al.'s experiment, the functioning of a normal cochlea reflected change in intracranial pressure [42]. In MD, however, cochlear functioning is not normal, by definition. As the model does not distinguish which part of the inner ear is being measured but considers it as a single whole, it can reasonably be considered applicable even in a pathological ear. TEOAE phase change in a test performed in an ear affected by MD during the acute phase may be attributed to the hair bundle of the outer hair cells (OHCs). OHC hair bundle inclination,

cases and no particular TF-markers were observed for the MD subgroup.

functioning (although partially compromised) cochlea.

142 Up to Date on Meniere's Disease

inducing opening of specific ion channels, compared to gating springs, determines OHC excitation level, which in turn defines the OHC resting point which may shift along the characteristic OHC input-output (I-O) curve, as faithfully reflected in the amplitudes of some types of OAE (quadratic distortion-product OAEs) or in the phase of others. The data from Büki et al showed that phase shift was significantly elevated beyond the normal interval in 18 of the MD patients with range, –80° to +145° and sensitivity, 90%. Overall, in patients, in whom the transient evoked OAEs (TEOAEs) were present, positive predictive value was 100% and negative predictive value was 92.3%.

Two different groups in Japan have assessed the effects of the glycerol test on the TEOAE variables, and have reported different success rates. In the study by Inoue et al. [44] two groups were assessed: one classified as Meniere (22 ears) and one as Meniere with cochlear losses (20 ears). Three hours after a 1.5 g/kg glycerol administration, patients from both groups were assessed with TEOAEs and pure tone audiometry. The authors report that the TEOAE evocation rate (i.e., identification of a robust TEOAE response) improved in both groups: in the MD group from 50% to 63.6% and in the cochlear MD group from 66.7% to 83.3%. The findings from Sakashita paper [45] are different. The glycerol effect on TEOAEs was decomposed on the effects on four aspects of the TEOAE waveform, including the "Total TEOAE Response Power", or the "Filtered TEOAE response power" in the 1–2.0 kHz range. They reported positive results in 11/22 ears and added that positive TEOAE results were present independently of the threshold improvement in the 1.0 and 2.0 kHz octaves. Interestingly they reported that a DPOAE protocol (a DPOAE growth function at 1.0, 1.5, 2.0 kHz) was more sensitive to the glycerol test. They concluded that the DPOAE values at 1.0 and 1.5 kHz are useful for a clinical practice.
