Role of prior intratympanic gentamicin and corticosteroids therapy on speech understanding in patients with Menière's disease after cochlear implantation

Meniere’s disease is the disease of the inner ear which is usually characterized by episodic vertigo, fluctuating sensorineural hearing loss, tinnitus, and fullness on the affected side of the ear [26]. The diagnosis of the disease is challenging due to the lack of a gold-standard diagnostic test. The agreed upon classification based on clinical symptoms helps in diagnosing ‘definite’ or ‘probable’ disease [24] Even though the disease prevalence is estimated to be 10–150 per 100,000 the difficulties in diagnosis makes it difficult to ascertain the true level of prevalence [4, 16]. It has been observed that the disease is more common in the fourth and fifth decades of life, with a higher incidence in females and Caucasians.

The diagnosis of definite MD is made with the following criteria: (1) two or more spontaneous episodes of vertigo lasting between 20 min and 12 h, (2) documented low- to mid-frequency SNHL during or after an episode of vertigo, (3) fluctuating symptoms in the affected ear, and (4) the aforementioned symptoms are not better accounted for by another vestibular disorder [26].

The first line management for symptomatic patients is usually conservative involving dietary changes such as reducing salt intake, caffeine, alcohol, and nicotine; and oral treatment with Betahistine or diuretics or a combination all of them with diuretics showing the least evidence [26]. Second line of treatment with intratympanic injection of corticosteroids (ITC) is considered when patients do not respond to medical management [34]. The third line treatment involving invasive endolymphatic sac surgery even though still widely performed is controversial with little evidence [23, 36]. The fourth line treatment is the partial or total medical ablative treatment with intratympanic gentamicin (ITG) usually reserved for patients who already suffer from considerable hearing loss [1]. The fifth line treatment is the total surgical ablation by surgical labyrinthectomy or vestibular neurectomy. The combination of surgical labyrinthectomy with cochlear implantation is advised in order to rehabilitate the hearing of the patients [42].

Regardless of the treatments offered, a large portion of the disease population will progress to profound hearing loss, resulting in functional deafness in one or both ears [19]. This makes hearing rehabilitation an important point to consider in these patients, with cochlear implantation gaining momentum in recent years as a viable treatment option.

On one hand, studies have shown varying degrees of post-operative success in hearing rehabilitation in these patients after cochlear implantation [25, 31, 38] and on the other hand there is a lack of long-term follow-up [8]. There is a specific lack of studies involving the effect of ITC or the ablative effect of ITG on the hearing rehabilitation with cochlear implantation. This is especially important considering that ITG and ITC are probably the most effective non-surgical treatments to treat vertigo in MD [47].

In this scenario before offering treatments with gentamicin and/or ITC, it is important to ascertain their short and long-term effects on hearing rehabilitation with CI since it is usually the last chance of hearing rehabilitation available to the patients. The aim of this study is to compare the post-operative speech understanding of patients who received CI with and without MD. It also aims to analyze the influence of ITG and ITC on the post-operative speech understanding of MD patients.

Hearing rehabilitation with CI is in the meantime routinely used to treat hearing loss in patients with MD. Although initial reports showed varied results compared to standard CI patients [25, 31, 38], larger studies including systematic reviews show comparable results in speech understanding to non-MD patients [2, 44]. These results could be reproduced in our study especially in terms of post-operative speech understanding.

When comparing with recent studies in detail, Prenzler et al. in 2017 report that among 27 MD patients implanted with CI, MD patients showed significantly better results in speech understanding compared to controls at the first fitting and at 1-year refitting, this effect could not be seen anymore [35]. Although not statistically significant, this result was similar to our study wherein the MD patients showed better speech understanding at initial fitting than the controls, but controls performed better with time. The study also showed that pre-operative PTA4 was better in MD patients compared to controls, which was similar to our study. Despite this, these patients did not benefit from best hearing aids (WRS65HA). This has been accounted to fluctuating hearing loss [28, 30, 43]. In addition, this also hints at a possible acoustic degradation over time in MD patients after CI. In fact, Masood et al. in 2020 reported that even though 27% of the MD patients achieved short-term functional hearing preservation, the long-term outcomes were less favorable. They also suggest that there can be degradation in acoustic hearing over time [27].

Another study by Chien et al. in 2022 report that among 29 Meniere patients who received CI, an overall statistically significant difference of 56% was found between mean pre- and post-operative speech recognition after 1 year, which is similar to our study [5]. The study also reports increasing mean post-operative scores at 1 month, 3 months, 6 months, 1 year, and after 1 year at 37.1%, 46.1%, 54.1%, 59.1%, and 66.8% respectively which are similar to our study although a repeated measures ANOVA analysis is missing in this study. However, the higher mean post-operative hearing improvement in patients aged less than 70 years when compared to older MD patients reported by Chen et al. was not seen in our study. In contrast our study showed that age did not have any influence on the post-operative hearing outcomes despite similar study population.

Our study shows varying post-operative speech understanding results after CI when comparing MD patients who received ITG or ITC with MD patients who received neither. The MD ears without prior ITC or ITG performed slightly worse over time compared to the control group but could be said to be comparable to controls since there was no statistical difference between individual means across time points. But the surprising results were from the MD patients treated with ITG or ITC prior to CI. Our study suggests fluctuating speech understanding in patients treated with ITG whereas the ITC patients show very promising speech understanding with dramatic improvement over time.

ITG even though reserved for MD patients with refractory vertigo and with considerable hearing loss, is still more widely used than ITC because of two reasons: ‘chemical labyrinthectomy’ with aminoglycosides is a well-known concept since introduced in 1948 by fowler [11] whereas ITC is a recent treatment method introduced in 2007 [3]. The second reason is that the evidence of disease control for ITC in MD patients is still rather questionable as shown in the Cochrane and systematic reviews [9, 45, 47] with very few studies showing control of disease symptoms [18, 21]. What needs to be considered here is that when ITG might be better at controlling vertigo, ITC has been shown to be better at hearing preservation but not effective in controlling vertigo. This is supported by the pathogenesis of the aminoglycosides, especially gentamicin, which is more sensitive to vestibular hair cells than cochlear hair cells [37, 39]. This deferential toxicity helps reducing vertigo attacks. The steroids on the other hand have shown benefits since immune-mediated response might also be a factor that causes the onset of MD [7, 10, 13]. Corticosteroids furthermore have been found to influence the ionic hemostasis regulation through modifications in the potassium transport consequently reducing the damage to intracochlear barrier [20]. In addition, steroids have been found to play a protective role by the water balance in the inner ear by aquaporins resulting in a possible hearing preservation [12]. Not to be forgotten at this point is that even though cochlear implants bypass the membranous labyrinth they are said to rely on the spiral ganglion for functionality [40]. Steroids may also help in reducing the loss of spiral ganglion neurons helping in hearing preservation [46].

The phenomenon of fluctuating post-operative hearing in MD patients with prior ITG treatment shown in our study has already been reported by case reports [17,29]. The underlying mechanism for fluctuation in hearing in MD patients is still not clear. It has been hypothesized that endolymphatic hydrops might alter the electrode position or disturb the electrode- neural interaction by changing the endolymph fluid potential. This fluctuation occurring only in ITG group and not in ITC group in our study is still harder to explain. We can only speculate that the ITC group as suggested by the prior pathogenesis plays a hearing protective role, which the ITG group lacks [14, 22, 32]. There has also been increased discussion in the last years suggesting that ITG might be more effective in controlling vertigo episodes than ITC with negligible hearing loss when used in low doses [6, 33]. Unfortunately, no current consensus exists on clinical guidelines for the use of gentamicin in terms of dose and duration. Thus, even though there is enough evidence for intratympanic drug treatment for Menière’s disease using ITG and ITC, proper counseling is needed in these patients especially about expectations of post-operative speech understanding when considering hearing rehabilitation with CI.

The role of active disease in MD should also be considered when discussing fluctuations in hearing. MD usually ‘burns out’ in the later phase with patients showing a hearing threshold of up to 60 dB or more pan-tonally resulting in a functionally deaf ear with much decreased speech understanding following an irreversible loss of the hair cells [15]. This is also the stage when the patients receive CI resulting in a lesser possibility of fluctuation in hearing. Notably though, the ‘attacks’ are found to persist, wherein the patients still report the “feeling of fullness” in the ear but without hearing loss or typical vertigo episodes. We have tried to clinically rule out active disease being a cause of the fluctuation by including only patients without a vertigo episode with-in 6 months prior to CI. Since ITG is said to mimic the ‘burned out’ phase resulting in a similar irreversible loss of the hair cells, the fluctuation seen in the ITG group in our study should be of concern needing further studies.

The small study population with heterogeneity is a limitation of this study. However MD being a rare disease, achieving a bigger study population in a single center has always been problematic. This necessitates more studies preferably multicentric with bigger study groups especially for ITG/ITC groups. The lack of the inclusion of vertigo control is another important limitation of the study since vertigo control is the main goal of the ITC and ITG treatments. The influence of different surgical techniques and electrodes on outcomes after CI should also be mentioned as possible confounding factors. Fortunately all the CIs in our center were done by specialized CI surgeons using similar techniques eliminating this factor. The influence of different electrodes used though could not be analyzed because of the small study population. Despite these limitations as far as we know this is the first study on the role of ITG and ITC on speech understanding in patients with Menière's disease after cochlear implantation.