Effect of Glycerol Administration on ECochG and VEMP Findings in Individual with Meniere's Disease

Abstract

The present study aimed to find the effect of glycerol administration on Electrocochleography (ECochG), cervical and ocular Vestibular Evoked Myogenic Potential (c-VEMP, o-VEMP) findings in individual with Meniere’s disease. Sixteen participants (32 ears) diagnosed with Meniere’s disease underwent ECochG, c-VEMP and o-VEMP for both pre and 1 h post-glycerol administration. Paired t-test indicated that the SP/AP ratio of ECochG measures was significantly improved with post-glycerol administration. There was no significant difference in the mean amplitude of o-VEMP and c-VEMP between pre and post-glycerol administration. However, while individual differences were compared, 75% of the participants reported either improvement in c-VEMP amplitude or newly emerging c-VEMP& o-VEMP. Based on the recommendation by Adams et al. (Otolaryngol Clin North Am 43(5):995–1009, 2010), the improvement on these tests results with post glycerol administration were considered as a significant indicator for the presence of Meniere’s disease.With post glycerol administration, the present study found that 84%of participants were found to have an improvement in the amplitude for ECochG measures. There was an improvement in the amplitude measures of o-VEMP and c-VEMP, which were observed in 75% and 68%of participants respectively with post-glycerol administration. Improvement in the amplitude of test measures with post-glycerol administration were observed to be more for cochlear potentials of ECochG followed by vestibular potentials of c-VEMP and o-VEMP. Thus, improvement of ECochG amplitude with post-glycerol administration might serve as an additional indicator for the presence of Meniere’s disease.

Introduction

The vestibular system works with the visual system, semi-circular canals, and central nervous system to help in balancing. Any disturbance to the vestibular system might result in vertigo, and one such disease which affects the person’s day today life is Meniere’s disease/Endolymphatic hydrops. Meniere [7] described that Meniere’s disease consisted of episodic vertigo and fluctuating hearing loss. American Academy of Otolaryngology (AAO)-Head and Neck Foundation [2] gave diagnostic guidelines for Meniere’s disease. Two or more spontaneous episodes of vertigo (each lasting for 20 min–12 h), with low to mid frequency sensorineural hearing loss in the affected ear, fluctuating aural symptoms (hearing, tinnitus, or fullness) is called definite Meniere’s disease.

An accurate diagnosis of Meniere’s disease is required for appropriate intervention. Various audiological tests including the Glycerol test, Electrocochleography (ECochG), and Vestibular Evoked Myogenic Potential (VEMP) assist in diagnosing Meniere’s disease. ECochG has been used as a standard test for diagnosing Meniere’s disease. The components of ECochG is summating potential(SP) which arises from the asymmetric transfer function of the inner hair cells and action potential (AP) which is produced by fibers within the distal portion of the eighth cranial nerve. SP/AP ratio is used to diagnose Meniere’s disease. Enhanced SP component and SP/AP ratio of more than 0.4 is indicative for Meniere’s disease [12]. According to Mori et al. [9] sensitivity of ECochG in diagnosing Meniere’s disease is 61%.

VEMP is a non-invasive test for assessing otolith function in Meniere’s disease. VEMP amplitude and amplitude asymmetric ratio are used to diagnose utricle and saccule (otolith organ) dysfunction. Absent or reduced amplitude of VEMP and amplitude asymmetric ratio of greater than 33% is indicative of otolith dysfunction in Meniere’s disease [11].The sensitivity of VEMP is 53% in diagnosing Meniere’s disease [6]. Belinchon, Garrigues, Tenias and Lopez [4] reported that different audio-vestibular test procedures (Glycerol test, ECochG, VEMP and Videonystagmography (VNG)) have different sensitivity in diagnosing Meniere’s disease. It is assumed that since Meniere’s disease pathology could independently affect different parts of the inner ear (cochlea, otolith organ), the results could also vary according to the morphological changes in the inner ear. Though, it is recommended to use multiple audio-vestibular test procedures to study the extent of Meniere’s disease, the sensitivity of these test procedures in diagnosing Meniere’s disease was continued to be low [8, 10, 13].

It is well known that glycerol administration improves cochlear function in an individual with Meniere’s disease. Several studies have reported, improvement in test findings after glycerol administration as it reduces endolymphatic pressure. Thus, the improvement in these test results post-glycerol administration was considered as an additional indicator for the presence of Meniere’s disease. Adams, Heidenreich and Kileny [1] compared ECochG and VEMP findings between pre and post glycerol administration and found to improve the sensitivity of these procedures in diagnosing Meniere’s disease. Mohammed, Said and Mahmoud [8] reported that sensitivity of ECochG in diagnosing Meniere’s disease improved from 48 to 71% when it is performed with glycerol administration. Murofushi [10] reported that VEMP amplitude was elevated or absent in 56% of the patients with Meniere’s disease. With glycerol administration, there is an improvement in amplitude, asymmetric ratio and sensitivity of VEMP post-glycerol administration to 60%.

However, these studies have found the effectiveness of these tests with post-glycerol administration on a single test. Thus, the present study aimed to find the effect of glycerol administration on multiple audio-vestibular tests such as ECochG, c-VEMP, and o-VEMP. Further, this study is attempted to see whether confirmation of Meniere’s can be increased by studying the improvement in post-glycerol administration on these tests. The present study will try to answer the question that which one of the tests can be used effectively to identify Meniere’s disease in post-glycerol administration.

Method

Study Design: Cross-Sectional Study Design

Study Population

The study population comprised of 16 participants (5 males and 11 females) with bilateral Meniere’s disease. Participants who were diagnosed to have Meniere’s disease with the complaint of triad symptoms (fluctuating hearing loss, tinnitus, giddiness, and aural fullness) participated in the study. Duration of the disease ranged from 2 weeks to 1 years (mean of 3 months) having affected with one ear progressing to bilateral Meniere’s disease. Among them, two participants had reoccurrence of Meinere’s disease after 4 years. The participant’s ages ranged between 26 and 56 years with a mean age of 42.75 years. Hearing loss of the participants ranged from mild to moderate sensorineural hearing with either low-frequency raising or flat configuration. Among 32 ears, mild degree were noticed in 12 ears remaining 20 ears had an moderate degree of sensorineural hearing loss. In addition, 14ears had flat configuration of audiogram and rising configuration of audiogram were seen in18 ears.

All participants underwent glycerol administration. Based on the recommendation by Klockhoff and Lindblom [5], An improvement of 10–12 dB in hearing threshold of any two frequencies with 1 h post glycerol administration was considered positive for Meinere’s disease. Using these criteria, the present study found that 52% of population did not show significant improvement with post glycerol administration. Through, 96% of participants (N = 31) had an improvement in pure tone average, significant improvement is noticed only in 52% of population. These results can be seen as most of participants (N = 24) in the present had an short onset of symptoms starting from 2 weeks to 3 months. Improvement in hearing threshold may not be significant as hearing loss is fluctuating in nature on initial days and also testing was carried out when there is not vertigo during testing (n = 16) 50% of population in the present study. Similarly, Zhao, Zhu and Liu [18] also reported higher sensitivity for glycerol test at the period of symptom onset (83%) than during the disease free intervals (43.1%).

Inclusion Criteria

The participants who were diagnosed with Meniere’s disease as per guidelines given by AAO (2020) were included in the study.

Exclusion Criteria

Participants with middle ear pathology, perilymph fistula, neurological disorders, tumors, and vestibular migraine were excluded from the study.

Procedure

The study procedure was explained and the willingness of the participants was obtained prior to the study. The written consent was obtained using the consent form approved by the Institutional Ethics Committee, Sri Ramachandra Institute of Higher Education and Research (SRIHER). The procedure was carried out in two steps.

Step 1 includes pre-glycerol evaluation of Electrocochleography (ECochG), Cervical Vestibular Evoked Myogenic Potential (c-VEMP), and Ocular Vestibular Evoked Myogenic Potential (o-VEMP).

Step 2 includes the same test procedures as in step 1 but after one-hour post-glycerol administration.

Step 1-Pre Glycerol Evaluation

Electrocochleography (ECochG)

The participants were instructed to lie down in a supine position and asked to remain as quiet as possible with eyes closed position. Before starting the recording, the participants were checked for any kind of middle ear infection or wax in the ear canal by an ENT specialist as it affects recording. After cleaning the ear canal by an ENT specialist, ER 3-C insert earphones along with gold foil tiptrode was inserted in the ear canal. The reference electrode was placed on the contralateral mastoid and the ground electrode was placed on the lower forehead. It was ensured that the absolute electrode impedance was less than 5KΩand the inter-electrode impedance was less than 2 KΩ. EEG was monitored throughout the recording. The clicks stimulus was presented at a 7.1/s repetition rate at 90dBnHL in an alternating polarity as it inhibits stimulus artifact and cochlear microphonics. The picked-up responses were amplified by 1, 00,000 times and filtered in the range of 10–1500 Hz. The responses were averaged for 2000 sweeps. Two waveforms were recorded for each ear separately to check for wave morphology and replicability. The SP and AP were marked with reference to the baseline.

Cervical Vestibular Evoked Myogenic Potential (c-VEMP)

Before the c-VEMP procedure, impedance audiometry was done to rule out middle ear pathology. The non-inverting (+) electrode was placed in the sternum with reference to the inverting (−) electrode in the sternocleido mastoid muscle and the ground electrode in the lower forehead. ER 3-C insert earphones were inserted into the ear canal. It was ensured that absolute electrode impedance was less than 5 kΩ and inter-electrode impedance was less than 2 kΩ. 500 Hz tone burst at 105dBnHL with a 5.1/s repetition rate in alternating polarity was used for recording the waveform. The picked-up response was amplified by 5000 times and filtered in the range of 10–1500 Hz. The response was averaged for 150 sweeps using a time window from − 10 to 100 ms. Patients were instructed to sit in an upright position and turn the head opposite to the stimulated ear. Electromyography (EMG) was monitored by ensuring similar muscle tension throughout the recording and also between pre and post-glycerol administration. Two waveforms were recorded for each ear separately to check for the wave morphology and replicability of the response. Sweep weighted added average waveform was used for analysis. Replicable positive peak P13 and negative peak N23 were marked. Normalized amplitude was calculated by correcting with pre-stimulus EEG and it is considered as the amplitude of P13N23 peaks.

Ocular Vestibular Evoked Myogenic Potential (o-VEMP)

The o-VEMP was recorded by placing thenon-inverting (+) electrode on the contra-lateral side underneath the eye, inverting electrode (−) on the contralateral cheekbone, and the ground electrode on the lower forehead. An ER 3-C insert earphone was inserted into the ear canal. It was ensured that absolute electrode impedance was less than 5 kΩ and inter-electrode impedance was less than 2 kΩ. 500 Hz tone burst at 105dBnHL with a 5.1/s repetition rate in alternating polarity was used for recording the waveform. Participants were asked to sit in an upright position and to gaze up at an angle of 30° when the stimulus was presented. The picked-up response was amplified by 25,000 times and filtered in the range of 10–1500 Hz. The response was averaged for 150 sweeps using a time window from − 10 to 100 ms. Two waveforms were recorded for each ear separately to check for wave morphology and replicability of the response. Sweep weighted added average waveform was used for analysis. Replicable negative peakN10 and positive peak P15 were marked. Normalized amplitude was calculated by correcting with pre-stimulus EEG and it was considered as the amplitude of N10P15 peaks.

Step 2—Post Glycerol Evaluation

Glycerol Administration

Glycerol was administered to the participants as per the recommendation given by Mohamed Said and Mahmoud [8]. Glycerol was diluted with 1:1 water and is given orally in the ratio of 1 ml per 1 kg of the participant using 85% glucose consistency. After 1 h’s administration of glycerol, the participants were tested again with the same test procedures that were carried out in the pre-glycerol evaluation process (i.e., ECochG, o-VEMP, and c-VEMP) using the same testing parameters and procedures. The order and ear of testing were randomized both for pre and post-glycerol evaluation to avoid order and ear effect.

Scoring and Interpretation

Electrocochleography

The amplitude of SP and AP was calculated from baseline for ECochG. SP/AP amplitude ratio was calculated using the following formulae by dividing the amplitude of SP from AP. SP/AP ratio of more than 0.4 was considered as indicative of endolymphatic hydrops [12].

Vestibular Evoked Myogenic Potential

Amplitude and latency of P13 and N23, amplitude and latency of N10and P15 were calculated for c-VEMP, o-VEMP respectively. The reduced amplitude or absent peaks were considered as indicative of saccullocollic and utricullo ocular reflex pathway dysfunction for c-VEMP and o-VEMP respectively [11]. Amplitude asymmetry ratio was not considered for the present study due to the presence of bilateral Meniere’s disease where both ears are affected.

Statistical Data Analysis

The data obtained with ECochG, c-VEMP, and o-VEMP measures were tabulated using Statistical Package for the Social Sciences (SPSS) software version 16.0. Mean, median, and standard deviation scores of ECochG, c-VEMP, and o-VEMP were calculated for all the participants between pre and post-glycerol administration. Paired t-test was used to find statistical significance of ECochG, c-VEMP, o-VEMP measures between pre and post-glycerol administration. Statistical significance is determined by looking at the p-value.

Results

Comparison of Electrocochleography Between Pre and Post Glycerol Administration

Mean and standard deviation of SP amplitude, AP amplitude and SP/AP amplitude ratio between pre and post glycerol administration for all the participants (32ears) with Meniere’s disease are given in Table 1. During pre glycerol evaluation, it was found that out of 32 ears diagnosed with Meniere’s disease, 20 ears (68%) showed positive for the presence of Meniere’s disease. There was increase in amplitude of SP, AP, post glycerol administration (Fig. 1). Results of Paired t-test indicated that there was a significant improvement in SP/AP ratio and AP amplitude with post glycerol evaluation compare to pre glycerol evaluation.

Table 1.

Mean ± SD and p-value of SP, AP amplitude and SP/AP ratio in ECochG measures between pre and post glycerol evaluation with the participant with Meniere’s disease (N = 32 ears)

Components	Pre-glycerol evaluation mean ± SD(µV)	Post-glycerol evaluation mean ± SD(µV)	p-value
SP (µV)	0.16 ± 0.12	0.13 ± 0.12	0.1384
AP (µV)	0.29 ± 0.17	0.38 ± 0.22	0.0531
SP/AP	0.66 ± 0.65	0.35 ± 0.26	0.0389

Fig. 1.

Shows the ECochG findings between pre and post glycerol administration

Comparison of Vestibular Evoked Myogenic Potential (VEMP) Between Pre and Post Glycerol Evaluation

C -VEMP and o-VEMP tests were able to detect the presence for Meniere’s disease in 31% and 61% of the participants respectively for a pre glycerol administration. Table 2 shows the mean of c-VEMP and o-VEMP amplitude in 32ears with Meniere’s disease between pre and post glycerol evaluation. From Table 2, it can be observed there was no significant difference in the c-VEMP and o-VEMP amplitude between pre and post-glycerol evaluation as per paired t-test results. However, the newly emerging VEMP waveform was considerably increased with post glycerol administration which will be discussed in the subsequent paragraph. Example of one patient showing improvement of c-VEMP with post glycerol administration is given in Fig. 2.

Table 2.

Mean ± SD and p-value of c-VEMP and o-VEMP amplitude between pre and post glycerol evaluation in participants with triad symptoms of Meniere’s disease (N = 32 ears)

Parameters	PRE glycerol evaluation mean ± SD(µV)	POST glycerol evaluation mean ± SD(µV)	p-value
c-VEMP amplitude	42.79 ± 50.79	50.18 ± 32.03	0.4248
o-VEMP amplitude	2.33 ± 3.64	2.82 ± 3.23	0.3077

Fig. 2.

Shows the c-VEMP findings between pre and post glycerol administration

Comparison of ECochG and VEMP Test Results Between Pre and Post Glycerol Evaluation

Improvement in any one measure of ECochG and VEMP amplitudeby 10% with post glycerol administration was considered as positive indicator for Meniere’s disease. This was chosen arbitrarily as there were no given standard criteria mentioned in the literature. In addition, Young (2012) has used improvement of 10% or more in VEMP amplitude with glycerol administration as criteria for the presence of Meniere’s disease in their study. Example of one patient showing improvement of c-VEMP with post glycerol administration is given in Fig. 3.

Fig. 3.

Shows the o-VEMP findings between pre and post glycerol administration

As it can be seen from Table 3 that 72% (23 ears) of the study participants had an improvement in AP amplitude and SP/AP amplitude ratio with post-glycerol administration. c-VEMP peaks were newly emerged in 18% of the participants with post-glycerol evaluation. An improvement in the c-VEMP and o-VEMP amplitude was seen in 46% and 31% of participants respectively. However, only 6% of the population had newly emerging o-VEMP peaks after glycerol administration.

Table 3.

Number and percentage of ears had improvement in ECochG and VEMP results with post-glycerol administration

Tests	Parameters	Percentage (no of ears) showed improvement in post glycerol administration	Overall improvement
ECochG	SP amplitude	15 (47%)	84%
	AP amplitude	23 (72%)
	SP/AP ratio	23 (72%)
c-VEMP	Newly emerging c-VEMP	6 (18%)	75%
	Improvement in c-VEMP amplitude	15 (46%)
	Newly emerging o-VEMP	2 (6%)	68%
	Improvement in o-VEMP amplitude	10 (31%)

While comparison was made on percentage of overall improvement among ECochG, c-VEMP and o-VEMP test results with post glycerol administration, Improvement was observed for cochlear potentials (ECochG) followed by vestibular potentials (c-VEMP & o-VEMP).

Discussion

Comparison of ECochG Findings Between Pre and Post Glycerol Administrations

The present study found out that there was a significant difference in SP/AP ratio (p < 0.001) and AP amplitude (p ≤ 0.05) between pre and post-glycerol administration. Similarly, several authors found improvement in AP amplitude with post glycerol administration [8, 14]. The authors postulated that improvement in hearing threshold post glycerol administration would have led to improvement in AP amplitude without affecting SP amplitude, especially in the early stages. According to the authors, this was because hair cells survive relatively intact in the early stages of Meniere’s disease. This theory supports the current study as there was a statistical difference observed in only AP amplitude with post glycerol evaluation. Mohamed, Said and Mahmoud [8] reported that glycerol (an osmotic diuretic drug) dehydrates the inner ear fluid, changing the inner ear pressure back to normal. This results in a subsequent improvement in inner ear function which in turn improves the amplitude of AP. As there was a significant improvement in SP/AP amplitude ratio post glycerol administration in the present study, it serves as a key indicator for the presence of Meniere’s disease.

Comparison of Vestibular Evoked Myogenic Potential (VEMP) Between Pre and Post Glycerol Evaluation

The present study found no significant difference in the c-VEMP and o-VEMP amplitude between pre and post-glycerol evaluation. However, presences of new VEMP as well as increase in VEMP amplitude were observed in 6% and 46% of participants respectively with post glycerol evaluation. According to Ben, Lee, Jin and Lee [3], glycerol would dehydrate the endolymph leading to reduced saccular hydrops associated with Meniere’s disease. This results in an improvement in the VEMP amplitude. Further, Young [17] suggested that improvement of 10% or more in VEMP amplitude with glycerol administration is considered positive for Meniere’s disease.Similar to the present study Ban Lee, Jin and Lee [3] reported that 39.3% of patients had a significant increase in the VEMP amplitude after glycerol administration. Murofushi (2016) reported 40% of his study population with probable Meniere’s disease had elevated or absent VEMP amplitude. With glycerol administration, 20% of the population showed the presence of VEMP. Valame and gore [16] reported 16% of the patients with Meniere’s disease had presence of c-VEMP response after glycerol intake. In addition, 26% of the population showed an increase in amplitude.

O-VEMP has newly emerged in only 6% of participants with post glycerol administration in the present study. Taylor et al. [15] reported that the o-VEMP when compared with the c-VEMP is a low-amplitude reflex and thus more likely to fall below the limits of detection. This may the reason for the reduced improvement in o-VEMP amplitude post glycerol administration in the present study.

There were lots of individual variations noticed for post glycerol administration in the present study. Improvement of test findings in post glycerol administration was not seen for all participants. Further, improvement was not similar across the tests of ECochG, c-VEMP, o-VEMP between the ears for the same individual. Future studies could explore whether these differences would imply different stages of Meniere’s disease or the effect of diuretic treatment for Meniere’s disease.

The present study indicated that ECochG measures showed major improvement with post glycerol evaluation followed by c-VEMP and o-VEMP. Thus, the present study concluded that a single test of ECochG might be used to improve the positive rate for the diagnosis of Meniere’s diseaseupto 84% by comparing with post glycerol administration. Results on glycerol administration were used only for assessments in the present study. Symptomatic management, life style modification, diet restriction were followed for the study partcipants with Meinere’s disease. Further studies can be carried out whether effects of glycerol administration can be used in treatment plan. There is a need for studies to validate if the improvement in these test results could be used to improve the sensitivity of tests.