Long Term Outcomes of Intratympanic Dexamethasone in Intractable Unilateral Meniere’s Disease

Abstract

To evaluate the long term effect of Intratympanic dexamethasone in intractable Meniere’s disease. 30 patients with refractory Meniere’s disease which did not respond to the standard medical management, were treated with Intratympanic dexamethasone injections. Post treatment hearing outcome and dizziness scores were compared with the pretreatment values respectively. The mean dizziness handicap inventory (DHI) score was reduced from 91.58 (range 80–100) to be 31.00 (p = 0.00) at 3 months of treatment. With the successive follow-up periods, the mean DHI scores were reduced to 51.50, 46.6, and 50.90 at the end of, 6, 12, and 24 months (p = 0.04, 0.35, and 0.49 respectively). Again at the end of 24 months, 23.80% of patients were free of vertigo (p = 0.01). No patient had improvement in the hearing (> 10 dB) in any of the follow-up periods and 6.6% demonstrated deterioration in hearing. There were no major intraoperative or postoperative complications detected. Intratympanic injection of steroid is a safe and effective method for treating intractable Meniere’s disease. Although short term improvement in the vertigo is well documented, still in 23% of the patients were found to be free of vertigo at even the end of 24 months. There was no significant improvement in hearing noticed, either in short term or in long term.

Introduction

Diuretics, salt-restricted diet and labyrinthine sedatives form the mainstay of treatment in Meniere’s disease. There is increasing evidence implicating autoimmunity and allergy as an etiological agent in Meniere’s disease as circulating immune complexes have been detected against the inner ear antigens [1]. Hence corticosteroids find a place in the management of this disorder which acts by virtue of their anti inflammatory and immunosuppressive action. They prevent a decrease in the cochlear blood flow and more effectively than vasodilators [2]. Shirwany et al. [3] demonstrated a 26% increase in the cochlear blood flow when the corticosteroid infusion was given. They may also act by increasing the sodium concentration in the stria vascularis. However prolonged use of these drugs systemically over a long duration as would be required in this condition may lead to various adverse effects such as impaired wound healing, avascular necrosis of the head of the femur, ocular effects, besides conditions like diabetes, peptic ulcer, and hypertension would preclude their use. Use of these corticosteroids by the intratympanic route may obviate these disadvantages. Also, the concentration of steroids in the inner ear fluids is much higher when administered intratympanically in contrast to when given systemically [4, 5]. We report the long-term effect of the Intratympanic dexamethasone in unilateral intractable Meniere’s disease.

Materials and Methods

The study was conducted at a tertiary care academic hospital. The study period was from October 2009 to April 2015. A total of 30 patients of unilateral Meniere’s disease (as diagnosed by the AAO-HNS criteria 1995) who had not responded to medical management with dietary restrictions, Betahistine hydrochloride and diuretics (Benzthiazide-25 mg plus triamterene 50 mg) were included in the study. Patients with cochlear hydrops, history of hypertension and those who had taken oral corticosteroids in the past 6 months were excluded. 0.3–0.5 ml of dexamethasone (4 mg/mL) was injected intratympanically in the anterosuperior quadrant of the tympanic membrane to allow for maximum filling of the middle ear space. The patient was asked to lie with the injected ear up for the next 30 min and swallow as little as possible during this time to allow the drug to remain for as long as possible in the middle ear. Injections were given at weekly intervals for 3 weeks. Post-treatment visits were done at 03, 06, 12 months, and at the end of 02 years (from the day of the first intratympanic dexamethasone injection) for the assessment giddiness and hearing outcome. Pure Tone Audiometry (PTA) was done at each follow-up visit and was compared with a pretreatment audiogram. A 10 dB change in the hearing thresholds at 500, 1000, 2000 and 3000 Hz was considered significant.

Vertigo was subjectively assessed at each follow up visit using the Jacobson’s Dizziness Handicap inventory (DHI) scale which consisted of 25 questions pertaining to the physical, emotional and functional disability experienced by the patient due to vertigo. Each question contains three options, ‘no’ (worth 0 points), ‘sometimes’ (worth 2 points) or a ‘yes’ (worth 4 points) as it is answered by the patient. Each patient could, therefore, score between 0 and 100 points. The lower the score, the lesser the dizziness handicap. Successful control of vertigo was defined as complete cessation of definite spells of vertigo. The pretreatment dizziness scores were compared with the post treatment scores for each patient at every follow-up visit. Any complications found were noted.

Statistical Analysis

The collected data were analyzed by the SPSS 16.0 for windows for statistical analysis. Continuous variables are presented as mean with 95% Confidence Intervals (CIs) and the difference is expressed as mean difference together with 95% CI.

Results

Total 30 patients were included in the study, of which 17 were males and 13 were females. The mean age of patients was 44 years (range 22–62) (mean age: 44.93 ± 11.38). The mean duration of the disease was 11 months (range 3–24 months). The patients’ data were demonstrated in the Table 1. The average follow-up period was 27 months (ranged 25–39 months). The mean DHI score before the ITD was 91.58 (range 80–100). In the first follow-up period i.e. at the end of 3 months, 14 (48%) patients were found to be free of vertigo (p = 0.00). During the second follow-up period, at the end of 6 months, 12 (40.90%) patients were found vertigo free (p = 0.00). At the end of 12 months, 25 patients could have been followed and of them, 9 patients (36%) were relieved completely from the vertigo (p = 0.00). Again at the end of 24 months, 21 patients could have attended to the vertigo clinic and of the 21 patients, 5 patients (23.80%) had a vertigo free life after the Intratympanic injection (p = 0.01) which has been mentioned in Fig. 1. When the vertigo free patients were considered between the two consecutive follow-up periods, it was found insignificant (p = 0.74, 0.83, 0.51 between the first/second, second/third, third/fourth respectively). When it was focused on an individual level, the mean DHI score before the treatment was found to be 91.58 (range 80–100). At the first follow-up period, the mean score was found to be 31.00 (p = 0.00). With the successive follow-up periods, the mean DHI scores were found to be 51.50, 46.6, and 50.90 at the end of, 6, 12, and 24 months, respectively as demonstrated in Fig. 2. The successive p values were found to be 0.04, 0.35, and 0.49. The average hearing thresholds before the ITD injection was 48.66 dB. At 03 months, the average hearing threshold was found to be 48.03 dB and at the end of 6 months it remained at 49.9 dB. In the third and fourth follow-up period, the average hearing thresholds were found to be 50.36 and 50 dB respectively as demonstrated in Fig. 3. When the DHI scores are compared between the two consecutive follow-up periods, it has been found that there was no significant difference detected (p = 0.14, 0.81, 0.47 between the first/second, second/third, third/fourth respectively).

Table 1.

Description of the demographic data in the study population (n = 30)

	Value	Range
Male	17
Female	13
Mean age of patients (year)	44	22–62
Mean duration of the disease (months)	11	3–24
Mean DHI score
Before the ITD	91.58	80–100
At 3 months	31.00
At 6 months	51.50
At 12 months	46.60
At 24 months	50.90
Mean hearing threshold (dB)
Before the ITD	48.60
At 3 months	48.03
At 6 months	49.90
At 12 months	50.36
At 24 months	50.00

DHI score dizziness handicap inventory score, ITD intratympanic dexamethasone

Fig. 1.

Shows the number of vertigo free patients in the consecutive followup period

Fig. 2.

Shows the mean DHI scores in the follow-up periods

Fig. 3.

Shows the hearing threshold status in the follow-up periods

When it was compared at the end of 24 months, it was evident that there was no significant improvement in the DHI score (p = 0.46). Similarly, there was no significant improvement in hearing threshold in the successive follow-up period, i.e. at the end of 3, 6, 12, 24 months in the postoperative period.(p = 1.00, 0.95, 0.50,0.25 respectively). Again when compared between the two consecutive follow-up periods, it was found that the difference in the improvement was insignificant. Of the 30 patients, 02 patients (6.6%) demonstrated significant hearing improvement, i.e. more than 10 dB improvement in the hearing thresholds at the end of 3 months which remained so at the end of 12 months and at the end of 24 months, 3 patients (14.28%) had deteriorated in hearing. Only one patient was found with a small central perforation at the end of 3 months which healed with conservative management.

Discussion

Systemic or IT steroid is considered as the mainstay of treatment in patients in patients with Meniere’s disease, who do not respond to the standard initial treatment, i.e. salt restriction diet, diuretic, and Betahistine. However, it is not advisable to prescribe the long-term use of the systemic steroid because of its complications like osteoporosis, diabetes, glaucoma, and cataracts. In contrast, IT corticosteroids are the safe alternative to patients with intractable Meniere’s disease, reducing the systemic complication [6]. Unlike the systemic steroid, later decreases the systemic side effects with increasing the local concentration of the steroid. Various old literature has reported the efficacy of the IT steroid in Meniere’s disease [7, 8]. Although IT gentamycin can be effectively used in controlling the symptoms of Meniere’s disease, still its use is limited because of the increased risk of the ototoxicity and imbalance [9]. In the present study, we have discussed the effect of IT dexamethasone in intractable unilateral Meniere’s disease those have not responded to the standard medical management. Of the 30 patients included in the study, definite improvement in vertigo was documented in the post treatment periods. At the first follow-up visit, 48% of patients were free of vertigo and in the subsequent visits, the values further decreased, which became 23% patients at the end of 24 months. Although the vertigo free patients have been gradually decreased with time, still significant no of patients (p < 0.05) became asymptomatic when compared with the preoperative patients.

Again, when compared with the preoperative giddiness, there was a significant decreased in the mean DHI scores in the first and second follow-up period (p ≤ 0.05). In the third and final follow-up period, although the DHI score has been decreased, it was not found to be significant (p ≥ 0.05). Although, the long term effect of Intratympanic dexamethasone in Meniere’s disease was not satisfactory, there was a definite decrease of both the vertigo free patients and mean DHI scores even at the end of 24 months, which has been supported by the past literature [10], later documented successful long term control of vertigo in 70% cases. Other studies have also supported the above long term results with the treatment of IT dexamethasone in intractable Meniere’s disease [11–14]. This significant control in vertigo albeit short term is probably due to the near direct application of corticosteroids to the area of immune dysfunction as opposed to when given systemically, where the drug may not cross the blood labyrinthine barrier as effectively. The different results in controlling the vertigo could be due to the varying study designs, type and dosing schedule of the steroid administered and also the different follow up period of the patients in the post treatment period. These differing results pose a challenge for the clinician while consenting the patients.

Although vertigo control was satisfactory, improvement in the hearing with the use of the IT steroid was not found to be encouraging in the management of Meniere’s disease. There was no significant improvement in hearing threshold found in the patients in the follow-up period when compared with the preoperative hearing. Again, there was no significant improvement in the hearing in between two consecutive follow-ups. Chandrashekhar et al. [5] reported that the concentration of steroids in the endolymph and perilymph is significantly higher when they are given intratympanically than when given intravenously. However, the Intratympanic use of corticosteroids did not translate into a significant improvement in hearing in the study. A well-designed randomized, double-blind crossover trial was conducted by Silverstein et al. [6] taking 29 patients of stage IV Meniere’s disease and the patients were treated with IT dexamethasone. Where he did not find any significant improvement in the hearing threshold. A Study conducted by Arriaga and Goldman [15] have also demonstrated the similar hearing outcome in patients with Meniere’s disease.

Although we did not have a significant improvement of hearing, dexamethasone did not significantly worsen the preoperative hearing as was evident in our study where 6.6% of patients and had a short term deterioration of hearing and that could be probably attributed to the fluctuating nature of hearing loss characteristically seen in this disease. Assuming, increased number of IT steroid injection could have been associated with a better hearing outcome, Leng et al. [16] have conducted a study comparing the clinical profile of patients between single and multiple injections for the treatment of Meniere’s disease and did not find a significant difference (p > 0.05).A study conducted by Martin Sanz et al. [17] where he compared the clinical outcomes in Meniere’s disease between fixed protocol and verses weekly IT dexamethasone of the same strength as in our study and found no significant difference between the results.

Although IT dexamethasone had a promising result in the vertigo outcome in the immediate postoperative period, its long term effect was not satisfactory. According to Parnes et al. [4] dexamethasone levels in the perilymph and the endolymph get significantly depleted within 6 h of administration, which could have led to the short term effect of an IT dexamethasone and made it necessary for increasing the frequency and dose of the medication. Again the hearing improvement was not significant both in the long term and short follow-up period, although there was no significant deterioration in the hearing threshold (< 10 dB in 6.665% cases). In contrast, Hamid et al. [18] using 24 mg/ml of dexamethasone in Meniere’s disease found better giddiness and hearing improvement in 90% cases. Therefore, probably using corticosteroids with a higher dosage/repeated dosing may lead to significant long term benefits, and this would merit further studies to standardize the dosing schedule.

Summary

Intratympanic dexamethasone can be a valid alternate to the systemic steroid to control the vertigo in patients of Meniere’s disease who are refractory to standard medical management. Although, the control of the vertigo is found to be short term, as described in the previous literature, in our study, 23% of patients, had a vertigo free life even after 24 months of Intratympanic injection of the steroid. Neither a short-term or long term improvement of the hearing was detected in our study, although there was no significant deterioration in the hearing. Although a small sample size, a better giddiness and hearing outcomes may be achieved with increasing the frequency/dose of dexamethasone.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest.