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Current role of transtympanic gentamicin therapy in the management of unilateral meniere’s disease
K. K. Desarda1, D. A. Bhisegaonkar 2
Abstract: Transtympanic gentamicin infusion is an alternative to surgical labyrinthectomy and Vestibular nerve section for the treatment of refractory vertigo associated with Meniere’s Gentamicin, the current drug of choice provides excellent vertigo control and is a less Invasive method to destroy the vestibular labyrinth. The goal of the treatment is to Eliminate the abnormal vestibular inputs from the vestibular inputs from the diseased ear Without adversely affecting the hearing. It’s salutary effect results from the damage of Both the sensory neuroepithelium and the dark cells of the labyrinth. Intratympanic Gentamicin may cause s. n. hearing loss In some patients {10–15%}. Despite this s. n. Loss, results are encouraging. 50 cases of unilateral Meniere’s disease were treated at KEM hospital, Pune, during 1996 to 2002 with the follow–up of 2 to 4 yrs. All cases were infused with gentamicin transtympanically for 4 to 6 weeks. N weekly basis with other surgical treatments are obviated by this treatment. This prospective study of gentamicin infusion revealed high success rate of controlling vertigo in about 92% patients. This treatment modality offers a less invasive but effective option for treating refractory vertigo of Meniere’s disease.

Key words: Gentamicin, Meniere’s, chemical labyrinthectomy, micro wick

Introduction
Meniere’s disease is a clinical disorder characterized by acute episodes of vertigo, fluctuating hearing loss, aural fullness & tinnitus2. 80% patients of Meniere’s disease are treated successfully by medical treatment. Remaining 20% who have failed medical treatment need either surgical or chemical ablation of vestibular function. Surgical procedures designed to prevent endolymphatic hydrops such as cochleostomy, endolymphatic sac shunt are falling out of favour due to high incidence of sensorineural hearing loss (20–30%). Vestibular nerve section, although very effective is a difficult surgery with significant morbidity and not uncommon complications

Schucknecht (1957) introduced transtympanic mode of Delivery with streptomycin4 & Beck Schmidt (1978) first used gentamicin by the Transtympamnic route5 for treating Meniere’s disease and proved the efficacy of the gentamycin infusion. The success rate was 92–100%2,4,5,6. This prospective study of 50 patients of unilateral Meniere’s disease in KEM hospital, Pune, during 1996–2002 revealed that intratympanic gentamicin therapy has a success rate of controlling vertigo in 92% with S. N. loss in 10–15% of the cases. This being a safe, less invasive and readily accepted treatment modality was the choice of treatment in controlling refractory vertigo of Meniere’s disease. The intratympanic gentamicin infusion (40mg/ml) buffered with 7.5% sodium bicarbonate solution was used slowly over a 10 minutes period. We have recorded our observations and post infusion results for over six years and found that gentamicin therapy is an ideal option to surgical labyrinthectomy. The ease with which gentamicin can be obtained and apparently lower incidence of its cochleotoxic side–effect has currently made it the preferred aminoglycoside for chemical treatment of Meniere’s disease.

Materials & methods:
(TABLE I, II, III)
50cases of 32 males & 18 females within age group Of 30–70 years of proved unilateral Meniere’s disease were treated with repeated transtympanic gentamicin infusion through the grommet for 4–6 weeks on weekly basis During the study, we have excluded CSOM., acoustic neuroma, acoustic trauma, barotraumas, diabetes, hypertension, cervical spondylosis & anaemia with the relevant investigations. Only unilateral Meniere’s disease cases were included in the study group. Prior to infusion, all patients were subjected to routine investigation such as PT Audiometry, Tone decay, SISI, caloric tests, MRI. brain especially for internal auditory meatus and posterior cranial fossa and all relevant biochemical tests. All 50 cases were given medical treatment for at least 3 months prior to gentamicin infusion therapy. The treatment includes diuretics, vasodilators, labyrinthine sedatives, antiallergics and steroids.

All cases were also informed about the side effects of this treatment such as sensorineural hearing loss in 10–15%, ataxia lasting for 4–6 weeks and imbalance until central compensatory mechanisms take over and the need for the head and neck Catwhorne Cooksey’s exercises after the treatment end–point. The infusion of gentamicin 40 mg/ml was used with dilution with 7.5% sodium bicarbonate solution. 10mg/ml gentamicin was slowly infused intratympanically by poster inferior quadrant myringotomy with grommet insertion.

The study ear was elevated by 45 degrees and infusion continued slowly over 10 minutes. The patient maintained the supine position with the study ear above for about 45 minutes post–infusion in the recovery room. The infusions were administered on weekly basis for 4–6 wks. Depending on clinical response in controlling vertigo. The end point of the treatment was total relief from vertigo and associated symptoms. The morbidity of unsteadiness/dysequilibrium, S.N. loss and the appearance of spontaneous nystagmus were cardinal signs of the efficacy of the gentamicin infusion.

Table I: Age distribution:
Age group (years) No. of cases
30–40
41–50
51–60
61–70
Total
06
13
22
09
50


 
Table II – The sex ratio:
Sex No. of cases
Male
Female
Total
32
18
50

Table III – Transtympanic infusions required:
No. of Infusions Cases
1–2
3–4
5–6
Total
10
23
17
50

The results (As per guidelines of AAO–HNS, 1985) 7:
Table IV: Vertigo Relief (n=50)

Vertigo control No. of patients Percentage
Complete 36 72
Substantial 10 20
Limited 02 04
Insignificant 02 04
Worse 00 00

Table V: Hearing loss (n=50)
Hearing loss No. of patients Percentage
Worsened 05 10
Unchanged 37 74
Improved 08 16


 
Table VI : Tinnitus control (n=50)
Tinnitus control No. of patients Percentage
Absent 09 18
Improved 36 72
Unchanged 05 10

Table VII: Aural Fullness Control (n=50)
Aural Fullness Control No. of patients Percentage
Absent 31 62
Improved 19 38
Unchanged 00 00

Table VIII : Post Treatment Caloric Response
Post Treatment Caloric Response No. of patients Percentage
No. response 36 72
Poor response 10 20
No. Change 04 08

Table IX: Comparison of Results
  Vertigo Control Hearing Loss
Beck & Schmidt (1978)5 95% 15%
Odkivist (1988) 8 95% 22%
Nedzelski (1993) 9 100% 37%
Lorne (1993) 10 100% 41%
Susanne & Pyykko (1995) 11 90% 32%
KEM Hospital Pune, Study (KKD) 92% 15%

It was observed that 4–6 wks period was taken to achieve excellent vertigo control. Post infusion audio vestibular tests were done in all cases to record the observations and results.


Results: (Table–IV, V, VI, VII, VIII)
During study, we have recorded complete control in 10 cases (20%), limited in 2 cases (4%) and insignificant in 2 cases (4%). The hearing loss worsened in 5 cases (10%), improved in 37 cases (74%) & improved in 6 cases (18%). The tinnitus was absent in 9 cases (18%), improved in 36 cases (72%), and unchanged in 5 cases (10%). The aural fullness was absent in 31 cases (62%), improved in 19 cases (38%) and unchanged in 0 cases (0%).

Discussion: (Table IX)
One of the exciting new developments in inner ear research is the feasibility to place medications directly into the inner ear. Transtympanic gentamicin infusion can be done by several methods such as transtympanic injection13, Micro Wick of Silverstien1, Microcatheter4, myringotomy & grommet, etc. the gentamicin is the current amino glycoside of choice because it is less cochleotoxic than streptomycin3 (John Shea, 1994) 13. Gentamicin has its ototoxic effect on the sensory neuroepithelium and it destroys the endolymph secreting cells (dark cells of utricle, base of ampullae & lateral wall of crus communes) 14.

We have chosen the myringotomy & grommet route for its simplicity and the repeated procedures required during the treatment. Since this is an office procedure, can be repeated on weekly basis, easily accepted by all the patients and is noninvasive and cost effective, this mode of drug delivery appeared to be the best to us.

Review of the literature revealed that results obtained in vertigo control and hearing loss are variable. Beck & Schmidt (1978) 5, had vertigo control was 95% and S. N. hearing loss was 15%. Odkivist (1988)8, had 95% vertigo control and 22% S. N. loss, Nedzelski (1992)9, had 100% vertigo control and 37% S.N. loss. Lorne (1993) 10 also had 100% vertigo control and 47% S. N.Loss. Susanne and Pyykko (1995)11 showed 90% vertigo control and 32% S.N. loss. Our study revealed 92% vertigo control and 15% S.N.loss.

From the study it appears that there are some disadvantages for gentamicin therapy such as 10–15% risk of hearing loss. Tinnitus and aural fullness may persist, and it is also difficult to regulate the actual degree of diffusion into perilymph bypassing the cohlea. It was also noted that there are various factors altering absorption of gentamicin in the inner ear like the thickness of round window membrane, scarring and adhesions in middle ear, head position and dependency or round window, potency of eustatian tube, rate of turnover of perilymph and endolymph and individual susceptibility to ototoxic gentamicin3.

The concentration of intratympanic gentamicin is most important in predicting the degree of ototoxicity while the duration of therapy appears to be less significant15. The optimal treatment regimen for Meniere’s disease will be such that vestibular hypo activity will be achieved but there will be bo hearing loss.

It was also observed during the study that the no response to gentamicin infusion is probably be due to be central lesion e.g. migraine, micro vascular compression or it may be a bilateral Meniere’s disease or it could be due to the round window adhesions (which prevents proper passage of the drug to the inner ear) or other causes of vertigo. Due respect must be given to the accurate diagnosis of the Meniere’s disease and until one is very very sure about the diagnosis, one should not try this treatment. The other modality of treatment is nonchemical ablation of the vestibular endorgan by ultrasonic and cryosurgery which is not easily available at all the centeres2.

In our study all cases were administered medical treatment for 3 months before the transtympanic infusion. The follow–up was kept on regular basis at 3 months, 6 months, and yearly after the completion of the treatment. It was our observation that six patients (12%) developed irritative nystagmus following transtympanic gentamicin perfusion during the treatment, which recovered in 2 weeks time. This unique new finding may represent a recovery phenomenon resulting from a temporarily reversible ototoxic effect in the treatment ear. Despite small percentage of S. N. loss (15%) the results are encouraging with gentamicin infusion treatment.

Conclusion
Transtympanic gentamicin infusion has a consistent vertigo control (92%), is relatively inexpensive, easy to perform under local anesthesia as an office procedure and without significant morbidity. This chemical ablation provides a reasonably safe and effective method for controlling acute, recurrent vertigo in patients of Meniere’s disease who have failed medical therapy.

We strongly recommend this modality of treatment for severe, unilateral, refractory intractable vertigo of Meniere’s disease before destructive surgery is contemplated because long–term success with the procedure is significantly greater than with sac surgery or vestibular neurectomy.

References Address for correspondence
Dr. K. K. Desarda
Benali, Karve Road, Nal Stop,
Pune 411 004, Maharashtra, India.

Contributed by Dr. K. K. Desarda