INTRODUCTIONMeniere's disease was described in 1861 and its main characteristics are vertigo, hearing loss, tinnitus and auricular fullness. Vertigo is usually the most disabling symptom; patients normally experience recurrent episodes of vertigo for a certain period of time, followed by an asymptomatic period that may last for months or even years. As episodes repeat, the hearing level normally decreases progressively.
Various therapeutic measures have been proposed, depending on the phase of the disease. In inter-episode period, the use of diuretics (chlorthalidone) is advocated, associated with a salt-restricted diet for undetermined time. During the phase with vertigo, labyrinthic sedative medication is associated or not with anxiolytic/tranquilizers.
It is estimated that 95% of the patients are well controlled with conservative clinical treatment. The remaining 5% are so-called intractable cases or patients with disabling symptoms5. These patients are candidates to classical surgical treatments: decompression of endolymphatic sac, vestibular neurectomy or labyrinthectomy. The use of intratympanic gentamicin surged as an alternative for surgical treatments, and cost-benefit ratio has proved it is more satisfactory.
Intratympanic use of gentamicin was described by Schuknecht in 19576. Some authors, such as Odkvist4, showed that gentamicin produces a chemical selective labyrinthectomy, since it is more toxic to the vestibule than to the cochlea. If applied to the middle ear at low doses and within long intervals, it produces a partial reduction of vestibular function and not ablation of this function1. This more conservative approach in the use of gentamicin minimizes the risk of having hearing loss because of the drug and enables better control of vestibular symptoms for most of the patients.
The present study aims at listing the indications for use of intratympanic gentamicin, present the procedure and show the results obtained by presenting a clinical case submitted to this kind of treatment.
MATERIAL AND METHODIndication and control exams
The candidates for this procedure are the patients with unilateral Meniere's disease whose clinical treatments were unsatisfactory.
Complete otoneurological assessment, including audiometric thresholds and caloric tests with electronystagmography, should be conducted before and after treatment. After each infiltration of gentamicin, we carry out audiometry to monitor cochlear toxicity.
Administration technique
The patient is positioned in back decubitus, head inclined to the side, maintaining the ear under surgical microscopic view. Anesthesia is applied to the tympanic membrane with phenol-soaked cotton placed on posterior-inferior quadrant. In a 1ml syringe (tuberculin) we place the gentamicin solution at 40 mg/ml concentration for the injection of the total volume of 1m1. For administration of gentamicin we use a 25 G 1/2 needle (needle for lumbar punch). After administration of gentamicin by puncture on the quadrant under anesthesia, the patient is kept in the same position for another 30 minutes. By doing that we are trying to concentrate the medication over the round window, for consequent diffusion to the inner ear.
Our protocol includes weekly injections, comprising a total of 4 sessions. This protocol should be modified for each patient, according to reactions and results obtained. Hearing losses detected at audiometty indicate immediate suspension of treatment. Vestibular symptomatology should be carefully analyzed: it is common to have dizziness in the first days after intratympanic injection, but persistence of relevant dizziness indicates the presence of active disease, and therefore, the need for continuous treatment. After some treatment sessions, the patient should be asymptomatic and the treatment will then be suspended.
CASE REPORTFemale patient, aged 46 years.
In 1993, she started having weekly episodes of severe rotation dizziness. Simultaneously, she experienced tinnitus and progressive hearing loss on the left. After 4-year clinical treatment, ineffective for prevention of dizziness episodes, the physicians decided to perform decompression of left endolymphatic sac in a surgery conducted in 1997. Two months after surgery, the patient started to have dizziness episodes again, which persisted every two months throughout 1997. In January 1998, the first intratympanic gentamicin application was made. Four injections within one to two weeks' intervals were made, until March 1998. After the third infiltration, she did not experience dizziness episodes anymore, and after one year and a half of follow-up, there has been total remission of vertigo symptomatology. Pre and post-otoneurological assessment in this patient showed slight improvement of hearing levels and reduction of post-treatment vestibular function showed at caloric tests.
RESULTSCaloric test on the left year:
Pre-treatment responses - 44°C = 6°/sec
- 30°C = 30°/sec
Post-treatment responses - 44°C = 4°/sec
- 30°C = 10°/sec
DISCUSSIONIndications for chemical labyrinthectomy through intratympanic gentamicin are similar to the indications of surgical labyrinthectomy. The ideal patient is the one that has frequent labyrinthic episodes and little response to clinical treatment. The hearing should be reduced in the affected ear and normal in the contralateral side.
Intratympanic injection aims at addressing gentamicin to the inner ear. Some routes of transport from middle ear to inner ear are conceived. The membrane of the window is relatively thin and transport of substance through this route is widely known3,2. Gentamicin, within perilymphatic space, would go to endolymphatic space and then into the hair cells, whose apex is bathed by endolymph. Concentration of gentamicin in hair cell continues to increase even when the injections are over, and its clearance from hair cells is very slow. These facts lead to continuous gentamicin ototoxicity even after termination of treatment7.
Absorption of gentamicin by inner ear is unpredictable. It is likely that part of the injected solution escapes through the auditory tube or return through the tympanic membrane perforation. The degree of permeability of the round window may also vary according to each case. It is probable that larger volumes of gentamicin inside the middle ear would promote a better contact with the roland window and better absorption by the inner ear. All these factors make it difficult to have an ideal standardized number of infiltration. Authors have reported different treatment protocols. Watanabe8 advocated the placement of ventilation shunt under local anesthesia in order to facilitate subsequent infiltration of garamicin, conducted weekly; in a group of 20 patients, they performed an average of 5 applications per patient. We recommend conducting two to three application within a relatively short time, followed by two to four weeks for clinical assessment. The absence of vertigo episodes in this period is a good parameter that the desired reduction of vestibular function has been achieved. The persistence of relevant symptoms would indicate one or more applications. Patients with recurrence of vertigo after 4 or 5 injections should be considered as candidates for surgical destructive treatment.
Relative contraindications for treatment:
o bilateral Meniere's disease;
o elderly patients;
o caloric tests showing absence of vestibular function in the ear to be treated.
CONCLUSIONIn the initial experiment we conducted and according to the literature, intratympanic gentamicin proved to be a treatment option for unilateral Meniere's disease that is simple to conduct and very safe. Its efficiency is confirmed by the vestibular function checked in caloric test, because we do not wish absence of this function, but rather a significant reduction of it, what would be followed by remission of vestibular symptomatology. In the large samples described in the literature, we observed that for most cases, hearing levels are maintained. There is still controversy as to the best treatment protocol, although studies tend to advocate weekly applications with a total of 4 to 6 sessions, monitoring hearing levels and vestibular symptomatology.
REFERENCES1. DRISCOLL, C. L. W.; KASPERBAUER, J. L.; FACER, G. W.; HARNER, S. G.; BEATTY, C. W. - Low dose intratympanic gentamicin and the treatment of Meniere's disease. Laryngoscope, 107: 83-89, 1997.
2. GOYCOOLEA, M. V. - The round window membrane under normal and pathological conditions. Acta Otolaryngol. (Stockh) [Supp] J, 493: 43-55, 1992.
3. NOMURA, Y. - Otological significance of the round window. Adv. Otorhinolaryngol., 33: 1-162, 1984.
4. ODKVIST, L. M.; BERGENIUSJ; MOLLER, C. - When and how to use gentamicin in the treatment of Meniere's disease. Acta Otolaryngol. (Stockh) [Supp] J, 526: 54-57, 1997.
5. RAUCH, S. D.; OAS, J. G. - Intratympanic gentamicin for treatment of intractable Meniere's disease: a preliminary report. Laryngoscope, 107: 49-55, 1997.
6. SCHUKNECHT, H. F. -Ablation therapy in the management of Meniere's disease. Acta Otolaryngol. (Supp] J, 132:1-42, 1957.
7. TRAN BA HUY, P.; BERNARD, P.; SCHACHT, J. - Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs. J. Clin. Invest., 77:1492-500, 1986.
8. WATANABE, S.; KATO, I.; TAKAHASHI, K.; YOSHINO, K.; TAKEYAMA, I. - Indications and results of gentamicin injection into the middle ear of patients with Meniere's disease. Acta Otolaryngol (Stockh) (Supp] J, 519: 282-285, 1995.
* Assistant Physician of the Service of Otorhinolaryngology of School of Medicine at Universidade de Santo Amaro.
** Resident Physician of the Service of Otorhinolaryngology of School of Medicine at Universidade de Santo Amaro.
Study conducted at the Service of Otorhinolaryngology of School of Medicine at Universidade de Santo Amaro.
Study presented at 4° Encontro Brasileiro de Trabalhos Científicos em Otorrinolaringologia (Porto Alegre, November/1998).
Address for correspondence: Dr. Roberto Alcantara Maia - Rua Jerônimo da Veiga, 164 - Cjto. 3A - 04536-000 São Paulo /SP - Tel/Fax: (55 11) 3061-1372.
Article submitted on September 10, 1999. Article accepted on December 9, 1999.
