A study on the outcome of various methods of administration of intratympanic dexamethasone in tinnitus of cochlear pathology

INTRODUCTION

Tinnitus has been defined as the conscious experience of a sound that originates in the head of the owner.¹ Subjective tinnitus is characterised by an individual perception of a sound in the absence of any physical sound and of course this cannot be heard by the observer.² The effect of tinnitus on an individual person varies, and the degree of annoyance is not directly related to the perception of tinnitus. Studies have indicated that inescapable and escapable pain involved different lamina of the (PAG) periaqueductal gray and the hypothalamic midbrain neural circuits.^3-5 Objective assessment of tinnitus is by tinnitogram which is a psychoacoustic measurement which is divided into a pitch-match test, loudness-match test.^6-9 The inner ear is found to be immunoresponsive. So the ability to deliver medications to inner ear provides more target specific treatment.¹⁰ First study for intratympanic (IT) steroids for tinnitus was done by Sakata et al which was a retrospective study, reported 75% improvement immediately after treatment.¹¹ Recent animal study done by Lee et al has concluded that intra cochlear concentration of IT steroids is much more than that of the systemic steroids.¹² It has been described that cochlear damage occurs due to various causes such as ototoxic agents, microvascular ischemia, virus, noise by inflammatory cytokines and reactive oxygen species.¹³ Anti-inflammatory and immuno suppressive actions of glucocorticoids would help in described conditions. Our study aims at evaluation and managing tinnitus which is subjective, with progressive sensorineural hearing loss (not sudden) and of cochlear type. We have adopted intratympanic medication by dexamethasone, which is one of the efficient method of management as our protocol and compare with its different methods.

METHODS

We did a prospective study on 56 patients who attended Neurotology OPD from 2009 to 2011 at Madras Medical College, Chennai - with subjective tinnitus of cochlear pathology underwent various methods of intra tympanic steroids viz tympanomeatal flap elevation, transtympanic injection, grommet insertion followed by steroid injection.

Patients who had subjective tinnitus with cochlear hearing loss and duration of tinnitus more than three months, age group 20 to 70 years, tinnitus that affects the daily routine, tinnitus with moderate to severe degree of hearing loss, patients with intact tympanic membrane patients willing to return for multiple repeat injections were included in the study.

Patients with age less than 20,greater than 70, patients with otosclerosis or conductive hearing loss and other infectious conditions of external and middle ear, patients with retrocochlear, vestibular pathology, hypertension, diabetes mellitus, thyroid hormone imbalance, patients who are likely to be affected from noise pollution and ototoxic drugs, patients allergic to steroids, patients with other clinical conditions in which steroids are contraindicated, patients not willing for procedure and patients with only hearing ear were excluded from the study.

After a six month of follow up (1^st month, 3^rd month and 6^th month) the values were noted and master chart prepared and statistical analysis done using SPSS 22 version software.

Preworkup procedure

Detailed initial patient assessment with history and the severity of tinnitus is graded accordingly.¹⁴ Mild - When it only bothers the subject in quiet environment, is not persistent and does not disturb sleep. Moderate - When it is constantly present, occasionally disturbs sleep and interferes with concentration. Severe –When it is constantly present inhibits sleep, prevents concentration and incapacitates the subject.

Patients were asked to fill up the following Tinnitus questionnaire (Annexure-I) both before and after the procedures.¹⁵

General examination, local examination including ENT examination, otomicroscopic examination, temporo-mandibular joint examination, systemic examination including cardiovascular system, respiratory system, central nervous system, per-abdomen were done routinely.

Investigations such as complete blood count, renal function test, chest X ray, electrocardiogram, pure tone audiometry, impendence audiometry, tinnitogram, special audiological tests, computered tomography and MRI brain (to rule out retrocochlear pathology), Oto acoustic emission, brainstem evoked response audiometry in certain indicated cases were done.

Patient work up such as informed written consent, injection tetanus toxoid intramuscularly started one day before procedure, injection 2% xylocaine test dose were performed.

Accessibility to middle ear can be either of the following procedures

• 1. Direct injection (IM-22G needle) through tympanic membrane (posteroinferior quadrant)
• 2. Tympanomeatal flap elevation and placing gelfoam soaked in dexamethasone 0.5 ml (single sitting) at round window niche.
• 3. Placing grommet in posteroinferior quadrant.

Procedure

Patient positioned and EAC infiltration given and with operating microscope and endoscopic guidance and by accessing the middle ear by previously described methods, intratympanic steroids (Dexamethasone 4 mg/ml) 0.5 ml or 2 mg at 2 weeks intervals for 4 sittings. Patient is instructed to swallow as little as possible to stay still for 15 minutes. Any side effects were noted immediately recorded. Results were analysed on the basis of pre and post treatment audiogram, tinnitogram and with patient questionnaire (2-improved, 1-not improved, 0-worsened). Positive result is considered mainly according to the symptomatic improvement in tinnitus and by other means such as tinnitogram.

RESULTS

Age distribution

Majority cases were in the fourth and fifth decade of life (Figure 1). Among them 20 were male and 36 were female.

Tinnitogram comparision

When comparing the pre and post tinnitogram, the reduction in tinnitus in terms of frequency (Hz) is statistically significant to that of the amplitude (dB). However in our study the main outcome measure was done by Tinnitus questionnaire because the Post treatment tinnitogram didn’t correspond with the subjective improvement of tinnitus severity (Tables 1-4).

Tinnitus severity distribution

In our study majority patients were having mild to moderate tinnitus (Figure 2).

Frequency distribution among intratympanic steroid group

Among the intratympanic groups transtympanic IT steroid was done in 11 patients, TM flap in 17 patients and grommet in 28 patients.

Frequency distribution of treatment outcome-intratympanic dexamethasone

Out of the 56 patients 33 got improved, 12 were not improved and 11 got worsening of the symptoms (Figure 3).

Comparison within intratympanic steroid group (Table 5 and 6)

Success rate for tympanomeatal flap was 70%, transtympanic was 63% and grommet was 50%.

But when comparing statistically all the three methods had the same effect.

a: 4 cells (44.4%) had expected count less than 5, minimum expected count is 2.16.

DISCUSSION

Intratympanic therapy is becoming an important treatment modality for many inner ear disorders. The current therapies aimed at Meniere’s disease, sudden sensorineural hearing loss (SSHL), noise induced hearing loss (NIHL); however intratympanic steroid therapy for cochlear tinnitus represents an evolutionary step in treatment modality. In our study 33 of 56 (59%) patients showed improvement in the outcome; 2 cases had disappearance of tinnitus. Even though it seems that 40-50 years age group responded well for intratympanic steroid therapy but it was not statistically significant. Post treatment tinnitogram was not corresponding with the subjective improvement of tinnitus severity therefore we considered the tinnitus history and questionnaire as the main mode of treatment outcome. Among the three methods of intratympanic steroids which all had equal effects, dexamethasone soaked gelfoam placement is a single time procedure.

One of the previous studies by She et al observed that intratympanic steroid injection has a positive effect on subjective tinnitus and may be considered to be an alternative treatment to subjective tinnitus.¹⁶ On comparing our study we had a positive effect in the control of subjective tinnitus (59%). Another study by Shulman, Goldstein observed that intratympanic drug therapy with steroid has resulted in both short- and long-term tinnitus relief in 7 of 10 patients (70%) identified to have a predominantly cochlear-type tinnitus.¹⁷ On comparing our study 33 of 56 (59%) patients showed varying degrees of relief from tinnitus and 2 cases had disappearance of tinnitus.

CONCLUSION

In our study, intratympanic dexamethasone was effective in subjective tinnitus of cochlear pathology. Age and sex of the patients had no influence on the methods of ITS treatment.The three methods of intratympanic dexamethasone (transtympanic, grommet insertion, tympanomeatal flap elevation) methods had equal outcome, noteworthy is the gelfoam soaked with dexamethasone which is a single time procedure. However transtympanic injection remains the easiest and cost effective compared to the other two methods.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

REFERENCES

1. 1. Hazell J. Incidence, classification and models of tinnitus- Harold Ludman, Tony wright- Diseases of the Ear: 6th Edition. Jaypee; 1998: 185-195.
2. 2. Moller AR. Tinnitus, Jackler R, Brackmann DE, editors. Neurotology: 2nd edition. Philadelphia: Elsevier Mosby; 2005: 182.
3. 3. Eggermont JJ, Langguth B. Pathophysiology of tinnitus: progress in brain research. Amsterdam: Elsevier; 2007: 19–35.
4. 4. Keay KA, Clement CI, Depaulis A, Bandler R. Different representations of inescapable noxious stimuli in the periaqueductal gray and upper cervical spinal cord of freely moving rats. Neuro Sci Lett. 2001;313:17–20.
5. 5. Lumb BM. Inescapable and escapable pain is represented in distinct hypothalamic-midbrain circuits: specific roles of Ad- and C- nociceptors, Exp Physiol. 2002;87:281.
6. 6. Goldstein B, Shulman A. Tinnitus evaluation. Tinnitus: diagnosis/treatment. San Diego: Singular Publishing Group, Inc; 1997: 293-318.
7. 7. Henry JA, Meikle MB. Psychoacoustic measures of tinnitus. J Am Acad Audiol. 2000;11(3):138-55.
8. 8. Tyler RS, Conrad-Armes D. Tinnitus pitch: a comparison of three measurement methods. Br J Audiol. 1983;17:101-7.
9. 9. Yang CW, Byun JY. Tinnitus Assessment. Hanyang Med Rev. 2016;36(2):109-12.
10. 10. Siedman MD, Vivek P. Intratympanic treatment of hearing loss with novel and traditional agents, Otolaryngologic Clin N Am. 2004;37:973-90.
11. 11. Sakata E, Itoh A, Itoh Y. Treatment of cochlear-tinnitus with dexamethasone infusion into the tympanic cavity. Int Tinnitus J. 1996;2:129-35.
12. 12. Lee JJ, Jang JH, Choo OS, Lim HJ, Choung YH. Steroid intra cochlear distribution differs by administration method: Systemic versus intratympanic injection. Laryngoscope. 2018;128:189–94.
13. 13. Shim HJ. Intratympanic Steroid Injection in Tinnitus Management: Hanyang Med Rev. 2016;36:125-30.
14. 14. Biswas A. The Tinnitus Dilemma: An introduction to Neurotology 2nd Edition. Bhalani Publishing House; 2006: 218.
15. 15. Langguth B, Goodey R, Azevedo A, Bjorne A, Cacace A, Crocetti A, et al. Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative Meeting, Regensburg, 2006. Prog Brain Res. 2007;166:525–36.
16. 16. She W, Dai Y, Du X, Chen F, Zhang Q, Jiang P, et al. A short term study on the efficacies of intratympanic prednisolone and dexamethasone injection for subjective tinnitus. J Clinical Otorhinolaryngol Head Neck Surg. 2008;22:871-7.
17. 17. Shulman A, Goldstein B. Intratympanic drug therapy (ITDT) with steroids for tinnitus control: a preliminary report. Int Tinnitus J. 2000;6(1):10-20.