Intratympanic steroid perfusion for the treatment of Meniere's disease: a retrospective study.

Abstract

We conducted a retrospective outcomes review of the charts of 22 patients with Meniere's disease who were treated with intratympanic perfusion of methylprednisolone and/or dexamethasone. Outcomes were determined by subjective assessment of vertigo control and by objective changes in audiometric pure-tone average (PTA) and speech discrimination score (SDS). These evaluations were made at the first postperfusion visit (short term) and at least 12 months later (long term). In the short term, 12 patients (54.5%) achieved vertigo control, 4 patients (18.2%) demonstrated a greater than 10-dB improvement in PTA, and 1 patient (4.5%) experienced an increase in SDS of at least 15%. In the long term, the corresponding numbers of patients were 4 (18.2%), 2 (9.1%), and 1 (4.5%). The level of hearing ultimately deteriorated in 9 patients (40.9%). These findings suggest that intratympanic steroid perfusion does not result in any long-term alleviation of vertigo or hearing loss. However, the short-term alleviation of vertigo seen in approximately half of these patients suggests that this treatment may be useful for the temporary relief of symptoms of Meniere's disease.

Introduction

Meniere's disease is characterized by recurrent, spontaneous, and episodic vertigo, hearing loss, tinnitus, and aural fullness. (1) Because the disease course often fluctuates, efforts to study outcomes of therapy can be difficult.

Initial management with a diuretic and a low-salt diet are frequently helpful in treating Meniere's disease. In the absence of any response to this regimen, systemic corticosteroids have long been used as a second-line treatment. Steroids theoretically downregulate the immunologic dysfunction that is believed to be an etiologic factor in some patients with Meniere's disease. Steroids are well known for both their anti-inflammatory and electrolyte-altering effects. Inner ear steroid receptors have been found in animal models as well as in human temporal bones. (2-4) Increased cochlear blood flow has also been proposed as a mechanism by which steroids act on the inner ear. (5,6)

Two advantages of intratympanic steroid perfusion are that it obviates the systemic side effects associated with oral steroids and it results in the delivery of high concentrations of medication to the inner ear end organ. In the perilymph, the concentration of steroids delivered via the intratympanic route is higher than that achieved via intravenous administration; the best concentration profile has been seen with methylprednisolone. (7,8) Factors that influence the passage of medication across the round window membrane include mechanical obstruction in the middle ear, the integrity of the round window membrane, the degree of inflammation in the round window membrane, and the molecular weight, concentration, liposolubility, and electrical charge associated with specific medications. (8,9) No steroid ototoxicity has been demonstrated in animal models. (6)

In this article, we describe our study of the efficacy of intratympanic steroid perfusion in patients with Meniere's disease as determined by subjective assessments of vertigo and by audiometric testing.

Patients and methods

Between Nov. 1, 1998, and Marcia 31, 2003, 22 patients with Meniere's disease underwent intratympanic steroid perfusion at the Virginia Commonwealth University Medical Center. All of these patients--12 women and 10 men, aged 24 to 78 years (mean: 52)--met the diagnostic criteria for definite Meniere's disease established by the American Academy of Otolaryngology--Head and Neck Surgery (AAO-HNS). (1) Follow-up ranged from 12 to 47 months (mean: 24.5). All patients had failed to respond to previous management with a diuretic and a low-salt diet.

The 22 patients had received between 1 and 5 perfusions (mean: 3) of 0.3 to 0.4 ml of steroid. Perfusions were administered in the office with a tuberculin syringe attached to a 1-inch, 30-gauge needle. Perfusions were delivered under a surgical microscope by inserting the needle into the posteroinferior aspect of the tympanic membrane. No local anesthesia was used. Patients remained in the supine position with their head turned for 20 minutes. While in this position, they were asked to refrain from swallowing; instead, they spit their saliva into a kidney basin. Patients returned for reassessment several weeks later.

Nine patients (40.9%) had received 80 mg/ml of methylprednisolone, 3 patients (13.6%) received 24 mg/ml of dexamethasone, 3 received 10 mg/ml of dexamethasone, and 7 (31.8%) received a combination of all three. The choice of medication was based on what was available at the time.

Successful control of vertigo was defined as the complete cessation of vertigo spells (AAO-HNS class A). To obtain objective data, audiograms had been obtained three times: just prior to perfusion, at the first postperfusion visit (range: 1 to 10 wk; mean: 3), and at the most recent visit. A significant change in heating was defined as a 10-dB change in pure-tone average (PTA) at 0.5, 1, 2, and 4 kHz or a change in speech discrimination score (SDS) of at least 15%. Heating loss was defined as either mild ([less than or equal to]40 dB PTA), moderate (41 to 60 dB), severe (61 to 80 dB), or profound (>80 dB). Assessment of low-frequency (0.25, 0.5, and 1 kHz) PTA, which is often affected in Meniere's disease, was performed in the same manner.

Results

Vertigo, short term. Cessation of vertigo was reported by 12 of the 22 patients (54.5%) at the first visit following the initial perfusion (short term).

Vertigo, long term. Cessation of vertigo at the most recent visit (long term) was reported by only 4 patients (18.2%). Of these 4 patients, 2 had been perfused with both 80 mg/ml of methylprednisolone and 24 mg/ml of dexamethasone on different occasions, 1 had received 80 mg/ml of methylprednisolone, and 1 had received 10 mg/ml of dexamethasone.

Audiometry, short term. At the first postperfusion visit, 21 of the 22 patients underwent audiometry (patient 4 refused testing). Four (19.0%) exhibited an improvement in PTA of at least l0 dB (table l). Only 1 patient (4.8%) exhibited an increase in SDS of at least 15% (table 2), but this patient did not demonstrate any improvement in short-term PTA (patient 18). Three patients (14.3%) had a short-term decrease in hearing of more than 10 dB, and 2 patients (9.5%) had a decrease in SDS of at least 15%. Of the 3 patients who had a decrease in heating, 1 patient's hearing loss progressed from mild to severe and 2 from moderate to severe.

With regard to changes in short-term low-frequency PTA, 5 of 21 patients (23.8%) had an improvement of at least 10 dB and 5 had a deterioration (table 3). Of those with deteriorated hearing, 1 patient had mild hearing loss, 2 progressed from mild to moderate heating loss, 1 from moderate to severe, and 1 from moderate to profound. In both patients who progressed to either severe or profound loss, hearing returned to baseline levels during the succeeding months.

Audiometry, long term. All 22 patients underwent follow-up audiometry at various times. Long-term bearing improvement was identified in 2 patients (9.1%; patients 2 and 3); 1 of these patients had received 3 perfusions of 80 mg/ml of methylprednisolone and the other had received 5 perfusions of 10 mg/ml of dexamethasone (table 1). Based on PTA, long-term heating declined by at least 10 dB in 9 patients (40.9%); 4 of these patients had received intratympanic perfusion of gentamicin in addition to a steroid. Of these 9 patients, hearing loss progressed from mild to moderate in 3, from mild to severe in 3, from moderate to severe in 2, and from moderate to profound in 1. In summary, 3 of the 9 patients had a moderate hearing loss, 5 had a severe loss, and 1 had a profound loss. Notably, the patient who had progressed to profound hearing loss had received intratympanic gentamicin.

With respect to long-term changes in SDS, 1 patient (4.5%) had an increase of at least 15% and 6 (27.3%) had a decrease (table 2).

Assessment of long-term low-frequency PTA revealed an improvement of at least 10 dB in 4 patients (18.2%) and a deterioration in 8 (36.4%) (table 3). Of these 8 patients, bearing loss progressed from mild to moderate in 2, from mild to severe in 2, from moderate to severe in 1, and from moderate to profound in l; heating declined within the moderate category in 2 patients. Thus, in the long term, 4 of the 8 patients had a moderate low-frequency hearing loss, 3 patients had a severe loss, and 1 had a profound loss. Five of the 8 patients had received intratympanic gentamicin.

Additional treatments. Overall, 10 patients (45.5%) had sought one or more escalating treatments for Meniere's disease; 6 received intratympanic gentamicin, 6 received oral methotrexate, and 1 underwent vestibular nerve section. Of note, both patients whose long-term PTA bad improved by at least 10 dB went on to seek additional treatment for intractable vertigo; 1 received methotrexate and 1 received both methotrexate and intratympanic gentamicin.

Complications. No tympanic membrane or middle ear complication was identified in any patient.

Discussion

Intratympanic steroid perfusion is a minimally invasive, nondestructive treatment for Meniere's disease that is associated with a low rate of complications.

The results of intratympanic steroid perfusion reported in the literature have been mixed:

* Itoh and Sakata studied the effects of intratympanic dexamethasone and intratympanic lidocaine on vertigo and tinnitus in 136 patients with Meniere's disease. (10) They found that the success rates of the steroid were 80% with respect to vertigo and 74% with respect to tinnitus.

* Silverstein et al investigated the effects of intratympanic dexamethasone and methylprednisolone on various subtypes of inner ear disease and tinnitus. (5) They found an initial benefit in 47% of patients, 60% of whom had Meniere's disease. This benefit waned slightly during a mean follow-up of 4.5 months.

* In a prospective review, Barrs et al achieved complete control of vertigo in 11 of 21 patients (52.4%) at 3 months and in 9 (42.9%) at 6 months. (11) However, they observed no change in hearing.

* Hamid, in a study of 60 patients over a 24-month period, demonstrated a 90% success rate in vertigo control and hearing improvement using a protocol that included 24 mg/ml of dexamethasone. (12)

* In the only prospective, randomized, double-blind, crossover study of intratympanic perfusion in Meniere's disease, Silverstein et al did not demonstrate any significant changes in bearing, tinnitus, caloric vestibular responses, or patients' subjective assessments of symptoms over a 6-week study period. (13)

* In a retrospective review, Arriaga and Goldman focused on short-term hearing following a single application of intratympanic dexamethasone in Gelfoam. (14) They found that only 6 of 19 patients (31.6%) experienced improvement.

As evidenced by these reports, research has not justified the initial enthusiasm for intratympanic steroid perfusion as a definitive therapy for active Meniere's disease. The variations in success rates may reflect the episodic natural history of Meniere's disease as well as the inclusion of patients with different stages of disease. (15)

Our study had inherent limitations, including its retrospective nature, other confounding treatments, and the fact that different brands and concentrations of steroids were used. With respect to the latter limitation, the 24-mg/ml concentration of dexamethasone had been discontinued by its manufacturer during the study period, which meant that only those patients who had been treated during the earlier portion of the study were perfused with this concentration. Moreover, a trend toward greater use of methylprednisolone had been influenced by a report on steroid pharmacokinetics by Parnes et al in 1999. (7)

The results of our study are similar to those of Barrs et al, who reported vertigo control during the immediate postperfusion period in many of their patients. (11) Also, short-term improvement in hearing was not identified in either study.

Our study did not reveal any long-term benefits in either hearing or vertigo control. In fact, almost half of our patients experienced a decline in hearing. Whether this finding reflects the natural history of Meniere's disease or is a manifestation of steroid perfusion or other treatments is subject to debate. The 1 patient in our study who progressed to long-term profound hearing loss had received intratympanic gentamicin following steroid perfusion.

The findings of our study suggest that steroid perfusion does not alter the course of Meniere's disease, although it may alleviate vertigo during the immediate postperfusion period. Therefore, steroid perfusion may be useful for treating acute exacerbations of Meniere's disease characterized by prominent vertiginous symptoms, especially in patients who cannot tolerate oral corticosteroids, such as diabetics. Furthermore, the perfusion of a steroid might also serve as a useful diagnostic test to determine which patients might respond to immunologic treatment. Prospective controlled studies are warranted to determine the validity of this treatment. For now, definitive therapy lies in other modalities of treatment.

Table 1. Pure-tone averages (PTA) at 0.5, 1, 2, and 4 kHz

                                   Short-term               Long-term
      Preperfusion  Postinjection   change     Most recent   change
Pt.     PTA (dB)      PTA (dB)       (dB) *     PTA (dB)     (dB) *

1          41            67           -26          68          -27
                                                             [dagger]
2          53            29           +24          42          +11
3          38            23           +15          26          +12
                                                             [dagger]
4          25            --            --          51          -26
5          56            57            -1          62          -6
6          15            15            0           45          -30
7          37            67           -30          68          -311
8          67            67            0           67           0
9          80            64           +16          72          +8
10         54            64           -10          66          -12
11         8             11            -3          13          -5
12         67            68            -1          60          +7
13         37            37            0           41          -4
14         31            38            -7          30          +1
15         17            16            +1          15          +2
16         31            28            +3          35          -4
17         25            11           +14          61         -36
                                                             [dagger]
18         56            63            -7          50          +6
                                                             [dagger]
19         52            55            -3          95          -43
                                                             [dagger]
20         35            29            +6          67          -32
21         36            34            +2          52          -16
22         32            31            +1          27          +5

* Plus and minus signs indicate the direction of change in hearing
ability rather than the difference in numerical PTA values.

[dagger] Indicates that this patient also received intratympanic
gentamicin.

Table 2. Speech discrimination scores (SDS)

      Preperfusion  Postinjection              Most recent
        SDS (%/HL     SDS (%/HL    Short-term  SDS (%/HL   Long-term
Pt.       [dB])         [dB])      change (%)     [dB])     change (%)

1        84/70          48/75         -36         75/95        -9 *
2        96/70          96/65          0         100/70         +4
3        100/70        100/60          0          84/55       -16 *
4        96/60           --            --         92/75         -4
5        96/75          96/75          0          90/75         -6
6        100/70        100/70          0          96/70         -4
7        68/75          68/75          0          40/85       -28 *
8         0/90          4/90           +4         8/90          +8
9         N/A           40/70          --         20/85         --
10       88/80          88/80          0          56/80        -32
11       100/45         92/45          -8        100/45         0
12       76/80          88/80         +12         80/80         +4
13       80/55          76/60          -4         92/60        +12
14       92/65          88/65          -4         92/65         0
15       96/55          96/55          0          96/60         0
16       96/60         100/60          +4        100/60         +4
17       96/50         100/45          +4         68/70       -28 *
18       12/100         40/80         +28         80/75       +68 *
19       100/55        100/55          0         100/50        0 *
20       96/70          96/60          0         48/100        -48
21       100/45         84/60         -16         52/70        -48
22       100/45         92/55          -8        100/50         0

* Indicates that this patient also received intratympanic gentamicin.

Table 3. Low-frequency (0.25, 0.5, and 1 kHz) pure-tone averages (PTA)

                                   Short-term               Long-term
      Preperfusion  Postinjection   change     Most recent   change
Pt.     PTA (dB)      PTA (dB)       (dB) *     PTA (dB)     (dB) *

1          50            90           -40          60         -10
                                                             [dagger]
2          66            52           +14          30         +36
3          57            33           +24          35         +22
                                                             [dagger]
4          28            --            --          35         -7
5          68            68            0           66         +2
6          15            16            -1          43         -28
7          21            48           -27          71         -50
                                                             [dagger]
8          60            53            +7          51          +9
9          81            65           +16          75          +6
10         65            40           +25          58          +7
11         8             20           -12          10          -2
12         75            83            -8          62          +13
13         11            15            -4          16          -5
14         46            53            -7          25          +21
15         23            23            0           23           0
16         37            31            +6          38          -1
17         36            58           -22          66          -30
                                                             [dagger]
18         45            73           -28          56          -11
                                                             [dagger]
19         60            62            -2          90          -30
                                                             [dagger]
20         50            39           +11          75          -25
21         26            19            +7          50          -24
22         20            21            -1          15          +5

* Plus and minus signs indicate the direction of change in hearing
ability rather than the difference in numerical PTA values.

[dagger] Indicates that this patient also received intratympanic
gentamicin.

References

(1.) Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Meniere's disease. American Academy of Otolaryngology--Head and Neck Foundation, Inc. Otolaryngol Head Neck Surg 1995;113:181-5.

(2.) ten Cate WJ, Curtis LM, Small GM, Rarey KE. Localization of glucocorticoid receptors and glucocorticoid receptor mRNAs in the rat cochlea. Laryngoscope 1993;103:865-71.

(3.) Pitovski DZ, Drescher MJ, Drescher DG. Glucocorticoid receptors in the mammalian inner ear: RU 28362 binding sites. Hear Res 1994;77: 216-20.

(4.) Rarey KE, Curtis LM. Receptors for glucocorticoids in the human inner ear. Otolaryngol Head Neck Surg 1996;115:38-41.

(5.) Silverstein H, Choo D, Rosenberg SI, et al. Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report). Ear Nose Throat J 1996;75:468-71, 474, 476.

(6.) Shirwany NA, Seidman MD, Tang W. Effect of transtympanic injection of steroids on cochlear blood flow, auditory sensitivity, and histology in the guinea pig. Am J Otol 1998;19:230-5.

(7.) Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner car fluids: An animal study followed by clinical application. Laryngoscope 1999;109:1-17.

(8.) Chandrasekhar SS, Rubinstein RY, Kwartler JA, et al. Dexamethasone pharmacokinetics in the inner ear: Comparison of route of administration and use of facilitating agents. Otolaryngol Head Neck Surg 2000;122:521-8.

(9.) Silverstein H, Rowan PT, Olds MJ, Rosenberg SI. Inner ear perfusion and the role of round window patency. AM J Otol 1997;18:586-9.

(10.) Itoh A, Sakata E. Treatment of vestibular disorders. Acta Otolaryngol Suppl 1991;481:617-23.

(11.) Barrs DM, Keyser JS, Stallworth C, McElween JR, Jr. Intratympanic steroid injections for intractable Meniere's disease. Laryngoscope 2001;111:2100-4.

(12.) Hamid MA. Intratympanic dexamethasone perfusion in Meniere's disease. Presented at the annual meeting of the American Neurotology Society; May 12-15, 2001; Palm Desert, Calif.

(13.) Silverstein H, Isaacson JE, Olds MJ, et al. Dexamethasone inner ear perfusion for the treatment of Meniere's disease: A prospective, randomized, double-blind, crossover trial. Am J Otol 1998;19:196-201.

(14.) Arriaga MA, Goldman S. Hearing results of intratympanic steroid treatment of endolymphatic hydrops. Laryngoscope 1998;108: 1682-5.

(15.) Silverstein H, Smouha E, Jones R. Natural history vs. surgery for Meniere's disease. Otolaryngol Head Neck Surg 1989;100:6-16.

From the Department of Otolaryngology--Head and Neck Surgery, Virginia Commonwealth University Medical Center, Richmond, Va.

Reprint requests: Kelley M. Dodson, MD, Box 980146, Department of Otolaryngology--Head and Neck Surgery, Virginia Commonwealth University, Richmond, VA 23298-0146. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

Originally presented at the annual meeting of the American Neurotology Society; May 3, 2003; Nashville, Tenn.