Clinical Indicators Useful in Predicting Response to the Medical Management of Meniere s Disease

Transcription

1 The Laryngoscope Lippincott Williams & Wilkins, Inc., Philadelphia 2000 The American Laryngological, Rhinological and Otological Society, Inc. Clinical Indicators Useful in Predicting Response to the Medical Management of Meniere s Disease Anand K. Devaiah, MD; Gregory A. Ator, MD Objectives: To identify factors that may correlate with responsiveness to medical management of Meniere s disease. Study Design: Retrospective chart review. Methods: The 1995 guidelines of the American Academy of Otolaryngology Head and Neck Surgery (AAOHNS) Committee on Hearing and Equilibrium were used for data acquisition and measuring clinical response. New patients with 2 years follow-up were evaluated and grouped as either medically or surgically treated. Patients were excluded for inadequate follow-up or prior otological surgery. Dietary sodium restriction (<1500 mg/d) and a diuretic were employed initially. A compliance rating system was devised to evaluate diet adherence. Patients whose medical management failed were offered surgery. Results: Of 65 patients reviewed, 29 patients qualified for analysis. Seventeen patients were treated medically (patients had either definite or possible Meniere s disease), and 12 patients required surgery. Patients with definite Meniere s disease were at a higher stage (based on audiogram) than patients with possible Meniere s disease (P.002). Patients who required surgery for Meniere s disease were at a higher stage than patients with either definite or possible disease (P <.001). Patients with definite disease had lower compliance than patients with possible disease (P.004), but both groups showed symptom improvement. Patients with possible disease had better control than patients with definite disease (P <.001). Hearing was stabilized in patients with possible disease and improved at 500 Hz in patients with definite disease (P.04). Conclusions: Sodium restriction and diuretic treatment response are correlated to clinical measures of Meniere s disease. Patients with possible Meniere s disease should be treated with aggressive medical therapy to prevent Presented at the Meeting of the Middle Section of the American Laryngological, Rhinological and Otological Society, Inc., Cincinnati, Ohio, January 21 23, From the Department of Otolaryngology Head and Neck Surgery, University of Kansas Medical Center, Kansas City, Kansas Editor s Note: This Manuscript was accepted for publication July 27, Send Correspondence to Gregory A. Ator, MD, Department of Otolaryngology Head and Neck Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A. GAtor@kumc.edu disease progression. Key Words: Meniere s disease, diet, sodium, diuretic, otology. Laryngoscope, 110: , 2000 INTRODUCTION Meniere s disease is treated initially with medical management. Furstenberg et al. 1,2 pioneered the use of salt restriction and diuretics in patients with Meniere s disease, and currently accepted medical regimens are derivatives of those original observations. Meniere s disease often poses a challenge in diagnosis and description. The variability in disease presentation can make it difficult to recognize, thus possibly delaying treatment. This has prompted the development of guidelines to promote accuracy in reporting and recognition. In 1995 new guidelines for the diagnosis and evaluation of therapy in Meniere s disease were introduced by the American Academy of Otolaryngology Head and Neck Surgery (AAOHNS) Committee on Hearing and Equilibrium. 3 These were initially developed by the Committee in 1972 and revised in 1985 with updated definitions of Meniere s disease, a new staging system, and a functional level assessment of the patient. 4,5 The clinical descriptors identified in the guidelines may be correlated with response to medical therapy. To our knowledge, no study has been performed to investigate this hypothesis and this is the subject of our work below. MATERIALS AND METHODS Patient Selection A retrospective chart review of the patients seen at the University of Kansas Medical Center was devised. Patients with Meniere s disease who were seen at least once during a 1-year period were selected. In this manner, a random patient sampling was obtained with at least 2 years of follow-up data and consistent treatment regimens. Sixty-five patients were screened for the study. Of these, 36 patients were excluded because of inadequate follow-up period, prior otological surgery, or incomplete symptom documentation. Patient Classification The 1995 the AAOHNS Committee on Hearing and Equilibrium guidelines for classifying and reporting Meniere s disease 1861

2 Compliance Category TABLE I. Categorization of Patient Compliance. % of Visits With Reported Dietary Compliance 1 No compliance Dietary compliance was categorized based on patient reports of daily sodium intake. The number of clinic visits with estimated complete dietary compliance (for that period of time since the previous clinic visit) was divided by the total number of documented visits, multiplied by 100, and rounded to the nearest whole number. Each patient s score was used to describe compliance in terms of categorical assignment. A score of 100% was reserved for patients who had written documentation of complete dietary compliance but was still grouped in category 5. patients were employed. Patients treated medically (n 17) were classified as having definite Meniere s disease (vertigo, hearing loss, fullness, or tinnitus, with no other causes); probable Meniere s disease (one episode of vertigo, hearing loss, fullness, or tinnitus, with no other causes); or possible Meniere s disease (vertigo without hearing loss, or sensorineural hearing loss and dysequilibrium). The category of certain Meniere s disease was not employed, as there no patients with corroborating histopathological evidence of Meniere s disease were enrolled in this study. Patients whose medical therapy failed and who required surgery for Meniere s disease were identified. These surgically treated patients (n 12) were analyzed for comparison with patients treated medically for Meniere s disease. Therapeutic Intervention All patients selected were initially treated with a lowsodium diet ( 1500 mg/d) and hydrochlorothiazide/triamterene combination diuretic (25/37.5 mg). All patients were counseled by the senior author (G.A.A.) in the same manner with regard to tabulating daily sodium intake, identifying high-sodium foods, and keeping a diet diary of daily sodium intake to ensure accurate compliance with the regimen. For patients with definite Meniere s disease not responding to medical intervention, the option of surgery was presented. Data Collection and Statistical Analysis Data were gathered according to 1995 the AAOHNS Committee on Hearing and Equilibrium guidelines. Pretreatment variables were determined from the 6 months before treatment. Post-treatment variables were determined 18 to 24 months after initiation of treatment. The pretreatment pure-tone average (PTA) for each patient was computed at the thresholds (in decibels) for 0.5, 1, 2, and 3 khz; the audiogram chosen was the poorest of those measured during the pretreatment period. Stage was defined using the PTA (stage 1: 25 db; stage 2: db; stage 3: db; stage 4: 70 db). All patients with Meniere s disease had a stage determination for comparison. The change in decibels between PTA frequencies of the pretreatment and posttreatment audiograms was measured to determine the effect of treatment on hearing. Discrimination scores in percent were also compared for each patient to further assess audiometric response to treatment. The functional level scale (based on subjective effect of vertigo on quality of life) was determined retrospectively using the specific Committee on Hearing and Equilibrium descriptions and finding the closest match to the patient descriptions of disability. The pretreatment and post-treatment functional level was examined to determine any subjective change in patient functioning. For each patient, the average number of vertigo spells per month in the post-treatment period were divided by the number of spells per month from the pretreatment period, multiplied by 100, and rounded to the nearest whole number. This number was then used to determine the class (A 0, B 1 40, C 41 80, D , E 120, F disability from vertigo resulting in beginning secondary therapy). Retrospective analysis of compliance was performed by applying a rating scale to each medically treated Meniere s disease patient (Table I). This rating scale was devised to estimate compliance with diet regimen based on the number of visits when compliance was noted, and determining the number of visits when strict compliance with the diet was not followed. One hundred percent compliance was defined as documented evidence of complete adherence to the diet regimen with a diet diary, but still grouped under category 5. For the purposes of this study, patients with Meniere s disease requiring surgical treatment had only stage computed for comparison purposes with medically treated patients. All patients with Meniere s disease requiring surgery were class F by definition. Statistics were calculated using computer spreadsheets. RESULTS Patient Demographics Of 65 new patients seen over the course of 2 years, 29 met qualifications to be included in our analysis. The male-to-female ratio was 1:3.8. The mean age of patients was 50.3 years (range, y). The ratio of afflicted ears analyzed was 1:1.4 (right to left). Seventeen patients were treated medically and 12 patients had medical therapy that failed and were then treated surgically. In patients treated medically, patients met criteria for either definite Meniere s disease (n 11) or possible Meniere s disease (n 6) categories. No patients had certain Meniere s disease or probable Meniere s disease. All Meniere s disease patients requiring surgery met classifications for definite Meniere s disease. Analysis of Stage The PTA for each patient was calculated according to Committee on Hearing and Equilibrium guidelines to determine the stage of disease. Figure 1 illustrates the distribution of patients for each treatment group and their stage. Patients with definite Meniere s disease had a significantly higher stage than those with possible Meniere s disease ( 2,n 17, P.002). Patients with Meniere s disease who required surgery were found to have a significantly higher stage than patients with disease categorized as definite or possible ( 2,n 29, P.001). Analysis of Compliance and Functional Level Using the devised compliance rating scale, the compliance of each patient to the dietary regimen of less than 1500 mg of sodium per day was assessed. Patients with definite Meniere s disease had a lower compliance than patients with possible Meniere s disease ( 2,n 17, P.004) (Fig. 2). Despite a significant difference in compliance, all medically treated Meniere s disease patients showed improvement of at least one functional level. 1862

3 Fig. 1. Distribution of stage for patients with Meniere s disease treated medically and surgically. The stage of each patient, as defined by the AAOHS Committee on Hearing and Equilibrium guidelines, was calculated for each patient treated medically or surgically. The number of patients at each stage with possible disease or definite disease or with disease requiring surgery is depicted. Patients with definite Meniere s disease were found at a statistically higher stage than those with possible disease ( 2,n 17, P.002). Patients with disease requiring surgery were at a significantly higher stage overall than the patients with definite disease or possible disease ( 2,n 29, P.001). Analysis of Class The number of vertiginous episodes during pretreatment and post-treatment intervals was used to determine class. This describes treatment response as a function of subjective vertigo control. Patients with possible Meniere s disease had better control of vertiginous symptoms (lower class) than patients with definite Meniere s disease as a group ( 2,n 17, P.001) (Fig. 3). Fig. 2. Distribution of patient compliance. Each patient was categorized for compliance with dietary regimen. The number of patients with definite or possible Meniere s disease for each compliance category is depicted. The combined results of both patient pools are depicted for comparison. Patients with definite Meniere s disease had a statistically lower compliance than patients with possible Meniere s disease ( 2,n 17, P.004). difference (definite Meniere s disease: range of %, possible Meniere s disease: range of %). DISCUSSION The observation that water retention exacerbates symptoms of Meniere s disease was first documented by Dederding. 6 In 1934 and 1941, Furstenberg published observations on sodium restriction and diuretic use (ammonium chloride) in the treatment of Meniere s disease. 1,2 These papers detailed how symptoms could be abated or stimulated by manipulating sodium intake and the subsequent water balance. In 1938 Hallpike and Cairns 7 Audiometric Measures The change in audiometric measures for each patient was determined by comparing the worst pretreatment and post-treatment audiograms. Comparisons were made between hearing thresholds (in decibels) at 0.5, 1, 2, and 3 khz. The difference between pretreatment and posttreatment thresholds was computed for each patient at each frequency. To compare the difference between each Meniere s disease classification group (definite disease vs. possible disease in this study), the results were pooled for each frequency within each group. This is depicted in Figure 4. Patients with possible Meniere s disease showed overall stabilization of hearing loss (minimal change in audiometric measures). There was a significant difference at 0.5 khz for patients with definite Meniere s disease compared with patients with possible Meniere s disease (t test; n 11,6; P.036). Patients with definite Meniere s disease showed significant improvement over all frequencies pooled compared with patients with possible Meniere s disease (by combining changes measured at each frequency for each group) (t test; n 11,6; P.044). Comparison of discrimination scores yielded no significant Fig. 3. Distribution of class for patients with Meniere s disease. To describe control of vertiginous symptoms, class was determined for each patient (as defined by the AAOHS Committee on Hearing and Equilibrium guidelines). Higher class category represents worse control of vertigo. Patients with possible Meniere s disease had better control of vertiginous symptoms (lower class) than patients with definite Meniere s disease as a group ( 2,n 17, P.001). 1863

4 Fig. 4. Average change in hearing levels. The pooled differences between pretreatment and post-treatment hearing thresholds for each patient with either definite or possible Meniere s disease. Results are separated for each frequency measured for stage, as described in the AAOHNS Committee on Hearing and Equilibrium guidelines. Error bars shown are SEM. Patients with possible Meniere s disease show overall stabilization of hearing with minimal change in audiometric measures. A statistically significant difference between patients with definite disease and patients with possible disease is seen at 500 Hz, with a greater change seen in definite disease (t test; n 11,6; P.036) demonstrated endolymphatic hydrops in patients with Meniere s disease and thus gave a histopathological correlate for Meniere s disease. These works collectively serve as much of the basis for modern treatment of this disease. These basic ideas were further championed by Klockhoff et al. 8,9 Symptom control was found to be superior in patients treated with sodium restriction and diuretics than in other medical regimens available at the time. Boles et al. 10 later reexamined the Furstenberg regimen as applied to patients followed at the University of Michigan. Again, sodium restriction and diuretic use were found to be effective in controlling the symptoms of most patients. Control of vertigo was considered the primary goal of earlier studies. Over time, the preservation of hearing became increasingly important as an outcome of long-term therapy Vestibular and cochlear manifestations of the disease have been further recognized as important endpoints of therapy. In 1985 the AAOHNS Committee on Hearing and Equilibrium updated their guidelines for describing and reporting treatment results in Meniere s disease. 5 The principle changes from the 1972 guidelines 4 were to further refine the evaluation and diagnosis of a disease that can present with a wide variety of symptom timings. Evaluation of both vestibular and auditory symptoms were emphasized. Santos et al. 14 published their treatment results using sodium restriction and diuretic therapy. They reported their results in accordance with the 1985 Guidelines. In a series of 54 patients examined retrospectively, they demonstrated an improvement in vertigo (79%), and an improvement in hearing (35%). The new standardized evaluation of vertigo and hearing parameters was shown to be successful, but other functional aspects of patient response were not fully addressed in these guidelines. To further refine the diagnostic criteria and symptomology of Meniere s disease, the AAOHNS Committee on Hearing and Equilibrium introduced the 1995 guidelines in the reporting of Meniere s disease. 3 The guidelines refined previous parameters and described new ones to further assess patient function and clinical measures in Meniere s disease. Making the diagnosis of Meniere s disease (with its remissions and exacerbations) is still difficult, but the updated parameters set forth by the Committee on Hearing and Equilibrium allowed improvements in our assessment of Meniere s disease. These parameters correlate with disease response, as shown in this study. The classification of Meniere s disease itself has a bearing on response. We demonstrate that the patients with possible Meniere s disease respond well to medical therapy. These patients all show improvement of their vertigo over 2 years of medical therapy and hearing stabilizes with only a minimal low-frequency hearing loss on average. Patients with possible Meniere s disease also achieve better control of vertigo than patients with definite Meniere s disease, as seen by comparing disease class. These findings support the idea that patients with possible Meniere s disease have early Meniere s disease but have not yet developed complete symptomology to classify them as having definite Meniere s disease. Our study shows that this population of patients can be effectively treated with medical therapy. Further long-term follow-up is needed to see if their symptoms worsen or if they can be weaned off their regimens without disease progression. Closer examination of audiometric measures in this study reveals more differences in the patients with possible and definite Meniere s disease. Where we note relative hearing stabilization in patients with possible disease, we find there is improvement in those with definite disease. In fact, the pretest audiograms of virtually all patients with possible disease reflect minimal dysfunction at this point in their presentation. The patients with definite disease show the greatest improvement (compared with similar changes seen in patients with possible disease) when examining the threshold at 0.5 khz. The finding of low-frequency hearing loss in Meniere s disease is well documented, and these findings support our data as well. No significant differences in discrimination scores were seen in our study. In examination of disease stage, it is apparent that patients with higher stage have worse symptoms. If the classification of Meniere s disease is viewed as a spectrum, increasing in definition and severity from possible to definite, higher stage is correlated with more certainty of Meniere s disease. Also, patients with higher stage are more likely to require surgical intervention for their disease because their symptoms cannot be controlled with medical therapy alone. This may assist in screening patients whose medical therapy is more likely to fail and allow prognostication including the possibility of surgical intervention.

5 Our measure of compliance suggests that it may not be as important in achieving success with medical therapy. Despite having a lower compliance rate, patients with definite Meniere s disease treated with medical therapy (who also had worse auditory and vertiginous symptoms than patients with possible Meniere s disease) still improved on medical therapy. This makes intuitive sense, as there are other regimens that are either less stringent or more stringent than 1500 mg/d of sodium intake and also show symptom improvement. 10,12,13 However, this may be a selection bias for patients with definite Meniere s disease that responded to medical therapy for other undefined reasons, as compared with those who required surgical intervention. Inaccuracies related to the self-reporting of the individual s diet compliance may have interfered with our results. Another explanation is that patients with possible Meniere s disease are in the early manifestation of the disease and more motivated to comply with medical therapy. The patients with definite Meniere s disease may be in the later manifestation of the disease, which has a natural history of extinguishing; this may render compliance less essential to therapeutic response. There are limitations inherent to a study of this nature. For example, compliance does not appear to be a significant factor in treatment response in our study. Nevertheless, there is a distinction seen between the groups of patients (those with definite disease and possible disease and those requiring surgery) in terms of the stage of disease. This indicates that a complex multifactorial relation exists that dictates how each patient will respond to restricted levels of sodium intake and diuresis. The further examination of clinical measures and their effectiveness in helping to tailor regimens of therapy is an area of future study. Another potential limitation is related to patient numbers. The number of patients treated with medical regimen is less than those treated with surgery in this series. The University of Kansas is a tertiary care center, so the pattern of referral is often one of patients who have failed other therapies before presentation. The window of opportunity in treating individuals medically may have passed, resulting in a higher number of those who require surgical intervention for their disease. This is supported by the high response rate of those referred with possible disease, and the fact that patients requiring surgery for Meniere s disease may have already suffered enough damage (as reflected in their stage at presentation) to warrant surgical intervention. Our response rate for treatment and the association with different clinical indicators suggest that these findings are not coincidental. CONCLUSION The early treatment of Meniere s disease with medical therapy is essential. Given that the initial presentation of Meniere s disease may vary, aggressive medical therapy of patients with even an incomplete Meniere s disease picture is warranted. Intervention at the earliest sign of disease may help stave off progression. By examining the signs, symptoms, and audiogram of the patient, a reasonable prediction of the response to medical therapy can be inferred. We do not recommend withholding medical therapy in those individuals who have an advanced stage of disease and offering only surgery; some patients with advanced disease respond to medical therapy and have meaningful improvement in their symptoms. The tools designed by the AAOHNS Committee on Hearing and Equilibrium are useful in assisting the otolaryngologist in delivering state-of-the-art diagnosis and treatment of patients with Meniere s disease. ACKNOWLEDGMENTS The authors thank Joy Pinder for her assistance with this project, as well as Irene Garrett for helping with manuscript preparation. BIBLIOGRAPHY 1. Furstenberg AC, Lashmet FH, Lathrop F. Meniere s symptom complex: medical treatment. Ann Otol Rhinol Laryngol 1934;43: Furstenberg AC, Richardson G, Lathrop FD. Meniere s Disease: addenda to medical therapy. Arch Otolaryngol 1941; 34: Monsell E, Balkany TA, Gates GA, Goldenberg RA, Meyerhoff WL, House JW. Committee on Hearing and Equilibrium guidelines for the Diagnosis and evaluation of therapy in Meniere s Disease. Otolaryngol Head Neck Surg 1995;113: Committee of Hearing and Equilibrium. Report of Subcommittee on equilibrium and its measurement. Trans Am Acad Ophthalmol Otolaryngol 1992;76: Pearson BW, Brackmann DE. Committee on Hearing and Equilibrium guidelines of reporting treatment results in Meniere s Disease. Otolaryngol Head Neck Surg 1985;93: Dederding D. Clinical and experimental examination in patients suffering from morbus Meniere including study of problems of bone conduction. Acta Otolaryngol (Stockh) 1929;1(Suppl 10). 7. Hallpike CS, Cairns H. Observation on the pathology of Meniere s syndrome. Proc R Soc Med 1938;31: Klockhoff I, Lindbloom U. Meniere s disease and hydrochlorothiazide a critical analysis of symptoms and therapeutic effects. Acta Otolaryngol (Stockh) 1967;63: Klockhoff I, Lindbloom U, Stahle J. Diuretic treatment of Meniere s disease: long-term results with chlorothiazide. Arch Otolaryngol 1974;100: Boles R, Rice DH, Hybels R, Work WP. Conservative management of Meniere s disease: Furstenberg regimen revisited. Ann Otol 1975;84: Arenberg IK, Bayer RF. Therapeutic options in Meniere s disease. Arch Otolaryngol 1977;103: Jackson CG, Glasscock ME, Davis WE, Hughes GB, Sismanis A. Medical management of Meniere s disease. Ann Otol 1981;90: Chui RTK, McCabe BF, Harker LA. Meniere s disease at the University of Iowa: 1973 to Otolaryngol Head Neck Surg 1982;90: Santos PM, Hall RA, Snyder JM, Hughes LF, Dobie RA. Diuretic and diet effect on Meniere s disease evaluated by the 1985 Committee on Hearing and Equilibrium Guidelines. Otolaryngol Head Neck Surg 1993;109: