Prevalence of vestibular disease in France: analysis of prescription data from a national health insurance database.

Vestibular problems are frequent reasons for primary care consultations. However, there is considerable uncertainty about the prevalence and cost of vestibular disorders. Despite ambiguous effectiveness data, the histamine analogue betahistine is widely and almost exclusively used for treatment of vertigo. Prescription of betahistine can, therefore, be used as a proxy estimate for prevalence. We used openly available claims data from the French health insurance data warehouse, defining annual prevalence of vestibular disease as the number of people who received at least one betahistine prescription that year. Dosage and pack size of each prescribed formulation were extracted to calculate the sum of betahistine in mg and the Defined Daily Dose (DDD) for age and sex strata and in total. To estimate the relative impact of one landmark trial, the BEMED study, we compared prescriptions from the years 2014/2015 to prescriptions in 2019/2022. A total of 735,121 (2014), 694,705 (2015), 614,431 (2019), and 562,476 (2022) persons filled in a prescription of betahistine. Patients were predominantly older and female. Average amount dispensed per year and per person increased from 4422.54 mg during the pre-BEMED period to 4736.90 mg during the post-BEMED period. DDD decreased from 130 Mio per year in 2014/2015 to 116 Mio per year in 2019/2022. Total costs for betahistine decreased by 42% from 21,615,037 Euro in 2014 to 12,894,249 Euro in 2022. Vestibular disease is frequent in France and has a relevant impact on population health. Despite conflicting clinical evidence, betahistine continues to be prescribed widely in medical practice.

Evaluation of changes in endolymphatic hydrops volume after medical treatments for Meniere's disease using 3D magnetic resonance imaging.

OBJECTIVE: To elucidate the relationship between vertigo and EH volume after medical treatment, we investigated changes in endolymphatic hydrops (EH) volume using inner ear magnetic resonance imaging (ieMRI) in relation to clinical results for vertigo and hearing after administration of the anti-vertiginous medications betahistine, adenosine triphosphate (ATP), isosorbide (ISO), and saireito (SAI) for Meniere's disease (MD). METHODS: We retrospectively enrolled 202 consecutive patients diagnosed with unilateral MD from 2015 to 2021 and assigned them to four groups: Group I (G-I), symptomatic oral medication with betahistine only (CONT); Group II (G-II), inner ear vasoactive oral medication (ATP); Group III (G-III), osmotic diuretic oral medication (ISO); and Group IV (G-IV), kampo oral medication (SAI). In total, 172 patients completed the planned one-year-follow-up, which included the assessment of vertigo frequency, hearing improvement, and changes in EH using ieMRI (G-I, n=40; G-II, n=42; G-III, n=44; G-IV, n=46). We constructed 3D MRI images semi-automatically and fused the 3D images of the total fluid space (TFS) of the inner ear and endolymphatic space (ELS). After fusing the images, we calculated the volume ratios of the TFS and ELS (ELS ratios). RESULTS: One year after treatment, vertigo was controlled with zero episodes per month in 57.5% (23/40) of patients in G-I, 78.6% (33/42) in G-II, 81.8% (36/44) in G-III, and 82.6% (38/46) in G-IV (statistical significance: G-I 10 dB in 5.0% (2/40) of patients in G-I, 16.7% (7/42) in G-II, 18.2% (8/44) in G-III, and 21.7% (10/46) in G-IV (statistical significance: G-I=G-II=G-III=G-IV). ELS ratios were significantly reduced after treatment only in the vestibule for G-II, G-III, and G-IV when compared with G-I. Especially among patients with complete control of vertigo after treatment, ELS ratios were significantly reduced after treatment in the vestibule and total inner ear for G-II; in the cochlea, vestibule, and total inner ear for G-III; and in the cochlea, vestibule, and total inner ear for G-IV compared with G-I. However, there were no significant findings in the relationship between hearing results and changes in ELS ratios. CONCLUSION: These results indicate that daily administration of anti-vertiginous medications including ATP, ISO, and SAI could be an effective treatment option for patients with MD at an early stage before it becomes intractable. Treatments to reduce EH might offer better control of vertigo rather than improve hearing.

A triple blind, placebo controlled, randomised controlled trial of betahistine dihydrochloride in the treatment of primary tinnitus.

OBJECTIVES: To evaluate the effectiveness of betahistine in the treatment of primary tinnitus. DESIGN: To evaluate the effectiveness of betahistine in the treatment of primary tinnitus. SETTING: Universidade estadual Paulista Julio de Mesquita Filho, Botucatu Medical School, São paulo, Brazil. PARTICIPANTS: Adult patients with primary tinnitus who had not undergone treatment for tinnitus in the last 6 months were included. Patients with profound sensorineural deafness, hearing aid users and patients with metabolic, neurological, psychiatric or decompensated cardiovascular diseases were excluded. STUDY GROUPS: in the betahistine group, patients received betahistine 24 mg every 12 h for 90 days; in the control group, patients received placebo tablets every 12 h for 90 days. MEAN OUTCOME MEASURES: Primary outcome measure: Tinnitus Handicap Inventory (THI). SECONDARY OUTCOME MEASURES: Clinical Global Impression Improvement (CGI-I) and a question of 'Yes' or 'No' to participants about their perception of improvement in symptoms. RESULTS: Of 284 participants initially identified, 62 were randomised (betahistine group n = 31; control group n = 31). Median age (IQR) 54 (48-60) years, with a balanced number of men and women. There was no difference in THI outcome between the study groups (median difference, -2 points; 95% CI, -8 to 6 points); the THI after the intervention was a median (IQR) 4 (-4 to 14) lower points in the betahistine group, and a median (IQR) 2 (-6 to 10) in the control group. There was no statistical difference in secondary outcome measures. Adverse events were mild and there was no statistical difference between groups. CONCLUSIONS: Betahistine dihydrochloride was ineffective in the treatment of primary tinnitus in adults.

Betahistine alleviates benign paroxysmal positional vertigo (BPPV) through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

BACKGROUND: Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. METHODS: We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. RESULTS: After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. CONCLUSION: Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

Betahistine alleviates benign paroxysmal positional vertigo (BPPV) through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway

BACKGROUND: Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. METHODS: We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. RESULTS: After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. CONCLUSION: Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

[Intervention strategies for residual dizziness after successful repositioning maneuvers in benign paroxysmal positional vertigo: a single center randomized controlled trial].

Objective: To compare the effects of different intervention strategies for the management of residual dizziness following successful canalith repositioning procedure (CRP) in patients with benign paroxysmal positional vertigo (BPPV). Methods: A total of 129 BPPV patients with residual dizziness following successful CRP were recruited during January 2019 and July 2019. They were randomly assigned into three groups with 43 cases in each group: the vestibular rehabilitation group received rehabilitation training for four weeks; betahistine group was given orally 12 mg betahistine three times a day for four weeks; and the control group had no specific treatment. The primary outcomes were daily activities and social participation assessed by the Vestibular Activities and Participation measure (VAP). Secondary outcomes includedbalance function assessed by sensory organization test (SOT) and the duration of residual symptoms. Stata15.0 software was used for statistical analysis. Results: The scores of VAP in the three groups decreased over time, but a more significant decrease was found in vestibular rehabilitation group. Further paired comparison showed that the difference between the vestibular rehabilitation group and the control group was of statistical significance (B=-3.88, χ2=18.29, P<0.01), while the difference between the betahistine group and the control group was not statistically significant (B=-0.96, χ2=1.16, P=0.28). The balance function of the three groups showed a trend of recovery over time, with no significant differences between groups (χ2=1.37, df=2, P>0.05). The median duration of residual dizziness for both vestibular rehabilitation and betahistine groups was 14 days, while that of control group was 19 days, with no significant difference between three groups[Log-rank (Mantel-Cox) test; χ2=1.82, df=2, P=0.40]. Conclusion: Vestibular rehabilitation can significantly improve the daily activities and social participation function in BPPV patients with residual symptoms following successful CRP, but its effects on shortening the duration of residual symptoms and promoting the recovery of balance function remain uncertain.

Pharmacologic and surgical therapies for patients with Meniere's disease: A systematic review and network meta-analysis.

BACKGROUND: Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs). METHODS: Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes. RESULTS: We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002). CONCLUSION: To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.

Effects of nimodipine combined with betahistine on CRP and other inflammatory cytokines and vascular endothelial function in patients with hypertensive cerebral vasospasm.

OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (p < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p < 0.05), but negatively correlated with changes in NO (p < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p < 0.05), and there were no significant differences of adverse reactions between the two groups (p > 0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body's aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.

Subjective benign paroxysmal positional vertigo in patients with osteoporosis or migraine / Vertigem posicional paroxística benigna subjetiva em pacientes com osteoporose ou migrânea

Abstract Introduction Subjective benign paroxysmal positional vertigo is a form of benign paroxysmal positional vertigo in which during the diagnostic positional maneuvers patients only present vertigo symptoms with no nystagmus. Objective To study the characteristics of subjects with subjective benign paroxysmal positional vertigo. Methods Prospective multicenter case-control study. All patients presenting with vertigo in the Dix-Hallpike test that presented to the participating hospitals were included. The patients were separated into two groups depending on whether nystagmus was present or not. An Epley Maneuver of the affected side was performed. In the follow-up visit, patients were checked to see if nystagmus and vertigo were present. Both groups of patients were compared to assess the success rate of the Epley maneuver and also to compare the presence of 19 variables. Results 259 patients were recruited, of which 64 belonged to the subjective group. Nystagmus was eliminated in 67.2% of the patients with benign paroxysmal positional vertigo. 89.1% of the patients with subjective benign paroxysmal positional vertigo remained unaffected by nystagmus, thus showing a significant difference (p = 0.001). Osteoporosis and migraine were the variables which reached the closest to the significance level. In those patients who were taking vestibular suppressors, the percentage of subjective benign paroxysmal positional vertigo was not significantly higher. Conclusions Subjective benign paroxysmal positional vertigo should be treated using the Epley maneuver. More studies are needed to establish a relationship between osteoporosis, migraine and subjective benign paroxysmal positional vertigo. The use of vestibular suppressants does not affect the detection of nystagmus.

Resumo Introdução A vertigem posicional paroxística benigna subjetiva é um tipo de vertigem posicional paroxística benigna na qual, durante as manobras posicionais diagnósticas, os pacientes apresentam apenas sintomas vertiginosos sem nistagmo. Objetivo Estudar as características de indivíduos com vertigem posicional paroxística benigna subjetiva. Método Estudo prospectivo multicêntrico de caso-controle. Foram incluídos todos os pacientes com vertigem no teste de Dix-Hallpike, que se apresentaram nos hospitais participantes. Os pacientes foram separados em dois grupos, dependeu da presença ou não do nistagmo. Uma manobra de Epley foi realizada no lado afetado. Na consulta de seguimento, os pacientes foram avaliados para verificar a presença ou não do nistagmo e da vertigem. Ambos os grupos de pacientes foram comparados para avaliar a taxa de sucesso da manobra de Epley e também para comparar a presença de 19 variáveis. Resultados Foram recrutados 259 pacientes, dos quais 64 pertenciam ao grupo subjetivo. O nistagmo foi eliminado em 67,2% dos pacientes com vertigem posicional paroxística benigna. Em 89,1% dos casos, os pacientes com vertigem posicional paroxística benigna subjetiva mantiveram-se não afetados pelo nistagmo, mostraram uma diferença significativa (p = 0,001). Osteoporose e enxaqueca foram as variáveis que atingiram o nível mais próximo ao de significância. Nos pacientes que tomavam supressores vestibulares, a porcentagem de vertigem posicional paroxística benigna subjetiva não foi significativamente maior. Conclusões A vertigem posicional paroxística benigna subjetiva deve ser tratada com a manobra de Epley. Mais estudos são necessários para estabelecer uma relação entre osteoporose, enxaqueca e vertigem posicional paroxística benigna subjetiva. O uso de supressores vestibulares não afeta a detecção do nistagmo.

Cinnarizine/betahistine combination vs. the respective monotherapies in acute peripheral vertigo: a randomized triple-blind placebo-controlled trial.

PURPOSE: To compare the efficacy of cinnarizine/betahistine combination with the respective monotherapies in patients with acute peripheral vertigo (APV). METHOD: A randomized, triple-blind placebo-controlled phase III trial was performed on 162 patients with APV to compare the efficacy of cinnarizine/betahistine combination with the respective monotherapies. Patients were randomly allocated into three groups (n = 54 each) of Bet. (betahistine and placebo), Cin. (cinnarizine and placebo), and Bet. + Cin. (betahistine and cinnarizine). The first group received cinnarizine tablets (25 mg) plus placebo three times a day, the second group received betahistine tablets (8 mg) plus placebo three times a day, and the third group received betahistine (8 mg) plus cinnarizine (25 mg) combination three times a day. The treatments were continued for 1 week. Patients were followed up to 3 days and 1 week after initiation of the treatments for changes in vertigo severity measured by visual grading scale (VAS), mean vertigo score (MVS), and mean concomitant symptom score (MCSS). RESULTS: Results showed a significant difference between the groups in VAS (p = 0.001), MVS (p = 0.0001), and MCSS (p = 0.0001) at 1-week follow-up, where the respective values were significantly lower in the Cin. + Bet. group as compared with the respective monotherapies. Efficacy and tolerability of the treatment were found to be higher in the Cin. + Bet. group at 3-day and 1-week follow-up periods (p = 0.0001, for all comparisons). None of the patients reported any side effects during the study. CONCLUSION: This study indicated the superiority of the cinnarizine/betahistine combination over the respective monotherapies in the treatment of APV. TRIAL REGISTRATION: IRCT20130710013947N9.

Approach to Ménière disease management.

OBJECTIVE: To provide family physicians with an updated approach to the diagnosis and management of Ménière disease (MD), detailing the natural course of MD and describing how to initiate medical therapy while awaiting consultation with otolaryngology-head and neck surgery. SOURCES OF INFORMATION: The approach is based on the authors' clinical practices and review articles from 1989 to 2018. Most of the cited studies provided level II or III evidence. MAIN MESSAGE: Ménière disease is an uncommon disorder of the inner ear causing vertigo attacks with associated unilateral hearing loss, tinnitus, and aural fullness. It has a degenerative course that often results in permanent sensorineural hearing loss. On average, MD stabilizes with no further vestibular attacks by about 8 years after the onset of symptoms; however, this is highly variable. Vertigo symptoms can be controlled through a combination of dietary salt restriction, stress reduction, and medical therapy (betahistine, diuretics, or both). These can be initiated by family physicians before consultation with otolaryngology-head and neck surgery. Symptoms refractory to such strategies can be treated using nonablative, and occasionally ablative, therapies. CONCLUSION: A thorough history is key to the approach to and management of MD and permits differentiating MD from other vestibular and nonvestibular conditions.

Therapeutic strategies in the treatment of Menière's disease: the Italian experience.

PURPOSE: Ménière's disease (MD) is an inner ear disorder of unknown etiology, whose pathological substrate is the endolymphatic hydrops. Different treatments have been proposed; however, evidence of their effectiveness is lacking. The aim of this study was to evaluate by a questionnaire which medical and surgical treatments are used in Italy for the treatment of MD and to compare them with those proposed in other countries. METHODS: An electronic questionnaire of 40 questions was formulated and sent to Italian otolaryngologist (ENT) divided into two groups: Group 1 ("generalists" 60.8%) and Group 2 ("neurotologist- NO" 39.2%). RESULTS: One hundred and twenty five ENT replied. Treatment of the acute phase, apart from symptomatics, was based on diuretics that are prescribed by 83.5% of respondents, steroids, prescribed by 66.7%, and vasodilators, prescribed by 22%. In the intercritical phase, 87.2% of respondents recommended low-salt diet, 78.4% of respondents prescribed betahistine, and 52.8% diuretics. Statistical analysis did not show correlation neither with the declared specialization nor with the number of patients treated. In case of failure of medical treatment, IT gentamicin was suggested by 48.8% of the respondents and IT steroids by 40.8%. Statistical analysis showed that generalists prefer IT steroids and NO IT gentamicin (p 0.019). In case of failure of both medical treatment and IT treatment, vestibular neurectomy was indicated by 58.4% of the respondents, 6.4% indicated endolymphatic sac surgery, and 2.4% surgical labyrinthectomy. CONCLUSION: In Italy, the treatment of MD stand on a gradual approach that starts from the dietary-behavioral changes and a pharmacological therapy based on betahistine. In refractory cases, IT treatment initially with steroids and, therefore, with gentamicin allows the control in vertigo in the majority of cases. In case of failure of IT treatment, VNS is the surgery of choice.

Population-Based Study on the Epidemiology of Ménière's Disease.

BACKGROUND AND OBJECTIVE: Ménière's disease (MD) is a disorder of the inner ear typically showing recurrent acute episodes of vertigo, hearing loss, and tinnitus. Epidemiologic studies on MD are scarce. We assessed the incidence rates (IRs) of MD and describe the characteristics of MD cases, comparing them to control patients without recorded evidence of MD. STUDY DESIGN: We conducted a retrospective population-based follow-up study and a nested case-control analysis using data from the UK-based Clinical Practice Research Datalink. METHODS: We identified patients between 18 and 79 years of age with an incident MD diagnosis between January 1993 and December 2014. We assessed the IRs of betahistine-treated MD. In the nested case-control analysis, we matched 4 controls to each MD case on sex, age, general practice, years of active history in the database, and calendar time. We conducted a χ2 test to present p values in order to compare the prevalence of demographics, comorbidities, and co-medication between cases and controls. RESULTS: We identified 5,508 MD cases and 22,032 MD-free controls (65.4% females). The overall IR for MD in the UK was 13.1 per 100,000 person-years. More cases were female, and the mean age at diagnosis was 55.4 ± 13.7 years. Smoking and alcohol consumption were less prevalent among MD cases. Depression, other affective disorders, sleeping disorders, anxiety, and migraine were more prevalent among MD cases than among controls. CONCLUSIONS: MD is uncommon in primary care in the UK with a preponderance among females.

Hearing function after betahistine therapy in patients with Ménière's disease / Função auditiva após terapia com beta-histina em pacientes com doença de Ménière

ABSTRACT INTRODUCTION: Preventing or reversing hearing loss is challenging in Ménière's disease. Betahistine, as a histamine agonist, has been tried in controlling vertigo in patients with Ménière's disease, but its effectiveness on hearing problems is not known. OBJECTIVE: To examine the effect of betahistine on hearing function in not-previously-treated patients with Ménière's disease and to define possible contributors in this regard. METHODS: A total of 200 not-previously-treated patients with definite unilateral Ménière's disease received betahistine by mouth (initial dose, 16 mg three times a day; maintenance dose, 24-48 mg daily in divided doses). Changes in indicators of hearing status before and six months after treatment were documented. Hearing loss was considered as the mean hearing level >25 dB HL at five frequencies. RESULTS: The mean duration of disease was 3.37 years. Six months after treatment the mean hearing level decreased by 6.35 dB compared to that at the baseline (p < 0.001). Both patients' age and the duration of disease correlated negatively with the improvement in hearing function. Post treatment hearing loss was independently associated with age, the initial hearing level and the chronicity of disease. The corresponding optimal cut-off points for predicating a persistent hearing loss 6 months after treatment were 47 years, 38 dB HL, and 1.4 years, respectively. CONCLUSION: Oral betahistine was significantly effective in preventing/reversing hearing deterioration in patients with Ménière's disease. Age, the hearing level on admission, and the disease duration were independent predictors of hearing status after treatment.

Resumo Introdução: Prevenir ou reverter a perda auditiva é um desafio na doença de Ménière. A betahistina, um agonista de histamina, tem sido testada no controle de vertigem em pacientes com doença de Ménière, mas sua eficácia em problemas de audição ainda não é conhecida. Objetivo: Analisar o efeito da betahistina na função auditiva em pacientes com doença de Ménière não tratados previamente, e definir possíveis contribuintes a esse respeito. Método: Um total de 200 pacientes sem tratamento prévio, e com diagnóstico definido de doença de Ménière unilateral, recebeu beta-histina por via oral (dose inicial de 16 mg três vezes ao dia; dose de manutenção de 24-48 mg por dia, em doses divididas). Alterações dolimiar auditivo antes e após seis meses de tratamento foram documentadas. Considerou-se como perda auditiva uma média do nível de audição > 25 dB NA em cinco frequências. Resultados: A média de duração da doença foi de 3,37 anos. Seis meses após o tratamento, a média do limiar auditivo diminuiu em 6,35 dB, em comparação com o valor da linha de base (p < 0,001). Tanto a idade dos pacientes quanto a duração da doença apresentaram correlação negativa com a melhora da função auditiva. A perda auditiva após o tratamento foi independentemente associada à idade, ao nível inicial de audição e à cronicidade da doença. Os pontos de corte ótimos correspondentes para prever uma perda auditiva persistente seis meses após o tratamento foram 47 anos, 38 dB HL e 1,4 ano, respectivamente. Conclusão: A betahistina oral foi significantemente eficaz na prevenção/reversão da deterioração auditiva em pacientes com doença de Ménière. Idade, nível de audição na admissão e duração da doença foram fatores preditivos independentes da condição auditiva após o tratamento.

Treatment of Meniere's disease with intratympanic dexamethazone plus high dosage of betahistine.

PURPOSE: The aim of the present study was to assess if the combined therapy of intratympanic dexamethasone (ITD) and high dosage of betahistine (HDBH) is able to provide increased vertigo control compared to ITD alone in patients suffering from definite unilateral Meniere's disease (MD). MATERIALS AND METHODS: Consecutive MD patients were enrolled and randomly divided in two groups, each comprising 33 cases. Group A received a combination of ITD and identical-appearing placebo pills while Group B received a combination of ITD and HDBH. ITD protocol consisted of three consecutive daily injections. HDBH comprised 144mg/day (48mg tid). The main outcome measures were: 1) vertigo class, pure tone average (PTA), speech discrimination score (SDS) and Functional Level Score (FLS) according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; 2) complete and substantial vertigo control according to the Kaplan-Meier survival method. RESULTS: Sixty two patients completed the 24-month follow-up. A complete vertigo control was achieved in 14 patients (44%) from Group A and in 22 patients (73.3%) from Group B, statistically significant (p=0.01). Complete vertigo relief is also significant according to the Kaplan-Meier method: p=0.027, log rank test. Substantial vertigo control was obtained in 21 patients (65.6%) in Group A and 27 patients (90%) in Group B. The difference is statistically significant, p=0.02. The difference is significant according to the Kaplan-Meier method: p=0.035, log rank test. No significant differences between hearing levels and tinnitus scores were demonstrated between the groups. CONCLUSIONS: Our preliminary results demonstrate that complete and substantial vertigo control is significantly higher in patients treated with a combination of HDBH and ITD.

Betahistine reduces postoperative nausea and vomiting after laparoscopic gynecological surgery.

BACKGROUND: Patients undergoing laparoscopic gynecological surgery are at high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of ondansetron plus betahistine with that of ondansetron alone in this patient population. METHODS: In this randomized, double-blinded study, 168 patients were randomly allocated to receive placebo (O group) or betahistine 18 mg (OB group) orally 3 hours before surgery and 24 hours thereafter. In both groups, ondansetron 4 mg was administered at the end of surgery and 8 mg were added to an intravenous patient-controlled analgesia (IV-PCA) fentanyl solution. The primary outcome was complete response (no PONV and no rescue antiemetics) during the first 48 hours after surgery. The severity of nausea, pain score, and adverse events were assessed. RESULTS: The incidence of complete response was significantly higher in OB group than in O group (69% vs. 46%, P=0.004). The severity of nausea was lower in OB group than in O group during 30 minutes to 6 hours and 6 to 24 hours after surgery (P=0.001 and P<0.001). Pain score was similar between the groups. The incidence of dizziness was lower in OB group than in O group (13% vs. 40%, P < 0.001). Six patients (7%) in OB group and 15 patients (18%) in O group required early IV-PCA discontinuation, primarily because of PONV and/or dizziness (P=0.038). CONCLUSIONS: Compared to ondansetron alone, ondansetron plus betahistine was more effective to prevent PONV and dizziness in high-risk patients undergoing laparoscopic gynecological surgery.

Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial.

Migrainous vertigo is a common cause of dizziness presenting to an otorhinolaryngology/otoneurology clinic. Although it causes a substantial burden to the individual and society there are no randomized controlled trails on prophylactic medication for this condition. Flunarizine, a calcium channel blocker has been used effectively in both migraine and vestibular conditions. This randomized control trial was undertaken in a tertiary academic referral center to evaluate the efficacy of flunarizine in patients with migrainous vertigo when compared to non-specific vestibular treatment of betahistine and vestibular exercises. The effect of flunarizine on two particularly disabling symptoms of vertigo and headache was studied. A total of 48 patients who were diagnosed with definitive migrainous vertigo completed the study of 12 weeks duration. Patients in arm A received 10-mg flunarizine daily along with betahistine 16 mg and paracetamol 1 gm during episodes, and arm B received only betahistine and paracetamol during episodes. Symptom scores were noted at the start of the study and at the end of 12 weeks. Analysis of the frequency of vertiginous episodes showed a significant difference between arm A and arm B (p = 0.010) and improvement in severity of vertigo between the two groups (p = 0.046). Headache frequency and severity did not improve to a significant degree in arm A as compared to arm B. The main side effects were weight gain and somnolence and this was not significantly different between the two groups. Flunarizine (10 mg) is effective in patients with migrainous vertigo who suffer from considerable vestibular symptoms.

Meta-analysis of clinical studies with betahistine in Ménière's disease and vestibular vertigo.

We present a meta-analysis of 12 double-blind, randomized, placebo-controlled clinical studies with betahistine in patients suffering from vestibular vertigo or Ménière's disease, based on both published and unpublished data. The clinical endpoint we used was the investigator's overall opinion on the response to treatment of the vertigo symptoms, after at least 1 month of treatment. We introduce a new effect parameter, the odds of a favorable treatment outcome, with the odds ratio as measure to compare the responses of betahistine and placebo patients. For each study a separate odds ratio was estimated (the study-specific odds ratio). All but one of the study-specific odds ratios were >1.0, meaning that with the new effect parameter there was evidence of an effect of betahistine on vertigo symptoms in 11 of the 12 studies. Four of the 12 studies showed a statistically significant effect in favor of betahistine compared to placebo. The meta-analytical (i.e., average) odds ratio was 2.58 (95% confidence interval 1.67-3.99), a statistically significant result. This means that on average, the likelihood of a favorable outcome is almost two times higher for patients treated with betahistine than for placebo-treated patients. Sub-analyses conducted for patients with Ménière's disease on one hand and with vestibular vertigo on the other hand also yielded statistically significant results. For Ménière's disease, the meta-analytical odds ratio was 3.37 (95% CI 2.14-5.29); for vestibular vertigo, the odds ratio was 2.23 (95% CI 1.20-4.14). Our meta-analysis supports the therapeutic benefit of betahistine on vertiginous symptoms in both Ménière's disease and vestibular vertigo.

Reabilitação vestibular com realidade virtual na doença de Ménière / Vestibular rehabilitation with virtual reality in Ménière's disease

A tecnologia de realidade virtual fornece uma grande variedade de estímulos que geram conflitos sensoriais em diferentes níveis de dificuldades e em ambiente seguro. OBJETIVO: Verificar o efeito de um programa de reabilitação vestibular do equilíbrio corporal com estímulos de realidade virtual em pacientes com doença de Ménière. Forma de estudo: Estudo clínico observacional. MÉTODO: Quarenta e quatro pacientes, com idade entre 18 e 60 anos e doença de Ménière definida, distribuídos em dois grupos - experimental (GE) e controle (GC) - fizeram uso de betaistina e dieta alimentar; o grupo experimental foi submetido adicionalmente a 12 sessões de reabilitação com realidade virtual da BRU TM. Os pacientes responderam ao Dizziness Handicap Inventory (DHI), à escala analógica de tontura e realizaram a posturografia com realidade virtual antes e após a intervenção. RESULTADOS: Após a intervenção, o GE apresentou valores significantemente menores do DHI (p < 0,001) e da escala analógica de tontura (p = 0,012) e valores significantemente maiores da área do limite de estabilidade (p = 0,016), em comparação com o GC. CONCLUSÃO: A reabilitação do equilíbrio corporal com estímulos de realidade virtual é eficaz na melhora da tontura, da qualidade de vida e do limite de estabilidade de pacientes com doença de Ménière.

Virtual reality technology can provide a wide range of sensory stimuli to generate conflicts of varying degrees of complexity in a safe environment. OBJECTIVE: To verify the effect of a virtual realitybased balance rehabilitation program for patients with Menière's disease. METHOD: This observational clinical study included 44 patients aged between 18 and 60 years diagnosed with Menière's disease submitted to a controlled randomized therapeutic intervention. The case and control groups took betahistine and followed a diet. Case group subjects underwent 12 rehabilitation sessions with virtual reality stimuli in a Balance Rehabilitation Unit (BRU TM). Patients were assessed based on DHI scores, the dizziness visual analogue scale, and underwent posturography with virtual reality before and after the intervention. RESULTS: After the intervention, the case group showed significantly lower scores in DHI (p < 0,001) and in the dizziness visual analog scale (p = 0.012), and had significantly greater limit of stability areas (p = 0.016) than controls. CONCLUSION: Virtual reality-based balance rehabilitation effectively improved dizziness, quality of life, and limit of stability of patients with Menière's disease.