Inhibitory effect of betahistine on polysynaptic neurons in the lateral vestibular nucleus

Summary Effects of betahistine, an antivertigo drug, were examined on the lateral vestibular nucleus (LVN) neurons of cats anesthetized with -chloralose. Spike generation of monosynaptic LVN neurons elicited by vestibular nerve stimulation remained unaffected with intravenous administration of betahistine up to 5 mg/kg and with iontophoretic application of the drug up to 200 nA. In contrast, the spike generation of polysynaptic I neurons in the LVN was dose-dependently inhibited by intravenous as well as iontophoretic application of betahistine. These results suggest that small doses of betahistine more selectively interfere with synaptic transmission in the polysynaptic I neurons than in the monosynaptic neurons.     

The effect of betahistine on vestibular habituation: comparison of rotatory and sway habituation training

This study was designed to investigate the effect of histaminergic agonists and antagonists on the acquisition of vestibular habituation. The experimental animals, pigeons, were subjected to unilateral rotatory and sway habituation training sessions. The habituation of postural reflexes and post-rotatory head nystagmus was assessed. Vestibular habituation in the control group was achieved by adopting the kinetic reflex posture after approximately 9 training sessions, and after 10 and 14 training sessions, respectively for 50% reduction of the total number of beats (TNB) and the duration of post-rotatory head nystagmus. In the sway adaptation test control pigeons needed nearly 15 training sessions while pigeons receiving betahistine adapted after approximately 8 sessions. Administration of histamine and, most notably, betahistine accelerated the process, while both H1 and H2 antagonists (clemastine, cimetidine) tended to retard it, indicating a less significant contribution of H2 receptors. The cholinergic agent physostigmine strongly retarded habituation while the anticholinergic agent scopolamine markedly accelerated it. In addition the adrenomimetic agent ephedrine also accelerated habituation while the adrenolytic agent droperidol retarded reduction of nystagmus beats. The results indicate that histaminergic receptors play a significant role in the vestibular habituation mechanism but are intricately involved with other types of receptors. Betahistine is clearly the agent of choice for attenuating vestibular effects.     

Double-blind,randomized, multicenter study comparing the effect of betahistine and flunarizine on the dizziness handicap in patients with recurrent vestibular vertigo

OBJECTIVE: The aim of this double-blind, randomized, multicenter study was to compare the efficacy of betahistine dihydrochloride (BH) and flunarizine (FL) using the Dizziness Handicap Inventory (DHI), a validated self-assessment questionnaire that has not previously been used in a clinical trial to evaluate antivertigo drugs. MATERIAL AND METHODS: Patients with recurrent vertigo of peripheral vestibular origin and who were severely handicapped by vertigo were randomized to an 8-week course of treatment with oral BH 48 mg daily or oral FL 10 mg daily. The efficacy endpoints were the total DHI score and the physical, functional and emotional subscores. RESULTS: Fifty-two patients completed the study. After 8 weeks of treatment the mean total DHI score and the physical subscore were significantly lower in the BH group compared to the FL group (7.5 and 3.6 points, respectively). The mean total DHI score as well as the three subscores decreased significantly after 4 and 8 weeks in both treatment groups. CONCLUSION: This study showed that at 8 weeks BH is significantly more effective than FL in terms of improving the total DHI score and the physical subscore. It was also established that the DHI is a useful and reliable method for evaluating the efficacy of antivertigo drugs.     

Effect of betahistine dihydrochloride on induced vestibular nystagmus: a double blind study

The effect of betahistine on vestibular nystagmus induced by means of a torsion swing was tested in 10 subjects. Each individual received, in a randomized double-blind study, 3 different single oral dosages of betahistine (8, 16 and 32 mg) on 3 different occasions. Electronystagmographic tracings were taken at different time-intervals after drug intake. At 3-4 hours after a dose of 8 mg betahistine the nystagmus duration was reduced by 35%, after 16 mg betahistine by 48% and after 32 mg betahistine by 59% (mean values). All these differences in dose-response are highly significant (P less than 0.0005). It can be concluded from these results, that a dose of 3 X 8 mg or 3 X 16 mg betahistine daily will be efficacious in maintenance treatment of vertigo, and a dose of 3 X 24 mg betahistine daily will have even more effect.     

The effect of the endolymphatic subarachnoid shunt operation on vestibular function.

Preoperative vestibular function was studied in 56 patients undergoing the endolymphatic subarachnoid shunt procedure for Ménière's disease by electronystagmographic recording of bithermal air caloric stimulation. Fifty-two percent had normal vestibular function while 48% had a reduced vestibular response on the affected side using 20% difference as being significant. Best results of surgery with relief of vertigo were found in the group of patients with normal preoperative vestibular function (82%) while the group with reduced vestibular response preoperatively showed 63% with a good result. Postoperatively, 81% had a reduced vestibular response in the operated-on ear with 62% obtaining relief of vertigo. In patients with normal vestibular function postoperatively excellent relief of vertigo was obtained. Of patients with normal vestibular function preoperatively, 69% developed a reduced vestibular response postoperatively with only 55% having relief of vertigo. The results of surgery could be predicted more accurately using the results of vestibular function tests than audiometric data. It appears that for best results the endolymphatic subarachnoid shunt procedure should be performed early in the course of Ménière's disease when hearing is fluctuating and vestibular function is normal.     

Smad5 基因敲除对小鼠前庭功能的影响

目的 观察Smad5基因敲除对小鼠前庭功能的影响,探讨Smad5基因是否为前庭功能相关基因.方法 参照Petrosini报告的动物失衡行为评分方法,观察28只实验小鼠的平衡状态.对头偏,躯干卷曲,肢体外展,强迫环形运动,头震等五项前庭失衡症状进行综合评分.20只Smad5基因缺陷小鼠(+/-)和15只野生鼠(+/+)进行颈髓硬膜表面短声诱发电位检测前庭功能.结果 动物失衡行为评分方法 进行综合评分,两组实验小鼠得分均为0分,表明两组动物在平衡功能粗测上无明显异常.颈髓硬膜表面短声诱发电位(CDM-CEP)检测Smad5(+/-)小鼠峰值潜伏期在85 dB SPL、95 dB SPL和105 dB SPL分别为6.85±0.23 ms、6.78±0.20 ms和6.70±0.43 ms.Smad5(+/+)小鼠峰值潜伏期在85 dB SPL、95 dB SPL和105 dB SPL分别为6.15±0.23 ms、6.12±0.20 ms和6.37±0.43 ms.结论 Smad5基因敲除导致CDM-CEP的潜伏期延长,表明Smad5基因敲除对小鼠的前庭功能有一定影响.     

Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology

Objective

The aim of this study was to evaluate the efficacy of a therapeutic pathway for vestibular migraine (VM) and complex dizziness of undetermined etiology (CDUE) with caffeine cessation and pharmacotherapy.

Study Design

This study is a retrospective chart review.

Intervention(s)

Patients were recommended to stop intake of caffeine and other putative migraine-triggering agents. Pharmacotherapy was initiated with nortriptyline or topiramate if symptoms persisted despite diet modification.

Main Outcome Measure

Self-reported dizziness is the main outcome measure.

Results

Vestibular migraine and CDUE were considered contributing factors to dizziness in 34 and 10, respectively, of 156 patients. Fourteen percent of patients reported improvement in symptoms upon caffeine cessation, whereas 46% of patients reported a reduction in dizziness after nortriptyline therapy (P = .007). Topiramate reduced symptoms in 25% of patients. In total, 75% of VM patients and 56% of patients with CDUE received sufficient benefit from this therapeutic pathway to not progress to other treatments.

Conclusions

Vestibular migraine and CDUE can be treated effectively with a therapeutic pathway consisting of caffeine cessation followed by pharmacotherapy.     

The effect of intra-tympanic dexamethasone on the vestibular function in patients with recurrent vertigo

Conclusion: The low clinical efficacy of the treatment for patients included in this work correlates with no noticeable effect on the vestibular function. Objective: To assess follow-up in patients with idiopathic and secondary Ménière’s disease after treatment with intra-tympanic dexamethasone and correlate clinical findings with changes in the vestibular-ocular reflex elicited after stimulation of each of the six semicircular canals. Methods: This is a single center retrospective review of patients presenting the clinical symptomatology of Meniérè’s disease treated with intra-tympanic dexamethasone. An audiometric evaluation was performed in each patient before and after treatment. The study cohort was divided into two groups: those evaluated after a short period of time and after a long period of time. Results: The study included 30 patients, mean age = 61 years. Differences in mean pure-tone average before and after treatment were non-significant for both treated (0.61 dB, p = 0.723) and untreated (0.59 dB, p = 0.609) ears. Vestibular–ocular reflex gain averages in the treated ear after treatment were 0.73 (superior semicircular canal), 0.86 (horizontal semicircular canal), and 0.69 (posterior semicircular canal). The gain did not vary significantly in the Superior (p = 0.194), the Horizontal (p = 0.646), or the Posterior Semicircular Canal (p = 0.820). Similar were obtained for the untreated ear.     

Effects of betahistine on patient-reported outcomes in routine practice in patients with vestibular vertigo and appraisal of tolerability: experience in the OSVaLD study

This was a 3-month multicentre, open-label post-marketing surveillance study of betahistine (24 mg b.i.d. or 16 mg t.i.d.) in patients with vertigo of peripheral vestibular origin. Study endpoints comprised on-treatment changes in the Dizziness Handicap Index (DHI), Hospital Anxiety and Depression Score (HADS) and the Short-Form (SF)-36v2. Total DHI score improved 37.2 points (of a 100-point scale) following betahistine treatment. Corresponding improvements occurred in all three DHI scale domains (all p < 0.001 vs baseline). Betahistine therapy was also accompanied by progressive, significant improvements in both HADS-A and HADS-D scores (p < 0.001), and improvements in the distribution profiles of anxiety and depression scores. Significant improvements in the Physical Component Summary and Mental Component Summary scores of the SF-36v2 were recorded during betahistine treatment. Betahistine was generally well tolerated. A total of 76 adverse drug reactions (ADRs) were recorded in 49 patients (2.4%), of which 75 were classified as mild or moderate and 54 were possibly related to betahistine. ADRs led to study drug discontinuation in 17 patients. These data illustrate that treatment with betahistine 48 mg/day in patients with recurrent peripheral vestibular vertigo is associated with improvements in objective measures of health-related quality of life and satisfactory tolerability.     

Influence of cochlear implantation on the vestibular function

The aim of the present study was to examine the influence of cochlear implantation on vestibular function. The function of the horizontal semicircular canal, the saccular function, and the incidence of vestibular symptoms were assessed before and after cochlear implantation. Twenty unilaterally cochlear implant patients were evaluated preoperatively, 1 and 6 months postoperatively, with caloric testing with electronystagmography (ENG) recordings and vestibular evoked myogenic potentials (VEMP) testing. A medical history was taken from every subject, noting the presence or absence of vertigo before and after the operation. A possible correlation between the appearance of postoperative vertigo and age, sex, implant side, preoperative caloric results and VEMP status, and postoperatively recorded changes in caloric and VEMP testing was also investigated. A statistically significant difference was found in the percentages of canal paresis (p = 0.01) and the percentages of VEMP waveform absence (p = 0.002) between the repeated measurements in the implanted side, whereas in the non-implanted side no difference was (p > 0.05) found. Four patients complained of postoperative vestibular symptoms. In three of them the symptoms lasted less than 6 months postoperatively, but the fourth patient was still dizzy 6 months after cochlear implantation. No correlation was found between the above-mentioned factors and the occurrence of postoperative vertigo. In conclusion, although changes of the peripheral vestibular function of the implanted side were recorded in our patients, permanent vertigo was rare. Predictive factors for the occurrence of postoperative vestibular symptoms could not be identified.