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Objective: Irritability is an emotional stress symptom that causes or exacerbates dizziness. Antidepressants may be helpful for some conditions that are accompanied by irritability; however, they do not completely inhibit irritability. Yokukansan (YKS), a traditional Japanese herbal medicine, has been used for neurosis, insomnia, and children's irritability and night crying. The study investigated the efficacy of YKS in nystagmus in patients with chronic dizziness and irritability., Methods: Twenty-two cases with chronic dizziness and irritability were reviewed retrospectively. The patients were divided into two groups: control patients (0-7 days of treatment) and YKS-treated patients (YKS cases; >7 days of treatment). Dizziness before and during (after, in the controls) YKS treatment was evaluated by scoring the nystagmus intensity on a 5-point scale. The average scores were calculated within a maximum of 6 months before and during or after treatment. The normalized scores were also calculated. The optimal treatment regimen was calculated via receiver operating characteristic (ROC) curve analysis., Results: There were six control cases (1 male, 5 females; mean age: 59.5 years). There were 16 YKS cases (3 males, 13 females; mean age: 61.8 years). While the group mean nystagmus intensity scores significantly decreased from 1.18 to 0.73 in the YKS cases, it did not change in the control cases. The group mean of the normalized nystagmus intensity scores during treatment was 0.73 in the YKS cases. The results of the ROC curve analysis indicated the optimal cut-off period of the YKS treatment was 10 days., Conclusion: The oral administration of YKS for more than 10 days was optimal. The treatments with YKS could be a good option for the treatments of vertigo., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To compare the efficacy of gentamicin and steroids in patients with Meniere's disease (MD)., Methods: The study protocol was structured in accordance with the Population, Intervention, Comparison and Outcome (PICO) framework. We used "Endnote" (Thomson ResearchSoft; Stanford, Connecticut, the United States) to retrieve database documents. A systematic literature search of Web of Science and PubMed Database through May 2020 was conducted using specific search terms. Inclusion criteria, exclusion criteria, vertigo improvement, and exact hearing changes were defined. Review Manager 5.3 (Cochrane) was used for data analysis., Results: A total of 80 articles were searched from Web of Science and 23 articles were searched from PubMed database. After further reviewing the specific points of the inclusion criteria and exclusion criteria, 9 papers were finally selected. Intratympanic gentamicin (ITG) was superior to intratympanic steroid (ITS) in reducing the number of vertigo attacks (odds ratio (OR) 3.08, 95% confidence intervals (CI) [2.05-3.65]), probability (P) < 0.01). As for hearing improvement, we did the analysis twice. With all the studies included, the odds of hearing improvement (by "x") was 0.31 among patients receiving gentamicin compared to those treated by steroids (OR 0.31, 95% CI [0.16-0.61]). But after removing one study with outlying results from the analysis, this effect disappeared. Hearing loss of ITG and ITS was not statistically significant (P = 0.29)., Conclusions: ITG is superior to ITS in reducing the number of vertigo attacks in the treatment of MD (P < 0.01); the impact on hearing is more heterogeneous in the studies. Overall, there was no clear difference between ITG and ITS on hearing improvement and on hearing loss., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the efficacy of a 4-week transtympanic dexamethasone perfusion using the Silverstein MicroWick TM in patients with Ménière's disease., Materials and Methods: A self-reported questionnaire was designed and sent to patients who underwent transtympanic dexamethasone perfusion using the Silverstein MicroWick TM from January 2017 to December 2020. A retrospective chart review was conducted to gather demographic and audiological data of those who responded., Results: Forty respondents were separated into Group 1 (n = 34), who required no further procedure, and Group 2 (n = 6), who required additional procedure for Ménière's disease. In Group 1, 50% reported subjective improvement in tinnitus, 59% in aural fullness, 79% in vertigo, and 21% in hearing loss after the MicroWick TM treatment. A statistical analysis of the scores revealed that the improvement in aural fullness and vertigo met significance (p = 0.03 and p = 0.002, respectively). In Group 2, no significant change was seen in their symptoms. Audiological data showed no significant change in the pure tone average or the word recognition score after the treatment., Conclusion: Transtympanic dexamethasone perfusion using the Silverstein MicroWick TM is a well-tolerated treatment option for patients with Ménière's disease. Our survey data suggest its significant efficacy in reducing aural fullness and vertigo attacks in these patients. Prospective studies will be conducted to further establish its potential role in successfully managing patients with Ménière's disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of topiramate and flunarizine hydrochloride in the prophylactic treatment of vestibular migraine prophylaxis. Methods: 47 patients with confirmed or probable vestibular migraine（VM） treated at the vertigo clinic of our neurology department from August 2020 to April 2021 were reviewed, and 42 patients were finally included. They were divided into topiramate group （n=22） and flunarizine hydrochloride group （n=20）. The two groups were treated with topiramate 50 mg daily and flunarizine hydrochloride 10 mg daily, respectively. The visual analogue scale, vertigo duration, vertigo frequency, and Dizziness Handicap Inventory （DHI） scores of patients with VM before and 3 months after treatment were compared. The anxiety screening scale （GAD-7） and depression screening scale （PHQ-9） were recorded to assess the improvement of patients' anxiety and depression, and the occurrence of adverse events. Results: Topiramate and flunarizine hydrochloride effectively reduced vertigo intensity, vertigo duration, and vertigo frequency in VM patients （ P <0.05）. Meanwhile, total DHI score, DHI physical （DHI-P）, DHI emotional （DHI-E）, DHI functional （DHI-F）, PHQ-9 and GAD-7 were significantly decreased（ P <0.05）. Furthermore, topiramate was superior to flunarizine hydrochloride in reducing vertigo intensity, vertigo duration, vertigo frequency, DHI-P, and DHI-F, while there was no significant difference between two drugs in improving patients' mood（ P >0.05）. No serious adverse events were reported in either group. Conclusion: This study suggests that topiramate and flunarizine hydrochloride are safe and effective in the prevention of VM, and the daily dose of topiramate 50 mg is superior to the daily dose of flunarizine hydrochloride 10 mg. However, there was no significant difference between the two drugs in terms of mood improvement., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Ménière disease is a disorder of the inner ear, characterized by rotational vertigo, hearing loss, tinnitus, and vegetative symptoms. The aim of the present research is to examine the effectiveness of betahistine and piracetam in the reduction of vertigo attacks in Ménière disease. To verify our hypothesis, 105 (31 male and 74 females, mean age [standard deviation], 57.4 [11.05]) adult patients with definite Ménière disease were enrolled in this investigation. Beside the analysis of the hospital records, the subjective complaints of the patients and the completed vertigo diaries were taken into consideration too. The statistical analysis was completed using the IBM SPSS version 24 software. Retrospective analysis, including a 12 years period was conducted. Based on our results, betahistine was successful in the reduction of attacks. Statistically significant decrease was achieved in frequency of dizziness ( P = .000331) and vertigo ( P < .00001) and in the duration of them ( P = .000098), although in the mean power of them was not ( P = .0887). The mean dose in the symptomatic treatment was determined as 87.5 ± 27.2 mg per day; however, there was no connection detected between the dose of the agent and the effectiveness of the symptomatic control. By using dual therapy (betahistine and piracetam), vertigo episodes appeared significantly less often ( P = .027, Odds ratio: 4.9, 95% confidence interval: 1.2-20.2). Finally, it can be concluded that betahistine is effective in Ménière disease, but the daily dose of it should be set up for every patient individually. The advantage of the dual therapy was also confirmed.

The number of older people has been increasing over recent decades in Western populations. Dizziness, imbalance, and vertigo constitute some of the most common complaints in older patients, and risk of falling is the most frequent and worrying consequence. It has been reported that 15-20% of the adult population experiences these debilitating symptoms. Among the diseases that may be associated with vertigo, the three classes of otological, central, and functional (psychological) dizziness may be distinguished. Overall, vestibular disorders account for 48% of vertiginous complaints in the older population. The main focus of this article is to review the forms of pharmacotherapy for vertigo, especially with regard to older patients, who may be treated simultaneously with other drugs for different comorbidities. Interactions with other drugs should be considered in the choice of a particular course of treatment. Moreover, overuse of pharmacotherapy for the management of vertigo in the elderly may prevent the development of the central compensatory mechanism that sustains both static and dynamic imbalance after a vertiginous crisis. In the majority of patients, vestibular and physical rehabilitation are strongly advised and rarely contraindicated., (© 2021. The Author(s).)

Background: Ménière's disease (MD), characterized by episodic vertigo attacks and fluctuating progressive hearing loss, is treated by low-dose intratympanic gentamicin (ITG) injections. Whether ITG causes hearing loss is controversial, and knowledge about its effects on the contralateral hearing and vestibular function is lacking., Aims/objectives: We aimed to evaluate the effect of ITG on bilateral auditory and otolith organ function in patients with unilateral refractory MD., Material and Methods: The data of 30 patients was collected, including history, and pure tone audiometry and vestibular-evoked myogenic potentials (VEMPs) results before and one month after ITG treatment. Changes in vertigo were assessed at a two-year follow-up., Results: One month after ITG injection, auditory thresholds between 125 Hz and 8 kHz on the injection side remained unchanged but have improved on the contralateral side at 125 Hz, 250 Hz, 1 kHz. The cervical and ocular VEMP solicitation rates on the injection side were lower than before the injection. Two years after treatment, vertigo was improved in 88.5% and complete controlled in 76.7% patients respectively., Conclusions and Significance: The intractable vertigo of MD can be effectively controlled by ITG injection. This can improve the low and medium frequency hearing level in the contralateral ear, suggesting that it might help prevent contralateral MD occurrence.

Objective: The aim of this study was to report relief of optokinetic-triggered vertigo (OKTV) with low-dose gabapentin in three patients with periodic vestibulocerebellar ataxia [episodic ataxia type 4 (EA4); OMIM 606552]., Methods: Clinical observations and analysis of video-recorded eye movements were used before and after gabapentin., Results: Gabapentin relieved vertigo of all three treated patients with EA4, particularly during activities that typically would induce vertiginous symptoms. Two patients reported 8-12 hours of sustained relief after the first 100 mg dose. One has benefited from 100-200 mg TID for 7 years. Video analysis of nystagmus revealed improved target tracking on smooth pursuit and a steadier gaze hold., Conclusions: Gabapentin effectively relieved the optokinetic-triggered vertigo in our patients with EA4. Mechanisms are postulated in terms of known tight gabapentin binding to the Purkinje cell voltage-gated calcium channel. The observations may offer insight into this rare disease's neuropathology. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Vertigo is not itself a disease, but rather a symptom of various syndromes and disorders that jeopardize balance function, which is essential for daily activities. It is an abnormal sensation of motion that usually occurs in the absence of motion, or when a motion is sensed inaccurately. Due to the complexity of the etiopathogenesis of vertigo, many pharmacological treatments have been tested for efficacy on vertigo. Among these drugs, cinnarizine, usually given together with dimenhydrinate, appears to be the first-line pharmacotherapy for the management of vertigo and inner ear disorders. Based on these considerations, the present non-interventional study aimed to investigate the clinical efficacy and tolerability of a fixed combination of cinnarizine (20 mg) and dimenhydrinate (40 mg) in patients suffering from vertigo-related symptoms. To this end, we enrolled 120 adults-70 males, and 50 females-with an average age of 64 years. Before beginning pharmacological treatment, all patients were screened for the intensity of vertigo, dizziness, and concomitant symptoms through the Visual Scale of Dizziness Disorders and Dizziness Handicap Inventory scales. At the end of the anamnestic evaluation, patients received the fixed-dose combination of cinnarizine (20 mg) plus dimenhydrinate (40 mg) 3 times daily, for 60 days. The results of this study provide further insight regarding the efficacy of the fixed combination when used to reduce symptoms of vestibular vertigo of central and/or peripheral origin, after both the 15- and 60-day therapies. Independent of the type of vertigo, the fixed combination was able to reduce dizziness- and vertigo-associated symptoms in more than 75% of all patients treated, starting from 15 days of therapy, and improving 60 days after starting the therapy. Interestingly, we also found differences between male and female patients in the framework of the pharmacological effects of therapy. This study provides further details concerning the therapeutic efficacy of the fixed combination of cinnarizine and dimenhydrinate, and also focuses attention on the possibility that these drugs could act in a gender-specific manner, paving the way for further research.

Background: Vertigo is a sense of movement or rotation of the patient's own or an external object. At present, western medicine treatment such as vestibular suppressant medications commonly used in clinical practice are ineffective and have adverse reactions. In traditional Chinese medicine, Linggui Zhugan Decoction (LZD) was used by doctors to warm yang for resolving fluid retention, strengthen the spleen and clear away dampness, with significant effect. Recently, some clinical studies have also shown that LZD has reliable effect in treating peripheral vertigo, but there is no systematic evidence. Therefore, this study aims to objectively evaluate the efficacy and safety of LZD in the treatment of peripheral vertigo., Methods: Eight electronic databases will be searched from inception to August 2020 by 2 independent researchers, in order to collect qualified randomized controlled trials (RCTs) on the LZD treatment for peripheral vertigo. The therapeutic effects according to Clinical efficacy will be adopted as the primary outcomes. RevMan V.5.3 software will be used for the data synthesis and the Cochrane's risk of bias assessment tool will be used to assess the risk of bias., Results: This review will conduct a high-quality synthesis on present evidence of LZD for peripheral vertigo., Conclusion: The conclusion of the study will indicate whether LZD is an effective treatment for peripheral vertigo by providing updated evidence., Prospero Registration Number: PROSPERO CRD 42021238817., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Vertigo is a well-known presenting complaint common in the main care offices as well as departments. It is also regarded as a symptom of vestibular dysfunction and has been expressed as a feeling of motion, specifically rotational motion. As patients grow older, vertigo also becomes a commonly presenting complaint. The current study will carry out a widespread systematic review to estimate clinical therapeutic effects of gastrodin in combination with betahistine on vertigo., Methods: We will systematically search different databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI), and WanFang to collect the randomised controlled studies that evaluate the efficiency of gastrodin and betahistine in treating patients with vertigo from their inception to November 2020. However, only studies in English or Chinese will be included. Two authors will independently perform selection, data extraction, and assessment of risk of bias for the included papers. Accordingly, any disagreements between the independent authors will be addressed via discussion or by consulting a third author when needful. Additionally, we will use RevMan 5.3 software to perform the data synthesis., Results: The efficiency of gastrodin and betahistine in treating patients with vertigo will be systematically evaluated., Conclusions: The current study aims to stipulate more consistent substantiation to explore whether gastrodin combined with betahistine is more effective for the treatment of vertigo., Registration Number: DOI 10.17605/OSF.IO/HQTZA (https://osf.io/hqtza/)., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Ménière's Disease (MD) is a chronic condition where patients suffer recurrent vertigo attacks. Evidence for treatment concepts are to this date low., Aims/objective: To evaluate the therapeutic effect of intratympanic lidocaine injections to reduce the number of attacks., Methods: Twenty patients diagnosed with definitive MD that were treated with 34 intratympanic lidocaine injections were included. Main outcome measures were the number of vertigo attacks in the previous four weeks, the attack free period and the subjective improvement of the condition., Results: Mean follow up after first lidocaine injection was 25.3 months (±22.2; range 1.9-79.7). Patients expressed subjective improvement in overall situation, vertigo, and aural fullness. The number of vertigo attacks before each assessment decreased from 7.1 (±5.9; range 2-20) per months at baseline to 1.9 (±3.8; range 0-15). 25% of the patients suffered no further attacks, the other patients had an average attack free period of 7.8 months (±15.4; range 0.2-58.4). Hearing thresholds remained unaffected. Repetitive injections proved effective., Conclusion and Significance: Intratympanic lidocaine is an effective nonsurgical and non-ablative therapy for MD. When patients experience an increase of attacks repetitive injections promise improvement.

This study aims to explore the long-term efficacy of triple semicircular canal plugging (TSCP) in the treatment of intractable ipsilateral delayed endolymphatic hydrops (DEH), so as to provide an alternative therapy for this disease. Forty-eight patients diagnosed with ipsilateral DEH referred to vertigo clinic of our hospital between Dec. 2010 and Dec. 2017, were included in this study for retrospective analysis. All patients were followed up for 2 years. Vertigo control and auditory functions were measured and analyzed. Pure tone audiometry, caloric test, and vestibular evoked myogenic potential (VEMP) were performed in two-year follow-up. Forty-five patients who accepted intratympanic gentamicin (26.7 mg/mL) twice given one week apart were selected as a control group. The total control rate of vertigo in TSCP group was 97.9% (47/48) in the two-year follow-up, with complete control rate of 83.3% (40/48) and substantial control rate of 14.6% (7/48). The rate of hearing loss was 22.9% (11/48). The total control rate of vertigo in intratympanic gentamicin group was 80.0% (36/45), with complete control rate of 57.8% (26/45) and substantial control rate of 22.2% (10/45), and the rate of hearing loss was 20.0% (9/45). The vertigo control rate of TSCP was significantly higher than that of intratympanic gentamicin (χ 2  = 6.01, p < 0.05). There was no significant difference of hearing loss rate between two groups. (χ 2  = 0.12, p > 0.05). TSCP, which can reduce vertiginous symptoms in patients with intractable ipsilateral DEH, represents an effective therapy for this disorder.

Objective: We provided diagnostic and therapeutic strategies for Meniere's disease in accordance with Japanese Clinical Practice Guideline of Meniere's disease and delayed endolymphatic hydrops 2nd ed. Tokyo: Kanehara Shuppan; 2020 edited by the Japan Society for Equilibrium Research., Methods: The Committee for Clinical Practice Guidelines was entrusted with a review of the scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment for Meniere's disease were produced, and the literature according to each of them including CQ was searched. The recommendations are based on the literature review and the expert opinion of a subcommittee., Results: Diagnosis criteria of Meniere's disease are classified into Meniere's disease with typical cochlear and vestibular symptoms, and atypical Meniere's disease with either cochlear symptoms or vestibular symptoms. Treatment of Meniere's disease was composed of lifestyle changes, medications such as anti-vertigo drugs and diuretics, middle ear positive pressure treatment, and selective destruction of the vestibule., Conclusion: Meniere's disease is diagnosed based on clinical histories and examination findings after processes of differential diagnosis. Treatment option of the disease should be selected in order of invasiveness, according to the severity of the disease and the response to each treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Background: This study aimed to compare the therapeutic efficacy of dimenhydrinate and metoclopramide in patients with nausea and vertigo., Methods: A prospective, double-blind, randomized clinical trial was performed on patients who presented to the emergency department (ED) with nausea and vertigo in the six month period between Nov 1st 2012 and May 1st 2013. Adult patients who were 18 to 65 years old presenting to the ED with nausea and vertigo or motion sickness were included in the study. A total of 200 patients were divided into 2 groups who were admitted to ED with complaints of vertigo accompanied by nausea. In the first group, 50 mg dimenhydrinate and 10 mg metoclopramide infusions were given intravenously for 15 min. The efficacy of treatment was measured by using a 10 mm Visual Analog Scale (VAS) performed at 0, 15 and the 30th minute. The primary outcome variable was a reduction in vertigo intensity documented on the VAS at the 30th minute after medication administration., Results: A total of 200 patients were included in the randomization (n=100 in both groups). The baseline vertigo VAS scores were 7.57±1.42 in the dimenhydrinate (DMT) group and 7.27±1.40 in the metoclopramide (MTP) group (p=0.09). In the 30th minute of treatment, the average vertigo VAS score was 2.46 ± 2.39 in the DMT group and 2.31±1.96 in the MTP group; no significant differences were detected between groups. The baseline nausea VAS scores were 7.62±1.48 in the DMT group and 7.45±1.27 in the MTP group (p=0.36). In the 30th minute of treatment the average vertigo VAS score decreased to 2.27±2.24 in the DMT group and 2.70±2.48 in the MTP group, no significant differences were detected between groups. No significant differences were detected between nausea VAS changes and vertigo VAS changes at 30th minutes of the treatment (p=0.06, p=0.85 respectively). Rescue medication need was similar in both treatment groups (p=0.94). No significant differences were detected about the side effects which are sedation (p=0.56) and hypotension (p=0.57)., Conclusions: In conclusion, this prospective, double-blind, randomized study showed that both DMT and MTP have similar efficacy in reducing nausea and vertigo symptoms in the ED., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients.

Introduction: The term Meniere disease (MD) gathers a set of rare diseases involving the inner ear characterized by episodic vertigo associated with fluctuating auditory symptoms. Five clinical subgroups of patients have been defined, including familial MD, autoimmune MD, and MD with migraine. The diagnosis is based on clinical criteria as no biomarker is available, but genetic factors have a significant contribution in familial and non-familial MD., Areas Covered: In this review, the authors summarize the pharmacological treatment for vertigo in MD, providing evidence from preclinical and clinical studies. However, evidence supporting the efficacy for betahistine, diuretics, and intratympanic administration of corticosteroids or gentamicin is limited., Expert Opinion: Randomized clinical trials should consider stratification by MD clinical subgroups. The treatment plan should be personalized according to the clinical subgroup, hearing stage, duration of the disease, vertigo attack profile, and comorbidities. The treatment should include therapeutic counseling, sodium-free diet, high-water intake, and a diary of vertigo attacks with symptoms during the episodes to improve phenotyping. Migraine or autoimmune comorbidities will also require pharmacotherapy. Genetic testing by exome/genome sequencing should be discussed with the patient for familial MD and individuals with an early onset for genetic counseling and future gene therapies.

Reversible splenial lesion syndrome (RESLES) is a clinico-radiological entity that defines a reversible lesion in the splenium of the corpus callosum (SCC) on magnetic resonance imaging (MRI). The clinical and radiological characteristics of RESLES are poorly defined and most RESLES literature is in the form of case reports. We reviewed the clinical and radiological data from 11 RESLES patients in order to more clearly describe the characteristics of this disorder in adults.Patients included in this study were diagnosed with RESLES from May 2012 to March 2018. We collected clinical, imaging, and laboratory data of 11 adult patients from Neurology Department of the Affliated Yantai Yuhuangding Hospital of Qingdao University. After analyzing various clinico-radiological features and laboratory parameters, including serum sodium, pathogen testing, cerebrospinal fluid (CSF) studies, electroencephalography (EEG), and MRI findings, we made a diagnosis of RESLES based on the criteria proposed previously by Garcia-Monco et al.Of the 11 patients, 7 (63.63%) were male and 4 (36.36%) were female, ranging in age from 24 to 62 years with an average age of 31.48 ± 11.47 years. Seven cases occurred in the months of winter and spring (December-March). The primary clinical symptoms were headache, seizure, disturbance of consciousness, mental abnormality, and dizziness. All 11 patients had lesions in the SCC and all the lesions disappeared or significantly improved on follow-up imaging that was done within a month of symptom resolution.We found 5 (45.45%) patients had a CSF opening pressure >180 mmH2O, in addition to elevated protein and(or) leukocytes levels in 3 (27.27%) patients. The serum sodium concentration in 6 (54.55%) patients was low (<137 mmol/L) and EEG showed nonspecific slowing in waves 4 (36.36%) patients.When we encounter clinical manifestations such as headache accompanied with mental symptoms, disturbance of consciousness or epilepsy, and brain MRI finds lesions of the corpus callosum, we should consider whether it is RESLES. In order to find out the possible cause of the disease, we should carefully inquire about the history of the disease, complete etiology examination, and CSF tests. Of course, it is one of the necessary conditions for the diagnosis that the lesions in the corpus callosum are obviously relieved or disappeared.

Introduction and Aim: Cinnarizine is indicated orally for treating vertigo associated with Ménière's syndrome and has a local anesthetic effect as well. The present study aims to develop an aural Cinnarizine mucoadhesive transfersomal gel to overcome the first-pass metabolism., Methods: Eighteen Cinnarizine transfersomes were prepared by the thin-film hydration technique using different types of phosphatidylcholine and edge activators in different ratios. Formulae were tested for their appearance, entrapment efficiency, and in-vitro drug release after eight hours. F1, F4, F7, F9, F10, and F12 were selected to be examined for particle size, polydispersity index, and zeta potential. According to the previous parameters, F1 and F10 were incorporated into gels using different polymers according to factorial design 23. The eight gels were tested for appearance, pH, mucoadhesion, spreadability, drug content, in-vitro drug release after eight hours, and rheology. The transfersomal gel F1A was subjected to FTIR analysis and in-vivo pharmacokinetic study., Results: The transfersomal dispersion colors were ranging between the white and yellow. Their EE % ranged from 64.36±1.985% to 94.09±1.74%, and their in-vitro release percentages were between 61.82±1.92% and 95.92±1.18%. Also, the vesicles PS ranged from 212.3±30.05nm to 2150±35.35nm, DI from 0.238±0.134 to 1±0.00 and zeta potential from -57.5±2.54 to +4.73±1.57 mV. The transfersomal gels showed pseudoplastic behavior, pH range of 5.5 to 8, a mucoadhesive force of 169.188±1.26 to 321.212±6.94 (dyne/cm 2 ×10 2 ), spreadability of 40 ±7.03mm to 138 ±3.77mm, and in-vitro drug release of 81.63±1.128% to 97.78±0.102%. The IR spectra of the (drug-excipients) physical mixture revealed that there were no shifts of incompatibility. The in-vivo pharmacokinetic study illustrated that [AUC] 0-24 of F1A was significantly higher than that of tablets at (P< 0.05), equivalent to 703.563±26.470 and 494.256±9.621ɲg.hr/mL respectively., Conclusion: The study revealed that Cinnarizine aural mucoadhesive targeted delivery provides an improved systemic bioavailability over the conventional oral route., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Abdelmonem et al.)

Purpose: The aim of our study is to investigate the effectiveness and safety of the treatment, based on vertigo diaries and pure tone audiograms., Methods: The complete medical documentation of 105 definite patients suffering from Ménière's disease was analyzed. In the studied group, nine patients were treated with intratympanic gentamycine. Long-term follow-up of the patients was carried out, using vertigo diaries, medical letters, anamnestic data, and pure tone audiograms. Audiometric results and vertigo complaints before and after treatment were contrasted using IBM SPSS V24 software., Results: Based on our analysis, vertigo attacks appeared significantly less often after gentamycine treatment [p < 0.001; Odds ratio 0.003 (95% CI 0.001-0.012)], which confirms the efficacy of the therapy. Pure tone stages before and after the application of gentamycine were contrasted using the Mann-Whitney U test. When comparing the audiometric results of long-term follow-ups by using the logistic regression, a statistically significant difference was observed between the treated and not treated groups [p = 0.001; Odds ratio 0.141 (95% CI 0.064-0.313)], and based on the survivorship curve hearing impairment was more common in the not treated group which also supports our results. Based on the non-parametric test, there was no significant difference (p = 0.84) between the pure-tone stages of the control group and of those treated with gentamycine., Conclusion: Our results indicate that intratympanic gentamycine is effective in controlling vertigo attacks, and there is no higher risk for hearing loss than in case of spontaneous progression of the disorder.

The present research was carried out with the objective to establish the clinical effect and safety of betahistine (48 mg daily), for the management of peripheral vestibular vertigo, in patients treated by primary care physicians in Colombia. An observational prospective cohort study was conducted including patients older than 15 years with clinical diagnosis of peripheral vestibular vertigo who were candidates to be treated with betahistine (48 mg daily). A sample size of 150 individuals was calculated, and weekly follow-ups were planned for 12 weeks. Rotatory movement sensation, loss of balance, and global improvement scale from 0 to 100 points were evaluated. Complete improvement was defined when the patient reached a level of 100 points. We calculated average weekly improvement, cumulative incidence of complete improvement, incidence rate of complete improvement, and the probability of complete improvement as a function of time. After the first week, the average improvement was 56.6 points (95% confidence interval [CI]: 50.4-62.7). At the end of week 12, it was 89.3 points (95% CI: 86.5-92.2). Sixty-one percent of the patients had achieved complete improvement at the end of the second week. After the sixth week, the percentage of cumulative improvement was 72%, and after 12 weeks of follow-up, the cumulative incidence of complete improvement was 73% (95% CI: 65%-80%). Based on the follow-up times, a complete improvement incidence rate of 16 cases per 100 people/week was calculated (95% CI: 13-19). We concluded that Betahistine (48 mg daily) has a positive effect, controlling the symptoms associated with benign paroxysmal vertigo, with an adequate safety profile.

Objectives: Vertigo in sudden sensorineural hearing loss (SSNHL) is hypothesized as an extension of the disease caused by the anatomical proximity of the cochlea and vestibule. The present study aimed to demonstrate the association of vestibular function test (VFT) results with SSNHL disease severity and prognosis., Materials and Methods: This study assessed clinical records of 263 SSNHL patients admitted to our hospital, between January 2010 and October 2017. Steroid treatment comprised high-dose intravenous dexamethasone (16 mg/d) or oral methylprednisolone (64 mg/d) for 4 days and tapered oral methylprednisolone for 8 days after discharge. Caloric tests were performed in all patients, and cervical vestibular-evoked myogenic potential (c-VEMP) and ocular VEMP (o-VEMP) tests were performed in 209 and 144 patients, respectively., Results: Ninety six patients had vertigo, and caloric abnormalities were observed in 119 patients. Initial PTA in patients with vertigo were worse than in those without vertigo (63.0 dB vs 72.7 dB, P = .002). Initial PTA in patients with abnormal o-VEMP was worse than in those with normal o-VEMP (61.4 dB vs 73.0 dB, P = .004). PTA improvement after steroid treatment in patients with vertigo was lower than in those without vertigo (25.0 dB vs 20.9 dB, P = .028). PTA improvement after treatment in patients with abnormal caloric results was lower than in those with normal caloric results (26.0 dB vs 18.4 dB, P = .013)., Conclusion: The functions of vestibular organs, particularly the utricle and lateral semicircular canal, are associated with disease severity and hearing outcome in SSNHL patients., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of on demand and low dose intratympanic gentamicin (ITG) in patients with intractable Meniere's disease (MD)., Study Design: Clinical chart review., Setting: Secondary care center., Patients: Subjects with MD who failed conventional treatment and underwent on demand ITG infiltration from June 2013 to December 2018., Intervention: 0.4 to 0.5 ml of buffered gentamicin were administered through an intratympanic route. A total of 5 mg in case of low dose and 20 mg as a standard dose., Main Outcome Measures: Vertigo control, Meniere's Disease Functional Level Scale (MDFLS), Dizziness Handicap Inventory (DHI), and pure tone audiometry pre and posttreatment., Results: Thirty-one patients, 16 women and 15 men with a mean age of 52.81 (22-79) years were included. The number of ITG injections ranged from 1 to 7, with a mean of 2.52 applications per patient. Mean interval between doses was 212.15 (21-1442) days. Average follow-up was 24.03 months. An improvement on MDFLS was seen on 77.4% (n = 24) patients. DHI score improved after gentamicin treatment (mean 55.23 versus 24.06, p ≤ 0.001). Thirty patients (96.8%) reached complete or substantial vertigo control. Only one patient did not achieve control. Hearing was preserved in 43.5% (n = 10) of analyzed audiograms, whereas 17.4% (n = 4) developed hearing loss greater than 20 dB, which was not statistically significant (p = 0.099)., Conclusions: In our study, on demand and low dose ITG was effective for vertigo control in patients with intractable MD. Individualized therapy is recommended in all patients to minimize vestibular and cochlear toxicity.

Introduction: Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking., Objective: To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis., Material and Methods: This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared., Results: 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them., Conclusion: The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere's disease (MD). Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gain and pure-tone threshold after low-dose ITG for MD. Methods: Sixteen patients with definite MD who were treated by low-dose ITG were retrospectively reviewed. We defined VOR gain difference as an amount of decreased gain in video head impulse test one month after ITG. Patients were classified into two groups: single injection vs. multiple injections. Multiple injections group was composed of patients with poor vertigo control after initial ITG who required second or third ITG later in follow up period. Results: VOR gain differences of both horizontal and posterior canal plane were higher than those of anterior canal plane. Between two groups, mean VOR gain difference of horizontal canal plane in multiple injections group was lower than that in single injection group. Only two patients showed increased pure-tone threshold more than 10 dB. Conclusion and significance: Our results suggest that ITG appears to cause a differential loss of function across three semicircular canals. Furthermore, if VOR gain difference of horizontal canal is relatively low after initial ITG, patient might have poor vertigo control and be required another ITG.

Background: Endolymphatic sac decompression surgery (ESDS) is commonly used for intractable Meniere's disease, but its effect remains controversial because of the low rate of vertigo control. Objectives: In the present study, we examined ESDS combined with posterior tympanotomy with local steroids as a new therapeutic strategy for intractable Meniere's disease. Materials and methods: This retrospective study enrolled 19 patients with Meniere's disease using ESDS combined with posterior tympanotomy with local steroids between 2015 and 2018. Postoperatively we recorded and evaluated changes in vertigo attack frequency and hearing level. Results: Vertigo episodes decreased from 3.6 ± 3.2 times preoperatively to 0.2 ± 0.5 times postoperatively, with 89.5% complete vertigo control rate. Mean PTA decreased from 40.5 ± 21.3 dB to 39.5 ± 17.5 dB postoperatively, with 21.1% improvement rate. Conclusions and significance: The present findings suggest that ESDS combined with posterior tympanotomy with local steroids could improve clinical results of hearing as well as vertigo control for intractable Meniere's disease.

A new and unique treatment for cervical vertigo with botulinum toxin is presented for a woman who sustained neck trauma from being hit by a wave. A diagnosis of cervical vertigo and cervical dystonia was confirmed by history, physical exam, dystonia on EMG exam, and a negative test for benign paroxysmal positional vertigo. She experienced consistent resolution of her vertigo symptoms and pain after each treatment for a total of 5 treatments with botulinum toxin to the upper cervical muscles.This report appears to be the first to demonstrate the missing link between vertigo and cervical dystonia with pain. Chemodenervation was effective in treating cervical vertigo and is likely to have altered the cervical proprioceptive input by relaxing the overactive muscles and/or by decompression of cervical nerves., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere's disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone., Methods: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered., Results: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group., Conclusion: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

Objective: To evaluate the efficacy and safety of modified-release (MR) betahistine (48 mg once daily) versus betaserc (24 mg twice daily) in patients with Meniere's disease or vestibular vertigo., Material and Methods: A multicentre, double-blind, randomized clinical study in patients with an established diagnosis of Meniere's disease (35%) or vestibular vertigo (65%) was carried out. A total of 264 patients were randomized (132 in each group).The inclusion criteria were a Dizziness Handicap Inventory (DHI) total score of more than 30 points and at least 2 vertigo attacks within the previous 4 weeks. The primary efficacy variable was the change in the DHI total score from baseline to after 12 weeks of treatment. The predefined non-inferiority margin was set at 9 points for the DHI total score., Results: After 12 weeks of treatment, the DHI total score was significantly ( p <0.001) decreased compared with baseline, by 32.0±20.7 in the betahistine MR group and by 31.8±19.8 in the betaserc group. The adjusted difference in the change in the DHI total score with a one-sided 97.5% CI was 0.9 (--; 5.3) points, the upper confidence limit (+5.3) fell below the predefined margin of non-inferiority of 9 points, and the non-inferiority of betahistine MR to betaserc was established. The treatment groups were comparable in terms of reduced scores for the functional, emotional and physical subdomains of DHI; reduced frequency, intensity and duration of vertigo attacks; decreased proportion of patients with prolonged attacks and severe symptoms during attacks; and scores on the Clinical Global Impression - Improvement scale. The safety profile of betahistine MR was comparable to that of betaserc, the most frequently reported adverse event was headache in both treatment groups., Conclusion: Betahistine MR (48 mg once daily) is non-inferior to betaserc (24 mg twice daily) in patients with Meniere's disease or vestibular vertigo and has a comparable safety profile.

Background: Cervical vertigo commonly concurs in patients with neck pain, but the concurrent mechanism of these 2 symptoms still remains unclear. We previously reported a bidirectional segmental nerve fiber connection between cervical spinal and sympathetic ganglia, which provided a hypothesis that this connection between the 2 ganglia may be the anatomic basis for the concurrence of neck pain and cervical vertigo. However, this concurrent mechanism needs biochemical and functional evidence., Objectives: This study aimed to investigate a possible noradrenergic pathway between cervical spinal and sympathetic ganglia., Study Design: We performed both clinical and laboratory research. Clinical observation was a prospective case-control study., Setting: Clinical study took place in our hospital; laboratory study was in an orthopedic laboratory., Methods: Cervical lamina block therapy used in patients with cervical vertigo was clinically evaluated; norepinephrine (NE) expressions in cervical sympathetic ganglia were analyzed using immunohistochemical staining after electrical stimulation to the cervical spinal ganglia; the influence of phentolamine local injection to the vertebrobasilar artery flow was experimentally measured., Results: Cervical lamina block therapy could significantly shorten the clinical hospital stays of patients with cervical vertigo (P = 0.000) and improve vertebral artery flow (P < 0.05). NE expressions in superior cervical sympathetic ganglia (SCG) or inferior cervical sympathetic ganglia (ICG) increased significantly when ipsilateral C2 to C3 or C6 to C8 spinal ganglia were electrically stimulated, respectively. Adrenergic receptor block with phentolamine significantly inhibited the decrease of basilar artery (BA) flow induced by electrical stimulation of the cervical spinal ganglia. The change range of BA flow caused by stimulations of C2 to C3 and C6 to C8 spinal ganglia was more than that of C4 and C5., Limitations: The inpatients observed in this clinical study might be influenced by some factors including emotion, diet, sleep, and others. The limitations of the laboratory study included animal species and small sample size., Conclusions: Adrenergic system could play a part in cervical spinal ganglia altering the vertebrobasilar artery system. It could provide a neurochemical foundation between neck pain and vertigo, and that segmental functional connections exist between cervical spinal and sympathetic ganglia., Key Words: Cervical vertigo, neck pain, cervical sympathetic ganglia, cervical spinal ganglia, noradrenaline.

Background and Objective: Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert ® ) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo., Methods: In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient's and investigator's judgment of global efficacy, the patient's rating of impairment of daily activities, and safety/tolerability of the treatments., Results: Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: - 0.093, 95% CI - 0.180; - 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient's ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients., Conclusion: The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders., Study Registration: EudraCT No. 2011-004025-27.

Introduction: Menière's disease (MD) is an uncommon cause of sudden profound vertigo. A variety of medical and surgical treatments have been used to manage this condition. This study reviewed the outcomes of patients treated with grommet insertion and transtympanic steroid injection., Methods: Patients diagnosed with MD between 2007 and 2017 were identified, and case notes and audiological data were retrieved for those managed by grommet (ventilation tube) insertion with and without transtympanic steroid injection., Results: Thirty-three patients were identified as being diagnosed with MD. Grommet insertion resulted in cessation or improvement of attacks in 91% of cases. The mean follow-up duration was 33.8 months (median: 29 months). The mean hearing threshold across the low frequencies improved from 57.2dBHL to 49.4dBHL ( p =0.031). Following the intervention, improved tinnitus was reported in 80% of cases. Twelve patients (36%) reported aural fullness prior to grommet insertion; all reported improved symptoms following the procedure., Conclusions: Early grommet insertion with transtympanic steroid injection, combined with customised vestibular physiotherapy, may provide an alternative first-line strategy for MD, preventing further true MD attacks. In some patients, it may significantly improve hearing thresholds.

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.

Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibular vertigo symptoms. Agents targeting the H 1 and H 3 receptors have been in clinical use for several decades as single agents. Nonetheless, effective management of vertigo proves elusive as many treatments largely address only associated symptoms, and with questionable efficacy. Additionally, the primary and limiting side effect of sedation is counterproductive to normal functioning and the natural recovery process occurring via central compensation. To address these issues, the timing of administration of betahistine, the mainstay H 3 antihistamine, can be fine-tuned, while bioavailability is also being improved. Other approaches include antihistamine combination studies, devices, physical therapy and behavioural interventions. Recently demonstrated expression of H 4 receptors in the peripheral vestibular system represents a new potential drug target for treating vestibular disorders. A number of novel selective H 4 antagonists are active in vestibular models in vivo. The preclinical potential of SENS-111 (Seliforant), an oral first-in-class selective H 4 antagonist is the only such molecule to date to be translated into the clinical setting. With an excellent safety profile and notable absence of sedation, encouraging outcomes in an induced vertigo model in healthy volunteers have led to ongoing clinical studies in acute unilateral vestibulopathy, with the hope that H 4 antagonists will offer new effective therapeutic options to patients suffering from vertigo., (© 2019 The British Pharmacological Society.)

Background: This study will systematically investigate the efficacy and safety of methylprednisolone for treatment of persistent vertigo (PV)., Methods: All following electronic databases will be searched from inception to the June 30, 2019 without language restrictions: MEDILINE, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database. All randomized controlled trials focusing on assessing the efficacy and safety of methylprednisolone for patients with PV will be fully considered for inclusion. Cochrane risk of bias tool will be used for assessing methodological quality, and RevMan 5.3 software (Cochrane Community, London, UK) will be utilized for statistical analysis., Results: This study will assess the efficacy and safety of methylprednisolone for PV via assessing primary outcome of vertigo, and secondary outcomes of somatization, depression, anxiety, health-related quality of life, and adverse events., Conclusion: This study will provide a high-quality evidence to judge whether methylprednisolone is an effective and safety therapy for patients with PV., Dissemination and Ethics: No individual data will be utilized in this study, thus, it does not need ethical approval. The results of this study will be published at peer-reviewed journals., Systematic Review Registration: PROSPERO CRD42019138890.

Objective: This study aimed to compare if vertigo improved in patients when the dexamethasone used in the intratympanic (IT) injection was applied at body temperature or at room temperature., Methods: The study included 54 patients who had undergone intratympanic treatment due to sudden hearing loss and tinnitus. The IT injection was administered to all patients, 2 times with 1-day intervals. Two different IT injection techniques were used for each patient: injecting dexamethasone at room temperature and injecting it at body temperature. Patients were asked to report the vertigo they felt immediately, and at 15 min after the injection using the visual analogue scale (VAS) and the four-point categorical rating scale (CRS-4)., Results: The level of vertigo immediately after injection was lower when the dexamethasone was injected at body temperature rather that at room temperature for both the VAS and CRS-4 (p < 0.05). However, no statistical differences in the VAS and CRS-4 self-report values between the two methods were found 15 min after the injection (p > 0.05)., Conclusion: Vertigo due to IT decreases within minutes. When the IT drugs are administered at body temperature, temporal vertigo due to injection is lower than when they are administered at room temperature., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To investigate the beneficial effects and safety of intratympanic steroid installation compared with placebo in patients with Menière's disease., Methods: We performed a systematic literature search in MEDLINE and EMBASE for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated the usage intratympanic steroids in patients aged 18 and above, with definite or probable Menière's disease. The quality of the identified existing reviews was assessed using the AMSTAR tool. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool and overall quality of the individual outcomes was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method., Results: The literature search provided four systematic reviews, from which one yielded a sufficient AMSTAR evaluation and subsequently provided three RCTs relevant for inclusion. Due to the lack of sufficient reporting of the data, quantitative synthesis was not applicable. In the qualitative synthesis for the primary outcome, the results from the RCTs showed that there was a slight indication of steroid treatment reducing the frequency of vertiginous attacks. No serious adverse events were reported. Based on the GRADE approach the quality for both findings is very low. No studies reported on the secondary outcomes., Conclusion: The effect of intratympanic steroid treatment in Menière's disease is questionable. There is a great need for further research to sufficiently assess whether steroid treatment may be considered as a safe and effective treatment for patients with Menière's disease.

A 41-year-old woman presented with recurrent dizziness. After an attack of dizziness, she felt edematous sensations in her hands. However, according to photographs taken during the attack, the edema on the back of the patient's hands and fingers appeared mild. Laboratory examinations revealed a low C4 and C1 inhibitor (INH) activity. A direct sequencing analysis of C1INH revealed a pathogenic gene mutation. Based on these results, she was diagnosed with hereditary angioedema (HAE) type 1. These findings indicate that HAE can cause recurrent dizziness, and it should therefore be included in the differential diagnosis in patients with recurrent neurologic symptoms, even in the absence of severe edema.

Purpose: To assess the efficacy of acetylleucine to improve or stop an attack of vertigo and dizziness (vertigo/dizziness)., Methods: Systematic review by 2 independent reviewers. Consultation of the Medline, Cochrane and ClinicalTrials.gov databases until September 2018. Keywords used: Acetylleucine, Tanganil®, Acetyl-DL-leucine, Acetyl-leucine. Trial selection: randomised controlled trials (RCTs) comparing acetylleucine against placebo., Results: Up until 2018, no RCTs have been published on the efficacy of acetylleucine in vertigo/dizziness., Conclusion: There is no solid evidence of the efficacy of acetylleucine in vertigo/dizziness. Given its frequent prescription and the cost generated for the French social security system, high-quality randomised trials should be carried out to assess its efficacy.

Background: Ménière's disease (MD) is a disorder of the inner ear, causing episodes of vertigo. Although surgery is reserved for intractable MD, intratympanic gentamicin (ITG) injection has become an alternative for controlling vertigo., Aims/objectives: To investigate the genetic basis of ITG efficacy., Material and Methods: We hypothesized that single nucleotide polymorphisms (SNPs) affect outcomes in patients with MD who receive ITG injections. Whole-exome sequencing was used to determine variations in coding regions., Results: Multivariate analysis revealed two SNPs, rs1052571 in caspase 9 (CASP9; p = .017) and rs3745274 in cytochrome P450 2B6 (p = .053), which were associated with susceptibility to ITG injections. Only the C-allele in the rs1052571 SNP was significantly associated with susceptibility (p = .027; odds ratio: 5.95; 95% confidence interval: 1.26-28.57, by Fisher's exact test)., Conclusions and Significance: Our results elucidated the role of the rs1052571 SNP and provide a genetic perspective on gentamicin efficacy (susceptibility) in treating intractable MD.

Objectives: The aim of the present study was to investigate current treatment practices and self-reported effectiveness in Ménière's disease., Materials and Methods: Members of two Italian Ménière's disease support (n=170) with ≥6-month history of Ménière's disease were administered an online survey about recent treatments. Vertigo episode count, work absenteeism, and limitations in family life, social life, work, or travel as included in the Social Life and Work Impact of Dizziness Questionnaire before and after recent treatments were queried., Results: Twenty-four different treatments were reported for Ménière's disease, with dietary modifications (55%), diuretics (47%), and betahistine (41%) being the most common. The majority (71%) received multiple simultaneous treatments. Prior to the most recent treatments, 78%-89% of respondents indicated limitations in family or social life, work, or traveling. After their most recent treatment, respondents reported improvements in mean vertigo episode counts (5.7±7.6 vs. 2.6±4.6, p<0.001), days off work per month (10.1±9.2 vs. 4.2±6.7, p<0.001), and proportions indicating limitations in any functional measure assessed (p<0.05). These findings were consistent regardless of treatment approach (p<0.05 for all). Intratympanic gentamicin provided the greatest reductions in vertigo count, functional limitations, and work absenteeism (p<0.01 for all), as well as the fewest respondents reporting post-treatment functional limitations (16%-37%)., Conclusion: Despite many treatment approaches targeting different proposed pathophysiology for Ménière's disease in this cross-sectional survey, all treatments are reported as effective by patients. These findings support a prominent placebo effect in Ménière's disease and highlight challenges in studying treatment outcomes; there is a critical need to better understand Ménière's disease.

Objectives: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menière's disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at long-term follow-up., Study Design: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires., Setting: Outpatient hospital clinic setting., Patients: Adult patients with definite unilateral refractory Menière's disease, who previously received intratympanic treatment in a comparative trial., Intervention: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL)., Outcome Measures: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability., Results: Forty six of the 60 original trial patients (77%) completed the survey, 24 from the gentamicin and 22 from the methylprednisolone group. Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p < 0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone = 5 and gentamicin = 3) required further injections for relapse after completing the original trial., Conclusion: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up.

Acute vertigo is a common problem in emergency departments. However, clinical strategies of acute vertigo care vary among care providers. The aim of the study was to investigate differences in diagnosis [Dix-Hallpike test, the head impulse, nystagmus, and the test of skew (HINTS) procedure, and imaging modalities] and treatment (pharmacological treatments and the Epley maneuver) by otolaryngologists and non-otolaryngologists in emergency medicine settings. We used a multicenter case-based survey for the study. Four clinical vignettes of acute vertigo (posterior canal benign paroxysmal positional vertigo, vestibular neuritis, Meniere disease, and nonspecific vertigo) were used. Total 151 physicians from all study sites participated in the study. There were 84 non-otolaryngologists (48 emergency physicians and 36 internists) and 67 otolaryngologists. The multivariate analysis indicated that otolaryngologists ordered fewer CT scans (odds ratio (OR), 0.20; 95% confidence interval (CI), 0.07-0.53) and performed fewer HINTS procedures (OR, 0.17; 95% CI, 0.06-0.46), but used the Dix-Hallpike method more often (OR, 2.36; 95% CI, 1.01-5.52) for diagnosis compared to non-otolaryngologists. For treatment, otolaryngologists were less likely to use the Epley method (OR, 0.19; 95% CI, 0.07-0.53) and metoclopramide (OR, 0.09; 95% CI, 0.01-0.97) and more likely to use sodium bicarbonate (OR, 20.50; 95% CI, 6.85-61.40) compared to non-otolaryngologists. We found significant differences in the acute vertigo care provided by non-otolaryngologists and otolaryngologists from a vignette-based research. To improve acute vertigo care, educational systems focusing on acute vertigo are needed., Competing Interests: The authors have declared that no competing interests exist.

Although histamine inhibitors have been used in the motility-associated vertigo, the link between histamine and sleep deprivation (SD)-induced vertigo has not been clearly demonstrated. The histamine plasma levels were assayed in the SD volunteers before SD and 24 h after SD. Pinnacle's automated sleep deprivation system was used to establish the female C57BL/6 mice SD model. Histidine decarboxylase inhibitor 4-bromo-3-hydroxybenzoic acid (BHOA), and antihistamine diphenhydramine (DPHM) were injected intraperitoneally to test their effects on SD-induced vertigo. Rotarod tests and vestibular scores 24 and 48 h post SD were utilized to assay the vestibular function. Western blot was used to determine the expression of histidine decarboxylase (HDC) in the vestibular, and PowerChrom was utilized to quantify the concentrations of cerebrospinal fluid (CSF) histamine. SD increased plasma concentration of histamine in humans. Upregulated HDC in the vestibular and increased CSF concentration of histamine can be detected in the SD mice, indicating vestibular dysfunction which can be ameliorated by both BHOA and DPHM. Histamine signaling inhibition may ameliorate SD-induced vertigo, and histamine can be considered as a potential treatment target.

Objective: To describe the long-term clinical vertigo control along with measured lateral canal vestibular function in patients with unilateral refractory Menière's disease (MD) treated with gentamicin transtympanic injections (TTI)., Study Design: Retrospective analytic study., Setting: Tertiary referral center., Patients: Thirty-eight patients treated by TTI for medically refractory unilateral MD, defined by the 1995 AAO-HNS criteria, between May 2006 and December 2012., Intervention(s): One-year course of treatment with gentamicin TTI following a low dose on-demand protocol. TTI were repeated in new courses of treatment when MD recurrence occurred., Main Outcome Measure(s): AAO-HNS class of control, caloric tests (CalT), recurrence rate., Results: After an average clinical follow-up of 71 months, all patients entered a class of control A (78%) or B (22%), with an average of 2.3 TTI received. The mean maximal obtained deficit was 88.5%, and the mean long-term deficit was 85.5%. Ten (26%) patients had disease recurrence requiring a new course of treatment. A value of the first CalT in the 3 months following the first TTI strictly higher than 78% was significantly associated with disease control and the absence of symptom recurrence (p≤0.01). In the "recurrence" group, four patients had a significantly lower mean value of all CalT performed after the first TTI when compared with other patients (p≤0.001), indicating gentamicin resistance CONCLUSION:: Achieving a sustainable vestibular deficit on caloric testing is key for MD symptom control after gentamicin TTI. Gentamicin resistance must be diagnosed early to adapt therapeutic strategies.

Background: Vertigo is a common annoying complaint needing emergent treatment. There are various treatment options for this condition with different outcomes and side effects., Objectives: Assessment and comparison of the effectiveness of Ondansetron and Promethazine in the treatment of acute peripheral vertigo., Materials and Methods: This clinical trial was conducted in an academic hospital in the north of Iran in 2017. A total of 170 eligible patients were randomly allocated to groups A: received intramuscular (IM) promethazine; and B: received intravenous (IV) Ondansetron, using quadripartite blocks. The severity of vertigo, nausea, blood pressure, heart rate, side-effects, need for re-administration, and the time to become asymptomatic were assessed before the injections, 30 min after and 2 h after the injections., Results: Excellent improvement in vertigo occurred in both groups (P < 0.001), with a more significant reduction in the promethazine-treated group (P < 0.001). Nausea was reduced more significantly in the ondansetron-treated group (P < 0.05). There were more side-effects seen in the promethazine-treated when compared to the group with ondansetron treatment (P < 0.001). No significant differences were seen in the blood pressures between groups (P > 0.05). Heart rates were reduced in both groups but the changes were insignificant (P > 0.05). The ondansetron-treated group showed a greater need for re-administration of the medication (50.6% vs. 27.1%). The relief score was significantly higher in the ondansetron-treated group compared with the group received promethazine (P < 0.001). The time to become asymptomatic showed no statistically significant difference between groups (p = 0.28)., Conclusion: Our results indicated that while promethazine cures peripheral vertigo more efficiently, ondansetron is more beneficial for the improvement of nausea and vomiting., (Copyright © 2018 Elsevier Inc. All rights reserved.)