Trauma-Induced Vestibular Dysfunction: Improved Repair Under Local Treatment With α1-Antitrypsin.

AIM: To characterize vestibular recovery in a mouse model of unilateral labyrinthotomy under local AAT and dexamethasone treatment. BACKGROUND: Alpha1-antitrypsin (AAT) is a circulating tissue-protective molecule that rises during inflammatory conditions and promotes inflammatory resolution. Its local concentration in human perilymph inversely correlates with the severity of inner ear dysfunction; concomitantly, mice that overexpress AAT and undergo inner ear trauma rapidly restore vestibular function. Locally applied AAT has yet to be examined in this context, nor has it been directly compared with anti-inflammatory corticosteroid treatment. METHODS: Wild-type mice C57BL/6 underwent a unilateral inner ear injury. Nine microliters of saline, clinical-grade AAT (180 µg/site), dexamethasone (4 mg/site), or both were applied locally on Days 0, 1, and 2 (n = 5/group). Vestibular function was assessed for 7 days. An in vitro human epithelial gap closure assay was performed using A549 cells in the presence of AAT and/or dexamethasone. RESULTS: Upon labyrinthotomy, all groups displayed severe vestibular dysfunction. Saline-treated mice showed the longest impairment. That group and the dexamethasone group displayed partial to no recovery, while AAT-treated mice exhibited complete recovery within 7 days; at this time point, dexamethasone-treated mice exhibited 50% recovery. Objective vestibular testing showed similar outcomes. In vitro, cotreatment with AAT and dexamethasone resulted in a gap closure dynamic that was superior to AAT alone at 6 h and superior to DEX alone at 48 h. CONCLUSION: Locally applied AAT treatment is superior to locally applied dexamethasone in promoting vestibular recovery in vivo. Ongoing studies are exploring the potential advantages of AAT combined with early low-dose dexamethasone therapy.

Effectiveness of Anti-Calcitonin Gene-Related Peptide Medication in Vestibular Migraine: A Retrospective Cohort Study in an Asian Population.

BACKGROUND: Migraine and dizziness often coexist, with vestibular migraine (VM) presenting with vestibular symptoms and headaches. Calcitonin gene-related peptide (CGRP) may be involved in motion-induced symptoms; however, studies on the use of anti-CGRP monoclonal antibodies (mAbs) for the treatment of VM have yielded conflicting results. This study aimed to clarify the effectiveness of anti-CGRP mAbs in VM treatment. METHODS: This retrospective observational cohort study, conducted between 1 January 2021 and 31 March 2023, assessed 12 Japanese patients with VM who were treated with anti-CGRP mAbs (CGRP group) for 6 months and 11 Japanese patients who received standard of care for VM and served as controls. Clinical questionnaires and equilibrium tests were administered, with primary outcomes including changes in Dizziness Handicap Inventory (DHI) scores compared with baseline values. Objective variables included the DHI score and explanatory variables included demographic data, balance test results, head-up tilt (HUT) test results, vestibular test results and questionnaire survey results. Analysis of variance was used to assess the treatment effects of anti-CGRP mAbs, and multivariate regression analysis was performed to identify mAb responders. RESULTS: After 6 months, the CGRP group showed significant improvements in DHI scores [0 versus 6 months, odds ratio (95% confidence interval): 22.01 (0.13-43.88)] and number of vertigo/dizziness attacks per month [0 versus 6 months: 10.28 (2.80-17.76)]. No significant difference was observed in the control group [DHI scores, 0 versus 6 months: 0.65 (-26.84 to 28.14); number of vertigo/dizziness attacks per month, 0 versus 6 months: - 8.07 (- 23.77 to 7.62)]. Multivariate regression analysis showed that autonomic function at baseline was associated with mAb response in patients [ß estimates (95% confidence interval): 3.63 (0.21-7.06)]. CONCLUSIONS: Treatment with anti-CGRP mAbs was more effective than conventional treatment in preventing migraine in patients with VM. While the identified factors associated with treatment responsiveness offer valuable insights into personalised treatment approaches, further prospective studies are warranted to validate the findings due to our study's retrospective design and limited sample size.

Histaminergic System and Vestibular Function in Normal and Pathological Conditions.

Most neurotransmitter systems are represented in the central and peripheral vestibular system and are thereby involved both in normal vestibular signal processing and the pathophysiology of vestibular disorders. However, there is a special relationship between the vestibular system and the histaminergic system. The purpose of this review is to document how the histaminergic system interferes with normal and pathological vestibular function. In particular, we will discuss neurobiological mechanisms such as neuroinflammation that involve histamine to modulate and allow restoration of balance function in the situation of a vestibular insult. These adaptive mechanisms represent targets of histaminergic pharmacological compounds capable of restoring vestibular function in pathological situations. The clinical use of drugs targeting the histaminergic system in various vestibular disorders is critically discussed.

Clinical features and outcome of 10 dogs with suspected idiopathic vestibular epilepsy.

BACKGROUND: In humans, vestibular epilepsy (VE) is described as focal seizures with transient signs of vestibular disease. In dogs, 2 cases of vestibular episodes, called vestibular paroxysmia, are reported. HYPOTHESIS/OBJECTIVES: The objective of this study was to define the clinical features, phenotypical manifestation, and outcome of suspected VE in dogs. ANIMALS: Ten dogs with recurrent vestibular episodes. METHODS: Retrospective study. Medical records between 2009 and 2023 were reviewed, and dogs with a normal neurological examination, a history of transient signs of vestibular disease, absence of abnormalities detected on blood exams and brain magnetic resonance imaging (MRI) or computed tomography (CT), besides a minimum 10-month follow-up were included. Clinical improvement was defined as a ≥50% reduction in frequency or the cessation of clinical signs after the onset of antiseizure medications (ASMs). RESULTS: Pugs were the most prevalent breed (5/10; 50%). In 2 cases, additional generalized tonic-clonic (GTC) seizures were reported. MRI exam was performed in most cases (9/10; 90%), whereas 1 dog underwent a CT scan (1/10; 10%). Electroencephalography (EEG) was carried out in 3 dogs that showed interictal spikes in the fronto-temporal and fronto-parietal areas. All cases received ASMs, with clinical improvement in 10/10 dogs (100%). CONCLUSION AND CLINICAL IMPORTANCE: The presence of GTC seizures, EEG interictal spikes, and responsiveness to ASMs supported the hypothesis of an epileptic origin of vestibular episodes and thus the existence of VE in these dogs, with a presumed idiopathic cause and apparent favorable outcome.

[Vestibular rehabilitation for peripheral vestibular hypofunction: an interdisciplinary consensus]. / Vestibulyarnaya reabilitatsiya pri perifericheskoi vestibulyarnoi gipofunktsii: mezhdistsiplinarnyi konsensus.

The literature review presents approaches to the management of patients with vestibular disorders. The principles of organization of vestibular rehabilitation in peripheral vestibular hypofunction, indications for appointment, factors influencing its implementation, technique, methods of evaluating effectiveness are considered in detail. Attention is drawn to the fact that the selection of exercises and the duration of vestibular rehabilitation is carried out individually and depends on many factors, including the nature of vestibular deficiency and the specific characteristics of the patient. The possibilities of using additional pharmacological therapy with histamine preparations, which can accelerate the onset of vestibular compensation, are shown. It is noted that vestibular rehabilitation is a safe and effective method of treating peripheral vestibular hypofunction and should be recommended to patients of all ages with vestibular disorders leading to limited social and physical activity.

Effect of public square dancing combined with serotonin reuptake inhibitors on persistent postural-perceptual dizziness (PPPD) in middle-aged and older women.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a functional vestibular disorder that causes chronic dizziness and limits daily activities. Although pharmacology, vestibular rehabilitation, and cognitive behavioral therapy have been proposed to have some efficacy, they have certain limitations. Some patients with PPPD report that public square dancing can effectively relieve the symptoms of dizziness and instability, and their mood improves. OBJECTIVE: To evaluate the effects of combining public square dancing with serotonin reuptake inhibitors (SSRIs/SNRIs) on the subjective sensations of dizziness, balance enhancement, anxiety, and depressive symptom regulation in middle-aged and older women with PPPD. MATERIALS AND METHODS: In this trial, 124 patients diagnosed with PPPD were enrolled. Among them, 64 patients were randomly assigned to the experimental group (EG), where they received square dance training combined with serotonin reuptake inhibitors. The remaining 60 cases were randomly assigned to the control group (CG), where they received only serotonin reuptake inhibitors and did not participate in organized sports activities, allowing them freedom in their daily lives. Data from the Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), Active-specific Balance Confidence Scale (ABC), and Vestibular Disorder Activities of Daily Living Scale (VADL) were collected and compared at the beginning, 3 months, and 6 months of the trial to evaluate the effect of public square dancing on middle-aged and older women with PPPD. RESULTS: There were no significant differences between the EG and CG before the trial. Compared with baseline measures, DHI, HADS, ABC, and VADL scores improved as the experiment progressed, and the improvements were more pronounced in the EG. CONCLUSION: Public square dancing combined with serotonin reuptake inhibitors has a positive impact on the subjective sensations of dizziness, balance enhancement, anxiety, and depressive symptom regulation in middle-aged and older women with PPPD.

Ondansetron in dogs with nausea associated with vestibular disease: A double-blinded, randomized placebo-controlled crossover study.

BACKGROUND: Nausea and emesis can be, among other signs, common manifestations of acute vestibular system dysfunction in dogs. Currently, antiemetic drugs, such as maropitant and metoclopramide, are used commonly, but do not appear to control nausea. A non-placebo-controlled preliminary study suggested good efficacy of 5-HT3-receptor antagonists, such as ondansetron, against nausea in dogs with vestibular syndrome. OBJECTIVES: To assess and confirm the effect of ondansetron on behavior suggestive of nausea in dogs with vestibular syndrome. ANIMALS: Fourteen dogs with vestibular syndrome and clinical signs of nausea presented to a neurology service. METHODS: Placebo-controlled, double-blinded, crossover study. Behavioral assessment was performed hourly for 4 hours using an established numerical rating scale. The criteria salivation, lip licking, vocalization, restlessness, lethargy, and general nausea were scored. The occurrence of emesis was recorded. After scoring at T0 (pre-dose) and T2 (2 hours post-dose) either ondansetron (0.5 mg/kg) or placebo was injected IV. Two hours post-dose, treatments were switched. Blood samples were collected to measure serum arginine vasopressin (AVP) concentration, which previously has been shown to correlate with clinical signs of nausea. RESULTS: Clinical resolution of nausea was observed 1 hour after administration of ondansetron, whereas serum AVP concentration decreased 4 hours after ondansetron administration. CONCLUSION AND CLINICAL IMPORTANCE: Administration of ondansetron IV is beneficial for dogs with nausea secondary to acute vestibular syndrome. Ondansetron substantially and rapidly decreased clinical signs of nausea behavior and stopped emesis.

Therapeutic effect of steroids on vestibular neuritis: Systematic review and meta-analysis.

OBJECTIVES: The present meta-analysis sought to assess further evidence for the efficacy of steroids in vestibular neuritis (VN). METHODS: The PubMed, EMBASE and Cochrane Library databases were searched through 30 August 2019. The main outcome measure was dizziness handicap inventory (DHI) and secondary outcomes included complete caloric recovery and improvement of canal paresis (CP). The follow-up times were divided into short, mid and long-term. RESULTS: Among 276 records identified, 5 studies (n = 253) were included in the analysis. The therapeutic effect of steroid on VN was confirmed (Hedges' g = 0.172, 95% CI 0.05-0.30, p = .006). Although there was no significant difference between steroids and control in the DHI score (Hedges' g = -0.323, 95% CI -0.533 to -0.113, p < .01), significant effect was seen on complete caloric recovery and improvement in CP (Hedges' g = 0.364, 95% CI 0.18-0.55, p < .0001; Hedges' g = 0.592, 95% CI 0.32-0.59, p < .0001). CONCLUSIONS: The results suggest that corticosteroids have an effect on the results of caloric tests for VN recovery, especially in long-term follow-up. However, in terms of dizziness handicap, we did not find any evidence of positive effect on corticosteroid. More data are required before recommendations can be made regarding management in patients on corticosteroids.

Pharmacotherapy of cerebellar and vestibular disorders.

PURPOSE OF REVIEW: Major therapeutic advances have been made in patients with episodic and progressive cerebellar ataxias, downbeat nystagmus and some vestibular disorders. We provide an update review on this subject highlighting important research findings from the last two years. RECENT FINDINGS: Recently, the use of omaveloxolone for 2 years significantly improved upright stability in Friedreich's ataxia patients. In an open-label study, N-acetyl-l-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. A 12-week treatment with dalfampridine was associated with improved standing balance in a subgroup of patients with multiple sclerosis. A gluten-free diet alone improved ataxia in half of patients with antiglutamic acid decarboxylase (GAD) ataxia, suggesting that gluten sensitivity might be part of the underlying pathogenesis in anti-GAD ataxia. In a head-to-head trial, both prolonged-release 4-aminopyridine (4-AP) and acetazolamide effectively reduced the attacks up to 60% in patients with episodic ataxia type 2 (EA2), albeit 4-AP had fewer adverse effects. Small observational studies have shown that patients with episodic vestibular syndrome who cannot be diagnosed as definite or probable vestibular migraine, might still improve vestibular symptoms following preventive treatment for migraine. The use of vitamin D supplementation in benign paroxysmal positional vertigo, steroids in acute unilateral vestibulopathy, and betahistine in Ménière's disease patients remains controversial. SUMMARY: Although the use of several therapies is being established in the treatment of cerebellar and vestibular disorders, there is an urgent need for prospective controlled therapeutic trials.

Follow-Up Study of Growth Hormone Therapy in Children with Kabuki Syndrome: Two-Year Treatment Results.

INTRODUCTION: Kabuki syndrome (KS) is a genetic disorder with characteristic facial dysmorphisms, short stature, hypertension, and obesity later in life. The aim of this study was to evaluate catch-up growth and cardiovascular markers before and during growth hormone (rhGH) treatment in KS children. METHODS: This prospective study included 18 children whose KS was genetically established. Each KS subject received rhGH for a period of 2 years. Several measurements were performed before and during treatment: anthropometry, glucose metabolism, lipid profile, markers for endothelial function, and low-grade inflammation. RESULTS: This study found an increase in delta height standard deviation score (SDS) for the whole group of 1.1 SDS after 2 years of rhGH treatment. Baseline metabolic profiles showed no cardiometabolic abnormalities in these children. Although 4 out of 18 children were obese, there were no signs of the metabolic syndrome. During rhGH treatment, serum low-density lipoprotein cholesterol concentrations decreased significantly (2.16-1.91 mmol/L, p = 0.04). Apolipoprotein B100 concentrations also showed a reduction after 24 months of treatment, but the other lipid and (apo)lipoprotein parameters did not change. While other endothelial function markers were stable, only vascular cell-adhesion molecule-1 concentrations increased (1,084-1,161 pg/mL, p < 0.01) during rhGH therapy. Furthermore, BMI and waist circumference improved during treatment. There were no signs of hypertension. CONCLUSIONS: At baseline and during rhGH therapy, there were no signs of the metabolic syndrome. This is the first study demonstrating that rhGH treatment in KS children is a safe and effective therapy and that it positively influences linear height without exerting adverse effects on a wide array of cardiovascular risk markers.

Current Insights into Treating Vertigo in Older Adults.

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.

The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome.

BACKGROUND: Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders. METHODS: Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed. RESULTS: All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999). CONCLUSIONS: The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.

[Betahistine in vestibular disorders: current concepts and perspectives]. / Sovremennye predstavleniya o roli betagistina v lechenii zabolevanii vestibulyarnoi sistemy.

The goal of this paper is to review the pharmacological profile of betahistine and evidence for using it in the treatment of common vestibular disorders. Betahistine is a weak agonist for histamine H1 receptors and strong antagonist for histamine H3 receptors. It demonstrates the maximum benefit in different types of peripheral vertigo, especially in Meniere's disease. The best results in decreasing intensity of vertigo, frequency of attacks and stimulation of vestibular compensation were obtained in daily dose 48 mg during 3 months. In benign paroxysmal positional vertigo betahistine is used to treat residual dizziness after successful treatment of otolithiasis and to reduce the severity of vertigo during repositioning maneuvers. In vestibular neuritis betahistine stimulates central compensation during vestibular rehabilitation. A new once-daily drug formulation of modified-release betahistine is non-inferior to traditional and has a comparable safety profile, and could improve patient adherence. The implication of betahistine in the treatment of central vestibular disorders is under-researched. The efficacy of betahistine in increasing of vestibular compensation in post-stroke central vestibular disorders, persistent postural-perceptual dizziness and its role in vestibular migraine need further investigation.

The Interconnections of Mal de Débarquement Syndrome and Vestibular Migraine.

OBJECTIVES/HYPOTHESIS: Mal de débarquement syndrome (MDDS) is characterized by a persistent rocking sensation, as though on a boat. It may occur following exposure to passive motion (motion-triggered MDDS [MT-MDDS]), or spontaneously (spontaneous-onset MDDS [SO-MDDS]). This study investigated the characteristics of MDDS patients with vestibular migraine (MDDS-VM) to those without (MDDS-O). STUDY DESIGN: Retrospective review. METHODS: Retrospective, single-center study of 62 patients with MDDS. Clinical characteristics, Dizziness Handicap Inventory (DHI), Migraine Disability Assessment Score (MIDAS), job impact, and optimal treatment(s) were studied. RESULTS: There were 23 MDDS-O (19 women), and 39 MDDS-VM (35 women) patients. Comparisons between MDDS-VM and MDDS-O showed significant differences in age of onset (41 vs. 52 years, P = .005), interictal visually induced dizziness (89.7% vs. 30.4%, P < .001), interictal head motion-induced dizziness (87.2% vs. 47.8%, P = .001), other vestibular sensations (59% vs. 13%, P < .001), interictal aural symptoms (25.6% vs. 0%, P = .008), number of interictal symptoms (4.3 vs. 2.3, P < .001), total DHI score (54.9 vs. 38.1, P = .005), DHI-P (physical domain) score (16.1 vs. 10, P = .004), DHI-F (functional domain) score (20.9 vs. 15.7, P = .016 MIDAS (4.6 vs. 32, P = .002), and job resignations (23.2% vs. 5%, P = .016). On the other hand, between-group comparisons for MT-MDDS and SO-MDDS did not reveal any significant differences whatsoever. For optimal treatment, venlafaxine was the most used (27.3%) in all groups. For MDDS-VM, antiepileptic drugs and migraine preventive vitamins were also useful in relieving symptoms. CONCLUSIONS: MDDS-VM patients appear to be more disabled than MDDS-O, in terms of severity of dizziness, job impact, and number of symptoms, but have good potential for improvement, particularly with migraine prophylactic treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1653-E1661, 2021.

Factors implicated in response to treatment/prognosis of vestibular migraine.

PURPOSE: To identify patient factors that influence response to therapy in patients with vestibular migraines. METHODS: A retrospective cohort study was performed at a university-based tertiary medical center. PATIENTS: 47 patients evaluated for treatment of definite vestibular migraine, per the Barany Society criteria, from 2015 to 2019. INTERVENTIONS: A protocol of antidepressants, antiepileptics, beta blockers, and vestibular rehabilitation. Patients failing initial therapy received botulinum toxin per the PREEMPT protocol. Vestibular rehabilitation for motion desensitization in case of known vestibular dysfunction. OUTCOME MEASURES: Quality of life measured per the dizziness handicap inventory (DHI). Pre- and post-treatment DHI scores (total and domain scores) and change in DHI were correlated against patient-specific variables to determine factors associated with change in response to therapy. Patient factors included demographic variables, medical comorbidities, comorbid otologic or pain symptoms, treatment modality, and initial DHI scores. RESULTS: 47 patients underwent therapy for vestibular migraine. This population had a significant DHI reduction of 17.3 ± 25.2 (p < 0.001) with therapy. Univariate analysis showed that female gender, comorbid benign paroxysmal positional vertigo, and high initial DHI were significantly associated with greater reduction in DHI scores (ß = - 7.92, p = 0.033; ß = - 18.65, p = 0.028; ß = - 0.458, p = 0.016, respectively). Conversely, cervicalgia and oscillopsia were significantly associated with a lower reduction in DHI scores (ß = 5.525, p = 0.024 and ß = 21.48, p = 0.027, respectively). CONCLUSIONS: Vestibular migraine is a complex disorder with heterogeneous response to therapy. This study shows that patient-specific factors of gender, cervicalgia, oscillopsia, BPPV, and high DHI scores on presentation may influence response to common vestibular migraine therapy.

Hair cell uptake of gentamicin in the developing mouse utricle.

Intratympanic injection of gentamicin has proven to be an effective therapy for intractable vestibular dysfunction. However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specifically vestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin-Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs. In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8-9 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl2 hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel-dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.

Alterações auditivas e vestibulares associadas ao uso da mefloquina: uma revisão integrativa / Auditory and vestibular changes associated with the use of mefloquine: an integrative review

RESUMO Objetivo descrever, por meio de revisão da literatura, alterações auditivas e/ou vestibulares relacionadas ao uso em curto ou em longo prazo da mefloquina. Estratégia de pesquisa trata-se de uma revisão integrativa, realizada nas seguintes bases de dados: PubMed, Web of Science, SciELO, LILACS, Scopus, ScienceDirect, Cochrane Library, Embase, OpenGrey, DissOnline e OAlster. Critérios de seleção foram incluídos estudos com participantes a partir de 18 anos de idade, que fizeram uso de mefloquina e que foram submetidos à avaliação auditiva e/ou questionário referente à função auditiva e vestibular. Foram excluídas revisões de literatura, capítulos de livros e estudos que utilizaram a mefloquina combinada a outros medicamentos. Resultados foram identificados 1.267 estudos nas bases de dados utilizadas, sendo selecionados 28 artigos para leitura completa. Destes, 12 foram incluídos na revisão, de acordo com os critérios de elegibilidade. Quatro artigos apontaram a presença de alterações vestibulares e auditivas, 2 indicaram apenas alterações auditivas e 6 apenas desordens vestibulares. No que se refere às manifestações auditivas, zumbido e perda auditiva foram os sintomas mais frequentes. Vertigem/tontura e desequilíbrio corresponderam às alterações vestibulares comumente apresentadas. Conclusão manifestações auditivas e vestibulares foram referidas em curto e longo prazo, após o tratamento com a droga. A descontinuação de seu uso possibilitou a reversão das manifestações, porém, em alguns casos, foi observada a permanência das afecções. Considera-se importante a realização de acompanhamento audiológico e vestibular durante a ingestão da mefloquina, visto o seu perfil de toxicidade e possíveis manifestações colaterais de caráter auditivo e vestibular.

ABSTRACT Objective To describe through a literature review auditory and/or vestibular alterations associated with the short or long-term use of mefloquine. Research strategy Integrative review performed on the following databases: Pubmed, Web of Science, Scielo, Lilacs, Scopus, Science Direct, Cochrane Library, Embase, Open Grey, DissOnline, OAlster. Selection Criteria The articles selected included studies with participants that were 18 years old or over, who used mefloquine and who were submitted to an auditory evaluation and/or a questionnaire regarding auditory and vestibular function. Literature reviews, book chapters, and studies using mefloquine associated with other drugs were excluded. Results 1,267 studies were identified in the databases used, 28 articles were selected for full reading, and out of these, twelve were included in the review according to the eligibility criteria. Four articles pointed out the presence of vestibular and auditory diseases, two indicated only auditory disorders, and six solely vestibular disorders. Regarding auditory manifestations, tinnitus and hearing loss (HL) were the most frequent symptoms. Vertigo/dizziness and imbalance matched to the vestibular changes were commonly observed. Conclusion Auditory and vestibular manifestations were referred to in the short and long-term after treatment with the drug. The discontinuation of its use made it possible to reverse the manifestations; however, in some cases, the permanence of the disorders was reported. Audiological and vestibular follow-up during mefloquine use is considered important, given its toxicity profile and possible side manifestations of an auditory and vestibular nature.

[Syncope, pain in the large joints, and painful swelling of the right eye in a 51-year-old patient : Pitfalls in the diagnosis and treatment of a rare disease]. / Synkope, Schmerzen der großen Gelenke und schmerzhafte Rötung des rechten Auges bei einer 51-jährigen Patientin : Fallstricke in Diagnostik und Therapie einer seltenen Erkrankung.

In the present case we report on a 51-year-old patient diagnosed with Cogan syndrome. This vasculitis of variable vessel size is a rare disease that poses a major challenge for the correct diagnostics and therapy. In the classic setting, it comprises a triad of non-syphilitic interstitial keratitis as well as hearing loss with vestibular dysfunction. A vascultis-related aortitis, an uncertain, more likely degenerative structure in combination with strongly elevated inflammation parameters was misinterpreted as infective endocarditis for a long time and treated with anti-infective medications. After diagnosis the patient recovered following treatment with high-dose steroids and in the further course cyclophosphamide and tumor necrosis factor­α blockers.

Vestibular prognosis in idiopathic sudden sensorineural hearing loss with vestibular dysfunction treated with oral or intratympanic glucocorticoids: a protocol for randomized controlled trial.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a rapid-onset sensorineural hearing impairment with unclear etiology and unsatisfying treatment effects. Vestibular dysfunction has been considered as a poor indicator in the clinical manifestations and prognosis of ISSNHL, which occurred in approximately 28-57% cases. Glucocorticoids, administered through oral or intratympanic way, are currently regularly and standardly applied for ISSNHL to improve the hearing outcome. However, the vestibular prognosis of ISSNHL after routine treatments remains seldom explored. This study aims to compare the effectiveness of oral and intratympanic glucocorticoids in ISSNHL with vestibular dysfunction in terms of the pattern and trajectory of possible process of vestibular function recovery. METHODS/DESIGN: A randomized, outcome-assessor- and analyst-blinded, controlled, clinical trial (RCT) will be carried out. Seventy-two patients with ISSNHL complaining of vestibular dysfunction appearing as vertigo or imbalance will be recruited and randomized into either oral or intratympanic glucocorticoid therapy group with a 1:1 allocation ratio. The primary outcomes will be vestibular function outcomes assessed by sensory organization test, caloric test, video head impulse test, cervical vestibular evoked myogenic potential, and ocular vestibular evoked myogenic potential; the secondary outcomes include self-reported vestibular dysfunction symptoms; dizziness-related handicap, visual analogue scale for vertigo and tinnitus; and pure tone audiometry. Assessments of primary outcomes will be performed at baseline and at 4 and 8 weeks post-randomization, while assessments of secondary outcomes will be performed at baseline and 1, 2, 4, and 8 weeks post-randomization. DISCUSSION: Previous intervention studies of ISSNHL included only hearing outcomes, with little attention paid on the prognosis of vestibular dysfunction. This trial will be the first RCT study focusing on the progress and prognosis of vestibular dysfunction in ISSNHL. The efficacy of two commonly used therapies of glucocorticoids will be compared in both auditory and vestibular function fields, rather than in the hearing outcome alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT03974867 . Registered on 23 July 2019.