Progress in protecting vestibular hair cells.

Vestibular hair cells are mechanosensory receptors that are capable of detecting changes in head position and thereby allow animals to maintain their posture and coordinate their movement. Vestibular hair cells are susceptible to ototoxic drugs, aging, and genetic factors that can lead to permanent vestibular dysfunction. Vestibular dysfunction mainly results from the injury of hair cells, which are located in the vestibular sensory epithelium. This review summarizes the mechanisms of different factors causing vestibular hair cell damage and therapeutic strategies to protect vestibular hair cells.

Concordancia interevaluador en la elección de tratamiento profiláctico para la migraña vestibular y papel de un algoritmo asistido para la elección de dicho tratamiento / Inter-rater agreement in the choice of prophylactic treatment for vestibular migraine and role of an assisted algorithm for this choice

ANTECEDENTES Y OBJETIVO: La migraña vestibular (MV) es una de las causas de síndrome vestibular episódico. Existen muchos fármacos disponibles para su profilaxis y actualmente su elección se realiza mayoritariamente según las comorbilidades del paciente. El objetivo de este artículo es medir la concordancia de un grupo de otorrinolaringólogos en la elección de profilaxis y evaluar el papel que ejerce sobre esta un algoritmo asistido para la elección de profilaxis. MATERIAL Y MÉTODO: Las historias clínicas de 10 pacientes con MV fueron ofrecidas a 10 otorrinolaringólogos, a los que se les pidió que seleccionasen para cada paciente el fármaco que considerasen más adecuado entre 5 opciones posibles. Se calcularon los índices κ de Fleiss entre los 10 otorrinolaringólogos solos y se recalcularon incluyendo al algoritmo como undécimoevaluador, y la κ de Cohen entre cada otorrinolaringólogo y el algoritmo. Se ofreció a los otorrinolaringólogos la opción de cambiar su respuesta tras conocer la respuesta del algoritmo, y ambos índices fueron calculados nuevamente. RESULTADOS: El índice κ de Fleiss fue de 0,302. Dicho índice se elevó a 0,343 tras introducir al algoritmo como evaluador. Tras ofrecer las soluciones propuestas por el algoritmo, se mejoró la κ de Cohen en 9 de los 10 evaluadores y la κ de Fleiss subió a 0,711. CONCLUSIONES: La concordancia entre otorrinolaringólogos para elegir profilaxis para la MV se define como «justa». Las respuestas del algoritmo para la elección de profilaxis se situaron próximas a la opinión media de los otorrinolaringólogos, elevando la concordancia entre ellos a «sustancial»

BACKGROUND AND OBJECTIVE: Vestibular migraine (VM) is a cause of episodic vestibular syndrome. There are many drugs available for its prophylaxis and currently the choice is mainly made according to the patient's comorbidities. The aim of this article was to measure the agreement of a group of otorhinolaryngologists in the choice of a prophylactic treatment and to evaluate the role of an assisted algorithm in the choice of this prophylaxis. MATERIAL AND METHOD: The medical records of 10 patients with VM were offered to 10 otolaryngologists who were asked to select for each patient the drug they considered most appropriate among five possible options. The Fleiss' κ index was calculated among the 10 otolaryngologists alone, recalculating it including the algorithm as the eleventh evaluator, and Cohen's κ index was calculated between each otolaryngologist and the answers of the algorithm. The otolaryngologists were offered the option to change their responses after knowing the responses of the algorithm and then both indexes were calculated again. RESULTS: The Fleiss' κ index was .302. This index was raised to .343 after introducing the algorithm as an evaluator. After offering the responses proposed by the algorithm, Cohen's κ was improved in 9 of the 10 evaluators, and Fleiss' κ rose to .711. CONCLUSIONS: The agreement between otorhinolaryngologists in choosing prophylaxis for MV can be defined as "fair". The responses of the algorithm for the choice of prophylaxis were close to the average opinion of the otolaryngologists, raising the agreement between them to "substantial"

Analysis of the effectiveness of the prophylaxis of vestibular migraine depending on the diagnostic category and the prescribed drug.

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.

Inter-rater agreement in the choice of prophylactic treatment for vestibular migraine and role of an assisted algorithm for this choice. / Concordancia interevaluador en la elección de tratamiento profiláctico para la migraña vestibular y papel de un algoritmo asistido para la elección de dicho tratamiento.

BACKGROUND AND OBJECTIVE: Vestibular migraine (VM) is a cause of episodic vestibular syndrome. There are many drugs available for its prophylaxis and currently the choice is mainly made according to the patient's comorbidities. The aim of this article was to measure the agreement of a group of otorhinolaryngologists in the choice of a prophylactic treatment and to evaluate the role of an assisted algorithm in the choice of this prophylaxis. MATERIAL AND METHOD: The medical records of 10 patients with VM were offered to 10 otolaryngologists who were asked to select for each patient the drug they considered most appropriate among five possible options. The Fleiss' κ index was calculated among the 10 otolaryngologists alone, recalculating it including the algorithm as the eleventh evaluator, and Cohen's κ index was calculated between each otolaryngologist and the answers of the algorithm. The otolaryngologists were offered the option to change their responses after knowing the responses of the algorithm and then both indexes were calculated again. RESULTS: The Fleiss' κ index was .302. This index was raised to .343 after introducing the algorithm as an evaluator. After offering the responses proposed by the algorithm, Cohen's κ was improved in 9 of the 10 evaluators, and Fleiss' κ rose to .711. CONCLUSIONS: The agreement between otorhinolaryngologists in choosing prophylaxis for MV can be defined as "fair". The responses of the algorithm for the choice of prophylaxis were close to the average opinion of the otolaryngologists, raising the agreement between them to "substantial".

Graded Combined Aerobic Resistance Exercise (CARE) to Prevent or Treat the Persistent Post-concussion Syndrome.

PURPOSE OF REVIEW: To review the growing body of indirect and direct evidence that suggests that exercise can be helpful for children, adolescents, and adults with persistent symptoms following a mild traumatic brain injury (mTBI). RECENT FINDINGS: The direct evidence shows that graded exercise assessments are safe, and that aerobic exercise interventions are associated with improvement of multiple symptoms and other benefits, including earlier return-to-sport. The indirect evidence supports this approach via studies that reveal the potential mechanisms, and show benefits for related presentations and individual symptoms, including headaches, neck pain, vestibular problems, sleep, stress, anxiety, and depression. We document the forms of exercise used for the post-acute management of mTBI, highlight the knowledge gaps, and provide future research directions. We recommend trialing a new approach that utilizes a graduated program of individually prescribed combined aerobic resistance exercises (CARE) if mTBI symptoms persist. This program has the potential to improve patient outcomes and add to the management options for providers.

Small molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki Syndrome.

Kabuki Syndrome (KS) is a rare disorder characterized by distinctive facial features, short stature, skeletal abnormalities, and neurodevelopmental deficits. Previously, we showed that loss of function of RAP1A, a RAF1 regulator, can activate the RAS/MAPK pathway and cause KS, an observation recapitulated in other genetic models of the disorder. These data suggested that suppression of this signaling cascade might be of therapeutic benefit for some features of KS. To pursue this possibility, we performed a focused small molecule screen of a series of RAS/MAPK pathway inhibitors, where we tested their ability to rescue disease-relevant phenotypes in a zebrafish model of the most common KS locus, kmt2d. Consistent with a pathway-driven screening paradigm, two of 27 compounds showed reproducible rescue of early developmental pathologies. Further analyses showed that one compound, desmethyl-Dabrafenib (dmDf), induced no overt pathologies in zebrafish embryos but could rescue MEK hyperactivation in vivo and, concomitantly, structural KS-relevant phenotypes in all KS zebrafish models (kmt2d, kmd6a and rap1). Mass spectrometry quantitation suggested that a 100 nM dose resulted in sub-nanomolar exposure of this inhibitor and was sufficient to rescue both mandibular and neurodevelopmental defects. Crucially, germline kmt2d mutants recapitulated the gastrulation movement defects, micrognathia and neurogenesis phenotypes of transient models; treatment with dmDf ameliorated all of them significantly. Taken together, our data reinforce a causal link between MEK hyperactivation and KS and suggest that chemical suppression of BRAF might be of potential clinical utility for some features of this disorder.

Prophylactic treatment of vestibular migraine / Tratamento profilático da migrânea vestibular

Abstract Introduction: Vestibular migraine (VM) is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including β-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce. Objective: To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic. Methods: Review of medical records from patients with VM according to the criteria of the Bárány Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS) for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used). Associations with clinical subgroups of patients were also assessed. Results: Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p < 0.001). Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p < 0.001) and headache (p < 0.015). The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug association did not show statistically significant results in relation to the use of a single drug. Conclusions: Prophylactic medications used to treat VM improve the symptoms of this disease, but there is no statistically significant difference between the responses of prophylactic drugs. The time of vestibular symptom seems to increase the benefit with prophylactic treatment.

Resumo Introdução: A migrânea vestibular (MV) é aceita atualmente como uma causa comum de vertigem episódica. O tratamento da MV envolve duas situações: as crises de sintomas vestibulares e o período intercrise. Para esse último, pode-se usar algum método de profilaxia. A recomendação atual é que se usem os mesmos medicamentos profiláticos usados para a enxaqueca, o que inclui os β-bloqueadores, antidepressivos e anticonvulsivantes. A recente definição diagnóstica da migrânea vestibular torna escasso o número de estudos sobre seu tratamento. Objetivo: Avaliar a eficácia do tratamento profilático usado em pacientes em um ambulatório de MV. Método: Revisão de prontuários de pacientes com MV pelos critérios da Bárány Society/International Headeache Society de 2012. Foram pesquisados os medicamentos usados e resposta ao tratamento obtida através da escala visual analógica (EVA) para tontura e cefaleia. Foram comparados os escores da EVA pré e pós-tratamento (a melhoria foi avaliada em conjunto e individualmente por droga usada). Também foram pesquisadas relações com subgrupos clínicos dos pacientes. Resultados: De 88 prontuários estudados, 47 foram elegíveis. Incluíram-se os pacientes que preenchiam os critérios diagnósticos para MV, foram excluídos os prontuários ilegíveis e aqueles de pacientes com outro distúrbio causador de tontura e/ou cefaleia que não preenchiam critérios de 2012 para MV. Apresentaram melhoria com a profilaxia 80,9% dos pacientes (p < 0,001). Amitriptilina, flunarizina, propranolol e topiramato apresentaram melhoria para sintomas vestibulares (p < 0,001) e para cefaleia (p < 0,015). Os quatro medicamentos foram eficazes de forma estatisticamente significante. Houve relação estatística positiva entre tempo de sintoma vestibular e melhoria clínica. Não houve benefício adicional para hipertensos que usaram anti-hipertensivos como profilaxia ou para os deprimidos que usaram antidepressivos em relação ao uso dos outros profiláticos. A associação de medicamentos não mostrou resultados estatisticamente significantes do uso de um medicamento isolado. Conclusões: Os medicamentos profiláticos usados para MV melhoram os sintomas dessa doença, porém não há diferença estatisticamente significante entre as respostas dos medicamentos profiláticos. O tempo de sintoma vestibular parece aumentar a melhoria obtida com o tratamento profilático.

Efficacy of microsurgical tumor removal for treatment of patients with intracanalicular vestibular schwannoma presenting with disabling vestibular symptoms.

OBJECTIVE The aim of this study was to analyze the efficacy and risks of microsurgery via the hearing-preserving retrosigmoid approach in patients with intracanalicular vestibular schwannoma (VS) suffering from disabling vestibular symptoms, with special attention to vertigo. METHODS This is a retrospective analysis of 19 patients with intracanalicular VS and disabling vestibular dysfunction as the main or only symptom (Group A). All of the patients reported having had disabling vertigo attacks. Subjective evaluation of the impairment of patients was performed before surgery, 3 weeks after surgery, 3 months after surgery, and 1 year after surgery, using the Dizziness Handicap Inventory (DHI). The main outcome measures were improvement in quality of life as measured using the DHI, and general and functional outcomes, in particular facial function and hearing. Patient age, preoperative tumor size, preoperative DHI score, and preservation of the nontumorous vestibular nerve were tested using a multivariate regression analysis to determine factors affecting the postoperative DHI score. The Mann-Whitney U-test was used to compare the postoperative DHI score at 3 weeks, 3 months, and 1 year after surgery with a control group of 19 randomly selected patients with intracanalicular VSs, who presented without vestibular symptoms (Group B). The occurrence of early postoperative discrete vertigo attacks was also compared between groups. RESULTS The preoperative DHI score was ≥ 54 in all patients. All patients reported having had disabling rotational vertigo before surgery. The only significant factor to affect the DHI outcome 3 weeks and 3 months after surgery was the preoperative DHI score. The DHI outcome after 1 year was not affected by the preoperative DHI score. Compared with the control group, the DHI score at 3 weeks and 3 months after surgery was significantly worse. There was no significant difference between the groups after 1 year. Vertigo was improved in all patients and completely resolved after 1 year in 17 patients. CONCLUSIONS Disabling vestibular dysfunction that affects quality of life should be considered an indication for surgery, even in otherwise asymptomatic patients with intracanalicular VS. Surgical removal of the tumor is safe and very effective in regard to symptom relief. All patients had excellent facial nerve function within 1 year after surgery, with a very good chance of hearing preservation.

Prophylactic treatment of vestibular migraine.

INTRODUCTION: Vestibular migraine (VM) is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including ß-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce. OBJECTIVE: To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic. METHODS: Review of medical records from patients with VM according to the criteria of the Bárány Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS) for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used). Associations with clinical subgroups of patients were also assessed. RESULTS: Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p<0.001). Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p<0.001) and headache (p<0.015). The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug association did not show statistically significant results in relation to the use of a single drug. CONCLUSIONS: Prophylactic medications used to treat VM improve the symptoms of this disease, but there is no statistically significant difference between the responses of prophylactic drugs. The time of vestibular symptom seems to increase the benefit with prophylactic treatment.

Assessment of D-methionine protecting cisplatin-induced otolith toxicity by vestibular-evoked myogenic potential tests, ATPase activities and oxidative state in guinea pigs.

To date, inadequate study has been devoted to the toxic vestibular effects caused by cisplatin. In addition, no electrophysiological examination has been conducted to assess cisplatin-induced otolith toxicity. The purposes of this study are thus two-fold: 1) to determine whether cervical vestibular-evoked myogenic potentials (VEMPs) and ocular VEMPs are practical electrophysiological methods of testing for cisplatin-induced otolith toxicity and 2) to examine if D-methionine (D-met) pre-injection would protect the otolith organs against cisplatin-induced changes in enzyme activities and/or oxidative status. Guinea pigs were intraperitoneally treated once daily with the following injections for seven consecutive days: sterile 0.9% saline control, cisplatin (5 mg/kg) only, D-met (300 mg/kg) only, or a combination of d-met (300 mg/kg) and cisplatin (5 mg/kg), respectively, with a 30 minute window in between. Each animal underwent the oVEMP and cVEMP tests before and after treatment. The changes in the biochemistry of the otolith organs, including membranous Na(+), K(+)-ATPase and Ca(2+)-ATPase, lipid peroxidation (LPO) levels and nitric oxide (NO) levels, were also evaluated. In the cisplatin-only treated guinea pigs, the mean amplitudes of the oVEMP tests were significantly (p<0.05) decreased when compared to the other three groups. In guinea pigs receiving both D-met and cisplatin, the amplitudes of their oVEMP tests were significantly larger (p<0.05) than those of the cisplatin-only group, but smaller (p<0.05) than those of the saline control or D-met-only group. However, no significant difference of the amplitudes of cVEMP tests was noted among the four groups. In comparison with the other three groups, the cisplatin-only group had the lowest (ps<0.05) mean Na(+), K(+)-ATPase and Ca(2+)-ATPase, and the highest (ps<0.05) LPO and NO levels. The oVEMP tests were feasible for the evaluation of cisplatin-related otolith dysfunction. D-Met attenuated the reduced ATPase activities and increased oxidative stress induced by cisplatin toxicity in the otolith organs.

[About the surgical treatment of vestibular window abnormalities].

The objective of the present study was to develop the sparing strategy for the surgical treatment of the patients presenting with malformations of the vestibular window based on the results of the evaluation of synopty of the main clues of the internal and middle ears. This article contains the analysis of the effectiveness of the surgical treatment of 17 patients with malformations of the vestibular window operated during the period from 2008 till 2013. It presents the results of investigations into the topographic relationships between the principal structures of the internal and middle ears of special importance for the assessment of the possibilities for the surgical treatment of such patients with the minimal risk of development of postoperative complications. The results of the surgical treatment were estimated based on the data of audiological studies in the early and late postoperative periods. It was shown that none of the patients developed the symptoms of dizziness, unstable gait or sensorineural impairment of hearing in the immediate postoperative period. Good functional results in the form of the reduced bone-air interval (15.2±1.0 dB) were achieved in 13 patients. Nevertheless, the considerable decrease in the sound conductivity in the late postoperative period observed in 64.7% of the patients related to the closure of the vestibular fistula dictates the necessity of developing the novel techniques for its prevention.

[Current aspects of ototoxicity : Local ototoxic effects, diagnosis, prevention, and treatment]. / Aktuelle Aspekte zur Ototoxizität : Lokale ototoxische Wirkungen, Diagnostik, Prävention und Therapie.

The otorhinolaryngologist is often involved in an interdisciplinary approach to diagnose ototoxic side effects. Under certain conditions, chemical agents-particularly drugs-can have ototoxic effects. This is not only true for systemic administration, but also for local application (e.g., transdermal and transtympanal). Identifying and avoiding ototoxicity is still a challenge in clinical practice. The audiological monitoring of patients receiving potentially cochleotoxic drugs is now standardized. For diagnosis of suspected vestibulotoxic effects, the video head impulse test and vestibular evoked myogenic potentials seem to be suitable procedures for objective assessment. The early detection of such ototoxic effects has important implications for the prevention of hearing and balance disorders. Recent studies show that intratympanic delivery of medications might play an important role in the limitation of ototoxically induced hearing loss. In peripheral vestibulopathies with episodic vertigo, which strongly affect quality of life, ototoxic effects can be used for therapeutic purposes.

Red ginseng delays age-related hearing and vestibular dysfunction in C57BL/6 mice.

Since Korean red ginseng (KRG) has been proven to protect against gentamicin-induced vestibular and hearing dysfunction, the effects of KRG on age-related inner ear disorder in C57BL/6 mice were investigated. While age-related hearing loss was detected at the age of 6months (32kHz) and 9months (16kHz) in the control group, it was significantly delayed (p<0.05) in the 150mg/kg KRG-treated group. Vestibular dysfunction was observed in the tail-hanging and swimming tests, with significantly different severity scores and swimming times detected between the control and 150mg/kg KRG-treated group at the age of 12months (p<0.05). Mice treated with 500mg/kg KRG exhibited irritability and aggravated inner ear dysfunction. Histological observation supported the findings of hearing and vestibular function defects. In conclusion, C57BL/6 mice showed early-onset hearing loss and progressive vestibular dysfunction with aging, which were delayed by treatment with 150mg/kg KRG. However, 500mg/kg KRG treatment may induce aggressive behavior.

Sensorial countermeasures for vestibular spatial disorientation.

Spatial disorientation is defined as an erroneous body orientation perceived by pilots during flights. Limits of the vestibular system provoke frequent spatial disorientation mishaps. Although vestibular spatial disorientation is experienced frequently in aviation, there is no intuitive countermeasure against spatial disorientation mishaps to date. The aim of this review is to describe the current sensorial countermeasures and to examine future leads in sensorial ergonomics for vestibular spatial disorientation. This work reviews: 1) the visual ergonomics, 2) the vestibular countermeasures, 3) the auditory displays, 4) the somatosensory countermeasures, and, finally, 5) the multisensory displays. This review emphasizes the positive aspects of auditory and somatosensory countermeasures as well as multisensory devices. Even if some aspects such as sensory conflict and motion sickness need to be assessed, these countermeasures should be taken into consideration for ergonomics work in the future. However, a recent development in aviation might offer new and better perspectives: unmanned aerial vehicles. Unmanned aerial vehicles aim to go beyond the physiological boundaries of human sensorial systems and would allow for coping with spatial disorientation and motion sickness. Even if research is necessary to improve the interaction between machines and humans, this recent development might be incredibly useful for decreasing or even stopping vestibular spatial disorientation.

[Dizziness from a psychosomatic perspective]. / Schwindel aus psychosomatischer Sicht.

Somatoform dizziness is one of the most frequent forms of dizziness besides vestibular neuritis and benign peripheral positional vertigo. Due to false diagnoses patients often suffer from the symptoms for months and even years and because of this the working and private activities are severely restricted. An early interdisciplinary diagnosis is very important and a specific psychosomatic therapy should be started as early as possible. Somatoform dizziness can be due to a variety of mental or psychosomatic disorders. It can occur without a preceding peripheral vestibular disorder (primary somatoform dizziness) or it can develop after a peripheral vestibular disorder (secondary somatoform dizziness). The clinical symptomatology, diagnosis and differential diagnosis are described and illustrated by clinical vignettes. Risk factors and preventive measures are briefly summarized.

Gentamicin ototoxicity: a 23-year selected case series of 103 patients.

OBJECTIVE: To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital. DESIGN AND SETTING: A retrospective case series of presentations to a balance disorders clinic between 1988 and 2010. MAIN OUTCOME MEASURES: Relationship between vestibulotoxicity and gentamicin dose or dosing profile; indications for prescribing gentamicin. RESULTS: 103 patients (age, 18-84 years; mean, 64 years) presented with imbalance, oscillopsia or both, but none had vertigo. Only three noted some hearing impairment after having gentamicin, but audiometric thresholds for all patients were consistent with their age. In all patients, the following tests gave positive results: a bilateral clinical head-impulse test, a vertical head-shaking test for vertical oscillopsia, and a foam Romberg test. In 21 patients, imbalance occurred during gentamicin treatment (ignored or dismissed by prescribers in 20) and in 66 after treatment; the remaining 16 could not recall when symptoms were first noticed, except that it was after gentamicin treatment in hospital. Total gentamicin dose range was 2-318 mg/kg (mean, 52 mg/kg), daily dose range was 1.5-5.6 mg/kg (mean, 3.5mg/kg), and duration was 1-80 days (mean, 17 days). Six patients had only a single dose; 26 had five or fewer doses. Serum gentamicin levels, measured in 82 patients, were in the recommended range in 59. Time to diagnosis ranged from 4 days to 15 years. Nephrotoxicity developed in 43 patients. Gentamicin dosage complied with contemporary or current Australian antibiotic guidelines in under half the patients. CONCLUSIONS: Gentamicin ototoxicity is vestibular, not cochlear, producing permanent loss of balance, but not of hearing. Gentamicin can be vestibulotoxic in any dose, in any regimen, at any serum level.

[Application of platelet-enriched plasma for the prevention of cochleovestibular disorders associated with piston stapedoplasty].

The present study was designed to evaluate the influence of sealing the labyrinthine vestibule with platelet-enriched plasma (PEP) on the development of cochleovestibular complications following piston stapedoplasty. The platelet-rich plasma was prepared by single-step centrifugation of the whole venous blood. Analysis of the data obtained showed that the use of PEP for sealing the periprosthetic space after stapedoplasty reduces the risk of development of sensorineural hearing impairment compared with the application of fatty tissue for the same purpose or a freely positioned prosthesis. Moreover, the use of PEP decreases the probability of the development of tympanophonia and its intensity after piston stapedoplasty.

Ethical issues in the development of a vestibular prosthesis.

During the development of a neural prosthesis, various ethical aspects have to be considered. These range from the basic design of the prosthesis and manufacturing of the various components and the system using biocompatible materials to extensive in vitro and in vivo testing and investigations in the animal model, before taking the final step and going to human trials. As medical systems, neural prostheses have to be proven absolutely safe before considering any clinical study. In this work, the various steps accompanying the development are described taking the example of a vestibular prosthesis currently developed within the European project CLONS.

Vestibular implants: the first steps in humans.

Currently there is no efficient treatment for patients with severe bilateral vestibular function impairment. Presence of oscillopsia is their main complaint. It has a significant negative impact on their quality of life. Recently it has been shown that angular vestibulo-ocular reflex can be partially restored in animals. In humans it is possible to elicit a nystagmic response by electric stimulation of ampullary parts of the vestibular nerve. Controlled eye movements can be generated by frequency and intensity modulation of the restored baseline firing rate of the vestibular nerve. During adaptation phase to the electric stimulus, patients experience nystagmus with associated inconveniences. By repetition of "on/off periods" the duration of the adaptation phase can be significantly decreased. Results show that permanent electric stimulation is necessary to maintain this "optimal" adaptation state.