[The "difficult" patient-pearls and pitfalls of vestibular diagnostic tests: Part 2 : Difficult aspects of vestibular laboratory testing]. / "Schwierige" Patient:innen ­ Vestibularisdiagnostik unter erschwerten Bedingungen: Teil 2 : Schwierige Aspekte der apparativen Vestibularisprüfung.

Patients with the cardinal symptoms "vertigo" or "dizziness" may be a real challenge for the treating otorhinolaryngologist. While the first part of this educational series was focused on history taking and bedside neurotological examination, the present paper is devoted to difficult aspects of vestibular laboratory testing, including getting the indication right, what to do if my patient is not able to fully cooperate during the tests, how to choose the adequate diagnostic procedure depending on the patient's comorbidities, how to interpret discordant results of various tests. Finally the paper addresses which conclusions can be drawn (and cannot be drawn) from normal findings in vestibular testing and how to communicate this result to the dizzy patient.

[Update on diagnostic procedures in third window syndromes. German version]. / Update zur Diagnostik der Drittfenstersyndrome.

BACKGROUND: The diagnosis of third window syndromes often poses a challenge in clinical practice. OBJECTIVE: This paper provides an up-to-date overview of diagnostic procedures in third window syndromes, with special emphasis on superior canal dehiscence syndrome (SCDS), large vestibular aqueduct syndrome (LVAS), and X-chromosomal malformation of the cochlea. MATERIALS AND METHODS: A literature search was performed in PubMed up to December 2023. Furthermore, a selection of the authors' own cases is presented. RESULTS: Audiovestibular tests for the diagnosis of third window syndromes are most often reported for patients with SCDS in the literature. In this context, cut-off values with different sensitivities and specificities have been defined for different outcome parameters of vestibular evoked myogenic potentials. Current developments include the application of electrocochleography, broadband tympanometry, video head impulse testing, and vibration-induced nystagmus. Genetic analyses are increasingly applied in LVAS. CONCLUSION: The diagnosis of third window syndromes is always based on the synthesis of patients' symptoms, clinical signs, audiovestibular test results, and imaging.

Physiological oculo-auricular-facial-mandibular synkinesis elicited in humans by gaze deviations.

Integrated motor behaviors involving ocular motion-associated movements of the head, neck, pinna, and parts of the face are commonly seen in animals orienting to a visual target. A number of coordinated movements have also been observed in humans making rapid gaze shifts to horizontal extremes, which may be vestiges of these. Since such integrated mechanisms point to a nonpathological coactivation of several anatomically separate cranial circuits in humans, it is important to see how the different pairs of integrative motor behaviors with a common trigger (i.e., ocular motion) manifest in relation to one another. Here, we systematically examined the pattern of eye movement-induced recruitment of multiple cranial muscles in humans. Simultaneous video-oculography and bilateral surface electromyograms of transverse auricular, temporalis, frontalis, and masseter muscles were recorded in 15 healthy subjects (8 females; 29.3 ± 5.2 yr) while they made head-fixed, horizontal saccadic, pursuit, and optokinetic eye movements. Potential chin laterotrusion linked to contractions of masticator muscles was captured with a jaw-fixed accelerometer. Our findings objectively show an orchestrated aural-facial-masticatory muscle response to a range of horizontal eye movements (prevalence of 21%-93%). These responses were most prominent during eccentric saccades. We further reveal distinctions between the various observed activation patterns in terms of their profile (transient or sustained), laterality (with respect to direction of gaze), and timing (with respect to saccade onset). Possible underlying neural substrates, their atavistic behavioral significance, and potential clinical applications for monitoring sensory attention and designing attention-directed hearing aids in the future are discussed.NEW & NOTEWORTHY Healthy humans exhibit different combinations of nonpathological, synkinetic gaze-associated movements with aural, facial, and/or masticatory muscles during different types of voluntary and reflexive horizontal eye movements. The manifestations of these collective phenomena are strongest during large-scale horizontal saccades and accompanied by a detectable horizontal chin movement. Auricular muscle activations occur equally on both sides, whereas the activation of facial and masticatory muscles is predominantly ipsilateral (in regard to gaze direction).

Corticosteroids in patients with vestibular neuritis: An updated meta-analysis.

Vestibular neuritis is a common neuro-otological entity. Therapeutically, corticosteroids are advised, although the evidence is limited. The objective of this review is to update meta-analyses of clinical trials that address the question of whether patients with vestibular neuritis treated with corticosteroids show better recovery than control patients. The electronic databases Medline, Scopus and Cochrane were searched for clinical trials for the years 1970-2020 without language restriction. Data were extracted, and outcome parameters were subjected to conventional and cumulative meta-analysis using a commercially available software program (www.meta-analysis.com). Finally, 15 trials with 363 participants in the treatment and 489 in the control groups were identified and could be included. Eight studies were judged to be at high risk of bias. The odds ratio (OR) for good outcome in the acute phase was 3.1 (95% CI 1.2-7.8; p = .015) in favour of steroid treatment leading to the number needed to treat (NNT) = 6 (95% CI 4-23). The odds ratio (OR) for restoration of vestibular function in the follow-up was 2.4 (95% CI 1.3-4.4; p = .004) for the benefit of steroid treatment resulting in a NNT = 7 (95% CI 5-18). The results of the cumulative statistics did not differ. The risk of adverse effects was higher in patients treated with steroids with an OR of 10.9 (95% CI 1.3-93.8; p = .015) and an estimated number needed to harm (NNH) = 4 (95% CI 3-19). The advantage for corticosteroids remained when differentiating between patients who participated in randomized or non-randomized clinical trials. Steroid treatment in vestibular neuritis resulted in a statistically significant benefit compared to control therapies. However, broad heterogeneity of the studies, mostly low-grade quality of studies, high risk of bias and broad confidence intervals put the findings into perspective allowing only a careful judgement of some benefit of corticosteroids. The findings, however, support the call for an adequately powered and well-designed randomized controlled trial to re-evaluate the effectiveness of corticosteroids.

[The "difficult" patient-Vestibular testing under difficult conditions : Part 1: History taking and clinical neurotological examination]. / Der "schwierige" Patient ­ Vestibularisdiagnostik unter erschwerten Bedingungen : Teil 1: Anamnese und klinisch-neurootologische Untersuchung.

Patients presenting with vertigo or dizziness may pose a real challenge for the clinical otorhinolaryngologist. This series of articles covers different aspects of the "difficult" dizzy patient. The first part is dedicated to pearls and pitfalls in history taking and clinical neurotological examination. It suggests possible solutions for challenging situations in history taking, such as definition of the expectations and aims, patients presenting with a long-winded history, patients' description of the symptom "vertigo", multiple vestibular syndromes in one patient, discrepancy between subjective symptoms and objective vestibular findings, cognitive bias and dealing with emotions. Furthermore, it offers practically oriented tips for the neurotological examination of patients with problems of the cervical spine, oculomotor disorders and anxiety.

Rare Disorders of the Vestibular Labyrinth: of Zebras, Chameleons and Wolves in Sheep's Clothing. / Seltene Erkrankungen des vestibulären Labyrinths: von Zebras, Chamäleons und Wölfen im Schafspelz.

The differential diagnosis of vertigo syndromes is a challenging issue, as many - and in particular - rare disorders of the vestibular labyrinth can hide behind the very common symptoms of "vertigo" and "dizziness". The following article presents an overview of those rare disorders of the balance organ that are of special interest for the otorhinolaryngologist dealing with vertigo disorders. For a better orientation, these disorders are categorized as acute (AVS), episodic (EVS) and chronic vestibular syndromes (CVS) according to their clinical presentation. The main focus lies on EVS sorted by their duration and the presence/absence of triggering factors (seconds, no triggers: vestibular paroxysmia, Tumarkin attacks; seconds, sound and pressure induced: "third window" syndromes; seconds to minutes, positional: rare variants and differential diagnoses of benign paroxysmal positional vertigo; hours to days, spontaneous: intralabyrinthine schwannomas, endolymphatic sac tumors, autoimmune disorders of the inner ear). Furthermore, rare causes of AVS (inferior vestibular neuritis, otolith organ specific dysfunction, vascular labyrinthine disorders, acute bilateral vestibulopathy) and CVS (chronic bilateral vestibulopathy) are covered. In each case, special emphasis is laid on the decisive diagnostic test for the identification of the rare disease and "red flags" for potentially dangerous disorders (e. g. labyrinthine infarction/hemorrhage). Thus, this chapter may serve as a clinical companion for the otorhinolaryngologist aiding in the efficient diagnosis and treatment of rare disorders of the vestibular labyrinth.

Physiology, clinical evidence and diagnostic relevance of sound-induced and vibration-induced vestibular stimulation.

PURPOSE OF REVIEW: To examine the recent literature concerning the neural basis and clinical evidence for the response of the labyrinth to sound and vibration: vestibular-evoked myogenic potentials (VEMPs) and vibration-induced nystagmus (VIN). RECENT FINDINGS: There are two streams of information from each otolith - a sustained stream (afferents with regular resting activity, signalling gravity and low-frequency linear accelerations) and a transient stream (afferents with irregular resting activity) signalling onset of linear acceleration, and sound and vibration. These irregular neurons are synchronized to each cycle of the stimulus. Neurons in the transient stream are tested by presenting sounds or vibration (500 Hz) and using surface electrodes to measure myogenic potentials from muscles activated by otolithic stimuli (VEMPs). 100 Hz vibration activates irregular canal afferents and causes a stimulus-locked VIN in patients with asymmetric canal function. These new tests of the transient system have one big advantage over older tests of the sustained system - they reliably show the effect of long-term unilateral vestibular loss. SUMMARY: The new physiological and anatomical evidence shows how sound and vibration activate otolith and canal receptors and so provides the scientific foundation for VEMPs and VIN, which are important tools for diagnosing vestibular disorders. VIDEO ABSTRACT: http://links.lww.com/CONR/A47.

Galvanic vestibular stimulation: from basic concepts to clinical applications.

Galvanic vestibular stimulation (GVS) plays an important role in the quest to understand sensory signal processing in the vestibular system under normal and pathological conditions. It has become a highly relevant tool to probe neuronal computations and to assist in the differentiation and treatment of vestibular syndromes. Following its accidental discovery, GVS became a diagnostic tool that generates eye movements in the absence of head/body motion. With the possibility to record extracellular and intracellular spikes, GVS became an indispensable method to activate or block the discharge in vestibular nerve fibers by cathodal and anodal currents, respectively. Bernie Cohen, in his attempt to decipher vestibular signal processing, has used this method in a number of hallmark studies that have added to our present knowledge, such as the link between selective electrical stimulation of semicircular canal nerves and the generation of directionally corresponding eye movements. His achievements paved the way for other major milestones including the differential recruitment order of vestibular fibers for cathodal and anodal currents, pronounced discharge adaptation of irregularly firing afferents, potential activation of hair cells, and fiber type-specific activation of central circuits. Previous disputes about the structural substrate for GVS are resolved by integrating knowledge of ion channel-related response dynamics of afferents, fiber type-specific innervation patterns, and central convergence and integration of semicircular canal and otolith signals. On the basis of solid knowledge of the methodology, specific waveforms of GVS are currently used in clinical diagnosis and patient treatment, such as vestibular implants and noisy galvanic stimulation.

Deficit in acoustic signal-in-noise detection in glycine receptor α3 subunit knockout mice.

Hearing is an essential sense for communication in animals and humans. Normal function of the cochlea of higher vertebrates relies on a fine-tuned interplay of afferent and efferent innervation of both inner and outer hair cells. Efferent inhibition is controlled via olivocochlear feedback loops, mediated mainly by acetylcholine, γ-aminobutyric acid (GABA) and glycine, and is one of the first sites affected by synapto- and neuropathy in the development of hearing loss. While the functions of acetylcholine, GABA and other inhibitory transmitters within these feedback loops are at least partially understood, especially the function of glycine still remains elusive. To address this question, we investigated hearing in glycine receptor (GlyR) α3 knockout (KO) and wildtype (WT) mice. We found no differences in pure tone hearing thresholds at 11.3 and 16 kHz between the two groups as assessed by auditory brainstem response (ABR) measurements. Detailed analysis of the ABR waves at 11.3 kHz, however, revealed a latency decrease of wave III and an amplitude increase of wave IV in KO compared to WT animals. GlyRα3 KO animals showed significantly impaired prepulse inhibition of the auditory startle response in a noisy environment, indicating that GlyRα3-mediated glycinergic inhibition is important for signal-in-noise detection.

Lack of brain-derived neurotrophic factor hampers inner hair cell synapse physiology, but protects against noise-induced hearing loss.

The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. We found that brain derived neurotrophic factor (BDNF) differentially influences IHC characteristics in the intact and injured cochlea. Using conditional knock-out mice (BDNF(Pax2) KO) we found that resting membrane potentials, membrane capacitance and resting linear leak conductance of adult BDNF(Pax2) KO IHCs showed a normal maturation. Likewise, in BDNF(Pax2) KO membrane capacitance (ΔC(m)) as a function of inward calcium current (I(Ca)) follows the linear relationship typical for normal adult IHCs. In contrast the maximal ΔC(m), but not the maximal size of the calcium current, was significantly reduced by 45% in basal but not in apical cochlear turns in BDNF(Pax2) KO IHCs. Maximal ΔC(m) correlated with a loss of IHC ribbons in these cochlear turns and a reduced activity of the auditory nerve (auditory brainstem response wave I). Remarkably, a noise-induced loss of IHC ribbons, followed by reduced activity of the auditory nerve and reduced centrally generated wave II and III observed in control mice, was prevented in equally noise-exposed BDNF(Pax2) KO mice. Data suggest that BDNF expressed in the cochlea is essential for maintenance of adult IHC transmitter release sites and that BDNF upholds opposing afferents in high-frequency turns and scales them down following noise exposure.

Specific and individualized instructions improve the efficacy of booklet-based vestibular rehabilitation at home - a randomized controlled trial (RCT).

BACKGROUND: Vestibular rehabilitation therapy (VRT) is effective for most patients with dizziness and imbalance. Home exercise programs are widely used. It is unknown, however, how specific the instructions for exercises have to be. OBJECTIVE: To evaluate the effects of expert assessment and instructions in a booklet-based home VRT program for patients with chronic dizziness. METHODS: Randomized controlled study on 74 participants with disabling dizziness for >3 months. All study participants received a booklet-based VRT for training at home. Participants were prescribed 20 minutes of exercise, twice a day. The intervention group (n = 37) received specific instructions (expert physiotherapist). The control group (n = 37) practiced without specific instructions. Primary outcome was the total score of the Dizziness Handicap Inventory (DHI-G). All outcomes were assessed at baseline, after 4 weeks, and at follow up 4 weeks later. RESULTS: Both groups improved (DHI-G 43.94±18.89 at inclusion to 33.06±19.67 at follow-up in controls and 42.82±16.60 to 22.65±19.12 in the intervention group). The intervention group, however, improved more (p = 0.014). CONCLUSIONS: We show a significant effect of expert physiotherapy guidance in home-based VRT. This strengthens the role of the physiotherapist in VRT: Tailored, personalized instructions are needed to get the best effect of VRT.

A Review of Neural Data and Modelling to Explain How a Semicircular Canal Dehiscence (SCD) Causes Enhanced VEMPs, Skull Vibration Induced Nystagmus (SVIN), and the Tullio Phenomenon.

Angular acceleration stimulation of a semicircular canal causes an increased firing rate in primary canal afferent neurons that result in nystagmus in healthy adult animals. However, increased firing rate in canal afferent neurons can also be caused by sound or vibration in patients after a semicircular canal dehiscence, and so these unusual stimuli will also cause nystagmus. The recent data and model by Iversen and Rabbitt show that sound or vibration may increase firing rate either by neural activation locked to the individual cycles of the stimulus or by slow changes in firing rate due to fluid pumping ("acoustic streaming"), which causes cupula deflection. Both mechanisms will act to increase the primary afferent firing rate and so trigger nystagmus. The primary afferent data in guinea pigs indicate that in some situations, these two mechanisms may oppose each other. This review has shown how these three clinical phenomena-skull vibration-induced nystagmus, enhanced vestibular evoked myogenic potentials, and the Tullio phenomenon-have a common tie: they are caused by the new response of semicircular canal afferent neurons to sound and vibration after a semicircular canal dehiscence.

A review of the geometrical basis and the principles underlying the use and interpretation of the video head impulse test (vHIT) in clinical vestibular testing.

This paper is concerned mainly with the assumptions underpinning the actual testing procedure, measurement, and interpretation of the video head impulse test-vHIT. Other papers have reported in detail the artifacts which can interfere with obtaining accurate eye movement results, but here we focus not on artifacts, but on the basic questions about the assumptions and geometrical considerations by which vHIT works. These matters are crucial in understanding and appropriately interpreting the results obtained, especially as vHIT is now being applied to central disorders. The interpretation of the eye velocity responses relies on thorough knowledge of the factors which can affect the response-for example the orientation of the goggles on the head, the head pitch, and the contribution of vertical canals to the horizontal canal response. We highlight some of these issues and point to future developments and improvements. The paper assumes knowledge of how vHIT testing is conducted.

Acute Unilateral Peripheral Vestibulopathy After COVID-19 Vaccination: Initial Experience in a Tertiary Neurotology Center.

Objective: The aim of the present study was to identify patients who developed acute unilateral peripheral vestibulopathy (AUPVP) after COVID-19 vaccination. Methods: For this single-center, retrospective study, we screened the medical records of our tertiary interdisciplinary neurotology center for patients who had presented with AUPVP within 30 days after COVID-19 vaccination (study period: 1 June-31 December 2021). The initial diagnosis of AUPVP was based on a comprehensive bedside neurotological examination. Laboratory vestibular testing (video head impulse test, cervical and ocular vestibular evoked myogenic potentials, dynamic visual acuity, subjective visual vertical, video-oculography, caloric testing) was performed 1-5 months later. Results: Twenty-six patients were diagnosed with AUPVP within the study period. Of those, n = 8 (31%) had developed acute vestibular symptoms within 30 days after COVID-19 vaccination (mean interval: 11.9 days, SD: 4.8, range: 6-20) and were thus included in the study. The mean age of the patients (two females, six males) was 46 years (SD: 11.7). Seven patients had received the Moderna mRNA vaccine and one the Pfizer/BioNTech mRNA vaccine. All patients displayed a horizontal(-torsional) spontaneous nystagmus toward the unaffected ear and a pathological clinical head impulse test toward the affected ear on initial clinical examination. Receptor-specific laboratory vestibular testing performed 1-5 months later revealed recovery of vestibular function in two patients, and heterogeneous lesion patterns of vestibular endorgans in the remaining six patients. Discussion and Conclusions: The present study should raise clinicians' awareness for AUPVP after COVID-19 vaccination. The relatively high fraction of such cases among our AUPVP patients may be due to a certain selection bias at a tertiary neurotology center. Patients presenting with acute vestibular symptoms should be questioned about their vaccination status and the date of the last vaccination dose. Furthermore, cases of AUPVP occurring shortly after a COVID-19 vaccination should be reported to the health authorities to help determining a possible causal relationship.

Combining vestibular rehabilitation with noisy galvanic vestibular stimulation for treatment of bilateral vestibulopathy.

OBJECTIVE: Noisy galvanic vestibular stimulation (nGVS) has been shown to partly restore vestibular function and to stabilize stance and gait in patients with incomplete bilateral vestibulopathy (BVP). Here, we examined potential synergistic effects of nGVS when combined with standardized vestibular rehabilitation training (VRT). METHODS: 23 patients with confirmed BVP received a 30-min vestibular rehabilitation training (VRT) program three times a week for 2 weeks. The intervention group (n = 12) was stimulated with nGVS (at individually determined optimal amplitudes) during training, whereas the control group (n = 11) received zero-amplitude nGVS (sham stimulation) during training. Outcome measurements assessed at baseline, after 2 weeks of training, and at 2-week follow-up included quantitative posturography, instrumented gait analysis, Timed Up and Go Test (TUG), Functional Gait Assessment (FGA), and clinical scores related to quality of life and balance confidence. RESULTS: After 2 weeks of VRT, all patients showed moderate improvement in balance. Irrespective of nGVS treatment, performance improved in the TUG (p < 0.013), and in the FGA (p < 0.040). Furthermore, base of support when walking with closed eyes was reduced after 2-week training (p < 0.003). Postural sway did not change. There was no difference between groups and thereby no evidence for an additional influence of nGVS on the VRT treatment effects. CONCLUSION: nGVS does not induce synergistic treatment effects in combination with VRT in patients with BVP when applied during treatment sessions. Hence, rather than being applied in parallel, nGVS and VRT might be complementary therapeutic options with nGVS being used during postural activities in daily life, e.g., walking.

Prevalence of Endolymphatic Hydrops in Cochlear Implant Candidates with Idiopathic Profound Sensorineural Hearing Loss.

OBJECTIVE: To determine the prevalence of endolymphatic hydrops (EH) in cochlear implant (CI) candidates with idiopathic profound sensorineural hearing loss (SNHL) and its influence on the preservation of audiovestibular function after cochlear implantation. STUDY DESIGN: Prospective case series. SETTING: Tertiary referral center. PATIENTS: CI candidates with idiopathic progressive SNHL, but without classic EH-associated symptoms. INTERVENTIONS: Delayed intravenous gadolinium-enhanced inner ear fluid-attenuated inversion recovery magnetic resonance imaging as well as pure-tone audiograms, video head impulse tests, and vestibular evoked myogenic potentials before and 4 weeks after cochlear implantation. MAIN OUTCOME MEASURES: Prevalence of EH before cochlear implantation, audiovestibular function before and after surgery in hydropic and nonhydropic ears. RESULTS: Thirty-two ears in 16 CI candidates were included. Nine ears (28%) with EH were detected. Although preoperative hearing thresholds, utricular function, and semicircular canal function were not different between the two groups, saccular function was reduced in hydropic ears. Ten subjects received a unilateral CI. Of these, 3 (30%) showed EH on the implanted side. There was no difference regarding postoperative hearing loss between the two groups, but the results point toward a higher vulnerability of hydropic ears with respect to loss of otolith function after cochlear implantation. CONCLUSIONS: This is the first study showing that EH can be assumed in about one third of CI candidates with idiopathic profound SNHL, but no classic EH-associated symptoms. Preliminary results suggest that EH has no influence on the preservation of cochlear function but could be a risk factor for loss of otolith function after cochlear implantation.

Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes.

Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo.

Developmental regulation of glycine receptors at efferent synapses of the murine cochlea.

Efferent olivocochlear feedback innervation modulates the stream of auditory information from cochlea to brainstem by regulating auditory nerve activity and controlling the contribution of cochlear outer hair cells to basilar membrane motion. In our previous work, we gave a first description of glycine receptors (GlyRs) in the rat cochlea indicating a possible localization at efferent cochlear synapses. Here, we analyze the developmental regulation of GlyR transcripts and protein within the developing murine organ of Corti (postnatal days P0-P21). Using quantitative RT-PCR, GlyRα1 and α2 were identified as the predominant GlyRα subunit transcripts before the onset of hearing (