Webinar-based continuing medical education in otorhinolaryngology during the COVID-19 pandemic in Germany: a longitudinal study.

OBJECTIVE: Reliance on webinars for continuing medical education (CME) has increased since the onset of the COVID-19 pandemic. Here, we aimed to evaluate the teaching methods used in these webinars. DESIGN: Retrospective, longitudinal study. SETTING: 20 CME-approved webinars, conducted March-December 2020 in Germany, and lasting 2.25 hours each. PARTICIPANTS: Otorhinolaryngologists pursuing CME credits. INTERVENTIONS: Postwebinar participant assessments of the speaker, effects on practical work, desired scientific content, technical quality, interactions, attention and future training behaviour. RESULTS: On average, 780 participants joined each webinar. The mean survey response rate was 35% (n=282). When asked how well the speaker had mastered the content, 38% responded 'very well', 44% responded 'well', 14% indicated 'satisfactory' and 4% chose 'sufficient'. The frequency of webinars was considered appropriate by 92%, too high by 4% and too low by 4% of participants. The measured attention of the participants was 90%. After the COVID-19 pandemic lockdown, 68% of participants preferred online teaching. The average costs per participant were €3.50 (about $4.25 or £3.15) per webinar. CONCLUSIONS: Although the pandemic context likely influenced the results, we conclude that periodic ear, nose and throat webinar training during COVID-19 in 2020 was an effective alternative delivery method. We found high attention rates, high levels of participant satisfaction and low costs. Evaluations and re-evaluations will be necessary to adapt teaching concepts successfully and ensure high levels of teaching and learning efficiency.

Magnesium as an intrinsic component of human otoconia.

OBJECTIVES: To investigate morphology changes of artificial otoconia (CGC) in the presence of magnesium during growth under in vitro conditions. METHODS: Investigating human otoconia by environmental scanning electron microscope and determining their magnesium content by energy-dispersive X-ray microanalysis (EDX). Comparing structural and morphological data of human and artificial otoconia (CGC, Ca1Mg0) without and with magnesium substitution (Ca1-xMgx). RESULTS: EDX- and X-ray data reveals that the inorganic component in human otoconia consists of calcite containing a minor amount of magnesium substitution (Ca1-xMgx). CGC containing magnesium (length 397.0 ± 146.4 µm, diameter 325.6 ± 100.1 µm) are slimmer and significantly smaller (p < .01) than pure CGC (length 548.6 ± 160 µm, diameter 373.0 ± 110.4 µm) and reveal a significant influence on the final morphology. The length/diameter ratio is significantly higher by incorporation of magnesium into CGC (1.84 ± 0.25 µm versus 1.48 ± 0.11 µm in pure CGC, p < .01), which brings the overall shape to a close relationship with human otoconia (1.98 ± 0.08 µm). CONCLUSIONS: Magnesium is an intrinsic component of human otoconia by partial substitution of calcium in the calcite crystal structure (Ca1-xMgx) and affects the development of the shape of artificial otoconia (calcite gelatin composites, CGC).

Amiodarone-associated bilateral vestibulopathy.

BACKGROUND: Bilateral vestibulopathy (BVP) is a debilitating disorder characterized by the hypofunction of both vestibular end organs or nerves. The most frequent identifiable causes of BVP are ototoxic drug effects, infectious and autoimmune disorders. The majority of cases, however, remain idiopathic. METHODS: Medical records of patients diagnosed with idiopathic BVP were examined in five dizziness clinics. RESULTS: We identified 126 patients with "idiopathic" BVP. Out of these, 15 patients had a history of Amiodarone treatment before the diagnosis of BVP, resulting in a 12% prevalence. CONCLUSION: The present report supports the hypothesis that Amiodarone can cause BVP. Vestibular examination in patients taking Amiodarone and suffering from balance-related symptoms are recommended, to recognize this adverse effect as early as possible and allow for an informed judgement on a potential dose reduction or withdrawal for recovery of the vestibular function.

ATP-sensitive K(+) channels (Kir6.1/SUR1) regulate gap junctional coupling in cochlear-supporting cells.

Using the double whole-cell patch-clamp technique, we found that the absence of intracellular ATP led to gap junction uncoupling in cochlear-supporting Hensen cells. The uncoupling was observed as a progressive reduction of the gap junctional electrical conductance from a starting value of approximately 40 nS to less than 0.04 nS within 10-20 min. The conductance rundown was partly avoided by at least 3 mM ATP and completely suppressed by 5 mM ATP or 5'-adenylyl-imidodiphosphate (AMP-PNP), the non-hydrolysable ATP analog, in the pipette filling solution, suggesting that ATP was needed as ligand and not as a hydrolysable energy supplier or substrate for enzymatic reactions. The effect of intracellular ATP was mimicked by the external application of barium, a nonselective blocker of inwardly rectifying K(+) (Kir) channels, and glibenclamide, an inhibitor of the ATP-sensitive Kir channels (KATP). Moreover a Ba(2+)-sensitive whole-cell inward current was observed in absence of internal ATP. We propose that the internal ATP kept the KATP channels in a closed state, thereby maintaining the gap junction coupling of Hensen cells. The immunostaining of guinea pig cochlear tissue revealed for the first time the expression of the KATP channel subunits Kir6.1 and SUR1 in Hensen cells and supported the proposed hypothesis. The results suggest that KATP channels, as regulator of the gap junction coupling in Hensen cells, could be the physiological link between the metabolic state of the supporting cells and K(+) recycling in the organ of Corti.

Horizontal VOR function shows frequency dynamics in vestibular schwannoma.

The objective of this retrospective study was to investigate the horizontal vestibulo-ocular reflex (hVOR) pathway with caloric test (low-frequency hVOR) and video head impulse test (vHIT) (high-frequency hVOR) in patients with sporadic vestibular schwannoma (69 patients, 27-86 years, mean age 58.1 years) and to compare both test methods in terms of their sensitivity and specificity to detect a retrocochlear lesion. Test results with a unilateral weakness (UWCaloric) >25 % (caloric test) or a Mean-GainvHIT <0.79/asymmetry ratio of Gain (AR-GainvHIT) >8.5 % and accompanied refixation saccades (vHIT) were considered abnormal. The overall sensitivity of the caloric test was 72 %. The evaluation of AR-GainvHIT detected more abnormal cases than did Mean-GainvHIT (44 vs. 36 %). In up to 4 %, a normal caloric test result was related to an abnormal vHIT. There was only a moderate correlation of UWCaloric and AR-GainvHIT (r = 0.54, p < 0.05) with a linear regression line intercept/slope of 32.2/0.9 (p < 0.05). Receiver operating characteristics curve analysis exhibited at a UWCaloric of 50 % a vHIT sensitivity/specificity/positive predictive value/negative predictive value of 0.45/0.9/0.94/0.42. Vestibular testing at varying frequencies provides deeper insights into hVOR function and is helpful in detecting a cerebello-pontine lesion. Whereas caloric test yields a high sensitivity for nerve dysfunction, vHIT test reveals a remaining function of hVOR in the high-frequency range.

Caloric stimulation and video-head impulse testing in Ménière's disease and vestibular migraine.

CONCLUSION: Both the bithermal caloric test and the video-head impulse test (vHIT) were more often abnormal in Ménière's disease (MD) than in vestibular migraine (VM). Horizontal vestibulo-ocular reflex (hVOR) evaluation with caloric test (low-frequency test) was significantly more often abnormal than vHIT (high-frequency test). Therefore, both tests can be used in a complementary way for frequency-selective testing of peripheral vestibular function. OBJECTIVES: To compare the results of caloric testing and vHIT in MD and VM and to determine which test is more sensitive to uncover peripheral vestibular hypofunction. METHODS: Patients with MD (n=30) or VM (n=23) were examined with the caloric test and vHIT. The parameters analyzed were the canal paresis factor for the caloric test and the hVOR gain on both sides in vHIT. RESULTS: The caloric test was abnormal in 67% of patients with MD and in 22% with VM (p=0.002), while the vHIT showed an hVOR deficit in 37% in MD and 9% in VM (p=0.025). In all, 28% of patients with an abnormal caloric test had a normal vHIT, whereas 6% of those with an abnormal vHIT had a normal caloric test. The sensitivity of vHIT compared with caloric testing was 55% for MD and 40% for VM. Neither the caloric test nor vHIT could detect significant differences between early (<5 years) or advanced stages (>5 years) of MD or VM.

Principles of calcite dissolution in human and artificial otoconia.

Human otoconia provide mechanical stimuli to deflect hair cells of the vestibular sensory epithelium for purposes of detecting linear acceleration and head tilts. During lifetime, the volume and number of otoconia are gradually reduced. In a process of degeneration morphological changes occur. Structural changes in human otoconia are assumed to cause vertigo and balance disorders such as benign paroxysmal positional vertigo (BPPV). The aim of this study was to investigate the main principles of morphological changes in human otoconia in dissolution experiments by exposure to hydrochloric acid, EDTA, demineralized water and completely purified water respectively. For comparison reasons artificial (biomimetic) otoconia (calcite gelatin nanocomposits) and natural calcite were used. Morphological changes were detected in time steps by the use of environmental scanning electron microscopy (ESEM). Under in vitro conditions three main dissolution mechanisms were identified as causing characteristic morphological changes of the specimen under consideration: pH drops in the acidic range, complex formation with calcium ions and changes of ion concentrations in the vicinity of otoconia. Shifts in pH cause a more uniform reduction of otoconia size (isotropic dissolution) whereas complexation reactions and changes of the ionic concentrations within the surrounding medium bring about preferred attacks at specific areas (anisotropic dissolution) of human and artificial otoconia. Owing to successive reduction of material, all the dissolution mechanisms finally produce fragments and remnants of otoconia. It can be assumed that the organic component of otoconia is not significantly attacked under the given conditions. Artificial otoconia serve as a suitable model system mimicking chemical attacks on biogenic specimens. The underlying principles of calcite dissolution under in vitro conditions may play a role in otoconia degeneration processes such as BPPV.

The inner structure of human otoconia.

BACKGROUND: The architecture of human otoconia has been only poorly understood up to now. Currently, it is assumed that otoconia contain a central core surrounded by a shell. OBJECTIVES: To investigate the inner structure of human otoconia. METHODS: Human otoconia were investigated by environmental scanning electron microscopy (ESEM). The diffraction behavior was analyzed using X-ray techniques (XRD). Focused ion beam (FIB) slices of otoconia were investigated by transmission electron microscopy (TEM). The results were correlated with observations on degenerate human otoconia and decalcification experiments using ethylenediaminetetraacetic acid (EDTA). Artificial otoconia (calcite-gelatine and calcite-gelatine/agarose composites) were investigated in the same way and compared with human otoconia. RESULTS: Human otoconia represent highly mosaic-controlled calcite-based nanocomposites. The inner structure is composed of 3 + 3 branches with an ordered arrangement of nanocomposite particles and parallel orientation of fibrils. The surrounding belly is less ordered and appears more porous. Degenerate otoconia show a successive dissolution of the belly region exposing to the inner structure (branches) in later stages of degeneration. Artificial otoconia reveal identical chemical, crystallographic and morphologic patterns. They are, however, larger in size. CONCLUSION: Human otoconia show an inner architecture consisting of a less dense belly region and 3 + 3 more dense branches meeting at a central point (center of symmetry). The differences in volume densities and the resulting solubility may play a role in BPPV. Artificial otoconia may serve as a model for further investigations.

Detection of human utricular otoconia degeneration in vital specimen and implications for benign paroxysmal positional vertigo.

Otoconia are assumed to be involved in inner ear disorders such as benign paroxysmal positional vertigo (BPPV). Up to now, the distinct structure and morphology of intact and degenerate human utricular otoconia has been only poorly investigated on vital specimen. In this study, human otoconia were obtained from the utricle in five patients undergoing translabyrinthine vestibular schwannoma surgery. Specimens were examined by environmental scanning electron microscopy. Intact and degenerate otoconia as well as fracture particles of otoconia and bone were analyzed by energy dispersive X-ray microanalysis (EDX) and powder X-ray diffraction (XRD). Intact otoconia reveal a uniform size showing characteristic symmetry properties. Degenerative changes can be observed at several stages with gradual minor and major changes in their morphology including fragment formation. EDX analyses reveal the characteristic chemical composition also for otoconia remnants. XRD shows that intact and degenerate otoconia as well as remnants consist of the calcite modification. In conclusion, electron microscopy serves as a standard method for morphological investigations of otoconia. Human utricular otoconia show a uniform outer morphology corresponding to a calcite-based nanocomposite. Morphological changes provide further evidence for degeneration of utricular otoconia in humans, which might be a preconditioning factor causing BPPV. In case of uncertain origin, particles can be clearly assigned to otoconial origin using EDX and XRD analyses.

Gentamicin-induced structural damage of human and artificial (biomimetic) otoconia.

CONCLUSIONS: Gentamicin causes irreversible structural damage of human and artificial otoconia by progressive dissolution of calcite. The inner architecture of otoconia is strongly affected by degradation scenarios during gentamicin exposure. Artificial otoconia can be used as a model system mimicking the chemical attacks for detailed investigations. OBJECTIVES: To investigate the chemical interactions of gentamicin with natural calcite and human and artificial otoconia under in vivo conditions. METHODS: Pure calcite crystals and artificial and human otoconia were exposed to gentamicin injection solutions at various concentrations. Morphological changes were observed in time steps by the use of environmental scanning electron microscopy (ESEM). RESULTS: Dissolution of pure calcite crystals results in the formation of well oriented nanoshoots indicating an irreversible chemical reaction with gentamicin. Human and artificial otoconia reveal irreversible structural changes of their surface areas as well as of their inner structure, resulting in characteristic changes at different gentamicin concentrations. Minor changes are first observed by surface alterations and dissolution of calcite in the belly region. Major changes result in further reduction of the belly area reaching the center of symmetry. Finally, a complete dissolution of the branches takes place. Artificial otoconia provide detailed insight into surface alterations.

Ocular vestibular evoked myogenic potential to air conducted sound stimulation and video head impulse test in acute vestibular neuritis.

BACKGROUND: Air-conducted (ACS) cervical VEMP (cVEMP) reflect both saccular and inferior vestibular nerve function. Ocular VEMP (oVEMP) to air and bone-conducted vibration (BCV) are critically discussed, whether they reflect predominantly utricular and superior vestibular nerve function. The video head impulse test (vHIT) accurately detects changes in the high frequency range (5-7 Hz) of the vestibular ocular reflex (VOR) in all 3 planes and can be used to assess semicircular canals (SCC) impairment. OBJECTIVES: To evaluate oVEMP and cVEMP in response to 500 Hz ACS stimulation and to compare these with vHIT results in acute unilateral vestibular neuritis (VN) to classify the probable involvement of SCC and otolith organs. MATERIALS AND METHODS: Patients with VN were studied. ACS oVEMP and ACS cVEMP (100 dB nHL 500 Hz tone burst stimulation) were recorded. The vHIT for the 3 SCC were performed simultaneously. RESULTS: ACS oVEMP and ACS cVEMP in combination with vHIT allows the differentiation of 4 types of VN: entire VN (EVN), superior VN (SVN), inferior VN (IVN), and ampullary VN (AVN). Lesions of EVN, SVN, and IVN may be either complete or partial. CONCLUSION: ACS oVEMP and ACS cVEMP to 500 Hz stimulation together with the vHIT allows a better differentiation of receptor involvement in VN. Results suggest a different origin of AC oVEMP and AC cVEMP to 500 Hz in complete SVN and IVN. Partial SVN and IVN may indicate a role of saccular fibers in oVEMP.

Detection of isolated covert saccades with the video head impulse test in peripheral vestibular disorders.

OBJECTIVES: The function of the semicircular canal receptors and the pathway of the vestibulo-ocular-reflex (VOR) can be diagnosed with the clinical head impulse test (cHIT). Recently, the video head impulse test (vHIT) has been introduced but so far there is little clinical experience with the vHIT in patients with peripheral vestibular disorders. The aim of the study was to investigate the horizontal VOR (hVOR) by means of vHIT in peripheral vestibular disorders. METHODS: Using the vHIT, we examined the hVOR in a group of 117 patients and a control group of 20 healthy subjects. The group of patients included vestibular neuritis (VN) (n=52), vestibular schwannoma (VS) (n=31), Ménière's disease (MD) (n=22) and bilateral vestibulopathy (BV) (n=12). RESULTS: Normal hVOR gain was at 0.96 ± 0.08, while abnormal hVOR gain was at 0.44 ± 0.20 (79.1% of all cases). An abnormal vHIT was found in VN (94.2%), VS (61.3%), MD (54.5%) and BV (91.7%). Three conditions of refixation saccades occurred frequently in cases with abnormal hVOR: isolated covert saccades (13.7%), isolated overt saccades (34.3%) and the combination of overt and covert saccades (52.0%). CONCLUSIONS: The vHIT detects abnormal hVOR changes in the combination of gain assessment and refixation saccades. Since isolated covert saccades in hVOR changes can only be seen with vHIT, peripheral vestibular disorders are likely to be diagnosed incorrectly with the cHIT to a certain amount.

The application of vestibular-evoked myogenic potentials in otoneurosurgery.

OBJECTIVE: To evaluate the applicability of vestibular-evoked myogenic potentials (VEMPs) in the diagnostics, intraoperative monitoring, and postoperative follow-up of patients in otoneurosurgery. STUDY DESIGN: A prospective study of patients who underwent either cochlear implantation (CI, n = 18) or were diagnosed with an acoustic neuroma (AN, n = 9) or with neuro(micro)vascular compression of the VIIIth nerve (NVC, n = 27) in the period 2002 to 2004. The follow-up was 1 year for all patients. SETTING: A tertiary-referral unit. RESULTS: VEMPs could be recorded in 64% of all patients before CI and in 22% after surgery. The patients with AN had normal VEMPs in 22% of all cases when first diagnosed. Normal VEMPs were found in 37% of those patients with NVC. From the 5 AN patients who had to be operated, only 1 had intact VEMPs after surgery. In contrast, after microvascular decompression all patients (4) had normal VEMPs. CONCLUSIONS: VEMPs are helpful in diagnosing patients with vertigo to better identify saccular defects. They are highly sensitive in the early diagnosis of retrocochlear lesions. SIGNIFICANCE: VEMPs can help to reliably identify patients with a retrocochlerar lesion at an early stage and can be used in intraoperative, neurophysiological monitoring. EBM RATING: C-4.

Calmodulin antagonists suppress gap junction coupling in isolated Hensen cells of the guinea pig cochlea.

The effect of calmodulin (CaM) antagonists W7, trifluoperazine (TFP) and a calmodulin inhibitory peptide on gap junction coupling in isolated Hensen cells of the organ of Corti was analysed by the double whole-cell patch-clamp technique. Addition of the conventional antagonists W7 and TFP in the micromolar range caused a rapid decrease of gap junction conductance after a delay of a few minutes in a dose-dependent manner. Fluorescence spectroscopy of cytoplasmic free calcium concentration ([Ca(2+)](i)) by Fura-2 showed no significant change of [Ca(2+)](i) by W7. Chelation of [Ca(2+)](i) by 10 mM BAPTA or use of nominally Ca(2+)-free external bath did not suppress the W7-induced gap junction uncoupling. The results suggest that W7 and TFP induce gap junction uncoupling at unchanged global [Ca(2+)](i) in Hensen cells. To obtain additional evidence for an involvement of CaM in regulating gap junction conductance a calmodulin inhibitory peptide, the MLCK peptide (250 nM), was added to the standard pipette solution. Again gap junction uncoupling was observed, but on a significantly slower time scale. This is the first study of an effect of calmodulin antagonists on gap junction coupling in isolated Hensen cells. The question whether the effect of calmodulin inhibitors is specific and involves CaM-dependent gating of gap junction coupling in Hensen cells is discussed.