The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

BACKGROUND: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission). METHODS: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. RESULTS: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.

Catch-Up Saccades in Vestibular Hypofunction: A Contribution of the Cerebellum?

Long-term deficits of the vestibulo-ocular reflex (VOR) elicited by head rotation can be partially compensated by catch-up saccades (CuS). These saccades are initially visually guided, but their latency can greatly decrease resulting in short latency CuS (SL-CuS). It is still unclear what triggers these CuS and what are the underlying neural circuits. In this study, we aimed at evaluating the impact of cerebellar pathology on CuS by comparing their characteristics between two groups of patients with bilateral vestibular hypofunction, with or without additional cerebellar dysfunction. We recruited 12 patients with both bilateral vestibular hypofunction and cerebellar dysfunction (BVH-CD group) and 12 patients with isolated bilateral vestibular hypofunction (BVH group). Both groups were matched for age and residual VOR gain. Subjects underwent video head impulse test recording of the horizontal semicircular canals responses as well as recording of visually guided saccades in the step, gap, and overlap paradigms. Latency and gain of the different saccades were calculated. The mean age for BVH-CD and BVH was, respectively, 67.8 and 67.2 years, and the mean residual VOR gain was, respectively, 0.24 and 0.26. The mean latency of the first catch-up saccade was significantly longer for the BVH-CD group than that for the BVH group (204 ms vs 145 ms, p < 0.05). There was no significant difference in the latency of visually guided saccades between the two groups, for none of the three paradigms. The gain of covert saccades tended to be lower in the BVH-CD group than in BVH group (t test; p = 0.06). The mean gain of the 12° or 20° visually guided saccades were not different in both groups. Our results suggest that the cerebellum plays a role in the generation of compensatory SL-CuS observed in BVH patients.

Allograft bone vs. bioactive glass in rehabilitation of canal wall-down surgery.

Canal wall-down (CWD) mastoidectomy creates a radical cavity that modifies the anatomy and physiology of the middle ear, thus preventing it from being self-cleaning and causing epidermal stagnation in the posterior cavities. Canal wall-down tympanomastoidectomy with reconstruction (CWDTwR) can obliterate such radical cavities. The main objective of this study was to compare postoperative results after CWDTwR by using either bone allografts or 45S5 bioactive glass as a filling tissue with an 18-month follow-up. This was a single-center observational trial including all patients undergoing CWDTwR. Patients were divided into two groups according to the filling material used: allograft bone (AB group) or 45S5 bioactive glass (BG group). Clinical monitoring was performed regularly, with control imaging performed at 18 months (CT scan and DW MRI). The two groups were compared with the t test for quantitative variables and the chi square test for qualitative variables (no revision surgery, audiometric results, complications, mastoid obliteration volume). Thirty-two patients underwent CWDTwR between October 2015 and 2018. The mean age was 48 years, and 71.9% (23/32) were men. A total of 46.9% (15/32) of the patients had undergone at least 3 middle-ear surgeries prior to CWDTwR. The most frequent preoperative symptom was otorrhea (100.0%, 32/32), and only 12.5% (4/32) experienced dizziness. Fifteen and 17 patients underwent surgery with bone allografts and 45S5 bioactive glass, respectively. At 18 months post-operation, 53.3% of the patients (8/15) in the AB group presented with recurrent otorrhea versus 5.9% (1/17) of patients in the BG group (p = 0.005). Seventy-eight percent (7/9) of symptomatic patients had undergone revision surgery at 18 months postoperation: 40.0% (6/15) in the AB group and 5.9% (1/17) in the BG group (p = 0.033). One patient's surgery was cancelled due to the COVID-19 pandemic, and one patient refused surgery. The effects of CWDTwR with bone allografts are disappointing in early follow-up, with significant resorption leading to a 40.0% revision surgery rate. 45S5 BG is a simple solution, with preliminary results that are superior to those of AB. However, prospective controlled studies with longer follow-up times are needed to evaluate the value of BG versus other synthetic materials (such as hydroxyapatite) in surgical management of CWDTwR.Trial registration: retrospectively registered.

Why should multiple dehiscences of the otic capsule be considered before surgically treating patients with superior semicircular canal dehiscence? A radiological monocentric review and a case series.

This review aims to draw attention to the multiple ipsilateral otic capsule dehiscences (OCDs), which may cause therapeutic failure in operated patients. A series of six severely disabled patients with symptoms and signs consistent with a superior semicircular canal dehiscence (SSCD) diagnosis, confirmed by a high-resolution CT scan, is presented here. Five of the patients underwent surgery, and in four of the cases, the postoperative results were poor and/or disappointing. The ethical principles underlying modern medicine encourage medical staff to learn from past experience even when the results are modest despite the accuracy of the treatment applied to a patient. Consequently, we reviewed the radiological records of symptomatic and asymptomatic patients diagnosed or referred to our center for confirmation over the past 5 years to determine the incidence of multiple OCD in this population. Multiple localizations of suspected OCD in the ipsilateral ear did not appear to be rare and were found in 29 of 157 patients (18.47%) in our retrospective review using high-resolution thin-sliced CT scans. The decision to perform surgery for a documented symptomatic superior SSCD should be made with caution only after ruling out concomitant lesser-known variants of OCD in the ipsilateral ear.

Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

BACKGROUND: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. METHODS: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. RESULTS: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

Virtual reality set-up for studying vestibular function during head impulse test.

Objectives: Virtual reality (VR) offers an ecological setting and the possibility of altered visual feedback during head movements useful for vestibular research and treatment of vestibular disorders. There is however no data quantifying vestibulo-ocular reflex (VOR) during head impulse test (HIT) in VR. The main objective of this study is to assess the feasibility and performance of eye and head movement measurements of healthy subjects in a VR environment during high velocity horizontal head rotation (VR-HIT) under a normal visual feedback condition. The secondary objective is to establish the feasibility of VR-HIT recordings in the same group of normal subjects but under altered visual feedback conditions. Design: Twelve healthy subjects underwent video HIT using both a standard setup (vHIT) and VR-HIT. In VR, eye and head positions were recorded by using, respectively, an imbedded eye tracker and an infrared motion tracker. Subjects were tested under four conditions, one reproducing normal visual feedback and three simulating an altered gain or direction of visual feedback. During these three altered conditions the movement of the visual scene relative to the head movement was decreased in amplitude by 50% (half), was nullified (freeze) or was inverted in direction (inverse). Results: Eye and head motion recording during normal visual feedback as well as during all 3 altered conditions was successful. There was no significant difference in VOR gain in VR-HIT between normal, half, freeze and inverse conditions. In the normal condition, VOR gain was significantly but slightly (by 3%) different for VR-HIT and vHIT. Duration and amplitude of head impulses were significantly greater in VR-HIT than in vHIT. In all three altered VR-HIT conditions, covert saccades were present in approximatively one out of four trials. Conclusion: Our VR setup allowed high quality recording of eye and head data during head impulse test under normal and altered visual feedback conditions. This setup could be used to investigate compensation mechanisms in vestibular hypofunction, to elicit adaptation of VOR in ecological settings or to allow objective evaluation of VR-based vestibular rehabilitation.

Training spatial hearing in unilateral cochlear implant users through reaching to sounds in virtual reality.

BACKGROUND AND PURPOSE: Use of unilateral cochlear implant (UCI) is associated with limited spatial hearing skills. Evidence that training these abilities in UCI user is possible remains limited. In this study, we assessed whether a Spatial training based on hand-reaching to sounds performed in virtual reality improves spatial hearing abilities in UCI users METHODS: Using a crossover randomized clinical trial, we compared the effects of a Spatial training protocol with those of a Non-Spatial control training. We tested 17 UCI users in a head-pointing to sound task and in an audio-visual attention orienting task, before and after each training.
Study is recorded in clinicaltrials.gov (NCT04183348). RESULTS: During the Spatial VR training, sound localization errors in azimuth decreased. Moreover, when comparing head-pointing to sounds before vs. after training, localization errors decreased after the Spatial more than the control training. No training effects emerged in the audio-visual attention orienting task. CONCLUSIONS: Our results showed that sound localization in UCI users improves during a Spatial training, with benefits that extend also to a non-trained sound localization task (generalization). These findings have potentials for novel rehabilitation procedures in clinical contexts.

Electrical Field Interactions during Adjacent Electrode Stimulations: eABR Evaluation in Cochlear Implant Users.

The present study investigates how electrically evoked Auditory Brainstem Responses (eABRs) can be used to measure local channel interactions along cochlear implant (CI) electrode arrays. eABRs were recorded from 16 experienced CI patients in response to electrical pulse trains delivered using three stimulation configurations: (1) single electrode stimulations (E11 or E13); (2) simultaneous stimulation from two electrodes separated by one (En and En+2, E11 and E13); and (3) stimulations from three consecutive electrodes (E11, E12, and E13). Stimulation level was kept constant at 70% electrical dynamic range (EDR) on the two flanking electrodes (E11 and E13) and was varied from 0 to 100% EDR on the middle electrode (E12). We hypothesized that increasing the middle electrode stimulation level would cause increasing local electrical interactions, reflected in characteristics of the evoked compound eABR. Results show that group averaged eABR wave III and V latency and amplitude were reduced when stimulation level at the middle electrode was increased, in particular when stimulation level on E12 reached 40, 70, and 100% EDR. Compound eABRs can provide a detailed individual quantification of electrical interactions occurring at specific electrodes along the CI electrode array. This approach allows a fine determination of interactions at the single electrode level potentially informing audiological decisions regarding mapping of CI systems.

European Reference Network for Rare Vascular Diseases (VASCERN): When and how to use intravenous bevacizumab in Hereditary Haemorrhagic Telangiectasia (HHT)?

Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular multisystemic disease that leads to epistaxis, anaemia due to blood loss, and arteriovenous malformations (AVMs) in organs such as the lungs, liver and brain. HHT prevalence is estimated at 1/6000, i.e. around 85,000 European citizens, and is served by the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN). HHT treatments depend on clinical manifestations, and span multiple different medical, surgical and interventional disciplines. Separate to local treatments in the nose, in severe settings, intravenous bevacizumab has been proposed as treatment option, and the purpose of the current article is to assess the use of intravenous bevacizumab in patients with HHT in 2022 according to available data.

Change in prey genotype frequency rescues predator from extinction.

Indirect evolutionary rescue (IER) is a mechanism where a non-evolving species is saved from extinction in an otherwise lethal environment by evolution in an interacting species. This process has been described in a predator-prey model, where extinction of the predator is prevented by a shift in the frequency of defended towards undefended prey when reduced predator densities lower selection for defended prey. We test here how increased mortality and the initial frequencies of the prey types affect IER. Combining the analysis of model simulations and experiments with rotifers feeding on algae we show IER in the presence of increased predator mortality. We found that IER was dependent on the ability of the prey to evolve as well as on the frequency of the defended prey. High initial frequencies of defended prey resulted in predator extinction despite the possibility for prey evolution, as the increase in undefended prey was delayed too much to allow predator rescue. This frequency dependency for IER was more pronounced for higher predator mortalities. Our findings can help informing the development of conservation and management strategies that consider evolutionary responses in communities to environmental changes.

Effect of Serious Gaming on Speech-in-Noise Intelligibility in Adult Cochlear Implantees: A Randomized Controlled Study.

Listening in noise remains challenging for adults with cochlear implants (CI) even after prolonged experience. Personalized auditory training (AT) programs can be proposed to improve specific auditory skills in adults with CI. The objective of this study was to assess serious gaming as a rehabilitation tool to improve speech-in-noise intelligibility in adult CI users. Thirty subjects with bilateral profound hearing loss and at least 9 months of CI experience were randomized to participate in a 5-week serious game-based AT program (n = 15) or a control group (n = 15). All participants were tested at enrolment and at 5 weeks using the sentence recognition-in-noise matrix test to measure the signal-to-noise ratio (SNR) allowing 70% of speech-in-noise understanding (70% speech reception threshold, SRT70). Thirteen subjects completed the AT program and nine of them were re-tested 5 weeks later. The mean SRT70 improved from 15.5 dB to 11.5 dB SNR after 5 weeks of AT (p < 0.001). No significant change in SRT70 was observed in the control group. In the study group, the magnitude of SRT70 improvement was not correlated to the total number of AT hours. A large inter-patient variability was observed for speech-in-noise intelligibility measured once the AT program was completed and at re-test. The results suggest that serious game-based AT may improve speech-in-noise intelligibility in adult CI users. Potential sources of inter-patient variability are discussed. Serious gaming may be considered as a complementary training approach for improving CI outcomes in adults.

High Heterogeneity of Temporal Bone CT Aspects in Osteogenesis Imperfecta Is Not Linked to Hearing Loss.

OBJECTIVES: To determine whether temporal bone computed tomography (CT) features are linked to the presence and type of hearing loss in osteogenesis imperfecta (OI) when considering hearing-impaired OI patients and normally hearing (NH) OI ones. A secondary objective was to assess whether other factors influence CT features in a large sample: age, type of mutation, or bone mineral density (BMD). METHODS: A total of 41 adults with OI underwent CTs and pure-tone audiometry in 82 ears. Hearing thresholds were normal in 64 out of 82 ears, and most had not been operated on for stapedectomy or stapedotomy. Ossicle density, footplates, oval and round windows, retrofenestral peri- and endolabyrinths, and temporal pneumatization were analyzed twice by an experienced radiologist. CT features were compared to hearing, age, collagen mutations, and bone mineral density. RESULTS: Unexpectedly a high prevalence of footplate, ossicle, and otic capsule anomalies was observed, even in NH ears. Footplate hypodensity or thickening was mostly found in ears without conductive hearing loss. There were significantly more retrofenestral anomalies or window obstruction in ears with a sensorineural hearing loss component than in ears without. Age was significantly higher in ears with middle layer hypodensity than in ears without. Patients with mutations were expected to have reduced collagen quantity and had significantly more footplate or retrofenestral anomalies than those with qualitative mutations. BMD was significantly higher in ears without temporal hyperpneumatization. CONCLUSION: Temporal bone CT features in OI are present in a large proportion of patients, had they hearing loss or not, and might be determined more by collagen mutation type than by age or BMD.

Feasibility of day-case pediatric cochlear implantation.

PURPOSE: Pediatric cochlear implantation is performed on an outpatient basis in an inconstant way. The aim of this study is to assess the feasibility of day-case pediatric cochlear implantation by determining the acceptability of outpatient-to-inpatient conversion rate (acceptability threshold of 5%) and to assess the safety by comparing outpatient and inpatient postoperative events. We also want to identify conversion predictive factors. METHODS: We conducted a monocentric retrospective study including 267 cases aged 6 months to 18 years who underwent unilateral cochlear implantation between 2016 and 2020. This population was divided into two groups: outpatient group (190 cases) and inpatient group (77 cases). RESULTS: Among the 190 cases scheduled as day surgery, 9 cases required conversion to conventional hospitalization which leads to an outpatient-to-inpatient conversion rate of 4.7%. Postoperative nausea and vomiting (PONV) were involved in all cases of conversion. Conversion predictive factors were the presence of an inner ear malformation at risk of gusher (OR 32.51, 95% CI [4.98-370.27], p 0.001) and the intraoperative administration of morphine (OR 8.52, 95% CI [1.38-86.84], p 0.035). There was no statistically significant difference in immediate postoperative complications (outpatient 14.2% vs inpatient 16.9% p 0.715), early-stage complications (outpatient 12.6% vs inpatient 10.4% p 0.812) and early-stage unplanned consultations (outpatient 4.7% vs inpatient 3.9% p 0.748) between outpatient and inpatient groups. Unplanned readmissions were found only in the outpatient group. CONCLUSION: Day-case pediatric cochlear implantation is a feasible and safe procedure even in infants. The outpatient-to-inpatient conversion rate of 4.7% is considered acceptable but requires anticipation of human and accommodation needs. No causes of conversion were life-threatening. The risk of postoperative complications and unplanned consultations are not influenced by the mode of hospitalization. Special attention should be paid to the prevention of PONV and the presence of inner ear malformations.

Intra-Cochlear Current Spread Correlates with Speech Perception in Experienced Adult Cochlear Implant Users.

Broader intra-cochlear current spread (ICCS) implies higher cochlear implant (CI) channel interactions. This study aimed to investigate the relationship between ICCS and speech intelligibility in experienced CI users. Using voltage matrices collected for impedance measurements, an individual exponential spread coefficient (ESC) was computed. Speech audiometry was performed to determine the intelligibility at 40 dB Sound Pressure Level (SPL) and the 50% speech reception threshold: I40 and SRT50 respectively. Correlations between ESC and either I40 or SRT50 were assessed. A total of 36 adults (mean age: 50 years) with more than 11 months (mean: 34 months) of CI experience were included. In the 21 subjects for whom all electrodes were active, ESC was moderately correlated with both I40 (r = -0.557, p = 0.009) and SRT50 (r = 0.569, p = 0.007). The results indicate that speech perception performance is negatively affected by the ICCS. Estimates of current spread at the closest vicinity of CI electrodes and prior to any activation of auditory neurons are indispensable to better characterize the relationship between CI stimulation and auditory perception in cochlear implantees.

The evolution of convex trade-offs enables the transition towards multicellularity.

The evolutionary transition towards multicellular life often involves growth in groups of undifferentiated cells followed by differentiation into soma and germ-like cells. Theory predicts that germ soma differentiation is facilitated by a convex trade-off between survival and reproduction. However, this has never been tested and these transitions remain poorly understood at the ecological and genetic level. Here, we study the evolution of cell groups in ten isogenic lines of the unicellular green algae Chlamydomonas reinhardtii with prolonged exposure to a rotifer predator. We confirm that growth in cell groups is heritable and characterized by a convex trade-off curve between reproduction and survival. Identical mutations evolve in all cell group isolates; these are linked to survival and reducing associated cell costs. Overall, we show that just 500 generations of predator selection were sufficient to lead to a convex trade-off and incorporate evolved changes into the prey genome.

Rapid Assessment of Non-Verbal Auditory Perception in Normal-Hearing Participants and Cochlear Implant Users.

In the case of hearing loss, cochlear implants (CI) allow for the restoration of hearing. Despite the advantages of CIs for speech perception, CI users still complain about their poor perception of their auditory environment. Aiming to assess non-verbal auditory perception in CI users, we developed five listening tests. These tests measure pitch change detection, pitch direction identification, pitch short-term memory, auditory stream segregation, and emotional prosody recognition, along with perceived intensity ratings. In order to test the potential benefit of visual cues for pitch processing, the three pitch tests included half of the trials with visual indications to perform the task. We tested 10 normal-hearing (NH) participants with material being presented as original and vocoded sounds, and 10 post-lingually deaf CI users. With the vocoded sounds, the NH participants had reduced scores for the detection of small pitch differences, and reduced emotion recognition and streaming abilities compared to the original sounds. Similarly, the CI users had deficits for small differences in the pitch change detection task and emotion recognition, as well as a decreased streaming capacity. Overall, this assessment allows for the rapid detection of specific patterns of non-verbal auditory perception deficits. The current findings also open new perspectives about how to enhance pitch perception capacities using visual cues.

Word Recognition and Frequency Selectivity in Cochlear Implant Simulation: Effect of Channel Interaction.

In cochlear implants (CI), spread of neural excitation may produce channel interaction. Channel interaction disturbs the spectral resolution and, among other factors, seems to impair speech recognition, especially in noise. In this study, two tests were performed with 20 adult normal-hearing (NH) subjects under different vocoded simulations. First, there was a measurement of word recognition in noise while varying the number of selected channels (4, 8, 12 or 16 maxima out of 20) and the degree of simulated channel interaction ("Low", "Medium" and "High"). Then, there was an evaluation of spectral resolution function of the degree of simulated channel interaction, reflected by the sharpness (Q10dB) of psychophysical tuning curves (PTCs). The results showed a significant effect of the simulated channel interaction on word recognition but did not find an effect of the number of selected channels. The intelligibility decreased significantly for the highest degree of channel interaction. Similarly, the highest simulated channel interaction impaired significantly the Q10dB. Additionally, a strong intra-individual correlation between frequency selectivity and word recognition in noise was observed. Lastly, the individual changes in frequency selectivity were positively correlated with the changes in word recognition when the degree of interaction went from "Low" to "High". To conclude, the degradation seen for the highest degree of channel interaction suggests a threshold effect on frequency selectivity and word recognition. The correlation between frequency selectivity and intelligibility in noise supports the hypothesis that PTCs Q10dB can account for word recognition in certain conditions. Moreover, the individual variations of performances observed among subjects suggest that channel interaction does not have the same effect on each individual. Finally, these results highlight the importance of taking into account subjects' individuality and to evaluate channel interaction through the speech processor.

Multi-operated cholesteatoma: when two surgeries are not enough.

PURPOSE: Most studies regarding residual and recurrent cholesteatoma focus on single relapse. This study examines patients who had to undergo at least three surgeries for complete eradication of their cholesteatoma, with the aim of bringing to light risk factors and assessing the functional impact of multiple surgeries on hearing. METHOD: We include 27 patients who underwent 3 consecutive surgeries for cholesteatoma between 2006 and 2016. This population represented 3.1% of all cholesteatoma operated on during that same period (868 patients). RESULTS: Cases of multi-residual and/or recurrent cholesteatoma (RRC) were significantly younger (13.1 years old), than single-RRC or cases with No-RRC (respectively, 28.0 and 38.5 years old) (p < 0.01). Furthermore, there was a significant difference in cholesteatoma location especially for combined attical and mesotympanic location between the three groups (no-RCC 26%; single-RRC 34% and multi-RRC 66%) (p < 0.01). There was also a significant difference in ossicular erosion of the malleus, incus and stapes between the three groups (p < 0.01). In our study, the type of surgery did not influence multi-RRC rates. We did not observe any significant impact on hearing between the first and third surgeries. Mean duration between the first and second surgeries was significantly shorter for multi-RRC (14.5 months SD 8.3) than for single-RRC (23.3 months SD 18.1) (p < 0.05). CONCLUSION: Special care should be given in case of combined attical and mesotympanic extension, ossicular erosion and young children. Delaying the realization of MRI, and/or of second-look surgery, could decrease the risk of multi-RRC.

Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS).

The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) has emerged progressively during the last 30 years. It was first outlined by the neurootology/neurophysiology community in the vestibular areflexic patients, through the description of patients slowly developing late-onset cerebellar ataxia and bilateral vestibulopathy. The characteristic deficit of visuo-vestibulo-ocular reflex (VVOR) due to the impaired slow stabilizing eye movements was put forward and a specific disease subtending this syndrome was suggested. The association to a peripheral sensory axonal neuropathy was described later on, with neuropathological studies demonstrating that both sensory neuropathy and vestibular areflexia were diffuse ganglionopathy. Clinical and electrophysiological criteria of CANVAS were then proposed in 2016. Besides the classical triad, frequent chronic cough, signs of dysautonomia and neurogenic pains were frequently observed. From the beginning of published cohorts, sporadic as well as familial cases were reported, the last suggestive of an autosomal recessive mode of transmission. The genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. This pathological expansion was found in 100% of the familial form and 92% of sporadic ones when the triad was complete. But using the genetic criteria, the phenotype of CANVAS seems to expand, for exemple including patients with isolated neuronopathy. We propose here to review the clinical, electrophysiological, anatomical, genetic aspect of CANVAS in light of the recent discovery of the genetic aetiology, and discuss differential diagnosis, neuropathology and physiopathology.