Reconstructive ossiculoplasty options in primary cholesteatoma surgeries with an intact stapes.

PURPOSE: In primary cholesteatoma patients, incus destruction with an intact and mobile stapes is a frequent finding. Different techniques have been described to restore the ossicular chain, including incus interposition, stapes augmentation and type III tympanoplasty. Controversy about postoperative hearing results in open versus closed surgical techniques exist. METHODS: We performed a retrospective analysis of clinical, surgical and audiometric data of patients with primary cholesteatoma surgery operated between 2010 and 2020, and a mobile stapes and one-stage ossicular reconstruction. Pre- and post-operative audiograms were compared for the different surgical groups, mainly focusing on postoperative air-bone gap. Mastoid pneumatization and ventilation was also considered. RESULTS: The mean postoperative air-bone gap (0.5-4 kHz) of the 126 included patients was 20 dB. Hearing after type III tympanoplasty (26 dB) was worse than incus interposition (19 dB) and stapes augmentation (20 dB). Hearing after an open (23 dB) versus closed (19 dB) surgical technique was significantly different. No improvement in air-bone gap was observed for the higher frequencies. CONCLUSION: A residual postoperative air-bone gap should be considered after primary cholesteatoma surgery with intact and mobile stapes. Incus interposition in closed cavity operation is the optimal situation, but open cavity surgery should not be avoided because of hearing. Extent of the disease is prioritized and poorer ventilation before and after surgery may affect postoperative hearing.

Twelve years of neonatal hearing screening: audiological and etiological results.

PURPOSE: Most developed countries have implemented some form of universal newborn hearing screening program. Early identification and rehabilitation of congenital hearing loss is important in functional outcome, and the need to identify the cause of hearing impairment has become clear. We aimed to evaluate audiological and etiological outcomes in a large group of patients with failed neonatal hearing screening. METHODS: We performed a retrospective chart analysis of patients who were referred to our tertiary referral center after failing neonatal hearing screening during a 12-year period (2007-2019). Screening was based on automated auditory brainstem response (AABR) or a combined approach of AABR and auditory steady-state response (ASSR) with chirp stimulus. Extensive audiometric testing was performed to confirm and determine the type and degree of hearing loss. In case of permanent hearing loss, a standardized etiological protocol was followed to determine the cause. RESULTS: Of the 802 referred newborns, hearing loss was confirmed by diagnostic ABR in 78%. Main causes of hearing loss included otitis media with effusion (56%, higher in patients screened by AABR/ASSR compared to AABR), a genetic disorder (12%), congenital cytomegalovirus infection (cCMV, 5%) and atresia/stenosis of the external ear canal (5%). Of the patients with permanent hearing loss, 15% showed changes in hearing loss severity over time. CONCLUSION: In the majority of newborns referred after failing universal neonatal hearing screening, hearing loss could be confirmed. The leading cause was reversible hearing loss due to otitis media with effusion, but hearing loss proved permanent in about 35% of referred newborns, with genetics as predominant cause. Follow-up of congenital hearing loss patients is important as deterioration as well as improvement was observed over time.

Otological manifestations in branchiootorenal spectrum disorder: A systematic review and meta-analysis.

Branchiootorenal spectrum disorder (BORSD) is a group of rare autosomal dominant entities characterized by branchiogenic malformations, hearing loss (HL) and renal anomalies. It comprises branchiootorenal syndrome and branchiootic syndrome, distinguished by the presence or absence of renal abnormalities. Pathogenic variants have been discovered in the following genes: EYA1, SIX5, SIX1 and SALL1. As the otological phenotype in BORSD is inconsistently reported, we performed a systematic review to provide an up-to-date overview, correlated with the genotype. Forty publications were included, describing 295 individual patients. HL was diagnosed in 95%, usually bilateral and mixed-type, and differed among the different genes involved. Mixed moderate-to-severe HL was the predominant finding in patients with EYA1 involvement, regardless of the presence of renal abnormalities. The sensorineural HL of profound severity was more prevalent in patients with SIX1 mutations. No significant differences among different mutation types or location within the genes could be observed. Structural otological manifestations, ranging from periauricular to inner ear anomalies, were common in both genes. Especially periauricular anomalies were more common and more severe in EYA1. In summary, otological differences among the different genes involved in BORSD are observed, so the molecular analysis is strongly advised.

Brain MRI findings in newborns with congenital cytomegalovirus infection: results from a large cohort study.

OBJECTIVE: To investigate the spectrum and frequency of abnormalities on brain MRI in a large cohort of live newborns with congenital CMV (cCMV) infection. METHODS: Institutional review board approval and informed consent for neonatal MRI and data collection were obtained. Between January 2010 and January 2018, brain MRI was performed in 196 live newborns diagnosed with cCMV. Images were independently reviewed by 2 pediatric radiologists, blinded to clinical data. RESULTS: cCMV infection was clinically symptomatic in 26/191 newborns (13.6%). Brain MRI showed abnormalities in 76/196 patients (38.8%). MRI was abnormal in 20/26 clinically symptomatic patients (76.9%): 76.9% showed white matter lesions, 61.5% subependymal cysts, 46.2% ventriculomegaly, 26.9% ventricular adhesions, 26.9% gyral abnormalities, 24.0% calcifications, 15.4% cerebellar anomalies. MRI was abnormal in 55/165 (33.3%) clinically asymptomatic patients: 30.9% had white matter lesions, 15.8% subependymal cysts, 4.2% ventriculomegaly, 2.4% ventricular adhesions, 1.2% gyral abnormalities, 0.6% calcifications, none had cerebellar anomalies. Concomitant brain lesions were seen in all patients with gyral abnormalities, cerebellar anomalies, and calcifications and nearly all patients with subependymal cysts and ventriculomegaly. In all but 4 patients with other detected brain lesions, white matter abnormalities were simultaneously present. In 33/74 patients (45.2%), white matter lesions were seen as a sole abnormality. CONCLUSION: White matter lesions were the most common detected abnormality on brain MRI in newborns with congenital CMV. Since brain abnormalities were seen in more than 30% of clinically asymptomatic and 75% of clinically symptomatic newborns, MRI should be advised in all newborns diagnosed with cCMV. KEY POINTS: • Neonatal brain MRI showed abnormalities in more than 30% of clinically asymptomatic and 75% of symptomatic newborns with congenital cytomegalovirus infection. • White matter lesions were by far the most common detected abnormality, followed by subependymal cysts and ventricular dilatation. • Lesions in cCMV were often multiple, with many patients showing concomitant lesions.

Congenital CMV-Associated Hearing Loss: Can Brain Imaging Predict Hearing Outcome?

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection is the leading cause of nonhereditary sensorineural hearing loss in childhood and is also associated with CNS abnormalities. The main objective is to investigate the prognostic value of neonatal cranial ultrasound (cUS) and cranial magnetic resonance imaging (cMRI) in predicting long-term hearing outcome in a large cohort of cCMV-infected symptomatic and asymptomatic patients. DESIGN: Data were prospectively collected from a multicentre Flemish registry of children with cCMV infection born between 2007 and 2016. Neonatal cUS and cMRI scans were examined for lesions related to cCMV infection. Audiometric results at different time points were analyzed. The imaging and audiometric results were linked and diagnostic values of cUS and cMRI were calculated for the different hearing outcomes. RESULTS: We were able to include 411 cCMV patients, of whom 40% was considered symptomatic at birth. Cranial ultrasound abnormalities associated with cCMV infection were found in 76 children (22.2% of the cUS scans), whereas cMRI revealed abnormalities in 74 patients (26.9% of the cMRI scans). A significant relation could be found between the presence of cUS or cMRI abnormalities and hearing loss at baseline and last follow-up. Cranial ultrasound and cMRI findings were not significantly correlated with the development of delayed-onset hearing loss. Specificity and sensitivity of an abnormal cUS to predict hearing loss at final follow-up were 84% and 43%, respectively compared with 78% and 39% for cMRI. Normal cUS and cMRI findings have a negative predictive value of 91% and 92%, respectively, for the development of delayed-onset hearing loss. CONCLUSIONS: Neuroimaging evidence of CNS involvement in the neonatal period is associated with the presence of hearing loss in children with a cCMV infection. Imaging abnormalities are not predictive for the development of delayed-onset hearing loss.

Auditory phenotype in Stickler syndrome: results of audiometric analysis in 20 patients.

Hearing loss in Stickler syndrome has received little attention due to the often more disabling ocular, orofacial and skeletal manifestations. Estimates suggest a global prevalence of sensorineural hearing loss (SNHL) ranging from 50 % to about 100 % though, depending on the underlying Stickler genotype. By performing extensive audiometric analysis in Stickler patients, we aimed to further elucidate the auditory phenotype. Twenty molecularly confirmed Stickler patients (age 10-62 year), of whom sixteen with type 1 Stickler syndrome (COL2A1 mutation) and four with type 2 Stickler syndrome (COL11A1 mutation) underwent an otological questionnaire, clinical examination, pure tone and speech audiometry, tympanometry and otoacoustic emission testing. Cross-sectional and longitudinal regression analysis of the audiograms was performed to assess progression. In type 1 Stickler syndrome, 75 % demonstrated hearing loss, predominantly in the high frequencies. No significant progression beyond presbyacusis was observed. All type 2 Stickler patients exhibited mild-to-moderate low- and mid-frequency SNHL and moderate-to-severe high-frequency SNHL. In both types, hearing loss was observed in childhood. Otoacoustic emissions were only detectable in 7/40 ears and had very low amplitudes, even in frequency bands with normal hearing on pure tone audiometry. Type 1 Stickler syndrome is characterized by a mild high-frequency SNHL, emerging in childhood and non-progressive. Absent otoacoustic emissions are a frequent finding. Patients with type 2 Stickler syndrome exhibit early-onset moderate SNHL affecting all frequencies with a sloping audiogram. Taking into account the visual impairment in many patients, we recommend regular auditory follow-up in patients with Stickler syndrome, especially in childhood.

Novel pathogenic COL11A1/COL11A2 variants in Stickler syndrome detected by targeted NGS and exome sequencing.

INTRODUCTION: Stickler syndrome is caused by mutations in genes encoding type II and type XI collagens. About 85% of the pathogenic variants is found in COL2A1 (Stickler type 1), whereas a minority of mutations has been reported in COL11A1 (Stickler type 2) and COL11A2 (Stickler type 3). Beside the typical skeletal and orofacial manifestations, ocular anomalies are predominantly present in type 1 and type 2, while hearing loss is more pronounced in type 2 and type 3. METHODS: We performed COL11A1 mutation analysis for 40 type 2 Stickler patients and COL11A2 mutation analysis for five type 3 Stickler patients, previously all COL2A1 mutation-negative, using targeted next-generation sequencing (NGS) whereas whole-exome sequencing (WES) was performed in parallel for two patients. Three patients were analyzed for both genes due to unclear ocular findings. RESULTS: In total 14 COL11A1 and two COL11A2 mutations could be identified, seven of which are novel. Splice site alterations are the most frequent mutation type, followed by glycine substitutions. In addition, six variants of unknown significance (VUS) have been found. Identical mutations and variants were identified with both NGS techniques. CONCLUSION: We expand the mutation spectrum of COL11A1 and COL11A2 in Stickler syndrome patients and show that targeted NGS is an efficient and cost-effective molecular tool in the genetic diagnosis of Stickler syndrome, whereas the more standardized WES might be an alternative approach.

Dissemination and implementation of the ARIA guidelines for allergic rhinitis in general practice.

BACKGROUND: Allergic rhinitis (AR) is a prevalent problem in general practice. The first evidence-based guidelines for AR, the ARIA guidelines, were published and have been updated repeatedly since 2001 in order to improve the care of AR patients. Very limited information, however, is available on the impact of these guidelines on everyday clinical practice. The aim of this study was to evaluate the dissemination and implementation of the ARIA guidelines in general practice. METHODS: Three hundred and fifty Flemish general practitioners (GPs) were recruited to complete a questionnaire covering their demographic and professional characteristics, awareness, perception and implementation of the ARIA guidelines. To assess compliance with the ARIA treatment recommendations, 4 fictitious case scenarios of AR were presented, in which the respondents were asked to select the treatment of choice. RESULTS: Of the 350 GPs included, only 31% were aware of the ARIA guidelines and 10% stated that they implement them. For the diagnosis of AR, 71% of the GPs ask specific IgE tests or perform skin prick tests, whereas only 29% perform an anterior rhinoscopy. ARIA users are more likely to screen for concomitant asthma. In the clinical-case section, there was a large variability in proposed therapeutic strategies. Adherence to the evidence-based ARIA treatment guidelines was low, but recent graduation was a significant predictor of compliance with these recommendations. CONCLUSIONS: The ARIA guidelines remain relatively unknown among Flemish GPs and even those who are aware of them still tend to treat AR independently of the guideline recommendations.

CHD7 Disorder-Not CHARGE Syndrome-Presenting as Isolated Cochleovestibular Dysfunction.

CHARGE syndrome, characterized by a distinct set of clinical features, has been linked primarily to mutations in the CHD7 gene. Initially defined by specific clinical criteria, including coloboma, heart defects, choanal atresia, delayed growth, and ear anomalies, CHARGE syndrome's diagnostic spectrum has broadened since the identification of CHD7. Variants in this gene exhibit considerable phenotypic variability, leading to the adoption of the term "CHD7 disorder" to encompass a wider range of associated symptoms. Recent research has identified CHD7 variants in individuals with isolated features such as autism spectrum disorder or gonadotropin-releasing hormone deficiency. In this study, we present three cases from two different families exhibiting audiovestibular impairment as the primary manifestation of a CHD7 variant. We discuss the expanding phenotypic variability observed in CHD7-related disorders, highlighting the importance of considering CHD7 in nonsyndromic hearing loss cases, especially when accompanied by inner ear malformations on MRI. Additionally, we underscore the necessity of genetic counseling and comprehensive clinical evaluation for individuals with CHD7 variants to ensure appropriate management of associated health concerns.

Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection.

Importance: Congenital cytomegalovirus (cCMV) is the major cause of congenital nonhereditary sensorineural hearing loss in children. Currently, criteria to identify infants at increased risk for unfavorable hearing outcome are lacking. Objective: To identify risk factors associated with cCMV-related hearing improvement, hearing deterioration, and late-onset hearing loss. Design, Setting, and Participants: This multicenter cohort study included patients from 6 secondary and tertiary hospitals enrolled in the Flemish CMV registry (Belgium). Newborns with untreated cCMV infection with at least 4-year audiological follow-up were included. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Data were collected for 15 years (January 1, 2007, to February 7, 2022) and analyzed from September 26, 2022, to January 16, 2023. Main Outcomes and Measures: Primary outcome was hearing evolution (per-ear analysis; described as stable hearing, improvement, or deterioration). The association of gestational characteristics, clinical findings, timing of seroconversion, viral load, and hearing status at birth with hearing evolution was investigated using effect sizes (Cramer V, odds ratio [OR], or Hedges g). Results: Of the 387 children, 205 of 385 with nonmissing data were male (53.2%), 113 (29.2%) had a symptomatic infection, and 274 (70.8%) had an asymptomatic infection. Every child was 4 years or older at final hearing evaluation. A total of 701 of 774 ears (90%) showed stable hearing (normal hearing or stable hearing loss since birth) over time. Late-onset hearing loss (normal hearing at birth followed by hearing loss) was present in 43 of 683 ears (6.3%). Among children with hearing loss present at birth, 24 of 34 ears (70.6%) had hearing deterioration, and 6 of 91 ears (6.6%) had hearing improvement. Prematurity was associated with a higher chance of hearing improvement (OR, 12.80; 95% CI, 2.03-80.68). Late-onset hearing loss was more prevalent in a first trimester infection (OR, 10.10; 95% CI, 2.90-34.48). None of the 104 ears of children with a third trimester seroconversion developed late-onset hearing loss. Conclusions and Relevance: Findings of this cohort study support that ongoing audiological follow-up for untreated children with congenital hearing loss is important, as the majority of patients had hearing deterioration. The timing of seroconversion was associated with the risk of developing late-onset hearing loss. These insights can aid in parental counseling, patient stratification, and follow-up. Future research should focus on the effect of treatment, the influence of determined risk factors, and the study of eventual new risk factors in patients at high risk to develop hearing loss.

Prevalence of allergic sensitization versus allergic rhinitis symptoms in an unselected population.

BACKGROUND: Allergic rhinitis (AR) is the most common allergic disorder and its prevalence has significantly increased worldwide, nowadays affecting up to 40% of the population in young adults. The objective of the present survey was to evaluate the prevalence of allergic sensitization and the prevalence of clinically diagnosed AR in a sample of the Belgian population, and to estimate the effect of age and gender. METHODS: We performed a cross-sectional population-based study at an annual public fair in Ghent. Participants underwent a skin prick test (SPT) to 3 aeroallergens: a mix of trees (hazel, alder, and birch), grass pollen, and house dust mite (HDM). The clinical relevance of sensitization was assessed by relating relevant symptoms of AR to the corresponding SPT. RESULTS: A total of 2,320 participants (1,475 females, median age 44.7 years, range 3-86) were included in this study. The standardized prevalence rates of sensitization were 13.2% for tree mix, 25.9% for grass pollen, and 25.9% for HDM. Sensitization to at least one of the allergens was present in 40.3% of the subjects. Symptomatic sensitization related to trees was reported in 9.7% of cases, grass-related AR was 17.6%, and HDM-related AR was 17.1%. The overall prevalence of AR was 30.9%. CONCLUSION: In this study we demonstrated a 40.3% prevalence of a positive SPT to one or more common aeroallergens. A clinical diagnosis of AR was present in 30.9% of cases, peaking in the third and fourth decades of life. It is to be expected that in the next decades, when this generation grows older, the general AR prevalence will further increase.

Cardiovascular risk factors among patients with acute unilateral inner ear hypofunction: A case-control study.

Objectives: To assess the prevalence of cardiovascular risk factors (CVRFs) and their impact on acute unilateral inner ear hypofunction (AUIEH), including acute unilateral peripheral vestibulopathy (AUPVP), sudden sensorineural hearing loss (SSNHL) and acute unilateral audiovestibular hypofunction (AUAVH). Methods: One hundred and twenty-five patients consecutively diagnosed with AUPVP, SSNHL or AUAVH and 250 sex- and age-matched controls were included. Cases presented a mean age of 58.6 ± 14.7 years and included 59 women and 66 men. The correlation between CVRFs (high blood pressure [HBP], diabetes mellitus [DM], dyslipidemia [DLP], cardiocerebrovascular disease [CCVD]) and AUIEH was assessed by multivariate conditional logistic regression analysis. Results: A higher prevalence of CVRFs was identified in patients than in controls (30 individuals with DM, 53 with HBP, 45 with DLP and 14 with a previous history of CCVD, p < .05). A significantly elevated risk of AUIEH was found in patients with two or more CVRFs (adjusted odds ratio [OR] 5.11; 95% CI 2.23-11.70). Previous CCVD individually predicted AUIEH (OR 8.41; 95% CI 2.36-29.88). Subgroup analysis showed the same tendency for AUPVP and SSNHL. Conclusion: Acute unilateral inner ear hypofunction patients presented significantly more CVRFs than controls, and the presence of two or more CVRFs was associated with AUIEH. Future studies evaluating vascular risk in AUIEH may include AUPVP and SSNHL patients from the same source population to better characterize risk profiles that can indicate a vascular origin. Level of Evidence: 3b.

Cardiovascular Risk and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: It was previously suggested that patients with idiopathic sudden sensorineural hearing loss (ISSNHL) have a higher risk of cardiovascular disease. The aim of this study is to determine if ISSNHL patients have an increased cardiovascular risk by means of a systematic review and meta-analysis. METHODS: A systematic literature review was performed using PubMed, Embase, Cochrane Libraries and Web of Science. Studies with a clear definition of ISSNHL, investigating an association between traditional vascular risk factors and ISSNHL were included. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, two reviewers extracted the data, assessed the risk of bias and performed the analysis of the collected evidence. RESULTS: Nineteen case-control studies and two cohort studies were included (102,292 patients). Individual studies argued for higher prevalence of hypercholesterolemia, diabetes mellitus (DM) and higher blood pressure (HBP) in ISSNHL patients with a range of odds ratios (ORs) from 1.03 to 19. Pooled analysis of adjusted ORs revealed a significantly increased risk of ISSNHL for patients with hypertriglyceridemia (OR 1.54; 95% confidence interval [CI] 1.18-2.02) and high levels of total cholesterol (TC) (OR 2.09; 95% CI 1.52-2.87 after sensitivity analysis), but not for HBP, DM, or high levels of low- and high-density lipoproteins. CONCLUSION: An association between higher vascular risk profile and ISSNHL seems apparent in high levels of triglycerides (TG) and TC, but more studies are needed to confirm this hypothesis due to the high levels of data heterogeneity in the literature. LEVEL OF EVIDENCE: NA Laryngoscope, 133:15-24, 2023.

Risk Factors for Hearing Loss at Birth in Newborns With Congenital Cytomegalovirus Infection.

Importance: With a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus (cCMV) infection is a major cause of congenital nonhereditary sensorineural hearing loss. Despite the large amount of research on cCMV-related hearing loss, it is still unclear which newborns are at risk of hearing loss. Objective: To identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth. Design, Setting, and Participants: This cross-sectional study of newborns with cCMV infection used data included in the Flemish CMV registry that was collected from 6 secondary and tertiary hospitals in Flanders, Belgium, over 15 years (January 1, 2007, to February 7, 2022). Data were analyzed March 3 to October 19, 2022. Patients were included in the study after confirmed diagnosis of cCMV infection and known hearing status at birth. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Main Outcomes and Measures: Primary outcome was hearing status at birth. Clinical, neurological, and laboratory findings along with the timing of seroconversion and blood viral load were separately considered as risk factors. Binary logistic regression was performed to identify independent risk factors for congenital hearing loss in newborns with cCMV. Effect sizes were measured using Hedges g, odds ratio, or Cramer V. Results: Of the 1033 newborns included in the study (553 of 1024 [54.0%] boys), 416 (40.3%) were diagnosed with symptomatic cCMV infection and 617 (59.7%) with asymptomatic cCMV infection. A total of 15.4% of the patients (n = 159) presented with congenital hearing loss; half of them (n = 80 [50.3%]) had isolated hearing loss. The regression model revealed 3 independent risk factors for congenital hearing loss: petechiae at birth (adjusted odds ratio [aOR], 6.7; 95% CI, 1.9-23.9), periventricular cysts on magnetic resonance imaging (MRI; aOR, 4.6; 95% CI, 1.5-14.1), and seroconversion in the first trimester (aOR, 3.1; 95% CI, 1.1-9.3). Lower viral loads were seen in patients with normal hearing compared with those with congenital hearing loss (median [IQR] viral load, 447.0 [39.3-2345.8] copies per milliliter of sample [copies/mL] vs 1349.5 [234.3-14 393.0] copies/mL; median difference, -397.0 [95% CI, -5058.0 to 174.0] copies/mL). Conclusions and Relevance: Findings of this cross-sectional study suggest that newborns with cCMV infection and petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Clinicians may use these risk factors to counsel parents in the prenatal and postnatal periods about the risk of congenital hearing loss. Moreover, linking clinical features to hearing loss may provide new insights into the pathogenesis of cCMV-related hearing loss. The importance of viral load as a risk factor for congenital hearing loss remains unclear.

Cerebral lateralization of praxis in right- and left-handedness: same pattern, different strength.

We aimed to investigate the effect of hand effector and handedness on the cerebral lateralization of pantomiming learned movements. Fourteen right-handed and 14 left-handed volunteers performed unimanual and bimanual tool-use pantomimes with their dominant or nondominant hand during fMRI. A left hemispheric lateralization was observed in the right- and left-handed group regardless of which hand(s) performed the task. Asymmetry was most marked in the dorsolateral prefrontal cortex (DLPFC), premotor cortex (PMC), and superior and inferior parietal lobules (SPL and IPL). Unimanual pantomimes did not reveal any significant differences in asymmetric cerebral activation patterns between left- and right-handers. Bimanual pantomimes showed increased left premotor and posterior parietal activation in left- and right-handers. Lateralization indices (LI) of the 10% most active voxels in DLPFC, PMC, SPL, and IPL were calculated for each individual in a contrast that compared all tool versus all control conditions. Left-handers showed a significantly reduced overall LI compared with right-handers. This was mainly due to diminished asymmetry in the IPL and SPL. We conclude that the recollection and pantomiming of learned gestures recruits a similar left lateralized activation pattern in right and left-handed individuals. Handedness only influences the strength (not the side) of the lateralization, with left-handers showing a reduced degree of asymmetry that is most readily observed over the posterior parietal region. Together with similar findings in language and visual processing, these results point to a lesser hemispheric specialization in left-handers that may be considered in the cost/benefit assessment to explain the disproportionate handedness polymorphism in humans.

Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.

BACKGROUND: Approximately 85% of nasal polyps (NPs) in white subjects are characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic differentiation and survival. OBJECTIVE: We sought to investigate the therapeutic potential of inhibiting IL-5 with a humanized mAb as treatment for severe nasal polyposis. METHODS: Thirty patients with severe nasal polyposis (grade 3 or 4 or recurrent after surgery) refractory to corticosteroid therapy were randomized in a double-blind fashion to receive either 2 single intravenous injections (28 days apart) of 750 mg of mepolizumab (n = 20) or placebo (n = 10). Change from baseline in NP score was assessed monthly until 1 month after the last dose (week 8). Computed tomographic scans were also performed at week 8. RESULTS: Twelve of 20 patients receiving mepolizumab had a significantly improved NP score and computed tomographic scan score compared with 1 of 10 patients receiving placebo at week 8 versus baseline. CONCLUSION: Mepolizumab achieved a statistically significant reduction in NP size for at least 1 month after dosing in 12 of 20 patients. IL-5 inhibition is a potential novel therapeutic approach in patients with severe eosinophilic nasal polyposis.

The Effect of (Val)ganciclovir on Hearing in Congenital Cytomegalovirus: A Systematic Review.

OBJECTIVE: To search for existing evidence of a beneficial effect of (val)ganciclovir on hearing in children with congenital cytomegalovirus (cCMV) infection and to identify future research questions. STUDY DESIGN: Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searches were performed in PUBMED, EMBASE, and WEB OF SCIENCE on December 15, 2021. METHODS: Studies providing ear-specific hearing results after treating children with cCMV-related hearing loss with (val)ganciclovir were retained. A meta-analysis [Peto odds ratio (OR), Review Manager 5.3] was performed to compare hearing outcome between treated and untreated children. The National Institutes of Health tool was used for quality assessment and heterogeneity was assessed with I2 statistics. RESULTS: Eighteen studies with a total of 682 treated patients were included for the systematic review. Our meta-analysis showed that treating symptomatic children with hearing loss resulted in more hearing improvement [Peto OR 7.72, 95% confidence interval (CI) 3.08-19.34] and less hearing deterioration (Peto OR 0.23, 95% CI 0.10-0.57). Relative to an improvement and deterioration rate of 9.4% and 28.2% in an untreated group, the rate of the treated group was 44.5% and 6.3%, respectively. CONCLUSIONS: There is sufficient evidence in literature to support treatment with (val)ganciclovir of children with symptomatic cCMV and hearing loss. However, still today, there is insufficient evidence of the potential beneficial role of (val)ganciclovir on hearing outcome of children with isolated hearing loss, late-onset hearing loss, and asymptomatic cCMV. The urgent need for future prospective, randomized clinical trials still exists. A standardization of definitions and treatment protocols would create uniformity in future studies. Laryngoscope, 132:2241-2250, 2022.

Hearing Loss in Stickler Syndrome: An Update.

Stickler syndrome is a connective tissue disorder characterized by ocular, skeletal, orofacial and auditory manifestations. Its main symptoms are high myopia, retinal detachment, joint hypermobility, early osteoarthritis, cleft palate, midfacial hypoplasia, micrognathia and hearing loss. Large phenotypical variability is apparent and partly explained by the underlying genetic heterogeneity, including collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, COL9A3) and non-collagen genes (BMP4, LRP2, LOXL3). The most frequent type of Stickler syndrome (COL2A1) is characterized by a rather mild high-frequency sensorineural hearing loss in about half of the patients. COL11A1- and COL11A2-related Stickler syndrome results in more frequent hearing loss, being moderate and involving all frequencies. Hearing loss in the rarer types of Stickler syndrome depends on the gene expression in the cochlea, with moderate to severe downsloping hearing loss for Stickler syndrome caused by biallelic type IX collagen gene mutations and none or mild hearing loss for the non-collagen genes. Inherent to the orofacial manifestations, middle ear problems and temporary conductive hearing loss, especially at young age, are also prevalent. Consequently, hearing loss should be actively sought for and adequately treated in Stickler syndrome patients given its high prevalence and the concomitant visual impairment in most patients.

Global Data on Ear and Hearing Screening in an Intellectual Disability Population.

Intellectual disability (ID) and hearing loss are frequent comorbid conditions, although otological problems often go unnoticed until picked up by screening. In the hearing program of Special Olympics (SO), athletes with ID are screened for otological problems. By retrospective analysis of all SO meetings between 2007 and 2017, more than 100,000 screenings could be included. Cerumen impaction was found in 40.7%, middle ear problems in 29.5% of those who failed hearing screening, and hearing loss confirmation in 26.9%. Prevalences for different world regions and country income groups are provided. The results emphasize the high prevalence of hearing loss in this ID population. Awareness among health care workers and active screening are required to reduce health disparities among this disadvantaged population.

Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?

Congenital hearing loss has an impact on almost every facet of life. In more than 50% of cases, a genetic cause can be identified. Currently, extensive genetic testing is available, although the etiology of some patients with obvious familial hearing loss remains unknown. We selected a cohort of mutation-negative patients to optimize the diagnostic yield for genetic hearing impairment. In this retrospective study, 21 patients (17 families) with negative molecular diagnostics for non-syndromic hearing loss (gene panel analysis) were included based on a positive family history with a similar type of hearing loss. Additional genetic testing was performed using a whole exome sequencing panel (WESHL panel v2.0) in four families with the strongest likelihood of genetic hearing impairment. In this cohort (n = 21), the severity of hearing loss was most commonly moderate (52%). Additional genetic testing revealed pathogenic copy number variants in the STRC gene in two families. In summary, regular re-evaluation of hearing loss patients with presumably genetic etiology after negative molecular diagnostics is recommended, as we might miss newly discovered deafness genes. The switch from gene panel analysis to whole exome sequencing or whole genome sequencing for the testing of congenital hearing loss seems promising.