Predictors of successful natural sleep MRI for sensorineural hearing loss in infants.

OBJECTIVES: Cochlear implantation (CI) in children with sensorineural hearing loss (SNHL) before 12 months of age (mo) improves language outcomes. MRI is important to assess CI candidacy. Anesthesia before 3 years old may increase risk of neurocognitive delay. Natural sleep MRI (NS-MRI) is an emerging technique to avoid anesthesia in infants, but relies on successful sleep for adequate imaging. Our multidisciplinary team hypothesized the following predictors of successful NS-MRI for CI evaluation: age, distance travelled, comorbidities, primary language, insurance type, HL characteristics, time and duration of MRI. METHODS: We performed retrospective review of children 0-12mo who attempted NS-MRI. The NS-MRI was successful if imaging was sufficient for definitive clinical management per the managing otolaryngologist. RESULTS: Among 26 patients (29 scans), the median age was 3.2mo (range: 1.2-6.8mo), distance travelled was 16.3 miles (range: 0.9 to 365 miles), 12 (46%) children had medical comorbidities. 8 (31%) had public insurance. 10 (38%) had bilateral HL. 52% (15/29) of scans were successful. Patients with comorbidities had significantly lower odds of successful NS-MRI (OR 0.09; 95% CI 0.01-0.54). Success was not associated with age, distance travelled, insurance type, primary language, HL characteristics, time or duration of MRI on univariable analysis. All 11 children who failed NS-MRI underwent hearing-aid fitting and/or imaging with sedation and CI as clinically indicated before 12mo. CONCLUSION: NS-MRI was successful in 52% of infants, regardless of age, demographics, HL or MRI characteristics. Unsuccessful NS-MRI did not result in delayed intervention. NS-MRI is an effective consideration for a broad range of infants with SNHL.

Racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing for sensorineural hearing loss.

Understanding racial and ethnic disparities in diagnostic rates of genetic testing is critical for health equity. We sought to understand the extent and cause of racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing (CGT) for sensorineural hearing loss (SNHL). We performed a retrospective cohort study at two tertiary children's hospitals on a diverse cohort of 240 consecutive pediatric patients (76% publicly insured, 82% non-White) with SNHL of unknown etiology who underwent CGT. Definite and possible genetic diagnoses were assigned for each patient, representing the likelihood of a genetic cause of hearing loss. Associations between diagnostic rates were examined. 3.8 ± 2.1 variants were detected per patient; this frequency did not vary between White/Asian and Hispanic/Black cohorts. Overall, 82% of variants were variants of uncertain significance (VUS). Compared with White and Asian subjects, variants identified among Hispanic and Black children were less likely to be classified as pathogenic/likely pathogenic (15% vs. 24%, p < 0.001), and Hispanic and Black children were less likely to have a definite genetic diagnosis (10% vs. 37%, p < 0.001). The adjusted odds ratio for definite genetic diagnosis in Black and Hispanic children compared with White and Asian children was 0.19. Expanding genetic diagnostic criteria to include predicted deleterious VUSs reduced these disparities between White/Asian and Hispanic/Black children, with comparable molecular diagnostic rates (41% vs. 38%, p = 0.72). However, in silico predictions are insufficiently valid for clinical use. Increased inclusion of underrepresented groups in genetic hearing-loss studies to clinically validate these variants is necessary to reduce racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing.

Associations between demographic factors and pediatric otolaryngology access disparities in the COVID-19 era.

OBJECTIVES: To assess the impact of demographic factors and telehealth on access to pediatric otolaryngology care during the COVID-19 pandemic, as measured by attendance. METHODS: Retrospective, observational study of all referrals to pediatric otolaryngology at a single, tertiary care pediatric hospital system in the US. All referrals placed to pediatric otolaryngology from March through December 2020 were compared with referrals between March and December 2019. Data on patient demographics, date of referral, duration between referral and appointment, appointment type, and diagnosis acuity were collected. A multivariate linear regression was used to evaluate the impact of the patient age, ethnicity, language, insurance, diagnosis acuity, time to appointment, and appointment type on attendance. RESULTS: This study included 1988 referrals placed between March 16th-December 31st, 2020 and 3704 referrals placed between March 16th-December 31st, 2019. In 2020, attendance proportions were significantly higher at 72% compared to 62% during 2019 (p < 0.001). In 2020, there was a significantly shorter duration between referral and appointment, averaging 10 days as compared to 26 days in 2019 (p < 0.001). Overall, Black and Hispanic patients, children over the age of one, publicly insured patients, and those with longer wait times were less likely to attend their appointments. Primary language and use of telehealth did not predict attendance. CONCLUSION: Early evidence has found significant healthcare access and outcome disparities across ethnicities during the COVID pandemic. However, there is limited data evaluating the effect of demographic factors or telehealth on access to pediatric otolaryngology care. This study identifies age, race and insurance type as predictors of access to pediatric otolaryngologic care, as measured by attendance.

Genetic Testing Leading to Early Identification of Childhood Ocular Manifestations of Usher Syndrome.

OBJECTIVES: Hearing-loss gene panel testing (HLGPT) is increasingly accessible as a first-line test in determining the etiology of sensorineural hearing loss (SNHL) in children. A major advantage of HLGPT is early identification of syndromic forms of SNHL, especially Usher syndrome, prior to the development of overt syndromic phenotype, which may impact management and counseling. Here, we describe early ocular findings in children with clinically non-syndromic SNHL identified by HLGPT as having two variants associated with Usher Syndrome. METHODS: A total of 184 children, ages 1 month - 15 years of age, evaluated at one tertiary pediatric children's hospital for clinically non-syndromic SNHL, underwent next-generation sequencing of 150 genes involved in hearing loss. Children with two variants in genes associated with Usher syndrome were referred for evaluation by pediatric ophthalmology. RESULTS: A total of 18/184 tested children had two variants in Usher syndrome-associated genes, including MYO7A, GPR98 (ADGRV1), USH2A, and PDZD7. SNHL varied from moderate to profound. 29% of the children who underwent clinical ophthalmology evaluation were found to have previously unidentified retinal abnormalities on retinal imaging or electroretinography consistent with inherited retinal degeneration. CONCLUSION: Among this ethnically and racially diverse pediatric population with apparently non-syndromic SNHL, HLGPT yielded a high proportion (10%) of children with two variants in genes associated with Usher syndrome. Early genetic testing allows early identification of variants conferring a diagnosis of Usher syndrome at a stage prior to visual symptoms. This allows for more informed genetic counseling, reproductive planning, and sensory deficit interventions. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2053-E2059, 2021.

Endoscopic percutaneous suture lateralization for neonatal bilateral vocal fold immobility.

OBJECTIVE: Bilateral vocal-fold immobility (BFVI) is a rare but significant cause of severe respiratory distress in neonates. The primary aim of treatment is to provide an adequate airway while minimizing adverse effects such as aspiration and dysphonia. Our objective here is to describe the outcomes of a series of neonates undergoing percutaneous endoscopic suture lateralization for BVFI using a novel technique. METHODS: In this retrospective case series, we present 6 neonates (mean age: 18 days) with BVFI from three tertiary academic medical centers. The etiologies included 4 idiopathic, 1 unspecified neurodegenerative disorder, and 1 acquired from cardiac surgery. All had stridor and respiratory distress with hypoxemia requiring respiratory support at diagnosis. Endoscopic vocal-fold lateralization was performed under spontaneous-breathing suspension laryngoscopy using a novel technique of percutaneous needle-directed placement of 4-0 prolene suture without use of specialized equipment. RESULTS: All patients had clinical improvement in stridor and respiratory support requirements and avoided tracheostomy. One patient had persistent aspiration after lateralization that resolved after suture removal. One patient required bilateral lateralization procedures. One patient expired of epilepsy due to neurodegenerative disease unrelated to airway pathology. At last follow-up (mean 12.6 months), 5/5 remaining patients were on room air without tracheostomy and feeding orally without aspiration; 4/5 had partial or complete return of vocal-fold function. CONCLUSION: Endoscopic percutaneous suture lateralization may be a safe and effective non-destructive primary treatment modality for neonatal BVFI. All neonates undergoing this procedure avoided tracheotomy.

Hearing outcomes of atresia surgery versus osseointegrated bone conduction device in patients with congenital aural atresia: a systematic review.

OBJECTIVE: To perform a systematic review, comparing hearing outcomes of atresiaplasty versus osseointegrated bone conduction device (OBCD) in congenital aural atresia (CAA) patients. DATA SOURCES: Approximately 107 studies, published from 1975 to 2012, evaluating hearing outcomes after atresiaplasty and/or OBCD in CAA patients were identified through a PubMed search. STUDY SELECTION: Articles that evaluated external auditory canal stenosis alone, did not report speech reception threshold (SRT), pure tone average (PTA), hearing gain, or air-bone gap (ABG) or had less than 5 patients were excluded. For authors or institutions with multiple reports, the largest or most recent study was included. Forty-one articles satisfied our inclusion and exclusion criteria. DATA EXTRACTION: The number and percentage of ears with a postoperative SRT, PTA, ABG less than 30 dB, and/or average hearing gain were extracted. The total number of ears and the timing of the postoperative audiogram were also noted. DATA SYNTHESIS: Of the atresiaplasty ears, 73.8% (95% CI, 62.2%-85.4%), had a SRT less than 30 dB (338 ears), 60.3% (95% CI, 45.8%-74.8%) had a PTA less than 30 dB (390 ears), and 68.9% (95% CI, 59.4%-78.3%) had an ABG less than 30 dB (852 ears). The average hearing gain was 24.1 dB (95% CI, 21.62-26.51) for 516 ears. Hearing outcomes deteriorated with time. Of OBCD patients, 95.9% (95% CI, 91.5%-100.0%) had a PTA less than 30 dB (77 ears), and 98.2% (95% CI, 94.5%-100.0%) had an ABG less than 30 dB (47 ears); the average hearing gain was 38.0 dB (95% CI, 33.14-45.22) in 100 ears. CONCLUSION: The OBCD has better hearing outcomes compared with atresiaplasty in patients with CAA.

Integrity and regeneration of mechanotransduction machinery regulate aminoglycoside entry and sensory cell death.

Sound perception requires functional hair cell mechanotransduction (MET) machinery, including the MET channels and tip-link proteins. Prior work showed that uptake of ototoxic aminoglycosides (AG) into hair cells requires functional MET channels. In this study, we examined whether tip-link proteins, including Cadherin 23 (Cdh23), regulate AG entry into hair cells. Using time-lapse microscopy on cochlear explants, we found rapid uptake of gentamicin-conjugated Texas Red (GTTR) into hair cells from three-day-old Cdh23(+/+) and Cdh23(v2J/+) mice, but failed to detect GTTR uptake in Cdh23(v2J/v2J) hair cells. Pre-treatment of wildtype cochleae with the calcium chelator 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA) to disrupt tip-links also effectively reduced GTTR uptake into hair cells. Both Cdh23(v2J/v2J) and BAPTA-treated hair cells were protected from degeneration caused by gentamicin. Six hours after BAPTA treatment, GTTR uptake remained reduced in comparison to controls; by 24 hours, drug uptake was comparable between untreated and BAPTA-treated hair cells, which again became susceptible to cell death induced by gentamicin. Together, these results provide genetic and pharmacologic evidence that tip-links are required for AG uptake and toxicity in hair cells. Because tip-links can spontaneously regenerate, their temporary breakage offers a limited time window when hair cells are protected from AG toxicity.

Spontaneous Cerebrospinal Fluid Leak through the Posterior Aspect of the Petrous Bone.

Spontaneous cerebrospinal fluid (CSF) leak through the posterior fossa (PF) aspect of the petrous bone is exceedingly rare. A case series allows analysis of etiologies and how they may differ from the more common middle fossa (MF) route of leakage. The design was a retrospective case series. The setting was a tertiary care institution. A series of three patients with PF spontaneous CSF leaks was identified. High-resolution imaging (CT and MRI) and intraoperative observations were evaluated. Both in this series and in previously reported cases, patients share the demographics typically found in the MF leak population. In our series, two patterns of PF CSF leak were identified: (1) large unilateral with cerebellar encephalocele and (2) small punctate defects just lateral to the endolymphatic sac. Two presented with simultaneous MF and PF leaks suggesting a shared etiology, at least in some cases, with a role for increased intracranial pressure. In spontaneous CSF leaks, it is important to evaluate the posterior petrous bone along with the tegmen. The concomitant appearance of MF with PF leaks points out the risk that repair via MF craniotomy could fail to identify a leakage site in the vicinity of the endolymphatic sac.