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Background: Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital. Methods: A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing. Results: EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital. Conclusions: By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited. [ABSTRACT FROM AUTHOR]

AbstractObjectiveDesignStudy sampleResultsConclusionThis study aimed to evaluate long-term cochlear implant (CI) outcomes in individuals with mono-allelic pathogenic variants in WFS1, which is associated with both Wolfram-like syndrome and DFNA6/14/38.Retrospective case series.Seven CI recipients, ranging from eight months to 58 years of age, were included in the study, including four with Wolfram-like syndrome and three with DFNA6/14/38. A total of ten cochlear implantations were performed among these subjects.At one-year post-implantation, a mean phoneme score of 90 ± 9% at 65 dB SPL in quiet was found, which remained stable up to ten years post-implantation with a mean phoneme score of 94 ± 6%. Despite these excellent outcomes, one subject achieved no speech recognition with CI and eventually became a non-user. This individual had a prolonged absence of auditory stimulation prior to implantation and encountered multiple challenges during rehabilitation.Individuals with Wolfram-like syndrome or DFNA6/14/38 demonstrate consistently good outcomes following implantation, which remain stable over time. These findings affirm cochlear implantation as an effective rehabilitation option for these individuals. Furthermore, the stable and good CI outcomes contradict the suggested link between WFS1-associated sensorineural hearing loss and auditory neuropathy. [ABSTRACT FROM AUTHOR]

The formin protein Diaph3 is an actin nucleator that regulates numerous cytoskeleton-dependent cellular processes through the activation of actin polymerization. Expression and activity of Diaph3 is tightly regulated: lack of Diaph3 results in developmental defects and embryonic lethality in mice, while overexpression of Diaph3 causes auditory neuropathy. It is known that Diaph3 homophilic interactions include the intramolecular interaction of its Dia-inhibitory domain (DID)- diaphanous autoregulatory domain (DAD) domains and the intermolecular interactions of DD-DD domains or FH2-FH2 domains. However, the physiological significance of these interactions in Diaph3 protein stability and activity is not fully understood. In this study, we show that FH2-FH2 interaction promotes Diaph3 activity, while DID-DAD and DD-DD interactions inhibit Diaph3 activity through distinct mechanisms. DID-DAD interaction is responsible for the autoinhibition of Diaph3 protein, which is disrupted by binding of Rho GTPases. Interestingly, we find that DID-DAD interaction stabilizes the expression of each DID or DAD domain against proteasomalmediated degradation. Disruption of DID-DAD interaction by RhoA binding or M1041A mutation causes increased Diaph3 activity and accelerated degradation of the activated Diaph3 protein. Further, the activated Diaph3 is ubiquitinated at K1142/1143/1144 lysine residues by the E3 ligase Stub1. Expression of Stub1 is causally related to the stability and activity of Diaph3. Knockdown of Stub1 in mouse cochlea results in hair cell stereocilia defects, neuronal degeneration, and hearing loss, resembling the phenotypes of mice overexpressing Diaph3. Thus, our study reports a novel regulatory mechanism of Diaph3 protein expression and activity whereby the active but not inactive Diaph3 is readily degraded to prevent excessive actin polymerization. [ABSTRACT FROM AUTHOR]

Aim: To estimate the Single-sided deafness (SSD) among sensorineural hearing loss (SNHL) in Tertiary Care Rehabilitation Centre. To determine the audiological characteristics, associated and medical problems, and rehabilitative approaches among SSD. Method: A retrospective study was conducted to report on demographic details, audiological evaluation, and hearing aid management among SSD clients. A total of 11,534 cases of SNHL were reported to the Audiology department at the tertiary care rehabilitative center at Mysuru between January 2014 and December 2017. Results: A total of 225 were diagnosed as having SSD, accounting for approximately two cases of SSD in a cohort of 100 SNHL cases (225/11,534*100). In addition, males are affected more than females. SSD is found to have more in the right ear than the left ear. Their major complaints were tinnitus and vertigo, apart from reduced hearing sensitivity from the affected ear. In the side of the ear with profound hearing loss among SSD clients showed normal middle ear status with absent acoustic reflexes, otoacoustic emissions, and auditory brainstem response. Only 54 individuals (24%) out of 225 SSD clients underwent a hearing aid trial. Twenty-one (9%) SSD clients purchased a hearing aid, and a minuscule seven (3%) of 225 SSD clients are using a hearing aid. The preference for hearing aid uptake was low because of the experience of vibratory sensation and having near-normal hearing in one ear. Conclusion: Two cases of SSD were observed among SNHL and they are less likely to get benefits from the hearing aid. [ABSTRACT FROM AUTHOR]

Background: The study explored the differences in audiological and non-audiological characteristics between congenital, early-onset, and late-onset auditory neuropathy spectrum disorder (ANSD). Ninety-five individuals diagnosed with ANSD were included in the study. They were divided into three groups congenital ANSD—children (30 individuals, 60 ears), adults with early-onset ANSD (30 individuals, 56 ears), and adults with late-onset ANSD (35 individuals, 62 ears). The non-audiological characteristics (gender, laterality, and risk factors) and audiological characteristics (behavioral and electrophysiological measures) were compared between the three groups. Results: Discriminant analyses showed that the pure tone average, audiogram configuration, and speech thresholds were the best auditory predictors of onset-based group differences in ANSD (congenital and early-onset versus late-onset ANSD). While the congenital and early-onset group showed poorer pure-tone and speech thresholds, along with flat configuration, the late-onset group demonstrated relatively better thresholds and other configurations (rising, tent-shaped, cookie-bite). In addition, long latency responses were delayed or absent in children with congenital ANSD, indicative of onset coding deficits at the cortical level. Conclusions: The study highlights the audiological differences between congenital, early-, and late-onset ANSD groups. These differences could be because of variations in etiology, pathophysiology, site of lesion, or genetic variability between the groups, which needs to be explored further. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of auditory neuropathy spectrum disorder (ANSD) is based on the existence of cochlear microphonics or otoacoustic emissions, as well as aberrant or nonexistent-evoked auditory brainstem responses. The outcomes of cochlear implantation (CI) are thought to be significantly influenced by genetic reasons in ANSD. Objective: The purpose of this systematic review was to gather more information regarding the relationship between various genetic variants and the outcomes of cochlear implantation in adult and pediatric patients with ANSD (both syndromic and non-syndromic). Methods: Electronic databases "Medline/PubMed, Google Scholar, ScienceDirect, Europe PMC, and Cochrane Library" were searched for this systematic review. For cohort studies, the Newcastle–Ottawa scale (NOS score) was used to assess the quality of the retrieved research. The standardized mean difference produced by the Cohen's d or Hedges' g tests was used to assess the effect size measure. Results: This comprehensive study showed that OTOF, GJB2, ATPA3, and OPA1 were among the genetic variants with improved CI outcomes. On the other hand, other genetic mutations displayed variable results (TMPRSS3) or worse CI outcomes (PJVK). For OTOF mutations, CI had a moderate effect (Hedges' g = 0.7), which led to good cochlear implant outcomes. The results of the GJB2 cochlear implant showed a significant effect size when pre- and post-implant assessments were compared. The results of CI for TMPRSS3 mutations were inconsistent, with one study demonstrating a negligible effect (Hedges' g = 0.2), and another study found a negative impact (Hedges' g = − 2.17). Poor CI results were indicated by PJVK mutations impacting CI outcomes. A significant impact was observed when comparing pre- and postimplantation outcomes (Cohen's d > 1) in cases of ATP1A3 mutations (CAPOS syndrome) and OPA1 mutations. In addition, early implantation produced better results than late implantation in certain genetic variations. Conclusion: Some genetic variants, such as OTOF, GJB2, ATPA3, and OPA1, had improved CI outcomes, according to data extraction and synthesis of the systematic review's findings. Conversely, PJVK displayed worse CI results and inconsistent results for TMPRSS3 genetic mutations. [ABSTRACT FROM AUTHOR]

AbstractObjectiveDesignStudy sampleResultsConclusionThis study aimed to explore the functional integrity of vestibulo-masseteric and sacculo-collic reflex pathways in individuals with Auditory Neuropathy (AN). The study also aimed at finding the correlation between mVEMP and cVEMP response parameters for AN and healthy individuals.Standard group comparison research designIndividuals with AN (n = 20); age-gender matched healthy individuals (n = 20) were recruited. Each participant underwent routine audiological evaluation; mVEMP and cVEMP testing. mVEMP and cVEMP were recorded using 500 Hz tone burst stimulus for all the participants.Most of the AN individuals had no mVEMP (ipsilateral & contralateral − 60%; bilateral − 50%) and cVEMP (60%) responses. There was no significant association (p > 0.05) between the duration of AN with mVEMP and cVEMP findings. However, a significant correlation (p < 0.05) was found for EMG rectified amplitude of mVEMP and cVEMP in AN.The results of this study suggested an impaired function of the vestibulomassteric and sacculocollic reflex pathways in individuals with AN. Vestibular evaluation should be included as a part of the regular test battery for individuals with AN. [ABSTRACT FROM AUTHOR]

Background: A delay in a child's capacity to develop language is one of the impacts of hearing loss. Children use amplification devices so they can develop spoken language skills comparable or equivalent to those of their peers without hearing loss. The aim of the study was to detect the effect of using different amplification devices on the development of the language in children. Methods: The study included three groups of 5-8 years old children, who used different hearing devices and had bilateral severe to profound sensorineural hearing loss. Each group consisted of ten children; one using binaural hearing aids, the second had a unilateral cochlear implant, and the third group received a bimodal fitting. They were submitted to the following: history taking, intelligence and mental status examination, auditory performance assessment, and Language assessment. Results: Bimodal and cochlear implant users have a significantly better aided response, speech understanding, and language performance than hearing aid users. There is a negative, moderate correlation between the aided hearing thresholds and treatment-related factors. Conversely, there is a positive, moderate correlation between the word recognition score, revised categories of auditory perception scale, language performance and the treatment-related factors. Conclusions: The aided responses and language development were better among studied cases with cochlear implants and cases with bimodal hearing than cases with hearing aids. Consequently, it is crucial to assess auditory performance and language skills in each child with severe to profound hearing loss individually in terms of hearing aid benefit and the need for cochlear implantation. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging (MRI), electric compound action potential (eCAP), and electric auditory brainstem response (eABR) are among the routine assessments performed before and/or after cochlear implantation. The objective of this review was to systematically summarize and critically appraise existing evidence of the prognostic value of eCAP, eABR, and MRI for predicting post--cochlear implant (CI) speech perception outcomes in children, with a particular focus on the lesion site. Method: The present systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Three electronic databases (ProQuest, PubMed, and Scopus) were searched with no restrictions on language, publication status, or year of publication. Studies on children identified with sensorineural hearing loss, auditory neuropathy spectrum disorder, cochlear nerve deficiency, or cochleovestibular nerve abnormalities reporting the relevance of eCAP, eABR, and/or MRI results to CI speech perception outcomes were included. The literature search yielded 1,887 publications. Methodological quality and strength of evidence were assessed by the Crowe Critical Appraisal Tool and the Grading of Recommendations Assessment, Development, and Evaluation tool, respectively. Results: Of the 25 included studies, the relevance of eCAP, eABR, and/or MRI findings to post-CI speech perception outcomes was reported in 10, 11, and 11 studies, respectively. The studies were strongly in support of the prognostic value of eABR and MRI for CI outcomes. However, the relevance of eCAP findings to speech perception outcomes was uncertain. Conclusion: Despite the promising findings, caution is warranted in interpreting them due to the observational and retrospective design of the included studies, as well as the heterogeneity of the population and the limited control of confounding factors within these studies. Supplemental Material: https://doi.org/10.23641/asha.26169859 [ABSTRACT FROM AUTHOR]

Adolescent substance use poses a critical public health challenge, intertwined with risk-taking behavior, criminality, functional impairment, and comorbid mental and physical health issues. Adolescents with bipolar spectrum disorders (BSD) exhibit heightened susceptibility to substance use, necessitating a nuanced exploration of the bipolar-substance use relationship. This study addressed gaps in the literature by employing a prospective, longitudinal design with 443 Philadelphia-area adolescents, tracking BSD symptoms and substance use. We predicted that BSD symptoms would be associated with increases in substance use, and that these effects would be more pronounced for individuals with a BSD and those with high reward sensitivity. Hypomanic symptoms predicted subsequent substance use, with a stronger association observed in individuals diagnosed with BSD. Contrary to expectations, depressive symptoms did not exhibit a similar relationship. Although the hypothesized moderating role of reward sensitivity was not supported, higher reward sensitivity predicted increased substance use. Symptoms and substance use are only captured for the month prior to each session due to the assessment timeline. This highlights the benefits of frequent assessments over a shorter time frame to monitor real-time changes. Alternative classification methods for reward sensitivity, such as brain or behavior-based assessments, might yield different results. This study's contributions include evaluating substance use broadly, utilizing a longitudinal design for temporal clarity, and shifting the focus from substance use predicting mood symptoms to the inverse. The findings underscore the need for continued exploration of mood symptom predictors of substance use, emphasizing the role of reward sensitivity. • Substance use (SU) among adolescents poses a critical public health challenge • Adolescents with a bipolar spectrum disorder (BSD) have greater susceptibility to SU • Heighted reward sensitivity (RS) also may exacerbate this vulnerability • Findings confirmed that hypomanic, but not depressive, symptoms led to increased SU • This relationship was more pronounced for individuals with a BSD but not elevated RS [ABSTRACT FROM AUTHOR]

Abstract Background The study explored the differences in audiological and non-audiological characteristics between congenital, early-onset, and late-onset auditory neuropathy spectrum disorder (ANSD). Ninety-five individuals diagnosed with ANSD were included in the study. They were divided into three groups congenital ANSD—children (30 individuals, 60 ears), adults with early-onset ANSD (30 individuals, 56 ears), and adults with late-onset ANSD (35 individuals, 62 ears). The non-audiological characteristics (gender, laterality, and risk factors) and audiological characteristics (behavioral and electrophysiological measures) were compared between the three groups. Results Discriminant analyses showed that the pure tone average, audiogram configuration, and speech thresholds were the best auditory predictors of onset-based group differences in ANSD (congenital and early-onset versus late-onset ANSD). While the congenital and early-onset group showed poorer pure-tone and speech thresholds, along with flat configuration, the late-onset group demonstrated relatively better thresholds and other configurations (rising, tent-shaped, cookie-bite). In addition, long latency responses were delayed or absent in children with congenital ANSD, indicative of onset coding deficits at the cortical level. Conclusions The study highlights the audiological differences between congenital, early-, and late-onset ANSD groups. These differences could be because of variations in etiology, pathophysiology, site of lesion, or genetic variability between the groups, which needs to be explored further.

Objectives. FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. Methods. A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results. In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient’s CI outcomes showed significant improvement over 1-year post-CI. Conclusion. A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.

Background: Cortical auditory evoked potentials (CAEPs) display both auditory processing and neurological activity in the auditory cortex. The purpose of this research is to evaluate the importance of CAEPs in identifying auditory processing disorders in patients with peripheral neuropathy (PN) in different pathologies. Sixty cases with PN of different pathologies represented the study group which was classified into two subgroups according to the underlying pathology of PN: those with either axonal PN (44 patients) and those with demyelinating PN (16 patients). The current study also included a control group of 40 healthy volunteers who did not have any peripheral or central auditory neurological disorders. CAEPs were recorded in both groups. Results: The study group's CAEP response showed significantly delayed latencies than the control groups. Comparing the two study subgroups revealed that the axonal PN group had significant delayed latencies of N1 and P2 components in comparison to the demyelinating PN group. Conclusion: Cortical auditory evoked potentials can be used efficiently to diagnosis central auditory processing disorders in patients with PN. CAEP latencies can be employed alone or in conjunction with amplitudes; however, CAEP latencies are more significant than amplitudes for such purpose. Both demyelinating and axonal PN are associated with impaired auditory processing; however, axonal PN patients are more likely to be affected, suggesting that axonal PN has a significantly drastic effect on the central auditory nervous system. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative wound infections after cochlear implantation are rare but sometimes serious and can lead to explantation. Therefore, perioperative antibiotic administration is often recommended. However, in clinical practice, the type and duration of antibiotic prophylaxis varies between different centers. The aim of this study was to investigate the role of perioperative antibiotic prophylaxis in preventing postoperative complications. Methods: 700 patients who underwent cochlear implantation between 2007 and 2019 were retrospectively evaluated with regard to wound infections within the first 28 postoperative days. These were classified into major and minor complications. Data were analyzed using the IBM statistical program SPSS. Results: In 670 out of 700 patients the type and duration of perioperative antibiotic administration could be reconstructed from the records. Of these 67 patients (10%) received antibiotics as a single shot, 158 patients (23.6%) were treated with antibiotics for a period of 48 h, and 445 patients (66.4%) received prolonged antibiotic therapy for more than 72 h. In total 64 patients (9.5%) showed abnormalities in wound assessment within the first 28 postoperative days after implantation. Major infections (1.6%) were detected in 11 patients. Overall, there was no statistically significant difference in wound infection rates between the group receiving single-shot antibiosis and the group receiving 48 h prophylaxis or antibiotic treatment > 72 h (p = 0.46). Conclusion: Patients receiving an antibiotic single shot do not appear to be at significantly increased risk for postoperative wound infections compared with patients with prolonged antibiotic treatment. Continuation of data collection across centers seems reasonable. [ABSTRACT FROM AUTHOR]

CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is a rare genetic disorder caused by the heterozygous mutation, c.2452G > A, in the ATP1A3 gene. CAPOS syndrome involves a characteristic episode in which neuropathy develops after a fever in childhood, and here, we describe the case of a patient with CAPOS syndrome. The patient had repeated episodes of a fever around 74 months of age. Although he could speak at 23 months of age, he presented with hearing difficulty after the fever. Pure-tone audiometry revealed moderate-to-severe bilateral sensorineural hearing loss, and auditory brainstem response (ABR) showed poor response in the both ears. Auditory stead-state response (ASSR) produced relatively consistent results compared to pure-tone audiometry. A mutation in the ATP1A3 gene was detected through genetic testing. In CAPOS syndrome, a genetic mutation leads to desynchronization during neural firing. We believe that this desynchronization in neural firing is responsible for the lack of response in the ABR and the presence of a response in the ASSR. In this patient, we attribute the response detection in ASSR to its greater tolerance for errors in the timing of neural firing compared to ABR. [ABSTRACT FROM AUTHOR]

Introduction: Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months. Methods: The primary endpoints were the response rate, defined as those patients with an increase of < 2 points on the Neurological Impairment Score (NIS) from baseline, and the change in the NIS score from baseline. Secondary endpoints included the Quantitative Sensory Test, 10-m walk test, quality of life (Norfolk), and disability (Rasch-built Overall Disability Scale). As safety parameters, the evidence of graft rejection, changes in immunosuppressive trough levels and changes in antiviral and allogeneic cellular immunity before and 12 months after tafamidis treatment were also assessed. Results: Six patients (85.7%) had responded at 18-months. Compared to baseline, we observed non-statistically significant improvement in mean NIS score at 6 months (− 2.54 points, CI − 5.92 to 0.84), 12 months (− 3.25 points; CI − 6.63 to 0.13), and 18 months (− 2.35 points; CI − 5.74 to 1.02). Changes in the Quantitative Sensory Test, 10-m walk tests and the quality of life and disability questionnaires were not statistically significant. The use of tafamidis did not induce relevant side effects or drug interactions. Also, no acute rejections events nor changes in functional adaptive immunity were observed. Conclusion: Our study supports the safety and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Tafamidis shows promise as a useful treatment in the clinical management of these patients. Future randomized placebo-controlled clinical trials with longer follow-up durations are needed. [ABSTRACT FROM AUTHOR]

This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aβ) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3β and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsConclusionProper electrode placement is essential for favorable hearing outcomes following cochlear implantation. Though often used, traditional intraoperative X-ray imaging is time consuming, exposes patients and staff to radiation, and poses interpretational challenges. The Nucleus® SmartNav System, utilizes electrode voltage telemetry (EVT) to analyze the positioning of the electrode array intraoperatively. This study investigates the efficacy of SmartNav in optimizing the efficiency and accuracy of assessing electrode placement.This prospective clinical study analyzed placement of 50 consecutive Cochlear Corporation cochlear implants conducted at a single institution between March of 2022 and June of 2023. Placement check of electrode array using SmartNav and X-ray was completed and individually assessed. A comparative analysis of SmartNav and X-ray completion times for electrode placement assessment was conducted.Subjects included nine ears with abnormal anatomy and three reimplants. SmartNav placement check required a total time of 2.12 min compared to X-ray imaging at 14.23 min (p = 1.6E-16, CI 95%). Both SmartNav and X-ray had excellent sensitivity of 100% in identifying appropriate electrode position (p = 1.0). Tip fold-over was identified using both modalities in 3 cases with noted easier interpretation using SmartNav.The Nucleus® SmartNav System significantly outperformed traditional X-ray imaging, offering a faster and more straightforward approach to assessing electrode positioning during cochlear implant surgery, thereby enhancing surgical efficiency and patient safety. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Hearing loss is the most common sensory deficiency at birth, and its association with vestibular dysfunction in children has been well-established. The primary aim of our study is to investigate the relationship between these two sensory deficits, their overall impact on children's development, and to establish a simple and effective screening protocol for clinical practice. Method: We conducted a comprehensive narrative literature review. Results: Our review includes a total of 41 publications focused on neurosensorial hearing loss and vestibular dysfunction in the paediatric population. Discussion: Our findings indicate that children with more significant hearing loss are at a higher risk of experiencing vestibular dysfunction. Certain specific conditions, such as congenital cytomegalovirus, inner ear malformations, auditory neuropathy spectrum disorders, sudden hearing loss, ototoxicity, and cochlear implants, are more frequently associated with both hearing loss and balance alterations. To ensure accurate diagnosis and referral to the diagnostic protocol, the evaluation of vestibular dysfunction must consider the patient's age and include assessments of motor development and balance. For young children, vestibular-evoked myogenic potentials and the head impulse test are the most well-tolerated tests. Conclusions: Early recognition of signs indicating vestibular dysfunction in children with neurosensorial hearing loss is crucial. Prompt diagnosis and early intervention are essential to minimize the impact on their quality of life and overall development. [ABSTRACT FROM AUTHOR]

Pelizaeus--Merzbacher disease (PMD) is an X-linked recessive rare disease condition in which audiological deficit is also observed. A 4-year-old male child with PMD underwent an audiological evaluation. The results suggested normal middle ear and outer hair cells functioning, with only peak I of the auditory brainstem response present until 30 dBnHL. Further, the cervical vestibular evoked myogenic potential showed delayed latencies with normal amplitudes. In this case report, we attempt to explain the audio-vestibular test results and correlate them with the pathophysiology. This is the first report on the cervical vestibular myogenic potentials in patients with PMD. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. The brain state involving phase-synchronization between default mode network and sensory networks is particularly related to sustained pain, likely indicating a shift toward internally directed self-referential processes. Growing evidence has suggested that time-varying functional connectivity between different brain regions might underlie the dynamic experience of pain. This study used a novel, data-driven framework to characterize the dynamic interactions of large-scale brain networks during sustained pain by estimating recurrent patterns of phase-synchronization. Resting-state functional magnetic resonance imaging signals were collected from 50 healthy participants before (once) and after (twice) the onset of sustained pain that was induced by topical application of capsaicin cream. We first decoded the instantaneous phase of neural activity and then applied leading eigenvector dynamic analysis on the time-varying phase-synchronization. We identified 3 recurrent brain states that show distinctive phase-synchronization. The presence of state 1, characterized by phase-synchronization between the default mode network and auditory, visual, and sensorimotor networks, together with transitions towards this brain state, increased during sustained pain. These changes can account for the perceived pain intensity and reported unpleasantness induced by capsaicin application. In contrast, state 3, characterized by phase-synchronization between the cognitive control network and sensory networks, decreased after the onset of sustained pain. These results are indicative of a shift toward internally directed self-referential processes (state 1) and away from externally directed cognitive control processes (state 3) during sustained pain. [ABSTRACT FROM AUTHOR]

Introduction One of the paths in the investigation of congenital sensorineural hearing loss (CSNHL) is to try to characterize its etiology through the inner ear evaluation using high resolution computer tomography (CT) scans. With minor malformation, it is not always possible for a simple visual inspection to recognize if the structure in the inner ear is normal or not. Objective To verify if measurements of the inner ear are predictive of sensorineural hearing loss (SNHL) and suggest cutoff points of size limits. Methods Retrospective cross-sectional study of inner ear CT scan measurements of 214 patients, 50 with congenital SNHL (CSNHL) and 164 acquired SNHL (ASNHL) (control group). Results In the CSNHL group, central bony island (CBI) were 0.48 mm smaller (p < 0.001), cochlear nerve aperture was (CNA) 0.10 mm smaller (p < 0.001), and cochlea height was (CH) 0.15 mm smaller (p < 0.001). Vestibular aqueduct (VA) and cochlea width (CW) were similar between groups (0.70 vs 0.72, p = 0.19, and 7.20 vs 7.15 p = 0.23). The predictive cutoff points for CSNHL were CBI = 3.6 mm, CAN = 1.4 mm, CH = 3.4 mm, CW = 7.0 mm, and VA = 0.9 mm. Conclusion Congenital sensorineural hearing loss determined a decrease in CBI, opening of the cochlear nerve (OCN), and CW. Thus, these measures, at the cutoff points indicated, should make us aware of the diagnosis of congenital hearing loss. [ABSTRACT FROM AUTHOR]

• BCB's role in schizophrenia's pathophysiology might be pivotal, yet poorly understood. • We report IPD of n=531 recent-onset psychosis individuals with CSF-diagnostics. • BCB's disruption appears highly prevalent early in schizophrenia-spectrum disorders. • No symptom severity differences between individuals with and without CSF alterations. • Males with elevated CSF/serum albumin ratios had higher PANSS positive scores. Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta -analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta -analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI −0.55–0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05–0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17–0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptomś severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdown and sex-related differences in SSDs clinical trials and treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: To determine and report the underlying cause of local inflammation causing recurrent neuropathy and multiple operations in a patient with a Barricaid® device. Methods: After removal of this patient's Barricaid® device, we sent local inflammatory tissue to pathology for histochemical analysis. Upon discovery of giant cells formation with polarizable foreign bodies, we performed a literature review regarding the Barricaid® device and its elements. Results: After two previous operations and three trials of conservative management, the presented patient underwent an L5/S1 TLIF with removal of her previously installed Barricaid® device. There were no signs of device instability/failure nor were there obvious signs of infection. Inflamed tissue proximal to the Barricaid® device was discovered, debrided, and sample sent to pathology. Removal of the Barricaid® device led to subsequent and durable relief of her symptoms. During review of this case, we discovered the polyethylene terephthalate (PET) weave used in the Barricaid® device is known to induce foreign body reactions, and this precise finding was seen in the majority of animal data submitted to the FDA for the device's acceptance. Conclusion: Given the constellation of this patient's symptoms, imaging, intraoperative, and pathology findings, previously published reports, and pre-approval data submitted to the FDA, we conclude that the inflammatory response to the PET weave in this patient's Barricaid® device was the ultimate cause of her continued neuropathy despite multiple prior surgical interventions. [ABSTRACT FROM AUTHOR]

Purpose: To report two cases of bilateral cochlear implantation (CI) in Charcot–Marie–Tooth disease (CMT) patients with novel mutations. Furthermore, we conducted a detailed literature review on the profile and outcomes of CI in this uncommon clinical circumstance. Case presentation: Case 1 involved a 25-year-old woman who was referred for sudden hearing loss (HL) in her left ear and had a 7-year history of HL in her right ear. She was diagnosed with CMT type 1 with a thymidine phosphorylase gene mutation. CI was performed on her left side because her hearing gradually worsened to deafness in both ears. At 3 months post-operation, her speech discrimination score without lip-reading improved from 0 to 100%. She underwent a second CI on her right ear 6 months after her first CI. Two years from her first operation, the speech discrimination score was 100%. Case 2 received her first CI on her right ear at the age of nine for her bilateral HL. She was diagnosed with CMT type 2 with a Twinkle mitochondrial DNA helicase gene mutation. Preoperatively, the speech discrimination score in both ear-aided conditions was 70%. At the 7-year post-operation follow-up, the speech discrimination score was 76%. A second CI was performed due to decreasing hearing ability in her left ear. The speech discrimination score showed 100% at 7 months after the second CI. Conclusions: CI is an effective hearing rehabilitation option for CMT patients with severe-to-profound SNHL. Neuro-otologists should consider CI as a treatment option, even though hearing loss in CMT is associated with auditory neuropathy spectrum disease (ANSD). [ABSTRACT FROM AUTHOR]

Aim: Intratympanic injection of corticosteroids (ITC) and gentamicin therapy (ITG) are widely used treatments for vertigo in Meniere's disease (MD). Even though studies show good results after cochlea implantation (CI) in MD patients when compared to non-MD groups, there is no indication on the effect of ITC and ITG prior to CI on hearing after CI. This study compares the post-operative hearing of CI patients with and without MD and patients who have received ITG or ITC prior to CI. Methods: In a retrospective case control study, adult patients with MD who received CI from 2002 till 2021 were compared to a matched control group of CI patients without MD. Patients with prior ITC/ITG were extracted from MD group. Pre-operative audiological results were measured and trends across post-operative monosyllabic word recognition score at 65 decibels (WRS65CI) at switch-on, 3–6 months, 1 year and last yearly value were analyzed across all groups. Results: 28 MD ears were compared with 33 control ears. From MD ears 9 had received ITG and 6 ITC prior to CI. WRS65CI increased significantly with time within MD and control groups, but no difference in WRS65CI was found between these 2 groups. ITG ears showed fluctuating WRS65CI after CI with no change across time, while ITC ears showed significant increase in trend of WRS65CI values across time. Conclusion: MD and non-MD patients showed comparable hearing results after CI. Prior ITC might positively influence hearing preservation after CI in MD patients whereas ITG group showed fluctuating hearing. [ABSTRACT FROM AUTHOR]

Spontaneous bursts of neural activity in the developing auditory system prior to hearing onset are generated by inner supporting cells (ISCs), which depolarize adjacent inner hair cells (IHCs) by locally increasing extracellular potassium. Restricted spatiotemporal IHC activation in the cochlea induces correlated firing of neurons aligned to isofrequency lamina within central auditory centers. Astrocyte calcium transients are induced by engagement of metabotropic glutamate receptors following glutamate spillover from active synapses during neuronal burst firing. Disruption of spontaneous activity in the cochlea leads to increased gain, impaired synaptic refinement, and altered tonotopic maps in auditory centers of the CNS. Spontaneous activity is preserved in many models of congenital deafness, which may enable initial circuit maturation, increasing the efficacy of later restorative interventions. Sensory systems experience a period of intrinsically generated neural activity before maturation is complete and sensory transduction occurs. Here we review evidence describing the mechanisms and functions of this 'spontaneous' activity in the auditory system. Both ex vivo and in vivo studies indicate that this correlated activity is initiated by non-sensory supporting cells within the developing cochlea, which induce depolarization and burst firing of groups of nearby hair cells in the sensory epithelium, activity that is conveyed to auditory neurons that will later process similar sound features. This stereotyped neural burst firing promotes cellular maturation, synaptic refinement, acoustic sensitivity, and establishment of sound-responsive domains in the brain. While sensitive to perturbation, the developing auditory system exhibits remarkable homeostatic mechanisms to preserve periodic burst firing in deaf mice. Preservation of this early spontaneous activity in the context of deafness may enhance the efficacy of later interventions to restore hearing. [ABSTRACT FROM AUTHOR]

Despite established exposure limits and safety standards, and the availability of carbon monoxide (CO) alarms, each year an estimated 50,000 people in the United States visit emergency departments for CO poisoning. Carbon monoxide poisoning can occur from brief exposures to high levels of CO or from longer exposures to lower levels. If the CO exposure is sufficiently high, unconsciousness and death occur quickly, and without symptoms. With non-lethal exposures to CO, common symptoms include headaches, nausea and vomiting, dizziness, general malaise, and altered mental status. Some patients may have chest pain, shortness of breath, and myocardial ischemia, and may require mechanical ventilation and treatment of shock. Individuals poisoned by CO often develop brain injury. As with brain injury from non-CO causes such as traumatic brain injury, the clinical expression of brain injury caused by CO poisoning includes the domains of cognition, affect, neurological, and somatic. Common problems are neurological: imbalance, motor weakness, neuropathies, hearing loss, tinnitus, Parkinson's-like syndrome, vestibular, gaze, auditory processing, cognitive, anxiety and depression, posttraumatic stress, personality change, persistent headaches, dizziness, sleep problems, and others. In addition, some will have cardiac or other problems. While breathing oxygen hastens the removal of carboxyhemoglobin (COHb), hyperbaric oxygen (HBO2) hastens COHb elimination and favorably modulates inflammatory processes instigated by CO poisoning, an effect not observed with breathing normobaric oxygen. Hyperbaric oxygen improves mitochondrial function, inhibits lipid peroxidation transiently, impairs leukocyte adhesion to injured microvasculature, and reduces brain inflammation caused by CO-induced adduct formation of myelin basic protein. Based upon supportive randomized clinical trials in humans and considerable evidence from animal studies, HBO² should be considered for all cases of acute symptomatic CO poisoning. Hyperbaric oxygen is indicated for CO poisoning complicated by cyanide poisoning, often concomitantly with smoke inhalation. [ABSTRACT FROM AUTHOR]

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AbstractObjectivesDesignStudy SampleResultsConclusionsA case of sudden sensorineural hearing loss following use of sildenafil was examined in detail over a period of three days from first report to recovery.Case study. The subject presented with sudden sensorineural hearing loss and diplacusis a day after onset. Testing involved detailed interview, standard audiometry, detailed inter-octave audiometry, and measurement of detailed psychophysical frequency tuning curves during a two day recovery period.One male aged in his thirties with otherwise normal hearing.Although standard audiometry was within normal limits, detailed inter-octave audiometry and psychophysical frequency tuning curves were consistent with a punctate unilateral intra-cochlear lesion that resolved over a period of three days.This is the first report of such a frequency-specific audiometric shift and diplacusis after sildenafil, and is not consistent with previous reports of direct ototoxic pharmacological effects. We propose that the lesion was most likely caused by a cochlear bleed, and may have been due to physical exertion rather than a direct pharmaceutical effect. The study highlights the important role of additional diagnostic testing that can be easily achieved in a clinical setting with minimal equipment [ABSTRACT FROM AUTHOR]

Background: Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of hereditary diseases caused by the gradual degeneration of the lower motor neuron. More than 30 genes associated with dHMN have been reported, while 70–80% of those with the condition are still unable to receive a genetic diagnosis. Methods: A 26-year-old man experiencing gradual weakness in his lower limbs was referred to our hospital, and data on clinical features, laboratory tests, and electrophysiological tests were collected. To identify the disease-causing mutation, we conducted whole exome sequencing (WES) and then validated it through Sanger sequencing for the proband and his parents. Silico analysis was performed to predict the pathogenesis of the identified mutations. A literature review of all reported mutations of the related gene for the disease was performed. Results: The patient presented with dHMN phenotype harboring a novel homozygous variant c.361G > C (p.Ala121Pro) in SORD, inherited from his parents, respectively. A121 is a highly conserved site and the mutation was categorized as "likely pathogenic" according to the criteria and guidelines of the American College of Medical Genetics and Genomics (ACMG). A total of 13 published articles including 101 patients reported 18 SORD variants. Almost all described cases have the homozygous deletion variant c.757delG (p.A253Qfs*27) or compound heterozygous state of a combination of c.757delG (p.A253Qfs*27) with another variant. The variant c.361G > C (p.Ala121Pro) detected in our patient was the second homozygous variant in SORD-associated hereditary neuropathy. Conclusion: One novel homozygous variant c.361G > C (p.Ala121Pro) in SORD was identified in a Chinese patient with dHMN phenotype, which expands the mutation spectrum of SORD-associated hereditary neuropathy and underscores the significance of screening for SORD variants in patients with undiagnosed hereditary neuropathy patients. [ABSTRACT FROM AUTHOR]

Background: Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum. Methods: PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment. Results: Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003). Conclusions: Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn. PROSPERO: CRD42022359018. Summations: • Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. • Although there is growing academic interest in the role of synaptic density in the pathophysiology of major mental disorders, we identified only five studies examining synaptic density in individuals with psychotic disorders. • Synaptic density was significantly lower in several brain regions including the anterior cingulate cortex, hippocampus, occipital, temporal, parietal and frontal cortices, in individuals with psychotic disorders relative to controls. Considerations: • Preliminary studies provide in vivo evidence for the presence of reduced synaptic density in early course and chronic schizophrenia, however, further investigation in larger samples is required prior to definitive conclusions being drawn regarding changes in synaptic density in schizophrenia. • Reduction in synaptic density was more significant in several brain regions of individuals with chronic schizophrenia when compared to healthy controls. Presently is difficult to draw definitive conclusions about whether synaptic density reduction is driving the disease or may be influenced by iatrogenic (e.g., pharmacotherapy, psychotherapy, neurostimulation), lifestyle (e.g., smoking, exercise, diet) or other environmental factors (e.g., stress, medical co-morbidity). [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of idiopathic sudden sensorineural hearing loss remains unclear, and no substantial breakthroughs have been achieved in its treatment. Therefore, we conducted this study with the aim to investigate the clinical features and prognostic factors of patients with idiopathic sudden sensorineural hearing loss and auditory nerve enhancement by using threedimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) of the inner ear. Methods: We retrospectively analyzed the clinical data of adult patients, who experienced sudden unilateral deafness and were admitted to the Department of Otolaryngology, Shandong Provincial ENT Hospital, between December 2020 and July 2021. Patients were divided into an auditory nerve enhancement group and a normal inner ear group, according to 3D-FLAIR MRI findings. Differences in sex, age, side, disease course, underlying diseases, dizziness/vertigo, vestibular function, degree of deafness, hearing classification, and treatment efficacy were analyzed. Results: Of the 112 cases of sudden idiopathic deafness, 16.07% exhibited enhancement of the auditory nerve on inner-ear 3D-FLAIR MRI. Statistically significant differences in the degree and type of hearing loss were detected between the two groups (p  <  0.05). The rates of abnormal results in the caloric, vestibular-evoked myogenic potential, and video head impulse tests were higher in the auditory nerve enhancement group. The cure rate (11.1%) in patients with auditory nerve enhancement was lower than that in patients with normal inner ear MRI findings (28.7%); however, the difference was not statistically significant. Conclusion: Findings from 3D-FLAIR MRI scans of the inner ear indicated that patients with sudden deafness and auditory nerve enhancement experienced severe hearing loss, aggravated vestibular function injury, and a significantly decreased cure rate. Prompt treatment, ideally within 2 weeks of disease onset, can facilitate hearing recovery [ABSTRACT FROM AUTHOR]

Background: Progressive auditory dysfunction is common in patients with generalized neurodegenerative conditions, but clinicians currently lack the diagnostic tools to determine the location/degree of the pathology and, hence, to provide appropriate intervention. In this study, we present the white-matter microstructure measurements derived from a novel diffusion-weighted magnetic resonance imaging (dMRI) technique in a patient with axonal auditory neuropathy and consider the findings in relation to the auditory intervention outcomes. Methods: We tracked the hearing changes in an adolescent with Riboflavin Transporter Deficiency (Type 2), evaluating the sound detection/discrimination, auditory evoked potentials, and both structural- and diffusion-weighted MRI findings over a 3-year period. In addition, we explored the effect of bilateral cochlear implantation in this individual. Results: Between the ages of 15 years and 18 years, the patient showed a complete loss of functional hearing ability. The auditory brainstem response testing indicated an auditory neuropathy with evidence of normal cochlear function but disrupted auditory neural activity. While three structural MRI assessments across this period showed a clinically normal cochleovestibular anatomy, the dMRI evaluation revealed a significant loss of fiber density consistent with axonopathy. The subsequent cochlear implant function was affected with the high levels of current required to elicit auditory sensations and concomitant vestibular and facial nerve stimulation issues. Conclusions: The case study demonstrates the ability of dMRI technologies to identify the subtle white-matter microstructure changes in the auditory pathway, which may disrupt the neural function in patients with auditory axonopathy. [ABSTRACT FROM AUTHOR]

Background Congenital hearing loss (HL), one of the most common paediatric chronic conditions, significantly affects speech and language development. Its early diagnosis and medical intervention can be achieved via newborn hearing screening. However, data on the prevalence and aetiology of congenital HL in infants who fail newborn hearing screening are limited. Methods The sample population included 153 913 infants who underwent newborn hearing screening, and the prevalence of congenital HL, defined as moderate to profound bilateral HL (BHL) or unilateral HL (UHL) (≥40 dB HL), in one prefecture of Japan was measured to minimize the loss-to-follow-up rate, a common factor affecting the screening procedure. Comprehensive aetiological investigation, including physiology, imaging, genetic tests, and congenital cytomegalovirus screening, was performed on children diagnosed with congenital HL. Results The calculated prevalence of congenital HL was 1.62 per 1000 newborns (bilateral, 0.84; unilateral, 0.77). More than half of the cases with congenital bilateral or severe to profound UHL showed genetic aetiology or cochlear nerve deficiency (CND), respectively. Approximately 4% and 6% of the cases of congenital BHL and UHL were associated with congenital cytomegalovirus infection and auditory neuropathy spectrum disorder, respectively. Conclusions This is an epidemiological and comprehensive aetiological study of congenital HL, as determined via newborn hearing screening according to its severity and laterality, in a large-scale general population of a developed country. Our findings can serve as a reference for optimizing care and intervention options for children with HL and their families. [ABSTRACT FROM AUTHOR]

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) hearing loss (HL) task force reviewed investigations on cochlear radiation dose-response relationships and risk factors for developing HL. Evidence-based dose-response data are quantified to guide treatment planning. A systematic review of the literature was performed to correlate HL with cochlear dosimetry. HL was considered present if a threshold exceeded 20 dB at any frequency. Radiation dose, ototoxic chemotherapy exposure, hearing profile including frequency spectra, interval to HL, and age at radiation therapy (RT) were analyzed. Literature was systematically reviewed from 1970 to 2021. This resulted in 739 abstracts; 19 met inclusion for meta-analysis, and 4 included data amenable to statistical modeling. These 4 studies included 457 cochleas at risk in patients treated with RT without chemotherapy, and 398 cochlea treated with chemotherapy. The incidence and severity of cochlear HL from RT exposure alone is related to dose and age. Risk of HL was <5% in cochlea receiving a mean dose ≤35 Gy but increased to 30% at 50 Gy. HL risk ranged from 25% to 40% in children under the age of 5 years at diagnosis, declining to 10% in older children for any radiation dose. Probability of similar severe HL occurred at doses 18.3 Gy higher for children <3 versus >3 years of age. High-frequency HL was most common, with average onset occurring 3.6 years (range, 0.4-13.2 years) after RT. Exposure to platinum-based chemotherapies added to the rates of HL at a given cochlear dose level, with 300 mg/m2 shifting the dose response by 7 Gy. In children treated with RT alone, risk of HL was low for cochlear dose <35 Gy and rose when dose exceeded 35 Gy without clear RT dose dependence. High-frequency HL was most prevalent, but all frequencies were affected. Children younger than 5 years were at highest risk of developing HL, although independent effects of dose and age were not fully elucidated. Future reports with more granular data are needed to better delineate time to onset of HL and the effects of chemoradiotherapy. [ABSTRACT FROM AUTHOR]

The present study attempted to understand the association between Auditory neuropathy spectrum disorder (ANSD) and Sickle cell anemia (SCA) and to recognize possible causative factors for the presence of ANSD in SCA individuals. Two cases, 24 years male and 17years female with a laboratory-confirmed diagnosis of Sickle cell anemia underwent detailed audiological evaluation i.e., pure tone audiometry, speech audiometry, immittance audiometry, otoacoustic emission, and auditory brainstem responses. Audiological evaluation revealed a bilateral moderate low-frequency sensorineural hearing loss in male and bilateral moderately severe sensorineural Hearing loss in female case with elevated Speech Recognition Threshold and poor Speech Identification Scores. 'A' type tympanogram with the absence of Acoustic reflexes and the presence of Otoacoustic emission with no distinct and reproducible peak V in Auditory Brainstem Response (ABR) at 90 dBnHL with the presence of ringing cochlear microphonics on polarity reversal collectively indicating bilateral ANSD in both cases. ANSD and SCA are reported to have a genetic basis of etiology. There might be possibilities that one genetic condition may be common in manifesting both conditions or one genetic condition can cause the presence of another genetic condition or can exaggerate the evolution of another genetic condition. Also, abnormal ABR findings indicate the possibility of neuropathological involvement in isolation or in combination with genetic abnormalities that need detailed investigation to understand non-genetic causative factors. Thus, paved the path for further research in this line and might provide better rehabilitative options. [ABSTRACT FROM AUTHOR]

Introduction: Auditory neuropathy spectrum disorder (ANSD) is a distinct type of SNHL that is characterized by the presence of otoacoustic emissions and/or cochlear microphonics. Cochlear implantation was initially not recommended for ANSD children, later studies showed variable outcomes among ANSD. CI is currently the intervention option of choice for many children with ANSD who are unable to obtain benefit from conventional amplification. Aim and Objectives: To review experiences with some of the preoperative and postoperative findings in a child who was diagnosed with auditory neuropathy and provided with cochlear implant. To describe changes in auditory function, which enabled to have significant improvement in hearing and communication skills through auditory verbal therapy (AVT) and regular follow ups. Study Design: Pre and postoperative, findings in cochlear implant recipient who was diagnosed with ANSD. Child received complete medical examinations, including related consultations in audiology, otorhinolaryngology, paediatrics, neurology, psychology, speech language pathology, and radiology. Methodology/Case Report: A 3-year-old-female have brought to the hospital with a C/o not responding to sounds, name call and unable to speak. Medical and Audiological evaluations were initiated. The hearing assessments of the child included appropriate behavioural audiometric techniques, objective measures of middle ear function, acoustic reflex studies, transient evoked (TEOAE), distortion product (DPOAE) otoacoustic emissions and auditory brainstem responses (ABR). Implanted with (HiRes Ultra CI HiFocus SlimJ Electrode), and objective measures were recorded intraoperatively electrode impedances and neural response telemetry (NRT) to assess the outcomes technically. These intraoperative objective measures were used to help program the speech processor for the child. Postoperatively, child has had regular follow-up with otorhinolaryngologist to assure complete healing of the surgical incision, to assess their general medical conditions, and audiologist for switch-on (speech processor) followed by mapping. The hearing and communication skills have been assessed, also continued Auditory Verbal Therapy (AVT) on a regular basis. Postoperatively, objective measures were recorded in regular intervals and monitored with therapy outcomes. Results: The child has shown significant improvement in sound detection, speech perception abilities, communication skills and shown evidence of progression of good NRT results, which were recorded and had no postoperative complications. Conclusion: Experience with cochlear implantation for child diagnosed with ANSD that effectively received and benefited from CI. A detailed and careful evaluations, audiological follow-ups and tailored rehabilitation plans, can be considered as a beneficial management approach for CI, especially who diagnosed with ANSD. The regular use of cochlear implant in this diagnosis can lead to a clear increase in speech comprehension, development and overall progress in quality of life. Success or lack of success with a CI appears to be somewhat dependent on the specific site of lesion (pre- or post-synaptic). Currently there are no clinical measures available to diagnose the specific site of lesion. Indeed, CI appears to be an effective rehabilitation modality for ANSD patients. This may be explained by the fact that the implanted electrode delivers synchronized electrical impulses directly to the auditory nerve, bypassing the presynaptic IHCs and its synapse involved in the unsynchronized firing of the auditory nerve described in ANSD. However, genetic studies that have proven to be essential in the knowledge of underlying mechanisms of ANSD represent a promising therapeutic approach in the management of ANSD. [ABSTRACT FROM AUTHOR]

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Methods: Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Data for the present study was collected from six follow-ups, with 311 individuals assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in the baseline cohort of 591 individuals and the subsample from the 25-year follow up. Results: In the baseline cohort and the 25-year subsample, the most common trajectory for individuals with schizophrenia spectrum disorders was no remission and no recovery. Among individuals with other psychotic disorders, in both the baseline and 25-year cohorts, the modal pattern was one of intermittent remission and recovery. Individuals with other psychotic disorders were more likely to experience stable remission (15.1%) and stable recovery (21.1%), outcomes that were rare among individuals with schizophrenia spectrum disorders (0% and 0.6%, respectively). Conclusions: The modal longitudinal pattern for individuals with other psychoses is one of multiple transitions into and out of symptomatic and functional recovery. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders. Efforts should be directed toward developing more effective treatments for this population. [ABSTRACT FROM AUTHOR]

This article discusses the role of PIEZO proteins in sensory transduction in auditory hair cells. The authors argue that PIEZOs do not meet the criteria to be considered components of the hair cell transduction complex, providing evidence from gene expression, protein localization, and genetic deletion studies. They conclude that TMC proteins, along with other transduction apparatus components, are crucial for sensory transduction in hair cells, while PIEZO proteins are not. The document provides a list of references to scientific articles exploring various aspects of mechanotransduction in auditory hair cells, offering valuable insights for researchers studying genetic forms of hearing loss. Another document contains a comprehensive list of references related to sensory transduction channels in auditory hair cells, including studies on the role of proteins and genes, effects of mutations and gene therapy, and more. These references can be used by library patrons to further explore the topic. [Extracted from the article]

This article discusses common misconceptions about hearing evaluation and provides recommendations for hearing evaluation based on current research. It highlights the limitations of relying solely on self-report as a measure of hearing loss and emphasizes the importance of using objective measures such as pure tone audiometry. The article also suggests including speech-in-competition tests and auditory processing evaluation in the assessment of hearing capacity. The authors recommend diagnostic assessment for individuals with reported hearing difficulties or communication challenges, and they provide guidelines for different age groups and specific cases. Collaboration with other professionals and the use of questionnaires are also recommended. [Extracted from the article]

Purpose: To compare the audiological outcomes, tympanic membrane (TM) healing rates and complication rates in patients undergoing endoscopic underlay and over–under tympanoplasty type I (TTI). Methods: The study includes 95 patients who underwent endoscopic TTI in the period between 2018 and 2023: 56% of the patients had the underlay technique and 41% had the over–under technique. Data regarding pre- and postoperative hearing, perforation characteristics, surgical procedures, graft types and complications were retrospectively analyzed. Audiometrical assessment included air conduction (AC) and bone conduction (BC) pure tone averages (PTA) and air–bone gap (ABG), pre- and postoperatively. Results: Both underlay and over–under techniques significant improved AC PTA, with a mean ABG improvements of 5.9 dB and 7.2 dB, respectively. There was no significant difference in BC PTA between pre- and post-operative, indicating no inner ear damage in both techniques. The over–under technique showed a significantly higher TM closure rate (94.4%) compared to the underlay technique (80.6%). Complications were rare, with only one case of TM lateralization requiring revision surgery. Conclusions: Endoscopic TTI is an effective treatment in improving auditory function in chronic middle ear diseases. In our cohort, the detachment of the umbo does not negatively influence the postoperative hearing results and does not increase rate of complications. Moreover, the over–under technique demonstrates superior TM closure rates, making it a valuable option for specific cases. However, future prospective studies with larger sample sizes and longer term follow-up are needed to validate these findings and provide more comprehensive insights. [ABSTRACT FROM AUTHOR]

Glaucoma refers to a spectrum of progressive optic neuropathies and remains the leading cause of irreversible blindness worldwide. Its insidious onset poses serious challenges to conventional diagnostic methods and clinicians striving to detect early-stage disease for timely and effective intervention. Artificial intelligence (AI) has demonstrated its ability to process and analyze large datasets which can help identify subtle changes in early glaucomatous clinical presentation. This study reviews the current state of AI utilization in glaucoma and elucidates the strengths and limitations of existing approaches. We dissect the role of AI in various domains: enhancing early detection and diagnosis, monitoring disease progression, and refining treatment strategies to optimize patient outcomes. Furthermore, we address the ethical, legal, and social implications, alongside the inherent limitations of AI in the clinical setting. Despite these challenges, AI holds transformative potential for glaucoma management. Future directions emphasize the need for interdisciplinary collaboration, advanced and explainable algorithm development, and equitable healthcare access to fully realize the promise of AI in combating this vision-threatening condition. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary transthyretin (ATTRv, v for variant) amyloidosis is a rare, progressive, fatal disease with multisystem manifestations, caused by pathogenic variants in the transthyretin (TTR) gene. Vutrisiran, an RNA interference therapeutic that results in rapid TTR knockdown, improved neuropathy and quality of life (QOL) versus external placebo in patients with ATTRv amyloidosis with polyneuropathy in the phase 3 HELIOS-A study (NCT03759379). This post hoc analysis evaluates the impact of baseline neuropathy severity on response to vutrisiran treatment. Methods: Patients were randomized (3:1) to vutrisiran (n = 122; 25 mg subcutaneous injection once every 3 months) or patisiran (n = 42; 0.3 mg/kg intravenous infusion once every 3 weeks), which served as a reference group. In this post hoc analysis, patients were grouped into quartiles of increasing baseline Neuropathy Impairment Score (NIS): Quartile (Q)1 ≥ 5.0 to ≤ 20.5; Q2 > 20.5 to ≤ 44.1; Q3 > 44.1 to ≤ 73.1; Q4 > 73.1 to ≤ 127.0. Mean change from baseline to Month 18 was summarized by quartile for a range of efficacy endpoints. Results: Across all baseline NIS quartiles, vutrisiran demonstrated benefit versus external placebo in measures of neuropathy severity (modified NIS + 7), QOL (Norfolk Quality of Life-Diabetic Neuropathy), disability (Rasch-built Overall Disability Scale), gait speed (10-m walk test), and nutritional status (modified body mass index). Overall, patients in lower versus higher NIS quartiles (less severe neuropathy) at baseline maintained better scores at Month 18. The external placebo group progressively worsened in all measures at Month 18. Conclusions: Vutrisiran demonstrated benefit in neurologic function and other key efficacy measures versus external placebo across all four baseline neuropathy severity quartiles. Patients initiating vutrisiran earlier in their disease course retained the highest neurologic function level after 18 months, highlighting the importance of early diagnosis and treatment. Trial Registration Number: ClinicalTrials.gov: NCT03759379. [ABSTRACT FROM AUTHOR]

Background and Objectives: Radicalization, a complex and multifaceted phenomenon, has been a subject of increasing concern in recent years, particularly due to its potential connection to acts of mass violence and terrorism. This systematic review examines the intricate link between radicalization and psychotic disorders, utilizing various sources such as observational studies, case reports, and series. It aims to highlight the prevalence of schizophrenia spectrum and other psychotic disorders among radicalized individuals and to define the role of mental health professionals in dealing with this issue, contributing to the development of prevention and treatment strategies. Materials and Methods: The methodology involved an extensive literature search across PubMed, Scopus, and APA PsycINFO up to 1 February 2024, adhering to PRISMA guidelines. The study focused on radicalization and psychotic disorders as defined by DSM-5 criteria, excluding other mental disorders. A population sample of 41 radicalized individuals diagnosed with psychotic disorders was selected, among which schizophrenia was identified as the predominant condition. Results: It was observed that 24% of these individuals passed away soon after committing their crimes, leading the researchers to rely on retrospective data for their diagnoses. The use of diverse assessment tools for psychiatric diagnosis and the lack of a standardized method for diagnosing or assessing involvement in the radicalization process were also noted. Despite limitations like reliance on observational studies and case reports, which result in low evidence quality and varied methodologies, our work provides a valuable contribution to clarifying the relationship between radicalization and psychotic disorders. However, further clinical studies are needed to delve deeper into these aspects. Conclusions: In conclusion, our review points out that individuals with psychotic disorders do not have a higher crime rate than the general population and warns against associating crimes with mental illness due to the stigma it creates. The lack of uniform psychiatric diagnostic tools and radicalization assessment highlights the need for more standardized risk assessment tools and validated scales in psychiatric diagnosis to better understand the relationship between radicalization and psychotic disorders and to develop integrated protocols. [ABSTRACT FROM AUTHOR]

Objectives: Current evidence supports the benefits of cochlear implants (CIs) in children with hearing loss, including those with auditory neuropathy spectrum disorder (ANSD). However, there is limited evidence regarding factors that hold predictive value for intervention outcomes. Design: This retrospective case-control study consisted of 66 children with CIs, including 22 with ANSD and 44 with sensorineural hearing loss (SNHL) matched on sex, age, age at CI activation, and the length of follow-up with CIs (1:2 ratio). The case and control groups were compared in the results of five open-set speech perception tests, and a Forward Linear Regression Model was used to identify factors that can predict the post-CI outcomes. Results: There was no significant difference in average scores between the two groups across five outcome measures, ranging from 88.40% to 95.65%. The correlation matrix revealed that younger ages at hearing aid fitting and CI activation positively influenced improvements in speech perception test scores. Furthermore, among the variables incorporated in the regression model, the duration of follow-up with CIs, age at CI activation, and the utilization of two CIs demonstrated prognostic significance for improved post-CI speech perception outcomes. Conclusions: Children with ANSD can achieve similar open-set speech perception outcomes as children with SNHL. A longer CI follow-up, a lower age at CI activation, and the use of two CIs are predictive for optimal CI outcome. [ABSTRACT FROM AUTHOR]

Purpose: As a first step towards developing a core outcome set (COS) for sciatic neuropathy, the goal of the current study was to perform a systematic review of the literature to identify outcome measures that have been previously reported in studies on sciatic neuropathy. Methods: A systematic review of the literature from 2000–2024 was performed utilizing PubMed and Medical Subject Headings (MeSH). Identified articles were screened according to study inclusion/exclusion criteria. Outcome measures reported in each included study were recorded and categorized into motor, sensory, pain, patient-reported outcomes, electrodiagnostic outcomes, imaging outcomes, and composite outcomes. Descriptive statistics were performed. Results: A total of 1586 articles were initially identified, and 31 articles met criteria for inclusion and underwent analysis. The most common outcome domain was pain. A pain outcome was reported in 17 (63%) studies. A motor outcome was reported in 10 (37%) studies; 6 (22%) reported a sensory outcome; 1 (4%) reported a composite outcome; 4 (15%) reported an electrodiagnostic outcome; 5 (19%) reported a patient-reported outcome; 3 (11%) reported an imaging outcome. Across the included studies, 21 unique outcomes were reported. Conclusions: We have identified the outcome measures that have previously been utilized in studies on sciatic neuropathy. Previously used outcome measures fell into seven domains: motor outcomes, sensory outcomes, pain outcomes, patient-reported outcomes, electrodiagnostic outcomes, imaging outcomes, and composite outcomes. Pain outcomes were most commonly used across the included studies. [ABSTRACT FROM AUTHOR]

Objectives: There is a limited understanding of the impact of cochlear implantation (CI) in patients with Charcot-Marie-Tooth disease (CMT), given the scarcity of reported cases. We aim to evaluate the audiological outcomes and quality of life (QoL) after CI in CMT. Methods: Multi-institutional, university-affiliated, tertiary-referral centers, retrospective chart review. Our cohort includes 5 patients with CMT. Patients' charts were reviewed for demographic characteristics, operation notes, and pre- and post-implantation audiology evaluation. Patients completed the Cochlear Implant Quality of Life-10 (CIQOL-10) Global questionnaire. Results: Pre-implantation, the mean pure tone average was 84.1 ± 7.2 dB, and the mean word recognition score was 2.4% in the implanted ear. AzBio sentence test was performed in quiet, revealing a mean of 4 ± 1.4% in the implanted ear. Post-implantation, PTA results were all within the mild hearing loss range (mean 33.0 ± 5.9 dB). Post-CI, AZ-Bio test results were 5%, 65%, and 74% (for 3 patients), and HINT scores were 55% and 58% (for 2 patients). The mean score of the CIQOL-10 questionnaire was 42.7 ± 10.47 (range 1-100). Patients were most satisfied with their ability to listen to the television or radio, have conversations in a quiet environment, and feel comfortable being themselves. Conclusion: To the best of our knowledge, this is the most extensive series of CI in CMT-associated sensorineural hearing loss and auditory neuropathy. Our cohort suggests that CI is a safe and reliable method for hearing rehabilitation that can achieve good speech performance and improve QoL in CMT patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Incomplete partition type II (IP-II) malformation is often accompanied by a large vestibular aqueduct (LVA). In IP anomalies, the patient’s auditory rehabilitation requirements are decided according to the presence of inner ear structures and the degree of hearing loss (HL). There has been limited research on auditory rehabilitation (AR) requirement selection in patients diagnosed with IP-II and LVA. This study investigated the typical characteristics of HL and AR choices in patients diagnosed with IP-II and LVA. METHODS: Patients with IP-II and LVA (n=55; 25 women and 30 men) were identified, and audiological evaluations were performed. The patient’s demographic characteristics, the type and degree of HL, the AR method, age at diagnosis, and educational status were retrospectively compared. RESULTS: The distribution of our 55 patients according to cochlear implants, hearing aids (HA), and bimodal applications was 29.1% (n=16), 43.6% (n=24), and 27.3% (n=15), respectively. Statistical analyses using chi-square tests found no significant differences in the incidence of dizziness/imbalance, tinnitus, HL progression, or the degree and onset of HL among the patients. CONCLUSION: The data revealed different audiological characteristics among patients with IP-II and LVA, as well as different AR solutions. The most widely used AR modality was found to be HA. Prediction of sudden versus progressive HL development among patients is challenging, and the characteristics of IP-II vary. Therefore, they should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Normal tension glaucoma (NTG) is a complex optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, despite normal intraocular pressure (IOP). This condition poses a unique clinical challenge due to the absence of elevated IOP, a major risk factor in typical glaucoma. Recent research indicates that up to 21% of NTG patients have a family history of glaucoma, suggesting a genetic predisposition. In this comprehensive review using PubMed studies from January 1990 to December 2023, our focus delves into the genetic basis of autosomal dominant NTG, the only known form of inheritance for glaucoma. Specifically exploring optineurin (OPTN), TANK binding kinase 1 (TBK1), methyltransferase-like 23 (METTL23), and myocilin (MYOC) mutations, we summarize their clinical manifestations, mutant protein behaviors, relevant animal models, and potential therapeutic pathways. This exploration aims to illuminate the intricate pathogenesis of NTG, unraveling the contribution of these genetic components to its complex development. [ABSTRACT FROM AUTHOR]