No abstract

Objective: To examine the effectiveness of Eustachian tube procedures for the treatment of baro-challenge Eustachian tube dysfunction.Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, databases, including PubMed (National Library of Medicine, National Institutes of Health), Scopus (Elsevier), and CINAHL (EBSCO), were searched for articles examining the effectiveness of Eustachian tube procedures for baro-challenge Eustachian tube dysfunction. Outcome measures included symptom resolution, ability to return to work, equalization problems (EP) scores, Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores, and pressure chamber testing parameters. Pooled meta-analysis was performed for dichotomous measures and ETDQ-7 scores.Results: Eleven articles with 81 patients were included. Seventy-two patients from 10 articles underwent balloon Eustachian tube dilation; nine patients in 1 study underwent laser Eustachian tuboplasty (LET). All 81 patients were preoperatively symptomatic with barometric pressure change, and 26/30 (86.7%) were unable to work due to symptoms. On meta-analysis, after balloon dilation Eustachian tuboplasty (BDET), 82.5% (n = 30 [95% confidence interval: 42%-100%]) had improvement in ability to valsalva, 79.1% (n = 16 [57.9%-94.1%]) in ability to return to work, and 84.3% (n = 69 [69.8%-94.7%]) in any symptom. Of 25 patients with individual ETDQ-7 scores, 79.1% [51.4, 96.9] had improvements after BDET. For four case series with 36 patients, ETDQ-7 scores decreased by 1.2 [0.7, 1.7] (p < 0.00001). Of 20 patients with preoperative ETDQ-7 scores >2.0, there was a mean decrease of 2.1 [1.3, 2.8] (p < 0.00001).Conclusion: From the available evidence, Eustachian tube procedures appear to be effective at improving symptoms of baro-challenge Eustachian tube dysfunction. However, higher quality evidence is needed to support making definite recommendations for the use of balloon Eustachian tube dilation or LET for these patients.

Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, language and cognitive deficits. A mouse model of this syndromic ASD (i.e., Mef2c +/or Mef2c-Het) recapitulates many of the MEF2C Haploinsufficiency syndrome-linked behaviors including communication deficits. We show here that Mef2c-Het mice exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types, and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.

Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, and language and cognitive deficits. A mouse model of this syndromic ASD (i.e., Mef2c+/- or Mef2c-Het) recapitulates many of the MEF2C Haploinsufficiency syndrome-linked behaviors including communication deficits. We show here that Mef2c-Het mice exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types, and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.