Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis.

OBJECTIVE: Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1- knock-out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the Fmr1-KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity. METHODS: RNA was isolated from cochlear nuclei of Fmr1-KO and WT mice. Using next-generation sequencing (RNA-seq), the transcriptomes of Fmr1-KO mice and WT mice (n = 3 each) were compared and analyzed using gene ontology programs. RESULTS: We identified 270 unique, differentially expressed genes between Fmr1-KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis. CONCLUSION: The loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, Kcnab2, which encodes a subunit of the Shaker voltage-gated potassium channel, is expressed at an abnormally low level in the Fmr1-KO cochlear nucleus. Kcnab2 and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1363-1371, 2024.

Airway Involvement and Intervention in Non-ACE-Inhibitor-Induced Angioedema.

OBJECTIVES: Characterize the presentation of patients with non-angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema and determine risk factors associated with patient disposition and possible need for airway intervention. METHODS: The medical records of adult patients in the Emergency Department (ED) and diagnosed with non-ACEI-induced angioedema over 4.5 years were included. Demographics, vital signs, etiology, timeline, presenting symptoms, physical exam including flexible laryngoscopy, medical management, and disposition were examined. Statistical analyses were conducted using SPSS V 23.0 software calculating and comparing means, standard deviations, medians, and correlation of categorical and ordinate variables. RESULTS: A total of 181 patients with non-ACEI-induced angioedema were evaluated with flexible laryngoscopy by otolaryngology. Notably, 11 patients (6.1%) required airway intervention and were successfully intubated. Statistically significant factors (p ≤ 0.05) associated with airway intervention included the diastolic blood pressure (DBP) and mean arterial pressure (MAP) (p = 0.006 and 0.01 respectively), symptoms of dysphonia (p = 0.018), the presence of oropharyngeal, supraglottic, and hypopharyngeal edema (p ≤ 0.001 for each site), and the number of edematous anatomic subsites documented on physical exam (p < 0.001). Other patient demographics, prior history of angioedema, heart rate, systolic blood pressure, symptom onset, number of symptoms at presentation, and medication administered in the ED did not correlate with airway intervention. CONCLUSION: Dysphonia, DBP, MAP, anatomic location of edema and edema in multiple sites are associated with airway intervention and a higher level of care in non-ACEI-induced angioedema and can be useful in risk assessment in patient management. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2282-2287, 2024.

Sebaceous Carcinoma of the Middle Ear: A Case Report.

Here we present the first case of sebaceous carcinoma of the middle ear. We discuss the treatment course and post treatment results after 11 years of follow up. We further summarize the available literature of sebaceous carcinoma of the temporal bone, which prior to this case was exclusively limited to the external auditory canal. Laryngoscope, 134:3769-3772, 2024.

The parietal notch (Brammer's pointer): Accuracy of a surface landmark for temporal bone surgery.

Hypothesis: The parietal notch is a reliable surface landmark of the sigmoid sinus at the sinodural angle. Background: Currently no surface landmark approximates the anterior border of the sigmoid sinus. Additionally, the temporal line may not accurately identify the tegmen near the sinodural angle. This study examines the reliability of the parietal notch as a surface landmark of the sigmoid sinus at the sinodural angle. Methods: Forty-seven cadaveric temporal bones were used to identify the parietal notch by two observers. The parietal notch and sinodural angle were labeled with radiopaque markers, mounted on foam, and CT imaged in the axial plane. The horizontal and vertical distances between the labeled landmarks were measured using PACS software. Results: The parietal notch location was identified in 43/47 specimens. The notch was posterior to the sinodural angle in 90.6% and superior in 65% of the specimens. The average horizontal and vertical distance between the two landmarks was 6.1 mm (SD = 5.4) and 0.8 mm (SD = 8.7), respectively. In 60% of the specimens the parietal notch was within 6 mm of the sinodural angle in the horizontal dimension. Conclusions: The parietal notch is identified in most temporal bones. It also approximates the anterior boarder of the sigmoid sinus and level of the tegmen due to its proximity to the sinodural angle. The parietal notch helps to define the posterosuperior margins of a mastoid dissection and may assist surgeons during mastoid surgery.