Prevalence of hearing loss in pseudohypoparathyroidism.

BACKGROUND: The main clinical features of pseudohypoparathyroidism (PHP)/inactivating parathyroid hormone/parathyroid hormone-related protein signaling disorders (iPPSD), including parathyroid hormone (PTH) resistance, brachydactyly and short stature, develop during middle and late childhood. Very few studies have addressed hearing loss in PHP/iPPSD patients, and these studies have yielded widely divergent conclusions. The aim of our study was to assess hearing and determine the predictive factors of hearing loss in patients with PHP/iPPSD. METHODS: Our retrospective cohort study was conducted between March 2019 and May 2020 in the Otolaryngology Department and the calcium phosphate reference center for rare diseases in Bicêtre Paris-Saclay Hospital, France. We retrospectively collected data from patients with PHP/iPPSDs (age, sex, genetic mutations, height, body mass index (BMI), PTH resistance, presence or absence of ectopic ossifications and brachydactyly). All patients underwent auditory investigations, including tonal and vocal audiometry. The primary outcome was the pure tone average (PTA). The PTA was compared with the norm according to the International Organization for Standardization. Hearing loss was defined as a PTA ≥ 20 db. RESULTS: The median age of the patients was 15.6 years [9.5, 28.5]. Thirty-six patients were diagnosed with iPPSD2, and eight were diagnosed with iPPSD3. Twenty-six of them (59%) were female. Hearing impairment was confirmed in 17 patients (39%). The mean PTA and the mean SRT of the deaf ears were 40 ± 26 db and 31 ± 14 db. The mean difference in the PTA between the patients and the normal controls was 11.4 db (p = 0.00002). Short stature and the presence of ectopic ossifications were two significant predictive factors of hearing loss (p = 0.009 and p = 0.03, respectively). Sex, BMI, PTH resistance, mutation category and brachydactyly were not associated with an increased risk of hearing loss (p = 0.19, p = 0.41, p = 0.13, p = 0.50, p = 0.19, respectively). CONCLUSION: Our study confirmed the frequency of hearing loss in patients with PHP/iPPSD disease (prevalence = 39%). A diagnosis of PHP/iPPSD should trigger auditory investigations and follow-up, especially when short stature and/or ectopic ossifications are present.

Infliximab for the Treatment of Inflammatory Labyrinthitis: A Retrospective Cohort Study.

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

Surgical techniques and functional evaluation for vestibular lesions in the mouse: unilateral labyrinthectomy (UL) and unilateral vestibular neurectomy (UVN).

OBJECTIVE: Unilateral labyrinthectomy (UL) and unilateral vestibular neurectomy (UVN) are two surgical methods to produce vestibular lesions in the mouse. The objective of this study was to describe the surgical technique of both methods, and compare functional compensation using vestibulo-ocular reflex-based tests. METHODS: UL and UVN were each performed on groups of seven and ten mice, respectively. Main surgical landmarks were the facial nerve, the external auditory canal and the sternomastoid and digastric muscles. For UL, the sternomastoid muscle was elevated to expose the mastoid, which was drilled to destroy the labyrinth. For UVN, the bulla was drilled opened and a transcochlear approach enabled the identification of the vestibulo-cochlear nerve exiting the brainstem, which was sectioned and the ganglion of Scarpa suctioned. Behaviour and vestibular function were analysed before surgery and at 1, 4, 7 days and at 1 month postlesion using sinusoidal rotation, off-vertical axis rotation, static head tilts and angular velocity steps. RESULTS: UL is a faster and safer procedure than UVN (operative time 16.3 vs 20.5 min, p = 0.19; survival rate 86% vs 60%, p = 0.25). UVN was more severe with significantly worse behavioural scores at day 4 and day 7 (p < 0.001). Vestibular compensation was overall similar during the first week and at 1 month (non-statistically significant difference). CONCLUSION: Both UL and UVN procedures can routinely be performed in the mouse with similar post-operative recovery and behavioural compensation. The operative risk of vascular or neurological damage is smaller in UL compared to UVN. UVN may be required for specific research protocols studying central cellular process specifically related to the destruction of the ganglion of Scarpa and following vestibular nerve degeneration.