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SACCULOCOLLIC PATHWAY DYSFUNCTION REVEALED BY VESTIBULAR EVOKED MYOGENIC POTENTIALS IN MOUSE MODEL WITH SPONTANEOUS ENDOLYMPHATIC HYDROPS

Kianoush Sheykholeslami, Cliff Megerian, Quing Zheng

Department of Otolaryngology-Head and Neck Surgery, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH, USA

■ OBJECTIVE: In humans, mutations in the Phex gene can cause X-linked hypophosphatemic rickets (XLH), a disease that primarily affects bone and tooth development. Some patients with XLHmanifest symptoms resembling Meniere’s disease. Male Phex Hyp-Duk/y mice exhibit inner ear abnormalities including hearing loss and circling behavior resembling compromised balance function. Inner ear histopathologic evaluation showed endolymphatic hydrops (ELH), thickening of the bone surrounding the cochlea with the presence of a precipitate in the scala tympani, and hydropic changes especially in the sacculus.. Hearing deterioration with age in this mutation appears to correlate qualitatively with loss of spiral ganglion cells as opposed to the loss of hair cells or severity of hydrops. The above findings prompted us to evaluate Phex Hyp-Duk/y mice as a possible model for ELH with pathological correlates reminiscent of the human condition, ELH. No mice study thus far has been focused on the vestibular system as one of the main systems involved in ELH and the nature of circling behavior in this mutation.

■ METHODS: Sound evoked vestibular myogenic potentials (VEMP) were recorded from semispinalis capitis muscles and the cervical spinal cord at the C3 level of adult normal and the mutant mice. Electrophysiological data were compared with histopathologic findings of the inner ear.

■ RESULTS: ABR recording, tympanography and microscopic examination of the middle ear revealed asymmetric mixed-type hearing loss and otitis media with effusion. In addition, we were able to record VEMPs from neck extensor muscles and cervical spinal cord at the level of spinal accessory nerve nucleus in mouse model. Normative data for the latency and threshold of the response peak were established. However, at the maximum sound intensity used (130 dB SPL), Phex Hyp-Duk/y mice didnot exhibit VEMPs responses, indicating a possible disturbance of the sacculocollic pathway.

■ CONCLUSIONS: Male Phex Hyp-Duk/y mice were exhibited mixed-type hearing loss, sacculocollic pathway dysfunction, and endolymphatic hydrops revealed by the absence of VEMPs and histological features of the labyrinthine hydrops. This is the first report of VEMPs in mice and the first report of an electrophysiological abnormality of the sacculocollic pathway in a mouse model with ELH.