Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System in Adults: Final Outcomes.

OBJECTIVE: To demonstrate the safety and effectiveness of the MED-EL Electric-Acoustic Stimulation (EAS) System, for adults with residual low-frequency hearing and severe-to-profound hearing loss in the mid to high frequencies. STUDY DESIGN: Prospective, repeated measures. SETTING: Multicenter, hospital. PATIENTS: Seventy-three subjects implanted with PULSAR or SONATA cochlear implants with FLEX electrode arrays. INTERVENTION: Subjects were fit postoperatively with an audio processor, combining electric stimulation and acoustic amplification. MAIN OUTCOME MEASURES: Unaided thresholds were measured preoperatively and at 3, 6, and 12 months postactivation. Speech perception was assessed at these intervals using City University of New York sentences in noise and consonant-nucleus-consonant words in quiet. Subjective benefit was assessed at these intervals via the Abbreviated Profile of Hearing Aid Benefit and Hearing Device Satisfaction Scale questionnaires. RESULTS: Sixty-seven of 73 subjects (92%) completed outcome measures for all study intervals. Of those 67 subjects, 79% experienced less than a 30 dB HL low-frequency pure-tone average (250-1000 Hz) shift, and 97% were able to use the acoustic unit at 12 months postactivation. In the EAS condition, 94% of subjects performed similarly to or better than their preoperative performance on City University of New York sentences in noise at 12 months postactivation, with 85% demonstrating improvement. Ninety-seven percent of subjects performed similarly or better on consonant-nucleus-consonant words in quiet, with 84% demonstrating improvement. CONCLUSION: The MED-EL EAS System is a safe and effective treatment option for adults with normal hearing to moderate sensorineural hearing loss in the low frequencies and severe-to-profound sensorineural hearing loss in the high frequencies who do not benefit from traditional amplification.

Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss.

The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with its expression on the surface of supporting cells in the inner ear, CTL2 contains 10 predicted membrane-spanning regions with multiple N-glycosylation sites. The 68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the transporter function of this molecule. CTL2 mRNA and protein are abundantly expressed in human inner ear. Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans.

Effects of trigeminal ganglion stimulation on the central auditory system.

A projection from the trigeminal ganglion to the ventral cochlear nucleus (VCN) of the guinea pig was recently described. The synaptic terminals of this projection terminate in the granule and magnocellular regions of the VCN. Stimulation of this projection has been shown to result in activation of neurons of the ventral cochlear nucleus. We investigated the effect of electrically stimulating the trigeminal ganglion on the central auditory system activity using 2-deoxyglucose (2-DG) autoradiographic techniques. Electrical stimuli were applied to the left trigeminal ganglion as bipolar pulses, 100 micros per phase, at intervals of 200 ms and an amplitude of 100 microA. Negative control animals were not stimulated. A positive control animal was stimulated in the left ear using a 1 kHz tone burst with 200 ms duration and an amplitude of 80 dB SPL. 2-DG was administered by intramuscular injection. Following a 1 h incorporation period, animals were sacrificed, the brains rapidly harvested, and prepared for autoradiography using standard techniques. Autoradiographs were analyzed using computer-assisted video densitometry to determine film optical density in the central auditory regions of interest. The cerebellum was also sampled as a gray matter indifferent intra-brain control region. Results showed systematic and significant differences between 2-DG uptake in the cochlear nucleus and higher auditory centers between control and stimulated animals. Trigeminally stimulated animals showed significantly higher uptake than unstimulated animals in all auditory centers examined, especially ipsilateral to the stimulation site. The activation pattern differs qualitatively from that seen with sound stimulation in that mainly contralateral pathways are activated with sound stimulation. These results demonstrate that a projection from the predominantly somatosensory trigeminal ganglion can influence the activity of central auditory neurons in a manner distinct from acoustic stimulation, suggesting activation of non-classical auditory pathways.