Sensory cell regeneration and stem cells: what we have already achieved in the management of deafness.

BACKGROUND/OBJECTIVE: Genetic manipulation of the cell-cycle exit, induction of new hair cells (HCs) through gene modification therapy, and introduction of stem cells (SCs) into damaged cochleas potentially offer exciting new strategies in treating sensorineural hearing loss. MATERIALS AND METHODS: Literature review from Medline and database sources. STUDY SELECTION: Ex vivo models, animal studies, in vitro studies, and review articles. DATA SYNTHESIS: Embryonic SCs, neural SCs, or bone marrow SCs survive in the mammalian inner ear after transplantation. The scala media and the modiolus seem more functionally appropriate injection sites. The clear evidence that transplanted neural SCs can adopt the morphologic phenotypes of HCs was the most significant milestone achieved in the related research. The normal cytoarchitecture in the organ of Corti may also be restored through mouse atonal homologue 1 transgene expression and transduction of the nonsensory cells, producing clinically measured improvement in hearing thresholds. Embryonic SC-derived neurons have the potential for synapse formation with auditory HCs and reinnervation of the auditory epithelia. However, fluctuations in survival rates, functional recovery of the spiral-ganglion neurons, integration to the host tissue, and potential immune barriers are also areas of utmost importance. CONCLUSION: There is an already exciting progress in the fields of sensory cell regeneration and SC research in an attempt to restore hearing or prevent deafness. However, further understanding of the underlying mechanisms of auditory genetics, continuing investigation of the human genome, refinement of the delivering techniques, and specification of the therapeutic strategies have to be developed before functional regeneration of the cochlea can be achieved in clinical practice.

Auditory neuropathy: endocochlear lesion or temporal processing impairment? Implications for diagnosis and management.

BACKGROUND/OBJECTIVE: Auditory neuropathy/dys-synchrony, characterized by absent auditory brainstem responses, normal otoacoustic emissions or cochlear microphonics, and word discrimination disproportional to the pure-tone audiogram, may be accompanied by perceptual consequences that could jeopardize language acquisition in affected children. However, the related evidence is constantly changing leading to a serious debate. The aim of the present paper is to review the current knowledge on auditory neuropathy/dys-synchrony, and to present the therapeutic strategies that can be employed in its management, taking into account the potentially underlying pathophysiology. MATERIALS/METHODS: Literature review from Medline and database sources. Related books were also included. STUDY SELECTION: Controlled clinical trials, prospective and retrospective cohort studies, nested-based case-control and analytical family studies, laboratory and electrophysiological studies, animal models, case-reports, joint statements and review articles. DATA SYNTHESIS: Auditory neuropathy/dys-synchrony, in contrast to what is widely believed, is a very frequent disease, responsible for approximately 8% of newly diagnosed cases of hearing loss in children per year. Hyperbilirubinemia and hypoxia represent major risk factors, whereas generalized neuropathic disorders, or a genetic substrate involving the otoferlin gene, are responsible for the phenotype of auditory neuropathy/dys-synchrony in certain cases. Auditory nerve myelinopathy and/or desynchrony of neural discharges are the most probable underlying pathophysiologic mechanisms. Genetic testing may be helpful in cases of non-syndromic prelingual children. Auditory neuropathy/dys-synchrony management aims at restoring the compromised processing of auditory information, either through conventional amplification and/or alternative forms of communication, or by cochlear implantation (combined with intensive speech and language therapy). CONCLUSION: Auditory neuropathy/dys-synchrony is more frequent than considered in the past, especially amongst hearing-impaired children. Accurate diagnosis, based on subjective and objective hearing assessment techniques (including the various electrophysiological assessment measures), and timely treatment of the affected children is of paramount importance, with hearing aids, intensive speech and language therapy (and sign language when indicated) providing the mainstay of habilitation, and cochlear implantation representing a valid therapeutic alternative.