Human Cochlear Histopathology Reflects Clinical Signatures of Primary Neural Degeneration

Abstract

Abstract Auditory neuropathy is a significant and understudied cause of human hearing loss, diagnosed in patients who demonstrate abnormal function of the cochlear nerve despite typical function of sensory cells. Because the human inner ear cannot be visualized during life, histopathological analysis of autopsy specimens is critical to understanding the cellular mechanisms underlying this pathology. Here we present statistical models of severe primary neuronal degeneration and its relationship to pure tone audiometric thresholds and word recognition scores in comparison to age-matched control patients, spanning every decade of life. Analysis of 30 ears from 23 patients shows that severe neuronal loss correlates with elevated audiometric thresholds and poor word recognition. For each ten percent increase in total neuronal loss, average thresholds across patients at each audiometric test frequency increase by 6.0 dB hearing level (HL). As neuronal loss increases, threshold elevation proceeds more rapidly in low audiometric test frequencies than in high frequencies. Pure tone average closely agrees with word recognition scores in the case of severe neural pathology. Histopathologic study of the human inner ear continues to emphasize the need for non- or minimally invasive clinical tools capable of establishing cellular-level diagnoses.