Cochlear neural degeneration is key to the variation in word scores among people with similar thresholds

Patients with Ménière's disease show lower word scores than those with other types of sensorineural hearing loss [Grant et al., 2022, Sci. Reports 12(1):8929]. We hypothesized that cochlear neural degeneration is a key driver of these differences among patients with similar audiograms. Here, we quantified histopathology in human cochleas with hearing loss from several etiologies and assessed the contribution of each cell type to word scores in a multivariable regression. We studied Ménière's cases (n = 44), contralateral (unaffected) ears of Ménière's cases (n = 10), age-matched normal-aging controls (n = 44), cases with platinum ototoxicity (cisplatin/carboplatin; n = 10), or aminoglycoside ototoxicity (n = 13), and age-matched controls for this (younger) group of ototoxic cases (n = 15). We quantified fractional survival of inner (IHC) and outer (OHC) hair cells, auditory-nerve (AN) peripheral axons, spiral ganglion cells (SGCs) and the stria. Ménière's ears showed the lowest survival of IHCs (<50 %), OHCs (<30 %), AN peripheral axons (<30 %), and stria (<60 %), as well as the worst mean thresholds (75.4 dB HL) and word scores (36.68 %). Pairwise correlations showed the strongest word-score associations with IHC survival in the apical half (R² = 0.404) and with AN axons in both apical (R² = 0.329) and basal (R² = 0.324) halves of the cochlea. Despite the massive loss of AN peripheral axons, SGC loss re age-matched controls was minimal. In a multivariable regression including all histological variables and thresholds (0.5-4 kHz), AN peripheral axons were the only significant histological predictor of word score. The survival of most SGCs helps explains why most Ménière's patients nevertheless perform well with cochlear implants.