Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 hrs post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five “normal” ears, aged 54 to 89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear.

Objectives Although published reports have not demonstrated a positive correlation between the number of residual spiral ganglion cells (SGC) and word recognition scores in patients with unilateral multichannel cochlear implants, this study was designed to retest this hypothesis in patients with bilateral multichannel cochlear implants. Materials and Methods From a pool of 133 temporal bones, all subjects with bilateral multichannel cochlear implants who were deafened bilaterally by the same etiology were studied. A total of 12 temporal bones from 6 subjects were identified and processed after death for histology. The SGCs were counted by standard techniques. The differences between left and right SGC counts as well as the differences in word recognition scores were calculated for each subject. Correlation analysis was performed between the differences of SGC counts and the differences of word recognition scores. Results Differences in SGC counts were highly correlated with the differences in word recognition scores (R=0.934, P-value= 0.006). Conclusion This study suggests higher residual SGCs predicted better performance after implantation in a given patient. The results also support attempts to identify factors which may promote survival of SGCs.

Microtia is a rare, congenital malformation of the external ear that in some cases has a genetic etiology. We ascertained a three-generation family with bilateral microtia and hearing loss segregating as an autosomal dominant trait. Exome sequencing of affected family members detected only seven shared, rare, heterozygous, nonsynonymous variants, including one protein truncating variant, a HOXA2 nonsense change (c.703C>T, p.Q235*). The HOXA2 variant was segregated with microtia and hearing loss in the family and was not seen in 6,500 individuals sequenced by the NHLBI Exome Sequencing Project or in 218 control individuals sequenced in this study. HOXA2 has been shown to be critical for outer and middle ear development through mouse models and has previously been associated with autosomal recessive bilateral microtia. Our data extend these conclusions and define HOXA2 haploinsufficiency as the first genetic cause for autosomal-dominant nonsyndromic microtia.

Introduction Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations resulting in defective repair of DNA damage. XP patients have a markedly increased risk of ultraviolet induced neoplasms and premature aging of sun-exposed tissue. About 25% of XP patients in the US have neurologic abnormalities including progressive sensorineural hearing loss (SNHL). Objective To describe the temporal bone histopathology in two individuals with Xeroderma Pigmentosum (XPA and XPD) with neurological degeneration and to discuss the possible causes of deafness in these patients. Methods Temporal bones were removed at autopsy and studied using light microscopy. Results In the case with XPD, the organ of Corti was missing throughout the cochlea, whereas the case with XPA demonstrated scattered presence of sensory cells in the middle and apical turns. In both cases, there was moderate-to-severe patchy atrophy of the stria vascularis in all turns, and cochlear neurons were severely atrophied compared to age-matched controls, with loss of both peripheral dendrites and central axons. There was severe degeneration of Scarpa’s ganglion in the case with XPA. Conclusion Two cases of XP with neurological degeneration are reported. The case with XPD demonstrated a more severe audiologic phenotype than XPA, although both had similar findings such as atrophy of the organ of Corti, stria vascularis and spiral ganglia leading to severe or profound SNHL by the third decade of life. It is not clear if the neuronal degeneration in the inner ear was primary or secondary to loss of neuroepithelial cells.

Intratympanic gentamicin treatment appears to be a long-lasting and effective treatment for MD with DAs.

In the present patients, Alström Syndrome began with a neurosensory hearing loss in early childhood that progressed to a profound loss in ten to twenty years. The auditory lesions were cochlear in origen according to the otoacoustic emissions and auditory brainstem responses.

Abnormal values in the interpeak I-III associated with normal distortion product OEA suggest neurotoxicity in the brainstem pathways. The statistical significance reached only in the left ear may be due to small number of cases studied.

Background Dandy's Syndrome, or bilateral vestibular hypofunction and oscillopsia, may cause chronic disequilibrium aggravated by head movement or in the presence of reduced light. It may be secondary to ototoxicity, central nervous system tumors, Meniere's Syndrome, infections or trauma, or may be idiopathic. Objective To describe the temporal bone histopathology in one individual with Idiopathic Dandy's Syndrome. Material and Methods Temporal bones from 1 individual were removed at autopsy and studied using light and Nomarski microscopy. Results In this case, the otopathology demonstrated vestibular atelectasis of the membranous labyrinth of the superior, lateral and posterior semicircular canals, but not the utricle or saccule bilaterally. The findings also included mild hair cell loss in the cristae of all semicircular canals and of the utricular and saccular maculae, and severely reduced neuronal count in Scarpa's ganglion bilaterally. There was also a scattered loss of inner and outer hair cells throughout the cochlea and moderate-to-severe loss of cochlear neurons bilaterally. Conclusion We have reported the histopathologic findings in a case of idiopathic Dandy's syndrome. Both temporal bones showed vestibular atelectasis of all three semicircular canals, preservation of normal saccule and utricle, and severe reduction of the neuronal population in Scarpa's ganglion bilaterally. Both ears also showed substantial degeneration of the spiral ganglion of the cochleas. Severe Scarpa's ganglion degeneration was also noted in the only other case of idiopathic Dandy's Syndrome in the literature. However, that other case had no evidence of vestibular atelectasis and had normal hearing.