Auditory Brainstem Response and Hearing Loss in MELAS: Post Mortem Analysis of Temporal Bone to Explain Abnormal ABR

Abstract

We observed a MELAS patient who came to our Clinical Center for moderate SNHL. The ABR from this patient displayed waves (Figure 1) with amplitude and latency too reduced to be considered within the normal range, but not completely absent as it would be expected considering his auditory threshold in pure tone audiometry (PTA).In an attempt to explain this observation, we reviewed the literature on the temporal bone aspect of MELAS patients. Loss of Spiral Ganglions (SGs) and atrophy of Stria Vascularis (SV) are typical findings in temporal bone of patients with MELAS even when the Organ of Corti is entirely preserved.In SGs and SV mitochondria are abundant [7], as they are necessary to support the high metabolic functions of these structures. In MELAS, mitochondria that have been damaged (by deletion/mutation in their DNA) increase the Redox Oxidative Species (ROS) concentration [8] and cell apoptosis [9] which reduce the number of inner ear cells (SG, VS and Hair cells) and, cause a malfunction of the remaining cells.ABR reflects the way the auditory signal travels from the retrocochlear portion (synapse, SGs, cochlear nerve and cochlear nuclei) (Waves I, III) to the cortex (wave V); if all the structures in the retro-cochlear hearing pathways function correctly, the ABR displays normal amplitude and latency; but damage in even one of the structures causes abnormal ABR latency and/or amplitude, which in turn alter the overall signal shape.We think that the abnormal ABR of our patient can be explained by the altered functions of residual SGs, which cannot sufficiently amplify the signal to generate an actual ABR wave. The numerous mitochondrial mutations observed in the temporal bone of patients with MELAS [10][11] support the idea that the residual SGs do not function well enough to allow a correct transmission of the impulse, which in turn leads to an abnormal ABR. Arguably, the high ABR variability in MELAS patients reported in the literature [2,3,4,6] is due to the stochastic segregation of mitochondria during embryogenesis; the concentration of damaged mitochondria could differ among patients just due to