Temporal bone histopathology in MELAS syndrome

Abstract

Objectives Describe the histopathology of the temporal bones in MELAS (myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes) syndrome. The syndrome results from a known point mutation in mitochondrial DNA. Methods Histopathology analysis of a pair of temporal bones from the oldest surviving MELAS syndrome temporal bone donor. Histopathologic findings were correlated with known premortem clinical data. Results The inner ears showed severe but incomplete atrophy of the stria vascularis for the length of the cochleae. In contrast, the organ of Corti and inner hair cells appeared intact with some loss of outer hair cells. Other than moderate loss at the basal turn, spiral ganglion cells numbers were normal. The vestibular neuroepithelium was mostly normal with the exception of moderate degeneration of the macula sacculi and partial collapse of the saccular wall on the right. The cerebral cortex had infarct‐like lesions with adjacent gliosis. Conclusion This is an analysis of the oldest patient with MELAS syndrome to date, an addition to only two previously published patients. It supports the notion that hearing loss is a result of dysfunction of the stria vascularis and not loss of hair cells or neurons. Patterns of vestibular pathology are in agreement to in‐vivo measurements. These findings support auditory rehabilitation with cochlear implants and may be relevant to hearing loss due to other mitochondrial mutations. Level of evidence 4

Cochlear Implantation in Patients with Mitochondrial Gene Mutation: Decline in Speech Perception in Retrospective Long-Term Follow-Up Study

“…Previous studies [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]40,41] and short-term observations in the present study indicate that patients with mtDNA mutations are good candidates for CI. Notably, however, the long-term observations in the present study also suggest that retrocochlear dysfunction may be responsible for the long-term deterioration of speech perception after CI in patients with mtDNA mutations.…”

“…Deafness associated with mtDNA abnormalities is mainly attributed to dysfunction of the inner ear [11][12][13][14][15], but the retrocochlear auditory pathway may also be involved [4,16,17,[21][22][23]. Short-term improvements in speech perception after CI may wane during long-term follow-up due to the degeneration of the spiral ganglion cells or cognitive decline due to progressive mitochondrial disorder.…”

“…Many spiral ganglion cells showed varying degrees of degenerative change, as evidenced by faint staining of the cytoplasm, loss of cell membrane outline, and loss of nuclear definition. Other histopathological examinations of the human temporal bone also demonstrated that mtDNA A3243G mutation can involve not only the stria vascularis and hair cells but also the spiral ganglion cells [22,23].…”

“…Cochlear implantation (CI) for patients with severe to profound hearing loss associated with mtDNA mutations has been reported [19,[21][22][23][28][29][30][31][32][33][34][35]. Howes et al [36] reported a case of MIDD with a speech score of 67% at one-month follow-up.…”

The Role of Primary Mitochondrial Disorders in Hearing Impairment: An Overview

“…Since then, various case reports have been published about subjects affected by PMDs and rehabilitated through the use of a CI, with encouraging results in terms of improvements in speech perception and sound detection and, hence, in quality-of-life perception [ 43 ]. Considering that, according to histopathology studies, atrophy of the stria vascularis is the most relevant cochlear change in m.3243A>G, while no major changes have been observed in spiral ganglion neurons, electrical stimulation is a feasible rehabilitative option [ 44 , 45 ]. Additionally, in patients with central nervous system degeneration, as observed in MELAS, the central auditory pathway is usually unaffected by the disease, resulting in CI-positive outcomes [ 46 , 47 ].…”