Hearing Impairment and Neuroimaging Results in Mitochondrial Diseases

Gabriella Cadoni; Guido Primiano; Pasqualina M Picciotti; Rosalinda Calandrelli; Jacopo Galli; Serenella Servidei; Guido Conti

doi:10.3390/jpm13091329

Hearing Impairment and Neuroimaging Results in Mitochondrial Diseases

J Pers Med. 2023 Aug 29;13(9):1329. doi: 10.3390/jpm13091329.

Authors

Gabriella Cadoni^{1

2}, Guido Primiano^{1

3}, Pasqualina M Picciotti^{1

2}, Rosalinda Calandrelli⁴, Jacopo Galli^{1

2}, Serenella Servidei^{1

3}, Guido Conti^{1

2}

Affiliations

¹ Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
² Dipartimento di Testa-Collo e Organi di Senso, Catholic University of the Sacred Heart, 00168 Rome, Italy.
³ Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
⁴ Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Abstract

Mitochondrial diseases (MDs) are heterogeneous genetic disorders characterized by mitochondrial DNA (mtDNA) defects, involving tissues highly dependent on oxidative metabolism: the inner ear, brain, eye, skeletal muscle, and heart. We describe adult patients with genetically defined MDs, characterizing hearing function and neuroimaging results. We enrolled 34 patients (mean age: 50.02 ± 15 years, range: 18-75 years; 20 females and 14 males) classified in four groups: MELAS, MIDD, PEO, and Encephalopathy/Polyneuropathy. Audiological evaluations included psychoacoustical tests (pure-tone and speech audiometry), electrophysiological tests (Auditory Brainstem Responses, ABRs), and Impedenzometry. Neuroimaging evaluations considered global MRI abnormalities or structural brain changes. In total, 19/34 patients carried the m.3243A > G mutation (6 affected by MELAS, 12 affected by MIDD, and 1 affected by PEO); 11 had an mtDNA deletion (all affected by PEO); 3 had nuclear genes associated with MDs (POLG1 and OPA1); and 1 patient had an mtDNA deletion without an identified nuclear gene defect (affected by PEO). Sensory neural, bilateral, and symmetrical hearing loss was present in 25 patients (73.5%) to different degrees: 9 mild, 9 moderate, 5 severe, and 2 profound. The severe/profound and mild hearing losses were associated with pantonal and high-frequency audiograms, respectively. Instead, moderate hearing losses were associated with both high-frequency (five cases) and pantonal (five cases) audiogram shapes. In addition, 21/25 patients showed a cochlear site of lesion (84%), and 4/25 (16%) showed a retrocochlear site. We found global MRI abnormalities or structural brain changes in 26/30 subjects (86.6%): 21 had white matter abnormalities, 15 had cortical atrophy, 10 had subcortical atrophy, 8 had basal nuclei involvement or cerebellar atrophy, 4 had stroke-like lesions or laminar necrosis, and 1 had cysts or vacuolated lesions. We concluded that genetic alterations are associated with different clinical presentations for both auditory function and neuroradiological findings. There is no fixed relationship between genotype and phenotype for the clinical conditions analyzed.

Keywords: MRI; brain changes; cochlear; deafness; mitochondrial diseases; mtDNA; retrocochlear.

Grants and funding

This research received no external funding.