Psychoacoustics and neurophysiological auditory processing in patients with Charcot‐Marie‐Tooth disease types 1A and 2A

Abstract

Background and purpose Hidden hearing loss has been reported in patients with Charcot‐Marie‐Tooth (CMT) disease; however, the auditory‐processing deficits have not been widely explored. We investigated the psychoacoustic and neurophysiological aspects of auditory processing in patients with CMT disease type 1A (CMT1A) and type 2A (CMT2A). Methods A total of 43 patients with CMT1A and 15 patients with CMT2A were prospectively enrolled. All patients with CMT disease had normal sound‐detection ability by using pure‐tone audiometry. Spectral‐ripple discrimination, temporal modulation detection and auditory frequency‐following response were compared between CMT1A, CMT2A and control groups. Results Although all participants had normal audiograms, patients with CMT disease had difficulty understanding speech in noise. The psychoacoustic auditory processing was somewhat different depending on the underlying pathophysiology of CMT disease. Patients with CMT1A had degraded auditory temporal and spectral processing. Patients with CMT2A had no reduced spectral resolution, but they showed further reduced temporal resolution than the patients with CMT1A. The amplitudes of the frequency‐following response were reduced in patients with CMT1A and CMT2A, but the neural timing remained relatively intact. Conclusions When we first assessed the neural representation to speech at the brainstem level, the grand average brainstem responses were reduced in both patients with CMT1A and CMT2A compared with healthy controls. As the psychoacoustic aspects of auditory dysfunctions in CMT1A and CMT2A were somewhat different, it is necessary to consider future auditory rehabilitation methods based on their pathophysiology.

Impacts of impaired mitochondrial dynamics in hearing loss: Potential therapeutic targets

“…Researchers have observed abnormal auditory function in some patients with neurodegenerative disease syndromes caused by impaired mitochondrial dynamics ( Cagalinec et al, 2016 ; Puusepp et al, 2018 ; Ham et al, 2019 ; Choi et al, 2020 ). Patients with autosomal dominant optic atrophy, induced by mitochondrial fusion gene OPA1 mutation, often experience hearing loss, which is similar to auditory neuropathy ( Ham et al, 2019 ).…”

“…The optic nerves of Opa1 delTTAG mutant mice show an obvious mitochondrial fusion impairment and neuronal death, and hearing function is also significantly impaired ( Sarzi et al, 2012 ). Mutation of another mitochondrial dynamics regulator, MFN2 , causes the patient to develop Charcot-Marie-Tooth disease, often accompanied by sensorineural deafness ( Choi et al, 2020 ). The mitochondrial fusion and localization in the neurons of Wfs1 knockout mice are impaired, and about 70% of patients with Wolfram syndrome caused by WFS1 mutation have sensorineural hearing loss ( Cagalinec et al, 2016 ).…”

Hereditary Neuropathies

“…Hearing loss is fairly common in most types of CMT. 9,10 Respiratory or bulbar symptoms may rarely occur in some subtypes. 11…”

“…Some hereditary neuropathies are associated with other symptoms or systemic involvement (eg, optic neuropathy in association with certain MFN2 variations, nephropathy in patients with INF2 variations, and central nervous system involvement in some GJB1 variations). Hearing loss is fairly common in most types of CMT 9,10 . Respiratory or bulbar symptoms may rarely occur in some subtypes 11…”

Hidden hearing loss in a Charcot-Marie-Tooth type 1A mouse model

“…CMT1A, the predominant subtype (>50% of CMT1 cases), is caused by the duplication of PMP22, a gene that encodes an integral membrane glycoprotein essential for the formation and maintenance of compact myelin (30,31). Interestingly, recent studies suggest that CMT1A patients might suffer from hearing difficulties consistent with HHL (32)(33)(34)(35). However, this has not been confirmed due to the lack of validated clinical HHL tests in humans (23,36).…”