Auditory Phenotypic Variability in Friedreich\u2019s Ataxia Patients

Gilbert Thomas-Black,Paola Giunti,Doris-Eva Bamiou,Nehzat Koohi

doi:10.1007/s12311-021-01236-9

Abstract

Auditory neural impairment is a key clinical feature of Friedreich’s Ataxia (FRDA). We aimed to characterize the phenotypical spectrum of the auditory impairment in FRDA in order to facilitate early identification and timely management of auditory impairment in FRDA patients and to explore the relationship between the severity of auditory impairment with genetic variables (the expansion size of GAA trinucleotide repeats, GAA1 and GAA2), when controlled for variables such as disease duration, severity of the disease and cognitive status. Twenty-seven patients with genetically confirmed FRDA underwent baseline audiological assessment (pure-tone audiometry, otoacoustic emissions, auditory brainstem response). Twenty of these patients had additional psychophysical auditory processing evaluation including an auditory temporal processing test (gaps in noise test) and a binaural speech perception test that assesses spatial processing (Listening in Spatialized Noise-Sentences Test). Auditory spatial and auditory temporal processing ability were significantly associated with the repeat length of GAA1. Patients with GAA1 greater than 500 repeats had more severe auditory temporal and spatial processing deficits, leading to poorer speech perception. Furthermore, the spatial processing ability was strongly correlated with the Montreal Cognitive Assessment (MoCA) score. To our knowledge, this is the first study to demonstrate an association between genotype and auditory spatial processing phenotype in patients with FRDA. Auditory temporal processing, neural sound conduction, spatial processing and speech perception were more severely affected in patients with GAA1 greater than 500 repeats. The results of our study may indicate that auditory deprivation plays a role in the development of mild cognitive impairment in FRDA patients.

Highlights

Friedreich’s Ataxia (FRDA) is the most frequent autosomal recessive inherited ataxia caused by mutations in the FXN gene
Mild/moderate hearing impairment was observed in 21 patients with GAA1 repeat lengths of more than 500
Previous research [11, 14] prompted us to investigate the relation between the severity of the auditory impairment, as shown on behavioural and physiological audiological assessments, and the expansion size of GAA1 repeats

Summary

Introduction

Friedreich’s Ataxia (FRDA) is the most frequent autosomal recessive inherited ataxia caused by mutations in the FXN gene. Sensorineural hearing loss as revealed in a pure-tone audiogram is seen in only 8 to 13% of FRDA patients but other types of hearing impairment, such as difficulty understanding speech in background noise, are present in more than 90% of these patients [1,2,3]. Preneural auditory responses from the cochlear outer hair cells are typically normal in more than 90% of the patients [4]. Most of these individuals show abnormalities in auditory neural and brainstem responses as a result of axonopathy in the eighth nerve and auditory brainstem, termed as “auditory neuropathy,” [4,5,6] which is Cerebellum (2021) 20:497–508 the cause of listening difficulties [4, 7, 8]. Patients with auditory neuropathy struggle to understand speech when background noise is present [9, 10] and show impaired ability to selectively attend to a particular voice based on its location [7]

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