Fabrice Giraudet1, Perrine Charles2, Thierry Mom1, Odile Boespflug-Tanguy3, Alexandra Dürr4, Paul Deltenre5, Paul Avan6. 1. Laboratory of Neurosensory Biophysics, UMR INSERM 1107, University Clermont Auvergne, Clermont-Ferrand, France. 2. APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 3. Assistance Publique des Hopitaux de Paris (APHP), Reference Center for Rare Diseases "Leukodystrophies," Child Neurology and Metabolic Disorders Department, Robert Debré University Hospital, Paris, France; Inserm, Paris Diderot University, UMR 1141, DHU PROTECT, Sorbonne Paris-Cite, Robert Debré University Hospital, Paris, France. 4. APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ICM, Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, Sorbonne Universités - UPMC Université Paris VI UMR-S1127, Paris, France. 5. CHU Brugmann, Université Libre de Bruxelles, Belgium. 6. Laboratory of Neurosensory Biophysics, UMR INSERM 1107, University Clermont Auvergne, Clermont-Ferrand, France; Centre Jean Perrin, Clermont-Ferrand, France. Electronic address: paul.avan@udamail.fr.
Abstract
OBJECTIVES: In patients with Friedreich ataxia (FRDA), mitochondrial failure leads to impaired cellular energetics. Since many FRDA patients have impaired hearing in noise, we investigated the objective consequences on standard auditory brainstem-evoked responses (ABRs). METHODS: In 37 FRDA patients, among whom 34 with abnormal standard ABRs, hearing sensitivity, speech-in-noise intelligibility and otoacoustic emissions were controlled. ABR recordings were split into four consecutive segments of the total time frame used for data collection, thus allowing the dynamics of ABR averaging to be observed. RESULTS: Most ears showed features of an auditory neuropathy spectrum disorder with flattened ABRs and impaired speech-in-noise intelligibility contrasting with near-normal hearing sensitivity and normal preneural responses. Yet split-ABRs revealed short-lived wave patterns in 26 out of 68 ears with flattened standard ABRs (38%). While averaging went on, the pattern of waves shifted so that interwave latencies increased by 35% on average. CONCLUSIONS: In FRDA, the assumption of stationarity used for extracting standard ABRs is invalid. The preservation of early split-ABRs indicates no short-term dyssynchrony of action potentials. A large decrease in conduction velocity along auditory neurons occurs within seconds, attributed to fast energetic failure. SIGNIFICANCE: This model of metabolic sensory neuropathy warns against exposure of metabolically-impaired patients to sustained auditory stimulation.
OBJECTIVES: In patients with Friedreich ataxia (FRDA), mitochondrial failure leads to impaired cellular energetics. Since many FRDApatients have impaired hearing in noise, we investigated the objective consequences on standard auditory brainstem-evoked responses (ABRs). METHODS: In 37 FRDApatients, among whom 34 with abnormal standard ABRs, hearing sensitivity, speech-in-noise intelligibility and otoacoustic emissions were controlled. ABR recordings were split into four consecutive segments of the total time frame used for data collection, thus allowing the dynamics of ABR averaging to be observed. RESULTS: Most ears showed features of an auditory neuropathy spectrum disorder with flattened ABRs and impaired speech-in-noise intelligibility contrasting with near-normal hearing sensitivity and normal preneural responses. Yet split-ABRs revealed short-lived wave patterns in 26 out of 68 ears with flattened standard ABRs (38%). While averaging went on, the pattern of waves shifted so that interwave latencies increased by 35% on average. CONCLUSIONS: In FRDA, the assumption of stationarity used for extracting standard ABRs is invalid. The preservation of early split-ABRs indicates no short-term dyssynchrony of action potentials. A large decrease in conduction velocity along auditory neurons occurs within seconds, attributed to fast energetic failure. SIGNIFICANCE: This model of metabolic sensory neuropathy warns against exposure of metabolically-impaired patients to sustained auditory stimulation.
Authors: Serena Viventi; Stefano Frausin; Sara E Howden; Shiang Y Lim; Rocio K Finol-Urdaneta; Jeffrey R McArthur; Kwaku Dad Abu-Bonsrah; Wayne Ng; Jason Ivanusic; Lachlan Thompson; Mirella Dottori Journal: Stem Cells Transl Med Date: 2021-03-18 Impact factor: 6.940