Transient Deafness Due To Temperature-Sensitive Auditory Neuropathy

Abstract

Objective: To define mechanisms accounting for transient deafness in three children(two siblings, ages 3 and 6, and an unrelated child, age 15) when they become febrile.Design: Audiometric tests (puretone audiometry, speech and sentence comprehension), tympanometry, middle ear muscle reflex thresholds, otoacoustic emissions (OAEs), and electrophysiological methods (auditory brain stem responses [ABRs], sensory evoked potentials, peripheral nerve conduction velocities) were used to test the children when they were afebrile and febrile.Results: ABRs, when afebrile, were abnormal with a profound delay of the IVV and absence of waves IIII. The ABR in one of the children, tested when febrile, showed no ABR components. Measures of cochlear receptor function using OAEs were normal in both febrile and afebrile states. Cochlear microphonic potentials were present in the three children, and a summating potential was likely present in two. When afebrile, there was a mild threshold elevation for all frequencies in the 15yrold and a mild elevation of thresholds for just low frequencies in the two siblings. Speech comprehension in quiet was normal but impaired in noise. One of the siblings tested when febrile had a profound elevation (>80 dB) of puretone thresholds and speech comprehension was absent. Acoustic reflexes subserving middle ear muscles and olivocochlear bundle were absent when febrile and when afebrile. No other peripheral or cranial nerve abnormalities were found in any of the children. Sensory nerve action potentials from median nerve in one of the children showed no abnormalities on warming of the hand to 39°C. Conclusion: These children have an auditory neuropathy manifested by a disorder of auditory nerve function in the presence of normal cochlear outer hair cell functions. They develop a conduction block of the auditory nerves when their core body temperature rises due, most likely, to a demyelinating disorder of the auditory nerve. The auditory neuropathy in the two affected siblings is likely to be inherited as a recessive disorder.

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations

“…One well-studied form of presynaptic AN is caused by mutations in the OTOF gene (Rodríguez-Ballesteros et al, 2003, 2008Santarelli et al, 2009;Starr et al, 1998;Varga et al, 2003). Otoferlin has been implicated in multivesicular release at the synapse between the IHCs and auditory nerve fibers.…”

“…Some individuals harboring missense mutations in the OTOF gene suffer from a particular disorder called temperature-sensitive auditory neuropathy (Marlin et al, 2010;Starr et al, 1998;Varga et al, 2006;Wynne et al, 2013). When afebrile, these patients have normal or only mildly elevated hearing thresholds.…”

“…Speech perception, gap detection and the spatial localization of sounds are affected as a consequence. The magnitude of these perceptual changes is independent of the changes in audibility (Starr et al, 1996(Starr et al, , 1998Zeng et al, 2005).…”

“Hearing” and Auditory Neuropathy: Lessons from Patients, Physiology, and Genetics

“…We know that the tests used to diagnose AN can improve in some children [20]. Moreover, adults fulfi lling the criteria for AN can be asymptomatic [21] or only symptomatic under certain conditions [22,23]. Such exceptions test the rule that implants should be used in AN without behavioral evidence of impaired auditory temporal processing.…”

Auditory nerve is affected in one of two different point mutations of the neurofilament light gene

“…Asymptomatic vestibular nerve dysfunction can also occur in subjects with auditory neuropathy (Fujikawa and Starr, 2000). And finally, the clinical expression of auditory neuropathy may also occur when individuals are febrile, as in a special variant known as ''temperature sensitive auditory neuropathy'' (Starr et al, 1998).…”