Auditory brainstem response findings and peripheral auditory sensitivity in adrenoleukodystrophy.

Area of Science:

• Neurology
• Audiology
• Genetics

Background:

• X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder affecting the nervous system and adrenal glands.
• Auditory brainstem response (ABR) testing is a valuable tool for assessing the integrity of the auditory pathway.
• Previous research has not fully elucidated the auditory pathway involvement in various X-ALD phenotypes.

Purpose of the Study:

• To investigate auditory brainstem response (ABR) abnormalities in individuals with X-linked adrenoleukodystrophy (X-ALD).
• To correlate ABR findings with different neurological phenotypes of X-ALD.
• To determine the association between ABR abnormalities and factors like age, VLCFA levels, and MRI scores.

Main Methods:

• Auditory brainstem response (ABR) measurements were obtained from 96 individuals diagnosed with X-linked adrenoleukodystrophy (X-ALD).
• Patients were categorized into five distinct neurological diagnostic groups: cerebral childhood/adolescent, pure adrenomyeloneuropathy (AMN), AMN with cerebral involvement, Addison's disease only, and symptomatic female heterozygotes.
• Statistical analyses were performed to identify predictors of ABR abnormalities and compare findings across groups.

Main Results:

• Marked ABR abnormalities were observed across all X-ALD groups, predominantly affecting Wave V, followed by Wave III and Wave I.
• Abnormalities in interpeak latencies (I-III, III-V, I-V) were common in all patient groups.
• AMN-cerebral and pure AMN groups exhibited the most frequent ABR abnormalities, while symptomatic female heterozygotes also showed significant impairment. Cerebral childhood/adolescent X-ALD showed the least impairment.
• Age was a significant predictor of bilateral ABR abnormalities, but VLCFA levels, MRI Loes score, and symptom duration were not independent predictors after adjusting for phenotype.
• Patients with AMN were more likely to have bilateral ABR abnormalities than the cerebral childhood/adolescent group, even after adjusting for multiple clinical and imaging variables.
• The prevalence of peripheral hearing loss did not exceed that of control groups, indicating no association with X-ALD.

Conclusions:

• Auditory sensitivity in X-ALD is generally not significantly impaired.
• ABR abnormalities are frequent in X-ALD and likely stem from lesions in the central auditory pathway, specifically the lateral lemniscus and inferior colliculus.
• These auditory pathway abnormalities progress slowly and are primarily associated with the adrenomyeloneuropathy (AMN) phenotype of X-ALD.