Sleep profile in cerebrotendinous xanthomatosis patients: a pilot study

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disorder caused by variant in CYP27A1. The classical neurological phenotype presents with neuropsychiatric symptoms related to the brain, cerebellum, and/or brainstem with various typical systemic manifestations. There is increasing literature reporting sleep disorders in lipid-storage disorders. However, to the date of this research, there are no published studies on sleep assessment in patients with CTX, nor description of most prevalent sleep patterns reported by these patients. Objective: To clinically characterize sleep patterns and sleep disorders in CTX. Methods: This was a retrospective observational study including patients with CTX. General clinical data was collected through chart review. Scales used for sleep disorders assessment (Epworth Sleepiness Scale, Morningness-eveningness Questionnaire and screening for restless legs syndrome) and results of wrist actigraphy and polysomnography performed in their medical care were collected to characterize the sleep profile of these patients. Results: We included four patients with CTX from our center. All of them had diagnoses confirmed by genetic testing and high plasma cholestanol levels. The patients had clinical history compatible with classical form of CTX. Four patients related sleep disturbances. Two patients related daytime sleepiness and two complained of intense snoring. Insomnia was reported by two patients. Two patients performed polysomnography. Both had reduced latency for sleep, reduced amount of REM sleep and increased amount of N2 and/or N1 sleep for age and gender. One of these patients had evidence of moderate obstructive sleep apnea (OSA). One patient performed actigraphy, showing a circadian rhythm of 24 hours, good sleep consolidation pattern with median sleep efficiency of 91% but a median of five awakenings every night. Sleep patterns or even animal models for sleep disturbances in CTX are still to be described. Hence, there is little literature hypothesizing about how sleep disorders develop in this population. The presence of leukoencephalopathy and cerebellum impairment may be two possible reasons for the presentation of sleep disorders in CTX observed in our patients. The cerebellum is an important region in regulation of sleep, modulating function in the genesis of sleep and regulatory function on body movements during sleep. Leukodystrophies are reported to present with sleep symptoms such as hypersomnolence, insomnia and sleep-related breath disorders loke OSA. Conclusion: Our study shows that CTX patients may suffer from impairment in the physiological process of sleep. It highlights that the sleep assessment of these patients should be part of medical practice. Our study had several limitations due to the small sample size. More controlled studies are still needed to evaluate and intervene in the sleep of these patients.