Sleep Disorders in Huntington’s Disease

Abstract

Huntington’s chorea (Huntington’s disease, HD) is a genetic disorder caused by autosomal dominant mutation, leading to progressive neurodegenerative changes in the central nervous system. Involuntary movements such as chorea occur typically in HD patients, accompanied by progressive cognitive and psychiatric disturbances. Other common symptoms of HD are circadian and sleep abnormalities, which are observed from the earliest stages of the disease or even before the occurrence of clinical symptoms. The most common sleep problems reported by HD patients include insomnia, difficulties in falling asleep, frequent nocturnal awakenings, and excessive daytime sleepiness. Also, specific changes in sleep architecture have been identified in HD. In this paper, we review studies on sleep and circadian rhythm disorders in HD. We outline findings concerning sleep patterns and disturbances of circadian rhythms in HD patients, as well as the role of psychiatric disorders and motor disorders in HD patients’ sleep problems. We also discuss problems related to the different methods of diagnosing sleep disorders in HD. Furthermore, the adverse effects of medication used for the treatment of core HD symptoms as one of the sources of sleep disturbances in HD are emphasized. In conclusion, the diversity and complexity of the determinants of sleep and circadian rhythm disorders in HD are highlighted. Finally, the relevance of effective treatment to improve patients’ functioning and quality of life as well as the potential relief of their cognitive and emotional symptoms is addressed.

Wake-Promoting and EEG Spectral Effects of Modafinil After Acute or Chronic Administration in the R6/2 Mouse Model of Huntington's Disease

“…3a). In R6/2 mice at 12 weeks, only the beta power at frequencies of [25][26][27][28][29][30] Hz increased in response to modafinil, whilst in R6/2 mice at 16 weeks, only the power of 29-30 Hz increased (Fig. 3b, c).…”

“…Alpha (10-14 Hz) power was reduced in WT and R6/2 mice at 16 weeks, but not in R6/2 mice at 12 weeks. For beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) power, the effect varied across the frequency range. For WT mice, the power at frequencies < 20 Hz decreased significantly, whilst power at frequencies > 29 Hz increased significantly (Fig.…”

“…However, the effect of only a single dose of modafinil was used. Given that HD patients may respond to drugs differently from normal subjects, and that modafinil is used as a cognitive enhancer in both normal and patient groups (for references, see [ 25 ]), modafinil remains an interesting candidate for treating sleep-wake disorder in HD [ 26 ].…”

MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases

“…HD patients show hyperkinetic movement disorders due to basal ganglion dysfunction. The most common sleep problems reported by HD patients are insomnia, difficulties in falling asleep, frequent nocturnal awakenings, and excessive daytime sleepiness [186].…”

Towards a comprehensive understanding of the contributions of mitochondrial dysfunction and oxidative stress in the pathogenesis and pathophysiology of Huntington's disease

“…Indeed, sleep disturbance in HD may contribute toward the patient and their caregiver's low quality of life (Goodman et al, ). Commonly reported sleep disturbances in HD include insomnia, REM sleep behavior disorders, reduced REM sleep, difficulties in falling asleep, advanced sleep phase, frequent nocturnal awakenings, periodic leg movements, and excessive daytime sleepiness (Arnulf et al, ; Herzog‐Krzywoszanska & Krzywoszanski, ). mHTT is believed to modulate REM sleep in HD (Arnulf et al, ).…”