Parkinson's disease, sleepiness and hypocretin/orexin

Extract

Sir, Sleepiness and disrupted sleep substantially impair quality of life in people with Parkinson's disease (PD) (Arnulf et al., 2000). The hypocretin/orexin neuropeptides stabilize wakefulness and sleep, and in two recent studies, Fronczek et al. (2007) and Thannickal et al. (2007) showed that patients with late-stage PD have a 38–45% loss of the hypothalamic hypocretin-producing neurons. These studies provide novel and important insights into the neuropathology of PD, but several questions remain about whether this partial loss of hypocretin neurons actually causes the sleep–wake disturbances of PD.

First, are the sleep-related symptoms of PD consistent with a loss of hypocretin neurons? Narcolepsy is caused by a 90–95% loss of the hypocretin neurons and is characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone with strong emotions), with fragmented sleep, sleep paralysis (immobility either at sleep onset or upon awakening), hypnagogic hallucinations and sleep-onset REM sleep (SOREM) during daytime naps (Bassetti and Aldrich, 1996; Peyron et al., 2000). Certainly, PD patients often have fragmented sleep, daytime sleepiness, SOREM, and hallucinations (Arnulf et al., 2000). Our own clinical experience, however, is not in agreement with the statements by Thannickal et al. that the daytime sleep attacks in PD resemble sleep attacks in narcolepsy, nor do we agree that sleep–wake disturbances are often more disturbing for PD patients than their motor symptoms. Furthermore, narcoleptics may have hypnagogic hallucinations at the transitions between wakefulness and sleep, but PD patients often have delusions and illusions rather than dream-like hallucinations (Aarsland et al., 1999). Last, cataplexy has not been reported to occur in PD. Therefore, while there are some similarities, the sleepiness and other symptoms of PD differ in many ways from those seen in narcolepsy.