Parkinson's disease, sleepiness and hypocretin/orexin

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 …