Sleepiness in Parkinson's disease.

Excessive daytime sleepiness is a disabling and vital problem in patients with PD. It affects around 33% patients and culminates in sleep attacks (without prodroma) in 1 to 4% of the patients. When monitored, short, narcolepsy-like naps with abnormal intrusion of REM sleep during daytime (and hypnagogic hallucinations as wakeful dreams) are observed in 33-41% patients, while other patients display naps with non REM sleep. Although insomnia, sleep apnea and periodic leg movements are common in these patients, there is no clear link between the night events and the level of sleepiness. Patients treated with dopamine agonists are two to three fold more exposed to sleep attacks than those on levodopa, with large variability between patients. Sleepiness may exist, to a lesser degree, before the onset of parkinsonism and before the use of dopamine agents, suggesting that other, disease-dependant factors contribute to the sleepiness. Most arousal systems are indeed damaged in PD brains, including the locus coeruleus (noradrenalin), the pedunculo-pontine nucleus and the basal forebrain (acetylcholine), the median raphe (serotonin), and the lateral hypothalamus (orexin), while histamine dopamine arousal system are normal. Treating patients with stimulants such as modafinil is only partially efficacious, while trials of anti-H3 drugs and sodium oxybate seem more active. Eventually, the recent stimulation of the pedunculopontine nucleus has stimulant or sedative effects in patients, depending on the frequency of stimulation. These results provide new insights into the mechanisms of arousal in PD.