RESUMEN
Patients with Parkinson's disease often complain of excessive daytime sleepiness which negatively impacts their quality of life. The pedunculopontine nucleus, proposed as a target for deep brain stimulation to improve freezing of gait in Parkinson's disease, is also known to play a key role in the arousal system. Thus, the putative control of excessive daytime sleepiness by pedunculopontine nucleus area stimulation merits exploration for treating Parkinson's disease patients. To this end, two adult nonhuman primates (macaca fascicularis) received a deep brain stimulation electrode implanted into the pedunculopontine nucleus area along with a polysomnographic equipment. Stimulation at low frequencies and high frequencies was studied, in healthy and then MPTP-treated nonhuman primates. Here, we observed that MPTP-treated nonhuman primates suffered from excessive daytime sleepiness and that low-frequency stimulation of the pedunculopontine nucleus area was effective in reducing daytime sleepiness. Indeed, low-frequency stimulation of the pedunculopontine nucleus area induced a significant increase in sleep onset latency, longer continuous periods of wakefulness and thus, a partially restored daytime wake architecture. These findings may contribute to the development of new therapeutic strategies in patients suffering from excessive daytime sleepiness.
RESUMEN
Parkinsonian patients often experience sleep/wake disturbances, which may appear at an early stage of the disease; however, these disturbances have not been fully described. To better understand the evolution of these disturbances with respect to disease progression, we aimed to characterize these clinical signs in a progressive nonhuman primate model of Parkinson's disease. Three adult macaques (Macaca fascicularis) were equipped with a polysomnographic telemetry system allowing the characterization of sleep/wake behavior via long-term neurophysiological recordings and underwent a modified multiple sleep latency test. Experiments were first performed in a healthy state and then during the progressive induction of a parkinsonian syndrome by intramuscular injections of low doses of MPTP. We observed an early onset of significant sleep/wake disturbances (i.e., before the appearance of motor symptoms). These disturbances resulted in (i) a disorganization of nighttime sleep with reduced deep sleep quality and (ii) an excessive daytime sleepiness characterized by sleep episodes occurring more rapidly in the morning and spreading through the middle of the day. The present study suggests that nighttime and daytime sleep/wake disturbances may appear early in the disease and should be considered in the development of biomarkers in further studies.