The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome

Context: Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like symptoms, such as sleep-onset rapid eye movement sleep and cataplexy, independent of obesity-related sleep disturbances, which suggests a disorder of the hypocretin neurons. Objective: We hypothesized that the narcolepsy-like symptoms in PWS are caused by a decline in the number of hypocretin neurons. Design: We estimated the number of hypocretin neurons in postmortem hypothalami using immunocytochemistry and an image analysis system. Setting: This study was conducted at the Netherlands Institute for Brain Research. Patients: Eight PWS adults, three PWS infants, and 11 controls were studied. Main Outcome Measure: The total number of hypocretin neurons in the lateral hypothalamus was measured. Results: There was no significant difference in the total number of hypocretin-containing neurons among the seven PWS patients ( in whom sufficient hypothalamic material was available to quantify total cell number) and seven age-matched controls, either in adults or in infants. A significant decline with age was found in adult PWS patients (r = -0.9; P = 0.037). Conclusions: We conclude that a decrease in the number of hypocretin neurons does not play a major role in the occurrence of narcolepsy-like symptoms in PWS.