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.