CSF orexin A (hypocretin-1) is decreased or absent in narcoleptic patients with cataplexy. Researchers at Christian-Albrechts University Kiel, Germany, analyzed olfactory sensation of 10 adult patients and 10 controls. Orexin-A was applied intranasally in 7 of the patients, and odor detection thresholds for 2-phenyl-ethyl alcohol were measured. Patients showed significantly lower scores for olfactory threshold, discrimination, and identification, separately, and for the total scores. In all patients, the odor detection olfactory threshold score increased after intranasal orexin A compared to placebo. Lack of CNS orexin is involved in the pathophysiological mechanism underlying olfactory dysfunction in narcolepsy. 
COMMENT. Orexin A and B are neuropeptides synthesizd by neurons in and around the lateral hypothalamus and olfactory tract. Orexin is involved in sleep wake regulation. Olfactory dysfunction, an early predictor of Parkinsonism, is also a sign of narcolepsy with cataplexy. Correction of the associated orexin A defciency in the CSF by intranasal administration will restore the olfactory sensation of patients with narcolepsy. The authors comment that orexin A intranasally is, theoretically, a promising treatment for narcolepsy and may be considered for future trial.