NARCOLEPSY IS characterized by sleepiness and abnormal rapid eye movement (REM) sleep events such as cataplexy, hypnagogic hallucinations, and sleep paralysis.^1-3 Prevalence is in 0.02% to 0.05% of the population,^4,5 with onset generally occuring in adolescence.^1-3 Quality of life is as impaired as in epilepsy or depression.⁶ Most cases are sporadic, but twin and family studies demonstrate the existence of genetic factors.^1,5 Current treatment involves psychostimulants for sleepiness and antidepressants for cataplexy.^2,7 γ-Hydroxybutyrate is used to consolidate nocturnal sleep and reduce cataplexy.^2,7,8

Research from JAMA Neurology — Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men — A Randomized Clinical Trial

The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th–75th percentile). We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821–31 229); controls: 36 842 (32 546–50 938); P = 0.016); (ii) the hypocretin-1 concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0–448.3); controls: 483.5 (433.5–512.3); P = 0.012) and (iii) the hypocretin-1 concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2–652.2); controls: 676.6 (467.5–883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin-1 concentration in the prefrontal cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.