OBJECTIVE: To determine the role of CSF hypocretin-1 in narcolepsy with and 
without cataplexy, Kleine-Levin syndrome (KLS), idiopathic and other 
hypersomnias, and several neurological conditions.
PATIENTS: 26 narcoleptic patients with cataplexy, 9 narcoleptic patients without 
cataplexy, 2 patients with abnormal REM-sleep-associated hypersomnia, 7 patients 
with idiopathic hypersomnia, 2 patients with post-traumatic hypersomnia, 4 
patients with KLS, and 88 patients with other neurological disorders.
RESULTS: 23 patients with narcolepsy-cataplexy had low CSF hypocretin-1 levels, 
while one patient had a normal hypocretin level (HLA-DQB1*0602 negative) and the 
other two had intermediate levels (familial forms). One narcoleptic patient 
without cataplexy had a low hypocretin level. One patient affected with 
post-traumatic hypersomnia had intermediate hypocretin levels. The KLS patients 
had normal hypocretin levels while asymptomatic, but one KLS patient (also 
affected with Prader-Willi syndrome) showed a twofold decrease in hypocretin 
levels during a symptomatic episode. Among the patients without hypersomnia, two 
patients with normal pressure hydrocephalus and one with unclear central vertigo 
had intermediate levels.
CONCLUSION: Low CSF hypocretin-1 is highly specific (99.1%) and sensitive 
(88.5%) for narcolepsy with cataplexy. Hypocretin ligand deficiency appears not 
to be the major cause for other hypersomnias, with a possible continuum in the 
pathophysiology of narcolepsy without cataplexy and idiopathic hypersomnia. 
However, partial hypocretin lesions without low CSF hypocretin-1 consequences 
cannot be definitely excluded in those disorders. The existence of normal 
hypocretin levels in narcoleptic patients and intermediate levels in other rare 
aetiologies needs further investigation, especially for KLS, to establish the 
functional significance of hypocretin neurotransmission alterations.