Temporal changes in the Cerebrospinal Fluid Level of Hypocretin-1 and Histamine in Narcolepsy

STUDY OBJECTIVES: To follow the temporal changes of cerebrospinal fluid biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. METHODS: From 2007 to 2015, 170 HLA DQB1*06:02-positive patients with primary narcolepsy and definite (n=155, 95 males, 36 children) or atypical cataplexy (n=15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively. Cerebrospinal fluid hypocretin-1 (n=6) and histamine/tele-methylhistamine (n=5) levels were assessed twice (median interval: 14.4 months) in four patients with definite and two with atypical cataplexy and hypocretin level >100pg/ml at baseline. . RESULTS: Cerebrospinal fluid hypocretin levels decreased from normal/intermediate to undetectable levels in three of the four patients with definite cataplexy and remained stable in the other (>250 pg/ml). Hypocretin level decreased from 106 to 27 pg/ml in one patient with atypical cataplexy, and remained stable in the other (101 and 106 pg/ml). Cerebrospinal fluid histamine and tele-methylhistamine levels remained stable, but for one patient showing increased frequency of cataplexy and a strong decrease (-72.5%) of tele-methylhistamine levels several years after disease onset. No significant association was found between relative or absolute change in hypocretin level and demographic/clinical features. CONCLUSIONS: These findings show that in few patients with narcolepsy with cataplexy, symptoms and cerebrospinal fluid marker levels can change over time. In these rare patients with cataplexy without baseline hypocretin deficiency, cerebrospinal fluid markers should be monitored over time with potential for immune therapies in early stages to try limiting hypocretin neuron loss.

2016
  • Lopez R
  • Barateau L
  • Evangelista E
  • Chenini S
  • Robert P
  • Jaussent I
  • Dauvilliers Y

CallNum: 

4.59
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  • Sleep
Sep 9;25():82