CSF-profile and hypocretin levels in children with narcolepsy type 1 and 2.

Background: Narcolepsy is a rare neurological disease caused by dysfunction of hypocretin-producing neurons. Hypocretin concentrations in the cerebrospinal fluid (CSF) of less than 110 pg/ml are considered pathological in adults.
Objectives: To compare hypocretin levels of children with narcolepsy type 1, type 2 and disease control groups, in addition to a detailed CSF analysis, clinical and polysomnographic parameters.
Methods: In a retrospective, cross-sectional study, children diagnosed with narcolepsy based on clinical and polysomnographic parameters, who received a CSF analysis and hypocretin measurement, in addition to controls, were included. CSF was analyzed for the presence of cells, total protein, lactate, intrathecal synthesis of antibodies against measles, rubella and/or varicella zoster, and oligoclonal bands. All children had a complete sleep study including a multiple sleep latency test (MSLT).
Results: 49 children with narcolepsy type 1, 15 children with type 2 and 37 children with other (suspected) neurological diseases were included. CSF routine analysis did not reveal any differences between the three groups. All children with narcolepsy type 1 had hypocretin levels of less than 110 pg/ml (range: 10-101 pg/ml). Hypocretin levels in type 2 patients ranged from 43 to 436 pg/ml (median 157 pg/ml). The median hypocretin level in the control cohort was 365 pg/ml (range: 153-583 pg/ml). In 4 children with narcolepsy type 2 the diagnosis was changed to narcolepsy level 1 because of a CSF hypocretin level of less than 110 pg/ml according to the recently proposed criteria, which consider the measurement of hypocretin in CSF.
Conclusion: Children with narcolepsy type 1 showed significantly lower CSF hypocretin levels than children with narcolepsy type 2 and controls. As suggested by the recently published narcolepsy criteria, hypocretin levels of less than 110 pg/ml should be used as an additional criterion for the presence of narcolepsy type 1 in children.
Competing Interests: Declaration of competing interest M.Otto received research support from the EU Joint Programm neurodegenerative diseases networks Genfi-Prox, the EU (MOOD-MARKER), the German Research Foundation/DFG (SFB1279), the foundation of the state Baden-Württemberg D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009) and the Thierry Latran Foundation. M. Otto gave scientific advice to Roche, Biogen, Axon, and Fujirebio. K.Rostasy received honoraria from UCB, Horizon, and Euroimmun, and serves as Consultant for Roche in the Operetta2 trial. A.Bertolini received travel funds from Octapharma, honoraria for the advisory board through Horizon. E.Wendel received travel funds from UCB. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)