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

Maike Josler; Ines El Naggar; Annikki Bertolini; Patrizia Kutz; Claudia Roll; Eva-Maria Wendel; Bernhard Schlüter; Andreas Hahn; Sandy Siegert; Anette Hackenberg; Sameer M Zuberi; Markus Otto; Kevin Rostásy

doi:10.1016/j.ejpn.2024.08.003

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

Eur J Paediatr Neurol. 2024 Aug 17:53:1-7. doi: 10.1016/j.ejpn.2024.08.003. Online ahead of print.

Authors

Affiliations

¹ Pediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Germany.
² Neonatology, Pediatric Intensive Care, Sleep Medicine, Children's Hospital Datteln, Witten/Herdecke University, Germany.
³ Department of Pediatric Neurology, Olgahospital / Klinikum Stuttgart, Stuttgart, Germany.
⁴ Pediatric Neurology, University Hospital Gießen, Gießen, Germany.
⁵ Pediatric Neurology, University Hospital for Pediatric and Adolescent Medicine, Medical University Vienna, Vienna, Austria.
⁶ Pediatric Neurology, University Childrens' Hospital Zürich, Zürich, Switzerland.
⁷ Pediatric Neurosciences Research Group, Royal Hospital for Children & School of Health & Wellbeing, University of Glasgow, Scotland, UK.
⁸ Department of Neurology, Medical University Halle, Halle an der Saale, Germany.
⁹ Pediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Germany. Electronic address: k.rostasy@kinderklinik-datteln.de.

PMID: 39226768
DOI: 10.1016/j.ejpn.2024.08.003

Abstract

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.

Keywords: CSF; Children; Hypocretin; Narcolepsy.