CSF Profile and Hypocretin in Children with Narcolepsy

Background/Purpose: Narcolepsy is a rare autoimmune disease of hypocretin-producing neurons. Decreased hypocretin concentrations in CSF are an important diagnostic marker. In adults, a value <110 pg/mL is considered pathological, and valid norms in childhood do not exist. Our aim is to compare hypocretin levels of narcolepsy patients with a control group to establish an additional diagnostic marker, as well as to perform a systematic examination of the CSF.

Methods: In a retrospective and prospective, cross-sectional, open-label, controlled study, children <18 years diagnosed with narcolepsy and hypocretin determination or with other noninflammatory CNS disease (control group) were included. CSF was also analyzed for intrathecal antibodies to common pathogens and oligoclonal immunoglobulin G, and the Reiber regimen was determined.

Results: Thirty-eight children with narcolepsy and 33 children in the comparison cohort were included. 38 (100%) of the narcolepsy patients had a hypocretin level <110 pg/mL, 18(47%) ≤40 pg/mL (detection limit of most laboratories) (range: 10–96 pg/mL). The median hypocretin level in the comparison cohort was 371 pg/mL, (range: 196–583 pg/mL). Of 21 narcolepsy patients with determination of intrathecal antibodies, 95% were negative. Oligoclonal bands were detected in only 8% (2 of 24). In the whole group (38) 13.2% showed elevated proteins and 26.3% elevated lactate. In the Reiber scheme, 14% each showed barrier dysfunction or specific antibody synthesis.

Conclusion: Children with narcolepsy showed significantly lower hypocretin levels in CSF than the comparison cohort. Thus, the hypocretin threshold of 110 pg/mL is also a good marker for narcolepsy in children and may be helpful with the diagnosis. In the extended CSF diagnostics, neither intrathecal antibodies against pathogens nor oligoclonal bands were found in large numbers, and all other abnormalities always affected less than one-fourth of the patients.

Publication History

Article published online:
28 October 2021