Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1

Hoeven, A.E. van der; Fronczek, R.; Schinkelshoek, M.S.; Roelandse, F.W.C.; Bakker, J.A.; Overeem, S.; ... ; Lammers, G.J. (2022)

Article / Letter to editor

Study Objectives: The diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level <= 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111-200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence. Methods: Retrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type ("typical" or "atypical" cataplexy). Results:  Compared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings. Conclusion: Individuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1.

• orexin-A
• cataplexy
• sleep disorder
• central disorders of hypersomnolence

• All authors: Hoeven, A.E. van der; Fronczek, R.; Schinkelshoek, M.S.; Roelandse, F.W.C.; Bakker, J.A.; Overeem, S.; Bijlenga, D.; Lammers, G.J.
• Date: 2022-03-07
• Journal: SLEEP
• Volume: 45
• Issue: 5
• DOI: doi:10.1093/sleep/zsac052