Idling for Decades: A European Study on Risk Factors Associated with the Delay Before a Narcolepsy Diagnosis.

Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990-2018) and the factors associated with the delay in Europe. We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay. The mean age at EDS onset and diagnosis of our patients was 20.9±11.8 (mean ± standard deviation) and 30.5±14.9 years old, respectively. Their mean and median diagnostic delay was 9.7±11.5 and 5.3 (interquartile range: 1.7-13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤2-year) and long (≥13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay. Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.

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© 2022 Zhang et al.

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Prof. Dr. Giuseppe Plazzi reports personal fees from Jazz Pharmaceuticals, Takeda, Idorsia, and Bioprojet, outside the submitted work. Dr Gert Jan Lammers reports grant for investigator initiated study, consultancy, and/or Member Advisory Board from Jazz Pharmaceuticals, UCB Pharma, and Bioprojet Pharma, outside the submitted work. Dr Sebastiaan Overeem reports consulting fees paid to institution from Bioproject, Takeda, Jazz Pharmaceuticals, and UCB Pharma, outside the submitted work. Dr Karel Sonka reports grants from Czech Ministry of Health, during the conduct of the study; personal fees for consulting fees or clinical trial fees from AOP Orphan, Jazz, Flamel-Avadel, and Sanofi, outside the submitted work. Prof. Dr. Birgit Högl reports speaker fees from Abbvie and Jazz, and consulting fees from Lundbeck, outside the submitted work. Dr Lucie Barateau reports funding for seminars from Bioprojet and Jazz, board engagement fees from Takeda, and travel reimbursements for conferences from UCB Pharma, outside the submitted work. Dr Rolf Fronczek reports grants and/or personal fees from Bioprojet for lecture fee and advisory board, research grant (co-applicant), research grants as co-applicant from Jazz Pharma, personal fees from Takeda for advisory board, outside the submitted work. The authors report no other conflicts of interest in this work.