부산대학교 도서관

Purpose: 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. Patients and Methods: 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. Results: The mean age at EDS onset and diagnosis of our patients was 20.9[ + or -]11.8 (mean [ + or -] standard deviation) and 30.5[ + or -]14.9 years old, respectively. Their mean and median diagnostic delay was 9.7[ + or -]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 ([less than or equal to]2-year) and long ([greater than or equal to]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. Conclusion: 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. Keywords: cataplexy, diagnostic delay, misdiagnosis, symptom onset, machine learning
Introduction Narcolepsy is a chronic neurological sleep disorder and considered a rare disease with an estimated prevalence of 0.02-0.07% worldwide. (1,2) Irresistible or imperative excessive daytime sleepiness (EDS) is usually [...]