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Objective: We validated the Narcolepsy Severity Scale (NSS) in adults with narcolepsy type 1 (NT1) to quantify the severity, frequency, and consequences of the 5 key narcolepsy symptoms over the last month, and we now developed the Pediatric NSS (NSS-P); thus, the aims of this study were to assess NSS-P psychometric properties, validity, and reliability, and to evaluate its responsiveness to treatment in a well-characterized sample of children and adolescents with NT1., Methods: The NSS was reformulated for children, and the item about driving was removed. The total score of the 14-item NSS-P ranges from 0 to 54, and higher scores reflect more severe disease. Children and adolescents (n = 209, 6-17 years of age) with NT1 diagnosed in 2 Reference Centers for Narcolepsy in France were consecutively asked to fill in the NSS-P. The scale was fully and correctly completed by 160 (10-18 years of age, 68 untreated). Moreover, 65 participants completed it twice (33 before/during treatment, and 32 under the same treatment). The NSS-P psychometric properties, score changes before/during treatment, and convergent validity with other clinical parameters were assessed., Results: The NSS-P showed adequate psychometric properties with significant item-total score correlations. Factor analysis indicated a 4-factor solution with good reliability. The NSS-P score was lower in treated than untreated patients with a mean difference of 3.71 ± 1.45, with a minimum clinically important difference between untreated and treated patients in the longitudinal sample estimated at 4 points. Four severity levels were defined (mild, moderate, severe, very severe) with between-group differences related to treatment. The NSS-P total score was associated with self-reported sleepiness, insomnia, and depressive symptoms. Its temporal stability was satisfactory., Discussion: We validated a brief instrument to assess NT1 symptom frequency, severity, and consequences in ≥10-year-old children and adolescents with 4 clinically relevant severity score ranges. This scale constitutes a relevant tool to improve and provide guidance for NT1 management in pediatric populations. The ease of administration, its good psychometric properties, and its sensitivity to detect symptom changes after treatment ensure future use of the NSS-P in clinical and research settings., (© 2021 American Academy of Neurology.)

Aim: The aim of the present study was to characterize patterns of use of methylphenidate (MPH), a prescription stimulant medication recommended in the treatment of attention deficit hyperactivity disorder (ADHD) and of narcolepsy, in France, both in children and adults, over a 3-year period., Methods: Using the French General Health Insurance database, limited to two areas covering approximately 4 million individuals, we made up a cohort of incident MPH users between July 2010 and June 2013. Splitting them into distinct age groups (18-24, 25-49 and ≥50 years of age for adults and <6, 6-11 and 12-17 years of age for children), we established the characteristics of these populations at MPH initiation and during follow-up according to the duration of treatment, quantities dispensed and coprescription with central nervous system (CNS) drugs., Results: We included a cohort of 3534 incident users, involving 30 238 dispensings of MPH, leading to an annual rate of 29 incident users per 100 000 in 2013. Children (66% of new users) were characterized by long-term use of MPH with few comedications. The group of 25-49-year-old patients were dispensed MPH more frequently than other groups, had the highest mean dose and were more often coprescribed other CNS drugs. The ≥50 year-old group was more often coprescribed antidepressants and antiparkinsonian drugs., Conclusions: Our pharmacoepidemiological study involving incident MPH users with a large number of characteristics showed different patterns of MPH use among children and adults. The results from the 25-49-year-old group suggested that MPH might be being used for medical conditions other than ADHD or narcolepsy in adults, and that it might be subject to misuse and/or abuse., (© 2018 The British Pharmacological Society.)

Objective: Deep-tendon reflexes are abolished during generalized cataplexy, but whether this is the case in partial cataplexy currently remains unknown. Partial cataplexy may mimic other neurologic/psychiatric phenomena, and knowledge of the reflexes status may provide information for differential diagnosis. We assessed whether deep-tendon reflexes are persistent during partial cataplexy., Methods: Five drug-free patients with typical diagnoses of narcolepsy and clear-cut partial cataplexy were diagnosed in Reference Narcolepsy Centers in France and Italy. Biceps and patellar reflexes were elicited by physicians in charge and video-documented during cataplexy. Reflexes were assessed several times for each patient in different conditions and for various localizations of cataplexy., Results: The absence of tendon reflexes and complete loss of muscle tone during generalized cataplexy was confirmed, but the persistence of those reflexes during several partial cataplectic attacks at different ages, gender, localization of cataplexy (upper limbs, face) and reflexes (biceps, patellar) in drug-naive or withdrawal conditions was documented., Conclusion: The persistence of tendon reflexes during several partial cataplexy episodes contrasts with their absence during generalized cataplexy. This discovery has clinical implications: the persistence of tendon reflexes does not rule out cataplexy diagnosis for partial attacks, whereas their transient abolishment or persistence during generalized attacks indicates cataplexy or pseudocataplexy, respectively., (Copyright © 2018. Published by Elsevier B.V.)

(1) Narcolepsy is characterised by sudden, overwhelming daytime drowsiness, sometimes associated with cataplexy (more or less complete loss of muscle tone during an emotional reaction). (2) Modafinil moderately reduces daytime drowsiness but has no effect on cataplexy. Methylphenidate, an amphetamine psychostimulant, seems to act on both drowsiness and cataplexy, although its clinical evaluation is limited to observational series. (3) Oxybic acid, long used in general anaesthesia, but also misused for recreational and criminal purposes (chemical or drug-induced submission), has been approved to treat adults with both narcolepsy and cataplexy, in the form of an oral solution of sodium oxybate. (4) The rationale behind the use of sodium oxybate is to re-establish a near-normal pattern of the different phases of sleep. Because of its short-lasting action, sodium oxybate has to be taken once at bedtime and then again 2.5 to 4 hours later. (5) Clinical evaluation mainly consists of 4 double-blind placebo-controlled trials of sodium oxybate. Three short-term trials, involving 136 patients treated for 4 weeks and 228 and 270 patients treated for 8 weeks, showed that sodium oxybate at a dose of 4.5 g to 9 g a day reduced the number of cataplexy attacks but that a dose of at least 6 g was needed to reduce daytime drowsiness. A trial involving 56 patients who had been taking sodium oxybate for nearly 2 years, assessed the effects of stopping versus continuing treatment. The results suggest that sodium oxybate is effective in the long term. (6) During clinical trials, 61% of patients had adverse effects attributed to sodium oxybate. These included gastrointestinal disorders (nausea (18%)), neurological disorders (dizziness (15%), headache (6%)), confusion (3%), and enuresis (7%). (7) Altered consciousness and respiratory depression occurred after a single intake of a dose two or three times higher than the recommended dose. (8) Misuse, especially to obtain chemical or drug-induced submission (i.e. as a 'date rape' drug), is facilitated by the odourless and colourless nature of the oral solution. (9) In practice, for some patients who are seriously affected by persistent episodes of cataplexy or drowsiness, despite treatment of narcolepsy, sodium oxybate is preferable to methylphenidate, which has been less thoroughly evaluated. However, the risks of misuse and overdose mean that this drug should only be proposed to patients in whom the benefits are likely to outweigh the risks.

Study Objectives: To publish the first English translations, with commentary, of the original reports describing narcolepsy and cataplexy by Westphal in German (1877) and by Gélineau in French (1880)., Methods: A professional translation service translated the 2 reports from either German or French to English, with each translation then being slightly edited by one of the authors. All authors then provided commentary., Results: Both Westphal and Gélineau correctly identified and described the new clinical entities of cataplexy and narcolepsy, with recurrent, self-limited sleep attacks and/or cataplectic attacks affecting 2 otherwise healthy people. Narcolepsy was named by Gélineau (and cataplexy was named by Henneberg in 1916). The evidence in both cases is sufficiently convincing to conclude that they were likely each HLA-DQB1*0602 positive and hypocretin deficient., Conclusions: The original descriptions of narcolepsy and cataplexy are now available in English, allowing for extensive clinical and historical commentary.

Objective: To measure the effect of age on Multiple Sleep Latency Test (MSLT)characteristics, sleep latency, and number of sleep-onset REM periods (SOREMP) in two large populations of narcoleptic patients with similar genetic backgrounds., Methods: Clinical and polygraphic information on the severity of the condition was obtained on 236 well-defined narcolepsy-cataplexy-human leukocyte antigen DR2-positive patients from Montpellier (France) and on 147 similar patients from Montreal (Canada)., Results: The results show a progressive decrease in the number of SOREMP with age and a progressive increase in the mean sleep latency on the MSLT as a function of age. This finding is also related to the severity of cataplexy as assessed from the clinical history with a progressive decrease in the frequency of cataplexy attacks with age. These results may reflect the progressive increase in sleep latency seen in normal aging and suggest that clinical improvement might be due to changes in the neural mechanisms responsible for SOREMP, which may weaken with age., Conclusions: The progressive decrease in the number of SOREMP and increase in the mean sleep latency on the MSLT as a function of age suggest that the current criteria used for diagnosis may be too stringent in older patients. The major influence of age on MSLT results should therefore be taken into account when diagnosing a narcoleptic patient.

Study Objectives: The aim of the study was to describe the clinical and polygraphical characteristics of narcoleptics, with and without cataplexy and to assess HLA predisposition across two different ethnic populations., Design and Setting: Patients were 126 men and 58 women referred to the Montpellier Sleep Disorders Center (Mtp) and 12 men and 8 women referred to the Fort-de-France Sleep Disorders Center (FdF) (Martinique, a French West Indy island) with symptoms of narcolepsy., Participants: Narcoleptics were included if they had both excessive daytime sleepiness and clear-cut cataplexy (for the group with cataplexy), a mean sleep latency of less than 8 minutes and at least two sleep onset REM periods., Interventions: N/A., Measurements and Results: Narcolepsy without clear-cut cataplexy was rare (12/172) in the Mtp population whereas it was as frequent as full-blown narcolepsy (10/10) in the FdF population. Comparison between narcoleptics with cataplexy from the Mtp and FdF populations revealed a younger age of onset, a trend towards more severe sleepiness and lower frequency of cataplexy in Martinicans. Comparison between narcoleptics without cataplexy from the Mtp and FdF population revealed a higher frequency of hypnagogic hallucinations and sleep paralysis and a trend towards more severe sleepiness in Martinicans. 4.2% of the Mtp and 15% of the FdF patients were negative for HLA DR2. However all of them were positive for HLA DQ1. Moreover, a tight association with HLA DRB1*1503 was observed in Martinicans in contrast with DRB1*1501 in the Mtp population. Association with HLA DQB1*0602 was observed in 99.4% of narcoleptics with cataplexy and in 89.5% of those without cataplexy., Conclusions: Narcolepsy is a heterogeneous clinical syndrome, the more so as ethnic origins are considered. A modulating effect of HLA and non-HLA genes on symptoms disease may explain these differences.

Background: Narcolepsy usually starts around adolescence; however, there is great variability in the clinical presentation of narcolepsy., Objective: To determine the age at onset in conjunction with severity of narcoleptic symptoms in two large populations of narcoleptic patients with a similar genetic background., Methods: Information on age at onset and severity of the condition was obtained in 317 patients with well-defined narcolepsy-cataplexy from Montpellier (France) and in 202 from Montreal (Canada)., Results: The mean age at onset was 23.4 years in Montpellier and 24.4 in Montreal. The age at onset was bimodal in two independent patient populations: a first peak occurring at 14.7 years, and a second peak occurring at 35. Age at onset clearly differentiates patients with a positive family history of narcolepsy (early onset) from those without a family history. Other clinical and polygraphic findings may indicate that young age at onset is associated with increased severity of the condition (higher frequency of cataplexy and decreased mean sleep latency on the Multiple Sleep Latency Test)., Conclusion: Bimodal distribution of age at onset of narcolepsy was found in two independent patient populations. Our data suggest that age at onset is genetically determined.