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Summary Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep‐related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep‐related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non‐sleep‐related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep‐onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin‐receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep. [ABSTRACT FROM AUTHOR]

Abstract Objectives To investigate whether cerebrospinal fluid (CSF) and serum ferritin levels differ between patients with narcolepsy type 1 (NT1) comorbid with restless legs syndrome (RLS) or periodic leg movements during sleep (PLMS), and patients with NT1 or controls without comorbid RLS or PLMS. Methods Sixty‐six drug‐free patients with NT1 (44 males, age 38.5 years [14–81]) were enrolled, including 20 with RLS, 18 with PLMS index ≥15/h (six with both RLS and PLMS). Thirty‐eight drug‐free patients (12 males, age 22.5 years [12–61]) referred for sleepiness complaint, but without central hypersomnia, RLS, PLMS were included as controls. Clinical, electrophysiological and biological (CSF/serum ferritin, orexin [ORX]) data were quantified. Results NT1 patients with and without RLS did not differ for age, gender, and body mass index (BMI). No between‐group differences were found for CSF ferritin, ORX, and serum ferritin levels. No CSF ferritin, ORX, and serum ferritin level differences were found between NT1 patients with and without PLMS, or with RLS or PLMS versus not. CSF‐ferritin levels were not different between NT1 and controls in adjusted analyses. CSF‐ferritin levels in the whole population correlated positively with age, serum‐ferritin, BMI, negatively with ORX, but not with PLMS index. In NT1, CSF‐ferritin levels correlated with age and serum‐ferritin but not with PLMS. Conclusion The absence of CSF ferritin deficiency in NT1 with comorbid RLS or PLMS indicates normal brain iron levels in that condition. This result suggests that the frequent association between RLS, PLMS, and NT1 is not based on alterations in brain iron metabolism, a pathophysiological mechanism involved in primary RLS.

The diagnosis of sleep disorders such as narcolepsy and insomnia currently requires experts to interpret sleep recordings (polysomnography). Here, the authors introduce a neural network analysis method for polysomnography that could reduce time spent in sleep clinics and automate narcolepsy diagnosis.

The article discusses the pharmacological management of narcolepsy in children and adolescents. It highlights the need for safe and effective treatments for young people with narcolepsy and mentions the European guidelines on the management of narcolepsy in adults and children. The article focuses on the efficacy and safety of pitolisant, a drug that has been approved by the European Medicine Agency for the treatment of narcolepsy in children and adolescents. It mentions a clinical trial that showed significant improvements in narcolepsy symptoms with pitolisant compared to a placebo. The article concludes by emphasizing the importance of early treatment for narcolepsy to prevent long-term consequences. [Extracted from the article]

Background: A rectal sub-region (SRR) has been previously identified by voxel-wise analysis in the inferior-anterior part of the rectum as highly predictive of rectal bleeding (RB) in prostate cancer radiotherapy. Translating the SRR to patient-specific radiotherapy planning is challenging as new constraints have to be defined. A recent geometry-based model proposed to optimize the planning by determining the achievable mean doses (AMDs) to the organs at risk (OARs), taking into account the overlap between the planning target volume (PTV) and OAR. The aim of this study was to quantify the SRR dose sparing by using the AMD model in the planning, while preserving the dose to the prostate.Material and Methods: Three-dimensional volumetric modulated arc therapy (VMAT) planning dose distributions for 60 patients were computed following four different strategies, delivering 78 Gy to the prostate, while meeting the genitourinary group dose constraints to the OAR: (i) a standard plan corresponding to the standard practice for rectum sparing (STDpl), (ii) a plan adding constraints to SRR (SRRpl), (iii) a plan using the AMD model applied to the rectum only (AMD_RECTpl), and (iv) a final plan using the AMD model applied to both the rectum and the SRR (AMD_RECT_SRRpl). After PTV dose normalization, plans were compared with regard to dose distributions, quality, and estimated risk of RB using a normal tissue complication probability model.Results: AMD_RECT_SRRpl showed the largest SRR dose sparing, with significant mean dose reductions of 7.7, 3, and 2.3 Gy, with respect to the STDpl, SRRpl, and AMD_RECTpl, respectively. AMD_RECT_SRRpl also decreased the mean rectal dose by 3.6 Gy relative to STDpl and by 3.3 Gy relative to SRRpl. The absolute risk of grade ≥1 RB decreased from 22.8% using STDpl planning to 17.6% using AMD_RECT_SRRpl considering SRR volume. AMD_RECT_SRRpl plans, however, showed slightly less dose homogeneity and significant increase of the number of monitor units, compared to the three other strategies.Conclusion: Compared to a standard prostate planning, applying dose constraints to a patient-specific SRR by using the achievable mean dose model decreased the mean dose by 7.7 Gy to the SRR and may decrease the relative risk of RB by 22%.

Background: Despite cognitive-behavioral therapy for insomnia (CBT-I) being the recommended treatment for insomnia disorder, its access remains very limited. Automated Internet-delivered CBT-I (eCBT-I) is an emerging cost-effective strategy for adults with insomnia, however no such program is currently available in French Language. We evaluated a French-speaking, eCBT-I intervention to improve insomnia disorder in comparison to minimal psychoeducation therapy (mPT).Methods: Forty-six adults with insomnia disorder were randomly allocated to eCBT-I or mPT. The eCBT-I program consisted of seven sessions that delivered the typical components of CBT-I during 12 weeks. The mPT provided structured and non-tailored information about sleep and insomnia during a 1 h session. Insomnia severity Index (ISI, primary outcome), measures of fatigue, sleepiness, anxiety, depressive symptoms and quality of life were collected at baseline and endpoint. Electronic sleep diaries were completed over 2 week periods pre- and post-intervention.Results: Compared to mPT, eCBT-I resulted in greater decrease in ISI scores between baseline and endpoint. Sleep diaries parameters improved in both groups, with a greater improvement in the eCBT-I group. Patients allocated to eCBT-I group also improved depressive, fatigue, anxiety symptoms, and quality of life. Among patients with CNS-active drug at baseline, 91.7% reduced or stopped their hypnotic medication, and 16.7% in the mPT group.Conclusions: The present eCBT-I program seems feasible, acceptable and effective in reducing insomnia severity and insomnia-related functional outcomes in this small clinically-derived population. Given the high prevalence of insomnia, our data are supportive of the use of such program as an effective alternative to treat insomnia in daily clinical practice in French speaking countries.

Abstract The pathophysiology of rapid eye movement sleep behavior disorder (RBD) associated with narcolepsy type 1 (NT1) is still poorly understood, potentially distinct from idiopathic RBD (iRBD), but may share affected common pathways. We investigated whether MIBG cardiac uptake differs between iRBD and NT1 comorbid with RBD. Thirty-four patients with NT1-RBD and 15 patients with iRBD underwent MIBG cardiac scintigraphy. MIBG uptake was measured by calculating the early and delayed heart to mediastinum (H/M) ratios. A delayed H/M ratio lower than 1.46 was considered abnormal based on a population of 78 subjects without neurological or cardiac diseases. Patients with iRBD were older, had an older RBD onset age and higher REM sleep phasic and tonic muscular activities than NT1-RBD. Lower delayed and early H/M ratios were associated with iRBD, but not with NT1-RBD, in crude and adjusted associations. The delayed H/M ratio differed between iRBD and controls, after adjustment, but not between patients with NT1-RBD and controls. In conclusion, the MIBG cardiac uptake difference between NT1-RBD and iRBD supports the hypothesis of different processes involved in RBD pathogenesis, providing for the first time a cardiac biomarker to differentiate those disorders.

Summary: Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra‐tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea–hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure‐treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea–hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea–hypopnea index. Sixty‐one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post‐stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham‐continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea–hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep. [ABSTRACT FROM AUTHOR]