Rethinking clinical trials in restless legs syndrome: A roadmap.

The number of large clinical trials of restless legs syndrome (RLS) have decreased in recent years, this coincides with reduced interest in developing and testing novel pharmaceuticals. Therefore, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force of global experts to examine the causes of these trends and make recommendations to facilitate new clinical trials. In our article, we delve into potential complications linked to the diagnostic definition of RLS, identify subpopulations necessitating more attention, and highlight issues pertaining to endpoints and study frameworks.

Prevalence and Course of Idiopathic Hypersomnia in the Wisconsin Sleep Cohort Study.

Background And Objectives: Idiopathic hypersomnia (IH) is a CNS disorder of hypersomnolence of unknown etiology. Due to the requirement for objective sleep testing to diagnose the disorder, there are currently no population-based estimates of the prevalence of IH nor data regarding the longitudinal course of IH in naturalistic settings.

Methods: Subjective and objective data from the Wisconsin Sleep Cohort study were used to identify cases with probable IH from participants with polysomnography and multiple sleep latency test data.

Repeated polysomnography and multiple sleep latency test in narcolepsy type 1 and other hypersomnolence disorders.

Background: The diagnosis of narcolepsy is based on clinical information, combined with polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT). PSG and the MSLT are moderately reliable at diagnosing narcolepsy type 1 (NT1) but unreliable for diagnosing narcolepsy type 2 (NT2). This is a problem, especially given the increased risk of a false-positive MSLT in the context of circadian misalignment or sleep deprivation, both of which commonly occur in the general population.

Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study.

Study Objectives: Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S.

Changed epidemiology of narcolepsy before, during, and after the 2009 H1N1 pandemic: a nationwide narcolepsy surveillance network study in mainland China, 1990-2017.

Study Objectives: Increased incidence of narcolepsy was reported in children during the 2009 H1N1 pandemic following Pandemrix, a H1N1 flu vaccine. A link with A(H1N1) pdm09 infections remains controversial. Using nationwide surveillance data from China (1990 to 2017), the epidemiology of narcolepsy was analyzed.

Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia.

Purpose: To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia.

Patients And Methods: Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18-75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10-14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP).

Validation of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) questionnaire in pediatric patients with narcolepsy with cataplexy aged 7-16 years.

Objective/background: The Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) measures daytime sleepiness, but had not previously been validated in children <12 years of age.

Patients/methods: Data from a sodium oxybate (SXB) study in pediatric participants with narcolepsy with cataplexy (ClinicalTrials.gov, NCT02221869) were used in this validation study.

Development of a lower-sodium oxybate formulation for the treatment of patients with narcolepsy and idiopathic hypersomnia.

Introduction: Sodium oxybate (SXB) is a standard of care for cataplexy, excessive daytime sleepiness, and disrupted nighttime sleep in narcolepsy. At recommended dosages in adults (6-9 g/night), SXB increases daily dietary intake of sodium by 1100-1640 mg. Because excess sodium intake is associated with increased blood pressure and cardiovascular risk, an oxybate formulation containing 92% less sodium than SXB (lower-sodium oxybate; LXB) was developed to provide an alternative oxybate treatment option.

Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study.

Background And Objectives: To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.

Methods: We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.

Results: We identified 46 patients with GFAP antibodies.

Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis.

Objective: Antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) characterize a limbic encephalitis (LE) strongly associated with HLA-DRB1*07:01, although some patients lack LGI1-Abs in CSF or do not carry this allele. Whether they represent a different subtype of disease or have different prognoses is unclear.

Methods: Retrospective analysis of clinical features, IgG isotypes, and outcome according to LGI1-Ab CSF positivity and DRB1*07:01 in a cohort of anti-LGI1 LE patients.

T cell reactivity to regulatory factor X4 in type 1 narcolepsy.

Type 1 narcolepsy is strongly (98%) associated with human leukocyte antigen (HLA) class II DQA1*01:02/DQB1*06:02 (DQ0602) and highly associated with T cell receptor (TCR) alpha locus polymorphism as well as other immune regulatory loci. Increased incidence of narcolepsy was detected following the 2009 H1N1 pandemic and linked to Pandemrix vaccination, strongly supporting that narcolepsy is an autoimmune disorder. Although recent results suggest CD4+ T cell reactivity to neuropeptide hypocretin/orexin and cross-reactive flu peptide is involved, identification of other autoantigens has remained elusive.

PSG Validation of minute-to-minute scoring for sleep and wake periods in a consumer wearable device.

Background: Actigraphs are wrist-worn devices that record tri-axial accelerometry data used clinically and in research studies. The expense of research-grade actigraphs, however, limit their widespread adoption, especially in clinical settings. Tri-axial accelerometer-based consumer wearable devices have gained worldwide popularity and hold potential for a cost-effective alternative.

Design of a deep learning model for automatic scoring of periodic and non-periodic leg movements during sleep validated against multiple human experts.

Objective: Currently, manual scoring is the gold standard of leg movement scoring (LMs) and periodic LMs (PLMS) in overnight polysomnography (PSG) studies, which is subject to inter-scorer variability. The objective of this study is to design and validate an end-to-end deep learning system for the automatic scoring of LMs and PLMS in sleep.

Methods: The deep learning system was developed, validated and tested, with respect to manual annotations by expert technicians on 800 overnight PSGs using a leg electromyography channel.

Validation of Multiple Sleep Latency Test for the diagnosis of pediatric narcolepsy type 1.

Objective: To validate polysomnographic markers (sleep latency and sleep-onset REM periods [SOREMPs] at the Multiple Sleep Latency Test [MSLT] and nocturnal polysomnography [PSG]) for pediatric narcolepsy type 1 (NT1) against CSF hypocretin-1 (hcrt-1) deficiency and presence of cataplexy, as no criteria are currently validated in children.

Methods: Clinical, neurophysiologic, and, when available, biological data (HLA-DQB1*06:02 positivity, CSF hcrt-1 levels) of 357 consecutive children below 18 years of age evaluated for suspected narcolepsy were collected. Best MSLT cutoffs were obtained by receiver operating characteristic (ROC) curve analysis by contrasting among patients with available CSF hcrt-1 assay (n = 228) with vs without CSF hcrt-1 deficiency, and further validated in patients without available CSF hcrt-1 against cataplexy (n = 129).

Factors associated with fatigue in patients with insomnia.

Although fatigue is common in insomnia, the clinical associates of fatigue in patients with insomnia are largely unknown. We aimed to investigate the clinical associates of fatigue in patients with insomnia. Patients visiting the Stanford Sleep Medicine Center completed the Insomnia Severity Index (ISI), Insomnia Symptom Questionnaire (ISQ), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9).

Solriamfetol for the Treatment of Excessive Sleepiness in OSA: A Placebo-Controlled Randomized Withdrawal Study.

Background: Excessive sleepiness (ES) is a common symptom of OSA, which often persists despite primary OSA therapy. This phase III randomized withdrawal trial evaluated solriamfetol (JZP-110) for the treatment of ES in adults with OSA.

Methods: After 2 weeks of clinical titration (n = 174) and 2 weeks of stable dose administration (n = 148), participants who reported improvement on the Patient Global Impression of Change (PGI-C) and had numerical improvements on the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) were randomly assigned to placebo (n = 62) or solriamfetol (n = 62) for 2 additional weeks.

Periodic limb movements in sleep: Prevalence and associated sleepiness in the Wisconsin Sleep Cohort.

Objectives: Periodic limb movements in sleep (PLMS) are thought to be prevalent in elderly populations, but their impact on quality of life remains unclear. We examined the prevalence of PLMS, impact of age on prevalence, and association between PLMS and sleepiness.

Methods: We identified limb movements in 2335 Wisconsin Sleep Cohort polysomnograms collected over 12 years.

Melatonin receptor type 1A gene linked to Alzheimer's disease in old age.

Disruption of the circadian rhythms is a frequent preclinical and clinical manifestation of Alzheimer's disease. Furthermore, it has been suggested that shift work is a risk factor for Alzheimer's disease. Previously, we have reported association of intolerance to shift work (job-related exhaustion in shift workers) with a variant rs12506228A, which is situated close to melatonin receptor type 1A gene (MTNR1A) and linked to MTNR1A brain expression levels.

Multiplex family with GAD65-Abs neurologic syndromes.

Objective: Neurologic autoimmune syndromes associated with anti-glutamate acid decarboxylase 65 antibodies (GAD65-Abs) are rare and mostly sporadic.

Methods: We describe a niece and her aunt with GAD65-Abs neurologic syndromes. High-resolution HLA typing of Class I and Class II alleles was performed using next-generation sequencing.