Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Previous studies have established that rare biallelic SYNJ1 mutations cause autosomal recessive parkinsonism and Parkinson's disease (PD). We analyzed 8165 PD cases, 818 early-onset-PD (EOPD, < 50 years) and 70,363 controls. Burden meta-analysis revealed an association between rare nonsynonymous variants and variants with high Combined Annotation-Dependent Depletion score (> 20) in the Sac1 SYNJ1 domain and PD (Pfdr = 0.

Conscious experiences during non-rapid eye movement sleep parasomnias.

Disorders of Arousal (DOA) are non-rapid eye movement (NREM) parasomnias traditionally regarded as unconscious states. However, recent research challenges this assumption. This narrative review aims to explore the presence and qualitative features of conscious experiences in patients with DOA during their episodes.

Comparative efficacy, safety and benefit/risk of alerting agents for excessive daytime sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.

Background: Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA.

RESTORE: Once-nightly oxybate dosing preference and nocturnal experience with twice-nightly oxybates.

Objective/background: Preference for extended-release, once-nightly sodium oxybate (ON-SXB, FT218) vs twice-nightly immediate-release (IR) oxybate was assessed in participants switching from IR oxybate to ON-SXB in an open-label/switch study, RESTORE (NCT04451668).

Patients/methods: Participants aged ≥16 years with narcolepsy who completed the phase 3 REST-ON trial, were oxybate-naive, or were on a stable IR oxybate dose (≥1 month) were eligible for RESTORE. For participants who switched from twice-nightly dosing to ON-SXB, initial doses were closest or equivalent to their previous nightly IR oxybate dose.

"I know when to stop": sentinels and counterstrategies against drowsy driving in narcolepsy and idiopathic hypersomnia.

Study Objectives: To collect prodromal symptoms experienced by participants with narcolepsy and idiopathic hypersomnia (considered "hypersomnolence experts") prior to drowsy driving and counterstrategies used to maintain alertness.

Methods: Systematic, face-to-face interview (using a semi-structured questionnaire), including clinical measures, frequency of car accidents/near misses, and symptoms experienced before impending drowsy driving episodes and counterstrategies.

Results: Among 61 participants (32 with narcolepsy, 29 with idiopathic hypersomnia; 56 drivers), 61% of drivers had at least one lifetime accident/near miss.

Barriers to therapy adherence in narcolepsy.

Background: Treatment adherence (TA) in narcolepsy is a complex phenomenon influenced by various factors beyond patient-related aspects. The management of narcolepsy involves non-pharmacological and symptomatic pharmacological treatment. Factors such as chronic daytime sleepiness, cognitive deficits, psychiatric comorbidities and adverse effects of pharmacological treatment are aspects of narcolepsy that could undermine TA, impacting patients' ability or willingness to consistently follow treatment plans.

Are rare heterozygous variants associated with Parkinson's disease?

Previous studies have suggested that rare biallelic mutations may cause autosomal recessive parkinsonism and Parkinson's disease (PD). Our study explored the impact of rare variants in non-familial settings, including 8,165 PD cases, 818 early-onset PD (EOPD, <50 years) and 70,363 controls. Burden meta-analysis using optimized sequence Kernel association test (SKAT-O) revealed an association between rare nonsynonymous variants in the Sac1 SYNJ1 domain and PD (P=0.

Effectiveness of an intervention program on physical activity in children with narcolepsy type 1.

Objectives: Physical activity (PA) is recommended as part of the management of narcolepsy type 1 (NT1). This study aimed at 1) characterizing PA in children and adolescents treated for NT1 using objective and subjective measurements, 2) evaluating how PA is associated with NT1 symptoms and comorbidities, and 3) evaluating the effects of an Adapted Physical Activity (APA) program on PA and clinical characteristics.

Patients/methods: Patients with NT1 from the National Reference Center of Narcolepsy (Lyon, France) were consecutively included in an APA intervention protocol.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Variants in the gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis.

Narcolepsy type 1 and Sydenham chorea - Report of 3 cases and review of the literature.

Objectives/background: Narcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1.

Pitolisant-supported bridging during drug holidays to deal with tolerance to modafinil in patients with narcolepsy.

Study Objectives: Modafinil is a common treatment for excessive daytime sleepiness (EDS) in narcolepsy. The long-term use of modafinil can lead to tolerance with the loss of efficacy and the continuous increase of its dose. Pharmacological strategies to deal with the tolerance to modafinil are lacking.

Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.

DNA methyltransferase type 1 (DNMT1) is a major enzyme involved in maintaining the methylation pattern after DNA replication. Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). We used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to explore the epigenomic and transcriptomic effects of mutations in DNMT1.

The immunopathogenesis of narcolepsy type 1.

Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing.

Association of Rare Variants in ARSA with Parkinson's Disease.

Background: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear.

Objectives: To study rare ARSA variants in PD.

Methods: To study rare ARSA variants (minor allele frequency < 0.

Association of rare variants in with Parkinson's disease.

Background: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and , which encodes for the enzyme arylsulfatase A, remains controversial.

Objectives: To evaluate the association between rare variants and PD.

Methods: To study possible association of rare variants (minor allele frequency<0.