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Sleep Jul 2023This White Paper addresses the current gaps in knowledge, as well as opportunities for future studies in pediatric sleep. The Sleep Research Society's Pipeline...
This White Paper addresses the current gaps in knowledge, as well as opportunities for future studies in pediatric sleep. The Sleep Research Society's Pipeline Development Committee assembled a panel of experts tasked to provide information to those interested in learning more about the field of pediatric sleep, including trainees. We cover the scope of pediatric sleep, including epidemiological studies and the development of sleep and circadian rhythms in early childhood and adolescence. Additionally, we discuss current knowledge of insufficient sleep and circadian disruption, addressing the neuropsychological impact (affective functioning) and cardiometabolic consequences. A significant portion of this White Paper explores pediatric sleep disorders (including circadian rhythm disorders, insomnia, restless leg and periodic limb movement disorder, narcolepsy, and sleep apnea), as well as sleep and neurodevelopment disorders (e.g. autism and attention deficit hyperactivity disorder). Finally, we end with a discussion on sleep and public health policy. Although we have made strides in our knowledge of pediatric sleep, it is imperative that we address the gaps to the best of our knowledge and the pitfalls of our methodologies. For example, more work needs to be done to assess pediatric sleep using objective methodologies (i.e. actigraphy and polysomnography), to explore sleep disparities, to improve accessibility to evidence-based treatments, and to identify potential risks and protective markers of disorders in children. Expanding trainee exposure to pediatric sleep and elucidating future directions for study will significantly improve the future of the field.
Topics: Adolescent; Humans; Child; Child, Preschool; Sleep; Polysomnography; Narcolepsy; Restless Legs Syndrome; Circadian Rhythm; Sleep Wake Disorders
PubMed: 36881684
DOI: 10.1093/sleep/zsad060 -
Australian Journal of General Practice Sep 2023Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting.
BACKGROUND
Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting.
OBJECTIVE
This article outlines the epidemiology, pathophysiology, diagnosis and management of RLS, with a focus on the primary care setting.
DISCUSSION
RLS is a clinical diagnosis, although mimics exist. Brain iron deficiency, dopaminergic dysfunction and genetics underpin the poorly understood pathophysiology of this common condition. After repleting iron stores, reviewing any exacerbating medications and attending to non-pharmacological management options, there are pharmacological options that prove to be effective, although with class-specific effects that need to be considered.
Topics: Humans; Restless Legs Syndrome; Dopamine; Iron Deficiencies
PubMed: 37666782
DOI: 10.31128/AJGP-02-23-6722 -
Brain : a Journal of Neurology Aug 2023The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of...
The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.
Topics: Humans; Parkinson Disease; Lewy Body Disease; REM Sleep Behavior Disorder; Prospective Studies; Disease Progression; Biomarkers; Prodromal Symptoms
PubMed: 36881989
DOI: 10.1093/brain/awad072 -
JAMA Neurology Jan 2024Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase.
IMPORTANCE
Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase.
OBJECTIVE
To investigate whether α-synuclein in neuronally derived serum-extracellular vesicles identifies individuals at risk of developing PD and related dementia.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, cross-sectional multicenter study of serum samples included the Oxford Discovery, Marburg, Cologne, and Parkinson's Progression Markers Initiative cohorts. Participants were recruited from July 2013 through August 2023 and samples were analyzed from April 2022 through September 2023. The derivation group (n = 170) included participants with isolated rapid eye movement sleep behavior disorder (iRBD) and controls. Two validation groups were used: the first (n = 122) included participants with iRBD and controls and the second (n = 263) included nonmanifest GBA1N409S gene carriers, participants with iRBD or hyposmia, and available dopamine transporter single-photon emission computed tomography, healthy controls, and patients with sporadic PD. Overall the study included 199 participants with iRBD, 20 hyposmic participants with available dopamine transporter single-photon emission computed tomography, 146 nonmanifest GBA1N409S gene carriers, 21 GBA1N409S gene carrier patients with PD, 50 patients with sporadic PD, and 140 healthy controls. In the derivation group and validation group 1, participants with polysomnographically confirmed iRBD were included. In the validation group 2, at-risk participants with available Movement Disorder Society prodromal markers and serum samples were included. Among 580 potential participants, 4 were excluded due to alternative diagnoses.
EXPOSURES
Clinical assessments, imaging, and serum collection.
MAIN OUTCOME AND MEASURES
L1CAM-positive extracellular vesicles (L1EV) were immunocaptured from serum. α-Synuclein and syntenin-1 were measured by electrochemiluminescence. Area under the receiver operating characteristic (ROC) curve (AUC) with 95% CIs evaluated biomarker performance. Probable prodromal PD was determined using the updated Movement Disorder Society research criteria. Multiple linear regression models assessed the association between L1EV α-synuclein and prodromal markers.
RESULTS
Among 576 participants included, the mean (SD) age was 64.30 (8.27) years, 394 were male (68.4%), and 182 were female (31.6%). A derived threshold of serum L1EV α-synuclein distinguished participants with iRBD from controls (AUC = 0.91; 95% CI, 0.86-0.96) and those with more than 80% probability of having prodromal PD from participants with less than 5% probability (AUC = 0.80; 95% CI, 0.71-0.89). Subgroup analyses revealed that specific combinations of prodromal markers were associated with increased L1EV α-synuclein levels. Across all cohorts, L1EV α-synuclein differentiated participants with more than 80% probability of having prodromal PD from current and historic healthy control populations (AUC = 0.90; 95% CI, 0.87-0.93), irrespective of initial diagnosis. L1EV α-synuclein was increased in at-risk participants with a positive cerebrospinal fluid seed amplification assay and was above the identified threshold in 80% of cases (n = 40) that phenoconverted to PD or related dementia.
CONCLUSIONS AND RELEVANCE
L1EV α-synuclein in combination with prodromal markers should be considered in the stratification of those at high risk of developing PD and related Lewy body diseases.
Topics: Female; Humans; Male; Middle Aged; alpha-Synuclein; Biomarkers; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Extracellular Vesicles; Lewy Body Disease; Parkinson Disease; REM Sleep Behavior Disorder; Retrospective Studies
PubMed: 38048087
DOI: 10.1001/jamaneurol.2023.4398 -
Journal of Personalized Medicine Jan 2024The relationship between sleep and epilepsy is bidirectional. Certain epilepsy syndromes predominantly or exclusively manifest during sleep, with seizures frequently... (Review)
Review
The relationship between sleep and epilepsy is bidirectional. Certain epilepsy syndromes predominantly or exclusively manifest during sleep, with seizures frequently originating from non-rapid eye movement (NREM) sleep. Interictal epileptiform discharges observed on electroencephalograms are most likely to be activated during the deep NREM sleep stage known as N3. Conversely, epileptiform discharges, anti-seizure medications (ASMs), as well as other anti-seizure therapies can exert detrimental effects on sleep architecture. Moreover, the co-occurrence of sleep disorders has the potential to exacerbate seizure control. Understating the relationship between sleep and epilepsy is crucial for healthcare providers. Addressing and managing sleep-related problems in individuals with epilepsy can potentially contribute to improved seizure control and overall well-being. At the same time, improving seizure control can improve sleep quality and quantity, thus further improving the health of individuals with epilepsy.
PubMed: 38276240
DOI: 10.3390/jpm14010118