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Sleep and circadian alterations are common in patients with Huntington’s disease (HD). Understanding the pathophysiology of these alterations and their association with disease progression and morbidity can guide HD management. We provide a narrative review of the clinical and basic-science studies centered on sleep and circadian function on HD. Sleep/wake disturbances among HD patients share many similarities with other neurodegenerative diseases. Overall, HD patients and animal models of the disease present with sleep changes early in the clinical course of the disease, including difficulties with sleep initiation and maintenance leading to decreased sleep efficiency, and progressive deterioration of normal sleep architecture. Despite this, sleep alterations remain frequently under-reported by patients and under-recognized by health professionals. The degree of sleep and circadian alterations has not consistently shown to be CAG dose-dependent. Evidence based treatment recommendations are insufficient due to lack of well-designed intervention trials. Approaches aimed at improving circadian entrainment, such as including light therapy, and time-restricted feeding have demonstrated a potential to delay symptom progression in some basic HD investigations. Larger study cohorts, comprehensive assessment of sleep and circadian function, and reproducibility of findings are needed in future in order to better understand sleep and circadian function in HD and to develop effective treatments.

Spinal anesthesia and peripheral nerve block anesthesia are used in total knee replacement. The aim of the study was to examine whether peripheral nerve block anesthesia would provide a more stable hemodynamic profile and analgesic effect in elderly patients undergoing total knee replacement, as compared to spinal anesthesia. This is a single-center case-control trial, with patients from our prospectively followed registry. The patients were divided into two groups, those with peripheral nerve block anesthesia and spinal anesthesia. Propensity score analysis was performed in 1:1 ratio. The primary outcome was analgesia with total analgesic effect and the secondary outcome was intraoperative hemodynamic status. The patients in peripheral nerve block anesthesia group had a longer length of analgesia (606.19±219.35 vs 359.48±106.82, P<0.01) and pain scores during 24h and 48h after the surgery were lower in the same group of patients (3.21±1.74 vs 5.02±2.23, P=0.037; 3.03±1.57 vs 5.67±2.51, P=0.028). Spinal anesthesia group had a larger number of patients with significant hypotension (3.84% vs 15.38%, P=0.01), as well as a larger number of patients who received vasopressors (0% vs 9.61%, P<0.01). Both anesthesia methods demonstrated sufficient analgesic efficacy in total knee replacement, although there was less pain severity and longer analgesic effect of peripheral nerve block anesthesia in patients who were 60 years old or older. Spinal anesthesia showed a significantly higher degree of hypotension than in those patients receivingperipheral nerve block anesthesia.

The previous year was another great success for the open source integrated circuit (IC) design ecosystem. It finished with two actions: the second IEEE Solid-State Circuits Society (SSCS) PICO open source IC design contest, known as the Chipathon, and the first Code-a-Chip travel grant award. The second Chipathon installment in 2022 attracted 55 teams across the globe, out of which volunteers selected 22 outstanding proposals. The finishing line was reached by 14 teams at the end of November (see the summaries in Figure 1 and Table 1), after months of global joint action, including weekly technical checkup meetings and conversations on the bustling IEEE-SSCS-DC-22 Slack channel.

There are currently no effective biomarkers for diagnosing Parkinson’s disease (PD) or tracking its progression. Here, we developed an artificial intelligence (AI) model to detect PD and track its progression from nocturnal breathing signals. The model was evaluated on a large dataset comprising 7,671 individuals, using data from several hospitals in the United States, as well as multiple public datasets. The AI model can detect PD with an area-under-the-curve of 0.90 and 0.85 on held-out and external test sets, respectively. The AI model can also estimate PD severity and progression in accordance with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (R= 0.94, P= 3.6 × 10–25). The AI model uses an attention layer that allows for interpreting its predictions with respect to sleep and electroencephalogram. Moreover, the model can assess PD in the home setting in a touchless manner, by extracting breathing from radio waves that bounce off a person’s body during sleep. Our study demonstrates the feasibility of objective, noninvasive, at-home assessment of PD, and also provides initial evidence that this AI model may be useful for risk assessment before clinical diagnosis.

Graphical Abstract

Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson’s disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. We hypothesized that gait disturbances in people with mild to moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

Sleep disorders are common among PD patients and affect quality of life. They are often under-recognized and under-treated. Mechanisms of sleep disorders in PD remain relatively poorly understood. Improved awareness of common sleep problems in PD. Tailored treatment and evidence for efficacy are lacking. The purpose of this review is to provide an overview and update on the most common sleep disorders in PD. We review specific features of the most common sleep disorders in PD, including insomnia, excessive daytime sleepiness, sleep-disordered breathing, restless legs syndrome, circadian rhythm disorders and REM sleep behavior disorders.

The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD represents an early prodromal stage of synucleinopathy when neuropathology may be more responsive to treatment. While clonazepam and melatonin are most commonly used as symptomatic treatments for RBD, clinical trials of symptomatic treatments are also needed to identify evidence-based treatments. A comprehensive framework for both disease-modifying and symptomatic treatment trials in RBD is described, including potential treatments in the pipeline, cost-effective participant recruitment and selection, study design, outcomes and dissemination of results. For disease-modifying treatment clinical trials, the recommended primary outcome is phenoconversion to an overt synucleinopathy, and stratification features should be used to select a study population at high risk of phenoconversion, to enable more rapid clinical trials. For symptomatic treatment clinical trials, objective polysomnogram-based measurement of RBD-related movements and vocalisations should be the primary outcome measure, rather than subjective scales or diaries. Mobile technology to enable objective measurement of RBD episodes in the ambulatory setting, and advances in imaging, biofluid, tissue, and neurophysiological biomarkers of synucleinopathies, will enable more efficient clinical trials but are still in development. Increasing awareness of RBD among the general public and medical community coupled with timely diagnosis of these diseases will facilitate progress in the development of therapeutics for RBD and associated neurodegenerative disorders.

This article focuses on irregular sleep-wake rhythm disorder (ISWRD) and its associations with several other comorbidities. Irregular sleep-wake rhythm disorder is a circadian disorder characterized by a lack of a clear sleep-wake pattern. The disorder has yet to be fully understood from pathophysiologic perspective. Treatments are available, but there is a need for development of novel interventions. The goal of this article is to focus on multiple aspects of ISWRD.

The aim of this study was to evaluate the effectiveness of a mobile augmented reality simulator for local anesthesia training with dental students who are administering inferior alveolar nerve block (IANB) for the first time. Participants in this prospective study conducted in 2016 were 41 fourth‐ and fifth‐year students randomly divided into two groups: a control group with 19 students and an experimental group with 22 students. In addition to theoretical instruction and exercises, students in the experimental group used the mobile augmented reality simulator in a dental office 2h weekly for four weeks. The Sony SmartBand‐2 was used to measure all students' heart rate five minutes before and during anesthesia administration. After anesthesia, students in both groups completed a post‐clinical questionnaire evaluating their knowledge and skills. The experimental group had a higher average score and/or a more limited range of responses on each item of the questionnaire than the control group. The average time for performing IANB in the experimental group was 50.0±14.3 seconds, while the control group's average was 68.4±25.5 seconds. In addition, the group that used the augmented reality simulator had an anesthesia success rate of 90.9% compared to 73.7% for the control group. Students in both groups had a statistically significant increase in heart rate while performing anesthesia. Overall, the students who used the mobile simulator in addition to their education in augmented reality carried out anesthetic procedures for IANB in a shorter period of time and had greater success than the students who used only the conventional educational methods.

Provides society information that may include news, reviews or technical notes that should be of interest to practitioners and researchers.

Provides society information that may include news, reviews or technical notes that should be of interest to practitioners and researchers.

So-called idiopathic rapid eye movement (REM) sleep behaviour disorder (RBD), formerly seen as a rare parasomnia, is now recognized as the prodromal stage of an α-synucleinopathy. Given the very high risk that patients with idiopathic RBD have of developing α-synucleinopathies, such as Parkinson disease (PD), PD dementia, dementia with Lewy bodies or multiple system atrophy, and the outstandingly high specificity and very long interval between the onset of idiopathic RBD and the clinical manifestations of α-synucleinopathies, the prodromal phase of this disorder represents a unique opportunity for potentially disease-modifying intervention. This Review provides an update on classic and novel biomarkers of α-synuclein-related neurodegeneration in patients with idiopathic RBD, focusing on advances in imaging and neurophysiological, cognitive, autonomic, tissue-specific and other biomarkers. We discuss the strengths, potential weaknesses and suitability of these biomarkers for identifying RBD and neurodegeneration, with an emphasis on predicting progression to overt α-synucleinopathy. The role of video polysomnography in providing quantifiable and potentially treatment-responsive biomarkers of neurodegeneration is highlighted. In light of all these advances, and the now understood role of idiopathic RBD as an early manifestation of α-synuclein disease, we call for idiopathic RBD to be reconceptualized as isolated RBD.

IMPORTANCE: Impaired sleep and alertness are some of the most common nonmotor manifestations of Parkinson disease (PD) and currently have only limited treatment options. Light therapy (LT), a widely available treatment modality in sleep medicine, has not been systematically studied in the PD population. OBJECTIVE: To determine the safety and efficacy of LT on excessive daytime sleepiness (EDS) associated with PD. DESIGN, SETTINGS, AND PARTICIPANTS: This randomized, placebo-controlled, clinical intervention study was set in PD centers at Northwestern University and Rush University. Participants were 31 patients with PD receiving stable dopaminergic therapy with coexistent EDS, as assessed by an Epworth Sleepiness Scale score of 12 or greater, and without cognitive impairment or primary sleep disorder. Participants were randomized 1:1 to receive bright LT or dim-red LT (controlled condition) twice daily in 1-hour intervals for 14 days. This trial was conducted between March 1, 2007, and October 31, 2012. Data analysis of the intention-to-treat population was conducted from November 1, 2012, through April 30, 2016. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in the Epworth Sleepiness Scale score comparing the bright LT with the dim-red LT. Secondary outcome measures included the Pittsburgh Sleep Quality Index score, the Parkinson’s Disease Sleep Scale score, the visual analog scale score for daytime sleepiness, and sleep log–derived and actigraphy-derived metrics. RESULTS: Among the 31 patients (13 males and 18 females; mean [SD] disease duration, 5.9 [3.6] years), bright LT resulted in significant improvements in EDS, as assessed by the Epworth Sleepiness Scale score (mean [SD], 15.81 [3.10] at baseline vs 11.19 [3.31] after the intervention). Both bright LT and dim-red LT were associated with improvements in sleep quality as captured by mean (SD) scores on the Pittsburg Sleep Quality Index (7.88 [4.11] at baseline vs 6.25 [4.27] after bright LT, and 8.87 [2.83] at baseline vs 7.33 [3.52] after dim-red LT) and the Parkinson’s Disease Sleep Scale (97.24 [22.49] at baseline vs 106.98 [19.37] after bright LT, and 95.11 [19.86] at baseline vs 99.28 [16.94] after dim-red LT). Bright LT improved several self-reported mean (SD) sleep metrics, including sleep fragmentation (number of overnight awakenings, 1.51 [1.03] at baseline vs 0.92 [0.97] after the intervention), sleep quality (sleep diary score, 3.03 [1.01] at baseline vs 3.53 [0.91] after the intervention), and ease of falling asleep (sleep diary score, 2.32 [0.89] at baseline vs 1.83 [0.88] after the intervention). Light therapy was associated with increased daily physical activity as assessed by actigraphy (average activity [SD] counts, 165.01 [66.87] at baseline vs 194.59 [87.81] after the intervention). CONCLUSIONS AND RELEVANCE: Light therapy was well tolerated and may be a feasible intervention for improving the sleep-wake cycles in patients with PD. Further studies are required to determine optimal parameters of LT for PD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01338649

Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects over one million individuals in the US alone. PD is characterized by a plethora of motor and non-motor manifestations, resulting from a progressive degeneration of dopaminergic neurons and disbalance of several other neurotransmitters. A growing body of evidence points to significant alterations of the circadian system in PD. This is not surprising given the pivotal role that dopamine plays in circadian regulation as well as the role of circadian influences in dopamine metabolism. In this review we present basic and clinical investigations that examined the function of the circadian system in PD.

BackgroundExcessive daytime sleepiness (EDS) is common and disabling in Parkinson’s disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD.MethodsThe Parkinson’s Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS.ResultsESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio.ConclusionsIn early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers.

Circadian rhythms have a major role in physiology and behavior. Circadian disruption has negative consequences for physiologic homeostasis at molecular, cellular, organ-system, and whole-organism levels. The onset of many cerebrovascular insults shows circadian temporal trends. Impaired sleep-wake cycle, the most robust output rhythms of the circadian system, is significantly affected by neurodegenerative disorders, may precede them by decades, and may also affect their progression. Emerging evidence suggests that circadian disruption may be a risk factor for these neurologic disorders. This article discusses the implications of circadian rhythms in brain disorders, with an emphasis on cerebrovascular and neurodegenerative disorders.

Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep–wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep–wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep–wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep–wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases.

IMPORTANCE Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. OBJECTIVE To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson’s Disease and Movement Disorders Center of Northwestern University. INTERVENTIONS Twenty-four hour monitoring of serum melatonin secretion. MAIN OUTCOMES AND MEASURES Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. RESULTS Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P &lt; .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson’s Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. CONCLUSIONS AND RELEVANCE Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.

The paper reports on hardness of thin amorphous films of the Cux(As38·5Se54I7·5)100–xtype for x?=?10, 15, 20 and 25 at- evaluated by microindentation measurements and instrumented nanoindentation testing. Values of determined microhardness are in the interval of 748–1137 MPa, while nanohardness are in the interval of 930–1591 MPa and can be regarded as moderate in the category of chalcogenide glasses. Isotropic mechanical properties on thin films surface are determined. Influence of copper on mechanical properties of As–Se–I films is discussed in terms of possible structural units in glass matrix.

Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.

The objective of this cross-sectional study was to test the hypothesis that patients with Parkinson disease (PD) and freezing of gait (PDFOG) would demonstrate sleep disturbances comparable to those seen in patients with REM sleep behavior disorder (RBD) and these changes would be significantly different from those in PD patients without FOG (PD-FOG) and age-matched controls.

Purpose:This article reviews the recent advances in understanding of the fundamental properties of circadian rhythms and discusses the clinical features, diagnosis, and treatment of circadian rhythm sleep disorders (CRSDs).

Parkinson disease (PD) is usually managed through outpatient clinical care. Reasons for hospital admissions are either directly related to PD or may reflect comorbidities. When hospitalized, patients with PD may face many challenges. Most commonly these are related to medication management, falls, mental status changes, infections, and emergence of psychiatric symptoms. Timely recognition and proper management of PD-specific hospitalization-related problems may be delayed, given the common lack of expertise in PD management of hospital physicians, nurses, and allied health professionals. With increasing prevalence of PD, it is expected that more patients will require inpatient hospital care. It is therefore very important to recognize problems that may arise upon hospitalization of a patient with PD and provide education to health care professionals involved in the inpatient care of patients with PD. This approach may lead to reductions in complication rates and duration of hospital stays. Aim: In this review, we outline the most common reasons for hospitalization of patients with PD, discuss challenges related to inpatient hospital care of patients with PD, and comment on future directions aimed at optimizing hospitalization outcomes in the population with PD.

Respiratory tract involvement occurs at some time during the course of most patients with sarcoidosis. There are many articles on lung function impairment in sarcoidosis, but the definite, unique guideline considering the correlation between the clinical, radiologic, and biochemical findings of the disease is lacking. During the last few years, most of the literature has focused on follow-up studies, presenting primarily the effects of the treatment on lung function impairment in patients with sarcoidosis. This study focuses on airflow impairment, diffusion impairment, and bronchial hyperresponsiveness in sarcoidosis. The topic has already been explored, but this time the authors emphasize lung function impairment and its correlation with the course of the disease. Considering the course of sarcoidosis, a significantly higher number of patients with diffusion impairment have the chronic form of the disease. The bronchial challenge test (BCT) was performed in patients with chronic sarcoidosis at the time they experienced relapse of disease activity. A high number of patients with positive BCT is significant in light of their disease. Further analyses, not only functional, but immunologic, are necessary to examine the potential correlation between positive BCT and the activity of sarcoidosis.