Brainstem changes causing reversible RBD in patients with spontaneous intracranial hypotension: a longitudinal neuroimaging study.

OBJECTIVE: This study aimed to investigate the prevalence of REM sleep behavior disorder (RBD) in patients with spontaneous intracranial hypotension (SIH) and longitudinally assess the effects of epidural blood patch (EBP) treatment on brainstem structures using a neuroimaging approach. METHODS: Twenty-two participants (10 SIH patients and 12 controls) underwent 3-Tesla Magnetic Resonance Imaging (MRI) scans. Midbrain and pons areas were measured on T1-weighted scans at baseline in both groups and three months after the first EBP in SIH patients to determine any MRI structural changes. The RBD Single-Questionnaire was used to screen SIH patients with symptoms suggestive of RBD for polysomnographic (PSG) recording. RESULTS: Half of the SIH patients (5/10) exhibited PSG-confirmed RBD. Baseline evaluation revealed deep brain swelling (DBS) on MRI scans in SIH-RBD patients. Following EBP treatment, significant changes in midbrain and pons morphometry were associated with complete clinical remission of RBD. Cross-sectional analysis showed larger midbrain and pons areas in SIH patients (with and without RBD) compared to controls. A midbrain area of 200 mm2 was identified as a cut-off value distinguishing SIH patients (with and without RBD) from controls individually. Longitudinal analysis demonstrated lower midbrain areas at follow-up compared to baseline in SIH patients. DISCUSSION: The study suggests that brainstem morphometric changes may underlie reversible RBD in SIH patients. Midbrain area measurement could serve as a dynamic biomarker for SIH, particularly in the presence of RBD, offering insights for clinical practice.

Surface-Based Morphometry Analysis of the Cerebral Cortex in Patients With Probable Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

INTRODUCTION: Strong indications support the notion that idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) acts as a precursor to multiple α-synucleinopathies, including Parkinson's disease and dementia with Lewy bodies. Despite numerous investigations into the alterations in cortical thickness and the volume of subcortical areas associated with this condition, comprehensive studies on the cortical surface morphology, focusing on gyrification and sulcal depth changes, are scarce. The purpose of this research was to explore the cortical surface morphology in individuals with probable iRBD (piRBD), to pinpoint early-phase diagnostic markers. METHODS: This study included 30 piRBD patients confirmed using the RBD Screening Questionnaire (RBDSQ) and 33 control individuals selected from the Parkinson's Progression Markers Initiative (PPMI) database. They underwent neurophysiological tests and MRI scans. The FreeSurfer software was utilized to estimate cortical thickness (CTH), cortical and subcortical volumetry, local gyrification index (LGI), and sulcus depth (SD). Subsequently, these parameters were compared between the two groups. Additionally, linear correlation analysis was employed to estimate the relationship between brain morphological parameters and clinical parameters. RESULTS: Compared to the healthy control (HC), piRBD patients exhibited a significant reduction in CTH, LGI, and cortical volume in the bilateral superior parietal, lateral occipital, orbitofrontal, temporo-occipital, bilateral rostral middle frontal, inferior parietal, and precentral brain regions. Moreover, a significant and notable correlation was observed between CTH and Geriatric Depression Scale (GDS), letter-number sequencing (LTNS), the Benton Judgment of Line Orientation (BJLO) test, and the symbol digit modalities test (SDMT) in several brain regions encompassing the motor cortex. CONCLUSION: Patients with piRBD displayed widespread atrophy in various brain regions, predominantly covering the motor and sensory cortex. Furthermore, LGI could serve as a prognostic biomarker of disease's progression in piRBD.

Epidemiology and burden of chronic insomnia disorder in Europe: an analysis of the 2020 National Health and Wellness Survey.

INTRODUCTION: Chronic insomnia disorder (CID) is considered a significant worldwide public health concern; however, its exact burden is unknown. We estimate its prevalence across France, Germany, Italy, Spain, and the United Kingdom, and assess the economic and humanistic burden for a broader insomnia population. METHODS: This retrospective, cross-sectional, observational study used 2020 National Health and Wellness Survey (NHWS) data. Patients reporting insomnia were characterized to define CID. Health-related quality of life (HRQoL), work productivity, and healthcare resource use (HCRU) outcomes were assessed in four cohorts according to insomnia diagnosis and treatment status and examined using multivariable analyses according to Insomnia Severity Index categories. RESULTS: Among 62,319 respondents, 9,035 (21.2%) reported experiencing insomnia over the previous 12 months. CID prevalence rates were 5.5% to 6.7% across the five countries and 6.0% overall. HRQoL outcomes were persistently poorer in cohorts of patients diagnosed with insomnia than those with undiagnosed insomnia. Undiagnosed and treated insomnia patients reported the highest work presenteeism and total work productivity impairment and the highest number of emergency room and hospitalization visits than patients with insomnia (either treated or untreated). After adjusting for covariates, patients with severe insomnia reported significantly worse EQ-5D-5L utility scores, higher absenteeism and presenteeism rates, and more healthcare provider visits over the past 6 months than patients without insomnia (all p < 0.01). CONCLUSIONS: Our prevalence rates for CID align with published literature. A diagnosis of insomnia, use of sleep medications, and severity of insomnia are associated with poor quality of life, loss of work productivity, and higher HCRU, confirming the high unmet need and substantial humanistic and economic burden of CID.

Many people experience poor quality of sleep, also known as insomnia, due to difficulties falling asleep, staying asleep, or problems waking up too early. While this may be short-lived for some people, others may experience long-term issues with their sleep quality. However, our understanding of the number of people affected by long-term sleep issues, and the burden that this can cause, is poorly known. The aim of this study was to update estimates of the percentage of adults across France, Germany, Italy, Spain, and the United Kingdom who experience chronic insomnia. The burden of chronic insomnia was also assessed. Our results show that 5.5% to 6.7% of adults across the five countries experience chronic insomnia. Diagnosed and treated insomnia patients reported the poorest quality of life, decreased work productivity, and higher healthcare resource use. It was also apparent that people experiencing moderate to severe insomnia had poor outcomes on an ongoing basis, despite receiving treatment for their sleep problems. Consequently, the burden of insomnia is substantial and comparable in size to other notoriously debilitating conditions. We conclude that ongoing poor sleep quality is costly for patients, healthcare systems, employers, and society.

The paradoxical impact of periodic limb movements on isolated REM sleep behavior disorder patients.

Recently, the α-synuclein origin and connectome model described two types of Parkinson's disease: "brain-first" and "body-first" subtypes. We aimed to investigate the role of periodic limb movements during sleep (PLMS) in identifying these subtypes starting from a prodromal stage of α-synucleinopathies. 191 patients with isolated REM sleep behavior disorder (iRBD) underwent video-polysomnography (vPSG), questionnaires, clinical interview, and neuropsychological battery. Patients who presented PLMS index (PLMSi) > 15 were compared with patients presenting PLMSi ≤ 15 on clinical questionnaires, vPSG, and neuropsychological domains with age as a covariate. Correlations were performed between PLMSi and vPSG and neuropsychological domains in both groups of iRBD. 48.2% of patients presented PLMSi > 15. iRBD subgroup with PLMSi > 15 performed better than the iRBD subgroup with PLMSi ≤ 15 in the executive function domain. In patients with PLMSi > 15 negative correlations were observed between PLMSi and some neuropsychological domains (memory, language, and executive function). Moreover, this subgroup was older and their PLMSi was positively correlated with wake-after-sleep onset and inversely correlated with total sleep time and sleep efficiency, suggesting a detrimental effect of PLM on sleep also in this cohort. Patients with PLMSi > 15 are characterized by a more preserved cognitive status, despite a more disrupted sleep. PLMSi could be explored in longitudinal studies concerning the "brain-first" and "body-first" model.

Exploring sex differences in periodic leg movements during sleep across the lifespan of patients with restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) and periodic leg movements during sleep (PLMS) are prevalent sleep disorders with significant implications for health and well-being. While previous research has highlighted sex-related disparities in RLS and PLMS prevalence, comprehensive understanding of these differences across the lifespan remains limited. This study aims to explore sex differences in RLS and PLMS across diverse age groups, spanning ages 2 to over 80 years, and to investigate the underlying mechanisms influenced by sex hormones. METHODS: A retrospective analysis was conducted on drug-free patients diagnosed with RLS, including 95 females (age range: 2-83.2 years) and 89 males (age range: 2-79.5 years). Polysomnographic recordings were analyzed to assess leg movement activity, including PLMS index and Periodicity index. RESULTS: A more rapid increase in PLMS index was observed in women starting before age 10, plateauing lower than men until around age 55. An increase in women occurred after 55, lasting over a decade, while in men, PLMS index continued to rise after 75. Conversely, Periodicity index displayed a simpler pattern, increasing progressively from prepuberty to around 35 in males and 45-50 in females. Females maintained a slightly higher Periodicity index than males for over a decade after this age. CONCLUSION: These findings underscore the complex interplay between sex hormones, age, and sleep disorders, highlighting the need for tailored approaches to diagnosis and management across diverse demographic cohorts. Further research is warranted to elucidate the underlying mechanisms and develop targeted interventions to optimize sleep health outcomes.

Sleep disorders and Parkinson's disease: is there a right direction?

In the last years, the hypothesis of a close relationship between sleep disorders (SDs) and Parkinson's disease (PD) has significantly strengthened. Whether this association is causal has been also highlighted by recent evidence demonstrating a neurobiological link between SDs and PD. Thus, the question is not whether these two chronic conditions are mutually connected, but rather how and when this relationship is expressed. Supporting this, not all SDs manifest with the same temporal sequence in PD patients. Indeed, SDs can precede or occur concomitantly with the onset of the clinical manifestation of PD. This review discusses the existing literature, putting under a magnifying glass the timing of occurrence of SDs in PD-neurodegeneration. Based on this, here, we propose two possible directions for studying the SDs-PD relationship: the first direction, from SDs to PD, considers SDs as potential biomarker/precursor of future PD-neurodegeneration; the second direction, from PD to SDs, considers SDs as concomitant symptoms in manifest PD, mainly related to primary PD-neuropathology and/or parkinsonian drugs. Furthermore, for each direction, we questioned SDs-PD relationship in terms of risk factors, neuronal circuits/mechanisms, and impact on the clinical phenotype and disease progression. Future research is needed to investigate whether targeting sleep may be the winning strategy to treat PD, in the context of a personalized precision medicine.

Decreased Delta/Beta ratio index as the sleep state-independent electrophysiological signature of sleep state misperception in Insomnia disorder: A focus on the sleep onset and the whole night.

PURPOSE: Sleep State Misperception (SSM) is described as the tendency of Insomnia Disorder (ID) patients to overestimate Sleep Latency (SL) and underestimate Total Sleep Time (TST). Literature exploring topographical components in ID with SSM is scarce and does not allow us to fully understand the potential mechanisms underlying this phenomenon. This study aims to evaluate the existence of sleep EEG topography alterations in ID patients associated with SSM compared to Healthy Controls (HC), focusing on two distinct periods: the Sleep Onset (SO) and the whole night. METHODS: Twenty ID patients (mean age: 43.5 ± 12.7; 7 M/13F) and 18 HCs (mean age: 41.6 ± 11.9; 8 M/10F) underwent a night of Polysomnography (PSG) and completed sleep diaries the following morning upon awakening. Two SSM indices, referring to the misperception of SL (SLm) and TST (TSTm), were calculated by comparing objective and subjective sleep indices extracted by PSG and sleep diary. According to these indices, the entire sample was split into 4 sub-groups: ID +SLm vs HC -SLm; ID +TSTm vs HC -TSTm. RESULTS: Considering the SO, the two-way mixed-design ANOVA showed a significant main effect of Groups pointing to a decreased delta/beta ratio in the whole scalp topography. Moreover, we found a significant interaction effect for the sigma and beta bands. Post Hoc tests showed higher sigma and beta power in anterior and temporo-parietal sites during the SO period in IDs +SLm compared to HC -SLm. Considering the whole night, the unpaired t-test revealed in IDs +TSTm significantly lower delta power during NREM, and lower delta/beta ratio index during NREM and REM sleep compared to HCs -TSTm. Finally, we found diffuse significant negative correlations between SSM indices and the delta/beta ratio during SO, NREM, and REM sleep. CONCLUSION: The main finding of the present study suggests that higher SL overestimation and TST underestimation are both phenomena related to diffuse cortical hyperarousal interpreted as a sleep state-independent electrophysiological correlate of the SSM, both during the SO and the whole night.

Sex-based disparities in dopamine agonist response in patients with restless legs syndrome.

This study aimed to investigate sex-related differences in the response to ropinirole and pramipexole in patients with restless legs syndrome (RLS). By analysing clinical parameters and polysomnographic (PSG) findings, we sought to elucidate the potential factors related to sex disparities modulating treatment responses and sleep quality in RLS. A total of 41 drug-free patients with RLS, aged ≥18 years, underwent two consecutive nocturnal PSG recordings, without medication at baseline; before the second night, 26 patients received an oral dose of 0.25 mg pramipexole whereas 15 received 0.5 mg ropinirole. After each PSG recording, patients self-evaluated the severity of their previous night symptoms by means of an ad hoc visual analogue scale (VAS). At baseline, sleep efficiency and percentage of Stage N2 tended to be higher in females while wakefulness after sleep onset was significantly higher in males. After treatment, total leg movements during sleep (LMS), periodic LMS (PLMS), and periodicity indexes were significantly lower in females than in males. The VAS score was lower after treatment in all patients, without differences between the two sexes. This study demonstrates a higher acute responsiveness of PLMS to dopamine agonists (pramipexole and ropinirole) in females than in males with RLS. These findings might be explained by differential sex-related expression of dopamine receptors, especially D3, within the central nervous system. In addition, our findings provide translational hints toward a better tailored and sex-specific approach to the treatment of RLS associated with PLMS, with dopamine agonist possibly associated with a better outcome in females than in males.

Gait Analysis and Magnetic Resonance Imaging Characteristics in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection. OBJECTIVE: The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients. METHODS: Thirty-eight polysomnography-confirmed iRBD patients and 28 age- and sex-matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine-hole peg test, five-times-sit-to-stand test, timed-up-and-go test, and 4-meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting-state networks, gray matter (GM) volume using voxel-based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer. RESULTS: iRBD patients relative to healthy subjects exhibited a poorer performance during the nine-hole peg test and five-times-sit-to-stand test, and greater asymmetry of arm-swing amplitude and stride length variability during dual-task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo-associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes. CONCLUSIONS: Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The dynamics of cyclic-periodic phenomena during non-rapid and rapid eye movement sleep.

Sleep is a complex physiological state characterized by distinct stages, each exhibiting unique electroencephalographic patterns and physiological phenomena. Sleep research has unveiled the presence of intricate cyclic-periodic phenomena during both non-rapid eye movement and rapid eye movement sleep stages. These phenomena encompass a spectrum of rhythmic oscillations and periodic events, including cyclic alternating pattern, periodic leg movements during sleep, respiratory-related events such as apneas, and heart rate variability. This narrative review synthesizes empirical findings and theoretical frameworks to elucidate the dynamics, interplay and implications of cyclic-periodic phenomena within the context of sleep physiology. Furthermore, it invokes the clinical relevance of these phenomena in the diagnosis and management of sleep disorders.

Sensory aspects of restless legs syndrome: Clinical, neurophysiological and neuroimaging prospectives.

Restless Legs Syndrome (RLS) is a complex sensorimotor disorder, classified among the sleep-related movement disorders. Although sensory symptoms appear as key features of the disorder, they are still poorly characterized from a clinical perspective and conceptualized from a pathophysiological point of view. In this review, we aim to describe the clinical and functional substrates of RLS, focusing mainly on its sensory symptoms and on their neurophysiological and anatomical correlates. Knowledge of both subjective sensory symptoms and objective sensory signs are still controversial. Current data also indicate that the sensory component of RLS seems to be subserved by anomalies of sensorimotor integration and by mechanism of central sensitization. Overall, electrophysiological findings highlight the involvement of multiple generators in the pathogenesis of RLS, eventually resulting in an increased nervous system excitability and/or alterations in inhibition within the somatosensory and nociceptive pathways. Structural and functional neuroimaging data show the involvement of several crucial areas and circuits, among which the thalamus appears to play a pivotal role. A holistic approach looking at brain connectivity, structural or functional abnormalities, and their interplay with molecular vulnerability and neurotransmitter alterations is warranted to disentangle the complex framework of RLS.

Large muscle group movements during sleep in restless leg syndrome: neurophysiological and clinical implications.

STUDY OBJECTIVES: Recently, criteria have been drawn up for large muscle group movements during sleep (LMM), defined as movements lasting for 3-45 seconds in adults, which are often accompanied by changes in sleep stage, arousals, and increases in heart rate. The aim of this study was to characterize LMM in restless legs syndrome (RLS) in order to better evaluate their impact on the neurophysiology of the disorder and, therefore, the possible clinical implications. METHODS: Consecutive, drug-free patients diagnosed with RLS and controls, aged 18 years or more, were retrospectively enrolled. Leg movement activity-short-interval (SILMS), periodic (PLMS), and isolated (ISOLMS) leg movements during sleep-and LMM were detected and scored. RESULTS: In total, 100 patients and 67 controls were recruited. All movement measures were significantly higher in RLS. A significant positive correlation was found between LMM and ISOLMS index but not PLMS index in both groups. LMM index showed a significant negative correlation with total sleep time, sleep efficiency, and percentage of sleep stages N3 and R, as well as a significant positive correlation with the number of awakenings, and percentage of sleep stages N1 and N2 only in patients with RLS. No significant correlation was found between either LMM or PLMS index and RLS severity. CONCLUSIONS: Different types of movements, including SILMS, ISOLMS, and LMM, play somewhat distinct roles in sleep neurophysiology in RLS. Notably, LMM, a newly recognized category of movements, demonstrates associations with sleep architecture instability and fragmentation, arousals, and awakenings, suggesting potential clinical implications.

Assessment and management of chronic insomnia disorder: an algorithm for primary care physicians.

BACKGROUND: Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers. METHODS: A panel of experts developed an algorithm for diagnosing and treating chronic insomnia disorder, based on current guidelines and experience in clinical practice. An online survey was conducted with primary care physicians from France, Germany, Italy, Spain, and the United Kingdom, who treat chronic insomnia patients, between January and February 2023. A sub-sample of participants provided open-ended feedback on the algorithm and gave suggestions for improvements. RESULTS: Overall, 106 primary care physicians completed the survey. Half (52%, 55/106) reported they did not regularly screen for insomnia and half (51%, 54/106) felt they did not have enough time to address patients' needs in relation to insomnia or trouble sleeping. The majority (87%,92/106) agreed the algorithm would help diagnose chronic insomnia patients and 82% (87/106) agreed the algorithm would help improve their clinical practice in relation to managing chronic insomnia. Suggestions for improvements were making the algorithm easier to read and use. CONCLUSION: The algorithm developed for, and tested by, primary care physicians to diagnose and treat chronic insomnia disorder may offer significant benefits to providers and their patients through ensuring standardization of insomnia diagnosis and management.

Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis.

The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed. Enrichment analysis by pathfindR tool was carried-out, with p-adjusted ≤0.001 and fold-change ≥2.5. Nine main different network groups were significantly dysregulated in RLS: infections, inflammation, immunology, neurodegeneration, cancer, neurotransmission and biological, blood and metabolic mechanisms. Genetic predisposition plays a key role in RLS and evidence indicates its inflammatory nature; the high involvement of mainly neurotropic viruses and the TORCH complex might trigger inflammatory/immune reactions in genetically predisposed subjects and activate a series of biological pathways-especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer of activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, and ferroptosis-involved in neurotransmitter mechanisms, synaptic plasticity, axon guidance, neurodegeneration, carcinogenesis, and metabolism.

A survey-based approach on restless legs syndrome: practices and perspectives among Italian neurologists.

INTRODUCTION: Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management. OBJECTIVE: This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neurologists regarding RLS diagnosis, management, and treatment, comparing approaches among general neurologists, movement disorder specialists, and sleep experts. METHODS: Members of the Italian Society of Neurology, the Italian Society of Parkinson and Movement Disorders, and the Italian Association of Sleep Medicine were invited to participate in a 19-question online survey. RESULTS: Among the 343 surveyed neurologists, 60% categorized RLS as a "sleep-related movement disorder." Forty% indicated managing 5-15 RLS patients annually, with sleep specialists handling the highest patient volume. Of note, only 34% adhered strictly to all five essential diagnostic criteria. The majority (69%) favored low-dosage dopamine agonists as their first-line treatment, with movement disorder specialists predominantly endorsing this approach, while sleep experts preferred iron supplementation. Regular screening for iron levels was widespread (91%), with supplementation typically guided by serum iron alterations. In cases of ineffective initial treatments, escalating dopamine agonist dosage was the preferred strategy (40%). CONCLUSIONS: These findings underscore a lack of a clear conceptualization of RLS, with a widespread misconception of the disorder as solely a movement disorder significantly influencing treatment approaches. Disparities in RLS understanding across neurology subspecialties underscore the necessity for improved diagnostic accuracy, targeted educational initiatives, and management guidelines to ensure consistent and effective RLS management.

Rapid eye movement sleep behavior disorder and its relation to Parkinson's disease: The potential of graph measures as brain biomarkers to identify the underlying physiopathology of the disorder.

Rapid eye movement behavior disorder (RBD) is a parasomnia characterized by the loss of skeletal muscle atonia during the rapid eye movement (REM) sleep phase. On the other hand, idiopathic RDB (iRBD) is considered the prelude of the various α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Consequently, over 40% of patients eventually develop PD. Recent neuroimaging studies utilizing structural magnetic resonance imaging (s-MRI), diffusion-weighted imaging (DWI), and functional magnetic resonance imaging (fMRI) with graph theoretical analysis have demonstrated that patients with iRBD and Parkinson's disease have extensive brain abnormalities. Thus, it is crucial to identify new biomarkers that aid in determining the underlying physiopathology of iRBD group. This review was conducted systematically on the included full-text articles of s-MRI, DWI, and fMRI studies using graph theoretical analysis on patients with iRBD, per the procedures recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature search was conducted through the PubMed and Google scholar databases concentrating on studies from September to January 2022. Based on the three perspectives of integration, segregation, and centrality, the reviewed articles demonstrated that iRBD is associated with segregation disorders in frontal and limbic brain regions. Moreover, this study highlighted the need for additional longitudinal and multicenter studies to better understand the potential of graph metrics as brain biomarkers for identifying the underlying physiopathology of iRBD group.

Turning alterations detected by mobile health technology in idiopathic REM sleep behavior disorder.

Idiopathic REM sleep Behavior Disorder (iRBD) is a condition at high risk of developing Parkinson's disease (PD) and other alpha-synucleinopathies. The aim of the study was to evaluate subtle turning alterations by using Mobile health technology in iRBD individuals without subthreshold parkinsonism. A total of 148 participants (23 persons with polysomnography-confirmed iRBD without subthreshold parkinsonism, 60 drug-naïve PD patients, and 65 age-matched controls were included in this prospective cross-sectional study. All underwent a multidimensional assessment including cognitive and non-motor symptoms assessment. Then a Timed-Up-and-Go test (TUG) at normal and fast speed was performed using mobile health technology on the lower back (Rehagait®, Hasomed, Germany). Duration, mean, and peak angular velocities of the turns were compared using a multivariate model correcting for age and sex. Compared to controls, PD patients showed longer turn durations and lower mean and peak angular velocities of the turns in both TUGs (all p ≤ 0.001). iRBD participants also showed a longer turn duration and lower mean (p = 0.006) and peak angular velocities (p < 0.001) compared to controls, but only in the TUG at normal speed. Mobile health technology assessment identified subtle alterations of turning in subjects with iRBD in usual, but not fast speed. Longitudinal studies are warranted to evaluate the value of objective turning parameters in defining the risk of conversion to PD in iRBD and in tracking motor progression in prodromal PD.

Boosting obstructive sleep apnea therapy by non-pharmacological approaches: A network meta-analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is the most common breathing-related sleep disorder with a considerable economic burden, low diagnosis and treatment rates. Continuous positive airway pressure (CPAP/PAP) is the principal therapy for OSA treatment; nevertheless, effectiveness is often limited by suboptimal adherence. The present network meta-analysis aims to systematically summarize and quantify different interventions' effects on CPAP/PAP adherence (such as mean usage CPAP or PAP in hours per night) in OSA patients, comparing Behavioral, Educational, Supportive and Mixed interventions in Randomized Control Trials (RCT). METHODS: We conducted a computer-based search using the electronic databases of Pubmed, Psycinfo, Scopus, Embase, Chinal and Medline until August 2022, selecting 50 RCT. RESULTS: By means of a random effect model network meta-analysis, results suggested that the most effective treatment in improving CPAP/PAP adherence was the Supportive approach followed by Behavioral Therapy focused on OSA treatment adherence. CONCLUSION: This network meta-analysis might encourage the most experienced clinicians and researchers in the field to collaborate and implement treatments for improving CPAP/PAP treatment adherence. Moreover, these results support the importance of multidisciplinary approaches for OSA treatment, which should be framed within a biopsychological model.