Sleep disorders and sleep disturbances in persons with multiple sclerosis: A population-based matched case-control study in Denmark.

Introduction Adverse sleep is common in multiple sclerosis (MS). Population-based studies including adequate control groups are lacking. We hypothesized that the prevalence of sleep disorders and other sleep disturbances would be higher in persons with MS than in controls. Methods We conducted a population-based study linking individual-level data from the Danish MS Registry (n=21,943 persons with MS) and the Danish Population Registry (n=109,715 matched controls) with information on sleep disorders from the Danish National Patient Registry and other sleep disturbances assessed by dispensed prescription drugs from the Danish National Prescription Registry. Results Prevalence of diagnosed sleep disorders in terms of central hypersomnia (0.15% vs. 0.06%), sleep disturbances (1.05% vs. 0.70%), and sleep movements (0.22% vs. 0.13%) and other sleep disturbances identified by dispensed central acting (10.73% vs. 1.10%) and hypnotic use (30.65% vs. 20.13%) medication was statistically significantly higher among persons with MS when compared to controls. We found no statistically significant difference in the prevalence of sleep apnea and parasomnia between groups. Stratified by sex and age at MS diagnosis, results for differences between persons with MS and controls were similar. Conclusion In this registry-based study, we found that the prevalence of several diagnosed sleep disorders was higher persons with MS than in controls, that is those reflecting insomnia and daytime symptoms including hypersomnia. Other sleep disturbances identified by dispensed prescription medication was markedly higher in persons with MS than controls.

The Ultra-Long-Term Sleep study: Design, rationale, data stability and user perspective.

Sleep deprivation and poor sleep quality are significant societal challenges that negatively impact individuals' health. The interaction between subjective sleep quality, objective sleep measures, physical and cognitive performance, and their day-to-day variations remains poorly understood. Our year-long study of 20 healthy individuals, using subcutaneous electroencephalography, aimed to elucidate these interactions, assessing data stability and participant satisfaction, usability, well-being and adherence. In the study, 25 participants were fitted with a minimally invasive subcutaneous electroencephalography lead, with 20 completing the year of subcutaneous electroencephalography recording. Signal stability was measured using covariance of variation. Participant satisfaction, usability and well-being were measured with questionnaires: Perceived Ease of Use questionnaire, System Usability Scale, Headache questionnaire, Major Depression Inventory, World Health Organization 5-item Well-Being Index, and interviews. The subcutaneous electroencephalography signals remained stable for the entire year, with an average participant adherence rate of 91%. Participants rated their satisfaction with the subcutaneous electroencephalography device as easy to use with minimal or no discomfort. The System Usability Scale score was high at 86.3 ± 10.1, and interviews highlighted that participants understood how to use the subcutaneous electroencephalography device and described a period of acclimatization to sleeping with the device. This study provides compelling evidence for the feasibility of longitudinal sleep monitoring during everyday life utilizing subcutaneous electroencephalography in healthy subjects, showcasing excellent signal stability, adherence and user experience. The amassed subcutaneous electroencephalography data constitutes the largest dataset of its kind, and is poised to significantly advance our understanding of day-to-day variations in normal sleep and provide key insights into subjective and objective sleep quality.

Automatic quantification of REM sleep without atonia reliably identifies patients with REM sleep behavior disorder: a possible screening tool?

BACKGROUND: REM Sleep Behavior Disorder (RBD) is characterized by absence of physiological muscle atonia during REM sleep (REM sleep without atonia, RWA). Nigro-striatal dopaminergic impairment is a feature of Parkinson disease (PD) and can be identified in prodromal stages as well, such as idiopathic RBD (iRBD). Aims of this study are to explore the efficacy of an automatic RWA quantification in identifying RBD patients and the correlation between RWA and nigro-striatal dopaminergic function. METHODS: Forty-five iRBD, 46 PD with RBD, 24 PD without RBD patients and 11 healthy controls were enrolled in the Genoa Center (group A) and 25 patients with iRBD (group B) were enrolled in the Danish Center. Group A underwent brain [123I]FP-CIT-SPECT and group B underwent brain [18F]PE2I-PET as measures of nigro-striatal dopaminergic function. Chin muscle activity was recorded in all subjects and analyzed by applying a published automatic algorithm. Correlations between RWA and nigro-striatal dopaminergic function were explored. RESULTS: The automatic quantification of RWA significantly differentiated RBD from non-RBD subjects (AUC = 0.86), although with lower accuracy compared with conventional visual scoring (AUC = 0.99). No significant correlation was found between RWA and nigro-striatal dopaminergic function. CONCLUSION: The automatic quantification of RWA is a reliable tool to identify subjects with RBD and may be used as a first-line screening tool, but without correlations with nigro-striatal dopaminergic functioning.

Evaluating routine blood and cerebrospinal fluid samples in narcolepsy patients.

Cerebrospinal fluid hypocretin-1 is proven to be a precise diagnostic marker of narcolepsy Type 1 (NT1). However other characteristics of cerebrospinal fluid and blood parameters have not yet been described. The objective of this study was to evaluate the differences in routine blood and cerebrospinal fluid analyses between NT1 patients and patients suspected of hypersomnia. We collected retrospectively all measures of cerebrospinal fluid hypocretin-1 between 2019 and 2022. This yielded 612 patients out of which 146 were diagnosed with NT1 and the rest (466 patients) were used as a control group. We selected the most relevant routine samples from both blood, plasma and cerebrospinal fluid and compared the two groups. The only significantly different analytes were plasma lactate dehydrogenase and cerebrospinal fluid hypocretin-1. No other differences were found between the groups including thyroid markers, markers of neuroendocrine function, inflammatory markers in blood or cerebrospinal fluid, markers of permeability of the blood brain barrier or metabolic markers in blood samples. We found no significant differences in routine blood or cerebrospinal fluid components, neuroendocrine function, neuroinflammation and metabolic markers. The results reflect that the hypocretin system does not seem to play a chronic major role in regulation of these markers. None of the parameters routinely measured in blood in these patients could differentiate between NT1 and non-NT1 disorders besides CSF-hcrt-1.

The effect of group-based cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: a randomized controlled trial.

OBJECTIVES: The primary objective was to compare the effect of cognitive behavioural therapy for insomnia (CBT-I) to usual care on sleep efficiency, measured by polysomnography (PSG) immediately after the intervention at week 7. Secondary objectives included comparing the longer-term effect on sleep- and RA-related outcomes at week 26. METHODS: In a randomized controlled trial using a parallel group design, the experimental intervention was 6 weeks' nurse-led group-based CBT-I; the comparator was usual care. Analyses were based on the intention-to-treat (ITT) principle; missing data were statistically modelled using repeated-measures linear mixed effects models adjusted for the level at baseline. RESULTS: The ITT population consisted of 62 patients (89% women), with an average age of 58 years and an average sleep efficiency of 83.1%. At primary end point, sleep efficiency was 88.7% in the CBT-I group, compared with 83.7% in the control group (difference: 5.03 [95% CI -0.37, 10.43]; P = 0.068) measured by PSG at week 7. Key secondary outcomes measured with PSG had not improved at week 26. However, for all the patient-reported key secondary sleep- and RA-related outcomes, there were statistically highly significant differences between CBT-I and usual care (P < 0.0001), e.g. insomnia (Insomnia Severity Index: -9.85 [95% CI -11.77, -7.92]) and the RA impact of disease (RAID: -1.36 [95% CI -1.92, -0.80]) at week 26. CONCLUSION: Nurse-led group-based CBT-I did not lead to an effect on sleep efficiency objectively measured with PSG. However, CBT-I showed improvement on all patient-reported key secondary sleep- and RA-related outcomes measured at week 26. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03766100.

Ambulatory Detection of Isolated Rapid-Eye-Movement Sleep Behavior Disorder Combining Actigraphy and Questionnaire.

BACKGROUND: Isolated rapid-eye-movement sleep behavior disorder (iRBD) is in most cases a prodrome of neurodegenerative synucleinopathies, affecting 1% to 2% of middle-aged and older adults; however, accurate ambulatory diagnostic methods are not available. Questionnaires lack specificity in nonclinical populations. Wrist actigraphy can detect characteristic features in individuals with RBD; however, high-frequency actigraphy has been rarely used. OBJECTIVE: The aim was to develop a machine learning classifier using high-frequency (1-second resolution) actigraphy and a short patient survey for detecting iRBD with high accuracy and precision. METHODS: The method involved analysis of home actigraphy data (for seven nights and more) and a nine-item questionnaire (RBD Innsbruck inventory and three synucleinopathy prodromes of subjective hyposmia, constipation, and orthostatic dizziness) in a data set comprising 42 patients with iRBD, 21 sleep clinic patients with other sleep disorders, and 21 community controls. RESULTS: The actigraphy classifier achieved 95.2% (95% confidence interval [CI]: 88.3-98.7) sensitivity and 90.9% (95% CI: 82.1-95.8) precision. The questionnaire classifier achieved 90.6% accuracy and 92.7% precision, exceeding the performance of the Innsbruck RBD Inventory and prodromal questionnaire alone. Concordant predictions between actigraphy and questionnaire reached a specificity and precision of 100% (95% CI: 95.7-100.0) with 88.1% sensitivity (95% CI: 79.2-94.1) and outperformed any combination of actigraphy and a single question on RBD or prodromal symptoms. CONCLUSIONS: Actigraphy detected iRBD with high accuracy in a mixed clinical and community cohort. This cost-effective fully remote procedure can be used to diagnose iRBD in specialty outpatient settings and has potential for large-scale screening of iRBD in the general population. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Autonomic dysfunction after mild acute ischemic stroke and six months after: a prospective observational cohort study.

INTRODUCTION: Autonomic dysfunction is prevalent in ischemic stroke patients and associated with a worse clinical outcome. We aimed to evaluate autonomic dysfunction over time and the tolerability of the head-up tilt table test in an acute stroke setting to optimize patient care. PATIENTS AND METHOD: In a prospective observational cohort study, patients were consecutively recruited from an acute stroke unit. The patients underwent heart rate and blood pressure analysis during the Valsalva maneuver, deep breathing, active standing, and head-up tilt table test if active standing was tolerated. In addition, heart rate variability and catecholamines were measured. All tests were performed within seven days after index ischemic stroke and repeated at six months follow-up. RESULTS: The cohort was comprised of 91 acute stroke patients, mean (SD) age 66 (11) years, median (IQR) initial National Institute of Health Stroke Scale 2 (1-4) and modified Ranking Scale 2 (1-3). The head-up tilt table test revealed 7 patients (10%) with orthostatic hypotension. The examination was terminated before it was completed in 15%, but none developed neurological symptoms. In the acute state the prevalence of autonomic dysfunction varied between 10-100% depending on the test. No changes were found in presence and severity of autonomic dysfunction over time. CONCLUSION: In this cohort study of patients with mild stroke, autonomic dysfunction was highly prevalent and persisted six months after index stroke. Head-up tilt table test may be used in patients who tolerate active standing. Autonomic dysfunction should be recognized and handled in the early phase after stroke.

Survival and long-term socioeconomic consequences of childhood and adolescent onset of brain tumours.

AIM: To evaluate survival distributions, long-term socioeconomic consequences, and health care costs in patients with childhood and adolescent onset of brain tumours in a Danish nationwide prospective cohort study. METHOD: A search of national registries identified 2283 patients (1198 males, 1085 females; mean age 9 years 6 months [SD 5 years 7 months]) diagnosed with a brain tumour between 1980 and 2015 and aged no older than 18 years at diagnosis. These were compared with sex-, age-, and residency-matched comparison individuals. Patients with malignant tumours were compared with those with benign tumours. Survival distributions were estimated by the Kaplan-Meier method and hazard ratio by the Cox proportional hazard model. Socioeconomic data at age 20 and 30 years were assessed. RESULTS: The probability of mortality was highest during the first year after tumour diagnosis. In young adulthood, the patients were generally less likely to be married, had lower grade-point averages, educational levels, and income, were less likely to be in employment, and had higher health care costs than comparison individuals. Patients with malignant tumours had worse outcomes with respect to education, employment, and health care costs than those with benign tumours. INTERPRETATION: A diagnosis of brain tumour in childhood and adolescence adversely affects survival and has negative long-term socioeconomic consequences, especially in patients with malignant tumours. These patients require continuous social support.

Subjective sleep assessment compared to polysomnography in mechanically ventilated critically ill ICU patients.

Sleep deprivation is expected in the intensive care unit (ICU) and is associated with delirium and increased mortality. Polysomnography (PSG) is the gold standard for sleep assessment, but practical issues limit the method. Hence, many ICUs worldwide use subjective sleep assessment (SSA) for sleep monitoring, but the agreement between SSA and PSG is unknown. The hypothesis was that the level of agreement between SSA and PSG was low and that total sleep time (TST) assessed with SSA would be overestimated compared to PSG in this existing cohort database. In this sub-analysis, 30 consecutive study participants underwent 15-h PSG recordings during two consecutive nights. The attending nurse performed an hourly subjective observer rating of sleep quantity during both nights, and the agreement between SSA and PSG was determined along with mean TST. Primary outcome: The level of agreement between SSA and PSG determined by Bland-Altman analysis. Secondary outcome: (1) The overall mean TST estimated by SSA compared to PSG in all study participants enrolled in the main study during both study nights, (2) TST for all study participants evaluated hourly during both study nights, (3) TST assessed with SSA compared to PSG in study participants sedated with dexmedetomidine during the second night and for study participants treated with placebo or non-sedation the first and second nights. The level of agreement between SSA and PSG was low. Mean TST estimated by SSA during the time interval 4.00 p.m. to 7.00 a.m. was 481 min (428;534, 95% CI) vs. PSG at 437 min (386;488, 95% CI) (p = .05). When sedated with dexmedetomidine, TST estimated using SSA was 650 min (571;729, 95% CI) versus PSG which was 588 min (531;645, 95% CI) (p = 0.56). For participants treated with placebo or non-sedation TST estimated with SSA was 397 min (343;450, 95% CI) versus PSG at 362 min (302;422, 95% CI) versus (p = 0.17). In mechanically ventilated critically ill ICU patients, the level of agreement between SSA and PSG was low, and there was a significant overestimation of mean TST. SSA should only be used under awareness that it is imprecise and overestimates TST.

Sleep quality and quantity determined by polysomnography in mechanically ventilated critically ill patients randomized to dexmedetomidine or placebo.

BACKGROUND: Abnormal sleep is commonly observed in the ICU and is associated with delirium and increased mortality. If sedation is necessary, it is often performed with gamma-aminobutyric acid agonists such as propofol or midazolam leading to an absence of restorative sleep. We aim to evaluate the effect of dexmedetomidine on sleep quality and quantity. METHODS: Thirty consecutive patients were included. The study was conducted as a double-blinded, randomized, placebo-controlled trial with two parallel groups: 20 patients were treated with dexmedetomidine, and 10 with placebo. Two 16 h of polysomnography recordings were done for each patient on two consecutive nights. Patients were randomized to dexmedetomidine or placebo after the first recording, thus providing a control recording for all patients. Dexmedetomidine was administered during the second recording (6 p.m.-6 a.m.). OBJECTIVE: To compare the effect of dexmedetomidine versus. placebo on sleep - quality and quantity. PRIMARY OUTCOME: Sleep quality, total sleep time (TST), Sleep efficiency (SE), and Rapid Eye Movement (REM) sleep determined by Polysomnography (PSG). SECONDARY OUTCOME: Delirium and daytime function determined by Confusion Assessment Method of the Intensive Care Unit and physical activity. Alertness and wakefulness were determined by RASS (Richmond Agitation and Sedation Scale). RESULTS: SE were increased in the dexmedetomidine group by; 37.6% (29.7;45.6 95% CI) versus 3.7% (-11.4;18.8 95% CI) (p < .001) and TST were prolonged by 271 min. (210;324 95% CI) versus 27 min. (-82;135 95% CI), (p < .001). No significant difference in REM sleep, delirium physical activity, or RASS score was found except for RASS night two. CONCLUSION: Total sleep time and sleep efficiency were significantly increased, without elimination of REM sleep, in mechanically ventilated ICU patients randomized to dexmedetomidine, when compared to a control PSG recording performed during non-sedation/standard care.

Melatonin use among children, adolescents, and young adults: a Danish nationwide drug utilization study.

We aimed to provide a detailed description of the use of melatonin in Danish children, adolescents, and young adults during 2012-2019. We identified melatonin users 0-24 years of age (n = 43,652; median age 16 years) via the Danish nationwide health registers. Melatonin is a prescription drug in Denmark. The incidence of melatonin use increased from 2.4 to 3.9/1000 person-years during 2012 to 2019. Among 6,557 incident users in 2019, 53% filled only a single prescription within the first 6 months. Long-term use was most common among the younger age groups, with 17% of 5-9-year-olds and 14% of 10-13-year-olds being in continued treatment (no treatment breaks) 12 months after their first melatonin prescription. Disregarding treatment breaks, 3 in 10 were using melatonin 12 months after their first melatonin prescription and this proportion was also highest among 5-9-year-olds (63%) and 10-13-year-olds (51%). Psychopathology was common among melatonin users with 75% registered with either a psychiatric disorder diagnosis (54%), a filled prescription for another psychotropic (58%), or a contact to a private practice psychiatrist (15%) within ± 12 months of treatment initiation. General practitioners authorized melatonin prescriptions to almost half of all new users (48%), while psychiatric specialists authorized 37% of first prescriptions. In conclusion, the incidence of melatonin use increased in Denmark from 2012 to 2019. A substantial proportion of users had concurrent psychopathology most likely explaining their use of melatonin. Long-term melatonin use was more common among the youngest age groups, which should be a focus of interest due to limited safety data.

Listening to music for insomnia in adults.

BACKGROUND: Insomnia is a common problem in modern society. It is associated with reduced quality of life and impairments in physical and mental health. Listening to music is widely used as a sleep aid, but it remains unclear if it can actually improve insomnia in adults. This Cochrane Review is an update of a review published in 2015. OBJECTIVES: To assess the effects of listening to music on sleep in adults with insomnia and to assess the influence of specific variables that may moderate the effect. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, nine other databases and two trials registers up to December 2021. In addition, we handsearched reference lists of included studies, and contacted authors of published studies to identify additional studies eligible for inclusion, including any unpublished or ongoing trials. SELECTION CRITERIA: Randomised controlled trials comparing the effects of listening to music with no treatment or treatment as usual (TAU) in adults complaining of sleep difficulties. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records for eligibility, selected studies for inclusion, extracted data and assessed risk of bias of the included studies. We assessed the certainty of the evidence using GRADE. The primary outcomes were sleep quality, insomnia severity, sleep-onset latency, total sleep time, sleep interruption, sleep efficiency and adverse events. Data on the predefined outcome measures were included in meta-analyses when consistently reported by at least two studies that were homogeneous in terms of participants, interventions and outcomes. We undertook meta-analyses using random-effects models. MAIN RESULTS: We included 13 studies (eight studies new to this update) comprising 1007 participants. The studies examined the effect of listening to prerecorded music daily, for 25 to 60 minutes, for a period of three days to three months. The risk of bias within the studies varied, with all studies being at high risk of performance bias, because of limited possibilities to blind participants to the music intervention. Some studies were at high risk of detection bias or other bias. Four studies reported funding from national research councils, three studies reported financial support from university sources and one study reported a grant from a private foundation. Five studies did not report any financial support. At the end of the intervention, we found moderate-certainty evidence for improved sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) in themusic groups compared to no intervention or TAU (mean difference (MD) -2.79, 95% confidence interval (CI) -3.86 to -1.72; 10 studies, 708 participants). The PSQI scale ranges from 0 to 21 with higher scores indicating poorer sleep. The size of the effect indicates an increase in sleep quality of the size of about one standard deviation in favour of the intervention. We found no clear evidence of a difference in the effects of listening to music compared to no treatment or TAU on insomnia severity (MD -6.96, 95% CI -15.21 to 1.28; 2 studies, 63 participants; very low-certainty evidence). We found low-certainty evidence that, compared to no treatment or TAU, listening to music may reduce problems with sleep-onset latency (MD -0.60, 95% CI -0.83 to -0.37; 3 studies, 197 participants), total sleep time (MD -0.69, 95% CI -1.16 to -0.23; 3 studies, 197 participants) and sleep efficiency (MD -0.96, 95% CI -1.38 to -0.54; 3 studies, 197 participants), but may have no effect on perceived sleep interruption (MD -0.53, 95% CI -1.47 to 0.40; 3 studies, 197 participants). In addition, three studies (136 participants) included objective measures of sleep-onset latency, total sleep time, sleep efficiency and sleep interruption and showed that listening to music may not improve these outcomes compared to no treatment or TAU. None of the included studies reported any adverse events. AUTHORS' CONCLUSIONS: The findings of this review provide evidence that music may be effective for improving subjective sleep quality in adults with symptoms of insomnia. More research is needed to establish the effect of listening to music on other aspects of sleep as well as the daytime consequences of insomnia.

Sleep-disordered breathing and cerebral small vessel disease-acute and 6 months after ischemic stroke.

PURPOSE: Sleep-disordered breathing (SDB) occurs frequently after stroke and is associated with poor functional outcome and increased mortality. The purpose of this study was to detect changes in SDB over time after acute ischemic stroke and investigate relationships between SDB and stroke etiologies with focus on cerebral small vessel disease. METHODS: From May 2015 to August 2016, we conducted an observational study of 99 patients with mild to moderate stroke (median age: 68 years, range 36-88; 56% men). Polysomnography was performed within 7 days of stroke onset (n = 91) and after 6 months (n = 52). The strokes were classified using the etiological TOAST classification. Total small vessel disease (SVD) scores were calculated based on MRIs. RESULTS: SDB, defined as an apnea-hypopnea index (AHI) ≥ 15, was found in 56% of patients in the acute state and in 44% at follow-up. AHI decreased over time (median change 4.7, 95% confidence interval [95% CI] 0.5-8.9; p = 0.03). Patients with AHI ≥ 15 in both the acute state and at follow-up had higher SVD score at follow-up (p = 0.003). AHI was not associated with ischemic stroke subgroups according to the TOAST classification. DISCUSSION: In conclusion, 6 months after stroke, AHI decreased, but 44% still had AHI ≥ 15. Persistent SDB in both the acute state and at follow-up was associated with a higher SVD score, but not to the TOAST subgroups. SDB evaluation should be offered to stroke patients, and the effect of SDB on cerebral small vessel disease needs to be further investigated using the well-defined SVD score. TRIAL REGISTRATION: clinicaltrials.gov NCT02111408, April 11, 2014.

The Association between Sleep Problems and Neuropsychological Deficits in Medication-naïve Children with ADHD.

BACKGROUND: Children with ADHD are reported to have sleep problems and neuropsychological deficits, but studies examining a potential association between the two are scarce and the use of varying methodology can complicate conclusions. PARTICIPANTS: A clinical sample of 59 medication-naïve children with ADHD between the ages of 6 and 14 years (71% male). METHODS: Children underwent polysomnography and multiple sleep latency test, and parent rated sleep habits on the Children's Sleep Habits Questionnaire. Children also completed an extensive neuropsychological battery of executive function and delay aversion tasks, and parents and teachers rated executive function behavior on the Behavior Rating Inventory of Executive Function. Linear regression analyses were conducted with each of the neuropsychological outcomes included as the outcome variable and the sleep parameters as the predictor variables. RESULTS: The correlations between sleep and neuropsychological outcomes were generally modest, but some sleep parameters (primarily sleep stages and sleep latencies) were associated with objectively and subjectively measured executive function and delay aversion. CONCLUSIONS: Using objective and subjective gold standard assessment procedures this study supports a (modest) association between sleep and neuropsychological function in children with ADHD.

Welfare consequences of early-onset Borderline Personality Disorder: a nationwide register-based case-control study.

Information regarding welfare consequences of early onset of Borderline Personality Disorder (BPD) is limited. This nationwide study aimed to estimate the educational and employment outcome and health care costs of patients with early-onset BPD compared with matched controls. All patients (< 19 years) with first diagnosis of BPD in the Danish Patient Register (NPR) during the period 1983-2015 were included. Health care costs and socioeconomic variables were extracted from national registers. A total of 171 patients was compared with 677 controls. At the age of 20 years, BPD patients had reached a statistically significantly lower educational level (including lower primary school grades) and employment status compared with the controls. When adjusting for the parents' educational level, BPD patients were nearly 22 times more likely to be unemployed (OR = 21.7, 95% CI 11.9, 39.6), and nearly 15 times more likely to be on disability pension (OR = 14.8, 95% CI 5.0, 43.9) than controls. Furthermore, the total health care costs were more than 8 times higher in the BPD group. Early onset of BPD was associated with lower educational and vocational outcome and increased health care costs as early as at the age of 20 years. Even after controlling for parents' lower socioeconomic status, the patients have poorer outcome than the control group. This underlines that initiatives to support patients in finishing school and secondary education is highly needed. Future prevention and early intervention programs should target patients with early-onset BPD and their families.

Morbidity, Mortality, and Conversion to Neurodegenerative Diseases in Patients with REM Sleep Behavior Disorder and REM Sleep without Atonia.

INTRODUCTION: The underlying pathophysiology of idiopathic REM sleep behavior disorder (iRBD) is not fully understood, although the condition is currently recognized as an early-stage alpha-synuclein disorder. We evaluated the morbidity, mortality, and rate of conversion to a neurodegenerative disorder in a national group of patients. METHODS: All patients in Denmark with a diagnosis of RBD between 2006 and 2013 were identified from the Danish National Patient Registry (NPR) records. We excluded patients who had received a diagnosis of narcolepsy or any of the following neurodegenerative diseases before their diagnosis of RBD: Parkinson's disease, multiple system atrophy, progressive supranuclear paralysis, Alzheimer's, and Lewy body dementia. We used randomly chosen controls matched for age, gender, and municipality. RESULTS: In total, 246 iRBD patients and 982 matched controls were analyzed. The mortality rate was the same in both groups. The morbidity rate was significantly higher in the years before and after an RBD diagnosis, due to a wide variety of disorders in the following major disease groups: mental/behavioral disorders; endocrine/metabolic diseases; diseases of the eye; diseases of the nervous, digestive, musculoskeletal, circulatory, and respiratory systems; abnormal findings not classified elsewhere; external causes; and factors influencing health status. The conversion rate from RBD to a neurodegenerative disease was 13% over the 8 years after a diagnosis of RBD. CONCLUSIONS: A diagnosis of RBD is associated with increased morbidity several years before and after a diagnosis is made. Patients have a higher risk of converting to a neurodegenerative disorder than matched controls. Mortality rates are unchanged.

Imagery rehearsal therapy and/or mianserin in treatment of refugees diagnosed with PTSD: Results from a randomized controlled trial.

Sleep disturbances are frequently part of the symptomatology in refugees with post-traumatic stress disorder (PTSD). It has been suggested that targeting sleep disturbances may enhance the outcome of PTSD treatment. However, randomized studies on the effect of treatment focusing on sleep disturbances in refugees with PTSD are lacking. The aim of this study was to examine add-on treatment with imagery rehearsal therapy (IRT) and/or mianserin against treatment as usual (TAU) alone in a sample of trauma-affected refugees with PTSD at 8-12 months follow-up. In a randomized controlled trial, 219 adult refugees diagnosed with PTSD and suffering from sleep disturbances were randomized to four groups (1:1:1:1) receiving, respectively, TAU, TAU + mianserin, TAU + IRT, and TAU + IRT + mianserin. The primary outcome was subjective sleep quality (Pittsburgh Sleep Quality Index) and the secondary outcomes included PTSD and depression symptoms, level of functioning and subjective well-being. The data were analysed using mixed models. The only significant effect of IRT was on level of functioning (p = .040, ES 0.44), whereas there was no significant effect of mianserin on any of the measured outcomes. Low adherence to both IRT (39%) and mianserin (20%) was observed. Contrary to our hypothesis, we did not find IRT or mianserin to be superior to TAU. The low adherence may potentially cause an underestimation of the effect of IRT and mianserin and indicates a necessity to further analyse the complex factors that may impact the motivation and ability of trauma-affected refugees to participate in and profit from available treatment options.

B-waves are present in patients without intracranial pressure disturbances.

Intracranial pressure (ICP) B-waves are defined as short, repeating elevations of ICP of up to 50 mmHg with a frequency of 0.5-2 waves/min. The presence of B-waves in overnight recordings is regarded as a pathological phenomenon. However, the physiology of B-waves is still not fully understood and studies with transcranial Doppler, as a surrogate marker for ICP, have suggested that B-waves could be a normal physiological phenomenon. We present four patients without known structural neurological disease other than a coincidentally found unruptured intracranial aneurysm. One of the patients had experienced well-controlled epilepsy for several years, but was included because ICP under these conditions is unlikely to be abnormal. Following informed consent, all four patients had a telemetric ICP probe implanted during a prophylactic operation with closure of the aneurysm. They underwent overnight ICP monitoring with simultaneous polysomnography (PSG) sleep studies at 8 weeks after the operation. These patients exhibited nocturnal B-waves, but did not have major structural brain lesions. Their ICP values were within the normal range. Nocturnal B-waves occurred in close association with sleep-disordered breathing (SDB) in rapid eye movement (REM) and non-REM sleep stages. SDB during REM sleep was associated with ramp-type B-waves; SDB during non-REM sleep was associated with the sinusoidal type of B-wave. We propose that B-waves are a physiological phenomenon associated with SDB and that the mechanical changes during respiration could have an essential and previously unrecognised role in the generation of B-waves.

Nocturnal eye movements in patients with idiopathic rapid eye movement sleep behaviour disorder and patients with Parkinson's disease.

Patients with idiopathic rapid-eye-movement (REM) sleep behaviour disorder (iRBD) have a high risk of converting into manifest α-synucleinopathies. Eye movements (EMs) are controlled by neurons in the lower brainstem, midbrain and frontal areas, and may be affected by the early neurodegenerative process seen in iRBD. Studies have reported impairment of the oculomotor function in patients with Parkinson's disease (PD) during wakefulness, but no studies have investigated EMs during sleep. We aimed to evaluate nocturnal EMs in iRBD and PD, hypothesizing that these patients present abnormal EM distribution during sleep. Twenty-eight patients with periodic limb movement disorder (PLMD), 24 iRBD, 23 PD without RBD (PDwoRBD), 29 PD and RBD (PDwRBD) and 24 controls were included. A validated EM detector automatically identified EM periods between lights off and on. The EM coverage was computed as the percentage of time containing EMs during stable wake after lights off, N1, N2, N3 and REM sleep. Between-group comparisons revealed that PDwRBD had significantly less EM coverage during wake and significantly higher EM coverage during N2 compared to controls and PLMD patients. PDwoRBD showed significantly less EM coverage during wake compared to controls and higher EM coverage during N2 compared to controls and PLMD. Finally, iRBD showed less coverage of EM during wake compared to controls. The same trend was observed between iRBD and controls in N2 but was not significant. The different profiles of EM coverage in iRBD and PD with/without RBD may mirror different stages of central nervous system involvement across neurodegenerative disease progression.