Sleep and circadian rhythms in adolescents with attempted suicide.

Sleep and circadian rhythm disorders are very common in adolescents and have been linked to suicidal ideation. However, little is known about adolescent sleep before a suicide attempt (SA). The objectives of this study were to compare the sleep of adolescents aged 13 to 18 over a period of 4 weeks before a SA compared to a non-SA group, then to analyze the association between sleep, support social and well-being based on information from validated questionnaires. In 2015, 250 adolescents were included, 55 were recruited the day after a SA in French hospitals (before SA evaluations were retrospective). Logistic regression analyzes showed that during school days, bedtime was equivalent in both groups, but sleep onset latency was significantly longer in SA (86 min vs. 52 min, p = 0.016), and wake-up time was earlier (6 h 22 vs. 6 h 47, p = 0.002), resulting in a shorter total sleep time of 44 min (OR = 0.76, CI 95% [0.61-0.93]) the month preceding SA. Adolescents with longer sleep time performed better on perceived psychological well-being (p = 0.005), relationship with parents (p = 0.011) and school environment (p < 0.001). Results indicate a significant change in the quantity and quality of adolescents' subjective sleep in the 4 weeks preceding SA requiring objective measures to study the predictive properties of sleep in SA.

Images: "Too much heat for my non-24-hour sleep-wake disorder!" A case report.

The non-24-hour sleep-wake disorder (N24SWD) is a rare condition, sometimes associated with blindness or with suprachiasmatic nuclei lesions, resulting in a free-running rhythm or hypernycthemeral syndrome. Synchronizers, such as light, when light perception remains, melatonin, food intakes, physical activity, social interactions, and temperature, play a key role in the treatment of N24SWD. In this report, we describe a case illustrating the impact of outdoor temperature in a 34-year-old man with N24SWD effectively treated through a combination of chronotherapy interventions. During 3 consecutive heat waves, he experienced a recurrence of his natural 25.5-hour free-running rhythm, with a consistent bedtime phase delay caused by temperature, resulting in the discontinuation of chronotherapy. After these heat waves, he was able again to resynchronize his rhythms with the combination of chronotherapeutics. This case report highlights that patients with N24SWD may be particularly at risk of relapse during heat waves, with direct implications for monitoring and reinforcing chronotherapies. CITATION: Garrivet J, d'Ortho M-P, Frija-Masson J, et al. "Too much heat for my non-24-hour sleep-wake disorder!" A case report. J Clin Sleep Med. 2024;20(2):329-333.

Restless legs syndrome in the dominant Parkinson's side related to subthalamic deep-brain stimulation.

BACKGROUND: Restless legs syndrome (RLS) has an increased estimated prevalence in patients with Parkinson's disease (PS). RLS frequently mimics symptoms intrinsic to PD, such as motor restlessness, contributing to making its diagnosis challenging in this population. We report the case of a patient with new-onset RLS following subthalamic deep-brain stimulation (DBS-STN). We assessed symptoms using suggested immobilization test (SIT) with both DBS-STN activated and switched off. CASE DESCRIPTION: A 59-year-old man with idiopathic PD developed disabling RLS following DBS-STN at age 58, with PD onset at 50 manifesting as left arm tremor. Despite improved motor symptoms during the month following surgery, the patient experienced left leg discomfort at rest, transiently alleviated by movements due to an irrepressible urge to move, and worsened at night. Symptoms had no temporal relationship with oral dopa-therapy and disappeared when DBS-STN was deactivated. A 1 h SIT assessed motor behavior with irrepressible urge to move, as well as sensory symptoms by visual analog scale. After 30 m DBS-STN was switched off followed by the appearance of tremor in the left arm while both motor and sensory symptoms of RLS disappeared in the left leg. DISCUSSION: The mechanisms of DBS-STN's impact on RLS remain controversial. We hypothesize the DBS-STN to induce in our patient a hyperdopaminergic tone. DBS-induced and DBS-ameliorated RLS represent interesting conditions to further understand the pathophysiology of RLS. Moreover, the present observation suggests that SIT can be a valuable tool to assess RLS in PD patients before and after DBS-STN in future prospective studies.

Major depressive disorder with hypersomnolence complaint: A comparison study with non-depressed individuals examining objective biomarkers.

BACKGROUND: Hypersomnolence is common in major depressive disorder (MDD), associated with more severe episodes, suicide and antidepressant resistance. Nevertheless, few studies used polysomnography (PSG) and multiple sleep latency test (MSLT) to characterize these patients. In this context, we compared patients visiting a sleep center for hypersomnolence complaint with MDD (HSC/MDD+) and without MDD (HSC/MDD-). METHODS: HSC/MDD+ and HSC/MDD- groups were defined according to DSM-5 criteria and CES-D scale, and had a 30 h-PSG with ad libitum-sleep and PSG followed by MLST. RESULTS: HSC/MDD+ had an increased self-declared total sleep time (sTST) of about 10 h30 similar to HSC/MDD- (630.8 ± 17.3 min-vs-616.5 ± 18.1 min, respectively, p = 0.39). Nevertheless, their objective TST (oTST) on ad libitum PSG was significantly longer and about 10 h50 (648.6 ± 23.9 min-vs-587.4 ± 19.0 min, respectively, p = 0.038). HSC/MDD+ also significantly better estimated their sleep duration, with a lower difference between their sTST and oTST compared to HSC/MDD- (10.0 ± 1.7 %-vs-17.4 ± 2.1 %, respectively, p = 0.009) and confirmed significantly more frequently the hypersomnia diagnosis -i.e. oTST>10H- (82.6 ± 8.1 %-vs-54.6 ± 10.9 %, respectively, p = 0.046). Using the Kupfer index (KI), we confirmed a reduced REM sleep latency in patients MDD/HSC+ (15.2 ± 10.0 %-vs-2.3 ± 2.3 %, respectively, p = 0.039). Both groups had comparable increased diurnal sleepiness assessed with the Epworth scale (14.1 ± 1.1-vs-14.8 ± 1.1, respectively, p = 0.65). HSC/MDD+ had less MSLT sleep latency <8 min (9.1 ± 5.1 %-vs-27.3 ± 6.8 %, respectively, p = 0.048). LIMITATIONS: Retrospective cross-sectional study. CONCLUSIONS: HSC/MDD+ accurately estimated their sleep duration, objectively confirmed hypersomnia and may specifically had a decreased Kupfer index.

Images: Sleep-related painful erection with concomitant hypnic headache.

Sleep-related painful erection (SRPE) is a parasomnia defined by the repetition of painful erections during REM sleep. Hypnic headache (HH) is a primary headache occurring exclusively at night, often during REM sleep. We report the observation of a 33-year-old man with simultaneous SRPE and HH. Physical examination was normal. Comprehensive urological and endocrine explorations excluded other organic differential diagnoses. Polysomnography revealed several awakenings in REM, due to SRPE and concurrent HH. Medication by baclofen at bedtime seemed to have resulted in a decrease of SRPE episodes, confirmed by polysomnography, but at the cost of excessive daytime sleepiness, and was discontinued by the patient. Caffeine intake at bedtime was proposed, but the patient was reluctant because he was concerned about worsening insomnia. At 9-months follow-up, the patient had accepted his medical condition, and was coping with both SRPE and HH. He felt reassured and wished no "overmedicalization". To our knowledge, the coexistence of both conditions has not yet been reported, yet their frequencies might be underestimated. We hypothesize a common underlying pathophysiology with a possible dysfunction of the vascular control and/or the autonomic nervous system and that could involve the hypothalamus. Somnologists should be aware of SRPE, potentially overlapping with hypnic headaches. SRPE should be considered in case of sleep maintenance insomnia. Patient reassurance seems to be central in the care process of SRPE.

Delaying circadian sleep phase under ultradian light cycle causes time-of-day-dependent alteration of cognition and mood.

Light exerts powerful and pervasive effects on physiology and behaviour. These effects can be indirect, through clock synchronization and phase adjustment of circadian rhythms, or direct, independent of the circadian process. Exposure to light at inappropriate times, as commonly experienced in today's society, leads to increased prevalence of circadian, sleep and mood disorders as well as cognitive impairments. In mice, exposure to an ultradian 3.5 h light/3.5 h dark cycle (T7) for several days has been shown to impair behaviour through direct, non-circadian, photic effects, a claim we challenge here. We first confirmed that T7 cycle induces a lengthening of the circadian period resulting in a day by day phase-delay of both activity and sleep rhythms. Spatial novelty preference test performed at different circadian time points in mice housed under T7 cycle demonstrated that cognitive deficit was restrained to the subjective night. Mice under the same condition also showed a modification of stress-induced despair-like behaviour in the forced swim test. Therefore, our data demonstrate that ultradian light cycles cause time-of-day-dependent alteration of cognition and mood through clock period lengthening delaying circadian sleep phase, and not through a direct photic influence. These results are of critical importance for the clinical applications of light therapy in the medical field and for today's society to establish lighting recommendations for shift work, schools, hospitals and homes.

Nightmares and Sleep Disturbances in Children with PTSD: A Polysomnographic and Actigraphy Approach Evaluation.

RATIONALE: Sleep disturbances (insomnia and nightmare symptoms) are the most sensitive and persistent symptoms of pediatric post-traumatic stress disorder (PTSD). Untreated, these sleep disturbances (SD) associated with PTSD are predictive of PTSD persistence and increased psychiatric complications. The aim of this study was to evaluate sleep and circadian rhythms in children with PTSD under both laboratory and ecological conditions in comparison with a control population and to test for the first time the hypothesis that SD and circadian rhythms are positively correlated with PTSD severity and its comorbidities. METHOD: This prospective pilot study evaluated PTSD, SD (insomnia, nightmares), and sleep-wake rhythms in 11 children with PTSD (aged 3-18), compared with the age and sex-matched control groups. Assessment of PTSD and subjective and objective measures of sleep and sleep-wake rhythms (questionnaires, 24-h in-laboratory video-polysomnography, 15-day at-home actigraphy recording) were performed between 1 and 6 months after the traumatic event. RESULTS: Children with PTSD had higher sleep fragmentation (increased wake-after-sleep onset, increased number of sleep stage changes) compared to controls, with a change in sleep microarchitecture (micro-arousal index at 14.8 versus 8.2, p = 0.039). Sleep fragmentation parameters correlated with PTSD symptomatology, insomnia, and post-traumatic nightmare severity. The within-group comparison revealed a better sleep architecture in the controlled (sleep laboratory) than in the ecological condition (at home) (total sleep time 586 versus 464 min, p = 0.018). CONCLUSIONS: Sleep and rhythm disturbances are strongly associated with PTSD in children. The assessment of SD in children with PTSD should be carried out systematically and preferentially under ecological conditions, and management of SD should integrate the environment (environmental design, psycho-education for the children and their parents) more fully into therapy focused on sleep and trauma.

Somno-Art Software identifies pathology-induced changes in sleep parameters similarly to polysomnography.

Polysomnographic sleep architecture parameters are commonly used to diagnose or evaluate treatment of sleep disorders. Polysomnography (PSG) having practical constraints, the development of wearable devices and algorithms to monitor and stage sleep is rising. Beside pure validation studies, it is necessary for a clinician to ensure that the conclusions drawn with a new generation wearable sleep scoring device are consistent to the ones of gold standard PSG, leading to similar interpretation and diagnosis. This paper reports on the performance of Somno-Art Software for the detection of differences in sleep parameters between patients suffering from obstructive sleep apnea (OSA), insomniac or major depressive disorder (MDD) compared to healthy subjects. On 244 subjects (n = 26 healthy, n = 28 OSA, n = 66 insomniacs, n = 124 MDD), sleep staging was obtained from PSG and Somno-Art analysis on synchronized electrocardiogram and actimetry signals. Mixed model analysis of variance was performed for each sleep parameter. Possible differences in sleep parameters were further assessed with Mann-Whitney U-test between the healthy subjects and each pathology group. All sleep parameters, except N1+N2, showed significant differences between the healthy and the pathology group. No significant differences were observed between Somno-Art Software and PSG, except a 3.6±2.2 min overestimation of REM sleep. No significant interaction 'group'*'technology' was observed, suggesting that the differences in pathologies are independent of the technology used. Overall, comparable differences between healthy subjects and pathology groups were observed when using Somno-Art Software or polysomnography. Somno-Art proposes an interesting valid tool as an aid for diagnosis and treatment follow-up in ambulatory settings.

Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis.

Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was conducted following PRISMA criteria, to assess the efficacy of melatonin and ramelteon compared with placebo on sleep quantity and quality in insomnia disorder, while also considering factors that may impact their efficacy. This review included 22 studies, with 4875 participants, including 925 patients treated with melatonin, 1804 treated with ramelteon and 2297 receiving a placebo. Most studies evaluated the acute efficacy of prolonged release (PR) melatonin in insomnia disorder. Compared with placebo, PR melatonin appears efficacious with a small to medium effect size on subjective sleep onset latency (sSOL) (p = 0.031; weighted difference = -6.30 min), objective sleep onset latency (oSOL) (p < 0.001; weighted difference = -5.05 min), and objective sleep efficiency (oSE) (p = 0.043; weighted difference = 1.91%). For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%). Ramelteon was efficacious with a large effect size at 4 weeks on objective total sleep time (oTST) (p = 0.010; weighted difference = 17.9 min), subjective total sleep time (sTST) (p = 0.006; weighted difference = 11.7 min), sSOL (p = 0.009; weighted difference = -8.74 min), and oSOL (p = 0.017; weighted difference = -14 min). Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min). PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes. PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Light therapy in insomnia disorder: A systematic review and meta-analysis.

In the management of insomnia, physicians and patients are seeking alternative therapeutics to sleeping pills, in addition to sleep hygiene and cognitive behavioural therapy. Bright light therapy (LT) has proven its efficacy in circadian and mood disorders. We conducted a systematic literature review and meta-analysis according to Cochrane and PRISMA guidelines and using the databases Medline, Cochrane, and Web of Science, with a special focus on light therapy and insomnia. Twenty-two studies with a total of 685 participants were included, five of which with a high level of proof. Meta-analysis was performed with 13 of them: light therapy for insomnia compared with control conditions significantly improved wake after sleep onset (WASO: SMD = -0.61 [-1.11, -0.11]; p = 0.017; weighted difference of 11.2 min ±11.5 based on actigraphy, and SMD = -1.09 [-1.43, -0.74] (p < 0.001) weighted difference of -36.4 min ±15.05) based on sleep diary, but no other sleep measures such as sleep latency, total sleep time (TST), or sleep efficiency. Qualitative analysis of the review showed some improvement mainly in subjective measures. Morning light exposure advanced sleep-wake rhythms and evening exposure led to a delay. No worsening was observed in objective nor subjective measures, except for TST in one study with evening exposure. A light dose-response may exist but the studies' heterogeneity and publication bias limit the interpretation. To conclude, light therapy shows some effectiveness for sleep maintenance in insomnia disorders, but further research is needed to refine the light parameters to be chosen according to the type of insomnia, in the hope of developing personalised therapeutics.

Pupillometry to differentiate idiopathic hypersomnia from narcolepsy type 1.

Idiopathic hypersomnia is poorly diagnosed in the absence of biomarkers to distinguish it from other central hypersomnia subtypes. Given that light plays a main role in the regulation of sleep and wake, we explored the retinal melanopsin-based pupil response in patients with idiopathic hypersomnia and narcolepsy type 1, and healthy subjects. Twenty-seven patients with narcolepsy type 1 (women 59%, 36 ± 11.5 years old), 36 patients with idiopathic hypersomnia (women 83%, 27.2 ± 7.2 years old) with long total sleep time (> 11/24 hr), and 43 controls (women 58%, 30.6 ± 9.3 years old) were included in this study. All underwent a pupillometry protocol to assess pupil diameter, and the relative post-illumination pupil response to assess melanopsin-driven pupil responses in the light non-visual input pathway. Differences between groups were assessed using logistic regressions adjusted on age and sex. We found that patients with narcolepsy type 1 had a smaller baseline pupil diameter as compared with idiopathic hypersomnia and controls (p < 0.05). In addition, both narcolepsy type 1 and idiopathic hypersomnia groups had a smaller relative post-illumination pupil response (respectively, 31.6 ± 13.9% and 33.2 ± 9.9%) as compared with controls (38.7 ± 9.7%), suggesting a reduced melanopsin-mediated pupil response in both types of central hypersomnia (p < 0.01). Both narcolepsy type 1 and idiopathic hypersomnia showed a smaller melanopsin-mediated pupil response, and narcolepsy type 1, unlike idiopathic hypersomnia, also displayed a smaller basal pupil diameter. Importantly, we found that the basal pupil size permitted to well discriminate idiopathic hypersomnia from narcolepsy type 1 with a specificity = 66.67% and a sensitivity = 72.22%. Pupillometry may aid to multi-feature differentiation of central hypersomnia subtypes.

A comparison of four methods to estimate dim light melatonin onset: a repeatability and agreement study.

Dim light melatonin onset (DLMO) is considered the most reliable circadian phase marker in humans. However, the methods to calculate it are diverse, which limits the comparability between studies. Given the key role of DLMO to diagnose circadian rhythm sleep-wake disorders and determine the optimal timing of chronotherapies, the establishment of clear and validated guidelines on the methodology to assess DLMO is very important. We performed a repeatability study (n = 31) and an agreement study (n = 62) in healthy young adults with hourly blood samples collected under dim light conditions (<8 lux) during a chronobiological protocol. We assessed the repeatability of DLMO with three different methods (fixed threshold, dynamic threshold and hockey stick) across two nights and assessed agreement of each method with the mean visual estimation made by four chronobiologists. Analyses included Bland-Altman diagrams, intraclass correlation coefficients and equivalence tests. The repeatability of the four methods across two nights ranged from good to perfect. The agreement study highlighted that the hockey stick showed equivalent or superior performance (ICC: 0.95, mean difference with visual estimation: 5 min) in healthy subjects compared to the dynamic and fixed thresholds. Thanks to its objective nature, the hockey stick method may provide better estimates than the mean of the visual estimations of several raters. These findings suggest that the hockey stick method provides the most reliable estimate of DLMO within the tested methods and should be considered for use in future studies.

Proteomic biomarkers of Kleine-Levin syndrome.

STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. METHODS: SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. RESULTS: Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases. CONCLUSIONS: Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.

Slow Wave Sleep Deficits in the Flinders Sensitive Line Rodent Model of Depression: Effects of Medial Forebrain Bundle Deep-Brain Stimulation.

Major Depressive Disorder (MDD) is an affective disorder typically accompanied by sleep disturbances. Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) is an emerging intervention for treatment-resistant depression, but its effect on sleep has not been closely examined. Here we aimed to characterise sleep deficits in the Flinders sensitive line, an established rodent model of depression, and investigate the consequences of MFB stimulation on sleep-related phenotypes. Rats were implanted with bilateral stimulation electrodes in the MFB, surface electrodes to record electrocorticography and electromyography for sleep scoring and electrodes within the prelimbic cortex, nucleus accumbens (NAc) and dorsal hippocampus. Recordings of sleep and oscillatory activity were conducted prior to and following twenty-four hours of MFB stimulation. Behavioural anti-depressant effects were monitored using the forced swim test. Previously unreported abnormalities in the Flinders sensitive line rats were observed during slow wave sleep, including decreased circadian amplitude of its rhythm, a reduction in slow wave activity and elevated gamma band oscillations. Previously established rapid eye movement sleep deficits were replicated. MFB stimulation had anti-depressant effects on behavioural phenotype, but did not significantly impact sleep architecture; it suppressed elevated gamma activity during slow wave sleep in the electrocorticogram and prelimbic cortex signals. Diverse abnormalities in Flinders sensitive line rats emphasise slow wave sleep as a state of dysfunction in affective disorders. MFB stimulation is able to affect behaviour and sleep physiology without influencing sleep architecture. Gamma modulation may represent a component of antidepressant mechanism.

The melanopsin-mediated pupil response is reduced in idiopathic hypersomnia with long sleep time.

Idiopathic hypersomnia (IH), characterized by an excessive day-time sleepiness, a prolonged total sleep time on 24 h and/or a reduced sleep latency, affects 1 in 2000 individuals from the general population. However, IH remains underdiagnosed and inaccurately treated despite colossal social, professional and personal impacts. The pathogenesis of IH is poorly known, but recent works have suggested possible alterations of phototransduction. In this context, to identify biomarkers of IH, we studied the Post-Illumination Pupil Response (PIPR) using a specific pupillometry protocol reflecting the melanopsin-mediated pupil response in IH patients with prolonged total sleep time (TST > 660 min) and in healthy subjects. Twenty-eight patients with IH (women 86%, 25.4 year-old ± 4.9) and 29 controls (women 52%, 27.1 year-old ± 3.9) were included. After correction on baseline pupil diameter, the PIPR was compared between groups and correlated to sociodemographic and sleep parameters. We found that patients with IH had a lower relative PIPR compared to controls (32.6 ± 9.9% vs 38.5 ± 10.2%, p = 0.037) suggesting a reduced melanopsin response. In addition, the PIPR was not correlated to age, chronotype, TST, nor depressive symptoms. The melanopsin-specific PIPR may be an innovative trait marker of IH and the pupillometry might be a promising tool to better characterize hypersomnia.

Direct Effects of Light on Sleep under Ultradian Light-Dark Cycles Depend on Circadian Time and Pulses Duration.

Ultradian light-dark cycles in rodents are a precious tool to study the direct effects of repeated light exposures on sleep, in order to better understand the underlying mechanisms. This study aims to precisely evaluate the effects of light and dark exposures, according to circadian time, on sleep and waking distribution and quality, and to determine if these effects depend on the duration of light and dark pulses. To do this, mice were exposed to 24 h-long ultradian light-dark cycles with different durations of pulses: T2 cycle (1 h of light/1 h of dark) and T7 cycle (3.5 h of light/3.5 h of dark). Exposure to light not only promotes NREM and REM sleep and inhibits wake, but also drastically alters alertness and modifies sleep depth. These effects are modulated by circadian time, appearing especially during early subjective night, and their kinetics is highly dependent on the duration of pulses, suggesting that in the case of pulses of longer duration, the homeostatic process could overtake light direct influence for shaping sleep and waking distribution.

Validation of Somno-Art Software, a novel approach of sleep staging, compared with polysomnography in disturbed sleep profiles.

Study Objectives: Integrated analysis of heart rate (electrocardiogram [ECG]) and body movements (actimetry) during sleep in healthy subjects have previously been shown to generate similar evaluation of sleep architecture and continuity with Somno-Art Software compared to polysomnography (PSG), the gold standard. However, the performance of this new approach of sleep staging has not yet been evaluated on patients with disturbed sleep. Methods: Sleep staging from 458 sleep recordings from multiple studies comprising healthy and patient population (obstructive sleep apnea [OSA], insomnia, major depressive disorder [MDD]) was obtained from PSG visual scoring using the American Academy of Sleep Medicine rules and from Somno-Art Software analysis on synchronized ECG and actimetry. Results: Inter-rater reliability (IRR), evaluated with 95% absolute agreement intra-class correlation coefficient, was rated as "excellent" (ICCAAAvg95% ≥ 0.75) or "good" (ICCAAAvg95% ≥ 0.60) for all sleep parameters assessed, except non-REM (NREM) and N3 sleep in healthy participants (ICCAAAvg95% = 0.43, ICCAAAvg95% = 0.56) and N3 sleep in OSA patients (ICCAAAvg95% = 0.59) rated as "fair" IRR. Overall sensitivity, specificity, accuracy, and Cohen's kappa coefficient of agreement (κ) on the entire sample were respectively of 93.3%, 69.5%, 87.8%, and 0.65 for wake/sleep classification and accuracy and κ were of 68.5% and 0.55 for W/N1+N2/N3/rapid eye movement (REM) classification. These performances were similar in healthy and patient population. Conclusions: The present results suggest that Somno-Art can be a valid sleep-staging tool in both healthy subjects and patients with OSA, insomnia, or MDD. It could complement existing non-attended techniques measuring sleep-related breathing patterns or be a useful alternative to laboratory-based PSG when this latter is not available.

Sleep and circadian rhythm characteristics in individuals from the general population during the French COVID-19 full lockdown.

The full 2-month lockdown to fight the coronavirus disease 2019 (COVID-19) pandemic in 2020 led to substantial disruption of daily life and routines. The present study aimed to comprehensively identify the lockdown's effects on sleep, daily rhythms and emotions of the French population. A survey was published online during the last week of the 2-month full lockdown and 1,627 individuals completed the online survey. The survey was self-administered and included standardised questionnaires. Sleep schedules were delayed during lockdown in more than half of the participants. New severe delayed sleep phase affected 10% of participants with sleep schedules delayed by ≥3 hr during the lockdown compared to before. A significant decrease in exposure to morning (p < 0.001) and evening natural light (p < 0.001), a significant increase in screen exposure time (with a significant screen exposure >3 hr during the evening for 45% of the participants during lockdown versus 18% before lockdown, p < 0.001), an increase in substance use for one-quarter of participants, a poorer sleep quality in 56% of participants, and less regular sleep schedules in 48% of participants were observed. We also found a poorer sleep quality in women than men during lockdown (p = 0.004). The French full lockdown had a severe impact on sleep quality, sleep-wake rhythms, and sleep behaviours. The implementation of public health strategies for the prevention and care of sleep-wake cycles during lockdown are therefore essential.

Stroke-related restless legs syndrome: Clinical and anatomo-functional characterization of an emerging entity.

BACKGROUND AND PURPOSE: Stroke-related restless legs syndrome (sRLS) secondary to ischemic lesions is an emerging entity and an interesting condition, but there are limited available data to help us further understand its underlying pathways. In this study, we characterized sRLS clinically, neuroanatomically and functionally. METHODS: Consecutive patients hospitalized in the Stroke Unit of the University Hospital of Strasbourg were assessed clinically and electrophysiologically for sRLS characteristics. They underwent brain magnetic resonance imaging for the neuroanatomical study of involved structures, and received functional evaluations with 18 F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography (PET) for glucose consumption, 123 I-FP-CIT ([123]I-2beta-carbometoxy-3beta-[4-iodophenyl]-N-[3-fluoropropyl]nortropane) single-photon emission computed tomography for dopamine reuptake and PET with 18 F-FDOPA ((3,4-dihydroxy-6-[18]F-fluoro-l-phenylalanine) for presynaptic dopaminergic synthesis. RESULTS: Sixteen patients with sRLS, eight women and eight men, aged 41-81 years, were included. The clinical characteristics of sRLS and idiopathic RLS were similar. Most patients presented with bilateral and symmetric de novo RLS. Eight patients had infarction in the lenticulostriate area (middle cerebral artery and internal carotid arteria). The body of the caudate nucleus was most commonly affected. Seven patients had sRLS secondary to ventral brainstem infarction (perforating branches of the basilar arteria) affecting the pons in six patients and the medulla oblongata in one patient. Both the corticospinal tract and the cortico-pontocerebellar fibres were lesioned in all patients with brainstem stroke. One patient had infarction in the left posterior cerebellar vermis and occipital area (posterior cerebral artery and superior cerebellar artery). Isotopic explorations showed a significantly increased dopaminergic tone in the striatum ipsilateral to lenticulostriate infarction. Dopamine fixation was normal in patients with stroke outside of the lenticulostriate area. CONCLUSIONS: Clinicians should be aware of the characteristics of sRLS for the appropriate diagnosis and treatment of this condition.