Prompt improvement of difficulty with sleep initiation and waking up in the morning and daytime somnolence by combination therapy of suvorexant and ramelteon in delayed sleep-wake phase disorder: a case series of three patients

Patients with delayed sleep-wake phase disorder (DSWPD) suffer from difficulties in sleep initiation at night, difficulties in waking up at the socially required time, and daytime somnolence. About half of the patients resist conventional light therapy and melatonin therapy. Therapy using hypnotics is not recommended due to its adverse effects. Recently, suvorexant, an orexin receptor antagonist, has become available for clinical use. The drug is relatively safer than traditional hypnotics such as benzodiazepines. We report three DSWPD patients who were successfully treated by the combination therapy of suvorexant and ramelteon. The first case was a 19-year-old woman who was experiencing difficulties in sleep initiation, difficulty in waking up in the morning, and daytime somnolence. She showed a prompt response to the combination therapy of suvorexant and ramelteon. Her sleep phase advanced, and her daytime somnolence reduced. The second and third cases were 21-year-old and 17-year-old men, respectively, who also showed significant sleep phase advances. Although case 2 was resistant to ramelteon treatment, his sleep phase advanced after suvorexant started. His difficulty in falling asleep and his habit of daytime napping disappeared after the combination therapy of suvorexant and ramelteon was started. Case 3 also showed a prompt response. His difficulties in falling asleep and waking up in the morning were ameliorated immediately after suvorexant with ramelteon was started. No obvious side effects were observed. Therapy using the combination therapy of suvorexant and ramelteon might be a reasonable option for DSWPD patients.     

Validation of the Japanese version of the Sleep Hygiene Practice Scale

ObjectiveThis study sought to validate the Japanese version of the Sleep Hygiene Practices Scale (SHPS-J).Patients/methodsA cross-sectional questionnaire-based study was conducted via the internet. In total, 854 participants (435 men, 419 women; mean age, 42.91 ± 11.54 years) were asked to complete all scales, and 283 of them were asked to complete the same scales two weeks later. The survey consisted of the SHPS-J, the Japanese version of the Insomnia Severity Index (ISI-J), and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J). The SHPS-J was developed according to the International Society for Pharmacoeconomics and Outcomes Research Task Force for Translation and Cultural Adaption. For the analysis, participants were divided into three groups: insomnia syndrome, insomnia symptoms, and good sleep groups.ResultsThe SHPS-J had good test-retest reliability (ICC: 0.55–0.76) and adequate internal consistency (α = 0.54–0.74), except with regard to eating/drinking behaviors. The factorial validity of the four-factor structure was confirmed through a confirmatory factor analysis; however, one item related to eating/drinking behaviors had no significant factor loading. The construct validity was confirmed through a correlation analysis between each domain of the SHPS-J and ISI-J (r = 0.19–0.60, p < 0.01). The results of clinical validation confirmed that all domains of the SHPS-J were significantly higher for individuals with insomnia than for good sleepers.ConclusionsThis study confirmed both the reliability and validity of the SHPS-J.     

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial

Objective/backgroundLemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2).Patients/methodsStudy 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored.ResultsFor all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache.ConclusionsLEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia.Clinical trial registrationClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.     

A transdiagnostic evaluation of contrast avoidance across generalized anxiety disorder,major depressive disorder,and social anxiety disorder

BackgroundThe contrast avoidance model (CAM) proposes that persons with generalized anxiety disorder (GAD) are sensitive to sharp increases in negative emotion or decreases in positive emotion (i.e., negative emotional contrasts; NEC) and use worry to avoid NEC. Sensitivity to and avoidance of NEC could also be a shared feature of major depressive disorder (MDD) and social anxiety disorder (SAD).MethodsIn a large college sample (N = 1409), we used receiver operating characteristics analysis to examine the accuracy of a measure of emotional contrast avoidance in detecting probable GAD, MDD, and SAD.ResultsParticipants with probable GAD, MDD, and SAD all reported higher levels of contrast avoidance than participants without the disorder (Cohen’s d = 1.32, 1.62 and 1.53, respectively). Area under the curve, a measure of predictive accuracy, was .81, .87, and .83 for predicting probable GAD, MDD, and SAD, respectively. A cutoff score of 48.5 optimized predictive accuracy for probable GAD and SAD, and 50.5 optimized accuracy for probable MDD.ConclusionA measure of emotional contrast avoidance demonstrated excellent ability to predict probable GAD, MDD, and SAD. Sensitivity to and avoidance of NEC appears to be a transdiagnostic feature of these disorders.     

Validation of the Japanese version of Stress and Anxiety to Viral Epidemics-9 (SAVE-9) and relationship among stress,insomnia, anxiety,and depression in healthcare workers exposed to coronavirus disease 2019

ObjectiveThis study aimed to validate the Japanese version of the 9-item Stress and Anxiety to Viral Epidemics scale (SAVE-9) and the relationships among the stress related to viral epidemics, insomnia, anxiety, and depression.Patients/methodsA cross-sectional questionnaire-based study was conducted online. In total, 1000 healthcare workers (579 men, 421 women; mean age: 43.11 ± 11.69 years) were asked to complete the SAVE-9, Athens Insomnia Scale, Generalized Anxiety Disorder-7 Scale, and Center for Epidemiological Studies Depression Scale. For the analysis, participants were divided into two groups: healthcare workers at a medical institution designated for COVID-19 (COVID institution) and those working at an institution not designated for COVID-19 (non-COVID institution).ResultsItem response theory analysis showed that the SAVE-9 and SAVE-6 (6-item version) had good structural validity and internal consistency (ω = 0.91 and 0.93). Correlation analysis for convergent validity showed a significant positive correlation between both the SAVE-9 and SAVE-6 and the other scales for insomnia, anxiety, and depression. In addition, both SAVE-9 and SAVE-6 scores were higher for workers in COVID institutions than for those in non-COVID institutions. Furthermore, stress related to viral epidemics was found to directly affect anxiety (β = 0.48) and depression (β = 0.25) and indirectly affect anxiety (β = 0.37) and depression (β = 0.54) via insomnia (β = 0.33).ConclusionsThis study confirmed that the reliability and validity of both the SAVE-9 and SAVE-6 and that insomnia mediated the effects of stress to viral epidemics on anxiety and depression symptoms.     

Genetic variants for morningness in relation to habitual sleep-wake behavior and diurnal preference in a population-based sample of 17,243 adults

ObjectiveAssociations of eveningness with health hazards benefit from analyzing to what extent the polygenic score for morningness correlates with the assessments of the behavioral trait of morningness-eveningness and chronotype.MethodsWith a population-based sample of 17,243 Finnish adults, aged 25–74 years, this study examines the associations of four feasible assessment methods of chronotype, a) biological the genetic liability based on the polygenic score for morningness (PGS_morn), b) the widely-used single item for self-assessed morningness/eveningness (MEQ_i19) of the original Morningness-Eveningness Questionnaire (MEQ), c) the behavioral trait of morningness-eveningness as assessed with the score on the shortened version (sMEQ) of the original MEQ, and d) the phase of entrainment as assessed with the habitual midpoint of sleep based on the self-reported sleep-wake schedule during weekend (Sleep_mid-wknd) as well as the sleep debt corrected midpoint of sleep (Sleep_mid-corr).ResultsAll self-report measures correlated with each other, but very weakly with the PGS_morn, which explained 1–2% of the variation in diurnal preference or habitual sleep-wake schedule. The influence of age was greater on Sleep_mid-wknd and Sleep_mid-corr than on the sMEQ or MEQ_i19, indicating that the diurnal preference might be a more stable indicator for morningness-eveningness than the sleep-wake schedule. Analyses of the discrepancies between sMEQ and MEQ_i19 indicated that eveningness can be over-estimated when relying on only the single-item self-assessment.ConclusionsThe current polygenic score for morningness explains only a small proportion of the variation in diurnal preference or habitual sleep-wake schedule. The molecular genetic basis for morningness-eveningness needs further elucidation.     

Comparison of clinical outcomes with left unilateral and sequential bilateral Transcranial Magnetic Stimulation (TMS) treatment of major depressive disorder in a large patient registry

BackgroundIt has been suggested that sequential bilateral (SBL) TMS, combining high frequency, left dorsolateral prefrontal cortex (DLPFC) stimulation and low frequency, right DLPFC stimulation, is more effective than unilateral TMS.ObjectiveTo contrast treatment outcomes of left unilateral (LUL) and SBL protocols.MethodsRegistry data were collected at 111 practice sites. Of 10,099 patients, 3,871 comprised a modified intent-to-treat (mITT) sample, defined as a primary MDD diagnosis, age ≥18, and PHQ-9 completion before TMS and at least one PHQ-9 assessment after baseline. The mITT sample received high frequency (10 Hz) LUL TMS exclusively (N = 3,327) or SBL TMS in at least 90% of sessions (N = 544). Completers (N = 3,049) were responders or had received ≥20 sessions and had an end of acute treatment PHQ-9 assessment. To control for site effects, a Matched sample (N = 653) included Completers at sites that used both protocols. To control for selection bias, the SBL group was also compared to a Restricted LUL group, drawn from sites where no patient switched to SBL after substantial exposure to LUL TMS. Secondary analyses were conducted on CGI-S ratings.ResultsThe LUL group had superior outcomes compared to the SBL group for multiple PHQ-9 and CGI-S continuous and categorical measures in the mITT, Completer and Matched samples, including in the specified primary analyses. However, outcome differences were not observed when comparing the Restricted LUL and SBL groups. Within SBL protocols, the LUL-RUL order had superior outcomes compared to the RUL-LUL order in all CGI-S, but not PHQ-9, measures.ConclusionsWhile limited by the naturalistic design, there was no evidence that SBL TMS was superior to LUL TMS. The sequential order of RUL TMS followed by LUL TMS may have reduced efficacy compared to LUL TMS followed by RUL TMS.     

Comparison of clinical outcomes with two Transcranial Magnetic Stimulation treatment protocols for major depressive disorder

BackgroundTranscranial magnetic stimulation (TMS) is an effective treatment for major depressive disorder (MDD). The rest time between pulse trains is the inter-train interval (ITI). Since 2016, some TMS clinicians have adopted a stimulation protocol with shorter ITIs than were used in regulatory clinical trials.ObjectiveTo contrast treatment outcomes with the Standard TMS protocol (38.5 min per session) and the “Dash” protocol, which, at the shortest ITI, has a session duration of 18.75 min.MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. Within the ITT sample, 613 patients were treated with the Standard NeuroStar 38-min protocol and 1493 patients with the new Dash protocol. CGI-S ratings were obtained in smaller samples. Treatment outcomes were also examined in subgroups considered Completers, as well as the subgroups who met criteria for Full Adherence to the Standard or Dash protocol parameters.ResultsIn the ITT, Completer, and Fully Adherent samples, response (58–72%) and remission (28–53%) rates were notably high across PHQ-9 and CGI-S ratings. The Standard and Dash protocols did not differ in number of treatment sessions, and both manifested strong antidepressant effects.ConclusionsThe Standard and Dash protocols did not meaningfully differ in efficacy.     

Prevalence and evolution of snoring and the associated factors in two-year-old children

ObjectivesTo evaluate the prevalence and persistence of snoring during the first two years of life in two Finnish birth cohorts and to assess the associated factors.Study designThe study population comprised 947 children from the CHILD-SLEEP (CS) and 1393 children from the FinnBrain (FB) birth cohorts. Questionnaires were provided to both parents when the child was 24 months of age. The questionnaire consisted of parts concerning the child's sleep and environmental factors.ResultsThe combined prevalence of habitual snoring in the two birth cohorts at the age of 24 months was 2.3% (95% CI 1.5–3.1), which is markedly lower than reported previously.Children suffering from recurrent infections (CS odds ratio (OR) 3.9, 95% CI 1.2–12.5) or asthma (FB OR 4.3, 1.4–13.5) snored habitually more often. Both the mother's (CS OR 3.2, 1.2–9.0) and father's (CS OR 3.4, 1.4–8.0) snoring every night added to the risk of the child snoring. In the multivariate models, parental snoring (CS adjusted odds ratio (OR_a) 2.8, 1.1–6.8), the mother's lower level of education (CS OR_a 2.9, 1.2–7.5, FB OR_a 2.1, 1.0–4.5), and the mother's lower monthly income (FB OR_a 2.9, 1.3–6.3) associated with the child's habitual snoring.ConclusionsThe prevalence of habitual snoring in two Finnish birth cohorts is lower than reported previously. The independent risk factors for habitual snoring at the age of two years were the parents' snoring and the mother's low income and low education.     

Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized,double-blind,placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m²) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.     

Intensified electrical stimulation targeting lateral and medial prefrontal cortices for the treatment of social anxiety disorder: A randomized,double-blind,parallel-group,dose-comparison study

BackgroundSocial Anxiety Disorder (SAD) is the most common anxiety disorder while remains largely untreated. Disturbed amygdala-frontal network functions are central to the pathophysiology of SAD, marked by hypoactivity of the lateral prefrontal cortex (PFC), and hypersensitivity of the medial PFC and the amygdala. The objective of this study was to determine whether modulation of the dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli.MethodsIn this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three tDCS arms (1-mA, 2-mA, sham). SAD symptoms, treatment-related variables (worries, depressive state, emotion regulation, quality of life), and attention bias to threatening stimuli (dot-probe paradigm) were assessed before and right after the intervention. SAD symptoms were also assessed at 2-month follow-up.ResultsBoth 1-mA and 2-mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Improving effect of the 2-mA protocol on avoidance symptoms, worries and depressive state was significantly larger than the 1-mA group. Only the 2-mA protocol reduced attention bias to threat-related stimuli, the avoidance symptom at follow-up, and depressive states, as compared to the sham group.ConclusionsModulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and might thereby result in therapeutic effects. These effects can be larger with 2-mA vs 1-mA intensities, though a linear relationship between intensity and efficacy should not be concluded. Our results need replication in larger trials.     

The Arousal Disorders Questionnaire: a new and effective screening tool for confusional arousals,Sleepwalking and Sleep Terrors in epilepsy and sleep disorders units

BackgroundArousal Disorders (DoA) include Confusional Arousals, Sleepwalking and Sleep Terrors. DoA diagnosis is mainly clinical but no validated questionnaires exist for DoA screening according to the criteria of the International Classification of Sleep Disorders, Third Edition. Recently our group proposed the Arousal Disorders Questionnaire (ADQ) as a new diagnostic tool for DoA diagnosis. The objective of this study was to evaluate the diagnostic accuracy of the ADQ in a sleep and epilepsy center.MethodsOne interviewer blinded to clinical and video-polysomnographic (VPSG) data administered the ADQ to 150 patients consecutively admitted to our Sleep and Epilepsy Centers for a follow-up visit. The final diagnosis, according to VPSG recordings of at least one major episode, classified patients either with DoA (DoA group) or with other sleep-related motor behaviors confounding for DoA (nDoA group).Results47 patients (31%) composed the DoA group; 56 patients with REM sleep behavior disorder, 39 with sleep-hypermotor epilepsy, six with night eating syndrome, and two with drug-induced DoA composed the nDoA group. The ADQ had a sensitivity of 72% (95% CI: 60–82) and a specificity of 96% (95% CI: 89–98) for DoA diagnosis; excluding the items regarding consciousness and episode recall, sensitivity was 83% (95% CI: 71–90) and specificity 93% (95% CI: 86–97).ConclusionsThe ADQ showed good accuracy in screening patients with DoA in a sleep and epilepsy center setting. Diagnostic criteria related to cognition and episode recall reduced ADQ sensitivity, therefore a better definition of these criteria is required, especially in adults.     

Sleep spindles in children with restless sleep disorder,restless legs syndrome and normal controls

ObjectiveTo analyze and identify differences in sleep spindles in children with restless sleep disorder (RSD), restless legs syndrome (RLS) and normal controls.MethodsPSG (polysomnography) from children with RSD, RLS and normal controls were analyzed. Sleep spindle activity was detected on one frontal and one central electrode, for each epoch of N2 and N3 sleep. Sleep spindle density, duration and intensity (density × duration) were then obtained and used for analysis.ResultsThirty-eight children with RSD, twenty-three children with RLS and twenty-nine controls were included. The duration of frontal spindles in sleep stage N2 was longer in children with RSD than in controls. Frontal spindle density and intensity tended to be increased in RSD children. No significant differences were found for central spindles.ConclusionChildren with RSD had longer frontal spindles. This finding may contribute to explain the occurrence of excessive movement activity during sleep and the presence of daytime symptoms.SignificanceRecent research has demonstrated that children with RSD have increased NREM instability and sympathetic activation during sleep. Analyzing sleep spindles in children with RSD in comparison with children with RLS and controls adds to our understanding of the pathophysiology or RSD and its effects on daytime impairment.     

A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation

BackgroundDeep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimulation paradigms in existing or prospective indications.ObjectiveProvide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on neuronal activity.MethodsIn patients with movement disorders, single-neuron recordings were acquired from the subthalamic nucleus, substantia nigra pars reticulata, ventral intermediate nucleus, or reticular thalamus during microstimulation across various frequencies (1–100 Hz) to assess single-pulse and frequency-response functions. Moreover, a biophysically-realistic computational framework was developed which generated postsynaptic responses under the assumption that electrical stimuli simultaneously activated all convergent presynaptic inputs to stimulation target neurons. The framework took into consideration the relative distributions of excitatory/inhibitory afferent inputs to model site-specific responses, which were in turn embedded within a model of short-term synaptic plasticity to account for stimulation frequency-dependence.ResultsWe demonstrated microstimulation-evoked excitatory neuronal responses in thalamic structures (which have predominantly excitatory inputs) and inhibitory responses in basal ganglia structures (predominantly inhibitory inputs); however, higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression. The model confirmed that site-specific responses could be simulated by accounting for local neuroanatomical/microcircuit properties, while suppression of neuronal activity during high-frequency stimulation was mediated by short-term synaptic depression.ConclusionsBrain-region-specific and frequency-dependant neuronal responses could be simulated by considering neuroanatomical (local microcircuitry) and neurophysiological (short-term plasticity) properties.     

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease

ObjectivesDespite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).MethodsIn this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the “pROC” package of R (version 1.16.2).ResultsThe area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912–1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.ConclusionsOur deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.     

Core body temperature changes in school-age children with circadian rhythm sleep–wake disorder

Objective/backgroundCore body temperature (CBT) is considered a valuable marker for circadian rhythm. This study aimed to investigate the changes in CBT that are associated with the symptoms of circadian rhythm sleep–wake disorder (CRSWD) post-treatment in children.Patients/methodsTwenty-eight school-age children [10 boys and 18 girls; mean age (±standard deviation), 13.68 ± 0.93 years] who were admitted to our hospital with CRSWD underwent treatment for 6–8 weeks according to the following protocol: lights-out for sleep at 21:00; phototherapy for waking at 6:00 or 7:00; light exercise everyday (eg, a 20- to 30-min walk). CBT was continuously measured for 24 h on the first day of admission and on the first day after treatment.ResultsThe mean time of sleep onset/offset (±standard deviation; in hours:minutes) 1 week before admission and 1 week after treatment were 23:53 ± 2:26/9:58 ± 2:15 and 21:17 ± 0:19/6:46 ± 0:32, respectively. The mean times of sleep onset and offset measured post-treatment were significantly earlier than those measured pre-treatment (p < 0.001). The mean CBT and mean minimum CBT during sleep were significantly lower on the first day post-treatment than on the first day of admission (p = 0.011 and p < 0.001, respectively).ConclusionsSymptom improvements in patients with CRSWD were associated with a decrease in CBT during sleep, suggesting that CBT may be a biomarker for improvements in CRSWD. These results help elucidate the cause of this sleep disorder.     

Thromboelastography 6s for assessment of platelet function during coil embolization of unruptured intracranial aneurysms

ObjectivesMethods for assessing platelet function in patients with neurovascular disease remain controversial and poorly studied. This study aimed to assess associations between thromboelastography 6s (TEG6s) measurements and postoperative ischemic complications in patients with unruptured intracranial aneurysms (UIAs) treated by coil embolization.MethodsEighty-four patients with UIAs taking a combined aspirin and clopidogrel protocol were retrospectively reviewed from January 2021 to May 2022. Blood samples were obtained for TEG6s to assess platelet function on the day of coil embolization. To identify acute ischemic complications, diffusion-weighted imaging (DWI) was performed within 24 h after coil embolization. Multivariate logistic regression analysis was conducted to identify potential risk factors for postoperative positive DWI (DWI (+)) lesions.ResultsForty-three of the 84 patients (51%) with DWI (+) lesions were identified. Compared with patients without DWI (+) lesions, Adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MA_ADP) was significantly higher (53.6 mm [Interquartile range (IQR): 48.3–58.3 mm] vs 46.7 mm [IQR: 36.8–52.2 mm]; p=0.001) and ADP inhibition rate (ADP%) was significantly lower (19% [IQR: 11–31%] vs 31% [IQR: 21–44%]; p=0.001) in DWI (+) patients. Multivariate analysis identified MA_ADP, ADP%, and procedure time as significant independent predictors of subsequent DWI (+) lesions (odds ratios: 1.07, 0.96, and 1.02, respectively). Based on receiver operating characteristic curve analysis, MA_ADP >50.9 mm and ADP% <28.8% were associated with postoperative DWI (+) lesions in patients undergoing coil embolization for UIAs.ConclusionsMA_ADP and ADP% as assessed by TEG6s can offer reliable parameters to predict postoperative ischemic complications after coil embolization of UIAs. Lower MA_ADP values and higher ADP% may decrease the risk of postoperative ischemic complications.