Development and validation of the hypersomnia-specific beliefs scale

Objective/BackgroundPatients with Central hypersomnia, especially Narcolepsy type 1 and Idiopathic Hypersomnia (NT1 and IHS) often have psychological frustration in their daily lives. We aimed to develop the first scale of hypersomnia-specific beliefs (HSB).Patients/methodsWe developed the HSB scale consisting of three factors (“aversion toward doze”, “hypersensitivity toward others” reactions about my doze”, and “sense of defeat caused by doze”) with 12 items through interviews to 11 patients with NT1 and IHS. Validity and reliability of the HSB were evaluated cross-sectionally with 166 patients with NT1 and IHS and 375 controls. Simultaneously, scores of patient health questionnaire −2(PHQ-2), mini-Social Phobia Inventory (mini-SPIN), and Epworth Sleepiness Scale (ESS) were obtained.ResultsThis 3-factor model had enough fitness (χ2 = 60.25, df = 51, p = 0.18, TLI = 0.99, CFI = 0.99, RMSEA = 0.03), Cronbach's α coefficient being 0.90. The intraclass correlation coefficient was 0.76. Also, the area under the receiver operating characteristic curve (AUC = 0.88) confirmed good discrimination ability. A cut-off score of 38 resulted in a sensitivity of 90% and a specificity of 75%. Multiple linear regression analyses showed that these scales were independently associated with the HSB score; the PHQ-2 (β = 0.24, p = 0.002), mini-SPIN (β = 0.29, p < 0.001) and ESS (β = 0.15, p = 0.048).ConclusionsOur data suggest that the HSB scale measured beliefs in NT1 and IHS patients with good validity, reliability, and discrimination ability. The HSB scale assesses the negative beliefs specific to patents with NT1 and IHS. This scale could be applied to the development of novel psychotherapeutic approach to patients with NT1 and IHS.     

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.     

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.     

Female and male sleep duration in association with the probability of conception in two representative populations of reproductive age in US and China

ObjectiveSleep duration has been found to affect some reproductive phenotypes but fecundability has been rarely researched. We aim to evaluate the association between female/male sleep duration and the probability of conception in two representative populations.MethodsThe present study uses two datasets, namely, a cross-sectional dataset of 9137 reproductive-age females in the US (National Health Interview Survey, NHIS) and a longitudinal dataset of 2687 reproductive-age females and their male mates in China (China Health and Nutrition Survey, CHNS). Logistic regression or mixed model was used to analyze the association between sleep duration and the probability of conception in the females of both populations and in CHNS males with adjustments for demographic, socioeconomic, behavioral, sleep health and reproductive factors.ResultsAn inverse association was observed between male sleep duration (≥8 h/day) and their mates' conception probability in the CHNS population (P = 0.012). Sleep of 9 h/day and ≥10 h/day in men was associated with 0.65 (0.41–1.02) fold and 0.53 (0.31–0.90) fold of conception probability when compared to 8 h/day sleep. On the other hand, a U-shaped association between female sleep duration and conception probability was observed in both populations. Each hour/day departure (longer or shorter) from 7 h/day sleep was associated with 1.26 (1.12–1.42, P < 0.001) and 1.21 (1.03–1.41, P = 0.019) fold conception probability in the NHIS and CHNS populations, respectively. An adjustment for potential confounders, including spouse characteristics did not substantially attenuate these associations.ConclusionsFemale and male sleep duration may be independent predictors of conception, suggesting there is an intervention target for reproductive health.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

Validation and confirmatory factor analysis of the pediatric Adherence Barriers to Continuous Positive Airway Pressure Questionnaire

ObjectiveTo evaluate and refine a newly proposed factor structure for the Adherence Barriers to Continuous Positive Airway Pressure Questionnaire (ABCQ) and to present psychometric data from a large, geographically diverse sample of children and young adults with sleep disordered breathing (SDB) treated with positive airway pressure (PAP).MethodsA sample of 181 patients prescribed PAP for treatment of SDB, ages 8–21 years, and caregivers (n = 234) of patients ages 2–21 years, completed the ABCQ during routine sleep medicine clinic visits. Adherence data from participants' PAP machines were obtained via electronic download, providing objective data on PAP adherence immediately preceding the clinic visit during which the ABCQ was completed.ResultsA three-factor structure (1. Behavior, Beliefs, Environment, 2. Emotional Barriers, & 3. Physical Barriers) exhibited good model fit in confirmatory factor analysis. Results indicate that the ABCQ has strong psychometric properties, including good internal consistency among subscales and strong convergent validity with objectively measured PAP adherence. Analysis of the Receiver Operator Characteristic Curve (ROC) yielded an ABCQ total cut-off score of 46.5 for patient report and 53.5 for caregiver report. Scores above the cutpoint predicted nonadherence to PAP, defined as failure to use PAP for ≥4 h on 70% of nights.ConclusionsThe three-factor ABCQ appears to be a useful patient- and caregiver-report instrument to measure barriers to PAP treatment in children and young adults with sleep disordered breathing.     

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial

ObjectivesLittle evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity.MethodsTwenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2.ResultsAt T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016).At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group.ConclusionstDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections.SignificanceThis study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.     

Sleep time and sleep-related symptoms across two generations – results of the community-based RHINE and RHINESSA studies

Study objectivesTo analyze the association between sleep-related symptoms and sleep length in parents and their children in relation to other risk factors in both generations.MethodThe participants were parents (n = 5,855, age 54.3 ± 6.5 years, 45.2% men) who participated in the community-based Respiratory Health in Northern Europe (RHINE) study and one random member of their adult offspring (n = 5,855, age 30.2 ± 7.7 years, 41.5% men) who participated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study. Both generations responded to identical questionnaires on sleep symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, nocturnal sweating, nocturnal gastroesophageal reflux (nGER), sleep time and excessive daytime sleepiness (EDS). Insomnia was defined as either, or both, DIS and DMS in combination with EDS.ResultsAll sleep variables except nocturnal sweating were more common in offspring whose parents had reported the same symptom. After adjusting for age, gender, BMI, smoking, physical activity, education, center and parents' total number of children, there were independent associations between sleep symptoms in parents and offspring for DIS (adj. OR, 95% CI: 1.52, 1.20–1.93), DMS (1.34, 1.15–1.56), snoring (1.45, 1.15,1.83), nGER (1.65, 1.15–2.37), insomnia (1.39, 1.13–1.73), short sleep time (<6 h/night) (2.51, 1.72–3.68) and EDS (1.48, 1.26,1.72). There were no independent relationships between symptoms in parents and offspring for EMA, nocturnal sweating or long sleep time (>9 h/night).ConclusionThe familiar aggregation of many sleep disturbances was not explained by investigated lifestyle and environmental factors. This supports a heritable factor in sleep problems.     

The prevalence of sleep problems among children in mainland China: a meta-analysis and systemic-analysis

BackgroundWe conducted a meta-analysis and systematic review to identify a reliable estimate of sleep problems prevalence among children in mainland China and to describe its epidemiological characteristics.MethodsRelevant studies were searched thoroughly via electronic databases included China National Knowledge Infrastructure, Wanfang, Weipu, PubMed, Embase and Medline databases from inception until December 2020. Prevalence estimates were calculated by random-effects models. The sources of heterogeneity were explored using subgroup analyses and Meta-regression analysis, and publication bias was estimated by funnel plots and Egger's Test.ResultsOverall, 66 studies were included in this meta-analysis, which revealed that the pooled prevalence of sleep problems was 37.6% (95%CI: 34.3–40.9%) with high heterogeneity (I² = 99.6%,P < 0.001). The incidence of snoring was 7.7%, choking or gasping was 0.9%, apnea was 1.5%, restless sleep was 11.3%, mouth breathing was 4.7%, hyperhidrosis was 17.2%, leg movements was 2.7%, bruxism was 9.6%, sleep talking was 0.7%, sleep-walking was 0.8%, nightmare was 5.1%, enuresis was 3.4%, night awakening was 6.7% and trouble falling asleep was 11.1%. The prevalence rate of sleep problems among males was higher than females (OR:1.01,95%CI:1.05–1.13). In all age groups, the prevalence rates of sleep problems increased with age, including infancy or early childhood group (33.3%), pre-school group (38.9%), school-age group (43.7%). The prevalence rate in South China (30.4%, 95%CI: 23.9–36.8%) was the lowest, and the highest prevalence rate was in West China (47.4%,95%CI:35.9–58.9%), which than any other region in China. The point estimate for sleep disorders prevalence obtained using the CSHQ criterion was higher than other criteria. Meta-regression indicated that age group could influence prevalence estimation (P = 0.011).ConclusionsOver the past two decades, the prevalence rate of sleep problems among children in mainland China has increased, significantly affecting two-fifth of the school-age children. The incidence of hyperhidrosis, restless sleep and trouble falling asleep were significantly higher than other sleep prombles. The prevalence rate of sleep problems in west China was significantly higher than in any other area. There is still a lack of guidelines on children's sleep problems in mainland China, so future research should pay special attention to the sleep problems of school-age children and children in economically backward areas.     

Unaltered EEG spectral power and functional connectivity in REM microstates in frequent nightmare recallers: are nightmares really a REM parasomnia?

BackgroundFrequent nightmares show signs of hyperarousal in NREM sleep. Nevertheless, idiopathic nightmare disorder is considered a REM parasomnia, but the pathophysiology of REM sleep in relation to frequent nightmares is controversial. Cortical oscillatory activity in REM sleep is largely modulated by phasic and tonic REM periods and seems to be linked to different functions and dysfunctions of REM sleep. Here, we examined cortical activity and functional synchronization in frequent nightmare recallers and healthy controls, during phasic and tonic REM.MethodsFrequent nightmare recallers (N = 22) and healthy controls (N = 22) matched for high dream recall spent two nights in the laboratory. Phasic and tonic REM periods from the second nights' recordings were selected to examine differences in EEG spectral power and weighted phase lag index (WPLI) across groups and REM states.ResultsPhasic REM showed increased power and synchronization in delta and gamma frequency bands, whereas tonic REM featured increased power and synchronization in the alpha and beta bands. In the theta band, power was higher during tonic, and synchronization was higher during phasic REM sleep. No differences across nightmare and control participants or patterns representing interactions between the groups and REM microstates emerged.ConclusionsOur findings do not support the idea that abnormal REM sleep power and synchronization play a role in the pathophysiology of frequent nightmares. Altered REM sleep in nightmare disorder could have been confounded with comorbid pathologies and increased dream recall, or might be linked to more specific state factors (nightmare episodes).     

The evaluation of sleep disturbances for Chinese frontline medical workers under the outbreak of COVID-19

ObjectiveTo evaluate sleep disturbances of Chinese frontline medical workers (FMW) under the outbreak of coronavirus disease 2019 (COVID-19), and make a comparison with non-FMW.MethodsThe medical workers from multiple hospitals in Hubei Province, China, volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status. Sleep disturbances were defined as PSQI>6 points or/and AIS>6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS, as well as prevalence of sleep disturbances between FMW and non-FMW.ResultsA total of 1306 subjects (801 FMW and 505 non-FMW) were enrolled. Compared to non-FMW, FMW had significantly higher scores of PSQI (9.3 ± 3.8 vs 7.5 ± 3.7; P < 0.001; Cohen's d = 0.47), AIS (6.9 ± 4.3 vs 5.3 ± 3.8; P < 0.001; Cohen's d = 0.38), anxiety (4.9 ± 2.7 vs 4.3 ± 2.6; P < 0.001; Cohen's d = 0.22) and depression (4.1 ± 2.5 vs 3.6 ± 2.4; P = 0.001; Cohen's d = 0.21), as well as higher prevalence of sleep disturbances according to PSQI > 6 points (78.4% vs 61.0%; relative risk [RR] = 1.29; P < 0.001) and AIS > 6 points (51.7% vs 35.6%; RR = 1.45; P < 0.001).ConclusionFMW have higher prevalence of sleep disturbances and worse sleep quality than non-FMW. Further interventions should be administrated for FMW, aiming to maintain their healthy condition and guarantee their professional performance in the battle against COVID-19.     

A meta-analysis of the relationship between subjective sleep and depressive symptoms in adolescence

BackgroundAdolescence is a risk period for the development of mental illness, as well as a time for pronounced change in sleep behaviour. While prior studies, including several meta-analyses show a relationship between sleep and depressive symptoms, there were many inconsistences found in the literature.ObjectiveTo investigate the relationship between subjective sleep and depressive symptoms.MethodsFollowing PRISMA guidelines, we conducted a literature search that yielded forty-nine recent studies (2014–2020) with adolescent samples aged 9 to 25-year-olds, and more than double the sample size of previous meta-analyses (N = 318,256).ResultsIn a series of meta-analyses, we show that while several common categories of subjective sleep are associated with depressive symptoms in adolescents, the strength of this relationship varies. Measures of sleep perception: poor sleep quality (r = 0.41), insomnia (r = 0.37), sleep disturbances (r = 0.36), wake after sleep onset (r = 0.31), and daytime sleepiness (r = 0.30) correlated more strongly with depressive symptoms, than measures of sleep behaviour: sleep latency (r = 0.22), and sleep duration (r = −0.19).ConclusionsThese findings suggest that in studies of depressive symptoms it may be important to assess an adolescent's perception about their sleep, in addition to their sleep/wake behaviours.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Objective measurement of limb bradykinesia using a marker-less tracking algorithm with 2D-video in PD patients

BackgroundQuantitative measurement of parkinsonian motor symptoms is crucial in clinical practice and in research. However, the widely used Unified PD Rating Scale (UPDRS) part III is based on a semi-quantitative evaluation with high inter- and intra-rater variability. Sensor-based measurements have been widely studied but are limited for their accessibility.MethodsWe analyzed 2D-RGB videos recording finger tapping and leg agility tests in 29 PD patients with a marker-less deep-learning based tracking algorithm. The tracking performance was validated with an accelerometer. Four parameters (mean amplitude, mean interpeak interval, amplitude variability and interpeak interval variability) were calculated from the position tracking.ResultsThe performance of the video-tracking was in good agreement with the accelerometer-based tracking (Intra-class correlation coefficient > 0.9 for the peak amplitude, and >0.6 for the interpeak interval). The video-tracking successfully captured variable aspects of limb bradykinesia that have a distinct correlation with the general parkinsonian motor symptoms and gait. In the finger-tapping task, the mean amplitude (R = −0.6, p = 2.4 × 10⁻⁶), amplitude variability (R = 0.36, p = 0.0092), mean interpeak interval (R = 0.34, p = 0.014), and interpeak interval variability (R = 0.66, p = 1.4 × 10⁻⁷) was significantly correlated with the UPDRS scores. In leg agility test, the mean amplitude (R = −0.58, p = 1.7 × 10⁻⁵), mean interpeak interval (R = 0.37, p = 0.0088) and interpeak interval variability (R = 0.7, p = 6.2 × 10⁻⁸) were significantly correlated with the UPDRS scores, but not with amplitude variability (R = 0.17, p = 0.26). Limb rigidity was significantly correlated with the interpeak interval (R = 0.40, p = 0.0036) and its variability (R = 0.59, p = 4.2 × 10⁻⁶) in the leg agility test.ConclusionThe video-based tracking could objectively measure limb bradykinesia in PD patients.     

Progressive microstructural alterations in subcortical nuclei in Parkinson's disease: A diffusion magnetic resonance imaging study

ObjectivesTo explore the microstructural alterations in subcortical nuclei in Parkinson's disease (PD) at different stages with diffusion kurtosis imaging (DKI) and tensor imaging and to test the performance of diffusion metrics in identifying PD.Methods108 PD patients (64 patients in early-stage PD group (EPD) and 44 patients in moderate-late-stage PD group (MLPD)) and 64 healthy controls (HC) were included. Tensor and kurtosis metrics in the subcortical nuclei were compared. Partial correlation was used to correlate the diffusion metrics and Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) score. Logistic regression and receiver operating characteristic analysis were applied to test the diagnostic performance of the diffusion metrics.ResultsCompared with HC, both EPD and MLPD patients showed higher fractional anisotropy and axial diffusivity, lower mean kurtosis (MK) and axial kurtosis in substantia nigra, lower MK and radial kurtosis (RK) in globus pallidus (GP) and thalamus (all p < 0.05). Compared with EPD, MLPD patients showed lower MK and RK in GP and thalamus (all p < 0.05). MK and RK in GP and thalamus were negatively correlated with UPDRS-III score (all p < 0.01). The logistic regression model combining kurtosis and tensor metrics showed the best performance in diagnosing PD, EPD, and MLPD (areas under curve were 0.817, 0.769, and 0.914, respectively).ConclusionsPD has progressive microstructural alterations in the subcortical nuclei. DKI is sensitive to detect microstructural alterations in GP and thalamus during PD progression. Combining kurtosis and tensor metrics can achieve a good performance in diagnosing PD.     

High frequency oscillations relate to cognitive improvement after epilepsy surgery in children

ObjectiveTo investigate how high frequency oscillations (HFOs; ripples 80–250 Hz, fast ripples (FRs) 250–500 Hz) and spikes in intra-operative electrocorticography (ioECoG) relate to cognitive outcome after epilepsy surgery in children.MethodsWe retrospectively included 20 children who were seizure free after epilepsy surgery using ioECoG and determined their intelligence quotients (IQ) pre- and two years postoperatively. We analyzed whether the number of HFOs and spikes in pre- and postresection ioECoGs, and their change in the non-resected areas relate to cognitive improvement (with ≥ 5 IQ points increase considered to be clinically relevant (=IQ+ group) and < 5 IQ points as irrelevant (=IQ− group)).ResultsThe IQ+ group showed significantly more FRs in the resected tissue (p = 0.01) and less FRs in the postresection ioECoG (p = 0.045) compared to the IQ− group. Postresection decrease of ripples on spikes was correlated with postoperative cognitive improvement (correlation coefficient = −0.62 with p = 0.01).ConclusionsPostoperative cognitive improvement was related to reduction of pathological HFOs signified by removing FR generating areas with subsequently less residual FRs, and decrease of ripples on spikes in the resection edge of the non-resected area.SignificanceHFOs recorded in ioECoG could play a role as biomarkers in the prediction and understanding of cognitive outcome after epilepsy surgery.     

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.     

Characterization of EEG-based functional brain networks in myotonic dystrophy type 1

ObjectiveIn the autosomal dominant, multisystem, chronic progressive disease myotonic dystrophy type 1 (DM1), cognitive deficits may originate from disrupted functional brain networks. We aimed to use network analysis of resting-state electro-encephalography (EEG) recordings of patients with DM1 and matched unaffected controls to investigate changes in network organization in large-scale functional brain networks and correlations with cognitive deficits.MethodsIn this cross-sectional study, 28 adult patients with genetically confirmed DM1 and 26 age-, sex- and education-matched unaffected controls underwent resting-state EEG and neuropsychological assessment. We calculated the Phase Lag Index (PLI) to determine EEG frequency-dependent functional connectivity between brain regions. Functional brain networks were characterized by applying concepts from graph theory and compared between-groups. Network topology was evaluated using the minimum spanning tree (MST). We evaluated correlations between network metrics and neuropsychological tests that showed statistically significant between-group differences.ResultsFunctional connectivity estimated as whole-brain median PLI for DM1 patients versus healthy controls was higher in theta band (0.141 [0.050] versus 0.125 [0.018], p = 0.029), and lower in the upper alpha band (0.154 [0.048] versus 0.182 [0.073], p = 0.038), respectively. Functional MST-constructed networks in DM1 patients were significantly dissimilar from healthy controls in the delta, (p = 0.009); theta, (p = 0.009); lower alpha, (p = 0.036); and upper alpha, (p = 0.008) bands. In evaluation of local MST network measures, trends toward networks with higher global integration in the theta band and lower global integration in the upper alpha band were observed. Compared to unaffected controls, DM1 patients performed worse on tests of attention, motor function, executive function and visuospatial memory. Visuospatial memory correlated with the global median PLI in the upper alpha band; the Stroop interference test correlated with betweenness centrality in this band.ConclusionThis study supports the hypothesis that brain changes in DM1 give rise to disrupted functional network organization, as modelled with EEG-based networks. Further study may help unravel the relations with clinical brain-related DM1 symptoms.SignificanceEEG network analysis has potential to help understand brain related DM1 phenotypes.FundingThis work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 305697 (OPTIMISTIC) and the Marigold Foundation.