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Min-Hee Lee,1 Seung Ku Lee,1 Robert J Thomas,2 Jee-Eun Yoon,3 Chang-Ho Yun,4,* Chol Shin1,5,* 1Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Department of Neurology, Uijeongbu Eulji Medical Center, Uijeongbu, Republic of Korea; 4Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 5Department of Pulmonary Sleep and Critical Care Medicine Disorder Center, College of Medicine, Korea University, Ansan, Republic of Korea*These authors contributed equally to this workCorrespondence: Chang-Ho YunDepartment of Neurology, Bundang Clinical Neuroscience Institute, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam, 13620, Republic of KoreaTel +82 31 787 7469Fax +82 31 787 4059Email ych333@gmail.comChol ShinDivision of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital and Institute of Human Genomic Study, Korea University Ansan Hospital, 516, Gojan-1-dong, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of KoreaTel +82 31 412 5541Fax +82 31 412 5604Email chol-shin@korea.ac.krPurpose: Obstructive sleep apnea (OSA) is associated with altered pairwise connections between brain regions, which might explain cognitive impairment and daytime sleepiness. By adopting a deep learning method, we investigated brain connectivity related to the severity of OSA and daytime sleepiness.Patients and Methods: A cross-sectional design applied a deep learning model on structural brain networks obtained from 553 subjects (age, 59.2 ± 7.4 years; men, 35.6%). The model performance was evaluated with the Pearson’s correlation coefficient (R) and probability of absolute error less than standard deviation (PAE

This study aimed to evaluate the effect of sleep duration on brain structures in the presence versus absence of sleep apnea in middle-aged and older individuals. The study investigated a population-based sample of 2,560 individuals, aged 49-80 years. The presence of sleep apnea and self-reported sleep duration were examined in relation to gray matter volume (GMV) in total and lobar brain regions. We identified ranges of sleep duration associated with maximal GMV using quadratic regression and bootstrap sampling. A significant quadratic association between sleep duration and GMV was observed in total and lobar brain regions of men with sleep apnea. In the fully adjusted model, optimal sleep durations associated with peak GMV between brain regions ranged from 6.7 to 7.0 hours. Shorter and longer sleep durations were associated with lower GMV in total and 4 sub-regions of the brain in men with sleep apnea.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is known as a maternally inherited mitochondrial disease with a m.3243A>G mutation in the MT-TL1 gene. Here, we report a case of targeted temperature management in a MELAS patient who had a cardiac arrest and severe lactic acidosis after recurrent seizures.

A close association has been reported between depression and migraine. However, information concerning the impacts of migraine on the clinical presentation and prevalence of depression in a population-based study is currently limited.Data from the Korean Headache-Sleep Study, a nationwide survey about headache and sleep for adults aged 19-69 years were used. Depression was defined when Patient Health Questionnaire-9 score ≥ 10.Of 2,695 participants who included in this study, 116 (4.3%), 143 (5.3%), and 1130 (41.9%) had depression, migraine, and non-migraine headache, respectively. Migraine (24/116 [20.5%] vs. 119/2579 [4.7%], p 0.001) and non-migraine headache (67/116 [58.1%] vs. 1063/2579 [41.3%], p 0.001) was more prevalent in the group of participants with depression than among participants without depression. Among participants with depression, there was no statistically differences in total Patient Health Questionnaire-9 (PHQ-9) scores among migraine, non-migraine headache, and non-headache groups (median with interquartile range, 12.0 [10.2-18.0] vs. 13.0 [11.0-16.0] vs. 12.0 [10.0-15.2], p = 0.514). Among subcomponent scores of PHQ-9, all subcomponent scores did not significantly differ by headache status except feeling tired or having little energy scores (non-migraine headache 2.0 [2.0-3.0] vs. non-headache 2.0 [1.0-2.0], p = 0.010).Diagnosis of depression based on PHQ-9 questionnaire and small sample size in subgroup analyses.Participants with depression exhibit an increased risk of migraine and non-migraine headache compared with participants without depression. Among participants with depression, the severity of depression did not significantly differ on the basis of headache status.

Background While obesity is linked with brain atrophy and dementia incidence, associations with regional adiposity are uncertain. Our goal was to determine whether cerebral gray matter volume is related to neck circumference (NC), a measure of regional adiposity having unique relationships with metabolic disorders and cardiovascular disease. Methods Magnetic resonance imaging and NC were cross-sectionally assessed from 2011 to 2014 in a population-based sample of 2916 men and women in the Korean Genome and Epidemiology Study. Results For men, NC was inversely associated with total and regional gray matter in the frontal, temporal, and occipital lobes after adjusting for age and intracranial brain volume. Associations were especially strong in the presence of diabetes. With further adjustment for indices of body composition and other characteristics, total and frontal gray matter in diabetic men were lowered by 6.1 mL (95% confidence interval: 2.5-9.7, P=0.004) and 2.9 mL (95% confidence interval: 1.0-4.9, P=0.017), respectively, per SD increase in NC (2.3 cm). For men without diabetes, and in all women, associations were less apparent. Conclusions In men with diabetes, NC was inversely associated with cerebral gray matter volume. The link between neck anthropometry and brain aging in diabetic men warrants further consideration.

Migraine neither presents with a definitive single symptom nor has a distinct biomarker; thus, its diagnosis is based on combinations of typical symptoms. We aimed to identify natural subgroups of migraine based on symptoms listed in the diagnostic criteria of the third edition of the International Classification of Headache Disorders. Latent class analysis (LCA) was applied to the data of the Korean Sleep-Headache Study, a nationwide population-based survey. We selected a three-class model based on Akaike and Bayesian information criteria and characterized the three identified classes as “mild and low frequency,” “photophobia and phonophobia,” and “severe and high frequency.” In total, 52.0% (65/125) of the participants were classified as “mild and low frequency,” showing the highest frequency of mild headache intensity but the lowest overall headache frequency. Meanwhile, “photophobia and phonophobia” involved 33.6% (42/125) of the participants, who showed the highest frequency of photophobia and phonophobia. Finally, “severe and high frequency” included 14.4% (18/125) of the participants, and they presented the highest frequency of severe headache intensity and highest headache frequency. In conclusion, LCA is useful for analyzing the heterogeneity of migraine symptoms and identifying migraine subtypes. This approach may improve our understanding of the clinical characterization of migraine.

Objective: Insomnia and depression are prevalent disorders that often co-occur. This study aimed to investigate the impact of clinically significant insomnia symptoms on the prevalence and clinical presentation of clinically significant depressive symptoms and vice versa.Methods: This study used data from the Korean Headache-Sleep Study (KHSS), a nationwide cross-sectional population-based survey regarding headache and sleep. Clinically significant insomnia symptoms were defined as Insomnia Severity Index (ISI) scores ≥ 10 and clinically significant depressive symptoms were defined as Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10, respectively. We referred clinically significant insomnia symptoms and clinically significant depressive symptoms as insomnia symptoms and depressive symptoms, respectively.Results: Of 2,695 participants, 290 (10.8%) and 116 (4.3%) were classified as having insomnia and depressive symptoms, respectively. The prevalence of depressive symptoms was higher among participants with insomnia symptoms than in those without insomnia symptoms (25.9 vs. 1.7%, respectively, P < 0.001). Among participants with depressive symptoms, the PHQ-9 scores were not significantly different between participants with and without insomnia symptoms (P = 0.124). The prevalence of insomnia symptoms was significantly higher among participants with depressive symptoms than in those without depressive symptoms (64.7 vs. 8.3%, respectively, P < 0.001). The ISI scores were significantly higher among participants with insomnia and depressive symptoms than in participants with insomnia symptoms alone (P < 0.001).Conclusions: Participants with depressive symptoms had a higher risk of insomnia symptoms than did those without depressive symptoms. The severity of depressive symptoms did not significantly differ based on insomnia symptoms among participants with depressive symptoms; however, the severity of insomnia symptoms was significantly higher in participants with depressive symptoms than in those without depressive symptoms.

Sleep fragmentation (SF) commonly occurs in several pathologic conditions and is especially associated with impairments of hippocampus-dependent neurocognitive functions. Although the effects of SF on hippocampus in terms of protein or gene levels were examined in several studies, the impact of SF at the metabolite level has not been investigated. Thus, in this study, the differentially expressed large-scale metabolite profiles of hippocampus in a rat model of SF were investigated using untargeted metabolomics approaches. Forty-eight rats were divided into the following 4 groups: 4-day SF group, 4-day exercise control (EC) group, 15-day SF group, and 15-day EC group (n = 12, each). SF was accomplished by forced exercise using a walking wheel system with 30-s on/90-s off cycles, and EC condition was set at 10-min on/30-min off. The metabolite profiles of rat hippocampi in the SF and EC groups were analyzed using liquid chromatography/mass spectrometry. Multivariate analysis revealed distinctive metabolic profiles and marker signals between the SF and corresponding EC groups. Metabolic changes were significant only in the 15-day SF group. In the 15-day SF group, L-tryptophan, myristoylcarnitine, and palmitoylcarnitine were significantly increased, while adenosine monophosphate, hypoxanthine, L-glutamate, L-aspartate, L-methionine, and glycerophosphocholine were decreased compared to the EC group. The alanine, aspartate, and glutamate metabolism pathway was observed as the common key pathway in the 15-day SF groups. The results from this untargeted metabolomics study provide a perspective on metabolic impact of SF on the hippocampus.

We investigated the prevalence of sleep problems, such as obstructive sleep apnea (OSA), insomnia, and daytime sleepiness in commercial motor vehicle (CMV) drivers compared with that in the general population. This is a cross-sectional study comparing sleep habits and sleep problems in 110 truck drivers with 1001 matched controls from the general population. The assessment was based on self-administered questionnaires that included the Berlin questionnaire, the insomnia severity index, and the Epworth sleepiness scale (ESS). Multivariate regression analysis was performed to determine whether CMV drivers were independently associated with these sleep problems compared with controls. The prevalence of a high risk of OSA and insomnia was 35.5% and 15.2%, respectively, in CMV drivers, which was significantly higher than in controls with a prevalence of 12.2% and 4.1%, respectively (P

OBJECTIVE This study was conducted to investigate sex differences in the prevalence and clinical presentation of migraine and probable migraine in a general population-based sample. BACKGROUND While there is research on sex differences in clinical characteristics and their impact on migraine headache, only few studies have investigated sex differences in probable migraine in population-based settings. Moreover, compared with Western countries, the prevalence of probable migraine in Asia is relatively high. This cross-sectional study was designed to investigate sex differences in the prevalence and clinical presentation of migraine and probable migraine in a general population-based sample. METHODS We used the data of the Korean Headache-Sleep Study, which is a nationwide survey on headache and sleep. RESULTS We interviewed 7430 people, and 3114 of them agreed to participate in our study (rejection rate, 58.1%). Among these people, 419 withdrew their participation during the interview. Ultimately, 2695 people completed our survey (cooperation rate, 36.3%). The prevalence of overall migraine and probable migraine was 350/1350 (25.9%) for women and 172/1345 (12.8%) for men (P

The fine structure of sleep electrocortical activity reflects health and disease. The current study provides normative data for sleep structure and electroencephalography (EEG) spectral power measures derived from overnight polysomnography (PSG) and examines the effect of age and sex among Korean middle-aged and older adults with or without obstructive sleep apnea (OSA). We analysed home PSG data from 1,153 adult participants of an ongoing population-based cohort study, the Korean Genome and Epidemiology Study. Sleep stages were visually scored and spectral power was measured on a single-channel EEG (C4-A1). We computed spectral power for five frequency ranges. The EEG power was reported in relative (%) and log-transformed absolute values (µV2 ). With ageing, the proportion of N1 sleep increased, whereas N3 decreased, which is more noticeable in men than in women. The amount of N3 was relatively low in this cohort. With ageing, relative delta power decreased and alpha and sigma power increased for the whole sleep period, which was more pronounced during REM sleep in non-OSA. For men compared with women, relative theta power was lower during REM and sigma and beta were higher during N1 sleep. The differences of relative powers by age and sex in OSA were comparable to those in non-OSA. In a community-based Korean population, we present normative data of sleep structure and spectral power for middle-aged or older adults of a non-Caucasian ethnicity. The values varied with age and sex and were not influenced by sleep apnea.

This study aimed to investigate sleep problems and comorbid conditions associated with fatigue in the general population. The data were obtained from a nationwide cross-sectional survey conducted in 2018. The Fatigue Severity Scale was used to assess fatigue. We examined sleep habits, such as workday sleep duration, chronotype, and free-day catch-up sleep, excessive daytime sleepiness (EDS), depression, and other comorbid conditions. We conducted multiple logistic regression analysis with the presence of fatigue as a dependent variable. Of 2,493 adults aged 19 to 92 years, 50% men, mean age was 47.9 ± 16.4 years. The average workday sleep duration was 7.1 ± 1.1 h, and the prevalence of fatigue was 31%. After adjusting for potential confounders, fatigue was associated with EDS (odds ratio [OR] 3.751, 95% confidence interval [CI] 2.928–4.805), depression (OR 3.736, 95% CI 2.701–5.169), perceived insufficient sleep (OR 1.516, 95% CI 1.249–1.839), free-day catch-up sleep (OR 1.123, 95% CI 1.020–1.235), less alcohol intake (OR 0.570, 95% CI 0.432–0.752), and physical inactivity (OR 0.737, 95% CI 0.573–0.948). On subgroup analysis, fatigue was additionally associated with short workday sleep duration (OR 0.899, 95% CI 0.810–0.997) in individuals without EDS. However, among those with EDS, only depression (OR 2.842, 95% CI 1.511–5.343) and less alcohol intake (OR 0.476, 95% CI 0.247–0.915) were associated with fatigue. Fatigue was significantly associated with depression independent of EDS. Further research is warranted to better understand the pathophysiological relationship between fatigue, depression, and sleep.

Background: Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is related to iron&ndash, dopamine dysregulation and immune system alteration. We aimed to assess the effects of serum hepcidin, an iron-regulating hormone, in drug-naive RLS patients compared to healthy controls and to evaluate its role in helping to predict clinical improvement after treatment with dopamine agonist. Methods: Nonanemic and drug-naive RLS patients (n = 18) and healthy controls (n = 15) were enrolled. The serum hepcidin and iron-related values in the serum were measured upon the first visit in both groups and 12 weeks later after dopaminergic treatment in 12 patients. Information about sociodemographic characteristics, sleep-related profiles, mood and anxiety was obtained upon the first visit in all participants as well as after treatment in RLS patients. Results: Serum hepcidin levels exhibited no significant differences between patients with drug-na&iuml, ve RLS and healthy controls at diagnosis (7.1 &plusmn, 2.4 vs. 7.0 &plusmn, 3.2 ng/mL, p = 0.357). Decreased hepcidin levels were significantly associated with decreased RLS severity (&beta, = 0.002, 95% CI = 0.00&minus, 0.00, p = 0.005) and improved quality of life (&beta, 7.01, p = 0.044) in a dose-dependent manner after 12 weeks of treatment with a dopamine agonist. This association was independent of age, sex, inflammatory markers, sleep quality, insomnia, daytime sleepiness, depression and anxiety. Conclusions: This study demonstrates the role of hepcidin in evaluating the positive therapeutic response in RLS.

A new concept of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep is proposed, that of multi-component integrative states that define stable and unstable sleep, respectively, NREMS, NREMUS REMS, and REMUS. Three complementary data sets are used: obstructive sleep apnea (20), healthy subjects (11), and high loop gain sleep apnea (50). We use polysomnography (PSG) with beat-to-beat blood pressure monitoring, and electrocardiogram (ECG)-derived cardiopulmonary coupling (CPC) analysis to demonstrate a bimodal, rather than graded, characteristic of NREM sleep. Stable NREM (NREMS) is characterized by high probability of occurrence of the US) has the opposite features: a fragmented and discontinuous integrated multicomponent network model of NREM sleep which captures sleep onset (e.g., ventrolateral preoptic area-based sleep switch) processes, synaptic homeostatic delta power kinetics, and the interaction of global and local sleep processes as reflected in the spatiotemporal evolution of cortical “UP” and “DOWN” states, while incorporating the complex dynamics of autonomic-respiratory-hemodynamic systems during sleep. Bimodality of REM sleep is harder to discern in health. However, individuals with combined obstructive and central sleep apnea allows ready recognition of REMS and REMUS (stable and unstable REM sleep, respectively), especially when there is a discordance of respiratory patterns in relation to conventional stage of sleep.

Background and purpose Identifying changes in the prevalence, disability, and management patterns of migraine is important for reducing the burden of this disease. However, data on the changes in these variables are scarce. Methods We compared data obtained in the 2009 Korean Headache Survey and the 2018 Korean Sleep-Headache Survey. Results The 1-year migraine prevalence did not differ significantly between 2018 and 2009 [5.2% (114/2,200) vs. 6.0% (91/1,507), p=0.492]. The number of days with missed activity due to headache during the previous 3 months was larger in the 2018 survey than in the 2009 survey [1.1±2.9 vs. 0.3±1.0 days (mean±standard deviation), p=0.013]. The number of days with reduced productivity during the previous 3 months did not differ significantly between the two surveys (0.8±2.8 vs. 1.4±1.4 days, p=0.679). The proportion of subjects with a substantial-to-severe headache impact (Headache Impact Test-6 score ≥56) was marginally larger in the 2018 survey than in the 2009 survey [42.1% (48/114) vs. 29.7% (27/91), p=0.066]. The rate of lifetime medical consultations did not differ between the 2018 and 2009 surveys [34.2% (39/114) vs. 30.8% (28/91), p=0.615]. Conclusions Migraine prevalence was stable over the 9-year period between the surveys, but disability due to missed activity was greater in 2018 than in 2009 in Korea.

Background and purpose Nonketotic hyperglycemia often causes transient visual field defects, but only scattered anecdotes are available in the literature. Methods We report a patient with homonymous superior quadrantanopsia due to nonketotic hyperglycemia and provide a systematic literature review of the clinical features of 40 previously reported patients (41 in total, including our case) with homonymous visual field defects in association with nonketotic hyperglycemia. Results The typical visual field defect was congruous (84.6%), homonymous hemianopsia (87.8%) with macular splitting (61.5%) or sparing (38.5%). It was transient and repetitive in 54.5% of the patients, but it developed as a persistent form in the remainder. Positive visual symptoms such as hallucinations and phosphenes developed in 73.2% of patients. Brain MRI revealed corresponding abnormalities in most patients (84.8%), characterized by a low-intensity white-matter signal or a high-intensity gray-matter signal on T2-weighted or fluid-attenuated inversion recovery images with diffusion restriction or gadolinium enhancement. Most (97.0%) patients recovered completely, with 48.5% treated by glycemic control alone and the remainder also receiving antiepileptic agents. Conclusions Nonketotic hyperglycemia should be considered a possible cause of transient visual field defects, especially when it is associated with repetitive positive visual symptoms and typical MRI findings in hyperglycemic patients.

We investigated both independent and interconnected effects of 3 lifestyle factors on brain volume, measuring yearly changes using large-scale longitudinal magnetic resonance imaging, in middle-aged to older adults. We measured brain volumes in a cohort (n = 984, 49-79 years) from the Korean Genome and Epidemiology Study group, using baseline and follow-up estimates after 4 years. In our analysis, the accelerated brain atrophy in normal aging was observed across regions (e.g., brain tissue: -0.098 ± 0.01 mL/y, p0.001). An independent lifestyle-specific trend of brain atrophy across time was also evident in men, where smoking (p = 0.012) and physical activity (p = 0.014) showed the strongest association with the atrophy rate. Linear regression analysis of the interconnected effect revealed that brain atrophy is mitigated by intense physical activity in smoking males. Lifestyle factors did not show any significant effect on brain volume in women. These results provide important information regarding lifestyle factors that affect brain aging in mid-to-late adulthood. Our findings may aid in the identification of preventive measures against dementia.

Background and purpose Sufficient sleep is an essential part of good health and well-being. Tension-type headache (TTH) is the most common type of primary headache and has negative impacts on the quality of life and work performance. We aimed to determinethe relationship between TTH and insufficient sleep in the general population. Methods This study used data from the Korean Headache Sleep Study, which was a population-based survey about headache and sleep among Korean adults. Insufficient sleep was defined when the discrepancy between sleep need and average sleep duration was at least 1 hour. Results Among the 2,695 included subjects, 570 (21.2%) and 727 (27.0%) were classified as having TTH and insufficient sleep, respectively. The prevalence of insufficient sleep was significantly higher among subjects with TTH than among those without headaches (28.8% vs. 20.4%). For subjects with TTH, the scores on a visual analogue scale (4.7±1.8 vs. 4.3±1.9, mean±SD) and the Headache Impact Test-6 (44.9±7.0 vs. 43.6±6.1) were much higher in subjects with insufficient sleep than in those without insufficientsleep. Multivariable analyses revealed that insomnia [odds ratio (OR)=2.1], poor sleep quality (OR=1.7), and short sleep duration (OR=6.9) were significantly associated with insufficient sleep in subjects with TTH. Conclusions Our findings suggest that insufficient sleep is prevalent among subjects with TTH and is linked to an exacerbation of TTH. Therefore, the proper evaluation and management of sleep may lead to the better management of TTH.

Sleep, a vital process of human being, is carefully orchestrated by the brain and consists of cyclic transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Autonomic tranquility during NREM sleep is characterized by vagal dominance and stable breathing, providing an opportunity for the cardiovascular-neural axis to restore homeostasis, in response to use, distress or fatigue inflicted during wakefulness. Abrupt irregular swings in sympathovagal balance during REM sleep act as phasic loads on the resting cardiovascular system. Any causes of sleep curtailment or fragmentation such as sleep restriction, sleep apnea, insomnia, periodic limb movements during sleep, and shift work, not only impair cardiovascular restoration but also impose a stress on the cardiovascular system. Sleep disturbances have been reported to play a role in the development of stroke and other cardiovascular disorders. This review aims to provide updated information on the role of abnormal sleep in the development of stroke, to discuss the implications of recent research findings, and to help both stroke clinicians and researchers understand the importance of identification and management of sleep pathology for stroke prevention and care.

Background Sleep disturbances are closely related to migraine. Nevertheless, information regarding the impact of short sleep duration and poor sleep quality on the clinical presentation of migraine at population level is limited. Methods This study was a nationwide population-based survey on adults aged 19–69 years. Headache frequency (attacks/month) and intensity (visual analogue scale, 0–10) were documented. Short sleep duration and poor sleep quality were defined as average sleep duration 5, respectively. The association of sleep parameters with headache frequency and intensity was analysed among migraineurs. Results Of 2695 participants, 143 (5.3%) had migraine. Headache frequency was significantly higher among migraineurs with short sleep duration (2.0 [1.0–12.0] vs. 1.0 [0.3–4.0], p = 0.048) and poor sleep quality (2.0 [0.6–4.7] vs. 1.0 [0.2–3.0], p = 0.009) than among those without. However, headache intensity was similar between migraineurs with short sleep duration and poor sleep quality. Multiple linear regression analyses revealed that short sleep duration was a significant contributing factor for headache frequency (β = 0.210, p = 0.015). Conclusions Self-reported short sleep duration (

Background Recent studies have shown a significant association between restless legs syndrome (RLS) and primary headache disorders. Nevertheless, information regarding the association between tension-type headache (TTH) and RLS is limited. This study aimed to investigate the association between RLS and TTH in a population-based sample. Methods We selected a stratified random population sample of Koreans aged 19–69 years and assessed them using a semi-structured interview designed to identify RLS, headache type, and clinical characteristics of TTH. We determined the prevalence and clinical impact of RLS in participants with TTH. Results Of the 2695 participants, 570 (21.2%) and 142 (5.3%) were classified as having TTH and RLS, respectively. Among the 570 individuals with TTH, 113 (19.8%) also met the criteria for probable migraine (PM). The prevalence of RLS was significantly higher among individuals with TTH than among those with non-headache (6.0% vs 3.6%, p = 0.018). The prevalence of RLS was significantly higher in subjects with TTH who fulfilled PM criteria than in those with non-headache participants (8.0% vs. 3.6%, p = 0.018). However, RLS prevalence in individuals with TTH who did not fulfil PM criteria did not differ from that of participants with non-headache (5.5% vs. 3.6%, p = 0.063). TTH participants with RLS had higher visual analogue scale scores for headache intensity (5.1 ± 2.0 vs. 4.3 ± 1.8, p = 0.038), and higher prevalence of anxiety (20.6% vs. 8.8%, p = 0.022) and depression (14.7% vs. 3.5%, p = 0.002) than TTH participants without RLS. Multivariable analyses revealed that headache aggravation by movement (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.1–5.2) and depression (OR = 3.5, 95% CI = 1.1–11.4) were significant indicators of RLS among individuals with TTH. Conclusions The prevalence of RLS was higher among individuals with TTH than among those with non-headache. Some clinical presentations varied in accordance with the presence of RLS among participants with TTH. Electronic supplementary material The online version of this article (doi:10.1186/s10194-017-0754-x) contains supplementary material, which is available to authorized users.

Anxiety, depression, and insomnia are highly prevalent among migraineurs and are associated with negative health consequences. Anxiety and depression, however, unlike insomnia, are usually underdiagnosed, due to less self-reporting of these two conditions. The aim of the present study was to evaluate the risk of anxiety and depression in migraineurs with self-reported insomnia, using a general population-based sample. We used data from a nationwide population-based survey on headache and sleep, the Korean Headache-Sleep Study. Of all 2,695 participants, 143 (5.3%), 268 (10.0%), 116 (4.3%), and 290 (10.8%) were classified as having migraine, anxiety, depression, and self-reported insomnia, respectively. The risk of anxiety (odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.0–16.7) and depression (OR = 3.3, 95% CI = 1.3–8.5) was significantly increased in migraineurs with self-reported insomnia. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for anxiety in migraineurs with self-reported insomnia were 46.5%, 89.0%, 64.5%, and 79.5%, respectively. For depression, the sensitivity, specificity, PPV, and NPV were 41.7%, 82.4%, 32.3%, and 87.5%, respectively. Self-reported insomnia is likely to be comorbid with anxiety and depression in migraineurs and could thus be a useful predictor of anxiety and depression in migraine.

Study Objectives Sleep behaviors are related to brain structure and function, but the impact of long-term changes in sleep timing on brain health has not been clearly addressed. The purpose of this study was to examine the association of longitudinal changes in sleep timing from middle to late-life with gray matter volume (GMV), an important marker of brain aging. Methods We enrolled 1798 adults (aged 49–82 years, men 54.6%) who underwent magnetic resonance imaging (MRI) between 2011 and 2014. Midsleep time (MST) on free days corrected for sleep debt on workdays was adopted as a marker of sleep timing. Data on MST were available at the time of MRI assessment and at examinations that were given 9 years earlier (2003–2004). Longitudinal changes in MST over the 9-year period were derived and categorized into quartiles. Subjects in quartile 1 were defined as “advancers” (MST advanced ≥ 1 h) while those in quartile 4 were defined as “delayers” (MST delayed ≥ 0.2 h). Quartiles 2–3 defined a reference group (MST change was considered modest). The relationship of GMV with MST changes over 9 years was investigated. Results Nine-year change in MST were significantly associated with GMV. Compared to the reference group, advancers had smaller GMVs in the frontal and temporal regions. A delay in MST was also associated with smaller cerebellar GMV. Conclusions In middle-to-late adulthood, the direction of change in MST is associated with GMV. While advancers and delayers in MST tend to present lower GMV, associations appear to differ across brain regions.

Excessive daytime sleepiness (EDS) is a prevalent sleep-related complaint across the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. However, the association between EDS and TTH is currently scarce. In the present study, we investigated the impact of EDS on the prevalence and clinical presentation of TTH. We utilized data from the Korean Headache-Sleep Study, a national survey that sought to identify headache and sleep characteristics in Korean adults. Participants with an Epworth sleepiness scale score greater or equal to 11 were considered as having EDS. Of the 2,695 participants enrolled, 570 (21.2%) and 313 (11.6%) had TTH and EDS, respectively. EDS was highly prevalent in individuals with chronic tension-type headache (CTTH) than in those without headache (35.7 vs. 9.4%, p < 0.001). The prevalence of EDS in episodic tension-type headache (ETTH) individuals with a headache frequency

Migraine attacks have a time preference of headache attack (TPHA). Chronotype is the propensity for an individual to sleep at a particular time during a 24-h period. However, limited evidence exists regarding the association between TPHA and chronotype in individuals with migraine or tension-type headache (TTH). The aim of the present study is to investigate TPHA and chronotype in individuals with migraine and TTH, which are two of the most common primary headaches. One hundred sixty-nine first-visit migraine and TTH participants were consecutively enrolled. Information on sleep onset time and wake up time on workdays and free days, and TPHA were investigated with a face-to-face interview using a questionnaire booklet. Chronotype was assessed, using the midpoint of sleep on free days, corrected for sleep extension on free days (MSFsc), by subtracting one-half of the average weekly sleep duration. Headache frequency per month, headache intensity, impact of headache, sleep quality, daytime sleepiness, insomnia severity, and mood status were also assessed. Time preference of headache attack was reported for 45.5% and 44.8% of participants with migraine and TTH, respectively. Migraineurs with TPHA had an earlier MSFsc than did migraineurs without TPHA (1:18 a.m. ± 282 min vs. 4:18 a.m. ± 186 min

Background Although probable migraine (PM) is common among headache sufferers, there is little knowledge of the prevalence and impacts of comorbid anxiety and depression in patients with PM. We assessed the prevalence and impact of anxiety and depression among PM sufferers in the general population. Methods We recruited Korean individuals aged 19–69 years via stratified random sampling and assessed headache type, anxiety, and depression among them using structured interviews. Results In a representative sample of 2695 individuals, 143 (5.3%) and 379 (14.1%) had migraine and PM, respectively. Fewer patients with PM had anxiety (17.7% vs. 30.1%, p = 0.002) and depression (8.7% vs. 16.8%, p = 0.007) compared to those with migraine. Prevalence of anxiety and depression was lower in people with PM than in those with migraine in univariable analysis, but insignificant after including headache intensity and headache frequency for adjustment. Headache frequency, headache intensity, and impact of headache were significantly higher among PM and migraine patients with anxiety and depression than among those without. Conclusions The prevalence of anxiety and depression was lower among individuals with PM compared to those with migraine. However, they were still prevalent and associated with an exacerbation of symptoms among individuals with PM.

Study Objectives To assess, using fractional anisotropy (FA) analysis, alterations of brain network connectivity in adults with obstructive sleep apnea (OSA). Abnormal networks could mediate clinical functional deficits and reflect brain tissue injury. Methods Structural brain networks were constructed using diffusion tensor imaging (DTI) from 165 healthy (age 57.99 ± 6.02 years, male 27.9%) and 135 OSA participants (age 59.01 ± 5.91 years, male 28.9%) and global network properties (strength, global efficiency, and local efficiency) and regional efficiency were compared between groups. We examined MRI biomarkers of brain tissue injury using FA analysis and its effect on the network properties. Results Differences between groups of interest were noted in global network properties (p-value < 0.05, corrected), and regional efficiency (p-value < 0.05, corrected) in the left middle cingulate and paracingulate gyri, right posterior cingulate gyrus, and amygdala. In FA analysis, OSA participants showed lower FA values in white matter (WM) of the right transverse temporal, anterior cingulate and paracingulate gyri, and left postcentral, middle frontal and medial frontal gyri, and the putamen. After culling fiber tracts through WM which showed significant differences in FA, we observed no group difference in network properties. Conclusions Changes in WM integrity and structural connectivity are present in OSA participants. We found that the integrity of WM affected brain network properties. Brain network analysis may improve understanding of neurocognitive deficits in OSA, enable longitudinal tracking, and provides explanations for specific symptoms and recovery kinetics.

Background Insomnia and migraine are closely related; insomnia aggravates migraine symptoms. This study was conducted to investigate the impact of migraine on the clinical presentation of insomnia symptoms. Methods The data of the Korean Headache-Sleep Study (KHSS) were used in the present study. The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep in Korean adults aged 19 to 69 years. If a participant’s Insomnia Severity Index (ISI) score ≥ 10, she/he was classified as having insomnia. The clinical presentation of insomnia symptoms was assessed using total and subcomponent scores of the ISI. Results Of 2695 participants, 290 (10.8%) and 143 (5.3%) individuals were assigned as having insomnia and migraine, respectively. The proportions of migraine (12.8% vs. 4.4%, p

Background: Restless legs syndrome (RLS) is a common sleep disorder, although it has a low prevalence in Asian populations. However, the reported RLS prevalence in ­Korean adults is mostly 4.5–12.1%, which is higher than that reported in other Asian populations. This study aimed to diagnose RLS and exclude mimicking conditions in 2 independent samples of Korean adults, and to compare its prevalence to that from previous studies performed in Asian countries. Methods: Study populations included a (1) nationwide stratified random sample (n = 2,824; age 19–79 years) and (2) community-based cohort (n = 2,685; age 47–79 years). We applied the Cambridge-Hopkins diagnostic questionnaire to diagnose RLS and differentiate it from RLS mimics. Sleep-related symptoms, mood, and medical conditions were compared between the RLS and non-RLS groups. Prior studies of the RLS prevalence in Asia were systematically reviewed and compared to our findings. Results: The adjusted RLS prevalence was 0.4 and 1.3% in populations 1 and 2, respectively. In both populations, subjects with RLS had more depression. The prevalence of RLS mimics was 5.1 and 2.6%, in populations 1 and 2, respectively. The RLS prevalence in Asia was higher when RLS was defined by the presence of essential clinical features and lower when a differential diagnosis was additionally implemented. Conclusions: The RLS prevalence in Korean adults considering RLS mimics is comparable to that in adults from other Asian countries (< 2%). The reported RLS prevalence varies depending on the diagnostic method employed.

Background Probable migraine (PM) is a subtype of migraine that is prevalent in the general population. Previous studies have shown that poor sleep quality is common among migraineurs and is associated with an exacerbation of migraine symptoms. However, information on the prevalence and clinical implication of poor sleep quality among individuals with PM is scarce. Thus, the aim of this study was to assess the prevalence and clinical impact of poor sleep quality in individuals with PM in comparison with those with migraine. Methods Two-stage cluster random sampling was used to perform the survey for sleep and headache in Korean general population. Participants with Pittsburgh Sleep Quality Index > 5 were considered as having poor sleep quality. Results Of 2695 participants, 379 (14.1%) had PM and 715 (26.5%) had poor sleep quality. Prevalence of poor sleep quality was 35.4% in the PM group, which was lower than that in the migraine group (47.6%, p = 0.011), but higher than that in the non-headache group (21.4%, p

We performed a retrospective study to identify factors associated with preoperative and late postoperative seizures in primary supratentorial meningiomas.Between July 2003 and December 2014, we extracted 303 consecutive patients who underwent primary resection for supratentorial meningiomas at a single institution. Univariate analysis and multivariate logistic regression analysis were performed to determine the associations of seizure occurrence and outcome.Forty-nine (16.2%) of the total 303 patients presented with preoperative seizures. The risk factors independently associated with preoperative seizures were vasogenic edema (OR 4.44, p = 0.001), parasagittal or parafalcine location (OR 2.20, p = 0.020), and absence of neurologic deficit (OR 0.30, p = 0.003). Among these patients, 33 (67.3%) were seizure free postoperatively (Engel Class I). Of the 303 patients, we observed late postoperative seizures in 35 (11.6%) patients. The associated risk factors included history of preoperative seizure (OR 3.96, p = 0.002), bigger tumor size (OR 1.04, p = 0.002), and continuation of anti-epileptic drugs (OR 4.74, p = 0.001). We analyzed that meningiomas with a largest diameter of greater than 45.5 mm were 4.2 times more likely to have late postoperative seizures than those with less diameter (HR 4.20, p 0.001). Ten (28.6%) of the 35 patients with late postoperative seizures experienced poor seizure control. The independently associated predictive factors were high grade meningiomas (WHO Grade II or III) (OR 10.66, p = 0.030) and history of postoperative adjuvant therapy (OR 12.58, p = 0.040).Identifying factors associated with preoperative or late postoperative seizures may help guide treatment strategies, eventually improving the quality of life for patients with meningiomas.

Objective To determine the prevalence, sleep characteristics, and comorbidities associated with a high risk for obstructive sleep apnea (OSA) in the Korean adult population. Methods We analyzed data from 2,740 subjects who responded to a nationwide questionnaire survey of sleep characteristics. Those who qualified under two or more symptom categories of the Berlin questionnaire were defined as “at high risk for OSA”. We investigated their socio-demographic information, sleep habits, and medical and psychiatric comorbidities. Logistic regression analyses were performed to identify factors and consequences significantly associated with a high risk for OSA. Results The prevalence of a high risk for OSA was 15.8% (95% confidence interval [CI] 14.5–17.2%). Multiple logistic regression analysis showed that old age (≥ 70 years, odds ratio [OR] 2.68) and body mass index ≥ 25 kg/m2 (OR 10.75) were significantly related with a high risk for OSA, whereas regular physical activity (OR 0.70) had a protective effect. Subjective sleep characteristics associated with a high risk for OSA were perceived insufficient sleep (OR 1.49), excessive daytime sleepiness (OR 1.88), and insomnia (OR 3.70). In addition, hypertension (OR 5.83), diabetes mellitus (OR 2.54), hyperlipidemia (OR 2.85), and anxiety (OR 1.63) were comorbid conditions independently associated with a high risk for OSA. Conclusions This is the first study to demonstrate the prevalence of a high risk for OSA in a nationwide representative sample of the Korean adult population. These findings elucidate the epidemiology and clinical characteristics of those at high risk for OSA.

Objective Recent studies have revealed a link between Toll-like receptor (TLR) signaling and the adipose tissue inflammation associated with obesity. Although TLR9 is known to play an important role in inflammation and innate immunity, its role in mediating adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the role of TLR9 in regulating immune cells in visceral adipose tissue and maintaining the metabolic homeostasis. Methods Wild-type and TLR9-deficient mice were fed with a high-fat diet, and the body weight gain, glucose tolerance, insulin sensitivity, and adipose tissue inflammation were examined. Results TLR9-deficient mice gained significantly more weight and body fat under a high-fat diet than wild-type mice and exhibited more severe glucose intolerance and insulin resistance. We also found a dramatic increase of M1 macrophages as well as TH1 cells in the adipose tissue of TLR9-deficient mice compared to wild-type mice. Furthermore, the levels of various proinflammatory cytokines and chemokines were higher in TLR9-deficient mice. Conclusions TLR9 signaling is involved in regulating adipose tissue inflammation and controlling obesity and the metabolic syndrome.

BACKGROUND A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O-6 methylguanine-DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma. METHODS In total, 103 consecutive patients with primary glioblastoma who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and 58 patients (56%) received LEV during temozolomide chemotherapy for at least 3 months. A Cox regression survival analysis was performed to adjust for confounding factors, including age, extent of lesion, Karnofsky performance scale score, extent of removal, and MGMT promoter methylation status. RESULTS The median progression-free survival (PFS) and overall survival (OS) for patients who received LEV in combination with temozolomide (PFS: median, 9.4 months; 95% confidence interval [CI], 7.5-11.3 months; OS: median, 25.7 months; 95% CI, 21.7-29.7 months) were significantly longer than those for patients who did not receive LEV (PFS: median, 6.7 months; 95% CI, 5.8-7.6 months; OS: median, 16.7 months; 95% CI, 12.1-21.3 months; P = .010 and P = .027, respectively). In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (hazard ratio [HR], 0.37; P = .016), MGMT promoter methylation (HR, 0.30; P = .002), and receipt of LEV (HR, 0.31; P

We aimed to determine the association between psychomotor vigilance task (PVT) performance and sleep-related factors including sleep duration, daytime sleepiness, poor sleep quality, insomnia, and habitual snoring in a population-based sample.This was a cross-sectional analysis from the ongoing prospective cohort study, the Korean Genome and Epidemiology Study. We measured PVT performance and documented demographics, sleep-related factors, life style, and medical conditions in community dwelling adults (N = 2499; mean age 57.1 ± 7.3; male 1259). Associations between PVT parameters and sleep-related factors were tested, adjusting for age, gender, smoking, alcohol use, education, body mass index, hypertension, diabetes, depression, and the interval between mid-sleep time and PVT test.High Epworth Sleepiness Scale (ESS, ≥8) was associated with slower mean reciprocal response speed (mean RRT) (3.69 ± 0.02 vs. 3.77 ± 0.01, p 0.001), higher probability for increased lapses (≥4) (OR 1.48, CI 1.12-1.88, p = 0.001), and more negative RRT slope (-0.036 ± 0.002 vs. -0.030 ± 0.001, p = 0.02). Older age, female gender, low education level, depressive mood, and the interval between mid-sleep and PVT test were also associated with poor performance. Sleep duration, habitual snoring, insomnia, or poor sleep quality (the Pittsburgh Sleep Quality Index score 5) was not related to PVT parameters.At the population level, our results revealed important modifiers of PVT performance, which included subjective reports of daytime sleepiness.

Background Tension-type headache (TTH) represents the most common type of headache among the general population. Although such headaches are usually mild in severity, some individuals with TTH experience severe symptoms and psychiatric comorbidities. Such patients may also experience sleep disturbances, which have been associated with headache exacerbation. Nevertheless, information regarding the prevalence and impact of insomnia among individuals with TTH in a population-based setting is limited. Therefore, the aim of the present study was to evaluate the prevalence and impact of insomnia among individuals with TTH using data from the Korean Headache-Sleep Study (KHSS). Methods We analysed data from the KHSS—a nation-wide, cross-sectional, population-based survey on headache and sleep involving Korean adults aged 19 to 69 years. Insomnia was defined as an Insomnia Severity Index score ≥ 10. Results Among 2695 participants, 570 (21.2%) and 290 (10.8%) were classified as having TTH and insomnia, respectively. Among individuals with TTH, 113 (19.8%) met the criteria for probable migraine (PM). The prevalence of insomnia among individuals with TTH was significantly higher than that among individuals without headache (13.2% vs. 5.8%, p

To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2±5.1/h; age 58.5±4.1 years; 9 male) and 19 controls (AHI 1.8±1.3/h; age 58.5±4.2 years; 9 male) underwent 60-min dynamic 11C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.

Background The primary metric extracted from the polysomnogram in patients with sleep apnea is the apnea-hypopnea index (or respiratory disturbance index) and its derivatives. Other phenomena of possible importance such as periods of stable breathing, features suggestive of high respiratory control loop gain, and sleep fragmentation phenotypes are not commonly generated in clinical practice or research. A broader phenotype designation can provide insights into biological processes, and possibly clinical therapy outcome effects. Methods The dataset used for this study was the archived baseline diagnostic polysomnograms from the Apnea Positive Pressure Long-term Efficacy Study (APPLES). The electrocardiogram (ECG)-derived cardiopulmonary coupling sleep spectrogram was computed from the polysomnogram. Sleep fragmentation phenotypes used thresholds of sleep efficiency (SE) ≤ 70%, non-rapid eye movement (NREM) sleep N1 ≥ 30%, wake after sleep onset (WASO) ≥ 60 min, and high frequency coupling (HFC) on the ECG-spectrogram ≤ 30%. Sleep consolidation phenotypes used thresholds of SE ≥ 90%, WASO ≤ 30 min, HFC ≥ 50% and N1 ≤ 10%. Multiple and logistic regression analysis explored cross-sectional associations with covariates and across phenotype categories. NREM vs. REM dominant apnea categories were identified when the NREM divided by REM respiratory disturbance index (RDI) was > 1. Results The data was binned first into mild, moderate, severe and extreme categories based on the respiratory disturbance index of

Background Sleep disorder and sleep complaints are common in subjects with migraine. Although the association between sleep disorders and migraine has been reported, the association between perceived insufficient sleep and migraine has rarely reported. The aim of this study is to evaluate the association between insufficient sleep and migraine using the data of the Korean Headache-Sleep Study (KHSS). Methods The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep for Korean adults aged 19 to 69 years. A difference of one hour or more between sleep need and average sleep time indicated insufficient sleep. Results Of 2,695 participants, 727 (27.0%) individuals were classified as having insufficient sleep. The prevalence of insufficient sleep among individuals with migraine (45.5%) was significantly higher compared to that among individuals with non-migraine headache (32.9%, p = 0.004) or among non-headache (20.4%, p

Objective The aim of this study was to evaluate sleep characteristics associated with drowsy driving in an adult population. Methods The study subjects consisted of 1675 adults aged 19 years or older who completed a population-based questionnaire survey on sleep habits. Experiences of drowsy driving were obtained from self-reported data. We investigated sleep-related variables including sleep duration, sleep efficiency, chronotype, subjective sleep perception, daytime sleepiness, sleep quality, and snoring. We performed multivariate logistic regression analysis to determine sleep characteristics independently associated with drowsy driving. Results The mean age of the subjects was 43.2 years, and 66.3% were men. The prevalence of self-reported drowsy driving was 23.6% (396 of 1675), and 33.1% of subjects experienced dozing at the wheel at least once a month. Multivariate analysis demonstrated that men, office and manual workers, excessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were independently associated with drowsy driving. Subgroup analyses revealed that reduced weekday sleep duration was a risk factor of drowsy driving in adults with perceived sufficient sleep. On the other hand, frequent alcohol drinking significantly increased risk of drowsy driving in the subgroup with perceived sleep insufficiency. Furthermore, ordinal regression analyses confirmed the association between sleep characteristics and drowsy driving across different drowsy driving frequencies. Conclusion Excessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were sleep-related risk factors for drowsy driving. In addition to maintaining healthy sleep habits, individuals at high risk should be encouraged to evaluate underlying sleep disorders or psychiatric problems to prevent drowsy driving.

Study objectives Research points to impaired cognitive performance in sleep clinic patients with obstructive sleep apnea (OSA). However, inconsistent findings from various epidemiologic studies make this relationship less generalizable. The current study investigated the association between OSA and functional outcome measures, such as cognition, daytime sleepiness, and quality of life, in a Korean general population sample. Methods A total of 1492 participants from the Korean Genome and Epidemiology Study (KoGES) were included in the analyses. The presence of OSA measured by overnight polysomnography (PSG) was defined by apnea-hypopnea index (AHI) >5. Cognitive performance was determined with scores from a comprehensive neuropsychological battery. Excessive daytime sleepiness and quality of life were additionally measured through subjective reports. Results After adjusting for various demographic and medical characteristics, OSA was independently associated with lower performance in the Digit Symbol Test (52.73 ± 17.08 vs. 58.72 ± 18.03, OSA vs. not, p = .02). Hypoxia measures were not related to cognitive performance. OSA was associated with higher odds of displaying excessive daytime sleepiness (odds ratio = 1.72, 95% CI: 1.05-2.80), but there was no significant relationship between OSA and quality of life. Conclusions Cognition was unexpectedly unaffected overall. However, OSA was associated with impairment in a multidomain test that taps skills generally associated with frontal lobe function. The results suggest that research on protective and adaptive brain mechanisms to OSA stress can provide unique insights into the brain-sleep interface. As the study runs longitudinally, it will enable future studies on the impact of OSA on cognitive decline.

Continuation of sleep is important for learning and memory. Some proteins are differentially expressed in specific brain regions by normal sleep/wake cycle or sleep deprivation, suggesting that specific proteins are regulated by sleep/wake cycle and could play an important role in regulation of normal brain function associated with sleep in the regions. The hippocampus is a major region of the brain accounting for memory formation and organization, and its specific function could be altered by change of synapse-related molecular components. To examine sleep fragmentation-induced alteration of proteins in the hippocampus, two-dimensional gel electrophoresis was performed. Thirty-six male Wistar rats were randomly divided into the home cage group, sleep fragmentation group, and exercise control group. Four day sleep fragmentation was accomplished by a forced walking wheel system with a wheel on/off cycle of 30-s on/90-s off to mimic the arousal that is common in patients with severe sleep apnea. Time interval of exercise control was set at 10 min on/30 min off. Of 58 spots that were differentially expressed among the groups, one protein was consistently reduced in the sleep fragmented group compared to other groups. The protein was identified as synapsin IIa by MALDI-TOF mass spectrometry. Real-time polymerase chain reaction and Western blot analysis confirmed downregulated expression of synapsin IIa and another isoform, synapsin IIb. The results suggest that sleep fragmentation induces molecular changes accounting for neurotransmitter release, integrity of the reserve synaptic vesicle pool, and synaptic plasticity.

Stroke is very common in patients with sleep disordered breathing, especially in the elderly. We report the case of a 26-year-old man who had been referred to us with a sudden left side motor weakness of the body, headache, chronic fatigue, and witnessed sleep apneas. Intracerebral hemorrhage in the right external capsule and putamen was identified upon brain computed tomography. He had hypertension which had not been diagnosed previously. On polysomnography, apnea-hypopnea index was 73.0/h and arousal index was 74.7/h, indicating severe sleep apnea. Continuous positive airway pressure titration was conducted to determine the optimal pressure to alleviate the respiratory disturbances. Treatment with antihypertensive medication reduced blood pressure (BP) from 197/145 mm Hg to 130/80 mm Hg after 10 days of use. Co-treatment with the medication and auto-adjustable positive airway pressure additionally decreased BP to 110/60 mm Hg and normalized respiratory disturbances. In addition to BP, left hemiparesis, morning headache, daytime sleepiness, and chronic fatigue were all improved. Early treatment of OSA could help facilitate the rehabilitation of or recovery of weakness in such patients.

OBJECTIVE The purpose of this study was to investigate whether the impact of obstructive sleep apnea (OSA) on glucose metabolism was different according to the presence or absence of obesity. RESEARCH DESIGN AND METHODS A total of 1,344 subjects >40 years old from the Korean Genome and Epidemiology Study were included. OSA was detected by home portable sleep monitoring. Plasma glucose, HbA1c, and insulin resistance were compared according to OSA and obesity status. The associations between OSA and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and diabetes were evaluated in subjects with and without obesity after adjusting for several confounding variables. The effect of visceral obesity on this association was evaluated in 820 subjects who underwent abdominal computed tomography scanning. RESULTS In subjects without obesity, fasting glucose, 2-h glucose after 75-g glucose loading, and HbA1c were higher in those with OSA than in those without after controlling for age, sex, and BMI. In addition, the presence of OSA in nonobese subjects was associated with a higher prevalence of IFG + IGT and diabetes after adjusting for several confounding variables (odds ratio 3.15 [95% CI 1.44–6.90] and 2.24 [1.43–3.50] for IFG + IGT and diabetes, respectively). Further adjustment for visceral fat area did not modify this association. In contrast, in those with obesity, none of the abnormal glucose tolerance categories were associated with OSA. CONCLUSIONS The presence of OSA in nonobese individuals is significantly associated with impaired glucose metabolism, which can be responsible for future risk for diabetes and cardiovascular disease.

Antiepileptic drugs are commonly given for perioperative prophylaxis after brain tumor surgery, and there has been growing interest in levetiracetam, a second-generation antiepileptic drug. This retrospective study compared the seizure outcomes, side effects and durability of levetiracetam with valproic acid after a craniotomy for supratentorial brain tumors.Between 2009 and 2012, 282 consecutive patients with a supratentorial brain tumor underwent a craniotomy at Seoul National University Bundang Hospital. Of these patients, 51 (18.1%) and 231 (81.9%) were pre-operatively administered levetiracetam and valproic acid, respectively. The postoperative seizure outcomes (within 1 month after surgery) and the long-term side effects of both drugs were evaluated.Of the 51 patients in the levetiracetam group, 4 (7.8%) experienced postoperative seizures after brain tumor surgery, and 15 (6.5%) of the 231 patients in the valproic acid group experienced postoperative seizures (p = 0.728). The long-term complication rate of the valproic acid group (26.8%; 62/231) was significantly higher than that of the levetiracetam group (9.8%; 5/51) [p = 0.010]. In the valproic acid group, 10 hepatotoxicities, 20 hyperammonemias and 10 hematologic abnormalities (6 thrombocytopenias, 3 pancytopenias, and 1 leucopenia) occurred. Moreover, 89 patients (38.5%) in the valproic acid group changed or added other anticonvulsants because of side effects or uncontrolled seizures, whereas only 9 patients (17.6%) in the levetiracetam group changed or added other anticonvulsants (p = 0.005).The postoperative seizure control rates of levetiracetam and valproic acid were not statistically significantly different; however, levetiracetam may be superior to valproic acid in terms of its safety and durability after supratentorial tumor surgery.

STUDY OBJECTIVE Obstructive sleep apnea (OSA) contributes to the development of systemic hypertension, and hypertension strongly predicts the development of white matter change (WMC). Thus, it is plausible that OSA mediates WMC. The goal of the current study is to determine whether a contextual relationship exists between OSA and cerebral WMC. DESIGN Cross-sectional analyses conducted in a population-based study. SETTING Korean community-based sample from the Korean Genome and Epidemiology Study (KoGES) who attended examinations in 2011 at a medical center. PARTICIPANTS There were 503 individuals (mean ± SD, age 59.63 ± 7.48 y) who were free of previously diagnosed cardiovascular and neurologic diseases. MEASUREMENTS AND RESULTS Participants underwent 1-night polysomnography and were classified as no OSA (obstructive apnea-hypopnea index [AHI] < 5, n = 289), mild OSA (AHI 5-15, n = 161), and moderate to severe OSA (AHI ≥ 15, n = 53). WMC was identified with brain magnetic resonance imaging (MRI) and was found in 199 individuals (39.56%). Multivariate logistic regression analyses adjusted for covariates revealed that moderate to severe OSA was significantly associated with the presence of WMC (odds ratio [OR] 2.08, 95%, confidence interval [CI] 1.05-4.13) compared with no OSA. Additional adjustment of hypertension to the model did not alter the significance of the association (OR 2.03, 95% CI 1.02-4.05). CONCLUSIONS Moderate to severe OSA is an independent risk factor for WMC in middle-aged and older individuals. Thus, early recognition and treatment of OSA could reduce the risk of stroke and vascular dementia.