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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.

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

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.

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 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.

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

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 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

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

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

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.

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.

Background & Aims Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4 + T-helper (T H ) cells with obesity and the effects of gut-tropic T H 17 cells in mice on a high-fat diet (HFD). Methods We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A−deficient HFD were compared with mice fed a vitamin A−sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and T H 17 cells (wild type or deficient in integrin β7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction. Results Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4 + T H cells. Intestinal tissues from obese mice had significant reductions in the proportion of T H 17 cells but increased proportion of T H 1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of T H 17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in vitro−differentiated gut-tropic T H 17 cells to obese mice reduced these metabolic defects, which required the integrin β7 subunit and IL17. Delivery of T H 17 cells to intestines of mice led to expansion of commensal microbes associated with leanness. Conclusions In mice, intestinal T H 17 cells contribute to development of a microbiota that maintains metabolic homeostasis, via IL17. Gut-homing T H 17 cells might be used to reduce metabolic disorders in obese individuals.

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but little is known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 White British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P

Although tension-type headache (TTH) is a frequent type of headache disorder and imposes a significant burden, there is scant information about the prevalence and impact of comorbid anxiety and depression among individuals with TTH. We investigated the prevalence and clinical impact of anxiety and depression among patients with TTH in the general population. We recruited Korean participants aged 19-69 years using a two-stage clustered random sampling method. To identify the presence of headache type, anxiety, and depression, we used a semi-structured interview using certain questionnaires. To assess the level of anxiety and depression, we used the Goldberg Anxiety Scale and Patient Health Questionnaire-9, respectively. Among 2,695 participants, 570 people (21.2%) had TTH during previous 1 year. In participants with TTH, the prevalence of anxiety (9.5% vs. 5.3%, p = 0.001) and depression (4.2% vs. 1.8%, p = 0.001) was significantly higher than that of non-headache participants. The prevalence of anxiety among TTH participants with > 15 attacks per month [21.4%, odds ratio (OR): 4.0] and 1-14 attacks per month (13.1%, OR: 2.2) was higher than that in those with < 1 attack per month (6.4%), however this tendency was not observed in participants with depression. Visual Analogue Scale (VAS) score [median 5.0 vs. 4.0, p = 0.010] and Headache Impact Test-6 (HIT-6) score [median 45.5 vs. 42.0, p < 0.001] were significantly higher among those with anxiety. Furthermore, VAS scores [median 5.0 vs. 4.0, p = 0.010] and HIT-6 scores [median 45.5 vs. 42.0, p = 0.027] were also significantly higher among TTH patients with depression than among those without depression. In conclusion, anxiety and depression were more prevalent in participants with TTH than in non-headache participants. These two conditions were associated with an exacerbation of headache symptoms in individuals with TTH.

SUMMARY This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005‐2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL )1 P = 0.004) and higher highly sensitive C-reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL )1 , P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74‐3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.

Background and Objective The association of sleep disturbance (SD) with cardiovascular disease is through its induction of autonomic dysregulation and inflammation, which also could be important pathophysiological mechanisms responsible for atrial fibrillation (AF). However, no study has fully elucidated the causal relationship between SD and AF. We investigated whether SD influences AF vulnerability in an in vivo rat model. Methods We divided 8-week-old Wister rats into 5 groups: 1) control, 2) 3-day SD, 3) 7-day SD, 4) 3-day sham SD, and 5) 7-day sham SD (n = 5 in each group), using the multiple platform method to create SD. We measured baseline heart rate, blood pressure (BP), and AF inducibility via burst atrial pacing (30 mA, 40 Hz, 30 seconds) by means of a transoesophageal electrode and used Sirius red staining to assess collagen deposition in the atriums. Results Baseline heart rate, diastolic BP and AF inducibility were significantly higher in the SD groups than in the control and sham condition groups (p < 0.05). However, there were no differences between the 3- and 7-day SD groups. Systolic BP and induced AF duration did not statistically differ among any of the experimental groups. The Sirius red staining showed no differences in collagen deposition among any of the experimental groups. Conclusions SD resulted in increase of AF inducibility in SD rats, suggesting that SD provides an atrial substrate for AF vulnerability, regardless of the disturbance period. However, induced AF duration showed no significant differences in SD rats.

Insomnia is a very common health problem affecting approximately 10-30% of the population in Western countries and approximately 23% of Korean adults.1-4 Medications based on chemical hypnotics, such as benzodiazepines, have the following adverse effects: diurnal ‘hangover’ effects, dependence, addiction, withdrawal symptoms, and subsequent drug-resistance.5 The demand for complementary and alternative medicines for treating insomnia is increasing, not only because patients wish to avoid the aforementioned adverse effects, but also because herbal/natural products are readily available and require no prescription from a doctor, in contrast to chemical drugs.6-8 Cynanchum wilfordii Hemsley (C. wilfordii)(Asclepiadaceae) is a perennial herb, whose roots have been widely used in Korea for treating insomnia, anxiety, anemia, senescence, and various geriatric diseases.9,10 However, despite its wide use in Korea, no objective studies evaluating its efficacy in treating or preventing insomnia exist. Therefore, in the present study, we evaluated C. wilfordii extract’s effects on the sleep-wake cycle in rats and compared it to valerian extract, an herbal product in widespread use for treating insomnia, to evaluate its possibilities as a natural hypnotic. Received: February 18, 2011 Revised: March 23, 2011 Accepted: April 1, 2011

OBJECTIVE α-Melanocyte–stimulating hormone (α-MSH) and agouti-related peptide (AgRP) control energy homeostasis by their opposing actions on melanocortin receptors (MC3/4R) in the hypothalamus. We previously reported that thyroid transcription factor-1 (TTF-1) controls feeding behavior in the hypothalamus. This study aims to identify the function of TTF-1 in the transcriptional regulation of AgRP and α-MSH synthesis for the control of feeding behavior. RESEARCH DESIGN AND METHODS TTF-1 activity in AgRP and pro-opiomelanocortin (POMC) transcription was examined using gel-shift and promoter assays and an in vivo model of TTF-1 synthesis inhibition by intracerebroventricular injection of an antisense (AS) oligodeoxynucleotide (ODN). Double immunohistochemistry was performed to colocalize TTF-1 and AgRP or α-MSH in the hypothalamic arcuate nucleus (ARC). To determine whether TTF-1 action on food intake is mediated through MC3/4R, we measured changes in food intake upon intracerebroventricular injection of MC3/4R antagonists (SHU9119 and AgRP) into rat brain preinjected with the AS ODN. RESULTS TTF-1 stimulated AgRP but inhibited POMC transcription by binding to the promoters of these genes. TTF-1 was widely distributed in the hypothalamus, but we identified some cells coexpressing TTF-1 and AgRP or α-MSH in the ARC. In addition, intracerebroventricular administration of leptin decreased TTF-1 expression in the hypothalamus, and AS ODN-induced inhibition of TTF-1 expression decreased food intake and AgRP expression but increased α-MSH expression. Anorexia induced by the AS ODN was attenuated by the administration of MC3/4R antagonists. CONCLUSIONS TTF-1 transcriptionally regulates synthesis of AgRP and α-MSH in the ARC and affects feeding behavior via the melanocortin pathway.

The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently observed in migraineurs and in patients with ischemic stroke. Previous studies have reported that the burden of WMLs did not increase with the intracardiac right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known to be associated with RLS in patients with stroke and dementia. The aim of the study was to demonstrate the difference in the size and location of WMLs, according to the existence of RLS in patients with headache. From the prospective headache registry, a total of 425 subjects (age, 30.8 ± 5.1 years; 303 women; 242 migraineurs; 183 patients with tension-type headache (TTH)) were retrospectively reviewed and evaluated for RLS and WMLs using M-mode power transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the association between RLS presence and the location and size of WMLs. The number of small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic signals (MES) ≥ 11, were higher in patients with migraine (small dWMLs, 6.23 vs. 4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no significant difference in the sum of periventricular WML grades or the total volume of dWMLs between TTH and migraine patients. Among the migraineurs, the patients with RLS more frequently had small dWMLs, aura, and heart disease compared to those without RLS. In addition, RLS were also independent predictors for the presence of small dWMLs from the multivariate binary regression analysis (p < 0.01; OR = 3.24; 95%CI 1.56-6.72). Small dWMLs are associated with RLS in young migraineurs. These results imply that paradoxical embolism may cause the small WMLs in some migraineurs.

Background: Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody. Methods: We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia. Results: AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia. Conclusions: Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.

Objectives: Obstructive sleep apnea (OSA) is known to increase the risk of cardiovascular diseases through endothelial damage or functional impairment. Endothelial progenitor cells (EPCs) are blood markers for endothelial functional reservoirs, and a reduction in the number of EPCs is associated with a greater cardiovascular risk. We investigated the EPC in patients with OSA. Methods: We prospectively enrolled consecutive subjects referred to our institution for the evaluation of habitual snoring or apnea. The subjects were diagnosed as OSA based on the results of overnight polysomnography. The number of colony-forming units (CFUs) on cell cultures for seven days was adopted as an EPC index. Results: CFU tends to show higher value in severe OSA than mild-to-moderate OSA (54.4±29.1 vs. 33.8±26.8; t-test, p=0.16). Other vascular risks have no effect on CFU level Conclusions: Severe OSA may induce the release of EPC from bone-marrow to peripheral blood to compensate on-going vascular injury. Further study is required to validate the relationship between OSA and EPC.

In the brain, aquaporin-1 (AQP-1), a water channel for high osmotic water permeability, is mainly expressed in the apical membrane of the ventricular choroid plexus and regulates formation of cerebrospinal fluid (CSF). Although the physiology of AQP-1 has been the subject of several publications, much less is known about the trans-acting factors involved in the control of AQP-1 gene expression. Here we report that TTF-1, a homeodomain-containing transcriptional regulator, is coexpressed with AQP-1 in the rat brain choroid plexus and enhances AQP-1 gene transcription by binding to conserved core TTF-1-binding motifs in the 5'-flanking region of the AQP-1 gene. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased AQP-1 synthesis and reduced CSF formation. In addition, blockade of TTF-1 synthesis increased survival of the animals following acute water intoxication-induced brain edema. These results suggest that TTF-1 is physiologically involved in the transcriptional control of AQP-1, which is required for CSF formation.

Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. However, little is known about the relationship between chronotype and metabolic disorders.The aim of this study was to examine whether late chronotype is related to metabolic abnormalities and body composition in middle-aged adults, independent of sleep duration and lifestyle.A total of 1620 participants aged 47-59 years were recruited from the Korean Genome and Epidemiology Study.Chronotype was assessed by the Morningness-Eveningness Questionnaire. Associations of chronotype with diabetes, metabolic syndrome, sarcopenia, and visceral obesity were analyzed. All participants underwent the oral glucose tolerance test, and body composition was measured with dual energy x-ray absorptiometry. Visceral obesity was designated as visceral fat area, measured by abdominal computed tomography, of100 cm(2).Chronotype was classified as morning in 29.6% of subjects, evening in 5.9%, neither morning nor evening in 64.5%. Evening type, when compared with morning type, was significantly associated with diabetes (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01-2.95), metabolic syndrome (OR, 1.74; 95% CI, 1.05-2.87), and sarcopenia (OR, 3.16; 95% CI, 1.36-7.33) after adjusting for confounding factors. Gender differences in the associations were evident. In men, evening type was associated with diabetes (OR, 2.98; 95% CI, 1.39-6.39) and sarcopenia (OR, 3.89; 95% CI, 1.33-11.33). Only metabolic syndrome was associated with evening type in women (OR, 2.22; 95% CI, 1.11-4.43).At the population level, evening chronotype was independently associated with diabetes, metabolic syndrome, and sarcopenia. These results support the importance of circadian rhythms in metabolic regulation.

Gastroesophageal reflux disease (GERD) is a common condition that is characterized by the repeated overflow of stomach contents into the esophagus.1 In Western countries, the approximate prevalence of GERD ranges from 10% to 20% when defined by at least one heartburn and/ or acid regurgitation episode per week.2-4 In Asia, the prevalence rate is lower than those of Western countries (less than 5%).5,6 Individuals with GERD typically suffer from heartburn, acid regurgitation, and sometimes chest pain during day and night.1,7 GERD is associated with a variety of esophageal complications (e.g., esophagitis, stricture, and Barrett’s esophagus) and extra-esophageal syndromes (e.g., reflux cough, reflux laryngitis, asthma, and sleep apnea).1,7-9 Gastroesophageal reflux (GER) can occur both during sleep and while awake, but it is much less common during sleep.10 GER occurring during sleep may induce discomfort and frequent arousal. Therefore it could be an important cause of disrupted sleep. In this study, we present a case of frequent arousal following nocturnal dyspnea caused by GERD.

폐쇄성 수면 무호흡 증후군(obstructive sleep apnea synd 은 과도한 주간 졸음증은 물론 심혈관 및 뇌혈관 rome) 질환과 같은 합병증을 유발하므로 조기 진단 및 적극적 치료 가 반드시 필요한 질환이다. 1-3 폐쇄성 수면 무호흡 증후군의 정도에 따라 금주 등 기본적인 행동 습관의 교정 이외에 지 속적 기도 양압술 치과 적 보조기구 수술 적 방법 등을 통 , , 해 적절히 치료해야 하는데, 4-5 국내의 경우 치료법으로 코골이 “ 수술로 알려진 구개수구개인두성형술 ” (uvulopalatopharyngoplasty, UPPP)만을 선호하는 경향이 있다 이 수술 방법 . 은 등과 같은 다른 상기도 교 maxillomandibular osteotomy 정술에 비해 덜 침습적이고 대체적으로 잘 순응할 수 있으나 폐쇄성 수면 무호흡증이 완벽하게 치료되는 경우는 드물어 수술 후 약 내외의 환자에게서 치료 효과가 있는 것으로 50% 알려져 있다. 6-7 따라서 후구개 부위에 국한된 폐쇄가 있는 , 경우나 경증의 폐쇄성 수면 무호흡증과 같이 제한된 예에서 신중하게 시행되어야 한다 그럼에도 불구하고 대다수의 폐 . 쇄성 수면 무호흡 증후군 환자에게 다른 치료 방법보다 우선 되어 첫 치료로 시행되고 있는 것이 현실이다 이에 저자들 . 은 첫 치료법으로 구개수구개인두성형술을 시행한 일련의 폐 쇄성 수면 무호흡 증후군 환자들을 대상으로 하여 수술 후 지속되는 주관적인 증상 유무를 분석함으로써 구개수구개인 두성형술의 효과를 평가하고자 하였다. * Address of correspondence Chang-Ho Yun, M.D. Department of Neurology, College of Medicine, Inha University 7-206, Sinheung-dong 3-ga, Jung-gu, Incheon, 400-711 Korea Tel: +82-32-890-3418, 3860, Fax: +82-32-890-3864 E-mail: ych333@inha.ac.kr 폐쇄성 수면 무호흡 증후군에서 구개수구개인두성형술의 효과

Self-induced hypoxia has been reported particularly in adolescents, and it can result in neurological injury. Here, we present a case of electroencephalogram (EEG) abnormalities induced by habitual neck compression differentiated from epileptic seizures by Tc-99m HMPAO SPECT. A 19-year-old male was admitted for evaluation of recurrent generalized tonic-clonic seizures. No interictal EEG abnormality was detected; however, abnormal slow delta waves were found immediately after habitual right neck compression. To differentiate EEG abnormalities due to a hemodynamic deficit induced by habitual neck compression from an epileptic seizure, Tc-99m HMPAO SPECT was performed immediately after right carotid artery compression. Abnormal delta waves were triggered, and cerebral hypoperfusion in the right internal carotid artery territory was detected on Tc-99m HMPAO SPECT. The slow delta wave detected on the EEG resulted from the cerebral hypoperfusion because of the habitual neck compression.