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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.

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.

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

Obstructive sleep apnea (OSA) is associated with cognitive impairment and brain structural alterations, but longitudinal outcomes are understudied.To examine the associations of OSA with cognition and white matter (WM) integrity over a 4-year period.This prospective cohort study was conducted in a community-based adult population among participants who had both baseline (2011-2014) and 4-year follow-up (2015-2018) polysomnography, diffusion tensor imaging, and cognitive assessment data. Participants with neurological disorders, anomalous findings on brain magnetic resonance imaging, or inadequate quality of the evaluations were excluded. Data were analyzed from March to November 2021.Participants were categorized depending on the presence vs absence of OSA at baseline and follow-up polysomnographic analysis.The main outcomes were proportional changes over a 4-year period in neuropsychological performance and WM integrity. The neuropsychological assessment battery included verbal and visual memory, verbal fluency, Digit Symbol-coding, Trail Making Test-A, and Stroop Test. WM integrity was assessed by fractional anisotropy, axial, and radial diffusivity. To examine interactions with age and sex, participants were subgrouped by age older than 60 years vs 60 years or younger and men vs women.A total of 1998 individuals were assessed for eligibility, and 888 were excluded based on exclusion criteria, leaving 1110 participants (mean [SD] age, 58.0 [6.0] years; 517 [46.6%] men) for analysis, including 458 participants grouped as OSA-free, 72 participants with resolved OSA, 163 participants with incident OSA, and 417 participants with persistent OSA. Incident OSA was associated with altered WM integrity and with concomitant changes in sustained attention compared with participants without OSA (eg, change in Digit Symbol-coding test score, -3.2% [95% CI, -5.2% to -1.2%]). Participants with resolved OSA showed better visual recall at the follow-up (change in Visual Reproduction-immediate recall test, 17.5% [95% CI, 8.9% to 26.1%]; change in Visual Reproduction-delayed recall test, 33.1% [95% CI, 11.3% to 54.9%]), with concordant changes in diffusion parameters at the relevant anatomic areas. In the older group only (age60 years), persistent OSA was associated with altered WM integrity and cognition (eg, Visual Reproduction-recognition test: β = -24.2 [95% CI, -40.7 to -7.7]). Sex also was associated with modifying the association of OSA with WM integrity of the left posterior internal capsule, the left genu of corpus callosum, and the right middle cerebellar peduncle only in men and with cognition only in women (eg, Visual Reproduction-immediate recall test: β = 33.4 [95% CI, 19.1 to 47.7]).These findings suggest that dynamic changes in OSA status were significantly associated with WM integrity and cognition, which varied by age and sex. It is possible that adequate interventions for OSA could better preserve brain health in middle to late adulthood.

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.

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.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.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.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.

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:While normative data on neuropsychological performance provide baseline metrics for the assessment and diagnosis of mild cognitive impairment and dementia, a lack of comparative normative data in non-Caucasian populations makes it difficult to conduct similar evaluations and studies in individuals from diverse backgrounds. The current paper aims to provide normative data on a range of cognitive measures in a Korean general population sample and investigate various demographic and health variables associated with cognitive performance in this representative population.Method(s):The study population was 1,528 stroke and dementia-free individuals who participated in the Korean Genome and Epidemiology study (KoGES) (mean age 60.43 ± 7.30, 52.42% female). All participants underwent a comprehensive neuropsychological test battery that included verbal and visual memory, language, attention, and executive function measures. A health examination and a questionnaire-based interview were also administered.Results:The majority of cognitive test results were associated with age, education, and gender. In general, higher education and younger age was associated with better cognitive performance. Explained variance increased modestly in models that included measures of general health and depressive symptoms.Conclusion:Normative data of cognitive performance in a community based Korean population are presented. These norms provide reference values in a non-Caucasian middle to older aged sample.

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.

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

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.

Objective We investigated seizure outcomes of patients with supratentorial meningiomas (ST-MNGs) treated with stereotactic radiosurgery (SRS). Methods One hundred and thirty-three patients with a total of 144 ST-MNGs, who were treated with SRS between 2009 and 2016, were included in this study. The mean age was 59.0 ± 11.9 years (range, 13–87 years). The mean follow-up duration was 49.8 ± 24.5 months (range, 9–96 months). The median tumor volume was 2.60 cm3 (range, 0.06–32.40 cm3), and the median marginal dose was 14.0 Gy (range, 11.0–20.0 Gy). Postradiosurgery peritumoral edema (PRPTE) was developed in 43 lesions (29.9%). Results New seizure attacks developed in 16 patients (12.0%) after SRS (first seizure attack in 14 [87.5%]; seizure aggravation in 2 [12.5%]). In 15 patients with new seizure attacks (93.8%), PRPTE was proved on magnetic resonance imaging. The mean interval between SRS and new seizure attack was 6.6 ± 7.1 (range, 0.23–28.8) months. Simple partial seizure was the most common type of seizure (n = 9 [56.3%]). Five patients (31.3%) were seizure-free with antiepileptic drug (AED) medication (3 [18.8%] withdrew AEDs during the follow-up period); however, the remaining 11 patients (68.7%) did not achieve seizure-free outcomes even with AED medication. Moreover, seizures became intractable in 8 patients (50.0%). From multivariate analysis, the significant predictors of post-SRS seizure attack were PRPTE (odds ratio, 53.99; 95% confidence interval, 5.214–559.1; P = 0.001) and brain-tumor contact-surface index (odds ratio, 2.466; 95% confidence interval, 1.183–5.138; P = 0.016). Conclusions The clinical outcomes of seizures after SRS for ST-MNGs fall short of our expectation, and seizures seem to be uncontrollable and even intractable.

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.

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.

Study objectives To determine if weekend catch-up sleep (CUS) impacts body mass index (BMI) in the general population. Methods A stratified random sample (2156 subjects; age 19-82 years old, 43.0 ± 14.5; 1183 male) from the general population was evaluated, in 2010, using face-to-face interviews about sociodemographic characteristics, height, weight, habitual sleep duration, and time-in-bed at night on weekdays and weekend, sleep-related profiles, mood and anxiety scales, and comorbid-medical conditions. Weekend CUS was identified when nocturnal sleep extension occurred over the weekend, and this was quantified. Average sleep duration, BMI, and chronotype were determined. The association of BMI with the presence and the amount of weekend CUS was analyzed, independent of average sleep duration, chronotype, and sociodemographic factors. Results BMI and average sleep duration was 23.0 ± 3.0 kg/m2 and 7.3 ± 1.2 hours, respectively. The weekend CUS group consisted of 932 subjects (43.2%) who slept longer on weekend than weekdays by 1.8 ± 1.1 hours. Weekend CUS subjects had a significantly lower BMI (22.8 ± 0.19 kg/m2) than the non-CUS (23.1 ± 0.19 kg/m2) group, after adjustment for age, sex, average sleep duration, chronotype, other sociodemographic factors, and anxiety/mood status (p = .01) The relationship between weekend CUS and BMI was dose-dependent (p = 0.02): Every additional hour of weekend CUS was associated with a decrease of 0.12 kg/m2 in BMI (95% confidence interval, -0.23 to -0.02). Conclusions Weekend sleep extension may have biological protective effects in preventing sleep-restriction induced or related obesity. The results suggest a simple population-level strategy to minimize effects of sleep loss.

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.

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.

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.

This study investigates health behaviors, health-related quality of life (HRQOL) and sleep among chronotypes in a community-based sample (n = 2,976). Analysis of covariance indicated evening types (E-types) had a significantly higher percentage of current smokers and more sleep-interfering behaviors compared to intermediate and morning types (M-type), and also lower physical activity and more sleep disturbance compared to M-types. E-types also had worse mental HRQOL compared to both chronotypes, and worse physical HRQOL compared to M-types. Exploratory analyses indicated E-types consumed more caffeinated beverages at night, smoked or ate heavy meals before bedtime, kept irregular sleep-wake schedules, and took more naps. Mediational analyses indicated that sleep-interfering behavior partially mediated the relationship between chronotype and sleep disturbance, and physical activity partially mediated the relationship between chronotype and mental HRQOL. E-types had more unhealthy behaviors, which may subsequently place them at higher risk for health problems.

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.

Previous reports have shown that cigarette smoking is associated with white matter hyperintensities (WMHs). However, it remains unclear whether this is true for all ages. We investigated the association between cigarette smoking, WMHs, and age. We retrospectively reviewed charts from 595 patients, who presented as outpatients from January 2007 to March 2010. Grading of periventricular WMHs (PVWMHs) and the scores of deep WMHs (DWMHs) was determined based on criteria established by the Rotterdam Scan Study. We compared the degree of WMHs between smokers and non-smokers, and those younger than the age of 65 years versus those above. In younger age group, smokers had higher grades of PVWMHs and more microbleeds than non-smokers. In the older age group, total burden of DWMHs was much greater in smokers than nonsmokers. Multivariate regression analysis showed that cigarette smoking was an independent risk factor for PVWMHs in the younger age group and for DWMHs in the older age group. The location of WMHs in association with smoking seems to differ among age groups. Age should be considered when interpreting the effects of smoking on the brain.

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.

We have previously reported that TTF-1, a homeodomain-containing transcription factor, regulates circadian rhythm of pituitary adenylate cyclase-activating polypeptide gene expression in the rat hypothalamus. In this study we found that TTF-1 mRNA was specifically expressed in the rat suprachiasmatic nucleus (SCN) and colocalized with Period 2 (Per2), a circadian feedback loop controller. Interaction between TTF-1 and Per1 and Per2 was demonstrated by immunoprecipitation and immunoblot assays. Moreover, TTF-1 and Per proteins additively stimulated a transcriptional activity of angiotensinogen (AoGen) gene. TTF-1 also activated in vitro rhythm of AoGen transcription determined by secretary alkaline phosphatase (SEAP) reporter system in the NIH3T3 cells. These results suggest that TTF-1 plays a role in the circadian rhythm regulation of the AoGen gene expression via interacting with Per proteins in the rat SCN.

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.

Thyroid transcription factor-1 (TTF-1) belongs to the Nkx family of homeodomain-containing proteins and regulates expression of several important genes in the brain. Our previous studies showed that TTF-1 plays an important role in water homeostasis in the subfornical organ of rats and is involved in cerebrospinal fluid formation by regulation of aquaporin-1 transcription in the choroid plexus. In this study, we examined changes in TTF-1 transcription in response to hypertonicity using promoter assays. TTF-1 was synthesized in several osmosensitive regions of the rat brain. TTF-1 promoter activity was diminished by treatment with hypertonic solutions in a time- and dose-dependent manner in brain-derived cell lines. Additionally, TTF-1 was involved in the regulation of angiotensinogen (Aogen) transcription under a hyperosmotic condition through specific binding domains in the Aogen promoter. These results suggest a possible role of TTF-1 in brain fluid homeostasis in response to changes in the osmotic environment.

Study Objectives: To investigate the prevalence of restless legs syn- drome (RLS) in Korea. Design: A large population-based telephone interview method using the Korean version of the Johns Hopkins telephone diagnostic interview for the RLS. Setting: A computer aided telephone interview method Participants: A total of 5,000 subjects (2,470 men and 2,530 women) were interviewed in depth. A representative sample aged 20 to 69 years was constituted according to a stratified, multistage random sampling method. Interventions: N/A Measurements and Results: Of the respondents, 373 respondents (7.5%) of the population (pop) met the criteria for the definite or prob - able RLS groups: 194 (3.9% of pop) respondents fulfilled the criteria for definite RLS and 179 (3.6% of pop) respondents fulfilled the criteria for probable RLS. The prevalence of RLS was generally higher for women than men (4.4% vs. 3.3% for definite, 8.7% vs. 6.2% for definite plus probable). About 90% of RLS individuals were experiencing symptoms at the time of the interview and this was similar for both RLS groups. Seventy-four respondents (1.48%) reported symptoms were moder- ately or severely distressing and were therefore classified as RLS "suf - ferers." Of those with a diagnosis of RLS sufferer, 24.3% reported being treated for their symptoms, compared to 12.4% of RLS not designated a "sufferer." Conclusion: RLS is common and underdiagnosed in Korea with nearly 1% of the population reporting disturbed sleep related to their RLS. These results are comparable to other countries.

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.

The purpose of this study was to document the frequency of sleep problems including poor sleep quality, excessive daytime sleepiness, and insomnia in subjects with epilepsy compared with healthy controls and to determine the factors associated with these sleep disturbances.We recruited 180 patients with epilepsy (age: 43.2 ± 15.6 years, men: 50.0%) and 2836 healthy subjects (age: 44.5 ± 15.0 years, men: 49.8%). Sleep and the anxiety/mood profiles were measured using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, Goldberg Anxiety Scale, and Patient Health Questionnaire-9 depression scale. Associations of sleep problems with epilepsy and other factors were tested by multiple logistic regression analysis, adjusted for age, gender, body mass index, alcohol intake, smoking, perceived sleep insufficiency, and habitual snoring.Sleep disturbances were more common in the group with epilepsy than in the controls (53.3% vs. 25.5%; p0.001). Poor sleep quality, excessive daytime sleepiness, and insomnia were significantly associated with epilepsy (odds ratio [95% confidence interval]: 3.52 [2.45-5.05], 2.10 [1.41-3.12], 5.91 [3.43-10.16], respectively). Depressive mood, anxiety, and perceived sleep insufficiency contributed to the presence of sleep disturbances. In the group with epilepsy, seizure remission for the past year related to a lower frequency of insomnia, whereas age, sex, type of epilepsy, and number of antiepileptic drugs were not correlated with sleep problems.Epilepsy was significantly associated with the higher frequency of sleep disturbances, which supports the importance of screening sleep problems in patients with epilepsy and providing available intervention.

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.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.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 TH 1 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.TLR9 signaling is involved in regulating adipose tissue inflammation and controlling obesity and the metabolic syndrome.

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.

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.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.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 .001.LEV may provide a survival benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome associated with anticonvulsant drugs is a rare but potentially life-threatening disease that occurs in response to arene oxide producing anticonvulsant such as phenytoin and carbamazepine. There have been many reports of cross reactivity among the anticonvulsants upon first exposure to the offending drugs. However, there has been few data describing the development of DRESS syndrome after switching medication from previously well-tolerated phenytoin to carbamazepine, and the induction of hypersensitivity to phenytoin by DRESS to carbamazepine. We experienced a case of a 40-yr-old man who had uncontrolled seizure that led to the change of medication from the long-term used phenytoin to carbamazepine. He developed DRESS syndrome after changing the drugs. We stopped carbamazepine and restored phenytoin for seizure control, but his clinical manifestations progressively worsened and he recovered only when both drugs were discontinued. Patch tests with several anticonvulsants showed positive reactions to both carbamazepine and phenytoin. Our case suggests that hypersensitivity to a previously tolerated anticonvulsant can be induced by DRESS to another anticonvulsant, and that the patch test may be a useful method for detecting cross-reactive drugs in anticonvulsant-associated DRESS syndrome.

Summary: Purpose: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery. Methods: One hundred ninety-three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty-one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status ≥2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors. Results: The seizure-free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET), and pathologies other than cortical dysplasia were significantly associated with a seizure-free outcome (p < 0.05). Multivariate analysis revealed that a focal lesion on MRI (p = 0.003), correct localization by FDG-PET (p = 0.007), and localized ictal onset on EEG (p = 0.01) were independent predictors of a good outcome. Conclusions: The presence of a focal lesion on MRI, correct localized hypometabolism on FDG-PET, or localized ictal rhythms on EEG were identified as predictors of a seizure-free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.

Weight loss has been reported to reduce the severity of obstructive sleep apnea (OSA), particularly in the obese population. However, prospective studies with polysomnography (PSG) for the precise evaluation of OSA are lacking especially in Asian countries. We evaluated the effects of surgical weight loss for treating OSA using PSG data obtained before and after surgery. We performed a prospective study analyzing the clinical and PSG data obtained from our cohort of bariatric surgical candidates with moderate to severe OSA, as confirmed by preoperative PSG. The patients underwent follow-up PSG at least 12 months after bariatric surgery (laparoscopic Roux-en-Y gastric bypass). Of the 47 patients (70.1 %) with moderate to severe OSA among 67 patients who underwent preoperative PSG, 10 patients underwent postoperative PSG. The mean apnea-hypopnea index (AHI) of these 10 patients significantly reduced from 51.0 ± 34.2 to 9.3 ± 12.9 events/h, while their mean body mass index (BMI) loss was from 39.9 ± 8.3 to 26.9 ± 4.4 kg/m2. Although the severity of OSA improved considerably, OSA resolution was achieved in only five patients (50 %). When compared to the patients who achieved OSA resolution, the patients with residual OSA showed a tendency to have lower minimum arterial oxygen saturation (SaO2) levels and higher supine AHI values in preoperative PSG. Surgical weight loss resulted in the significant improvement of OSA associated with obesity. However, OSA remained in a considerable proportion of patients even after substantial weight loss. We recommend that postoperative PSG be considered for the evaluation of residual OSA, especially in patients with low minimum SaO2 levels and high supine AHI in preoperative PSG.