Telomeric repeat evolution in the phylum Nematoda revealed by high-quality genome assemblies and subtelomere structures.

Telomeres are composed of tandem arrays of telomeric-repeat motifs (TRMs) and telomere-binding proteins (TBPs), which are responsible for ensuring end-protection and end-replication of chromosomes. TRMs are highly conserved owing to the sequence specificity of TBPs, although significant alterations in TRM have been observed in several taxa, except Nematoda. We used public whole-genome sequencing data sets to analyze putative TRMs of 100 nematode species and determined that three distinct branches included specific novel TRMs, suggesting that evolutionary alterations in TRMs occurred in Nematoda. We focused on one of the three branches, the Panagrolaimidae family, and performed a de novo assembly of four high-quality draft genomes of the canonical (TTAGGC) and novel TRM (TTAGAC) isolates; the latter genomes revealed densely clustered arrays of the novel TRM. We then comprehensively analyzed the subtelomeric regions of the genomes to infer how the novel TRM evolved. We identified DNA damage-repair signatures in subtelomeric sequences that were representative of consequences of telomere maintenance mechanisms by alternative lengthening of telomeres. We propose a hypothetical scenario in which TTAGAC-containing units are clustered in subtelomeric regions and pre-existing TBPs capable of binding both canonical and novel TRMs aided the evolution of the novel TRM in the Panagrolaimidae family.

Sirtuin 3 regulates astrocyte activation by reducing Notch1 signaling after status epilepticus.

Sirtuin3 (Sirt3) is a nicotinamide adenine dinucleotide enzyme that contributes to aging, cancer, and neurodegenerative diseases. Recent studies have reported that Sirt3 exerts anti-inflammatory effects in several neuropathophysiological disorders. As epilepsy is a common neurological disease, in the present study, we investigated the role of Sirt3 in astrocyte activation and inflammatory processes after epileptic seizures. We found the elevated expression of Sirt3 within reactive astrocytes as well as in the surrounding cells in the hippocampus of patients with temporal lobe epilepsy and a mouse model of pilocarpine-induced status epilepticus (SE). The upregulation of Sirt3 by treatment with adjudin, a potential Sirt3 activator, alleviated SE-induced astrocyte activation; whereas, Sirt3 deficiency exacerbated astrocyte activation in the hippocampus after SE. In addition, our results showed that Sirt3 upregulation attenuated the activation of Notch1 signaling, nuclear factor kappa B (NF-κB) activity, and the production of interleukin-1ß (IL1ß) in the hippocampus after SE. By contrast, Sirt3 deficiency enhanced the activity of Notch1/NF-κB signaling and the production of IL1ß. These findings suggest that Sirt3 regulates astrocyte activation by affecting the Notch1/NF-κB signaling pathway, which contributes to the inflammatory response after SE. Therefore, therapies targeting Sirt3 may be a worthy direction for limiting inflammatory responses following epileptic brain injury.

USP11 modulates mitotic progression and senescence by regulating the p53-p21 axis through MDM2 deubiquitination.

USP11 is overexpressed in colorectal cancer (CRC) and breast cancer tissues compared to normal tissues, suggesting a role in promoting cell proliferation and inhibiting cell death. In this study, we observed that depleting USP11 inhibits cell proliferation and delays cell cycle progression. This depletion leads to increased p53 protein levels due to an extended half-life, resulting in elevated p21 mRNA levels in a p53-dependent manner. The rise in p53 protein upon USP11 depletion is linked to a reduced half-life of MDM2, a known E3 ligase for p53, via enhanced polyubiquitination of MDM2. These findings indicate that USP11 might act as a deubiquitinase for MDM2, regulating the MDM2-p53-p21 axis. Additionally, USP11 depletion promotes the induction of senescent cells in a manner dependent on its deubiquitinase activity. Our findings provide insights into the physiological significance of high USP11 expression in primary tumors and its reduction in senescent cells, highlighting its potential as a therapeutic target.

Risk Factors and Temporal Patterns of Poststroke Epilepsy across Stroke Subtypes: Insights from a Nationwide Cohort Study in Korea.

INTRODUCTION: We aimed to investigate the risk factors associated with poststroke epilepsy (PSE) among patients with different subtypes of stroke, focusing on age-related risk and time-varying effects of stroke subtypes on PSE development. METHODS: A retrospective, nationwide, population-based cohort study was conducted using Korean National Health Insurance Service-National Sample Cohort data. Patients hospitalized with newly diagnosed stroke from 2005 to 2015 were included and followed up for up to 10 years. The primary outcome was the development of PSE, defined as having a diagnostic code and a prescription for anti-seizure medication. Multivariable Cox proportional hazard models were used to estimate PSE hazard ratios (HRs), and time-varying effects were also assessed. RESULTS: A total of 8,305 patients with ischemic stroke, 1,563 with intracerebral hemorrhage (ICH), and 931 with subarachnoid hemorrhage (SAH) were included. During 10 years of follow-up, 4.6% of patients developed PSE. Among patients with ischemic stroke, significant risk factors for PSE were younger age (HR = 1.47), living in rural areas (HR = 1.35), admission through the emergency room (HR = 1.33), and longer duration of hospital stay (HR = 1.45). Time-varying analysis revealed elevated HRs for ICH and SAH, particularly in the first 2 years following the stroke. The age-specific HRs also showed an increased risk for those under the age of 65, with a noticeable decrease in risk beyond that age. CONCLUSION: The risk of developing PSE varies according to stroke subtype, age, and other demographic factors. These findings underscore the importance of tailored poststroke monitoring and management strategies to mitigate the risk of PSE.

Multi-functional regulation of cGAS by the nuclear localization signal2 (NLS2) motif: Nuclear localization, enzyme activity and protein degradation.

Cyclic GMP-AMP synthase (cGAS), which recognizes double-stranded DNA (dsDNA) and activates the innate immune system, is mainly localized in the cytosol, but also shows nuclear localization. Here, we sought to determine the role of nuclear cGAS by mutating known nuclear localization signal (NLS) motifs in cGAS and assessing its functionality by monitoring phosphorylation of the downstream target, interferon regulatory factor-3 (IRF3). Interestingly, NLS2-mutated cGAS failed to promote phosphorylation of IRF3, reflecting the loss of its ability to produce cyclic GMP-AMP (cGAMP). We further found that insertion of an NLS from SV40 large T antigen could not restore this loss of activity, indicating that this loss was attributable to the mutation of NLS2 itself, but not dependent on the inability of cGAS to enter the nucleus. NLS2-mutant cGAS protein also showed decreased stability dependent on polyubiquitination, an effect that was independent of both its loss of catalytic function and its inability to enter into the nucleus. Collectively, these findings indicate that the NLS2 motif of cGAS is not only involved in regulating the subcellular localization of cGAS protein but also influences its stability and enzymatic activity through independent mechanisms, highlighting the novel roles of NLS2 in regulating the intracellular functions of cGAS.

MRI-Based Radiomics Approach for Differentiating Juvenile Myoclonic Epilepsy from Epilepsy with Generalized Tonic-Clonic Seizures Alone.

BACKGROUND: The clinical presentation of juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCA) is similar, and MRI scans are often perceptually normal in both conditions making them challenging to differentiate. PURPOSE: To develop and validate an MRI-based radiomics model to accurately diagnose JME and GTCA, as well as to classify prognostic groups. STUDY TYPE: Retrospective. POPULATION: 164 patients (127 with JME and 37 with GTCA) patients (age 24.0 ± 9.6; 50% male), divided into training (n = 114) and test (n = 50) sets in a 7:3 ratio with the same proportion of JME and GTCA patients kept in both sets. FIELD STRENGTH/SEQUENCE: 3T; 3D T1-weighted spoiled gradient-echo. ASSESSMENT: A total of 17 region-of-interest in the brain were identified as having clinical evidence of association with JME and GTCA, from where 1581 radiomics features were extracted for each subject. Forty-eight machine-learning combinations of oversampling, feature selection, and classification algorithms were explored to develop an optimal radiomics model. The performance of the best radiomics models for diagnosis and for classification of the favorable outcome group were evaluated in the test set. STATISTICAL TESTS: Model performance measured using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Shapley additive explanations (SHAP) analysis to estimate the contribution of each radiomics feature. RESULTS: The AUC (95% confidence interval) of the best radiomics models for diagnosis and for classification of favorable outcome group were 0.767 (0.591-0.943) and 0.717 (0.563-0.871), respectively. SHAP analysis revealed that the first-order and textural features of the caudate, cerebral white matter, thalamus proper, and putamen had the highest importance in the best radiomics model. CONCLUSION: The proposed MRI-based radiomics model demonstrated the potential to diagnose JME and GTCA, as well as to classify prognostic groups. MRI regions associated with JME, such as the basal ganglia, thalamus, and cerebral white matter, appeared to be important for constructing radiomics models. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

The association between social jetlag and depression is independent of sleep debt.

OBJECTIVES: To investigate whether the association between SJLsc (sleep-corrected social jetlag) and depressive mood is significant and independent of sleep debt. METHODS: Participants from the general adult population were interviewed using structured questionnaires on sleep duration, weekday/weekend sleep schedules, and depressive mood (Patient Health Questionnaire-9). Social jetlag (SJL) was measured by SJLsc and standard SJL (SJLs). SJLs was the absolute difference between mid-sleep time on free days (MSF) and workdays (MSW). For SJLsc, both MSF and MSW were adjusted for average sleep duration across the week according to the direction of sleep debt. Sleep debt was defined by sleep extension on free days. The association of SJL with depression was investigated, and covariates included age, sex, sociodemographic factors, insomnia symptoms, sleep duration, and sleep debt. RESULTS: A total of 1982 individuals (1089 men; age 43.1 ± 14.4 years) were analyzed. SJL was present in 24.6% measured by SJLsc and 51.0% by SJLs. SJLsc and SJLs were significantly associated with depressive mood (r = 0.06, P = 0.02; r = 0.06, P = 0.01, respectively), independent of sleep debt. Sleep debt was also associated with depression (r = 0.07, P < 0.01). CONCLUSIONS: By adopting sleep-corrected formula for SJL, this study found that misaligned and insufficient sleep, at levels occurring in routine social life, can negatively affect mood. Minimizing social jetlag and sleep deprivation may promote individual psychological well-being.

Vascular endothelial growth factor receptor-3 regulates astroglial glutamate transporter-1 expression via mTOR activation in reactive astrocytes following pilocarpine-induced status epilepticus.

Recent evidence has shown that the vascular endothelial growth factor (VEGF) system plays a crucial role in several neuropathological processes. We previously reported an upregulation of VEGF-C and its receptor, VEGFR-3, in reactive astrocytes after the onset of status epilepticus (SE). However, it remains unknown, which molecules act as downstream signals following VEGFR-3 upregulation, and are involved in reactive astrogliosis after SE. Therefore, we investigated whether VEGFR-3 upregulation within reactive astrocytes is associated with the activation of mammalian target of rapamycin (mTOR) signaling, which we confirmed by assaying for the phosphorylated form of S6 protein (pS6), and whether VEGFR-3-mediated mTOR activation induces astroglial glutamate transporter-1 (GLT-1) expression in the hippocampus after pilocarpine-induced SE. We found that spatiotemporal expression of pS6 was consistent with VEGFR-3 expression in the hippocampus after SE, and that both pS6 and VEGFR-3 were highly expressed in SE-induced reactive astrocytes. Treatment with the mTOR inhibitor rapamycin decreased astroglial VEGFR-3 expression and GLT-1 expression after SE. Treatment with a selective inhibitor for VEGFR-3 attenuated astroglial pS6 expression as well as suppressed GLT-1 expression and astroglial reactivity in the hippocampus after SE. These findings demonstrate that VEGFR-3-mediated mTOR activation could contribute to the regulation of GLT-1 expression in reactive astrocytes during the subacute phase of epilepsy. In conclusion, the present study suggests that VEGFR-3 upregulation in reactive astrocytes may play a role in preventing hyperexcitability induced by continued seizure activity.

Targeting mutant KRAS with CRISPR-Cas9 controls tumor growth.

KRAS is the most frequently mutated oncogene in human tumors, and its activating mutations represent important therapeutic targets. The combination of Cas9 and guide RNA from the CRISPR-Cas system recognizes a specific DNA sequence and makes a double-strand break, which enables editing of the relevant genes. Here, we harnessed CRISPR to specifically target mutant KRAS alleles in cancer cells. We screened guide RNAs using a reporter system and validated them in cancer cells after lentiviral delivery of Cas9 and guide RNA. The survival, proliferation, and tumorigenicity of cancer cells in vitro and the growth of tumors in vivo were determined after delivery of Cas9 and guide RNA. We identified guide RNAs that efficiently target mutant KRAS without significant alterations of the wild-type allele. Doxycycline-inducible expression of this guide RNA in KRAS-mutant cancer cells transduced with a lentiviral vector encoding Cas9 disrupted the mutant KRAS gene, leading to inhibition of cancer cell proliferation both in vitro and in vivo. Intra-tumoral injection of lentivirus and adeno-associated virus expressing Cas9 and sgRNA suppressed tumor growth in vivo, albeit incompletely, in immunodeficient mice. Expression of Cas9 and the guide RNA in cells containing wild-type KRAS did not alter cell survival or proliferation either in vitro and in vivo. Our study provides a proof-of-concept that CRISPR can be utilized to target driver mutations of cancers in vitro and in vivo.

Prevalence and Characteristics of Restless Legs Syndrome in Korean Adults: A Study in Two Independent Samples of the General Population.

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.

Sex Differences in Prevalence, Symptoms, Impact, and Psychiatric Comorbidities in Migraine and Probable Migraine: A Population-Based Study.

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 < .001, respectively). The prevalence of migraine (107/1350 [7.9%] vs 36/1345 [2.7%], P < .001) and probable migraine (243/1350 [18.0%] vs 136/1345 [10.1%], P < .001) was significantly higher among women than among men. Headache frequency per month (median [interquartile range]) (1.0 [0.3-3.0] vs 0.8 [0.3-2.0], P = .037), the visual analog scale score for headache intensity (5.0 [4.0-7.0] vs 5.0 [3.0-6.0], P = .019), and the impact of headache {Headache Impact Test-6 score (47.0 [42.0-54.0] vs 44.0 [42.0-51.8], P = .013)} were significantly higher among women with probable migraine than men. Headache frequency per month (2.0 [0.4-4.0] vs 1.0 [0.3-2.0], P = .073), headache intensity (6.0 [5.0-8.0] vs 6.0 [4.2-7.0], P = .281), and the impact of headache (55.0 [48.0-61.0] vs 49.0 [46.3-60.8], P = .225) were not significantly different between women and men with migraine. Other comorbidities or associated symptoms, such as anxiety and depression, were not significantly different between women and men with migraine and probable migraine, except for nausea in probable migraine. CONCLUSION: Women experience more severe symptoms and a higher impact of headache than men among participants with probable migraine. Our findings suggest that women with PM need a more intensive evaluation and treatment than men with PM.

High risk of obstructive sleep apnea, insomnia, and daytime sleepiness among commercial motor vehicle drivers.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001 for both). Although CMV drivers showed higher ESS scores than controls, the prevalence of daytime sleepiness did not differ between the two groups (19.1% vs. 16.8%, P = 0.54). After adjusting for covariates, CMV drivers had 3.68 times higher odds (95% CI 2.29-5.84) of OSA and 2.97 times higher odds (95% CI, 1.46-6.06) of insomnia compared with controls. However, the degree of daytime sleepiness was not independently associated with CMV drivers. CONCLUSIONS: The prevalence of OSA and insomnia in CMV drivers was higher than that in the general population. Daytime sleepiness was associated with increased BMI, depression, OSA, and short sleep duration, regardless of CMV driving as an occupational factor.

Increased Superoxide Dismutase 2 by Allopregnanolone Ameliorates ROS-Mediated Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus.

Excessive production of reactive oxygen species (ROS), along with dysfunction of the antioxidant defense system, such as that involving superoxide dismutase (SOD), may play a major role in neuronal death following status epilepticus (SE). Neurosteroids, which are allosteric modulators of the GABAA receptor in cerebral metabolism, have been suggested as being neuroprotective in various animal models; however, their effect to preventing ROS has not been examined. Herein, we investigate the neuroprotective role of allopregnanolone, the prototypical neurosteroid in the brain, in relation to the ROS-mediated neuronal injury. Adult male C57BL/6 mice were subjected to SE and treated with allopregnanolone. Hippocampal cell death was assessed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and ROS production was investigated by in situ detection of oxidized hydroethidine. SOD2 expression was analyzed by both western blot and immunofluorescent staining in the hippocampal subfields. In mice treated with allopregnanolone after SE, hippocampal cell death, DNA fragmentation, oxidative DNA damage, and ROS production were reduced significantly compared to mice subjected to vehicle treatment after SE. Hippocampal SOD2 expression was significantly increased by allopregnanolone. These finding suggest that allopregnanolone plays a neuroprotective role, with not only anticonvulsant but also antioxidant effects, by increasing SOD2 in pilocarpine-induced SE model.

Short sleep duration and poor sleep quality among migraineurs: A population-based study.

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 <6 h/day and Pittsburgh Sleep Quality Index score >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 (ß = 0.210, p = 0.015). Conclusions Self-reported short sleep duration (<6 h per day) is associated with an increased headache frequency among migraineurs in a population-based setting.

Impact of migraine on the clinical presentation of insomnia: a population-based study.

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 <  0.001) and non-migraine headache (59.0% vs. 39.9%, p <  0.001) were higher among individuals with insomnia compared to those without insomnia. Among participants with insomnia, total ISI scores were not significantly different among participants with migraine, non-migraine, and non-headache [median and interquartile range: 13.0 (11.0-17.5) vs. 13.0 (11.0-17.5) vs. 12.0 (11.0-16.0), p = 0.245]. ISI scores for noticeability of sleep problems to others were significantly higher among participants with migraine [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.011] and non-migraine headache [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.001] compared to those without headache history. Other ISI subcomponent scores did not significantly differ between headache status groups. CONCLUSIONS: Participants with insomnia had an increased risk of migraine and non-migraine headache compared to those without insomnia. Among participants with insomnia, overall insomnia severity was not significantly influenced by the headache status.

Poor sleep quality in migraine and probable migraine: a population study.

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 < 0.001). The PM participants with poor sleep quality showed increased headache frequency (median [interquartile range]: 2.0 [0.3-4.0] vs. 1.0 [0.2-2.0]; p = 0.001) and headache intensity (visual analogue scale, 6.0 [4.0-7.0] vs. 5.0 [3.5-6.0]; p = 0.003) compared to PM participants who had no poor sleep quality. CONCLUSIONS: Poor sleep quality was prevalent among participants with PM. It was associated with an exacerbation of PM symptoms. Our findings suggest that proper evaluation and treatment for poor sleep quality are needed in the management of PM.

Anxiety and depression in probable migraine: A population-based study.

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.

Insomnia in tension-type headache: a population-based study.

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 < 0.001). However, among the TTH group, the prevalence of insomnia did not significantly differ between participants fulfilling PM criteria and those not fulfilling PM criteria (14.2% vs. 12.9%, p = 0.725). Among individuals with TTH, headache frequency [median and interquartile range (IQR): 1.0 (0.3-3.0) vs. 0.4 (0.2-1.0), p = 0.002], visual analogue scale scores for headache intensity [median and IQR: 5.0 (4.0-7.0) vs. 4.0 (3.0-6.0), p < 0.001], Headache Impact Test-6 scores [median and IQR: 46.0 (40.0-52.0) vs. 42.0 (38.0-46.0), p < 0.001], anxiety prevalence (28.0% vs. 6.7%, p < 0.001), and depression prevalence (21.3% vs. 1.6%, p < 0.001) were significantly higher in those with insomnia than in those without insomnia. CONCLUSIONS: Our findings indicate that insomnia is prevalent among individuals with TTH. Moreover, insomnia was associated with exacerbation of headache symptoms and psychiatric comorbidities. Therefore, identification of insomnia among individuals with TTH is required to improve the management of headache symptoms in such patients.

Insufficient sleep is prevalent among migraineurs: a population-based study.

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 < 0.001). Average sleep time did not differ among migraine, non-migraine headache, and non-headache groups (7.3 ± 1.2 vs. 7.2 ± 1.2 vs. 7.3 ± 1.4, p = 0.207). Multivariable logistic regression analyses demonstrated that migraine had an increased odds ratio (OR) for insufficient sleep after adjusting for sociodemographic variables, short sleep time, insomnia, poor sleep quality, anxiety, and depression (OR = 1.8, 95% confidence interval [CI] = 1. 2 - 2.7, p = 0.002). CONCLUSIONS: The prevalence of insufficient sleep was significantly higher among migraineurs compared to that in non-migraine headache or non-headache group.

Restless legs syndrome and tension-type headache: a population-based study.

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.