Global Gene Expression of T Cells Is Differentially Regulated by Peritoneal Dendritic Cell Subsets in an IL-2 Dependent Manner

Dendritic cells (DCs) in peripheral tissues may have a unique role to regulate innate and adaptive immune responses to antigens that enter the tissues. Peritoneal cavity is the body compartment surrounding various tissues and organs and housing diverse immune cells. Here, we investigated the specialized features of classical DC (cDC) subsets following the intraperitoneal injection of a model antigen ovalbumin (OVA). Peritoneal cDC1s were superior to cDC2s in activating OVA-specific CD8 T cells, while both cDCs were similar in stimulating OVA-specific CD4 T cells. Each peritoneal cDC subset differentially regulated the homing properties of CD8 T cells. CD8 T cells stimulated by cDC1s displayed a higher level of lung-homing receptor CCR4, whereas those stimulated by cDC2s prominently expressed various homing receptors including gut-homing molecules CCR9 and α4β7. Also, we found that cDC1s played a dominating role over cDC2s in controlling the overall gene expression of CD8 T cells. Soluble factor(s) emanating from CD8 T cells stimulated by peritoneal cDC1s were responsible for mediating this dominance of cDC1s, and we identified IL-2 as a soluble factor regulating the global gene expression of T cells. Collectively, our study indicates that different peritoneal cDC subsets effectively diversify T cell responses by altering the level of cytokines, such as IL-2, in the milieu.ope

Excessive Daytime Sleepiness in Tension-Type Headache: A Population Study

Excessive daytime sleepiness (EDS) is a prevalent sleep-related complaint across the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. However, the association between EDS and TTH is currently scarce. In the present study, we investigated the impact of EDS on the prevalence and clinical presentation of TTH. We utilized data from the Korean Headache-Sleep Study, a national survey that sought to identify headache and sleep characteristics in Korean adults. Participants with an Epworth sleepiness scale score greater or equal to 11 were considered as having EDS. Of the 2,695 participants enrolled, 570 (21.2%) and 313 (11.6%) had TTH and EDS, respectively. EDS was highly prevalent in individuals with chronic tension-type headache (CTTH) than in those without headache (35.7 vs. 9.4%, p < 0.001). The prevalence of EDS in episodic tension-type headache (ETTH) individuals with a headache frequency <1 per month (8.3%, p = 0.511) and ETTH individuals with a headache frequency of 1-14 per month (13.5%, p = 0.054) was not significantly different from that in individuals without headache (9.4%). TTH participants with EDS had a higher headache frequency per month (4.3 ± 8.1 vs. 1.7 ± 4.2, p = 0.013), more severe headache intensity (Visual Analog Scale, 5.0 [3.0-6.0] vs. 4.0 [3.0-6.0], p = 0.008), a higher impact of headache (Headache Impact Test-6 score, 47.1 ± 7.3 vs. 43.5 ± 7.6, p < 0.001), and a higher prevalence of depression (12.7 vs. 3.2%, p < 0.001) than TTH participants without EDS. Consequently, CTTH is associated with higher EDS prevalence compared to ETTH and without headache. Moreover, TTH with EDS had more severe TTH symptoms compared to TTH without EDS.ope

Differences in Characteristics and Comorbidity of Cluster Headache According to the Presence of Migraine

BACKGROUND AND PURPOSE: Cluster headache (CH) can present with migrainous symptoms such as nausea, photophobia, and phonophobia. In addition, an overlap between CH and migraine has been reported. This study aimed to determine the differences in the characteristics of CH according to the presence of comorbid migraine. METHODS: This study was performed using data from a prospective multicenter registry study of CH involving 16 headache clinics. CH and migraine were diagnosed by headache specialists at each hospital based on third edition of the International Classification of Headache Disorders (ICHD-3). We interviewed patients with comorbid migraine to obtain detailed information about migraine. The characteristics and psychological comorbidities of CH were compared between patients with and without comorbid migraine. RESULTS: Thirty (15.6%) of 192 patients with CH had comorbid migraine, comprising 18 with migraine without aura, 1 with migraine with aura, 3 with chronic migraine, and 8 with probable migraine. Compared to patients with CH without migraine, patients with CH with comorbid migraine had a shorter duration of CH after the first episode [5.4±7.4 vs. 9.0±8.2 years (mean±standard deviation), p=0.008], a lower frequency of episodic CH (50.0% vs. 73.5%, p=0.010), and a higher frequency of chronic CH (13.3% vs. 3.7%, p=0.033). Psychiatric comorbidities did not differ between patients with and without comorbid migraine. The headaches experienced by patients could be distinguished based on their trigeminal autonomic symptoms, pulsating character, severity, and pain location. CONCLUSIONS: Distinct characteristics of CH remained unchanged in patients with comorbid migraine with the exception of an increased frequency of chronic CH. The most appropriate management of CH requires clinicians to check the history of preceding migraine, particularly in cases of chronic CH.ope

Factors Associated with Incidental Neuroimaging Abnormalities in New Primary Headache Patients

Background and purpose: Deciding whether or not to perform neuroimaging in primary headache is a dilemma for headache physicians. The aim of this study was to identify clinical predictors of incidental neuroimaging abnormalities in new patients with primary headache disorders. Methods: This cross-sectional study was based on a prospective multicenter headache registry, and it classified 1,627 consecutive first-visit headache patients according to the third edition (beta version) of the International Classification of Headache Disorders (ICHD-3β). Primary headache patients who underwent neuroimaging were finally enrolled in the analysis. Serious intracranial pathology was defined as serious neuroimaging abnormalities with a high degree of medical urgency. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with incidental neuroimaging abnormalities. Results: Neuroimaging abnormalities were present in 170 (18.3%) of 927 eligible patients. In multivariable analysis, age ≥40 years [multivariable-adjusted odds ratio (aOR)=3.37, 95% CI=2.07-6.83], male sex (aOR=1.61, 95% CI=1.12-2.32), and age ≥50 years at headache onset (aOR=1.86, 95% CI=1.24-2.78) were associated with neuroimaging abnormalities. In univariable analyses, age ≥40 years was the only independent variable associated with serious neuroimaging abnormalities (OR=3.37, 95% CI=1.17-9.66), which were found in 34 patients (3.6%). These associations did not change after further adjustment for neuroimaging modality. Conclusions: Incidental neuroimaging abnormalities were common and varied in a primary headache diagnosis. A small proportion of the patients incidentally had serious neuroimaging abnormalities, and they were predicted by age ≥40 years. These findings can be used to guide the performing of neuroimaging in primary headache disorders.ope

Prevalence Rates of Primary Headache Disorders and Evaluation and Treatment Patterns Among Korean Neurologists

Background and purpose: Several studies have found that the prevalence of migraine is higher among healthcare professionals than in the general population. Furthermore, several investigations have suggested that the personal experiences of neurologists with migraine can influence their perception and treatment of the disease. This study assessed these relationships in Korea. Methods: A survey was used to investigate the following characteristics among neurologists: 1) the prevalence rates of migraine, primary stabbing headache, and cluster headache, and 2) their perceptions of migraine and the pain severity experienced by patients, diagnosing migraine, evaluation and treatment patterns, and satisfaction and difficulties with treatment. Results: The survey was completed by 442 actively practicing board-certified Korean neurologists. The self-reported lifetime prevalence rates of migraine, migraine with aura, primary stabbing headache, and cluster headache were 49.8%, 12.7%, 26.7%, and 1.4%, respectively. Few of the neurologists used a headache diary or validated scales with their patients, and approximately half were satisfied with the effectiveness of preventive medications. Significant differences were observed between neurologists who had and had not experienced migraine, regarding certain perceptions of migraine, but no differences were found between these groups in the evaluation and preventive treatment of migraine. Conclusions: The high self-reported lifetime prevalence rates of migraine and other primary headache disorders among Korean neurologists may indicate that these rates are underreported in the general population, although potential population biases must be considered. From the perspective of neurologists, there is an unmet need for the proper application of headache diaries, validated scales, and effective preventive treatments for patients. While the past experiences of neurologists with migraine might not influence how they evaluate or apply preventive treatments to migraine, they may influence certain perceptions of the disease.ope

Suicidality and Its Risk Factor in Migraine Patients

Background Migraine patients have a higher frequency of suicidality than people without migraine. The aim of this study was to identify suicidality and its risk factors in migraine patients. Methods We enrolled 358 migraine patients from 11 hospitals. We collected data regarding their clinical characteristics and the patients completes the questionnaires. We also interviewed patients with the Mini International Neuropsychiatric Interview (MINI)plus version 5.0.0 to identify their suicidality. The International Classification of Headache Disorders, third edition, beta version was used in headache diagnosis. Results The frequency of suicidality in migraine patients was 118 (33.0%). Migraine patients with suicidality were more likely to have a major depressive disorder or generalized anxiety disorder than those without suicidality. Among variables, risk factors for suicidality in migraine patients were female (odds ratio [OR], 4.110; 95% confidence interval [CI], 1.55310.878; p=0.004), attack duration (OR, 2.559; 95% CI, 1.2105.413; p=0.011), Patient Health Questionnaire9 (OR, 1.111; 95% CI, 1.0381.189; p=0.002), and Generalized Anxiety Disorder7 (OR, 1.194; 95% CI, 1.1011.294; p<0.001). Conclusions Suicidality in migraine patients is common. Therefore, clinicians who take care of migraine patients should be concerned about suicidality and its risk factors such as female gender, attack duration, depression or anxiety.ope

Vitamin D deficiency in patients with cluster headache: a preliminary study

BACKGROUND: Cluster headache is famous for attacks with seasonal and diurnal periodicity. This diurnal and seasonal variation might be related to sunlight and vitamin D metabolism. We investigated the serum vitamin D levels in patients with cluster headache. METHODS: We enrolled patients with cluster headache and age- and sex-matched migraineurs and normal controls. From October 2016 to March 2018, non-fasting serum 25(OH)D concentrations were measured using a chemiluminescent immunoassay. Vitamin D deficiency was defined as a concentration < 20 ng/mL. RESULTS: The study enrolled 28 patients with cluster headache, 36 migraineurs, and 36 normal controls. In the patients with cluster headache, the serum 25(OH)D concentration averaged 14.0 ± 3.9 ng/mL and 92.8% had vitamin D deficiency. There was no significant difference among the patients with cluster headache, migraineurs, and controls. In the patients with cluster headache, there was no difference in the serum 25(OH)D concentrations between men and women, cluster and remission periods, first and recurrent attack, presence and absence of daily or seasonal periodicity, and 3-month recurrence. In the 14 patients with seasonal periodicity, patients with periodicity of winter to spring had a trend of lower serum 25(OH)D concentrations than those with periodicity of summer to autumn (12.30 ± 1.58 vs. 16.96 ± 4.69 ng/mL, p = 0.097). CONCLUSIONS: Vitamin D deficiency is common in patients with cluster headache, but the role of vitamin D deficiency is uncertain, except for its seasonal influence.ope

The impact of remission and coexisting migraine on anxiety and depression in cluster headache

Background: Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission. Methods: We analyzed data from 222 consecutive CH patients and 99 age- and sex-matched controls using a prospective multicenter registry. Anxiety or depression was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9), respectively. Moderate-to-severe anxiety or depression was defined as a score of ≥10 at baseline (during a cluster bout). We assessed for changes in anxiety and depression during CH remission periods. Results: Among the CH patients, the prevalence of moderate-to-severe anxiety and depression was seen in 38.2% and 34.6%, respectively. Compared with controls, CH patients were associated with moderate-to-severe anxiety and depression (multivariable-adjusted odds ratio [aOR] = 7.32, 95% confidence intervals [CI] = 3.35-15.99 and aOR = 4.95, 95% CI = 2.32-10.57, respectively). CH patients with migraine were significantly more likely to have moderate-to-severe anxiety and depression (aOR = 32.53, 95% CI = 6.63-159.64 and aOR = 16.88, 95% CI = 4.16-68.38, respectively), compared to controls without migraine. The GAD-7 and PHQ-9 scores were significantly reduced between cluster bout and remission periods (from 6.8 ± 5.6 to 1.6 ± 2.8; P < 0.001, and from 6.1 ± 5.0 to 1.8 ± 2.4; P < 0.001, respectively). Conclusions: Our results indicate that CH patients are at increased risk of anxiety and depression, especially in the presence of coexisting migraine. However, the anxiety and depression can improve during remission periods.ope

A Case of Exercise Induced Cardiac Cephalalgia Relieved after Coronary Artery Bypass Graft

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Impact of cluster headache on employment status and job burden: a prospective cross-sectional multicenter study

BACKGROUND: Cluster headaches (CH) are recurrent severe headaches, which impose a major burden on the life of patients. We investigated the impact of CH on employment status and job burden. METHODS: The study was a sub-study of the Korean Cluster Headache Registry. Patients with CH were enrolled from September 2016 to February 2018 from 15 headache clinics in Korea. We also enrolled a headache control group with age-sex matched patients with migraine or tension-type headache. Moreover, a control group including individuals without headache complaints was recruited. All participants responded to a questionnaire that included questions on employment status, type of occupation, working time, sick leave, reductions in productivity, and satisfaction with current occupation. The questionnaire was administered to participants who were currently employed or had previous occupational experience. RESULTS: We recruited 143 patients with CH, 38 patients with other types of headache (migraine or tension-type headache), and 52 headache-free controls. The proportion of employees was lower in the CH group compared with the headache and headache-free control groups (CH: 67.6% vs. headache controls: 84.2% vs. headache-free controls: 96.2%; p = 0.001). The CH group more frequently experienced difficulties at work and required sick leave than the other groups (CH: 84.8% vs. headache controls: 63.9% vs. headache-free controls: 36.5%; p <  0.001; CH: 39.4% vs. headache controls: 13.9% vs. headache-free controls: 3.4%; p <  0.001). Among the patients with CH, sick leave was associated with younger age at CH onset (25.8 years vs. 30.6 years, p = 0.014), severity of pain rated on a visual analogue scale (9.3 vs. 8.8, p = 0.008), and diurnal periodicity during the daytime (p = 0.003). There were no significant differences with respect to the sick leave based on sex, age, CH subtypes, and CH recurrence. CONCLUSIONS: CH might be associated with employment status. Most patients with CH experienced substantial burdens at work.ope