Differences in Neuropathology between Nitroglycerin-Induced Mouse Models of Episodic and Chronic Migraine.

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed. Mechanical thresholds were similar. Notable neuropathological distinctions were observed in Sp5C and ACC. ACC showed increased c-Fos and NeuN expression in CM (p < 0.001) and unchanged in EM. Sp5C had higher c-Fos and NeuN expression in EM (p < 0.001). Iba1 was upregulated in Sp5C of EM and ACC of CM (p < 0.001). Proinflammatory markers were strongly expressed in Sp5C of EM and ACC of CM. CGRP expression was elevated in both regions and was higher in CM. VIP exhibited higher levels in the Sp5C of EM and ACC of CM, whereas PACAP and substance P were expressed in the Sp5C in both models. Despite similar thresholds, distinctive neuropathological differences in Sp5C and ACC between EM and CM models suggest a role in the EM to CM transformation.

Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea.

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Treatment pattern and response for cluster headache in Korea: A prospective multicenter observation study.

BACKGROUND: Only limited data are available regarding the treatment status and response to cluster headache in an Asian population. Therefore, this study aimed to provide a real-world treatment pattern of cluster headache and the response rate of each treatment in an Asian population. METHODS: Patients with cluster headache were recruited between September 2016 and January 2019 from 16 hospitals in Korea. At the baseline visit, we surveyed the patients about their previous experience of cluster headache treatment, and acute and/or preventive treatments were prescribed at the physician's discretion. Treatment response was prospectively evaluated using a structured case-report form at 2 ± 2 weeks after baseline visit and reassessed after three months. RESULTS: Among 295 recruited patients, 262 experiencing active bouts were included. Only one-third of patients reported a previous experience of evidence-based treatment. At the baseline visit, oral triptans (73.4%), verapamil (68.3%), and systemic steroids (55.6%) were the three most common treatments prescribed by the investigators. Most treatments were given as combination. For acute treatment, oral triptans and oxygen were effective in 90.1% and 86.8% of the patients, respectively; for preventive treatment, evidence-based treatments, i.e. monotherapy or different combinations of verapamil, lithium, systemic steroids, and suboccipital steroid injection, helped 75.0% to 91.8% of patients. CONCLUSION: Our data provide the first prospective analysis of treatment responses in an Asian population with cluster headache. The patients responded well to treatment despite the limited availability of treatment options, and this might be attributed at least in part by combination of medications. Most patients were previously undertreated, suggesting a need to raise awareness of cluster headache among primary physicians.

Predicting Role of Prestroke Glycemic Variability Estimated by Glycated Albumin for Reperfusion and Prognosis after Endovascular Treatment.

INTRODUCTION: Glycated hemoglobin is widely used for the diagnosis of diabetes, but it is not accurately correlated with blood glucose fluctuations. We evaluated the impact of prestroke glycemic variability, measured by glycated albumin (GA) on reperfusion rate and stroke outcomes after endovascular treatment (EVT). METHODS: We consecutively collected 310 EVT-treated patients for 60 months using a multicenter registry database. Primary outcome was unsuccessful reperfusion defined by modified Thrombolysis in Cerebral Infarction grade 0 to 2a. Secondary outcomes were occurrence of early neurologic deterioration (END), symptomatic hemorrhagic transformation (SHT) and a 3-month poor outcome (modified Rankin Scale >2). GA was measured in the morning after hospital admission with overnight fasting and determined to reflect high prestroke glycemic variability (GA ≥16.0%). RESULTS: Over the median follow-up of 60 months of 310 patients, there were 64 (20.6%) events of unsuccessful reperfusion, 66 (21.3%) of END, 21 (6.8%) of SHT, and 180 (58.1%) of 3-month poor outcome. In the higher GA group (130, 41.9%), proportion of unsuccessful reperfusion, END, SHT, and poor outcome were higher than lower GA group. The multivariate analysis showed that higher GA was associated with unsuccessful reperfusion after EVT (adjusted odds ratio 4.13; 95% confidence interval [CI], 1.93-8.85). The area under the receiver operating characteristic of GA (0.644; 95% CI: 0.634-0.740) for predicting poor outcome was better than that of glycated hemoglobin (0.586; 95% CI: 0.529-0.642, p for DeLong's pairwise comparison = 0.005). CONCLUSION: GA, reflecting prestroke glycemic variability, could be a reliable parameter for predicting reperfusion rate and acute ischemic stroke outcome in this study.

The association between malnutrition status and hemorrhagic transformation in patients with acute ischemic stroke receiving intravenous thrombolysis.

OBJECTIVES: We evaluated the impact of malnutrition as estimated by the controlling nutritional status (CONUT) score and prognostic nutritional index (PNI) on hemorrhagic transformation (HT) and stroke outcomes after intravenous thrombolysis (IVT). MATERIALS AND METHODS: Using a multicenter registry database, we enrolled 808 patients with acute ischemic stroke who received IVT between August 2013 and May 2021. We defined malnutrition as a CONUT score ≥ 2 and low PNI. The primary outcome measure was the occurrence of symptomatic HT contributing to early neurologic deterioration (END-SHT) after IVT. Multivariable analysis was performed to analyze the association between CONUT score, PNI, and END-SHT after IVT. RESULTS: The rate of END-SHT was higher with increasing CONUT scores and PNI values. In the multivariable analysis, CONUT score ≥ 5 and low PNI were significantly associated with END-SHT (odds ratio [95% confidence interval], CONUT score ≥ 5: 12.23 [2.41-62.07], p = 0.003; low PNI: 4.98 [1.76-14.09], p = 0.003). The receiver operating characteristic curve showed that both the CONUT score and PNI had good predictive ability. The cutoff values for CONUT and PNI were 5 and 42.3, respectively, for END-SHT. CONCLUSION: Malnutrition, as denoted by a higher CONUT score and lower PNI, was associated with END-SHT. The joint application of both nutritional markers could be useful in predicting END-SHT after IVT.

Auditory or Audiovisual Stimulation Ameliorates Cognitive Impairment and Neuropathology in ApoE4 Knock-In Mice.

We hypothesized that auditory stimulation could reduce the progression of Alzheimer's disease (AD), and that audiovisual stimulation could have additional effects through multisensory integration. We exposed 12 month old Apoetm1.1(APOE*4)Adiuj mice (a mouse model of sporadic AD) to auditory (A) or audiovisual stimulation (AV) at 40 Hz for 14 days in a soundproof chamber system (no stimulation, N). Behavioral tests were performed before and after each session, and their brain tissues were assessed for amyloid-beta expression and apoptotic cell death, after 14 days. Furthermore, brain levels of acetylcholine and apoptosis-related proteins were analyzed. In the Y-maze test, the percentage relative alternation was significantly higher in group A than in group N mice. Amyloid-beta and TUNEL positivity in the hippocampal CA3 region was significantly lower in group A and group AV mice than in group N mice (p < 0.05). Acetylcholine levels were significantly higher in group A and group AV mice than in group N mice (p < 0.05). Compared to group N mice, expression of the proapoptotic proteins Bax and caspase-3 was lower in group A, and expression of the antiapoptotic protein Bcl-2 was higher in group AV. In a mouse model of early-stage sporadic AD, auditory or audiovisual stimulation improved cognitive performance and neuropathology.

Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.

BACKGROUND: Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status. RESULTS: Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age. CONCLUSIONS: In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.

Characteristics of pre-cluster symptoms in cluster headache: A cross-sectional multicentre study.

BACKGROUND: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. METHODS: In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. RESULTS: The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3-14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). CONCLUSIONS: The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.

Clinical characteristics of pre-attack symptoms in cluster headache: A large series of Korean patients.

BACKGROUND: Previous studies have reported notable differences in demographic and clinical features of cluster headache between Western and Asian populations, including lower prevalence of the chronic type and in women. Recently, prodromal symptoms of migraine and pre-attack symptoms of cluster headache have drawn attention regarding their potential pathophysiological implications and pre-emptive treatment. However, pre-attack symptoms of cluster headache have not been studied in the Asian population. METHODS: A total of 136 patients with cluster headache (21 first-onset, 110 episodic, and five chronic cases) were recruited in this multi-center study between October 2018 and December 2019. We evaluated the characteristics of pre-attack symptoms in a current bout using a structured questionnaire. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with presence of pre-attack symptoms. RESULTS: Pre-attack symptoms were reported in 71.3% of our patients with cluster headache. When present, pre-attack symptoms occurred at a median of 20 minutes (range 1-120) before the attack. The prevalence of local and painful, local and painless sensory, autonomic, and general symptoms was 58.8%, 14.7%, 11.0%, and 30.1%, respectively. Multivariable logistic regression analysis revealed that higher number of bouts was associated with higher prevalence of pre-attack symptoms (OR = 1.464, p = 0.044). CONCLUSIONS: Pre-attack symptoms were frequently observed in Korean patients with cluster headache, which was consistent with previous Western studies.

Pre-Stroke Glycemic Variability Estimated by Glycated Albumin Is Associated with Early Neurological Deterioration and Poor Functional Outcome in Prediabetic Patients with Acute Ischemic Stroke.

INTRODUCTION: Whether glycemic variability prior to stroke increases the risk of stroke outcomes in prediabetic patients presenting with acute ischemic stroke is still unclear. We evaluated whether pre-stroke glycemic variability, estimated by glycated albumin (GA), increased early neurological deterioration (END) and functional outcomes in prediabetic patients with acute ischemic stroke. METHODS: A total of 215 acute ischemic stroke patients with prediabetes were evaluated. The primary outcome was END, defined as an incremental increase in the National Institutes of Health Stroke Scale score by ≥1 point in motor power or ≥2 points in the total score within the 7 days after admission. The secondary outcome was poor functional status defined by a modified Rankin Scale at 3 months. Higher GA (≥16.0%) was determined to reflect glycemic fluctuation prior to ischemic stroke. RESULTS: Of the 215 prediabetic patients, 77 (35.8%) were in the higher GA group. In prediabetic patients, END occurrence and poor functional status were higher in the higher GA group than in the lower GA group. The multivariate analysis showed that a higher GA was associated with an increased risk of END occurrence and poor functional outcomes at 3 months (adjusted odds ratio [95% confidence interval], 4.58 [1.64-12.81], p = 0.004 and 2.50 [1.19-5.25], p = 0.02, respectively). CONCLUSION: Pre-stroke glycemic variability estimated by GA was associated with END occurrence and poor functional outcome after ischemic stroke in patients with prediabetes.

Temporal changes of circadian rhythmicity in cluster headache.

OBJECTIVE: To investigate the temporal changes of circadian rhythmicity in relation to the disease course in patients with cluster headache. METHODS: In this multicenter study, patients with cluster headache were recruited between September 2016 and July 2018. We evaluated the patients for circadian rhythmicity and time of cluster headache attacks in the current bout and any experience of bout-to-bout change in circadian rhythmicity. We analyzed the patterns of circadian rhythmicity in relation to the disease progression (the number of total lifetime bouts, grouped into deciles). RESULTS: Of the 175 patients in their active, within-bout period, 86 (49.1%) had circadian rhythmicity in the current bout. The prevalence of circadian rhythmicity in the active period was overall similar regardless of disease progression. Sixty-three (46.3%) out of 136 patients with ≥2 bouts reported bout-to-bout changes in circadian rhythmicity. The most frequent time of cluster headache attacks was distributed evenly throughout the day earlier in the disease course and dichotomized into hypnic and midday as the number of lifetime bouts increased (p = 0.037 for the homogeneity of variance). When grouped into nighttime and daytime, nighttime attacks were predominant early in the disease course, while daytime attacks increased with disease progression (up to 7th deciles of total lifetime bouts, p = 0.001) and decreased in patients with the most advanced disease course (p = 0.013 for the non-linear association). CONCLUSIONS: Circadian rhythmicity is not a fixed factor, and changes according to the disease course. Our findings will be valuable in providing a new insight into the stability of functional involvement of the suprachiasmatic nucleus in the pathophysiology of cluster headache.

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.

Association between Osteoporosis and Cognitive Impairment during the Acute and Recovery Phases of Ischemic Stroke.

Background and objectives: Little is known about the effect of osteoporosis on cognitive function in the acute and recovery phases of stroke. Early bone mineral density assessments during acute stroke may be a useful marker of cognitive function. We evaluated the effect of osteoporosis on cognitive function at the early and recovery phase of ischemic stroke in patients aged >50 years. Materials and Methods: We retrospectively examined consecutive patients with acute stroke hospitalized between 2016 and 2018. Osteoporosis was defined as a T-score <-2.5 for the femoral neck or lumbar spine bone mineral density. The primary outcome was cognitive impairment measured by the Korean Mini-Mental State Examination in the acute phase and recovery phase of ischemic stroke. Results: Of the 260 included subjects (107 men and 153 women), 70 (26.9%) had osteoporosis. Cognitive impairment was more severe in the osteoporosis group than in the non-osteoporosis group (30.5% versus 47.1%, p = 0.001). After the recovery phase of stroke, the proportion of patients with cognitive impairment remained higher in the osteoporosis group. The multivariate analysis revealed a correlation between a low femoral neck bone mineral density and severe cognitive impairment in the acute and recovery phases of stroke (adjusted odds ratio (OR) 4.09, 95% confidence interval (CI) 1.11-15.14 in the acute phase, and adjusted OR 11.17, 95% CI 1.12-110.98 in the recovery phase). Conclusions: Low bone mineral density is associated with poor cognitive function in the acute and recovery phases of stroke.

Field testing the diagnostic criteria of cluster headache in the third edition of the International Classification of Headache Disorders: A cross-sectional multicentre study.

BACKGROUND: *These authors are shared first authors. The recently published third edition of the International Classification of Headache Disorders (ICHD-3) revised the criteria for accompanying symptoms of cluster headache (CH) and the remission period of chronic cluster headache (CCH). This study aimed at testing the validity of the ICHD-3 criteria for CH by using data from the Korean Cluster Headache Registry. METHODS: Consecutive patients with CH and probable cluster headache (PCH) were prospectively recruited from 15 hospitals. We analysed the validity of the revised ICHD-3 criteria for CH against the beta version of the third edition of the ICHD (ICHD-3ß). RESULTS: In total, 193 patients were enrolled: 140 (72.5%), 5 (2.6%) and 22 (11.4%) had episodic cluster headache (ECH), CCH, and PCH, respectively. The remaining 26 (13.5%) had CH with undetermined remission periods. One patient with ECH and one with PCH had only forehead and facial flushing and were diagnosed with PCH and non-cluster headache, respectively, according to the ICHD-3. Four participants with ECH according to the ICHD-3ß had remission periods of > 1 month and between 1 and 3 months and were newly diagnosed with CCH according to the ICHD-3. CONCLUSION: The change from ICHD-3ß to ICHD-3 resulted in few differences in the diagnoses of CH and PCH.

Increased suicidality in patients with cluster headache.

OBJECTIVE: To investigate suicidality related to cluster headache and factors associated with increased suicidality in cluster headache patients. METHODS: In this multicenter study, 193 cluster headache patients were recruited between September 2016 and August 2018. Patients were asked about their suicidality during and between attacks, specifically about passive suicidal ideation, active suicidal ideation, suicide plan, and suicide attempt. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with high ictal suicidality (sum of positive response ≥ 2). Patients were followed up when they were in the between-bouts period. RESULTS: A total of 175 cluster headache patients in the in-bout period were included in this study. Passive suicidal ideation, active suicidal ideation, suicidal planning, and suicidal attempt were reported by 111 (64.2%), 62 (35.8%), 10 (5.8%), and four (2.3%) patients during attacks; seven (4.0%), six (3.5%), five (2.9%) and two (1.2%) patients interictally; and none (0%), one (1.9%), one (1.9%), and none (0%) among patients in the between-bouts period. Factors associated with high ictal suicidality were longer disease duration, the Headache Impact Test score, and the Patient Health Question-9 score (multivariable OR = 1.90 per 10-year increase in disease duration, 95% CI = 1.18-3.05, p = 0.008; multivariable OR = 3.19 per 10-point increase in HIT-6, 95% CI = 1.73-5.87, p < 0.001; multivariable OR = 2.11 per 10-point increase in PHQ-9, 95% CI = 1.13-3.95, p = 0.020, respectively). CONCLUSIONS: Cluster headache attack carries a high suicidality compared to the interictal or between-bouts state. An intensive treatment to reduce cluster headache burden may be helpful to alleviate suicide risk in cluster headache patients.

Differences of Cluster Headache on the Basis of Sex in the Korean Cluster Headache Registry.

BACKGROUND: Most of the clinical characteristics of cluster headache (CH) have been established through the observation of men with CH. Epidemiological data of CH in women are scarce especially in the Asian population. Here, we sought to assess the prevalence and clinical characteristics of women with CH in comparison to men in a prospective CH registry. METHODS: Data used in this study were obtained from the Korean Cluster Headache Registry, a prospective, cross-sectional, multicenter headache registry that collected data from consecutive patients diagnosed with CH. Demographics and clinical characteristics were compared between the sexes. RESULTS: In total, 250 patients were enrolled in this study; 41 (16.4%) were women (male to female ratio 5.1:1). Mean age of onset did not differ between women and men (30.7 ± 15.5 vs 29.0 ± 11.1 years). The clinical features of CH in women and men were similar, with no differences in pain severity, duration, and attack frequency. Among autonomic features, facial and forehead sweating was significantly rare in women (4.9%) compared to men with CH (33.0%). Headache-related disability assessed by Headache Impact Test-6 did not differ between the sexes; however, depression scale assessed by Patients Health Questionnaire-9 (11.0 ± 8.5 vs 7.0 ± 5.8, P = .009) and stress (Perceived Stress Scale 4, 7.5 ± 3.4 vs 6.4 ± 3.0, P = .045) were significantly higher in women with CH. CONCLUSIONS: Although decreasing male preponderance was suggested in recent Western CH studies, CH in women is still far less prevalent than in men in the Korean population. Clinical and demographic characteristics were similar between the sexes. However, psychiatric comorbidities might be highly associated in women with CH.

Validity and Reliability of the Fibromyalgia Rapid Screening Tool Among Individuals with Chronic Daily Headache: A Clinic-Based Study.

BACKGROUND: Fibromyalgia is a common chronic pain disorder typically associated with headache disorders, particularly chronic daily headache. However, fibromyalgia is typically underdiagnosed and undertreated. The Fibromyalgia Rapid Screening Tool questionnaire is a brief, self-administered questionnaire composed of six "yes/no" questions for detecting fibromyalgia. The Fibromyalgia Rapid Screening Tool questionnaire has demonstrated high sensitivity and specificity among patients with chronic diffuse pain conditions. This study assessed the validity and reliability of the aforementioned questionnaire for detecting fibromyalgia among patients with chronic daily headache. METHODS: Consecutive first-visit headache patients with primary chronic daily headache (≥15 days/month for three or more months) at the outpatient clinics of four university hospitals were enrolled in this study from April 2015 to October 2015, and the validity and reliability of the Fibromyalgia Rapid Screening Tool questionnaire for determining fibromyalgia were evaluated. Fibromyalgia was diagnosed according to the American College of Rheumatology criteria of 2010. RESULTS: A total of 171 patients with primary chronic daily headache were recruited, and 100 (58.4%) were determined to have fibromyalgia. Receiver operating characteristic curve analysis revealed that a cutoff score of 5 (corresponding to the number of positive items) provided the highest rate of correct identification of patients (77.2%), with a sensitivity of 70.0% and specificity of 87.3%. The positive and negative predictive values were 88.6% and 67.4%, respectively. The Cronbach's alpha coefficient was 0.684. CONCLUSIONS: The Fibromyalgia Rapid Screening Tool is a valid and reliable instrument for identifying fibromyalgia among patients with chronic daily headache.

Dizziness Handicap and Its Contributing Factors in Patients With Migraine.

OBJECTIVE: Dizziness is frequently reported in patients with migraine. However, its assessment is often neglected in clinical practice. We investigated the dizziness handicap experienced by patients with migraine and its contributing factors. METHODS: A total of 361 migraine outpatients (270 women, 91 men; mean age 39.01 ± 11.2 years) were given the Korean Dizziness Handicap Inventory (KDHI) questionnaire (total score: 100 points; cutoff: 29). The Headache Impact Test, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Pittsburgh Sleep Quality Index were also administered. Clinical data such as age, sex, number of headache attacks per month, pain intensity on the visual analog scale, and average sleep hours were collected to find contributing factors. Comparisons were made between chronic and episodic migraine. RESULTS: A total of 153 patients were classified as having dizziness handicap (M+DH) and 208 had migraine without dizziness handicap (M-DH). Patients with M+DH experienced more headache attacks per month than patients with M-DH (P = 0.010). The proportion of patients with chronic migraine was larger in the M+DH group (29.4% vs. 17.3%, P = 0.006). Patients with M+DH showed higher scores than patients with M-DH in all the KDHI subscales. Multivariable logistic regression showed headache impact, pain intensity, anxiety, and depression to be significantly associated with dizziness handicap. CONCLUSION: The data suggest that patients with migraine, especially those with chronic-type migraine, experience physical, emotional, and functional handicaps due to dizziness. Dizziness handicap is related to headache impact, anxiety, and depression. Targeted management of such factors is required to reduce the severity of subjective discomfort.

Stress Is Associated with Poor Outcome of Acute Treatment for Chronic Migraine: A Multicenter Study.

Background: Chronic migraine (CM) is associated with severe psychological symptoms and disabilities. Information on the relationship between stress and the outcomes of acute CM treatment is limited. Methods: We evaluated the clinical presentation and stress levels of patients with CM who visited the neurology departments of 14 hospitals between September and December 2015. The patients were divided into stress and reference groups on the basis of the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K). Quality of life was evaluated using EuroQol Five Dimension Questionnaire Three-Level. The Migraine Assessment of Current Therapy questionnaire was used to assess the outcomes of acute treatment. Results: This study included 186 CM patients. On the basis of the BEPSI-K score, 79 and 107 patients were assigned to the stress and reference groups, respectively. The stress group had more patients with poor outcomes of acute treatment than the reference group (67.1% vs 40.2%, P < 0.001). In a multivariate analysis, female gender (odds ratio [OR] = 3.266, 95% confidence interval [CI] = 1.172-9.103, P = 0.024), the number of headache-free days per month (OR = 0.932, 95% CI = 0.883-0.985, P = 0.012), and BEPSI-K score (OR = 1.667, 95% CI = 1.051-2.643, P = 0.030) predicted poor outcomes of acute treatment. Conclusions: High levels of stress were reported by 42.5% of patients with CM. The association between stress and the outcomes of acute treatment suggests that stress is an important clinical variable for improving the management of CM.

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.