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.

Dysbiosis of Fecal Microbiota in Tg2576 Mice for Alzheimer's Disease during Pathological Constipation.

Tg2576 transgenic mice for Alzheimer's disease (AD) exhibited significant phenotypes for neuropathological constipation, but no research has been conducted on the association of the fecal microbiota with dysbiosis. The correlation between fecal microbiota composition and neuropathological constipation in Tg2576 mice was investigated by examining the profile of fecal microbiota and fecal microbiota transplantation (FMT) in 9-10-month-old Tg2576 mice with the AD phenotypes and constipation. Several constipation phenotypes, including stool parameters, colon length, and histopathological structures, were observed prominently in Tg2576 mice compared to the wild-type (WT) mice. The fecal microbiota of Tg2576 mice showed decreases in Bacteroidetes and increases in the Firmicutes and Proteobacteria populations at the phylum level. The FMT study showed that stool parameters, including weight, water content, and morphology, decreased remarkably in the FMT group transplanted with a fecal suspension of Tg2576 mice (TgFMT) compared to the FMT group transplanted with a fecal suspension of WT mice (WFMT). The distribution of myenteric neurons and the interstitial cells of Cajal (ICC), as well as the enteric nervous system (ENS) function, remained lower in the TgFMT group. These results suggest that the neuropathological constipation phenotypes of Tg2576 mice may be tightly linked to the dysbiosis of the fecal microbiota.

Laxative Effects of Phlorotannins Derived from Ecklonia cava on Loperamide-Induced Constipation in SD Rats.

This study investigated the laxative effects of phlorotannins (Pt) derived from Ecklonia cava (E. cave) on chronic constipation by evaluating alterations in stool parameters, gastrointestinal motility, histopathological structure, mucin secretion, gastrointestinal hormones, muscarinic cholinergic regulation, and fecal microbiota in SD rats with loperamide (Lop)-induced constipation subjected to Pt treatment. Stool-related parameters (including stool number, weight, and water contents), gastrointestinal motility, and length of intestine were significantly enhanced in the Lop+Pt-treated group as compared to the Lop+Vehicle-treated group. A similar recovery was detected in the histopathological and cytological structure of the mid-colon of Lop+Pt-treated rats, although the level of mucin secretion remained constant. Moreover, rats with Lop-induced constipation subjected to Pt treatment showed significant improvements in water channel expression, gastrointestinal hormone secretions, and expression of muscarinic acetylcholine receptors M2/M3 (mAChRs M2/M3) and their mediators of muscarinic cholinergic regulation. Furthermore, the Lop+Pt-treated group showed a significant recovery of Bifidobacteriaceae, Muribaculaceae, Clostridiaceae, and Eubacteriaceae families in fecal microbiota. Taken together, these results provide the first evidence that exposure of SD rats with Lop-induced constipation to Pt improves the constipation phenotype through the regulation of membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.

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.

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.

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.

Midbrain infarction presenting with monocular elevation palsy and ptosis: topographic lesion analysis.

A combination of monocular elevation palsy and ptosis is usually characteristic of an extra-axial lesion of the superior branch of the third nerve. We report an unusual case of monocular elevation palsy and ipsilateral ptosis due to midbrain infarction involving the third nerve fascicle. In addition, we conducted a review of the literature of similar cases and produced an overlay image of the magnetic resonance scans from these reports. The overlapping regions primarily were located in the midbrain between the red nucleus and cerebral peduncle. This correlated with involvement of the lateral portion of the third nerve fascicle containing fibers to the superior rectus and levator palpebrae.

Novel Inhibitor of Keap1-Nrf2 Protein-Protein Interaction Attenuates Osteoclastogenesis In Vitro and Prevents OVX-Induced Bone Loss In Vivo.

Keap1 interacts with Nrf2 by assisting in its ubiquitination and subsequent proteolysis. By preventing ROS accumulation during RANKL-induced osteoclastogenesis, Nrf2 activation can prevent the differentiation of osteoclasts. Additionally, inhibiting the Keap1-Nrf2 PPI can be an effective strategy for triggering Nrf2 to regulate oxidative stress. Structure-based virtual screening was performed to discover a potentially novel Keap1-Nrf2 PPI inhibitor wherein KCB-F06 was identified. The inhibitory effects of KCB-F06 on osteoclastogenesis were investigated in vitro through TRAP staining and bone resorption assays. An ovariectomy-induced osteoporosis mouse model was applied to evaluate KCB-F06's therapeutic effects in vivo. Lastly, the underlying mechanisms were explored using real-time PCR, Western blotting, and co-IP assays. KCB-F06 was discovered as a novel Keap1-Nrf2 PPI inhibitor. As a result, the expression of antioxidants (HO-1 and NQO1) was suppressed, hence reducing ROS accumulation during osteoclastogenesis. Subsequently, this caused the inactivation of RANKL-induced IKB/NF-kB signaling. This eventually led to the downregulation of osteoclast-specific proteins including NFATc1, which is an essential transcription factor for osteoclastogenesis. These results demonstrated that Nrf2 activation in osteoclasts is a valuable tool for osteoclastic bone loss management. In addition, KCB-F06 presents as an alternative candidate for treating osteoclast-related bone diseases and as a novel small molecule that can serve as a model for further Keap1-NRF2 PPI inhibitor development.

Porous Carbon Interlayer Derived from Traditional Korean Paper for Li-S Batteries.

A carbonized interlayer effectively helps to improve the electrochemical performance of lithium-sulfur (Li-S) batteries. In this study, a simple and inexpensive carbon intermediate layer was fabricated using a traditional Korean paper called "hanji". This carbon interlayer has a fibrous porous structure, with a specific surface area of 91.82 m2 g-1 and a BJH adsorption average pore diameter of 26.63 nm. The prepared carbon interlayer was utilized as an intermediary layer in Li-S batteries to decrease the charge-transfer resistance and capture dissolved lithium polysulfides. The porous fiber-shaped carbon interlayer suppressed the migration of polysulfides produced during the electrochemical process. The carbon interlayer facilitates the adsorption of soluble lithium polysulfides, allowing for their re-utilization in subsequent cycles. Additionally, the carbon interlayer significantly reduces the polarization of the cell. This simple strategy results in a significant improvement in cycle performance. Consequently, the discharge capacity at 0.5 C after 150 cycles was confirmed to have improved by more than twofold, reaching 230 mAh g-1 for cells without the interlayer and 583 mAh g-1 for cells with the interlayer. This study demonstrates a simple method for improving the capacity of Li-S batteries by integrating a functional carbon interlayer.

An Analysis of the Determinants of the Health-Related Quality of Life in Asian Patients With Cluster Headaches During Cluster Periods Using the Time Trade-Off Method.

BACKGROUND AND PURPOSE: Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. METHODS: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. RESULTS: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. CONCLUSIONS: Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

Safety, high-performing and effects of the N/P ratio of a solid lithium ion battery using PEGDME based polymer electrolytes.

In this study, we report on the electrochemical properties of a solid state lithium ion battery (LIB) using a poly (ethylene glycol) dimethyl ether (PEGDME)-based solid polymer electrolyte (P-SPE). The LIB is prepared using a LiFePO4 (LFP) cathode and graphite anode material with P-SPE, and the kinetic properties of the lithium ions in the P-SPE are investigated. The synthesized P-SPE is shown to be suitable solid polymer electrolyte candidate for LIB applications. LFP and graphite are selected as electrode materials to validate their effectiveness in different battery cells with respect to their high energy density and inherent safety. The five-layer stacked 5 × 6 cm2 pouch-type LIB demonstrates a high capacity of 90 mAh (0.6 mAh/cm2) or more in the initial cycle, and it shows cycle stability with a capacity decrease of 20% over 500 cycles. We test the manufactured pouch-type full cells under extreme conditions (e. g., cutting, crushing and exposure of the battery cell to the atmosphere). LIBs using the developed P-SPE are promising solid polymer electrolyte candidates for wearable LIB as well as high energy LIB applications.

Embedded Oxidized Ag-Pd-Cu Ultrathin Metal Alloy Film Prepared at Low Temperature with Excellent Electronic, Optical, and Mechanical Properties.

Most transparent conducting materials are based on Sn:In2O3 (ITO). When applied onto flexible substrates, ITO can be prepared in an oxide-metal-oxide (OMO) configuration, typically ITO/Ag/ITO, where the ductility of the embedded metal layer is intended to reduce the mechanical brittleness and improve the electrical conductivity of the OMO multilayer. Hitherto, the lower limit of the thickness of the Ag layer has been limited by the percolation threshold, which limits the Ag layer to be thicker than ∼10 nm to avoid agglomeration and to ensure conductivity and structural stability. Metal layers of thicknesses below 10 nm are, however, desirable for obtaining OMO coatings with better optical properties. It is known that agglomeration of the metal layer can, to some extent, be suppressed when substituting Ag by an Ag-Pd-Cu (APC) alloy. APC-based OMO films exhibit excellent optical and electrical properties, but still continuous APC films well below 10 nm thickness cannot be achieved. In this work we demonstrate that controlled oxidation of APC results in smooth, ultrathin APC:O continuous coatings (of thickness ∼5 nm) on ITO-coated PET substrates. Moderate oxidation yields superficial PdOx formation, which suppresses Ag agglomeration, while still maintaining excellent conductivity. On the other hand, extensive oxidation of APC leads to extensive Pd oxide nucleation deteriorating the conductivity of the film. The ITO/APC:O/ITO films exhibit low resistivity, attributed to a high Hall mobility associated with suppressed agglomeration, good stability in high humidity/temperature environments, superior transmittance in the visible and infrared region, and excellent mechanical bending properties, thus providing new opportunities for fabricating superior transparent conducting coatings on polymer substrates.

Synthesis and Electrochemical Performance of Microporous Hollow Carbon from Milkweed Pappus as Cathode Material of Lithium-Sulfur Batteries.

Microtube-like porous carbon (MPC) and tube-like porous carbon-sulfur (MPC-S) composites were synthesized by carbonizing milkweed pappus with sulfur, and they were used as cathodes for lithium-sulfur batteries. The morphology and uniformity of these materials were characterized using X-ray powder diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy with an energy-dispersive X-ray analyzer, thermogravimetric analysis, and X-ray photoelectron spectrometry. The electrochemical performance of the MPC-S cathodes was measured using the charge/discharge cycling performance, C rate, and AC impedance. The composite cathodes with 93.8 wt.% sulfur exhibited a stable specific capacity of 743 mAh g-1 after 200 cycles at a 0.5 C.

Diagnostic Delay and Its Predictors in Cluster Headache.

OBJECTIVE: Cluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH. METHODS: Data from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, <1 year; 2nd tertile, 1-6 years; and 3rd tertile, ≥7 years). RESULTS: Overall, 445 patients were evaluated. The mean duration of diagnosis delay was 5.7 ± 6.7 years, (range, 0-36 years). Regarding the age of onset, majority of young patients (age <20 years) belonged to the third tertile (60%), whereas minority of old patients (>40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42-14.48], chronic CH (aOR = 8.87, 95% CI = 2.66-29.51), and probable CH (aOR = 4.12, 95% CI = 1.48-11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95-0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93-0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay (p = 0.041). CONCLUSIONS: Patients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH.

Clinical features of cluster headache without cranial autonomic symptoms: results from a prospective multicentre study.

Although cranial autonomic symptoms (CAS) are typical in cluster headache (CH), some individuals with CH show no CAS during their headache attacks. Probable cluster headache (PCH) is a subtype of CH that fulfils all but one criterion of CH. This study aimed to investigate the frequency and clinical features of CH and PCH without CAS in comparison to those with CAS. We analysed data from the Korea Cluster Headache Registry, a prospective multicentre registry involving data from 16 hospitals. Of the 216 participants with CH and 26 with PCH, 19 (8.8%) and 7 (26.9%), respectively, did not have CAS. Participants with CH without CAS exhibited less severe anxiety (General Anxiety Disorder-7 score, median [interquartile range], 2.0 [1.0-6.0] vs 8.0 [3.0-12.0], p = 0.001) and depression (Patient Health Questionnaire-9 score, 3.0 [1.0-7.0] vs 7.0 [3.0-11.0], p = 0.042) than those with CAS. Among participants with PCH, headache intensity was less severe in participants without CAS than in those with CAS (numeric rating scale, 8.0 [7.0-8.0] vs 9.5 [8.0-10.0], p = 0.015). In conclusion, a significant proportion of participants with CH and PCH did not have CAS. Some clinical features of CH and PCH differed based on the presence of CAS.

A case of recurrent neuro-Behçet's disease after tooth extraction.

We report a 39-yr-old man with neuro-Behçet's disease (NBD) in remission who developed left-sided ataxia with a sensory deficit about 10 days after tooth extraction. Several years ago, he experienced a similar episode of relapse after tooth extraction. Brain magnetic resonance imaging showed a newly developed right thalamic lesion. In cerebrospinal fluid, lymphocyte-dominant pleocytosis and mild elevation of IgG were found. Immunologic factors may be important in the pathogenesis of NBD because of the time delay between tooth extraction and relapse. Careful observation and prevention are needed before dental procedures in patients with NBD.

Clinical factors influencing the impact of cluster headache from a prospective multicenter study.

Although many patients with cluster headaches (CH) are disabled by their condition, few studies have examined this in detail. This cross-sectional, multicenter observational study prospectively collected demographic and clinical questionnaire data from 224 consecutive patients with CH. We assessed headache impact using the six-item Headache Impact Test (HIT-6) and evaluated the factors associated with the impact of CH. Participants with a HIT-6 score ≥ 60 were classified into a severe impact group. The majority (190, 84.8%) of the participants were classified into the severe impact group. These patients were characterized by younger age, earlier onset of CH, longer duration of each headache attack, higher pain intensity, more cranial autonomic symptoms, a higher proportion of depression or anxiety, higher score of stress, and lower score of quality of life. The anxiety (OR = 1.19, 95% CI: 1.08-1.31, p = 0.006), greater pain intensity (OR = 1.06, 95% CI: 1.02-1.10, p = 0.002), and age (OR = 0.99, 95% CI: 0.99-1.00, p = 0.008) were significant predictors for a severe impact of CH patients. According to the HIT-6 results, most of the CH patients were significantly affected by CH. As well as pain intensity, anxiety and age modulated CH's impact on their lives.