Epidemiology, burden and clinical spectrum of cluster headache: a global update.

BACKGROUND: This narrative review aims to broaden our understanding of the epidemiology, burden and clinical spectrum of cluster headache based on updated findings with a global perspective. METHODS: We conducted a literature search on the following topics: (a) epidemiology; (b) burden: quality of life, disability, economic burden, job-related burden and suicidality; and (c) clinical spectrum: male predominance and its changes, age, pre-cluster and pre-attack symptoms, aura, post-drome, attack characteristics (location, severity, duration and associated symptoms), bout characteristics (attack frequency, bout duration and bout frequency), circadian and seasonal rhythmicity and disease course. RESULTS: New large-scale population-based reports have suggested a lower prevalence than previous estimations. The impact of cluster headache creates a significant burden in terms of the quality of life, disability, economic and job-related burdens and suicidality. Several studies have reported decreasing male-to-female ratios and a wide age range at disease onset. The non-headache phases of cluster headache, including pre-cluster, pre-attack and postictal symptoms, have recently been revisited. The latest data regarding attack characteristics, bout characteristics, and circadian and seasonal rhythmicity from different countries have shown variability among bouts, attacks, individuals and ethnicities. Studies on the disease course of cluster headache have shown typical characteristics of attacks or bouts that decrease with time. CONCLUSIONS: Cluster headache may be more than a "trigeminal autonomic headache" because it involves complex central nervous system phenomena. The spectrum of attacks and bouts is wider than previously recognised. Cluster headache is a dynamic disorder that evolves or regresses over time.

Effect of Smoking on the Development of Migraine in Women: Nationwide Cohort Study in South Korea.

Background: Smoking is known to be a significant risk factor for various diseases. Migraine, a condition requiring careful lifestyle management, currently lacks specific guidelines advocating for smoking cessation as a preventive measure. Although cross-sectional studies have suggested a potential link between smoking and an increased risk of migraine, the findings have been inconsistent and conflicting. To date, there has been no longitudinal study which investigated the effect of smoking on the risk of migraine in a prospective setting. Objective: This longitudinal study aimed to investigate the impact of smoking on the incidence of migraine in women and examine the modifying effect of menopausal status. Methods: Using nationally representative National Health Insurance Service (NHIS) data, women aged ≥40 years who participated in national breast cancer screening in 2009 were followed-up until the end of 2019. Baseline data on smoking status (non-, ex-, and current smoker) as well as the duration and amount of cigarette smoking were collected. A Cox proportional hazards regression model was used to examine the independent effect of smoking on the risk of incident migraine after adjusting for demographics, comorbidities, and female reproductive factors. The results were stratified by menopausal status, and an interaction analysis (smoking × menopause) was performed. Results: In total, 1,827,129 women were included in the analysis. Women with a history of smoking exhibited a higher risk of developing migraine, compared with nonsmokers. Specifically, a higher risk of migraine was observed in women with past (adjusted hazard ratio [HR] 1.044, 95% CI 1.000-1.089) and current cigarette use (adjusted HR 1.050, 95% CI, 1.023-1.079) than in nonsmokers. The effect was greater in premenopausal women (adjusted HR 1.140, 95% CI, 1.108-1.172) than in postmenopausal women (adjusted HR 1.045, 95% CI 1.018-1.073; P<.001). The risk increased with an increased amount of smoking, with a greater association in premenopausal women (P<.001). Conclusions: Smoking increases the risk of migraine in women, with a dose-dependent relationship. Menopause modifies this effect. Our findings suggest that smoking is an important modifiable risk factor of migraine, with a higher impact in premenopausal women. The interaction between smoking and estrogen may increase the vulnerability of the migraine brain.

Eosinophilic meningoencephalitis successfully treated with glucocorticoids and intravenous immunoglobulin: a case report.

Eosinophilic meningoencephalitis is a rare inflammatory condition of the central nervous system. As a limited number of cases has been reported, debate remains on the optimal treatment. We present a case of idiopathic eosinophilic meningoencephalitis successfully treated with glucocorticoids and intravenous immunoglobulin (IVIG). After extensive evaluation to rule out other possible causes, the patient was treated with intravenous (IV) dexamethasone and showed significant improvement within a few days. However, neurologic impairment persisted, and follow-up lumbar puncture results showed only a mild decrease in pleocytosis. Even after an additional 5 days of IV methylprednisolone, cerebrospinal fluid (CSF) pleocytosis persisted, and brain magnetic resonance imaging (MRI) showed an increase in enhanced lesions, implying persistent neuroinflammation. The patient was maintained on high-dose oral prednisolone for 2 months, and additional immune-modulatory effects were treated with IVIG. Follow-up MRI at 2 months showed a significant decrease in the extent of multiple enhanced lesions and a normalized CSF profile. The patient was maintained on regular maintenance doses of IVIG for an additional 6 months without any neurologic signs or symptoms. Inflammation is the key pathophysiology underlying neurological damage in eosinophilic meningoencephalitis. A literature review revealed that corticosteroid treatment is the only anti-inflammatory treatment used in cases of idiopathic meningoencephalitis, resulting in sufficient response in most patients but only partial response or death in a few cases. This is the first case report of IVIG use in idiopathic eosinophilic meningoencephalitis, suggesting the possibility of a new treatment modality for refractory cases.

Predictors of galcanezumab response in a real-world study of Korean patients with migraine.

To assess factors associated with galcanezumab response in a real-world study of Korean patients with migraine. Predictors of the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP(-R) mAb) have been rarely investigated in Asians. We prospectively recruited and followed up patients with migraine who received monthly galcanezumab treatment in a single university hospital from June 2020 to October 2021. We defined the treatment response with ≥ 50% reduction in moderate/severe headache days in the 3rd month of treatment compared to baseline. Responders and non-responders were compared in terms of demographics, disease characteristics and severity, and previous response to migraine prophylactic treatments. Potential predictors of anti-CGRP(-R) mAb response were tested by using the univariable and multivariable logistic regression analyses. Among 104 patients (81.7% female; mean age 42.0 ± 13.02; 76.9% chronic migraine; and 45.5% medication overuse headache) included, 58 (55.7%) were responders. Non-responders had more chronic migraine, medication overuse headache, monthly headache days, days with acute medication, and daily headaches (i.e. chronic migraine persisting everyday without remission). The multivariable logistic analysis showed chronic migraine (OR 0.05 [95% CI 0.00-0.82], p = 0.036) and the number of previously failed preventive medication classes (OR 0.55 [95% CI 0.33-0.92], p = 0.024] were independently associated with treatment response. Chronic migraine and multiple failures from preventive medication are associated with poor galcanezumab response. Further studies are needed to investigate if earlier treatment before disease chronification or multiple failures may lead to a greater therapeutic gain from anti-CGRP(-R) mAb treatment.

Electrocardiographic anxiety profiles improve speech anxiety.

The present study was to set out in efforts to determine the effect of electrocardiographic (ECG) feedback on the performance in speech anxiety. Forty-six high school students participated in a speech performance educational program. They were randomly divided into two groups, an experimental group with ECG feedback (N = 21) and a control group (N = 25). Feedback was given with video recording in the control, whereas in the experimental group, an additional ECG feedback was provided. Speech performance was evaluated by the Korean Broadcasting System (KBS) speech ability test, which determines the 10 different speaking categories. ECG was recorded during rest and speech, together with a video recording of the speech performance. Changes in R-R intervals were used to reflect anxiety profiles. Three trials were performed for 3-week program. Results showed that the subjects with ECG feedback revealed a significant improvement in speech performance and anxiety states, which compared to those in the control group. These findings suggest that visualization of the anxiety profile feedback with ECG can be a better cognitive therapeutic strategy in speech anxiety.

Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-alpha.

Paeonol, a major phenolic component of Moutan Cortex, was known to have antiaggregatory, antioxidant and antiinflammatory activities. In the present study, we tried to elucidate the effects of paeonol on anaphylactic reaction and its mode of action. Paeonol significantly inhibited histamine release from the rat peritoneal mast cells (RPMCs) treated with compound 48/80, a mast cell degranulator. The release of tumor necrosis factor (TNF)-alpha mast cell activating cytokine was significantly suppressed in RBL-2H3 mast cells pretreated with anti-dinitrophenyl (DNP) immunoglobulin E (IgE) in a dose-dependent manner. Paeonol significantly inhibited IgE production in B cells activated by anti-CD40 mAb, recombinant interleukin-4 (rIL-4) and recombinant histamine releasing factor (rHRF). Paeonol effectively downregulated the expression of IL-4 in the activated B cells by reverse transcription-polymerase chain reaction (RT-PCR). We also confirmed that paeonol effectively inhibited anaphylactic shock in mice by 90% at a dose of 0.5 mg/mouse versus PBS treated control 2 h after the i.p. injection of compound 48/80. These results suggest that paeonol has antianaphylatic activity by regulating histamine and TNF-alpha.

AFM nanolithography on a mixed LB film of hexadecylamine and palmitic acid.

An evenly mixed Langmuir film of hexadecylamine (HDA) and palmitic acid (PA) was prepared on the air-water interface and transferred to a Si substrate for the fabrication of nano-sized patterns. Vibrational spectrum of the transferred film shows that all acid groups of PAs were deprotonated and amine groups of HDAs were protonated by an acid-base reaction. The effect of mixing ratios in atomic force microscopy anodization lithography on the mixed films was investigated in terms of the line width of the protruded pattern. While the line width fabricated on PA film was 221 nm, the width on the mixed film was reduced to 84 nm under the same lithographic conditions. It is believed that the phenomenon was originated from the mixed structure from the interaction of HDA and PA. The chemical composition difference caused by the presence of ammonium cation in resist resulted in reducing the line width fabricated in the mixed Langmuir-Blodgett film.

Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in fibrosarcoma cells.

BACKGROUND: We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. METHODOLOGY/PRINCIPAL FINDINGS: We showed that PO (IC(50) = 17.3 microg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC(50) over 200 microg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 microg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 microg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells.

Paeonol exerts anti-angiogenic and anti-metastatic activities through downmodulation of Akt activation and inactivation of matrix metalloproteinases.

Paeonol (2'-hydroxy-4'-methoxyacetophenone) is known to possess anti-inflammatory and anti-proliferative activities. Recently there is evidence that anti-inflammatory agents may be useful in the setting of angiogenesis-related diseases. Thus in the present study the anti-angiogenic activity of paeonol and its mechanism were investigated in vitro and in vivo. Paeonol significantly inhibited proliferation of basic fibroblast growth factor (bFGF)-stimulated human umbilical vein endothelial cells (HUVECs). Paeonol also significantly inhibited migration and tube formation of bFGF-stimulated HUVECs in vitro. In addition, paeonol significantly suppressed neovessel formation on bFGF-treated chick chorioallantoic membrane (CAM) and disrupted bFGF-induced neovascularization in Matrigel plug assay in vivo. Furthermore, paeonol downregluated Akt phosphorylation in bFGF-stimulated HUVECs and reduced expression of matrix metalloproteinases-2 and -9 in HT1080 human fibrosarcoma cells. The Akt inhibitor LY294002 synergistically potentiated paeonol-induced inactivation of Akt and vascular endothelial growth factor in bFGF-treated HUVECs. Taken together, these findings suggest that paeonol can be a potent suppressor of angiogenesis and metastasis partially through inhibition of Akt signaling pathway and matrix metalloproteinase activity.

Effects of the ethyl acetate fraction of Spatholobi caulis on tumour cell aggregation and migration.

The ethyl acetate (EA) fraction obtained from a methanol extract of Spatholobi caulis (Leguminosae) has been investigated for anti-metastatic activities in vitro. The EA fraction of Spatholobi caulis inhibited platelet aggregation induced by B16BL6 melanoma cells with an IC(50) of 50 microgram/mL. The EA fraction significantly inhibited HT1080 cancer cell invasion through a matrigel-coated filter with an IC(50) of 25 microgram/mL. Messenger RNA expression of uPA was effectively decreased in HT1080 cells by the EA fraction of Spatholobi caulis with an IC(50) of 30 microgram/mL, but the expressions of MMP-2 (matrix metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) were not changed. These findings indicated that the EA fraction suppressed tumour cell invasion by downregulation of uPA (urokinase-type plasminogen activator). Taken together, these results suggest that the EA fraction of Spatholobi caulis may have anti-metastatic activities by blocking tumour cell-induced platelet aggregation (TCIPA) and tumour cell invasion.