Pub Date : 2024-08-12DOI: 10.1186/s10194-024-01832-0
Zhi-feng Chen, Xiang-meng Kong, Cheng-hao Yang, Xin-yu Li, Hong Guo, Zhao-wei Wang
Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15–39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. Between 1990 and 2021, the worldwide prevalence of migraine among 15–39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35–39 age group. Notably, female rates consistently exceeded male rates across all age categories. The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.
{"title":"Global, regional, and national burden and trends of migraine among youths and young adults aged 15–39 years from 1990 to 2021: findings from the global burden of disease study 2021","authors":"Zhi-feng Chen, Xiang-meng Kong, Cheng-hao Yang, Xin-yu Li, Hong Guo, Zhao-wei Wang","doi":"10.1186/s10194-024-01832-0","DOIUrl":"https://doi.org/10.1186/s10194-024-01832-0","url":null,"abstract":"Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15–39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. Between 1990 and 2021, the worldwide prevalence of migraine among 15–39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35–39 age group. Notably, female rates consistently exceeded male rates across all age categories. The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141935497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1186/s10194-024-01835-x
Gabriel Bsteh, Stefan Macher, Nik Krajnc, Wolfgang Marik, Martin Michl, Nina Müller, Sina Zaic, Jürgen Harreiter, Klaus Novak, Christian Wöber, Berthold Pemp
Management of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop concept. Here, we aimed to evaluate effects of this one-stop concept on subjective patient satisfaction and economic outcome in patients with IIH. In a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding subjective patient satisfaction (assessed by the Vienna Patient Inventory). Multivariable binary linear regression models were used to adjust for confounders. Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, management within IC concept was associated with statistically significantly higher subjective patient satisfaction (beta = 0.93; p < 0.001) with the strongest effects observed in satisfaction with treatment accessibility and availability (beta = 2.05; p < 0.001). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of IC in these groups. Interdisciplinary integrated management of IIH statistically significantly and clinically meaningfully improves patient satisfaction – particularly in socioeconomically underprivileged patient groups. Providing structured central coordination to facilitate and improve access to interdisciplinary management provides means to further improve outcome.
{"title":"An interdisciplinary integrated specialized one-stop outpatient clinic for idiopathic intracranial hypertension – a comprehensive assessment of patient satisfaction","authors":"Gabriel Bsteh, Stefan Macher, Nik Krajnc, Wolfgang Marik, Martin Michl, Nina Müller, Sina Zaic, Jürgen Harreiter, Klaus Novak, Christian Wöber, Berthold Pemp","doi":"10.1186/s10194-024-01835-x","DOIUrl":"https://doi.org/10.1186/s10194-024-01835-x","url":null,"abstract":"Management of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop concept. Here, we aimed to evaluate effects of this one-stop concept on subjective patient satisfaction and economic outcome in patients with IIH. In a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding subjective patient satisfaction (assessed by the Vienna Patient Inventory). Multivariable binary linear regression models were used to adjust for confounders. Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, management within IC concept was associated with statistically significantly higher subjective patient satisfaction (beta = 0.93; p < 0.001) with the strongest effects observed in satisfaction with treatment accessibility and availability (beta = 2.05; p < 0.001). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of IC in these groups. Interdisciplinary integrated management of IIH statistically significantly and clinically meaningfully improves patient satisfaction – particularly in socioeconomically underprivileged patient groups. Providing structured central coordination to facilitate and improve access to interdisciplinary management provides means to further improve outcome.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1186/s10194-024-01825-z
Yungang Cao, Mei Huang, Fangwang Fu, Keyang Chen, Kun Liu, Jinming Cheng, Yan Li, Xiaozheng Liu
The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been used to evaluate glymphatic system function in patients with migraine. However, since the diffusion tensor model cannot accurately describe the diffusion coefficient of the nerve fibre crossing region, we proposed a diffusion kurtosis imaging ALPS (DKI-ALPS) method to evaluate glymphatic system function in patients with migraine. The study included 29 healthy controls and 37 patients with migraine. We used diffusion imaging data from a 3T MRI scanner to calculate DTI-ALPS and DKI-ALPS indices of the two groups. We compared the DTI-ALPS and DKI-ALPS indices between the two groups using a two-sample t-test and performed correlation analyses with clinical variables. There was no significant difference in DTI-ALPS index between the two groups. Patients with migraine showed a significantly increased right DKI-ALPS index compared to healthy controls (1.6858 vs. 1.5729; p = 0.0301). There was no significant correlation between ALPS indices and clinical variables. DKI-ALPS is a potential method to assess glymphatic system function and patients with migraine do not have impaired glymphatic system function.
沿血管周围空间的弥散张量成像分析（DTI-ALPS）方法已被用于评估偏头痛患者的淋巴系统功能。然而，由于弥散张量模型无法准确描述神经纤维交叉区域的弥散系数，我们提出了一种弥散峰度成像 ALPS（DKI-ALPS）方法来评估偏头痛患者的淋巴系统功能。研究对象包括 29 名健康对照组和 37 名偏头痛患者。我们使用 3T 磁共振成像扫描仪的弥散成像数据计算两组患者的 DTI-ALPS 和 DKI-ALPS 指数。我们使用双样本 t 检验比较了两组患者的 DTI-ALPS 和 DKI-ALPS 指数，并进行了与临床变量的相关性分析。两组患者的 DTI-ALPS 指数无明显差异。与健康对照组相比，偏头痛患者的右侧DKI-ALPS指数明显增加（1.6858 vs. 1.5729; p = 0.0301）。ALPS指数与临床变量之间没有明显的相关性。DKI-ALPS是一种评估甘液系统功能的潜在方法，偏头痛患者的甘液系统功能并没有受损。
{"title":"Abnormally glymphatic system functional in patients with migraine: a diffusion kurtosis imaging study","authors":"Yungang Cao, Mei Huang, Fangwang Fu, Keyang Chen, Kun Liu, Jinming Cheng, Yan Li, Xiaozheng Liu","doi":"10.1186/s10194-024-01825-z","DOIUrl":"https://doi.org/10.1186/s10194-024-01825-z","url":null,"abstract":"The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been used to evaluate glymphatic system function in patients with migraine. However, since the diffusion tensor model cannot accurately describe the diffusion coefficient of the nerve fibre crossing region, we proposed a diffusion kurtosis imaging ALPS (DKI-ALPS) method to evaluate glymphatic system function in patients with migraine. The study included 29 healthy controls and 37 patients with migraine. We used diffusion imaging data from a 3T MRI scanner to calculate DTI-ALPS and DKI-ALPS indices of the two groups. We compared the DTI-ALPS and DKI-ALPS indices between the two groups using a two-sample t-test and performed correlation analyses with clinical variables. There was no significant difference in DTI-ALPS index between the two groups. Patients with migraine showed a significantly increased right DKI-ALPS index compared to healthy controls (1.6858 vs. 1.5729; p = 0.0301). There was no significant correlation between ALPS indices and clinical variables. DKI-ALPS is a potential method to assess glymphatic system function and patients with migraine do not have impaired glymphatic system function.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1186/s10194-024-01828-w
Xinyue Sun, Bohong Chen, Yi Qi, Meng Wei, Wanying Chen, Xiaoyu Wu, Qingfan Wang, Jiahao Li, Xiangyu Lei, Guogang Luo
Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93–0.96); p = 2.70e − 10; Replication cohort: OR(95%CI) = 0.93(0.91–0.94); p = 4.21e − 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87–0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85–0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83–0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.
{"title":"Multi-omics Mendelian randomization integrating GWAS, eQTL and pQTL data revealed GSTM4 as a potential drug target for migraine","authors":"Xinyue Sun, Bohong Chen, Yi Qi, Meng Wei, Wanying Chen, Xiaoyu Wu, Qingfan Wang, Jiahao Li, Xiangyu Lei, Guogang Luo","doi":"10.1186/s10194-024-01828-w","DOIUrl":"https://doi.org/10.1186/s10194-024-01828-w","url":null,"abstract":"Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93–0.96); p = 2.70e − 10; Replication cohort: OR(95%CI) = 0.93(0.91–0.94); p = 4.21e − 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87–0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85–0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83–0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1186/s10194-024-01801-7
Lei Zhao, Yilan Tang, Yiheng Tu, Jin Cao
Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer’s disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.
偏头痛是一种神经系统疾病，有很大的遗传因素，其特点是头痛反复发作且持续时间长。以往的流行病学研究报告显示，偏头痛患者患痴呆症的风险较高。神经影像学研究也显示，在偏头痛和痴呆症的共同发病区域存在结构性脑萎缩。然而，这些研究都是观察性的，无法确定因果关系。本研究旨在利用孟德尔随机法（MR）探讨偏头痛与痴呆症之间的遗传因果关系，以及脑结构变化在这一关联中的中介作用。我们收集了偏头痛及其两个亚型，以及四种常见痴呆类型（包括阿尔茨海默病（AD）、血管性痴呆、额颞叶痴呆和路易体痴呆）的全基因组关联研究（GWAS）摘要统计。此外，我们还收集了七种纵向脑部测量指标的 GWAS 统计摘要，这些指标描述了脑部结构随年龄变化的特征。利用这些 GWAS，我们进行了双样本 MR 分析，以研究偏头痛及其两个亚型对痴呆症和脑结构变化的因果效应。为了探索偏头痛与痴呆之间可能存在的脑结构变化中介作用，我们进行了两步磁共振中介分析。磁共振分析表明，遗传预测偏头痛与AD风险增加之间存在显著关联（OR = 1.097，95% CI = [1.040，1.158]，p = 7.03 × 10-4）。此外，偏头痛明显加速了大脑皮层总面积（每年-65.588平方厘米，95% CI = [-103.112，-28.064]，p = 6.13 × 10-4）和丘脑体积（每年-9.507立方厘米，95% CI = [-15.512，-3.502]，p = 1.91 × 10-3）的逐年萎缩。无先兆偏头痛（MO）亚型增加了罹患注意力缺失症的风险（OR = 1.091，95% CI = [1.059，1.123]，p = 6.95 × 10-9），并加速了皮层总表面积的年度萎缩（每年-31.401 cm2，95% CI = [-43.990，-18.811]，p = 1.02 × 10-6）。两步磁共振中介分析显示，丘脑萎缩部分中介了偏头痛对AD的因果效应，占总效应的28.2%。这项全面的磁共振研究为偏头痛对注意力缺失症的因果效应提供了遗传学证据，并确定纵向丘脑萎缩是这一关联的潜在中介。这些发现可为偏头痛患者预防注意力缺失症风险的脑干预目标提供依据。
{"title":"Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy","authors":"Lei Zhao, Yilan Tang, Yiheng Tu, Jin Cao","doi":"10.1186/s10194-024-01801-7","DOIUrl":"https://doi.org/10.1186/s10194-024-01801-7","url":null,"abstract":"Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer’s disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1186/s10194-024-01802-6
Jianxiong Gui, Xiaoyue Yang, Chen Tan, Lingman Wang, Linxue Meng, Ziyao Han, Jie Liu, Li Jiang
Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.
{"title":"A cross-tissue transcriptome-wide association study reveals novel susceptibility genes for migraine","authors":"Jianxiong Gui, Xiaoyue Yang, Chen Tan, Lingman Wang, Linxue Meng, Ziyao Han, Jie Liu, Li Jiang","doi":"10.1186/s10194-024-01802-6","DOIUrl":"https://doi.org/10.1186/s10194-024-01802-6","url":null,"abstract":"Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29DOI: 10.1186/s10194-024-01769-4
Gabriel Gárate, Julio Pascual, Marta Pascual-Mato, Jorge Madera, María Muñoz-San Martín, Vicente González-Quintanilla
Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker. Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age. Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2–54.4) and 4.6 (2.4–6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women. We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations.
{"title":"Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience","authors":"Gabriel Gárate, Julio Pascual, Marta Pascual-Mato, Jorge Madera, María Muñoz-San Martín, Vicente González-Quintanilla","doi":"10.1186/s10194-024-01769-4","DOIUrl":"https://doi.org/10.1186/s10194-024-01769-4","url":null,"abstract":"Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker. Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age. Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2–54.4) and 4.6 (2.4–6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women. We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations. ","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29DOI: 10.1186/s10194-024-01776-5
Qing-Feng Tao, Yan-Bing Huang, Lu Yuan, Yun-Zhou Shi, Di Qin, Kun Ye, Wen-Yan Peng, Chao-Rong Xie, Hui Zheng
Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence. Acupuncture showed better improvement than sham acupuncture in reducing headache frequency of tension-type headache (TTH), but the lack of comparisons between acupuncture and first-line drugs impedes recommendation of acupuncture for TTH. Our indirect treatment comparison meta-analysis found similar effect between acupuncture and tricyclic antidepressants (TCAs) in reducing TTH frequency with very low certainty of evidence. Similar effect between acupuncture and TCAs were also observed in reducing headache intensity with very low certainty of evidence. Acupuncture had a lower rate of adverse events than amitriptyline with very low certainty of evidence.
在减少紧张型头痛（TTH）发作频率方面，针灸比假针灸有更好的改善效果，但针灸相对于TTH一线药物的疗效尚不清楚，这妨碍了对TTH药物不耐受的患者推荐使用针灸治疗。我们旨在通过间接治疗比较（ITC）荟萃分析来估计针灸与三环类抗抑郁药（TCAs）之间的相对疗效。我们检索了 Ovid Medline、Embase 和 Cochrane 图书馆从数据库开始到 2023 年 4 月 13 日的数据。纳入了TCAs或针灸预防成人TTH的随机对照试验。主要结果是头痛频率。次要结果为头痛强度、应答率和不良事件发生率。采用贝叶斯随机效应模型进行ITC荟萃分析，并采用GRADE方法评估证据的可信度。共纳入了 34 项试验，涉及 4426 名参与者。在降低TTH频率方面，针灸与TCAs具有相似的效果（阿米替林：平均差[MD]-1.29，95% CI -5.28至3.02；阿米替林酰胺：MD -0.05，95% CI -3.02）：MD -0.05，95% CI -6.86至7.06）和降低TTH强度（阿米替林：MD 2.35，95% CI -6.86至7.06）：MD 2.35，95% CI -1.20 至 5.78；氯米帕明：MD 1.83，95% CI -4.23至8.20）。阿米替林的不良反应发生率高于针灸（OR 4.73，95% CI 1.42 至 14.23）。针灸在降低TTH头痛频率方面的效果与TCAs相似，针灸的不良反应率低于阿米替林，证据的确定性很低。在降低紧张型头痛（TTH）的头痛频率方面，针灸比假针灸有更好的改善效果，但针灸与一线药物之间缺乏比较，这阻碍了针灸治疗TTH的推荐。我们的间接治疗比较荟萃分析发现，针灸与三环类抗抑郁药（TCAs）在降低TTH频率方面的效果相似，但证据的确定性很低。在降低头痛强度方面，针灸与三环类抗抑郁药的疗效相似，但证据的确定性很低。与阿米替林相比，针灸的不良反应发生率更低，但证据确定性很低。
{"title":"Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis","authors":"Qing-Feng Tao, Yan-Bing Huang, Lu Yuan, Yun-Zhou Shi, Di Qin, Kun Ye, Wen-Yan Peng, Chao-Rong Xie, Hui Zheng","doi":"10.1186/s10194-024-01776-5","DOIUrl":"https://doi.org/10.1186/s10194-024-01776-5","url":null,"abstract":"Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence. Acupuncture showed better improvement than sham acupuncture in reducing headache frequency of tension-type headache (TTH), but the lack of comparisons between acupuncture and first-line drugs impedes recommendation of acupuncture for TTH. Our indirect treatment comparison meta-analysis found similar effect between acupuncture and tricyclic antidepressants (TCAs) in reducing TTH frequency with very low certainty of evidence. Similar effect between acupuncture and TCAs were also observed in reducing headache intensity with very low certainty of evidence. Acupuncture had a lower rate of adverse events than amitriptyline with very low certainty of evidence.","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26DOI: 10.1186/s10194-024-01770-x
Phuong Thao Tran, Maryse Lapeyre-Mestre, Baricault Berangere, Michel Lanteri-Minet, A. Palmaro, Anne Donnet, Joëlle Micallef
{"title":"Triptan use in elderly over 65 years and the risk of hospitalization for serious vascular events","authors":"Phuong Thao Tran, Maryse Lapeyre-Mestre, Baricault Berangere, Michel Lanteri-Minet, A. Palmaro, Anne Donnet, Joëlle Micallef","doi":"10.1186/s10194-024-01770-x","DOIUrl":"https://doi.org/10.1186/s10194-024-01770-x","url":null,"abstract":"","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1186/s10194-024-01764-9
C. Argoff, Steven Herzog, Ryan Smith, Sameer V. Kotak, Liza Sopina, Yvonna Saltarska, Seema Soni-Brahmbhatt, Fawad A. Khan
{"title":"Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study","authors":"C. Argoff, Steven Herzog, Ryan Smith, Sameer V. Kotak, Liza Sopina, Yvonna Saltarska, Seema Soni-Brahmbhatt, Fawad A. Khan","doi":"10.1186/s10194-024-01764-9","DOIUrl":"https://doi.org/10.1186/s10194-024-01764-9","url":null,"abstract":"","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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