Pub Date : 2024-09-18DOI: 10.1001/jamaneurol.2024.2920
Amber Salter, Samantha Lancia, Kaarina Kowalec, Kathryn C. Fitzgerald, Ruth Ann Marrie
ImportanceMultiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists.ObjectiveTo evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS.Design, Setting, and ParticipantsA 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024.ExposureComorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders.Main Outcomes and MeasuresThe main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging.ResultsA total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14).Conclusions and RelevanceIn this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.
{"title":"Comorbidity and Disease Activity in Multiple Sclerosis","authors":"Amber Salter, Samantha Lancia, Kaarina Kowalec, Kathryn C. Fitzgerald, Ruth Ann Marrie","doi":"10.1001/jamaneurol.2024.2920","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.2920","url":null,"abstract":"ImportanceMultiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists.ObjectiveTo evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS.Design, Setting, and ParticipantsA 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024.ExposureComorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders.Main Outcomes and MeasuresThe main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging.ResultsA total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14).Conclusions and RelevanceIn this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":29.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1001/jamaneurol.2024.2831
Rachel F Buckley, Mabel Seto
{"title":"How Is the X Chromosome Involved in Alzheimer Disease?","authors":"Rachel F Buckley, Mabel Seto","doi":"10.1001/jamaneurol.2024.2831","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.2831","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1001/jamaneurol.2024.2876
Jonas Graf, Manas K Akmatov, Sven G Meuth, Helen Tremlett, Jakob Holstiege
{"title":"Updated Multiple Sclerosis Incidence, 2015-2022.","authors":"Jonas Graf, Manas K Akmatov, Sven G Meuth, Helen Tremlett, Jakob Holstiege","doi":"10.1001/jamaneurol.2024.2876","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.2876","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1001/jamaneurol.2024.2843
Michael E Belloy, Yann Le Guen, Ilaria Stewart, Kennedy Williams, Joachim Herz, Richard Sherva, Rui Zhang, Victoria Merritt, Matthew S Panizzon, Richard L Hauger, J Michael Gaziano, Mark Logue, Valerio Napolioni, Michael D Greicius
Importance: The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.
Objectives: To perform the first large-scale X chromosome-wide association study (XWAS) of AD.
Design, setting, and participants: This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program. Risk of AD was evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024. Genetic data available from high-density single-nucleotide variant microarrays and whole-genome sequencing and summary statistics for multitissue expression and protein quantitative trait loci available from published studies were included, enabling follow-up genetic colocalization analyses. A total of 1 629 863 eligible participants were selected from referred and volunteer samples, 477 596 of whom were excluded for analysis exclusion criteria. The number of participants who declined to participate in original studies was not available.
Main outcome and measures: Risk of AD, reported as odds ratios (ORs) with 95% CIs. Associations were considered at X chromosome-wide (P < 1 × 10-5) and genome-wide (P < 5 × 10-8) significance. Primary analyses are nonstratified, while secondary analyses evaluate sex-stratified effects.
Results: Analyses included 1 152 284 participants of non-Hispanic White, European ancestry (664 403 [57.7%] female and 487 881 [42.3%] male), including 138 558 individuals with AD. Six independent genetic loci passed X chromosome-wide significance, with 4 showing support for links between the genetic signal for AD and expression of nearby genes in brain and nonbrain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of SLC9A7 (OR, 1.03; 95% CI, 1.02-1.04) and colocalization analyses prioritizing both the SLC9A7 and nearby CHST7 genes. Of these 6 loci, 4 displayed evidence for escape from X chromosome inactivation with regard to AD risk.
Conclusion and relevance: This large-scale XWAS of AD identified the novel SLC9A7 locus. SLC9A7 regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid β accumulation. Overall, this study advances our knowledge of AD genetics and may provide novel biological drug targets. The results further provide initial insights into elucidating the role of the X chromosome in sex-based differences in AD.
重要性:在阿尔茨海默病(AD)中,X 染色体一直是个谜,但它占基因组的 5%,并携带着在大脑中表达的很高比例的基因,这使它成为阿尔茨海默病中未探索的遗传变异的潜在来源,因而特别具有吸引力:进行首次大规模的X染色体全基因组AD关联研究(XWAS):这是一项对病例对照、家族、人群和纵向AD相关队列中遗传关联研究的荟萃分析,这些队列来自美国阿尔茨海默病遗传学联合会、阿尔茨海默病测序项目、英国生物库、芬兰健康登记处和美国百万退伍军人计划。通过病例对照逻辑回归分析评估阿尔茨海默病风险。数据分析时间为 2023 年 1 月至 2024 年 3 月。从高密度单核苷酸变异微阵列和全基因组测序中获得的遗传数据,以及从已发表研究中获得的多组织表达和蛋白质定量性状位点的汇总统计数据都被纳入其中,以便进行后续的遗传共定位分析。从转介样本和志愿者样本中共筛选出 1 629 863 名符合条件的参与者,其中 477 596 人因分析排除标准而被排除。拒绝参与原始研究的参与者人数不详:AD风险,以几率比(ORs)和95% CIs的形式报告。在 X 染色体范围内考虑相关性(P 结果):分析包括 1 152 284 名非西班牙裔白人、欧洲血统的参与者(664 403 名女性[57.7%]和 487 881 名男性[42.3%]),其中包括 138 558 名 AD 患者。有 6 个独立的基因位点通过了 X 染色体范围内的显著性鉴定,其中 4 个位点显示出 AD 基因信号与附近基因在大脑和非大脑组织中的表达之间的联系。在这 4 个基因位点中,有一个位点通过了保守的全基因组显著性分析,其主导变异位于 SLC9A7 的一个内含子上(OR,1.03;95% CI,1.02-1.04),共定位分析优先考虑 SLC9A7 和附近的 CHST7 基因。在这 6 个基因位点中,有 4 个基因位点显示了摆脱 X 染色体失活的证据,这与 AD 风险有关:这项大规模的 AD XWAS 发现了新的 SLC9A7 基因位点。SLC9A7调节高尔基体分泌区的pH平衡,预计会对淀粉样β的积累产生下游影响。总之,这项研究增进了我们对AD遗传学的了解,并可能提供新的生物药物靶点。研究结果进一步为阐明X染色体在AD性别差异中的作用提供了初步见解。
{"title":"Role of the X Chromosome in Alzheimer Disease Genetics.","authors":"Michael E Belloy, Yann Le Guen, Ilaria Stewart, Kennedy Williams, Joachim Herz, Richard Sherva, Rui Zhang, Victoria Merritt, Matthew S Panizzon, Richard L Hauger, J Michael Gaziano, Mark Logue, Valerio Napolioni, Michael D Greicius","doi":"10.1001/jamaneurol.2024.2843","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.2843","url":null,"abstract":"<p><strong>Importance: </strong>The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.</p><p><strong>Objectives: </strong>To perform the first large-scale X chromosome-wide association study (XWAS) of AD.</p><p><strong>Design, setting, and participants: </strong>This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program. Risk of AD was evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024. Genetic data available from high-density single-nucleotide variant microarrays and whole-genome sequencing and summary statistics for multitissue expression and protein quantitative trait loci available from published studies were included, enabling follow-up genetic colocalization analyses. A total of 1 629 863 eligible participants were selected from referred and volunteer samples, 477 596 of whom were excluded for analysis exclusion criteria. The number of participants who declined to participate in original studies was not available.</p><p><strong>Main outcome and measures: </strong>Risk of AD, reported as odds ratios (ORs) with 95% CIs. Associations were considered at X chromosome-wide (P < 1 × 10-5) and genome-wide (P < 5 × 10-8) significance. Primary analyses are nonstratified, while secondary analyses evaluate sex-stratified effects.</p><p><strong>Results: </strong>Analyses included 1 152 284 participants of non-Hispanic White, European ancestry (664 403 [57.7%] female and 487 881 [42.3%] male), including 138 558 individuals with AD. Six independent genetic loci passed X chromosome-wide significance, with 4 showing support for links between the genetic signal for AD and expression of nearby genes in brain and nonbrain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of SLC9A7 (OR, 1.03; 95% CI, 1.02-1.04) and colocalization analyses prioritizing both the SLC9A7 and nearby CHST7 genes. Of these 6 loci, 4 displayed evidence for escape from X chromosome inactivation with regard to AD risk.</p><p><strong>Conclusion and relevance: </strong>This large-scale XWAS of AD identified the novel SLC9A7 locus. SLC9A7 regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid β accumulation. Overall, this study advances our knowledge of AD genetics and may provide novel biological drug targets. The results further provide initial insights into elucidating the role of the X chromosome in sex-based differences in AD.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1001/jamaneurol.2024.2835
Neha Aggarwal
{"title":"Behind the Brow That Furrows.","authors":"Neha Aggarwal","doi":"10.1001/jamaneurol.2024.2835","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.2835","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1001/jamaneurol.2024.2811
Young Nam Kwon, Boram Kim, Jun-Soon Kim, Kyung Seok Park, Da-Young Seo, Hyunjin Kim, Eun-Jae Lee, Young-Min Lim, Hyunjin Ju, Yeon Hak Chung, Ju-Hong Min, Tai-Seung Nam, Sooyoung Kim, Eunhee Sohn, Kyong Jin Shin, Jin Myoung Seok, Sunyoung Kim, Jong Seok Bae, Sukyoon Lee, Seong-Il Oh, Yu Jin Jung, Jinseok Park, Seung Hyun Kim, Ki Hoon Kim, Ho Jin Kim, Jae Ho Jung, Seong-Joon Kim, Seung Woo Kim, Myoung-Jin Jang, Jung-Joon Sung, Patrick Waters, Ha Young Shin, Sung-Min Kim
<p><strong>Importance: </strong>A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion.</p><p><strong>Objective: </strong>To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus.</p><p><strong>Design, setting, and participants: </strong>This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration.</p><p><strong>Exposures: </strong>Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days).</p><p><strong>Main outcomes and measures: </strong>A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment.</p><p><strong>Results: </strong>Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not.</p><p><strong>Conclusions and relevance: </strong>Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction
{"title":"Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Young Nam Kwon, Boram Kim, Jun-Soon Kim, Kyung Seok Park, Da-Young Seo, Hyunjin Kim, Eun-Jae Lee, Young-Min Lim, Hyunjin Ju, Yeon Hak Chung, Ju-Hong Min, Tai-Seung Nam, Sooyoung Kim, Eunhee Sohn, Kyong Jin Shin, Jin Myoung Seok, Sunyoung Kim, Jong Seok Bae, Sukyoon Lee, Seong-Il Oh, Yu Jin Jung, Jinseok Park, Seung Hyun Kim, Ki Hoon Kim, Ho Jin Kim, Jae Ho Jung, Seong-Joon Kim, Seung Woo Kim, Myoung-Jin Jang, Jung-Joon Sung, Patrick Waters, Ha Young Shin, Sung-Min Kim","doi":"10.1001/jamaneurol.2024.2811","DOIUrl":"10.1001/jamaneurol.2024.2811","url":null,"abstract":"<p><strong>Importance: </strong>A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion.</p><p><strong>Objective: </strong>To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus.</p><p><strong>Design, setting, and participants: </strong>This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration.</p><p><strong>Exposures: </strong>Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days).</p><p><strong>Main outcomes and measures: </strong>A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment.</p><p><strong>Results: </strong>Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not.</p><p><strong>Conclusions and relevance: </strong>Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1001/jamaneurol.2024.2780
Augusto Rachão, Pedro Pereira, Miguel Grunho
{"title":"A Unique Case of Opioid-Induced Myoclonus.","authors":"Augusto Rachão, Pedro Pereira, Miguel Grunho","doi":"10.1001/jamaneurol.2024.2780","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.2780","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1001/jamaneurol.2024.1105
Maria Neimann Herskind, Jakob Bie Granild-Jensen, Mette Thorup Bendixen
{"title":"Distinct Magnetic Resonance Imaging in a Child With a TACO1 Variant.","authors":"Maria Neimann Herskind, Jakob Bie Granild-Jensen, Mette Thorup Bendixen","doi":"10.1001/jamaneurol.2024.1105","DOIUrl":"10.1001/jamaneurol.2024.1105","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1001/jamaneurol.2024.2293
Timothy R Sampson
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Pub Date : 2024-09-01DOI: 10.1001/jamaneurol.2024.2404
Babak B Navi, Cenai Zhang, Benjamin Miller, Mary Cushman, Scott E Kasner, Mitchell S V Elkind, David L Tirschwell, W T Longstreth, Richard A Kronmal, Morin Beyeler, Jordan Elm, Richard M Zweifler, Joseph Tarsia, Carlo W Cereda, Giovanni Bianco, Gianluca Costamagna, Patrik Michel, Joseph P Broderick, David J Gladstone, Hooman Kamel, Christopher Streib
Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke.
Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke.
Design, setting, and participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024.
Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined.
Main outcomes and measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage.
Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]).
Conclusions and relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin.
重要性:约 10%-15%的缺血性脑卒中与癌症有关;癌症相关脑卒中,尤其是隐源性脑卒中,复发率和大出血率很高。关于癌症和隐源性中风患者不同抗血栓策略的安全性和有效性的数据有限:比较阿哌沙班与阿司匹林在预防癌症史和隐源性卒中患者不良临床结局方面的疗效:对近期发生隐源性卒中且有心房性心脏病生物标志物证据的1015名患者的数据进行事后分析,这些患者参加了心房性心脏病和抗血栓药物预防隐源性卒中(ARCADIA)试验,该试验是一项多中心、随机、双盲临床试验,于2018年至2023年在北美185个卒中中心进行。数据分析从2023年10月15日开始,至2024年5月23日结束:口服阿哌沙班,5 毫克(或 2.5 毫克,如果符合标准),每天两次 vs 口服阿司匹林,81 毫克,每天一次。主要结果和测量指标:这项事后分析的主要结果是重大缺血或重大出血事件的复合结果。主要缺血性事件包括复发性缺血性中风、心肌梗死、全身性栓塞、症状性深静脉血栓或肺栓塞。主要出血事件包括症状性颅内出血和任何主要颅外出血:1015名参与者(中位数[IQR]年龄为68[60-76]岁;551[54.3%]名女性)中,137人(13.5%)有癌症病史。有癌症病史患者的随访中位数(IQR)为 1.5(0.6-2.5)年,无癌症病史患者的随访中位数(IQR)为 1.5(0.6-3.0)年。与无癌症病史者相比,有癌症病史者发生重大缺血或大出血事件的风险更高(危险比 [HR],1.73;95% CI,1.10-2.71)。在有癌症病史的参与者中,随机接受阿哌沙班治疗的61人中有8人(13.1%)和随机接受阿司匹林治疗的76人中有16人(21.1%)发生了严重缺血或大出血事件;但是,两组之间的风险没有显著差异(HR,0.61;95% CI,0.26-1.43)。在随机接受阿哌沙班与阿司匹林治疗的癌症患者中,发生的事件包括复发性中风(5 [8.2%] vs 9 [11.8%])、重大缺血性事件(7 [11.5%] vs 14 [18.4%])和重大出血事件(1 [1.6%] vs 2 [2.6%]):结论和相关性:在ARCADIA试验的参与者中,与阿司匹林相比,有癌症病史的阿哌沙班患者发生重大缺血性和出血性事件的风险没有显著差异:试验注册:ClinicalTrials.gov Identifier:试验注册:ClinicalTrials.gov Identifier:NCT03192215。
{"title":"Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial.","authors":"Babak B Navi, Cenai Zhang, Benjamin Miller, Mary Cushman, Scott E Kasner, Mitchell S V Elkind, David L Tirschwell, W T Longstreth, Richard A Kronmal, Morin Beyeler, Jordan Elm, Richard M Zweifler, Joseph Tarsia, Carlo W Cereda, Giovanni Bianco, Gianluca Costamagna, Patrik Michel, Joseph P Broderick, David J Gladstone, Hooman Kamel, Christopher Streib","doi":"10.1001/jamaneurol.2024.2404","DOIUrl":"10.1001/jamaneurol.2024.2404","url":null,"abstract":"<p><strong>Importance: </strong>Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke.</p><p><strong>Objective: </strong>To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke.</p><p><strong>Design, setting, and participants: </strong>Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024.</p><p><strong>Exposures: </strong>Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined.</p><p><strong>Main outcomes and measures: </strong>The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage.</p><p><strong>Results: </strong>Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]).</p><p><strong>Conclusions and relevance: </strong>Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03192215.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}