JAMA neurology最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;Patients were categorized based on the time to treat the first acute MOGAD attack: early (&lt;5 days), intermediate (5-14 days), and late (not treated within 14 days).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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 &lt; .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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;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}

{"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}

{"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}

{"title":"Fecal Microbiome Transplants For Parkinson Disease.","authors":"Timothy R Sampson","doi":"10.1001/jamaneurol.2024.2293","DOIUrl":"10.1001/jamaneurol.2024.2293","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":"141788032","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}

{"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}