Pub Date : 2025-01-27DOI: 10.1161/STROKEAHA.124.049575
Marco Foddis, Sonja Blumenau, Susanne Mueller, Clemens Messerschmidt, Clarissa Rocca, Alistair T Pagnamenta, Katarzyna Winek, Matthias Endres, Andreas Meisel, Arianna Tucci, Jose Bras, Rita Guerreiro, Dieter Beule, Ulrich Dirnagl, Celeste Sassi
Background: Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning Ide locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory. Given IDE critical role in vascular plasticity, we hypothesized Ide CNV may have explained PcomA variability in C57BL/6J inbred mice.
Methods: We applied a combination of techniques (T2-weighted magnetic resonance imaging, time-of-flight angiography, cerebral blood flow imaging, and histology) to characterize the collaterome in 77 C57BL/6J bilateral common carotid artery stenosis, middle cerebral artery occlusion, naive, and sham mice and performed on these Taqman genotyping, exome sequencing, and RNA sequencing. We then investigated the hypothesis that IDE structural variants (CNVs, gain/loss of function mutations) may have influenced the cerebrovascular phenotype in a large cohort of 454 040 cases and controls (UK Biobank, Genomics England).
Results: We detected an Ide CNV in a bilateral common carotid artery stenosis mouse with 2 patent PcomAs (minor allele frequency, 1.3%), not segregating with the PcomA patency phenotype. In addition, 2 heterozygous IDE CNVs, resulting in loss of function were found in 1 patient with hereditary ataxia, a patient with hereditary congenital heart disease, and 2 healthy individuals (minor allele frequency 9×10-6). Moreover, we report 4 IDE loss of function point mutations (p.Leu5X, p.Met394ValfsX29, p.Pro14SerfsX26, p.Leu889X, minor allele frequency 0.02%) present also in controls or inherited from healthy parents.
Conclusions: Ide CNV and loss of function variants are rare, do not crucially influence PcomA variability in C57BL/6J inbred mice, and do not cause a vascular phenotype in humans.
{"title":"<i>Ide</i> Copy Number Variant Does Not Influence Stroke Severity in 2 C57BL/6J Mouse Models nor in Humans: An Exploratory Study.","authors":"Marco Foddis, Sonja Blumenau, Susanne Mueller, Clemens Messerschmidt, Clarissa Rocca, Alistair T Pagnamenta, Katarzyna Winek, Matthias Endres, Andreas Meisel, Arianna Tucci, Jose Bras, Rita Guerreiro, Dieter Beule, Ulrich Dirnagl, Celeste Sassi","doi":"10.1161/STROKEAHA.124.049575","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049575","url":null,"abstract":"<p><strong>Background: </strong>Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning <i>Ide</i> locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory. Given <i>IDE</i> critical role in vascular plasticity, we hypothesized <i>Ide</i> CNV may have explained PcomA variability in C57BL/6J inbred mice.</p><p><strong>Methods: </strong>We applied a combination of techniques (T2-weighted magnetic resonance imaging, time-of-flight angiography, cerebral blood flow imaging, and histology) to characterize the collaterome in 77 C57BL/6J bilateral common carotid artery stenosis, middle cerebral artery occlusion, naive, and sham mice and performed on these Taqman genotyping, exome sequencing, and RNA sequencing. We then investigated the hypothesis that <i>IDE</i> structural variants (CNVs, gain/loss of function mutations) may have influenced the cerebrovascular phenotype in a large cohort of 454 040 cases and controls (UK Biobank, Genomics England).</p><p><strong>Results: </strong>We detected an <i>Ide</i> CNV in a bilateral common carotid artery stenosis mouse with 2 patent PcomAs (minor allele frequency, 1.3%), not segregating with the PcomA patency phenotype. In addition, 2 heterozygous <i>IDE</i> CNVs, resulting in loss of function were found in 1 patient with hereditary ataxia, a patient with hereditary congenital heart disease, and 2 healthy individuals (minor allele frequency 9×10<sup>-6</sup>). Moreover, we report 4 <i>IDE</i> loss of function point mutations (p.Leu5X, p.Met394ValfsX29, p.Pro14SerfsX26, p.Leu889X, minor allele frequency 0.02%) present also in controls or inherited from healthy parents.</p><p><strong>Conclusions: </strong><i>Ide</i> CNV and loss of function variants are rare, do not crucially influence PcomA variability in C57BL/6J inbred mice, and do not cause a vascular phenotype in humans.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047949","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 : 2025-01-24DOI: 10.1161/STROKEAHA.124.048305
Jae W Song, Huy Q Phi, Manisha Koneru, Quy Cao, Jeremy Rubin, Yu Sakai, Lamya Ibrahim, Sonya E Zhou, John H Woo, Scott E Kasner, Luca Saba, Brett L Cucchiara
Background: A modified computed tomography angiography (CTA)-based Carotid Plaque Reporting and Data System (Plaque-RADS) classification was applied to a cohort of patients with embolic stroke of undetermined source to test whether high-risk Plaque-RADS subtypes are more prevalent on the ipsilateral side of stroke. With the widespread use of CTA for stroke evaluation, a CTA-based Plaque-RADS would be valuable for generalizability.
Methods: A retrospective observational cross-sectional study was conducted at a single integrated health system comprised of 3 hospitals with a comprehensive stroke center between October 1, 2015, and April 1, 2017. Patients with unilateral anterior circulation stroke and <50% carotid stenosis on CTA were retrospectively identified. Maximum plaque thickness and ulceration were assessed by a neuroradiologist blinded to the stroke side. A semiautomated segmentation software measured intraplaque hemorrhage volumes. Modified CTA-based Plaque-RADS classification was defined as (1) no plaque, (2) plaque thickness <3 mm, (3) plaque thickness ≥3 mm or ulcerated, and (4) plaque with intraplaque hemorrhage >50 mm3 irrespective of plaque thickness. High-risk plaque subtypes (Plaque-RADS 3 and 4) were compared with low-risk subtypes (Plaque-RADS 1 and 2).
Results: Ninety-four patients (55% women; median age, 66 years) were included. CTA-based Plaque-RADS categories for plaques ipsilateral to the stroke side were as follows: (1) 14.9%, (2) 42.6%, (3) 41.5%, and (4) 1.1%. Carotid plaques contralateral to stroke side were Plaque-RADS: (1) 21.3%, (2) 46.8%, (3) 31.9%, and (4) 0%. When compared with the contralateral side, plaques ipsilateral to the stroke side were significantly associated with high-risk Plaque-RADS subtypes in a mixed-effects logistic model adjusting for age and sex (adjusted odds ratio, 2.10 [95% CI, 1.20-3.71]; P=0.01).
Conclusions: Carotid plaque ipsilateral to the stroke side was significantly associated with CTA-based high-risk Plaque-RADS subtypes in an embolic stroke of undetermined source cohort. A CTA-based Plaque-RADS classification may be useful for identifying potentially causative carotid plaque phenotypes in patients with embolic stroke of undetermined source.
{"title":"Prevalence of High-Risk CTA-Based Carotid Plaque-RADS Subtypes in Patients With Embolic Stroke of Undetermined Source.","authors":"Jae W Song, Huy Q Phi, Manisha Koneru, Quy Cao, Jeremy Rubin, Yu Sakai, Lamya Ibrahim, Sonya E Zhou, John H Woo, Scott E Kasner, Luca Saba, Brett L Cucchiara","doi":"10.1161/STROKEAHA.124.048305","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.048305","url":null,"abstract":"<p><strong>Background: </strong>A modified computed tomography angiography (CTA)-based Carotid Plaque Reporting and Data System (Plaque-RADS) classification was applied to a cohort of patients with embolic stroke of undetermined source to test whether high-risk Plaque-RADS subtypes are more prevalent on the ipsilateral side of stroke. With the widespread use of CTA for stroke evaluation, a CTA-based Plaque-RADS would be valuable for generalizability.</p><p><strong>Methods: </strong>A retrospective observational cross-sectional study was conducted at a single integrated health system comprised of 3 hospitals with a comprehensive stroke center between October 1, 2015, and April 1, 2017. Patients with unilateral anterior circulation stroke and <50% carotid stenosis on CTA were retrospectively identified. Maximum plaque thickness and ulceration were assessed by a neuroradiologist blinded to the stroke side. A semiautomated segmentation software measured intraplaque hemorrhage volumes. Modified CTA-based Plaque-RADS classification was defined as (1) no plaque, (2) plaque thickness <3 mm, (3) plaque thickness ≥3 mm or ulcerated, and (4) plaque with intraplaque hemorrhage >50 mm<sup>3</sup> irrespective of plaque thickness. High-risk plaque subtypes (Plaque-RADS 3 and 4) were compared with low-risk subtypes (Plaque-RADS 1 and 2).</p><p><strong>Results: </strong>Ninety-four patients (55% women; median age, 66 years) were included. CTA-based Plaque-RADS categories for plaques ipsilateral to the stroke side were as follows: (1) 14.9%, (2) 42.6%, (3) 41.5%, and (4) 1.1%. Carotid plaques contralateral to stroke side were Plaque-RADS: (1) 21.3%, (2) 46.8%, (3) 31.9%, and (4) 0%. When compared with the contralateral side, plaques ipsilateral to the stroke side were significantly associated with high-risk Plaque-RADS subtypes in a mixed-effects logistic model adjusting for age and sex (adjusted odds ratio, 2.10 [95% CI, 1.20-3.71]; <i>P</i>=0.01).</p><p><strong>Conclusions: </strong>Carotid plaque ipsilateral to the stroke side was significantly associated with CTA-based high-risk Plaque-RADS subtypes in an embolic stroke of undetermined source cohort. A CTA-based Plaque-RADS classification may be useful for identifying potentially causative carotid plaque phenotypes in patients with embolic stroke of undetermined source.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029721","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 : 2025-01-24DOI: 10.1161/STROKEAHA.124.047070
Dearbhla M Kelly, Eoin M Kelleher, Peter M Rothwell
Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.
{"title":"The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease.","authors":"Dearbhla M Kelly, Eoin M Kelleher, Peter M Rothwell","doi":"10.1161/STROKEAHA.124.047070","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.047070","url":null,"abstract":"<p><p>Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029722","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 : 2025-01-17DOI: 10.1161/STROKEAHA.124.049459
Marshall Kirsch, James Dolbow, Sophia Sundararajan
{"title":"Memory in the Balance: Exploring Ischemic Amnesia in Posterior Circulation Stroke.","authors":"Marshall Kirsch, James Dolbow, Sophia Sundararajan","doi":"10.1161/STROKEAHA.124.049459","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049459","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011878","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 : 2025-01-17DOI: 10.1161/STROKEAHA.124.049079
Zihan Sun, Eric L Harshfield, Frank-Erik de Leeuw, Stephen Burgess, Adam S Butterworth, Niels P Riksen, Ziad Mallat, Hugh S Markus
Background: Endothelial dysfunction and inflammation have been implicated in the pathophysiology of cerebral small vessel disease (SVD). However, whether they are causal, and if so which components of the pathways represent potential treatment targets, remains uncertain.
Methods: Two-sample Mendelian randomization (MR) was used to test the association between the circulating abundance of 996 proteins involved in endothelial dysfunction and inflammation and SVD. The genetic instruments predicting protein levels were obtained from the Iceland 36K (n=35 892) and the UK Biobank Proteomics (n=34 557) cohorts, both of which were longitudinal studies with follow-up from 2000 to 2023 and 2006 to 2023, respectively. SVD was represented by lacunar stroke (n=6030 cases) and 5 neuroimaging features (white matter hyperintensities [n=55 291], diffusion tensor imaging metrics: mean diffusivity [n=36 460] and fractional anisotropy [n=36 533], extensive white matter perivascular space burden [n=9324 cases], and cerebral microbleeds [n=3556 cases]). Among the proteins supported by causal evidence from the MR, cross-sectional analysis was performed to assess their associations with cognitive performance; survival analysis with Fine-Gray models was applied to examine their associations with incident all-cause dementia and stroke within the UK Biobank Proteomics cohort.
Results: MR suggested COL2A1 (collagen type II α-1 chain) was associated with lacunar stroke (odds ratio, 0.89 [95% CI, 0.86-0.91]; P=5×10-5). Moreover, 12 proteins related to endothelial function and inflammation were associated with neuroimaging features of SVD. Cross-sectional analyses showed 5 of the 13 proteins (EPHA2 [ephrin type-A receptor 2], METAP1D [methionine aminopeptidase 1D, mitochondrial], FLT4 [vascular endothelial growth factor receptor 3], COL2A1, and TIMD4 [T-cell immunoglobulin and mucin domain-containing protein 4]) were associated with cognitive performance with effects concordant with their MR findings. Survival analyses with the Fine-Gray models indicated that 5 of the 13 proteins (EPHA2, METAP1D, FLT4, APOE [apolipoprotein E], and PDE5A [cGMP-specific 3',5'-cyclic phosphodiesterase]) were associated with the risk of all-cause dementia or stroke independent of age and sex, consistent with their MR evidence.
Conclusions: Our findings suggest that endothelial-platelet activation and complement-mediated regulation of inflammation play roles in SVD and identify potential therapeutic targets and pathways.
{"title":"Proteins Involved in Endothelial Function and Inflammation Are Implicated in Cerebral Small Vessel Disease.","authors":"Zihan Sun, Eric L Harshfield, Frank-Erik de Leeuw, Stephen Burgess, Adam S Butterworth, Niels P Riksen, Ziad Mallat, Hugh S Markus","doi":"10.1161/STROKEAHA.124.049079","DOIUrl":"10.1161/STROKEAHA.124.049079","url":null,"abstract":"<p><strong>Background: </strong>Endothelial dysfunction and inflammation have been implicated in the pathophysiology of cerebral small vessel disease (SVD). However, whether they are causal, and if so which components of the pathways represent potential treatment targets, remains uncertain.</p><p><strong>Methods: </strong>Two-sample Mendelian randomization (MR) was used to test the association between the circulating abundance of 996 proteins involved in endothelial dysfunction and inflammation and SVD. The genetic instruments predicting protein levels were obtained from the Iceland 36K (n=35 892) and the UK Biobank Proteomics (n=34 557) cohorts, both of which were longitudinal studies with follow-up from 2000 to 2023 and 2006 to 2023, respectively. SVD was represented by lacunar stroke (n=6030 cases) and 5 neuroimaging features (white matter hyperintensities [n=55 291], diffusion tensor imaging metrics: mean diffusivity [n=36 460] and fractional anisotropy [n=36 533], extensive white matter perivascular space burden [n=9324 cases], and cerebral microbleeds [n=3556 cases]). Among the proteins supported by causal evidence from the MR, cross-sectional analysis was performed to assess their associations with cognitive performance; survival analysis with Fine-Gray models was applied to examine their associations with incident all-cause dementia and stroke within the UK Biobank Proteomics cohort.</p><p><strong>Results: </strong>MR suggested COL2A1 (collagen type II α-1 chain) was associated with lacunar stroke (odds ratio, 0.89 [95% CI, 0.86-0.91]; <i>P</i>=5×10<sup>-5</sup>). Moreover, 12 proteins related to endothelial function and inflammation were associated with neuroimaging features of SVD. Cross-sectional analyses showed 5 of the 13 proteins (EPHA2 [ephrin type-A receptor 2], METAP1D [methionine aminopeptidase 1D, mitochondrial], FLT4 [vascular endothelial growth factor receptor 3], COL2A1, and TIMD4 [T-cell immunoglobulin and mucin domain-containing protein 4]) were associated with cognitive performance with effects concordant with their MR findings. Survival analyses with the Fine-Gray models indicated that 5 of the 13 proteins (EPHA2, METAP1D, FLT4, APOE [apolipoprotein E], and PDE5A [cGMP-specific 3',5'-cyclic phosphodiesterase]) were associated with the risk of all-cause dementia or stroke independent of age and sex, consistent with their MR evidence.</p><p><strong>Conclusions: </strong>Our findings suggest that endothelial-platelet activation and complement-mediated regulation of inflammation play roles in SVD and identify potential therapeutic targets and pathways.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011883","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 : 2025-01-17DOI: 10.1161/STROKEAHA.124.047683
Evan Houldin, Edna M Babbitt, Rosalind Hurwitz, Marwan N Baliki, Leora R Cherney
Background: Attention is known to play an important role in language, and attentional deficits have been associated with language impairments in people with aphasia (PWA). A prior study by our laboratory indicated that behavioral measures for PWA participating in an intensive comprehensive aphasia program (ICAP) clustered into 1 language and 1 attention-related factor, with each factor correlated with independent resting state functional connectivity (rsFC) networks. The present study includes additional attention measures and participants to better assess the relationship between attention, language, and rsFC.
Methods: PWA participated in 120 hours of ICAP therapy over 4 weeks, between April 2018 and August 2022. Participants were evaluated with the Western Aphasia Battery and Conners' Continuous Performance Test, pre- and post-ICAP. rsFC data were collected during functional magnetic resonance imaging scans pre- and post-ICAP. Principal component analysis identified behavioral score associations pre- and post-ICAP. FC matrices and graph measures were evaluated for both PWA and healthy controls.
Results: Twenty-three PWA participated (19 included in the final analysis). Data for 179 age and sex-matched healthy controls were taken from a public data set. The principal component analysis indicated 1 language and 2 attention-related principal components (PCs). The attention PCs were labeled Attention Accuracy and Attention Rate, in accordance with their best-associated behavioral measures. Importantly, each PC was associated with distinct networks, including higher-order networks, so-called because of their involvement in higher-order cognition. Notably, the language PC was significantly correlated with the ventral attention-memory-retrieval network rsFC (r=0.67, P=0.003) and the default mode-frontoparietal network rsFC (r=-0.56, P=0.019). Attention Accuracy was significantly correlated with cingulo-opercular-subcortical network rsFC (r=0.60, P=0.011). Attention Rate was significantly negatively correlated with visual-somatomotor network rsFC (r=-0.74, P=0.0007).
Conclusions: This study supports the notion that language improvements for PWAs participating in an ICAP are associated with distinct network changes. Importantly, these networks are not restricted to language networks but also include attention, and task-control networks.
{"title":"Language and Attention Networks Have Distinct Roles in Language Improvement Following an Intensive Comprehensive Aphasia Program.","authors":"Evan Houldin, Edna M Babbitt, Rosalind Hurwitz, Marwan N Baliki, Leora R Cherney","doi":"10.1161/STROKEAHA.124.047683","DOIUrl":"10.1161/STROKEAHA.124.047683","url":null,"abstract":"<p><strong>Background: </strong>Attention is known to play an important role in language, and attentional deficits have been associated with language impairments in people with aphasia (PWA). A prior study by our laboratory indicated that behavioral measures for PWA participating in an intensive comprehensive aphasia program (ICAP) clustered into 1 language and 1 attention-related factor, with each factor correlated with independent resting state functional connectivity (rsFC) networks. The present study includes additional attention measures and participants to better assess the relationship between attention, language, and rsFC.</p><p><strong>Methods: </strong>PWA participated in 120 hours of ICAP therapy over 4 weeks, between April 2018 and August 2022. Participants were evaluated with the Western Aphasia Battery and Conners' Continuous Performance Test, pre- and post-ICAP. rsFC data were collected during functional magnetic resonance imaging scans pre- and post-ICAP. Principal component analysis identified behavioral score associations pre- and post-ICAP. FC matrices and graph measures were evaluated for both PWA and healthy controls.</p><p><strong>Results: </strong>Twenty-three PWA participated (19 included in the final analysis). Data for 179 age and sex-matched healthy controls were taken from a public data set. The principal component analysis indicated 1 language and 2 attention-related principal components (PCs). The attention PCs were labeled Attention Accuracy and Attention Rate, in accordance with their best-associated behavioral measures. Importantly, each PC was associated with distinct networks, including higher-order networks, so-called because of their involvement in higher-order cognition. Notably, the language PC was significantly correlated with the ventral attention-memory-retrieval network rsFC (<i>r</i>=0.67, <i>P</i>=0.003) and the default mode-frontoparietal network rsFC (<i>r</i>=-0.56, <i>P</i>=0.019). Attention Accuracy was significantly correlated with cingulo-opercular-subcortical network rsFC (<i>r</i>=0.60, <i>P</i>=0.011). Attention Rate was significantly negatively correlated with visual-somatomotor network rsFC (<i>r</i>=-0.74, <i>P</i>=0.0007).</p><p><strong>Conclusions: </strong>This study supports the notion that language improvements for PWAs participating in an ICAP are associated with distinct network changes. Importantly, these networks are not restricted to language networks but also include attention, and task-control networks.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011944","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 : 2025-01-17DOI: 10.1161/STROKEAHA.124.049151
Paul D Johnson, Jennifer J Majersik
There is a large burden of stroke in the United States, and extensive systems of care have been established to address it. The resources devoted to stroke centers are analogous to those of trauma centers, both sharing many strict requirements for certification, clinical preparedness, quality improvement, data management, and reporting. However, trauma programs partly defray these costs through a trauma activation billing code, a billable fee that is charged for activation of the trauma team under strict criteria. There are potential benefits to establishing an analogous national stroke code activation fee. Although a billable stroke code activation fee may increase financial burden on patients, this may be counterbalanced by the significant potential for individual and societal benefits. Providing additional financial support for stroke systems of care may improve acute stroke treatment, reduce stroke burden and poststroke disability, and reduce inequality by broadening the reach of stroke systems of care to disadvantaged communities. Further evaluation of the costs and benefits of implementing a stroke code activation fee based on that currently used by trauma centers is needed.
{"title":"Case for Establishing a National Stroke Activation Fee in the United States: Learning From Trauma Centers.","authors":"Paul D Johnson, Jennifer J Majersik","doi":"10.1161/STROKEAHA.124.049151","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049151","url":null,"abstract":"<p><p>There is a large burden of stroke in the United States, and extensive systems of care have been established to address it. The resources devoted to stroke centers are analogous to those of trauma centers, both sharing many strict requirements for certification, clinical preparedness, quality improvement, data management, and reporting. However, trauma programs partly defray these costs through a trauma activation billing code, a billable fee that is charged for activation of the trauma team under strict criteria. There are potential benefits to establishing an analogous national stroke code activation fee. Although a billable stroke code activation fee may increase financial burden on patients, this may be counterbalanced by the significant potential for individual and societal benefits. Providing additional financial support for stroke systems of care may improve acute stroke treatment, reduce stroke burden and poststroke disability, and reduce inequality by broadening the reach of stroke systems of care to disadvantaged communities. Further evaluation of the costs and benefits of implementing a stroke code activation fee based on that currently used by trauma centers is needed.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011942","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 : 2025-01-17DOI: 10.1161/STROKEAHA.124.048743
Joonsang Yoo, Hyunsun Lim, Kwon-Duk Seo
Background: Carotid artery stenting (CAS) is an alternative treatment for patients with carotid artery stenosis who are not eligible for carotid endarterectomy. Dual antiplatelet therapy (DAPT) after CAS aims to prevent ischemic stroke. However, its optimal duration remains unclear. We aimed to determine the optimal duration of DAPT by identifying the differences in clinical events that occur depending on the DAPT maintenance period.
Methods: Data were obtained from the nationwide database of the Korean Health Insurance Review and Assessment Service between 2007 and 2019. Patients who received CAS, as identified by procedure codes, were divided into 2 groups according to the duration of DAPT (aspirin and clopidogrel): those who maintained DAPT for at least 90 days but for <6 months (short-DAPT group) and those who maintained it for longer (long-DAPT group). The primary outcome was a composite of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage within 12 months of switching to single antiplatelet therapy. Statistical analyses used inverse probability of treatment weighting to balance baseline characteristics, with Cox regression and Fine and Gray competing risk models used to assess outcomes.
Results: Of the 12 034 patients who underwent CAS, 2529 and 9505 were assigned to the short-DAPT and long-DAPT groups, respectively. In the short-DAPT group, ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage occurred in 41 (1.6%), 22 (0.9%), and 4 (0.2%) patients, respectively. In the long-DAPT group, ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage occurred in 108 (1.1%), 87 (0.9%), and 4 (0.04%) patients, respectively. The primary outcome did not differ significantly between the groups (2.5% versus 2.1%; adjusted hazard ratio of long-DAPT to short-DAPT, 0.869 [95% CI, 0.652-1.158]; P=0.337).
Conclusion: Short-duration DAPT can be recommended, as it does not differ from long-duration DAPT in terms of clinical efficacy and adverse events after CAS.
背景:颈动脉支架植入术(CAS)是不适合颈动脉内膜切除术的颈动脉狭窄患者的一种替代治疗方法。双重抗血小板治疗(DAPT)旨在预防缺血性脑卒中。然而,其最佳持续时间尚不清楚。我们的目的是通过确定DAPT维持时间不同所发生的临床事件的差异来确定DAPT的最佳持续时间。方法:数据来自韩国健康保险审查评估服务中心2007 - 2019年的全国数据库。根据DAPT(阿司匹林和氯吡格雷)持续时间将接受CAS的患者分为2组:维持DAPT至少90天的患者,但结果:在接受CAS的12034例患者中,分别有2529例和9505例患者被分配到短DAPT组和长DAPT组。短时间dapt组缺血性卒中41例(1.6%),胃肠道出血22例(0.9%),颅内出血4例(0.2%)。长时间dapt组缺血性脑卒中108例(1.1%),胃肠道出血87例(0.9%),颅内出血4例(0.04%)。两组间主要结局无显著差异(2.5% vs 2.1%;长dapt与短dapt的校正风险比为0.869 [95% CI, 0.652-1.158];P = 0.337)。结论:短时间DAPT与长时间DAPT在临床疗效和不良事件方面没有差异,可以推荐短时间DAPT。
{"title":"Optimal Duration of Dual Antiplatelet Therapy After Carotid Artery Stenting: A Nationwide Cohort Study.","authors":"Joonsang Yoo, Hyunsun Lim, Kwon-Duk Seo","doi":"10.1161/STROKEAHA.124.048743","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.048743","url":null,"abstract":"<p><strong>Background: </strong>Carotid artery stenting (CAS) is an alternative treatment for patients with carotid artery stenosis who are not eligible for carotid endarterectomy. Dual antiplatelet therapy (DAPT) after CAS aims to prevent ischemic stroke. However, its optimal duration remains unclear. We aimed to determine the optimal duration of DAPT by identifying the differences in clinical events that occur depending on the DAPT maintenance period.</p><p><strong>Methods: </strong>Data were obtained from the nationwide database of the Korean Health Insurance Review and Assessment Service between 2007 and 2019. Patients who received CAS, as identified by procedure codes, were divided into 2 groups according to the duration of DAPT (aspirin and clopidogrel): those who maintained DAPT for at least 90 days but for <6 months (short-DAPT group) and those who maintained it for longer (long-DAPT group). The primary outcome was a composite of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage within 12 months of switching to single antiplatelet therapy. Statistical analyses used inverse probability of treatment weighting to balance baseline characteristics, with Cox regression and Fine and Gray competing risk models used to assess outcomes.</p><p><strong>Results: </strong>Of the 12 034 patients who underwent CAS, 2529 and 9505 were assigned to the short-DAPT and long-DAPT groups, respectively. In the short-DAPT group, ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage occurred in 41 (1.6%), 22 (0.9%), and 4 (0.2%) patients, respectively. In the long-DAPT group, ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage occurred in 108 (1.1%), 87 (0.9%), and 4 (0.04%) patients, respectively. The primary outcome did not differ significantly between the groups (2.5% versus 2.1%; adjusted hazard ratio of long-DAPT to short-DAPT, 0.869 [95% CI, 0.652-1.158]; <i>P</i>=0.337).</p><p><strong>Conclusion: </strong>Short-duration DAPT can be recommended, as it does not differ from long-duration DAPT in terms of clinical efficacy and adverse events after CAS.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011881","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}
Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.
Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8. The primary outcome was a combination of death or functional dependency (modified Rankin Scale score ≥3) at 90 days.
Results: At the 90-day follow-up, the primary outcome of death or functional dependency was not different between early- and delayed-treatment groups according to the history of hypertension; the odds ratios (95% CIs) associated with the early-treatment group were 1.11 (0.91-1.36) and 1.38 (0.92-2.08) for participants with and without a history of hypertension. However, the ordinal logistic regression showed that early antihypertensive treatment was associated with the odds of a higher modified Rankin Scale score in patients without hypertension (odds ratio, 1.35 [95% CI, 1.01-1.82]), but not in those with hypertension (odds ratio, 0.95 [95% CI, 0.82-1.10]; P=0.04 for interaction).
Conclusions: Early antihypertensive treatment did not reduce the odds of dependency or death at 90 days by hypertension history among patients with ischemic stroke but worsened functional outcomes for patients without hypertension in the ordinal analysis.
{"title":"Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History.","authors":"Xuewei Xie, Chongke Zhong, Xin Liu, Yuesong Pan, Aili Wang, Yufei Wei, Dacheng Liu, Tan Xu, Yong Jiang, Mengxing Wang, Jing Jing, Xia Meng, Katherine Obst, Chung-Shiuan Chen, David Wang, Yilong Wang, Yonghong Zhang, Jiang He, Yongjun Wang, Liping Liu","doi":"10.1161/STROKEAHA.124.049242","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049242","url":null,"abstract":"<p><strong>Background: </strong>We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.</p><p><strong>Methods: </strong>CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8. The primary outcome was a combination of death or functional dependency (modified Rankin Scale score ≥3) at 90 days.</p><p><strong>Results: </strong>At the 90-day follow-up, the primary outcome of death or functional dependency was not different between early- and delayed-treatment groups according to the history of hypertension; the odds ratios (95% CIs) associated with the early-treatment group were 1.11 (0.91-1.36) and 1.38 (0.92-2.08) for participants with and without a history of hypertension. However, the ordinal logistic regression showed that early antihypertensive treatment was associated with the odds of a higher modified Rankin Scale score in patients without hypertension (odds ratio, 1.35 [95% CI, 1.01-1.82]), but not in those with hypertension (odds ratio, 0.95 [95% CI, 0.82-1.10]; <i>P</i>=0.04 for interaction).</p><p><strong>Conclusions: </strong>Early antihypertensive treatment did not reduce the odds of dependency or death at 90 days by hypertension history among patients with ischemic stroke but worsened functional outcomes for patients without hypertension in the ordinal analysis.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03479554.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979699","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}