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Time-Dependent Efficacy of Thrombolysis Before Thrombectomy: Registry of Stroke Care Quality (RES-Q)
That author's affiliation: St. Anne's University Hospital Brno
First author institution: St. Anne's University Hospital Brno
Last author institution: Second Department of Neurology, National and Kapodistrian University of Athens,Medical School, Attikon Hospital, GREECE
Stroke, Ahead of Print.
Background:Randomized evidence suggests that the association of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) may be time-dependent. We evaluated whether treatment timing modifies the association of IVT+EVT versus EVT alone with short-term in-hospital outcomes.Methods:We conducted a multinational observational registry cohort study using RES-Q data (2022–2024) from 38 countries. Among 3,132 eligible anterior-circulation large-vessel occlusion patients treated with EVT, 3,009 comprised the analytic cohort (IVT+EVT or EVT alone). Primary outcome was ordinal modified Rankin Scale (mRS) at discharge; secondary outcomes were mRS 0–2 at discharge and in-hospital survival. Time strata were ≤100, >100–150, >150–255, and >255 minutes. Confounding was addressed with stabilized inverse probability of treatment weighting (IPTW; weights truncated at 10) using a propensity score including arrival mode, admission location/department, vascular risk factors (hypertension, diabetes, hyperlipidemia, atrial fibrillation, prior stroke, smoking), imaging type, and baseline NIHSS. For EVT-only patients, onset-to-needle time was predicted only to assign time strata.Results:The mean age was 69.2 years (SD 13.2) and 45.6% were female. Treatment-by-time interaction was significant for ordinal discharge mRS (p=0.002) and mRS 0–2 at discharge (p=0.02). IVT+EVT was associated with better outcomes in the earliest treatment windows: at ≤100 minutes, ordinal mRS odds ratio (OR) 1.99 (95% CI, 1.49–2.63), in-hospital survival OR 1.81 (1.13–2.92), and mRS 0–2 OR 1.76 (1.24–2.51); at >100–150 minutes, ordinal mRS OR 1.58 (1.21–2.06) and mRS 0–2 OR 1.64 (1.16–2.31). Associations were attenuated beyond 150 minutes.Conclusions:In routine practice, early IVT before EVT was most consistently associated with improved discharge outcomes.
Background:Randomized evidence suggests that the association of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) may be time-dependent. We evaluated whether treatment timing modifies the association of IVT+EVT versus EVT alone with short-term in-hospital outcomes.Methods:We conducted a multinational observational registry cohort study using RES-Q data (2022–2024) from 38 countries. Among 3,132 eligible anterior-circulation large-vessel occlusion patients treated with EVT, 3,009 comprised the analytic cohort (IVT+EVT or EVT alone). Primary outcome was ordinal modified Rankin Scale (mRS) at discharge; secondary outcomes were mRS 0–2 at discharge and in-hospital survival. Time strata were ≤100, >100–150, >150–255, and >255 minutes. Confounding was addressed with stabilized inverse probability of treatment weighting (IPTW; weights truncated at 10) using a propensity score including arrival mode, admission location/department, vascular risk factors (hypertension, diabetes, hyperlipidemia, atrial fibrillation, prior stroke, smoking), imaging type, and baseline NIHSS. For EVT-only patients, onset-to-needle time was predicted only to assign time strata.Results:The mean age was 69.2 years (SD 13.2) and 45.6% were female. Treatment-by-time interaction was significant for ordinal discharge mRS (p=0.002) and mRS 0–2 at discharge (p=0.02). IVT+EVT was associated with better outcomes in the earliest treatment windows: at ≤100 minutes, ordinal mRS odds ratio (OR) 1.99 (95% CI, 1.49–2.63), in-hospital survival OR 1.81 (1.13–2.92), and mRS 0–2 OR 1.76 (1.24–2.51); at >100–150 minutes, ordinal mRS OR 1.58 (1.21–2.06) and mRS 0–2 OR 1.64 (1.16–2.31). Associations were attenuated beyond 150 minutes.Conclusions:In routine practice, early IVT before EVT was most consistently associated with improved discharge outcomes.
Improving Readability of Stroke Clinical Trial Consent Forms Using Artificial Intelligence
That author's affiliation: University of Michigan
First author institution: Northwell, New Hyde Park, NY
Last author institution: University of Michigan, Ann Arbor
Stroke, Ahead of Print.
BACKGROUND:Informed consent forms (ICFs) for clinical trials are often written above the recommended eighth-grade level. We aimed to compare the readability of original ICFs used for National Institutes of Health–funded stroke-related clinical trials with ICFs edited for readability using artificial intelligence.METHODS:Publicly available ICFs associated with National Institutes of Health–funded stroke-related clinical trials were accessed through ClinicalTrials.gov (search period: inception to August 12, 2025). Using ChatGPT-4o, we created a customized Generative Pre-Trained Transformer (GPT) designed to lower the reading level to eighth grade or below while maintaining ICF content. We processed each ICF using this GPT to create edited ICFs. Standard readability metrics, including the Flesch-Kincaid grade level (primary outcome), were compared between original and edited ICFs using pairedttests or the McNemar test (cross-sectional design). We also assessed semantic similarity using the MPNet language model, which produced continuous scores from 0 (no similarity) to 1 (perfect similarity).RESULTS:ICFs were available for 46 stroke trials, including behavioral (n=21), device (n=15), drug (n=5), and other (n=5) intervention types. Mean reading levels were 11.52 for the original and 9.47 for the GPT-edited ICFs using the Flesch-Kincaid grade level (P<0.001). Only 1 (2%) of the original ICFs and 18 (39%) of the GPT-edited ICFs had a Flesch-Kincaid reading level at or below eighth grade (P<0.001). Both the Simple Measure of Gobbledygook and Gunning Fog Index favored the GPT-edited ICFs by 1 to 2 grade levels. The Flesch Reading Ease score favored the GPT-edited ICFs by about 8 points. The mean similarity score was 0.85 (SD=0.04).CONCLUSIONS:GPT-edited ICFs achieved a readability reduction of approximately 2 grade levels compared with the original ICFs while preserving high semantic similarity. Customized GPTs may be a useful tool to improve the readability of clinical trial ICFs.
BACKGROUND:Informed consent forms (ICFs) for clinical trials are often written above the recommended eighth-grade level. We aimed to compare the readability of original ICFs used for National Institutes of Health–funded stroke-related clinical trials with ICFs edited for readability using artificial intelligence.METHODS:Publicly available ICFs associated with National Institutes of Health–funded stroke-related clinical trials were accessed through ClinicalTrials.gov (search period: inception to August 12, 2025). Using ChatGPT-4o, we created a customized Generative Pre-Trained Transformer (GPT) designed to lower the reading level to eighth grade or below while maintaining ICF content. We processed each ICF using this GPT to create edited ICFs. Standard readability metrics, including the Flesch-Kincaid grade level (primary outcome), were compared between original and edited ICFs using pairedttests or the McNemar test (cross-sectional design). We also assessed semantic similarity using the MPNet language model, which produced continuous scores from 0 (no similarity) to 1 (perfect similarity).RESULTS:ICFs were available for 46 stroke trials, including behavioral (n=21), device (n=15), drug (n=5), and other (n=5) intervention types. Mean reading levels were 11.52 for the original and 9.47 for the GPT-edited ICFs using the Flesch-Kincaid grade level (P<0.001). Only 1 (2%) of the original ICFs and 18 (39%) of the GPT-edited ICFs had a Flesch-Kincaid reading level at or below eighth grade (P<0.001). Both the Simple Measure of Gobbledygook and Gunning Fog Index favored the GPT-edited ICFs by 1 to 2 grade levels. The Flesch Reading Ease score favored the GPT-edited ICFs by about 8 points. The mean similarity score was 0.85 (SD=0.04).CONCLUSIONS:GPT-edited ICFs achieved a readability reduction of approximately 2 grade levels compared with the original ICFs while preserving high semantic similarity. Customized GPTs may be a useful tool to improve the readability of clinical trial ICFs.
Characteristics of Unsuccessful Recanalization Following Endovascular Thrombectomy: Cohort Study (EVATRISP Collaboration)
That author's affiliation: Hadassah-Hebrew University
Institution (first & last author): Hadassah-Hebrew University Medical Center
Stroke, Ahead of Print.
BACKGROUND:Successful target vessel recanalization in patients with large vessel occlusion stroke is associated with favorable clinical outcomes. Conversely, unsuccessful recanalization (UR) is associated with higher chances of poor outcomes. UR occurs in up to 30% of endovascular thrombectomy (EVT) procedures, and there are significant knowledge gaps in identifying factors associated with UR.METHODS:Prospectively enrolled EVT-treated patients from the EVATRISP registry, which included patients from 18 academic medical centers across Europe between the years 2015 and 2024, were retrospectively studied. Patients had to have data on prestroke and 3-month functional status and recanalization status at the end of EVT. UR was defined as a modified Thrombolysis in Cerebral Infarction score <2b and compared with successful recanalization (modified Thrombolysis in Cerebral Infarction ≥2b). Regression analyses were performed to identify predictors of UR, and a predictive tool was subsequently constructed.RESULTS:Of the 15 549 patients enrolled in EVATRIPS, 10 942 fulfilled entry criteria and were included in the current analysis. Overall, 8000 (73%) achieved successful recanalization, while 2942 (27%) had UR. In multivariate analysis, factors independently associated with higher odds of UR included older age, higher prestroke mRS, wake-up stroke, interhospital transfer for EVT, higher National Institutes of Health Stroke Scale score at presentation, tPA (tissue-type plasminogen activator) administration, and occlusion of the M2 segment of the middle cerebral artery or proximal anterior or posterior cerebral arteries. Dyslipidemia and occlusion of the M1 middle cerebral artery or basilar artery were associated with successful recanalization. UR was associated with poor clinical outcomes, and higher mortality rates. A predictive tool derived from these variables demonstrated limited discriminatory ability (area under the curve, 0.579 [95% CI, 0.567–0.591];P<0.001).CONCLUSIONS:UR is frequent among patients undergoing EVT and is associated with poor clinical outcomes. Although several pre-EVT factors were independently associated with UR, accurately predicting which patients will experience UR remains highly challenging. Our findings suggest that all eligible patients should undergo EVT.
BACKGROUND:Successful target vessel recanalization in patients with large vessel occlusion stroke is associated with favorable clinical outcomes. Conversely, unsuccessful recanalization (UR) is associated with higher chances of poor outcomes. UR occurs in up to 30% of endovascular thrombectomy (EVT) procedures, and there are significant knowledge gaps in identifying factors associated with UR.METHODS:Prospectively enrolled EVT-treated patients from the EVATRISP registry, which included patients from 18 academic medical centers across Europe between the years 2015 and 2024, were retrospectively studied. Patients had to have data on prestroke and 3-month functional status and recanalization status at the end of EVT. UR was defined as a modified Thrombolysis in Cerebral Infarction score <2b and compared with successful recanalization (modified Thrombolysis in Cerebral Infarction ≥2b). Regression analyses were performed to identify predictors of UR, and a predictive tool was subsequently constructed.RESULTS:Of the 15 549 patients enrolled in EVATRIPS, 10 942 fulfilled entry criteria and were included in the current analysis. Overall, 8000 (73%) achieved successful recanalization, while 2942 (27%) had UR. In multivariate analysis, factors independently associated with higher odds of UR included older age, higher prestroke mRS, wake-up stroke, interhospital transfer for EVT, higher National Institutes of Health Stroke Scale score at presentation, tPA (tissue-type plasminogen activator) administration, and occlusion of the M2 segment of the middle cerebral artery or proximal anterior or posterior cerebral arteries. Dyslipidemia and occlusion of the M1 middle cerebral artery or basilar artery were associated with successful recanalization. UR was associated with poor clinical outcomes, and higher mortality rates. A predictive tool derived from these variables demonstrated limited discriminatory ability (area under the curve, 0.579 [95% CI, 0.567–0.591];P<0.001).CONCLUSIONS:UR is frequent among patients undergoing EVT and is associated with poor clinical outcomes. Although several pre-EVT factors were independently associated with UR, accurately predicting which patients will experience UR remains highly challenging. Our findings suggest that all eligible patients should undergo EVT.
Core Blood-Brain Barrier Disruption in Patients With Large Vessel Occlusion
That author's affiliation: Johns Hopkins University School of Medicine
First author institution: Johns Hopkins University School of Medicine
Last author institution: Department of Neurosciencies, Germans Trias I Pujol University Hospital, Badalona, Spain
Stroke, Ahead of Print.
BACKGROUND:Multimodal imaging has expanded treatment for patients with acute ischemic stroke with large vessel occlusion. Blood-brain barrier (BBB) disruption measured in the ischemic core is associated with hemorrhagic transformation. However, the associations between core BBB disruption (cBBBD) and baseline clinical/imaging variables, as well as 3-month outcome, have not been explored.METHODS:This is a retrospective multicenter analysis of consecutive anterior circulation patients with acute ischemic stroke with large vessel occlusion, presenting over a 4-year time period, who were transferred from a primary to a comprehensive stroke center for possible endovascular therapy, with magnetic resonance imaging that included perfusion-weighted imaging before transfer. Magnetic resonance imaging scans were processed using RAPID software to generate penumbral imaging variables. Perfusion-weighted images were processed to detect and quantify contrast leakage; cBBBD was calculated as the average of all leaky voxels in the ischemic core. Poor functional outcome was defined as a modified Rankin Scale score of >2 at 3 months. Linear regression was used except for the outcome, which used logistic regression, controlling for age, stroke severity, and baseline functional status.RESULTS:Out of 411 patients transferred for endovascular therapy, 291 were included in this analysis with a median age of 74 years; 49% were female patients. The median National Institutes of Health Stroke Scale score was 13, the mean core volume was 32.3 mL, and the mean cBBBD was 2.1%. 71% of patients underwent endovascular therapy. Admission National Institutes of Health Stroke Scale score (P<0.001) and glucose level (P=0.033) were independently correlated with cBBBD. All imaging variables correlated strongly with cBBBD (P<0.001). The strongest correlation was 0.50, observed between cBBBD and mismatch ratio (r2=0.254). Increasing cBBBD was independently associated with poor functional outcome (adjusted odds ratio, 1.16 [CI, 1.03–1.32];P=0.019; n=279), indicating that for every 1% increase in cBBBD, the odds of having a poor functional outcome increase by 16%.CONCLUSIONS:In acute ischemic stroke with large vessel occlusion, disruption of the BBB in the core lesion is independently associated with clinical outcome. cBBBD represents a new imaging profile for acute stroke that may help guide treatments.
BACKGROUND:Multimodal imaging has expanded treatment for patients with acute ischemic stroke with large vessel occlusion. Blood-brain barrier (BBB) disruption measured in the ischemic core is associated with hemorrhagic transformation. However, the associations between core BBB disruption (cBBBD) and baseline clinical/imaging variables, as well as 3-month outcome, have not been explored.METHODS:This is a retrospective multicenter analysis of consecutive anterior circulation patients with acute ischemic stroke with large vessel occlusion, presenting over a 4-year time period, who were transferred from a primary to a comprehensive stroke center for possible endovascular therapy, with magnetic resonance imaging that included perfusion-weighted imaging before transfer. Magnetic resonance imaging scans were processed using RAPID software to generate penumbral imaging variables. Perfusion-weighted images were processed to detect and quantify contrast leakage; cBBBD was calculated as the average of all leaky voxels in the ischemic core. Poor functional outcome was defined as a modified Rankin Scale score of >2 at 3 months. Linear regression was used except for the outcome, which used logistic regression, controlling for age, stroke severity, and baseline functional status.RESULTS:Out of 411 patients transferred for endovascular therapy, 291 were included in this analysis with a median age of 74 years; 49% were female patients. The median National Institutes of Health Stroke Scale score was 13, the mean core volume was 32.3 mL, and the mean cBBBD was 2.1%. 71% of patients underwent endovascular therapy. Admission National Institutes of Health Stroke Scale score (P<0.001) and glucose level (P=0.033) were independently correlated with cBBBD. All imaging variables correlated strongly with cBBBD (P<0.001). The strongest correlation was 0.50, observed between cBBBD and mismatch ratio (r2=0.254). Increasing cBBBD was independently associated with poor functional outcome (adjusted odds ratio, 1.16 [CI, 1.03–1.32];P=0.019; n=279), indicating that for every 1% increase in cBBBD, the odds of having a poor functional outcome increase by 16%.CONCLUSIONS:In acute ischemic stroke with large vessel occlusion, disruption of the BBB in the core lesion is independently associated with clinical outcome. cBBBD represents a new imaging profile for acute stroke that may help guide treatments.
Home-Based Supervised Cardiorespiratory Interval Training Decreases Poststroke Fatigue and Improves Cardiorespiratory Fitness: A Randomized Controlled Trial
That author's affiliation: Karolinska Institutet
First author institution: Umeå University
Last author institution: Karolinska Institutet
Stroke, Ahead of Print.
BACKGROUND:Poststroke fatigue (PSF) affects nearly half of all stroke survivors and significantly hinders rehabilitation and daily functioning. There is no established treatment. Low cardiorespiratory fitness may contribute to PSF, suggesting aerobic training as a potential intervention.METHODS:In this 2-center, randomized, open-label, blinded end point trial, we evaluated a home-based, supervised cardiorespiratory interval training program (HS-CITP) in individuals with PSF (Swedish Fatigue Assessment Scale score ≥28) 1 to 7 months poststroke. Participants were randomized (1:1) to either HS-CITP or usual care with self-directed activity after early supported discharge. The intervention consisted of 35-minute cycling sessions performed 3 times per week at 70% to 80% of maximum heart rate for 8 weeks. The study was powered to detect a 9-point between-group difference on the Swedish Fatigue Assessment Scale. The primary outcome was self-reported fatigue (Swedish Fatigue Assessment Scale score) at 8 weeks (postintervention), and the secondary outcome was peak oxygen uptake (mL/kg per minute) at 8 weeks. Analyses were performed according to the intention-to-treat principle using adjusted between-group comparisons.RESULTS:Forty-five participants were randomized; the mean age was 64 years, and 56% were women. Forty-three participants completed the postintervention assessment (HS-CITP: n=22; control: n=21). Adherence to HS-CITP was 92%, and no adverse events were reported. In adjusted analyses, compared with the control group, HS-CITP significantly reduced fatigue (between-group mean difference −5.35 Swedish Fatigue Assessment Scale score points [95% CI −9.03 to −3.67];P<0.001) and improved cardiorespiratory fitness (+4.48 mL/kg per minute [95% CI, 3.41–5.54];P<0.001). No significant group-by sex interaction was observed.CONCLUSIONS:Supervised home-based interval training significantly reduced PSF and improved cardiorespiratory fitness, with good adherence and no safety concerns. These findings support integrating structured aerobic exercise into stroke rehabilitation. Larger, longer-term trials are needed to confirm durability, determine the optimal timing poststroke, and evaluate other exercise modalities.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03458884.
BACKGROUND:Poststroke fatigue (PSF) affects nearly half of all stroke survivors and significantly hinders rehabilitation and daily functioning. There is no established treatment. Low cardiorespiratory fitness may contribute to PSF, suggesting aerobic training as a potential intervention.METHODS:In this 2-center, randomized, open-label, blinded end point trial, we evaluated a home-based, supervised cardiorespiratory interval training program (HS-CITP) in individuals with PSF (Swedish Fatigue Assessment Scale score ≥28) 1 to 7 months poststroke. Participants were randomized (1:1) to either HS-CITP or usual care with self-directed activity after early supported discharge. The intervention consisted of 35-minute cycling sessions performed 3 times per week at 70% to 80% of maximum heart rate for 8 weeks. The study was powered to detect a 9-point between-group difference on the Swedish Fatigue Assessment Scale. The primary outcome was self-reported fatigue (Swedish Fatigue Assessment Scale score) at 8 weeks (postintervention), and the secondary outcome was peak oxygen uptake (mL/kg per minute) at 8 weeks. Analyses were performed according to the intention-to-treat principle using adjusted between-group comparisons.RESULTS:Forty-five participants were randomized; the mean age was 64 years, and 56% were women. Forty-three participants completed the postintervention assessment (HS-CITP: n=22; control: n=21). Adherence to HS-CITP was 92%, and no adverse events were reported. In adjusted analyses, compared with the control group, HS-CITP significantly reduced fatigue (between-group mean difference −5.35 Swedish Fatigue Assessment Scale score points [95% CI −9.03 to −3.67];P<0.001) and improved cardiorespiratory fitness (+4.48 mL/kg per minute [95% CI, 3.41–5.54];P<0.001). No significant group-by sex interaction was observed.CONCLUSIONS:Supervised home-based interval training significantly reduced PSF and improved cardiorespiratory fitness, with good adherence and no safety concerns. These findings support integrating structured aerobic exercise into stroke rehabilitation. Larger, longer-term trials are needed to confirm durability, determine the optimal timing poststroke, and evaluate other exercise modalities.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03458884.
Prevalence and Association of Atherosclerosis to Ischemic Stroke in Patients With Atrial Fibrillation on Anticoagulation
That author's affiliation: Alfried Krupp Hospital
First author institution: Alfried Krupp Hospital
Last author institution: Department of Neurology, Heidelberg University Hospital, Germany
Stroke, Ahead of Print.
BACKGROUND:Approximately, 20% of ischemic strokes in patients with atrial fibrillation occur despite anticoagulation. These breakthrough strokes are associated with a high risk of recurrence, but underlying mechanisms remain incompletely understood. In particular, the association between carotid atherosclerosis and breakthrough strokes has not been sufficiently assessed.METHODS:We analyzed data from the prospective, multicenter, RASUNOA-Prime cohort study (Registry of Acute Stroke Under Novel Oral Anticoagulants–Prime), conducted at 46 German stroke centers between 2015 and 2020. Eligible patients had atrial fibrillation and an ischemic stroke within 24 hours before admission. Of 2737 patients, computed tomography angiography was available for 1464 (53.5%). Patients were grouped according to prestroke anticoagulation with direct oral anticoagulants, vitamin K antagonists, or no oral anticoagulation. Carotid atherosclerosis, including stenosis or occlusion and nonstenosing vulnerable plaques, was assessed by core laboratory computed tomography angiography readings. Carotid arteries served as observational units, with presence of atherosclerosis as binary outcome and laterality of carotid-territory ischemia as explanatory variable in generalized linear mixed models. Laterality of atherosclerosis was assessed as ipsilateral if present on the side of carotid-territory ischemia.RESULTS:Any carotid atherosclerosis was identified in 81% of 1464 patients with available computed tomography angiography. Extracranial carotid stenosis ≥50% or occlusion was present in 17%. Among 792 patients with unilateral carotid-territory ischemia and no stenosis, ipsilateral vulnerable carotid plaques were detected in 34% (no oral anticoagulation 28%, direct oral anticoagulants 38%, vitamin K antagonists 38%), including patients with bilateral plaques, whereas 5% had contralateral vulnerable plaques only. In direct oral anticoagulant–treated patients, odds of ipsilateral vulnerable plaque were significantly higher than in nonanticoagulated patients (odds ratio, 4.4 [95% CI, 1.6–11.8];P=0.004).CONCLUSIONS:Stenosing and nonstenosing carotid atherosclerosis represents a frequent comorbidity in patients with breakthrough strokes, which may contribute to their high risk of recurrence. Longitudinal studies including advanced vascular imaging are needed to clarify the impact of atherosclerosis on stroke recurrence after breakthrough strokes in patients with atrial fibrillation.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT02533960.
BACKGROUND:Approximately, 20% of ischemic strokes in patients with atrial fibrillation occur despite anticoagulation. These breakthrough strokes are associated with a high risk of recurrence, but underlying mechanisms remain incompletely understood. In particular, the association between carotid atherosclerosis and breakthrough strokes has not been sufficiently assessed.METHODS:We analyzed data from the prospective, multicenter, RASUNOA-Prime cohort study (Registry of Acute Stroke Under Novel Oral Anticoagulants–Prime), conducted at 46 German stroke centers between 2015 and 2020. Eligible patients had atrial fibrillation and an ischemic stroke within 24 hours before admission. Of 2737 patients, computed tomography angiography was available for 1464 (53.5%). Patients were grouped according to prestroke anticoagulation with direct oral anticoagulants, vitamin K antagonists, or no oral anticoagulation. Carotid atherosclerosis, including stenosis or occlusion and nonstenosing vulnerable plaques, was assessed by core laboratory computed tomography angiography readings. Carotid arteries served as observational units, with presence of atherosclerosis as binary outcome and laterality of carotid-territory ischemia as explanatory variable in generalized linear mixed models. Laterality of atherosclerosis was assessed as ipsilateral if present on the side of carotid-territory ischemia.RESULTS:Any carotid atherosclerosis was identified in 81% of 1464 patients with available computed tomography angiography. Extracranial carotid stenosis ≥50% or occlusion was present in 17%. Among 792 patients with unilateral carotid-territory ischemia and no stenosis, ipsilateral vulnerable carotid plaques were detected in 34% (no oral anticoagulation 28%, direct oral anticoagulants 38%, vitamin K antagonists 38%), including patients with bilateral plaques, whereas 5% had contralateral vulnerable plaques only. In direct oral anticoagulant–treated patients, odds of ipsilateral vulnerable plaque were significantly higher than in nonanticoagulated patients (odds ratio, 4.4 [95% CI, 1.6–11.8];P=0.004).CONCLUSIONS:Stenosing and nonstenosing carotid atherosclerosis represents a frequent comorbidity in patients with breakthrough strokes, which may contribute to their high risk of recurrence. Longitudinal studies including advanced vascular imaging are needed to clarify the impact of atherosclerosis on stroke recurrence after breakthrough strokes in patients with atrial fibrillation.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT02533960.
Characterizing the metabolomes of microglia, astrocytes and neurons in ageing and Alzheimer’s brains
That author's affiliation: UT Southwestern First author institution: Unknown Last author institution: UT Southwestern
Yu, Li and colleagues explore the metabolome of neurons, microglia and astrocytes under normal, ageing and Alzheimer’s disease conditions. They find enrichment of glutathione and polyamine metabolism in microglia, which decreased with ageing and in Alzheimer’s disease.
The cognitive consequences of hypoglycemia in diabetes
Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
Hypoglycemia is a frequent and often serious complication of diabetes management. While its acute effects on cognition are well documented, growing evidence suggests that recurrent or severe hypoglycemia exposure may also contribute to long-term cognitive ...
Hypoglycemia is a frequent and often serious complication of diabetes management. While its acute effects on cognition are well documented, growing evidence suggests that recurrent or severe hypoglycemia exposure may also contribute to long-term cognitive ...
Early Inflammatory Biomarkers Associated With Functional Outcomes in Acute Cerebral Venous Thrombosis: CLOT-VENUS Substudy
Stroke, Ahead of Print.
BACKGROUND:Inflammatory serum biomarkers, including neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are associated with outcomes in acute cerebrovascular diseases. However, their prognostic role in cerebral venous thrombosis remains uncertain. We aimed to assess the prognostic value of these biomarkers in acute cerebral venous thrombosis by identifying optimal thresholds and internally validating their predictive performance.METHODS:This retrospective observational cohort study included adults diagnosed with acute cerebral venous thrombosis from the international CLOT-VENUS registry (Collaboration on Cerebral Venous Thrombosis Study; 2004–2024), including 2 comprehensive stroke centers in the United States and Mexico. Biomarkers of interest (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, PLR, SII) were calculated from admission complete blood counts. The primary outcome was functional status at 6 months, measured by the modified Rankin Scale dichotomized as 0 to 2 versus 3 to 6. Secondary outcomes included modified Rankin Scale score at discharge and mortality. Associations were tested with multivariable logistic regression adjusted for clinically relevant covariates. Optimal biomarker cutoffs were identified using stratified bootstrap receiver operating characteristic analysis and internally validated with out-of-bag testing.RESULTS:Of 432 patients, 394 met the inclusion criteria, and complete data were available for 339 of those patients. Median age was 40 years [interquartile range, 27–45], and 65.2% were female. Elevated biomarkers at admission were associated with modified Rankin Scale score 3 to 6 at discharge and 6 months. At 6 months, optimal cutoff values for neutrophil-to-lymphocyte ratio >4.88 (adjusted odds ratio [aOR], 2.19;P=0.044), monocyte-to-lymphocyte ratio >0.54 (aOR, 2.32;P=0.027), PLR>161.04 (aOR, 3.33;P=0.003), and SII>1388.58 (aOR, 2.03;P=0.049). Similar associations occurred at discharge using the same thresholds. PLR and SII notably predicted mortality at discharge (PLR aOR, 6.33;P=0.008, and SII aOR, 3.93;P=0.031) and at 6 months (PLR aOR, 7.19;P=0.004, and SII aOR, 4.69;P=0.010).CONCLUSIONS:Elevated admission levels of neutrophil-to-lymphocyte ratio, PLR, monocyte-to-lymphocyte ratio, and SII are independently associated with poor discharge and 6-month outcomes in patients with acute cerebral venous thrombosis. These accessible biomarkers may aid early risk stratification. Further studies should validate and explore its usefulness in clinical models for personalized management.
BACKGROUND:Inflammatory serum biomarkers, including neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are associated with outcomes in acute cerebrovascular diseases. However, their prognostic role in cerebral venous thrombosis remains uncertain. We aimed to assess the prognostic value of these biomarkers in acute cerebral venous thrombosis by identifying optimal thresholds and internally validating their predictive performance.METHODS:This retrospective observational cohort study included adults diagnosed with acute cerebral venous thrombosis from the international CLOT-VENUS registry (Collaboration on Cerebral Venous Thrombosis Study; 2004–2024), including 2 comprehensive stroke centers in the United States and Mexico. Biomarkers of interest (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, PLR, SII) were calculated from admission complete blood counts. The primary outcome was functional status at 6 months, measured by the modified Rankin Scale dichotomized as 0 to 2 versus 3 to 6. Secondary outcomes included modified Rankin Scale score at discharge and mortality. Associations were tested with multivariable logistic regression adjusted for clinically relevant covariates. Optimal biomarker cutoffs were identified using stratified bootstrap receiver operating characteristic analysis and internally validated with out-of-bag testing.RESULTS:Of 432 patients, 394 met the inclusion criteria, and complete data were available for 339 of those patients. Median age was 40 years [interquartile range, 27–45], and 65.2% were female. Elevated biomarkers at admission were associated with modified Rankin Scale score 3 to 6 at discharge and 6 months. At 6 months, optimal cutoff values for neutrophil-to-lymphocyte ratio >4.88 (adjusted odds ratio [aOR], 2.19;P=0.044), monocyte-to-lymphocyte ratio >0.54 (aOR, 2.32;P=0.027), PLR>161.04 (aOR, 3.33;P=0.003), and SII>1388.58 (aOR, 2.03;P=0.049). Similar associations occurred at discharge using the same thresholds. PLR and SII notably predicted mortality at discharge (PLR aOR, 6.33;P=0.008, and SII aOR, 3.93;P=0.031) and at 6 months (PLR aOR, 7.19;P=0.004, and SII aOR, 4.69;P=0.010).CONCLUSIONS:Elevated admission levels of neutrophil-to-lymphocyte ratio, PLR, monocyte-to-lymphocyte ratio, and SII are independently associated with poor discharge and 6-month outcomes in patients with acute cerebral venous thrombosis. These accessible biomarkers may aid early risk stratification. Further studies should validate and explore its usefulness in clinical models for personalized management.
Endovascular Thrombectomy Versus Standard Medical Management in Acute Anterior Cerebral Artery Occlusion Stroke: The ORIENTAL-MeVO Registry Study
Stroke, Ahead of Print.
BACKGROUND:The benefit of endovascular thrombectomy (EVT) in patients with stroke with proximal large vessel occlusion in the anterior circulation has been confirmed by several randomized controlled trials. However, evidence regarding EVT for anterior cerebral artery occlusion (ACAo) remains limited. This study aimed to compare clinical outcomes between EVT and standard medical management (SMM) in patients with ACAo.METHODS:This retrospective multicenter study examined data from patients with acute ischemic stroke caused by ACAo (A1/A2/A3 segments) within 24 hours of symptom onset across 25 Chinese centers between September 2019 and September 2024. Eligible patients had ACAo verified by computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography, a prestroke modified Rankin Scale score of ≤2, and received either EVT or SMM exclusively. Patients were excluded due to clot migration from proximal major arteries to the anterior cerebral artery, multiterritory occlusion, or absence of 90-day modified Rankin Scale score data. The primary outcome was the 90-day modified Rankin Scale score distribution. Safety outcomes encompassed 24-hour symptomatic intracranial hemorrhage and 90-day mortality rates. Propensity score matching and inverse probability of treatment weighting analyses were conducted to equilibrate baseline confounders between the EVT and SMM groups.RESULTS:A total of 343 patients with ACAo met the inclusion criteria and were enrolled across all participating centers. Following adjustment for confounders using inverse probability of treatment weighting, the EVT group had statistically significant improvement in 90-day modified Rankin Scale score (adjusted odds ratio, 2.14 [95% CI, 1.59–2.89];P<0.001), excellent functional outcome (aRR, 1.77 [95% CI, 1.27–2.48];P<0.001) and functional independence (aRR, 2.35 [95% CI, 1.63–3.39];P<0.001) compared with the SMM group. Safety outcomes, including symptomatic intracranial hemorrhage and mortality, showed no significant differences between groups. Subgroup analysis revealed improved secondary outcomes in patients with baseline National Institutes of Health Stroke Scale score ≥6.CONCLUSIONS:EVT for ACAo is associated with better clinical outcomes compared with SMM, particularly in patients with moderate to severe stroke, without increased risk of symptomatic intracranial hemorrhage or 90-day mortality.REGISTRATION:URL:www.chictr.org.cn; Unique identifier: ChiCTR2500096954.
BACKGROUND:The benefit of endovascular thrombectomy (EVT) in patients with stroke with proximal large vessel occlusion in the anterior circulation has been confirmed by several randomized controlled trials. However, evidence regarding EVT for anterior cerebral artery occlusion (ACAo) remains limited. This study aimed to compare clinical outcomes between EVT and standard medical management (SMM) in patients with ACAo.METHODS:This retrospective multicenter study examined data from patients with acute ischemic stroke caused by ACAo (A1/A2/A3 segments) within 24 hours of symptom onset across 25 Chinese centers between September 2019 and September 2024. Eligible patients had ACAo verified by computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography, a prestroke modified Rankin Scale score of ≤2, and received either EVT or SMM exclusively. Patients were excluded due to clot migration from proximal major arteries to the anterior cerebral artery, multiterritory occlusion, or absence of 90-day modified Rankin Scale score data. The primary outcome was the 90-day modified Rankin Scale score distribution. Safety outcomes encompassed 24-hour symptomatic intracranial hemorrhage and 90-day mortality rates. Propensity score matching and inverse probability of treatment weighting analyses were conducted to equilibrate baseline confounders between the EVT and SMM groups.RESULTS:A total of 343 patients with ACAo met the inclusion criteria and were enrolled across all participating centers. Following adjustment for confounders using inverse probability of treatment weighting, the EVT group had statistically significant improvement in 90-day modified Rankin Scale score (adjusted odds ratio, 2.14 [95% CI, 1.59–2.89];P<0.001), excellent functional outcome (aRR, 1.77 [95% CI, 1.27–2.48];P<0.001) and functional independence (aRR, 2.35 [95% CI, 1.63–3.39];P<0.001) compared with the SMM group. Safety outcomes, including symptomatic intracranial hemorrhage and mortality, showed no significant differences between groups. Subgroup analysis revealed improved secondary outcomes in patients with baseline National Institutes of Health Stroke Scale score ≥6.CONCLUSIONS:EVT for ACAo is associated with better clinical outcomes compared with SMM, particularly in patients with moderate to severe stroke, without increased risk of symptomatic intracranial hemorrhage or 90-day mortality.REGISTRATION:URL:www.chictr.org.cn; Unique identifier: ChiCTR2500096954.
Motor Impairment and Adaptation in a Novel Nonhuman Primate Model of Internal Capsule Infarct
Stroke, Ahead of Print.
BACKGROUND:Loss of hand control is a major source of poststroke disability, particularly when infarcts involve subcortical white matter. Yet, most preclinical models target the cortex and infer recovery from task performance without quantifying whether improvements reflect restoration or adaptation. To address this, we developed a novel nonhuman primate model of focal internal capsule infarct. This study is exploratory and hypothesis-testing, including prespecified hypotheses regarding motor impairment and adaptation.METHODS:Three adult male rhesus macaques (Macaca mulatta, 5–10 years) received stereotactically guided ET-1 (endothelin-1) injections (0.5 µg/µL; 9–10 µL total) into the left posterior limb of the internal capsule in a within-subject preinfarct versus postinfarct design. Infarcts were characterized by magnetic resonance imaging and postmortem histology. Motor function was tested with a center-out joystick task and a Klüver board task using standard behavioral metrics; hand posture was additionally scored by blinded raters to quantify adaptation. Preinfarct versus postinfarct comparisons used generalized linear mixed models with per-session random effects; adaptation covariates were evaluated using likelihood-ratio tests.RESULTS:Magnetic resonance imaging and histology confirmed focal posterior limb of the internal capsule–centered infarcts with variable volumes. All animals significantly reduced contralesional hand use postinfarct (Fisher exact test; allP<0.05). Generalized linear mixed models showed reduced center-out success rates in 2 animals (P<0.01) and increased path length in one (P=0.0015). Pooled generalized linear mixed models showed significant postinfarct increases in retrieval time (estimate=0.73 s;P<0.0001) and digit flexions (estimate=0.727;P<0.0001). Two animals developed a compensatory wrist-extended, digit-flexed posture by 4 weeks; augmenting generalized linear mixed models with these postural features significantly improved fit (likelihood-ratio tests;P<0.0001).CONCLUSIONS:This model recapitulates key features of human subcortical stroke, including persistent distal motor deficits, shifts in hand preference, systematic motor adaptation, and interindividual variability, establishing a translationally oriented platform for studying stroke mechanisms and evaluating recovery-promoting interventions.
BACKGROUND:Loss of hand control is a major source of poststroke disability, particularly when infarcts involve subcortical white matter. Yet, most preclinical models target the cortex and infer recovery from task performance without quantifying whether improvements reflect restoration or adaptation. To address this, we developed a novel nonhuman primate model of focal internal capsule infarct. This study is exploratory and hypothesis-testing, including prespecified hypotheses regarding motor impairment and adaptation.METHODS:Three adult male rhesus macaques (Macaca mulatta, 5–10 years) received stereotactically guided ET-1 (endothelin-1) injections (0.5 µg/µL; 9–10 µL total) into the left posterior limb of the internal capsule in a within-subject preinfarct versus postinfarct design. Infarcts were characterized by magnetic resonance imaging and postmortem histology. Motor function was tested with a center-out joystick task and a Klüver board task using standard behavioral metrics; hand posture was additionally scored by blinded raters to quantify adaptation. Preinfarct versus postinfarct comparisons used generalized linear mixed models with per-session random effects; adaptation covariates were evaluated using likelihood-ratio tests.RESULTS:Magnetic resonance imaging and histology confirmed focal posterior limb of the internal capsule–centered infarcts with variable volumes. All animals significantly reduced contralesional hand use postinfarct (Fisher exact test; allP<0.05). Generalized linear mixed models showed reduced center-out success rates in 2 animals (P<0.01) and increased path length in one (P=0.0015). Pooled generalized linear mixed models showed significant postinfarct increases in retrieval time (estimate=0.73 s;P<0.0001) and digit flexions (estimate=0.727;P<0.0001). Two animals developed a compensatory wrist-extended, digit-flexed posture by 4 weeks; augmenting generalized linear mixed models with these postural features significantly improved fit (likelihood-ratio tests;P<0.0001).CONCLUSIONS:This model recapitulates key features of human subcortical stroke, including persistent distal motor deficits, shifts in hand preference, systematic motor adaptation, and interindividual variability, establishing a translationally oriented platform for studying stroke mechanisms and evaluating recovery-promoting interventions.
How processing choices effect repeatability in BOLD–CVR imaging
Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
Cerebrovascular reactivity (CVR) is increasingly recognized as a valuable clinical biomarker, making accurate, and reliable quantification essential, particularly in the absence of a gold-standard reference. However, both the acquisition and processing of ...
Cerebrovascular reactivity (CVR) is increasingly recognized as a valuable clinical biomarker, making accurate, and reliable quantification essential, particularly in the absence of a gold-standard reference. However, both the acquisition and processing of ...