Search Results for: Stroke

Stroke, Ahead of Print. BACKGROUND:The SPAN (Stroke Preclinical Assessment Network) is a confirmatory trial platform to test the efficacy and safety of candidate cerebroprotective interventions in acute stroke. As the largest multicenter preclinical stroke trial to date, the SPAN1 trial (first SPAN) prospectively captured many biological and procedural variables, revealing a high degree of heterogeneity introduced by the multicenter approach that may impact stroke outcomes. Here, we examined the biological and procedural predictors of tissue and neurological outcomes after focal cerebral ischemic stroke in rats.METHODS:SPAN1 enrolled and randomized 698 rats to various active treatment arms or controls. Rats were subjected to transient middle cerebral artery occlusion for 60 (spontaneously hypertensive rats) or 120 minutes (young, healthy Sprague-Dawley rats) and followed for 1 month. Nine biological and procedural independent variables (sex, weight, strain, intervention arm, site, endovascular filament silicone tip coating characteristics, anesthesia duration, and intervention protocol) and 5 dependent outcome variables (weight loss, 4-point neuroscore, corner test, infarct volume, and mortality) were captured. Multivariable regression was used to identify independent predictors of each outcome readout and determine their effect sizes.RESULTS:Spontaneously hypertensive rats exhibited larger infarcts than Sprague-Dawley rats, particularly among females. Neuroscores were also worse in spontaneously hypertensive rats. Prolonged anesthesia exposure was associated with smaller cortical and hippocampal infarcts. Filament thickness and length showed a complex association with different regional infarct volumes, neuroscores, weight loss, and corner test outcomes. Mortality was worse among females. Bivariate analysis of dependent variables revealed moderate correlations among the tissue and neurological outcomes.CONCLUSIONS:Using the large and multicenter, prospective SPAN1 dataset, our multivariable analyses identified several predictors influencing rat middle cerebral artery occlusion outcomes and refuted others previously reported. Investigators should consider whether biological and procedural predictors identified herein should be standardized, accounted for, or stratified during subject allocation to decrease variability and avoid confounders in future multicenter preclinical trials.

New England Journal of Medicine, Ahead of Print.

Stroke, Ahead of Print. Background:Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (.088” inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial.Methods:SUMMIT MAX was a prospective, randomized, controlled, open label clinical trial of patients with ICA and MCA M1 occlusions, comparing the super large bore HiPoint Reperfusion system (Route 92 Medical) to the Vecta Aspiration system (Stryker Neurovascular) (NCT05018650). We hypothesized that the effectiveness and safety of the HiPoint reperfusion system was non-inferior (12.5% non-inferiority margin) to the Vecta Aspiration system. The primary effectiveness endpoint was successful reperfusion, defined as mTICI ≥ 2b as adjudicated by an independent core lab, using only the assigned study device, with any use of a non-study device prior to or following use of study device defined as failure. The primary safety endpoint was symptomatic intracranial hemorrhage (sICH) within 24h (-8/+24) post-procedure.Results:There were 250 patients enrolled of whom 166 met criteria for the modified intent-to-treat population: 89 in HiPoint and 77 in Vecta. The median age was 69; 54.2% were female. Successful reperfusion with any adjunctive therapy counted as a failure was 77.5% (69/89) in the HiPoint group versus 50.6% (39/77) in the Vecta group (p

Stroke, Ahead of Print. BACKGROUND:For patients with acute ischemic stroke due to a large vessel occlusion admitted in primary stroke centers, helicopter transfer to comprehensive stroke centers is often used to expedite access to mechanical thrombectomy. Some studies have suggested that vibrations generated during helicopter transport might enhance intravenous thrombolysis (IVT) efficacy. We aimed to evaluate the impact of helicopter transfer, compared with ground transportation, on interhospital recanalization and functional outcomes.METHODS:We conducted a retrospective analysis of 2 prospectively collected cohorts of anterior circulation acute ischemic stroke due to a large vessel occlusion patients transferred to 2 comprehensive stroke centers (Stanford, CA, November 2019 to January 2023, and Montpellier, France, January 2015 to January 2017) for mechanical thrombectomy consideration with arterial imaging both at the primary stroke center and on comprehensive stroke center arrival. The primary outcome was interhospital recanalization, determined by comparison of the baseline and posttransfer arterial imaging and defined as revised arterial occlusive lesion scores of 2b to 3. The association between transportation mode (helicopter versus ground) and interhospital recanalization was studied in logistic regression analysis, adjusting for pretransfer IVT use, occlusion site, and transfer duration.RESULTS:Among 520 included patients, 315 (61%) were transferred by helicopter and 259 (50%) received IVT before transfer. Interhospital recanalization rates were similar between helicopter and ground transfers in both the overall cohort (23% versus 19%;P=0.30) and the IVT subgroup (36% versus 33%;P=0.61). Adjusted analyses confirmed no association between helicopter transport and interhospital recanalization (adjusted odds ratio, 1.23 [95% CI, 0.72–2.11];P=0.44). Favorable 3-month functional outcome (modified Rankin Scale score, 0–2) rates were also similar between helicopter and ground transfers in both unadjusted (35% versus 40%;P=0.29) and adjusted analyses (adjusted odds ratio, 1.12 [95% CI, 0.67–1.88];P=0.67).CONCLUSIONS:In this multicenter observational cohort study, helicopter transfer was not associated with improved interhospital recanalization or favorable functional outcomes compared with ground transport. These findings do not support the hypothesis that vibrations during helicopter transport enhance IVT efficacy.

Stroke, Ahead of Print.

Stroke, Ahead of Print. Recently, 6 randomized trials evaluated the efficacy and safety of endovascular thrombectomy in patients with large core stroke. This review examines the differences in clinical and imaging eligibility and their impact on the interpretation of evidence and potential neuroimaging workflow. Pending results of a planned patient-level meta-analysis, it also evaluates clinical outcomes and thrombectomy treatment effect across those trials, overall and within selected clinical and imaging subgroups most relevant to clinical practice. Additionally, the implications of extending thrombectomy eligibility to patients with large core stroke on stroke systems of care and societal benefits are discussed.

Stroke, Ahead of Print. BACKGROUND:Parenchymal border macrophages (PBMs) reside at the interface between the central nervous system and the periphery. They are known to mediate the accessibility of the substances to the brain. However, no one has examined their role in poststroke Aβ (amyloid-β) clearance.METHODS:Permanent focal cerebral ischemia was induced in 8- to 10-week-old C57/Bl6 male mice by distal middle cerebral artery occlusion. The clodronate liposomes were administered into the cerebral spinal fluid at 7 days before stroke to deplete the PBM population. Sensorimotor and cognitive functions, glymphatic system, and Aβ accumulation were assessed for up to 34 days after stroke.RESULTS:The Aβ accumulated along brain blood vessels after stroke in both the ipsilateral and contralateral hemispheres. When PBMs were depleted, glymphatic drainage of Aβ was markedly reduced, and this was accompanied by deterioration of cognitive function, highlighting a critical role for PBMs in poststroke Aβ disposal. A possible mechanism relates to MANF (mesencephalic astrocyte-derived neurotrophic factor). MANF derived from PBMs suppressed astrocytic stress and maintained glymphatic drainage when supplemented into the cerebral spinal fluid. In the chronic phase of stroke, MANF production in PBMs was downregulated, and consequently, glymphatic impairments were exacerbated, which led to ongoing Aβ accumulation and cognitive decline.CONCLUSIONS:In summary, supplementation of MANF not only mitigates the adverse impacts of PBM depletion but also exerts therapeutic effects that improve glymphatic system function. We thus propose that this represents a promising strategy to prevent poststroke cognitive impairment.

Stroke, Ahead of Print. BACKGROUND:Stroke is increasingly understood as a network disorder with symptoms often arising from disruption of white matter connectivity. Previous connectome-based lesion-symptom mapping studies revealed that poststroke motor deficits are not only associated with damage to the core sensorimotor network but also with nonsensorimotor connections. However, whether task-specific initial impairment and outcome are based on distinct disconnection patterns remains unknown.METHODS:To address this question, we included lesion information and assessments of distinct aspects of upper limb motor impairment of 113 patients with early subacute stroke (mean age, 65.95 years). We used connectome-based lesion-symptom mapping, based on a normative structural connectome, and a machine learning algorithm to predict individual levels of task-specific motor impairment and outcome >3 months later.RESULTS:We identified task-specific disconnection patterns that significantly predicted initial motor impairment and outcome and a task-general reach-to-grasp network including both sensorimotor and nonsensorimotor areas. More complex reach-to-grasp movements showed a substantial overlap in disconnections for the prediction of impairment and outcome. Conversely, disconnections indicative of more basal aspects of motor control substantially differed between the prediction of initial impairment and outcome at the chronic stage poststroke. Similarly, the significance of interhemispheric disconnections changed in a task- and time-dependent fashion.CONCLUSIONS:In summary, our study identified distinct disconnection patterns indicative of specific aspects of motor impairment and outcome after stroke, highlighting a time- and task-dependent role of the contralesional hemisphere and suggesting a domain-general compensatory role of nonsensorimotor temporal areas. From a mechanistic perspective, differences in disconnection patterns predictive of initial motor impairment versus outcome suggest a stronger dependence of basal motor control on the brain’s structural reserve during motor recovery. Our results extend our current network-level understanding of task-specific motor impairment and recovery, and emphasize the potential of connectome-based lesion-symptom mapping for future clinical applications.

The effect of colchicine on subsequent stroke within 90 days may differ according to the presence of sICAS. Aging might be associated with an increased risk of early recurrent stroke in the patients with sICAS receiving colchicine treatment. Future prospective studies are needed to confirm these results.

Circulation, Ahead of Print. Background:Vascular smooth muscle cells (vSMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. vSMC contractility and function depend on smooth muscle alpha-actin 2 (ACTA2). The pathogenic variantACTA2 c.536G >A(p. R179H) causes multisystemic smooth muscle dysfunction syndrome (MSMDS), a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high-risk early mortality from aneurysms or stroke. No effective treatments exist for MSMDS.Methods:To develop a comprehensive therapy for MSMDS, we utilized CRISPR-Cas9 adenine base editing to correct theACTA2R179H mutation. We generated isogenic human induced pluripotent stem cell (iPSC) lines and humanized mice carrying this pathogenic missense mutation. iPSC-SMCs were evaluated for key functional characteristics, including proliferation, migration, and contractility. The adenine base editor (ABE) ABE8e-SpCas9-VRQR under control of either a SMC-specific promoter or a CMV promoter, and an optimized single guide RNA (sgRNA) under control of U6 promoter were delivered intravenously to humanized R179H mice using adeno-associated virus serotype 9 (AAV9) and phenotypic outcomes were evaluated.Results:The R179H mutation causes a dramatic phenotypic switch in human iPSC-SMCs from a contractile to a synthetic state, a transition associated with aneurysm formation. Base editing prevented this pathogenic phenotypic switch and restored normal SMC function. In humanized mice, the ACTA2R179H/+mutation caused widespread smooth muscle dysfunction, manifesting as decreased blood pressure, aortic dilation and dissection, bladder enlargement, gut dilation, and hydronephrosis. In vivo base editing rescued these pathological abnormalities, normalizing smooth muscle function.Conclusions:This study demonstrates the effectiveness of adenine base editing to treat MSMDS and restore aortic smooth muscle function. By correcting theACTA2R179H mutation, the pathogenic phenotypic shift in SMCs was prevented, key aortic smooth muscle functions were restored, and life-threatening aortic dilation and dissection were mitigated in humanized mice. These findings underscore the promise of gene-editing therapies in addressing the underlying genetic causes of smooth muscle disorders and offer a potential transformative treatment for patients facing severe vascular complications.

Objectives
The influence of short-term variations in blood pressure (BP) in acute stroke on clinical outcomes remains uncertain. Our study explores the relationship between BP variability (BPV) from stroke admission up to 72 hours and in-hospital and 1-year mortality.

Design
Retrospective observational cohort study.

Setting
Hamad General Hospital (HGH) a tertiary care stroke centre in Qatar.

Participants
2820 participants were initially included. After the exclusion of ineligible subjects, 2554 patients (82.5% male, median age 53±9 years) were included. 893 (34.96%) were from the Middle East and North Africa, 1302 (50.98%) were from South Asia, 258 (10.10%) from Southeast Asia, 9 (0.35%) were from East Asia and 92 (3.60%) were from other regions. Eligible participants were adult patients above 18 years of age who presented with acute ischaemic or haemorrhagic stroke. Excluded individuals were those younger than 18 years, had incomplete data, had transient ischaemic attack (TIA), had severe hypoglycaemia on admission (

Stroke, Ahead of Print. BACKGROUND:Poststroke cognitive impairment is associated with disability and decreased quality of life. We assessed whether individual or collective magnetic resonance imaging (MRI) biomarkers can aid in predicting cognitive impairment after lacunar infarction (LACI).METHODS:We conducted a retrospective analysis of data from the American Stroke Association Bugher Small Vessel Study, which included 134 patients within 2 years of an acute LACI, enrolled between 2007 and 2012 at 4 North Carolina hospitals. MRI brain measures at the time of the stroke included as follows: 1, total number of LACIs (index LACI and nonindex radiographic lacunes); 2, size of the largest lacune; 3, ventricular size; 4, cerebral atrophy; 5, radiographic locations (supratentorial, infratentorial, or both); and 6, white matter disease (WMD) extent. WMD extent, cerebral atrophy, and ventricular size were graded using the CHS (Cardiovascular Health Study) scores. The primary outcomes were as follows: 1, total score on Short-Form Montreal Cognitive Assessment to assess global cognition; and 2, time to complete TRAIL Making Test Part B (TMT-B) to evaluate executive function. Regression analyses were used to assess the association between the 6 MRI measures and cognitive function adjusting for demographic and clinical variables.RESULTS:One hundred thirty-four participants completed Short-Form Montreal Cognitive Assessment testing and 100 completed TMT-B at a mean of 76.5 (SD, 172.7) days from the index LACI. There were no associations between MRI characteristics and Short-Form Montreal Cognitive Assessment. On univariable analyses, cerebral atrophy (β=35 [95% CI, 14.17–55.83];P=0.0010), ventricular size (β=40.1 [95% CI, 22.24–57.96];P

Objective
This study aims to observe the correlation between infarction pattern and intracranial arterial stenosis (ICAS) on magnetic resonance and functional outcome in acute ischaemic stroke (AIS) patients after reperfusion therapy.

Design
This is a post hoc analysis of the Third China National Stroke Registry (CNSR-III) study.

Setting
The data was derived from the CNSR-III study, which was a nationwide clinical registry of ischaemic stroke or transient ischaemic attack based in China.

Participants
Patients with anterior circulation AIS who underwent reperfusion therapy were included for analysis. The patients were divided into single acute infarction and multiple acute infarctions (MAIs) based on the diffusion-weighted imaging findings. Additionally, patients were categorised according to the degree of ICAS assessed by magnetic resonance angiography as either ≥50% or

Objective
This study aims to observe the correlation between infarction pattern and intracranial arterial stenosis (ICAS) on magnetic resonance and functional outcome in acute ischaemic stroke (AIS) patients after reperfusion therapy.

Design
This is a post hoc analysis of the Third China National Stroke Registry (CNSR-III) study.

Setting
The data was derived from the CNSR-III study, which was a nationwide clinical registry of ischaemic stroke or transient ischaemic attack based in China.

Participants
Patients with anterior circulation AIS who underwent reperfusion therapy were included for analysis. The patients were divided into single acute infarction and multiple acute infarctions (MAIs) based on the diffusion-weighted imaging findings. Additionally, patients were categorised according to the degree of ICAS assessed by magnetic resonance angiography as either ≥50% or

Stroke, Ahead of Print. BACKGROUND:Accumulating evidence links air pollution exposure to late-life cognitive deterioration. Whether air pollution alters brain structure remains poorly understood. Thus, we aimed to quantify the association between long-term exposure to particulate matter ≤2.5 µm and ≤10 µm (PM2.5and PM10, respectively) and late-life brain structural changes.METHODS:In the Swedish National Study on Aging and Care in Kungsholmen, Stockholm, 555 participants free from dementia underwent brain magnetic resonance imaging (MRI) scans at baseline and after 6 years (cohorts 8.7 μg/m3had on average an annual shrinkage of total brain tissue volume of 0.22 (95% CI, −0.43 to −0.01) and an annual increase of 0.25 (95% CI, 0.07–0.43) of the white matter hyperintensities as compared with participants exposed to PM2.5

Stroke, Ahead of Print. BACKGROUND:The most common cause of arterial ischemic stroke in healthy children, focal cerebral arteriopathy (FCA), can progress rapidly over days with worsening brain injury. A 2017 retrospective Swiss study of corticosteroid treatment for FCA changed practice. To assess its impact, we compared the FCA cohorts from the 2 VIPS (Vascular Effects of Infection in Pediatric Stroke) prospective cohort studies.METHODS:The VIPS II study prospectively enrolled 205 children (29 days to 18 years) with arterial ischemic stroke at 22 centers, December 2016 to January 2022. The local team measured 12-month outcomes using the pediatric stroke outcome measure. A neuroradiologist and pediatric vascular neurologist independently reviewed all clinically obtained imaging and clinical data to classify the cause of arterial ischemic stroke. The neuroradiologist measured the FCA Severity Score on vascular imaging performed at any time poststroke. We compared the VIPS II FCA cohort to the previously published FCA cohort from VIPS I (2010–2014; 37 centers).RESULTS:Of 75 children with definite arteriopathy enrolled in VIPS II, 32 (43%) had FCA, compared with 41 of 127 (32%) of definite arteriopathy cases in VIPS I. The median age was 11.3 years (56% male) in VIPS I and 11.4 years (55%) in VIPS II. Treatment with intravenous corticosteroids increased from 2 of 41 (5%) of FCA patients in VIPS I to 18 of 32 (56%) in VIPS II. The VIPS II FCA cases were more severe at baseline (median FCA Severity Score 6 versus 4;P=0.006). There were no significant differences in either the change in FCA Severity Score (baseline to maximum) or the 12-month neurological outcomes.CONCLUSIONS:Treatment of FCA with corticosteroids increased dramatically between the VIPS I and VIPS II studies. VIPS II cases were more severe at baseline, but we observed no significant difference in disease progression or neurological outcomes. Given the low level of evidence supporting corticosteroid therapy, pediatric stroke centers should enroll FCA patients into ongoing FCA corticosteroid treatment trials.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifiers: NCT04873583 and NCT06040255.