Search Results for: Stroke

Stroke, Ahead of Print. BACKGROUND:After stroke, impairment of hand sensorimotor control leads to improperly scaled and directed fingertip forces that disrupt object manipulation. The objective of this study was to determine the efficacy of finger force magnitude and direction training using 3-dimensional versus 1-dimensional biofeedback to enhance poststroke upper extremity motor recovery.METHODS:A double-blind randomized controlled trial took place in the Veterans Affairs laboratory from 2020 to 2023. Forty-five stroke survivors were randomly assigned to the experimental or control group. Both groups received 18 training sessions to generate digit force in the target magnitude and direction. The experimental group trained with visual feedback on the digit force magnitude in 3 dimensions. The control group trained with 1-dimensional visual feedback on the digit force magnitude along the target direction only. The primary outcome was the change in upper extremity function assessed using the Action Research Arm Test post-intervention.RESULTS:Baseline characteristics were comparable between the groups (mean age, 59 years, 60% male, 40% Black). The change between pretraining and posttraining Action Research Arm Test scores was significantly greater for the experimental group than for the control group (experimental mean, 3.5 [CI, 2.2–4.8] versus control mean, 0.8 [CI, −0.5 to 2.1];P=0.005). This difference was maintained at 1-month follow-up. Secondary analysis showed that individuals in the experimental group whose stroke occurred within a year prior improved more (mean, 6.1 [CI, 4.0–8.3]) than others (P

Stroke, Ahead of Print. Neonatal stroke, occurring within the first 28 days after birth, affects >1 in every 2500 newborns. The weekly adjusted risk of stroke in a term newborn is 3-fold greater than for a male smoker aged 50 to 59 years with diabetes and hypertension. Neonatal stroke has profound clinical and socioeconomic implications, causing cerebral palsy, epilepsy, and various motor, sensory, and cognitive disabilities. Currently, there is no treatment for the brain damage that neonatal stroke causes. Hydrogels, with their tunable elasticity and stiffness, shear-thinning properties, and ability to deliver therapeutic agents locally in a controlled manner, offer significant potential for tissue repair and regeneration. In this review, we synthesize the current knowledge on biocompatible hydrogels, providing insights into how they can be engineered to address the pathophysiology of neonatal stroke and their previous use in repairing severe focal lesions in the adult central nervous system. By exploring cutting-edge hydrogel therapies, this review aims to provide a comprehensive perspective on the potential of hydrogel therapy to improve outcomes for infants suffering from severe brain injury due to neonatal stroke.

Background
Stroke is a leading cause of disability among older adults worldwide, often resulting in significant physical, cognitive and emotional impairments that require long-term care. With ageing populations and increasing stroke prevalence, the demand for appropriate and sustainable long-term care is growing. However, designing care models that align with the complex needs and preferences of elderly patients who had a stroke remains a challenge. This study employs a discrete choice experiment (DCE) to measure and quantify patients’ preferences for long-term care. The primary objectives of this study are as follows: (1) identify and examine the key attributes and levels of long-term care that are most valued by this patient population, (2) assess patients’ preferences for long-term care and explore the role of each attribute on overall preference and (3) explore heterogeneity in preferences based on participants’ characteristics through subgroup analyses.

Methods
The research was conducted in accordance with the design programme of the DCE study. Seven attributes were developed through a systematic literature review, in-depth interviews and experts consultation. A partial factorial survey design was generated through an orthogonal experimental design to optimise the choice scenario sets. We plan to conduct a DCE questionnaire survey in Suzhou, Jiangsu Province, China, and recruit at least 500 participants. The final data will be analysed through a mixed logit model and a latent class model to explore the preference of elderly patients who had a stroke with disabilities for long-term care.

Ethics and dissemination
This study was approved by the Ethics Committee of Nanjing Medical University-Affiliated Suzhou Hospital (K-2024-096 K01). All participants will be required to provide informed consent. The findings of this study will be disseminated and shared with interested patient groups and the general public through a variety of channels, including online blogs, policy briefs, national and international conferences, and peer-reviewed journals.

Stroke, Ahead of Print. BACKGROUND:Hemorrhagic transformation (HT) frequently occurs in acute ischemic stroke patients with a large vessel occlusion undergoing endovascular therapy (EVT), significantly impacting functional outcomes. We aimed to determine whether an early fibrinogen depletion coagulopathy (FDC) was associated with HT following bridging therapy (ie,intravenous thrombolysis [IVT] followed by EVT), and to identify its associated factors.METHODS:We retrospectively analyzed prospectively collected data from 296 patients with acute ischemic stroke with a large vessel occlusion who underwent EVT alone or bridging therapy, with fibrinogen levels measured both before baseline imaging and at the start of the EVT procedure. FDC was defined as a fibrinogen level 1.0 g/L from baseline. The primary outcome was the occurrence of any HT at 24 to 36 hours. Secondary outcomes included symptomatic HT, parenchymal hematomas, and 3-month mortality. The relationships between FDC and outcomes were studied using multivariable logistic regression analyses, adjusting for relevant confounders. We also studied baseline characteristics associated with FDC occurrence.RESULTS:Of the 296 patients enrolled, 102 (34.5%) experienced HT, and 54 (18.2%) developed FDC. FDC was strongly associated with IVT use (53/161 [32.9%] versus 1/135 [0.7%] in IVT-treated and non-IVT-treated patients, respectively;P

Stroke, Ahead of Print. INTRODUCTION:Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of interest.METHODS:OPTIMAS was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7–14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality.RESULTS:We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67–1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36–2.25];Pinteraction=0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD (Pinteractionvalues of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively).CONCLUSIONS:Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03759938.

Stroke, Ahead of Print. BACKGROUND:Early initiation of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation and acute ischemic stroke is beneficial and safe. Whether prior acute reperfusion therapy modifies the treatment effect of early versus late DOAC initiation is unknown.METHODS:For this post hoc analysis of the multicenter, randomized controlled ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation), all participants with data concerning reperfusion treatment were included. The primary outcome was the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Patients were divided into 4 groups based on prior reperfusion therapy: no treatment, intravenous thrombolysis (IVT), endovascular treatment (EVT), or IVT combined with EVT. We performed logistic regression adjusted for age, hypertension, infarct location/size, pre-modified Rankin Scale, NIHSS, and hemorrhagic transformation, including the interaction term between treatment groups (early versus late DOAC) and reperfusion strategy.RESULTS:We included 1973 of 2013 (98%) patients of the ELAN trial population, with a median age of 77 (71–84) years and of whom 899 (46%) were female. Of them, 1015 (51%) underwent no prior reperfusion treatment, 519 (26%) IVT, 190 (10%) EVT, and 249 (13%) IVT+EVT. We did not identify an interaction for any of the outcome events between prior reperfusion therapy and timing of DOAC initiation. Rates were numerically lower in the early DOAC-initiated group for the following: no reperfusion therapy, 17 (3.3%) versus 24 (4.8%; adjusted odds ratio, 0.69 [95% CI, 0.36–1.28]); EVT, 1 (1.2%) versus 7 (6.4%; adjusted odds ratio, 0.25 [95% CI, 0.03–1.21]); and EVT+IVT, 3 (2.4%) versus 4 (3.3%; adjusted odds ratio, 0.76 [95% CI, 0.17–3.23]). In patients who had received IVT, the rates were 3% (n=8) in the early group versus 2% (n=5) in the late group (adjusted odds ratio, 1.52 [95% CI, 0.52–4.84]).CONCLUSIONS:Prior reperfusion therapy does not modify the effect of early versus late DOAC initiation on clinical outcomes in patients with atrial fibrillation and acute ischemic stroke.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Introduction
Stroke is a leading cause of death and disability worldwide. Stroke survivors and their caregivers often face profound social isolation and various participation restrictions, resulting in frustration and adverse health outcomes. Dyad-focused interventions, which address both survivor and caregiver needs, are essential during the transition process. However, few interventions equally prioritise the outcomes of both survivors and caregivers. This study aims to evaluate the efficacy of a newly developed dyad-focused strategy training intervention in enhancing participation among stroke survivors and their caregivers.

Methods and analysis
This study employs a single-blind, parallel-group randomised controlled trial with allocation concealment and assessor blinding. We aim to enrol 138 stroke survivor-caregiver dyads, randomly assigned in a 1:1 ratio to either the experimental intervention group or the control group. Both groups will receive their usual rehabilitation plus 45–60 min sessions of the intervention twice weekly for a total of 12 sessions. Outcome measures, including the Participation Measure-3 Domains, 4 Dimensions, General Self-Efficacy Scale and Activity Measure for Post-Acute Care, will be collected at baseline, post-intervention and at 3-month, 6-month and 12-month follow-ups. Data will be analysed using multiple linear regression and mixed-effects regression models. Qualitative indepth interviews with participants, caregivers and therapists will be conducted post intervention, transcribed and thematically analysed.

Ethics and dissemination
Ethics approval was obtained from the Ethics Committee of Taipei Medical University (approval number: N202203083), National Taiwan University Hospital (approval number: 202207096RINA) and Taipei Tzu Chi Hospital (approval number: 11 M-107). Findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals.

Trial registration number
NCT05571150; Preresults.

Stroke, Ahead of Print. Stroke remains a leading cause of death and disability worldwide. While well-established risk factors play a major role, genetic predisposition is a crucial determinant of stroke susceptibility, with heritability estimates up to 39% for ischemic stroke and 29% for intracerebral hemorrhage. Advances in next-generation sequencing and genome-wide association studies have identified numerous genetic loci associated with stroke risk, paving the way for the development of genetic risk scores. These scores aggregate information from multiple genetic variants to estimate an individual’s stroke risk, offering a promising tool for personalized risk stratification that complements traditional clinical models. While GRSs have demonstrated strong predictive potential for primary stroke events in population-based settings, their integration into clinical practice remains limited. Emerging evidence suggests that GRSs could add value in clinical decision-making, for instance, for stratifying ischemic stroke risk in patients with atrial fibrillation, assessing intracerebral hemorrhage risk in anticoagulant users, and predicting vascular risk factor control in stroke survivors. The incorporation of GRSs with multiomics data and machine learning may further refine risk assessment, driving personalized prevention strategies for both primary and secondary stroke preventions. A major challenge is the limited applicability of GRS across diverse populations, as most genome-wide association studies have been conducted in individuals of European ancestry. Addressing this limitation is critical for ensuring equitable and effective implementation of GRSs in clinical settings. As methodologies continue to evolve, integrating GRS into stroke research could significantly enhance risk assessment and support precision medicine approaches tailored to individual patients.

Stroke, Ahead of Print. BACKGROUND:Poor cerebrovascular reactivity is associated with a higher risk of cerebrovascular disease. The most common method to study cerebrovascular reactivity in aging adults, transcranial Doppler ultrasound, yields measurements in large intracranial arteries, but not in regional brain parenchyma that may be more impaired in some disease processes. Measurements derived from transcranial Doppler ultrasound suggest that there are sex differences in cerebrovascular reactivity for aging adults. We investigated the association between age and sex on cerebrovascular reactivity using blood oxygen level dependent (BOLD) magnetic resonance imaging in a representative group of aging adults.METHODS:This cross-sectional study investigated BOLD cerebrovascular reactivity to CO2in a representative group of aging adults, 51 to 83 years old. We manipulated end-tidal carbon dioxide with breathing exercises and evaluated changes in 6 brain regions: whole brain, white matter, cortical gray matter, subcortical gray matter, left hippocampus, and right hippocampus. We used 1 linear regression per region to investigate the effects of age, sex, and their interaction on BOLD cerebrovascular reactivity.RESULTS:We report an age-by-sex interaction for all brain regions (P≤0.050), except cortical gray matter (P=0.062). For white matter and subcortical gray matter, female participants trended toward an age-related BOLD cerebrovascular reactivity increase (P≤0.058), while male participants did not change with age (P >0.580). In the whole brain and bilateral hippocampi, the age trends for each sex were in opposite directions but not significant (P >0.211). We report a main effect of sex (female greater than male participants) for subcortical gray matter and the right hippocampus (P≤0.048) and no main effect of age in any model.CONCLUSIONS:We present the first report of age-related BOLD cerebrovascular reactivity increases in older female participants and higher BOLD cerebrovascular reactivity in older female compared with male participants. Sex and age-by-sex-based differences seem to be driven by changes in white matter, subcortical gray matter, and bilateral hippocampi.

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.