Stroke最新文献

Novel strategies are needed for the treatment of acute ischemic stroke when revascularization therapies are not clinically appropriate or are unsuccessful. rKLK1 (recombinant human tissue kallikrein-1), a bradykinin-producing enzyme, offers a promising potential solution. In animal studies of acute stroke, there is a marked 36-fold increase in bradykinin B2 receptor on brain endothelial cells of the ischemic region. Due to this environment, rKLK1-generated bradykinin will exert a potent local vasodilation and increase brain perfusion via 3 synergistic signaling pathways downstream to the B2 receptor. Because of its preferential effect on ischemic tissue, systemic adverse effects such as hypotension are avoided with proper dosing. In addition, with initial vasodilation through recruitment of preexisting collaterals, rKLK1 promotes long-term benefit of brain perfusion by promoting new collateral formation. With an extended course of therapy for weeks after acute ischemic stroke, these multifaceted effects may also reduce the risk of stroke recurrence. A prior phase II trial demonstrated a favorable impact on clinical outcomes and recurrent strokes, particularly among patients who were not eligible for mechanical thrombectomy. A phase II/III trial has launched in this population, though opportunities for combination revascularization therapies deserve further investigation.

As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter injury, their risk factors, and comorbidities on cognitive performance among a diverse, nondemented, stroke-free population with cognitive complaints over an extended period of observation. The Diverse VCID (Diverse Vascular Cognitive Impairment and Dementia) study is designed to fill this knowledge gap through 3 assessments of clinical, behavioral, and risk factors; neurocognitive and magnetic resonance imaging measures; fluid biomarkers of Alzheimer disease, vascular inflammation, angiogenesis, and endothelial dysfunction; and measures of genetic risk collected prospectively over a minimum of 3 years in a cohort of 2250 individuals evenly distributed among Americans of Black/African, Latino/Hispanic, and non-Hispanic White backgrounds. The goal of this study is to investigate the basic mechanisms of small vessel cerebrovascular injury, emphasizing clinically relevant assessment tools and developing a risk score that will accurately identify at-risk individuals for possible treatment or clinical therapeutic trials, particularly individuals of diverse backgrounds where vascular risk factors and disease are more prevalent.

There is a large burden of stroke in the United States, and extensive systems of care have been established to address it. The resources devoted to stroke centers are analogous to those of trauma centers, both sharing many strict requirements for certification, clinical preparedness, quality improvement, data management, and reporting. However, trauma programs partly defray these costs through a trauma activation billing code, a billable fee that is charged for activation of the trauma team under strict criteria. There are potential benefits to establishing an analogous national stroke code activation fee. Although a billable stroke code activation fee may increase financial burden on patients, this may be counterbalanced by the significant potential for individual and societal benefits. Providing additional financial support for stroke systems of care may improve acute stroke treatment, reduce stroke burden and poststroke disability, and reduce inequality by broadening the reach of stroke systems of care to disadvantaged communities. Further evaluation of the costs and benefits of implementing a stroke code activation fee based on that currently used by trauma centers is needed.

Background: Communicative ability after stroke influences patient outcomes. Limited research has explored the impact of aphasia when it intersects with cultural or linguistic differences on receiving stroke care and patient outcomes. We investigated associations between requiring an interpreter and the provision of evidence-based stroke care and outcomes for people with aphasia in the inpatient rehabilitation setting.

Methods: Retrospective patient-level data from people with aphasia were aggregated from the Australian Stroke Foundation National Stroke Audit-Rehabilitation Services (2016-2020). Multivariable regression models compared adherence to processes of care (eg, home assessment complete, type of aphasia management) and in-hospital outcomes (eg, length of stay, discharge destination) by the requirement of an interpreter. Outcome models were adjusted for sex, stroke type, hospital size, year, and stroke severity factors.

Results: Among 3160 people with aphasia (median age, 76 years; 56% male), 208 (7%) required an interpreter (median age, 77 years; 52% male). The interpreter group had a more severe disability on admission, reflected by reduced cognitive (6% versus 12%, P=0.009) and motor Functional Independence Measure scores (6% versus 12%, P=0.010). The interpreter group were less likely to have phonological and semantic interventions for their aphasia (odds ratio, 0.57 [95% CI, 0.40-0.80]) compared with people not requiring an interpreter. They more often had a carer (68% versus 48%, P<0.001) and were more likely to be discharged home with supports (odds ratio, 1.48 [95% CI, 1.08-2.04]). The interpreter group had longer lengths of stay (median 31 versus 26 days, P=0.005).

Conclusions: Some processes of care and outcomes differed in inpatient rehabilitation for people with poststroke aphasia who required an interpreter compared with those who did not. Equitable access to therapy is imperative and greater support for cultural/linguistic minorities during rehabilitation is indicated.

Background: Stroke incidence is decreasing in older ages but increasing in young adults. These divergent trends are at least partially attributable not only to diverging trends in stroke risk factors but may also be due to differences in the impact of stroke risk factors at different ages. To address this latter possibility, we used Mendelian randomization to assess differences in the association of stroke risk factors between early-onset ischemic stroke ([EOS]; onset 18-59 years) and late-onset ischemic stroke ([LOS]; onset ≥60 years).

Methods: We identified genetic variants from the GWAS Catalog for use as instrumental variables to proxy conventional stroke risk factors and then estimated the effects of these variants on risk factors in younger and older individuals in the UK Biobank. We then used these estimates to estimate the causal effects of stroke risk factors on EOS (n=6728 cases) and LOS (n=9272) cases from SiGN (Stroke Genetic Network) and the EOSC (Early-Onset Stroke Consortium). Lastly, we compared odds ratios between EOS and LOS, stratified by TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtypes, to determine if differences between estimates could be attributed to differences in stroke subtype distributions.

Results: EOS was associated with higher levels of body mass index, blood pressure, type 2 diabetes, and lower levels of HDL (high-density lipoprotein) cholesterol (all P≤0.002), whereas LOS was associated with higher levels of systolic blood pressure (P=0.0001). The causal effect of body mass index on stroke was significantly stronger for EOS than for LOS (odds ratio, 1.26 versus 1.03; P=0.008). After the subtype-stratified analysis, the difference in causal effect sizes between EOS and LOS for body mass index diminished and was no longer significant.

Conclusions: These results support a causal relationship between body mass index, blood pressure, type 2 diabetes, and HDL cholesterol levels with EOS and blood pressure levels in LOS. Interventions that target these traits may reduce stroke risk.

Background: Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in patients with ischemic stroke.

Methods: This is a predefined substudy to the RESIST (Remote Ischemic Conditioning in Patients With Acute Stroke Trial) randomized clinical trial conducted in Denmark. RIC was started in the ambulance and continued at the hospital for seven days. Blood samples were collected at different time points: prehospital in the ambulance, in-hospital upon arrival, 2 hours postadmission, and 24 hours postadmission. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence.

Results: Of 1500 prehospital randomized patients, 486 patients were included in this study between July 28, 2020, and November 11, 2023, and had blood samples taken. Of these, 249 (51%) had AIS, and here RIC treatment was not associated with increased RBC maximal deformability (RIC, 0.549; sham, 0.548; P=0.31), RBC NO (RIC, 35 301 median fluorescence intensity; sham, 34979 median fluorescence intensity; P=0.89), or nitrite (RIC, 0.036 µmol/L; sham, 0.034 µmol/L; P=0.38), but RIC treatment was associated with a significantly reduced aggregation pressure and a slower erythrocyte aggregation rate (RIC, 323.76 millipascal; sham, 352.74 millipascal; P=0.0113).

Conclusions: Prehospital and in-hospital RIC significantly reduced erythrocyte aggregation rate in patients with acute ischemic stroke, while there was no change in RBC deformability, NO content, or whole blood nitrite levels.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777.

Recovery trajectories in intracerebral hemorrhage (ICH) are recognized as distinct from those observed in ischemic stroke. This narrative review aims to clarify the pathophysiology underlying ICH recovery patterns, highlighting the unique timeline and nature of functional improvements seen in ICH survivors. Population-based cohort studies tracking functional outcomes in a longitudinal fashion, along with randomized clinical trial data with standardized outcome assessments, have demonstrated that ICH recovery generally has a delayed onset in the first weeks, followed by a steep early subacute stage recovery (typically up to 3 months) continuing in protracted, gradual improvements beyond 3 to 6 months. Understanding these recovery patterns, and how these differ from ischemic stroke, is crucial for providing accurate prognostic information, facilitating targeted health care delivery, and optimizing therapeutic interventions and the design of ICH randomized trials. This article synthesizes current evidence on early- and late-stage functional recovery trajectories in primary, spontaneous ICH and cognitive outcomes, emphasizing the clinical and research implications of these recovery patterns.