Stroke最新文献

Background: Synthetic magnetic resonance imaging (MRI) is an innovative MRI technology that enables the acquisition of multiple quantitative values, including T1 and T2 values, proton density, and myelin volume, in a single scan. Although the usefulness of myelin measurement with synthetic MRI has been reported for assessing several diseases, investigations in patients with stroke have not been reported. We aimed to explore the utility of myelin quantification using synthetic MRI in predicting outcomes in patients with acute ischemic stroke.

Methods: Patients with acute ischemic stroke (n=101) with a premorbid modified Rankin Scale score ≤2 were enrolled. We performed MRI with a 3 T scanner, acquiring synthetic MRI data in addition to data acquired using the routine protocol; we measured total myelin volume (TMV) using synthetic MRI software. After hospitalization, a synthetic MRI was performed when the patient's condition was stable, with a median of 7 days from onset to MRI. We examined the factors related to good stroke outcomes (defined by a modified Rankin Scale score of ≤2 at 3 months).

Results: Patients with larger TMV were younger, were more frequently male, and had higher body mass index. In addition, TMV was associated with the severity of white matter hyperintensities and total small vessel burden scores. The patients with good outcomes (n=66) had larger TMVs than those without (144.85±22.19 versus 126.62±21.81 mL, P<0.001). Multivariable analysis revealed that the TMV quartiles were independently associated with good functional outcomes (odds ratio, 2.54 [95% CI, 1.12-6.70]; P=0.025) after adjusting for baseline clinical characteristics including initial stroke severity, acute brain infarct volume, and brain parenchymal volume.

Conclusions: A large TMV quantified using synthetic MRI was independently associated with good functional outcomes after adjusting for several confounding factors. TMV, which suggests the validity of myelin quantification, might be a useful indicator for predicting stroke outcomes.

Stroke mimics and chameleons remain a major challenge to the clinician and clinical investigator. Misdiagnosis of stroke can result in significant harm to our patients, as well as unnecessary financial costs to the health care systems internationally. The approach to stroke mimics and chameleons has evolved over time with the development of clinical scales and technology. The combination of these tools with clinical acumen can minimize diagnostic errors to the benefit of patients.

Background: Subarachnoid hemorrhage (SAH) is associated with significant mortality and morbidity. The impact of SAH on human glymphatic function remains unknown.

Methods: This prospective, controlled study investigated whether human glymphatic function is altered after SAH, how it differs over time, and possible underlying mechanisms. Glymphatic enrichment was examined by intrathecal contrast-enhanced magnetic resonance imaging (MRI, glymphatic MRI), utilizing the MRI contrast agent gadobutrol (Gadovist, Bayer AG, GE; 0.50 mmol) as a cerebrospinal fluid (CSF) tracer. The distribution of the tracer in the brain and the subarachnoid and ventricular CSF spaces was assessed using standardized multi-phase MRI T1 sequences, and between-group differences in percentage change of standardized T1 signal unit ratios over time were analyzed by linear mixed models.

Results: The study comprised 27 patients with SAH (19 female/8 male; 59.3±10.2 years) who were examined <3 months (n=5), 3 to 6 months (n=10), 6 to 12 months (n=5), or >12 months (n=7) after bleed. A sex- and age-matched control group of 22 individuals (15 female/7 male; 55.5±10.5 years) underwent the same glymphatic MRI protocol but had no neurological or CSF disease. The patients with SAH showed a marked impairment of glymphatic enrichment throughout the brain (particularly addressing the cerebral cortex and subcortical white matter), especially after 24 hours. The glymphatic impairment was accompanied by redistribution of CSF tracer from subarachnoid spaces toward ventricles. These alterations were most pronounced after 3 to 6 months and less after 12 months, though with interindividual variation. CSF tracer transport within perivascular subarachnoid spaces was impaired and coincided with impaired glymphatic enrichment.

Conclusions: Human glymphatic function is severely impaired by SAH, particularly shortly after the event. Glymphatic failure is associated with redistribution of CSF from subarachnoid spaces toward ventricles. SAH-related impairment of fluid transport within perivascular subarachnoid spaces may contribute to reduced glymphatic influx. Since patient groups are small, care should be made when concluding about the impact of time on glymphatic function.

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.

Background: Several social and biological factors are shown to differentially affect stroke outcomes between men and women. We evaluated whether clinical outcomes and endovascular thrombectomy (EVT) treatment effects differed between the sexes in patients presenting with large ischemic stroke.

Methods: The SELECT2 trial (A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke) was a randomized controlled trial assessing the efficacy and safety of EVT in patients with large strokes across the United States, Canada, Europe, Australia, and New Zealand between October 2019 and September 2022. In this subanalysis, baseline characteristics and clinical and imaging outcomes were compared between women and men, each further divided into cohorts receiving medical treatment without and with EVT. Functional outcomes at 90-day and 1-year follow-ups were assessed using regression models, adjusting for potential confounders. Sex-related effect modification was examined.

Results: Women accounted for 145 (41%) of 352 patients enrolled in the SELECT2 trial. Seventy-one (49%) of 145 women and 109 (53%) of 207 men underwent EVT. Endovascular intervention was associated with better functional outcomes (women: adjusted generalized odds ratio, 1.73 [1.22-2.45]; men: adjusted generalized odds ratio, 1.66 [1.24-2.23]; P-int: 0.94), functional independence (women: EVT, 20% versus medical management, 4%; adjusted risk ratio [aRR], 5.04 [1.59-16.02]; men: EVT, 20% versus medical management, 9%; aRR, 1.99 [0.99-4.02]; P-int: 0.20), and independent ambulation (women: EVT, 39% versus medical management, 16%; aRR, 2.44 [1.40-4.24]; men: EVT, 38% versus medical management, 20%; aRR, 1.98 [1.29-3.03]; P-int: 0.67) in both men and women at 90-day follow-up, without significant heterogeneity. Similar results were observed at 1-year follow-up. In women, as age increased (aRR, 0.97 [95% CI, 0.95-0.99]; P=0.004 per year) and core volume estimates increased (aRR, 0.99 [95% CI, 0.98-1.00]; P=0.015 per mL increase), the rate of independent ambulation after EVT decreased. A similar association of age and core volume was seen in men.

Conclusions: EVT treatment benefit was maintained in both women and men, with higher rates of functional independence and independent ambulation as compared with medical management. Age and estimated core infarct volume were independently associated with independent ambulation in both male and female patients. EVT should be equally considered for patients of both sexes meeting large core eligibility criteria.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03876457.

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials-randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol-accelerate the investigation of multiple therapeutic options within a single infrastructure. This in turn has the potential to accelerate access to new interventions for patients with stroke that can save lives and improve outcomes. In the context of acute ischemic stroke, 2 new platform trials have been established, the STEP trial (StrokeNet Thrombectomy Endovascular Platform) and ACT-GLOBAL (A Multi-Factorial, Multi-Arm, Multi-Stage, Randomised, Global Adaptive Platform Trial for Stroke), to address multiple therapeutic questions simultaneously using a multifactorial design including Bayesian modeling and other adaptive features. These trials are designed to maximize the information obtained from each participant, to align clinical research more closely with the complexities of clinical care, and to accelerate the identification of effective therapies. This article explores conceptual, practical, and statistical considerations in the design and implementation of adaptive platform trials and highlights their potential to accelerate the identification of new therapies, management, and rehabilitation in stroke.

Background: Although the presence of amyloid deposits is associated with a more severe cognitive status in patients with stroke at baseline, its influence on the subsequent cognitive outcome has not been extensively assessed. The primary objective of the present study of the IDEA3 (Imagerie des dépôts amyloïdes cérébraux par florbetapir AV-45 et diagnostic des déficits cognitifs et démence post Accident Vasculaire Cérébral) cohort was to determine the influence of amyloid positron emission tomography (PET) status on the 5-year cognitive outcome.

Methods: This longitudinal study performed in Amiens University Hospital (inclusions: October 2014 to October 2019; last visits: October 2018 to February 2023) has included 91 patients with stroke (ischemic stroke, 89%; hemorrhagic stroke, 11%) with florbetapir PET data at baseline (positive, n=14). Patients underwent annually comprehensive clinical and cognitive assessments for 5 years after the PET scan. The primary outcome was incident dementia; secondary outcomes were incident cognitive impairment, total prevalence of cognitive impairment, and modified Rankin Scale score.

Results: A survival analysis (mean poststroke follow-up, 80.4±27 months) showed that the incidence of incident dementia was higher in the PET-positive patients (odds ratio, 9.6 [95% CI, 2.5-36.9]; P=0.001), as was the incidence of incident cognitive impairment (odds ratio, 10 [95% CI, 1.9-52.3]; P=0.003). A Cox regression analysis showed that the association between amyloid status and the incidences of dementia (P=0.001) and cognitive impairment (P=0.007) was still significant after adjustment for age, education, prestroke modified Rankin Scale score and cognitive impairment, stroke type, and the PET status×stroke type interaction. Considering the overall prevalence at the last follow-up in the whole study population (n=91 patients), PET positivity was associated with an elevated risk of dementia (odds ratio, 6 [95% CI, 1.76-20.5]; P=0.002) and poststroke cognitive impairment (odds ratio, 6.25 [95% CI, 1.77-22]; P=0.002). The final modified Rankin Scale score did not differ (P=0.3) according to PET status.

Conclusions: Our results demonstrate the major impact of amyloid deposition on the stroke outcome and emphasized the need for comprehensive etiologic workup in patients with poststroke cognitive impairment.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02813434.