Journal of Stroke最新文献

Background and purpose: Although blood pressure (BP) elevation is common in acute ischemic stroke, and guidelines recommend reducing systolic BP to <185 mm Hg prior to reperfusion therapy, the safety and efficacy of active BP lowering in the hyperacute phase before endovascular thrombectomy (EVT) remain uncertain.

Methods: We conducted a retrospective analysis of a prospective hospital-based registry that included consecutive patients with anterior circulation large-vessel occlusion who underwent EVT between 2016 and 2024. Patients were categorized into the active BP lowering in the emergency department (ED) group or the absence of BP lowering in the ED group based on whether they received intravenous antihypertensive treatment prior to EVT. The primary outcome was the distribution of the modified Rankin Scale (mRS) scores at 3 months. Propensity score matching and multivariable regression analyses were also performed.

Results: Of the 492 included patients, 53 (10.8%) received active BP lowering in the ED. After propensity score matching, patients who underwent active BP lowering showed a worse distribution of 3-month mRS scores compared with those who did not receive BP lowering (adjusted odds ratio, 0.38; 95% confidence interval [CI], 0.18 to 0.80; P=0.013). The active BP lowering group exhibited greater infarct volume growth (adjusted β coefficient, 33.4; 95% CI, 18.2 to 48.7; P<0.001), whereas the incidence of symptomatic intracerebral hemorrhage did not differ between groups.

Conclusions: Active BP lowering in the ED before EVT was associated with worse functional outcomes and increased infarct growth without a corresponding reduction in the occurrence of symptomatic intracerebral hemorrhage. These findings highlight the need for caution in initiating antihypertensive therapy before reperfusion and support further investigations to define optimal pre-EVT BP management.

Pharmacogenomic variations may significantly influence responses to commonly prescribed stroke medications. Despite accumulating evidence, genetic testing has not yet been widely integrated into stroke care. This review summarizes current evidence and provides practical guidance for clinical implementation. Pharmacogenomic studies and clinical guidelines related to antiplatelet agents, anticoagulants, and statins were reviewed, with particular emphasis on East Asian populations. Substantial evidence supports genotype-guided use of clopidogrel (CYP2C19), warfarin (CYP2C9, VKORC1, CYP4F2), and statins (SLCO1B1, ABCG2). For aspirin, PTGS1/2 and PEAR1 variants have been investigated; however, current data remain insufficient for clinical application. Regarding direct oral anticoagulants (DOACs), candidate genes such as ABCB1 and CES1 demonstrate pharmacokinetic associations, though robust clinical outcome data are lacking. Distinct allele frequencies in East Asians-such as higher prevalence of CYP2C19 and ABCG2 variants-underscore the need for population-specific strategies. Beyond single-gene approaches, polygenic risk scores, pharmacogenomic panels, and integration with multi-omics data and artificial intelligence represent promising directions for personalized therapy. Pharmacogenomic testing can enhance stroke pharmacotherapy, particularly in populations with high frequencies of actionable variants. Broader implementation requires rapid testing platforms, clinician education, tailored clinical guidelines, and real-world validation of aspirin, DOACs, and multi-gene approaches. Future research should expand population-specific studies and integrate pharmacogenomics within the broader framework of precision medicine to ensure equitable clinical benefit.

Background and purpose: Whether perfusion-diffusion mismatch modifies treatment effect of mechanical thrombectomy (MT) for large strokes is poorly known. To address this question, we conducted a post hoc secondary analysis of the Large Stroke Therapy Evaluation (LASTE) randomized controlled trial (RCT).

Methods: The LASTE RCT compared MT plus best medical treatment (BMT) to BMT alone in patients with large infarct (Alberta Stroke Program Early CT Score 0-5) in the 0-7-hour timewindow. This secondary analysis was restricted to patients with available baseline MR perfusionweighted imaging. We investigated the potential heterogeneity of MT treatment according to the presence of perfusion-diffusion mismatch, defined as a mismatch ratio ≥1.2, calculated as the time-to-maximum >6 seconds cerebral volume divided by ischemic core volume. The primary outcome was better functional outcome (favorable shift in the distribution of modified Rankin Scale [mRS] at 90 days, analyzed using generalized odds ratio [GenOR]).

Results: A total of 102/324 patients were included, among whom 55 (54%) had a perfusiondiffusion mismatch. No significant treatment effect heterogeneity by diffusion-perfusion mismatch was observed for the primary outcome (GenOR for better functional outcome: 1.70 [95% confidence interval, CI, 0.95 to 3.05] and 1.04 [95% CI, 0.57 to 1.87] in patients with and without mismatch, respectively; ratio of GenORs: 1.63 [95% CI, 0.71 to 3.74]; P for heterogeneity=0.24) or for the secondary efficacy and safety outcomes.

Conclusions: Our study found no evidence of heterogeneity of treatment effect with respect to benefit or safety in patients with unrestricted infarct size at baseline treated with MT by presence of perfusion-diffusion mismatch. An individual participant-data meta-analysis of RCT is needed for definitive conclusions.

Background and purpose: Stroke impairs cognition and movement. Although clinical severity and infarct volume can predict functional outcomes, variability in patient responses requires advanced structural and functional connectivity methods. Disconnection markers were tested to predict functional outcomes after acute ischemic stroke using diffusion tensor imaging.

Methods: A probabilistic approach was used to quantify brain damage from white matter (WM) disconnections affecting cortical areas, using lesion masking on a tractography atlas and parcellation of gray matter into functional network nodes. Forty-three patients with acute ischemic stroke were grouped according to functional improvement (change in modified Rankin Scale score from 3-5 at discharge to 0-2 at 3-month follow-up). Significantly different structural disconnection measures between the groups were combined into a principal component and included in a logistic regression model to evaluate prediction accuracy. Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity of the disconnected WM tracts were analyzed.

Results: Baseline structural disconnections in the mid-posterior and central corpus callosum predicted poor functional outcomes at 3 months, and increased somatomotor network (SMN) disconnection severity correlated with poor recovery. Age, National Institutes of Health Stroke Scale score, and structural disconnections significantly predicted functional outcomes in logistic regression models. The first principal component analysis of the dysconnectivity measures explained 88% of the total variance and improved prediction accuracy from 53.8% to 76.9%. Differences in FA and RD in the region of interest of the corpus callosum between outcome groups were statistically significant.

Conclusions: Predictive outcome markers from probabilistic structural disconnection mapping in acute stroke emphasize preserving interhemispheric corpus callosum and SMN connections.

Background and purpose: In patients with ischemic stroke and isolated cervical internal carotid artery occlusion (c-ICA-O), endovascular therapy (EVT) can improve cerebral perfusion. To maintain vessel patency, EVT is frequently combined with carotid artery stenting (CAS). We assessed the efficacy and safety of emergent CAS during EVT for isolated c-ICA-O.

Methods: This retrospective multinational cohort study (42 centers) included consecutive patients who underwent EVT for isolated c-ICA-O within 24 hours from the time last seen well. Patients who underwent emergent CAS were compared with those who did not. Co-primary outcomes were c-ICA vessel patency and symptomatic intracerebral hemorrhage (sICH) 24 hours post-EVT. Secondary outcomes included any intracerebral hemorrhage (ICH) at 24 hours and disability at 3 months (modified Rankin Scale [mRS] shift). Outcomes were adjusted using inverse probability of treatment weighting.

Results: Of 317 patients (mean age, 68.6 years [standard deviation, 12.9]; median National Institutes of Health Stroke Scale 11 [interquartile range, 6-17]; 26.8% female), 219 (69.1%) underwent CAS, whereas 98 (30.9%) did not. At 24 hours, vessel patency was more common after CAS (83.5% vs. 40.7%; adjusted odds ratio [aOR], 9.45; 95% confidence interval [CI], 4.91-18.17); sICH rates did not differ (2.3% vs. 3.1%; aOR, 0.92; 95% CI, 0.18-4.73). Any ICH was more common after CAS (19.3% vs. 9.3%; aOR, 2.50; 95% CI, 1.12-5.60). CAS was not associated with mRS at 3 months (adjusted common odds ratio, 0.98; 95% CI, 0.62-1.56).

Conclusions: In patients undergoing EVT for isolated c-ICA-O, emergent CAS was technically effective and reasonably safe. More frequent vessel patency in patients who underwent CAS did not translate into improved functional outcome at 3 months.

Background and purpose: Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD).

Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert's syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al.

Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41-2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43-2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45-2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson-Neyman analyses showed cut-off concentrations of 22.3-22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not.

Conclusions: Mildly elevated TBIL may modify the association between hypertension and CSVD.