BackgroundSince large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death.MethodsTo delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3–6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset.ResultsAmong 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3–6) within 3–6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53–5.63, p < 0.0001). Mortality within 3–6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5–6.68), p < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8–55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8–81.3%) of poststroke dependence or death and 95.6% (CI: 89.0–98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality.ConclusionLVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes.

Background and Purpose- The purpose of this study is to evaluate the relationship between neutrophil-to-lymphocyte ratio (NLR) at admission with safety and efficacy outcomes in acute stroke patients with large vessel occlusion after mechanical thrombectomy. Methods- Consecutive large vessel occlusion patients treated with mechanical thrombectomy during a 4-year period were evaluated. Outcome measures included symptomatic intracranial hemorrhage, 3-month mortality, successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/3), and 3-month functional independence (modified Rankin Scale scores of 0-2). Results- A total of 293 large vessel occlusion patients underwent mechanical thrombectomy (median admission NLR, 3.5; interquartile range [IQR], 1.7-6.8). In initial univariable analyses, higher median admission NLR values were documented in patients with symptomatic intracranial hemorrhage (8.5; IQR, 4.7-11.3) versus (3.9; IQR, 1.9-6.5); P<0.001 and individuals who were dead at 3-months (5.4; IQR, 2.8-9.6) versus (4.0; IQR, 1.8-6.4); P=0.004. Lower NLR values were recorded in patients with 3-month functional independence (3.7; IQR, 1.7-6.5) versus (4.3; IQR, 2.6-8.3); P=0.039. After adjustment for potential confounders, a 1-point increase in NLR was independently associated with higher odds of symptomatic intracranial hemorrhage (odds ratio, 1.11; 95% CI, 1.03-1.20; P=0.006) and 3-month mortality (odds ratio, 1.08; 95% CI, 1.01-1.16; P=0.014). Conclusions- Higher admission NLR is an independent predictor of symptomatic intracranial hemorrhage and 3-month mortality in large vessel occlusion patients treated with mechanical thrombectomy, and it may identify a target group for testing adjunctive anti-inflammatory therapies.

Objective: The substantial clinical improvement in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT), combined with the poor response of proximal intracranial occlusions to intravenous thrombolysis (IVT), led to questions regarding the utility of bridging therapy (BT; IVT followed by MT) compared to direct mechanical thrombectomy (dMT) for AIS patients with large vessel occlusion (LVO). Methods: We aimed to investigate the comparative safety and efficacy of BT and dMT in AIS patients. We included all observational studies and post hoc analyses from randomized controlled clinical trials that provided data on the outcomes of AIS patients with LVO stratified by IVT treatment status prior to MT. Results: We identified 38 eligible observational studies (11,798 LVO patients, mean age = 68 years, 56% treated with BT). In unadjusted analyses, BT was associated with a higher likelihood of 3-month functional independence (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.32-1.76), 3-month functional improvement (common OR [cOR] for 1-point decrease in modified Rankin Scale score = 1.52, 95% CI = 1.18-1.97), early neurological improvement (OR = 1.21, 95% CI = 1.83-1.76), successful recanalization (OR = 1.22, 95% CI = 1.02-1.46), and successful recanalization with ≤2 device passes (OR = 2.28, 95% CI = 1.43-3.64) compared to dMT. BT was also related to a lower likelihood of 3-month mortality (OR = 0.64, 95% CI = 0.57-0.73). In the adjusted analyses, BT was independently associated with a higher likelihood of 3-month functional independence (adjusted OR = 1.55, 95% CI = 1.26-1.91) and lower odds of 3-month mortality (adjusted OR = 0.80, 95% CI = 0.66-0.97) compared to dMT. The two groups did not differ in functional improvement (adjusted cOR = 1.24, 95% CI = 0.89-1.74) or symptomatic intracranial hemorrhage (adjusted OR = 0.87, 95% CI = 0.61-1.25).Interpretation: BT appears to be associated with improved functional independence without evidence for safety concerns, compared to dMT, for AIS patients with LVO.

Limited data exist evaluating the effect of blood pressure (BP) on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with mechanical thrombectomy (MT). We sought to evaluate the association of BP levels on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with MT. Studies were identified that reported the association of systolic BP (SBP) or diastolic BP levels before, during, or after MT on the outcomes of patients with acute ischemic stroke treated with MT. Unadjusted and adjusted analyses of studies reporting odds ratios (OR adj ) per 10 mm Hg BP increment were performed. Our analysis included 25 studies comprising 6474 patients. Higher pre-MT mean SBP ( P =0.008) and post-MT maximum SBP ( P =0.009) levels were observed in patients who died within 3 months. Patients with 3-month functional independence were noted to have lower pre-MT ( P <0.001) and post-MT maximum SBP levels ( P <0.001). In adjusted analyses, increasing post-MT maximum SBP and diastolic BP levels were associated with 3-month mortality (OR adj , 1.19 [95% CI,1.00–1.43]; I 2 =78%, P value for Cochran Q test: 0.001) and symptomatic intracranial hemorrhage (OR adj , 1.65 [95% CI, 1.11–2.44]; I 2 =0%, P value for Cochran Q test: 0.80), respectively. Increasing pre- and post-MT mean SBP levels were associated with lower odds of 3-month functional independence (OR adj , 0.86 [95% CI, 0.77–0.96]; I 2 =18%, P value for Cochran Q test: 0.30) and (OR adj , 0.80 [95% CI, 0.72–0.89]; I 2 =0%, P value for Cochran Q test: 0.51), respectively. In conclusion, elevated BP levels before and after MT are associated with adverse outcomes among patients with acute ischemic stroke with large vessel occlusion.

Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.

The benefit of mechanical thrombectomy (MT) in patients with stroke presenting with mild deficits (National Institutes of Health Stroke Scale [NIHSS] score <6) owing to emergency large-vessel occlusion (ELVO) remains uncertain. OBJECTIVE To assess the outcomes of patients with mild-deficits ELVO (mELVO) treated with MT vs best medical management (bMM). DATA SOURCES We retrospectively pooled patients with mELVO during a 5-year period from 16 centers. A meta-analysis of studies reporting efficacy and safety outcomes with MT or bMM among patients with mELVO was also conducted. Data were analyzed between 2013 and 2017. STUDY SELECTION We identified studies that enrolled patients with stroke (within 24 hours of symptom onset) with mELVO treated with MT or bMM. MAIN OUTCOMES AND MEASURES Efficacy outcomes included 3-month favorable functional outcome and 3-month functional independence that were defined as modified Rankin Scale scores of 0 to 1 and 0 to 2, respectively. Safety outcomes included 3-month mortality and symptomatic and asymptomatic intracranial hemorrhage (ICH). RESULTS We evaluated a total of 251 patients with mELVO who were treated with MT (n = 138; 65 women; mean age, 65.2 years; median NIHSS score, 4; interquartile range [IQR], 3-5) or bMM (n = 113; 51 women; mean age, 64.8; median NIHSS score, 3; interquartile range [IQR], 2-4). The rate of asymptomatic ICH was lower in bMM (4.6% vs 17.5%; P = .002), while the rate of 3-month FI (after imputation of missing follow-up evaluations) was lower in MT (77.4% vs 88.5%; P = .02). The 2 groups did not differ in any other efficacy or safety outcomes. In multivariable analyses, MT was associated with higher odds of asymptomatic ICH (odds ratio [OR], 11.07; 95% CI, 1.31-93.53; P = .03). In the meta-analysis of 4 studies (843 patients), MT was associated with higher odds of symptomatic ICH in unadjusted analyses (OR, 5.52; 95% CI, 1.91-15.49; P = .002; I 2 = 0%). This association did not retain its significance in adjusted analyses including 2 studies (OR, 2.06; 95% CI, 0.49-8.63; P = .32; I 2 = 0%). The meta-analysis did not document any other independent associations between treatment groups and safety or efficacy outcomes. CONCLUSIONS AND RELEVANCE Our multicenter study coupled with the meta-analysis suggests similar outcomes of MT and bMM in patients with stroke with mELVO, but no conclusions about treatment effect can be made. The clinical equipoise can further be resolved by a randomized clinical trial.

Differential leukocyte counts on admission were independently associated with clinical outcomes in patients with AIS treated with IVT. These inflammatory biomarkers are potential targets for adjunctive neuroprotection in this stroke subgroup.

Background and PurposeAlthough arbitrary blood pressure (BP) thresholds exist for acute ischemic stroke (AIS) patients eligible for intravenous thrombolysis (IVT), current international recommendations lack clarity on the impact of mean pre- and post-IVT BP levels on clinical outcomes. MethodsEligible studies involving IVT-treated AIS patients were identified that reported the association of mean systolic BP (SBP) or diastolic BP levels before and after IVT with the following outcomes: 3-month favorable functional outcome (modified Rankin Scale [mRS] scores of 0–1) and 3-month functional independence (mRS scores of 0–2), 3-month mortality and symptomatic intracranial hemorrhage (sICH). Unadjusted analyses of standardized mean differences and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed using random-effects models. ResultsWe identified 26 studies comprising 56,513 patients. Higher pre- (P=0.02) and posttreatment (P=0.006) SBP levels were observed in patients with sICH. Patients with 3-month functional independence had lower post-treatment (P<0.001) SBP whereas trended towards lower pre-treatment (P=0.06) SBP. In adjusted analyses, elevated pre- (ORadj, 1.08; 95% confidence interval [CI], 1.01 to 1.16) and post-treatment (ORadj, 1.13; 95% CI, 1.01 to 1.25) SBP levels were associated with increased likelihood of sICH. Increasing pre- (ORadj, 0.91; 95% CI, 0.84 to 0.98) and post-treatment (ORadj, 0.70; 95% CI, 0.57 to 0.87) SBP values were also related to lower odds of 3-month functional independence. ConclusionsWe found that elevated BP levels adversely impact AIS outcomes in patients receiving IVT. Future randomized-controlled clinical trials will provide definitive data on the aforementioned association.