OBJECTIVETo assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced ...neuroimaging.
METHODSWe performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes3-month favorable functional outcome (FFO; modified Rankin Scale mRS scores 0–1), 3-month functional independence (FI; mRS scores 0–2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR).
RESULTSWe identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio OR 1.48, 95% confidence interval CI 1.12–1.96), FI (OR 1.42, 95% CI 1.07–1.90), sICH (OR 5.28, 95% CI 1.35–20.68), and CR (OR 3.29, 95% CI 1.90–5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93–3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR ORadj 1.62, 95% CI 1.20–2.20), functional improvement (ORadj 1.42, 95% CI 1.11–1.81), and sICH (ORadj 6.22, 95% CI 1.37–28.26). There was no association between IVT and FI (ORadj 1.61, 95% CI 0.94–2.75) or all-cause mortality (ORadj 1.75, 95% CI 0.93–3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses (I = 0).
CONCLUSIONIVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH.
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 (ORadj) 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 (ORadj, 1.19 95% CI,1.00–1.43; I=78%, P value for Cochran Q test0.001) and symptomatic intracranial hemorrhage (ORadj, 1.65 95% CI, 1.11–2.44; I=0%, P value for Cochran Q test0.80), respectively. Increasing pre- and post-MT mean SBP levels were associated with lower odds of 3-month functional independence (ORadj, 0.86 95% CI, 0.77–0.96; I=18%, P value for Cochran Q test0.30) and (ORadj, 0.80 95% CI, 0.72–0.89; I=0%, P value for Cochran Q test0.51), 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.
OBJECTIVE:Our aim was to evaluate the diagnostic yield of transesophageal echocardiography (TEE) in consecutive patients with ischemic stroke (IS) fulfilling the diagnostic criteria of embolic ...strokes of undetermined source (ESUS).
METHODS:We prospectively evaluated consecutive patients with acute IS satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary care stroke centers during a 12-month period. We also performed a systematic review and meta-analysis estimating the cumulative effect of TEE findings on therapeutic management for secondary stroke prevention among different IS subgroups.
RESULTS:We identified 61 patients with ESUS who underwent investigation with TEE (mean age 44 ± 12 years, 49% men, median NIH Stroke Scale score = 5 points interquartile range3–8). TEE revealed additional findings in 52% (95% confidence interval CI40%–65%) of the study population. TEE findings changed management (initiation of anticoagulation therapy, administration of IV antibiotic therapy, and patent foramen ovale closure) in 10 (16% 95% CI9%–28%) patients. The pooled rate of reported anticoagulation therapy attributed to abnormal TEE findings among 3,562 acute IS patients included in the meta-analysis (12 studies) was 8.7% (95% CI7.3%–10.4%). In subgroup analysis, the rates of initiation of anticoagulation therapy on the basis of TEE investigation did not differ (p = 0.315) among patients with cryptogenic stroke (6.9% 95% CI4.9%–9.6%), ESUS (8.1% 95% CI3.4%–18.1%), and IS (9.4% 95% CI7.5%–11.8%).
CONCLUSIONS:Abnormal TEE findings may decisively affect the selection of appropriate therapeutic strategy in approximately 1 of 7 patients with ESUS.
BACKGROUND AND PURPOSE—Endovascular intervention for emergent large-vessel occlusion (ELVO) has evolved rapidly during the past decade. The question of whether pretreatment with intravenous ...thrombolysis (IVT) has a significant impact on the functional outcome of patients with ELVO still remains unanswered.
METHODS—We conducted a systematic review and meta-analysis of all available randomized controlled trials evaluating the efficacy of endovascular therapy (ET) for acute ischemic stroke. We performed a mixed-effects subgroup analysis of the reported odds ratios on the association of ET (versus standard therapy) with 3-month functional outcome, stratified by pretreatment with IVT.
RESULTS—Six randomized controlled trials were included, comprising 1916 total patients (49.1% receiving ET with IVT pretreatment and 5.6% receiving ET without IVT pretreatment). In the subgroup analysis, ET was associated with a higher likelihood of better 3-month functional outcome in both the subgroup of patients with (odds ratio=1.83; 95% confidence interval, 1.37–2.44; P<0.001) and without (odds ratio=2.47; 95% confidence interval, 1.32–4.63; P=0.001) pretreatment with IVT. We documented no significant effect of IVT pretreatment on the 3-month functional outcome of patients with ELVO undergoing ET, suggesting that ET is effective in all patients with ELVO. Heterogeneity was documented in the IVT pretreatment subgroup (I=68.3%; P for Cochran Q=0.014), but not in the subgroup that did not receive IVT pretreatment (I=0%, P for Cochran Q=0.927). The risk of bias was considered to be generally low in the qualitative assessment of the included trials.
CONCLUSIONS—Our observation provides evidence and further reassurance to stroke clinicians regarding the efficacy of ET in ELVO independent of pretreatment with IVT.
Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a ...systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62–0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59–0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75–0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention.
There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.
We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal.
Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval CI 36%-66%;
= 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3;
= 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors.
Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination.
The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).
Although statins have been associated with increased risk of spontaneous intracerebral hemorrhage, their relationship with cerebral microbleeds (CMBs) formation is poorly understood. We ...systematically reviewed previously published studies reporting on the association between CMBs presence and current statin use.
We performed a systematic search in MEDLINE and SCOPUS databases on October 24, 2019 to identify all cohorts from randomized-controlled clinical trials or observational studies reporting on CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Random effects model was used to calculate the pooled estimates. We included 7 studies (n = 3734 participants): unselected general population n = 1965, ischemic stroke n = 849, hemorrhagic stroke n = 252 and patients with hypertension over the age of 60 n = 668. Statin use was not associated with CMBs presence in either unadjusted (OR = 1.15, 95%CI: 0.76–1.74) or adjusted analyses (OR = 1.09, 95%CI: 0.64–1.86). Statin use was more strongly related to lobar CMB presence (OR = 2.01, 95%CI: 1.48–2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR = 2.26, 95%CI: 0.86–5.91). Except for the analysis on the unadjusted probability of lobar CMBs presence, considerable heterogeneity was present in all other analyses (I2 > 60%). Our findings suggest that statin treatment seems not to be associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.
•The relationship of statins with cerebral microbleeds (CMBs) formation is unknown.•This meta-analysis evaluates the association between CMBs presence and statin use.•Unadjusted and adjusted analyses uncovered no association of statins with CMBs presence.•Statin use was related to a two-fold higher chance for lobar CMB presence.•This association was consistent, but no statistically significant, in adjusted analysis.
Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between ...cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ to alarm clinicians in recognizing COVID-19-related stroke.
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