Key PointsQuestionDoes the use of adjunct intra-arterial thrombolysis following an angiographically successful thrombectomy improve functional outcomes in patients with large vessel occlusion acute ischemic stroke?FindingsIn this randomized clinical trial that included 121 adults, treatment with intra-arterial alteplase compared with placebo resulted in a modified Rankin Scale score of 0 or 1 in 59.0% vs 40.4% of patients at 90 days. This difference was statistically significant.MeaningAmong patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days; however, the findings should be considered preliminary until replicated.

C urrent guidelines recommend the assessment of vascular risk factors, target organ damage, and blood pressure (BP) levels to guide the treatment on primary hypertension.1 Besides BP levels, other BP-related features, such as the nocturnal dipping 2 or more recently, visit-to-visit or long-term BP variability (BPV), have been independently associated with clinical cardiovascular outcomes in a recent systematic review and meta-analysis. 3 Also, the prognostic value of BPV measured with ambulatory BP monitoring (ABPM) for 24 hours (also value-to-value or short-term BPV) has been evaluated. Data on short-term BPV from 11 populations 4 suggest a positive association between measures of short-term BPV and cardiovascular death or any (fatal and nonfatal) event. Although the contribution of short-term BPV to the prediction of cardiovascular events was shown to be small (<1%), this is still a matter of debate because results from individual studies support significant contributions. 5,6 It has been also suggested that the prognostic significance of BPV on stroke risk is weaker for short-term than for longterm BPV in treated hypertension. 7 However, these data need further investigation taking into account not only between subject BPV but also within subject BPV.Moreover, several indices of short-term BPV have been related to the presence of subclinical damage in one or multiple organs, including the heart, kidney, and vessels, independently of BP levels. [8][9][10] About the brain, hypertension is a major risk factor for cerebral small vessel disease (CSVD), which is an Abstract-Blood pressure (BP) variability is associated with stroke risk, but less is known about subclinical cerebral small vessel disease (CSVD). We aimed to determine whether CSVD relates to short-term BP variability independently of BP levels and also, whether they improve CSVD discrimination beyond clinical variables and office BP levels. This was a cohort study on asymptomatic hypertensives who underwent brain magnetic resonance imaging and 24-hour ambulatory BP monitoring. Office and average 24-hour, daytime and nighttime BP levels, and several metrics of BP variability (SD, weighted SD, coefficient of variation, and average real variability [ARV]) were calculated. Definition of CSVD was based on the presence of lacunar infarcts and white matter hyperintensity grades. Multivariate analysis and integrated discrimination improvement were performed to assess whether BP variability and levels were independently associated with CSVD and improved its discrimination. Four hundred eighty-seven individuals participated (median age, 64; 47% women). CSVD was identified in 18.9%, related to age, male sex, diabetes mellitus, use of treatment, ambulatory BP monitoring-defined BP levels, and ARV of systolic BP at any period. The highest prevalence (33.7%) was found in subjects with both 24-hour BP levels and ARV elevated. BP levels at any period and ARV (24 hours and nocturnal) emerged as independent predictors of CSVD, and discrimination was incrementally improv...

We found that, in a cohort of hypertensive individuals, the arterial stiffness is associated with the total load of the cSVD, especially with lacunes and basal ganglia EPVS.

Five recent randomized controlled trials provided clear evidence that endovascular thrombectomy (EVT) improves outcomes after acute ischemic stroke caused by large vessel occlusions (LVOs), [1][2][3][4][5] and current guidelines recommend EVT in addition to intravenous thrombolysis (IVT) within 4.5 hours among patients with anterior circulation strokes and LVO. 6,7 Patients eligible for IVT should receive it without delay even if EVT is being considered, but the particular benefit of IVT is not yet well established. Moreover, in the real world, a significant proportion of acute ischemic stroke patients receive IVT at local stroke centers where EVT is not available. Such centers apply a drip and ship protocol when an EVT candidate is identified, with the necessary subsequent transfer causing a delayed puncture. In this context, building up evidence of the specific role of IVT when added to EVT among LVO patients is necessary to reorganize stroke systems of care accordingly. We compared direct EVT (dEVT) against combined IVT+EVT in patients with anterior circulation strokes caused by LVO. MethodsWe used data included in the SONIIA registry (Sistema Online d'Informació de l'Ictus Agut), a government-mandated, populationbased, externally audited, prospective database that includes all acute ischemic stroke patients treated with reperfusion therapies in the region Background and Purpose-Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. Methods-Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. Results-We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). of Catalonia from January 2011. Further details of this registry have been published elsewhere. 8 Briefly, the database includes relevant baseline information (prestroke medical history, medications and functional status, time of stroke onset and hospital arrival, severity, time of neuro/ vascular imaging, IVT and groin puncture time, and complications) and the neurological situation at 24 to 36 hours post-treatment, including symptomatic bleedings. Outcome variables at 3 months are good outcome (modif...

BackgroundSilent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline.Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined.ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline.Methods/DesignCohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia.On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed.Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors.DiscussionImproving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.

Computed tomography perfusion (CTP) allows the estimation of pretreatment ischemic core after acute ischemic stroke. However, CTP-derived ischemic core may overestimate final infarct volume. We aimed to evaluate the accuracy of CTP-derived ischemic core for the prediction of final infarct volume according to time from stroke onset to recanalization in 104 patients achieving complete recanalization after mechanical thrombectomy who had a pretreatment CTP and a 24-h follow-up MRI-DWI. A range of CTP thresholds was explored in perfusion maps at constant increments for ischemic core calculation. Time to recanalization modified significantly the association between ischemic core and DWI lesion in a non-linear fashion ( p-interaction = 0.018). Patients with recanalization before 4.5 h had significantly lower intraclass correlation coefficient (ICC) values between CTP-predicted ischemic core and DWI lesion ( n = 54; best threshold relative cerebral blood flow (rCBF) < 25%, ICC = 0.673, 95% CI = 0.495–0.797) than those with later recanalization ( n = 50; best threshold rCBF < 30%, ICC = 0.887, 95% CI = 0.811–0.935, p = 0.013), as well as poorer spatial lesion agreement. The significance of the associations between CTP-derived ischemic core and clinical outcome at 90 days was lost in patients recanalized before 4.5 h. CTP-derived ischemic core must be interpreted with caution given its dependency on time to recanalization, primarily in patients with higher chances of early recanalization.

T he most effective treatment approach in acute ischemic stroke is early reperfusion, which includes the administration of the r-tPA (recombinant tissue-type plasminogen activator) or the use of mechanical thrombectomy (MT). 1 However, less than half of patients who are treated obtain permanent clinical benefits.1 Early blood-brain barrier (BBB) disruption is one of the main mechanisms implicated in reperfusion ineffectiveness, and it has been associated to the severity of ischemia, adverse effects of thrombolytic drugs, and thrombectomy-related direct vessel damage.2 In experimental brain ischemia, MT causes direct vessel injury in the intimal and medial layers of the arterial wall.3-5 Besides direct mechanical injury, ischemia itself, thrombus inflammatory components, and r-tPA-related toxicity may also compromise the integrity of the endothelial surface.6 Overall, these changes may result in increased endothelial permeability and can be imaged with contrast-enhanced magnetic resonance imaging (MRI). 7,8 Likewise, postgadolinium enhancement of the cerebrospinal fluid space visible on postcontrast fluidattenuated inversion recovery (FLAIR) is an established neuroimaging marker of blood-cerebrospinal fluid barrier (BCSFB) or BBB disruption. In acute ischemic stroke, it has been associated with increased risk of hemorrhage, poor clinical outcome, r-tPA-induced reperfusion injury, and poor early neurological recovery after MT.9-12 However, whether there is a link between vessel wall enhancement and diffuse BCSFB disruption has not been studied previously. Thus, clarifying this potential relationship may be of relevance for Background and Purpose-Less than half of acute ischemic stroke patients treated with mechanical thrombectomy obtain permanent clinical benefits. Consequently, there is an urgent need to identify mechanisms implicated in the limited efficacy of early reperfusion. We evaluated the predictors and prognostic significance of vessel wall permeability impairment and its association with blood-cerebrospinal fluid barrier (BCSFB) disruption after acute stroke treated with thrombectomy. Methods-A prospective cohort of acute stroke patients treated with stent retrievers was analyzed. Vessel wall permeability impairment was identified as gadolinium vessel wall enhancement (GVE) in a 24-to 48-hour follow-up contrast-enhanced magnetic resonance imaging, and severe BCSFB disruption was defined as subarachnoid hemorrhage or gadolinium sulcal enhancement (present across >10 slices). Infarct volume was evaluated in follow-up magnetic resonance imaging, and clinical outcome was evaluated with the modified Rankin Scale at day 90. Results-A total of 60 patients (median National Institutes of Health Stroke Scale score, 18) were analyzed, of whom 28 (47%) received intravenous alteplase before mechanical thrombectomy. Overall, 34 (57%) patients had GVE and 27 (45%) had severe BCSFB disruption. GVE was significantly associated with alteplase use before thrombectomy and with more stent retriever passes, along with the pr...

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