Elena López-Cancio

Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke

BACKGROUND We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).

Design and Validation of a Prehospital Stroke Scale to Predict Large Arterial Occlusion The Rapid Arterial Occlusion Evaluation Scale

Background and Purpose— We aimed to develop and validate a simple prehospital stroke scale to predict the presence of large vessel occlusion (LVO) in patients with acute stroke. Methods— The Rapid Arterial oCclusion Evaluation (RACE) scale was designed based on the National Institutes of Health Stroke Scale (NIHSS) items with a higher predictive value of LVO on a retrospective cohort of 654 patients with acute ischemic stroke: facial palsy (scored 0–2), arm motor function (0–2), leg motor function (0–2), gaze (0–1), and aphasia or agnosia (0–2). Thereafter, the RACE scale was validated prospectively in the field by trained medical emergency technicians in 357 consecutive patients transferred by Emergency Medical Services to our Comprehensive Stroke Center. Neurologists evaluated stroke severity at admission and LVO was diagnosed by transcranial duplex, computed tomography, or MR angiography. Receiver operating curve, sensitivity, specificity, and global accuracy of the RACE scale were analyzed to evaluate its predictive value for LVO. Results— In the prospective cohort, the RACE scale showed a strong correlation with NIHSS (r=0.76; P<0.001). LVO was detected in 76 of 357 patients (21%). Receiver operating curves showed a similar capacity to predict LVO of the RACE scale compared with the NIHSS (area under the curve 0.82 and 0.85, respectively). A RACE scale ≥5 had sensitivity 0.85, specificity 0.68, positive predictive value 0.42, and negative predictive value 0.94 for detecting LVO. Conclusions— The RACE scale is a simple tool that can accurately assess stroke severity and identify patients with acute stroke with large artery occlusion at prehospital setting by medical emergency technicians.

The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study: Prevalence and risk factors

BACKGROUND AND PURPOSE The ongoing population-based Barcelona-Asymptomatic Intracranial Atherosclerosis (Barcelona-AsIA) study is a prospective study that plans to investigate the natural history of asymptomatic intracranial atherosclerosis (AsIA) in a Caucasian-Mediterranean population, which remains unknown until now. The present study aims to determine the prevalence of AsIA and associated risk factors in the final study cohort. METHODS Crossover, population-based study of a representative sample (randomly selected from our reference population) older than 50 with a moderate-high vascular risk assessed by the vascular equation REGICOR and prior history of neither stroke nor ischemic heart disease. Anthropometric, demographic, clinical data and blood samples were collected at baseline. All individuals underwent a complete extracranial and transcranial color-coded duplex (TCCD) examination. TCCD criteria were used to identify and classify the degree of intracranial stenoses. RESULTS A total of 933 subjects (64% men, mean age 66.3 years) were included in the study. One or more intracranial stenoses were detected at baseline in 80 subjects (8.6%) of whom 31 (3.3%) had moderate-severe lesions. The higher the REGICOR scores the greater the prevalence of AsIA (6.6%, 10.2% and 25% for REGICOR scores 5-9, 10-14 and ≥15, p<0.001). Diabetes (OR 2.95; 95% CI (1.68-5.18); p<0.001), age (OR 1.05; 95% CI (1.02-1.08); p=0.001) and hypertension (OR 1.78; 95% CI (1.02-3.13); p=0.04) were independently associated with any degree of AsIA, while diabetes (OR 2.85; 95% CI (1.16-6.96); p=0.02) and age kept independently associated with moderate-severe AsIA. CONCLUSION The prevalence of AsIA and moderate-severe AsIA in stroke-free Caucasians with a moderate-high vascular risk were 8.6% and 3.3% respectively. Diabetes and age were independently associated with moderate-severe AsIA.

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

Background and Purpose— We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. Methods— We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ⩽ or >80 years; onset-to-groin puncture ⩽ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ⩽2) and mortality at 3 months by multivariate modeling. Results— We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ⩽6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. Conclusions— This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Study

Background and Purpose— Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. Methods— The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. Results— After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD–extracranial atherosclerotic disease. Conclusions— Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular pathway involved in the development of ICAD from its asymptomatic stage.

Structural brain changes and cognition in relation to markers of vascular dysfunction

The aim was to investigate the relationship between blood markers of vascular dysfunction with brain microstructural changes and cognition. Eighty-six participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. We assessed correlations of blood levels of inflammatory biomarkers (C-reactive protein [CRP] and resistin) and fibrinolysis inhibitors (plasminogen activator inhibitor-1 [PAI-1] and A-lipoprotein (Lp (a)) with fractional anisotropy (FA) measurements of diffusion tensor images (DTI), regional gray matter (GM) volumes and performance in several cognitive domains. Increasing levels of C-reactive protein and PAI-1 levels were associated with white matter (WM) integrity loss in corticosubcortical pathways and association fibers of frontal and temporal lobes, independently of age, sex and vascular risk factors. PAI-1 was also related to lower speed and visuomotor/coordination. None of the biomarkers were related to gray matter volume changes. Our findings suggest that inflammation and dysregulation of the fibrynolitic system may be involved in the pathological mechanisms underlying the WM damage seen in cerebrovascular disease and subsequent cognitive impairment.

Association Between Time to Reperfusion and Outcome Is Primarily Driven by the Time From Imaging to Reperfusion

Background and Purpose— A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear. Methods— We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0–2) was described via adjusted odds ratios (ORs) for every 30-minute delay. Results— Median admission National Institutes of Health Stroke Scale was 17.0 (14.0–20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59–0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67–1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54–0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35–0.9) but not in ASPECTS≥8 (OR, 0.99; 95% CI, 0.68–1.44). Conclusions— Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

The Metabolic Syndrome Is Associated With a Higher Resistance to Intravenous Thrombolysis for Acute Ischemic Stroke in Women Than in Men

Background and Purpose— The metabolic syndrome (MetS) might confer a higher resistance to intravenous thrombolysis in acute middle cerebral artery (MCA) ischemic stroke. MetS increases the risk of stroke in women to a greater extent than in men. We aimed to investigate whether there might be sex differences in the impact of MetS on the response to intravenous thrombolysis for acute MCA ischemic stroke. Methods— We prospectively studied consecutive ischemic stroke patients, treated with intravenous tissue-type plasminogen activator according to SITS-MOST criteria, with an MCA occlusion on prebolus transcranial Doppler examination. Resistance to thrombolysis was defined as the absence of complete MCA recanalization 24 hours after tissue-type plasminogen activator infusion by transcranial Doppler criteria. MetS was diagnosed according to the criteria established by the American Heart Association/National Heart, Lung, and Blood Institute 2005 statement. Results— A total of 125 patients (75 men, 50 women; mean age, 67.6±11 years) were included. MetS was diagnosed in 76 (61%) patients. Resistance to clot lysis at 24 hours was observed in 53 (42%) patients. Two multivariate-adjusted, logistic-regression models identified that MetS was associated with a higher resistance to tissue-type plasminogen activator, independently of other significant baseline variables (odds ratio=9.8; 95% CI, 3.5 to 27.8; P=0.0001) and of the individual components of the MetS. The MetS was associated with a significantly higher odds of resistance to thrombolysis in women (odds ratio=17.5; 95% CI, 1.9 to 163.1) than in men (odds ratio=5.1; 95% CI, 1.6 to 15.6; P for interaction=0.0004). Conclusions— The effect of MetS on the resistance to intravenous thrombolysis for acute MCA ischemic stroke appears to be more pronounced in women than in men.

Influence of antiplatelet pre‐treatment on the risk of intracranial haemorrhage in acute ischaemic stroke after intravenous thrombolysis

Background:  Pre‐treatment with antiplatelet agents (AP) is present amongst 30% of acute stroke patients. Previous studies have shown conflicting results on the effect of these drugs regarding haemorrhagic transformation after thrombolytic therapy. The hypothesis that pre‐treatment with AP may increase the risk of cerebral haemorrhage (ICH) after intravenous tissue plasminogen activator (tPA) was assessed.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror’s regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.