María Hernández-Pérez

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.

Safety and Efficacy of Solitaire Stent Thrombectomy Individual Patient Data Meta-Analysis of Randomized Trials

Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and 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 (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29–5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Conclusions— Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups.

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.

Ankle-brachial index in screening for asymptomatic carotid and intracranial atherosclerosis

OBJECTIVE To evaluate usefulness of ankle-brachial index (ABI) in the screening for asymptomatic cervico-cerebral atherosclerosis (CCA) against traditional vascular risk assessment. METHODS This study included a random population sample of 933 Caucasians without prior cardiovascular disease but with a moderate and high vascular risk (REGICOR score 5-9% and ≥ 10%). Presence and degree of CCA was evaluated by color-coded duplex and significant stenosis >50% (SCCA) confirmed by MRA. RESULTS Prevalence of significant carotid and/or intracranial stenosis was 6% in the whole population, but increased up to 25% among those subjects with ABI ≤ 0.9 regardless of REGICOR score. Using REGICOR ≥ 10%, the likelihood ratio (LR) for the detection of SCCA was 1.8, while using ABI ≤ 0.90 the LR was 6.0. After multivariate regression analysis, low ABI was independently associated with SCCA whereas REGICOR score was not. Less than 40% of subjects with SCCA were taking antiplatelet drugs or statins at the moment of diagnosis. CONCLUSION ABI emerged as a useful and simple tool in identifying asymptomatic SCCA in our population. This finding may be important for improving stroke primary prevention strategies.

Hyperintensity of Distal Vessels on FLAIR Is Associated with Slow Progression of the Infarction in Acute Ischemic Stroke

Background: Hyperintensity of distal vessels on FLAIR-MRI has been associated with a higher grade of arterial collaterals and a smaller infarct volume in acute stroke patients. No studies analyze the influence of the hyperintense vessel (HV) sign on the speed of the ischemia progression during the first hours. Our aim was to study the association of the HV sign with progression of infarction in acute stroke patients. Methods: From a prospectively derived stroke database, we retrospectively selected acute stroke patients with a large artery occlusion of the anterior circulation admitted to our comprehensive stroke center with available baseline CT scan and a multimodal MRI carried out thereafter to make a decision about endovascular treatment. Progression of the ischemic area was calculated as the difference in the Alberta Stroke Program Early CT Scan (ASPECTS) score between CT scan and diffusion-weighted imaging (DWI). Slow progression was considered as no change or 1 point decrease on the ASPECTS score between both exams. The presence of HV on FLAIR sequence was graded as absent, subtle or prominent by two readers. Results: A total of 70 patients were included in the study. Mean time between baseline CT and MRI was 124 ± 82 min. ASPECTS score on baseline CT was 10 in 34% of patients, 9 in 49% and 8 or less in 17%. ASPECTS score was 2 (1–3) points lower in the DWI and this decrease did not correlate with the time elapsed between the two exams. Distal HV sign was observed in 57/70 (81%) patients (subtle in 33 and prominent in 24). HV was more frequently observed in patients with proximal artery occlusion. There were no differences regarding stroke severity, stroke subtype and ASPECTS score on baseline CT between groups. Patients with prominent HV showed a lower progression of the ischemic area [median ASPECTS score decrease, 1 (1–0)] compared with patients with subtle HV [median ASPECTS score decrease, 2 (2–1)] and patients with absence of HV [median ASPECTS score decrease, 3 (4–3)] (p < 0.001). Prominent HV was independently associated with slow progression of ischemia in a multivariate logistic regression analysis adjusted by systolic blood pressure on admission, site of occlusion and time elapsed between both neuroimaging exams compared to the absence of HV (OR, 16.2; 95% CI, 2.1–123.1) and to subtle HV sign (OR, 6.1; 95% CI, 1.5–23.9). Conclusion: HV sign on FLAIR, especially if prominent, is associated with a slow progression of the ischemic area in acute stroke patients with cerebral artery occlusion of the anterior circulation. This radiological sign may predict the speed of the ischemia progression, opening an opportunity for reperfusion therapies in longer time windows.

Natural History of Acute Stroke due to Occlusion of the Middle Cerebral Artery and Intracranial Internal Carotid Artery

The natural history of acute ischemic stroke (AIS) due to anterior circulation large artery occlusion is not well established. This information is essential for assessment of clinical benefit derived from recanalization therapies.

Prestroke Physical Activity Is Associated with Good Functional Outcome and Arterial Recanalization after Stroke due to a Large Vessel Occlusion

Background: Although multiple studies and meta-analyses have consistently suggested that regular physical activity (PhA) is associated with a decreased stroke risk and recurrence, there is limited data on the possible preconditioning effect of prestroke PhA on stroke severity and prognosis. We aimed to study the association of prestroke PhA with different outcome variables in patients with acute ischemic stroke due to an anterior large vessel occlusion. Methods: The Prestroke Physical Activity and Functional Recovery in Patients with Ischemic Stroke and Arterial Occlusion trial is an observational and longitudinal study that included consecutive patients with acute ischemic stroke admitted to a single tertiary stroke center. Main inclusion criteria were: anterior circulation ischemic stroke within 12 h from symptom onset; presence of a confirmed anterior large vessel occlusion, and functional independence previous to stroke. Prestroke PhA was evaluated with the International Physical Activity Questionnaire and categorized into mild, moderate and high levels by means of metabolic equivalent (MET) minutes per week thresholds. The primary outcome measure was good functional outcome at 3 months (modified Rankin scale ≤2). Secondary outcomes were severity of stroke at admission, complete early recanalization, early dramatic neurological improvement and final infarct volume. Results: During the study period, 159 patients fulfilled the above criteria. The mean age was 68 years, 62% were men and the baseline NIHSS score was 17. Patients with high levels of prestroke PhA were younger, had more frequently distal occlusions and had lower levels of blood glucose and fibrinogen at admission. After multivariate analysis, a high level of prestroke PhA was associated with a good functional outcome at 3 months. Regarding secondary outcome variables and after adjustment for relevant factors, a high level of prestroke PhA was independently associated with milder stroke severity at admission, early dramatic improvement, early arterial recanalization after intravenous thrombolysis and lower final infarct volume. The beneficial association of prestroke PhA with stroke outcomes was already present with a cutoff point of 1,000 MET min/week, a level of PhA easily achieved by walking 1 h/day during 5 days or by doing a vigorous aerobic activity 1 h/day twice a week. Conclusions: Prestroke PhA is independently associated with favorable stroke outcomes after a large vessel occlusion. Future research on the underlying mechanisms is needed to understand this neuroprotective effect of PhA.

Diffusion tensor imaging as a prognostic biomarker for motor recovery and rehabilitation after stroke

PurposeDespite improved acute treatment and new tools to facilitate recovery, most patients have motor deficits after stroke, often causing disability. However, motor impairment varies considerably among patients, and recovery in the acute/subacute phase is difficult to predict using clinical measures alone, particularly in severely impaired patients. Accurate early prediction of recovery would help rationalize rehabilitation goals and improve the design of trials testing strategies to facilitate recovery.MethodsWe review the role of diffusion tensor imaging (DTI) in predicting motor recovery after stroke, in monitoring treatment response, and in evaluating white matter remodeling. We critically appraise DTI studies and discuss their limitations, and we explore directions for future study.ResultsGrowing evidence suggests that combining clinical scores with information about corticospinal tract (CST) integrity can improve predictions about motor outcome. The extent of CST damage on DTI and/or the overlap between the CST and a lesion are key prognostic factor that determines motor performance and outcome. Three main strategies to quantify stroke-related CST damage have been proposed: (i) measuring FA distal to the stroke area, (ii) measuring the number of fibers that go through the stroke with tractography, and (iii) measuring the overlap between the stroke and a CST map derived from healthy age- and gender-matched controls.ConclusionRecovery of motor function probably involves remodeling of the CST proper and/or a greater reliance on alternative motor tracts through spontaneous and treatment-induced plasticity. DTI-metrics represent promising clinical biomarkers to predict motor recovery and to monitor and predict the response to neurorehabilitative interventions.

Endovascular treatment improves cognition after stroke A secondary analysis of REVASCAT trial

Objective: To investigate the effect of endovascular treatment on cognitive function as a prespecified secondary analysis of the REVASCAT (Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours) trial. Methods: REVASCAT randomized 206 patients with anterior circulation proximal arterial occlusion stroke to Solitaire thrombectomy or best medical treatment alone. Patients with established dementia were excluded from enrollment. Cognitive function was assessed in person with Trail Making Test (TMT) Parts A and B at 3 months and 1 year after randomization by an investigator masked to treatment allocation. Test completion within 5 minutes, time of completion (seconds), and number of errors were recorded. Results: From November 2012 to December 2014, 206 patients were enrolled in REVASCAT. TMT was assessed in 82 of 84 patients undergoing thrombectomy and 86 of 87 control patients alive at 3 months and in 71 of 79 patients undergoing thrombectomy and 72 of 78 control patients alive at 1 year. Rates of timely TMT-A completion were similar in both treatment arms, although patients undergoing thrombectomy required less time for TMT-A completion and had higher rates of error-free TMT-A performance. Thrombectomy was also associated with a higher probability of timely TMT-B completion (adjusted odds ratio 3.17, 95% confidence interval 1.51–6.66 at 3 months; and adjusted ratio 3.66, 95% confidence interval 1.60–8.35 at 1 year) and shorter time for TMT-B completion. Differences in TMT completion times between treatment arms were significant in patients with good functional outcome but not in those who were functionally dependent (modified Rankin Scale score >2). Poorer cognitive outcomes were significantly associated with larger infarct volume, higher modified Rankin Scale scores, and worse quality of life. Conclusions: Thrombectomy improves TMT performance after stroke, especially among patients who reach good functional recovery. ClinicalTrials.gov identifier: NCT01692379. Classification of evidence: This study provides Class I evidence that for patients with stroke from acute anterior circulation proximal arterial occlusion, thrombectomy improves performance on the TMT at 3 months.