Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines. METHODS: We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis. RESULTS: During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9-17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4-14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10-1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05-1.32]), per unit increase logeIL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09-1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04-1.21], per unit increase logehsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04-1.21]; hsCRP, RR, 1.09 [95% CI, 1.04-1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00-1.19]; hsCRP, RR, 1.05 [95% CI, 1.00-1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09-1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07-1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08-1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93-1.43]). CONCLUSIONS: Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.

Determinants and Trends of the Use of Intravenous Thrombolysis for Minor Stroke: A Population-Based Study, 2016 to 2020.

BACKGROUND: We analyzed the main factors associated with intravenous thrombolysis (IVT) in patients with minor ischemic stroke. METHODS: Data were obtained from a prospective, government-mandated, population-based registry of stroke code patients in Catalonia (6 Comprehensive Stroke Centers, 8 Primary Stroke Centers, and 14 TeleStroke Centers). We selected patients diagnosed with ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) ≤5 at hospital admission from January 2016 to December 2020. We excluded patients with a baseline modified Rankin Scale score of ≥3, absolute contraindication for IVT, unknown stroke onset, or admitted to hospital beyond 4.5 after stroke onset. The main outcome was treatment with IVT. We performed univariable and binary logistic regression analyses to identify the most important factors associated with IVT. RESULTS: We included 2975 code strokes; 1433 (48.2%) received IVT of which 30 (2.1%) had a symptomatic hemorrhagic transformation. Patients treated with IVT as compared to patients who did not receive IVT were more frequently women, had higher NIHSS, arrived earlier to hospital, were admitted to a Comprehensive Stroke Centers, and had large vessel occlusion. After binary logistic regression, NIHSS score 4 to 5 (odds ratio, 40.62 [95% CI, 31.73-57.22]; P<0.001) and large vessel occlusion (odds ratio, 16.39 [95% CI, 7.25-37.04]; P<0.001) were the strongest predictors of IVT. Younger age, female sex, baseline modified Rankin Scale score of 0, earlier arrival to hospital (<120 minutes after stroke onset), and the type of stroke center were also independently associated with IVT. The weight of large vessel occlusion on IVT was higher in patients with lower NIHSS. CONCLUSIONS: Minor stroke female patients, with higher NIHSS, arriving earlier to the hospital, presenting with large vessel occlusion and admitted to a Comprehensive Stroke Centers were more likely to receive intravenous thrombolysis.

Effect of Direct Transportation to Thrombectomy-Capable Center vs Local Stroke Center on Neurological Outcomes in Patients With Suspected Large-Vessel Occlusion Stroke in Nonurban Areas: The RACECAT Randomized Clinical Trial.

Importance: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective: To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants: Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions: Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures: The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death]) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results: Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21]); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance: In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

The Role of Vascular Imaging atReferral Centers in the Drip and Ship Paradigm.

BACKGROUND: In drip-and-ship protocols, non-invasive vascular imaging (NIVI) at Referral Centers (RC), although recommended, is not consistently performed and its value is uncertain. We evaluated the role of NIVI at RC, comparing patients with (VI+) and without (VI-) vascular imaging in several outcomes. METHODS: Observational, multicenter study from a prospective government-mandated population-based registry of code stroke patients. We selected acute ischemic stroke patients, initially assessed at RC from January-2016 to June-2020. We compared and analyzed the rates of patients transferred to a Comprehensive Stroke Center (CSC) for Endovascular Treatment (EVT), rates of EVT and workflow times between VI+ and VI- patients. RESULTS: From 5128 ischemic code stroke patients admitted at RC; 3067 (59.8%) were VI+, 1822 (35.5%) were secondarily transferred to a CSC and 600 (11.7%) received EVT. Among all patients with severe stroke (NIHSS ≥16) at RC, a multivariate analysis showed that lower age, thrombolytic treatment, and VI+ (OR:1.479, CI95%: 1.117-1.960, p=0.006) were independent factors associated to EVT. The rate of secondary transfer to a CSC was lower in VI+ group (24.6% vs. 51.6%, p<0.001). Among transferred patients, EVT was more frequent in VI+ than VI- (48.6% vs. 21.7%, p<0.001). Interval times as door-in door-out (median-minutes 83.5 vs. 82, p= 0.13) and RC-Door to puncture (median-minutes 189 vs. 178, p= 0.47) did not show differences between both groups. CONCLUSION: In the present study, NIVI at RC improves selection for EVT, and is associated with receiving EVT in severe stroke patients. Time-metrics related to drip-and-ship model were not affected by NIVI.

Sex-Related Differences in Clinical Features, Neuroimaging, and Long-Term Prognosis After Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Differences in sex in the incidence, presentation, and outcome of events after ischemic stroke have been studied in depth. In contrast, only limited data are available after transient ischemic attack (TIA). We aim to assess sex-related differences in the presentation, cause, neuroimaging features, and predictors of long-term prognosis in patients with TIA. METHODS: We carried out a prospective cohort study of consecutive patients with TIA from January 2006 to June 2010. Nondefinitive TIA events were defined by the presence of isolated atypical symptoms. The risk of stroke recurrence (SR) and composite of major vascular events were stratified by sex after a median follow-up time of 6.5 (interquartile range, 5.0-9.6) years. RESULTS: Among the 723 patients studied, 302 (41.8%) were female and 79 (10.9%) suffered a nondefinitive TIA event. Vascular territory diffusion-weighted imaging patterns (odds ratio, 1.61 [95% CI, 0.94-2.77]), and nondefinitive TIA events (odds ratio, 2.66 [95% CI, 1.55-4.59]) were associated with women, whereas active smoking (odds ratio, 0.30 [95% CI, 0.15-0.58]) and large artery atherosclerosis causes (odds ratio, 0.50 [95% CI, 0.29-0.83]) were related to men. The risk of SR was similar in both sexes (12.6% [95% CI, 8.9-16.3] for women versus 14.3% [95% CI, 11.0-17.6] for men). In contrast, the risk of major vascular events was significantly lower in women than in men (17.5% [95% CI, 13.2-21.8] versus 23.8% [95% CI, 19.7-27.9]). In both sexes, after adjusting for age, large artery atherosclerosis was associated with SR (hazard ratio, 3.22 [95% CI, 1.42-7.24] and hazard ratio, 2.00 [95% CI, 1.14-3.51]). In a Kaplan-Meier analysis, females with positive diffusion-weighted imaging (P=0.014) and definitive TIA (log-rank test P=0.022) had a significantly higher risk of SR. CONCLUSIONS: Despite similar risks of SR, there were sex-related differences in baseline characteristics, presenting symptoms, patterns of acute ischemic lesions, cause, and outcomes. These findings encourage further research into optimal preventive strategies that take into account these differences.

Impact of COVID-19 Infection on the Outcome of Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: We evaluated whether stroke severity, functional outcome, and mortality are different in patients with ischemic stroke with or without coronavirus disease 2019 (COVID-19) infection. METHODS: A prospective, observational, multicentre cohort study in Catalonia, Spain. Recruitment was consecutive from mid-March to mid-May 2020. Patients had an acute ischemic stroke within 48 hours and a previous modified Rankin Scale (mRS) score of 0 to 3. We collected demographic data, vascular risk factors, prior mRS score, National Institutes of Health Stroke Scale score, rate of reperfusion therapies, logistics, and metrics. Primary end point was functional outcome at 3 months. Favourable outcome was defined depending on the previous mRS score. Secondary outcome was mortality at 3 months. We performed mRS shift and multivariable analyses. RESULTS: We evaluated 701 patients (mean age 72.3±13.3 years, 60.5% men) and 91 (13%) had COVID-19 infection. Median baseline National Institutes of Health Stroke Scale score was higher in patients with COVID-19 compared with patients without COVID-19 (8 [3-18] versus 6 [2-14], P=0.049). Proportion of patients with a favourable functional outcome was 33.7% in the COVID-19 and 47% in the non-COVID-19 group. However, after a multivariable logistic regression analysis, COVID-19 infection did not increase the probability of unfavourable functional outcome. Mortality rate was 39.3% among patients with COVID-19 and 16.1% in the non-COVID-19 group. In the multivariable logistic regression analysis, COVID-19 infection was a risk factor for mortality (hazard ratio, 3.14 [95% CI, 2.10-4.71]; P<0.001). CONCLUSIONS: Patients with ischemic stroke and COVID-19 infection have more severe strokes and a higher mortality than patients with stroke without COVID-19 infection. However, functional outcome is comparable in both groups.

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke.

BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia.

INTRODUCTION: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. METHODS: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. RESULTS: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. CONCLUSION: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately.

Basal IL-6 and S100b levels are associated with infarct volume.

OBJECTIVES: The study of biomarkers related to the infarct volume of acute ischaemic stroke (AIS) is a valuable clinical strategy. We conducted a prospective study to evaluate the relationship between a wide panel of biomarkers involved in different biochemical pathways and lesion volume. MATERIALS & METHODS: We studied 332 patients with AIS. Infarct volume was calculated from diffusion weighted imaging (DWI). Blood samples were drawn within 24 h of symptom onset to test a panel of biomarkers that included high-sensitivity C-reactive protein (hs-CRP), IL-6, neuron-specific enolase (NSE), N-terminal pro-B-type natriuretic peptide (NT-ProBNP), S100b, troponin and IL-10. RESULTS: The median lesion volume was 2.5 cc (IQR: 0.6-15.3). Patients with previous atrial fibrillation, cardioembolic aetiology and total anterior circulation infarct TACI classification had higher lesion volumes than those without them. Patients with previous recent TIA had smaller ischaemic lesions than those without it. Age and NIHSS were significantly correlated with lesion volume. In a linear regression analysis adjusted by aetiology, S100b and IL-6 emerged as the only biomarkers independently associated with infarct volume. In contrast, previous recent TIA and small-vessel disease were inversely related to infarct volume. CONCLUSIONS: The correlation between the two blood marker levels and ischaemic lesion volume would support the use of these biomarkers as a surrogate endpoint in AIS, especially in centres without DWI 24/7 but these could not substitute basic neuroimaging. Our findings should be further explored in larger, preferably multicentre studies.

A Less Frequent Etiology of Limb Shaking Syndrome: A Severe Middle Cerebral Artery Stenosis.

BACKGROUND: Limb Shaking Syndrome (LSS) is usually associated with internal carotid occlusion. There are few reported-cases in context of middle cerebral artery stenosis. METHODS: We presented LSS in a patient with middle cerebral artery stenosis disease. RESULTS: The patient was a 62-year-old man, smoker, with high blood pressure who suffered left hemifacial and limbs myoclonus. He was initially diagnosed with focal seizures and he started antiepileptic treatment. However, he repeated the episodes. The electroencephalogram showed no abnormalities, and a vascular study with ultrasounds and angio-MRI evidenced severe middle cerebral stenosis. Finally, a diagnosis of Limb Shaking Syndrome was established and he started antiplatelet and high dose lipid-lowering treatment. CONCLUSION: Not all abnormal movements are due to epileptic seizures. When we evaluate a patient with vascular risk factors it is important to perform a complete vascular study to discard not only critical carotid stenosis but also intracranial disease.

Stroke Risk Analysis, a System With a High Detection Rate of Atrial Fibrillation in Stroke and Transient Ischemic Attack.

Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R_AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R_AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; P<0.0001). hSRA detected R_AF patterns in 92 patients. 35 out of the 92 R_AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R_AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R_AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.

Vascular Occlusion Evolution in Endovascular Reperfusion Candidates Transferred from Primary to Comprehensive Stroke Centers.

BACKGROUND: The evolution of the symptomatic intracranial occlusion during transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) for endovascular treatment (EVT) is not widely known. Our aim was to identify factors related to partial or complete recanalization (REC) at CSC arrival in patients with a documented large vessel occlusion (LVO) in PSC transferred for EVT evaluation to better define the workflow at CSC of this group of patients. METHODS: We conducted an observational, multicenter study from a prospective, government-mandated, population-based registry of stroke patients with documented LVO at PSC transferred to CSC for EVT from January 2017 to June 2019. The primary end point was defined as partial or complete REC that precluded EVT at CSC arrival (REC). We evaluated the association between baseline, treatment variables and time intervals with the presence of REC. RESULTS: From 589 patients, the rate of REC at CSC was 10.5% in all LVO patients transferred from PSC to CSC for EVT evaluation. On univariate analysis, lower PSC-NIHSS (median 12vs.16, p = 0.001), tPA treatment at PSC (13.7 vs. 5.0%; p = 0.001), presence of M2 occlusion on PSC (16.8 vs. 9%; p = 0.023), and clinical improvement at CSC arrival (21.7 vs. 9.6% p = 0.001) were associated with REC at CSC. On multivariate analysis, clinical improvement at CSC arrival (p < 0.001, OR: 5.96 95% CI: 2.5-13.9) and PSC tPA treatment predicted REC (p = 0.003, OR: 4.65, 95% CI: 1.73-12.4). CONCLUSION: REC at CSC arrival occurs exceptionally in patients with a documented LVO on PSC. Repeating a second vascular study before EVT would not be necessary in most patients. Despite its modest effect, tPA treatment at PSC was an independent predictor of REC.

Induced neuroprotection by remote ischemic perconditioning as a new paradigm in ischemic stroke at the acute phase, a systematic review.

BACKGROUND: Remote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. Some clinical trials just finished, and a few others are still ongoing; gather the current knowledge and pull it down to influence the present and future studies was the goal of this paper. METHODS: A systematic review of published research papers and/or registered clinical trials since 2000 was performed. RESULTS: Nineteen studies were identified and only four studies were completed. All of them have demonstrated that RIPerC is safe, feasible and well tolerated in IS patients. However, a high heterogeneity of clinical trial characteristics was observed: five (26.3%) randomized clinical trials (RCTs) included only thrombolytic-treated patients, three (15.8%) RCTs only thrombectomy-treated patients, and five (26.3%) RCTs required radiological confirmation of IS. Temporal inclusion criteria vary from 4 h to 48 h. Most of the clinical trials used 4 cycles of RIPerC in the upper non-affected limb. Interestingly, only three (16.7%) RCTs applied RIPerC during the transportation in the ambulance. Neuroimaging outputs were the main endpoints when endovascular therapy was applied; functional outcome is also the main endpoint in large-medium size studies. CONCLUSIONS: This review summarizes the completed and ongoing clinical trials on RIPerC in IS patients, where RIPerC has been used alone or in combination with recanalization therapies. Ongoing clinical trials will provide new information on the best RIPerC intervention strategy and potentially improve the functional outcome of IS patients; definition of new RIPerC strategies would ideally aim at enhancing tissue preservation, promoting neurological recovery, and stratify patients to improve treatment feasibility.

Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project.

BACKGROUND: Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. METHODS: Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. RESULTS: Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects. CONCLUSIONS: The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner. Trial registration NCT03228459 (clinicaltrials.gov).

Age- and Sex-Specific Risk Profiles and In-Hospital Mortality in 13,932 Spanish Stroke Patients.

BACKGROUND: In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients. METHODS: We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages <18 years were excluded. Patients were organised by age group and sex. We compared female and male patient cohorts within and across age groups univariately and used multivariable logistic regression to adjust for confounders in differential in-hospital mortality. RESULTS: The median (percentiles 2.5 and 97.5%) age was 78 (41-92) years old for women and 71 (41-92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient's age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications - partial anterior circulatory infarct and total anterior circulatory infarct - were significant prognostic factors for men aged <60 years and for those in the 60-69 years range respectively. CONCLUSION: Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.

Pre-Existing Cerebral Small Vessel Disease Limits Early Recovery in Patients with Acute Lacunar Infarct.

BACKGROUND AND PURPOSE: To assess whether neuroimaging markers of chronic cerebral small vessel disease (cSVDm) influence early recovery after acute ischemic stroke (AIS). METHODS: Retrospective analysis of patients diagnosed with AIS and included in the Spanish Neurological Society Stroke Database. INCLUSION CRITERIA: (1) Brain MRI performed after acute stroke and (2) Premorbid modified Rankin scale (mRS) = 0. EXCLUSION CRITERIA: (1) Uncommon stroke etiologies, (2) AIS not confirmed on neuroimaging, or (3) Old territorial infarcts on neuroimaging. Patients scored from 0 to 2 according to the amount of cSVDm. Patients were divided into lacunar ischemic stroke (LIS) and nonlacunar ischemic stroke (NLIS) groups according to TOAST classification. PRIMARY OUTCOME: Distribution of mRS at discharge. SECONDARY OUTCOMES: NIHSS improvement more than or equal to 3 at 24 hours and at discharge, NIHSS worsening more than or equal to 3 points at 24 hours. RESULTS: We studied 4424 patients (3457 NLIS, 967 LIS). The presence of cSVDm increased the risk of worsening 1 category on the mRS at discharge in the LIS group ([1] cSVDm: OR 1.89 CI 95% 1.29-2.75, P = .001. [2] cSVDm: OR 1.87, CI 95% 1.37-2.56 P = .001) and was an independent factor for not achieving an improvement more than or equal to 3 points on the NIHSS at discharge for all the patients and the LIS group (all stroke patients: [1] cSVDm: OR 0.81 CI 95% .68-.97 P = .022. [2] cSVD: OR 0.58 CI95% .45-.77, P = .001./LIS: [1] cSVDm: OR 0.64, CI 95% .41-.98, P = .038. [2] cSVDm: OR 0.43, CI 95% .24-.75 P = .003). CONCLUSIONS: Pre-existing SVD limits early functional and neurological recovery after AIS, especially in LIS patients.

Anti-inflammatory approaches to ischaemic stroke prevention.

Stroke is a major cause of neurological morbidity and mortality. Atherosclerosis is a major contributor to first and recurrent stroke. A growing evidence base indicates that inflammation is a key process in the pathogenesis of atherosclerosis, leading to thromboembolic events. In this review, we summarise the evidence linking inflammation to stroke risk and discuss clinical trials addressing the 'inflammation hypothesis' in coronary disease and stroke. Trial registration number CONVINCE trial ClinicalTrials.gov number; NCT 02898610; Pre-results.

Telestroke in Catalonia: Increasing Thrombolysis Rate and Avoiding Interhospital Transfers.

OBJECTIVES: The study aimed to evaluate the impact of a telestroke network on acute stroke care in Catalonia, by measuring thrombolysis rates, access to endovascular treatment, and clinical outcome of telestroke patients in a population-based study. METHODS: Telestroke network was implemented on March 2013 and consists of 12 community hospitals and 1 expert stroke neurologist 24 h/7 day, covering a population of 1.3 million inhabitants. Rest of the population (6.2 million) of Catalonia is covered by 8 primary stroke centers (PSC) and 6 comprehensive stroke centers (CSC). After a 2-way videoconference and visualization of neuroimaging on a web platform, the stroke neurologist decides the therapeutic approach and/or to transfer the patient to another facility, entering these data in a mandatory registry. Simultaneously, all patients treated with reperfusion therapies in all centers of Catalonia are prospectively recorded in a mandatory and audited registry. RESULTS: From March 2013 to December 2015, 1,206 patients were assessed by telestroke videoconference, of whom 322 received intravenous thrombolysis (IVT; 33.8% of ischemic strokes). Baseline and 24 h NIHSS, rate of symptomatic hemorrhage, mortality, and good outcome at 3 months were similar compared to those who received IVT in PSC or CSC (2,897 patients in the same period). The door-to-needle time was longer in patients treated through telestroke, but was progressively reduced from 2013 to 2015. Percentage of patients receiving thrombectomy after IVT was similar in patients treated through telestroke circuit, compared to those treated in PSC or CSC (conventional circuit). Population rates of IVT*100,000 inhabitants in Catalonia increased from 2011 to 2015, especially in areas affected by the implementation of telestroke network, achieving rates as high as 16 per 100,000 inhabitants. Transfers to another facility were avoided after telestroke consultation in 46.8% of ischemic, 76.5% of transient ischemic attacks, and 23.5% of hemorrhages. CONCLUSIONS: Telestroke favors safe and effective thrombolysis, helps to increase the population rate of IVT, and avoids a large number of interhospital transfers.

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10-03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10-09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03). CONCLUSIONS: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.