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[Rationale] In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated., [Aims] To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL., [Sample size estimates] Two hundred forty patients will be enrolled, 120 in every treatment arm., [Methods and design] A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months., [Study outcomes] Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage., [Discussion] This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL., [Trial registration] The trial is registered as NCT05225961. February, 7th, 2022.

[Background] Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke., [Methods] The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed., [Findings] Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55–7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52–6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72–6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group., [Interpretation] Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.

[Background and Purpose] Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia., [Methods] Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003-2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0-2) and death at 90 days., [Results] Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02)., [Conclusions] In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.

Supplemental material, sj-docx-1-wso-10.1177_17474930221095965 for Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study by Irene Escudero-Martínez, Marius Matusevicius, Ana Pavia-Nunes, Petr Sevcik, Miroslava Nevsimalova, Viiu-Marika Rand, Janika Kõrv, Manuel Cappellari, Robert Mikulik, Danilo Toni and Niaz Ahmed in International Journal of Stroke.

[Background] Atrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk., [Methods] The present study followed a cross-sectional design. 70 patients with a history of AF and CHADS2 score ≤1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany., [Results] 45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.99–23.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment., [Conclusions] BMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.

[Background and objective] We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS–International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies., [Methods] We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014–2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST., [Results] Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44–47), 46.0% (42–50), 38% (35–41) and 37% (35–41), respectively; death was 19.2% (19–21), 15.3% (12.7–18.4), 29.2% (27–32) and 28.6% (27–31); and SICH was 3.6% (3–4), 4.4% (3.0–6.4), 5.8% (4.7–7.1) and not available., [Conclusion] Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Silent brain infarcts (SBI), defined as a finding on neuroimaging without neurological symptoms, are associated with a higher risk of future stroke, cognitive decline and higher mortality rates. For these reasons, SBI should be considered as an initial manifestation of cerebrovascular disease that requires secondary prevention and not only as an incidental finding. Atrial Fibrillation (AF) has been previously identified as a cause of SBI. At present, the most commonly used tools to estimate the embolic risk in patients with AF are CHADS2 and CHA2DS2VASc scores. Patients who score ≥2 are treated with oral anticoagulation (OAC) for thromboembolism prevention, but in those who score less than 2, clinical practice is not constant, and a proportion of these patients might be undertreated. For both scoring systems, a previous history of stroke or TIA scores 2 points, which means a high embolic risk and therefore, indicates starting anticoagulation. A percentage of patients with AF who score 0–1 on the CHADS2 or CHA2DS2VASc score (or 2 if 1 point is female sex) might present SBI if scanned with a high field MRI (3 Tesla, [3T]). This theoretically low to moderate risk population would not receive any treatment as stroke prevention or they would receive antiplatelet treatment. However, if an SBI is detected on an MRI, we suggest that a more aggressive prevention strategy should be implemented in this population. We hypothesize that a significant percentage of patients with AF and theoretically low/moderate embolic risk might present SBI if screened with MRI and that SBI could be associated with less adherence to a healthy lifestyle and with cognitive decline. The main aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low/moderate embolic risk according to CHADS2 and CHA2DS2VASc. Secondary aims include to determine the association of SBI with Mediterranean diet (MeD) and physical activity and to evaluate cognitive and psychol

[Background] Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage., [Aim] To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage., [Methods] We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging., [Results] We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1–3) vs. 2 (1–3) without hemorrhage, p = 0.4)., [Conclusion] The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

[Background] Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI., [Objectives] The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS2 and CHA2DS2VASc score., [Methods] Patients with a history of AF based on medical records who scored 0–1 in the CHADS2 score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50 years and with absence of neurological symptoms., [Results] 66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA2DS2VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07–13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15–8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33–7.63)., [Conclusions] LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS2 and in the low-risk population according to CHA2DS2VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention.

Previous studies have shown the potential of microRNAs (miRNA) in the pathological process of stroke and functional recovery. Bone marrow mononuclear cell (BM-MNC) transplantation improves recovery in experimental models of ischemic stroke that might be related with miRNA modifications. However, its effect on circulating miRNA has not been described in patients with stroke. We aimed to evaluate the circulating levels of miRNAs after autologous BM-MNC transplantation in patients with stroke. We investigate the pattern of miRNA-133b and miRNA-34a expression in patients with ischemic stroke included in a multicenter randomized controlled phase IIb trial (http://www.clinicaltrials.gov; unique identifier: NCT02178657). Patients were randomized to 2 different doses of autologous intra-arterial BM-MNC injection (2×106/kg or 5×106/kg) or control group within the first 7 days after stroke onset. We evaluate plasma concentration of miRNA-113b and miRNA-34a at inclusion and 4, 7, and 90 days after treatment. Thirteen cases (8 with 2×106/kg BM-MNC dose and 5 with 5×106/kg dose) and 11 controls (BM-MNC non-treated) were consecutively included. Mean age was 64.1±12.3 with a mean National Institutes of Health Stroke Scale score at inclusion of 14.5. Basal levels of miRNA were similar in both groups. miR-34a-5p and miR-133b showed different expression patterns. There was a significant dose-dependent increase of miRNA-34a levels 4 days after BM-MNC injection (fold change 3.7, p<0.001), whereas miRNA-133b showed a significant increase in the low-dose BM-MNC group at 90 days. Intra-arterial BM-MNC transplantation in patients with ischemic stroke seems to modulate early circulating miRNA-34a levels, which have been related to precursor cell migration in stroke and smaller infarct volumes.

[Objectives] The detection of cervical arterial dissection (CAD) has been rising in recent years owing to advanced imaging techniques. The aim of this study was to explore whether wide implementation of endovascular treatment for ischemic stroke has an impact on the diagnosis of CAD., [Methods] We included all patients with CAD diagnosed at two university hospitals in Seville, Spain from January 2015 to December 2017. We collected clinical variables and information on imaging techniques used for the diagnosis. Implementation of 24 hour/365 day mechanical thrombectomy began in Seville on 15 August 2016. We compared diagnosis rates of CAD performed before and after this date., [Results] We identified 41 patients with CAD. We found 13 patients diagnosed before (1.1% of all ischemic strokes) and 28 (2.2%) after implementation of neurointerventional therapy. In 17 patients, diagnosis was made in the acute phase. Dissection was not suspected according to computed tomography angiography in 11 patients owing to small dissections (n = 2) or total occlusion (n = 9)., [Conclusions] CAD diagnoses have been rising in recent years, essentially owing to continuous improvement in imaging techniques. Rapid access to arteriography for thrombectomy is increasing the diagnoses of CAD, even in patients with a low suspicion of dissection.

[Background and objective] The optimal timing for initiation of dabigatran after acute ischaemic stroke (AIS) is not established. We aimed to evaluate initiation timing and clinical outcomes of dabigatran in AIS patients with non-valvular atrial fibrillation (NVAF)., [Design] Retrospective study based on prospectively collected data in SITS (Safe Implementation of Treatment in Stroke) Thrombolysis and Thrombectomy Registry from July 2014 to July 2018., [Participants] European NVAF patients (≥18 years) hospitalised after first-ever ischaemic stroke., [Setting] A multinational, observational monitoring register., [Intervention] Dabigatran initiation within 3 months after the ischaemic stroke., [Primary and secondary outcomes] The primary outcome was time from first-ever ischaemic stroke (index event) to dabigatran initiation. Additional outcomes included physicians’ reasons for delaying dabigatran initiation beyond acute hospital discharge and outcomes within 3 months of index event., [Methods] We identified patients with NVAF who received dabigatran within 3 months of the index event. We performed descriptive statistics for baseline and demographic data and clinical outcomes after dabigatran initiation., [Results] In total, 1489 patients with NVAF received dabigatran after AIS treated with thrombolysis and/or thrombectomy. Of these, 1240 had available initiation time. At baseline, median age was 75 years; 53% of patients were women, 15% were receiving an oral anticoagulant, 29% acetylsalicylic acid and 4% clopidogrel. Most patients (82%) initiated dabigatran within 14 days after the index event. Patients initiating earlier had lower stroke severity from median NIHSS 8 (IQR 6–13) if initiated within 7 days to NIHSS 15 (9–19) if initiated between 28 days and 3 months. Most common reasons for delaying initiation were haemorrhagic transformation or intracranial haemorrhage, stroke severity and infarct size. Few thrombotic/haemorrhagic events occurred within 3 months after the index event (20 of 926 patients, 2.2% with the available data)., [Conclusions] Our findings, together with previous observational studies, indicate that dabigatran initiated within the first days after an AIS is safe in patients treated with intravenous thrombolysis, endovascular thrombectomy or both., [Trial registration number] SITS Thrombolysis and Thrombectomy Registry (NCT03258645).