Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial.

BACKGROUND AND PURPOSE: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. METHODS: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. RESULTS: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage  among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). CONCLUSIONS: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.

Perfusion Imaging Predicts Favorable Outcomes after Basilar Artery Thrombectomy.

OBJECTIVE: Perfusion imaging identifies anterior circulation stroke patients who respond favorably to endovascular thrombectomy (ET), but its role in basilar artery occlusion (BAO) is unknown. We hypothesized that BAO patients with limited regions of severe hypoperfusion (time to reach maximum concentration in seconds [Tmax] > 10) would have a favorable response to ET compared to patients with more extensive regions involved. METHODS: We performed a multicenter retrospective cohort study of BAO patients with perfusion imaging prior to ET. We prespecified a Critical Area Perfusion Score (CAPS; 0-6 points), which quantified severe hypoperfusion (Tmax > 10) in cerebellum (1 point/hemisphere), pons (2 points), and midbrain and/or thalamus (2 points). Patients were dichotomized into favorable (CAPS ≤ 3) and unfavorable (CAPS > 3) groups. The primary outcome was a favorable functional outcome 90 days after ET (modified Rankin Scale = 0-3). RESULTS: One hundred three patients were included. CAPS ≤ 3 patients (87%) had a lower median National Institutes of Health Stroke Scale score (NIHSS; 12.5, interquartile range [IQR] = 7-22) compared to CAPS > 3 patients (13%; 23, IQR = 19-36; p = 0.01). Reperfusion was achieved in 84% of all patients, with no difference between CAPS groups (p = 0.42). Sixty-four percent of reperfused CAPS ≤ 3 patients had a favorable outcome compared to 8% of nonreperfused CAPS ≤ 3 patients (odds ratio [OR] = 21.0, 95% confidence interval [CI] = 2.6-170; p < 0.001). No CAPS > 3 patients had a favorable outcome, regardless of reperfusion. In a multivariate regression analysis, CAPS ≤ 3 was a robust independent predictor of favorable outcome after adjustment for reperfusion, age, and pre-ET NIHSS (OR = 39.25, 95% CI = 1.34->999, p = 0.04). INTERPRETATION: BAO patients with limited regions of severe hypoperfusion had a favorable response to reperfusion following ET. However, patients with more extensive regions of hypoperfusion in critical brain regions did not benefit from endovascular reperfusion. ANN NEUROL 2022;91:23-32.

Magnetic Resonance Imaging or Computed Tomography for Suspected Acute Stroke: Association of Admission Image Modality with Acute Recanalization Therapies, Workflow Metrics, and Outcomes.

OBJECTIVE: To examine rates of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), door-to-needle (DTN) time, door-to-puncture (DTP) time, and functional outcome between patients with admission magnetic resonance imaging (MRI) versus computed tomography (CT). METHODS: An observational cohort study of consecutive patients using a target trial design within the nationwide Swiss-Stroke-Registry from January 2014 to August 2020 was carried out. Exclusion criteria included MRI contraindications, transferred patients, and unstable or frail patients. Multilevel mixed-effects logistic regression with multiple imputation was used to calculate adjusted odds ratios with 95% confidence intervals for IVT, MT, DTN, DTP, and good functional outcome (mRS 0-2) at 90 days. RESULTS: Of the 11,049 patients included (mean [SD] age, 71 [15] years; 4,811 [44%] women; 69% ischemic stroke, 16% transient ischemic attack, 8% stroke mimics, 6% intracranial hemorrhage), 3,741 (34%) received MRI and 7,308 (66%) CT. Patients undergoing MRI had lower National Institutes of Health Stroke Scale (median [interquartile range] 2 [0-6] vs 4 [1-11]), and presented later after symptom onset (150 vs 123 min, p < 0.001). Admission MRI was associated with: lower adjusted odds of IVT (aOR 0.83, 0.73-0.96), but not with MT (aOR 1.11, 0.93-1.34); longer adjusted DTN (+22 min [13-30]), but not with longer DTP times; and higher adjusted odds of favorable outcome (aOR 1.54, 1.30-1.81). INTERPRETATION: We found an association of MRI with lower rates of IVT and a significant delay in DTN, but not in DTP and rates of MT. Given the delays in workflow metrics, prospective trials are required to show that tissue-based benefits of baseline MRI compensate for the temporal benefits of CT. ANN NEUROL 2022;92:184-194.

Cerebral perfusion imaging predicts final infarct volume after basilar artery thrombectomy.

OBJECTIVES: Cerebral perfusion imaging may be used to identify the ischemic core in acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation; however, perfusion parameters that predict the ischemic core in AIS patients with a basilar artery occlusion (BAO) are poorly described. We determined which cerebral perfusion parameters best predict the ischemic core after successful endovascular thrombectomy (EVT) in BAO patients. MATERIALS AND METHODS: We performed multicenter retrospective study of BAO patients with perfusion imaging before EVT and a DWI after successful EVT. The ischemic core was defined as regions on CTP, which were co-registered to the final DWI infarct. Various time-to-maximum (Tmax) and cerebral blood flow (CBF) thresholds were compared to final infarct volume to determine the best predictor of the final infarct. RESULTS: 28 patients were included in the analysis for this study. Tmax >8s (r2: 0.56; median absolute error, 16.0 mL) and Tmax >10s (r2: 0.73; median absolute error, 11.3 mL) showed the strongest agreement between the pre-EVT CTP study and the final DWI. CBF <38% (r2: 0.76; median absolute error, 8.2 mL) and CBF <34% (r2: 0.76; median absolute error, 9.1 mL) also correlated well with final infarct volume on DWI. CONCLUSIONS: Pre-EVT CT perfusion imaging is useful to predict the final ischemic infarct volume in BAO patients. Tmax >8s and Tmax >10s were the strongest predictors of the post-EVT final infarct volume.

Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia: A Matched Comparison.

BACKGROUND: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain. METHODS: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias. RESULTS: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42-2.16]; P<0.001), the coarsened exact matching (n=332-524, using multiple imputations of missing values; OR, 1.60 [1.08-2.36]; P=0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20-2.15]; P=0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59-4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30-3.75]), dependency or death (OR, 1.42 [0.91-2.23]), or mortality (OR, 1.65 [0.94-2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76-5.04]), dependency or death (OR, 1.49 [1.07-2.07]), and mortality (OR, 1.65 [1.11-2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73-4.29]). CONCLUSIONS: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

OBJECTIVE: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: ß -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: an observational study and individual patient data pooled analysis.

OBJECTIVE: The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start. METHODS: This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH. RESULTS: A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke. CONCLUSIONS: Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.

Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis.

BACKGROUND: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. METHODS: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. RESULTS: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). CONCLUSIONS: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

Association of the COVID-19 outbreak with acute stroke care in Switzerland.

BACKGROUND AND PURPOSE: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020. METHODS: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019. RESULTS: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07). CONCLUSIONS: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained.

Acute neurological disease as a trigger or co-occurrence of transient global amnesia: a case series and systematic review.

BACKGROUND: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate lesions on diffusion-weighted imaging (hippocampal punctate diffusion lesion, HPDL). The recent literature suggests that TGA may be triggered by acute neurological conditions. OBJECTIVE: To study patients with TGA triggered by an acute neurological disease. METHODS: We retrospectively reviewed patients from two neurology centres with TGA (with or without HPDL) in whom an acute neurological condition could be identified as trigger. We also performed a systematic review of the literature of this situation using predefined search terms. RESULTS: We identified 38 patients (median age 62 years, 55.3% female): 6 from our centres and 32 from the literature. Acute neurovascular diseases that preceded or were associated with TGA included ischemic and haemorrhagic strokes, convexity subarachnoid haemorrhage, and reversible cerebral vasoconstriction syndrome. As non-vascular acute neurological diseases, we identified migraine and peripheral-origin vertigo. The clinical manifestation of the neurological trigger showed a variable temporal relation with TGA onset; in some cases preceding and in others co-occurring with TGA manifestation. In some cases, presumed neurological triggers were asymptomatic and diagnosed from the neuroimaging done for the TGA. CONCLUSIONS: Acute vascular and non-vascular neurological events may trigger TGAs or may occur simultaneously. In the first case, such an acute neurological disease may activate direct pathways within the nervous systems leading to TGA, or alternatively elicit a bodily sympathetic overactivity cascade. In the second case, both neurological events may be the result of a common external stressor.

Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study.

AIMS: Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients. METHODS AND RESULTS: For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged <60 years was 3.64 (95% CI 1.76-7.52) per unit log10Lp(a) increase and 4.04 (95% CI 1.73-9.43) using the established cut-off ≥100 nmol/l. For 152 recurrent cerebrovascular events, we did not find a significant association in the whole cohort. However, Lp(a) levels ≥100 nmol/l were associated with an increased risk for recurrent events among patients who were either <60 years [adjusted hazard ratio (HR) 2.40, 95% CI 1.05-5.47], had evident LAA stroke aetiology (adjusted HR 2.18, 95% CI 1.08-4.40), or had no known atrial fibrillation (adjusted HR 1.60, 95% CI 1.03-2.48). CONCLUSION: Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged <60 years or with evident arteriosclerotic disease.

Renal Safety of Multimodal Brain Imaging Followed by Endovascular Therapy.

BACKGROUND AND PURPOSE: Contrast-enhanced noninvasive angiography and perfusion imaging are recommended to identify eligible patients for endovascular therapy (EVT) in extended time windows (>6 hours or wake-up). If eligible, additional intraarterial contrast exposure will occur during EVT. We aimed to study the renal safety in the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) population, selected with contrast-enhanced multimodal Imaging and randomized to EVT versus medical management. METHODS: In the randomized DEFUSE 3 trial population, we compared changes in serum creatinine between baseline (before randomization) and 24 hours later. The primary outcome was the relative change in creatinine level between baseline and 24 hours in the EVT versus medical arm. The secondary outcome was a comparison between computed tomography (CT) versus magnetic resonance imaging selection in the EVT arm. The safety outcome was a comparison of the proportion of patients with criteria for contrast-associated kidney injury in the EVT versus medical arm and a comparison between CT versus magnetic resonance imaging selection in the EVT arm. RESULTS: In the DEFUSE 3 population (n=182, age 69±13, 51% female), mean creatinine decreased from a baseline of 0.98±0.33 mg/dL to 0.88±0.28 mg/dL at 24 hours (P<0.001). There was no difference in change between treatment groups: relative to baseline, there was a 6.3% reduction in the EVT group versus 9.2% in the medical group, P=0.294. Absolute decrease -0.08±0.18 in EVT versus -0.12±0.18 in medical, P=0.135; Among patients treated with EVT, there was no difference in 24-hour creatinine level changes between patients who were selected with CT angiography/CT perfusion (-0.08±0.18) versus magnetic resonance imaging (-0.07±0.19), P=0.808 or 6.8% reduction versus 4.8%, P=0.696. In the EVT arm, contrast-associated kidney injury was encountered in 4 out of 91 (4.4%) versus 2/90 (2.2%) in the medical arm P=0.682. In the EVT arm, contrast-associated kidney injury was evenly distributed between magnetic resonance imaging (1/22, 4.6%) versus CT 3 out of 69 (4.4%), P=1.0. CONCLUSIONS: Perfusion imaging before EVT was not associated with evidence of decline in renal function. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

Extracellular Vesicle Surface Markers as a Diagnostic Tool in Transient Ischemic Attacks.

Background and Purpose: Extracellular vesicles (EVs) are promising biomarkers for cerebral ischemic diseases, but not systematically tested in patients with transient ischemic attacks (TIAs). We aimed at (1) investigating the profile of EV-surface antigens in patients with symptoms suspicious for TIA; (2) developing and validating a predictive model for TIA diagnosis based on a specific EV-surface antigen profile. Methods: We analyzed 40 subjects with symptoms suspicious for TIA and 20 healthy controls from a training cohort. An independent cohort of 28 subjects served as external validation. Patients were stratified according to likelihood of having a real ischemic event using the Precise Diagnostic Score, defined as: unlikely (score 0­1), possible-probable (score 2­3), or very likely (score 4­8). Serum vesicles were quantified by nanoparticle tracking analysis and EV-surface antigen profile characterized by multiplex flow cytometry. Results: EV concentration increased in patients with very likely or possible-probable TIA (P<0.05) compared with controls. Nanoparticle concentration was directly correlated with the Precise Diagnostic score (R=0.712; P<0.001). After EV immuno-capturing, CD8, CD2, CD62P, melanoma-associated chondroitin sulfate proteoglycan, CD42a, CD44, CD326, CD142, CD31, and CD14 were identified as discriminants between groups. Receiver operating characteristic curve analysis confirmed a reliable diagnostic performance for each of these markers taken individually and for a compound marker derived from their linear combinations (area under the curve, 0.851). Finally, a random forest model combining the expression levels of selected markers achieved an accuracy of 96% and 78.9% for discriminating patients with a very likely TIA, in the training and external validation cohort, respectively. Conclusions: The EV-surface antigen profile appears to be different in patients with transient symptoms adjudicated to be very likely caused by brain ischemia compared with patients whose symptoms were less likely to due to brain ischemia. We propose an algorithm based on an EV-surface-antigen specific signature that might aid in the recognition of TIA.

Maintenance of Acute Stroke Care Service During the COVID-19 Pandemic Lockdown.

[Figure: see text].

SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group.

[Figure: see text].

Collaterals are a major determinant of the core but not the penumbra volume in acute ischemic stroke.

PURPOSE: Determinants of early loss of ischemic tissue (core) or its prolonged survival (penumbra) in acute ischemic stroke (AIS) are poorly understood. We aimed to identify radiological associations of core and penumbra volumes on CT perfusion (CTP) in a large cohort of AIS. METHODS: In the ASTRAL registry (2003-2016), we identified consecutive AIS patients with proximal middle cerebral artery (MCA) occlusion. We calculated core and penumbra volumes using established thresholds and the mismatch ratio (MR). We graded collaterals into three categories on CT-angiography. We used clot burden score (CBS) to quantify the clot length. We related CTP volumes to radiological variables in multivariate regression analyses, adjusted for time from stroke onset to first imaging. RESULTS: The median age of the 415 included patients was 69 years (IQR = 21) and 49% were female. Median admission NIHSS was 16 (11) and median delay to imaging 2.2 h (1.9). Lower core volumes were associated with higher ASPECTS (hazard ratio = 1.08), absence of hyperdense MCA sign (HR = 0.70), higher CBS (i.e., smaller clot, HR = 1.10), and better collaterals (HR = 1.95). Higher penumbra volumes were related to lower CBS (i.e., longer clot, HR = 1.08) and proximal intracranial occlusion (HR = 1.47), but not to collaterals. Higher MR was found in absence of hyperdense MCA sign (HR = 1.28), absence of distal intracranial occlusion (HR = 1.39), and with better collaterals (HR = 0.52). CONCLUSIONS: In AIS, better collaterals were associated with lower core volumes, but not with higher penumbra volumes. This suggests a major role of collaterals in early tissue loss and their limited significance as marker of salvageable tissue.