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Background and Purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology.Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20).Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (pConclusions: Our findings suggest that cryptogenic stroke among COVID-19 patients carries a significant risk of early mortality. [ABSTRACT FROM AUTHOR]

Background: Transfer protocols from primary to comprehensive stroke centers are crucial for endovascular treatment success. Aim: To evaluate clinical and neuroimaging data of transferred patients and their likelihood of presenting a large infarct core at comprehensive stroke center arrival. Methods: Retrospective analysis of population-based mandatory prospective registry of acute stroke patients evaluated for endovascular treatment. Consecutive patients evaluated at primary stroke center with suspected large vessel occlusion and PSC-ASPECTS ≥ 6 transferred to a comprehensive stroke center were included. PSC and CSC-ASPECTS, time-metrics, and clinical data were analyzed. Results: During 28 months, 1185 endovascular treatment candidates were transferred from PC to comprehensive stroke center in our public stroke network, 477 had an anterior circulation syndrome and available neuroimaging information and were included. Median baseline NIHSS was 13 (8–19). On arrival to comprehensive stroke center, large vessel occlusion was confirmed in 60.2% patients, and 41.2% received endovascular treatment. Median interfacility ASPECTS decay was 1 (0–2) after a median of 150.7 (SD 101) min between both CT-acquisitions. A logistic regression analysis adjusted by age, time from symptoms to PC-CT, and time from PC-CT to CSC-CT showed that only a baseline NIHSS and PSC-ASPECTS independently predicted a CSC-ASPECTS < 6. ROC curves identified baseline NIHSS ≥ 16 and PSC-ASPECTS ≤ 7 as the best cut-off points. The rate of CSC-ASPECTS < 6 increased from 7% to 57% among patients with NIHSS ≥ 16 and PSC-ASPECS ≤ 7. Conclusion: After a median transfer time >2 h, only 11.9% showed ASPECTS < 6 at the comprehensive stroke center. Activation of endovascular treatment teams should not require confirming neuroimaging on arrival and repeating neuroimaging at comprehensive stroke center should only be performed in selected cases. [ABSTRACT FROM AUTHOR]

Background and purpose: Ischemic stroke (IS) and hemorrhagic stroke (HemS) typically lead to a breakdown of the blood–brain barrier with neural antigen presentation. This presentation could potentially generate destructive auto-immune responses. Pre-existing antineuronal and antiglial antibodies (AA), predominantly NMDA receptor antibodies, have been reported in patients with stroke. This article summarizes three independent prospective studies, the Lübeck cohort (LC), Barcelona cohort (BC), and Heidelberg cohort (HC), exploring the frequency and clinical relevance of AA in patients with acute stroke (AS). Methods: In all cohorts together, 344 consecutive patients admitted with AS (322 × IS, 22 × HemS) were screened for AA in serum at admission. Clinical outcome parameters as well as a second AA screening were available at 30 days in the LC or at 90 days in the BC. A control group was included in the BC (20 subjects free from neurological disease) and the HC (78 neurological and ophthalmological patients without evidence for stroke). Results: The rate of positivity for AA was similar in control subjects and AS patients (13%, 95% CI [7%, 22%] vs. 13%, 95% CI [10%, 17%]; p = 0.46) with no significant difference between cohorts (LC 25/171, BC 12/75, HC 9/98). No patient had developed new AA after 30 days, whereas 2 out of 60 patients had developed new AA after 90 days. AA positive patients did not exhibit significant differences to AA negative patients in stroke subtype (LC, BC), initial stroke severity (BC, LC, HC), infarct volume (BC), and functional status at admission (BC, LC, HC) and follow-up (BC, LC). Conclusions: AS does not induce AA to a relevant degree. Pre-existing AA can be found in the serum of stroke patients, but they do not have a significant association with clinical features and outcomes. [ABSTRACT FROM AUTHOR]

Rationale: Optimal pre-hospital delivery pathways for acute stroke patients suspected to harbor a large vessel occlusion have not been assessed in randomized trials. Aim: To establish whether stroke subjects with rapid arterial occlusion evaluation scale based suspicion of large vessel occlusion evaluated by emergency medical services in the field have higher rates of favorable outcome when transferred directly to an endovascular center (endovascular treatment stroke center), as compared to the standard transfer to the closest local stroke center (local-SC). Design: Multicenter, superiority, cluster randomized within a cohort trial with blinded endpoint assessment. Procedure: Eligible patients must be 18 or older, have acute stroke symptoms and not have an immediate life threatening condition requiring emergent medical intervention. They must be suspected to have intracranial large vessel occlusion based on a pre-hospital rapid arterial occlusion evaluation scale of ≥5, be located in geographical areas where the default health authority assigned referral stroke center is a non-thrombectomy capable hospital, and estimated arrival at a thrombectomy capable stroke hospital in less than 7 h from time last seen well. Cluster randomization is performed according to a pre-established temporal sequence (temporal cluster design) with three strata: day/night, distance to the endovascular treatment stroke center, and week/week-end day. Study outcome: The primary endpoint is the modified Rankin Scale score at 90 days. The primary safety outcome is mortality at 90 days. Analysis: The primary endpoint based on the modified intention-to-treat population is the distribution of modified Rankin Scale scores at 90 days analyzed under a sequential triangular design. The maximum sample size is 1754 patients, with two planned interim analyses when 701 (40%) and 1227 patients have completed follow-up. Hypothesized common odds ratio is 1.35. [ABSTRACT FROM AUTHOR]

Objective Stroke patients with good collateral circulation achieve the best recovery after mechanical thrombectomy (MT) but strict imaging selection may result in untreated patients that could benefit from MT. We assessed whether the extent of collaterals had modifying effects on the amount of ischemic tissue saved from infarction with MT over best medical treatment (BMT). Methods This was a single center cohort of consecutive patients (n=339) with proximal occlusions in the carotid territory. Patients were categorized according to a four point category scale on CT angiography as having good (scores 2--3) or poor (scores 0--1) collaterals. The primary outcome measure was the interaction between collaterals and MT on infarct growth. The secondary outcome assessed the treatment effect of MT over BMT on functional status in relation to collateral status. Safety outcomes were mortality and symptomatic intracranial hemorrhage. Results Collaterals had a modifying effect of MT on infarct growth (P=0.004), with a greater reduction in 96 patients with poor collaterals (38.8 mL) than in 243 patients with good collaterals (1.9 mL). There was also a significant (P<0.001) interaction between the effect of MT and functional outcome in relation to collateral status, with more benefits of MT in patients with poor collaterals. MT was associated with lower mortality than BMT in patients with poor collaterals only. Conclusion Compared with BMT, the use of MT in the early time window in large vessel stroke results in a more substantial limitation of infarct growth in patients with poor collaterals. [ABSTRACT FROM AUTHOR]

Background: Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim: To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods: Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results: The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions: Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent. [ABSTRACT FROM AUTHOR]

Background: A significant proportion of stroke patients presenting with mild symptoms does not have a successful recovery, especially when a large vessel is occluded. IV thrombolysis is safe and may benefit patients presenting with mild symptoms. In this study, we tested whether endovascular therapy (ET) is superior to medical therapy in these patients. Methods: Observational, prospectively collected, multicenter study of 78 consecutive patients admitted from 2009 to 2012 within 6 h of stroke, with NIHSS ≤5 at presentation or during initial diagnostic work-up and large vessel occlusion. Data for patients undergoing ET and/or IV thrombolysis were taken from the SONIIA registry of reperfusion therapies in Catalonia, or from our local stroke registry if no reperfusion therapy was delivered. We compared risk factors, clinical course, collateral circulation, revascularization rates, hemorrhagic complications, infarct volume, and the functional outcome at 3 months of patients treated with ET and those not receiving ET. Ordinal regression was used to assess the independent effect of ET on functional outcome. Results: Baseline characteristics were similar for ET (n = 34) and medically (n = 44) treated patients, except for older age in the latter. The occlusions were located in the terminal internal carotid artery (1%), M1 segment of the middle cerebral artery (33%), M2 segment (30%), posterior circulation (31%), and 5% of the patients had tandem lesions, with no significant differences between groups. Most patients in both treatment groups had good collateral flow. The rate of successful revascularization (91.2 vs. 63.4%; p = 0.006) and the risk of symptomatic intracranial hemorrhage (11.8 vs. 0%; p = 0.033) were higher in the ET group. The NIHSS scores were similar at hospital arrival, after initial neuroimaging, and at 24 h in both treatment groups and there were no significant differences in the infarct volume in a follow-up MRI. At 3 months, 35.9% of the patients had some disability. The functional outcome was similar in both treatment groups in univariate analysis and also in models adjusted for age and initial NIHSS or for variables associated to functional outcome on univariate comparison. Conversely, IV thrombolysis was associated with significantly greater chances of full recovery after adjusting for baseline differences (OR 3.70, p = 0.015). Conclusions: One third of stroke patients with mild symptoms and large vessel occlusions do not have a successful recovery. ET is effective to recanalize the occluded vessel but increases the risk of serious bleeding significantly without improving the functional outcome, and is therefore not justified routinely in these patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend withholding antithrombotic therapy (ATT) for at least 24 h in patients with acute ischemic stroke treated with thrombolytic therapy. Herein, we report a retrospective analysis of a single-centre experience on the safety and efficacy of antithrombotic therapy (ATT) started before or after 24 h of intravenous thrombolysis in a cohort of acute ischemic stroke patients. Methods: A total of 139 patients (Rapid ATT group) received antithrombotic therapy before 24 h of thrombolysis, and 33 patients (Standard ATT group) after 24 h. The brain parenchyma and vessel status were assessed using simple CT scan on admission, multimodal CT scan at the end of thrombolysis, and angio-CT/MRI scan at day 3. Functional outcome was scored using the modified Rankin Scale (mRS) at day 90. Results: The two ATT groups had similar demographics, stroke subtypes, baseline NIHSS, thrombolytic strategies, vessel-patency rates at the end of thrombolysis, and incidence of bleeding complications at follow up. At day 3, the Rapid ATT group had a non-significant improved vessel-patency rate than the Standard ATT group. At day 90, a greater proportion of patients in the rapid ATT group had shifted down the mRS, and had improved in the NIHSS score. Conclusions: ATT initiated before 24 h of intravenous thrombolytic therapy in acute stroke patients disclosed no safety concerns compared with a conventional antithrombotic therapy delay of 24 h and showed better functional outcome at follow up. The value of early initiation of ATT after thrombolysis deserves further assessment in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Abstract: Heat shock protein 70 (Hsp-70) can act as a danger signal and activate immune responses. We studied the presence of Hsp-70 in lymphoid tissue and plasma of acute stroke patients and asymptomatic controls free of neurological disease. Immunofluorescence, Western blotting, qRT-PCR and flow cytometry studies were performed. Plasma Hsp-70 concentration at day 7 was similar in patients and controls, whereas patients disclosed stronger immunoreactivity to Hsp-70 in lymphoid tissue than controls. Most Hsp-70+ cells were antigen presenting cells located in T cell zones. Stronger immunoreactivity to Hsp-70 was associated with smaller infarctions and better functional outcome. [Copyright &y& Elsevier]

Purpose To assess the reliability of the Fazekas score on brain CT in acute stroke patients. Methods Two raters evaluated the Fazekas score in 157 CT scans from consecutive patients with acute stroke. Results The Fazekas scores on brain CT scans showed consistent (weighted κ, 0.73) and moderate (weighted κ, 0.56) interobserver agreement for periventricular and deep white matter areas, respectively. Intraobserver reliability was substantial for both areas (weighted κ, 0.85 and 0.8). Conclusion The Fazekas score on CT can be used to reliably grade white matter changes, and can be a useful tool when MRI is not available. [ABSTRACT FROM AUTHOR]