Objective To assess the feasibility, safety and preliminary efficacy of intra-arterial thrombolysis (IAT) compared with standard intravenous thrombolysis (IVT) for acute ischemic stroke. Methods Eligible patients with ischemic stroke, who were devoid of contraindications, started IVT within 3 h or IAT as soon as possible within 6 h. Patients were randomized within 3 h of onset to receive either intravenous alteplase, in accordance with the current European labeling, or up to 0.9 mg/kg intra-arterial alteplase (maximum 90 mg), over 60 min into the thrombus, if necessary with mechanical clot disruption and/or retrieval. The purpose of the study was to determine the proportion of favorable outcome at 90 days. Safety endpoints included symptomatic intracranial hemorrhage (SICH), death and other serious adverse events. Results 54 patients (25 IAT) were enrolled. Median time from stroke onset to start to treatment was 3 h 15 min for IAT and 2 h 35 min for IVT (p,0.001). Almost twice as many patients on IAT as those on IVT survived without residual disability (12/25 vs 8/29; OR 3.2; 95% CI 0.9 to 11.4; p50.067). SICH occurred in 2/25 patients on IAT and in 4/29 on IVT (OR 0.5; CI 0.1 to 3.3; p50.675). Mortality at day 7 was 5/25 (IAT) compared with 4/29 (IVT) (OR 1.6; CI 0.4 to 6.7; p50.718). There was no significant difference in the rate of other serious adverse events. Conclusions Rapid initiation of IAT is a safe and feasible alternative to IVT in acute ischemic stroke. Trial registration number NCT00540527.Although intravenous alteplase administered within 3 h of symptom onset is the only approved medication for the treatment of acute ischemic stroke, 1 this approach has known limitations. A major issue is that intravenous alteplase may be ineffective in patients with occlusions of the large arteries, such as the internal carotid artery, 2 3 carotid T segment 4 and the proximal (M1) segment of the middle cerebral artery. Intra-arterial thrombolysis (IAT) offers some theoretical advantages over intravenous thrombolysis (IVT) 7 : (a) angiographic planning allows customization of treatment strategy; (b) locoregional injection allows a much higher concentration of the drug where needed and the overall dosage administered to the patient is limited to the minimum necessary; (d) mechanical devices may either speed up the recanalization process or make it possible in drug resistant cases.Recanalization rates have been related to improved clinical outcome 8 and there are data suggesting that in patients with large vessel occlusions reperfusion rates with IAT are superior to those obtained with IVT. However, compared with IVT, intra-arterial treatment requires more time consuming and invasive procedures, and expensive techniques that are available only in highly specialized centers with a neurointerventional team. Although previous randomized controlled trials (RCTs) on IAT provided promising results, 6 9 10 their generalization remains questionable as they were performed in highly selected patients. 11As a result, ...

Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types. In models of stroke, the principal mechanism by which any improvement has been observed, has been attributed to the release of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however, issues still need to be addressed for use in human subjects.

Background: Valid and reliable ischemic stroke subtype determination is crucial for well-powered

Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses.