Endovascular therapy (EVT) is a standard-of-care treatment for selected patients with acute ischemic stroke (AIS) who harbor large vessel occlusions in the anterior circulation and present less than 6 hours from symptom onset.^1-3 However, numerous questions remain regarding best practices for EVT, including which anesthetic strategy results in the best clinical outcomes.³

Background and Purpose—: Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Methods—: Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not progressing to infarction after 1 month. Results—: Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent ( P =0.006), and National Institutes of Health Stroke Scale score on admission was lower ( P =0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction ( P =0.0003). Conclusions—: Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00975962.

Background and Purpose—: Angiographic revascularization grading after intra-arterial stroke therapy is limited by poor standardization, making it unclear which scale is optimal for predicting outcome. Using recently standardized criteria, we sought to compare the prognostic performance of 2 commonly used reperfusion scales. Methods—: Inclusion criteria for this multicenter retrospective study were acute ischemic stroke attributable to middle cerebral artery M1 occlusion, intra-arterial therapy, and 90-day modified Rankin scale score. Post–intra-arterial therapy reperfusion was graded using the Thrombolysis in Myocardial Infarction (TIMI) and Modified Thrombolysis in Cerebral Infarction (mTICI) scales. The scales were compared for prediction of clinical outcome using receiver-operating characteristic analysis. Results—: Of 308 patients, mean age was 65 years, and median National Institutes of Health Stroke Scale score was 17. The mean time from stroke onset to groin puncture was 305 minutes. There was no difference in the time to treatment between patients grouped by final TIMI (ie, 0 versus 1 versus 2 versus 3) or mTICI grades (ie, 0 versus 1 versus 2a versus 2b versus 3). Good outcome (modified Rankin scale, 0–2) was achieved in 32.5% of patients, and mortality rate was 25.3% at 90 days. There was a 6.3% rate of parenchymal hematoma type 2. In receiver-operating characteristic analysis, mTICI was superior to TIMI for predicting 90-day modified Rankin scale 0 to 2 (c-statistic: 0.74 versus 0.68; P <0.0001). The optimal threshold for identifying a good outcome was mTICI 2b to 3 (sensitivity 78.0%; specificity 66.1%). Conclusions—: mTICI is superior to TIMI for predicting clinical outcome after intra-arterial therapy. mTICI 2b to 3 is the optimal biomarker for procedural success.

Background and Purpose —The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). Methods —DWI and PWI were performed in 11 patients ≤6 hours after the onset of symptoms of acute ischemic stroke. Regions of interest (ROIs) were placed covering the ischemic core (ROI 1), the penumbra that progressed to infarction on the basis of follow-up scans (ROI 2), and the penumbra that recovered (ROI 3). The ratios of relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and apparent diffusion coefficient were calculated as lesion ROIs relative to the contralateral mirror ROIs. Results —The post hoc analysis showed that the penumbra progressed to infarction at the following cutoff values: rCBF 1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. Conclusions —The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically.

The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.

Background and Purpose—: MRI using diffusion-weighted imaging (DWI) is the most sensitive diagnostic imaging modality for early detection of ischemia, but how accurate is it and how much does perfusion-weighted imaging (PWI) add to the sensitivity have to be known. Methods—: In this single-center study, we collected epidemiological, imaging, and outcome data on all patients with stroke undergoing MRI-based treatment with intravenous tissue-type plasminogen activator at our center from 2004 to 2010. The DWI negative patients were identified, and we calculated the sensitivity and specificity of DWI and additional PWI for diagnosing acute ischemic stroke. We compared DWI positive and negative patients to identify characteristics associated with DWI negativity. Results—: Five hundred sixty-nine consecutive patients were treated with intravenous tissue-type plasminogen activator on the basis of an acute MRI. A DWI lesion was evident in 518 patients. Forty-seven patients were DWI negative; however, a relevant PWI lesion was found in 33 of these patients. Four stroke mimics were treated with intravenous tissue-type plasminogen activator and 1 of these patients had a DWI lesion. Thus, 8% of all patients with stroke were DWI negative. The combination of DWI and PWI resulted in a sensitivity of 97.5% for the ischemic stroke diagnosis. DWI negativity was associated with less severe strokes, location in the posterior circulation, a longer time from onset to scan, and an improved 90-day outcome. The cause of small-vessel disease was more likely to be DWI negative. Conclusions—: The combination of DWI and PWI before intravenous tissue-type plasminogen activator confirms the diagnosis in 97.5% of all ischemic strokes.