BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support).

A n outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan, China, in December 2019 and has rapidly spread around the world to become a pandemic (1). Italy was the second epicenter of the spread of the disease, and at the time of writing has a total of 222 104 cases and 31 106 deaths (1). Several studies have described the spectrum of chest imaging features of COVID-19 (2). However, to date, only a few case reports have described COVID-19-associated neurologic imaging findings (3-8). The purpose of our study was to systematically characterize neurologic symptoms and neuroimaging features in hospitalized patients with COVID-19 from multiple institutions in Italy.

Recent positive trials have thrust acute cerebral perfusion imaging into the routine evaluation of acute ischemic stroke. Updated guidelines state that in patients with anterior circulation large vessel occlusions presenting beyond 6 hours from time last known well, advanced imaging selection including perfusion-based selection is necessary. Centers that receive patients with acute stroke must now have the capability to perform and interpret CT or magnetic resonance perfusion imaging or provide rapid transfer to centers with the capability of selecting patients for a highly impactful endovascular therapy, particularly in delayed time windows. Many stroke centers are quickly incorporating the use of automated perfusion processing software to interpret perfusion raw data. As CT perfusion (CTP) is being assimilated in real-world clinical practice, it is essential to understand the basics of perfusion acquisition, quantification, and interpretation. It is equally important to recognize the common technical and clinical diagnostic challenges of automated CTP including ischemic core and penumbral misclassifications that could result in underestimation or overestimation of the core and penumbra volumes. This review highlights the pitfalls of automated CTP along with practical pearls to address the common challenges. This is particularly tailored to aid the acute stroke clinician who must interpret automated perfusion studies in an emergency setting to make time-dependent treatment decisions for patients with acute ischemic stroke.

SUMMARY:The acetazolamide (ACZ) challenge test is a useful clinical tool and a reliable predictor of critically reduced perfusion. In patients with chronic steno-occlusive disease, the ability to maintain normal cerebral blood flow by reducing vascular resistance secondary to autoregulatory vasodilation is compromised. Identification of the presence and degree of autoregulatory vasodilation (reflecting the cerebrovascular reserve) is a significant prognostic factor in patients with chronic cerebrovascular disease. The pharmacologic challenge of a vasodilatory stimulus such as ACZ can also be used to optimize the treatment strategies for these patients. The pathophysiology, methods, and clinical applications of the ACZ challenge test are discussed in this article. Viability of the cerebral parenchyma is dependent on the ability of the brain vasculature to provide adequate levels of cerebral blood flow (CBF). In patients with chronic stenoocclusive disease, the ability to maintain normal CBF by reducing vascular resistance is compromised. Identification of the degree of autoregulatory vasodilation reflects cerebrovascular reserve (CVR), which is a significant prognostic factor in chronic cerebrovascular disease.1-5 Flow reserve can be assessed with the use of paired blood flow measurements, with the initial measurement obtained at baseline and the second, after a vasodilatory stimulus, such as acetazolamide (ACZ). 6 Pathophysiology of Chronic Cerebrovascular DiseaseChronic cerebral hypoperfusion is usually the result of occlusion or stenosis of large arteries in the neck or the circle of Willis. Clinical symptoms and manifestations of brain ischemia in patients with chronic cerebrovascular disease (CVD) develop as a consequence of 2 main mechanisms: embolic events from atherosclerotic plaques resulting in local compromise of blood flow and systemic hemodynamic alterations that further reduce an already compromised cerebral perfusion state. 7The hemodynamic changes due to a decline in cerebral perfusion pressure have been studied by many investigators. 6,[8][9][10][11] Chronic CBF restriction causes a progressive decrease in cerebral perfusion pressure (CPP). Initially, decreases of CPP cause varying degrees of autoregulatory vasodilation of small distal arterioles.12 Powers 10 and Powers et al 11 proposed a 2-stage classification of hemodynamic impairment in patients with CVD. In stage I (autoregulatory vasodilation), autoregulation reduces cerebral vascular resistance. CBF and oxygen extraction fraction (OEF) are not significantly changed. Increases of cerebral blood volume (CBV) and mean transit time (MTT) are 2 parameters that reflect this initial phase of compensatory autoregulatory vasodilation. Further decreases of CPP beyond cerebral autoregulatory vasodilation capacity eventually result in stage II (autoregulatory failure), characterized by decreases of CBF and increases of OEF. When the CBF decreases, neurons increase the fraction of oxygen extracted from the blood to maintain normal neurologic function. ...

Background and Purpose The STroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5–6, 2015 in Washington, D.C. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. Methods This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the U.S. Food and Drug Administration (FDA) to discuss stroke imaging research priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. Results The imaging session summarized and compared the imaging components of the recent positive endovascular trials, and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. Conclusions Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

IMPORTANCE Advances in treatment of traumatic brain injury are hindered by the inability to monitor pathological mechanisms in individual patients for targeted neuroprotective treatment. Spreading depolarizations, a mechanism of lesion development in animal models, are a novel candidate for clinical monitoring in patients with brain trauma who need surgery.OBJECTIVE To test the null hypothesis that spreading depolarizations are not associated with worse neurologic outcomes. DESIGN, SETTING, AND PARTICIPANTSThis prospective, observational, multicenter cohort study was conducted from February 2009 to August 2013 in 5 level 1 trauma centers. Consecutive patients who required neurological surgery for treatment of acute brain trauma and for whom research consent could be obtained were enrolled; participants were excluded because of technical problems in data quality, patient withdrawal, or loss to follow-up. Primary statistical analysis took place from April to December 2018. Evaluators of outcome assessments were blinded to other measures.INTERVENTIONS A 6-contact electrode strip was placed on the brain surface during surgery for continuous electrocorticography during intensive care. MAIN OUTCOMES AND MEASURESElectrocorticography was scored for depolarizations, following international consensus procedures. Six-month outcomes were assessed by the Glasgow Outcome Scale-Extended score. RESULTS A total of 157 patients were initially enrolled; 19 were subsequently excluded. The 138 remaining patients (104 men [75%]; median [interquartile range] age, 45 [29-64] years) underwent a median (interquartile range) of 75.5 (42.2-117.1) hours of electrocorticography. A total of 2837 spreading depolarizations occurred in 83 of 138 patients (60.1% incidence) who, compared with patients who did not have spreading depolarizations, had lower prehospital systolic blood pressure levels (mean [SD], 133 [31] mm Hg vs 146 [33] mm Hg; P = .03), more traumatic subarachnoid hemorrhage (depolarization incidences of 17 of 37 [46%], 18 of 32 [56%], 22 of 33 [67%], and 23 of 30 patients [ 77%] for Morris-Marshall Grades 0, 1, 2, and 3/4, respectively; P = .047), and worse radiographic pathology (in 38 of 73 patients [52%] and 42 of 60 patients [70%] for Rotterdam Scores 2-4 vs 5-6, respectively; P = .04). Of patients with depolarizations, 32 of 83 (39%) had only sporadic events that induced cortical spreading depression of spontaneous electrical activity, whereas 51 of 83 patients (61%) exhibited temporal clusters of depolarizations (Ն3 in a 2-hour span). Nearly half of those with clusters (23 of 51 [45%]) also had depolarizations in an electrically silent area of the cortex (isoelectric spreading depolarization). Patients with clusters did not improve in motor neurologic examinations from presurgery to postelectrocorticography, while other patients did improve. In multivariate ordinal regression adjusting for baseline prognostic variables, the occurrence of depolarization clusters had an odds ratio of 2.29 (95% CI, 1.13-4.65; P = .02) for worse ...

Background and Purpose Although perfusion abnormality is an increasingly important therapeutic target, the natural history of tissue at risk without reperfusion treatment is understudied. Our objective was to determine how time affects penumbral salvage and infarct growth in untreated acute ischemic stroke patients and whether collateral status affects this relationship. Methods We utilized a prospectively-collected, multicenter acute stroke registry to assess acute stroke patients who were not treated with intravenous thrombolysis or endovascular treatment. We analyzed baseline CT angiogram and CT perfusion within 24 hours of stroke onset along with follow-up imaging, and assessed time from stroke onset to baseline imaging, ASPECTS, vessel occlusion, collaterals, ischemic core and penumbra. Penumbral salvage and infarct growth was calculated. Correlations between time and penumbral salvage and infarct growth were evaluated with Spearman correlation. Penumbral salvage and infarct growth were compared between subjects with good versus poor collateral status using the Wilcoxon rank sum test. Clinical and imaging factors affecting penumbral salvage and infarct growth were evaluated by linear regression. Results Among 94 untreated stroke patients eligible for this analysis, the mean age was 65, median NIHSS was 13, and median (range) time from stroke onset to baseline imaging was 2.9 (0.4–23) hours. There was no correlation between time and salvaged penumbra (r= 0.06; p=0.56) or infarct growth (r=−0.05; p=0.61). Infarct growth was higher among those with poor collaterals versus good collaterals (median 52.3 vs 0.9 cc; p<0.01). Penumbral salvage was lower among those with poor collaterals compared to those with good collaterals (poor 0 [0, 0]; good 5.9 cc [0, 29.4]; p<0.01). Multivariable linear regression demonstrated that collaterals, but not time, were significantly associated with infarct growth and penumbral salvage. Conclusion In this natural history study, penumbral salvage and infarct growth was less time dependent and more a measure of collateral flow.

N euroimaging abnormalities of cerebral white matter lesions (WML), lacunes, and brain atrophy are related to underlying cerebral small-vessel disease (SVD) and are more common in those with stroke and cardiovascular risk factors, in particular hypertension.1,2 Studies of patients with acute ischemic stroke report that WML and cerebral atrophy on baseline computed tomography (CT) are related to poor functional outcome, suggesting that the preexisting markers of Background and Purpose-The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure-lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods-We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography (<6 hours of intracerebral hemorrhage onset) by 3 independent neurologists blind to clinical data. Results-WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02-1.98), 1.47 (1.08-1.99), and 1.64 (1.21-2.22), respectively (all P for trend <0.05). There was no association between lacunes and outcomes. There were no significant differences in the effects of intensive blood pressure-lowering across subgroups of cerebral SVD. Conclusions-Preexisting