Treatment options in acute stroke are limited by a dearth of safe and effective regimens for recanalization of an occluded cerebrovascular tributary, as well as by the fact that patients present only after the occlusive event is established. We hypothesized that even if the site of major arterial occlusion is recanalized after stroke, microvascular thrombosis continues to occur at distal sites, reducing postischemic flow and contributing to ongoing neuronal death. To test this hypothesis, and to show that microvascular thrombosis occurs as an ongoing, dynamic process after the onset of stroke, we tested the effects of a potent antiplatelet agent given both before and after the onset of middle cerebral arterial (MCA) occlusion in a murine model of stroke. After 45 min of MCA occlusion and 23 h of reperfusion, fibrin accumulates in the ipsilateral cerebral hemisphere, based upon immunoblotting, and localizes to microvascular lumena, based upon immunostaining. In concordance with these data, there is a nearly threefold increase in the ipsilateral accumulation of 111 In-labeled platelets in mice subjected to stroke compared with mice not subjected to stroke. When a novel inhibitor of the glycoprotein IIb/IIIa receptor (SDZ GPI 562) was administered immediately before MCA occlusion, platelet accumulation was reduced 48%, and fibrin accumulation was reduced by 47% by immunoblot densitometry. GPI 562 exhibited a dose-dependent reduction of cerebral infarct volumes measured by triphenyltetrazolium chloride staining, as well as improvement in postischemic cerebral blood flow, measured by laser doppler. GPI 562 caused a dose-dependent increase in tail vein bleeding time, but intracerebral hemorrhage (ICH) was not significantly increased at therapeutic doses; however, there was an increase in ICH at the highest doses tested. When given immediately after withdrawal of the MCA occluding suture, GPI 562 was shown to reduce cerebral infarct volumes by 70%. These data support the hypothesis that in ischemic regions of brain, microvascular thrombi continue to accumulate even after recanalization of the MCA, contributing to postischemic hypoperfusion and ongoing neuronal damage. ( J. Clin. Invest. 1998. 102:1301-1310.)

Background and Purpose-Neutrophil (PMN) recruitment mediated by increased expression of intercellular adhesion molecule-1 expression (ICAM-1, CD54) in the cerebral microvasculature contributes to the pathogenesis of tissue injury in stroke. However, studies using blocking antibodies against the common ␤ 2 -integrin subunit on the PMN, the counterligand for ICAM-1 (CD18), have demonstrated equivocal efficacy. The current study tested the hypothesis that mice deficient in CD18 would be protected in the setting of reperfused but not nonreperfused stroke. Methods-Two groups of mice were studied, those whose PMNs could express CD18 (CD18 ϩ/ϩ) and those mice hypomorphic for the CD-18 gene (CD18 Ϫ/Ϫ). PMNs obtained from CD18 Ϫ/Ϫ or CD18 ϩ/ϩ mice were fluorescently labeled and tested for binding to murine brain endothelial monolayers. Using a murine model of focal cerebral ischemia in which an occluding suture placed in the middle cerebral artery (MCA) is removed after 45 minutes (transient ischemia, reperfused stroke) or left in place (permanent ischemia, nonreperfused stroke), cerebral infarct volumes (% ipsilateral hemisphere by TTC staining), cerebral blood flow (CBF, % contralateral hemisphere by laser-Doppler flowmetry), and survival (%) were examined 24 hours after the initial ischemic event. Adoptive transfer studies used

Arteriovenous malformations (AVMs) in the pediatric population are relatively rare but reportedly carry a higher rate of rupture than in adults. This could be due to the fact that most pediatric AVMs are only detected after rupture. We aimed to review the current literature regarding the natural history and the clinical outcome after multimodality AVM treatment in the pediatric population, as optimal management for pediatric AVMs remains controversial. A multidisciplinary approach using multimodality therapy if needed has been proved to be beneficial in approaching these lesions in all age groups. Microsurgical resection remains the gold standard for the treatment of all accessible pediatric AVMs. Embolization and radiosurgery should be considered as an adjunctive therapy. Embolization provides a useful adjunct therapy to microsurgery by preventing significant blood loss and to radiosurgery by decreasing the volume of the AVM. Radiosurgery has been described to provide an alternative treatment approach in certain circumstances either as a primary or adjuvant therapy.

A s of this writing, the growing coronavirus disease 2019 (COVID-19) pandemic has suspended international travel, has injected instability in global financial markets, and has led to widespread school and business closures. There are increased calls for social distancing, avoidance of unnecessary physical contacts/interactions, and even mandatory isolation in some countries. These restrictions are leading hospitals and healthcare systems to suspend elective procedures and limit staff interactions with patients to essential personnel only.The currently reported overall case fatality rate of COVID-19 is 2.3% in the general population, and is higher (14.8%) in patients >80 years of age. 1 Further, patients with COVID-19 requiring hospitalization suffer a number of cardiovascular complications including arrhythmias (16.7% of patients) 2 and heart failure (23% of patients), 3 raising the risk for acute ischemic stroke (AIS). Indeed, cerebrovascular complications have been reported in 5% to 6% of patients with severe COVID-19. 4,5 In this context, emergent delivery of endovascular therapy (EVT) requires careful planning and deliberation with special attention to patient selection, resource utilization, and the safety of healthcare providers.With the goal of minimizing the negative impact of COVID-19 on acute stroke patients and healthcare providers, we assembled a multidisciplinary working group to develop consensus-based recommendations and an algorithm for evaluation and treatment of acute stroke patients eligible for EVT during the COVID-19 pandemic. The role of intravenous thrombolysis is not addressed here because EVT presents unique challenges compared with intravenous drug administration.Three populations of potential thrombectomy patients are highlighted: (1) emergency department (ED) patients with stroke and suspected COVID-19, (2) admitted patients with COVID-19 who develop stroke, and (3) patients with stroke who present to a hospital with constrained resources due to COVID-19. Recommendations are discussed and a clinical algorithm is proposed with anticipated decision points of care. This algorithm takes into account the American Heart Association/American Stroke Association (AHA/ASA) EVT guidelines, the safety of patients and staff, the predictors of mortality in patients with COVID-19, and the appropriate utilization of scarce resources.Our working group concluded that diagnosis with COVID-19 is not necessarily a contraindication to EVT for stroke. However, particular care must be taken when preparing patients with COVID-19 for EVT to ensure staff safety. In addition, it may be reasonable during these times of extreme resource limitation to modify current EVT protocols including patient selection and post-EVT care, and to avoid EVT in unstable, severely critically ill patients with COVID-19. Methods SettingOur Comprehensive Stroke Center is a large, urban, tertiary care academic medical center performing >200 thrombectomies a year. The center also serves as the only Level I Trauma Center in the region and...

Background and Purpose: Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality. Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this. We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities. Methods: Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke. We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year. Results: Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%–46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana. Results compared with the prior year and time trend analyses were consistent. Reperfusion treatments also appeared to decline by 31% (95% CI, 3%–51%), and specifically thrombolysis by 33% (95% CI, 4%–55%), but this finding had less precision. Conclusions: Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly. Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study. Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.