Background and Purpose: When the coronavirus disease 2019 (COVID-19) outbreak became paramount, medical care for other devastating diseases was negatively impacted. In this study, we investigated the impact of the COVID-19 outbreak on stroke care across China. Methods: Data from the Big Data Observatory Platform for Stroke of China consisting of 280 hospitals across China demonstrated a significant drop in the number of cases of thrombolysis and thrombectomy. We designed a survey to investigate the major changes during the COVID-19 outbreak and potential causes of these changes. The survey was distributed to the leaders of stroke centers in these 280 hospitals. Results: From the data of Big Data Observatory Platform for Stroke of China, the total number of thrombolysis and thrombectomy cases dropped 26.7% ( P <0.0001) and 25.3% ( P <0.0001), respectively, in February 2020 as compared with February 2019. We retrieved 227 valid complete datasets from the 280 stroke centers. Nearly 50% of these hospitals were designated hospitals for COVID-19. The capacity for stroke care was reduced in the majority of the hospitals. Most of the stroke centers stopped or reduced their efforts in stroke education for the public. Hospital admissions related to stroke dropped ≈40%; thrombolysis and thrombectomy cases dropped ≈25%, which is similar to the results from the Big Data Observatory Platform for Stroke of China as compared with the same period in 2019. Many factors contributed to the reduced admissions and prehospital delays; lack of stroke knowledge and proper transportation were significant limiting factors. Patients not coming to the hospital for fear of virus infection was also a likely key factor. Conclusions: The COVID-19 outbreak impacted stroke care significantly in China, including prehospital and in-hospital care, resulting in a significant drop in admissions, thrombolysis, and thrombectomy. Although many factors contributed, patients not coming to the hospital was probably the major limiting factor. Recommendations based on the data are provided.

Background and Purpose The clinical significance of early (i.e. within the first 24 hours) uptake of ferumoxytol by macrophages in the wall of human cerebral aneurysms is not clear. The purpose of this study was to determine whether early uptake of ferumoxytol suggests unstable cerebral aneurysm. Methods Thirty unruptured aneurysms in 22 patients were imaged with MRI 24 hours after infusion of ferumoxytol. Eighteen aneurysms were also imaged 72 hours after infusion of ferumoxytol. Aneurysm dome tissue was collected from four patients with early MRI signal changes, five patients with late signal changes, and five other patients with ruptured aneurysms. The tissue was immunostained for expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal-prostaglandin-E2 synthase-1 (mPGES-1) and macrophages. Results In 23% (7/30) of aneurysms, there was pronounced early uptake of ferumoxytol. Four aneurysms were clipped. The remaining three aneurysms were managed conservatively; all three ruptured within six months. In 53% (16/30) of aneurysms, there was pronounced uptake of ferumoxytol at 72 hours. Eight aneurysms were surgically clipped and eight were managed conservatively; none ruptured or increased in size after six months. Expression of COX-2, mPGES-1, and macrophages was similar in unruptured aneurysms with early uptake of ferumoxytol and ruptured aneurysms. Expression of these inflammatory molecules was significantly higher in aneurysms with early uptake of ferumoxytol versus aneurysms with late uptake. Conclusions Uptake of ferumoxytol in aneurysm walls within the first 24 hours strongly suggests aneurysm instability and probability of rupture within six months, and may warrant urgent intervention.

Objective Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced-MRI. Methods and Results 19 unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were utilized. Protocol A: infusion of 2.5mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B: infusion of 5mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by two neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histologic analysis. Fifty percent(5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian-Blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian-Blue. Conclusions Imaging with T2*-GE-MRI at 72 hours post-infusion of 5mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.

The application of dual antiplatelet therapy in stent-assisted coiling of acutely ruptured aneurysms is associated with an increase in the risk of hemorrhagic complications following ventriculostomy or VP shunt placement, as compared with its use in a coiling procedure without a stent.

BackgroundInflammatory cells and molecules may play a critical role in formation and rupture of cerebral aneurysms. Recently, an epidemiologic study reported that acetylsalicylic acid (ASA) decreases the risk of aneurysm rupture. The goal of this study was to determine the effects of ASA on inflammatory cells and molecules in the walls of human cerebral aneurysms, using radiographic and histological techniques.Methods and ResultsEleven prospectively enrolled patients harboring unruptured intracranial aneurysms were randomized into an ASA‐treated (81 mg daily) group (n=6) and an untreated (control) group (n=5). Aneurysms were imaged at baseline using ferumoxytol‐enhanced MRI to estimate uptake by macrophages. After 3 months, patients were reimaged before undergoing microsurgical clipping. Aneurysm tissues were collected for immunostaining with monoclonal antibodies for cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2), microsomal prostaglandin E2 synthase‐1 (mPGES‐1), and macrophages. A decrease in signal intensity on ferumoxytol‐enhanced MRI was observed after 3 months of ASA treatment. Expression of COX‐2 (but not COX‐1), mPGES‐1, and macrophages was lower in the ASA group than in the control group.ConclusionsThis study provides preliminary radiographical and histological evidence that ASA may attenuate the inflammatory process in the walls of human cerebral aneurysms.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01710072.

F low diverters are now routinely used at several institutions for treatment of an expanding population of intracranial aneurysms. 7,8,13,18 The Pipeline Embolization Device (PED) is a flow diverter that has received significant attention in the recent literature. 7,17,18 The PED was approved by the FDA in 2011 for treatment of large and giant wide-necked aneurysms of the internal carotid artery (ICA). In most series the PED was used for the treatment of large, giant, complex, and fusiform aneurysms, with favorable results. Many investigators, however, remain wary of flow diverters, citing the lack of long-term safety data as well as the risk of distal parenchymal hemorrhage and delayed aneurysm rupture.Currently, there are few data on the use of the PED in small aneurysms amenable to conventional endovascular techniques. 1,14,19,20 Therefore, the safety and efficacy of the device in this subgroup remains unknown. We present the results of the largest series of small intracranial aneurysms treated with the PED to date. Methods Study DesignThis is a retrospective review of a single-center experience with use of the PED to treat small intracranial aneurysms. The study protocol was approved by the Thomas Jefferson University Institutional Review Board.abbreviatioNS ICA = internal carotid artery; MCA = middle cerebral artery; mRS = modified Rankin Scale; PED = Pipeline Embolization Device; SAH = subarachnoid hemorrhage. obJect Flow diverters are increasingly used for treatment of intracranial aneurysms. In most series, the Pipeline Embolization Device (PED) was used for the treatment of large, giant, complex, and fusiform aneurysms. Little is known about the use of the PED in small aneurysms. The purpose of this study was to assess the safety and efficacy of the PED in small aneurysms (≤ 7 mm). MethoDS A total of 100 consecutive patients were treated with the PED at the authors' institution between May 2011 and September 2013. Data on procedural safety and efficacy were retrospectively collected. reSultS The mean aneurysm size was 5.2 ± 1.5 mm. Seven patients (7%) had sustained a subarachnoid hemorrhage. All except 5 aneurysms (95%) arose from the anterior circulation. The number of PEDs used was 1.2 per aneurysm. Symptomatic procedure-related complications occurred in 3 patients (3%): 1 distal parenchymal hemorrhage that was managed conservatively and 2 ischemic events. At the latest follow-up (mean 6.3 months), 54 (72%) aneurysms were completely occluded (100%), 10 (13%) were nearly completely occluded (≥ 90%), and 11 (15%) were incompletely occluded (< 90%). Six aneurysms (8%) required further treatment. Increasing aneurysm size (OR 3.8, 95% CI 0.99-14; p = 0.05) predicted retreatment. All patients achieved a favorable outcome (modified Rankin Scale Score 0-2) at follow-up. coNcluSioNS In this study, treatment of small aneurysms with the PED was associated with low complication rates and high aneurysm occlusion rates. These findings suggest that the PED is a safe and effective alternative to conventional endovasc...

Summary A number of mitochondrial diseases arise from Single Nucleotide Variant (SNV) accumulation in multiple mitochondria. Here we present a method for identification of variants present at the single mitochondrion level in individual mouse and human neuronal cells allowing for extremely high resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high confidence variants in mouse and one in human that were present in multiple mitochondria across cells. The pattern of variation revealed by single mitochondrion data shows surprisingly pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci suggests inheritance of variants across generations resulting in Poisson jackpot lines with large SNV load. Comparison of human and mouse variants suggests that the two species might employ distinct modes of somatic segregation. Single mitochondrion resolution revealed mitochondria mutational dynamics that we hypothesize to affect risk probabilities for mutations reaching disease thresholds.