Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. MethodsWe applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. FindingsIn 2019, there were 12•2 million (95% UI 11•0-13•6) incident cases of stroke, 101 million (93•2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6•55 million (6•00-7•02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11•6% [10•8-12•2] of total deaths) and the third-leading cause of death and disability combined (5•7% [5•1-6•2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70•0% (67•0-73•0), prevalent strokes increased by 85•0% (83•0-88•0), deaths from stroke increased by 43•0% (31•0-55•0), and DALYs due to stroke increased by 32•0% (22•0-42•0). During the same period, age-standardised rates of stroke incidence decreased by 17•0% (15•0-18•0), mortality decreased by 36•0% (31•0-42•0), prevalence decreased by 6•0% (5•0-7•0), and DALYs decreased by 36•0% (31•0-42•0). However, among people younger than 70 years, prevalence rates increased by 22•0% (21•0-24•0) and incidence rates increased by 15•0% (12•0-18•0). In 2019, the age-standardised stroke-related mortality rate was 3•6 (3•5-3•8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3•7 (3•5-3•9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62•4% of all incident strokes in 2019 (7•63 million [6•57-8•96]), while intracerebral haemorrhage constituted 27•9% (3•41 million [2•97-3•91]) and subarachnoid haemorrhage constituted 9•7% (1•18 million [1•01-1•39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79•6 million [67•7-90•8] DALYs or 55•5% [48•2-62•0] of total stroke DALYs), high bodymass index (34•9 million [22•3-48•6] DALYs or 24•3% [15•7-33•2]), high fasting plasma glucose (28•9 million [19•8-41•5] DALYs or 20•2% [13•8-29•1]), ambient particulate matter pollution (28•7 million [23•4-33•4] DALYs or 20•1% [16•6-23•0]), and smoking (25•3 million [22•6-28•2] DALYs or 17•6% [16•4-19•0]...

Although arsenic is a well-established human carcinogen, the mechanisms by which it induces cancer remain poorly understood. We previously showed arsenite to be a potent mutagen in humanhamster hybrid (AL) cells, and that it induces predominantly multilocus deletions. We show here by confocal scanning microscopy with the fluorescent probe 5,6-chloromethyl-2,7-dichlorodihydrofluorescein diacetate that arsenite induces, within 5 min after treatment, a dose-dependent increase of up to 3-fold in intracellular oxyradical production. Concurrent treatment of cells with arsenite and the radical scavenger DMSO reduced the fluorescent intensity to control levels. ESR spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-1-hydroxypiperidine (TEMPOL-H) as a probe in conjunction with superoxide dismutase and catalase to quench superoxide anions and hydrogen peroxide, respectively, indicates that arsenite increases the levels of superoxide-driven hydroxyl radicals in these cells. Furthermore, reducing the intracellular levels of nonprotein sulfhydryls (mainly glutathione) in A L cells with buthionine S-R-sulfoximine increases the mutagenic potential of arsenite by more than 5-fold. The data are consistent with our previous results with the radical scavenger DMSO, which reduced the mutagenicity of arsenic in these cells, and provide convincing evidence that reactive oxygen species, particularly hydroxyl radicals, play an important causal role in the genotoxicity of arsenical compounds in mammalian cells.

In ventilated stroke patients admitted to the ICU, arterial hyperoxia was independently associated with in-hospital death as compared with either normoxia or hypoxia. These data underscore the need for studies of controlled reoxygenation in ventilated critically ill stroke populations. In the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in ventilated stroke patients.

Arsenic is an important environmental carcinogen that affects millions of people worldwide through contaminated water supplies. For decades, arsenic was considered a nongenotoxic carcinogen. Using the highly sensitive A L mutation assay, we previously showed that arsenic is, indeed, a potent gene and chromosomal mutagen and that its effects are mediated through the induction of reactive oxygen species. However, the origin of these radicals and the pathways involved are not known. Here we show that mitochondrial damage plays a crucial role in arsenic mutagenicity. Treatment of enucleated cells with arsenic followed by rescue fusion with karyoplasts from controls resulted in significant mutant induction. In contrast, treatment of mitochondrial DNA-depleted (R 0 ) cells produced few or no mutations. Mitochondrial damage can lead to the release of superoxide anions, which then react with nitric oxide to produce the highly reactive peroxynitrites. The mutagenic damage was dampened by the nitric oxide synthase inhibitor, N G -methyl-L-arginine. These data illustrate that mitochondria are a primary target in arsenic-induced genotoxic response and that a better understanding of the mutagenic/carcinogenic mechanism of arsenic should provide a basis for better interventional approach in both treatment and prevention of arsenic-induced cancer. (Cancer Res 2005; 65(8): 3236-42)

In ventilated TBI patients admitted to the ICU, arterial hyperoxia was independently associated with higher in-hospital case fatality. In the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in critically ill ventilated TBI patients.

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Cerebral vasospasm occurs frequently after aneurysmal subarachnoid and contributes to delayed cerebral ischemia. In this article we address systematic problems with the literature on vasospasm and then review both established and experimental treatment options.

Background and purpose: Coronavirus disease 2019 (COVID-19) is a global pandemic that causes flu-like symptoms. There is a growing body of evidence suggesting that both the central and peripheral nervous systems can be affected by SARS-CoV-2, including stroke. We present three cases of arterial ischemic strokes and one venous infarction from a cerebral venous sinus thrombosis in the setting of COVID-19 infection who otherwise had low risk factors for stroke. Methods: We retrospectively reviewed patients presenting to a large tertiary care academic US hospital with stroke and who tested positive for COVID-19. Medical records were reviewed for demographics, imaging results and lab findings. Results: There were 3 cases of arterial ischemic strokes and 1 case of venous stroke: 3 males and 1 female. The mean age was 55 (48-70) years. All arterial strokes presented with large vessel occlusions and had mechanical thrombectomy performed. Two cases presented with stroke despite being on full anticoagulation. Conclusions: It is important to recognize the neurological manifestations of COVID-19, especially ischemic stroke, either arterial or venous in nature. Hypercoagulability and the cytokine surge are perhaps the cause of ischemic stroke in these patients. Further studies are needed to understand the role of anticoagulation in these patients.