Editorial [ Hot Topic:Stroke Bugs: Current and Emerging Concepts Relevant to Infection in Cerebrovascular Disease] (Guest Editors: Hedley CA Emsley and Angel Chamorro)

In this fascinating special topic issue, contributors from various centres in the UK, Europe and the US have reviewed a range of subjects on the theme of infection and stroke. What is perhaps most surprising is that relatively little attention has been devoted to such a clinically important topic until very recently. The relationships between infection and stroke are wide ranging, as illustrated by the diversity of topics covered in this collection. Infection occurring before and after stroke has huge clinical implications, and a better knowledge of mechanisms in paediatric as well as adult populations - and in other specific populations such as individuals with HIV infection - is likely to be increasingly important from a global perspective. Relatively recent developments also include the increasing recognition of VZV vasculopathy in stroke, and the concept of aggregate chronic infectious burden in stroke risk. In addition to well established risk factors for infection poststroke, evidence for poststroke immunodepression is increasing. Models of infection before and after stroke should facilitate the investigation of new targets. From a clinical viewpoint there is increasing recognition that greater account needs to be taken of infection when considering both established and novel acute stroke treatments. The swine flu pandemic has of course also brought influenza into sharp focus and there can be little doubt about the importance of vaccination uptake in appropriate groups. Catherine Amlie-Lefond and Heather Fullerton have reviewed the topical and important subject of infection and childhood ischaemic stroke in a comprehensive manner. They have considered potential mechanisms to include vascular injury (including arteriopathy and vasculitis) and effects on the coagulation system. One senses a somewhat dynamic relationship between paediatric stroke and infection - for example, whilst there has been a diminished role of meningitis in areas with widespread vaccination uptake, the potential role of minor infections in the pathogenesis of childhood stroke is probably of increasing importance and interest. In Myles Connor's review of HIV and stroke, he also opens by discussing a range of proposed mechanisms through which HIV infection causes stroke, before covering a range of other key issues. Perhaps of particular note is the role of antiretroviral therapy - whilst life expectancy is increased, thereby inherently increasing the duration of exposure to conventional stroke risk factors, antiretroviral therapy also causes pro-atherosclerotic metabolic and endothelial dysfunction. New antiretroviral agents would ideally eradicate HIV without the accompanying drug induced vascular dysfunction associated with current drugs. In contrast to the role of individual infectious pathogens, Mitchell Elkind discusses the relatively recent concept that aggregate burden of several common chronic bacterial and viral (particularly herpes virus) infections may contribute to stroke risk via both atherosclerosis and atherosclerosis-independent mechanisms. It seems likely that a range of host factors, including genetic, interact with such infections to influence vascular disease risk. He highlights the fact that further studies will be needed to determine the role of antibiotics or vaccines in this context. Steve Hopkins and I (HE) have discussed the emerging concept of poststroke immunodepression. After briefly reviewing innate and adaptive immune responses after stroke, we have considered the experimental and clinical evidence for poststroke immunodepression and discussed potential mechanisms. Odilo Engel and Andreas Meisel have considered the impact of infections after stroke as well as pre-existing infection predisposing to stroke, and relate these topics to models of strokeassociated pneumonia and pre-stroke infection. Their discussion also covers poststroke immunodepression in the experimental setting, importantly highlighting its apparent dependence upon severity of cerebral ischaemia, indeed consistent with the concept that in stroke patients the occurrence of poststroke immunodepression is associated with greater stroke severity [1]. Future research in this field should better define immune changes that follow acute stroke, the potential utility of markers of immunodepression beyond existing clinical markers such as the National Institutes of Health Stroke Scale score to predict complications, and the implications of immunodepression for novel therapeutic strategies in stroke. Maria Nagel, Ravi Mahalingam, Randall Cohrs and Don Gilden have provided an overview of the difficult topic of viral vasculopathies and stroke, concentrating on VZV for which the greatest evidence base exists. Indeed perhaps a striking common theme in this collection of articles is the apparent importance of herpes viruses in stroke. In addition to the article by Don Gilden and colleagues, herpes viruses feature in the discussion by Amlie-Lefond & Fullerton in terms of VZV vasculopathy and paediatric stroke, in the review by Elkind insofar as the association of herpes virus infections with subclinical measures of atherosclerosis and clinical outcome, and in the account by Connor given the implication of VZV in HIV vasculopathy.