Elsevier

The Lancet Neurology

Volume 7, Issue 4, April 2008, Pages 341-353
The Lancet Neurology

Review
Acute ischaemic stroke and infection: recent and emerging concepts

https://doi.org/10.1016/S1474-4422(08)70061-9Get rights and content

Summary

The relation between acute ischaemic stroke and infection is complex. Infection appears to be an important trigger that precedes up to a third of ischaemic strokes and can bring about stroke through a range of potential mechanisms. Infections that present subsequent to stroke also complicate up to a third of cases of stroke and might worsen outcome. Inflammatory responses, which are a defence mechanism against infection but can also be a pathogenic mechanism that precipitates stroke and neurological sequelae, are important features. Although factors such as stroke severity and dysphagia are important predictors of poststroke infection, there is evidence from experimental and clinical settings of impaired immunity or brain-induced immunodepression after stroke. Greater understanding of the relation between inflammation and both infection and ischaemic mechanisms is needed. This might be particularly important because new treatment strategies for acute ischaemic stroke are being investigated, including those that modulate cytokines and the immune system.

Introduction

There is considerable interest in the role of inflammatory mechanisms in ischaemic stroke. Much of this interest has focused on CNS and peripheral inflammatory responses to cerebral ischaemic injury and the identification of suitable targets in the inflammatory cascade for intervention. However, inflammation also includes important aspects of the host immune response to infection. The occurrence of infection, whether preceding or following ischaemic stroke, is becoming well recognised and is accompanied by an expansion in the literature in recent years. This has led to experimental and clinical developments in our understanding of how acute infection can trigger stroke and how preceding infection can influence outcome. Simultaneously, there has been progress in understanding the risk of poststroke infection, including the emerging concept of brain-induced immunodepression and how this might affect clinical outcome. Improvements in our understanding of preceding and poststroke infection are also important in terms of current and emerging treatment strategies for ischaemic stroke. The aim of this Review is to present a coherent account of the association between infection before or after acute ischaemic stroke and the implications for treatment by bringing together evidence from clinical and experimental studies.

Section snippets

Chronic infection and conventional stroke risk factors

The capacity of chronic infections to induce inflammation in tissues might provide a link to the progression of atherosclerotic plaques.1, 2, 3 Prospective seroepidemiological studies could help to establish potential causal links between particular chronic infections and stroke, although the contribution to overall stroke risk might be small.4 However, a range of infections can increase risk when associated with conventional stroke risk factors and genetic predisposition.2 As with acute

Frequency of poststroke infection

The frequency of poststroke infection has been the focus of several studies (table 2),49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 which have been done in various settings, including developing and developed countries. Direct comparisons between these studies is difficult when factors such as differences in study design, selection bias, setting, location, definition of infections, and poststroke reporting interval are taken into account. The studies also

Preceding infection

The recognition that vulnerable individuals might have a short-term increased risk of stroke in association with acute systemic infection could have important implications for clinical practice. There is no evidence to support targeting more intensive stroke prevention strategies to patients with a history of stroke or risk factors for stroke during acute infections, but this is an interesting and important area for future study. Emphasising the importance of compliance in patients already on

Conclusions

The associations between infection and acute ischaemic stroke are complex (figure 2). Acute infection is an important trigger for stroke; the reported prevalence of infection in the week preceding stroke ranges from 10–35%, during which time infection confers at least a 2–3-times increased risk of stroke. Possible mechanisms include changes in atherosclerotic plaque stability, alterations in immunohaematological mechanisms, proinflammatory cytokine activation, platelet activation, and

Search strategy and selection criteria

References for this Review were identified by searches of PubMed from 1966 until January, 2008, with the terms “ischaemic” or “ischemic” and “stroke” and “infection”. Articles were also identified through searches of the authors' own files. Only articles published in English were reviewed. Articles about the association between HIV infection and stroke were excluded; a comprehensive discussion of HIV-associated stroke was deemed to be beyond the scope of the present Review.

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