Review
Infectious causes of stroke

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Summary

Most infectious pathogens have anecdotal evidence to support a link with stroke, but certain pathogens have more robust associations, in which causation is probable. Few dedicated prospective studies of stroke in the setting of infection have been done. The use of head imaging, a clinical standard of diagnostic care, to confirm stroke and stroke type is not universal. Data for stroke are scarce in locations where infections are probably most common, making it difficult to reach conclusions on how populations differ in terms of risk of infectious stroke. The treatment of infections and stroke, when concomitant, is based on almost no evidence and requires dedicated efforts to understand variations that might exist. We highlight the present knowledge and emphasise the need for stronger evidence to assist in the diagnosis, treatment, and secondary prevention of stroke in patients in whom an infectious cause for stroke is probable.

Introduction

Stroke is a leading cause of death and disability worldwide.1 Although established risk factors for stroke exist,2, 3 some infectious pathogens might confer additional risk either by increasing baseline tendency or having a direct causal role. Similarly to the prevention of traditional risk factors for stroke, several infections could be prevented and their disease incidence reduced. Because about 85% of strokes now occur in low-income and middle-income countries,4 infectious strokes might be particularly important to consider in locations where few data are available. We review the range and influence of infectious organisms on stroke, with special consideration for regions where infectious diseases are most prevalent.

Section snippets

Systemic Infections

Ischaemic stroke has been associated with systemic infection and linked to the outcomes of chronic or indolent infections. Several findings suggest a possible association between systemic infection and stroke. The epidemiology of ischaemic stroke is insufficiently explained by the prevalence of traditional cerebrovascular risk factors.5 A substantial proportion of patients who have had an ischaemic stroke lack these risk factors, and no apparent cause of stroke is identified in up to a third of

Infective endocarditis

Infective endocarditis is a notable cause of cardioembolic stroke. Stroke occurred in 17% of 2781 adult inpatients with infective endocarditis enrolled in a prospective cohort study done in 25 countries.19 The risk of stroke was highest at presentation of infective endocarditis and declined within 1–2 weeks after antibiotics were initiated. In another study38 of 1437 patients, the incidence of stroke fell from 4·8 per 1000 patient-days in the first week of antibiotic treatment to 1·7 per 1000

Bacterial meningitis

The prevalence of stroke complicating meningitis depends on the bacterium and definition of stroke. In a prospective, case-control study in the Netherlands, brain infarction (focal neurological signs diagnosed by a neurologist with CT confirmation) occurred in 174 (25%) of 696 patients with bacterial meningitis.14 Findings from a retrospective series of pneumococcal meningitis identified a similar proportion of patients with ischaemic stroke (17 [20%] of 87),15 which was higher than the 15%

Encephalitis and stroke

The division between meningitis and encephalitis is often indistinct. Patients included in previous studies of bacterial meningitis could also have had encephalitis. Characterisation of a hypodensity on a CT scan as infarction versus cerebritis is often difficult, but the temporal and radiographic characteristics of the neurological deficit may help. Symptoms from cerebritis usually evolve more gradually compared with acute stroke. Radiographically, infarction results in hypodensity confined to

When to investigate for infectious causes

Patients who have had strokes caused by infection might be misdiagnosed if lumbar puncture is not done. However, lumbar puncture is not indicated when evaluating a typical patient (an elderly person with atherosclerotic risk factors with sudden-onset focal neurological deficits). The clinical symptoms that might indicate infectious causes include a history of antecedent fever, rash, and known prior infections. For immunocompromised patients, the suspicion should be higher and CSF should be

Treatment

Management of infection-related strokes focuses on treatment of the underlying infection with appropriate antimicrobial drugs and prevention of medical complications, but several questions remain unanswered. The following are clinically important situations in which not many data exist.

Treatment of systemic infections that precede or accompany stroke requires prompt initiation of effective antimicrobial therapy. The treatment of specific pathogens should generally follow established guidelines

Conclusions

The criteria for causality in infections and stroke—namely temporality, specificity, consistency of findings, strength of association, coherence, and biological gradient141—are not well described in scientific literature for most associated organisms. However, for some organisms causality seems probable. To date, most large studies are from high-income settings, and almost no data derive from low-income country settings where infectious strokes are seemingly more common. These populations

Search strategy and selection criteria

We identified publications through a search of PubMed and Google Scholar for original research articles, case series, and case reports published between Jan 1, 1973, and Feb 10, 2014, although we focused on articles published within the past 20 years. Our search terms were “infections” OR “bacteria” OR “bacterial infection*” OR “virus” OR “fungus” OR “parasite” AND “stroke” OR “intracranial haemorrhage” OR “ischaemic stroke” OR “vasculitis” and specific pathogen and disease names including

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