Chronic infections and risk of stroke: possible explanation for cryptogenic stroke

ABSTRACT

The association of certain infections as a potential cause of stroke has been known for some time. The complications of bacterial or fungal endocarditis resulting in emboli, mycotic aneurysm and subarachnoid hemorrhage; meningeal infiltration by spirochetes and inflammatory cells seen in neurosyphilis; strokes by direct invasion of cerebral blood vessels in tuberculous meningitis as well as other basilar meningitides; and cerebral vasculitis in association with varicella zoster infection are the few examples. More recent interest has been focused on chronic infections by common organisms such as Helicobacter Pylori and Chlamydia Pneumonie and their role in atherosclerosis processes. This article reviews the current literature highlighting the association of these infections to atherosclerotic processes which ultimately result in strokes. The pathophysiology of stroke is variable. Large artery atherosclerosis accounts for the main pathogenesis in myocardial infarction, whereas thrombo-embolism, lipohyalinosis, hypercoagulable states and arterial dissection are some of the pathogenetic-mechanisms involved in stroke. Still 30-40% of strokes have no apparent etiology [cryptogenic strokes]. This shows the diversity and variability of the cerebral vasculature when compared with the coronary vasculature. The risk factors for stroke therefore need to be investigated independently of those for atherosclerosis and MI. It would be also imperative to consider the temporal profile of the associated infective process. Acute infections, may cause or contribute to acute stroke by promoting a pro-inflammatory or pro-coagulant effect at the time of the infection for example acute bronchitis could alter inflammatory and coagulation parameters, leading to sudden atherosclerotic plaque rupture or thrombosis, precipitating a clinical event. Alternatively, chronic, subclinical infection with certain organisms may be one of several potential underlying causes of the chronic inflammatory process of atherosclerosis. Both acute and chronic processes could occur together in any one individual, as well. Similarly, it should be taken into consideration if the infective process is localized or systemic. The presence of a chronic infection anywhere in the body, for example, could promote systemic pro-inflammatory changes, including monocyte and macrophage activation, cytokine release, hypercoagulability, or systemic changes in other mechanisms of atherogenesis, such as lipid metabolism. Direct vessel invasion and infection, alternatively, may contribute to local changes in the vessel wall that lead to atherogenesis, progression of plaque growth, or plaque rupture. Thus, if infections were shown to play an important role in the initiation or progression of atherosclerosis, the implications for clinical practice and stroke prevention would be significant. Although much of the data on the role of infection in atherosclerosis is based on association of organisms with atherosclerosis, and thus does not clearly provide proof of causality, more experimental data is becoming available from in vitro work, animal studies, and even clinical trials