Original Article
The Detrimental Effect of Aging on Leptomeningeal Collaterals in Ischemic Stroke

https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.03.014Get rights and content

Background

Aging is associated with decreased penumbral salvage in patients with ischemic stroke. Another critical factor that determines the fate of penumbra tissue is the degree of collateral circulation, which decreases significantly with aging in experimental models of stroke. In this study, we sought to identify whether these observations could be translated to humans and, therefore, analyzed the effect of patient age on extent of leptomeningeal collaterals in patients with ischemic stroke.

Methods

Computed tomography angiography (CTA) source images were used to assess the degree of collateral circulation in a retrospective series of patients with proximal middle cerebral artery (MCA) occlusion. Bivariate and multivariate analyses were used to explore the relationship between patient age and degree of collateral circulation.

Results

A total of 70 patients were included into the study. Older age (P = .005), history of hypertension (P = .036), higher admission National Institutes of Health Stroke Scale (NIHSS) scores (P = .013), and increased time to CTA (P = .013) were associated with inadequate collaterals in bivariate analyses. In multivariate analysis, older age (P = .008) and higher NIHSS scores (P = .032) remained as the only significant independent variables that were associated with inadequate collaterals. A 10-year increment in patient age increased the odds of inadequate collateral circulation by 1.87 (95% confidence interval: 1.18-2.97).

Conclusion

Our findings show that there is a significant interplay between patient age and adequacy of leptomeningeal collateral circulation in patients with proximal MCA occlusion. The relationship could contribute to adverse tissue outcome and thereby to unfavorable clinical outcome observed in elderly patients with ischemic stroke.

Introduction

The leptomeningeal collateral network plays an important role in cerebral blood flow dynamics in the setting of acute ischemic stroke. The presence of adequate collaterals has been shown to be associated with improved tissue outcome,1 better response to intravenous or intra-arterial thrombolysis,2, 3, 4 lower risk of hemorrhagic transformation,5 and favorable clinical outcome.2, 4, 6 However, the extent of collateral circulation varies widely among individuals,7 and there are no well-defined variables that might be used to predict the adequacy of collaterals.8 The identification of factors that play a role in the collateral reserve following an acute vascular occlusion will not only be important in understanding the variability in cerebral hemodynamics in the acute stroke setting but also might prove to be useful in patient selection for collateral augmenting therapies.

Experimental studies have shown that aging causes a significant decrease in the number of leptomeningeal collaterals, together with increased tortuosity and vascular resistance in these vessels.9, 10 It is also well established from human studies that age has a detrimental effect on cerebrovascular reactivity.11 More importantly, older age is associated with increased risk of conversion of penumbra tissue into infarction in patients with acute ischemic stroke,12 which might theoretically be a reflection of impaired collateral reserve in elderly patients. In this study, we therefore analyzed whether patient age affected the extent of leptomeningeal collateral circulation in a cohort of patients presenting with middle cerebral artery (MCA) occlusion. Furthermore, we assessed the role of leukoaraiosis (LA) burden, a factor closely related to aging and impaired cerebrovascular reactivity, in this relationship.

Section snippets

Study Population

This study was a retrospective analysis of patients with a diagnosis of ischemic stroke secondary to M1 segment MCA occlusion, who were admitted to a tertiary care center over a period of 5 years. Patients were identified from a departmental database to which all patients with a diagnosis of stroke are consecutively entered. The analyses were restricted to patients who had computed tomography angiography (CTA) within 24 hours of symptom onset. The study was approved by the local institutional

Results

We identified a total of 112 patients with proximal MCA occlusion during the study period. Forty-two patients had not undergone CTA within 24 hours of symptom onset and were excluded from the study. The remaining 70 patients (45 female and 25 male) comprised the study population. Eight of these patients did not have MRI, and the analyses regarding LA volume were, therefore, restricted to 62 patients.

The median (IQR) age of the study population was 72 (55-76) years. The median (IQR) time to CTA

Discussion

Our findings show that there is a significant interplay between patient age and the adequacy of leptomeningeal collateral circulation in patients with proximal MCA occlusion. The odds of inadequate collaterals increased by approximately 2-fold with each decade of aging. This relationship persisted when corrected for other variables that might possibly affect the collateral reserve, including vascular risk factors, stroke etiology, and time of imaging.

The collateral circulation plays a critical

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    Disclosures: None.

    Sources of funding: None.

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