Abstract

Background: Ageing and metabolic syndrome are associated with poor leptomeningeal collateral status. Animal studies suggest that collateral rarefaction and consequent decrease in vascular efficiency may result in increase in white matter hyperintensities. Using mediational analysis, we test if the known effect of ageing and metabolic syndrome on development of white matter hyperintensities is mediated through collateral status. Methods: Data are from the Keimyung Stroke Registry. Consecutive patients with M1 segment middle cerebral artery (MCA) ± intracranial internal carotid artery (ICA) occlusions on baseline CT-angiography (CTA) and brain MRI done within 90 minutes after admission CT/CTA, from May 2004 to July 2009, were included. Baseline and follow-up imaging was analyzed blinded to all clinical information. Two raters assessed leptomeningeal collaterals on baseline CTA by consensus, using previously validated regional leptomeningeal score (rLMC). FLAIR volume of white matter hyperintensities (ml) was measured in the unaffected hemisphere using Quantomo® software. The template of Baron and Kenney along with two tests (Sobel’s and Aroian’s) was used to test for the presence of mediation. Results: Baseline characteristics (n=120): mean age 67.4±11.4 years, male (53.3%), median baseline NIHSS 14 (IQR 11-20), and median stroke symptom onset to CTA 166 minutes (IQR 96-262). Poor collateral status at baseline (rLMC score 0-10) was seen in 42/120 (35%). Mean periventricular hyperintensity (PVH) volume was 6.5 ml (SD=6.0) while mean white matter hyperintensity (WMH-total) volume was 8.6 ml (SD=8.0). Higher age was associated with increased PVH and WMH-total (p<0.01) while metabolic syndrome was associated with increased PVH only (p=0.03). We did not find statistical evidence of leptomeningeal collaterals mediating the association between ageing and PVH/WMH-total or between metabolic syndrome and PVH (Sobel’s and Aroian’s test p>0.05). Conclusion: The effect of ageing and metabolic syndrome on development of white matter hyperintensities is independent of an effect mediated through the poor collateral status.

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