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. 2015 Sep 2:15:158.
doi: 10.1186/s12883-015-0416-z.

The presence of cerebral and/or systemic endothelial dysfunction in patients with leukoaraiosis--a case control pilot study

Matija Zupan  1 , Mišo Šabović  2 , Marjan Zaletel  3 , Katarina Šurlan Popovič  4 , Bojana Žvan  5
Affiliations

The presence of cerebral and/or systemic endothelial dysfunction in patients with leukoaraiosis--a case control pilot study

Matija Zupan et al. BMC Neurol. .

Abstract

Background: In spite of high prevalence and clinical relevance of leukoaraiosis (LA), its pathophysiology is still incompletely understood. Theories of ischaemic genesis and a leaky blood-brain barrier are contradictory yet could share a common denominator-endothelial dysfunction (cerebral, systemic or both), which has not been studied thoroughly in LA.

Methods: Thirty patients with LA (58 years (SD 7)) and 30 gender- and age-matched controls without LA (55 years (SD 6)) were recruited. The vascular risk factors (VRF) were identical in both groups. Cerebral endothelial function was determined by cerebrovascular reactivity to L-arginine (CVR). Systemic endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery after hyperaemia. All participants underwent a brain MRI to search for radiological signs of LA that was classified according to the Fazekas score. Linear regression was used to explore the correlation between CVR and FMD in patients with LA. A 95 % confidence interval was used. For any statistical test used in the study, p ≤ 0.050 was regarded as statistically significant.

Results: We found a marked and significant decrease in both CVR (9.6 % (SD 3.2) vs. 15.8 % (SD 6.1), p < 0.001) and FMD (4.8 % (SD 3.1) vs. 7.4 % (SD 3.8), p = 0.004) in LA patients compared to controls. Both CVR (7.4 % (SD 3.1) vs. 12.2 % (SD 2.6), p = 0.001) and FMD (3.0 % (SD 2.2) vs. 6.4 % (SD 3.1), p = 0.011) were significantly decreased in LA subgroup Fazekas 3 compared to subgroup Fazekas 1. CVR and FMD significantly positively correlated (b = 0.192, 95 % CI = 0.031-0.354, p = 0.02).

Conclusions: The results of our pilot study suggest that patients with LA have a significant impairment of both cerebral and systemic endothelial function that is larger than could be expected based on present VRF. Endothelial dysfunction increases in parallel with LA severity and correlates between cerebral and systemic arterial territory. Overall, our results suggest a so far unknown "intrinsic" generalised endothelial dysfunction in patients with LA that could be involved in LA pathophysiology. This interesting issue needs to be confirmed in larger samples since it could help better understand the mechanisms underlying LA.

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Figures

Fig. 1
Fig. 1
Flow-mediated dilatation (FMD) distribution in control group and leukoaraiosis (LA) group (a) and in the subgroups of LA (b). SD indicates standard deviation
Fig. 2
Fig. 2
Cerebrovascular reactivity to L-arginine (CVR) distribution in control group and leukoaraiosis (LA) group (a) and in the subgroups of LA (b). SD indicates standard deviation
Fig. 3
Fig. 3
Linear regression showing positive correlation between cerebrovascular reactivity to L-arginine (CVR) and flow-mediated dilatation (FMD) (a) and the display of regression standardised residuals (b) in patients with leukoaraiosis
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