Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Cerebrovasc Dis 2009;27:519–526 DOI: 10.1159/000212672 Endothelial Dysfunction in Lacunar Stroke: A Systematic Review Iris L.H. Knottnerus a Hugo Ten Cate b, c Jan Lodder a, b Fons Kessels d Robert J. van Oostenbrugge a, b a Department of Neurology, b Cardiovascular Research Institute Maastricht (CARIM), c Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, and d Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Centre, Maastricht, The Netherlands rent literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endo- thelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well- defined cases and combine multiple methods to evaluate endothelial function. Copyright © 2009 S. Karger AG, Basel Introduction Lacunar infarction accounts for a quarter of all isch- emic strokes [1]. By definition, lacunar infarcts are small infarcts (2–20 mm in diameter) located in the basal gan- glia, the deep cerebral white matter or the brainstem and are the result of occlusion of a single small perforat- ing cerebral artery [2]. Fisher observed that this occlu- sion could be caused either by a general destructive pro- cess of the microvessels termed segmental arterial dis- organization (arteriolosclerosis or lipohyalinosis) or by a local atherosclerotic process termed microatheroma- tosis [3] . The endothelium has a variety of physiological func- tions, such as the expression of adhesion molecules, maintenance of adequate vessel tone and hemostasis. En- dothelial cell activation is – among others – characterized Key Words Endothelium  Vessel wall  Lacunar stroke  Endothelial dysfunction  Cerebral small-vessel disease Abstract Background: Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cere- bral small-vessel disease in lacunar stroke patients. Meth- ods: We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunc- tion in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and in- formative quality. The papers were categorized into sub- headings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium. Results: 29 articles were eligible for fur- ther analysis. We found 16 publications on regulation of vas- cular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilata- tion and CO 2 reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular en- dothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion mole- cules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers. Conclusions: The cur- Received: October 31, 2008 Accepted: February 2, 2009 Published online: April 16, 2009 I.L.H. Knottnerus Department of Neurology Maastricht University Medical Centre, PO Box 5800 NL–6202 AZ Maastricht (The Netherlands) Tel. +31 43 387 5062, Fax +31 43 387 7055, E-Mail iris.knottnerus@neurologie.azm.nl © 2009 S. Karger AG, Basel 1015–9770/09/0275–0519$26.00/0 Accessible online at: www.karger.com/ced