Statins and cerebral perfusion in patients with leukoaraiosis – a translational proof- of-principal MRI study Experimental models from our group have shown that the upregulation of endothelial nitric oxide (NO) synthase with subsequent augmentation of cerebral blood flow (CBF) are among the pleiotropic effects of statins (1,2). Reductions of cerebral vasoreactivity (CVR) and regional CBF (rCBF) are hallmarks of leukoaraiosis, which is in part due to endothelial dysfunction and reduced endothelial NO produc- tion. However, conflicting results have been reported regarding the efficacy of statins to increase rCBF in patients with leukoaraiosis (3,4). These discrepancies may partly be due to different methods. We had previously established an magnetic resonance imaging (MRI) protocol including L-arginine infusions to measure CVR (5). In a translational attempt to demonstrate the effects of statins on cerebral perfusion, we used this protocol in eight statin-naive patients with known leukoaraiosis [two female, four with cerebral autosomal dominant arteriopathy with subcor- tical infarcts and leukoencephalopathy (CADASIL), mean age 56 11 years, Fazekas score 3, interquartile range (IQR) 2–3]. After ethics approval and informedconsent,treatmentwithsimv- astatin (80 mg/day) was initiated after an MRI session; imaging at 1·5T included perfusion scans, was followed by a 30 mins infusion of L-arginine and a second scan upon completion of the infusion. A follow-up with the identical protocol took place eight-weeks after initiationoftreatmentwithsimvastatin. The study received funding from the German Federal Ministry of Educa- tion and Research via the Competence Network Stroke. There was a median increase of rCBF in white matter by 17·5% after treat- ment(IQR14·1to21·8%; P = 0·02) and a median change of CVR in gray matter by15·6%(IQR13·5to17·5%; P = 0·01). CVR in white matter showed no signifi- cant change (median 4·7%, IQR –05·2 to 15·5%; P = 0·64). For illustration see Fig. 1. Takentogether,thissuccessfulbench- to-bedside translation provided MRI evidence of an improved cerebral per- fusion in patients with leukoaraiosis after simvastatin. This may encourage the use of our methodology in rand- omized trials testing new treatment strategies for these patients. Martin Ebinger 1,2 *, Peter Brunecker 1 , Jörg Schultze-Amberger 3 , Karen Gertz 2 , Bianca Müller 2 , Jochen B. Fiebach 1 , Martin Dichgans 4 , and Matthias Endres 1,2 1 Center for Stroke Research Berlin (CSB), Berlin, Germany 2 Klinik und Hochschulambulanz für Neurologie, Charité – Universitätsmedizin Berlin, Berlin, Germany 3 Klinikum Ernst von Bergmann, Potsdam, Germany 4 Neurologische Klinik, Universitätsklinikum der Ludwigs-Maximilians-Universität München, Munich, Germany References 1 Endres M, Laufs U, Huang Z et al. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 1998; 95:8880–5. 2 Yamada M, Huang Z, Dalkara T et al. Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment. J Cereb Blood Flow Metab 2000; 20:709–17. 3 Sterzer P, Meintzschel F, Rosler A, Lanfer- mann H, Steinmetz H, Sitzer M. Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small-vessel disease. Stroke 2001; 32:2817–20. 4 Lavallee PC, Labreuche J, Gongora-Rivera F et al. Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease. Stroke 2009; 40:1721–8. 5 BruneckerP,EndresM,NolteCH et al.Evlu- ation of an AIF correction algorithm for dynamic susceptibility contrast-enhanced perfusion MRI. Magn Reson Med 2008; 60:102–10. Correspondence: Martin Ebinger*, Center for Stroke Research Berlin (CSB), Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. E-mail: martin.ebinger@charite.de DOI: 10.1111/j.1747-4949.2012.00807.x Fig. 1 Coregistered images of patient C. On the left, T2-weighted image; changes in regional cerebral blood flow (middle) and CVR (right) after eight-weeks of treatment with simvastatin. Letter to the editor © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization Vol 7, October 2012, E5 E5