IL-6, PF-4, sCD40 L, and homocysteine are associated with the radiological progression of cerebral small-vessel disease: a 2-year follow-up study Jacek Staszewski,1 Renata PiusiÅ?ska-Macoch,1 Bogdan Brodacki,1 Ewa Skrobowska,2 Adam StÄ?pieÅ?1 1Clinic of Neurology, 2Department of Radiology, Military Institute of Medicine, Warsaw, Poland Background: Endothelial dysfunction (ED) is involved in the pathogenesis of cerebral small vessel disease (SVD), however, it is not clear if specific biomarkers related to ED are associated with radiological progression of SVD.Methods: A single-center, prospective cohort study was conducted among consecutive, adult patients with SVD. Logistic regression was used to analyze the association of each baseline biomarker (highest vs lowest tertile) and the MRI radiological outcome after 2 years. The mean Z-score for vascular inflammation (VI) combined soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble platelet selectin (sP-selectin), CD40 ligand (sCD40 L), platelet factor-4 (PF-4) and homocysteine; Z-score for systemic inflammation (SI) combined high-sensitivity C-reactive protein (hsCRP), interleukin-1α and -6 (IL-1α and IL-6, respectively) and tumor necrosis factor-α (TNF-α). Results: The study group comprised 123 patients (age, mean±SD: 72.2±8 years, 49% females), with lacunar stroke (n=49), vascular dementia (n=48), and vascular parkinsonism (n=26). Moreover, 34.9% patients experienced radiological progression, 43% had progression of isolated white matter lesions (WMLs), 23.2% had new lacunes, and 34.8% had both WMLs progression and new lacunes. After adjustment for confounders (age, sex, blood pressure, MRI lesions load), the PF-4 (OR; 95% CI 5.5; 1.5–21), sCD40L (4.6; 1.1–18.6), IL-6 (7.4; 1.48–37), Z-score for VI (4.5; 1.1–18.6), and, marginally, homocysteine (4.1; 0.99–17) were associated with the risk of any radiological progression; further, homocysteine (2.4; 1.4–14), Z-score for SI (2.1; 1.2–14) and, marginally, IL-6 (6.0; 0.95 -38) were related to the development of new lacunes; PF-4 (7.9; 1.6–38) and, marginally, the Z-score for VI (4.2; 0.9–19.5) were correlated with the risk of WMLs progression. Additional adjustment for clinical SVD manifestations did not significantly alter the results. Conclusion: The data supports the concept that ED modulates the radiological progression of SVD and WMLs and lacunes are associated with different inflammatory markers. Keywords: cerebral small-vessel disease, radiological progression, IL-6, PF-4, sCD40 L, homocysteine

Purpose: The role of biomarkers in the prediction of acute ischemic stroke (AIS) outcome or response to thrombolytic therapy (with recombinant tissue plasminogen activator [rt-PA]) remains limited. The aim of this study was to evaluate whether mean platelet volume (MPV) could predict short-term functional outcome in patients with AIS following rt-PA treatment. Patients and methods: This was a retrospective analysis of 237 AIS patients (mean age 71.04±0.8 years, 50.6% women) consecutively admitted to a tertiary care center between 2011 and 2015. Results: The mean MPV in the cohort was 9.8±0.35 fL (lowest tertile 8.8 fL). Patients in the lowest tertile compared to median and highest tertiles were less often dependent (modified Rankin scale [mRS] ≥3) at admission (87.2% vs 96.1% and 96.1%, respectively, P=0.04) and less often had a poor stroke outcome (mRS 4–6) at discharge (28.2% vs 55.3% and 44.7%, P<0.01). However, there was no significant difference between tertiles with regard to AIS etiology, CT (Alberta Stroke Program Early CT) score, frequency of stroke due to large artery occlusion, risk of secondary hemorrhage, and early neurologic deterioration. Multivariable analysis after adjustment for confounders showed that patients in the second and third tertiles had a significantly higher risk of poor stroke outcome (OR =1.9, 95% CI =1.01–4), lack of early improvement (OR =1.91, 95% CI =1.05–3.47), lower chance of good outcome (mRS 0–2; OR =0.38, 95% CI =0.18–0.78), or minor stroke at discharge (OR =0.47, 95% CI =0.26–0.84). Receiver operating characteristic analysis for prediction of poor stroke outcome showed that the optimal cut-off point of MPV was 8.8 fL (area under the curve 0.586 [0.512–0.659], P=0.03) with a sensitivity of 82.7% and a specificity of 43.9%. Conclusion: Disabling or fatal ischemic stroke in thrombolyzed patients was observed more often in patients with high admission MPV. The prognostic value of MPV was independent of other well-defined individual risk factors.