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256 Scientific Programme 22. European Stroke Conference © 2013 S. Karger AG, Basel 17 Translational stroke research Role of Plasma Biomarkers in Diagnosis of Ischemic Stroke Subtypes S. Lorenzano1, N.S. Rost2, K. Arai3, L. Batista4, T. Thankachan5, R.E. Green6, A.T. Som7, G.J. Harris8, J.B. Blumberg9, S.K. Feske10, E.H. Lo11, K.L. Furie12 Massachusetts General Hospital and Harvard Medical School, Boston, USA1, Massachusetts General Hospital and Harvard Medical School, Boston, USA2, Massachusetts General Hospital and Harvard Medical School, Boston, USA3, Massachusetts General Hospital and Harvard Medi-cal School, Boston, USA4, Massachusetts General Hospital and Harvard Medical School, Boston, USA5, Massachusetts General Hospital and Harvard Medical School, Boston, USA6, Massachusetts General Hospital and Harvard Medical School, Boston, USA7, Massachusetts General Hospital and Harvard Medical School, Boston, USA8, Tufts University, Boston, USA9, Massachusetts General Hospital and Harvard Medical School, Boston, USA10, Massachusetts Gen-eral Hospital and Harvard Medical School, Boston, USA11, Massachusetts General Hospital/Harvard Medical School and Rhode Island Hospital/Alpert Medical School of Brown University, Boston, USA12 Background:Identifying underlying stroke etiology plays critical role in acute management and sec-ondary prevention strategies. Despite advanced diagnostics, up to 35% of ischemic strokes (IS) re-main undetermined. We sought to evaluate the association between IS subtypes and plasma levels of biomarkers as representative of distinct etiologies underlying stroke subtypes. Methods:We prospectively measured plasma high sensitivity-CRP, matrix metalloproteinase(M-MP)- 2, MMP-9, F2-isoprostane(F2-isoP), Oxygen Radical Absorbance Capacity assay(ORAC), homocysteine and urinary 8-oxo-7,8-dihydro-2’-deoxyguoanosine, in patients within 9 h of IS onset. Stroke subtype was assigned by a stroke neurologist according to the Causative Classification of Stroke System(CCSS) criteria. Results: 489 subjects were enrolled mean(SD) age 70.1(15.1) y; 43.4% female; median(IQR) NIHSS 6(3-13); 40.7% received IV tPA. Among these IS, 51% were of cardioembolic(CE),17% atherothrombotic,7% lacunar,5% other, and 20% of undetermined subtype.Patients with CE stroke were older, more likely to be female, non-smokers, have AF and CHF, but not carotid stenosis(all p<0.05).CE subtype was associated with greater stroke severity, and baseline levels of MMP-2(p=0.001) and ORAC(p=0.008), as compared to other CCSS subtypes. In multivariate logistic regression analysis, baseline MMP-2(OR 2.8, 95%CI 1.3-5.8; p=0.006) and ORAC(OR 2.6, 95% CI 1.3-5.1; p=0.007) were independently asso-ciated with CE stroke subtype. Conversely, the “other” stroke subtype was associated with lower levels of MMP-2(OR 0.1, 95%CI 0.02-0.3; p=0.001), and homocysteine levels were independently correlated with undetermined subtype(OR 2.2, 95%CI 1.2-4.1; p=0.008). Conclusions:In IS patients, hyperacute plasma biomarkers are associated with specific stroke subtypes, reflective of the under-lying pathophysiology. If validated in future studies, plasma biomarkers may play valuable role in early diagnosis and guide management of specific IS subtypes. 16 Translational stroke research Toward the Development of a Blood-Based Diagnostic Test for Acute Ischaemic Stroke N. Hasan1, V. Abdul-Salam2, W. Whiteley3, P. Sandercock4, R. Edwards5, P. Sharma6 Imperial College London, London, UNITED KINGDOM1, Imperial College London, London, UNITED KINGDOM2, University of Edinburgh, Edinburgh, UNITED KINGDOM3, University of Edinburgh, Edinburgh, UNITED KINGDOM4, Imperial College London, London, UNITED KING-DOM5, Imperial College London, London, UNITED KINGDOM6 Background: Prompt diagnosis of acute ischaemic stroke (AIS) is vital for preventing and reducing neuronal damage and possible death. However, stroke management and diagnosis is predominantly reliant upon CT (which can be unremarkable in acute stages of stroke) or MRI (which is expensive and often difficult to access). Our aim is to develop a blood test for AIS to be used at the bedside in the first few hours of stroke using a whole-proteome strategy. Methods: In a pilot study, blood was taken from 20 patients with confirmed AIS acutely (<24hrs fol-lowing stroke), and again at 3-month follow-up. Plasma samples from these patients were analysed with SELDI-TOF mass spectrometry using weak cation exchange arrays (CM10 Proteinchip) at pH3, 4, 6 and 8. Protein peak clustering and classification analysis were performed using Ciphergen Biomarker Wizard and Biomarker Pattern software, and Student’s T-Tests were used to examine sig-nificant protein ion expression differences between acute and follow-up samples. The workflow was repeated in a further 104 plasma samples from individuals diagnosed with AIS, TIA or stroke mim-ic, divided into independent Training (20 AIS, 10 TIA, 10 stroke mimic) and Test (32 AIS, 16 TIA, 16 stroke mimic) sets. Results: One biomarker elucidated in the pilot study was replicated in the Training set (pH4 m/ z3255; p=2.22x10-6, fold difference=2.17) as well as 3 additional markers at pH4 and pH8. Further-more, we found one protein ion of high intensity which could differentiate ischaemic events (AIS and TIA) from stroke mimics (relative intensity=16-55, p=5.08x10-6, fold difference=1.89). This result was reproduced in the Test set at pH4 (p=9.83x10-10, fold difference=1.49). Conclusions: This study confirms the value of proteomics for diagnostic biomarker elucidation. Replication of candidate markers in independent sample sets provides further supportive evidence for the potential value of protein biomarkers in a blood-based diagnostic test for AIS.


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