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Tiedt, S.* ; Brandmaier, S. ; Kollmeier, H.* ; Duering, M.* ; Artati, A. ; Adamski, J. ; Klein, M.* ; Liebig, T.* ; Holdt, L.M.* ; Teupser, D.* ; Wang-Sattler, R. ; Schwedhelm, E.* ; Gieger, C. ; Dichgans, M.*

Circulating metabolites differentiate acute ischemic stroke from stroke mimics.

Ann. Neurol. 88, 736-746 (2020)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Objective Early discrimination of patients with ischemic stroke (IS) from stroke mimics (SMs) poses a diagnostic challenge. The circulating metabolome might reflect pathophysiological events related to acute IS. Here, we investigated the utility of early metabolic changes for differentiating IS from SM. Methods We performed untargeted metabolomics on serum samples obtained from patients with IS (N = 508) and SM (N = 349; defined by absence of a diffusion weighted imaging [DWI] positive lesion on magnetic resonance imaging [MRI]) who presented to the hospital within 24 hours after symptom onset (median time from symptom onset to blood sampling = 3.3 hours; interquartile range [IQR] = 1.6-6.7 hours) and from neurologically normal controls (NCs; N = 112). We compared diagnostic groups in a discovery-validation approach by applying multivariable linear regression models, machine learning techniques, and propensity score matching. We further performed a targeted look-up of published metabolite sets. Results Levels of 41 metabolites were significantly associated with IS compared to NCs. The top metabolites showing the highest value in separating IS from SMs were asymmetrical and symmetrical dimethylarginine, pregnenolone sulfate, and adenosine. Together, these 4 metabolites differentiated patients with IS from SMs with an area under the curve (AUC) of 0.90 in the replication sample, which was superior to multimodal cranial computed tomography (CT; AUC = 0.80) obtained for routine diagnostics. They were further superior to previously published metabolite sets detected in our samples. All 4 metabolites returned to control levels by day 90. Interpretation A set of 4 metabolites with known biological effects relevant to stroke pathophysiology shows unprecedented utility to identify patients with IS upon hospital arrival, thus encouraging further investigation, including multicenter studies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ct Perfusion; Identification; Biomarkers; Discovery; Diagnosis; Infarction; Point
ISSN (print) / ISBN 0364-5134
e-ISSN 1531-8249
Journal Annals of Neurology
Quellenangaben Volume: 88, Issue: 4, Pages: 736-746 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Molekulare Endokrinologie und Metabolismus (MEM)