Circulating metabolites differentiate acute ischemic stroke from stroke mimics
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Circulating metabolites differentiate acute ischemic stroke from stroke mimics. / Tiedt, Steffen; Brandmaier, Stefan; Kollmeier, Hanna; Duering, Marco; Artati, Anna; Adamski, Jerzy; Klein, Matthias; Liebig, Thomas; Holdt, Lesca M; Teupser, Daniel; Wang-Sattler, Rui; Schwedhelm, Edzard; Gieger, Christian; Dichgans, Martin.
In: ANN NEUROL, Vol. 88, No. 4, 10.2020, p. 736-746.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Circulating metabolites differentiate acute ischemic stroke from stroke mimics
AU - Tiedt, Steffen
AU - Brandmaier, Stefan
AU - Kollmeier, Hanna
AU - Duering, Marco
AU - Artati, Anna
AU - Adamski, Jerzy
AU - Klein, Matthias
AU - Liebig, Thomas
AU - Holdt, Lesca M
AU - Teupser, Daniel
AU - Wang-Sattler, Rui
AU - Schwedhelm, Edzard
AU - Gieger, Christian
AU - Dichgans, Martin
N1 - © 2020 American Neurological Association.
PY - 2020/10
Y1 - 2020/10
N2 - 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. ANN NEUROL 2020;88:736-746.
AB - 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. ANN NEUROL 2020;88:736-746.
U2 - 10.1002/ana.25859
DO - 10.1002/ana.25859
M3 - SCORING: Journal article
C2 - 32748431
VL - 88
SP - 736
EP - 746
JO - ANN NEUROL
JF - ANN NEUROL
SN - 0364-5134
IS - 4
ER -