High-throughput metabolite profiling: identification of plasma taurine as a potential biomarker of functional outcome after aneurysmal subarachnoid hemorrhage

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OBJECTIVE

Metabolite profiling (or metabolomics) can identify candidate biomarkers for disease and potentially uncover new pathways for intervention. The goal of this study was to identify potential biomarkers of functional outcome after subarachnoid hemorrhage (SAH).

METHODS

The authors performed high-throughput metabolite profiling across a broad spectrum of chemical classes (163 metabolites) on plasma samples taken from 191 patients with SAH who presented to Massachusetts General Hospital between May 2011 and October 2016. Samples were drawn at 3 time points following ictus: 0–5, 6–10, and 11–14 days. Elastic net (EN) and LASSO (least absolute shrinkage and selection operator) machine learning analyses were performed to identify metabolites associated with 90-day functional outcomes as assessed by the modified Rankin Scale (mRS). Additional univariate and multivariate analyses were then conducted to further examine the relationship between metabolites and clinical variables and 90-day functional outcomes.

RESULTS

One hundred thirty-seven (71.7%) patients with aneurysmal SAH met the criteria for inclusion. A good functional outcome (mRS score 0–2) at 90 days was found in 79 (57.7%) patients. Patients with good outcomes were younger (p = 0.002), had lower admission Hunt and Hess grades (p < 0.0001) and modified Fisher grades (p < 0.0001), and did not develop hydrocephalus (p < 0.0001) or delayed cerebral ischemia (DCI) (p = 0.049). EN and LASSO machine learning methods identified taurine as the leading metabolite associated with 90-day functional outcome (p < 0.0001). Plasma concentrations of the amino acid taurine from samples collected between days 0 and 5 after aneurysmal SAH were 21.9% (p = 0.002) higher in patients with good versus poor outcomes. Logistic regression demonstrated that taurine remained a significant predictor of functional outcome (p = 0.013; OR 3.41, 95% CI 1.28–11.4), after adjusting for age, Hunt and Hess grade, modified Fisher grade, hydrocephalus, and DCI.

CONCLUSIONS

Elevated plasma taurine levels following aneurysmal SAH predict a good 90-day functional outcome. While experimental evidence in animals suggests that this effect may be mediated through downregulation of pro-inflammatory cytokines, additional studies are required to validate this hypothesis in humans.

ABBREVIATIONS AUC = area under the curve; DCI = delayed cerebral ischemia; EN = elastic net; GLM = generalized linear model; LASSO = least absolute shrinkage and selection operator; mRS = modified Rankin Scale; QQQ MS = triple-quadrupole mass spectrometry; SAH = subarachnoid hemorrhage.
Article Information

Contributor Notes

Correspondence W. Taylor Kimberly: Massachusetts General Hospital, Boston, MA. wtkimberly@mgh.harvard.edu.INCLUDE WHEN CITING Published online November 22, 2019; DOI: 10.3171/2019.9.JNS191346.

C.J.S. and A.A. contributed equally to this work.

Disclosures Dr. Patel reports consultant relationships with Penumbra, Inc., and Medtronic, Inc.
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