Potential role of plasma branched-chain amino acids in the differential diagnosis of acute cerebral venous thrombosis

Abstract

Cerebral venous thrombosis (CVT) is a special and easily misdiagnosed or undiagnosed subtype of stroke. To identify specific biomarkers with a high predictive ability for the diagnosis of acute CVT, we performed metabolomic analysis in plasma samples from acute CVT patients and healthy controls and confirmed the results in validation cohorts. In the discovery stage, there were 343 differential metabolites, and the caffeine metabolism pathway and the biosynthesis pathway for the branched chain amino acids (BCAAs) valine, leucine, and isoleucine were two significant pathways between the CVT and healthy cohorts. The area under the curve (AUC) for metabolites associated with valine, leucine, and isoleucine biosynthesis was 0.934. In the validation stage, the BCAA concentrations demonstrated an AUC of 0.935 to differentiate patients with acute CVT from the control cohort. In addition, BCAAs combined with D-dimer levels were used to establish a diagnostic model for CVT, and the AUC was 0.951, showing good diagnostic efficacy of separating CVT patients from the control cohort. BCAAs as plasma biomarkers deserve to be further studied and even developed in clinical CVT management.

Metabolomic profiling of deep vein thrombosis

“… 37 Although the sensitivity and specificity of the detection assay alone are not very high, leucine and isoleucine are other BCAAs, 50 which were also found to be elevated in DVT patients. Furthermore, BCAAs have been used as independent predictive molecules to distinguish cerebral vein thrombosis patients from healthy controls; 51 thus, a combined assay to detect BCAAs may help to identify a panel of candidate biomarkers for the diagnosis of DVT.…”