The Potential of Precision: A Scoping Review of Patient Metabolic Patterns After Traumatic Brain Injury

Despite the injury burden, categorization and prognostication of traumatic brain injury (TBI) severity is primarily based on a combination of clinical examination, imaging, and certain adjuncts such as electroencephalogram and intracranial pressure monitors. Understanding metabolite patterns after TBI may serve as a more precise method to describe and prognosticate injury severity, guide treatment, and serve as a valuable adjunct to current diagnostic and treatment modalities. In this review, we aim to consolidate current metabolomics research on patients sustaining a TBI, describing how metabolite changes are associated with TBI severity, treatment, and outcomes, with a specific focus on studies of clinically accessible samples (blood and/or urine).

We performed a scoping review of the literature and screened articles using Covidence software. Articles detailing post-TBI metabolites in patient blood and/or urine samples were included, while studies describing data solely from cerebrospinal fluid samples, pediatric populations, or animal studies were excluded.

We included 28 articles from our initial search yield of 771. Commonly increased metabolites in the acute phase included decanoic acid, lysophosphatidylcholine (LPC), 2-hydroxybutyrate (all increased in moderate to severe TBI), certain amino acids, and various LPCs (decreased in moderate to severe TBI). After 48 h, octanoic acid, decanoic acid, and LPC increased while glucose, pyruvate, and N-acetylaspartate decreased. LPC and methionine were associated with improved prognosis, while glutamate and octanoic acid were associated with worse prognosis.

Based on our review, amino acids generally decline with greater injury severity, while lipids increase early in severe TBI patients. Choline phospholipids are strong predictors of TBI patient outcomes. Early metabolically targeted TBI therapies may result in improved outcomes in moderate to severely injured patients. Further research is warranted to examine if metabolite biomarkers can serve as prognostication tools or guides for therapy.