(1728) Blood Biomarkers Are Related to Isolated Diffuse Axonal Injury and Patient Outcomes

Introduction: Isolated diffuse axonal injury (DAI) is characterized by novel biomarkers and clinical outcomes after moderate-severe TBI (msTBI).

Methods: Subjects (n=882) were enrolled within 4h of msTBI (GCS 4-12) in the NIH-funded ProTECTIII/ BioProTECT trials at 45 US trauma centers. Serum samples were collected at baseline (BL < 4h), 24h, and 48h post-injury. Participants with neuroradiology-confirmed isolated DAI (DAI+) and complete biomarker sets were identified (n=18). Age/sex matched DAI- controls were identified as having normal neuroimaging and discharge GCS=15 (n=11). Blood biomarkers of susceptible neuronal cells were analyzed (n=187) using Multiplexed Olink® proximity extension assays, with inter-plate normalization. Outcome measures from ProTECTIII included disability rating scale (DRS) and Glasgow Outcome Scale, Extended (GOS-E) at 6 months post-TBI. Poor outcome was defined by sliding dichotomy (DRS≥6 or GOS-E≤5). Temporal changes in novel biomarker expression were measured across cohorts and correlated with outcomes. Paired Welch’s T-tests with Bonferroni-Holm correction, χ2 analyses, and multivariable regression models were utilized; significance was defined as p< 0.05 (R4.3.3_RStudio, SAS).

Results: DAI+ subjects expressed significantly higher levels of brain injury biomarkers at baseline (BL) than DAI- subjects: GB-2008 (p < 0.05), GB-2009 (p < 0.001), and GB-2040 (p < 0.05). At 24h post-injury, 8 biomarkers remained higher in the DAI+ cohort (p < 0.02). At 48h post-injury, 15 biomarkers were higher in DAI+ (p < 0.05). Seven biomarkers were elevated across all timepoints for DAI+ only, including a novel mitochondrial marker, GB-0183. One signal transduction protein, GB-2007, was expressed equally across groups at BL, increased in DAI+ at 24h (p < 0.03), and remained low in DAI-. Age-adjusted NfL expression was increased in patients with poor outcome in DAI+ versus DAI- groups over time (p < 0.03). Logistic regression analyses of age, DAI status, and biomarker expression illustrated a significant relationship between 4 biomarkers and poor outcome: GB-2032, GB-2045, GB-2131, GB-2165 (p < 0.05).

Conclusions: Isolated DAI is associated with unique blood biomarker and outcome profiles in msTBI patients. Novel biomarkers can provide data-driven guidance for triage, diagnosis, and management.