LAUSR

Following traumatic brain injury (TBI), cerebral metabolic dysfunction, characterized by an elevated cerebral microdialysis (CMD) lactate/pyruvate (LP) ratio, is associated with poor outcome. However, the exact pathophysiological mechanisms underlying this association are not entirely established. In this pre-planned analysis of the BIOmarkers of AXonal injury after Traumatic Brain Injury (BIO-AX-TBI) prospective study, we investigated any associations of LP ratio with brain structure volume change rates at 1 year. Fourteen subjects underwent acute-phase (0-96 hours post-TBI) CMD monitoring and had longitudinal magnetic resonance imaging (MRI) quantification of brain volume loss between subacute phase (14 days-6 weeks) and at 1 year after TBI, recalculated as an annual rate. On average, CMD showed an elevated (>25) LP ratio (31 [IQR 24-34]), indicating acute cerebral metabolic dysfunction. Annualized whole brain and total grey matter (GM) volume change rates were abnormally reduced (-3.2% [-9.3 - -2.2] and -1.9% [-4.4 - 1.7], respectively). Reduced annualized total GM volume correlated significantly with elevated CMD LP ratio (Spearman ρ = -0.68, p-value = 0.01) and low CMD glucose (ρ = 0.66, p-value = 0.01). After adjusting for age, admission GCS and CT Marshall score, CMD LP ratio remained strongly associated with 1-year total GM volume change rate (p<0.001; multivariable analysis). No relationship was found between WM volume changes and CMD metabolites. We demonstrate a strong association between acute post-traumatic cerebral metabolic dysfunction and 1-year grey matter atrophy, reinforcing the role of CMD LP ratio as an early biomarker of poor long-term recovery after TBI.