Axonal injury after TBI can be reliably quantified using plasma NfL, which predicts long-term functional outcomes and progressive neurodegeneration.

Reduced quantitative PLR correlates with postanoxic brain injury and, when compared to standard multimodal assessment, is highly accurate in predicting long-term prognosis after CA. This is the first prognostication study to show the value of automated pupillometry using a blinded approach to minimize self-fulfilling prophecy. Ann Neurol 2017;81:804-810.

This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

Adaptive metabolic response to injury includes the utilization of alternative energy substrates -such as ketone bodies (KB) -to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n ¼ 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and b-hydroxybutyrate). Nutrition -from fasting vs. stable nutrition state -was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] mmol/L vs. 13.1 [6.5-64.3] mmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] mmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p ¼ 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.