Prognostic significance of blood-brain barrier disruption in patients with severe nonpenetrating traumatic brain injury requiring decompressive craniectomy

Abstract

Object The authors assessed the risk factors and outcomes associated with blood-brain barrier (BBB) disruption in patients with severe, nonpenetrating, traumatic brain injury (TBI) requiring decompressive craniectomy. Methods At 2 major neurotrauma centers in Western Australia, a retrospective cohort study was conducted among 97 adult neurotrauma patients who required an external ventricular drain (EVD) and decompressive craniectomy during 2004–2012. Glasgow Outcome Scale scores were used to assess neurological outcomes. Logistic regression was used to identify factors associated with BBB disruption, defined by a ratio of total CSF protein concentrations to total plasma protein concentration > 0.007 in the earliest CSF specimen collected after TBI. Results Of the 252 patients who required decompressive craniectomy, 97 (39%) required an EVD to control intracranial pressure, and biochemical evidence of BBB disruption was observed in 43 (44%). Presence of disruption was associated with more severe TBI (median predicted risk for unfavorable outcome 75% vs 63%, respectively; p = 0.001) and with worse outcomes at 6, 12, and 18 months than was absence of BBB disruption (72% vs 37% unfavorable outcomes, respectively; p = 0.015). The only risk factor significantly associated with increased risk for BBB disruption was presence of nonevacuated intracerebral hematoma (> 1 cm diameter) (OR 3.03, 95% CI 1.23–7.50; p = 0.016). Although BBB disruption was associated with more severe TBI and worse long-term outcomes, when combined with the prognostic information contained in the Corticosteroid Randomization after Significant Head Injury (CRASH) prognostic model, it did not seem to add significant prognostic value (area under the receiver operating characteristic curve 0.855 vs 0.864, respectively; p = 0.453). Conclusions Biochemical evidence of BBB disruption after severe nonpenetrating TBI was common, especially among patients with large intracerebral hematomas. Disruption of the BBB was associated with more severe TBI and worse long-term outcomes, but when combined with the prognostic information contained in the CRASH prognostic model, this information did not add significant prognostic value.

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

“…Consistent with observations in animal models, evidence of acute BBB permeability following severe TBI in humans is provided by reports of elevations in CSF to serum albumin quotient (50)(51)(52)(53) and in serum S100² levels (50-53) after injury. Of note, such evidence of acute BBB disruption following TBI might predict a population of patients with poor longterm outcome (52).…”

“…Consistent with observations in animal models, evidence of acute BBB permeability following severe TBI in humans is provided by reports of elevations in CSF to serum albumin quotient (50)(51)(52)(53) and in serum S100² levels (50-53) after injury. Of note, such evidence of acute BBB disruption following TBI might predict a population of patients with poor longterm outcome (52). Furthermore, neuroimaging evidence of BBB disruption has been reported in patients following TBI, even after clinically mild or moderate injury; in some cases persisting for years at the site of focal injury (contusions) and with greater frequency in patients with post-traumatic epilepsy (54).…”

“…Studies suggest that these acute BBB disruptions may confer worse long-term outcome following TBI clinically (52), although the relative role of this pathology is unknown. Indeed, acute BBB opening after TBI may simply be one of many common pathological features of a more severely injured brain, which collectively contribute to poor outcome.…”

Astroglial activation and altered amyloid metabolism in human repetitive concussion

“…5,6 Evidence from animal models and limited clinical studies of moderate to severe TBI suggest that astrogliosis, increased inflammatory activity, as well as disruption of the blood-brain barrier (BBB) are additional important processes in TBI. [7][8][9][10] A PCS diagnosis is mainly based on selfreported clinical symptoms. 11 In contrast, a CTE diagnosis can only be made postmortem.…”

Assessing Blood Brain Barrier Permeability in Traumatic Brain Injury Research

“…BBB disruption has been defined as a total cerebrospinal fluid (CSF) protein concentration to total plasma protein concentration ratio greater than 0.007 [6,34]. Proteins such as S100B are released by astrocytes in areas of tissue injury and can be measured via jugular vein or peripherally [35].…”