Differential disruption of blood-brain barrier in severe traumatic brain injury

Abstract

Background: Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood-brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)-plasma albumin quotient of ≥0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI.

Methods: We recruited 30 patients, all of whom were receiving hypertonic 20 % saline infusion for intracranial hypertension and had external ventricular drains in situ. Simultaneous CSF and blood samples were obtained. Biochemical testing was performed for sodium, osmolality, potassium, glucose, albumin, immunoglobulin-G, and total protein.

Results: Eleven patients (37 %) showed evidence of impairment of passive BBB function, with a CSF-plasma albumin quotient of ≥0.007. There were strong positive correlations seen among CSF-plasma albumin quotient and CSF-plasma immunoglobulin-G quotient and CSF-plasma total protein quotient (r = 0.967, P < 0.001 and r = 0.995, P < 0.001, respectively). We also found a higher maximum intracranial pressure (24 vs. 21 mmHg, P = 0.029) and a trend toward increased mortality (27 vs. 11 %, P = 0.33) in patients with BBB disruption.

Conclusions: In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF-plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF-plasma albumin quotient for evaluating BBB dysfunction.