αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients

Abstract

In this study we assessed the clinical utility of quantitative assessments of alphaII-spectrin breakdown products (SBDP145 produced by calpain, and SBDP120 produced by caspase-3) in cerebrospinal fluid (CSF) as markers of brain damage and outcome after severe traumatic brain injury (TBI). We analyzed 40 adult patients with severe TBI (Glasgow Coma Scale [GCS] score <or=8) who underwent ventriculostomy. Patients requiring CSF drainage for other medical reasons served as controls. CSF samples were taken at admission and every 6 h thereafter for a maximum of 7 days and assessed using novel quantitative fragment-specific ELISAs for SBDPs. Outcome was assessed using the 3-month Glasgow Outcome Scale. Mean CSF levels of SBDPs were significantly higher in TBI patients than in controls at all time points examined. Different temporal release patterns of CSF SBDP145 and SBDP120 were observed. SBDP145 provided accurate diagnoses at all time points examined, while SBDP120 release was more accurate 24 h after injury. Within 24 h after injury, SBDP145 CSF concentrations significantly correlated with GCS scores, while SBDP120 levels correlated with age. SBDP levels were significantly higher in patients who died than in those who survived. SBDP145 levels (>6 ng/mL) and SBDP120 levels (>17.55 ng/mL) strongly predicted death (odds ratio 5.9 for SBDP145, and 18.34 for SBDP120). The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment.

FIG. 1.

Mean ± standard error of the mean concentrations of cerebrospinal fluid (CSF) βII-spectrin breakdown product (SBDP)145 and SBDP 120 over 7 days for severe traumatic brain injury (TBI) patients and for control subjects (single time point only).

FIG. 2.

Receiver-operating characteristic (ROC) curves and area under the curve (AUC) values for βII-spectrin breakdown product (SBDP)145 and SBDP120 concentrations in CSF samples obtained at 6 h (A), 24 h (B), and at day 3 (C), and day 7 (D) post-injury. Note that the AUC values for SBDP120 increased over time.

FIG. 3.

Box and whisker graphs showing frequency distributions of value for samples obtained at 6 h and 24 h, and at day 7 post-injury. There were significant differences in βII-spectrin breakdown product (SBDP)145 cerebrospinal fluid (CSF) levels between patients with severe TBI and controls at all time points (6 h: p = 0.0002; 24 h: p = 0.0003, and over study duration p = 0.0001). Significant differences in SBDP120 CSF levels were observed at all time points (24 h: p = 0.0146, and over study duration p = 0.0001), except at 6 h post-injury (p = 0.0734). The bottom and top of the boxes represent the 25th and 75th percentile, respectively. The band near the middle is the median. Lower and upper whiskers represent data within 1.5 of the interquartile range. Outliers are plotted as small circles.

FIG. 4.

βII-Spectrin breakdown product (SBDP)145 levels, but not SBDP 120 levels, within the first 24 h were significantly lower in patients with higher hospital admission Glasgow Coma Scale (GCS) scores (6–8; 10.10 ± 2.807 ng/mL), than in patients with lower hospital admission GCS scores (3–5; 25.93 ± 7.428 ng/mL; p = 0.03 by Mann-Whitney U test). *p < 0.05.

FIG. 5.

Scatterplot and linear regression showing significant relationship between βII-spectrin breakdown product (SBDP)120 average levels in the first 24 h post-injury and age (r = 0.37; p = 0.03) in severe traumatic brain injury patients

FIG. 6.

(A) Over 7 days after injury βII-spectrin breakdown product (SBDP)145 and SBDP120 levels were significantly higher in patients who died than in those who survived (0.54 ng/mL versus 2.7 ng/mL; *p < 0.0001 and p = 0.0004, respectively). (B) Mean SBDP120 concentrations were statistically significantly higher in patients who died than in surviving patients at 6 h post-injury (p = 0.02), and (C) 24 h post-injury (p = 0.03).