Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury

Abstract

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities. CSF and serum samples of 15 SCI and ten healthy participants were included in the study. The neurological assessments were scored on admission and at discharge from the hospital using the American Spinal Injury Association Impairment Score (AIS) grades. The CSF and serum concentrations of SBDP150, S100B, GFAP, NF-L, UCHL-1, Tau, and IL-6 were significantly higher in SCI patients when compared with the control group. The CSF GBDP 38/44K, UCHL-L1, S100B, GFAP, and Tau levels were significantly higher in the AIS A patients. This study demonstrated a strong correlation between biomarker levels in the diagnosis and injury severity of SCI but no association with short-term outcomes. Future prospective controlled studies need to be done to support the results of this study.

Keywords: ASIA impairment scale; American Spinal Injury Association; GFAP breakdown product; S100 calcium-binding protein-B; biomarker; diagnostic and prognostic markers; glial fibrillary acidic protein; injury severity; interleukin; neurofilament light chain; spinal cord injury; ubiquitin C-terminal hydrolase-L1; αII-spectrin breakdown product.

Figure 1

CSF biomarker (αII-spectrin, SBDP150/145, GFAP, GBDP 38/44K) levels measured using immunoblotting in the diagnosis of SCI and comparison between SCI and healthy control groups: (A) representative images from immunoblotting for αII-spectrin, SBDP 150/145, GFAP, and GBDP38/44K (B–E); quantification shown as the median, interquartile range (box), and upper and lower values (whiskers) for αII-spectrin (B), SBDP150/145 K (C), GFAP (D), and GBDP 38/44K (E). ** Denotes statistical results compared between patients with SCI (n = 15) and healthy control (n = 10) groups. Note: **, *** p values < 0.05 and 0.005 vs. control.

Figure 2

Ability of CSF αII-spectrin, SBDP150/145, GFAP, and GBDP 38/44K levels to predict injury severity (AIS grade) measured by immunoblotting. * Denotes statistical results compared to initial AIS grade A (n = 11) and AIS grade B (n = 6) patients in SCI group. Quantification is shown as the median, interquartile range (box), and upper and lower values (whiskers). Note: *, **, *** p values < 0.05, 0.01 and 0.001 between groups.

Figure 3

The ability of CSF biomarker levels measured with immunoblotting to predict AIS improvements (ΔAIS = discharge AIS − initial AIS; ΔAIS 0 = no changes; ΔAIS 1–2 = improvement in AIS grade 1 or 2.

Figure 4

CSF biomarker (SBDP150, UCH-L, S100B, Tau, GFAP, NF-L, IL-6) levels measured by ELISA in the diagnosis of SCI and a comparison between SCI and healthy control groups. ** Denotes statistical results compared between patients with SCI (n = 15) and healthy control (n = 10) groups. Quantification is shown as median, interquartile range (box), and upper and lower values (whiskers). Note: **, *** p values < 0.05, 0.005 vs. control.

Figure 5

Ability of CSF SBDP150, UCH-L, S100β, Tau, GFAP, NF-L, and IL-6 levels to predict injury severity (AIS grade) measured by ELISA. * Denotes statistical results compared to initial AIS grade A (n = 11) and AIS grade B (n = 6) patients in SCI group. Quantification is shown as the median, interquartile range (box), and upper and lower values (whiskers). Note: *, ** p values < 0.05, and 0.01 between AIS grade A and grade B patients.

Figure 6

The ability of CSF biomarker (CSF SBDP150, UCH-L, S100B, Tau, GFAP, NF-L, and IL-6) levels measured by ELISA to predict AIS improvements (ΔAIS = discharge AIS − initial AIS; ΔAIS 0 = no changes, ΔAIS 1–2 = improvement in AIS grade 1 or 2 grade).

Figure 7

** Denotes statistical results compared between patient with SCI (n = 15) and healthy control (n = 10) groups. Quantification shown as median, interquartile range (box), and upper and lower values (whiskers). Note: **, *** p values < 0.05, 0.005 vs. control.

Figure 8

The ability of serum SBDP150, UCH-L, S100B, Tau, GFAP, NF-L, and IL-6 levels to predict injury severity (AIS grade) was measured by ELISA. * Denotes statistical results compared to initial AIS grade A (n = 11) and AIS grade B (n = 6) patients in the SCI group. Quantification is shown as the median, interquartile range (box), and upper and lower values. Note: * p < 0.05.

Figure 9

Ability of serum biomarker (SBDP150, UCH-L, S100B, Tau, GFAP, NF-L, and IL-6) levels measured by ELISA to predict AIS improvement (ΔAIS = initial AIS − discharge AIS; ΔAIS 0 = no changes; ΔAIS 1–2 = improvement in AIS grade 1 or 2 grade). Note: * p < 0.05.