Protein Profiling in Serum and Cerebrospinal Fluid Following Complex Surgery on the Thoracic Aorta Identifies Biological Markers of Neurologic Injury

Abstract

Surgery on the arch or descending aorta is associated with significant risk of neurological complications. As a consequence of intubation and sedation, early neurologic injury may remain unnoticed. Biomarkers to aid in the initial diagnostics could prove of great value as immediate intervention is critical. Twenty-three patients operated in the thoracic aorta with significant risk of perioperative neurological injury were included. Cerebrospinal fluid (CSF) and serum were obtained preoperatively and in the first and second postoperative days and assessed with a panel of 92 neurological-related proteins. Three patients suffered spinal cord injury (SCI), eight delirium, and nine hallucinations. There were markers in both serum and CSF that differed between the affected and non-affected patients (SCI; IL6, GFAP, CSPG4, delirium; TR4, EZH2, hallucinations; NF1). The study identifies markers in serum and CSF that reflect the occurrence of neurologic insults following aortic surgery, which may aid in the care of these patients.

Keywords: Biomarkers; Cardiovascular surgery; Neurologic injury; Thoracic aortic disease.

Fig. 1

The proteins differing most significantly in serum (a–e) and CSF (a, b, f–h) postoperatively compared with preoperatively. D0 = preoperatively, D1 = postoperative day 1, D2 = postoperative day 2. NPX S/N: normalized expression as explained in methods. N = serum; D0:22, D1:19, D2:18, CSF; D0:20, D1:15, D2:15

Fig. 2

The proteins differing most significantly in serum (a–e) and CSF (e–j) in the patients that suffered postoperative spinal cord injury (SCI) compared to those that did not postoperatively. NPX S/N: normalized expression as explained in methods. D0_neg = preoperative levels in patients with no postoperative injury, D0_pos = preoperative levels in patients postoperatively injured, D1 + D2_neg = all patients that did not suffer SCI postoperatively. D1 + D2_pos = all patients that suffered SCI postoperatively. N = CSF: D0_neg:18, D0_pos:2, D1 + D2_neg:26, D1 + D2_pos:4, Serum n = D0_neg:21, D0_pos:1, D1 + D2_neg:35, D1 + D2_pos:2

Fig. 3

The proteins differing most significantly in serum (a–c) and CSF (d–f) in the patients that suffered postoperative delirium compared to those that did not postoperatively. NPX S/N: normalized expression as explained in methods. D0_neg = preoperative levels in patients with no postoperative delirium, D0_pos = preoperative levels in patients with postoperative delirium, D1 + D2_neg = all patients that did not suffer delirium postoperatively. D1 + D2_pos = all patients that suffered delirium postoperatively. N = CSF: D0_neg:14, D0_pos:6, D1 + D2_neg:18, D1 + D2_pos:12, Serum n = D0_neg:15, D0_pos:7, D1 + D2_neg:24, D1 + D2_pos:13

Fig. 4

The proteins differing most significantly in serum (a–b) and CSF (c–f) in the patients that suffered postoperative hallucinations compared to those that did not postoperatively. NPX S/N: normalized expression as explained in methods. D0_neg = preoperative levels in patients with no postoperative hallucinations, D0_pos = preoperative levels in patients with in patients with postoperative hallucinations, D1 + D2_neg = all patients that did not suffer hallucinations postoperatively. D1 + D2_pos = all patients that suffered hallucinations postoperatively. N = CSF: D0_neg:11, D0_pos:9, D1 + D2_neg:12, D1 + D2_pos:18, Serum n = D0_neg:13, D0_pos:9, D1 + D2_neg:20, D1 + D2_pos:17