Elevated neuron-specific enolase level is associated with postoperative delirium and detection of phosphorylated neurofilament heavy subunit: A prospective observational study

BACKGROUND: Delirium is the most common central nervous system complication after surgery. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage within the central cervous system and is associated with the severity of postoperative delirium. Neuron-specific enolase and S100 calcium-binding protein β have been identified as possible serum biomarkers of postoperative delirium. This study examined the association of the levels of these markers with incidence of postoperative delirium and detection of phosphorylated neurofilament heavy subunit. METHODS: This study represents a post hoc analysis of 117 patients who participated in a prospective observational study of postoperative delirium in patients undergoing cancer surgery. Patients were clinically assessed for development of postoperative delirium within the first five days of surgery. Serum levels of phosphorylated neurofilament heavy subunit, neuron-specific enolase, and S100 calcium-binding protein β levels were measured on postoperative day 3. RESULTS: Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Neuron-specific enolase level (P < 0.0001) and the proportion of patients positive for phosphorylated neurofilament heavy subunit (P < 0.0001) were significantly higher in the group of patients with postoperative delirium. Neuron-specific enolase level discriminated between patients with and without clinically diagnosed postoperative delirium with significantly high accuracy (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.79–0.95; P < 0.0001). Neuron-specific enolase level was associated with incidence of postoperative delirium independently of age (adjusted odds ratio, 8.291; 95% Cl, 3.506−33.286; P < 0.0001). The AUC for the serum neuron-specific enolase level in detecting phosphorylated neurofilament heavy subunit was significant (AUC, 0.78; 95% CI, 0.66–0.90; P < 0.0001). CONCLUSION: Elevated serum neuron-specific enolase was associated with postoperative delirium independent of age as well as detection of phosphorylated neurofilament heavy subunit in serum. Serum neuron-specific enolase and phosphorylated neurofilament heavy subunit might be useful as biomarkers of postoperative delirium. TRIAL REGISTRATION: University Medical Information Network (UMIN) trial ID: UMIN000010329; https://clinicaltrials.gov/.