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/.

Serum Neuron-Specific Enolase Thresholds for Predicting Postcardiac Arrest Outcome

Background and ObjectivesTo determine thresholds of serum neuron-specific enolase (NSE) for prediction of poor outcome after cardiac arrest with >95% specificity using a unique method of multiple thresholds meta-analysis.MethodsData from a systematic review by the European Resuscitation Council (ERC 2014) were updated with literature searches from PubMed, Cochrane, and Scopus until August 2020. Search terms included the MeSH terms “heart arrest” and “biomarkers” and the text words “cardiac arrest,” “neuron specific enolase,” “coma” and “prognosis.” Cohort studies with comatose cardiac arrest survivors aged >16 years undergoing targeted temperature management (TTM) and NSE levels within 96 hours of resuscitation were included. Poor outcome was defined as cerebral performance category 3–5 at hospital discharge or later. Studies without extractable contingency tables were excluded. A multiple thresholds meta-analysis model was used to generate summary receiver operating characteristic curves for various time points. NSE thresholds (and 95% prediction intervals) for >95% specificity were calculated. Evidence appraisal was performed using a method adapted from the American Academy of Neurology grading criteria.ResultsData from 11 studies (n = 1,982) at 0–24 hours, 21 studies (n = 2,815) at 24–48 hours, and 13 studies (n = 2,557) at 48–72 hours was analyzed. Areas under the curve for prediction of poor outcomes were significantly larger at 24–48 hours and 48–72 hours compared to 0–24 hours (0.82 and 0.83 vs 0.64). Quality of evidence was very low for most studies because of the risk of incorporation bias—knowledge of NSE levels potentially influenced life support withdrawal decisions. To minimize falsely pessimistic predictions, NSE thresholds at the upper 95% limit of prediction intervals are reported. For prediction of poor outcome with specificity >95%, upper limits of the prediction interval for NSE were 70.4 ng/mL at 24–48 hours and 58.6 ng/mL at 48–72 hours. Sensitivity analyses excluding studies with inconsistent TTM use or different outcome criteria did not substantially alter the results.ConclusionsNSE thresholds for highly specific prediction of poor outcome are much higher than generally used. Future studies must minimize bias by masking treatment teams to the results of potential predictors and by prespecifying criteria for withdrawal of life support.

Evaluation of serum neuron specific enolase levels among patients with primary and secondary burning mouth syndrome

Introduction Burning mouth syndrome is a painful condition of the oral cavity with ambiguous pathogenesis and diagnosis. Neuron-specific enolase is increased in several conditions including peripheral neuropathy of diabetes, ophthalmopathies, spinal cord injuries and tumors. Evidence on association of burning mouth syndrome and neuron-specific enolase is limited. Aim This study aims to evaluate neuron-specific enolase levels in primary and secondary burning mouth syndrome patients and compare the levels of neuron-specific enolase with associated conditions in secondary burning mouth syndrome. Methods One hundred and twenty-eight patients of more than 18 years of age with no gender predilection and having clinical symptoms of burning mouth syndrome and 135 healthy subjects were included. All the patients fulfilled Scala’s criteria for the diagnosis of burning mouth syndrome, including “primary” (idiopathic) and “secondary” (resulting from identified precipitating factors) burning mouth syndrome patients. Blood samples were obtained from burning mouth syndrome patients. Serum neuron-specific enolase was evaluated using enzyme-linked immunosorbent assay. To compare means and standard deviations, among primary and secondary burning mouth syndrome, data was analysed with analysis of variance and multiple comparisons test. Results The mean age of the study participants for burning mouth syndrome and healthy subjects was 53.30 and 51.6 years, respectively. Amongst the secondary burning mouth syndrome group, 32 (25%) of the patients had menopause, 15 (11.7%) had diabetes, eight (6.2%) of the patients had nutritional deficiency, seven (5.4%) had combined diabetes, menopause, and depression, six (4.6%) had combined diabetes and depression, four (3.1%) were diagnosed with Sjögren’s syndrome. A minor percentage of 2.3% (three) had gastroesophageal reflux disease, while the remaining three (2.3%) patients in the secondary burning mouth syndrome group were on anti-depressants. There was a statistically significant increase in the levels of neuron-specific enolase in primary burning mouth syndrome as compared to the secondary burning mouth syndrome and healthy groups. Among the subgroups of secondary burning mouth syndrome, diabetic individuals showed a significant increase in neuron-specific enolase level when compared with other conditions in the secondary burning mouth syndrome patients. Discussion and conclusion: The raised serum neuron-specific enolase levels in patients suffering from primary burning mouth syndrome highlight a possible neuropathic mechanism. It was also increased in the sub-group of secondary burning mouth syndrome patients having diabetes. Although it cannot be ascertained whether the deranged values in the diabetic group were due to burning mouth syndrome or due to diabetes, the raised quantity of neuron-specific enolase in the primary burning mouth syndrome group is a reliable diagnostic indicator. Future studies on the assessment of neuron-specific enolase levels as a diagnostic tool for onset and management of primary and secondary burning mouth syndrome are recommended.

SURG-19. EVALUATION OF SERUM NEURON SPECIFIC ENOLASE, INTERFERON-ALPHA, AND INTERFERON-GAMMA IN RESPONSE TO LASER ABLATION OF HIGH GRADE GLIOMAS

BACKGROUND The blood-brain barrier (BBB) is a formidable obstacle in the treatment of gliomas. It has been speculated that the BBB may be temporarily disrupted in laser ablation, a relatively new treatment used for newly diagnosed and recurrent high grade gliomas (HGG). BBB disruption can be measured non-invasively through serum neuron specific enolase (NSE) levels. In addition to disrupting the BBB, laser ablation could trigger an immune response in brain that has yet to be studied. Interferon-alpha (IFN-α) and interferon-gamma (IFN-ɣ) are cytokines used as serum markers for an immune response. OBJECTIVE To measure NSE and IFN-α and IFN-ɣ as serum markers for BBB disruption and brain immune response activation, respectively, in patients undergoing laser ablation for recurrent high grade gliomas. METHODS Sixteen patients with recurrent HGG underwent laser ablation from 2/2017 to 12/2019. All 16 patients had gross total ablation of the contrast enhancing mass. Serum levels of NSE, IFN-α, IFN-ɣ were measured pre-operatively and at 24 hours, 2 weeks, and 8-16 weeks post-operatively, depending on adjuvant treatment received post-operatively. RESULTS Levels of NSE consistently increased 24 hours post-operatively (2.28±0.37 ng/ml) compared to pre-operative levels (1.62±0.29 ng/ml), p=0.032. Afterwards, NSE decreased and reached baseline by 2 weeks postoperatively (2 weeks- 1.67±0.29 ng/ml, 8 weeks- 1.85±0.91 ng/ml, 12 weeks- 0.81±0.33 ng/ml, 16 weeks- 1.23±0.93 ng/ml). Compared to their pre-operative levels, IFN-α and IFN-ɣ (85.46±35.29 and 1.62±0.47 pg/ml, respectively) did not display a significant difference in their serum levels (p=0.26-0.72 and 0.14-0.60, respectively, for IFN-α and IFN-ɣ) at any post-operative measurement time. Conclusions: Elevated NSE levels following laser ablation in HGG indicate a temporary disruption of the BBB that persists for approximately 2 weeks without eliciting an accompanying immune reaction in brain. Correlation studies with DCE-MRI are on-going.