Use of Serum Neuron-Specific Enolase Level to Predict Adverse Neurologic Outcomes after Aortic Surgery
07 February 2019
11 March 2019
19 April 2019 (online)
In the recent article by Kimura et al evaluating predictive performance of serum neuron-specific enolase (NSE) level for neurologic injury after thoracic aortic surgery, the receiver-operating characteristic (ROC) curve analysis showed that the cutoff value of serum NSE level was 34.14 ng/mL for neurologic injury with a sensitivity of 0.769 and a specificity of 0.851, and 43.56 ng/mL for permanent neurologic dysfunction with a sensitivity of 1.000 and a specificity of 0.963. Furthermore, the linear regression analysis indicated a significant correlation between serum NSE level and infarction volume. Given that neurologic injury remains a devastating complication of thoracic and thoracoabdominal aortic surgery, their findings have potential implications. Other than the limitations described in the Discussion section, however, we noted several issues in this study that need further clarifications and discussions.
First, postoperative neurologic injury occurred in 12 patients (20%); with respect to the severity of neurologic injury, five and seven patients had temporary neurologic dysfunction and permanent neurologic dysfunction, respectively. As more than 60% of patients included in this study underwent total arch replacement with cardiopulmonary bypass and patients with suspected postoperative neurologic injury only underwent brain computed tomography or magnetic resonance imaging examination, we are very interested to know whether all of adverse postoperative neurologic outcomes which occurred in 12 patients were attributable to brain injury. The available evidence indicates that neurological injury by spinal ischemia is one of the most dangerous complications after thoracic and thoracoabdominal aortic surgery, with an incidence of 0.5 to 40%. Furthermore, it has been shown that serum NSE level can well reflect the degree of acute spinal cord injury and is a potential biomarker for prognosis of acute spinal cord injury. Thus, we are concerned that unknown spinal cord injury by acute ischemia during aortic surgery would have contributed to their findings.
Second, based on the ROC curve analysis, the authors provided the cutoff values, area under ROC curves, sensitivities and specificities of serum NSE level for postoperative neurologic injury, and permanent neurologic dysfunction. After the ROC curve analysis, however, the authors did not further provide the Youden indexes at the optimal cutoff values, positive and negative predictive values of serum NSE level for adverse postoperative neurologic outcomes. The Youden index is a direct measure of diagnostic accuracy at the optimal cutoff value, that is, the maximum overall correct classification rate that a biomarker can achieve. A biomarker with a large area under the ROC curve may have an unsatisfactory overall correct classification rate at the optimal cutoff point, and vice versa. Thus, not providing Youden index, positive and negative predictive values of serum NSE level have resulted in difficulty determining whether it is a good predictor of adverse neurologic outcomes after thoracic aortic surgery.
Finally, the mean NSE level was significantly higher on the day after surgery than on the day before surgery in patients without and with adverse neurologic outcomes. Perhaps, the use of early postoperative serum NSE elevation (ΔNSE, defined as a difference between the NSE on the day after surgery and preoperative baseline NSE) should further improve predictive ability of serum NSE for adverse neurologic outcomes after thoracic aortic surgery. We believe that their findings would be more clinically valuable, if this study design had included this issue.
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