Association of Changes in Plasma Neurofilament Light and Tau Levels With Anesthesia and Surgery

Abstract

IMPORTANCE Anesthesia and surgery are believed to act on the central nervous system by a fully reversible mechanism innocuous to nerve cells. Evidence that neurological sequelae may follow would challenge this belief and would thereby suggest a need to reassess theories of the mechanism of anesthetic action or the response of the central nervous system to surgery. OBJECTIVE To measure 2 biomarkers of neurological injury (neurofilament light and tau) in plasma in a series of timed collections before and after anesthesia and surgery. DESIGN, SETTING, AND PARTICIPANTS These 2 related observational studies (CAPACITY and ARCADIAN) recruited patients 60 years and older who were undergoing general anesthesia for surgeries performed within a tertiary hospital. Blood samples were taken immediately before surgical anesthesia was administered and then sequentially after surgery at 30-minute, 6-hour, 24-hour, and 48-hour intervals. Sampling took place from January 2014 to August 2015. Data analysis took place from October 2016 to February 2017. MAIN OUTCOMES AND MEASURES Plasma neurofilament light and tau. RESULTS A total of 30 patients were enrolled (13 from the CAPACITY study and 17 from the ARCADIAN study). The mean (SD) age was 69.1 (7.0) years, and 18 members (59%) of the participant group were female; 22 (73%) were undergoing joint arthroplasty. Mean neurofilament light increased at each measurement from a combined baseline mean (SD) of 22.3 (20.4) pg/mL to a maximal combined mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 67% (95% CI, 45%-89%; P < .001), at 48 hours postoperatively. The level of tau increased significantly from baseline at every measurement, from a combined baseline mean (SD) of 3.1 (1.3) pg/mL to a maximal combined mean (SD) of 10.8 (9.5) pg/mL, a peak increase of 257% (95% CI, 154%-361%; P < .001), at 6 hours postoperatively. After 6 hours, the mean level began to return to baseline but remained elevated after 48 hours. CONCLUSIONS AND RELEVANCE Neurofilament light is a specific marker of axonal injury and has been shown to indicate neuronal damage in a number of diseases. Tau proteins are an integral component of axonal integrity, and increased tau indicates neuronal damage. The increases in both neurofilament light and tau over 48 hours after surgery suggest that general anesthesia and surgery may be associated with neuronal damage in the short term. Further investigations will be required to study any association with clinical outcomes. These preliminary findings demand that we question the prevailing assumption that anesthesia and surgery are innocuous, transient, and without injurious changes to the central nervous system.

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

“…In our cohort, there were no other reported events as trauma episodes, stroke, anesthesia during surgery, or metabolic diseases that were supposed to be associated with sNfL increase. [33][34][35][36] However, we are not able to completely exclude such factors. In MS, sNfL peaks can indicate subclinical disease activity even when clinical parameters and cerebral MRI seem to be stable.…”

A case series on the value of tau and neurofilament protein levels to predict and detect delirium in cardiac surgery patients

“…The development of the NfL was completely different to tau and GFAP (ref. 26 ). The increase of NfL over time might indicate that this biomarker is relevant for the detection and monitoring of the emerging delirium.…”

Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium

“…In elective surgery patients undergoing general anesthesia, sNFL has been found to increase to a maximum of 48 h postoperatively [42]. Damage to peripheral nerves during surgery, noxious effects of anesthesia [43], and systemic physiological reactions could be possible underlying mechanisms.…”