Neurofilament Light Chain levels during admission after out-of-hospital cardiac arrest is associated with cognitive performance at 3-months follow-up

Abstract

Abstract Background Patients who are resuscitated from out-of-hospital cardiac arrest (OHCA) and hospitalized in coma are at high risk of mortality or brain injury with consequent cognitive impairment, and new therapy are wanted. Biomarkers of brain injury, including Neuron-specific enolase (NSE) and Neurofilament light chain (NfL), predict mortality from cerebral injury. However, prognostication of cognitive dysfunction after discharge in OHCA survivors is challenging. Montreal Cognitive Assessment (MoCA) is a recommended standardized cognitive function testing which is used in the months following OHCA. Nevertheless, prognostic methods assessed in the initial phase of admittance which identify patients at risk of developing cognitive impairment are needed. Purpose To investigate the effect of tocilizumab administered at admission after OHCA on cognitive performance assessed by MoCA at 3-month follow-up, and to investigate the association to time-to-ROSC, and NSE as well as NfL levels during index admission with MoCA at follow-up. Methods The IMICA trial evaluated tocilizumab for reducing systemic inflammation after OHCA and randomized 80 comatose adult patients at admission to an infusion of either tocilizumab (8mg/kg, maximum 800mg) or placebo. NSE at 48 hours was measured as part of routine biochemistry based on serum samples, and NFL at 48 hours was measured in serum samples from the biobank. Time-to-ROSC was reported from pre-hospital data and cognitive performance at 3 months follow-up were assessed by the MoCA test. The association between MoCA and time-to-ROSC, NSE and NfL was assessed by Spearman’s correlation analyses. Results At follow-up, 35 patients had a MoCA test performed, while 28 patients were deceased, and 17 were alive without having an available MoCA score. There was no difference in MoCA scores at follow-up in the tocilizumab group compared to placebo group (p=0.72), and therefore results for both groups were pooled for analyses. NfL was found to be inversely correlated with MoCA score, r = -0.49, p = 0.003 (Figure), while there were no correlations with MoCA for time-to-ROSC or NSE (p = 0.46 and p = 0.34). Conclusions NfL measured at 48 hours after admission was inversely correlated with cognitive performance at 3 months for survivors of OHCA.