Sustained Axonal Degeneration in Prolonged Disorders of Consciousness

Abstract

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.

An innovative approach for the evaluation of prolonged disorders of consciousness using NF-L and GFAP biomarkers: a pivotal study

“…Recently, Bagnato et al (2021) found that the serum NF-L levels of patients with pDoC after traumatic brain injury or hypoxic-ischemic brain injuries at 1–3 months post-injury were more than 19 times higher than those of matched HC, and almost 5 times higher at 6 months post-injury. This study has adopted the conventional ELISA kit as a detection technique, less sensitive than the single-molecule array method for serum NF-L detection; however, comparisons between subpopulations were performed in small numbers of patients, which also represents our limitation 17 . Moreover, the temporal window of 6 months adopted for clinical use did not show results for one year after brain injury 17 , 29 .…”

“…This study has adopted the conventional ELISA kit as a detection technique, less sensitive than the single-molecule array method for serum NF-L detection; however, comparisons between subpopulations were performed in small numbers of patients, which also represents our limitation 17 . Moreover, the temporal window of 6 months adopted for clinical use did not show results for one year after brain injury 17 , 29 .…”

“…In particular, the Neurofilament light chain (NF-L) marker 15 , a 68 kDa cytoskeletal neuron-specific protein, is a biomarker for acute and post-acute brain conditions following a severe brain injury caused by an anoxic, hemorrhagic, or traumatic event 16 , 17 . After the neuronal injury, serum NF-L levels rise rapidly and remain elevated for prolonged periods even 1 year after trauma 18 , 19 .…”

The implication of a diversity of non-neuronal cells in disorders affecting brain networks

“…microglial phagocytic activity, contact with neurons ("satellite microglia"), secretion of pro-inflammatory cytokines, and synaptic pruning (Ramlackhansingh et al, 2011;Donat et al, 2017;Krukowski et al, 2021). SC, as indexed by increased NFL levels (Adams et al, 2000;Guldenmund et al, 2016;Bagnato et al, 2017Bagnato et al, , 2021. microglial phagocytosis of astrocytic endfeet and thus loss of BBB integrity (van Vliet et al, 2020;Heithoff et al, 2021).…”

Biomarkers of Brain Injury: A Window on Mechanisms of Injury and Recovery in the Brain

“…Accordingly, biomarkers may also be applied in the evaluation of pathophysiological mechanisms operating in chronic brain injuries. In this Special Issue of Brain Sciences, Bagnato et al [8] report on the assessment of serum NFL levels in 70 patients with prolonged disorders of consciousness following traumatic or hypoxicischemic brain injury. Compared with those of healthy matched controls, serum NFL levels were higher in these patients up to 6 months after injury.…”