The Potential Role of Neurofilament Light in Mild Traumatic Brain Injury Diagnosis: A Systematic Review

Mild traumatic brain injury (mTBI) is an insult to the CNS often overlooked at the time of presentation due to variable symptomatology and undetectable nature on CT/MRI. Increased exposure to repetitive head injuries results in a high prevalence of mTBI among athletes and military personnel. While most patients fully recover with rest, some are at risk for long-lasting neurocognitive dysfunction, leading to a high morbidity and cost burden on the healthcare system. Currently, there are no unified symptom-based criteria or gold standard objective measurement for mTBI. Neurofilament light (Nf-L) is a highly sensitive biomarker for axonal injury with the potential to serve as an objective serum measurement for mTBI. This systematic review investigates the ability of Nf-L to accurately diagnose acute mTBI in athletes and military personnel. A comprehensive literature search of PubMed, Scopus, and Google Scholar from 2010 to 2021 using keywords neurofilament light chain, mTBI, concussion, athletes, and military identified 239 articles for eligibility screening. Ten articles met the inclusion criteria for qualitative analysis, with extracted data including Nf-L levels, recovery characteristics, and neuroimaging results. Of the 10 studies meeting inclusion criteria, one was military-related, five were sports-related, and four were mixed-focus. Six studies investigated the association between mTBI and Nf-L levels within 24 hours of injury. Four of these studies involved athletes, with three showing evidence of acute Nf-L elevations. No evidence of acute Nf-L elevations was reported among military personnel or emergency department patients. Nf-L elevations were recorded at various time points greater than 24 hours post-injury in athletes (two studies) and emergency department patients (one study). Positive associations were found between Nf-L levels and loss of consciousness/post-traumatic amnesia (one study), positive neuroimaging findings (three studies), and prolonged recovery times (three studies). We are unable to conclude whether Nf-L has the capacity for acute diagnosis of mTBI or the optimal time for serum measurement. Nf-L does, however, shows promise as a prognostic factor for mTBI complications, neuroimaging findings, and recovery. Additional studies are warranted, as the use of Nf-L in early diagnosis of mTBI in the future would improve clinical management while decreasing complications and healthcare costs.