Neurofilament light as a biomarker in traumatic brain injury

Abstract

<jats:sec><jats:title>Objective:</jats:title><jats:p>To determine if serum neurofilament light (NfL) correlates with cerebrospinal fluid (CSF) NfL, TBI diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of traumatic axonal injury (TAI).</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Participants were prospectively enrolled in Sweden and the United States between 2011-2019. The Swedish cohort included 45 hockey players with acute concussion (AC) sampled at six days, 31 repetitive concussion (RC) with persistent post-concussive symptoms (PCS) assessed with paired CSF and serum (median, 1.3 years after concussion), 28 preseason controls, and 14 non-athletic controls. Our second cohort included 230 clinic-based participants (162 with TBI and 68 controls. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n=30), 90 (n=48), and 180 (n=59) days, and 1 (n=84), 2 (n=57), 3 (n=46), 4 (n=38), and 5 (n=29) years after injury.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>In athletes with paired specimens, CSF and serum NfL were correlated (r=0.71, <jats:italic>p&lt;</jats:italic>0.0001). CSF and serum NfL distinguished players with PCS &gt;1-year from PCS ≤1-year (Area Under the Receiver-Operating Characteristic Curve [AUROC], 0.81 and 0.80). The AUROC for PCS &gt;1-year <jats:italic>vs</jats:italic> preseason controls were 0.97. In the clinic-based cohort, NfL at enrolment distinguished patients with mild <jats:italic>vs</jats:italic> moderate <jats:italic>vs</jats:italic> severe TBI (<jats:italic>p&lt;</jats:italic>0.001 and <jats:italic>p=</jats:italic>0.048). Serum NfL decreased over the course of five years (ß=–0.09 log pg/mL, <jats:italic>p&lt;</jats:italic>0.0001), but remained significantly elevated compared to controls. Serum NfL correlated with measures of functional outcome, MRI brain atrophy, and DTI estimates of TAI.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>Serum NfL shows promise as a biomarker for acute and repetitive sports-related concussion and patients with subacute and chronic TBI.</jats:p></jats:sec><jats:sec><jats:title>Classification of Evidence:</jats:title><jats:p>This study provides Class III evidence that increased concentrations of NfL distinguish TBI from controls.</jats:p></jats:sec>

Analysis of Brain Injury Biomarker Neurofilament Light and Neurodevelopmental Outcomes and Retinopathy of Prematurity Among Preterm Infants

“…Early postnatal NfL levels in the very preterm infants corresponded with levels observed after adult brain injury. 5 At 2 months of age, levels decreased to ranges observed in healthy adults. 38 …”

“…NfL constitutes a part of the neuronal cytoskeleton and shows promise in evaluating acute and chronic severity and the course of neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, and multiple sclerosis, 1 , 2 , 3 as well as hypoxic and traumatic brain injuries. 4 , 5 Data on NfL in the preterm infant are sparse. The protein has historically been measured in cerebrospinal fluid (CSF), but methodological advances now allow quantification of NfL in serum using single-molecule array (Simoa) technology, which strongly correlates with levels measured in the CSF.…”

Extracellular vesicle concentrations of glial fibrillary acidic protein and neurofilament light measured 1 year after traumatic brain injury

“…This analysis is part of the Long-term Clinical Correlates of Traumatic Brain Injury study (NCT01132898, 05/28/2010), an ongoing longitudinal, natural history study of TBI at the National Institutes of Health. The methods of this study have been described previously 10 , 11 .…”

“…Blood-based biomarkers may provide the ability to diagnose TBI and to predict patient outcomes following a TBI. Numerous studies have assessed the utility of serum or plasma glial fibrillary acidic protein (GFAP)—an astrocytic cytoskeleton protein released after astrocytic cell death—and neurofilament light (NfL)—an axonal protein associated with damaged axons—as diagnostic and prognostic markers of TBI 5 – 11 . Recently, another avenue for TBI biomarker research has been investigated: quantifying proteins contained in extracellular vesicles (EVs).…”

Red Cell Distribution Width to Platelet Count Ratio as a Promising Indicator of Mortality for Acute Traumatic Brain Injury: a Study on Large ICU&nbsp;Cohorts

“…In addition, various researches have focused on exploring diagnostic and prognostic biomarkers for TBI in recent years. Although some potential biomarkers, including S100B, NSE, GFAP, UCH-L1, Neuro lament light and Tau have been reported with diagnostic or prognostic values in clinical trials, most of them have not been used in clinical work due to the lack of clinically compatible analysis platforms that ensure standardization and reproductive testing, except for S100B and Neuro lament light which was only used in diagnosis of mild TBI and chronic TBI [4][5][6][7].…”