Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports

Shahim, Pashtun; Zetterberg, Henrik; Tegner, Yelverton; Blennow, Kaj

doi:10.1212/wnl.0000000000003912

Cited by 295 publications

(292 citation statements)

References 25 publications

Supporting

Mentioning

265

Contrasting

Unclassified

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 82%

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

Akgün

Kretschmann

Haase

et al. 2019

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

ObjectiveTo evaluate individual neurofilament light chain (NfL) variation over the time of disease course and the potential of NfL measurement to predict treatment response in patients with MS.MethodsWe investigated 15 patients with MS after immune reconstitution treatment with alemtuzumab (ATZ). Monthly serum NfL (sNFL) measurements were correlated with Expanded Disability Status Scale (EDSS), MRI, and relapse activity over an observational period of up to 102 months.ResultsBefore ATZ, sNfL was significantly increased in correlation with previous relapse/MRI activity. After ATZ, sNfL decreased quickly within the first 6 months. In patients classified as NEDA-3, sNfL declined and persisted at an individual low steady-state level of <8 pg/mL. During follow-up, 34 sNfL peaks with a >20 fold increase could be detected, which were associated with clinical or MRI disease activity. Even patient-reported relapse-suspicious symptoms, which have not been confirmed because relapses were accompanied by sNfL, increase, proposing sNfL assessment as a marker for relapse activity. sNfL started to increase earliest 5 months before, peaked at clinical onset, and recovered within 4–5 months. sNfL presented at higher levels in active patients requiring ATZ retreatment compared with responder patients. During 2 documented pregnancies, sNfL was at a low level, whereas a postpartum transient sNfL increase was seen without any signs of activity.ConclusionsThis study applied a long-term high-frequency sNfL assessment in an ATZ-treated cohort, allowing a holistic profiling on the individual level and highlighted that sNfL can eminently complement the individual clinical and MRI monitoring in clinical practice.

show abstract

Section: Discussionmentioning

confidence: 82%

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

Akgün

Kretschmann

Haase

et al. 2019

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

show abstract

“…Of note, previous studies have investigated the abovementioned markers in TBI patients and found evidence for increases in NFL, 53, 54 GFAP ,55 and Tau 56 concentrations, as well as decreased MBP ,57 in cerebral spinal fluid and/or serum. While serum and CSF were not analyzed in this study, RmTBI did affect expression of these markers in brain tissue in a similar manner.…”

Section: Discussionmentioning

confidence: 94%

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Wright

O’Brien

Shultz

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveWhether sex differences contribute to the heterogeneity of mild traumatic brain injury (mTBI) and repeated mTBI (RmTBI) outcomes in adolescents is unknown. Therefore, this study examined changes in, and differences between, male and female rats following single mTBI and RmTBI.MethodsRats were given a single mTBI, RmTBI (i.e., 3x), or sham injuries. Injuries were administered using a lateral impact model that mimics forces common in human mTBI. After the final injury, rats underwent extensive behavioral testing to examine cognition, motor function, and anxiety‐ and depressive‐like behavior. Postmortem analyses investigated gene expression and structural changes in the brain.ResultsMany of the outcomes exhibited a sex‐dependent response to RmTBI. While all rats given RmTBI had deficits in balance, motor coordination, locomotion, and anxiety‐like behavior, only male rats given RmTBI had short‐term working memory deficits, whereas only females given RmTBI had increased depressive‐like behavior. Volumetric and diffusion weighted MRI analyses found that while RmTBI‐induced atrophy of the prefrontal cortex was greater in female rats, only the male rats exhibited worse white matter integrity in the corpus callosum following RmTBI. Sex‐dependent changes in brain expression of mRNA for glial fibrillary acidic protein, myelin basic protein, and tau protein were also observed following injury.InterpretationThese findings suggest that in adolescent mTBI, sex matters; and future studies incorporating both male and females are warranted to provide a greater understanding of injury prognosis and better inform clinical practice.

show abstract

“…It is not clear if these rapid tau changes represent axonal injury or release of pre-existing interstitial fluid tau into the blood across an injured blood-brain barrier (the latter seems more likely from a pathophysiological standpoint). Serum NfL correlates strongly with CSF NfL, is increased in active professional fighters [82], in ice hockey players with postconcussive syndrome [83] and in retired fighters who have neurological symptoms [82]. The marker increases over time in American football athletes over the course of a season, suggesting that it may be sensitive to repetitive subconcussive head impacts [84].…”

Section: Fluid Biomarkersmentioning

confidence: 99%

Head trauma in sports – clinical characteristics, epidemiology and biomarkers

et al. 2018

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post‐traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10–15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid‐based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers.

show abstract

Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports

Abstract: The results from these 2 independent cohort studies suggest that serum NFL is a highly sensitive biomarker for concussion.

Cited by 295 publications

References 25 publications

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

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

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Head trauma in sports – clinical characteristics, epidemiology and biomarkers

Contact Info

Product

Resources

About