TY - JOUR
T1 - Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms:
T2 - A cohort study
AU - Eggertsen, Peter Preben
AU - Palmfeldt, Johan
AU - Pedersen, Asger Roer
AU - Frederiksen, Oana-Veronica
AU - Olsen, Rikke Katrine Jentoft
AU - Nielsen, Jørgen Feldbæk
PY - 2024/5
Y1 - 2024/5
N2 - BACKGROUND: Concussion leads to persistent post-concussion symptoms (PPCS) in up to one-third of those affected. While previous research has linked the initial trauma to elevated serum levels of neurofilament light chain (NFL), inflammatory markers, and neurotoxic metabolites within the kynurenine pathway, few studies have explored their relevance in PPCS. This study aims to investigate these biomarkers in PPCS patients, elucidating their relevance in the prolonged phase of concussion.METHODS: Serum samples from 86 PPCS individuals aged 18-30 years, 2-6 months post-trauma were analyzed, with 54 providing follow-up samples after seven months. NFL was measured using single-molecule array (Simoa) technology, 13 inflammatory markers via a Luminex immunoassay, and five kynurenine metabolites using liquid chromatography-mass spectrometry. A control group of 120 healthy anonymous blood donors was recruited for comparison.RESULTS: No significant NFL differences were found in PPCS participants compared with healthy individuals (p = 0.22). Intriguingly, a subset (9.3%) of PPCS participants initially exhibited abnormally high NFL levels (>9.7 pg/mL), which normalized upon follow-up (p = 0.032). Additionally, serum levels of the inflammatory markers, monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1/CCL11 were 25-40% lower than in healthy individuals (p ≤ 0.001). As hypothesized, PPCS participants exhibited a 22% reduction in the ratio of kynurenic acid to quinolinic acid (neuroprotective index) (p < 0.0001), indicating a shift towards the formation of neurotoxic metabolites.CONCLUSION: NFL may serve as a biomarker to monitor recovery, and future studies should investigate the potential therapeutic benefits of modulating the kynurenine pathway to improve PPCS.
AB - BACKGROUND: Concussion leads to persistent post-concussion symptoms (PPCS) in up to one-third of those affected. While previous research has linked the initial trauma to elevated serum levels of neurofilament light chain (NFL), inflammatory markers, and neurotoxic metabolites within the kynurenine pathway, few studies have explored their relevance in PPCS. This study aims to investigate these biomarkers in PPCS patients, elucidating their relevance in the prolonged phase of concussion.METHODS: Serum samples from 86 PPCS individuals aged 18-30 years, 2-6 months post-trauma were analyzed, with 54 providing follow-up samples after seven months. NFL was measured using single-molecule array (Simoa) technology, 13 inflammatory markers via a Luminex immunoassay, and five kynurenine metabolites using liquid chromatography-mass spectrometry. A control group of 120 healthy anonymous blood donors was recruited for comparison.RESULTS: No significant NFL differences were found in PPCS participants compared with healthy individuals (p = 0.22). Intriguingly, a subset (9.3%) of PPCS participants initially exhibited abnormally high NFL levels (>9.7 pg/mL), which normalized upon follow-up (p = 0.032). Additionally, serum levels of the inflammatory markers, monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1/CCL11 were 25-40% lower than in healthy individuals (p ≤ 0.001). As hypothesized, PPCS participants exhibited a 22% reduction in the ratio of kynurenic acid to quinolinic acid (neuroprotective index) (p < 0.0001), indicating a shift towards the formation of neurotoxic metabolites.CONCLUSION: NFL may serve as a biomarker to monitor recovery, and future studies should investigate the potential therapeutic benefits of modulating the kynurenine pathway to improve PPCS.
KW - Biomarker
KW - Concussion
KW - Mild traumatic brain injury
KW - PCS
KW - Post-concussion syndrome
KW - mTBI
KW - Chemokine CCL2/blood
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Young Adult
KW - Adolescent
KW - Adult
KW - Biomarkers/blood
KW - Female
KW - Post-Concussion Syndrome/blood
KW - Kynurenine/blood
KW - Cohort Studies
KW - Neurofilament Proteins/blood
UR - http://www.scopus.com/inward/record.url?scp=85190509881&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2024.123016
DO - 10.1016/j.jns.2024.123016
M3 - Journal article
C2 - 38636323
SN - 0022-510X
VL - 460
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
M1 - 123016
ER -