The goal of this study was to investigate the biomarkers, neurofilament light chain, inflammatory markers, calcitonin-gene-related peptide, and metabolites from the kynurenine pathway in patients with severe post-concussive symptoms. The main question it aimed to answer was: * Are the biomarker concentrations significantly changed in patients with severe post-concussive symptoms compared to healthy individuals? * Do the biomarker concentrations change at follow-up? Participants were recruited from a recently published randomized controlled trial (Clinicaltrials.gov no. NCT02337101 / PMID: 31891145 ). The biomarker concentrations were compared to a healthy control group recruited from the Blood Bank at Aarhus University Hospital in 2022.
In the previously published RCT-study (PMID: 31891145), 86 participants with severe post-concussive symptoms provided blood samples at baseline (4 months after the concussion). Severe post-concussive symptoms were defined as having a Rivermead Post Concussion Questionnaire \>20. Around 7 months later, a follow-up blood sample was obtained from 54 participants. These blood samples were used to investigate blood biomarkers for the condition.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
86
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
Neurofilament light chain at baseline (primary outcome)
The investigators hypothesized: The concentration of neurofilament light chain (ng/L) is significantly increased at baseline in patients compared to the healthy control group.
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Neurofilament light chain at follow-up (primary outcome)
The investigators hypothesized: 1)The neurofilament light chain concentration (ng/L) normalizes (decreases) at follow-up compared to the baseline concentration in patients.
Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Self-reported post-concussion symptoms score (primary outcome)
The symptom score was measured at both baseline and follow-up using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) which is a self-reported questionnaire. The Rivermead Post-Concussion Symptoms Questionnaire contains 16 items which is rated from 0 (not experienced) to 4 (a severe problem). The total score thus ranges on a scale between 0-64.
Time frame: The baseline symptom score (RPQ) was obtained from the patients up to 7 months after the concussion (4 months median), and the follow-up score was obtained up to 16 months (10.5 median) after the concussion
Calcitonin-gene related peptide at baseline (CGRP)
The investigators hypothesized: The concentration of calcitonin gene-related peptide (pg/mL) is decreased compared to the healthy control group at baseline
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Calcitonin-gene related peptide at follow-up (CGRP)
The investigators hypothesized: The CGRP concentrations (pg/mL) will normalize (increase) at follow-up compared to baseline.
Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Quinolinic acid at baseline
The investigators hypothesized that: The concentration of the neurotoxic metabolite, quinolinic acid (measured in nM), is increased in patients compared to healthy controls
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Quinolinic acid at follow-up
The investigators hypothesized: The quinolinic acid concentration (nM) normalizes (decreases) at follow-up compared to the baseline concentration.
Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Neuroprotective index at baseline
The investigators hypothesized: The ratio between the neuroprotective metabolite kynurenic acid (KYNA) and the neurotoxic metabolite quinolinic acid (KynA/QUIN) is lower than the ratio in healthy individuals at baseline. A higher ratio means a better outcome.
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Neuroprotective index at follow-up
The investigators hypothesized: The ratio between the neuroprotective metabolite kynurenic acid (KYNA) and the neurotoxic metabolite quinolinic acid (QUIN) normalizes (increases) at follow-up compared to baseline. A higher ratio thus means a better outcome.
Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Inflammatory markers at baseline
The investigators hypothesized that: Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) (both pg/mL) are increased in patients compared to healthy controls.
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Inflammatory markers at baseline
The investigators hypothesized: Basic fibroblast growth factor (Basic FGF), Eotaxin, interferon gamma (IFN-y), interleukin 1 beta (IL-1B), interleukin 8 (IL-8), interleukin 9 (IL-9), interleukin 17 (IL17), Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and Macrophage Inflammatory Protein beta (MIP-1b) (all pg/mL) are significantly increased in patients compared to controls (hypothesis is based on a recent study (PMID: 32326805)
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Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Inflammatory markers at follow-up
TNF-α and IL-6 (both pg/mL) decreases at follow-up compared to the baseline value in patients.
Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.