Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study.

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.

Characterization of persistent post-traumatic headache and management strategies in adolescents and young adults following mild traumatic brain injury.

Characteristics of persistent post-traumatic headache (PTH) in young individuals are poorly known leading to diagnostic problems and diverse management. We aimed to describe headache phenotypes and self-reported management strategies in young individuals with PTH following mild traumatic brain injury (mTBI). A comprehensive structured questionnaire was used to evaluate headache phenotypes/characteristics and management strategies to relieve headache in 107, 15-30-year-old individuals with PTH. Around 4 months post-injury, migraine-like headache in combination with tension-type like headache (40%) was the most commonly encountered headache phenotype followed by migraine-like headache (36%). Around 50% reported aura-like symptoms before/during the headache attack. Medication-overuse headache was diagnosed in 10%. Stress, sleep disturbances, and bright lights were the most common trigger factors. More than 80% reported that their headache was worsened by work-related activity and alleviated by rest/lying down. Simple analgesics were commonly used (88%) whereas prophylactic drugs were rarely used (5%). Bedrest and physiotherapy were also commonly used as management strategies by 56% and 34% of the participants, respectively. In conclusion, most young individuals with PTH after mTBI presented with combined migraine-like and tension-type-like headache followed by migraine-like headache, only. Preventive headache medication was rarely used, while simple analgesics and bedrest were commonly used for short-term headache relief.

Design of an early intervention for persistent post-concussion symptoms in adolescents and young adults: A feasibility study.

BACKGROUND: About 5-15 % of patients with concussion experience persistent post-concussion symptoms (PCS) longer than 3 months post-injury. OBJECTIVE: To explore the feasibility of a new intervention for young patients with persistent PCS and long-term changes after intervention. METHODS: Thirty-two consecutive patients (15-30 years) with persistent PCS 2-4 months post-injury were recruited from a cohort study or referred to a non-randomized feasibility study of an individually tailored, 8-week, multidisciplinary intervention. Assessment was performed at baseline, end of intervention (EOI), and at 3- and 12-month follow-up (FU). Main measures were The Experience of Service Questionnaire (ESQ), Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and The Quality of Life after Brain Injury - Overall Scale (QOLIBRI-OS). RESULTS: Twenty-three (72%) patients completed the intervention. The ESQ demonstrated high patient satisfaction. There was a decrease of PCS and an increase in quality of life from baseline to EOI: RPQ score -8.9 points, 95% CI 4.5 to 13.3, p < 0.001; QOLIBRI-OS score +10.5 points, 95% CI 2.5 to 18.5, p = 0.010. Improvement was maintained at 3- and 12-month FU. CONCLUSION: The new early intervention is feasible and may prevent chronification of PCS. An RCT is currently performed to evaluate the effect of the intervention.

Diffusion MRI findings in patients with extensive and minimal post-concussion symptoms after mTBI and healthy controls: a cross sectional study.

PRIMARY OBJECTIVES: We hypothesized that the microstructure of the corpus callosum, thalamus and hippocampus, as measured with diffusion and Mean of the Kurtosis Tensor (MKT) MRI, differs between healthy subjects and patients with extensive and minimal post-concussion symptoms (PCS) and that MKT measures correlate with PCS severity and self-reported cognitive symptoms. RESEARCH DESIGN: A cross-sectional study comparing patients with extensive PCS and patients with minimal PCS 2-5 months after mild traumatic brain injury (mTBI) with each other and with an external healthy control group. METHODS AND PROCEDURES: Diffusion MRI was obtained in 25 patients with extensive PCS and in 25 patients with minimal PCS as measured by the Rivermead Post-concussion Symptoms Questionnaire. The patients were matched on age, sex and time since accident. Data from an external healthy control group (n = 27) was included. MAIN OUTCOME AND RESULTS: There was no difference in MKT between the two groups with mTBI and no correlation between MKT and PCS. There was no difference between the three groups in other diffusion measures. CONCLUSIONS: Our results did not point to microstructural changes in the corpus callosum, thalamus and hippocampus in relation to PCS after mTBI.