Serum calcitonin gene-related peptide in patients with persistent post-concussion symptoms, including headache: a cohort study

• Published in: Journal of neurology Vol. 271; no. 5; pp. 2458 - 2472
• Main Authors: Eggertsen, Peter Preben, Palmfeldt, Johan, Schytz, Henrik Winther, Hay, Debbie, Olsen, Rikke Katrine Jentoft, Nielsen, Jørgen Feldbæk
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2024; Springer Nature B.V
• Subjects: Adolescent; Adult; Biomarkers - blood; Blood donors; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - blood; Cohort analysis; Cohort Studies; Concussion; Enzyme-linked immunosorbent assay; Female; Follow-Up Studies; Headache; Headaches; Humans; Male; Medicine; Medicine & Public Health; Migraine; Neurology; Neuroradiology; Neurosciences; Original Communication; Parathyroid hormone; Peptides; Phenotypes; Post-Concussion Syndrome - blood; Post-Traumatic Headache - blood; Post-Traumatic Headache - etiology; Serum levels; Young Adult; PCS; Biomarker; Mild traumatic brain injury; Concussion; Post-traumatic headache; CGRP
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-024-12181-y

Background
Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology, and post-traumatic headache (PTH) frequently presents with migraine-like features. Despite several clinical similarities, few studies have explored CGRP in PTH and concussion. This study investigates serum CGRP levels in patients with persistent post-concussion symptoms (PPCS), including PTH.
Methods
This cohort study was based on serum samples from individuals aged 18–30 years with PPCS who participated in a previously published randomized controlled trial of a non-pharmacological intervention. The primary outcome was serum CGRP concentrations, determined at baseline before randomization and at follow-up 7 months later, using an enzyme-linked immunosorbent assay (ELISA). CGRP levels at baseline were compared with healthy anonymous blood donors in the same age group.
Results
Baseline serum samples were collected from 86 participants with PPCS. The participants were most often female (78%) and migraine-like headache was the most frequent headache phenotype (74%). Serum CGRP levels were higher in participants with PPCS than in 120 healthy individuals (median: 158.5 pg/mL vs. 76.3 pg/mL, p = 0.050). A stratified analysis revealed that females with PPCS had a fivefold higher median than healthy females (166.3 pg/mL vs. 32.1 pg/mL, p = 0.0006), while no differences were observed in males (p = 0.83). At follow-up, CGRP levels decreased with a median change of  – 1.3 pg/mL (95% confidence interval:  – 17.6–0, p = 0.024).
Discussion
Elevated serum levels of CGRP in patients with PPCS and a decrease over time suggest an involvement of CGRP in PTH/PPCS. If confirmed in other studies, it could pave the way for CGRP-targeted therapies, which could have clinical significance.