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

Peter Preben Eggertsen*, Johan Palmfeldt, Henrik Winther Schytz, Debbie Hay, Rikke Katrine Jentoft Olsen, Jørgen Feldbæk Nielsen

*Corresponding author for this work
1 Citation (Scopus)


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.

Original languageEnglish
JournalJournal of Neurology
Issue number5
Pages (from-to)2458-2472
Number of pages15
Publication statusPublished - 2024


  • Adolescent
  • Adult
  • Biomarkers/blood
  • Calcitonin Gene-Related Peptide/blood
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Post-Concussion Syndrome/blood
  • Post-Traumatic Headache/blood
  • Young Adult
  • PCS
  • Biomarker
  • Mild traumatic brain injury
  • Post-traumatic headache
  • Concussion
  • CGRP


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