TY - JOUR

T1 - Hypersensitivity to Calcitonin Gene–Related Peptide in Post-Traumatic Headache

AU - Ashina, Håkan

AU - Iljazi, Afrim

AU - Al-Khazali, Haidar M.

AU - Christensen, Casper E.

AU - Amin, Faisal M.

AU - Ashina, Messoud

AU - Schytz, Henrik W.

PY - 2020

Y1 - 2020

N2 - Objective: To demonstrate that calcitonin gene–related peptide (CGRP) induces headache exacerbation with migraine-like features in patients with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). Methods: A randomized, double-blind, placebo-controlled, two-way crossover study was conducted. Analyses were intention-to-treat. Eligible patients were aged 18 to 65 years and had a history of persistent PTH after mild TBI for at least 12 months. Patients were randomized to receive an intravenous infusion of 1.5μg/min of CGRP or placebo (isotonic saline) over 20 minutes on two separate experimental days. A 12-hour observational period was used to evaluate the following outcomes: (1) difference in incidence of headache exacerbation with migraine-like features and (2) difference in area under the curve for headache intensity scores. Results: Thirty patients (mean age = 37 years, 25 women [83%]) were randomized and completed the study. During the 12-hour observational period, 21 of 30 patients (70%) developed headache exacerbation with migraine-like features after CGRP, compared with 6 patients (20%) after placebo (p < 0.001). The baseline-corrected area under the curve for headache intensity scores was significantly larger after CGRP, compared with placebo (p < 0.001). Interpretation: Patients with persistent PTH are hypersensitive to CGRP, which underscores its pathophysiological importance. Furthermore, CGRP-targeted therapies might provide a novel mechanism-based treatment option for patients with persistent PTH. ANN NEUROL 2020;88:1220–1228.

AB - Objective: To demonstrate that calcitonin gene–related peptide (CGRP) induces headache exacerbation with migraine-like features in patients with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). Methods: A randomized, double-blind, placebo-controlled, two-way crossover study was conducted. Analyses were intention-to-treat. Eligible patients were aged 18 to 65 years and had a history of persistent PTH after mild TBI for at least 12 months. Patients were randomized to receive an intravenous infusion of 1.5μg/min of CGRP or placebo (isotonic saline) over 20 minutes on two separate experimental days. A 12-hour observational period was used to evaluate the following outcomes: (1) difference in incidence of headache exacerbation with migraine-like features and (2) difference in area under the curve for headache intensity scores. Results: Thirty patients (mean age = 37 years, 25 women [83%]) were randomized and completed the study. During the 12-hour observational period, 21 of 30 patients (70%) developed headache exacerbation with migraine-like features after CGRP, compared with 6 patients (20%) after placebo (p < 0.001). The baseline-corrected area under the curve for headache intensity scores was significantly larger after CGRP, compared with placebo (p < 0.001). Interpretation: Patients with persistent PTH are hypersensitive to CGRP, which underscores its pathophysiological importance. Furthermore, CGRP-targeted therapies might provide a novel mechanism-based treatment option for patients with persistent PTH. ANN NEUROL 2020;88:1220–1228.

U2 - 10.1002/ana.25915

DO - 10.1002/ana.25915

M3 - Journal article

C2 - 32959458

AN - SCOPUS:85092081314

VL - 88

SP - 1220

EP - 1228

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 6

ER -