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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00010

Plasma calcitonin gene-related peptide: A potential biomarker for diagnosis and therapeutic responses in pediatric migraine

  • 1Department of Pediatrics, College of Medicine, National Taiwan University, Taiwan
  • 2Department of Pediatrics, National Taiwan University Hospital, Taiwan
  • 3Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taiwan
  • 4Clinical Center for Neuroscience and Behavioral, National Taiwan University Hospital, Taiwan
  • 5Department of Internal Medicine, National Taiwan University Hospital, Taiwan
  • 6Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taiwan
  • 7Faculty of Pharmaceutical Sciences, UCSI University, Malaysia
  • 8Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taiwan
  • 9Graduate Institute of Acupuncture Science, China Medical University, Taiwan

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine.
Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM) and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least two weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA.
Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p=0.001). The mean plasma CGRP level in migraineurs either during (291±60 pg/ml) or between (240±48) attacks was higher than in NM patients (51±5 pg/ml, p=0.006 and 0.018, respectively) and NH controls (53±6 pg/ml, p=0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364±62 pg/ml, n=47) than those not (183±54 pg/ml, n=21) (p=0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437±131 pg/ml, n=14 vs. 67±19 pg/ml, n=6, p=0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives.
Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Keywords: pediatric migraine, Calcitonin Gene-Related Peptide, Plasma biomarker, Anti-migraine drugs, Topiramate

Received: 13 Aug 2018; Accepted: 07 Jan 2019.

Edited by:

Pasquale Parisi, Sapienza University of Rome, Italy

Reviewed by:

Francesco Nicita, Bambino Gesù Children Hospital (IRCCS), Italy
Piero Pavone, Università degli Studi di Catania, Italy  

Copyright: © 2019 Fan, Kuo, Lee, Chang and Chiou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Pi-Chuan Fan, Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan,