{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:22:47Z","timestamp":1784024567869,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/01578."],"award-info":[{"award-number":["PI15\/01578."]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Previous studies have reported increased brain deposits of iron in patients with chronic migraine (CM). This study aims to determine the relation between iron deposits and outcome after treatment with OnabotulinumtoxinA (OnabotA). Demographic and clinical data were collected for this study through a prospective cohort study including 62 CM patients treated with OnabotA in the Hospital Cl\u00ednico Universitario de Santiago de Compostela (Spain). Demographic and clinical variables were registered. Selected biomarkers in plasma during interictal periods (calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX3)) and neuroimaging changes (iron deposits in the red nucleus (RN), substantia nigra (SN), globus pallidus (GP), and periaqueductal gray matter (PAG), and white matter lesions (WML)) were determined. Subjects were classified in responders (\u226550% reduction in headache days) or non-responders (&lt;50%). Responders to treatment were younger (mean age difference = 12.2; 95% confidence interval (CI): 5.4\u201318.9, p = 0.001), showed higher serum levels of CGRP (\u226550 ng\/mL) and PTX3 (\u22651000 pg\/mL) and smaller iron deposits in the GP and PAG (mean difference = 805.0; 95% CI: 37.9\u20131572.1 \u03bcL, p = 0.040 and mean difference = 69.8; 95% CI: 31.0\u2013108.6 \u03bcL, p = 0.008; respectively). Differences in PAG iron deposits remained significant after adjusting for age (mean difference = 65.7; 95% CI: 22.8\u2013108.6 \u03bcL, p = 0.003) and were associated with poor response to OnabotA after adjustment for clinical and biochemical variables (odds ratio (OR) = 0.963; 95% CI: 0.927\u20130.997, p = 0.041). We conclude that larger PAG iron deposits are associated with poor response to OnabotA in CM.<\/jats:p>","DOI":"10.3390\/toxins12080479","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T12:15:38Z","timestamp":1596111338000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Iron Deposits in Periaqueductal Gray Matter Are Associated with Poor Response to OnabotulinumtoxinA in Chronic Migraine"],"prefix":"10.3390","volume":"12","author":[{"given":"Clara","family":"Dom\u00ednguez Vivero","sequence":"first","affiliation":[{"name":"Department of Neurology, Headache Unit, Hospital Clinico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yago","family":"Leira","sequence":"additional","affiliation":[{"name":"UCL Eastman Dental Institute and NIHR UCLH Biomedical Research Centre, University College London, London WC1E 6BT, UK"},{"name":"Medical-Surgical Dentistry (OMEQUI) Research Group, Health Research Institute of Santiago de Compostela, 15704 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Saavedra Pi\u00f1eiro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Headache Unit, Hospital Clinico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiana","family":"Rodr\u00edguez-Osorio","sequence":"additional","affiliation":[{"name":"Department of Neurology, Headache Unit, Hospital Clinico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0368-7031","authenticated-orcid":false,"given":"Pedro","family":"Ramos-Cabrer","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Imaging, Molecular Imaging Unit, CIC biomaGUNE, 20018 Donostia-San Sebastian, Spain"},{"name":"Ikerbasque, The Basque Foundation for Science, 48013 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Villalba Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital Cl\u00ednico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-8690","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Sobrino","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1039","authenticated-orcid":false,"given":"Francisco","family":"Campos","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Castillo","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Leira","sequence":"additional","affiliation":[{"name":"Department of Neurology, Headache Unit, Hospital Clinico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/00004647-199902000-00001","article-title":"The trigeminovascular system in humans: Pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation","volume":"19","author":"May","year":"1999","journal-title":"J. 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