{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:29:19Z","timestamp":1788848959108,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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":"crossref","award":["PI24\/01254"],"award-info":[{"award-number":["PI24\/01254"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Occipital nerve stimulation (ONS) is an effective therapy for patients with refractory chronic cluster headache (rCCH); however, it is not without complications, and to date, there are no conclusive findings regarding factors that would allow the prediction of treatment response. The primary objective of this study is to identify such factors to improve patient selection. Methods: This single-center prospective observational study will be conducted at the Department of Neurology, Hospital Universitario La Paz (Madrid, Spain). Given the low prevalence of rCCH, a convenience sampling approach will be adopted, with an expected enrollment of a minimum of 15 patients over 24 months of the study. The study is structured into three periods: Pre-ONS (pre-implantation), ONS (implantation), and Post-ONS (follow-up at 12 months). During the pre-implantation phase, patients will undergo a multidimensional assessment encompassing structural 3T brain magnetic resonance imaging (MRI), blood analysis (calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating peptide 38 (PACAP38), and vasoactive intestinal peptide (VIP)), neuropsychological evaluation, auditory evoked potentials, algometry (pressure pain threshold, temporal summation, conditioned pain modulation), and transcutaneous electrical nerve stimulation (TENS). Follow-up visits will be conducted at 3, 6, and 12 months post-implantation. Results: This study aims to identify biomarkers or their combinations capable of reliably predicting patients who would benefit from ONS. Conclusions: Through this multidimensional assessment, this study seeks to identify predictive factors of response to ONS, thereby improving patient selection, optimizing healthcare resources, and advancing the understanding of treatment response mechanisms.<\/jats:p>","DOI":"10.3390\/brainsci16030256","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T13:37:37Z","timestamp":1772026657000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictors of Response to Occipital Nerve Stimulation in Patients with Refractory Chronic Cluster Headache: Protocol for a Prospective Observational Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Leonardo","family":"Portocarrero-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0115-088X","authenticated-orcid":false,"given":"Alfonso","family":"Gil-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"CranioSPain Research Group, Centro Superior de Estudios Universitarios La Salle, Universidad Aut\u00f3noma de Madrid, 28023 Madrid, Spain"},{"name":"Departamento de Fisioterapia, Centro Superior de Estudios Universitarios La Salle, Universidad Aut\u00f3noma de Madrid, 28023 Madrid, Spain"},{"name":"Departamento de Fisioterapia, Hospital Universitario La Paz-Carlos III, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-3171","authenticated-orcid":false,"given":"Jos\u00e9 Francisco","family":"Paz-Sol\u00eds","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Rom\u00e1n-Arag\u00f3n","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Mansilla-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Elizagaray-Garc\u00eda","sequence":"additional","affiliation":[{"name":"CranioSPain Research Group, Centro Superior de Estudios Universitarios La Salle, Universidad Aut\u00f3noma de Madrid, 28023 Madrid, Spain"},{"name":"Departamento de Fisioterapia, Centro Superior de Estudios Universitarios La Salle, Universidad Aut\u00f3noma de Madrid, 28023 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Rizea","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00fal","family":"Mar\u00edn-Esteban","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-8328","authenticated-orcid":false,"given":"Cristina","family":"Utrilla","sequence":"additional","affiliation":[{"name":"Radiology Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia Mar\u00eda","family":"de-Toro-Ca\u00f1izares","sequence":"additional","affiliation":[{"name":"CranioSPain Research Group, Centro Superior de Estudios Universitarios La Salle, Universidad 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-6269","authenticated-orcid":false,"given":"Javier","family":"D\u00edaz-de-Ter\u00e1n","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, Spain"},{"name":"Hospital La Paz Institute for Health Research\u2014IdiPAZ (La Paz University Hospital\u2014Universidad Aut\u00f3noma de Madrid), 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2018). 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