{"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":1788848959693,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Research Institute IdiPAZ\u2014Instituto de Investigaci\u00f3n Sanitaria del Hospital Universitario La Paz, Madrid, Spain"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Cluster headache (CH) is a debilitating primary headache disorder characterized by severe unilateral pain attacks. Chronic CH (CCH) poses significant treatment challenges, especially in refractory cases. Neuromodulation, including repetitive transcranial magnetic stimulation (rTMS), offers a potential alternative; however, evidence for its efficacy in CCH is lacking. Methods: A randomized, double-blind, placebo-controlled, crossover pilot study was conducted. Eligibility criteria included patients with refractory CCH (rCCH), who were then randomized to receive two treatment sequences: A, rTMS followed by sham stimulation, or B, sham followed by rTMS, separated by a one-month washout, with a follow-up period of 3 months. The primary endpoint was to analyze efficacy by assessing the change in the number of attacks per week (APW). Secondary endpoints included treatment tolerability and changes in intensity, duration, and use of rescue medication. The trial was registered with ClinicalTrials.gov (NCT06917144). Results: Eight patients were enrolled and randomized with a 50% probability of assignment to either treatment arm. Despite this, five patients were allocated to sequence A and three to sequence B. Three patients completed the entire study; five received treatment with rTMS and six with sham. The APW change during rTMS showed a change of (mean \u00b1 SD) +2.2 (10.8) attacks per week (p = 0.672). Two patients achieved complete remission during the rTMS phase, though symptoms returned by the washout period. In comparison with sham, the difference was also not statistically significant. No significant changes were observed in secondary endpoints. Side effects (two cases) were mild and transient. Conclusions: This pilot study suggests that rTMS may provide clinical benefits for rCCH in selected cases, though its effects seem transient. Adherence to treatment remains a critical challenge.<\/jats:p>","DOI":"10.3390\/brainsci15060554","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:16:03Z","timestamp":1747980963000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluating Repetitive Transcranial Magnetic Stimulation for Refractory Chronic Cluster Headache Prevention: Insights from a Randomized Crossover Pilot Trial"],"prefix":"10.3390","volume":"15","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"}]},{"given":"Cristian","family":"Rizea","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Exuperio","family":"D\u00edez-Tejedor","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, Spain"},{"name":"Hospital La Paz Institute for Health Research, IdiPAZ, La Paz University Hospital, Universidad Aut\u00f3noma de Madrid, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1766-4183","authenticated-orcid":false,"given":"Mois\u00e9s","family":"Le\u00f3n-Ruiz","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital La Paz, 28046 Madrid, 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, IdiPAZ, La Paz University Hospital, Universidad Aut\u00f3noma de Madrid, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition","volume":"38","author":"Olesen","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10072-024-07708-0","article-title":"Profile of refractory chronic cluster headache","volume":"46","author":"Membrilla","year":"2025","journal-title":"Neurol. 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