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Migraine headache and concomitant symptoms might be just coincidental or due to inflammatory MS activity, which is highly relevant for patients. Headache in general has been shown to be attributed to inflammatory cerebral MS lesions in the central pain matrix. The question whether migraine headache is associated with a different lesion pattern and non-painful migraine symptoms are associated with specific brain lesions sites needs further clarification. This study aimed to assess the presence of specific lesion clusters in patients with MS and comorbid migraine via voxel-based lesion symptom mapping (VLSM). Patients with multiple sclerosis and headache were prospectively identified and included in a university neurological center. As a subgroup study, patients with migraine were identified. Demographic and clinical data were assessed, and lesion volumes calculated. Cerebral lesion sites were correlated voxel-wise with presence and absence of headache using non-parametric permutation tests. A cohort of multiple sclerosis patients served as controls for the VLSM-analysis. 22 multiple sclerosis patients with migraines were included, as well as 92 controls without headache. Clinical characteristics did not differ in both groups. The VLSM-analysis showed associations between migraine and lesion clusters in the left hippocampus and bilateral thalamus. Visual aura was associated with posterior brain lesions, whilst vertigo was related to cerebellar lesions. In patients with sensory disturbances, lesions in the bilateral basal ganglia were found. MS lesions in the left hippocampus and bilateral thalamus were associated with migraine in multiple sclerosis patients. The lesion pattern indicates that migraine in MS may be facilitated by lesions in the CNS pain processing network, hypothetically through disinhibition. Visual aura in migraineurs with MS was associated with posterior, vertigo with cerebellar lesions and sensory disturbances with lesions in the basal ganglia. Hence, our data indicates that different concomitant non-painful migraine symptoms are associated with lesion sites in the related brain regions of cerebral control of the respective neurological functions. Whether MS lesions might alter brain excitability and facilitate cortical spreading depression in migraine aura remains speculative.<\/jats:p>","DOI":"10.1007\/s10548-026-01182-x","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T06:24:58Z","timestamp":1772605498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Migraine is Related to Multiple Sclerosis Brain Lesions in the Central Pain Network with Several Migraine Phenotypes Exhibiting Different Lesion Patterns"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-4044","authenticated-orcid":false,"given":"Kilian","family":"Fr\u00f6hlich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosmas","family":"Macha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Kr\u00e4mer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Haupenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Sekita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnd","family":"D\u00f6rfler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klemens","family":"Winder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Mrochen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"issue":"5","key":"1182_CR1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10194-010-0237-9","volume":"11","author":"I Kister","year":"2010","unstructured":"Kister I, Caminero AB, Monteith TS, Soliman A, Bacon TE, Bacon JH, Kalina JT, Inglese M, Herbert J, Lipton RB (2010) Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course. 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