{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:02:12Z","timestamp":1793314932201,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study sought to determine if individuals with medically refractory migraine headache have volume or diffusion abnormalities on neuroimaging compared to neurotypical individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>Neuroimaging biomarkers in headache medicine continue to be limited. Early prediction of medically refractory headache and migraine disorders could result in earlier administration of high efficacy therapeutics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single-center, retrospective, case control study was performed. All patients were evaluated clinically between 2014 and 2018. Individuals with medically refractory migraine headache (defined by ICDH-3 criteria) without any other chronic medical diseases were enrolled. Patients had to have failed more than two therapeutics and aura was not exclusionary. The initial MRI study for each patient was reviewed. Multiple brain regions were analyzed for volume and apparent diffusion coefficient values. These were compared to 81 neurotypical control patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 79 patients with medically refractory migraine headache were included and compared to 74 neurotypical controls without headache disorders. Time between clinical diagnosis and neuroimaging was a median of 24 months (IQR: 12.0\u201337.0). Comparison of individuals with medically refractory migraine headache to controls revealed statistically significant differences in median apparent diffusion coefficient (ADC) in multiple brain subregions (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). <jats:italic>Post-hoc<\/jats:italic> pair-wise analysis comparing individuals with medically refractory migraine headache to control patients revealed significantly decreased median ADC values for the thalamus, caudate, putamen, pallidum, amygdala, brainstem, and cerebral white matter. No volumetric differences were observed between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In individuals with medically refractory MH, ADC changes are measurable in multiple brain structures at an early age, prior to the failure of multiple pharmacologic interventions and the diagnosis of medically refractory MH. This data supports the hypothesis that structural connectivity issues may predispose some patients toward more medically refractory pain disorders such as MH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.898219","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T05:58:54Z","timestamp":1655186334000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Early Onset Diffusion Abnormalities in Refractory Headache Disorders"],"prefix":"10.3389","volume":"13","author":[{"given":"Jonathan D.","family":"Santoro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K.","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily S.","family":"McKenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"MacEachern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils D.","family":"Forkert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen W.","family":"Yeom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1177\/0333102413485658","volume":"33","year":"2013","journal-title":"Cephalalgia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s11916-013-0341-z","article-title":"Epidemiology of migraine and headache in children and adolescents","volume":"17","author":"W\u00f6ber-Bing\u00f6l","year":"2013","journal-title":"Curr Pain Headache Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/dmcn.14338","article-title":"Episodic and chronic migraine in children","volume":"62","author":"Youssef","year":"2020","journal-title":"Dev Med Child Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","volume":"18","year":"2019","journal-title":"Lancet Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/head.13281","article-title":"The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies","volume":"58","author":"Burch","year":"2018","journal-title":"Headache"},{"key":"B6","doi-asserted-by":"publisher","first-page":"935","DOI":"10.3174\/ajnr.A5582","article-title":"Brain diffusion abnormalities in children with tension-type and migraine-type headaches","volume":"39","author":"Santoro","year":"2018","journal-title":"AJNR Am J Neuroradiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s10194-019-1071-3","article-title":"White matter changes in chronic and episodic migraine: a diffusion tensor imaging study","volume":"21","author":"Planchuelo-G\u00f3mez","year":"2020","journal-title":"J Headache Pain"},{"key":"B8","doi-asserted-by":"publisher","first-page":"711","DOI":"10.3390\/brainsci10100711","article-title":"Alternative microstructural measures to complement diffusion tensor imaging in migraine studies with standard MRI acquisition","volume":"10","author":"Planchuelo-G\u00f3mez","year":"2020","journal-title":"Brain Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s00062-013-0203-4","article-title":"Diagnostics to look beyond the normal appearing brain tissue (NABT)? 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