{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:20:25Z","timestamp":1791930025784,"version":"4.3.4"},"reference-count":88,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Portuguese Foundation for Science and Technology","award":["FCT-2024.01355.BD"],"award-info":[{"award-number":["FCT-2024.01355.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Background\/Objectives: Pediatric multiple sclerosis (MS) is a rare and complex neuroinflammatory disease characterized by demyelination and neurological dysfunction in individuals under 18 years of age. This systematic review and activation likelihood estimation (ALE) meta-analysis aimed to synthesize the existing literature on functional and structural brain alterations in pediatric MS patients. Methods: Following the PRISMA guidelines, we analyzed 21 studies involving 917 pediatric MS patients and 320 healthy controls, assessing brain structure and function using MRI and fMRI techniques. Results: The results reveal consistent alterations in brain regions critical for cognitive and motor functions, including reduced brain volume, increased lesion load, and disrupted functional connectivity, particularly in the thalamus, cerebellum, and hippocampus. The ALE meta-analysis identified significant activation clusters in the dorsal anterior cingulate cortex, angular gyrus, and superior parietal lobes, regions associated with cognition, attention, and working memory. Conclusions: These findings suggest that pediatric MS uniquely affects brain development, contributing to cognitive impairments that differ from those observed in adult MS. Our study underscores the importance of early diagnosis and tailored therapeutic interventions to mitigate neurodevelopmental disruptions and improve long-term outcomes in pediatric MS patients.<\/jats:p>","DOI":"10.3390\/pediatric17030057","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T09:26:48Z","timestamp":1747128408000},"page":"57","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional and Structural Alterations in Pediatric Multiple Sclerosis: A Systematic Review and a Preliminary Activation Likelihood Estimation Functional Magnetic Resonance Imaging Meta-Analysis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2702-8789","authenticated-orcid":false,"given":"Nicoletta","family":"Cera","sequence":"first","affiliation":[{"name":"Faculty of Psychology and Education Sciences, University of Porto, 4200-135 Porto, Portugal"},{"name":"Cross I&D Lisbon Research Center, Escola Superior de Sa\u00fade da Cruz Vermelha Portuguesa, 1300-125 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7659-686X","authenticated-orcid":false,"given":"Joana","family":"Pinto","sequence":"additional","affiliation":[{"name":"Faculty of Psychology and Education Sciences, University of Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Faustino","sequence":"additional","affiliation":[{"name":"Cross I&D Lisbon Research Center, Escola Superior de Sa\u00fade da Cruz Vermelha Portuguesa, 1300-125 Lisbon, Portugal"},{"name":"Institute of Biophysics and Biomedical Engineering, Faculty of Science, University of Lisbon, 1749-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S1474-4422(14)70093-6","article-title":"Multiple sclerosis in children: An update on clinical diagnosis, therapeutic strategies, and research","volume":"13","author":"Waldman","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2217\/nmt-2016-0046","article-title":"Pediatric multiple sclerosis: Updates in epidemiology, clinical features and management","volume":"6","author":"Narula","year":"2016","journal-title":"Neurodegener Dis. 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