{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T04:01:18Z","timestamp":1793073678117,"version":"4.5.0"},"reference-count":122,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Magnetic resonance imaging (MRI) is often used to evaluate disease-related brain changes in patients with aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To use a meta-analysis for assessment of quantitative volumetric brain and spinal cord changes in patients with AQP4-IgG+ NMOSD and healthy participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>We analyzed volume estimates of the brain, gray matter, white matter, thalamus, T2\/FLAIR-brain lesions, as well as mean upper cervical cord area (MUCCA). Inclusion criteria included patients with AQP4-IgG+ NMOSD, MRI-based segmentation data, and matched healthy participants. Data from NMOSD patients with mixed\/unknown serostatus or significant comorbidities were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources:<\/jats:title>\n                    <jats:p>We searched MEDLINE through Pubmed for peer-reviewed articles published between 05\/2006 (revised NMOSD diagnostic criteria) and 01\/2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Standardized mean differences and pooled effect sizes (Hedges\u2019\n                      <jats:italic toggle=\"yes\">g<\/jats:italic>\n                      ) were determined with random-effects models, adjusting for duplicate reporting, outliers, and small study effects. Metaregressions were used to determine clinical associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Evidence of pooled data showed that whole brain volume (\n                      <jats:italic toggle=\"yes\">g<\/jats:italic>\n                      \u2009=\u2009\u22120.61, 95% confidence interval (CI): \u22120.91 to \u22120.32,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001,\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <jats:sub>pat\/con<\/jats:sub>\n                      \u2009=\u2009385\/325,\n                      <jats:italic toggle=\"yes\">k<\/jats:italic>\n                      \u2009=\u200911) and gray matter volume (\n                      <jats:italic toggle=\"yes\">g<\/jats:italic>\n                      \u2009=\u2009\u22120.40, 95% CI: \u22120.72 to \u22120.09,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.018,\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <jats:sub>pat\/con<\/jats:sub>\n                      \u2009=\u2009259\/267,\n                      <jats:italic toggle=\"yes\">k<\/jats:italic>\n                      \u2009=\u20099) were significantly different between patients and healthy participants. Heterogeneity was moderate (\u03c4\u00b2\u2009=\u20090.08 and \u03c4\u00b2\u2009=\u20090.09, respectively). Moreover, we found a large effect for reduced MUCCA (\n                      <jats:italic toggle=\"yes\">g<\/jats:italic>\n                      \u2009=\u2009\u22120.99, 95% CI: \u22121.59 to \u22120.39,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.007,\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <jats:sub>pat\/con<\/jats:sub>\n                      \u2009=\u2009189\/162,\n                      <jats:italic toggle=\"yes\">k<\/jats:italic>\n                      \u2009=\u20097) with moderate heterogeneity (\u03c4\u00b2\u2009=\u20090.31). No conclusive evidence emerged for changes in thalamic or white matter volume. Bias analysis did not indicate that smaller studies affected effect sizes. A systematic review of voxel-based morphometry revealed that reduced gray matter volume was most likely in the bilateral thalamus (\u2a7d69%) and occipital (44%), frontal (27%), and temporal cortices (27%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>AQP4-IgG+ NMOSD patients have specific global and local central nervous system volume reductions, potentially induced by astrocytic damage and demyelination. Volumetric outcomes may therefore inform MRI-guided disease monitoring and endpoints in clinical studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>PROSPERO (CRD42024493121). This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562864251394843","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T11:04:20Z","timestamp":1765019060000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Brain volumetry and spinal cord imaging in patients with AQP4-IgG+ NMOSD\u2014a systematic review and meta-analysis"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-6650","authenticated-orcid":false,"given":"Josephine","family":"Heine","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, Berlin 10117, Germany"},{"name":"Experimental and Clinical Research Center, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-9513","authenticated-orcid":false,"given":"Claudia","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"Experimental and Clinical Research Center, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"Neuroscience Clinical Research Center, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0214-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.7.964"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23721"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1116-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl371"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.103118"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31826e9a96"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211018987"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.233099"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/jon.13137"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/17562864211014389"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001367"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12827-x"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26951"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000216139.44259.74"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1040"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.02.046"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-11910-z"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s42451-018-0051-1"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000504"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-5-13"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/0962280219889080"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/ebmental-2019-300117"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i03"},{"key":"e_1_3_4_29_2","unstructured":"Harrer M Cuijpers P Furukawa T et al. dmetar: companion R Package for the guide \u2018Doing meta-analysis in R\u2019. 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