{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T08:14:05Z","timestamp":1783498445853,"version":"3.55.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007458","name":"Deutschen Multiple Sklerose Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006254","name":"Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006254","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clinical\u2013neurological examination may underestimate internuclear ophthalmoplegia (INO). We investigated immersive virtual reality (VR)-based eye-tracking in patients with multiple sclerosis (MS), other neurological disorders (ND), and healthy controls (HC) to detect INO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective monocentric study, 471 participants (243 MS, 104 ND, 124 HC) underwent horizontal prosaccade testing (\u00b1\u200910\u00b0,\u2009\u00b1\u200920\u00b0) using VR-based oculography. INO was determined in a blinded manner based on software-generated reports comparing adduction and abduction velocities. VR-based and clinical assessments were compared using Cohen\u2019s kappa (\u03ba). Associations with demographic and clinical variables were analyzed using logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      VR-based assessment identified 43 cases of INO (40 ND, 3 HC). Agreement between VR-based and clinical assessment was moderate (\n                      <jats:italic>\u03ba<\/jats:italic>\n                      \u2009=\u20090.42; 92.5% observer agreement;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009414). Three cases were identified clinically only, whereas 28 were detected by VR-based assessment only.\n                    <\/jats:p>\n                    <jats:p>\n                      Within MS, agreement was similar (\n                      <jats:italic>\u03ba<\/jats:italic>\n                      \u2009=\u20090.45; 89.1% agreement;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009238), with 23 cases detected by VR only and three clinically only. In MS, VR-based INO was associated with male sex (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035), higher expanded disability status scale (EDSS) and brainstem functional system scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), longer disease duration and older age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), and visual complaints (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007). In multivariable analysis, disease duration (OR 1.12, 95% CI 1.01\u20131.24), brainstem involvement (OR 21.59, 1.30\u2013358.07), and clinical INO (OR 8.18, 1.43\u201346.96) were associated with VR-based INO.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>VR-based eye-tracking showed moderate agreement with clinical assessment and identified additional cases of INO associated with markers of disease burden. These findings support further evaluation of VR-derived measures as complementary digital biomarkers of brainstem dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13906-x","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:50:16Z","timestamp":1780735816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virtual reality-based oculography detects internuclear ophthalmoplegia in multiple sclerosis and other neurological disorders"],"prefix":"10.1007","volume":"273","author":[{"given":"Emilie","family":"Reuter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Luerweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Katsimpoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Haselon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bratek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zacaria","family":"Assfoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Schuetrumpf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Klimas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Jessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Saft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Ayzenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lena","family":"Fisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Pitarokoili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Schneider-Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremias","family":"Motte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-299X","authenticated-orcid":false,"given":"Anke","family":"Salmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"13906_CR1","doi-asserted-by":"publisher","first-page":"e2299","DOI":"10.1212\/WNL.0000000000007499","volume":"92","author":"JA Nij Bijvank","year":"2019","unstructured":"Nij Bijvank JA, van Rijn LJ, Balk LJ et al (2019) Diagnosing and quantifying a common deficit in multiple sclerosis: internuclear ophthalmoplegia. Neurology 92:e2299\u2013e2308. https:\/\/doi.org\/10.1212\/WNL.0000000000007499","journal-title":"Neurology"},{"key":"13906_CR2","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1007\/s00415-008-0819-5","volume":"255","author":"M Jozefowicz-Korczynska","year":"2008","unstructured":"Jozefowicz-Korczynska M, Lukomski M, Pajor A (2008) Identification of internuclear ophthalmoplegia signs in multiple sclerosis patients. Saccade test analysis. J Neurol 255:1006\u20131011. https:\/\/doi.org\/10.1007\/s00415-008-0819-5","journal-title":"J Neurol"},{"key":"13906_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103824","volume":"63","author":"SN Hof","year":"2022","unstructured":"Hof SN, Loonstra FC, de Ruiter LRJ et al (2022) The prevalence of internuclear ophthalmoparesis in a population-based cohort of individuals with multiple sclerosis. Mult Scler Relat Disord 63:103824. https:\/\/doi.org\/10.1016\/j.msard.2022.103824","journal-title":"Mult Scler Relat Disord"},{"key":"13906_CR4","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1097\/WNO.0000000000002116","volume":"44","author":"JA Kraker","year":"2024","unstructured":"Kraker JA, Xu SC, Flanagan EP et al (2024) Ocular manifestations of Multiple Sclerosis: a population-based study. J Neuroophthalmol 44:157\u2013161. https:\/\/doi.org\/10.1097\/WNO.0000000000002116","journal-title":"J Neuroophthalmol"},{"key":"13906_CR5","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1097\/WNO.0000000000000507","volume":"37","author":"E Nerrant","year":"2017","unstructured":"Nerrant E, Tilikete C (2017) Ocular motor manifestations of Multiple Sclerosis. J Neuroophthalmol 37:332\u2013340. https:\/\/doi.org\/10.1097\/WNO.0000000000000507","journal-title":"J Neuroophthalmol"},{"key":"13906_CR6","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1007\/s00415-022-11428-w","volume":"270","author":"R Omary","year":"2023","unstructured":"Omary R, Bockisch CJ, de Vere-Tyndall A et al (2023) Lesion follows function: video-oculography compared with MRI to diagnose internuclear ophthalmoplegia in patients with multiple sclerosis. J Neurol 270:917\u2013924. https:\/\/doi.org\/10.1007\/s00415-022-11428-w","journal-title":"J Neurol"},{"key":"13906_CR7","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1007\/s00415-017-8607-8","volume":"264","author":"ST Aw","year":"2017","unstructured":"Aw ST, Chen L, Todd MJ et al (2017) Vestibulo-ocular reflex deficits with medial longitudinal fasciculus lesions. J Neurol 264:2119\u20132129. https:\/\/doi.org\/10.1007\/s00415-017-8607-8","journal-title":"J Neurol"},{"key":"13906_CR8","doi-asserted-by":"publisher","first-page":"3533","DOI":"10.1007\/s10072-022-05967-3","volume":"43","author":"S-H Lee","year":"2022","unstructured":"Lee S-H, Kim J-M, Kim J-S (2022) Update on the medial longitudinal fasciculus syndrome. Neurol Sci 43:3533\u20133540. https:\/\/doi.org\/10.1007\/s10072-022-05967-3","journal-title":"Neurol Sci"},{"key":"13906_CR9","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1111\/jon.12847","volume":"31","author":"MT Kleinsorge","year":"2021","unstructured":"Kleinsorge MT, Ebert A, F\u00f6rster A et al (2021) MRI topography of lesions related to internuclear ophthalmoplegia in patients with multiple sclerosis or ischemic stroke. J Neuroimaging 31:471\u2013474. https:\/\/doi.org\/10.1111\/jon.12847","journal-title":"J Neuroimaging"},{"key":"13906_CR10","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1600-0404.2004.00278.x","volume":"110","author":"I Bola\u00f1os","year":"2004","unstructured":"Bola\u00f1os I, Lozano D, Cant\u00fa C (2004) Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients. Acta Neurol Scand 110:161\u2013165. https:\/\/doi.org\/10.1111\/j.1600-0404.2004.00278.x","journal-title":"Acta Neurol Scand"},{"key":"13906_CR11","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1212\/01.wnl.0000123093.37069.6d","volume":"62","author":"JS Kim","year":"2004","unstructured":"Kim JS (2004) Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction. Neurology 62:1491\u20131496. https:\/\/doi.org\/10.1212\/01.wnl.0000123093.37069.6d","journal-title":"Neurology"},{"key":"13906_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1097\/WNO.0000000000001534","volume":"42","author":"MM Hamza","year":"2022","unstructured":"Hamza MM, Alas BF, Huang C et al (2022) Internuclear ophthalmoplegia characterizes multiple sclerosis rather than neuromyelitis optica spectrum disease. J Neuroophthalmol 42:239\u2013245. https:\/\/doi.org\/10.1097\/WNO.0000000000001534","journal-title":"J Neuroophthalmol"},{"key":"13906_CR13","doi-asserted-by":"publisher","first-page":"e281","DOI":"10.1097\/WNO.0000000000001262","volume":"42","author":"LG Manrique","year":"2022","unstructured":"Manrique LG, Zhang X, Kathryn L et al (2022) Mild bilateral internuclear ophthalmoplegia: the diagnostic role of the vertical posterior canal vestibulo-ocular reflex in acute brainstem demyelination, a clinical-radiologic correlation. J Neuroophthalmol 42:e281\u2013e288. https:\/\/doi.org\/10.1097\/WNO.0000000000001262","journal-title":"J Neuroophthalmol"},{"key":"13906_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/frvir.2025.1502679","author":"A Coito","year":"2025","unstructured":"Coito A, Naidu A, Lehmann J et al (2025) Test-retest reliability of gaze precision of a novel virtual reality-based medical device. Front Virtual Real. https:\/\/doi.org\/10.3389\/frvir.2025.1502679","journal-title":"Front Virtual Real"},{"key":"13906_CR15","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1212\/wnl.33.11.1444","volume":"33","author":"JF Kurtzke","year":"1983","unstructured":"Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444\u20131452. https:\/\/doi.org\/10.1212\/wnl.33.11.1444","journal-title":"Neurology"},{"key":"13906_CR16","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","volume":"17","author":"AJ Thompson","year":"2018","unstructured":"Thompson AJ, Banwell BL, Barkhof F et al (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17:162\u2013173. https:\/\/doi.org\/10.1016\/S1474-4422(17)30470-2","journal-title":"Lancet Neurol"},{"key":"13906_CR17","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/S1474-4422(22)00431-8","volume":"22","author":"B Banwell","year":"2023","unstructured":"Banwell B, Bennett JL, Marignier R et al (2023) Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: international MOGAD Panel proposed criteria. Lancet Neurol 22:268\u2013282. https:\/\/doi.org\/10.1016\/S1474-4422(22)00431-8","journal-title":"Lancet Neurol"},{"key":"13906_CR18","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","volume":"85","author":"DM Wingerchuk","year":"2015","unstructured":"Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177\u2013189. https:\/\/doi.org\/10.1212\/WNL.0000000000001729","journal-title":"Neurology"},{"key":"13906_CR19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/0025-5564(75)90075-9","volume":"24","author":"A Bahill","year":"1975","unstructured":"Bahill A, Clark MR, Stark L (1975) The main sequence, a tool for studying human eye movements. Math Biosci 24:191\u2013204. https:\/\/doi.org\/10.1016\/0025-5564(75)90075-9","journal-title":"Math Biosci"},{"key":"13906_CR20","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1212\/01.wnl.0000085863.54218.72","volume":"61","author":"TC Frohman","year":"2003","unstructured":"Frohman TC, Frohman EM, O\u2019Suilleabhain P et al (2003) Accuracy of clinical detection of INO in MS: corroboration with quantitative infrared oculography. Neurology 61:848\u2013850. https:\/\/doi.org\/10.1212\/01.wnl.0000085863.54218.72","journal-title":"Neurology"},{"key":"13906_CR21","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1111\/ene.14723","volume":"28","author":"JA Nij Bijvank","year":"2021","unstructured":"Nij Bijvank JA, S\u00e1nchez Aliaga E, Balk LJ et al (2021) A model for interrogating the clinico-radiological paradox in multiple sclerosis: internuclear ophthalmoplegia. Eur J Neurol 28:1617\u20131626. https:\/\/doi.org\/10.1111\/ene.14723","journal-title":"Eur J Neurol"},{"key":"13906_CR22","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1111\/j.1749-6632.2011.06156.x","volume":"1233","author":"K Sakaie","year":"2011","unstructured":"Sakaie K, Takahashi M, Dimitrov I et al (2011) Diffusion tensor imaging the medial longitudinal fasciculus in INO: opportunities and challenges. Ann N Y Acad Sci 1233:307\u2013312. https:\/\/doi.org\/10.1111\/j.1749-6632.2011.06156.x","journal-title":"Ann N Y Acad Sci"},{"key":"13906_CR23","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1007\/s00415-007-0591-y","volume":"254","author":"S Khanna","year":"2007","unstructured":"Khanna S, Liao K, Kaminski HJ et al (2007) Ocular myasthenia revisited: insights from pseudo-internuclear ophthalmoplegia. J Neurol 254:1569\u20131574. https:\/\/doi.org\/10.1007\/s00415-007-0591-y","journal-title":"J Neurol"},{"key":"13906_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31577-1","volume":"8","author":"R Zargari Marandi","year":"2018","unstructured":"Zargari Marandi R, Madeleine P, Omland \u00d8 et al (2018) Eye movement characteristics reflected fatigue development in both young and elderly individuals. Sci Rep 8:13148. https:\/\/doi.org\/10.1038\/s41598-018-31577-1","journal-title":"Sci Rep"},{"key":"13906_CR25","doi-asserted-by":"publisher","DOI":"10.16910\/jemr.13.4.6","author":"WH Zangemeister","year":"2020","unstructured":"Zangemeister WH, Heesen C, R\u00f6hr D et al (2020) Oculomotor fatigue and neuropsychological assessments mirror multiple sclerosis fatigue. J Eye Mov Res. https:\/\/doi.org\/10.16910\/jemr.13.4.6","journal-title":"J Eye Mov Res"},{"key":"13906_CR26","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1001\/jamaneurol.2024.1123","volume":"81","author":"S-U Lee","year":"2024","unstructured":"Lee S-U, Kim H-J, Choi J-Y et al (2024) Expanding clinical spectrum of Anti-GQ1b Antibody Syndrome: a review. JAMA Neurol 81:762\u2013770. https:\/\/doi.org\/10.1001\/jamaneurol.2024.1123","journal-title":"JAMA Neurol"},{"key":"13906_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.605902","volume":"11","author":"A Evoli","year":"2020","unstructured":"Evoli A, Iorio R (2020) Controversies in ocular myasthenia gravis. Front Neurol 11:605902. https:\/\/doi.org\/10.3389\/fneur.2020.605902","journal-title":"Front Neurol"},{"key":"13906_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193866","volume":"13","author":"JY Winder","year":"2018","unstructured":"Winder JY, Roos RAC (2018) Premanifest Huntington\u2019s disease: examination of oculomotor abnormalities in clinical practice. PLoS One 13:e0193866. https:\/\/doi.org\/10.1371\/journal.pone.0193866","journal-title":"PLoS One"},{"key":"13906_CR29","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1212\/01.wnl.0000227890.87398.c1","volume":"67","author":"T Blekher","year":"2006","unstructured":"Blekher T, Johnson SA, Marshall J et al (2006) Saccades in presymptomatic and early stages of Huntington disease. Neurology 67:394\u2013399. https:\/\/doi.org\/10.1212\/01.wnl.0000227890.87398.c1","journal-title":"Neurology"},{"key":"13906_CR30","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1136\/bjophthalmol-2020-317267","volume":"105","author":"AR Vosoughi","year":"2021","unstructured":"Vosoughi AR, Ling J, Tam KT et al (2021) Ophthalmic manifestations of myelin oligodendrocyte glycoprotein-IgG-associated disorder other than optic neuritis: a systematic review. Br J Ophthalmol 105:1591\u20131598. https:\/\/doi.org\/10.1136\/bjophthalmol-2020-317267","journal-title":"Br J Ophthalmol"},{"key":"13906_CR31","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1001\/jamaneurol.2023.1135","volume":"80","author":"M Hittle","year":"2023","unstructured":"Hittle M, Culpepper WJ, Langer-Gould A et al (2023) Population-based estimates for the prevalence of multiple sclerosis in the United States by race, ethnicity, age, sex, and geographic region. JAMA Neurol 80:693\u2013701. https:\/\/doi.org\/10.1001\/jamaneurol.2023.1135","journal-title":"JAMA Neurol"},{"key":"13906_CR32","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1177\/1352458514528762","volume":"20","author":"T Kalincik","year":"2014","unstructured":"Kalincik T, Buzzard K, Jokubaitis V et al (2014) Risk of relapse phenotype recurrence in multiple sclerosis. Mult Scler 20:1511\u20131522. https:\/\/doi.org\/10.1177\/1352458514528762","journal-title":"Mult Scler"},{"key":"13906_CR33","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1136\/jnnp-2022-328994","volume":"93","author":"M Magyari","year":"2022","unstructured":"Magyari M, Koch-Henriksen N (2022) Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 93:716\u2013722. https:\/\/doi.org\/10.1136\/jnnp-2022-328994","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"13906_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.836337","volume":"13","author":"Q Ji","year":"2022","unstructured":"Ji Q, Dong H, Lee H et al (2022) Clinical characteristics and outcomes of multiple sclerosis and neuromyelitis optica spectrum disorder with brainstem lesions as heralding prodrome. Front Neurol 13:836337. https:\/\/doi.org\/10.3389\/fneur.2022.836337","journal-title":"Front Neurol"},{"key":"13906_CR35","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/ana.26843","volume":"95","author":"S Knowles","year":"2024","unstructured":"Knowles S, Middleton R, Cooze B et al (2024) Comparing the pathology, clinical, and demographic characteristics of younger and older-onset multiple sclerosis. Ann Neurol 95:471\u2013486. https:\/\/doi.org\/10.1002\/ana.26843","journal-title":"Ann Neurol"},{"key":"13906_CR36","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.3062","author":"H Le Hua","year":"2024","unstructured":"Le Hua H, Solomon AJ, Tenembaum S et al (2024) Differential diagnosis of suspected multiple sclerosis in pediatric and late-onset populations: a review. JAMA Neurol. https:\/\/doi.org\/10.1001\/jamaneurol.2024.3062","journal-title":"JAMA Neurol"},{"key":"13906_CR37","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/S1474-4422(22)00184-3","volume":"22","author":"JS Graves","year":"2023","unstructured":"Graves JS, Krysko KM, Le Hua H et al (2023) Ageing and multiple sclerosis. Lancet Neurol 22:66\u201377. https:\/\/doi.org\/10.1016\/S1474-4422(22)00184-3","journal-title":"Lancet Neurol"},{"key":"13906_CR38","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1007\/s00221-021-06283-6","volume":"240","author":"O Rock","year":"2022","unstructured":"Rock O, Albonico A, Javadian F et al (2022) Oblique saccades in internuclear ophthalmoplegia. Exp Brain Res 240:861\u2013869. https:\/\/doi.org\/10.1007\/s00221-021-06283-6","journal-title":"Exp Brain Res"},{"key":"13906_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/frvir.2025.1595694","author":"E Reuter","year":"2025","unstructured":"Reuter E, Luerweg J, Schneider R et al (2025) Case report: improvement of diplopia due to severe internuclear ophthalmoplegia by 4-aminopyridine documented using a novel virtual reality-based oculography headset. Front Virtual Real. https:\/\/doi.org\/10.3389\/frvir.2025.1595694","journal-title":"Front Virtual Real"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13906-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-13906-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13906-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T07:21:09Z","timestamp":1783495269000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-13906-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,6]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["13906"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-13906-x","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,6]]},"assertion":[{"value":"19 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"ER, JL, MK, JH, ZA, CSch, DB, and JJ report no disclosures. RK reports Research Funding from Heinrich und Alma Vogelsangstiftung,\u00a0LFB Group France, and Ruhr University Bochum. Travel Funding from Takeda, Grifols, Ruhr University Bochum. Speaker Honoraria from CSL Behring. CSa received speaker honoraria for activities with Alnylam, travel grants from Alnylam, VICO and Novartis; and his research is supported by Biogen Idec, CHDI and German Huntington Foundation. He has received consulting fees from Novartis, VICO, Teitur, WAVE, Prilenia, Alnylam, and Arrowhead. IA received research support and personal honoraria from Alexion, Amgen, Argenx, Roche, and Sanofi. ALF holds shares in Novartis, Novo Nordisk, and Coloplast. She received travel grants from CSL and consulting fees and honoraria from Takeda. Research is supported by GBS\/CIDP Foundation International, Ruhr-University Bochum, and Agricola Stiftung Ruhr. KP received honoraria for lectures and research funding from CSL Behring and Ruhr University Bochum. CSG received consulting and speaker honoraria from Alexion Pharmaceuticals, Amgen, Amicus Therapeutics, argenx, Hormosan Pharma, Immunovant, Janssen, Lupin Pharmaceuticals, Novartis, Roche, Sanofi-Genzyme, and UCB Pharma, as well as travel grants from Alexion Pharmaceuticals. RG holds shares in Merck, Novartis, Kyverna Therapeutics Inc. and Roche. He has received consulting fees from Novartis, Merck, Roche, and Biogen; honoraria from Novartis; lecture fees from Biogen, BMS, Eisai, Genesis, Janssen, Merck, Novartis, Roche, Sanofi, Sandoz, and TIBUA, and third-party funding from Biogen, Novartis, TIBUA, and Sanofi. JM received speaker honoraria for activities with Alnylam, Biogen Idec, travel grants from Biogen Idec, Novartis AG, Teva, and Eisai GmbH; and his research is supported by Biogen Idec, Novartis AG, GBS\/CIDP Foundation International, Klaus TschiraFoundation and Ruhr-University, Bochum, regional association of North Rhine-Westphalia of the German MS Society (DMSG Landesverband NRW). RS has received speaker honoraria from Bayer HealthCare, Alexion Pharma, Novartis Pharma, and Roche Pharma AG, congress travel support from Merck, Biogen Idec GmbH, and has received research scientific grant support from Novartis Pharma. AS received speaker\u2019s honoraria from Merck, Neuraxpharm, Novartis, Roche, and Sanofi; consulting fees from Neuraxpharm and research support by the regional association of North Rhine-Westphalia of the German MS Society (DMSG Landesverband NRW) and Novartis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was approved by the ethics committee of the Medical Faculty of Ruhr University Bochum, Bochum, Germany (approval number 23\u20137934-BR) and conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"372"}}