{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:11:09Z","timestamp":1791389469666,"version":"4.3.3"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In multiple sclerosis, remyelination trials have yet to deliver success like that achieved for relapse rates with disease course modifying treatment trials. The challenge is to have a clinical, functional outcome measure. Currently, there are none that have been validated, other than visual evoked potentials in optic neuritis. Like vision, quick eye movements (saccades) are heavily dependent on myelination. We proposed that it is possible to extrapolate from demyelination of the medial longitudinal fasciculus in the brainstem to quantitative assessment of cortical networks governing saccadic eye movements in multiple sclerosis.<\/jats:p>\n                  <jats:p>We have developed and validated a double-step saccadic test, which consists of a pair of eye movements towards two stimuli presented in quick succession (the demonstrate eye movement networks with saccades protocol). In this single-centre, cross-sectional cohort study we interrogated the structural and functional relationships of double-step saccades in multiple sclerosis. Data were collected for double-step saccades, cognitive function (extended Rao\u2019s Brief Repeatable Battery), disability (Expanded Disability Status Scale) and visual functioning in daily life (National Eye Institute Visual Function Questionnaire). MRI was used to quantify grey matter atrophy and multiple sclerosis lesion load. Multivariable linear regression models were used for analysis of the relationships between double-step saccades and clinical and MRI metrics. We included 209 individuals with multiple sclerosis (mean age 54.3 \u00b1 10.5 years, 58% female, 63% relapsing-remitting multiple sclerosis) and 60 healthy control subjects (mean age 52.1 \u00b1 9.2 years, 53% female).<\/jats:p>\n                  <jats:p>The proportion of correct double-step saccades was significantly reduced in multiple sclerosis (mean 0.29 \u00b1 0.22) compared to controls (0.45 \u00b1 0.22, P &amp;lt; 0.001). Consistent with this, there was a significantly larger double-step dysmetric saccadic error in multiple sclerosis (mean vertical error \u22121.18 \u00b1 1.20\u00b0) compared to controls (\u22120.54 \u00b1 0.86\u00b0, P &amp;lt; 0.001). Impaired double-step saccadic metrics were consistently associated with more severe global and local grey matter atrophy (correct responses\u2014cortical grey matter: \u03b2 = 0.42, P &amp;lt; 0.001), lesion load (vertical error: \u03b2 = \u22120.28, P &amp;lt; 0.001), progressive phenotypes, more severe physical and cognitive impairment (correct responses\u2014information processing: \u03b2 = 0.46, P &amp;lt; 0.001) and visual functioning. In conclusion, double-step saccades represent a robust metric that revealed a novel eye-movement impairment in individuals with multiple sclerosis. Double-step saccades outperformed other saccadic tasks in their statistical relationship with clinical, cognitive and visual functioning, as well as global and local grey matter atrophy. Double-step saccades should be evaluated longitudinally and tested as a potential novel outcome measure for remyelination trials in multiple sclerosis.<\/jats:p>","DOI":"10.1093\/brain\/awac474","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T22:37:22Z","timestamp":1671489442000},"page":"2476-2488","source":"Crossref","is-referenced-by-count":20,"title":["A novel eye-movement impairment in multiple sclerosis indicating widespread cortical damage"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6956-6369","authenticated-orcid":false,"given":"Jenny A","family":"Nij Bijvank","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Department of Neurology, Vrije Universiteit Amsterdam, MS Centre and Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"},{"name":"Amsterdam UMC, Department of Ophthalmology, Vrije Universiteit Amsterdam, Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam N","family":"Hof","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Neurology, Vrije Universiteit Amsterdam, MS Centre and Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanos E","family":"Prouskas","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, MS Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-6959","authenticated-orcid":false,"given":"Menno M","family":"Schoonheim","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, MS Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard M J","family":"Uitdehaag","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Neurology, Vrije Universiteit Amsterdam, MS Centre and Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurentius J","family":"van Rijn","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Ophthalmology, Vrije Universiteit Amsterdam, Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"},{"name":"Department of Ophthalmology, Onze Lieve Vrouwe Gasthuis , 1091 AC Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-9749","authenticated-orcid":false,"given":"Axel","family":"Petzold","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Neurology, Vrije Universiteit Amsterdam, MS Centre and Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"},{"name":"Amsterdam UMC, Department of Ophthalmology, Vrije Universiteit Amsterdam, Neuro-ophthalmology Expertise Centre Amsterdam, Amsterdam Neuroscience , 1081 HZ Amsterdam , The Netherlands"},{"name":"Moorfields Eye Hospital, The National Hospital for Neurology and Neurosurgery and the Queen Square Institute of Neurology, UCL , London EC1V 2PD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"2023060100283512900_awac474-B1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"2023060100283512900_awac474-B2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11940-021-00677-1","article-title":"Early aggressive treatment approaches for multiple sclerosis","volume":"23","author":"Simpson","year":"2021","journal-title":"Curr Treat Options Neurol"},{"key":"2023060100283512900_awac474-B3","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1016\/S0140-6736(17)32346-2","article-title":"Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): A randomised, controlled, double-blind, 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