{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:55:01Z","timestamp":1781499301979,"version":"3.54.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Abnormalities of eye movements occur early in the disease course of Huntington\u2019s disease, often preceding clinical motor diagnosis. The increasing availability of digital eye tracking tools indicate a potential role for eye movements as biomarkers of prognosis and progression in Huntington\u2019s disease, yet the optimal set of oculomotor tasks to measure is currently unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We explored the clinical progression of the six oculomotor items of the Unified Huntington\u2019s Disease Rating Scale in data from the Enroll-HD (\n                      <jats:italic>N<\/jats:italic>\n                      \u202f=\u202f4,775) and PREDICT-HD (\n                      <jats:italic>N<\/jats:italic>\n                      \u202f=\u202f969) observational studies and their association with time to clinical motor diagnosis and functional decline in time-dependent survival models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Vertical eye movements were affected in larger proportions of participants before motor diagnosis than horizontal eye movements. Stepwise Cox proportional hazard regression analyses identified saccade velocity, vertical smooth pursuit, and horizontal saccade initiation as independently significant predictors of progression to motor manifest disease and functional decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oculomotor progression follows a distinct pattern in early Huntington\u2019s disease, which should be kept in mind when developing digital eye tracking paradigms to be used as biomarkers in future observational studies and clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1844433","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:27:56Z","timestamp":1781497676000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the prognostic value of early oculomotor abnormalities in Huntington\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Ahmad","family":"Kaddoura","sequence":"first","affiliation":[{"name":"Department of Neurology, Oslo University Hospital","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solveig E. J.","family":"Dalbro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen R.","family":"van Walsem","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Pihlstr\u00f8m","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington's disease: a clinical review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur J Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1007\/s00415-010-5632-2","article-title":"Huntington's disease: changes in saccades and hand-tapping over 3 years","volume":"257","author":"Antoniades","year":"2010","journal-title":"J Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1212\/WNL.33.10.1268","article-title":"Abnormal ocular motor control in Huntington's disease","volume":"33","author":"Leigh","year":"1983","journal-title":"Neurology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1212\/WNL.41.6.875","article-title":"Saccades in Huntington's disease: predictive tracking and interaction between release of fixation and initiation of saccades","volume":"41","author":"Tian","year":"1991","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1212\/WNL.38.3.427","article-title":"Saccades in Huntington's disease: slowing and dysmetria","volume":"38","author":"Lasker","year":"1988","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1212\/01.wnl.0000227890.87398.c1","article-title":"Saccades in presymptomatic and early stages of Huntington disease","volume":"67","author":"Blekher","year":"2006","journal-title":"Neurology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S1474-4422(10)70276-3","article-title":"Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis","volume":"10","author":"Tabrizi","year":"2011","journal-title":"Lancet Neurol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1212\/01.wnl.0000218215.43328.88","article-title":"Identification of an oculomotor biomarker of preclinical Huntington disease","volume":"67","author":"Golding","year":"2006","journal-title":"Neurology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s00415-025-13600-4","article-title":"Eye manifestations in Huntington's disease: an update on the potential of ocular biomarkers","volume":"273","author":"Woods","year":"2026","journal-title":"J Neurol"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcag102","article-title":"Advances in ocular motor and pupil biomarkers for neurological disorders","volume":"8","author":"Coito","year":"2026","journal-title":"Brain Commun"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s00415-026-13666-8","article-title":"Eye tracking as a digital biomarker in neurodegenerative diseases","volume":"273","author":"Giacomini","year":"2026","journal-title":"J Neurol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/S1474-4422(14)70238-8","article-title":"Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study","volume":"13","author":"Paulsen","year":"2014","journal-title":"Lancet Neurol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S1474-4422(13)70088-7","article-title":"Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data","volume":"12","author":"Tabrizi","year":"2013","journal-title":"Lancet Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12874-018-0592-9","article-title":"Joint modeling of multivariate longitudinal data and survival data in several observational studies of Huntington's disease","volume":"18","author":"Long","year":"2018","journal-title":"BMC Med Res Methodol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3233\/JHD-170236","article-title":"PREDICT-HD Investigators of the Huntington Study Group. Dynamic prediction of motor diagnosis in Huntington's disease using a joint modeling approach","volume":"6","author":"Li","year":"2017","journal-title":"J Huntingtons Dis"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0193866","DOI":"10.1371\/journal.pone.0193866","article-title":"Premanifest Huntington's disease: examination of oculomotor abnormalities in clinical practice","volume":"13","author":"Winder","year":"2018","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1001\/archneur.63.6.883","article-title":"Preparing for preventive clinical trials: the predict-HD study","volume":"63","author":"Paulsen","year":"2006","journal-title":"Arch Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"667420","DOI":"10.3389\/fneur.2021.667420","article-title":"Enroll-HD: an integrated clinical research platform and worldwide observational study for Huntington's disease","volume":"12","author":"Sathe","year":"2021","journal-title":"Front Neurol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/mds.870110204","article-title":"Unified Huntington's disease rating scale: reliability and consistency","volume":"11","year":"1996","journal-title":"Huntington Study Group"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/S1474-4422(22)00120-X","article-title":"A biological classification of Huntington's disease: the integrated staging system","volume":"21","author":"Tabrizi","year":"2022","journal-title":"Lancet Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3233\/JHD-210475","article-title":"Standardizing the CAP score in Huntington's disease by predicting age-at-onset","volume":"11","author":"Warner","year":"2022","journal-title":"J Huntingtons Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1002\/ajmg.b.31232","article-title":"Indexing disease progression at study entry with individuals at-risk for Huntington disease","author":"Zhang","year":"2011","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"ref23","first-page":"1109","author":"Leigh","year":"2015"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1016\/j.clinph.2013.05.002","article-title":"Horizontal and vertical eye movement metrics: what is important?","volume":"124","author":"Bonnet","year":"2013","journal-title":"Clin Neurophysiol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1159\/000076777","article-title":"Decline of vertical gaze and convergence with aging","volume":"50","author":"Oguro","year":"2004","journal-title":"Gerontology"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1844433\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:27:59Z","timestamp":1781497679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1844433\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":25,"alternative-id":["10.3389\/fneur.2026.1844433"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1844433","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]},"article-number":"1844433"}}