{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:39:37Z","timestamp":1773797977436,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004168","name":"Universit\u00e4t zu L\u00fcbeck","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004168","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Biallelic intronic repeat expansions in the\n                      <jats:italic>RFC1<\/jats:italic>\n                      gene are associated with the cerebellar ataxia, neuropathy, and vestibular areflexia (bilateral vestibulopathy) syndrome (CANVAS). Oculomotor abnormalities may serve as a state marker exclusively reflecting the midline cerebellar involvement in CANVAS, i.e., independent of the combined disorders affecting the patient\u2019s postural control stance and gait.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Slow and fast eye movements of 15 CANVAS patients and 14 healthy subjects were compared using a high-resolution video-based eye tracker allowing to record visually-guided saccades, gaze-holding function and smooth pursuit paradigms. Scores of cognitive impairment were related to oculomotor performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Saccades (latency, metria, velocity) were normal. Small amplitude omnidirectional gaze-holding deficit was found in 70% of patients, with downbeat nystagmus (60%) being more common than upbeat nystagmus (13%). Latency of initial acceleration of smooth pursuit was prolonged and there was severe impairment of smooth pursuit eye movements. Montreal Cognitive Assessment (MoCA) scores were lower in patients and correlated with saccade and pursuit latency and initial acceleration. Disease duration and vestibulopathy correlated with no oculomotor abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cerebellar oculomotor dysfunction affected mainly smooth pursuit and gaze holding function at eccentric gaze positions, but it did neither comprise spontaneous nystagmus nor saccade abnormalities. Prolonged latencies in initial pursuit acceleration might be related to the patient\u2019s cognitive decline, but normal saccade latencies point to cerebellar oculomotor neurodegeneration. Smooth pursuit impairment was not related to disease duration and vestibulopathy, contrariwise pursuit impairment became worse with larger functional impairment. Oculomotor abnormalities in CANVAS are in line with midline cerebellar impairment without evidence for extracerebellar (brainstem) brain involvement.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13678-4","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T07:54:19Z","timestamp":1771055659000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oculomotor abnormalities in patients with cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) reflect midline cerebellar impairment"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8111-6281","authenticated-orcid":false,"given":"Renana","family":"Storm","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bente","family":"L\u00fcbbers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Borsche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmelie","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"N\u00fcmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Ganos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Br\u00fcggemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-2294","authenticated-orcid":false,"given":"Christoph","family":"Helmchen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Sprenger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"13678_CR1","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41588-019-0372-4","volume":"51","author":"A Cortese","year":"2019","unstructured":"Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, Humphrey J, Jaunmuktane Z, Sivakumar P, Polke J, Ilyas M, Tribollet E, Tomaselli PJ, Devigili G, Callegari I, Versino M, Salpietro V, Efthymiou S, Kaski D, Wood NW, Andrade NS, Buglo E, Rebelo A, Rossor AM, Bronstein A, Fratta P, Marques WJ, Zuchner S, Reilly MM, Houlden H (2019) Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 51:649\u2013658. https:\/\/doi.org\/10.1038\/s41588-019-0372-4","journal-title":"Nat Genet"},{"key":"13678_CR2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1007\/s00415-025-13433-1","volume":"272","author":"LE Ariello","year":"2025","unstructured":"Ariello LE, Gold DR, Millar JL, Schubert MC, Mu W, Rosenthal L, Rastall DPW (2025) Video head impulse test differentiates RFC1-CANVAS, FGF14-SCA27B, and idiopathic late-onset cerebellar ataxias. J Neurol 272:679. https:\/\/doi.org\/10.1007\/s00415-025-13433-1","journal-title":"J Neurol"},{"key":"13678_CR3","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1007\/s00415-023-12050-0","volume":"271","author":"M Borsche","year":"2024","unstructured":"Borsche M, Thomsen M, Szmulewicz DJ, Lubbers B, Hinrichs F, Lockhart PJ, Lohmann K, Helmchen C, Bruggemann N (2024) Bilateral vestibulopathy in RFC1-positive CANVAS is distinctly different compared to FGF14-linked spinocerebellar ataxia 27B. J Neurol 271:1023\u20131027. https:\/\/doi.org\/10.1007\/s00415-023-12050-0","journal-title":"J Neurol"},{"key":"13678_CR4","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1002\/mds.29750","volume":"39","author":"K Dujardin","year":"2024","unstructured":"Dujardin K, Tard C, Digle E, Herlin V, Mutez E, Davion JB, Wissocq A, Delforge V, Kuchcinski G, Huin V (2024) Cognitive impairment is part of the phenotype of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Mov Disord 39:892\u2013897. https:\/\/doi.org\/10.1002\/mds.29750","journal-title":"Mov Disord"},{"key":"13678_CR5","doi-asserted-by":"crossref","unstructured":"Leigh RJ, Zee DS (2015) The Neurology of Eye Movements. In:Oxford University Press","DOI":"10.1093\/med\/9780199969289.001.0001"},{"key":"13678_CR6","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10755-8","author":"GM Halmagyi","year":"2021","unstructured":"Halmagyi GM, Kumar K, McGarvie LA (2021) The visually enhanced vestibulo-ocular reflex in CANVAS. J Neurol. https:\/\/doi.org\/10.1007\/s00415-021-10755-8","journal-title":"J Neurol"},{"key":"13678_CR7","doi-asserted-by":"publisher","first-page":"e541","DOI":"10.1212\/WNL.0000000000012080","volume":"97","author":"M Strupp","year":"2021","unstructured":"Strupp M, Frenzel C, Goldschagg N, Halmagyi GM (2021) Teaching video neuroimage: one bedside test, 2 clinical signs: one vestibular, the other ocular motor. Neurology 97:e541\u2013e542. https:\/\/doi.org\/10.1212\/WNL.0000000000012080","journal-title":"Neurology"},{"key":"13678_CR8","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1007\/s00415-025-13150-9","volume":"272","author":"M Dupre","year":"2025","unstructured":"Dupre M, Hermann R, Vidoni L, Quadrio I, Latour P, Subtil F, Froment Tilikete C (2025) Impact of the intronic RFC1 expansion size in CANVAS phenotype: an oculomotor study. J Neurol 272:442. https:\/\/doi.org\/10.1007\/s00415-025-13150-9","journal-title":"J Neurol"},{"key":"13678_CR9","doi-asserted-by":"publisher","first-page":"e2912","DOI":"10.1212\/WNL.0000000000010744","volume":"95","author":"M Gisatulin","year":"2020","unstructured":"Gisatulin M, Dobricic V, Zuhlke C, Hellenbroich Y, Tadic V, Munchau A, Isenhardt K, Burk K, Bahlo M, Lockhart PJ, Lohmann K, Helmchen C, Bruggemann N (2020) Clinical spectrum of the pentanucleotide repeat expansion in the RFC1 gene in ataxia syndromes. Neurology 95:e2912\u2013e2923. https:\/\/doi.org\/10.1212\/WNL.0000000000010744","journal-title":"Neurology"},{"key":"13678_CR10","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1002\/mds.20781","volume":"21","author":"T Schmitz-H\u00fcbsch","year":"2006","unstructured":"Schmitz-H\u00fcbsch T, Tezenas du Montcel S, Baliko L, Boesch S, Bonato S, Fancellu R, Giunti P, Globas C, Kang JS, Kremer B (2006) Reliability and validity of the international cooperative ataxia rating scale: a study in 156 spinocerebellar ataxia patients. Mov Disord 21:699\u2013704","journal-title":"Mov Disord"},{"key":"13678_CR11","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1002\/mds.25042","volume":"27","author":"C Helmchen","year":"2012","unstructured":"Helmchen C, Pohlmann J, Trillenberg P, Lencer R, Graf J, Sprenger A (2012) Role of anticipation and prediction in smooth pursuit eye movement control in Parkinson\u2019s disease. Mov Disord 27:1012\u20131018","journal-title":"Mov Disord"},{"key":"13678_CR12","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.parkreldis.2018.10.016","volume":"61","author":"A Sprenger","year":"2019","unstructured":"Sprenger A, Hanssen H, Hagedorn I, Prasuhn J, Rosales RL, Jamora RDG, Diesta CC, Domingo A, Klein C, Br\u00fcggemann N (2019) Eye movement deficits in X-linked dystonia-parkinsonism are related to striatal degeneration. Parkinsonism Relat Disord 61:170\u2013178","journal-title":"Parkinsonism Relat Disord"},{"key":"13678_CR13","doi-asserted-by":"publisher","first-page":"e1369","DOI":"10.1212\/WNL.0000000000011528","volume":"96","author":"A Traschutz","year":"2021","unstructured":"Traschutz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schutz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schols L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M, Group RFCS (2021) Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1 disease. Neurology 96:e1369\u2013e1382. https:\/\/doi.org\/10.1212\/WNL.0000000000011528","journal-title":"Neurology"},{"key":"13678_CR14","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s12311-025-01894-z","volume":"24","author":"E Pretegiani","year":"2025","unstructured":"Pretegiani E, Garces P, Antoniades CA, Sobanska A, Kovacs N, Ying SH, Gupta AS, Perlman S, Szmulewicz DJ, Pane C, Nemeth AH, Jardim LB, Coarelli G, Kuzmiak M, Milovanovic A, Traschutz A, Tarnutzer AA (2025) Best oculomotor endpoints for clinical trials in hereditary ataxias: a systematic review and consensus by the ataxia global initiative working group on digital-motor biomarkers. Cerebellum 24:141. https:\/\/doi.org\/10.1007\/s12311-025-01894-z","journal-title":"Cerebellum"},{"key":"13678_CR15","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1177\/01945998211008398","volume":"166","author":"M Costales","year":"2022","unstructured":"Costales M, Casanueva R, Suarez V, Asensi JM, Cifuentes GA, Dineiro M, Cadinanos J, Lopez F, Alvarez-Marcos C, Otero A, Gomez J, Llorente JL, Cabanillas R (2022) CANVAS: a new genetic entity in the otorhinolaryngologist\u2019s differential diagnosis. Otolaryngol Head Neck Surg 166:74\u201379. https:\/\/doi.org\/10.1177\/01945998211008398","journal-title":"Otolaryngol Head Neck Surg"},{"key":"13678_CR16","doi-asserted-by":"publisher","first-page":"2886","DOI":"10.1007\/s00415-024-12229-z","volume":"271","author":"D Pellerin","year":"2024","unstructured":"Pellerin D, Heindl F, Traschutz A, Rujescu D, Hartmann AM, Brais B, Houlden H, Dufke C, Riess O, Haack T, Strupp M, Synofzik M (2024) RFC1 repeat expansions in downbeat nystagmus syndromes: frequency and phenotypic profile. J Neurol 271:2886\u20132892. https:\/\/doi.org\/10.1007\/s00415-024-12229-z","journal-title":"J Neurol"},{"key":"13678_CR17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1136\/jnnp-2023-331490","volume":"95","author":"D Pellerin","year":"2024","unstructured":"Pellerin D, Wilke C, Traschutz A, Nagy S, Curro R, Dicaire MJ, Garcia-Moreno H, Anheim M, Wirth T, Faber J, Timmann D, Depienne C, Rujescu D, Gazulla J, Reilly MM, Giunti P, Brais B, Houlden H, Schols L, Strupp M, Cortese A, Synofzik M (2024) Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy. J Neurol Neurosurg Psychiatry 95:175\u2013179. https:\/\/doi.org\/10.1136\/jnnp-2023-331490","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"13678_CR18","doi-asserted-by":"publisher","DOI":"10.1111\/ene.70228","volume":"32","author":"S Coulette","year":"2025","unstructured":"Coulette S, Lecler A, Le Cossec C, Philibert M, Gaymard B, Delmaire C, Charbonneau F, Torcello JM, Brandel JP, Wenta J, Gueguen A, Desjardins C (2025) Video-oculography as a key diagnostic tool for SCA27B: a real-life experience. Eur J Neurol 32:e70228. https:\/\/doi.org\/10.1111\/ene.70228","journal-title":"Eur J Neurol"},{"key":"13678_CR19","doi-asserted-by":"publisher","first-page":"2908","DOI":"10.1007\/s00415-013-7147-0","volume":"260","author":"C Helmchen","year":"2013","unstructured":"Helmchen C, Glasauer S, Sprenger A (2013) Inverse eye position dependency of downbeat nystagmus in midline medullary lesion. J Neurol 260:2908\u20132910. https:\/\/doi.org\/10.1007\/s00415-013-7147-0","journal-title":"J Neurol"},{"key":"13678_CR20","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1007\/s00415-010-5806-y","volume":"258","author":"T Sander","year":"2011","unstructured":"Sander T, Sprenger A, Marti S, Naumann T, Straumann D, Helmchen C (2011) Effect of 4-aminopyridine on gravity dependence and neural integrator function in patients with idiopathic downbeat nystagmus. J Neurol 258:618\u2013622. https:\/\/doi.org\/10.1007\/s00415-010-5806-y","journal-title":"J Neurol"},{"key":"13678_CR21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12311-025-01825-y","volume":"24","author":"M Szymanska Heydel","year":"2025","unstructured":"Szymanska Heydel M, Heindl F, Hartmann A, Borsche M, Traschutz A, Straumann D, Strupp M, Tarnutzer AA (2025) The spectrum of peripheral-vestibular deficits and their change over time in CANVAS\/RFC1-related ataxia systematic review and meta-analysis of quantitative head-impulse testing. Cerebellum 24:67. https:\/\/doi.org\/10.1007\/s12311-025-01825-y","journal-title":"Cerebellum"},{"key":"13678_CR22","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1093\/brain\/awn177","volume":"131","author":"LJ Bour","year":"2008","unstructured":"Bour LJ, van Rootselaar AF, Koelman JHTM, Tijssen MAJ (2008) Oculomotor abnormalities in myoclonic tremor: a comparison with spinocerebellar ataxia type 6. Brain 131:2295\u20132303. https:\/\/doi.org\/10.1093\/brain\/awn177","journal-title":"Brain"},{"key":"13678_CR23","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.clinph.2023.07.006","volume":"154","author":"S Inomata-Terada","year":"2023","unstructured":"Inomata-Terada S, Fukuda H, Tokushige S-i, Matsuda S-i, Hamada M, Ugawa Y, Tsuji S, Terao Y (2023) Abnormal saccade profiles in hereditary spinocerebellar degeneration reveal cerebellar contribution to visually guided saccades. Clin Neurophysiol 154:70\u201384. https:\/\/doi.org\/10.1016\/j.clinph.2023.07.006","journal-title":"Clin Neurophysiol"},{"key":"13678_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1125651","volume":"15","author":"D Rane","year":"2023","unstructured":"Rane D, Dash DP, Dutt A, Dutta A, Das A, Lahiri U (2023) Distinctive visual tasks for characterizing mild cognitive impairment and dementia using oculomotor behavior. Front Aging Neurosci 15:1125651","journal-title":"Front Aging Neurosci"},{"key":"13678_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.883213","volume":"13","author":"C Helmchen","year":"2022","unstructured":"Helmchen C, Machner B, Schwenke H, Sprenger A (2022) Bilateral lesion of the cerebellar fastigial nucleus: effects on smooth pursuit acceleration and non-reflexive visually-guided saccades. Front Neurol 13:883213. https:\/\/doi.org\/10.3389\/fneur.2022.883213","journal-title":"Front Neurol"},{"key":"13678_CR26","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2546","volume":"12","author":"M Borsche","year":"2022","unstructured":"Borsche M, Tadic V, K\u00f6nig IR, Lohmann K, Helmchen C, Br\u00fcggemann N (2022) Head impulse testing in bilateral vestibulopathy in patients with genetically defined CANVAS. Brain Behav 12:e32546","journal-title":"Brain Behav"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13678-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-13678-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13678-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:05:26Z","timestamp":1773785126000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-13678-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["13678"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-13678-4","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"15 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 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":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study protocol was approved by the local Ethics Committee of the University of Luebeck (AZ 20\u2013358) in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"143"}}