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Preataxic carriers (Scale for Assessment and Rating of Ataxia score\u2009&lt;\u20093) expected to start ataxia in \u22644\u2009years were considered near onset (PAN). Progressions of ataxic and preataxic carriers, considering status at the end of the study, were described according to the start (or its prediction) of gait ataxia (TimeToAfterOnset) and according to the study time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 35 ataxics, 38 preataxics, and 22 noncarriers were included. The \u201cTimeToAfterOnset\u201d timeline showed that Neurological Examination Scale for Spinocerebellar Ataxias (NESSCA; effect size, 0.09), Inventory of Non\u2010Ataxia Symptoms (INAS0.07), and the vestibulo\u2010ocular reflex gain (0.12) progressed in preataxic carriers, and that most slopes accelerate in PAN, turning similar to those of ataxics. In the study time, NESSCA (1.36) and vertical pursuit gain (1.17) significantly worsened in PAN, and 6 of 11 PANs converted to ataxia. For a clinical trial with 80% power and 2\u2010year duration, 57 PANs are needed in each study arm to detect a 50% reduction in the conversion rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NESSCA, INAS, vestibulo\u2010ocular reflex, and vertical pursuit gains significantly worsened in the preataxic phase. The \u201cTimeToAfterOnset\u201d timeline unveiled that slopes of most variables are small in preataxics but increase and reach the ataxic slopes from 4\u2009years before the onset of ataxia. For future trials in preataxic carriers, we recommend recruiting PANs and using the conversion rate as the primary outcome. \u00a9 2022 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29226","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T10:48:53Z","timestamp":1663757333000},"page":"26-34","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Progression of Clinical and Eye Movement Markers in Preataxic Carriers of <scp>Machado\u2010Joseph<\/scp> Disease"],"prefix":"10.1002","volume":"38","author":[{"given":"Camila Maria","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias M\u00e9dicas Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"},{"name":"Centros de Pesquisa Cl\u00ednica e Experimental Hospital de Cl\u00ednicas de Porto Alegre  Porto 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