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We modelled the change in SARA (Scale for Assessment and Rating of Ataxia) score <jats:italic>versus<\/jats:italic> Time Since Onset of symptoms using non-linear mixed effect models for a population of 173 patients with ARSACS included in the prospective real-world multicenter Autosomal Recessive Cerebellar Ataxia (ARCA) registry. We used the Multivariate Imputation Chained Equation (MICE) algorithm to impute missing covariates, and a covariate selection procedure with a pooled p-value to account for the multiply imputed data sets. We then investigated the impact of covariates and population parameter uncertainty on the prediction of the individual trajectories up to 5 years after their last visit. A four-parameter logistic function was selected. Men were estimated to have a 25% lower SARA score at disease onset and a moderately higher maximum SARA score, and time to progression (T50) was estimated to be 35% lower in patients with age of onset over 15 years. The population disease progression rate started slowly at 0.1 points per year peaking to a maximum of 0.8 points per year (at 36.8 years since onset of symptoms). The prediction intervals for SARA scores 5 years after the last visit were large (median 7.4 points, Q1-Q3: 6.4\u20138.5); their size was mostly driven by individual parameter uncertainty and individual disease progression rate at that time.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1208\/s12248-024-00925-7","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:03:03Z","timestamp":1714521783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prediction of Individual Disease Progression Including Parameter Uncertainty in Rare Neurodegenerative Diseases: The Example of Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS)"],"prefix":"10.1208","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0951-7514","authenticated-orcid":false,"given":"Niels","family":"Hendrickx","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Mentr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Trasch\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Gagnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ARCA Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"EVIDENCE-R. 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Within the last 24 months, he has received consulting fees from Biogen, UCB and Vico Therapeutics, all unrelated to the present manuscript.Dr. Synofzik has received consultancy honoraria from Ionis, UCB, Prevail, Orphazyme, Servier, Reata, GenOrph, AviadoBio, Biohaven, Zevra, and Lilly, all unrelated to the present manuscript.Drs Hooker and Karlsson has received consultancy fees from, and own stock in Pharmetheus, all unrelated to this manuscript.Dr Comets has received consultancy fees from Sanofi, unrelated to this manuscript.The other authors have no potential conflicts of interest to report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Relevant Conflicts Of Interest\/Financial Disclosures"}},{"value":"For this study data from the ARCA Registry (arca-registry.org) was used. No new personal data was collected and\/or processed. Probands recruited to the ARCA Registry study consented to secondary use of their data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}],"article-number":"57"}}