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Clinical data from 30 patients treated at four university centers in Germany, Switzerland, and France were analyzed. Except for three patients previously enrolled in the ALCAT randomized crossover trial, treatments were initiated as part of routine care and were not standardized for dose or duration. Analyses were based on medical records, including patient-reported outcomes and physician assessments. Four patients from Strasbourg underwent SARA and SDFS assessments before and during treatment; SARA total scores for three ALCAT participants were obtained from the original study dataset. Twelve patients received 4-AP only, seven ADLL only, and eleven both treatments at different time points. Median treatment duration was 29 days for 4-AP and 53 days for ADLL. Subjective improvement was reported in 3\/22 patients (13.6%) treated with 4-AP and 3\/15 (20.0%) treated with ADLL. Objective gait improvement was observed in 2\/13 patients (15.4%) on 4-AP and in 2\/10 (20.0%) on ADLL. No effects on downbeat nystagmus were observed. Exploratory analyses revealed no significant differences in SARA total scores between ADLL and placebo or baseline; neither SARA nor SDFS scores improved in Strasbourg patients. Responses to 4-AP and ADLL in\n                    <jats:italic>RFC1<\/jats:italic>\n                    -related disorders were rare and limited, suggesting that neurodegenerative dysfunction of cerebellar circuits in\n                    <jats:italic>RFC1<\/jats:italic>\n                    -disease\u2014in contrast to certain genetic cerebellar disorders such as SCA27B\u2014is unlikely to be improved to clinically relevant thresholds by these agents.\n                  <\/jats:p>","DOI":"10.1007\/s12311-026-01982-8","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:53:08Z","timestamp":1775807588000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RFC1-related disorders: A case series of 4-aminopyridine and acetyl-DL-leucine treatment"],"prefix":"10.1007","volume":"25","author":[{"given":"F.","family":"Heindl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Trasch\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Synofzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Anheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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Heindl, A. Trasch\u00fctz, A.M. Hartmann, I. Giegling and C. Adrion declare no conflicts of interest. M. Strupp is Joint Chief Editor of the Journal of Neurology, Editor in Chief of Frontiers of Neuro-otology and Section Editor of F1000. He has received speaker\u2019s honoraria from Abbott, Auris Medical, Biogen, Eisai, Gr\u00fcnenthal, GSK, Henning Pharma, Interacoustics, J&J, MSD, NeuroUpdate, Otometrics, Pierre-Fabre, TEVA, UCB, and Viatris. He received support for clinical studies from Decibel, U.S.A., Cure within Reach, U.S.A. and Heel, Germany. He distributes \u201cM-glasses\u201d and \u201cPositional vertigo App\u201d. He acts as a consultant for Bulbitec, Heel and Vertify. He is a scientific founder, investor and share-holder of IntraBio.M. Synofzik has received consultancy honoraria from UCB, Prevail, Orpha zyme, Biogen, Servier, Reata, GenOrph, AviadoBio, Biohaven, Zevra, Lilly, Quince, Neurocrine, Insmed, and Solaxa, all unrelated to the present manuscript.T. Wirth reported grants from Direction G\u00e9n\u00e9rale de l\u2019Offre de soins, France Parkinson, and Association Connaitre les Syndromes C\u00e9r\u00e9belleux, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Ipsen and Biogen, payment for expert testimony from Abbvie, Support for attending meetings and\/or travel from Homeperf, Lundbeck and The Movement Disorders Society.A. A. Tarnutzer has received consultant and\/or speaker fees from Mitsubishi Tanabe Pharma, AstraZeneca, Teva Pharma, Neuraxpharma, Angelini Pharma and Schwabe Pharma, all unrelated to the present manuscript.D. Rujescu served as consultant for Boehringer-Ingelheim and Janssen, received honoraria from Boehringer-Ingelheim, Gerot Lannacher, Indorsia, Janssen and Pharmagenetix, received research\/travel support from Angelini, Boehringer-Ingelheim, Janssen and Schwabe, and served on advisory boards of AC Immune, Boehringer-Ingelheim, Indorsia, Roche and Rovi.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"50"}}