{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:14:56Z","timestamp":1791490496221,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ataxia\u2010telangiectasia (AT) is characterized by progressive cerebellar ataxia, oculomotor apraxia, immunodeficiency, and increased cancer susceptibility. No disease\u2010modifying treatment is available. This systematic review aimed to evaluate the efficacy and safety of pharmacological interventions for ataxia in pediatric AT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      A systematic search was conducted across MEDLINE, Scopus, Web of Science, and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      through December 2025. Eligible studies included randomized controlled trials (RCTs) and single\u2010arm interventional studies evaluating pharmacological treatments for cerebellar ataxia in patients aged \u2264\u200918\u2009years with genetically confirmed AT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirteen studies (3 RCTs, 10 single\u2010arm trials) involving 314 participants (mean age 10.87\u2009years) were included. Interventions included betamethasone, erythrocyte\u2010encapsulated dexamethasone (eDSP), nicotinamide riboside (NR), leucine derivatives, and amantadine. Betamethasone demonstrated transient improvements in the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale (ICARS) scores, with dose\u2010dependent systemic toxicity. eDSP showed favorable tolerability but was ineffective in phase 3 trials, although subgroup analyses suggested a potential benefit in children aged 6\u20139\u2009years. NR supplementation improved SARA and AT Neurological Examination Scale Toolkit (AT\u2010NEST) scores in open\u2010label studies. Leucine derivatives showed mixed results. Amantadine showed benefits in patients with extrapyramidal symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The recurrent pattern of promising open\u2010label findings followed by negative phase 3 results highlights a translational gap attributable to methodological limitations, including small sample sizes, heterogeneous populations, and variable outcome measures. The non\u2010linear disease progression and age\u2010dependent treatment response further complicate trial design. Current evidence remains insufficient to guide clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>PROSPERO number: CRD420251184721<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70683","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:19:51Z","timestamp":1782969591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological Treatment of Cerebellar Ataxia in Pediatric Ataxia\u2010Telangiectasia: A Systematic Review"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2683-0052","authenticated-orcid":false,"given":"Fabiola","family":"Panvino","sequence":"first","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-1471","authenticated-orcid":false,"given":"Roberto","family":"Paparella","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Urciuolo","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4717-699X","authenticated-orcid":false,"given":"Serena","family":"Galosi","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1828-4035","authenticated-orcid":false,"given":"Carlotta","family":"Spagnoli","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Leuzzi","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(07)70054\u20106"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7792600"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.39346"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/336577a0"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010011811\u2010132509"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1006610"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181af33bd"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27319"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25394"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102018\u2010105635"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22016"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2020.1810570"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00220\u20105"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28788"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311\u2010024\u201001746\u20102"},{"key":"e_1_2_12_17_1","unstructured":"J. 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