{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:03:23Z","timestamp":1773745403202,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cerebellum"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1\u20132% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.<\/jats:p>","DOI":"10.1007\/s12311-020-01222-7","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T17:03:50Z","timestamp":1609952630000},"page":"454-461","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Treatment Response of Deferiprone in Infratentorial Superficial Siderosis: a Systematic Review"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-7301","authenticated-orcid":false,"given":"Andreas","family":"Flores Martin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya","family":"Shanmugarajah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Hoggard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios","family":"Hadjivassiliou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"issue":"9","key":"1222_CR1","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1097\/00005053-190809000-00027","volume":"35","author":"RC Hamill","year":"1908","unstructured":"Hamill RC. Report of a case of melanosis of the brain, cord and meninges. J Nerv Ment Dis. 1908;35(9):594.","journal-title":"J Nerv Ment Dis"},{"issue":"1","key":"1222_CR2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/bf00686141","volume":"13","author":"JT Hughes","year":"1969","unstructured":"Hughes JT, Oppenheimer DR. Superficial siderosis of the central nervous system. A report on nine cases with autopsy. Acta Neuropathol. 1969;13(1):56\u201374. https:\/\/doi.org\/10.1007\/bf00686141.","journal-title":"Acta Neuropathol"},{"issue":"1","key":"1222_CR3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3174\/ajnr.A1628","volume":"31","author":"N Kumar","year":"2010","unstructured":"Kumar N. Neuroimaging in superficial siderosis: an in-depth look. Am J Neuroradiol. 2010;31(1):5\u201314. https:\/\/doi.org\/10.3174\/ajnr.A1628.","journal-title":"Am J Neuroradiol"},{"issue":"3","key":"1222_CR4","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/ana.24850","volume":"81","author":"D Wilson","year":"2017","unstructured":"Wilson D, Chatterjee F, Farmer SF, Rudge P, McCarron MO, Cowley P, et al. Infratentorial superficial siderosis: classification, diagnostic criteria, and rational investigation pathway. Ann Neurol. 2017;81(3):333\u201343. https:\/\/doi.org\/10.1002\/ana.24850.","journal-title":"Ann Neurol"},{"issue":"5","key":"1222_CR5","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1097\/00005072-199109000-00005","volume":"50","author":"AH Koeppen","year":"1991","unstructured":"Koeppen AH, Borke RC. Experimental superficial siderosis of the central nervous system. I. Morphological observations. J Neuropathol Exp Neurol. 1991;50(5):579\u201394. https:\/\/doi.org\/10.1097\/00005072-199109000-00005.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"1","key":"1222_CR6","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/ncpneuro0356","volume":"3","author":"M Levy","year":"2007","unstructured":"Levy M, Turtzo C, Llinas RH. Superficial siderosis: a case report and review of the literature. Nat Clin Pract Neurol. 2007;3(1):54\u20138; quiz 59. https:\/\/doi.org\/10.1038\/ncpneuro0356.","journal-title":"Nat Clin Pract Neurol"},{"issue":"2","key":"1222_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0304-3940(93)90326-G","volume":"153","author":"RF Regan","year":"1993","unstructured":"Regan RF, Panter SS. Neurotoxicity of hemoglobin in cortical cell culture. Neurosci Lett. 1993;153(2):219\u201322. https:\/\/doi.org\/10.1016\/0304-3940(93)90326-G.","journal-title":"Neurosci Lett"},{"issue":"2","key":"1222_CR8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/0014-4886(79)90080-3","volume":"66","author":"AD Rosen","year":"1979","unstructured":"Rosen AD, Frumin NV. Focal epileptogenesis after intracortical hemoglobin injection. Exp Neurol. 1979;66(2):277\u201384. https:\/\/doi.org\/10.1016\/0014-4886(79)90080-3.","journal-title":"Exp Neurol"},{"issue":"7","key":"1222_CR9","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s41582-018-0020-0","volume":"14","author":"D Bulters","year":"2018","unstructured":"Bulters D, Gaastra B, Zolnourian A, Alexander S, Ren D, Blackburn SL, et al. Haemoglobin scavenging in intracranial bleeding: biology and clinical implications. Nat Rev Neurol. 2018;14(7):416\u201332. https:\/\/doi.org\/10.1038\/s41582-018-0020-0.","journal-title":"Nat Rev Neurol"},{"issue":"Pt 4","key":"1222_CR10","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1093\/brain\/118.4.1051","volume":"118","author":"JM Fearnley","year":"1995","unstructured":"Fearnley JM, Stevens JM, Rudge P. Superficial siderosis of the central nervous system. Brain. 1995;118(Pt 4):1051\u201366. https:\/\/doi.org\/10.1093\/brain\/118.4.1051.","journal-title":"Brain"},{"issue":"3","key":"1222_CR11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/0300-483x(95)03301-u","volume":"108","author":"AM Fredenburg","year":"1996","unstructured":"Fredenburg AM, Sethi RK, Allen DD, Yokel RA. The pharmacokinetics and blood-brain barrier permeation of the chelators 1,2 dimethly-, 1,2 diethyl-, and 1-[ethan-1'ol]-2-methyl-3-hydroxypyridin-4-one in the rat. Toxicology. 1996;108(3):191\u20139. https:\/\/doi.org\/10.1016\/0300-483x(95)03301-u.","journal-title":"Toxicology"},{"key":"1222_CR12","doi-asserted-by":"publisher","first-page":"bcr2013010099","DOI":"10.1136\/bcr-2013-010099","volume":"2013","author":"N Huprikar","year":"2013","unstructured":"Huprikar N, Gossweiler M, Callaghan M, Bunge P. Agranulocytosis with deferiprone treatment of superficial siderosis. BMJ Case Rep. 2013;2013:bcr2013010099. https:\/\/doi.org\/10.1136\/bcr-2013-010099.","journal-title":"BMJ Case Rep"},{"issue":"10","key":"1222_CR13","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1002\/ajh.24479","volume":"91","author":"F Tricta","year":"2016","unstructured":"Tricta F, Uetrecht J, Galanello R, Connelly J, Rozova A, Spino M, et al. Deferiprone-induced agranulocytosis: 20 years of clinical observations. Am J Hematol. 2016;91(10):1026\u201331. https:\/\/doi.org\/10.1002\/ajh.24479.","journal-title":"Am J Hematol"},{"issue":"1","key":"1222_CR14","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.3174\/ajnr.A2331","volume":"32","author":"M Levy","year":"2011","unstructured":"Levy M, Llinas RH. Deferiprone reduces hemosiderin deposits in the brain of a patient with superficial siderosis. AJNR Am J Neuroradiol. 2011;32(1):E1\u20132. https:\/\/doi.org\/10.3174\/ajnr.A2331.","journal-title":"AJNR Am J Neuroradiol"},{"issue":"6","key":"1222_CR15","doi-asserted-by":"publisher","first-page":"E99","DOI":"10.3174\/ajnr.A3186","volume":"33","author":"M Levy","year":"2012","unstructured":"Levy M, Llinas RH. Update on a patient with superficial siderosis on deferiprone. AJNR Am J Neuroradiol. 2012;33(6):E99\u2013100. https:\/\/doi.org\/10.3174\/ajnr.A3186.","journal-title":"AJNR Am J Neuroradiol"},{"issue":"1","key":"1222_CR16","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1161\/strokeaha.111.628032","volume":"43","author":"M Levy","year":"2012","unstructured":"Levy M, Llinas R. Pilot safety trial of deferiprone in 10 subjects with superficial siderosis. Stroke. 2012;43(1):120\u20134. https:\/\/doi.org\/10.1161\/strokeaha.111.628032.","journal-title":"Stroke"},{"key":"1222_CR17","doi-asserted-by":"publisher","first-page":"bcr2013009916","DOI":"10.1136\/bcr-2013-009916","volume":"2013","author":"G Cummins","year":"2013","unstructured":"Cummins G, Crundwell G, Baguley D, Lennox G. Treatment of superficial siderosis with iron chelation therapy. BMJ Case Rep. 2013;2013:bcr2013009916. https:\/\/doi.org\/10.1136\/bcr-2013-009916.","journal-title":"BMJ Case Rep"},{"issue":"7","key":"1222_CR18","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1007\/s10072-014-1709-5","volume":"35","author":"T Schirinzi","year":"2014","unstructured":"Schirinzi T, Sancesario G, Anemona L, Pisani A, Sancesario G. CSF biomarkers in superficial siderosis: a new tool for diagnosis and evaluation of therapeutic efficacy of deferiprone--a case report. Neurol Sci. 2014;35(7):1151\u20132. https:\/\/doi.org\/10.1007\/s10072-014-1709-5.","journal-title":"Neurol Sci"},{"issue":"2","key":"1222_CR19","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1017\/cjn.2016.329","volume":"44","author":"PH Kuo","year":"2017","unstructured":"Kuo PH, Kuo SH, Lo RY. Deferiprone reduces hemosiderin deposition in superficial siderosis. Can J Neurol Sci. 2017;44(2):219\u201320. https:\/\/doi.org\/10.1017\/cjn.2016.329.","journal-title":"Can J Neurol Sci"},{"issue":"4","key":"1222_CR20","first-page":"195","volume":"17","author":"E Derle","year":"2018","unstructured":"Derle E. Iron chelation in treatment of superficial siderosis. Iran J Neurol. 2018;17(4):195\u20136.","journal-title":"Iran J Neurol"},{"issue":"3","key":"1222_CR21","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/cns.12792","volume":"24","author":"RA Kessler","year":"2018","unstructured":"Kessler RA, Li X, Schwartz K, Huang H, Mealy MA, Levy M. Two-year observational study of deferiprone in superficial siderosis. CNS Neurosci Ther. 2018;24(3):187\u201392. https:\/\/doi.org\/10.1111\/cns.12792.","journal-title":"CNS Neurosci Ther"},{"issue":"7","key":"1222_CR22","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1007\/s10072-019-03847-x","volume":"40","author":"G Cossu","year":"2019","unstructured":"Cossu G, Abbruzzese G, Forni GL, Matta G, Pinto V, Ruffinengo U, et al. Efficacy and safety of deferiprone for the treatment of superficial siderosis: results from a long-term observational study. Neurol Sci. 2019;40(7):1357\u201361. https:\/\/doi.org\/10.1007\/s10072-019-03847-x.","journal-title":"Neurol Sci"},{"issue":"9","key":"1222_CR23","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1007\/s10072-019-03791-w","volume":"40","author":"M Levy","year":"2019","unstructured":"Levy M. Ten years of iron chelation in a patient with superficial siderosis. Neurol Sci. 2019;40(9):1947\u20139. https:\/\/doi.org\/10.1007\/s10072-019-03791-w.","journal-title":"Neurol Sci"},{"issue":"1","key":"1222_CR24","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00415-019-09577-6","volume":"267","author":"Y Sammaraiee","year":"2020","unstructured":"Sammaraiee Y, Banerjee G, Farmer S, Hylton B, Cowley P, Eleftheriou P, et al. Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis. J Neurol. 2020;267(1):239\u201343. https:\/\/doi.org\/10.1007\/s00415-019-09577-6.","journal-title":"J Neurol"},{"issue":"1","key":"1222_CR25","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/j.1749-6632.1998.tb10478.x","volume":"850","author":"A Cohen","year":"1998","unstructured":"Cohen A, Galanello R, Piga A, Vullo C, Tricta F. A multi-center safety trial of the oral iron chelator deferiprone. Ann N Y Acad Sci. 1998;850(1):223\u20136. https:\/\/doi.org\/10.1111\/j.1749-6632.1998.tb10478.x.","journal-title":"Ann N Y Acad Sci"},{"key":"1222_CR26","doi-asserted-by":"publisher","unstructured":"Fisher SA, Brunskill SJ, Doree C, Chowdhury O, Gooding S, Roberts DJ. Oral deferiprone for iron chelation in people with thalassaemia. Cochrane Database Syst Rev. 2013;8. https:\/\/doi.org\/10.1002\/14651858.CD004839.pub3.","DOI":"10.1002\/14651858.CD004839.pub3"},{"issue":"5","key":"1222_CR27","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1182\/blood-2002-10-3280","volume":"102","author":"AR Cohen","year":"2003","unstructured":"Cohen AR, Galanello R, Piga A, De Sanctis V, Tricta F. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood. 2003;102(5):1583\u20137. https:\/\/doi.org\/10.1182\/blood-2002-10-3280.","journal-title":"Blood"},{"key":"1222_CR28","unstructured":"European Medicines Agency: Deferiprone Lipomed - European Medicines Agency. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/ferriprox-epar-product-information_en.pdf. Accessed 3 July 2020."}],"container-title":["The Cerebellum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12311-020-01222-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12311-020-01222-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12311-020-01222-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T10:37:46Z","timestamp":1624012666000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12311-020-01222-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,6]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["1222"],"URL":"https:\/\/doi.org\/10.1007\/s12311-020-01222-7","relation":{},"ISSN":["1473-4222","1473-4230"],"issn-type":[{"value":"1473-4222","type":"print"},{"value":"1473-4230","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,6]]},"assertion":[{"value":"26 November 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}