{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:42:16Z","timestamp":1784166136469,"version":"3.55.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Recent cell-based and animal experiments have demonstrated an effective reduction in botulinum neurotoxin A (BoNT\/A) by copper. Aim: We aimed to analyze whether the successful symptomatic BoNT\/A treatment of patients with Wilson\u2019s disease (WD) corresponds with unusually high doses per session. Among the 156 WD patients regularly seen at the outpatient department of the university hospital in D\u00fcsseldorf (Germany), only 6 patients had been treated with BoNT\/A during the past 5 years. The laboratory findings, indications for BoNT treatment, preparations, and doses per session were extracted retrospectively from the charts. These parameters were compared with those of 13 other patients described in the literature. BoNT\/A injection therapy is a rare (&lt;4%) symptomatic treatment in WD, only necessary in exceptional cases, and is often applied only transiently. In those cases for which dose information was available, the dose per session and indication appear to be within usual limits. Despite the evidence that copper can interfere with the botulinum toxin in preclinical models, patients with WD do not require higher doses of the toxin than other patients with dystonia.<\/jats:p>","DOI":"10.3390\/toxins13040241","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T04:29:14Z","timestamp":1616992154000},"page":"241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effective Treatment of Neurological Symptoms with Normal Doses of Botulinum Neurotoxin in Wilson\u2019s Disease: Six Cases and Literature Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-7684","authenticated-orcid":false,"given":"Harald","family":"Hefter","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3593-1852","authenticated-orcid":false,"given":"Sara","family":"Samadzadeh","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/0014-4800(67)90007-X","article-title":"Experimental botulism in monkeys\u2014A clinical pathological study","volume":"6","author":"Herrero","year":"1967","journal-title":"Exp. Mol. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","article-title":"Botulinum toxin as a biological weapon: Medical and public health management","volume":"285","author":"Arnon","year":"2001","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"802","DOI":"10.15585\/mmwr.mm6429a6","article-title":"Large Outbreak of Botulism Associated with a Church Potluck Meal--Ohio, 2015","volume":"64","author":"McCarty","year":"2015","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1001\/jama.1997.03550050095041","article-title":"Botulism Surveillance and Emergency Response: A Public Health Strategy for a Global Challenge","volume":"278","author":"Shapiro","year":"1997","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/milmed\/148.12.901","article-title":"The covert use of chemical and biological warfare against United States Strategic Forces","volume":"148","author":"Hooper","year":"1983","journal-title":"Mil. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.toxicon.2015.06.019","article-title":"The thioredoxin reductase\u2014Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles","volume":"107","author":"Pirazzini","year":"2015","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.febslet.2012.11.007","article-title":"The thioredoxin reductase-thioredoxin system is involved in the entry of tetanus and botulinum neurotoxins in the cytosol of nerve terminals","volume":"587","author":"Pirazzini","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23784","DOI":"10.1016\/S0021-9258(20)80452-9","article-title":"Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E","volume":"268","author":"Schiavo","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7264","DOI":"10.1021\/jacs.7b01084","article-title":"Metal Ions Effectively Ablate the Action of Botulinum Neurotoxin A","volume":"139","author":"Bremer","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1474-4422(14)70190-5","article-title":"Wilson\u2019s disease and other neurological copper disorders","volume":"14","author":"Bandmann","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41572-018-0018-3","article-title":"Wilson disease","volume":"4","author":"Litwin","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1055\/s-2007-971173","article-title":"Wilson\u2019s disease","volume":"27","author":"Pfeiffer","year":"2007","journal-title":"Semin. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.parkreldis.2018.01.007","article-title":"Long-term outcome of neurological Wilson\u2019s disease","volume":"49","author":"Hefter","year":"2019","journal-title":"Park. Rel. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.parkreldis.2011.05.002","article-title":"Prognostic significance of neurologic examination findings in Wilson\u2019s disease","volume":"17","author":"Burke","year":"2011","journal-title":"Park. Relat. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1749-6632.2009.05109.x","article-title":"Neurologic Wilson\u2019s disease","volume":"1184","author":"Lorincz","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cz\u0142onkowska, A., Litwin, T., Dzie\u017cyc, K., Karli\u0144ski, M., Bring, J., and Bjartmar, C. (2018). Characteristics of a newly diagnosed Polish cohort of patients with neurological manifestations of Wilson disease evaluated with the Unified Wilson\u2019s Disease Rating Scale. BMC Neurol., 18.","DOI":"10.1186\/s12883-018-1039-y"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/B978-0-444-63625-6.00018-5","article-title":"Symptomatic treatment of neurologic symptoms in Wilson disease","volume":"142","author":"Litwin","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"European Association for Study of Liver (2012). EASL Clinical Practice Guidelines: Wilson\u2019s disease. J. Hepatol., 56, 671\u2013685.","DOI":"10.1016\/j.jhep.2011.11.007"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/hep.22261","article-title":"Diagnosis and treatment of Wilson disease: An update","volume":"47","author":"Roberts","year":"2008","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000316066","article-title":"Evaluation of the symptomatic treatment of residual neurological symptoms in Wilson disease","volume":"64","author":"Leinweber","year":"2010","journal-title":"Eur. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/BF00315332","article-title":"Wilson\u2019s disease: Normalisation of cortically evoked motor responses with treatment","volume":"238","author":"Meyer","year":"1991","journal-title":"J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/mds.870060409","article-title":"Abnormal conduction in corticospinal pathways in Wilson\u2019s disease: Investigation of nine cases with magnetic brain stimulation","volume":"6","author":"Meyer","year":"1991","journal-title":"Mov. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1590\/S0004-282X2012000600005","article-title":"Jaw-opening oromandibular dystonia secondary to Wilson\u2019s disease treated with botulinum toxin type A","volume":"70","author":"Teive","year":"2012","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hassell, T.J.W., and Charles, D. (2020). Treatment of blepharospasm and oromandibular dystonia with botulinum toxins. Toxins, 12.","DOI":"10.3390\/toxins12040269"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.toxicon.2008.04.079","article-title":"Importance of botulinum toxin in symptomatic treatment of Wilson\u2019s disease","volume":"51","author":"Joan","year":"2008","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.5114\/ninp.2013.38230","article-title":"Acute focal dystonia induced by a tricyclic antidepressant in a patient with Wilson disease: A case report","volume":"47","author":"Litwin","year":"2013","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/BF00184123","article-title":"Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson\u2019s disease","volume":"19","author":"Kuwert","year":"1992","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF00870672","article-title":"Relationship between striatal glucose consumption and copper excretion in patients with Wilson\u2019s disease treated with D-penicillamine","volume":"241","author":"Hefter","year":"1993","journal-title":"J. Neurol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/4\/241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:10:18Z","timestamp":1760364618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/4\/241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["toxins13040241"],"URL":"https:\/\/doi.org\/10.3390\/toxins13040241","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,29]]}}}