{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:02:22Z","timestamp":1789664542224,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized center who had been listed for liver transplantation during the last ten years and two newly diagnosed homozygous twins were recruited for this retrospective study. The mean duration of conventional treatment was 7.3 years (range: 0.25 to 36.2 years). A custom Wilson disease score with seven motor items, three non-motor items, and 33 biochemical parameters of the blood and urine, as well as the MELD score, was determined at various checkup visits during treatment. These data were extracted from the charts of the patients. Results: Treatment was initiated with severity-dependent doses (\u2265900 mg) of D-penicillamine (DPA) or triethylene-tetramin-dihydrochloride (TRIEN). The motor score improved in 10 and remained constant in 8 patients. Worsening of neurological symptoms was observed only in two patients who developed comorbidities (myasthenia gravis or hemispheric stroke). The neurological symptoms continuously improved over the years until the majority of patients became only mildly affected. In contrast to this slow recovery of the neurological symptoms, the MELD score and liver enzymes had already started to improve after 1 month and rapidly improved over the next 6 months in 19 patients. The cholinesterase levels continued to increase significantly (p &lt; 0.0074) even further. One patient whose MELD score indicated further progression of liver disease received an orthotopic liver transplantation 3 months after the diagnosis of WD and the onset of DPA treatment. Conclusions: Neurological and hepatic symptoms both respond to copper chelation therapy. For patients with acute liver failure, the first 4 months are critical. This is the time span in which patients have to wait either for a donor organ or until significant improvement has occurred under conventional therapy. For patients with severe neurological symptoms, it is important that they are treated with fairly high doses over several years.<\/jats:p>","DOI":"10.3390\/jcm12144861","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:32:10Z","timestamp":1690248730000},"page":"4861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-7684","authenticated-orcid":false,"given":"Harald","family":"Hefter","sequence":"first","affiliation":[{"name":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodor S.","family":"Kruschel","sequence":"additional","affiliation":[{"name":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Novak","sequence":"additional","affiliation":[{"name":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6288-8821","authenticated-orcid":false,"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[{"name":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"},{"name":"Department of Neurology, Kliniken Maria Hilf GmbH M\u00f6nchengladbach, 41063 M\u00f6nchengladbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Departments of Neurology, University 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":"Departments of Neurology, University of D\u00fcsseldorf, Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany"},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Unverst\u00e4t zu Berlin, Experimental and Clinical Research Center, 13125 Berlin, Germany"},{"name":"Department of Regional Health Research and Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark"},{"name":"Department of Neurology, Slagelse Hospital, 4200 Slagelse, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/brain\/34.4.295","article-title":"Progressive lenticular degeneration: A familial nervous disease associated with cirrhosis of the liver","volume":"34","author":"Wilson","year":"1912","journal-title":"Brain"},{"key":"ref_2","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":"15","author":"Bandmann","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_3","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. 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