{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:40:34Z","timestamp":1776091234250,"version":"3.50.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004769","name":"Universit\u00e0 degli Studi di Pavia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The objective is to investigate the presentation, complications, management, and outcomes of copper deficiency-induced neurological pathologies due to Wilson disease (WD) overtreatment. We examined the case of a WD patient who developed a low thoracic dorsal myelopathy due to chronic hypocupremia from excessive zinc therapy. A comprehensive literature review was conducted to identify similar cases. Ten additional cases of neurological pathology resulting from copper deficiency in the context of WD over-treatment were identified, all occurring during therapy with zinc salts. Myelopathy and peripheral neuropathy were the most common complications, while two additional groups reported leukoencephalopathy. Early cytopenia was often associated with copper deficiency-related neurological pathology appearing early in the context of copper deficiency. WD patients undergoing treatment, especially with zinc salts, should be closely monitored to prevent over-treatment and the consequent copper deficiency. Regular complete blood counts could provide early detection of copper deficiency, avoiding irreversible neurological damage. Swift recognition of new neurological signs not consistent with WD and timely discontinuation of the decoppering therapy are critical for improving outcomes. The optimal management, including the potential benefit of copper supplementation in patients with WD and subsequent therapy adjustments, remains unclear and necessitates further investigation. Despite the general poor functional neurological outcomes, there were some exceptions that warrant further exploration.<\/jats:p>","DOI":"10.1007\/s10072-023-07126-8","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T13:02:10Z","timestamp":1697634130000},"page":"987-996","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neurological complications due to copper deficiency in the context of Wilson disease treatment: a case report with long-term follow-up and review of the literature"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1153-3613","authenticated-orcid":false,"given":"Danilo","family":"Tornabene","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Bini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Gastaldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Vegezzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Asteggiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Marchioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Diamanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"7126_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s004150170118","volume":"248","author":"B Schleper","year":"2001","unstructured":"Schleper B, Stuerenburg HJ (2001) Copper deficiency-associated myelopathy in a 46-year-old woman. J Neurol 248:8. https:\/\/doi.org\/10.1007\/s004150170118","journal-title":"J Neurol"},{"key":"7126_CR2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s00415-010-5511-x","volume":"257","author":"SR Jaiser","year":"2010","unstructured":"Jaiser SR, Winston GP (2010) Copper deficiency myelopathy. J Neurol 257:6. https:\/\/doi.org\/10.1007\/s00415-010-5511-x","journal-title":"J Neurol"},{"key":"7126_CR3","doi-asserted-by":"publisher","first-page":"10","DOI":"10.4065\/81.10.1371","volume":"81","author":"N Kumar","year":"2006","unstructured":"Kumar N (2006) Copper deficiency myelopathy (human swayback). Mayo Clin Proc 81:10. https:\/\/doi.org\/10.4065\/81.10.1371","journal-title":"Mayo Clin Proc"},{"key":"7126_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/ejh.12020","volume":"90","author":"AA Gabreyes","year":"2013","unstructured":"Gabreyes AA, Abbasi HN, Forbes KP, Mcquaker G, Duncan A, Morrison I (2013) Hypocupremia associated cytopenia and myelopathy: a national retrospective review. Eur J Haematol 90:1. https:\/\/doi.org\/10.1111\/ejh.12020","journal-title":"Eur J Haematol"},{"key":"7126_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jhep.2011.11.007","volume":"56","author":"P Ferenci","year":"2012","unstructured":"Ferenci P et al (2012) EASL Clinical Practice Guidelines: Wilson\u2019s disease. J Hepatol 56:3. https:\/\/doi.org\/10.1016\/j.jhep.2011.11.007","journal-title":"J Hepatol"},{"key":"7126_CR6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.gastrohep.2012.03.008","volume":"35","author":"J Lozano Herrero","year":"2012","unstructured":"Lozano Herrero J, Mu\u00f1oz Bertr\u00e1n E, Ortega Gonz\u00e1lez I, G\u00f3mez Esp\u00edn R, L\u00f3pez Esp\u00edn MI (2012) Myelopathy secondary to copper deficiency as a complication of treatment of Wilson\u2019s disease. Gastroenterol Hepatol. 35:10. https:\/\/doi.org\/10.1016\/j.gastrohep.2012.03.008","journal-title":"Gastroenterol Hepatol."},{"key":"7126_CR7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.pjnns.2014.05.002","volume":"48","author":"K Dziezyc","year":"2014","unstructured":"Dziezyc K, Litwin T, Soba\u0144ska A, Cz\u0142onkowska A (2014) Symptomatic copper deficiency in three Wilson\u2019s disease patients treated with zinc sulphate. Neurol Neurochir Pol 48:3. https:\/\/doi.org\/10.1016\/j.pjnns.2014.05.002","journal-title":"Neurol Neurochir Pol"},{"key":"7126_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/imj.14694","volume":"50","author":"LM Wu","year":"2020","unstructured":"Wu LM, Ekladious A, Wheeler L, Mohamad AA (2020) Wilson disease: copper deficiency and iatrogenic neurological complications with zinc therapy. Intern Med J 50:1. https:\/\/doi.org\/10.1111\/imj.14694","journal-title":"Intern Med J"},{"key":"7126_CR9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1212\/WNL.0b013e318219fac8","volume":"76","author":"FP Da Silva-J\u00fanior","year":"2011","unstructured":"Da Silva-J\u00fanior FP, MacHado AAC, Lucato LT, Can\u00e7ado ELR, Barbosa ER (2011) Copper deficiency myeloneuropathy in a patient with Wilson disease. Neurology 76:19. https:\/\/doi.org\/10.1212\/WNL.0b013e318219fac8","journal-title":"Neurology"},{"key":"7126_CR10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00415-013-6963-6","volume":"260","author":"T Teodoro","year":"2013","unstructured":"Teodoro T et al (2013) Recovery after copper-deficiency myeloneuropathy in Wilson\u2019s disease. J Neurol 260:7. https:\/\/doi.org\/10.1007\/s00415-013-6963-6","journal-title":"J Neurol"},{"key":"7126_CR11","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/mus.21425","volume":"40","author":"A Foubert-Samier","year":"2009","unstructured":"Foubert-Samier A et al (2009) Axonal sensory motor neuropathy in copper-deficient Wilson\u2019s disease. Muscle Nerve 40:2. https:\/\/doi.org\/10.1002\/mus.21425","journal-title":"Muscle Nerve"},{"key":"7126_CR12","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515578770","author":"M Cortese","year":"2015","unstructured":"Cortese M et al (2015) Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: the EnvIMS study. Mult Scler. https:\/\/doi.org\/10.1177\/1352458515578770","journal-title":"Mult Scler"},{"key":"7126_CR13","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1136\/jnnp.2009.188896","volume":"81","author":"J Horvath","year":"2010","unstructured":"Horvath J, Beris P, Giostra E, Martin PY, Burkhard PR (2010) Zinc-induced copper deficiency in Wilson disease. J Neurol, Neurosurg Psychiatry 81:12. https:\/\/doi.org\/10.1136\/jnnp.2009.188896","journal-title":"J Neurol, Neurosurg Psychiatry"},{"key":"7126_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4103\/0028-3886.25146","volume":"54","author":"SK Narayan","year":"2006","unstructured":"Narayan SK, Kaveer N (2006) CNS demyelination due to hypocupremia in Wilson\u2019s disease from overzealous treatment. Neurol India 54:1. https:\/\/doi.org\/10.4103\/0028-3886.25146","journal-title":"Neurol India"},{"key":"7126_CR15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.seizure.2010.07.018","volume":"19","author":"G Benbir","year":"2010","unstructured":"Benbir G, Gunduz A, Ertan S, Ozkara C (2010) Partial status epilepticus induced by hypocupremia in a patient with Wilson\u2019s disease. Seizure 19:9. https:\/\/doi.org\/10.1016\/j.seizure.2010.07.018","journal-title":"Seizure"},{"key":"7126_CR16","doi-asserted-by":"crossref","unstructured":"EA Roberts and ML Schilsky (2008) \u201cAASLD practice guidelines diagnosis and treatment of Wilson disease\u202f: an update,\u201d Hepatology.","DOI":"10.1002\/hep.22261"},{"key":"7126_CR17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1097\/MPG.0000000000001787","volume":"66","author":"P Socha","year":"2018","unstructured":"Socha P et al (2018) Wilson\u2019s disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 66:2. https:\/\/doi.org\/10.1097\/MPG.0000000000001787","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"7126_CR18","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/mds.23520","volume":"26","author":"A Cortese","year":"2011","unstructured":"Cortese A, Zangaglia R, Lozza A, Piccolo G, Pacchetti C (2011) Copper deficiency in Wilson\u2019s disease: peripheral neuropathy and myelodysplastic syndrome complicating zinc treatment. Movement Disorders 26:7. https:\/\/doi.org\/10.1002\/mds.23520","journal-title":"Movement Disorders"},{"key":"7126_CR19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/mds.23970","volume":"26","author":"FP Da Silva-J\u00fanior","year":"2011","unstructured":"Da Silva-J\u00fanior FP, Lucato LT, Machado AAC, Barbosa ER (2011) Copper deficiency in Wilson\u2019s disease: an avoidable complication of treatment. Movement Disorders 26:13. https:\/\/doi.org\/10.1002\/mds.23970","journal-title":"Movement Disorders"}],"container-title":["Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-023-07126-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10072-023-07126-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-023-07126-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T02:05:13Z","timestamp":1707530713000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10072-023-07126-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,18]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["7126"],"URL":"https:\/\/doi.org\/10.1007\/s10072-023-07126-8","relation":{},"ISSN":["1590-1874","1590-3478"],"issn-type":[{"value":"1590-1874","type":"print"},{"value":"1590-3478","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,18]]},"assertion":[{"value":"7 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable for this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}