{
  "abstract": "Background: Penicillamine can trigger early neurological worsening in patients with Wilson’s disease (WD). We evaluated a very conservative regimen, starting at 125 mg/day and increasing the does stepwise at months 1, 3, and 6, combined with zinc, focusing on clinical outcomes, urinary copper, exchangeable copper (CuEXC), and plasma neurofilament light (NfL).\n\nMethods: We retrospectively analyzed 25 treatment-naïve patients with neurological WD who received penicillamine at 125 mg/day, with 125-mg/day increments at months 1, 3, and 6, plus zinc gluconate. Neurological status (UWDRS), 24-h urinary copper, CuEXC, and NfL were assessed at baseline and at 1, 3, 6, and 12 months. Neurological worsening was defined as an increase of more than 2 points in the UWDRS-N.\n\nResults: Nine patients (36%) experienced neurological worsened, all within the first 3 months. Patients who remained stable ( n = 16) showed progressive improvement in UWDRS scores and a sustained decline in CuEXC. Patients who experienced worsening had a blunted increase in urinary copper at 1 month and no significant reduction in CuEXC. ROC curve analysis showed that a 1-month urinary copper level above 473.85 μg/day was associated with a lower risk of worsening. Plasma NfL showed a mild, transient elevation in both groups at 1 month, followed by a decline only in the stable groups; however, between-group differences were not statistically significant.\n\nConclusion: Neurological worsening remains frequent (36%) despite the ultra-low starting doses. A simple 1-month urinary copper threshold of 473.85 μg/day may help identify patients with more favorable outcomes. CuEXC and NfL changes parallel clinical courses but require larger validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yue Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Mansi Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangxue Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Huajing You"
    },
    {
      "affs": [
        0
      ],
      "name": "Xunhua Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Dingbang Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d2gwh6s8dah2m.bib",
  "cited_by": 0,
  "doi": "10.3389/fneur.2026.1946980",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1946980/full",
  "id": "d2gwh6s8dah2m",
  "issns": [
    "1664-2295"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1946980/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC346-429"
    ],
    [
      "openalex",
      "2916|Trace Elements in Health"
    ]
  ],
  "openalex": "W7223675442",
  "pdf_url": "https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2026.1946980/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/d2gwh6s8dah2m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:16Z",
      "native_id": "10.3389/fneur.2026.1946980",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1946980/full"
    },
    {
      "first_seen": "2026-10-30T13:47:30Z",
      "native_id": "701bb58a6dd2457ea947a070e6f9a5a0",
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      "url": "https://doi.org/10.3389/fneur.2026.1946980"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC346-429",
      "subfield": "neurology"
    }
  ],
  "title": "Urinary copper at 1 month predicts early neurological worsening in treatment-naïve Wilson’s disease on ultra-low dose penicillamine",
  "title_text": "Urinary copper at 1 month predicts early neurological worsening in treatment-naïve Wilson’s disease on ultra-low dose penicillamine",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:30Z",
  "url": "https://research.draconitic.com/paper/d2gwh6s8dah2m",
  "venue": "Frontiers in Neurology",
  "versions": []
}