Urinary copper at 1 month predicts early neurological worsening in treatment-naïve Wilson’s disease on ultra-low dose penicillamine
- 1Department 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
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).
Methods: 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.
Results: 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.
Conclusion: 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.
Related
- Integrating Single-Molecule Variant Phenotyping with Clinical Features Predicts Outcomes in KIF1A-Associated Neurological Disorder
- Urinary Extracellular Vesicle–Associated EphA2 Predicts Intravesical Recurrence in Bladder Cancer
- Treatment Optimization with Add-On Kampo Therapy in Highly Refractory Migraine Patients with Inadequate Response or Re-Worsening During CGRP Monoclonal Antibody Therapy: A Real-World Treatment Episode Analysis
- Dynamic Changes in Serum Glial Fibrillary Acidic Protein Levels Predicts Early Neurological Deterioration After Intravenous Thrombolysis in Minor Stroke.
- Catatonic Features That May Be Mistaken for Worsening Autism Show Treatment-Associated Improvement: Implications for Later Regression
BibTeX
@article{luo2026urinary,
title = {{Urinary copper at 1 month predicts early neurological worsening in treatment-naïve Wilson’s disease on ultra-low dose penicillamine}},
author = {Yue Luo and Mansi Cai and Jie Yang and Xiangxue Zhou and Chao Wu and Huajing You and Xunhua Li and Dingbang Chen},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1946980},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1946980/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Urinary copper at 1 month predicts early neurological worsening in treatment-naïve Wilson’s disease on ultra-low dose penicillamine
AU - Yue Luo
AU - Mansi Cai
AU - Jie Yang
AU - Xiangxue Zhou
AU - Chao Wu
AU - Huajing You
AU - Xunhua Li
AU - Dingbang Chen
PY - 2026
DA - 2026/10/26
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1946980
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1946980/full
AB - 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). Methods: 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. Results: 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. Conclusion: 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.
SN - 1664-2295
ER -