Introduction Wilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled. However, in almost 50% of WD patients, neurological symptoms persist despite treatment, and in up to 10% of patients, neurological deterioration is irreversible. International guidelines on WD treatment do not recommend liver transplantation (LT) as a treatment for neurological symptoms in WD. However, such treatment has been assessed in retrospective analyses, case and series reports. We aimed to systematically assess all available evidence on the effectiveness and safety of LT in WD patients with neurological presentation. Methods This systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified by searching the PubMed database (up to 6 April 2021) and by screening reference lists. Results Based on the systematic literature review, 48 articles were identified, showing outcomes of LT in 302 WD patients with neurological symptoms. Of these patients, major improvement was found in 215 cases (71.2%), with no difference in neurological status before and after LT in 21 cases (6.9%). There were 29 deaths (9.6%), neurological worsening in 24 cases (7.9%), and 13 cases (4.3%) were lost to follow-up. Conclusions The results suggest that LT is a promising method of WD management in patients with severe, neurological symptoms, particularly if the patient has not responded to pharmacological de-coppering treatment. Further studies of LT in these patients are warranted.

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Background: Clinical scales and neuroimaging are used to monitor nervous system injury in Wilson's disease, while data on serum markers are scarce. Objective: To investigate whether serum concentrations of neurofilament light chain (sNfL) correlate with brain injury in Wilson's disease patients. Methods: In 61 treatment-naïve patients, the Unified Wilson's Disease Rating Scale and a validated semiquantitative brain magnetic resonance imaging scale were compared with concentrations of sNfL. Results: Concentrations of sNfL were significantly higher in patients with neurological disease compared with patients presenting with other forms (39.7 AE 73.4 pg/mL vs. 13.3 AE 9.2 pg/mL; P < 0.01). Moreover, the sNfL concentration positively correlated with neurological severity scores and with acute and chronic brain damage based on the neuroimaging scale. Conclusions: Neurofilament light chain concentrations may be used as a marker of brain injury in Wilson's disease, in addition to the clinical and neuroimaging disease severity scales.

Background In Wilson’s disease (WD), early neurological deterioration after treatment initiation is associated with poor outcomes; however, data on this phenomenon are limited. Our study analysed the frequency and risk factors of early neurological deterioration in WD. Methods Early neurological deterioration, within 6 months from diagnosis, was defined based on the Unified Wilson’s Disease Rating Scale (UWDRS): any increase in part II or an increase of ≥ 4 in part III. In total, 61 newly diagnosed WD patients were included. UWDRS scores, brain magnetic resonance imaging (MRI) scores, copper metabolism parameters, treatment type and serum neuro-filament light chain (sNfL) concentrations at diagnosis were analysed as potential risk factors of early deterioration. Results Early neurological deterioration was observed in 16.3% of all WD patients; all cases of worsening occurred in the neurological phenotype (27.7%). Higher scores were seen in those who deteriorated compared with those who did not for UWDRS part II (4.3 ± 5.0 vs 2.0 ± 5.9; p < 0.05), UWDRS part III (21.5 ± 14.1 vs 9.3 ± 16.4; p < 0.01) and MRI-assessed chronic damage (3.2 ± 1.6 vs 1.4 ± 2.2; p = 0.006); all these variables indicated the initial severity of neurological disease. Pre-treatment sNfL concentrations were significantly higher in patients who deteriorated compared with those who did not (33.2 ± 23.5 vs 27.6 ± 62.7 pg/mL; p < 0.01). In univariate logistic regression amongst all patients, chronic damage MRI scores, UWDRS part III scores and sNfL concentrations predicated early deterioration. In the neurological WD, only sNFL were a significant predictor. In bivariate logistic regression amongst all patients, sNfL remained the only significant predictor of deterioration when corrected for MRI scores. Conclusion sNfL concentrations are a promising biomarker of the risk of early neurological deterioration in WD.

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Introduction Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson’s disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors. Methods Using PRISMA guidelines, a systematic review of available data on early neurological deteriorations was performed by searching the PubMed database and reference lists. Random effects meta-analytic models summarized cases of neurological deterioration by disease phenotype. Results Across the 32 included articles, 217 cases of early neurological deterioration occurred in 1512 WD patients (frequency 14.3%), most commonly in patients with neurological WD (21.8%; 167/763), rarely in hepatic disease (1.3%; 5/377), and with no cases among asymptomatic individuals. Most neurological deterioration occurred in patients treated with d-penicillamine (70.5%; 153/217), trientine (14.2%; 31/217) or zinc salts (6.9%; 15/217); the data did not allow to determine if that reflects how often treatments were chosen as first line therapy or if the risk of deterioration differed with therapy. Symptoms completely resolved in 24.2% of patients (31/128), resolved partially in 27.3% (35/128), did not improve in 39.8% (51/128), with 11 patients lost to follow-up. Conclusions Given its occurrence in up to 21.8% of patients with neurological WD in this meta-analysis of small studies, there is a need for further investigations to distinguish the natural time course of WD from treatment-related early deterioration and to develop a standard definition for treatment-induced effects.

Background and purposeWilson's disease (WD) is a rare autosomal recessive disorder causing excessive copper deposition and a spectrum of manifestations, particularly neurological and hepatic symptoms. We analysed the clinical characteristics of patients with WD admitted to the country's only reference centre, which provided long‐term care to most adult patients in Poland over seven decades (pre‐1959 to 2019).MethodsElectronic prospective data collection began in the 2000s and, for prior years, medical records were analysed retrospectively. Demographic and clinical characteristics, treatment and outcomes were analysed by decade of diagnosis. Life‐years lost were estimated in patients with WD compared with the general population. Kaplan–Meier curves were used for a time‐to‐death analysis using 2000–2009 as a reference.ResultsIn total, 929 patients were analysed. The number of patients increased from 21 before 1959 to 315 for 2000 to 2009 period. Mostly males were diagnosed before the 1990s, but the numbers of female patients diagnosed increased thereafter. Initially, most patients presented with neurological manifestations; however, the incidence of hepatic manifestations and asymptomatic presentations increased over time as patients were diagnosed early and consequently were more independent at diagnosis. Fewer Kayser‐Fleischer rings were detected recently. Prior to 1970, patients were treated with D‐penicillamine (DP); however, since the introduction of zinc, both therapies have been used as often. Since the 1990s, switches between DP and zinc were recorded in 6%–7% of patients. Consistent improvement in survival has been observed over the years.ConclusionsThis is the largest cohort of patients with WD reported in Poland, with the longest follow‐up. Earlier diagnosis and prognosis have improved over seven decades.