Liver and Bile
J Hepatol. 2023;79(2):321–8
Neurological worsening in Wilson disease – Clinical classification and outcome
Background and aims: Prevention of neurological worsening (NW) under therapy is an unmet need in the management of Wilson disease (WD). In this study, the authors aimed to characterize the occurrence, associated outcomes and potential reversibility of NW in WD.
Methods: From a total cohort of 457 patients with WD, 128 patients with WD and neurological features at any time point (all Caucasian, 63 females, median age at diagnosis 22 years) were identified by chart review at University Hospital Heidelberg and grouped according to initial presentation. The timing and occurrence of NW was assessed following a structured clinical examination during clinical visits.
Results: Early NW (within the first 3 months of therapy) was observed in 30 out of 115 patients (26.1%) with neurological or mixed presentation and never in patients with a purely hepatic or asymptomatic presentation (0%). Late NW (after > 12 months) was seen in a further 23 patients (20%) with neurological or mixed presentation and in 13 out of 294 patients (4.4%) with a hepatic or asymptomatic presentation. The median time from start of treatment to late NW was 20 months. Only 3 patients experienced NW between 3 and 12 months. NW was observed with D-penicillamine, trientine and zinc therapy and was reversible in 15 out of 30 patients (50%) with early NW and in 29 out of 36 patients (81%) with late NW.
Conclusions: In this study, the authors identified 2 peaks in neurological worsening (NW): an early (≤ 3 months) treatment-associated peak and a late (> 12 months of treatment) adherence-associated peak. Early paradoxical NW was attributed to treatment initiation and pre-existing neurological damage, and was not observed in those with a hepatic or asymptomatic presentation. Late NW is likely to be associated with non-adherence.