Objective: To study the pattern of neurological worsening (NW) in patients undergoing treatment for Wilson disease (WD).

Background: WD is an inherited disorder of copper metabolism. Treatment involves copper chelation and can reverse neurological disability and prevent disease-related mortality. However, some patients develop worsening of neurological signs during treatment. This can be drug-induced, or due to non-compliance, disease progression, intercurrent illnesses or emergent psychosis.^a,b

Methods: From 2005-2016 we prospectively recruited 120 consecutive patients visiting our Wilson Disease Clinic and tracked their neurological disability during treatment using Tier 2 of the Global Assessment Scale for Wilson disease (GAS for WD).^b All received penicillamine (125-2000mg/day) except for 5 who were on trientine (300-1800mg/day).

Results: Among the 120 patients (72 male; 48 female) we observed 64 instances of NW in 44 patients (30 male). The earliest signs of NW were irritability, or worsening of dysarthria, Wilson’s facies or Kayser-Fleischer rings. Non-compliance with treatment was the commonest cause and was seen in 16 patients during the early intensive phase of copper chelation and in 18 patients during the maintenance phase. Most of these patients defaulted on treatment multiple times. Drug-induced NW was seen in 12 patients; 11 on penicillamine (mean dose 900mg; range 750-1750mg) and 1 on trientine (900mg). The time between initiation of treatment and NW varied widely (mean 2.8 months; range 0.5-14 months). In 10 patients such worsening was reversible over an average period of 1.2 months (range 0.5-4 months) with brief down-titration of the drug. However, in 2 it led to long term disability. NW due to disease progression was seen in 4 patients in the first few months of treatment initiation and improved with ongoing copper chelation. Emergent psychosis and intercurrent illnesses accounted for 11 and 3 cases of NW, respectively. These also improved with continued chelation.

Conclusions: NW is seen over one-third of the patients undergoing treatment for WD with non-compliance being the most common cause. Monitoring neurological disability using GAS for WD scale enables one to detect such worsening, identify its cause, and respond appropriately (by encouraging compliance, down-titrating the dose, or continuing treatment course).

References: ^a  Aggarwal A, Bhatt M. The pragmatic treatment of Wilson’s disease. Movement Disorders Clinical Practice 2014;1:14-23

^b Aggarwal A, Aggarwal N, Nagral A, Jankharia G, Bhatt M. A novel Global Assessment Scale for Wilson’s disease (GAS for WD). Mov Disord 2009;24:509–518.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurological-worsening-in-patients-undergoing-treatment-for-wilson-disease-frequency-causes-and-outcomes/