Neurological features of Wilson's Disease precipitated by liver tranplantation
The debate concerning the pathogenesis of neurological features in Wilson’s Disease continues. We present a case which confronts some accepted concepts, and raises other issues regarding the risks of liver transplantation for patients with Wilson’s Disease.
We review the case of a 50 year old gentleman, newly diagnosed with chronic liver disease due to Wilson’s Disease and with minimal neurological involvement. The diagnosis was based on the combination of low serum caeruloplasmin, elevated 24-hour urinary copper excretion, presence of Kayser-Fleischer rings, and compatible liver histology. Penicillamine chelation was tried for less than two weeks, but was poorly tolerated and was discontinued. An orthotopic liver was subsequently transplanted and excellent graft function was attained. However, in the weeks to months following transplantation, the patient developed extrapyramidal and frontal lobe disconnection signs characteristic of neurological Wilson’s Disease. This deterioration occurred despite evidence of biochemically normal copper metabolism. Treatment with dimercaprol (BAL, British Anti-Lewisite) and zinc sulfate has yielded no improvement at two years post transplant, and there was no symptomatic gain from levodopa for parkinsonism.
It is usual to see stabilisation or improvement of neurological symptoms following liver transplantation for Wilson’s Disease. The occurrence of profound neurological deterioration, as seen in this patient, has not previously been reported. The mechanism underlying this is uncertain, although we postulate unrestrained chelation therapy provided by the transplanted liver, in an older patient relatively naïve to ‘decoppering’ therapies. This case example supports the theory that symptomatic neurological Wilson’s Disease is due to the toxicity of free copper, rather than copper accumulation.