Rewiring motivation: a landmark case of transplant-induced recovery from chronic apathy in Wilson’s disease

Introduction

Wilson’s disease (WD) is a rare autosomal recessive disorder characterized by impaired copper metabolism and toxic accumulation in the liver and brain. Although classically associated with hepatic and neurological manifestations, psychiatric symptoms are increasingly recognized as core features of its clinical spectrum. These symptoms may precede or overshadow somatic involvement, contributing to diagnostic delay and therapeutic challenges. The longitudinal course of neuropsychiatric manifestations and the reversibility of severe, treatment-resistant syndromes remain poorly understood.

Liver transplantation (LT) is the standard treatment for WD with acute or end-stage liver failure. However, its role in patients with predominant neuropsychiatric symptoms remains controversial. Clear criteria guiding transplantation in this subgroup are lacking, and outcomes across varying neuropsychiatric presentations are not well established.

We report a case of a 34-year-old male with prominent psychiatric manifestations of WD who demonstrated marked clinical improvement following LT, highlighting the potential reversibility of severe neuropsychiatric dysfunction.

Case Report

A 34-year-old male with cirrhosis secondary to advanced WD was referred for evaluation of pervasive apathy, psychomotor slowing, and chronic insomnia. Psychiatric symptoms began insidiously during adolescence, initially presenting as emotional detachment, social withdrawal and anxiety. Over time, these evolved into severe and persistent syndrome characterized by profound avolition, affective flattening and progressive cognitive inefficiency, resulting in marked functional decline across social and occupational domains.

Repeated neurological examinations were unremarkable, with no evidence of extrapyramidal signs, cerebellar dysfunction, or overt hepatic encephalopathy. These findings contrasted with the severity of behavioral impairment. Multiple pharmacological treatments, including adequate trials of antidepressants, failed to produce meaningful clinical improvement.

In the context of progressive liver disease and refractory neuropsychiatric symptoms, the patient underwent LT.

The post-transplant course was marked by a rapid and profound clinical transformation. Within weeks, there was restoration of energy, normalization of sleep–wake regulation, and a striking re-emergence of intrinsic motivation. Collateral reports confirmed increased emotional expressivity, renewed social engagement, and recovery of initiative. The patient regained the capacity for sustained, goal-directed activity, alongside improved cognitive responsiveness and environmental reactivity. These improvements were robust and sustained over time, with no emergence of neurological motor abnormalities.

Conclusions

This case suggests that severe, longstanding neuropsychiatric symptoms in WD may represent a reversible neurobiological state rather than irreversible structural damage. The rapid recovery following liver transplantation supports a model in which disrupted copper metabolism exerts functionally suppressive effects on neural systems regulating motivation.

To our knowledge, this is the first report of a profound, chronic apathy syndrome in WD demonstrating sustained remission after LT. These findings underscore the importance of considering metabolic etiologies in treatment-resistant apathy, particularly with early onset and insidious progression. They also highlight the potential for targeted somatic interventions to restore higher-order psychiatric function, challenging traditional boundaries between psychiatry, neurology and hepatology.

References

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