Wilson's disease

Wilson's disease is caused by impaired biliary excretion of copper results in accumulation within organs including the brain (Pfeiffer 2016).

• Slowly progressive hepatic symptoms are a common initial manifestation with liver abnormalities appearing at an average of 11-15 years old. However, neurologic dysfunction is also a typical initial manifestation with symptom onset around 20 years of age, most commonly basal-ganglia based abnormalities (tremor, dystonia). Cerebellar dysfunction occurs in 30% of individuals (Pfeiffer 2016).
• Psychiatric dysfunction ranges from psychosis to more subtle personality change; depression is common
• Dementia is uncommon but can occur in advanced stages of disease; more common is mild cognitive impairment (Pfeiffer 2016), present in approximately 25% of patients (Litwin et al, 2018).
  • Wide range of domains can be affected, but are most frequently in the executive functioning domain (Litwin et al, 2018)
  • Cognitive dysfunction can occur in absence of cortical association or hepatic encephalopathy (Ala et al, 2007).

Diagnosis

• In patients presenting with neurologic or psychiatric dysfunction, a combination of Kayser-Fleischer rings on slit lamp examination, elevated 24-hour urinary copper, and decreased ceruloplasmin essentially confirms diagnosis
• Brain imaging demonstrates abnormalities in patients with neurological symptoms, most characteristically basal ganglia, but also frequently brainstem and thalamus. T2 hyperintensity lesions may also be found in midbrain, thalamus, pons, cerebellum, as well as cortical atrophy and white matter changes (Ala et al, 2007).

Treatment

• Treatment for neuropsychiatric presentation involves initial chelation therapy (trientine vs penicillamine) and zinc maintenance therapy (Pfeiffer 2016).
  • Most neuropsychiatric symptoms improve following treatment with anti-copper agents. There are no guidelines for treatment of psychiatric manifestations (Litwin et al, 2018).

References

Ala, A., Walker, A. P., Ashkan, K., Dooley, J. S. & Schilsky, M. L. Wilson’s disease. Lancet Lond. Engl. 369, 397–408 (2007). https://pubmed.ncbi.nlm.nih.gov/17276780/

Litwin, T. et al. Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment. Ther. Adv. Psychopharmacol. 8, 199–211 (2018). https://pubmed.ncbi.nlm.nih.gov/29977520/

Pfeiffer, R. F. Wilson Disease. Contin. Minneap. Minn 22, 1246–1261 (2016). https://pubmed.ncbi.nlm.nih.gov/27495207/