Initial Treatment for CNS Wilson's Disease
The initial treatment for Central Nervous System (CNS) Wilson's disease should be chelation therapy with trientine, which is preferred over D-penicillamine due to its better safety profile, at a dosage of 750-1500 mg/day in 2-3 divided doses. 1
Treatment Algorithm for CNS Wilson's Disease
First-line therapy:
- Trientine: 750-1500 mg/day in 2-3 divided doses 1
- Better safety profile than D-penicillamine with fewer neurological deterioration cases
Alternative first-line therapy (if trientine unavailable):
- D-penicillamine: 750-1500 mg/day in 2-3 divided doses 1
- Note: Higher risk of neurological deterioration compared to trientine
For patients with decompensated cirrhosis without encephalopathy:
- Combination therapy with a chelator and zinc, separated by 5-6 hours 1
Monitoring Treatment Efficacy
Monitor 24-hour urinary copper excretion:
- Target for chelation therapy: 200-500 μg/day (3-8 μmol/day) 1
- Check every 3 months during first year of treatment
Monitor liver function tests every 3 months during first year 1
Monitor non-ceruloplasmin bound copper levels for normalization 1
Important Considerations for CNS Wilson's Disease
- Neurological deterioration is a significant concern with chelation therapy, especially with D-penicillamine 2
- Zinc therapy has fewer neurological side effects but acts more slowly than chelators 2, 3
- Tetrathiomolybdate shows promise for initial treatment of neurological patients with less risk of neurological worsening, but remains experimental 1
Dietary Management
- Avoid foods with high copper content (shellfish, nuts, chocolate, mushrooms, and organ meats) 2, 1
- Dietary management alone is insufficient and must be used alongside medical treatment 1
Adjunctive Therapy
- Antioxidants, particularly vitamin E, may have a role as adjunctive treatment due to low serum and hepatic vitamin E levels in Wilson's disease 2, 1
- However, rigorous studies supporting antioxidant use are lacking 2
Pitfalls and Caveats
- Neurological deterioration can occur with chelation therapy, particularly with D-penicillamine
- Complete blood count and regular urinalysis should be performed for all patients on chelators to monitor for side effects 1
- Gastric irritation is the main side effect of zinc therapy, occurring in approximately 10% of patients 4
- Over-treatment and induction of copper deficiency can occur with long-term therapy, which is particularly concerning in children as copper is required for growth 4
While zinc therapy is effective for maintenance treatment and presymptomatic patients with fewer neurological side effects, chelation therapy with trientine remains the preferred initial treatment for symptomatic CNS Wilson's disease due to its more rapid action in reducing copper levels and controlling neurological symptoms.