TREATMENT OF WILSON DISEASE WITH AMMONIUM TETRATHIOMOLYBDATE .2. INITIAL THERAPY IN 33 NEUROLOGICALLY AFFECTED PATIENTS AND FOLLOW-UP WITH ZINC THERAPY

Objective: To test the efficacy and toxic effects of ammonium tetrathi omolybdate in the initial treatment of a relatively large series of pa tients with neurologic symptoms and signs caused by Wilson disease. Tw o key aspects of efficacy are to preserve the neurologic function pres ent at the onset of therapy and to maximize the opportunity for long-t erm recovery. Design: An open study of 33 patients treated for 8 weeks each, including further follow-up data on the original 17 patients. N eurologic function was evaluated by frequent quantitative neurologic a nd speech pathology examinations. Several copper-related variables wer e studied to evaluate the effect of the drug on copper, and several bi ochemical and clinical variables were studied to evaluate potential to xic effects. Patients were then followed up at yearly intervals, with follow-up periods of 1 to 8 years reported. Setting: A university hosp ital referral setting. Intervention: Patients were generally treated f or 8 weeks with tetrathiomolybdate, followed by zinc maintenance thera py. Main Outcome Measures: Neurologic function was evaluated by quanti tative neurologic and motor speech examinations and magnetic resonance imaging scans of the brain. Results: During the 8 weeks of tetrathiom olybdate administration, only 1 of the 33 patients showed deterioratio n in neurologic function. Copper status and potential further toxic ef fects were generally well controlled quickly. Evaluation of data from individual patients revealed evidence of a toxic side effect in only 1 patient, who exhibited reversible anemia. During the ensuing period o f follow-up of 1 to 6 years, neurologic recovery in most patients was good to excellent. Conclusions: Tetrathiomolybdate appears to be an ex cellent form of initial treatment in patients with Wilson disease who present with neurologic symptoms and signs. In contrast to penicillami ne therapy, initial treatment with tetrathiomolybdate rarely allows fu rther, often irreversible, neurologic deterioration.