ABSTRACT
The clinical courses, cerebrospinal fluid (CSF) and serum copper concentrations and urinary copper excretions under different schemes of drug treatment in four patients with cerebral manifestations of Wilson's disease were monitored over 6-11 years. CSF copper concentration measurements were performed from the beginning of therapy onwards in three patients and from 16 months after initial treatment onwards in the fourth. CSF copper levels decreased slowly over the years in parallel with clinical improvements, and increased in one patient who interrupted therapy for 2 years. These findings confirm our hypothesis that the concentration of copper in the CSF is a valuable quantitative parameter reflecting the normalization of copper in the brain. Copper measurements during phases of initial neurological deterioration in two patients receiving D-penicillamine, and in one patient receiving D-penicillamine and zinc sulphate, revealed decreased free serum copper and CSF copper levels.
Subject(s)
Brain/metabolism , Chelation Therapy , Copper/cerebrospinal fluid , Hepatolenticular Degeneration/cerebrospinal fluid , Penicillamine/therapeutic use , Sulfates/therapeutic use , Zinc Compounds/therapeutic use , Adult , Ceruloplasmin/analysis , Chelation Therapy/adverse effects , Copper/analysis , Female , Hepatolenticular Degeneration/drug therapy , Hepatolenticular Degeneration/psychology , Humans , Male , Neurocognitive Disorders/etiology , Penicillamine/adverse effects , Zinc SulfateABSTRACT
In five patients with cerebral manifestation of Wilson's disease, copper was measured in CSF, serum, urine and liver, and ceruloplasmin was determined in CSF and serum. CSF copper was found to be elevated in all cases, especially in the four examined before therapy. Two patients were followed up for a period of 3 years, while undergoing therapy with chelating substances. In case 1, the data and the clinical course are presented in detail: prior to therapy, the daily urinary copper excretion had been elevated, and this increased during the initial treatment stages. The serum copper concentration, which was already low, decreased quickly the during the initial stages of therapy, and remained at a low level during further treatment. In contrast to its level in serum, the copper level in the CSF was up to 3-fold the normal range and fell only very slowly as clinical symptoms improved. These findings suggest transport of copper from the CNS to the CSF. The copper concentration in CSF appears to be a valuable parameter for diagnosis and monitoring therapy in patients with cerebral manifestation of Wilson's disease.