Penicillamine neurological symptoms

Data on zinc in the treatment of Wilson disease are derived from uncontrolled studies using different zinc preparations (zinc sulfate, zinc acetate) at different doses (75-250 mg d ) (Ferenci, 1997). The efficacy of zinc was assessed by four different approaches. First, patients successfully decoppered by d-penicillamine were switched to zinc and the maintenance of their asymptomatic condition was monitored. Most patients maintained a negative copper balance and no symptomatic recurrences occurred. Some patients, however, died of liver failure after treatment was switched to zinc. Stremmel observed the occurrence of severe neurological symptoms in a 25 year old asymptomatic sibling 4 months after switching from d-penicillamine to zinc (Ferenci, 1997). 

The Second group of symptomatic patients switched to zinc as alternate treatment due to intolerance to D-penicillamine. Sixteen case histories have been published so far. Liver function and neurological symptoms improved in three and five patients, respectively. One patient further deteriorated neurologically and... 

If a decoppering agent is used for treatment, the compliance can be tested by repeated measurements of the 24 h urinary copper excretion. This approach is not useful if patients are treated with zinc. The dose of d-penicillamine can be lowered if in a compliant patient urinary copper excretion decreases over time and stabilizes at < 500 p g/day. Efficacy of treatment can be monitored by the determination of free copper in serum, and depending on the presenting symptoms. Liver disease can be assessed by routine liver function tests. Repeated liver biopsies with measurement of hepatic copper content are not helpful. Improvement of neurological symptoms can be documented by clinical examination or by auditory evoked brainstem potentials. In addition, some of the MRI abnormalities are fully reversible on treatment. 

Nervous system Initial worsening of neurological symptoms in patients with Wilson s disease after the start of treatment with copper chelators such as penicillamine is an established clinical problem. In such patients ammonium tetrathiomolybdate can be effective and neurological worsening... 

It is indicated to prevent and treat isoniazid, hydralazine, penicillamine and cycloserine induced neurological disturbances, mental symptoms in women on oral contraceptives, pyridoxine responsive anaemia and homocystinuria, morning sickness and hyperemesis gravidarum, convulsions in infants and children. 

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