No abstract

Of 837 epileptics over 16 years of age treated with mono- or combined hydantoin therapy 20.3% showed radiographic signs of anticonvulsant osteomalacia. With the exception of the patients with severe disturbances of the skeletal system no positive correlation was found with duration of therapy. The percentage of moderate bone changes was the highest in the patients treated for 1 to 2 years; the percentage of severe bone changes in the group treated over 10 years. The rate of osteomalacia correlated with the total dose of hydantoin, phenobarbital, or primidone; the correlation with the dose per year was even more evident. The risk of osteomalacia rose distinctly with doses over 3000 equivalent units/year. The patients with combined hydantoin-barbiturate treatment showed a higher risk than those treated with phenytoin alone. The rate of osteomalacia was the highest in the patients aged under 20 years and over 50 years. Males showed a relatively higher rate of osteomalacia than females, they were treated however with a higher dose per year. The chemical parameters blood alkaline phosphatase and 25-hydroxycholecalciferol corresponded to the radiographic signs, whereas calcium and anorganic phosphate showed no correlation. Early routine radiologic and chemical control especially of the epileptic patients with high risk of osteomalacia should be routinely performed in future.

Of 117 patients treated with anticonvulsants reduced plasma biotin levels were found in over 80% of cases. Significant negative correlations with the average daily dose and the total amount of anticonvulsants as well as with the plasma phenytoin level were also evident. It is proposed that the lowering of biotin--which is a co-factor of the carboxylating enzyme system--is an important mechanism in mode of action of anticonvulsants. Reduced biotin levels possibly lead to an accumulation of carbon dioxide or a diminution of aspartate in brain tissue. Low biotin levels may also be the cause of some well known side effects of anticonvulsants such as cerebellar disturbances and dermatitis. In comparison to the other epileptics the patients with cerebellar symptoms showed significantly lowered plasma biotin levels.