Effect of treatment on the metabolism of tryptophan in childhood epilepsy.

In a previous paper (Hughes, Bower, Raine, and Syed, 1966) it was shown that about one-third of patients with childhood epilepsy showed, on admission, an abnormality of tryptophan metabolism characterized by a high excretion of xanthurenic acid inthe urine followingan oral load oftryptophan. This is usually accompanied by high excretion of certain other metabolites of tryptophan having in common that their metabolism is dependent upon an enzyme for which pyridoxine is an essential co-factor. The present findings extend those of an earlier study (Bower, 1961; Bower and Hughes, 1961) in which it was also shown that treatment of patients with infantile spasms with ACTH or corticosteroids (the form of therapy still favoured for this condition) resulted in a reduction in the excretion of xanthurenic acid in all cases. At that time, the effect of pyridoxine, a deficiency of which most conveniently accounted for the biochemical abnormality, had been examined in only 3 patients with somewhat equivocal results. We present further studies of the biochemical and clinical effects of pyridoxine and of corticotrophin and steroids both singly and in combination. In addition to xanthurenic acid, several other pyridoxine-dependent metabolites have been studied, and the effect on these of withdrawal of treatment for various periods has been examined. This study also gives consideration to the value of the initial xanthurenic acid excretion in response to a tryptophan load, in predicting the clinical response to the two alternative forms of therapy, pyridoxine and corticosteroids. In a small number of patients an attempt has been made to determine the smallest dose of pyridoxine or ACTH required to restore the xanthurenic acid excretion to normal. It is found that all forms of therapy reduce the excretion of xanthurenic acid and, where it was abnormal initially, restore it to normal levels. It is