Adrenocorticotropic hormone therapy for infantile spasms alters pyruvate metabolism in the central nervous system

To clarify the mechanism of action of adrenocorticotropic hormone (ACTH) in treating infantile spasms, we evaluated the effects of ACTH on the metabolism of pyruvate in the central nervous system (CNS) of children with infantile spasms. We measured the levels of lactate and pyruvate in cerebrospinal fluid (CSF) and serum, before and during ACTH treatment in 12 children with infantile spasms. We evaluated statistically any correlation between the observed metabolic changes and the clinical response of ACTH. ACTH therapy significantly elevated the levels of lactate and pyruvate in the CSF and serum. The effect was not dose-dependent. During ACTH therapy, the serum levels of lactate and pyruvate and the ratio of lactate to pyruvate (L:P ratio) were unrelated to these levels in CSF. Patients who showed a good initial response to treatment had a significantly higher CSF level of pyruvate and a lower L:P ratio during therapy than did those with a poor initial response. This is the first report that ACTH therapy administered for infantile spasms alters pyruvate metabolism in the CNS. This metabolic change may be involved in part in the action of ACTH in relieving infantile spasms.