The effects of adrenocorticotrophin hormone (ACTH) in 23 children with intractable epilepsies and its mechanism of action are reported from the Department of Paediatric Neurology, Royal Hospital for Sick Children, Edinburgh, UK. Patients ranged in age from 8 months to 9 years. The epileptic syndrome diagnoses were West syndrome in 5, Lennox-Gastaut in 7, Landau-Kleffner in 6, and unclassified in 4. The EEG showed generalized electrical status in 16 and focal status in 5. Initial treatment with diazepam (0.2 mg/kg) showed a positive electrophysiologic response in 17 patients, all of whom subsequently responded to ACTH. ACTH 0.5 mg daily for 2 weeks abolished seizures completely in 9 and reduced seizure frequency in 10. Epileptic discharges in the EEG were also abolished in 15 after ACTH. The mechanism of action proposed is independent of the effect on the adrenal, similar to that of benzodiazepines, not restricted to infantile spasms, and is probably related to the production of neurosteroids and extracellular adenosine in the brain, which modulate the GABA receptor. 
COMMENT. Evidence that ACTH may be effective in the treatment of intractable epilepsies of various patterns and syndromes, not restricted to infantile spasms, is further supported by this study. Antiepileptic effects in children with Lennox Gastaut and Landau Kleffner syndromes have been well documented in previous reports. ACTH effectiveness in children with status absence epilepsy and generalized tonic-clonic seizures refractory to AEDs has also been reported . Hypsarrhythmia is not a sine qua non for ACTH therapy. (Progress in Pediatric Neurology II. 1994:102).
ACTH and experimental seizures in adrenalectomized animals. Laboratory studies at the Division of Neurology, Children’s Memorial Hospital, Chicago, in 1965, demonstrated a reduction in the seizure threshold following adrenalectomy and in both intact and adrenalectomized young rats, following ACTH. Measurements of brain and plasma electrolytes showed that the reduced seizure threshold was correlated with an increase in the concentration of intracellular sodium in the brain. The ACTH effects on seizure threshold and brain sodium were independent of the adrenal. Animals with seizure thresholds experimentally lowered by methods other than adrenalectomy might demonstrate the anticonvulsant effect of ACTH observed clinically.