Aetiopathogenesis of infantile epileptic spasms syndrome and mechanisms of action of adACTH/corticosteroids in children: A scoping review

Infantile epileptic spasms syndrome (IESS) is a rare disorder causing seizures in infancy, known as epileptic spasms. Doctors know of some causes (such as a stroke), but often no clear cause is found, and they do not understand what changes within the body to cause IESS. IESS is also different to other seizure disorders as the main treatments are steroids or adrenocorticotrophin hormone (ACTH). It is not clear how steroids/ACTH work to stop seizures or if they reverse changes that caused IESS.

In this review, we summarize studies on IESS in children looking at its causes and how steroids/ACTH work. We found over 120 studies and identified five main ideas: (1) changes to gene function; (2) stress system overactivation; (3) inflammation; (4) altered communication between nerve cells; and (5) cellular energy use. The evidence supporting these ideas was limited in most studies, which made it difficult to make clear conclusions. Researchers think that these ideas overlap and interact with each other, i.e. stress affecting gene function. This also explains the variability within IESS and why treatment responses are different in some children.

We suggest future studies compare typically developing children to those who have IESS. This could show differences at the cellular level and in body pathways, revealing how steroids/ACTH might work to change these processes. The long-term goal is ‘precision medicine’, personalizing treatment for each child to improve their well-being.