Treatment of infantile spasms: why do we know so little?

Introduction: Infantile spasms (IS) is an epileptic syndrome with typical onset within the first 2 years of life. This condition might be caused by several etiologies. IS is associated with pathological neuronal networks; however, definite hypotheses on neurobiological processes are awaited.Areas covered: Changes in NMDA and GABAB receptors and increase of Ca(2+) conductance are some of the possible pathophysiological mechanisms. Animals models can help, but most have only some features of IS. Outcome is strongly affected by etiology and the timing of treatment, which relies still on ACTH, oral steroids and vigabatrin. No significant differences in terms of efficacy have been documented, though combination of ACTH and vigabatrin seems to be associated with better long-term outcome. Despite the increasing knowledge about etiology and pathophysiology of IS, in the last years no new treatments approaches have been recognized to be able to modify the neurobiological process underlying IS. Precision medicine has far to come in IS.Expert opinion: Recently, no new therapeutic options for IS have emerged, probably due to the lack of reliable animal models and to the extreme variability in etiologies. Consequently, the outlook for patients and families is poor and early recognition and intervention remain research priorities.