ABSTRACT
Introduction
Infantile spasm (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 Ca2+ conductance are some of the possible pathophysiological mechanisms. Animal 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 a combination of ACTH and vigabatrin seems to be associated with better long-term outcomes. Despite the increasing knowledge about the etiology and pathophysiology of IS, in the last years, no new treatment 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.
Article highlights
Infantile spasms represent a severe, age-dependent condition that is associated with acute and long-term neurological morbidity.
Different animal models have been developed, though most have only some of the features typical of infantile spasms.
Three main treatments are considered ‘standard’ for IS: ACTH, oral steroids (prednisolone), and vigabatrin, and combination of ACTH and vigabatrin seem to provide the best long-term outcome.
Infantile spasms represent a condition that requires a targeted therapeutic approach that might be able to modify the underlying neurobiological process, in order to improve the overall outcome.
Acknowledgments
The authors would like to thank Dr. David Macari for the English editing of the final version of the manuscript.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Disclosure
N Specchio has received funding from Biomarin and Livanova. N Pietrafusa and F Vigevano have recieved funding from Zogenix, Biomarin, and P Curatolo has received funding from Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.