Biochemical mechanisms in pathogenesis of infantile epileptic spasm syndrome

Abstract

The molecular mechanisms leading to infantile epileptic spasm syndrome (IESS) remain obscure. The only common factor seems to be that the spasms are restricted to a limited period of infancy, during a certain maturational state. Here the current literature regarding the biochemical mechanisms of brain maturation in IESS is reviewed, and various hypotheses of the pathophysiology are put together. They include: (1) imbalance of inhibitory (NGF, IGF-1, ACTH, GABA) and excitatory factors (glutamate, nitrites) which distinguishes the different etiological subgroups, (2) abnormality of the hypothalamic pituitary adrenal (HPA) axis linking insults and early life stress, (3) inflammation (4) yet poorly known genetic and epigenetic factors, and (5) glucocorticoid and vigabatrin action on brain development, pinpointing at molecular targets of the pathophysiology from another angle. An altered maturational process may explain why so many, seemingly independent etiological factors lead to the same clinical syndrome and frequently to developmental delay. Understanding these factors can provide ideas for novel therapies.

Keywords: Brain maturation; Developmental delay; Infantile epileptic spasms syndrome; Infantile spasms; Molecular mechanisms; West syndrome.