Pathophysiology of massive infantile spasms: Perpective on the putative role of the brain adrenal axis

Abstract

Massive infantile spasms are an age‐specific seizure syndrome of infancy. Uniquely, the spasms respond to hormonal manipulation using adrenocorticotropic hormone(ACTH) or glucocorticoids. A hypothesis explaining the efficacy of hormonal therapy, age ‐specificity, multiple causative factors, and spontaneous resolution of infantile spasms is presented. Corticotropin‐releasing hormone(CRH), an excitant neuropeptide supressed by ACTH/Steroids, is implicated. Evidence for the age‐specific vonvulsant properties of CRH is presented, and a putative secenario in which a stressinduced enhancement of endogenous CRH‐mediated seizures is discussed. Clinical resting of the CRH‐Excess theory and its therapeutic implication are suggested.