Pathophysiology of massive infantile spasms: perspective on the putative role of the brain adrenal axis.
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 suppressed by ACTH/steroids, is implicated. Evidence for the age-specific convulsant properties of CRH is presented, and a putative scenario in which a stress-induced enhancement of endogenous CRH-mediated seizures is discussed. Clinical testing of the CRH-excess theory and its therapeutic implications are suggested.
Department of Neurology, University of Southern California, Los Angeles.
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Baram
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007223:Infant; D013036:Spasms, Infantile / Q000378:metabolism / Q000503:physiopathology*
D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone