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.

The human brain is a tremendously complex and still enigmatic three-dimensional structure, composed of countless interconnected neurons and glia. The temporal evolution of the brain throughout life provides a fourth dimension, one that influences every element of the brain's function in health and disease. This temporal evolution contributes to the probability of seizure generation and to the type and the nature of these seizures. The age-specific properties of the brain also influence the consequences of seizures on neuronal structure and behavior. These, in turn, govern epileptic activity and cognitive and emotional functions, contributing to the diverse consequences of seizures and epilepsy throughout life.

Model of Infantile Spasms Induced by N-methyl-D-aspartic Acid in Prenatally Impaired Brain. Velisek L, Jehle K, Asche S, Veliskova J. Ann Neurol 2007;61(2):109–119. OBJECTIVE: Infantile spasms (a catastrophic epileptic syndrome of childhood) are insensitive to classic antiepileptic drugs. New therapies are limited by lack of animal models. Here we develop a new model of flexion spasms based on prenatal exposure to betamethasone combined with postnatal administration of N-methyl-D-aspartic acid (NMDA) and determine brain structures involved in the induction of flexion spasms. METHODS: Pregnant rats received two doses of betamethasone on day 15 of gestation. Offspring was injected with NMDA on postnatal day 15. Effects of adrenocorticotropin therapy on the development of age-specific flexion spasms were determined and electroencephalographic correlates recorded. C-fos immunohistochemistry and [14C]2-deoxyglucose imaging identified brain structures involved in the development of flexion spasms. RESULTS: Prenatal betamethasone exposure sensitizes rats to development of NMDA-induced spasms and, most importantly, renders the spasms sensitive to adrenocorticotropin therapy. Ictal electroencephalogram results correspond to human infantile spasms: electrodecrement or afterdischarges were observed. Imaging studies defined three principal regions involved in NMDA spasms: limbic areas (except the dorsal hippocampus), hypothalamus, and the brainstem. INTERPRETATION: Despite certain limitations, our new model correlates well with current infantile spasm hypotheses and opens an opportunity for development and testing of new effective drugs.