Pathogenesis of infantile spasms: a model based on developmental desynchronization.

ABSTRACT

Infantile spasms is a severe epileptic encephalopathy of infancy. The fundamental cause is unknown, although a number of predisposing conditions are recognized. In this article, the authors critically review current knowledge concerning the pathophysiologic basis of infantile spasms and propose a new model based on developmental desynchronization. It is suggested that infantile spasms may result from a particular temporal desynchronization of two or more central nervous system developmental processes, resulting in a specific disturbance of brain function. The disturbance of function is postulated to be crucially dependent on an unbalanced maturational pattern, in which certain brain systems become dysfunctional owing to divergent developmental status. An important aspect of this model is the idea that disturbed function of a specific kind can result from multiple causative factors, and so can be associated with a variety of different anatomic and/or biochemical abnormalities. Thus, this concept is compatible with the observed diversity of pathologic findings and multiplicity of etiological associations observed in infantile spasms patients.