Epilepsy with myoclonus and post-natal development of the motor system in humans: a hypothesis

Epilepsy with myoclonus is thought to be linked to the motor system. At birth, development of the central nervous system in humans is far from being achieved. Post-natal changes take place at different levels in this neuronal system. These modifications suggest that the motor cortex is a highly dynamic structure during post-natal development. They may account for the age-dependence of various epileptic syndromes. (1) The number of synapses increases during the early post-natal years and then decreases to reach the adult level around puberty. (2) Neurons differentiate and synthesize various neurotransmitters. (3) Dendrites grow actively and participate in the formation of local cortical circuits. (4) Electrophysiological properties of cortical neurons change during the first months of rodent development. This could reflect modifications of the ion channels present in the cell membrane. (5) The pyramidal tract myelinate and exuberant collaterals are selectively removed. These two processes are dependent on neuronal electrical activity. It has been demonstrated that selective collateral stabilization is promoted by glutamate release and stimulation of the N-methyl-D-aspartate (NMDA) receptor. So, seizures occurring during the neonatal period may interact with these normal developmental features. Furthermore, neuronal electrical activity and seizures stimulate the transcription of specific messenger RNAs coding for neurotrophic factors like nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). The overproduction of neurotrophic factors leads to maldevelopment of the cortex.