Chronic uncontrolled seizure activity was linked to specific positional changes of the X chromosome in neurons of cortical seizure foci from both male and female patients at Yale University School of Medicine, New Haven, Connecticut. In normal female neurons, X homologs were typically either on the nucleolus or on the nuclear membrane, whereas one or both X chromosome signals were moved interiorly in seizure foci of 2 representative female patients. There was a gradient of X positional changes spreading from the seizure focus toward normal surrounding cortex. In seizure foci there was a decrease of 25% in membrane plus nucleolar signal neurons compared to more normal specimens, and a concomitant increase of 27% of cells with interior signals in seizure foci. These X chromosome movements were limited to epileptic foci and were not simply the consequence of generalized seizure activity. 
COMMENT. Specifically altered nuclear patterns may become established and create the genetic memory for intractable seizures. These changes in chromosome arrangements may be caused by various lesions, including trauma, developmental abnormalities, and toxic factors. These studies provide a new approach to the mechanism of kindling, based on structural rearrangements of the X chromosome rather than functional alterations of the neuronal membrane and synapses.