Idiopathic generalized epilepsy - Lack of significant microdysgenesis

Background: The idiopathic generalized epilepsies (IGE) are classically reg arded as due to a functional abnormality. However, microscopic microdysgene tic changes have been reported in the majority of cases by one group. Objec tive: To independently evaluate the microscopic microdysgenetic changes in a controlled, blinded study. Methods: Five brains with IGE and five age-mat ched control brains were collected. Blocks were taken from nine standardize d Brodmann areas, both hippocampi, and cerebellum. Slides were examined ind ependently by two neuropathologists blinded to patient group, who qualitati vely scored microdysgenetic features on standardized data sheets. The resul ts were compared and any discrepancies were rescored by the pathologists to gether using a double-header microscope. Quantitative neuronal profile coun ts in the molecular layer in standardized Brodmann areas of frontal cortex and in deep frontal white matter were performed. Results: Microdysgenetic f eatures in nine Brodmann areas, hippocampi, and cerebellum were not increas ed in brains from subjects with IGE compared with control brains. Quantitat ive neuronal profile counts in the molecular layer of frontal cortex and de ep frontal white matter were not increased in IGE compared with controls. C onclusions: This controlled, blinded study did not replicate the results of previous reports of microdysgenesis in IGE. Although factors such as syndr ome heterogeneity and sample size may explain the discrepancy, technical fa ctors could also play a role. The current ion channel hypothesis for the pa thogenesis of IGE does not preclude microscopic or ultramicroscopic abnorma lities and the search for these should continue.