Microdysgenesis in temporal lobe epilepsy - A quantitative and immunohistochemical study of white matter neurones

Microdysgenesis is a microscopic cortical malformation considered to act as a substrate for seizures in some patients with generalized epilepsy. It is also recognized to involve the temporal lobe in a proportion of patients w ith intractable temporal lobe epilepsy, but the incidence of this abnormali ty, its relationship to mesial temporal lobe sclerosis and relevance to epi leptogenesis remain unknown. This is partly due to a lack of well-defined q uantitative pathological diagnostic criteria. To begin to address these iss ues, we have carried out a rigorous quantitative analysis, using three-dime nsional cell counting methods, of several components of microdysgenesis in temporal lobectomy specimens. White matter, cortical and layer I neuronal d ensities (NDs) were measured using immunohistochemistry for the neuronal ma rkers neuronal nuclear antigen and calbindin D-28-K. Patients with a seizur e-free outcome (Class I) showed significantly more microdysgenetic features including higher white matter ND (P < 0.05), particularly of small (<10 mu m diameter) neurones (P < 0.01), higher layer I ND (P < 0.05) and increased numbers of Cajal-Retzius-like calbindin-positive neurones (P < 0.05). We a lso demonstrated that white matter ND was independent of the degree of temp oral lobe gliosis as assessed by quantitation of glial fibrillary acidic pr otein-immunoreactive cells. These findings suggest that microdysgenesis may be a significant lesion in temporal lobe epilepsy in terms of post-surgica l prognosis.