Reorganization of Parvalbumin Immunopositive Perisomatic Innervation of Principal Cells in Focal Cortical Dysplasia Type IIB in Human Epileptic Patients.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. As several studies have revealed, the abnormal functioning of the perisomatic inhibitory system may play a role in the onset of seizures. Therefore, we wanted to investigate whether changes of perisomatic inhibitory inputs are present in FCD. Thus, the input properties of abnormal giant- and control-like principal cells were examined in FCD type IIB patients. Surgical samples were compared to controls from the same cortical regions with short postmortem intervals. For the study, six subjects were selected/each group. The perisomatic inhibitory terminals were quantified in parvalbumin and neuronal nuclei double immunostained sections using a confocal fluorescent microscope. The perisomatic input of giant neurons was extremely abundant, whereas control-like cells of the same samples had sparse inputs. A comparison of pooled data shows that the number of parvalbumin-immunopositive perisomatic terminals contacting principal cells was significantly larger in epileptic cases. The analysis showed some heterogeneity among epileptic samples. However, five out of six cases had significantly increased perisomatic input. Parameters of the control cells were homogenous. The reorganization of the perisomatic inhibitory system may increase the probability of seizure activity and might be a general mechanism of abnormal network activity.

Investigation of synapses in the cortical white matter in human temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.