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.