Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy

The underlying cause of neocortical involvement in temporal lobe epilepsy ( TLE) remains a fundamental and unanswered question. Magnetic resonance imag ing has shown a significant loss in temporal lobe volume, and it has been p roposed that neocortical circuits are disturbed functionally because neuron s are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of pa tients with or without hippocampal sclerosis (HS). Results provide the surp rising finding that TLE patients have significant atrophy of neocortical gr ay matter but no loss of neurons. Neurons are also significantly larger, de ndritic trees appear sparser, and spine density is noticeably reduced in TL E specimens compared with controls. The increase in neuronal density we fou nd in TLE patients is therefore attributable to large neurons occupying a m uch smaller volume than in normal brain. Neurons in the underlying white ma tter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects H S and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not se condary to cell loss. In both gray and white matter, neuronal hypertrophy m eans more perikaryal surface area is exposed for synaptic contacts and emer ges as a hallmark of this disease.