Nihal de Lanerolle

Regional Distributions of Hippocampal Na+, K+‐ATPase, Cytochrome Oxidase, and Total Protein in Temporal Lobe Epilepsy

Summary Na+, K+‐ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+, K+‐ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie‐stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump densityhnit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.

Differential Glutamate Dehydrogenase (GDH) Activity Profile in Patients with Temporal Lobe Epilepsy

Summary:  Purpose: Pathophysiologic mechanisms underlying temporal lobe epilepsy (TLE) are still poorly understood. One major hypothesis links alterations in energy metabolism to glutamate excitotoxicity associated with seizures in TLE. The purpose of this study was to determine whether changes in the activities of enzymes critical in energy and neurotransmitter metabolism contributed to the alterations in metabolic status leading to the excitotoxic effects of glutamate.

Medial temporal lobe epilepsy without hippocampal atrophy

The incidence and structural basis of nonlesional medial temporal lobe epilepsy (MTLE) without hippocampal atrophy (HA) is not known. Reports suggest that 5–15% of patients with hippocampal sclerosis (HS) do not have HA. We reviewed 57 patients with MTLE who underwent magnetic resonance imaging (MRI) volumetric studies, anteromedial temporal lobectomy (TL), and quantitative cell counts of the resected hippocampus and who had at least 1 year of surgical follow-up. We compared demographic, pathologic, and outcome data among patients with and without HA. Ten of the 57 patients did not have HA. Nine of the 10 patients had depth EEG for localization of seizure onset because of discordance or insufficient localization. Five patients had pathologic evidence of HS. Longer duration of epilepsy correlated inversely with the presence of HA. Outcome was not significantly different between patients with and without HA. We conclude that the incidence of MTLE and HS without HA is 9%. Except for duration of epilepsy, there were no differences in the clinical syndrome or surgical outcome of patients with and without HA.

Radiosurgery in Epilepsy – Pathological Considerations

Radiosurgery is being investigated as an alternative to open surgical resection for patients with medial temporal lobe epilepsy. Additionally, the biological effects of mesial temporal radiosurgery are being evaluated using several animal models. The mechanisms through which radiosurgery exerts antiepileptic effects have not yet been proven, but time and dose dependency have been repeatedly demonstrated. Thus, there is a need to carefully examine the histological changes in patients who have undergone radiosurgical treatment of epilepsy.

Metabolic injury in a variable rat model of post–status epilepticus

In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40–50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation.