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Summary: Purpose: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE.
Methods: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T1-weighted three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects.
Results: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC–Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec–Hip coupling.
Conclusions: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.
Mesial temporal lobe epilepsy (MTLE) is the most frequent type of drug-resistant TLE. It is frequently associated with hippocampal neuronal loss and gliosis, particularly in the CA1 subfield and the dentate hilus (Ammon's horn sclerosis). It is classically thought that the hippocampus is the most important structure in the generation of MTLE seizures (1). However, increasing evidence suggests that mesial temporal structures other than the hippocampus participate in seizure generation, and in particular, the entorhinal cortex (EC) (2–6). The EC is located in the medial part of the temporal lobe and plays a central role in processing high-level sensory information to the hippocampus (7). The extensive reciprocal connections between the EC, the hippocampus, and other brain areas make it a potential candidate for generation and propagation of MTLE seizures. Indeed, numerous in vitro experimental studies using hippocampal–entorhinal preparations have shown that the EC is able to generate spontaneous ictal events and that the EC may have a lower threshold for seizure generation than does the hippocampus (8–13). In addition, neuropathologic studies (14) have reported a characteristic pattern of neuropathologic change consisting of neuronal loss in layer III of the anterior portion of the EC. Recently several neuroradiologic studies (15–21) demonstrated diminution in the volume of EC ipsilateral to the epileptic side in patients with TLE. The rate of patients exhibiting a significant reduction in EC volumes ranges from 52% (18) to 96% (22).
However, the relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether the degree of atrophy of the EC, as demonstrated by quantitative magnetic resonance imaging (MRI), is correlated with the role of this structure in mesial temporal lobe seizures, particularly its tendency to generate epileptic activity and its degree of interaction with the hippocampus.
In this study, the activity of EC and hippocampus was studied by using intracerebral recordings (stereoelectroencephalography, SEEG) performed in patients with MTLE undergoing presurgical evaluation. We then used a statistical measure of SEEG signal interdependencies (also referred to as degree of “synchrony” or “association”) that provides an estimation of the degree and direction of coupling between EC and hippocampus. We made the assumption that the degree of interdependency between the EC and hippocampus SEEG activity correlates to the degree of involvement of the EC in the generation of epileptic activity, thus providing a means of quantification.
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Whatever the pathophysiologic mechanisms involved, results of this study indicate that volumetric analysis of the EC may help to predict the epileptogenic role of this structure in MTLE. The study adds futher evidence that the organization of the epileptogenic zone in MTLE can not readily be reduced to a single “focus” and that a more complex network configuration is probably responsible for the initiation of seizure activity.
However, studies including a larger population of patients are mandatory to confirm these results and to establish whether differences may be observed in these different subtypes of MTLE, particularly with regard to ultimate surgical outcome.