Abstract

Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning.

Highlights

  • Mesial temporal lobe epilepsy (TLE) is the most common form of focal epilepsy, and is characterized by seizure focus in the mesial temporal lobe from where it can spread into other neocortical regions

  • In this work we investigate two models describing the dynamics of epilepsy

  • The purpose of this work is to develop network theoretic models of regional atrophy dynamics resulting from each of the above hypotheses, and to statistically determine which model is a better descriptor of the spatial patterning of real

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Summary

Introduction

Mesial temporal lobe epilepsy (TLE) is the most common form of focal epilepsy, and is characterized by seizure focus in the mesial temporal lobe from where it can spread into other neocortical regions. Based on their aspect on the structural MRI and histopathology, two subtypes of TLE are distinguished. One that is characterized by prominent hippocampal atrophy or mesial-temporal sclerosis (TLE-MTS) and one where the hippocampus appears completely normal (TLE-no) In both cases, new morphometric analysis using MRI shows consistent evidence of extra-hippocampal and extratemporal atrophy [1,2,3,4,5,6]. In most cases damaged regions tend to be functionally and anatomically connected to the hippocampus and other medial temporal structures [3, 11,12,13]

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