Widespread neocortical abnormalities in temporal lobe epilepsy with and without mesial sclerosis

Center for Imaging of Neurodegenerative Diseases and Department of Radiology, University of California, San Francisco, CA 94121, USA.
NeuroImage (Impact Factor: 6.36). 03/2009; 46(2):353-9. DOI: 10.1016/j.neuroimage.2009.02.020
Source: PubMed


Extrafocal structural abnormalities have been consistently described in temporal lobe epilepsy (TLE) with mesial temporal lobe sclerosis (TLE-MTS). In TLE without MTS (TLE-no) extrafocal abnormalities are more subtle and often require region of interest analyses for their detection. Cortical thickness measurements might be better suited to detect such subtle abnormalities than conventional whole brain volumetric techniques which are often negative in TLE-no. The aim of this study was to seek and characterize patterns of cortical thinning in TLE-MTS and TLE-no.
T1 weighted whole brain images were acquired on a 4 T magnet in 66 subjects (35 controls, 15 TLE-MTS, 16 TLE-no). Cortical thickness measurements were obtained using the FreeSurfer software routine. Group comparisons and correlation analyses were done using the statistical routine of FreeSurfer (FDR, p=0.05).
TLE-MTS and TLE-no showed both widespread temporal and extratemporal cortical thinning. In TLE-MTS, the inferior medial and posterior temporal regions were most prominently affected while lateral temporal and opercular regions were more affected in TLE-no. The correlation analysis showed a significant correlation between the ipsilateral hippocampal volume and regions of thinning in TLE-MTS and between inferior temporal cortical thickness and thinning in extratemporal cortical regions in TLE-no.
The pattern of thinning in TLE-no was different from the pattern in TLE-MTS. This finding suggests that different epileptogenic networks could be involved in TLE-MTS and TLE and further supports the hypothesis that TLE-MTS and TLE-no might represent two distinct TLE syndromes.

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Available from: Susanne G Mueller, Jan 20, 2014
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    • "In the current study, the multivariate analysis of variance also showed significant impairment of inhibitory control in patients with TLE and in patients with OLE, as compared to controls. Such findings are in line with previous studies (Corcoran & Upton, 1993; Hermann, Seidenberg, Lee, Chan, & Rutecki, 2007; Horner, Flashman, Freides, Epstein, & Bakay, 1996; Kim, Lee, Yoo, Kang, & Lee, 2007) and indirectly support the idea that occurrence of executive dysfunction in both epileptic disorders might be due to a widespread cortical or subcortical involvement beyond the lobe from which the seizures arise (Dabbs, Jones, Seidenberg, & Hermann, 2009; Mueller et al., 2009; Riley, Moore, Cramer, & Lin, 2011). However, the lack of any correlation of dysexecutive scores with the two factors identified by the discriminant analysis would suggest that these cognitive impairments are not specific of either TLE or OLE. "
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    ABSTRACT: Objective: To compare cognitive profiles of occipital lobe epilepsy (OLE) and temporal lobe epilepsy (TLE) and to investigate whether impairment of visuospatial functions is a specific deficit of OLE. Method: Eighteen patients with OLE, 18 patients with TLE, and 18 controls underwent a neuropsychological battery assessing memory, visuospatial functions, and frontal/executive functions. Results: Multivariate analysis evidenced poorer performance of patients with TLE and patients with OLE relative to controls on tasks assessing verbal and non-verbal long-term memory, frontal functions, and visuospatial functions. Patients with OLE had poorer performance than patients with TLE on visuospatial tasks, whereas patients with TLE performed worse than patients with OLE on verbal long-term memory test. Discriminant analysis identified two canonical discriminant functions: The first explained 53.3% of the variance, and the second explained 46.7% of the variance. The first function included verbal and non-verbal memory tests distinguishing controls from both OLE and TLE, whereas the second factor including a visuoconstructional test distinguished OLE from TLE and controls. Conclusions: The results demonstrate that visuoconstructional dysfunction is related to OLE and support the idea that alterations of occipito-parietal stream may be specific to patients with OLE.
    Full-text · Article · Sep 2015 · Journal of Neuropsychology
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    • "In contrast, when comparing post-to pre-surgery GM status, we found a relative gain in volume in multiple regions in the GO but not in the PO patients. Most of the regions showing gain were located in the contralateral (non-resected) frontal and temporal lobes, suggesting that these changes were not directly caused by the resection (Mueller et al., 2009), but other mechanisms involved in seizure control. It is important to note that the controls did not show any significant GM volume change or gain, when comparing data across the scanning sessions, noting that the time interval between this group3s scans and the interval between pre-and postsurgical scans for the patients did not differ. "
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    ABSTRACT: Voxel-based morphometry Refractory temporal lobe epilepsy Frontal GM abnormalities Brain surgery Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre-and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.
    Full-text · Article · Aug 2015 · Clinical neuroimaging
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    • "Structural covariance analysis may detect manifestations of persistent functional–trophic crosstalk, maturational interchange, as well as common developmental and pathological influences [48,52–57]. In TLE, several covariance analyses have mapped abnormal structural correlations between mesiotemporal and neocortical regions [25] [32] [58], between thalamic and neocortical regions [30] [59], and within corticocortical networks [59]. "
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    ABSTRACT: Recent years have witnessed a paradigm shift in the study and conceptualization of epilepsy, which is increasingly understood as a network-level disorder. An emblematic case is temporal lobe epilepsy (TLE), the most common drug-resistant epilepsy that is electroclinically defined as a focal epilepsy and pathologically associated with hippocampal sclerosis. In this review, we will summarize histopathological, electrophysiological, and neuroimaging evidence supporting the concept that the substrate of TLE is not limited to the hippocampus alone, but rather is broadly distributed across multiple brain regions and interconnecting white matter pathways. We will introduce basic concepts of graph theory, a formalism to quantify topological properties of complex systems that has recently been widely applied to study networks derived from brain imaging and electrophysiology. We will discuss converging graph theoretical evidence indicating that networks in TLE show marked shifts in their overall topology, providing insight into the neurobiology of TLE as a network-level disorder. Our review will conclude by discussing methodological challenges and future clinical applications of this powerful analytical approach. Copyright © 2015 Elsevier Inc. All rights reserved.
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