Voxel-based morphometry of unilateral temporal lobe epilepsy reveals abnormalities in cerebral white matter
Introduction
The majority of traditional region-of-interest-based quantitative volumetric magnetic resonance (MR) imaging studies in temporal lobe epilepsy have focused on neural regions involved in the genesis and propagation of seizures. Volumetric abnormalities (atrophy) are evident in hippocampus Jack et al., 1992, Quigg et al., 1997, Tasch et al., 1999, Woermann et al., 1998, associated mesial temporal lobe structures including amygdala Kalviainen et al., 1997, Martin et al., 1999, fornix Kuzniecky et al., 1999, Martin et al., 1999, and entorhinal cortex (Bernasconi et al., 1999); as well as thalamus and basal ganglia (DeCarli et al., 1998). In addition, atrophy has been reported in extrahippocampal temporal lobe regions (Moran et al., 2001) and extratemporal areas such as the cerebellum Bohnen et al., 1998, Lawson et al., 2000a, Lawson et al., 2000b, Sandok et al., 2000.
Considerably fewer quantitative MR studies of temporal lobe epilepsy have examined whole brain volumes or volumes of extratemporal gray or white matter, but the findings to date suggest that abnormalities in brain structure extend well outside the neuronal networks responsible for seizure generation and propagation. Sisodiya et al. (1997) described widespread occult structural abnormalities occurring in visually normal appearing MRIs in 27 patients with hippocampal sclerosis. Marsh et al. (1997) reported significant bilateral volumetric reductions in frontoparietal regions in 14 males with temporal lobe epilepsy. Lee et al. (1998) reported reduced whole brain volume in 27 patients with temporal lobe epilepsy, and Theodore et al. (2003) recently described reduced whole brain volume in patients with temporal lobe epilepsy with a history of complex febrile convulsions.
Comparing patients with temporal lobe epilepsy (n = 58) to healthy controls (n = 62), we recently reported that significant volumetric reductions were particularly evident in cerebral white matter, both ipsilateral and contralateral to the side of temporal lobe seizure onset (Hermann et al., 2003a). Closer examination of the corpus callosum in patients with chronic temporal lobe epilepsy revealed significant volumetric reduction of this major white matter tract (Hermann et al., 2003b), as well as lower diffusion anisotropy and higher diffusivity in directions perpendicular to the axons on DTI (Arfanakis et al., 2002). However, much remains to be clarified regarding the nature and distribution of abnormalities suggested by region-of-interest-based approaches. For instance, the distribution of white matter abnormality within and between lobar regions of interest remains unclear. In addition, many specific and important gray matter structures (such as the thalamus) are not routinely quantified in standard lobar-based segmentation programs, and potential differences in the patterns of white or gray matter abnormality remain to be determined.
Voxel-based morphometry (VBM) is a technique used to examine regional morphological differences in gray or white matter between groups. Methods of VBM have been described that include an automated approach to the distribution and localization of whole-brain morphometric abnormalities that are less restricted to the limitations associated with traditional region of interest approaches (Good et al., 2001). To date, VBM studies of temporal lobe epilepsy have focused on gray matter abnormalities Keller et al., 2002a, Keller et al., 2002b, Woermann et al., 1999, and no investigation has examined the presence or distribution of abnormalities in white matter using VBM.
The purpose of this investigation is to comprehensively characterize the distribution of abnormalities in gray and white matter in patients with unilateral temporal lobe epilepsy. As will be demonstrated, abnormalities in cerebral white matter in unilateral temporal lobe epilepsy were significant, affected temporal and extratemporal regions ipsilateral to the side of seizure onset, and were equal in magnitude to abnormalities detected in gray matter.
Section snippets
Subjects
Subjects were patients with temporal lobe epilepsy (n = 25, 13 unilateral left TLE, 12 unilateral right TLE) and healthy controls (n = 62). Selection criteria for epilepsy patients included the following: (a) chronological age from 14 to 60 years, (b) complex partial seizures of unilateral temporal lobe origin demonstrated by ictal EEG monitoring of spontaneous seizures, (c) absence of MRI abnormalities other than atrophy on clinical reading, and (d) no other neurological disorder. The majority
Gray Matter
Table 2 details the regions of gray matter volume decrease that were apparent at P < 0.05, corrected for multiple comparisons across the entire search volume. Cluster size is included for reader convenience, but all inferences are drawn from voxelwise tests. Additionally, results will be discussed in relation to their voxelwise correspondence with anatomical structures. While presented in tables for completeness, results indicating volume differences of only a few voxels are difficult to
Discussion
This report confirms and extends previous findings concerning structural brain abnormalities observed in patients with unilateral temporal lobe epilepsy. In addition, an extensive degree of temporal lobe white matter abnormality is demonstrated. These findings, their implications, potential significance, and the limitations of this investigation are reviewed in the material to follow.
Acknowledgements
This study was supported by NIH NS 2RO1-37738 and NIH RO1 RR16591-02.
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