Temporal Lobe Epilepsy: More than Hippocampal Pathology
Authors: Cascino Gregory D. 
Published: September 2005

Voxel-based Morphometry of the Thalamus in Patients with Refractory Medial Temporal Lobe Epilepsy Bonilha L, Rorden C, Castellano G, Cendes F, Li LM Neuroimage 2005;25:1016–1021 Previous research has suggested that patients with refractory medial temporal lobe epilepsy (MTLE) show gray matter atrophy both within the temporal lobes and in the thalamus. However, these studies have not distinguished between different nuclei within the thalamus. We examined whether thalamic atrophy correlates with the nuclei's connections to other regions in the limbic system. T1-weighted MRI scans were obtained from 49 neurologically healthy control subjects and 43 patients diagnosed with chronic refractory MTLE that was unilateral in origin (as measured by ictal EEG and hippocampal atrophy observed on MRI). Measurements of gray matter concentration (GMC) were made by using automated segmentation algorithms. GMC was analyzed both voxel by voxel (preserving spatial precision) as well as using predefined regions of interest. Voxel-based morphometry revealed intense GMC reduction in the anterior portion relative to posterior thalami. Furthermore, thalamic atrophy was greater ipsilateral to the MTLE origin than on the contralateral side. Here we demonstrate that the thalamic atrophy is most intense in the thalamic nuclei that have strong connections with the limbic hippocampus. This finding suggests that thalamic atrophy reflects this region's anatomic and functional association with the limbic system rather than a general vulnerability to damage. Ipsilateral and Contralateral MRI Volumetric Abnormalities in Chronic Unilateral Temporal Lobe Epilepsy and Their Clinical Correlates Seidenberg M, Kelly KG, Parrish J, Geary E, Dow C, Rutecki P, Hermann B Epilepsia 2005;46:420–430 Purpose To assess the presence, extent, and clinical correlates of quantitative MR volumetric abnormalities in ipsilateral and contralateral hippocampus, and temporal and extratemporal lobe regions in unilateral temporal lobe epilepsy (TLE). Methods In total, 34 subjects with unilateral left ( n = 15) or right ( n = 19) TLE were compared with 65 healthy controls. Regions of interest included the ipsilateral and contralateral hippocampus as well as temporal, frontal, parietal, and occipital lobe gray and white matter. Clinical markers of neurodevelopmental insult (initial precipitating insult, early age of recurrent seizures) and chronicity of epilepsy (epilepsy duration, estimated number of lifetime generalized seizures) were related to MR volume abnormalities. Results Quantitative MR abnormalities extend beyond the ipsilateral hippocampus and temporal lobe with extratemporal (frontal and parietal lobe) reductions in cerebral white matter, especially ipsilateral but also contralateral to the side of seizure onset. Volumetric abnormalities in ipsilateral hippocampus and bilateral cerebral white matter are associated with factors related to both the onset and the chronicity of the patients’ epilepsy. Conclusions These cross-sectional findings support the view that volumetric abnormalities in chronic TLE are associated with a combination of neurodevelopmental and progressive effects, characterized by a prominent disruption in ipsilateral hippocampus and neural connectivity (i.e., white matter volume loss) that extends beyond the temporal lobe, affecting both ipsilateral and contralateral hemispheres. MR Volumetric Analysis of the Piriform Cortex and Cortical Amygdala in Drug-refractory Temporal Lobe Epilepsy Gonçalves Pereira PM, Insaustid R, Artacho-Pérulad E, Salmenperäe T, Kälviäinene R, Pitkänen A AJNR Am J Neuroradiol 2005;26:319–332 Purpose The assessment of patients with temporal lobe epilepsy (TLE) traditionally focuses on the hippocampal formation. These patients, however, may have structural abnormalities in other brain areas. Our purpose was to develop a method to measure the combined volume of the human piriform cortex and cortical amygdala (PCA) by using MRI and to investigate PCA atrophy. Methods The definition of anatomic landmarks on MRIs was based on histologic analysis of 23 autopsy control subjects. Thirty-nine adults with chronic TLE and 23 age-matched control subjects were studied. All underwent high-spatial-resolution MRI at 1.5 T, including a tilted T1-weighted 3D dataset. The PCA volumes were compared with the control values and further correlated with hippocampal, amygdale, and entorhinal cortex volumes. Results The normal volume was 530 ± 59 mm3 (422-644) (mean ± 1 SD [range]) on the right and 512 ± 60 mm3 (406-610) on the left PCA (no asymmetry, and no age or sex effect). The intraobserver and interobserver variability were 6% and 8%, respectively. In right TLE patients, the mean right PCA volume was 18% smaller than that in control subjects ( p < 0.001) and 15% smaller than in left TLE ( p < 0.001). In left TLE, the mean left PCA volume was 16% smaller than in control subjects ( p < 0.001) and 19% smaller than in right TLE ( p < 0.001). Overall, 18 (46%) of the 39 patients had a greater than 20% volume reduction in the ipsilateral PCA. Bilateral atrophy was found in 7 (18%) of 39. Patients with hippocampal volumes of at least 2 SDs below the control mean had an 18% reduction in the mean PCA volume compared with patients without hippocampal atrophy ( p < 0.001). Ipsilaterally, hippocampal ( r = 0.756, p < 0.01), amygdaloid ( r = 0.548, p < 0.01), and entorhinal ( r = 0.500, p < 0.01) volumes correlated with the PCA volumes. Conclusions The quantification of PCA volume with MRI showed that the PCA is extensively damaged in chronic TLE patients, particularly in those with hippocampal atrophy.