Abstracts

Rationale: Mesial temporal sclerosis (MTS) is the most common lesion found in patients with temporal lobe epilepsy (TLE) and is associated with good surgical outcome. Although much is known regarding the abnormalities present in the gray matter (e.g. neuronal loss and gliosis of the mesial temporal structures), the white matter directly underlying it has not received as much attention. In recent years, however, diffusion tensor imaging (DTI) has demonstrated that several white matter bundles exhibit abnormalities (Arfanakis, Magn Reson Imaging 2002;20:511-9; Concha, Ann Neurol 2005;57:188-96; Gross et al, Epilepsia 2006;47:1360-1363; Focke, Neuroimage 2008;40: 728-737) that, based on animal models, are presumed to be compatible with microscopic tissue changes (Beaulieu, NMR Biomed 2002;15,435-55). The fornix (principal hippocampal output) of patients with TLE, in particular, shows reduced water diffusion anisotropy only in the presence of MTS (Concha, submitted). The purpose of this study is to evaluate the differences in micro-structural characteristics of the fimbria/fornix in patients with TLE and their relationship to the presence of MTS. Methods: Eleven patients with TLE undergoing temporal lobe resections were recruited for this study. Six patients had evidence of MTS on post-surgical histopathology (MTS+), while the other five patients did not (MTS-). All subjects were scanned pre-operatively using a 1.5 T Siemens scanner using DTI (2×2×2 mm3 voxel size). The DTI characteristics of the fornix were assessed pre-operatively using tractography. A section of the fimbria/fornix (2-3 mm in length) was resected during surgery and immediately fixed. Ultra-thin sections of the white matter tract were obtained cross-sectionally to the axons. Ten electron microphotographs (3500X) were obtained per patient and subsequently analyzed blinded to diagnosis. The axonal diameters, both with and without the myelin sheaths, were manually assessed, as well as the axonal count. Myelin content, membrane circumference and extra-axonal fraction were estimated from these diameters assuming circular axonal profiles and averaged per patient. Differences between the two TLE groups were evaluated using Student's t-tests, and correlations between DTI parameters and histological characteristics with Pearson's correlation coefficient. Results: MTS+ patients had overall less myelin content (p=0.012) and a larger extra-axonal fraction (p=0.004) than the MTS- patients (Figure 1). Axonal density and membrane circumference correlated positively with water diffusion anisotropy (r=0.52, p=0.049 and r=0.59,p=0.029, respectively; Figure 2), while extra-axonal fraction correlated negatively (r=-0.49, p=0.065; Figure 2). Conclusions: Our findings show the first direct evidence of important differences in the micro-structure of the white matter directly underlying the hippocampus that are dependent on the presence of MTS. Such abnormalities are amenable to detection in-vivo and non-invasively using DTI.