Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres Longitudinal hippocampal and extra-hippocampal microstructural and macrostructural changes following temporal lobe epilepsy surgery Cameron A. Elliott a , Donald W. Gross b , B. Matt Wheatley a , Christian Beaulieu c , Tejas Sankar a, ⁎ a Division of Neurosurgery, University of Alberta, Edmonton, Alberta, Canada b Division of Neurology, University of Alberta, Edmonton, Alberta, Canada c Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada ARTICLE INFO Keywords: Diffusion Diffusion tensor imaging Post-operative MRI Volume ABSTRACT Objectives: 1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippo- campus—using longitudinal diffusion tensor imaging (DTI)—following surgery for temporal lobe epilepsy (TLE). 2) Characterize the downstream extra-hippocampal volumetric changes of the fornix and mammillary bodies after TLE surgery. 3) Examine the relationship between these measures and seizure/cognitive outcome. Methods: Serial structural and DTI brain MRI scans were collected in 25 TLE patients pre- and post-surgery (anterior temporal lobectomy, ATL – 13; selective amygdalohippocampectomy, SelAH – 12) and in 12 healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were computed with manual hippocampal tracings as volumes of interest following co- registration to anatomical images. Fornix and mammillary body volumetry was performed by manual seg- mentation. Results: After surgery, the non-resected hippocampus showed significant postoperative decline in FA (p = 0.0001), with increase of MD (p = 0.01) and RD (p = 0.0001). In contrast to the timing of our previously reported volume changes where atrophy is observed in the first week, diffusion changes occurred late, taking 1–3 years to develop and are not significant at one week after surgery. Diffusion changes are accompanied by delayed limbic circuit volume loss in the mammillary bodies (35%; p < 0.0001) and fornix (24%; p < 0.0001) com- pared to baseline. There was no correlation between postoperative diffusion or structural changes and memory score nor did the degree of postoperative change in hippocampal DTI parameters, mammillary body volume or fornix volume vary significantly based on seizure outcome. Significance: Differences observed in the timing of postoperative volume (first week) and FA/MD (one year) changes would suggest that early contralateral hippocampal atrophy is not secondary to fluid shifts (dehydra- tion) while the late DTI changes suggest ongoing microstructural changes extending beyond the early post- operative period. Postoperative hippocampal diffusion changes are accompanied by delayed mammillary body and fornix volume loss which did not differ when stratified by seizure outcome nor was correlated with degree of hippocampal diffusion change. Finally, we did not identify any significant correlation between postoperative diffusion parameter change and memory performance. 1. Introduction Surgical treatment of medically refractory temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) is associated with excellent short term seizure control compared to non-operative treatment (Wiebe et al., 2001). However, seizure control decays over time, such that by 10 years after surgery less than half of patients remain seizure free (de Tisi et al., 2011; McIntosh et al., 2004). Reliable prediction of post- operative seizure outcome remains challenging. Recently, using long- itudinally-obtained structural MRI scans in patients undergoing surgery for TLE, early and progressive post-operative volume loss of the non- resected (i.e., contralateral) hippocampus was identified (Elliott et al., 2016). This post-operative contralateral hippocampal volume loss was significantly more pronounced amongst patients with seizure recur- rence at two years after surgery but was uncorrelated with surgical approach or neurocognitive outcome. At present, the mechanisms un- derlying this phenomenon of contralateral hippocampal volume loss are not yet known. Whether post-operative atrophy extends beyond the contralateral hippocampus, especially within structures having direct hippocampal connections, is also an open question. https://doi.org/10.1016/j.eplepsyres.2018.01.008 Received 11 October 2017; Received in revised form 17 December 2017; Accepted 4 January 2018 ⁎ Corresponding author at: 2D Department of Surgery, Walter C. Mackenzie Health Sciences Centre, 8440-112St NW, Edmonton, Alberta, T6G 2B7, Canada. E-mail address: tsankar@ualberta.ca (T. Sankar). Epilepsy Research 140 (2018) 128–137 Available online 06 January 2018 0920-1211/ © 2018 Elsevier B.V. All rights reserved. T