Patterns of subregional mesiotemporal disease progression in temporal lobe epilepsy

Abstract

Objective: Evidence for disease progression in the mesiotemporal lobe is mainly derived from global volumetry of the hippocampus. In this study, we tracked progressive structural changes in the hippocampus, amygdala, and entorhinal cortex in drug-resistant temporal lobe epilepsy at a subregional level. Furthermore, we evaluated the relation between disease progression and surgical outcome.

Methods: We combined cross-sectional modeling of disease duration in a large cohort of patients (n = 134) and longitudinal analysis in a subset that delayed surgery (n = 31). To track subregional pathology, we applied surface-shape analysis techniques on manual mesiotemporal labels.

Results: Longitudinal and cross-sectional designs showed consistent patterns of progressive atrophy in hippocampal CA1, anterolateral entorhinal, and the amygdalar laterobasal group bilaterally. These regions also exhibited more marked age-related volume loss in patients compared with controls. We found a faster progression of hippocampal atrophy in patients with a seizure frequency ≥6 per month. High rates of contralateral entorhinal cortex atrophy predicted postsurgical seizure relapse.

Conclusion: We observed progressive atrophy in hippocampal, amygdalar, and entorhinal subregions that frequently display neuronal loss on histology. The bilateral character of cumulative atrophy highlights the importance of early surgery. In patients who nevertheless delay this procedure, serial scanning may provide markers of surgical outcome.

Figure 1. Surface-based analysis of progressive mesiotemporal structural changes in TLE: Cross-sectional findings

Effects of duration of epilepsy on local volume changes are mapped on the hippocampus (A), entorhinal cortex (B), and amygdala (C). For each structure, linear regression fits are shown. Significances are thresholded at FDR <0.05. *Faster progression of atrophy in TLE-HA (i.e., with hippocampal atrophy) relative to TLE-NV (i.e., with normal hippocampal volume). For each structure, schematic boundaries of subdivisions are outlined on the template. C = caudal; CA = cornu ammonis; Cl = caudal limit; CM = centromedial nuclear group; DG = dentate gyrus; FDR = false discovery rate; Int = intermediate; LB = laterobasal nuclear group including lateral, basolateral, basomedial, and accessory basal nuclei; Lc = lateral caudal; Lr = lateral rostral; O = olfactory; R = rostral; SF = superficial nuclear group including cortical nuclei; TLE = temporal lobe epilepsy; TLE-HA = TLE–hippocampal atrophy; TLE-NV = TLE–normal hippocampal volume.

Figure 2. Surface-based analysis of progressive mesiotemporal structural change in TLE: Longitudinal findings

Regions of significant atrophy (in mm/y) are mapped on the hippocampus (A), entorhinal cortex (B), and amygdala (C). For each significant cluster, mixed-effects model fits are shown. Significances are thresholded at FDR <0.05. *Faster progression of atrophy in TLE-HA relative to TLE-NV. C = caudal; CA = cornu ammonis; Cl = caudal limit; CM = centromedial nuclear group; DG = dentate gyrus; FDR = false discovery rate; Int = intermediate; LB = laterobasal nuclear group including lateral, basolateral, basomedial, and accessory basal nuclei; Lc = lateral caudal; Lr = lateral rostral; O = olfactory; R = rostral; SF = superficial nuclear group including cortical nuclei; TLE = temporal lobe epilepsy; TLE-HA = TLE–hippocampal atrophy; TLE-NV = TLE–normal hippocampal volume.

Figure 3. Surface-based predictors of surgical outcome

(A) Cross-sectional mapping of the interaction between duration of epilepsy and postsurgical outcome. (B) Longitudinal mapping of the interaction between interscan interval and postsurgical outcome. Maps display regions where progressive atrophy is more marked in non–seizure-free (NSF) patients (Engel class II–IV) relative to seizure-free (SF) patients (Engel class I); inset scatter plots show the post hoc mean effect in significant clusters. See figure 1 for details on the statistical thresholding. C = caudal; Cl = caudal limit; FDR = false discovery rate; Int = intermediate; Lc = lateral caudal; Lr = lateral rostral; O = olfactory; R = rostral.