Spatial Transcriptomics, Histopathology, and Magnetic Resonance Subfield Segmentation of Hippocampal Sclerosis Compared to Normal Hippocampus: A Proof-of-Concept Study
Despite recent major advances in work-up and treatment of Drug Resistant Mesial Temporal Lobe Epilepsy (MTLE) with Hippocampal Sclerosis (HS), the underlying pathophysiology of this disease remains elusive. Depending on the type of HS, as defined by the histopathologic International League Against Epilepsy (ILAE), studies report variable post-surgical seizure freedom durations, with diverse underlying pathophysiology and gene expression. We here describe our initial experience with incorporating spatial transcriptomics along with Magnetic Resonance Imaging (MRI) and histopathology in a patient with Drug Resistant MTLE and HS compared to the hippocampus of an age-sex matched control case. Cases were assessed by MRI hippocampal subfields segmentation, neuropathology, and spatial transcriptomics to identify candidate genes that play a role in the biology of HS.  A significant finding was a partial inhibition of the methyl-CpG-binding protein 2 (MeCP2) gene in all subfields of the hippocampus, which is important for neuronal survival and differentiation. Together, our results have shown the feasibility of hippocampal subfield segmentation on MRI and direct correlation with histology and spatial transcriptomics to identify key areas of gene dysregulation in epilepsy. These novel methods can be used to implement personalized medicine and discovery of new drug targets. Overall design: Compare one pathologically diagnosed case of hippocampal sclerosis (ILAE type 1) to a age-sex matched control.