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Spatial Transcriptomics, Histopathology, and Magnetic Resonance Subfield Segmentation of Hippocampal Sclerosis Compared to Normal Hippocampus: A Proof-of-Concept Study

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288888 | GEO | 2026/02/06

REPOSITORIES: GEO

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Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment

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Spatial Transcriptomics, Histopathology, and Magnetic Resonance Subfield Segmentation of Hippocampal Sclerosis Compared to Normal Hippocampus: A Proof-of-Concept Study

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