Pathology-specific lipid alterations with triacylglycerol as a potential biomarker in Focal cortical dysplasia (FCD) and Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS)

Neuroscience. 2024 Dec 21:566:72-86. doi: 10.1016/j.neuroscience.2024.12.038. Online ahead of print.

Abstract

Focal Cortical Dysplasia (FCD) & Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) are two common pathologies of drug-resistant focal epilepsy (DRE). Inappropriate localization of the epileptogenic zones (EZs) in FCD is a significant contributing factor to the unsatisfactory surgical results observed in FCD cases. Currently, no molecular or cellular indicators are available which can aid in identifying the epileptogenic zones (EZs) in FCD. Phospholipid modifications in healthy and malignant tumour tissues have been documented and used to demarcate tumour boundaries. The objective of this research was to analyze and evaluate the lipid profiles in a manner that takes into account the specific disease and subtype. The technique of liquid chromatography and tandem mass spectrometry was utilized to detect changes in lipids in surgically resected brain samples from patients with FCD and MTLE-HS, in comparison to non-epileptic controls. Significant upregulation of TAGs was seen in both FCD and MTLE-HS. Additionally, the levels of triglycerides in the plasma of peripheral blood were measured in patients with FCD, MTLE-HS, and healthy individuals as controls. These findings suggest that employing distinct lipid mass spectra could be an effective method for identifying the EZs in FCD. The unique lipid mass spectra of cortical tissues from patients with FCD can be utilized for real-time surgical guidance. Additionally, the plasma triglyceride (TAG) level has the potential to act as a biomarker once validated on a larger cohort.

Keywords: Drug-resistant epilepsy (DRE); Epileptogenic zone (EZ); Focal cortical dysplasia (FCD); Mass spectrometry; Mesial Temporal Sclerosis (MTLE-HS).