Abstract
Focal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.
Highlights
Focal cortical dysplasia is the most commonly encountered developmental malformation that causes drug resistant focal epilepsy, in children [1]
Presurgical assessment was done for each patient, and the pathology was determined by analysing convergent data on Magnetic resonance imaging (MRI), video EEG, fluoro-2-deoxyglucose positron emission tomography (FDG-Positron emission tomography (PET)) and magnetoencephalography (MEG), further confirmed by histopathological examinations by neuropathologists
We used surgically resected graded tissues from 9 Focal cortical dysplasia (FCD) type II patients (F1–F9) and eight controls (A1–A8) for Differentially expressed genes (DEGs) RNA sequencing (RNAseq) read summary is provided in the Fig. 2A
Summary
Focal cortical dysplasia is the most commonly encountered developmental malformation that causes drug resistant focal epilepsy, in children [1]. Its anatomopathological position and cellular appearance are highly variable and influence the cortical architecture and unique neuronal subpopulations, and the junction of gray-white matter and sub-cortical. The most frequent subtype is FCD type II, mainly localized in the frontal and parietal lobes and can range from either small and almost invisible bottom‐of‐sulcus dysplasia to larger dysplastic regions covering more than a single gyrus. Because dysplastic tissue contains atypical neuronal networks that are highly susceptible to abnormal excitation, FCD is thought to be intrinsically epileptogenic. Surgery is an effective alternative treatment as it offers seizure freedom or a significant reduction in seizures for those patients with drug-resistant epilepsy (DRE). Epilepsy surgical outcome is influenced by a number of factors, including epilepsy type, underlying pathology, and the most significant accurate localization of the epileptogenic zone (EZ) and precise details of its association with the eloquent cortex for complete and safe removal using a variety of clinical, neuroimaging, and neurophysiological tests [6,7,8]
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