Neuropathology and epilepsy surgery - 2024 update

Area of Science:

• Neuroscience and Neuropathology
• Epileptology
• Human Brain Organization

Background:

• Neuropathology of surgically resected brain tissue offers insights into human neuroscience, neuronal hyperexcitability, and glio-neuronal interactions.
• Focal epilepsies, particularly mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), present opportunities for understanding disease mechanisms.
• Recent discoveries include somatic mutations in SLC35A2 in MOGHE and advancements in personalized medicine for intractable epilepsy.

Purpose of the Study:

• To review recent neuropathological findings in focal epilepsies, focusing on novel disease entities and genetic discoveries.
• To highlight advancements in personalized treatment strategies, exemplified by MOGHE and galactose supplementation.
• To discuss the genomic landscape of cortical malformations and regional variant accumulation.

Main Methods:

• Analysis of neurosurgically resected brain tissue from patients with focal epilepsies.
• Review of recent publications (2022-2023) on neuropathology, genetics, and clinical trials in epilepsy.
• Integration of findings from molecular biology, genetics, and clinical data.

Main Results:

• Discovery of MOGHE and its association with SLC35A2 mutations, leading to altered glycosylation.
• Successful pilot clinical trial of galactose supplementation for MOGHE patients with SLC35A2 mutations.
• Identification of new candidate genes (e.g., PTPN11) for cortical malformations and insights into regional variant accumulation (e.g., MTOR, BRAF).

Conclusions:

• Neuropathological studies are crucial for understanding focal epilepsies and developing personalized therapies.
• Targeted genetic and metabolic interventions show promise in treating specific epilepsy subtypes.
• Ongoing research explores links between epilepsy, neurodevelopmental disorders, and neurodegenerative diseases like Alzheimer's.