Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis

Area of Science:

• Neuropathology
• Epileptology
• Molecular Genetics

Background:

• Focal cortical dysplasia (FCD) is a leading cause of pediatric treatment-resistant epilepsy.
• The International League Against Epilepsy (ILAE) classification categorizes FCD histopathologically.
• mTOR pathway mutations are increasingly recognized as a key etiology in FCD.

Purpose of the Study:

• Determine FCD incidence in epilepsy patients.
• Investigate FCD histomorphological and immunohistochemical features.
• Correlate clinicopathological findings and demonstrate mTOR pathway activation for targeted therapy development.

Main Methods:

• Retrospective analysis of 183 surgical epilepsy tissue samples.
• Histopathological subtyping of FCD according to ILAE classification.
• Immunohistochemical staining using NeuN, neurofilament H (NF-H), and pS6 antibodies to assess mTOR pathway activation.

Main Results:

• FCD was diagnosed in 32 cases (17.5%).
• NeuN staining identified specific architectural changes in FCD subtypes Ia, IIIa, and Ib.
• pS6 expression, indicating mTOR pathway activation, was prominent in dysmorphic neurons and balloon cells of all FCD type II cases.

Conclusions:

• pS6 expression in FCD type II supports its genetic basis.
• While mTOR pathway mutations are implicated, they don't fully explain activation in all FCD type II cases.
• Integrated clinicopathological and genetic classification, alongside mTOR pathway inhibitors, represent future therapeutic directions.