Seizure occurrence in FCD type II is predicted by lesion position and linked to cytoarchitectural alterations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F25%3A10506367" target="_blank" >RIV/00216208:11130/25:10506367 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=9~QhpKHXXV" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=9~QhpKHXXV</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40478-025-02166-x" target="_blank" >10.1186/s40478-025-02166-x</a>

Result language

angličtina

Original language name

Seizure occurrence in FCD type II is predicted by lesion position and linked to cytoarchitectural alterations

Original language description

Focal cortical dysplasia (FCD) is a common malformation of cortical development and a major cause of early-onset, drug-resistant epilepsy. FCD type II is defined by abnormal lamination, altered cellular composition, and pathological cells, notably dysmorphic neurons (DNs) and balloon cells. DNs are thought to drive epileptogenicity through both cell-autonomous and non-cell-autonomous mechanisms, the latter including not only aberrant connectivity but also indirect modulation of excitability in local cell populations. We performed a multiscale structural and morphological analysis to elucidate the basis of FCD epileptogenicity and the impact of somatic mTOR mutations during brain development. Using a mouse model of FCD type II, we show that lesions in frontal and motor cortical regions are the strongest predictors of spontaneous seizure occurrence. This localization-dependent epileptogenicity offers an experimental explanation for the higher clinical epileptogenicity of frontal FCDs and suggests that posterior lesions may remain silent-an open question in human pathology. In our model, FCD tissue displayed considerable expansion, with cortical thickness up to ~ 20% in seizure-bearing animals. This expansion coincided with an overall ~ 40% reduction in neuronal density, consistent with tissue hypertrophy. DN density did not differ between seizure and non-seizure animals, challenging the notion that higher DN load directly predicts epileptogenesis. At the microscopic level, we describe DN axonal pathologies, including giant varicosities. In the cortex, these appeared as vesicle-filled boutons, whereas along callosal axons they were frequent but largely empty. Bouton density was markedly reduced in FCD cortex. Together, these findings leave the net synaptic effect of dysmorphic neurons unresolved, challenging the assumption that axonal hypertrophy translates into increased excitatory drive. While morphological abnormalities in FCD type II are well documented, their functional consequences remain incompletely understood. Here, we used macro- and microscopic structural features of FCDII to assess seizure susceptibility, providing new insights into epileptogenesis.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Acta Neuropathologica Communications

ISSN

2051-5960

e-ISSN

2051-5960

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

22

Pages from-to

251

UT code for WoS article

001636046800002

EID of the result in the Scopus database

2-s2.0-105024236352