Architecture and cellular composition of focal cortical dysplasia type II - qualitative review of histological studies

Sep 28, 2026

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Focal cortical dysplasia (FCD) is a cortical developmental malformation strongly linked to drug-resistant epilepsy, with childhood prevalence but also occurring in adults. Type II FCD is marked by cortical disorganisation and abnormal cellular features, often associated with hyperactivation of the mTOR signalling pathway driven by somatic mutations. After decades of research, the architecture remains incompletely understood due to variability in samples, cohorts, and protocols. This review synthesises histological evidence on FCD architecture, focusing on cortical dislamination, balloon cells, dysmorphic neurons, and inhibitory interneuron composition, and highlights sampling-bias considerations for future single-cell and spatial studies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Introduction

Focal cortical dysplasia classifications and histological features

Review focus: architecture hallmarks and neuronal composition

Key histological hallmarks

Cortical dislamination

Balloon cells

Dysmorphic neurons

Inhibitory interneurons and GABAergic signalling

Implications for future single-cell and spatial studies

Minimising sampling bias

TYPE Review PUBLISHED 19 December 2025 DOI 10.3389/fncel.2025.1708220 OPEN ACCESS EDITED BY Giampaolo Milior, Commissariat à l’Energie Atomique et aux Energies Alternatives, France REVIEWED BY Diogo F. T. Veiga, St. Jude Children’s Research Hospital, United States Yue-Shan Piao, Xuanwu Hospital, Capital Medical University, China Dimitar Metodiev, Mnogoprofilna Bolnica za Aktivno Lecenie Nadezda, Bulgaria *CORRESPONDENCE Thomas Blauwblomme [thomas.blauwblomme@aphp.fr](thomas.blauwblomme@aphp.fr) †These authors have contributed equally to this work RECEIVED 18 September 2025 REVISED 10 November 2025 ACCEPTED 21 November 2025 PUBLISHED 19 December 2025 CITATION Castaño-Martín R, Metais A, Ciura S and Blauwblomme T (2025) Architecture and cellular composition of focal cortical dysplasia type II: qualitative review of histological studies. Front. Cell. Neurosci. 19:1708220 . doi: 10.3389/fncel.2025.1708220 COPYRIGHT © 2025 Castaño-Martín, Metais, Ciura and Blauwblomme. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Architecture and cellular composition of focal cortical dysplasia type II: qualitative review of histological studies Reyes Castaño-Martín 1, Alice Metais 2,3, Sorana Ciura 1† and Thomas Blauwblomme 1,4,5*† 1Translational Research in Neuroscience Lab, Institut Imagine, Université Paris Cité, Paris, France, 2Institute of Psychiatry and Neuroscience of Paris, Université Paris Cité, Paris, France, 3Service de Neuropathologie, GHU-Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, Paris, France, 4Université de Paris Cité, Paris, France, 5Department of Pediatric Neurosurgery Hôpital Necker, Assistance Publique Hôpitaux de Paris, Paris, France Focal cortical dysplasia (FCD) is a malformation of cortical development strongly associated with drug-resistant epilepsy, particularly in children but also observed in adults. FCD type II is specifically characterised by cortical disorganisation and the presence of abnormal cells. This condition has been widely linked to hyperactivation of the mTOR signalling pathway, secondary to somatic mutations. After five decades of research, the comprehensive understanding of FCD architecture remains incomplete, with significant variability across studies, influenced by differences in tissue samples, cohort characteristics, and experimental protocols. This review aims to synthesise current knowledge on FCD architecture to clarify how the cerebral cortex is altered in FCD. We particularly focus on the hallmarks of FCD: cortical dislamination, balloon cells, and dysmorphic neurons. Additionally, we explore recent insights into the composition of cortical neuronal populations, emphasising the role of inhibitory interneuron populations, which have gained attention following discoveries regarding the involvement of GABAergic signalling in epileptogenesis. Overall, our review highlights key considerations for future single-cell and spatial studies aimed at minimising sampling bias. KEYWORDS focal cortical dysplasia, dislamination, balloon cells, dysmorphic neurons, interneurons 1 Introduction Focal cortical dysplasia (FCD) is a malformation of cortical development (MCD) described 50 years ago. Taylor et al. described in a series of lobar resections from patients with focal epilepsy a characteristic feature, the tissue harbouring “large bizarre neurons, grotesque cells probably of glial origin and a global appearance reminiscent yet distinct to tuberous sclerosis”(Taylor et al., 1971). The development of epilepsy surgery enabled to col

FAQs

What defines focal cortical dysplasia type II at the histological level?

Type II is characterised by cortical dislamination and abnormal cells, specifically dysmorphic neurons (IIa) or dysmorphic neurons together with balloon cells (IIb).

Why does the review argue that the understanding of FCD architecture is still incomplete?

Across studies, findings vary due to differences in tissue samples, cohort characteristics, and experimental protocols, which affects how architectural features are characterised.

How does inhibitory interneuron composition relate to epileptogenesis in FCD?

The review emphasises composition of cortical neuronal populations, highlighting inhibitory interneuron populations and linking attention to discoveries involving GABAergic signalling in epileptogenesis.

Sep 28, 2026

Uploaded by Finn