A developmental and genetic classification for malformations of cortical development: update 2012

Barkovich, A. James; Guerrini, Renzo; Kuzniecky, Ruben; Jackson, Graeme D.; Dobyns, William B.

doi:10.1093/brain/aws019

Cited by 906 publications

(919 citation statements)

References 270 publications

(536 reference statements)

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“…1c) [28,31]. These findings support the inclusion of GNT within the group of MCD (such as FCD and TSC), characterized by cortical dysgenesis with abnormal cell proliferation ( [5]; Table 2). Mutational analysis of TSC1 and TSC2 failed to identify mutations in GGs [32], and only a somatic mutation in intron 32 of the TSC2 gene was reported in one GG patient in glial cells, but not in dysplastic neurons [33].…”

Section: Pathogenesis and Molecular Geneticssupporting

confidence: 67%

“…In 2005, Barkovich et al [93] developed a classification of MCD based on the major stages of cortical development that are possibly affected. Recently, this classification system has been revised [5] on the basis of new developments in molecular biology, genetics, and imaging features of MCD and neuropathological classifications (Table 2).…”

Section: MCDmentioning

confidence: 99%

“…Developmental brain lesions, in particular glioneuronal tumors (GNT) and malformations of cortical development (MCD) are among the most common causes of pharmacologically intractable epilepsy (for reviews see [1][2][3][4][5]). …”

Section: Introductionmentioning

confidence: 99%

“…This integrated approach is fostered by a strong interaction between the fields of neurogenetics and basic neuroscience, and requires the implementation of new molecular diagnostic techniques in human tissue. The increasing knowledge in genetics, imaging, and pathologic features of epileptogenic developmental lesions has provided the basis for proposing new classification systems [5,6], which are used to evaluate clinical outcome and to guide more targeted studies for the identification of new antiepileptic drugs. Major advances in our understanding of the molecular pathogenesis and the pro-epileptogenic cellular mechanisms of a variety of focal developmental lesions have been made over the last decade, resulting in interesting scientific discoveries.…”

Section: Introductionmentioning

confidence: 99%

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Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

Aronica

Crino

2014

Neurotherapeutics

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Section: Pathogenesis and Molecular Geneticssupporting

confidence: 67%

Section: MCDmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

Aronica

Crino

2014

Neurotherapeutics

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“…MCDs are usually highly epileptogenic, which may result from major changes in the pattern of gene expression involved in neuronal excitability 5. Focal cortical dysplasias (FCDs) are a subtype of MCD affecting >25% of all patients undergoing surgery for the treatment of refractory epilepsy 6.…”

mentioning

confidence: 99%

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

Avansini

Torres

Vieira

et al. 2018

Annals of Neurology

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ObjectiveFocal cortical dysplasias (FCDs) are an important cause of drug‐resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II.MethodsWe used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study.Resultshsa‐let‐7f (p = 0.039), hsa‐miR‐31 (p = 0.0078), and hsa‐miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2‐target, is upregulated (p < 0.001). In vitro experiments showed that hsa‐miR‐34a downregulates NEUROG2 by binding to its 5′‐untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway.InterpretationOur findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa‐miR‐34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623–635

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From bedside to bench: New insights in epilepsy‐associated tumors based on recent classification updates and animal models on brain tumor networks

Cases‐Cunillera,

Friker,

Müller

et al. 2024

Molecular Oncology

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Low‐grade neuroepithelial tumors (LGNTs), particularly those with glioneuronal histology, are highly associated with pharmacoresistant epilepsy. Increasing research focused on these neoplastic lesions did not translate into drug discovery; and anticonvulsant or antitumor therapies are not available yet. During the last years, animal modeling has improved, thereby leading to the possibility of generating brain tumors in mice mimicking crucial genetic, molecular and immunohistological features. Among them, intraventricular in utero electroporation (IUE) has been proven to be a valuable tool for the generation of animal models for LGNTs allowing endogenous tumor growth within the mouse brain parenchyma. Epileptogenicity is mostly determined by the slow‐growing patterns of these tumors, thus mirroring intrinsic interactions between tumor cells and surrounding neurons is crucial to investigate the mechanisms underlying convulsive activity. In this review, we provide an updated classification of the human LGNT and summarize the most recent data from human and animal models, with a focus on the crosstalk between brain tumors and neuronal function.

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A developmental and genetic classification for malformations of cortical development: update 2012

Cited by 906 publications

References 270 publications

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

From bedside to bench: New insights in epilepsy‐associated tumors based on recent classification updates and animal models on brain tumor networks

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