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Epilepsy related to developmental tumors and malformations of cortical development.

ABSTRACT: Structural abnormalities of the brain are increasingly recognized in patients with neurodevelopmental delay and intractable focal epilepsies. The access to clinically well-characterized neurosurgical material has provided a unique opportunity to better define the neuropathological, neurochemical, and molecular features of epilepsy-associated focal developmental lesions. These studies help to further understand the epileptogenic mechanisms of these lesions. Neuropathological evaluation of surgical specimens from patients with epilepsy-associated developmental lesions reveals two major pathologies: focal cortical dysplasia and low-grade developmental tumors (glioneuronal tumors). In the last few years there have been major advances in the recognition of a wide spectrum of developmental lesions associated with a intractable epilepsy, including cortical tubers in patients with tuberous sclerosis complex and hemimegalencephaly. As an increasing number of entities are identified, the development of a unified and comprehensive classification represents a great challenge and requires continuous updates. The present article reviews current knowledge of molecular pathogenesis and the pathophysiological mechanisms of epileptogenesis in this group of developmental disorders. Both emerging neuropathological and basic science evidence will be analyzed, highlighting the involvement of different, but often converging, pathogenetic and epileptogenic mechanisms, which may create the basis for new therapeutic strategies in these disorders.

SUBMITTER: Aronica E

PROVIDER: S-EPMC3996119 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Epilepsy related to developmental tumors and malformations of cortical development.

Aronica Eleonora E Crino Peter B PB

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20140401 2

Structural abnormalities of the brain are increasingly recognized in patients with neurodevelopmental delay and intractable focal epilepsies. The access to clinically well-characterized neurosurgical material has provided a unique opportunity to better define the neuropathological, neurochemical, and molecular features of epilepsy-associated focal developmental lesions. These studies help to further understand the epileptogenic mechanisms of these lesions. Neuropathological evaluation of surgica ...[more]

PMID: 24481729

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Project description:BackgroundThe most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG). This study aimed to characterize the possible neurometabolic abnormalities and heterogeneity in different MCDs subtypes using proton magnetic resonance spectroscopy (1H-MRS).MethodsIn this prospective cross-sectional study, we recruited 29 patients with MCDs and epilepsy, including ten with GMH, ten with FCD, and nine with PMG, as well as 25 age- and sex-matched healthy controls (HC) from the Epilepsy Center of West China Hospital of Sichuan University between August 2018 and November 2021. Inclusion criteria for the patients were based upon typical magnetic resonance imaging (MRI) findings of MCDs and full clinical assessment for epilepsy. Single-voxel point-resolved spectroscopy was used to acquire data from both the lesion and the normal-appearing contralateral side (NACS) in patients and from the frontal lobe in HC. Metabolite measures, including N-acetyl aspartate (NAA), myoinositol (Ins), choline (Cho), creatine (Cr), and glutamate + glutamine (Glx) concentrations, were quantitatively estimated with linear combination model (LCModel) software and corrected for the partial volume effect of cerebrospinal fluid (CSF).ResultsThe NAA concentration was lower and the Ins concentration was higher in the MCDs lesions than in the NACS and in HC (P=0.002-0.007), and the Cho and Cr concentrations were higher in MCDs lesions than in HC (P=0.001-0.016). Moreover, the Cho concentration was higher in NACS than in HC (P=0.015). In the GMH lesions, the only metabolic alteration was an NAA reduction (GMH_lesion vs. HC: P=0.001). In the FCD lesions, there were more metabolite abnormalities than in the other two subtypes, particularly a lower NAA and a higher Ins than in HC and NACS (P=0.012-0.042). In the PMG lesions, Cr (lesion vs. HC or NACS: P=0.017-0.021) and Glx (lesion vs. NACS: P=0.043) were increased, while NAA was normal. Correlation analysis revealed that the Cr concentration in MCDs lesions was positively correlated with seizure frequency (r=0.411; P=0.027).ConclusionsBased upon 1H-MRS, our study demonstrated that different MCDs subtypes exhibited variable metabolic features, which may be associated with distinct functional and cytoarchitectural properties.

Project description:ObjectiveMalformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting it's mineral composition. We used QSM to investigate abnormal tissue composition in a group of children with focal epilepsy with comparison to effective transverse relaxation rate (R2*) and Synchrotron radiation X-ray fluorescence (SRXRF) elemental maps. Our primary hypothesis was that reductions in χ would be found in FCD lesions, resulting from alterations in their iron and calcium content. We also evaluated deep grey matter nuclei for changes in χ with age.MethodsQSM and R2* maps were calculated for 40 paediatric patients with suspected MCD (18 histologically confirmed) and 17 age-matched controls. Patients' sub-groups were defined based on concordant electro-clinical or histopathology data. Quantitative investigation of QSM and R2* was performed within lesions, using a surface-based approach with comparison to homologous regions, and within deep brain regions using a voxel-based approach with regional values modelled with age and epilepsy as covariates. Synchrotron radiation X-ray fluorescence (SRXRF) was performed on brain tissue resected from 4 patients to map changes in iron, calcium and zinc and relate them to MRI parameters.ResultsCompared to fluid-attenuated inversion recovery (FLAIR) or T1-weighted imaging, QSM improved lesion conspicuity in 5% of patients. In patients with well-localised lesions, quantitative profiling demonstrated decreased χ, but not R2*, across cortical depth with respect to the homologous regions. Contra-lateral homologous regions additionally exhibited increased χ at 2-3 mm cortical depth that was absent in lesions. The iron decrease measured by the SRXRF in FCDIIb lesions was in agreement with myelin reduction observed by Luxol Fast Blue histochemical staining. SRXRF analysis in two FCDIIb tissue samples showed increased zinc and calcium in one patient, and decreased iron in the brain region exhibiting low χ and high R2* in both patients. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus.ConclusionQSM non-invasively revealed cortical/sub-cortical tissue alterations in MCD lesions and in particular that χ changes in FCDIIb lesions were consistent with reduced iron, co-localised with low myelin and increased calcium and zinc content. These findings suggest that measurements of cortical χ could be used to characterise tissue properties non-invasively in epilepsy lesions.

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Epilepsy related to developmental tumors and malformations of cortical development.

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Epilepsy related to developmental tumors and malformations of cortical development.

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