scholarly journals Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Thomas Bonduelle ◽  
Till Hartlieb ◽  
Sara Baldassari ◽  
Nam Suk Sim ◽  
Se Hoon Kim ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Cortical Development ◽  
Digital Pcr ◽  
Malformations Of Cortical Development ◽  
Rare Type ◽  
Malformation Of Cortical Development ◽  
Neurosurgical Treatment ◽  
Molecular Etiology ◽  
Cell Densities ◽  
Targeted Gene Sequencing

AbstractFocal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated with pediatric drug-resistant focal epilepsy, and amenable to neurosurgical treatment. MOGHE is histopathologically characterized by clusters of increased oligodendroglial cell densities, patchy zones of hypomyelination, and heterotopic neurons in the white matter. The molecular etiology of MOGHE remained unknown so far. We hypothesized a contribution of mosaic brain variants and performed deep targeted gene sequencing on 20 surgical MOGHE brain samples from a single-center cohort of pediatric patients. We identified somatic pathogenic SLC35A2 variants in 9/20 (45%) patients with mosaic rates ranging from 7 to 52%. SLC35A2 encodes a UDP-galactose transporter, previously implicated in other malformations of cortical development (MCD) and a rare type of congenital disorder of glycosylation. To further clarify the histological features of SLC35A2-brain tissues, we then collected 17 samples with pathogenic SLC35A2 variants from a multicenter cohort of MCD cases. Histopathological reassessment including anti-Olig2 staining confirmed a MOGHE diagnosis in all cases. Analysis by droplet digital PCR of pools of microdissected cells from one MOGHE tissue revealed a variant enrichment in clustered oligodendroglial cells and heterotopic neurons. Through an international consortium, we assembled an unprecedented series of 26 SLC35A2-MOGHE cases providing evidence that mosaic SLC35A2 variants, likely occurred in a neuroglial progenitor cell during brain development, are a genetic marker for MOGHE.

Clinical Implementation of Targeted Gene Sequencing for Malformation of Cortical Development

2020 ◽  
Vol 103 ◽  
pp. 27-34
Author(s):  
Sangbo Lee ◽  
Se Hee Kim ◽  
Borahm Kim ◽  
Seung-Tae Lee ◽  
Jong Rak Choi ◽  
...  
Keyword(s):  
Cortical Development ◽  
Gene Sequencing ◽  
Clinical Implementation ◽  
Malformation Of Cortical Development ◽  
Targeted Gene Sequencing

scholarly journals Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy

2020 ◽  
Author(s):  
Sara Lorio ◽  
Jan Sedlacik ◽  
Po-wah So ◽  
Harold G Parks ◽  
Roxane Gunny ◽  
...  
Keyword(s):  
Synchrotron Radiation ◽  
Focal Epilepsy ◽  
Red Nucleus ◽  
Cortical Development ◽  
Susceptibility Mapping ◽  
Transverse Relaxation Rate ◽  
Drug Resistant ◽  
Malformations Of Cortical Development ◽  
X Ray ◽  
Age Related

Objective Malformations 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 its 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. Methods QSM (χ) and R2* maps were calculated for 40 paediatric patients with suspected FCD (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* were performed within lesions, using a surface-based approach with comparison to homologous regions, and globally 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. Results Compared to fluid‐attenuated inversion recovery (FLAIR) or T1‐weighted imaging, QSM improved lesion conspicuity in 5% of patients. In patients with well-localised and confirmed FCDIIb 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 2-3mm 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, and decreased iron in the brain region exhibiting low χ and high R2*. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus, but these changes were not altered in epilepsy. Conclusion QSM 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. Theses findings suggests that the measurements of cortical χ measurements could be used to detect and delineate epilepsy lesions.

scholarly journals Prevalence of Nonlesional Focal Epilepsy in an Adult Epilepsy Clinic

2013 ◽  
Vol 40 (2) ◽  
pp. 198-202 ◽  
Author(s):  
Dang Khoa Nguyen ◽  
Manuela Temgoua Mbacfou ◽  
Dong Bach Nguyen ◽  
Maryse Lassonde
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Focal Epilepsy ◽  
Vascular Malformations ◽  
Cortical Development ◽  
Hippocampal Atrophy ◽  
Imaging Data ◽  
Malformations Of Cortical Development ◽  
Resonance Imaging ◽  
Magnetic Resonance Imaging Mri

Purpose:To evaluate the prevalence of nonlesional focal epilepsy in an adult epilepsy clinic and its refractoriness to antiepileptic drug therapy.Background:Focal epilepsy is frequently, but not always, associated with structural epileptogenic lesions identifiable on magnetic resonance imaging (MRI).Methods:We analyzed the data from all patients evaluated at an adult epilepsy clinic from January 2002 to December 2011. Clinical and paraclinical findings were used to diagnose focal epilepsy. Magnetic resonance imaging were reviewed and classified as normal, with an epileptogenic lesion, or with a lesion of unclear epileptogenicity. Epileptogenic lesions were further categorized as tumours, vascular malformations, gliosis (including hippocampal atrophy/sclerosis), and malformations of cortical development. Our study group included patients with no lesions on MRI. Pharmacoresistance of patients with nonlesional focal epilepsy was assessed using the ILAE and Perucca's criterias.Results:Out of 1521 patients evaluated (mean age 44 years; range 14-93 years), 843 had focal epilepsy. Magnetic resonance imaging data, available for 806 (96%) subjects, showed epileptogenic lesions in 65%, no obvious epileptogenic lesions in 31% and lesions of unclear epileptogenicity in 4%. Magnetic resonance imaging-identified lesions included gliosis due to an acquired insult (52% including 17% of hippocampal atrophy or sclerosis), tumours (29%), vascular malformations (16%) and malformations of cortical development (10%). Fifty-two percent of nonlesional focal epileptic patients were drug-refractory.Conclusion:In a tertiary epilepsy clinic, close to a third of patients with focal epilepsy were found to be nonlesional, half of which were drug-resistant.

scholarly journals Epileptic Patient with Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia and Epilepsy (MOGHE): A Case Report and Review of the Literature

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
A. Verentzioti ◽  
I. Blumcke ◽  
A. Alexoudi ◽  
P. Patrikelis ◽  
A. Siatouni ◽  
...  
Keyword(s):  
Case Report ◽  
White Matter ◽  
Frontal Lobe ◽  
Epileptic Patient ◽  
Focal Epilepsy ◽  
Cortical Development ◽  
Resected Specimen ◽  
Frontal Lobe Epilepsy ◽  
Review Of The Literature ◽  
Malformation Of Cortical Development

Introduction. There is an emerging interest in the literature about MOGHE (Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia and Epilepsy). We report the case of an epileptic patient with MOGHE. Case Report. A 33-year-old male patient was suffering from refractory focal epilepsy since adolescence. MRI demonstrated increased T2/FLAIR signal intensity of right frontal lobe. Presurgical evaluation led to definition of epileptogenic network in a specific area of right frontal lobe. The resected specimen revealed MOGHE. Discussion. MOGHE appears to be a brain entity which shares some unique histopathological features. Review of the literature is in accordance with our patient’s findings. The major neuropathological finding consists of areas with blurred gray-white matter boundaries due to heterotopic neurons in white matter and increased numbers of subcortical oligodendroglial cells with increased proliferation. MR abnormalities are present in T2/FLAIR sequences. It concerns patients with refractory frontal lobe epilepsy and appears to associate with unfavourable postsurgical outcome in seizure control. Conclusion. More cases are needed in order to establish more data about this distinct entity in frontal lobe epilepsy. This could be valuable knowledge to patients and doctors concerning expectations or management of undesirable outcome in frontal lobe epilepsy surgery.

Focal epilepsy due to malformations of cortical development: Long-term outcome and prognosis predictors

2021 ◽  
Vol 429 ◽  
pp. 117708
Author(s):  
Laura Licchetta ◽  
Andrea Teglia ◽  
Cipriano Di Mauro ◽  
Francesco Toni ◽  
Luca Vignatelli ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Cortical Development ◽  
Malformations Of Cortical Development ◽  
Term Outcome ◽  
Long Term Outcome

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE): a widespread disease with an apparently focal epilepsy

2021 ◽  
Vol 23 (2) ◽  
pp. 407-411
Author(s):  
Raghavendra Seetharam ◽  
Javeria Nooraine ◽  
Radhika Mhatre ◽  
Jaychandran Ramachandran ◽  
Rajesh B. Iyer ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Cortical Development ◽  
Malformation Of Cortical Development

scholarly journals Assessment of the response to antiepileptic drugs in epileptic patients with structural lesion(s) on neuroimaging

2020 ◽  
Vol 56 (1) ◽  
Author(s):  
Maha Atef Zaki ◽  
Lamiaa Nazeeh ElSherif ◽  
Reham Mohamed Shamloul
Keyword(s):  
Brain Imaging ◽  
Antiepileptic Drugs ◽  
Seizure Control ◽  
Focal Epilepsy ◽  
Cortical Development ◽  
Poor Response ◽  
Malformations Of Cortical Development ◽  
Combined Use ◽  
Antiepileptic Medications ◽  
Response Group

Abstract Background Focal epilepsy is the most common form of epilepsy in adults. Advances in brain imaging allowed better identification of different structural lesions underlying focal epilepsy. However, the response to antiepileptic drugs in lesional epilepsy is heterogeneous and difficult to anticipate. This study aimed to evaluate the response to antiepileptic drugs (AED) in patients with lesional epilepsy and to identify the predictors for poor seizure control. Methods One hundred and sixty-five patients with lesional epilepsy were included; the clinical diagnosis of epilepsy and seizure classification was based on the revised criteria of the International League Against Epilepsy (ILAE). Patients were subjected to full clinical assessment, MRI brain imaging epilepsy protocol, and EEG monitoring. All subjects were followed in the epilepsy clinic for at least 6 months. Results 75.8% of patients with lesional epilepsy showed poor response to antiepileptic medications. Cerebromalatic lesions related to brain trauma was the most frequently encountered (21.8%). Malformations of cortical development were significantly associated with poor response to AED (p = 0.040). Polytherapy and the combined use of 1st- and 2nd-generation AED were higher in the poor response group. Logistic regression analysis revealed that younger age at seizure onset and abnormal EEG findings was 0.965 times and 2.5 times more associated with poor seizure control, respectively. Conclusion This study revealed that patients with lesional epilepsy who develop seizures in their early life, who suffer from malformations of cortical development, or who show abnormal EEG findings are more suspected to show poor response to AED.

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