Focal cortical dysplasia: Updates

Focal cortical dysplasias (FCDs) represent the third most frequent cause of drug-resistant focal epilepsy in adults (after hippocampal sclerosis and tumours) submitted to surgery, and the most common in the pediatric age group. The International League Against Epilepsy (ILAE) classification of focal cortical dysplasia is still a reference and consists of a three-tiered system: FCD type I refers to isolated abnormalities in cortical layering; FCD type II refers to cases with abnormalities in cortical architecture and dysmorphic neurons with or without balloon cells; and FCD type III refers to abnormalities in cortical layering associated with other lesions. Recent studies have demonstrated that somatic mutations occurring post-zygotically during embryonal development and leading to mosaicism, underlie most brain malformations. The molecular pathogenesis of FCD type II is associated with activation of the mTOR pathway. Pathogenic variants in this pathway are recognized in up to 63% of cases and may occur both through single activating variants in activators of the mTOR signaling pathway or double-hit inactivating variants in repressors of the signaling pathway. The newly described mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy, has been found to show recurrent pathogenic variants in SLC35A2 with mosaicism. The present review describes the lesions of FCD and discusses the molecular pathogenesis and proposal for a revised classification.

Spectrum of Mri Findings in Pediatric Epilepsy–Medical and Surgical Causes of Epilepsy in Children And its’ Radiological Correlation

@#Introduction: Epilepsy is the common condition encountered in both adults and pediatric population. It occurs as a result of various spectrum of etiology ranging from infections to tumors. EEG and Neurosonogram can characterize the type of epilepsy; however, imaging is the only tool to identify the lesion, its location, and extent and resection possibility. CT was the only modality before the era of MRI. However, CT was only used to identify the lesion with hemorrhage and calcification. It is having the disadvantage of having poor spatial resolution and using radiation. The era of MRI has changed the imaging due to its higher spatial resolution, gray white matter differentiation, status of myelination and non-utilization of radiation. Purpose: The aim of study was to detect and characterize various lesions causing epilepsy in pediatric age group (0-12 years) and also to detect frequency with which they occurred using MRI. Methods: The study was performed on 50 children under the age of 12 years over a period of 1 year who presented with epilepsy. Patients with trauma and febrile seizure disorders were excluded. Conventional and contrast MRI was performed in all cases and lesions were characterized in location, signal intensity, and other features. Results: The mean age group of the study population was 1-5 years. Generalized seizures constituted the major seizure group. Our study shows infection as the most common etiology followed by mesial temporal sclerosis and Focal cortical dysplasia. It was followed by neoplastic etiology, phacomatosis and demyelinating diseases. Conclusion: MRI is the imaging modality of choice in the evaluation of pediatric patients presenting with epilepsy. Proper MRI seizure protocol helps to establish the correct diagnosis, plan the management according to diagnosis as well as helps in prognosis.

Pathological Classification of Focal Cortical Dysplasia (FCD) : Personal Comments for Well Understanding FCD Classification

In 2011, the International League against Epilepsy (ILAE) proposed a first international consensus of the classification of focal cortical dysplasia (FCD). This FCD classification had been widely used in worldwide. In this review paper, the authors would like to give helpful comments for better understanding of the current FCD classification. Especially, the basic concepts of FCD type I, such as “radial”, “tangential” and “microcolumn” will be discussed with figures. In addition, the limitations, genetic progress and prospect of FCD will be suggested.

Application of multimodal epilepsy assessment system in focal cortical dysplasia-related epilepsy / 第二军医大学学报

Objective: To propose a multimodal epilepsy assessment system to guide the surgical treatment of patients with focal cortical dysplasia (FCD)-related epilepsy, and to explore its significance in improving the prognosis of patients with FCD-related epilepsy. Methods: Twenty-two epilepsy patients with FCD confirmed by postoperative pathology, who underwent surgical treatment at Second Hospital of Lanzhou University from Oct. 2016 to Nov. 2018, were enrolled. All patients were evaluated by multimodal epilepsy assessment system during the perioperative period. The assessment techniques included onset symptom assessment, structural imaging, long-term scalp video electroencephalogram monitoring, positron emission tomography-computed tomography, image fusion analysis, and magnetic resonance imaging (MRI). Engel efficacy grading system was used to assess the prognosis. Engel I grade was defined as good control for epilepsy and Engel II to IV as poor control. Fisher exact test was used to explore the influences of gender, age, pathological type, MRI examination, lesion location, duration of disease, and electroencephalogram-clinical characteristic-anatomical localization consistency on the prognosis of patients. Results: Twenty-two patients (13 males and 9 females) underwent surgical resection of the lesions, and were followed up for 4 to 28 months. There were 18 cases of Engel I grade, 2 cases of Engel II grade, 1 case of Engel III grade, and 1 case of Engel IV grade, with the good control rate being 81.8% (18/22). Fisher exact test analysis showed that disease duration and electroencephalogram-clinical characteristic-anatomical localization consistency were independent factors of efficacy of FCD-related epilepsy (P = 0.045 and 0.005). While age, lesion location, gender, pathological type and MRI findings had no significant effect on prognosis (all P < 0.05). Conclusion: The multimodal epilepsy assessment system can more accurately locate epileptogenic foci of patients with FCD-related epilepsy, providing a theoretical basis for epilepsy surgery. It is a comprehensive and accurate assessment method for epileptogenic foci.

Pathological Classification of Focal Cortical Dysplasia (FCD) : Personal Comments for Well Understanding FCD Classification

In 2011, the International League against Epilepsy (ILAE) proposed a first international consensus of the classification of focal cortical dysplasia (FCD). This FCD classification had been widely used in worldwide. In this review paper, the authors would like to give helpful comments for better understanding of the current FCD classification. Especially, the basic concepts of FCD type I, such as “radial”, “tangential” and “microcolumn” will be discussed with figures. In addition, the limitations, genetic progress and prospect of FCD will be suggested.

Clinico-pathological investigations of a distinct variant of focal cortical dysplasia characterized by neuronal loss of layer four / 中华神经科杂志

Objective To investigate the clinical pathologic features of a distinct variant of focal cortical dysplasia (FCD) characterized by neuronal loss of layer four.Methods Between 2005 and 2017,approximately 3 000 surgeries were performed for the treatment of intractable epilepsy at Xuanwu Hospital,Capital Medical University and Yuquan Hospital,Tsinghua University.Retrospective analysis of clinic-pathological data of patients with epilepsy surgery was made and histological manifestations of neuronal loss of cortical layer four were included in this study.Results In this cohort,25 patients (22 males and three females) were identified with early onset pharmaco-resistant epilepsy and regionally circumscribed neuronal loss of cortical layer four in surgical specimens from the occipital lobe.Histologically,except for neuronal loss in cortical layer four in all cases,glial scar lesions were found in some patients.Thus the histology of those cases can be subdivided into two groups:group A (13 cases):neuronal loss of cortical layer four without glial scar lesions;and group B (12 cases):neuronal loss of cortical layer four with glial scar lesions.Due to the prominent horizontal disorganization of cortical layering and lack of any other microscopically visible principle lesion,group A should be classified hitherto as FCD International League Against Epilepsy (ILAE) type Ⅰ b,however,group B with scar lesions and cortical dysplasia around the main leision,should be classified as FCD ILAE type Ⅲd.This retrospective analysis of clinical histories revealed a perinatal distress in 20 patients (80％),suggesting an acquired pathomechanism.Magnetic resonance imaging revealed abnormal signals in the occipital lobe in all patients,and signal changes suggestive of encephalomalacia were found in 18 patients.Surgical treatment achieved favorable seizure control (Engel class Ⅰ and Ⅱ) in 18 patients (75％ among 24 available follow up).Comparion of the two groups with age at epilepsy onset (group A:5.00±2.76,group B:5.01±3.78),the proportion of perinatal distress (group A:11/13,group B:9/12) and the follow-up results (favorable seizure control of the two groups was 9/13,9/11 respectively) showed that there was no statistically significant difference between the two groups.Conculsion Neuronal loss of cortical layer four in the occipital lobe should be classified as a distinct variant of FCD ILAE type Ⅲd.

The application research of magnetoencephalograph combined with neuronavigation in the operation of frontal and temporal epilepsy caused by focal cortical dysplasia / 实用医学杂志

Objective To investigate the value of magnetoencephalograph(MEG)combined neuronavigation in the operation of frontal and temporal epilepsy caused by focal cortical dysplasia(FCD). Methods The data of 44 cases of frontal and temporal epilepsy caused by FCD were analyzed retrospectively. The location of epileptogenic zone and assessment IQ ,memory and language of patients were tested before operation;MEG examination confirmed the language dominance hemisphere and clarified the scope of language function. The surgical navigation system was guided by the American medtronic steal health 7 surgical navigation system to protect the neurological function. IQ,memory and language examination were measured 1 year after operation,and the data were analyzed before and after operation. The patients were followed up for 13~ 44 months after operation,according to Engel′s classification standard,the curative effect of epilepsy was determined. Results MEG can accurately localize the location of the language functional areas and FCD Epileptogenic zone. Of the 44 language functional areas ,28 had the left hemisphere and 16 were on the right side. Statistics showed that the verbal IQ and total IQ increased(P<0.05)in 1 year after operation,and there was no significant change in memory quotient and operation IQ(P >0.05). FCD patients recovered well ,and no language and limb function damaged. The curative effect of epilepsy:18 cases of Engel′sⅠgrade,22 cases of Engel′sⅡgrade;4 cases of Engel′sⅢgrade. Conclusions MEG combined with neuronavigation plays an important role in the localization ,localization and guidance of epileptogenic zone in patients with refractory frontal and temporal epilepsy caused by FCD ,which can protect the cortex function,avoid serious postoperative complications,and improve the therapeutic effect of epilepsy.

Ganglioglioma: a clinicopathological study of 19 cases / 临床与实验病理学杂志

Purpose To study the clinicopathologic features of ganglioglioma. Methods The clinicopathologic data of the cases pathologically diagnosed as ganglioglioma that underwent resection of epileptic focus were retrospectively analyzed. Results In the 19 cases studied, the mean onset age was 9.1 years, and the duration of disease was 9.3 years. MRI images showed abnormal signals. The majority of the site was temporal lobe (14/19, 73.7％). The tumors showed heterogeneity and often accompanied by focal cortical dysplasias (13/19, 68.4％). Immunohistochemical staining showed CD34 positive in 18 cases, Nestin positive in 16 cases, and BRAF-V600E positive in 6 case. The positive expression rate of CD34 and Nestin did not have significant differences. Conclusion The diagnosis of ganglioglioma relies on pathological observations combined with clinical features and neuroradiological examinations. Differential diagnosis should be done from other tumors or cortical dysplasia. Immunohistochemical staining of CD34 and Nestin can help diagnosis.

Discontinuing Antiepileptic Drugs after Pediatric Epilepsy Surgery for Focal Cortical Dysplasia

PURPOSE: Antiepileptic drugs (AEDs) can be discontinued in a subset of patients after surgery. We aimed to identify the factors related to successful AED withdrawal after surgery in pediatric patients with focal cortical dysplasia (FCD). METHODS: The study included 134 patients who underwent resective surgery for FCD at Severance Hospital between 2003 and 2014. Age of seizure onset, epilepsy duration, and location and histopathological classification of the FCD were compared between patients who experienced seizure recurrence and those who did not. The interval between surgery and initiation of AED reduction was also compared. RESULTS: In total, 134 patients were included. The median age at seizure onset was 1.0 year (interquartile range [IQR], 0.3–5.0). The median follow-up duration was 6.0 years (IQR, 1.0–13.0). AED withdrawal was attempted in 89 (66%), and 61 (69%) patients remained seizure-free. Of 61 patients, 38 (62%) were successfully weaned off all AEDs. Seizures recurred in 28 (31%) patients. The mean duration between surgery and initiation of AED reduction did not significantly differ between the seizure recurrence (4.5 months, IQR, 2.7–8.7) and non-recurrence groups (1.9 months, IQR, 0.5–5.4) (P<0.006). Patients who had FCD type IIb (39% vs. 7%, P=0.004) were more likely to be in the non-recurrence group than in the recurrence group (P=0.031). CONCLUSION: Surgical resection offers patients with FCD an opportunity to completely discontinue their AEDs. Early AED discontinuation may be pursued in patients with FCD in cases of complete resection.

The analysis of gene expression profile and related signal pathways in focal cortical dysplasia / 实用医学杂志

Objective To investigate the potential pathogenesis of Focal cortical dysplasia (FCD), we performed cDNA microarray analysis to obtain gene expression profile of FCD. Methods Three FCD samples and three normal controls were enrolled. Total RNA of the brain tissues were extracted. The difference gene expressions between FCD group and control group was detected using Affymetrix gene chip. The up and down-regulated genes were confirmed by Real-time PCR. Further, the related signal pathways involved in the pathogenic mechanisms of FCD were predicted by bioinformatics. Result In FCD, two up-regulated genes C21orF2 and AU152162 and 5 down-regulated genes ENPP2, ANLN, IP6K3, UGT8, and AZGP were found. Compared the FCD samples with the normal controls , there were significantly different in all down-regulated genes (P 0.05). Using bioinformatics analysis, the ENPP2 , UGT8 , and AZGP1 protein which located in the cell membrane or secreted into the extracellular matrix may be involved in the formation of the myelin sheath and the development of the nervous system by the lipid metabolism and LPA signaling pathway. Conclusion ENPP2, UGT8 and AZGP1 may be involved in pathogenesis of FCD through the process of myelin sheath formation and LPA signal pathway , which warrants further study to know their roles in the pathogenesis of FCD.

Correlation study of MRI features and pathological typing in focal cortical dysplasia / 实用放射学杂志

Objective To explore the correlations of the MRI findings and its pathological typing in the focal cortical dysplasia (FCD) .Methods MR images of 74 patients with FCD confirmed by operation and histopathologic examination were analysed retro‐spectively .MRI findings with FCD were divided into three subtypes including radial band type ,hyperintensity type and mild type . The correlation of the FCD MRI findings and pathological typing is analysed .Results In 74 patients with FCD ,there were radial band type in 12 cases ,hyperintensity type in 32 cases ,and mild type in 30 cases respectively .M RI finding of radial band type FCD showed a tail of increased T2WI/FLAIR signal tapering down to the lateral ventricle .Hyperintensity type FCD showed increased T2 WI/FLAIR signal in the cortex and subcortical white matter ,accompanied with focal cortical thickening .Mild type FCD showed T2 WI/FLAIR subtle hyperintense signal in cortex with or without focal cortical thickening ,but there was no hyperintense signal in subcortical white matter .Most of radial band type FCD were ⅡB in pathology .Most of hyperintensity FCD were ⅡA and ⅡB .Mild type FCD was more found to beⅠA orⅠB .Conclusion Analysing MRI features would improve the accurate diagnosis of FCD and help to infer the pathological type .

Neuropathological findings in 38 children with temporal lobe intractable epilepsy / 临床儿科杂志

ObjectivesTo explore the neuropathological characteristics of children with temporal intractable epilepsy. MethodsA retrospective analysis of the pathological characteristics was conducted in 38 children who underwent epilepsy surgery from December 2011 to December 2013.ResultsAmong 38 patients, aged 2.5-14 years, 21 boys and 17 girls, 21 cases had focal cortical dysplasia (FCD), 1 case had FCDⅠa, 2 cases had FCDⅠb, 1 case had FCDⅡa, 3 cases had FCDⅡb, 5 cases had CDⅢa, 1 case had FCDⅢb, 1 case had FCDⅢc, 6 cases had FCDⅢd. Three cases had microdysgenesis, 3 cases had simple hippocampal sclerosis, 7 cases had neoplasms, 5 cases had dysembryoplastic neuroepithelial tumor, 2 cases had astroglioma, 2 cases had encephalitis, 2 cases had arachnoid cyst. ConclusionsFCD is the most common form that causes temporal lobe intractable ep-ilepsy in children. FCDIIId is the most common subtype in FCD.

Displasia cortical focal, aspectos neurofisiológicos, imaginológicos e histológicos / Focal cortical dysplasia, aspects of neurophysiologic, imaginological and histological

INTRODUÇÃO: Displasia cortical focal é uma das formas mais frequentes de malformações do desenvolvimento cortical, estando intimamente relacionada com epilepsia de difícil controle em crianças e adultos. Caracterizam-se por alterações histológicas, imaginológicas e eletrofisiológicas peculiares. OBJETIVO: Fazer uma revisão sucinta dos principais aspectos imaginológicos, histológicos e neurofisiológicos das displasias corticais focais. MÉTODOS: Revisão bibliografia. CONCLUSÃO: As displasias corticais focais têm características clínicas peculiares, A prevalência de epilepsia refrataria entre pacientes com displasia cortical focal é bastante elevada. A RM de crânio apresenta alterações distintas a doença, podendo em muitos casos ser normal e se correlaciona com os achados histológicos. Descargas contínuas e surtos paroxísticos de alta frequência são altamente sugestivos de epilepsia devido à displasia cortical focal.

INTRODUCTION: Focal cortical dysplasia is one of the most common ways of malformation of the cortical development where they are intimate related among hard control epilepsy on children and adults. It's characterized by peculiar histological, imaginological and electrophysiological amendment. PURPOSE: To make a succinct review of the main aspects of imaginological, histological and neurophysiologic focal cortical dysplasias. METHOD: Bibliographic review. CONCLUSION: The focal cortical dysplasias have peculiar clinical features. The prevalence of refractory epilepsy among focal cortical dysplasia patients is highly elevated. The skull magnetic resonance image (MRI) presents specific amendments to the disease that could be normal in many cases and correlates with histological results. Continuous discharges and high frequency paroxistic bursts are highly pointed as epilepsy due the Focal cortical dysplasia.

Displasias corticales como causa de epilepsia y sus representaciones en las imágenes: [revisión] / Cortical dysplasia as a cause of epilepsy and its images respresentation: [review]

Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures, which are clinically classified as generalized or partial. Approximately, 30 percent of patients with partial epilepsy is refractory to medical treatment. Within the refractory group we must discard the presence of cortical dysplasia as an underlying cause of the crisis. Cortical dysplasias are a type of malformations of cortical development (MCD) that are increasingly recognized as a cause of refractory epilepsy. From the radiological point of view this kind of pathology is of particular interest since imaging manifestations can be subtle or may show completely normal examinations. The aim of this paper is to review the literature, describing the imaging appearance of the normal cortical development, the classifications of cortical malformations, mainly cortical dysplasias, by highlighting the most frequent radiological signs. We also examine the current role of positron emission tomography (PET) in epilepsy, which in conjunction with magnetic resonance imaging findings and electrophysiological studies are used to define a possible surgical treatment. Through this treatment we expect to be provided with details of histopathological alterations found in the surgical specimen to be compared to the radiographic changes revealed in the pre-surgical study.

La epilepsia es una alteración neurológica crónica caracterizada por crisis convulsivas recurrentes y espontáneas, que clínicamente se clasifican como generalizadas o parciales, dentro de las cuales aproximadamente el 30 por ciento de los pacientes con epilepsia parcial son refractarios al tratamiento médico. Dentro del grupo refractario debemos descartar la presencia de una displasia cortical como causa subyacente de las crisis. Las displasias corticales son un tipo de malformaciones del desarrollo cortical que en forma cada vez más frecuente se reconocen como causante de epilepsia refractaria. Desde el punto de vista radiológico, este tipo de patología tiene especial interés debido a que las manifestaciones imaginológicas pueden ser sutiles o presentar exámenes completamente normales. El objetivo de este artículo es realizar una revisión de la literatura, describiendo el desarrollo cortical normal con su aspecto en imágenes, las clasificaciones de las malformaciones corticales y en especial de las displasias corticales, destacando los signos radiológicos más frecuentes. Además revisaremos el rol en la actualidad de la Tomografía por Emisión de Positrones (PET) en epilepsia, que en conjunto con las imágenes por resonancia magnética y los estudios electrofisiológicos se utilizan para definir un eventual tratamiento quirúrgico, el que una vez realizado nos da detalles del análisis de las alteraciones histopatológicas en la pieza quirúrgica versus las alteraciones radiológicas visualizadas en el estudio pre-quirúrgico.

Surgically Treated Intractable Child Epilepsy with Focal Cortical Dysplasia : Clinical and Electroencephalographic Findings

PURPOSE: Widespread use of MRI now gives us increased insights into the different expressions of cortical malformations. We carried out this study to characterize the clinical and EEG features of focal cortical dysplasia(FCD) which also caused intractable epilepsy requiring surgical treatment. METHODS: A retrospective analysis was conducted in 8 children. The history of seizures, imaging studies, electroencephalographic findings, pathologic results, and surgical outcomes were reviewed. RESULTS: The onset ages of clinical seizure were from 4 days after birth to 36 months. The fre quency of seizures were from multiple times a day to a few times a month. Five out of 8 FCD patients had global developmental delays with more degrees of delay in language. Only 2 out of 8 patients showed clinical partial seizures only. The scalp EEG disclosed localized interictal epileptiform activity in all 8 patients and localized continuous slow waves in 7 out of 8 patients. Ictal scalp EEG onset demonstrated a predominantly localized EEG seizure activity in 6 patients. Ictal invasive EEG findings were variable in each patient and the patterns of ictal EEG were demonstrated. Five out of 8 patients became seizure-free. One patient had one episode of seizure during the 16 months follow up period. Two patients did not have significant relief from seizures. CONCLUSION: The patients with FCD had varied spectrums of clinical manifestation, MRI and EEG findings. Five out of 8 FCD patients had complete relief from seizures, one patient has had one short, simple, partial seizure since surgery, but 2 patients with FCD in the frontal area did not experience significant relief from seizures.