• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.288-295
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• 2019

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.

• BMB Reports
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• v.49 no.2
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• pp.71-72
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• 2016

Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.321-327
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• 2019

Focal cortical dysplasia (FCD) is the major cause of intractable focal epilepsy in childhood leading to epilepsy surgery. The overall seizure freedom after surgery ranges between 50-75% at 2 years after surgery and the long-term seizure freedom remain relatively stable. Seizure outcome after surgery depends on a various factors such as pathologic etiologies, extent of lesion, and types of surgery. Therefore, seizure outcome after surgery for FCD should be analyzed carefully considering cohorts' characteristics. Studies of pediatric epilepsy surgery emphasize the early surgical intervention for a better cognition. Early surgical intervention and cessation of seizure activity are important for children with intractable epilepsy. However, there are limited data on the cognitive outcome after surgery in pediatric FCD, requiring further investigation. This paper reviews the seizure and cognitive outcomes of epilepsy surgery for FCD in children. Several prognostic factors influencing seizure outcome after surgery will be discussed in detail.

• Journal of Korean Neurosurgical Society
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• v.52 no.5
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• pp.466-471
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• 2012

Objective : The aim of this study was to devise an objective clustering method for magnetoencephalography (MEG) interictal spike sources, and to identify the prognostic value of the new clustering method in adult epilepsy patients with cortical dysplasia (CD). Methods : We retrospectively analyzed 25 adult patients with histologically proven CD, who underwent MEG examination and surgical resection for intractable epilepsy. The mean postoperative follow-up period was 3.1 years. A hierarchical clustering method was adopted for MEG interictal spike source clustering. Clustered sources were then tested for their prognostic value toward surgical outcome. Results : Postoperative seizure outcome was Engel class I in 6 (24%), class II in 3 (12%), class III in 12 (48%), and class IV in 4 (16%) patients. With respect to MEG spike clustering, 12 of 25 (48%) patients showed 1 cluster, 2 (8%) showed 2 or more clusters within the same lobe, 10 (40%) showed 2 or more clusters in a different lobe, and 1 (4%) patient had only scattered spikes with no clustering. Patients who showed focal clustering achieved better surgical outcome than distributed cases (p=0.017). Conclusion : This is the first study that introduces an objective method to classify the distribution of MEG interictal spike sources. By using a hierarchical clustering method, we found that the presence of focal clustered spikes predicts a better postoperative outcome in epilepsy patients with CD.

• Journal of Korean Neurosurgical Society
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• v.56 no.3
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• pp.248-253
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• 2014

Objective : Cortical dysplasia (CD) is one of the common causes of epilepsy surgery. However, surgical outcome still remains poor, especially with frontal lobe epilepsy (FLE), despite the advancement of neuroimaging techniques and expansion of surgical indications. The aim of this study was to focus on surgical strategies in terms of extent of resection to improve surgical outcome in the cases of FLE with CD. Methods : A total of 11 patients of FLE were selected among 67 patients who were proven pathologically as CD, out of a total of 726 epilepsy surgery series since 1992. This study categorized surgical groups into three according to the extent of resection : 1) focal corticectomy, 2) regional corticectomy, and 3) partial functional lobectomy, based on the preoperative evaluation, in particular, ictal scalp EEG onset and/or intracranial recordings, and the lesions in high-resolution MRI. Surgical outcome was assessed following Engel's classification system. Results : Focal corticectomy was performed in 5 patients and regional corticectomy in another set of 5 patients. Only 1 patient underwent partial functional lobectomy. Types I and II CD were detected with the same frequency (45.45% each) and postoperative outcome was fully satisfactory (91%). Conclusion : The strategy of epilepsy surgery is to focus on the different characteristics of each individual, considering the extent of real resection, which is based on the focal ictal onset consistent with neuroimaging, especially in the practical point of view of neurosurgery.

• 대한핵의학회:학술대회논문집
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• 1997.05a
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• pp.177-177
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• 1997

• Journal of Korean Neurosurgical Society
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• v.29 no.7
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• pp.861-867
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• 2000

Purpose : Neuronal migration disorder(NMD) is a major underlying pathology of patients with intractable epilepsy. The role of NMD on seizure susceptibility or epileptogenecity, however, has not been documented. Methods : External irradiation of total amount of 250 cGY was performed to the fetal rats on days 16(E16) and 17(E17) of gestation. After delivery, the rats of 230-260g were decapitated for the histopathologic study. Epileptog-enecity of the NMD was studied by observing electroclinical events after intraperitoneal kainic acid(KA) injection in the control rats and NMD rats. Results : Histopathologic findings revealed focal and/or diffuse cortical dysplasia consisting of dyslamination of the cerebral cortex and appearance of the cytomegalic neurons, neuronal heterotopia in the periventricular white matter, dispersion of the pyramidal layer and the dentate gyrus of the hippocampus, and agenesis of the corpus callosum. Abnormal expression of neurofilaments protein(NF-M/H) was characteristically observed in the dysplastic neurons of the neocortex and hippocampus. Early ictal onset and prolonged ictal activity on EEG and clinical seizures were observed from the NMD rats unlike with the control rats. Conclusions : Exteranl irradiation on the fetal rats produced NMD. And the rats with NMD were highly susceptible to kainic acid provoked seizures. This animal model would be useful to study the pathophysiology of clinically relevant NMDs.

• Toxicological Research
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• v.17
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• pp.11-16
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• 2001

The development of the central nervous system is a continuous process during the embryonic and fetal periods. For a better understanding of congenital anomalies of central nervous system, three major events of normal development, i.e., neurulation (3 to 4 weeks), brain vesicle formation (4 to 7 weeks) and mantle formation (over 8 weeks) should be kept in mind. The first category of anomalies is neural tube defect. Neural tube defects encompass all the anomalies arise in completion of neurulation. The second category of central nervous system anomalies is disorders of brain vesicle formation. This is anomaly that applies for "the face predicts the brain". Holoprosencephaly covers a spectrum of anomalies of intracranial and midfacial development which result from incomplete development and septation of midline structures within the forebrain or prosencephalon. The last category of central nervous system malformation is disorders involving the process of mantle formation. In the human, neurons are generated in two bursts, the first from 8 to 10 weeks and next from 12 to 14 weeks. By 16 weeks, most of the neurons have been generated and have started their migration into the cortex. Mechanism of migration disorders are multifactorial. Abnormal migration into the cortex, abnormal neurons, faulty neural growth within the cortex, unstable pial-glial border, degeneration of neurons, neural death by exogenous factors are some of the proposed mechanism. Agyria-pachygyria are characterized by a four-layerd cortex. Polymicrogyria is gyri that are too numerous and too small, and is morphologically heterogeneous. Cortical dysplasia is characterized by the presence Q[ abnormal neurons and glia arranged abnormally in focal areas of the cerebral cortex. Neuroglial malformative lesions associated with medically intractable epilepsy are hamartia or hamartoma, focal cortical dysplasia and microdysgenesis.ysgenesis.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.272-287
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• 2019

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

• Investigative Magnetic Resonance Imaging
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• v.14 no.2
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• pp.126-133
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• 2010

Purpose : The study was to evaluate the localization of the abnormal gyral and sulcal patterns obtained by means of brain surface rendering imaging. Materials and Methods : Nineteen patients with cortical dysplasia who underwent brain surface rendering MR imaging were included in this study. We acquired MP-RAGE sequence and created the 3-D surface rendering MR images by using $VoxelPlus^{(R)}$. Anatomical locations and configurations of abnormal gyri and sulci were reviewed. Results : Abnormal gyral and sulcal patterns were seen 18 in 19 patients. The configuration and orientation of affected gyri and sulci were clearly evaluated in the brain surface rendering images. In a lissencephaly, the a cortex was not delineated and showed markedly thick and smooth gyral pattern. In a schizencephaly, there were wheel shaped broad gyral pattern around the cleft. In a hemimegalencephaly, an affected hemisphere were enlarged and displayed thick and wide gyral pattern. In CBPS, the insular cortex was exposed and the gyri of the lesion were thickened. In focal cortical dysplasia, there were irregular serrated or thick and enlarged gyri. Conclusion : Brain surface rendering MR imaging is useful for the evaluation of a detailed gyral pattern and accurate involvement site of abnormal gyri.