• 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.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.

• 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.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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.19 no.1
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• pp.26-30
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• 2019

PCDH19-related epilepsy is an inherited disease occurring in female patients and characterized by early onset seizure, intellectual disability, and behavioral disturbances. It is caused by de novo or familial heterozygous variation of the PCDH19 gene located on Xq22.1. Our patient was hospitalized for multiple focal seizures. The magnetic resonance imaging was normal and electroencephalogram showed focal epileptiform discharges. The child's development did not progress; she began to manifest, cognitive, behavioral and language delays. Because of that, we performed an epilepsy gene panel test. We report a case of epilepsy with mental retardation limited to female patients with mutation of PCDH19.

• Journal of Sensor Science and Technology
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• v.20 no.1
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• pp.19-24
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• 2011

Brain disorders such as epilepsy is a condition that affects an estimated 2.7 million Americans, 50,000,000 worldwide, approximately 200,000 new cases of epilepsy are diagnosed each year. Of the major chronic medical conditions, epilepsy is among the least understood. Scientists are conducting research to determine appropriate treatments, such as the use of drugs, vagus nerve stimulation, brain stimulation, and Peltier chip-based focal cooling. However, brain stimulation and Peltier chip-based stimulation processes cannot effectively stop seizures. This paper presents simulation of a novel heat enchanger network(HEN) technique designed to stop seizures by using a neural cooling probe to stop focal and spontaneous seizures by cooling the brain. The designed probe was composed of a U-shaped tube through which cold fluid flowed in order to reduce the temperature of the brain. The simulation results demonstrated that the neural probe could cool a 7 $mm^2$ area of the brain when the fluid was flowing atb a velocity of 0.55 m/s. It also showed that the neural cooling probe required 23 % less energy to produce cooling when compared to the Peltier chip-based cooling system.

• Journal of Genetic Medicine
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• v.18 no.2
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• pp.137-141
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• 2021

Genetic causes of developmental and epileptic encephalopathy (DEE) have been rapidly uncovered from mid-2010s. The mutations of gene enconding calcium channel, voltage-dependent, P/Q type, alpha 1A subunit (CACNA1A) are recently detected in DEE, which gene is already known well in familial hemiplegic migrine type 1 or episodic ataxia type 2. Ketogenic diet therapy (KDT) is effective in some DEE, which data is short in CACNA1A encephalopathy. A 3-month-old male with global developmental delay and multidrug-resistant focal seizures was diagnosed as epilepsy of infancy with migrating focal seizures (EIMFS). Brain magnetic resonance imaging and metabolic screening were all normal. Whole exome sequencing revealed two variants of CACNA1A: c.899A>C, and c.2808del that is from his mother. His seizures disappeared within 3 days whenever on KDT, which recurred without it. To our knowledge, this rare case of EIMFS with novel mutations of CACNA1A, is the first report in CACNA1A encephalopathy becoming seizure-free on KDT.

• Clinical and Experimental Pediatrics
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• v.63 no.5
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• pp.171-177
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• 2020

Low-grade epilepsy-associated neuroepithelial tumors (LEATs) are responsible for drug-resistant chronic focal epilepsy, and are the second-most common reason for epilepsy surgery in children. LEATs are extremely responsive to surgical treatment, and therefore epilepsy surgery should be considered as a treatment option for LEATs. However, the optimal time for surgery remains controversial, and surgeries are often delayed. In this review, we reviewed published article on the factors associated with seizure and cognitive outcomes after epilepsy surgery for LEATs in children to help clinicians in their decision whether to pursue epilepsy surgery for LEATs. The achievement of gross total resection may be the most important prognostic factor for seizure freedom. A shorter duration of epilepsy, a younger age at surgery, and extended resection of temporal lobe tumors have also been suggested as favorable prognostic factors in terms of seizure control. Poor cognitive function in children with LEATs is associated with a longer duration of epilepsy and a younger age at seizure onset.

• 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.

• Annals of Clinical Neurophysiology
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• v.9 no.2
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• pp.69-74
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• 2007

Electroencephalogram (EEG) is a representative diagnostic tool in epilepsy. However, there are several points of debate on the role of EEG in diagnosis and management of epilepsy. We suggest that EEG has some limitations for differential diagnosis from nonepileptic episodic diseases, classification of epilepsy, prediction of recurrence, and evaluation of treatment response. Interictal EEG cannot diagnose or exclude epilepsy because interictal epileptic discharge (IED) is frequently absent in epilepsy and can appear in nonepileptic conditions. Although EEG is helpful in classification of epilepsy, focal spikes in generalized epilepsy and secondary bilateral synchrony in localization related epilepsy cause interrater disagreement. It is controversial whether EEG predicts recurrence after the first seizure in adults. The predictive value of EEG in antiepileptic drug (AED) withdrawal is not absolute. The prognosis after AED withdrawal depends on epilepsy syndrome. Many studies could not confirm the value of EEG in assessing the treatment response. After all, epilepsy is clinically diagnosed and assessed. Interictal EEG alone does not provide decisive information and routine follow-up of EEG is not recommended.