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.
Classification ; Consensus ; Embryology ; Epilepsy ; Humans ; Malformations of Cortical Development ; Pathology

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

Cortical dysplasia (CD) is considered to be a malformative lesion of the neocortex which exhibits a spectrum of pathologic changes reflecting a disturbance in the process of its development. CD is recently recognized as a major cause of intractable epilepsy with non-neoplastic lesions. Mischel et al. proposed that CD can be graded mild, moderate and severe with regard to nine specific microscopic abnormalities: mild CD consists of 1) cortical laminar disorganization, 2) single heterotopic white matter neurons, 3) neurons in the cortical molecular layer, 4) persistent remnants of the subpial granular cell layer, and 5) marginal glioneuronal heterotopia; moderate CD displays 6) polymicrogyria and 7) white matter neuronal heterotopia; severe CD phows 8) neuronal cytomegaly with associated cytoskeletal abnormalities and 9) balloon cell change. We reassessed 71 cases of cortical dysplasia to elucidate the proportion and histologic features of each group, using Mischel's grading system. CD was most frequently found in the temporal lobe with 50 cases (70%). Mild CD was predominently seen and was noted in 61 cases (86%) Cortical laminar disorganization and single heterotopic white matter neurons were identified in all mild CD cases. Neurons in the cortical molecular layer, persistent subpial granular cell layer, and marginal glioneuronal heterotopia were also noted in case numbers 40, 3, and 1 of mild CD, respectively. Moderate CD was composed of 2 cases with polymicrogyria, and the remaining 8 cases had severe CD. All moderate and severe CD were associated with the various histological features of mild CD. Thirty eight cases (51%) of CD showed dual pathology, composed of both CD and hippocampal sclerosis, and 5 cases of dysembryoplastic neuroepithelial tumor also had CD. Neurofilament immunostain revealed disarray of abnormally beaded axons in CD. We believe that the grading system of CD is very important to the evaluation and classification of CD.
Axons ; Classification ; Epilepsy ; Malformations of Cortical Development* ; Neocortex ; Neoplasms, Neuroepithelial ; Neurons ; Pathology ; Sclerosis ; Temporal Lobe

OBJECTIVE: The advent of high resolution magnetic resonance imaging(MRI) contributed to the preoperative localization of epileptogenic area. Even the discrete lesion visualized on MRI can be often correlated with seizure onset zone. If MRI does not, however, show any lesions in the extratemporal epilepsy, it imposes a significant challenge. This study is designed to evaluate the surgical treatment of extratemporal lobe epilepsy in which MRI does not show any lesion, to define the surgical strategy and to investigate the underlying pathology. METHODS: We studied the nineteen patients with MRI-negative extratemporal epilepsy who underwent resective surgery after careful preoperative investigation between 1993 and 1995. RESULTS: Scalp EEG could not lateralize the epileptogenic foci in 9 patients. Intracranial EEG recording was performed in all patients with successful localization: depth electrode study in 12, and subdural grid and strip study in 7 patients. Resection was performed in frontal(n=14), in parietal(n=3), and in multilobar area(n=2). Pathological findings comprised cortical dysplasia in 10, gliosis in 7, and collagenoma in one patients. The surgical outcome was classified as seizure free in 10, rare seizures in 2, significant reduction in 5, and no change in 2 patients. CONCLUSION: MRI-invisible extratemporal epilepsy can be managed surgically with promising results. Cortical dysplasia and gliosis are two major pathological findings in this context though MRI does not demonstrate any lesions.
Electrodes ; Electroencephalography ; Epilepsy* ; Gliosis ; Humans ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; Pathology ; Scalp ; Seizures

BACKGROUND: Mesial temporal sclerosis (MTS) is a well-known cause of temporal lobe epilepsy. Coexistence with cortical dysplasia (CD) has been reported, but its role is not well recognized. This study aims to determine whether there is any difference about clinical feature and surgical outcome between patients with MTS and coexistent CD (group 1) and patients with isolated MTS (group 2). METHODS: Retrospectively, surgical series of 45 patients (male:22, female:23) diagnosed as temporal lobe epilepsy were reviewed. We excluded patients who had another pathology (e. g., tumor, vascular malformation) except MTS or CD. The pathology, case histories, interictal EEG, and surgical outcome were compared. RESULTS: There was a tendency for group 1 patients to have earlier seizure onset age (10.9+/-6.35 versus 14.5+/-6.03, p=0.06) There was no statistically significant difference in the history of febrile convulsions (68.4% versus 53.8%, p>0.16) No statistically significant difference between groups were also found in disease duration, the head trauma/mental retardation history, seizure frequency, interictal EEG, and surgical outcome. CONCLUSIONS: CD in MTS appears to have an influence on seizure onset. The relationships among CD, febrile convulsion, and mesial temporal sclerosis must be more investigated.
Age of Onset ; Electroencephalography ; Epilepsy, Temporal Lobe* ; Head ; Humans ; Malformations of Cortical Development* ; Pathology* ; Retrospective Studies ; Sclerosis* ; Seizures ; Seizures, Febrile ; Temporal Lobe*

BACKGROUND: Mesial temporal sclerosis (MTS) is a well-known cause of temporal lobe epilepsy. Coexistence with cortical dysplasia (CD) has been reported, but its role is not well recognized. This study aims to determine whether there is any difference about clinical feature and surgical outcome between patients with MTS and coexistent CD (group 1) and patients with isolated MTS (group 2). METHODS: Retrospectively, surgical series of 45 patients (male:22, female:23) diagnosed as temporal lobe epilepsy were reviewed. We excluded patients who had another pathology (e. g., tumor, vascular malformation) except MTS or CD. The pathology, case histories, interictal EEG, and surgical outcome were compared. RESULTS: There was a tendency for group 1 patients to have earlier seizure onset age (10.9+/-6.35 versus 14.5+/-6.03, p=0.06) There was no statistically significant difference in the history of febrile convulsions (68.4% versus 53.8%, p>0.16) No statistically significant difference between groups were also found in disease duration, the head trauma/mental retardation history, seizure frequency, interictal EEG, and surgical outcome. CONCLUSIONS: CD in MTS appears to have an influence on seizure onset. The relationships among CD, febrile convulsion, and mesial temporal sclerosis must be more investigated.
Age of Onset ; Electroencephalography ; Epilepsy, Temporal Lobe* ; Head ; Humans ; Malformations of Cortical Development* ; Pathology* ; Retrospective Studies ; Sclerosis* ; Seizures ; Seizures, Febrile ; Temporal Lobe*

PURPOSE: Epilepsy surgery has become increasingly available in children with medically intractable epilepsy including temporal lobe epilepsy(TLE). TLE in children, however, has many different clinical and electrophysiologic characteristics which make presurgical evaluation difficult. The aim of this study is to evaluate the electroencephalographic(EEG) features which might be one of the predictors of postsurgical seizure outcomes in TLE. METHODS: Standard EEG, video-EEG, subdural or depth EEG were investigated in 12 children who underwent anterior temporal lobectomy, and their seizure semiology, MRI, and pathologic findings were also reviewed. Postsurgical seizure outcomes were divided into favorable(class I, II) and unfavorable(class III, IV) groups by using the Engel's classification. RESULTS: Half of the patients showed favorable outcomes, whose pathologic findings revealed hippocampal sclerosis or gliosis. Such pathologic findings were not demonstrated in MRI. Interictal epileptiform discharges were concordant with the location of the ictal onset in only 2 cases of the favorable outcomes. For the other 4 cases in the favorable group, focal ictal onset patterns were clearly evident in video-EEG monitorings or invasive EEG studies. Six cases in the unfavorable group showed unlocalized or multifocal interictal or ictal discharges -extratemporal, bitemporal or generalized epileptic activities- even in the invasive EEG studies. Five of them revealed cortical dysplasia in the pathology. CONCLUSION: The postsurgical seizure outcomes of hippocampal sclerosis or gliosis were more favorable than those of cortical dysplasia. Invasive EEG recordings should be considered for the localization of epileptic foci in the presurgical evaluation of children with intractable TLE.
Anterior Temporal Lobectomy ; Child* ; Classification ; Electroencephalography ; Epilepsy ; Gliosis ; Humans ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; Pathology ; Sclerosis ; Seizures ; Temporal Lobe*

BACKGROUND: Intractable partial epilepsy is the most frequent manifestation in cortical dysplasia (CD). The surgical removal of the epileptogenic focus in CD is the main therapeutic option for achieving seizure control. However, it is dif-ficult to predict surgical outcome by current diagnostic methods. We investigated 35 subjects with intractable epilepsy due to CD, in order to know the relationship the extent of lesion in a magnetic resonance imaging (MRI), the epilepto-genic foci in invasive electroencephalography (IEEG), pathologic grading, and surgical outcome. METHODS: We reviewed clinical findings (the seizure history, MRI), IEEG findings (interictal and ictal EEG), pathologic findings and surgical outcomes retrospectively and compared them. All the patients ranged in age from 2 to 45 years (mean: 21.8+10.8years). The time of their seizure onset ranged from 6 months to 31 years (mean:9.4+6.6years). The postopera-tive follow-up period ranged from 7 to 45months (mean:26+14months). RESULTS: Regarding MRI findings, the lesions were focal (within one lobe) in 10, diffuse (more than one lobe) in 7, and no abnormalities in 18 subjects. The ictal onset zones of ictal IEEG had one focus in 18, two in 7, three in 7, and four in 3 subjects. The area of focus was focal in 15, regional in 14, lobar in 4, and in diffuse areas in 2 subjects. Pathologic grading revealed mild in 18, moderate in 5, and severe changes in 13 subjects. Their surgical outcomes were: Engel's class I in 20, class II in 7, class III in 6, and class IV in 2 subjects. The relationships among clinical features, IEEG, regarding pathology and surgical outcomes, revealed that severe pathologic grading had a significant correlation with earlier ictal onset zones (p=0.003), and diffuse MRI lesions. Diffuse ictal onset zones had poor surgical outcomes (p<0.010). CONCLUSIONS: Cortical dysplasia may have a diverse pattern of epileptogenic foci in MRI and IEEG. The earlier the seizure onset is, the severe pathologic grading becomes. When the lesions in MRI as well as the ictal onet zones in IEEG were diffuse, the surgical outcome was poor.
Electroencephalography* ; Epilepsies, Partial ; Epilepsy* ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging* ; Malformations of Cortical Development* ; Pathology ; Retrospective Studies ; Seizures

Epilepsy is a common cerebral disease, and may cause sudden death. Although electric activity study of epileptic brain had been emphasized in the past, the neuropathological study of epilepsy has become a main focus in clinical and forensic medicine recently. This article reviews the recent progress in neuropathology of epilepsy including developmental disorder, abnormal tumoral proliferation, hippocampal sclerosis, dual pathological alteration, and mossy fiber sprouting. Its significance in forensic medicine, particularly for the diagnosis of sudden unexpected death in epilepsy, is discussed.
Brain/pathology* ; Brain Neoplasms/pathology* ; Cause of Death ; Death, Sudden/etiology* ; Epilepsy/physiopathology* ; Forensic Pathology ; Hippocampus/pathology* ; Humans ; Malformations of Cortical Development/pathology* ; Sclerosis/pathology*

Many pathological surveys of brain tissue in patients with intractable epilepsy have been reported. There have been, however, few studies focused on the differences between childhood and adults in pathological alterations of brain. We retrospectively analyzed histopathology of 164 lobectomy specimens for intractable epilepsy in view of the differences between children and adults. Among 164 cases, 28 cases were children (less than 15 years) and 136 cases adults. We compared frequency of histopathologic features, distribution of involved cortex (temporal or extratemporal lobe), previous injury histories, such as brain trauma, encephalitis or febrile seizure, and coexistence of other lesions (dual pathology) between two groups. Pathologic alterations were encountered in 92% of 164 patients. In children focal cortical dysplasia (n=16, 57.1%), neoplasm (n=8, 28.6%), hippocampal sclerosis (n=6, 21.4%), cortical tuber (n=1, 3.6%), leukomalacia (n=1, 3.6%), and Rasmussen's encephalitis (n=1, 3.6%) were observed, whereas focal cortical dysplasia (n=81, 59.6%), hippocampal sclerosis (n=80, 58.8%), neoplasm (n=19, 14%), and cerebral cysticercosis (n=3, 2.2%) were found in adults. Pediatric patients had a higher proportion of severe focal cortical dysplasia (17.9% in children, 0.7% in adults). Neoplasia and extratemporal lobe involvement were more commonly found in children (28.6%, 50%) than in adults (14.0%, 24.3%), whereas hippocampal sclerosis and dual pathology were more common in adults (58.8%, 44.9%) than in children (21.4%, 17.9%). Previous injury history was statistically significant in patients with hippocampal sclerosis, and lent support to the hypothesis that hippocampal sclerosis is related with acquired lesions. Incidence of focal cortical dysplasia was nearly similar in both adult (59.6%) and pediatric groups (57.1%), and supported the hypothesis that focal cortical dysplasia is developmental abnormality occurring during a prenatal period.
Adult* ; Brain ; Brain Injuries ; Child* ; Cysticercosis ; Encephalitis ; Epilepsy ; Epilepsy, Temporal Lobe ; Humans ; Incidence ; Malformations of Cortical Development ; Pathology ; Retrospective Studies ; Sclerosis ; Seizures* ; Seizures, Febrile