Epileptogenic Properties of Balloon Cells in Cortical Tubers of Tuberous Sclerosis: Upregulation of Drug Resistance Proteins

OBJECTIVES: Balloon cells and dysplastic neurons are histopathological hallmarks of the cortical tubers of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) of the Taylor type. They are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. P-glycoprotein (P-gp) is the product of multidrug resistance gene (MDR1), and it maintains intracellular drug concentration at a relatively low level. The authors investigated expression of P-gp in balloon cells and dysplastic neurons of cortical tubers in patients with TSC. METHODS: An immunohistochemical study using the primary antibody for P-gp, as an indicative of drug resistance, was performed in the cortical tuber tissues in two patients of surgical resection for epilepsy and six autopsy cases. RESULTS: Balloon cells of each lesion showed different intensity and number in P-gp immunopositivity. P-gp immunopositivity in balloon cells were 28.2%, and dysplastic neurons were 22.7%. These immunoreactivities were more prominent in balloon cells distributed in the subpial region than deeper region of the cortical tubers. Capillary endothelial cells within the cortical tubers also showed P-gp immunopositivity. CONCLUSION: In this study, the drug resistance protein P-glycoprotein in balloon cells and dysplastic neurons might explain medically refractory epilepsy in TSC.

A Study of Ulegyria as Pathognomonic Aspects of Congenital Bilateral Perisylvian Syndrome

OBJECTIVE: Congenital bilateral perisylvian syndrome (CBPS) has been defined as a characteristic malformative perisylvian polymicrogyria (PMG) in patients with clinical symptoms of pseudobulbar palsy and epileptic seizures. For the present study, we investigate clinicopathologic features of CBPS associated with timing of lesion formation. METHODS: Clinicopathologic features of CBPS from 6 patients with surgical resection of the cerebral lesions due to medically intractable seizures were studied. RESULTS: Seizure onset ranged from 1 to 10years (average 6.7years) of age, and average duration of seizure was 23years. All had complex partial seizures, and two patients had additional tonic clonic seizures. Magnetic resonance (MR) images showed polymicrogyria, atropic gyri with gliosis. In the histopathologic examination, the cortical lesions revealed features of ulegyria ; atrophic and sclerotic gyri, laminar loss of neurons, extensive lobular gliosis throughout the gray and white matter, neuronoglial nodule formation, and many amyloid bodies. Unlayered or four-layered PMG was not identified. CONCLUSION: Above data suggest that CBPS might be caused by ulegyria resulting from developmental cortical defect during early fetal stage or acquired hypoxic/ischemic injury in prenatal or postnatal life.

c-JUN Expression and Apoptotic Cell Death in Kainate-Induced Temporal Lobe Epilepsy

Following kainate (KA)-induced epilepsy, rat hippocampal neurons strongly ex-press immediate early gene (IEG) products, i.e., c-FOS and c-JUN, and neural stress protein, HSP72. Prolonged expression of c-JUN and c-FOS 48 hr after cerebral ischemia has been underwent delayed neuronal death. However, it is not yet clear whether IEGs actually assume the essential roles in the cell death process or simply as a by-product due to external stimuli because of the prolonged expression of c-FOS, more than one week, on intact CA2 neurons of the hippocampus in a KA-induced epilepsy model. This study investigated the relationships between prolonged expression of c-JUN and hippocampal neuronal apoptosis in a KA-induced epilepsy model. Epileptic seizure was induced in rats by a single microinjection of KA (1g/l) into the left amygdala. Characteristic seizures and hippocampal neuronal injury were developed. The expression of c-JUN was evaluated by immunohistochemistry, and neuronal apoptosis by in situ end labeling. The seizures were associated with c-JUN expression in the hippocampal neurons, of which the level showed a positive correlation with that of apoptosis. Losses of hippocampal neurons, especially in the CA3 region, were partly caused by apoptotic cell death via a c-JUN-mediated signaling pathway. This is thought to be an important component in the pathogenesis of hippocampal neuronal injury via KA-induced epilepsy.

A Case of Brain Stem Anaplastic Oligodendroglioma with Exophytic Growth

No abstract available.

Neuropathologic studies of cerebral cortical dysplasia

Cortical dysplasia(CD) represents a spectrum of neuropathologic changes reflecting a derangement of the normal process of neocortical development. We have presented 32 patients who underwent cortical recectiom for intractable seizures and demonstrated the neuropathologic features, which could be explained by a disturbance in the process of neural development in the farm. It could be characterized by light microscopic features: cortical laminar disorganization, neurons in the molecular layer, subpial re=ants of granule calls, remnants of marginal glioneuronal heterotopia, neuronal heterotopia in the white matter, polymicrogyria, neuronal cytomegaly and balloon cell change. Even though cortical dyslamimtion was the consistent finding of all the cases, the neuronal cytomegaly and balloon cell change were diagnostic hallmarks in the study. The cytomegatic neurons were strongly reactive to silver impregration and to immunohistochemical marrkers of neurons, such as neurofilament protein (NF, 68 and 200 kDa) and neuron-specific enolase(NSE). They showed hypertrophic endoplmmic reticul= and increased number of mitochondria in their cytoplasm and incomplete synapses in electron microscopic study. The balloon cells were positively stained by glial fibrillary acidic protein, NSE and vimentin and were filled with intermediate filaments in their cytoplasm. These results indicated that both cytomegalic neurons and balloon cells are produced by faulty cell differentiation involving neuroblast in the former, and both neuronal and glial stem cell lines in the latter.

Anatomicophysiologic Monitoring in the Surgery of Central Area

In the surgery of central area, identifying the motor cortex in front of central sulcus is imperative to prevent loss of motor function. Twenty five patients with tumors or intractable epilepsy near the central sulcus were operated on at the Department of Neurosurgery of Chonbuk National University Hospital, from September. 1991 to December 1993. An estimated localization of lesions was performed with Callosal Grid System, which is a methodolgy made available by the development of high quality of magnetic resonance imaging, digital subtraction angiography and high resolution computerized tomography. This system allowed us to be oriented to the motor cortex as well as permitted assessment of the extent of resection. This was further delineated by direct electrical stimulation, which confirmed the functional motor cortex and made it possible to maximized the tumor resection near and in the motor cortex. The combination of direct cortical stimulation(functional mapping) and the use of the Callosal Grid System(anatomical mapping) allowed us to identify the spatial relationship between them as well as to maximize the tumor resection in most cases without injury to the central area, so that the better outcome is guaranted.

Indications for and types of intracranial electrode EEG studies in the presurgical evaluation of epileptic patients

Os autores discutem as indicaçöes, as vantagens e os tipos de eletrodos intracranianos utilizados na avaliaçäo pré-cirurgica dos pacientes epilépticos. Säo discutidas as indicaçöes formais tais como: (1) a possibilidade de epilepsia extratemporal sem lesöes associadas nos estudos de neuroimagem, (2) pacientes com epilepsia do lobo temporal e com (a) atividade epileptógena sem predominancia de lado e sem esclerose hipocampal no exame de ressonância nuclear magnética; (b) atividade epileptógena interictal/ictal associada à lesäo temporal ou extratemporal; (c) anormalidade temporal unilateral nos exames de neurimagem associadas à crise epiléptica com padräo clínico extratemporal. É discutida a indicaçäo nas epilepsias neocorticais associadas a lesöes cerebrais que é, provavelmente, a mais debatida das indicaçöes