Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurosurgical resection of an epileptic focus was performed in eleven patients suffering from drug resistant focal epilepsy. The clinical result was favourable in nine cases and corresponds to the earlier results. The routinely processed biopsy specimens obtained from the brain resections were stained with haematoxylin-eosin and with specific antisera to GFAP, S-100, NSE, laminin, and fibronectin using the peroxidase-antiperoxidase technique. The main pathological finding was gliosis in eight cases, neuronal degeneration in two cases, and a vascular malformation in one case. The anti-GFAP as a specific marker of astrocytes made the astroglial proliferation clearly visible, demonstrating an astroglial scar in four cases and a moderately to strongly increased amount of astroglial cells in another four cases. Anti-S-100 and anti-fibronectin are not as specific markers. They stained both neurones and glial cells with comparable results to that of anti-GFAP but with a lower specificity and sensitivity. Anti-NSE showed decreased amounts of neurones in most of the heavily gliotic lesions and also stained glial cells in some cases. Anti-laminin stained the pial and vascular basement membranes and revealed an increased vasculature in two cases. From these results, it appears that GFAP immunostaining is a highly demonstrative means for the visualization of astrogliosis in epileptic lesions and may be of help in identifying slight focal changes. An exact demonstration of neuronal loss or other neuronal changes still waits for a more specific marker than NSE. A favourable clinical outcome after neurosurgery seems to be associated with the patients showing a clearly gliotic brain lesion in one temporal lobe.
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PMID:Histopathological and immunohistochemical changes in neurosurgically resected epileptic foci. 343 49

At variance with the rat, previous observations disclosed the presence of long interlaminar astroglial processes in the cerebral cortex of adult nonhuman primates. To examine its presence in human cerebral cortex, samples of frontal and temporal cerebral cortices were obtained during programmed brain surgery from a young patient with an intraventricular astrocytoma, and from one young and two adult patients with frontal and temporal lobe focal epilepsy, respectively. Samples of the visual cortex were also obtained at an autopsy of an 84-year-old woman without any known neurological disease. Brain tissues were processed for GFAP-IR immunocytochemistry. Long, interlaminar, GFAP-IR astroglial processes of usually 300-500 microm, but occasionally reaching almost 1,000 microm, were observed. These processes resembled those previously described in the cerebral cortex of adult New World monkeys. Available data suggest that they may represent a predominant characteristic in postnatal primate cerebral cortex. EM analysis of club-like endings disclosed a multilamellar organization of GFAP-IR intermediate filaments, and the presence of mitochondria and amorphous, electron dense material. Their possible function is yet to be determined.
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PMID:Immunocytochemical and electron microscope observations on astroglial interlaminar processes in the primate neocortex. 916 61

Cortical dysplasia (CD) is now recognized as one of the major causes of pediatric focal neocortical epilepsy, and surgical procedures have been considered early in life. However, the mechanisms involved in seizure generation and intractability in these patients are still unknown. We analyzed with immunocytochemistry for various antibodies the brain tissue from 4 children (10 months to 6 years old) with focal epilepsy due to focal CD in order to study the inhibitory and excitatory circuits in dysplastic areas. Our group had similar histopathological and clinical characteristics. In all patients we found areas of cortical disorganization with dysplastic neurons and balloon cells. We studied distributions of glial cells with glial fibrillary acidic protein (GFAP) and neurons with microtubule-associated protein 2 (MAP-2). Gliosis was present in all cases, and GFAP stained also some balloon cells. Dysplastic neurons were darkly stained by MAP-2, and we also found balloon cells weakly stained with MAP-2 in the same areas where GFAP was positive, suggesting coexpression of neuronal and glial markers in some of these cells. There was an increased expression of glutamate receptors, especially GluR2/3, but also N-methyl-D-aspartate receptors in dysplastic cortex. The inhibitory circuit does not seem to be decreased, rather we notice an increased amount of glutamate-decarboxylase-positive terminals around some of the big neurons. We discuss the possible role of these findings as mechanisms of epilepsy.
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PMID:Focal cortical dysplasia in children. 1057 50

Microdysgenesis is a subtle malformation, which is often found in specimens from epilepsy surgery. It is, however, not clear whether the changes are focal or diffuse. A recent autopsy case offered an opportunity to investigate whether microdysgenesis found after temporal lobe surgery was focal or widespread in the brain. The entire brain of a 20-year-old patient who died suddenly and unexpectedly was examined histologically. Microdysgenesis had previously been diagnosed after a left temporal lobectomy performed because of therapy-resistant seizures. A light microscopic examination was performed on specimens stained with Luxol-fast blue-cresyl violet and polyclonal antibodies to glial fibrillary acidic protein. Widespread microdysgenesis with irregular nerve cell distribution in the cortex and an increased number of nerve cells in cortical layer I and in the white matter was found in the right temporal and parietal lobes and bilaterally in the frontal and occipital lobes. The post-mortem examination confirmed the previous diagnosis of microdysgenesis and showed that the changes were widespread in a patient who was operated on because of focal epilepsy.
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PMID:Widespread microdysgenesis in therapy-resistant epilepsy--a case report on post-mortem findings. 1190 14

Newer MRI methods can detect cerebral abnormalities not identified on routine imaging in patients with focal epilepsy. Correlation of MRI with histopathology is necessary to understand the basis of MRI abnormalities and subsequently predict histopathology from in vivo MRI. The aim of this study was to determine if particular quantitative MR parameters were associated with particular histological features. Nine patients with temporal lobe epilepsy were imaged at 1.5 T using standard presurgical volumetric and quantifiable sequences: magnetization transfer and FFT2. The resected temporal lobe was registered with the volumetric MRI data according to our previously described method to permit correlation of the modalities. Stereologically measured neuronal densities and field fraction of GFAP, MAP2, synaptophysin and NeuN immunohistochemistry were obtained. Analyses were performed in the middle temporal gyrus and compared with quantitative MRI data from the equivalent regions. There was a significant Spearman Rho negative correlation between NeuN field fraction and the T2 value in gray matter (correlation coefficient -0.72, p=0.028). There were no significant correlations between any neuropathological and MR measures in white matter. These preliminary findings suggest that T2 in gray matter is sensitive to the proportion of neuronal tissue. Novel quantitative MRI measures acquired with higher field strength magnets, and so with superior signal to noise ratios, may generate data that correlate with histopathological measures. This will enable better identification and delineation of the structural causes of refractory focal epilepsy, and will be of particular benefit in patients in whom current optimal MRI does not identify a relevant abnormality.
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PMID:Correlation of quantitative MRI and neuropathology in epilepsy surgical resection specimens--T2 correlates with neuronal tissue in gray matter. 1755 88

Focal epilepsy often develops following traumatic, ischemic, or infectious brain injury. While the electrical activity of the epileptic brain is well characterized, the mechanisms underlying epileptogenesis are poorly understood. We have recently shown that in the rat neocortex, long-lasting breakdown of the blood-brain barrier (BBB) or direct exposure of the neocortex to serum-derived albumin leads to rapid upregulation of the astrocytic marker GFAP (glial fibrillary acidic protein), followed by delayed (within 4-7 d) development of an epileptic focus. We investigated the role of astrocytes in epileptogenesis in the BBB-breakdown and albumin models of epileptogenesis. We found similar, robust changes in astrocytic gene expression in the neocortex within hours following treatment with deoxycholic acid (BBB breakdown) or albumin. These changes predict reduced clearance capacity for both extracellular glutamate and potassium. Electrophysiological recordings in vitro confirmed the reduced clearance of activity-dependent accumulation of both potassium and glutamate 24 h following exposure to albumin. We used a NEURON model to simulate the consequences of reduced astrocytic uptake of potassium and glutamate on EPSPs. The model predicted that the accumulation of glutamate is associated with frequency-dependent (>100 Hz) decreased facilitation of EPSPs, while potassium accumulation leads to frequency-dependent (10-50 Hz) and NMDA-dependent synaptic facilitation. In vitro electrophysiological recordings during epileptogenesis confirmed frequency-dependent synaptic facilitation leading to seizure-like activity. Our data indicate a transcription-mediated astrocytic transformation early during epileptogenesis. We suggest that the resulting reduction in the clearance of extracellular potassium underlies frequency-dependent neuronal hyperexcitability and network synchronization.
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PMID:Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? 1971 Mar 12

Rasmussen encephalitis (RE) is a rare neurologic disorder of childhood characterized by unihemispheric inflammation, progressive neurologic deficits, and intractable focal epilepsy. The pathogenesis of RE is still enigmatic. Adenosine is a key endogenous signaling molecule with anticonvulsive and anti-inflammatory effects, and our previous work demonstrated that dysfunction of the adenosine kinase (ADK)-adenosine system and astrogliosis are the hallmarks of epilepsy. We hypothesized that the epileptogenic mechanisms underlying RE are related to changes in ADK expression and that those changes might be associated with the development of epilepsy in RE patients. Immunohistochemistry was used to examine the expression of ADK and glial fibrillary acidic protein in surgically resected human epileptic cortical specimens from RE patients (n = 12) and compared with control cortical tissues (n = 6). Adenosine kinase expression using Western blot and enzymatic activity for ADK were assessed in RE versus control samples. Focal astrogliosis and marked expression of ADK were observed in the lesions of RE. Significantly greater ADK expression in RE versus controls was demonstrated by Western blot, and greater enzymatic activity for ADK was demonstrated using an enzyme-coupled bioluminescent assay. These results suggest that upregulation of ADK is a common pathologic hallmark of RE and that ADK might be a target in the treatment of epilepsy associated with RE.
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PMID:Upregulation of adenosine kinase in Rasmussen encephalitis. 2412 82

Pediatric focal epilepsies often involve more extratemporal regions than adult epilepsies. This study aims to investigate the population of oligodendroglia-like cells (OLCs) in the pediatric focal epilepsy patients requiring surgery. We hypothesize that OLCs are one of the factors that extend the pediatric epileptic network in intractable epilepsy. Thirty (18 female) patients (1.8-16.9 years old with a mean of 9.7 years), who underwent resective surgery for the intractable epilepsy from 2010 to 2012 were retrospectively studied. Seizure types consisted of epileptic spasms in nine patients, partial seizures in 17 patients and partial seizure with secondary generalization in four patients. Eight autopsy cases without neurological disease served as controls. The neuropathology examination utilized the H&E/LFB stain and immunohistochemical staining for NeuN, GFAP and Olig2 as a marker of OLCs. OLCs were counted in three sites: (a) gray matter, (b) junction of gray/white matter, and (c) white matter. We also examined the correlation between the density of OLC among the three sites and the clinical features. Fifteen (50%) patients underwent multiple lobe resections, consisting of both temporal and extratemporal lobe resections in 12 patients and extratemporal lobe resections in 3 patients. The other 15 (50%) patients underwent single lobe resection including 3 (10%) patients with temporal lobectomy sparing hippocampus. Pathological diagnosis of epilepsy patients was as follows: 14 (47%) patients=focal cortical dysplasia (type I, 4; II, 9; III, 1); 6 (20%)=oligodendrogliosis; 6 (20%)=astrocytic gliosis; 2 (7%)=hyaline protoplasmic astrocytopathy and 2 (7%)=tuberous sclerosis complex. The numbers of OLCs at all three sites in epilepsy group were significantly higher than those of control group (p<0.001). In the epilepsy group, there was a significant difference among the number of OLCs at gray matter, junction of gray and white matter, and white matter (p<0.001). The number of OLCs significantly increased from gray matter and junction of gray/white matter to white matter. In the control group, there was no difference among the number of OLCs at three sites. There was no significant difference in the numbers of OLCs between focal cortical dysplasia types I and II. The significantly increased OLCs, especially in the white matter may contribute to the extensive epileptic network in children with intractable focal epilepsy.
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PMID:Increased population of oligodendroglia-like cells in pediatric intractable epilepsy. 2463 59