Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known that epilepsy patients diagnosed with neocortical temporal lobe epilepsy (NTLE), differ from those diagnosed with mesial temporal lobe epilepsy (MTLE), e.g., in hippocampal (HPC) pathology. In the present studies, we tested the hypothesis that NTLE and MTLE subtypes of human epilepsy might differ in regards to their HPC monoamine neurochemistry. Monoamine neurotransmitters were studied in separate signals and within s with semiderivative microvoltammetry, used in combination with stearate indicator, Ag-AgCl reference and stainless steel auxiliary microelectrodes. Anterior HPC specimens from the patients' epileptogenic zone, defined by electrocorticography, were resected neurosurgically from 13 consecutive patients with intractable temporal lobe epilepsy. Four patients were diagnosed with NTLE and nine with MTLE. The criteria for the diagnosis of NTLE versus MTLE was absence versus presence of HPC sclerosis, respectively, based on MRI examination of resected tissue. In addition, NTLE patients demonstrated seizure onset in anterolateral temporal neocortex on electroencephalography (EEG). HPC subparcellations studied were: (a) Granular Cells of the Dentate Gyrus (DG), (b) Polymorphic Layer of DG and (c) Pyramidal Layer: subfields, CA1 and CA2. Dopamine (DA), serotonin (5-HT), norepinephrine (NE) and ascorbic acid (AA) (co-factor in DA to NE synthesis), exhibited separate and characteristic half-wave potentials in millivolts. Each half-wave potential, i.e., the potential at which maximum current was generated, was experimentally established in vitro. Concentrations of neurotransmitters found in HPC subparcellations were interpolated from calibration curves derived in vitro from electrochemical detection of monoamines and AA in saline phosphate buffer. Significant differences between subtypes in concentration of monoamines were analyzed by the Mann Whitney rank sum test and those differences in probability distribution of monoamines were analyzed by the Fisher Exact test; in each case, P<0.01 was the criteria selected for determining statistical significance. DA concentrations were higher in NTLE compared with MTLE in each HPC subparcellation [P=0.037, 0.024 and 0.007, respectively (P<0.01)] and DA occurred more frequently in NTLE in the Pyramidal Layer [P=0.077 (P<0.01)]. AA was present in one NTLE patient. NE concentrations were higher in MTLE vs. NTLE in each subparcellation [P=0.012, 0.067 and 0.07, respectively (P<0.01)] and NE occurred more frequently in MTLE in Granular Cells of DG and Pyramidal Layer [P=0.052 and 0.014, respectively (P<0.01)]. In MTLE, NE concentrations in the CA1 subfield of the Pyramidal Layer were decreased vs. the CA2 subfield [P=0.063 (P<0.01)]. Serotonin was found in every HPC subparcellation of each subtype but 5-HT concentrations were higher in NTLE vs. MTLE in the Granular Cells of DG and the Pyramidal Layer (CA1 subfield) [P=0.076 and 0.095, respectively (P<0.01)]. Thus, this preliminary study showed that marked differences in HPC monoamine neurochemistry occurred in NTLE patients as compared with MTLE patients.
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PMID:Monoamine neurotransmitters in resected hippocampal subparcellations from neocortical and mesial temporal lobe epilepsy patients: in situ microvoltammetric studies. 1099 35

The hippocampus, amygdala complex, and entorhinal region represent anatomically linked limbic structures of the mesiotemporal lobe. Chronic seizures and mnestic deficits in patients with pharmacoresistant mesial temporal lobe epilepsy (TLE) appear to correlate with distinct patterns of histopathological alterations in these areas. The complex anatomical organization of the amygdala and entorhinal region, however, render a detailed neuropathological evaluation of surgical specimens difficult. In this study, we present a combined cytoarchitectonical, pigmentarchitectonical, myelinarchitectonical, and immunohistochemical reconstruction of the amygdala, entorhinal region, and hippocampus from surgical TLE specimens (n = 20) in order to analyze their regional and cellular patterns of pathology. Anterior mesiotemporal lobes dissected in different spatial planes were obtained from 4 autopsy control patients and used for the characterization of neuroanatomical landmarks. Lateral, basal, and granular subnuclei of the amygdala were consistently identified in the surgical specimens. Major histopathological alterations included neuronal cell loss as revealed by extracellular lipofuscin accumulation, glial satellitosis, as well as cellular and fibrillary gliosis. The regional distribution of neuropathological changes varied considerably between different subnuclei but the lateral nucleus was more often involved than basal and granular nuclei. These amygdala nuclei appeared to be more severely affected compared to the adjacent entorhinal region. In addition, patients presenting with secondary generalized tonic-clonic seizures showed significantly more damage in mesiotemporal structures. Pathological alterations in the amygdala and entorhinal region were found to be associated with Ammon's horn sclerosis in most but not all cases. Our findings reveal the amygdala as a major target for epilepsy-associated neuronal cell damage. Significant variations in the lesional pattern among patients with chronic TLE would also be compatible with different spreading pathways of epileptogenic activity within the mesial temporal lobe.
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PMID:Subregional pathology of the amygdala complex and entorhinal region in surgical specimens from patients with pharmacoresistant temporal lobe epilepsy. 1107 81

Anterior temporal lobectomy offers a high chance of seizure-free outcome in patients suffering from drug-refractory complex partial seizure (CPS) originating from the temporal lobe. Other than EEG, several functional and morphologic imaging methods are used to define the spatial seizure origin. The present study was undertaken to compare the merits of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), magnetic resonance imaging (MRI) and single-voxel proton MR spectroscopy (MRS) for the lateralization of temporal lobe seizure foci. The clinical charts and imaging data of 43 consecutive CPS patients were reviewed. Based on surface EEG, 31 patients were classified with temporal lobe epilepsy (TLE; 25 lateralized, 6 not lateralized) and 12 with non-temporal lobe epilepsy. All were examined by FDG-PET, MRS and MRI within 6 weeks. FDG-PET and MRI were interpreted visually, while the N-acetyl-aspartate to creatine ratio was used for MRS interpretation. One FDG-PET scan was invalid due to seizure activity post injection. The MR spectra could not be evaluated in five cases bilaterally and three cases unilaterally for technical reasons. A total of 15 patients underwent anterior temporal lobectomy. All showed a beneficial postoperative outcome. When the proportions of agreement between FDG-PET (0.77), MRI (0.58) and MRS (0.56) and surface EEG in TLE cases were compared, there were no significant differences (P>0.10). However, FDG-PET showed a significantly higher agreement (0.93) than MRI (0.60; P=0.03) with the side of successful temporal lobectomy. The concordance of MRS with the side of successful temporal lobectomy was intermediate (0.75). When the results of functional and morphologic imaging were combined, no significant differences were found between the rates of agreement of FDG-PET/MRI and MRS/MRI with EEG (0.80 vs 0.68; P=0.50) and with the side of successful temporal lobectomy (0.87 vs 0.92; P=0.50) in TLE cases. However, MRS/MRI showed significantly more lateralized temporal lobe abnormalities in non-temporal lobe epilepsy cases than FDG-PET/MRI (0.90 vs. 0.17; P<0.01). Although FDG-PET seems to be the most reliable and stable method for this purpose, we conclude that in TLE cases it may be justified to perform MRS, which is less expensive, faster and has no radiation exposure, in combination with MRI before FDG-PET, since FDG-PET offers little additional diagnostic information if MRS and MRI indicate the same seizure focus lateralization.
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PMID:Inter-modality comparisons of seizure focus lateralization in complex partial seizures. 1168 97

To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single-dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE.
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PMID:Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy. 1176 Aug 74

Mice lacking ClC-3 chloride channels, encoded by the Clcn3 gene, undergo neurodegeneration of the hippocampal formation and retina [Neuron, 29 (2001) 185-196; Genes Cells, 7 (2002) 597-605]. We independently created a mouse lacking the Clcn3 gene which demonstrated similar central nervous system abnormalities, including early postnatal degeneration of retinal photoreceptors. However, we observed a characteristic spatial-temporal sequence of hippocampal neurodegeneration that differs from the pattern previously reported. Anterior-to-posterior degeneration and astrogliosis of the dentate gyrus and hippocampus progressed over months. Sequential loss of hippocampal neuronal subpopulations began in the dentate gyrus and progressed to CA3, followed by CA1 neurons. Projection neurons of the entorhinal cortex degenerated, secondary to the loss of their synaptic targets within the hippocampal formation. Other characteristics of the Clcn3(-/-) mice included an abnormal gait, kyphosis, and absence of hindlimb escape extension upon tail elevation. Spontaneous seizures were observed in four adult Clcn3(-/-) mice, and one mouse died during the event. We hypothesized that neuronal injury may be related to recurrent seizures. Clcn3(-/-) mice had normal serum electrolytes and pH, and exhibited neither hyperglycemia nor rebound hypoglycemia following a glucose load. They displayed a greatly reduced susceptibility to pentylenetetrazole-induced seizures and an abnormally prolonged sedation to benzodiazepines. There was no change in vulnerability to kainic acid-induced seizures. Immunostaining revealed a progressive loss of GABA synthesizing cells in the dentate gyrus. The death of these cells was preceded by increased GABA(A) receptor immunoreactivity. These data suggest that GABA(A) inhibitory neurotransmission is altered in Clcn3(-/-) mice. The increase in GABA(A) receptor density may represent a compensatory response either to chronic excessive excitatory stimuli or reduced inhibitory input from local GABAergic interneurons within the dentate gyrus.
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PMID:Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels. 1247 Aug 59

The generation of properly functioning circuits during brain development requires precise timing of cell migration and differentiation. Disruptions in the developmental plan may lead to neurological and psychiatric disorders. Neocortical circuits rely on inhibitory GABAergic interneurons, the majority of which migrate from subcortical sources. We have shown that the pleiotropic molecule hepatocyte growth factor/scatter factor (HGF/SF) mediates interneuron migration. Mice with a targeted mutation of the gene encoding urokinase plasminogen activator receptor (uPAR), a key component in HGF/SF activation and function, have decreased levels of HGF/SF and a 50% reduction in neocortical GABAergic interneurons at embryonic and perinatal ages. Disruption of interneuron development leads to early lethality in most models. Thus, the long-term consequences of such perturbations are unknown. Mice of the uPAR-/- strain survive until adulthood, and behavior testing demonstrates that they have an increased anxiety state. The uPAR-/- strain also exhibits spontaneous seizure activity and higher susceptibility to pharmacologically induced convulsions. The neocortex of the adult uPAR-/- mouse exhibits a dramatic region- and subtype-specific decrease in GABA-immunoreactive interneurons. Anterior cingulate and parietal cortical areas contain 50% fewer GABAergic interneurons compared with wild-type littermates. However, interneuron numbers in piriform and visual cortical areas do not differ from those of normal mice. Characterization of interneuron subpopulations reveals a near complete loss of the parvalbumin subtype, with other subclasses remaining intact. These data demonstrate that a single gene mutation can selectively alter the development of cortical interneurons in a region- and cell subtype-specific manner, with deficits leading to long-lasting changes in circuit organization and behavior.
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PMID:Genetic disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy, and behavioral dysfunction. 1253 22

Neurologists have been analyzing the clinical behaviors that occur during seizures for many years. Several ictal behaviors have been defined in temporal lobe epilepsy (TLE). Ictal behaviors are especially important in the evaluation of epilepsy surgery candidates. We propose a new lateralizing sign in TLE originating from the nondominant hemisphere-the "hush" sign. Our patients were 30- and 21-year old women (Cases 1 and 2, respectively). Their epileptogenic foci were localized to the right mesial temporal region after noninvasive presurgical investigations. Case 1 had no cranial MRI abnormality, whereas cranial MRI revealed right hippocampal atrophy in Case 2. These women repeatedly moved their right index fingers to their mouth while puckering their lips during complex partial seizures. We have named this ictal behavior the "hush" sign. Anterior temporal lobectomy with amygdalohippocampectomy was performed in both patients, and pathological examinations revealed hippocampal sclerosis. The "hush" sign no longer occurred after seizures were controlled. They were seizure free as of 30 and 31 months of follow-up, respectively. We believe that the "hush" sign may be supportive of a diagnosis of TLE originating from the nondominant hemisphere. This sign may occur as a result of ictal activation of a specific brain region in this hemisphere.
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PMID:Hush sign: a new clinical sign in temporal lobe epilepsy. 1582 Mar 60

We investigated the role of the temporal pole (TP) in 48 consecutive patients with drug-refractory temporal lobe epilepsy (TLE). Chronic depth recordings of TP cortex activity were used in association with video recording of ictal symptoms during 48 spontaneous seizures. In 23 cases (48%, group 1) the TP was involved at the onset of the seizure, before or concurrently with the hippocampus. In the remaining 25 patients (52%, group 2) the TP was involved 16.4 +/- 13.8 s after the hippocampus. A past history of febrile seizures was found in both groups, with no statistical difference. Ictal symptoms did not differentiate TP seizures from seizures originating in the hippocampus but the first clinical sign occurred sooner in group 1 compared with group 2 (respectively 10.56 +/- 9 and 25.7 +/- 19 s, respectively, P = 0.005). Loss of awareness also occurred sooner in the case of TP seizures compared with mesiotemporal lobe (MTL) seizures (22.9 +/- 22.6 versus 42.2 +/- 18.6 s, P = 0.0002). MRI data analysis showed that hippocampal sclerosis was present in both groups of patients, although it was more frequent in patients with MTL onset. Anterior temporal white matter changes were found ipsilateral to the epileptogenic area and tended to be more frequent in patients with TP seizures. All the patients underwent tailored anterior temporal lobectomy that included the TP, the hippocampus, the parahippocampal gyrus and the anterior part of the lateral temporal cortex. A better postoperative outcome was achieved in group 1 compared with group 2 (Engel class 1, 95 and 72% respectively, P = 0.04). We conclude that the frequent TP involvement at the onset of seizures could be a supplementary explanation for some failures of selective amygdalohippocampectomy, which should be addressed preferentially to well-selected patients. Moreover, the involvement of the TP cortex at the onset of the seizures is a good predicting factor for postoperative seizure outcome.
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PMID:The temporopolar cortex plays a pivotal role in temporal lobe seizures. 1585 32

This article reviews two commonly held myths regarding temporal lobe epilepsy-it is a static disorder with minimal morbidity and mortality, and epileptogenic tissue impairs only the functions of the seizure focus-and one myth concerning temporal lobe functions-they contain areas of nonfunctional, "silent" cortex. Chronic temporal lobe epilepsy can cause progressive structural, cognitive, and behavioral changes. Aside from the seizure focus, primary epileptogenic cortex may have a deleterious influence on distant brain areas. Removing this "nociferous" cortex and reducing the antiepileptic drug burden can improve cognitive or behavioral and metabolic function in areas remote from the resection. Anterior temporal lobectomy often removes functional tissue that may or may not be epileptogenic. Because normal brain does not contain functionless, "silent" areas, the procedure can have negative as well as positive cognitive or behavioral consequences. To improve the outcomes of focal cortical resections for seizure control, we need to better define functional and nociferous cortex and more clearly understand their boundaries and interactions.
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PMID:The myth of silent cortex and the morbidity of epileptogenic tissue: implications for temporal lobectomy. 1619 51

Recent data have demonstrated that insular seizures can mimic those encountered in temporal lobe epilepsy (TLE), as well as nocturnal hypermotor attacks suggestive of nocturnal frontal lobe epilepsy (NFLE). To illustrate some of the issues raised by these observations, we report our first two patients with suspected TLE and NFLE, respectively, in whom we originally demonstrated an insular ictal onset zone. Patient 1 suffered from daytime seizures characterised by a rising and distressing epigastric sensation rapidly followed by oro-alimentary automatisms, associated with right temporal scalp-EEG ictal discharge. Neuroimaging showed consistent right temporal abnormalities, including MRI signs of hippocampal sclerosis, anterior and mesial glucose hypometabolism, and mesial decrease of benzodiazepine receptors. Intra-cerebral EEG investigation was primarily performed because of several ictal signs and symptoms suggesting a rapid involvement of the perisylvian region, and showed that the patient suffered two types of seizure, one of which arose from the mesial temporal structures, the other was sleep-related and originated in the posterior-inferior portion of the insula. Anterior temporal lobectomy failed to control this second type of seizure. Patient 2 suffered from brief, nocturnal, hypermotor seizures characterised by an indefinable aura followed by agitation, body rolling, scream and pelvic thrust. Interictal and ictal scalp-EEG failed to detect epileptiform discharges, whereas neuroimaging showed left mesial frontal, glucose hypometabolism and decreased benzodiazepine receptors associated with a left fronto-basal arachnoidal cyst. Invasive EEG monitoring was performed with the aim of identifying an orbital or mesial frontal ictal onset, but eventually demonstrated that the seizure originated in the anterior-superior portion of the left insula. The patient did not undergo surgery and died of SUDEP two years later. We discuss the heterogeneity of insular seizure semiology according to functional anatomy, the clinical signs and symptoms that might suggest an insular ictal onset, the indications and types of invasive EEG monitoring that are needed to identify an insular epileptogenic zone definitively, as well as potential surgical treatment.
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PMID:Avoid falling into the depths of the insular trap. 1701 71


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