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PubMed2000

Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances.

Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE. During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.

Adult↗

PubMed2003

Dentate granule cell GABA(A) receptors in epileptic hippocampus: enhanced synaptic efficacy and altered pharmacology.

The dentate gyrus (DG) normally functions as a filter, preventing propagation of synchronized activity into the seizure-prone hippocampus. This filter or 'gatekeeper' attribute of the DG is compromised in various pathological states, including temporal lobe epilepsy (TLE). This study examines the role that altered inhibition may play in the deterioration of this crucial DG function. Using the pilocarpine animal model of TLE, we demonstrate that inhibitory synaptic function is altered in principal cells of the DG. Spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in dentate granule cells (DGCs) from epileptic animals were larger, more sensitive to blockade by zinc and less sensitive to augmentation by the benzodiazepine type site 1 modulator zolpidem. Furthermore, mIPSCs examined during a quiescent period following injury but preceding onset of epilepsy were significantly smaller than those present either in control or in TLE DGCs, and had already acquired sensitivity to blockade by zinc prior to the onset of spontaneous seizures. Rapid agonist application experiments demonstrated that prolonged (>35 ms) exposure to zinc is required to block GABAA receptors (GABAARs) in patches pulled from epileptic DGCs. Therefore, zinc must be tonically present to block DGC GABAARs and alter DG function. This would occur only during repetitive activation of mossy fibres. Thus, in the pilocarpine animal model of TLE, an early, de novo, expression of zinc-sensitive GABAARs is coupled with delayed, epilepsy-induced development of a zinc delivery system provided by aberrant sprouting of zinc-containing mossy fibre recurrent collaterals. The temporal and spatial juxtaposition of these pathophysiological alterations may compromise normal 'gatekeeper' function of the DG through dynamic zinc-induced failure of inhibition, predisposing the hippocampal circuit to generate seizures.

Animals↗

PubMed2000

Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry.

The significance of benzodiazepine receptor (BZR) concentration in comparison with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed with temporal lobe epilepsy (TLE) without hippocampal signal change on T2-weighted magnetic resonance imaging (MRI) scans. Focus lateralization was achieved by clinical, electroencephalographic and neuropsychological examinations. Three-dimensional positron emission tomography (PET) and MRI scans were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding, normalized to average cortical values for glucose metabolism (rCMRglc) and volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of interest (VOI) were used for calculation of asymmetries between clinically affected and unaffected sides. Eleven out of 14 TLE patients presented a significant reduction in hippocampal volume. In nine of these 11 patients hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced. In two patients without hippocampal volume asymmetry FMZ binding was markedly reduced in the mesial temporal lobe appropriately to the clinically diagnosed side. In our study volumetry is therefore the most sensitive tool for the detection of hippocampal abnormality in TLE. However, in cases without hippocampal atrophy the reduction of FMZ may indicate functional impairment of BZR before neuronal loss becomes evident. Our results emphasize the complementary nature of these tests in TLE patients.

Adult↗

PubMed2001

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study.

PURPOSE: To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. METHODS: Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). RESULTS: The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. CONCLUSIONS: A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe

Adolescent↗

PubMed2001

Postictal diffusion-weighted imaging for the localization of focal epileptic areas in temporal lobe epilepsy.

PURPOSE: Diffusion-weighted MR imaging (DWI) is a novel technique to delineate focal areas of cytotoxic edema of various etiologies. We hypothesized that DWI may also detect the epileptogenic region and adjacent areas during the ictal and early postictal periods in patients with temporal lobe epilepsy (TLE). METHODS: We studied patients with intractable TLE (n = 9), due to hippocampal sclerosis (HS, n = 7), left mesial temporal lobe tumor (n = 1), and of unknown etiology (n = 1). Informed consent was obtained before inclusion in the study. All patients with single short seizures were scanned immediately after EEG-documented seizures (between 45 and 150 min); one of two patients in status was scanned 14 h after cessation of seizures. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps. RESULTS: We found significant decreases in ADC postictally in one of six patients with TLE due to HS and single short seizures. One patient with an incompletely resected temporal lobe tumor also exhibited ADC abnormalities. One patient in focal status epilepticus revealed a decrease in ADC, and one patient with a continuous aura had no DWI abnormality. CONCLUSIONS: Postictal DWI technique may occasionally help delineate epileptic areas in some patients with TLE. Yield is low in patients with HS and single short seizures: it may be higher in patients with tumor or status epilepticus.

Adolescent↗

PubMed2001

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study.

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.

Adult↗

PubMed2002

Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy.

PURPOSE: To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy. METHODS: The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis. RESULTS: The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with non-dysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue. CONCLUSIONS: Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types.

Adolescent↗

PubMed2003

Association analysis of a polymorphism of interleukin 1 beta (IL-1 beta) gene with temporal lobe epilepsy in a Chinese population.

PURPOSE: Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS+) is one of the most common medically intractable epilepsies. Although the pathogenesis of HS+ still remains highly controversial, genetics may play a role as a predisposing factor. Previous evidence in a Japanese population shows that the homozygotes for allele 2 at position -511 of the interleukin (IL)-1 beta gene promoter region (IL-1 beta-511*2/2) confers susceptibility to the development of HS. However, this result has not been confirmed in populations of European ancestry. Given that the discrepancy may be attributed to ethnic differences, our aim in this study was to test the validity of a previous report in another Asian population. METHODS: This study consisted of total 112 nonlesional TLE patients of Chinese ancestry, and 115 ethnically matched control subjects. A 304-base pair fragment in position of IL-1 beta-511 was amplified by polymerase chain reaction (PCR). The PCR products were digested with restriction enzyme AvaI, and run on a 12% polyacrylamide gel. We compared the frequency of this gene variation among 67 refractory TLE-HS+ patients, 45 patients without HS (TLE-HS-), and normal control subjects. RESULTS: The heterozygous type (-511*1/2) is the most common genotype in our patient groups and controls. Allele 1 (-511C) and allele 2 (-511T) showed equal frequency ( approximately 50%), which is similar to that (46%) in Japanese. Analysis of genotype and allele distribution showed no significant difference among the three groups (p > 0.05). CONCLUSIONS: In contrast with the lower frequency in the white population (35 and 34%) and higher rate in the population of African ancestry (60%), the allele -511T frequency in our present study is approximately 50%, indicating differences in the distribution of allele frequencies in IL-1 beta-511 among different ethnic groups. In this Chinese population, however, we still did not find a strong association between IL-1 beta-511 polymorphism and the development of HS.

Adult↗

PubMed2003

Presurgical evaluation of epilepsy by brain diffusion: MR-detected effects of flumazenil on the epileptogenic focus.

PURPOSE: After focal status epilepticus, focal alterations of the apparent diffusion coefficient (ADC) have been demonstrated in the epileptogenic zone by using diffusion-weighted magnetic resonance (MR)imaging (DWI). Effects of flumazenil on an epileptogenic focus have been demonstrated by EEG recordings, but not by functional MRI. We hypothesized that dynamic spatiotemporal alterations of brain diffusion of the epileptogenic focus after application of flumazenil will be detectable by DWI and correlate with the epileptogenic zone. METHODS: Twelve adult patients considered for epilepsy surgery with medically intractable temporal lobe epilepsy (TLE; n = 7), extratemporal lobe epilepsy (ETE; n = 2), and TLE+ETE (n = 3) were prospectively examined with DWI interictally (serving as baseline) and 10 min after application of 1 mg flumazenil i.v. RESULTS: The baseline interictal ADC was significantly elevated in the hippocampus on the ictogenic side in the patients with TLE (p = 0.002) as compared with healthy volunteers. The following changes of the mean ADC were seen in different regions of interest (ROIs) after injection of flumazenil: decreases in the hippocampus on the seizure-onset side by 14.8% (p = 0.005); decreases in the parahippocampal gyrus on both sides by 6.8% (epileptogenic side; p = 0.044) or 7.9% (nonepileptogenic side; NS), respectively; decreases in the cortex on the nonictogenic side by 7.9% (p = 0.047); and no significant changes of the ADC in the other ROIs. CONCLUSIONS: ADC decreases measured after application of flumazenil were seen in the seizure-onset zone as revealed by EEG and structural MRI and are an indicator of focus localization in patients with TLE.

Adult↗

PubMed2003

A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague-Dawley rats induced by Coriaria lactone and its possible mechanism.

PURPOSE: The aim of this study was to develop a new animal model of pharmacoresistant temporal lobe epilepsy (TLE) by repeated intramuscular injection of Coriaria lactone (CL) at subthreshold dosages and to explore the mechanisms that might be involved. METHODS: Healthy male Sprague-Dawley rats (n = 160) were randomized into four groups during the kindling process: three groups (n = 50 for each group) received CL injection at subthreshold dosages (1.25, 1.5, and 1.75 mg/kg, respectively), and ten received normal saline (NS) injection as a control group. The maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) was administered as monotherapy to different groups of kindled rats for 1 month (n = 20 for each group). Changes in EEG recording, seizure number, intensity (expressed as grade 1-5 according to Racine stage), and duration, including spontaneous seizures during different interventions, were compared. The expression of P-170, a multiple drug resistance gene (MDR1) encoding P-glycoprotein, was measured in brain samples from different groups of experimental rats by using an image analysis and measurement system (ImagePro-Plus 4.0). RESULTS: A total of 70 (46.7%) rats were fully kindled with a median of 15 (seven to 20) CL injections. Electrocorticogram (ECoG) including hippocampal (EHG) monitoring revealed the temporal lobe origins of epileptiform potentials, which were consistent with the behavioral changes observed. Spontaneous seizures occurred with frequency and diurnal patterns similar to those of human TLE. The antiepileptic drugs (AEDs) tested lacked a satisfactory seizure control. The maximal P-170 expression was in the kindled rats with AED treatment; the next highest was in the kindled rats without AED intervention. Nonkindled SD rats with CL injection also had increased P-170 expression compared with control SD rats. CONCLUSIONS: The study provided a simple and stable animal TLE kindling model with pharmacoresistant properties. The pharmacoresistance observed in the kindled rats to CBZ, VPA, and PHT at maximal human adult dosages together with the increased P-170 expression was a distinct feature of this model. This model might be used in further investigations of the mechanisms involved in pharmacoresistant TLE and for developing new AEDs.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

A study of the relationship between metabolism using 1H-MRS and function using several neuropsychological tests in temporal lobe epilepsy.

Several investigators have reported on the relationship between metabolism, using magnetic resonance spectroscopy (MRS), and function, using neuropsychological tests in temporal lobe epilepsy (TLE) patients, but the opinions regarding the results remain in contention. The aim of this study is to examine the relationship between metabolism, using proton MRS ((1)H-MRS), and function using several neuropsychological tests in the temporal lobes of TLE patients. We studied 29 TLE patients at our hospital using(1)H-MRS and neuropsychological tests. We used a clinical 1.5 T MR unit. We conducted five neuropsychological tests to examine the function of the left or right temporal lobe. There were significant correlations between the N-acetylaspartate/creatine + phosphocreatine (NAA/Cr) ratios and the scores of almost all of the neuropsychological tests for the temporal lobe function ipsilateral to the spike focus. However, in two Wechsler Memory Scale-Revised (WMS-R) subtests we found no significant correlation in the ipsilateral side. These findings suggest that the NAA/Cr ratios, which reflect neural metabolism, are closely related to function in the temporal lobes of TLE patients. The disparity between the results in two subtests of WMS-R show that several tests may be necessary in order to assess temporal lobe function.

Adolescent↗

PubMed2004

Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.

The properties of gamma-aminobutyric acid (GABA) type A receptors (GABA(A) receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABA(A) receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat alpha 1 beta 2 gamma 2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABA(A) receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABA(A) receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABA(A)-receptor beta 1, beta 2, beta 3, and gamma 2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABA(A) receptors. Blockage of phosphatases stabilizes the TLE GABA(A) receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy.

Adult↗

PubMed2004

The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells.

The proline-rich homeodomain protein (PRH/Hex) is important in the control of cell proliferation and differentiation and in the regulation of multiple processes in embryonic development. We have shown previously that PRH contains two domains that can independently bring about transcriptional repression. The PRH homeodomain represses transcription by binding to TATA box sequences, whereas the proline-rich N-terminal domain of PRH can repress transcription when attached to a heterologous DNA-binding domain. The Groucho/transducin-like enhancer of split (TLE) family of proteins are transcriptional co-repressors that interact with a number of DNA-bound transcription factors and play multiple roles in development. Here we demonstrate that the proline-rich N-terminal domain of PRH binds to TLE1 in vitro and in yeast two-hybrid assays. We show that PRH and TLE proteins are co-expressed in hematopoietic cells and interact in co-immunoprecipitation assays. We demonstrate that TLE1 increases repression by PRH in transient transfection assays and that titration of endogenous TLE proteins by co-expression of Grg5, a natural trans-dominant negative protein, alleviates transcriptional repression by PRH. Finally, we show that a mutation in the PRH N-terminal domain that blocks the PRH-TLE1 interaction in vitro eliminates co-repression. We discuss these results in terms of the roles of PRH and TLE in cell differentiation and development.

Amino Acid Motifs↗

PubMed1996

Does naming contribute to memory self-report in temporal lobe epilepsy?

The present study evaluated the hypothesis (Mayeux et al., 1980) that visual confrontation naming deficits may underlie the memory complaint in patients with temporal lobe epilepsy (TLE). Thirty-nine patients with medically refractory left (n = 23) and right (n = 16) TLE were compared with an epilepsy control group with idiopathic primary generalized epilepsy (n = 38). All subjects completed selected subtests of the Multilingual Aphasia Examination and Wechsler Memory Scale (Form 1) together with a measure specifically designed for quantification of the memory complaint in TLE. Objective verbal memory test performance, confrontation naming, repetition, and comprehension were unrelated to memory self-report. Controlled Oral Word Association was the only measure to exert an influence on memory self-ratings, and this relationship was specific to the TLE group. The hypothesis of Mayeux et al. (1980) was not specifically supported, but the present findings do suggest that cognitive processes reflected in orthographically based and internally generated word retrieval play a role in memory self-report.

Adult↗

PubMed2004

Significant discrepancies between immediate and delayed WMS-III indices are rare in temporal lobe epilepsy patients.

Initial factor analysis of Wechsler Memory Scale-Third Edition (WMS-III) standardization data resulted in a five-factor model that included separate immediate (IMM) and delayed (DEL) memory factors for auditory (AUD) and visual (VIS) memory. However, recent factor analyses that revealed three factors--AUD, VIS, and working memory--were discovered to be more accurate. Continued use of separate WMS-III IMM and DEL indices has been recommended because future studies with clinical groups might support this distinction. Data from this investigation of 88 temporal lobe epilepsy (TLE) patients suggested separate IMM and DEL WMS-III indices are not necessary in this population. Results were as follows: 1) There was no significant difference between the IMM and DEL indices for AUD or VIS memory. 2) The percentage of individuals with a significant difference between the IMM and DEL indices (IMM minus DEL >11 or <-12) was similar for our TLE group and the standardization sample. 3) The mean percent retention standard score (SS) was at the average level for the four memory subtests, and for each subtest only about 10% of the TLE patients had impaired scores. 4) Hippocampal volumes correlated significantly with both IMM and DEL indices. These data suggest that combining the appropriate WMS-III IMM and DEL memory subtest scores to form AUD and VIS memory indices is appropriate for TLE patients.

Adult↗

PubMed1996

Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal neocortical lesions. A clinical and electroencephalographic study of 46 pathologically proven cases.

This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an individual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an individual patient.

Adolescent↗

PubMed2000

Opposite ictal perfusion patterns of subtracted SPECT. Hyperperfusion and hypoperfusion.

To investigate the patterns of ictal perfusion and related clinical factors, single photon emission computed tomography (SPECT) subtraction was performed in 61 patients who had undergone epilepsy surgery. In addition to the ictal hyperperfusion region, the ictal hypoperfusion area was obtained by SPECT subtraction. The ictal perfusion patterns of subtracted SPECT were classified into focal hyperperfusion, hyperperfusion-plus, combined hyperperfusion-hypoperfusion and focal hypoperfusion only. The concordance rate of seizure localization was 91.8% in the combined analysis of ictal hyperperfusion-hypoperfusion by SPECT subtraction, 85.2% in hyperperfusion images of SPECT subtraction and 68.9% in the visual inspection of ictal SPECT. Ictal hypoperfusion occurred less frequently in temporal lobe epilepsy (TLE) than in extra-TLE. Mesial temporal hyperperfusion alone was seen only in mesial TLE while lateral temporal hyperperfusion alone was observed only in neocortical TLE. Hippocampal sclerosis had a much lower incidence of ictal hypoperfusion than other pathologies. Some patients showed ictal hypoperfusion at the epileptic focus with ictal hyperperfusion in the neighbouring brain regions where ictal discharges propagated. Hypoperfusion as well as hyperperfusion in ictal SPECT should be considered for localizing epileptic focus. The mechanism of ictal hypoperfusion could be an intra-ictal early exhaustion of seizure focus or a steal phenomenon associated with the propagation of ictal discharges to adjacent brain areas.

Adolescent↗

PubMed2002

Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy.

In patients suffering from temporal lobe epilepsy (TLE), increased extracellular glutamate levels in the epileptogenic hippocampus both during and after clinical seizures have been reported. These increased glutamate levels could be the result of malfunctioning and/or downregulation of glutamate transporters (also known as EAATs; excitatory amino acid transporters). In this study, the distribution of protein and mRNA of EAAT subtypes was examined in the hippocampus of TLE patients with hippocampal sclerosis (HS group) and without hippocampal sclerosis (non-HS group), and in autopsy controls without neurological disorders. EAAT protein localization was studied by immunohistochemistry on paraffin sections using specific poly- and monoclonal antibodies against the glial glutamate transporters EAAT1 and EAAT2 and the neuronal glutamate transporter EAAT3. Antibody specificity was shown by immunoblotting. In the HS group, a small decrease in EAAT1-immunoreactivity (IR) was observed in CA4 and in the polymorphic and supragranular layer of the dentate gyrus, compared with the control group. The strongest changes were found for EAAT2 levels. In the non-HS group, increased EAAT2-IR was detected in the CA1 and CA2 field, compared with non-epileptic controls. EAAT2-IR was decreased in the HS compared with the non-HS group. Fewer EAAT3-positive cells were found in the HS group than in the non-HS and control group. In both TLE groups, increased EAAT3 levels were observed in individual neurones. In the HS group, the percentage of EAAT3-IR neurones was increased in CA2 and in the granule cell layer of the dentate gyrus. Radioactive in situ hybridization for EAAT1-3 confirmed our immunohistochemical results. Non-radioactive in situ hybridization showed that not only astrocytes, but also neurones express EAAT2 mRNA. Taken together, differences in both mRNA and protein levels of glutamate transporter subtypes were found in specific regions in the TLE hippocampus, with most severe changes found for EAAT2 and EAAT3 levels. The results indicate an upregulation of EAAT2 protein expression in CA1 and CA2 in neurones in the non-HS group. This is in line with decreased EAAT2 protein levels in the HS group, since these hippocampi are characterized by severe neuronal cell loss. The functional consequences (glutamate transport capacity) of the reported changes in EAAT2 and EAAT3 remain to be determined.

Adult↗