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PubMed1996

Preservation of calretinin-immunoreactive neurons in the hippocampus of epilepsy patients with Ammon's horn sclerosis.

Selective neuronal vulnerability and aberrant axonal reorganization in the hippocampus may play an important role for the pathogenesis of pharmaco-resistant temporal lobe epilepsy (TLE). Interneurons containing calcium-binding proteins (CaBPs) are candidates for pathogenetically relevant neurons in the hippocampus of patients with TLE. Here we have examined the cellular localization and distribution of calretinin (CR), a recently discovered CaBP, in the hippocampus of 35 patients with TLE. There was a striking preservation of CR-immunoreactive neurons in TLE patients with Ammon's horn sclerosis (AHS). No significant differences in the distribution of CR-immunoreactive neurons were observed between patients with lesion-associated TLE and control patients without epilepsy. However, a subpopulation of CR-immunoreactive interneurons with morphological features of Cajal-Retzius-like cells, which are only transiently detectable in the normally developing hippocampus, was markedly increased in epilepsy patients with AHS. This increase did not correlate with the duration of the epileptic disorder. Another significant finding was a striking increase and reorganization of CR-immunoreactive neuropil throughout the entire molecular layer of the dentate gyrus (DG-ML) in patients with AHS as compared to patients with focal lesions and control specimens. Ultrastructural analysis identified the CR-immunoreactive axonal profiles as components of an inhibitory, intrinsic neuronal system. The presence of a CR-positive, aberrant cell population, in combination with sprouting of CR-positive axonal processes may significantly alter the gating function of the dentate gyrus and thereby increase hippocampal epileptogenicity in epilepsy patients with AHS.

Adolescent↗

PubMed2003

The role of hippocampal sclerosis in topiramate-related depression and cognitive deficits in people with epilepsy.

PURPOSE: To clarify the role of hippocampal sclerosis (HS) in developing psychiatric and cognitive adverse events during therapy with topiramate (TPM) in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the data of 70 patients with TLE and HS and 128 patients with cryptogenic TLE matched for age, sex, starting dose, and titration schedule of TPM. They were selected from the first consecutive 431 patients started on TPM between 1995 and 1999. RESULTS: Patients with HS were more likely to develop cognitive adverse events (CAEs; p = 0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p = 0.007). However, regression analysis demonstrated that only HS was a predictive factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3; p = 0.02). CONCLUSIONS: Patients with TLE and HS were more prone to develop CAEs and depression than were patients with cryptogenic TLE, during TPM therapy, despite the same titration schedule. The presence of HS and not duration of epilepsy or polytherapy regimen represented the main risk factor.

Adult↗

PubMed2004

Correlation between 1H MRS and memory before and after surgery in mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate neuronal loss and gliosis, may be used as a sensitive tool for lateralization of temporal lobe epilepsy (TLE). Although the correlation between the memory functions and 1H MRS has been investigated, its predictive value after surgery has not been studied previously. This study evaluated memory and 1H MRS values of medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE-HS) before and after selective amygdalohippocampectomy (SAH). METHODS: Twenty-two patients underwent memory tests and 1H MRS investigation before and 6 months after SAH and were compared with nine control subjects. RESULTS: The 1H MRS scores were found to be significantly low on the pathological side of the patients. Both right-sided 1H MRS of right TLE and left-sided 1H MRS values of left TLE patients were correlated only with verbal memory scores. Statistical analysis did not reveal any significance for nonverbal memory scores for both TLE groups on either side, which showed no significant correlation between material specificity and 1H MRS findings. Conversely, regression analyses demonstrated that high right- and low left-sided 1H MRS values obtained before surgery may predict a decline in verbal learning scores after surgery. CONCLUSIONS: 1H MRS can be considered as a useful tool to determine the lateralization in patients with MTLE-HS before the surgery. Although only a weak relation exists between the MRS values and memory scores, presurgical MRS scores may be predictive for a possible deterioration in verbal memory after surgery. However, further studies with higher numbers of cases are needed for confirmation of the results.

Adolescent↗

PubMed1993

Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein.

Mouse and human cDNA encoding AES (amino-terminal enhancer of split) and ESG (enhancer of split groucho) proteins with strong similarity to Drosophila enhancer of split groucho protein were isolated and sequenced. Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids. The amino acid sequences of mouse and human AES proteins were found to exhibit approximately 50% identity to the amino-terminal region of Drosophila groucho, mouse ESG and human transducin-like enhancer of split (TLE) proteins. Mouse AES transcripts of 1.5 kb and 1.2 kb were abundantly expressed in muscle, heart and brain. Human AES transcripts of 1.6 kb and 1.4 kb were predominantly present in muscle, heart and placenta. Mouse ESG (homolog of human TLE 3) transcripts of 3.3 kb and 4.0 kb were found only in testis, while human TLE 1 transcripts of 4.5 kb was more abundant in muscle and placenta compared to heart, brain, lung, liver, kidney and pancreas. Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines.

Amino Acid Sequence↗

PubMedDate not supplied

Memory function in childhood epilepsy syndromes.

OBJECTIVE: Children with epilepsy are at risk of specific cognitive deficits. We aimed to compare and characterize the memory function of children with childhood absence epilepsy (CAE), frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). METHODS: Epilepsy syndrome was identified by clinical data, seizure semiology, interictal and ictal electroencephalogram (EEG). Seventy children aged 6-18 years with CAE, FLE or TLE had neuropsychological assessment including memory function. After adjusting for epilepsy variables, neuropsychological results of the syndrome groups and normative data were compared. RESULTS: Children from all three syndrome groups were at risk of memory difficulties. The duration of epilepsy correlated negatively with memory function. Children with TLE had the worst memory function, significantly lower in verbal memory tasks than children with CAE (P = 0.02) and children with FLE (P = 0.01). The performance of children with TLE was significantly below the normed mean across all verbal and most visual tasks. Compared to the normed means, children with FLE had results that were statistically lower in some verbal and visual tasks, and children with CAE were lower in two visual tasks only. CONCLUSIONS: This study demonstrates memory dysfunction in three common childhood epilepsy syndromes. Children with TLE had the greatest impairment, children with FLE had memory difficulties not previously reported, and children with CAE had subtle memory deficits. Qualitative differences were also evident. Longer duration of intractable epilepsy was associated with reduced memory ability. Memory function and its potential impact on academic achievement are vital considerations when managing children with epilepsy.

Adolescent↗

PubMed2006

Identifying the affected hemisphere by (1)H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI.

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.

Adult↗

PubMed1999

Properties of single NMDA receptor channels in human dentate gyrus granule cells.

1. Cell-attached single-channel recordings of NMDA channels were carried out in human dentate gyrus granule cells acutely dissociated from slices prepared from hippocampi surgically removed for the treatment of temporal lobe epilepsy (TLE). The channels were activated by L-aspartate (250-500 nM) in the presence of saturating glycine (8 microM). 2. The main conductance was 51 +/- 3 pS. In ten of thirty granule cells, clear subconductance states were observed with a mean conductance of 42 +/- 3 pS, representing 8 +/- 2 % of the total openings. 3. The mean open times varied from cell to cell, possibly owing to differences in the epileptogenicity of the tissue of origin. The mean open time was 2.70 +/- 0.95 ms (range, 1.24-4.78 ms). In 87 % of the cells, three exponential components were required to fit the apparent open time distributions. In the remaining neurons, as in control rat granule cells, two exponentials were sufficient. Shut time distributions were fitted by five exponential components. 4. The average numbers of openings in bursts (1.74 +/- 0.09) and clusters (3.06 +/- 0.26) were similar to values obtained in rodents. The mean burst (6.66 +/- 0.9 ms), cluster (20.1 +/- 3.3 ms) and supercluster lengths (116.7 +/- 17.5 ms) were longer than those in control rat granule cells, but approached the values previously reported for TLE (kindled) rats. 5. As in rat NMDA channels, adjacent open and shut intervals appeared to be inversely related to each other, but it was only the relative areas of the three open time constants that changed with adjacent shut time intervals. 6. The long openings of human TLE NMDA channels resembled those produced by calcineurin inhibitors in control rat granule cells. Yet the calcineurin inhibitor FK-506 (500 nM) did not prolong the openings of human channels, consistent with a decreased calcineurin activity in human TLE. 7. Many properties of the human NMDA channels resemble those recorded in rat hippocampal neurons. Both have similar slope conductances, five exponential shut time distributions, complex groupings of openings, and a comparable number of openings per grouping. Other properties of human TLE NMDA channels correspond to those observed in kindling; the openings are considerably long, requiring an additional exponential component to fit their distributions, and inhibition of calcineurin is without effect in prolonging the openings.

Animals↗

PubMedDate not supplied

Depressive symptomatology in a general hospital sample of outpatients with temporal lobe epilepsy: a controlled study.

We compared temporal lobe epilepsy (TLE) outpatients attending a general hospital with depressed psychiatric patients and normal control subjects to investigate depressive symptomatology. Both clinician-rated measures and self-report questionnaires were used. Rates of depressive and anxious symptomatology in TLE subjects were higher than those in a normal control sample, but TLE subjects did not differ significantly from controls on anxiety measures. The depressed psychiatric group scored higher than the TLE and control groups on both depression and anxiety measures. Rates of depressive symptomatology in the TLE group were lower than those reported in previous studies for persons attending specialist epilepsy clinics, but similar to the findings of one community study.

Adult↗

PubMed1998

Astrocytes from human hippocampal epileptogenic foci exhibit action potential-like responses.

PURPOSE: We studied Na+ channel expression and the ability to generate action potential (AP)-like responses in primary cultures of human astrocytes by whole cell patch-clamp recording techniques. METHODS: Tissue samples from 22 patients with various classifications of temporal lobe epilepsy (TLE) were plated to form separate astrocyte cultures from three regions; the hippocampus, parahippocampus, and anterolateral temporal neocortex. RESULTS: The resting membrane potential of seizure focus astrocytes (MTLE, mesial TLE) was significantly depolarized (approximately -55 mV) as compared with cortical astrocytes (-80 mV). Hippocampal astrocytes from other substrates for TLE (MaTLE, mass-associated TLE; PTLE, paradoxical TLE) in which the hippocampus is not the seizure focus displayed resting membrane potentials similar to those of neocortical astrocytes (approximately -75 mV). Astrocytes from the seizure focus (MTLE) displayed much larger tetrodotoxin (TTX)-sensitive Na+ currents with -66-fold higher Na+ channel density (113.5 +/- 17.41 pA/pf) than that of comparison neocortical astrocytes (1.7 +/- 3.7 pA/pf) or than that of the hippocampal and parahippocampal astrocytes of the MaTLE and PTLE groups. As a consequence of this higher channel density, seizure focus astrocytes were capable of generating AP-like responses. However, at the resting potential, most Na+ channels are inactive and no spontaneous firing was observed. In contrast, astrocytes in the comparison neocortex from all groups and the hippocampus and parahippocampus from the MaTLE and PTLE groups could not fire AP-like responses even after large current injections. CONCLUSIONS: The function of Na+ channels in these astrocytes is unclear. However, the marked differences in seizure focus astrocytes as compared with cortical and nonseizure focus hippocampal astrocytes suggest a more active role for astrocytes associated with hyperexcitable neurons at a seizures focus.

Action Potentials↗

PubMed1998

Regional distribution of interictal 31P metabolic changes in patients with temporal lobe epilepsy.

PURPOSE: We compared the 31P metabolites in different brain regions of patients with temporal lobe epilepsy (TLE) with those from controls. METHODS: Ten control subjects and 11 patients with TLE were investigated with magnetic resonance imaging (MRI) and [31P]MR spectroscopic imaging (MRSI). [31P]MR spectra were selected from a variety of brain regions inside and outside the temporal lobe. RESULTS: There were no asymmetries of inorganic phosphate (Pi), pH, or phosphomonoesters (PME) between regions in the left and right hemispheres of controls. In patients with TLE, Pi and pH were higher and PME was lower throughout the entire ipsilateral temporal lobe as compared with the contralateral side and there were no significant asymmetries outside the temporal lobe. The degree of ipsilateral/contralateral asymmetry for all three metabolites was substantially greater for the temporal lobe than for the frontal, occipital, and parietal lobes, and these asymmetries provided additional data for seizure localization. As compared with levels in controls, Pi and pH were increased and PME were decreased on the ipsilateral side in patients with TLE. There were changes in Pi, pH, and PME on the contralateral side in persons with epilepsy as compared with controls, contrary to changes on the ipsilateral side. CONCLUSIONS: Our findings provide some insight into the metabolic changes that occur in TLE and may prove useful adjuncts for seizure focus lateralization or localization.

Adult↗

PubMed1999

Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection.

PURPOSE: Unilateral intrahippocampal injections of kainic acid (KA) in rats produce spontaneous recurrent limbic seizures and morphologic changes in hippocampus that resemble hippocampal sclerosis in patients with medically refractory mesial temporal lobe epilepsy (MTLE), that form of temporal lobe epilepsy (TLE) associated with hippocampal sclerosis. Interictal in vivo electrophysiologic studies have revealed high-frequency (250-500 Hz) oscillations, termed fast ripples (FRs). These oscillations may uniquely occur in or adjacent to the site of hippocampal KA injection, in areas that generate spontaneous seizures. Similar field potentials also have been demonstrated in the epileptogenic region of patients with TLE. We have now characterized ictal electrographic patterns in this rat model for comparison with those in human TLE and begun to evaluate the role of FRs in the transition to ictus in the KA-treated rat. METHODS: Rats received unilateral intrahippocampal injections of KA and, after the development of spontaneous seizures, were implanted with multiple fixed and moveable microelectrodes for single unit, field potential, and EEG recording. They were then monitored by using video-EEG telemetry for several weeks to capture and evaluate electrographic and behavioral seizure types. Results were correlated with Timm's stain demonstration of mossy fiber sprouting. RESULTS: Low-voltage fast (LVF) and hypersynchronous electrographic ictal-onset patterns were seen in the KA-treated rat that resembled similar ictal-onset patterns in patients with TLE. Hypersynchronous, but not LVF, ictal discharges were associated with recurrent FRs. As in the human, hypersynchronous ictal onsets originated predominantly in hippocampus, whereas LVF ictal onsets more often involved extrahippocampal structures. LVF ictal onsets occurred during wakefulness or paradoxical sleep and were usually associated with motor behavior, whereas hypersynchronous ictal onsets occurred during slow-wave sleep or periods of immobility and were not associated with motor behavior unless there was transition to another ictal electrographic pattern. Mossy fiber sprouting did not correlate with the frequency of ictal EEG discharges exhibited by each rat but was greater in those rats that demonstrated frequent behavioral seizures. CONCLUSIONS: The electrographic features of spontaneous seizures in the KA-treated rat resemble those of patients with medically refractory TLE with respect to EEG pattern and localization. Our data suggest that hypersynchronous ictal onsets represent epileptogenic disturbances in hippocampal circuits, whereas LVF ictal onsets may involve extrahippocampal areas having more direct connections to the motor system. Hypersynchronous seizures may involve the same neuronal mechanisms that generate interictal FRs.

Animals↗

PubMed2000

A psychosocial approach to epileptic patients.

A psychoeducational approach was taken with 174 epileptic patients. Using this approach, no family problems were recognized among patients with idiopathic generalized epilepsy (IGE) or among those with symptomatic generalized epilepsy (SGE). However, 11 patients with temporal lobe epilepsy (TLE) and I patient with non-temporal lobe epilepsy (non-TLE) did exhibit family problems indicating that such problems involving IGE or SGE cases can be prevented through educational programs using a psychoeducational approach. This fails, however, to prevent such problems for TLE or non-TLE cases. Furthermore, small group psychotherapy was given to 10 patients with intractable TLE. They were directed to make self-evaluations regarding therapeutic factors originally introduced by Yalom but specially modified for these particular patients. Relatively high evaluations were given on every factor when compared with the results of individual psychotherapy. These results point out the importance of providing such psychotherapeutic approaches as group psychotherapy and self-help groups in addition to educational programs in order to enhance the quality of life (QOL) of epileptic patients and their families.

Epilepsy↗

PubMed2005

GABA receptor 1 polymorphism (G1465A) and temporal lobe epilepsy.

PURPOSE: To reevaluate the genetic contribution of the polymorphism G1465A of the gene coding for gamma-aminobutyric acid (GABA)(B) receptor 1 subunit [GABA(B)(1)] in a sample of French patients with temporal lobe epilepsy (TLE) and to perform an exploratory analysis in other phenotypic subgroups. METHODS: The 134 patients were genotyped for the polymorphism G1465A. This sample was divided in two groups. The first one had patients with nonlesional TLE, and the second one, with lesional TLE. Then these two groups were compared with a sample of 145 healthy individuals. RESULTS: The genotype and allele distributions for the polymorphism G1465A showed no difference between patients and controls. CONCLUSIONS: The association between the variant G1465A and the sample of patients could not be replicated, so these results exclude a major effect of this polymorphism in the susceptibility to nonlesional TLE. Larger samples should be tested to determine whether the G1465A in exon 7 of the GABA(B)(1) receptor gene is a susceptibility factor for nonlesional TLE.

Adolescent↗

PubMed2006

Normalization of quality of life three years after temporal lobectomy: a controlled study.

PURPOSE: The goal of epilepsy surgery is not merely to control previously intractable seizures, but also to improve quality of life (QOL). Our goals were to assess, in our Middle Eastern population, the QOL of adults with temporal lobe epilepsy (TLE) 3 years after temporal lobectomy as compared with matched TLE patients who did not undergo surgery and with healthy individuals in the same community. METHODS: Twenty consecutive TLE patients who underwent temporal lobectomy 3 years previously were matched in the following variables: age, sex, seizure frequency, seizure duration, age at onset of epilepsy, duration of epilepsy, and number of medications, with 17 TLE patients who underwent the presurgical evaluation and subsequent optimization of medical therapy but did not undergo surgery. They were also matched for age, sex, educational level, income, and residence with 20 healthy individuals. All groups were interviewed by using the ESI-55 questionnaire. RESULTS: Compared with the nonsurgery group, QOL was significantly better in the surgery group (85% seizure free) in the well-being, functioning, and role-limitation domains. QOL was similar in the surgery and healthy control groups in all domains and scales. The nonsurgery group scored significantly lower than healthy controls in the functioning and role-limitation domains. CONCLUSIONS: Intractable TLE was associated with marked impairments in QOL despite continued attempts to optimize medical therapy. Three years after temporal lobectomy QOL in our patient population achieved levels similar to those of matched healthy individuals. To our knowledge, this is the first study to report normalization of QOL after temporal lobectomy, in any population.

Adaptation, Psychological↗

PubMed1999

Verbal semantic memory in temporal lobe epilepsy.

OBJECTIVES: Temporal lobe epilepsy (TLE) may determine memory difficulties not explained by episodic memory impairment. The present study was aimed to verify the presence of specific semantic memory dysfunctions in TLE and to explore their relations to epilepsy variables. SUBJECTS AND METHODS: Forty-seven patients with lateralized temporal (n = 26) or extra-temporal lobe epilepsy (n = 21) and 23 healthy subjects were compared. Picture Naming and Pointing to a Picture were used to explore expressive and receptive vocabulary and the Semantic Questionnaire evaluated semantic judgment of verbally presented items. The Selective Reminding Procedure for word list learning and Story Recall were used to assess episodic memory. Spontaneous speech and the Token Test controlled for language disturbances, and Raven's Coloured Progressive Matrices were used to evaluate abstract reasoning ability. RESULTS: Multivariate analysis of variance of test scores showed significant impairment of semantic memory in patients with left TLE compared to healthy controls, whereas episodic memory was impaired in left temporal and extra-temporal epilepsy (as measured by word learning) and all epilepsy groups (as measured by Story Recall). In the TLE groups, naming abilities were more compromised than single-word comprehension and semantic judgment - which were not significantly affected. No deficits in language abilities or in abstract reasoning were found in any patient group. Factor analysis of memory tests scores in the patients produced two factors, one semantic and the other episodic. Regression analysis revealed that the semantic factor was related to abstract reasoning, left hemisphere lateralization of seizures, and age of seizure onset; while the episodic factor was related to age. CONCLUSIONS: Left TLE may determine significant verbal semantic memory compromise, maybe due to impaired access to the semantic-lexical storage. In non-aphasic epilepsy patients, comparison of performance on semantic and episodic memory tests may be useful for assessing the nature of memory failures, and may complement clinical and neurophysiological means for defining the epileptic center.

Adolescent↗

PubMed2000

Morphometric MRI analysis of the parahippocampal region in temporal lobe epilepsy.

Despite neuropathological and electrophysiological evidence for the involvement of parahippocampal structures in temporal lobe epilepsy (TLE), little attention has been paid to morphometric changes in these structures, and the relation of these changes to TLE. We performed high-resolution MRI volumetric analysis to examine in vivo the morphology of the parahippocampal region in 20 healthy subjects and 6 TLE patients with MRI evidence of unilateral hippocampal atrophy. In normal controls the standardized volume of the left entorhinal cortex (EC) was 1305 +/- 138 mm3 and that of the right EC was 1376 +/- 170 mm3; the left perirhinal cortex (PC) was 2900 +/- 554 mm3 and the right PC was 2771 +/- 486 mm3; the left posterior parahippocampal cortex (PPC) was 2499 +/- 583 mm3 and the right PPC was 2234 +/- 404 mm3. Using a 2 standard deviation cutoff from the mean of normal controls, we found ipsilateral to the seizure focus: (i) a reduction in the volume of the EC in all patients; (ii) a reduction of the PC in 2/6 (33%) patients; (iii) no reduction in the volume of the PPC in any patient. In 3/6 (50%) of patients, the EC was also abnormally small contralateral to the seizure focus. In patients with unilateral TLE, the EC is the most affected structure within the parahippocampal region. Whether this is due to a primary role of the EC in the genesis of TLE or is the consequence of its pivotal position in the reciprocal flow of information between the hippocampus and the neo- and limbic cortices remains to be explored.

Adult↗

PubMed2002

Role for the mortality factors MORF4, MRGX, and MRG15 in transcriptional repression via associations with Pf1, mSin3A, and Transducin-Like Enhancer of Split.

mSin3A and Transducin-Like Enhancer of Split (TLE) are two histone deacetylase (HDAC)-containing corepressors that function to repress transcription at targeted genes. Pf1 is a plant homeodomain zinc finger protein that interacts with both mSin3A and TLE, suggesting that it coordinates their function. Here we show that mSin3A and TLE interact with members of the mortality factor (MORF) family of putative transcriptional regulators. This family comprises MORF on chromosome 4 (MORF4) and MORF-related genes on chromosomes X and 15 (MRGX and MRG15, respectively) and is proposed to contribute to cellular senescence. Consistent with a role in transcription, we demonstrate that Gal4 fusions to each MORF family member repress transcription from a Gal4-dependent luciferase reporter. By using both mapping experiments and a dominant negative form of TLE, we show that repression by MORFs requires associations with mSin3A and TLE. Therefore, common functions of the MORFs are likely elicited through the action of a MORF/mSin3A/TLE complex. While the MORFs may have common functions, MRG15, but not MRGX or MORF4, interacted with Pf1. Therefore, MRG15 may have functions that are distinct from those of MRGX and MORF4. Consistent with this hypothesis, Pf1 reduced transcriptional repression by Gal4-MRG15 but it had no effect on repression by MRGX and MORF4. Pf1 has independent binding sites for MRG15 and mSin3A. In addition, Pf1 and MRG15 bind different domains on mSin3A. Together, these data suggest that the unique functions of MRG15 are elicited through the action of an MRG15/Pf1/mSin3A complex.

Animals↗

PubMed2003

Amygdala volumetry in "imaging-negative" temporal lobe epilepsy.

OBJECTIVE: Although amygdala abnormalities are sometimes suspected in "imaging-negative" patients with video EEG confirmed unilateral focal epilepsy suggestive of temporal lobe epilepsy (TLE), amygdala asymmetry is difficult to assess visually. This study examined a group of "imaging-negative" TLE patients, estimating amygdala volumes, to determine whether cryptic amygdala lesions might be detected. METHODS: Review of video EEG monitoring data yielded 11 patients with EEG lateralised TLE and normal structural imaging. Amygdala volumes were estimated in this group, in 77 patients with pathologically verified hippocampal sclerosis (HS), and in 77 controls. RESULTS: Seven of 11 "imaging-negative" cases had both significant amygdala asymmetry and amygdala enlargement, concordant with seizure lateralisation. Although significant amygdala asymmetry occurred in 35 of 77 HS patients, it was never attributable to an abnormally large ipsilateral amygdala. Compared with patients with HS, patients with amygdala enlargement were less likely to have suffered secondarily generalised seizures (p<0.05), and had an older age of seizure onset (p<0.01). CONCLUSION: Abnormal amygdala enlargement is reported in seven cases of "imaging-negative" TLE. Such abnormalities are not observed in patients with HS. It is postulated that amygdala enlargement may be attributable to a developmental abnormality or low grade tumour. It is suggested that amygdala volumetry is indicated in the investigation and diagnosis of "imaging-negative" TLE.

Adult↗