PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “TLE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

Abnormal T2 relaxation time in the cerebellar vermis of adults sexually abused in childhood: potential role of the vermis in stress-enhanced risk for drug abuse.

Recent studies suggest that childhood sexual abuse (CSA) elicits a cascade of neurohumoral events that affect brain development and is also a risk factor for the later development of substance abuse. We hypothesize that the cerebellar vermis may be a key region linking these observations. The vermis has a protracted ontogeny and a high density of glucocorticoid receptors, rendering it highly susceptible to early stress. The vermis modulates dopamine turnover in the accumbens and receives direct dopamine input through fibers with dopamine transporters. To test this hypothesis, steady-state functional magnetic resonance imaging (fMRI) (T2 relaxometry) was performed to assess resting blood flow in the vermis of 24 young adults (18-22 years) selected by screening from a large community sample. Eight subjects had a history of repeated CSA but were unmedicated and not under psychiatric care. Sixteen subjects were age-matched controls who had no personal or family history of Axis I psychiatric disorders. All subjects were screened to exclude known abnormalities affecting brain development, and any history of drug or alcohol abuse. CSA subjects had higher T2 relaxation time (T2-RT) than controls in the vermis but not in cerebral or cerebellar hemispheres. Vermal T2-RT correlated strongly with Limbic System Checklist (LSCL-33) ratings of temporal lobe epilepsy (TLE)-like symptomatology. From 537 prescreened young adults we found that their frequency of substance use was associated with a monotonic increase in LSCL-33 ratings and depression scores. Together these findings suggest that early trauma may interfere with the development of the vermis, and produce neuropsychiatric symptoms associated with drug use.

Adolescent↗

Groucho/TLE family proteins and transcriptional repression.

The Drosophila Groucho (Gro) protein is the prototype for a large family of corepressors, examples of which are found in most metazoans. This family includes the human transducin-like Enhancer of split (TLE) proteins. As corepressors, Gro/TLE family proteins do not bind to DNA directly, but rather are recruited to the template by DNA-bound repressor proteins. Gro/TLE family proteins are required for many developmental processes, including lateral inhibition, segmentation, sex determination, dorsal/ventral pattern formation, terminal pattern formation, and eye development. These proteins are characterized by a conserved N-terminal glutamine-rich domain and a conserved C-terminal WD-repeat domain. The primary role of the glutamine-rich domain is apparently to mediate tetramerization, while the WD-repeat domain may mediate interactions with DNA-bound repressors. The glutamine rich and WD-repeat domains are separated by a less conserved region containing domains that have been implicated in transcriptional repression and nuclear localization. In addition to encoding full-length Gro/TLE family proteins, most metazoan genomes encode truncated family members that contain the N-terminal oligomerization domain, but lack the C-terminal WD-repeat domain. These truncated proteins may negatively regulate full-length Gro/TLE proteins, perhaps by sequestering them in non-productive complexes. Gro/TLE family proteins probably repress transcription by multiple mechanisms. For example, a glycine/proline-rich domain in the central variable region functions to recruit the histone deacetylase Rpd3 to the template. This histone deacetylase then presumably silences transcription by altering local chromatin structure. Other repression domains in Gro may function in a histone deacetylase-independent manner. Many aspects of Gro/TLE protein function remain to be explored, including the possible post-translational regulation of Gro/TLE activity as well as the mechanisms by which Gro/TLE proteins direct repression at a distance.

Animals↗

Time sequence and types of memory deficits after experimental status epilepticus.

P35 rats subjected to kainate induced status epilepticus (SE) subsequently underwent four consecutive series of the Morris Water Maze. They demonstrated, compared with controls, an early (P46-49), and subsequent (P60-63) disturbance in acquisition, but not in long term retention, of spatial memory. They eventually achieved performance levels similar to those of controls (P74-77, P91-94). These data support the hypothesis that acquisition, but not long term retention, of spatial material is impaired in this model of temporal lobe epilepsy (TLE), probably due to the hippocampal injury that occurs after SE.

Animals↗

Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy.

PURPOSE: To analyze the spatio-temporal relationship between seizure propagation and interictal epileptiform discharges (IEDs) in patients with bitemporal epilepsy. METHODS: We investigated 18 adult patients with intractable temporal lobe epilepsy (TLE) who had undergone continuous video-EEG monitoring during presurgical evaluation. Only those patients were selected who had independent IEDs over both temporal lobes. Two authors evaluated the ictal and interictal EEG data independently. RESULTS: We analyzed 52 lateralized seizures of 18 patients. Thirty-one seizures showed ipsilateral seizure spread exclusively, whereas in 21 seizures the contralateral hemisphere was also involved. In lateralized seizures without contralateral propagation, we found that spikes ipsilateral to the seizure onset occurred postictally in a greater ratio than preictally (P<0.001). In lateralized seizures with contralateral propagation, we found no significant changes in the postictal spike distribution. CONCLUSIONS: Our findings showed that the lateralization of IEDs may depend on the brain areas involved by the preceding seizures, suggesting that spikes can be influenced by the seizure activity, and are not independent signs of epileptogenicity.

Electroencephalography↗

Semiology of temporal lobe epilepsy in children and adolescents. Value in lateralizing the seizure onset zone [corrected].

PURPOSE: To determine the frequency and lateralizing value of clinical seizure symptoms in children and adolescents with drug-resistant temporal lobe epilepsy (TLE). METHODS: Patients enrolled had to be <18 years of age and seizure free at follow-up for at least 12 months after epilepsy surgery. Patients were assigned to two age groups, children (age<12 years) and adolescents (age>12 and <18 years). Video-tapes were reviewed blinded to patients' demographic data and results of additional investigations by two independent raters. Clinical signs of known lateralizing significance in adults and additional clinical signs without lateralizing value were assessed. RESULTS: 14 patients (eight boys; 2-18 years) fulfilled the inclusion criteria. Inter-observer agreement was excellent (kappa coefficient: 0.82). Compared with adult series, no differences were found concerning overall occurrence of lateralizing signs and lateralizing accuracy. There were age-related differences, however, concerning the occurrence of individual signs: secondary generalization, complex automatisms and version were less frequent in children than in adolescents. CONCLUSIONS: Clinical signs of lateralizing value can also be found in children and adolescents, provided that the evaluation protocols used consider developmental aspects.

Adolescent↗

The role of seizure-induced neurogenesis in epileptogenesis and brain repair.

Data accumulated over the past four decades have led to the widespread recognition that neurogenesis, the birth of new neurons, persists in the hippocampal dentate gyrus and rostral forebrain subventricular zone (SVZ) of the adult mammalian brain. Neural precursor cells located more caudally in the forebrain SVZ are thought to also give rise to glia throughout life. The continued production of neurons and glia suggests that the mature brain maintains an even greater potential for plasticity after injury than was previously recognized. Underscoring this idea are recent findings that seizures induced by various experimental manipulations increase neurogenesis in the adult rodent dentate gyrus. Although neurogenesis and gliogenesis in persistent germinative zones are altered in adult rodent models of temporal lobe epilepsy (TLE), the effects of seizure-induced neurogenesis in the epileptic brain, in terms of either a pathological or reparative role, are only beginning to be explored. Emerging data suggest that altered neurogenesis in the epileptic dentate gyrus may be pathological and promote abnormal hyperexcitability. However, the presence of endogenous neural progenitors in other proliferative regions may offer potential strategies for the development of anti-epileptogenic or neuronal replacement therapies.

Animals↗

Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy.

Outcome studies concerning memory after pediatric temporal lobe surgery in the treatment of epilepsy are rare and have not yielded consistent results. In the present study, 55 children and adolescents with temporal lobe epilepsy (TLE; 26 left, 29 right, 6-17 years) performed a verbal memory test before and 3 as well as 12 months after different types of temporal lobe resections (anterior lobectomy, amygdalo-hippocampectomy (AH), lesionectomy (LX)). Groups did not significantly differ before surgery. Three months after surgery, the left resected group showed a decline in learning and delayed recall, and performed significantly lower than the right resected group. Recoveries were evident 1 year after surgery. The postoperative memory declines were associated with a left-sided resection and a higher preoperative performance. Comparisons on the different resection types suggest a special risk in patients undergoing a left-sided AH. In summary, our results indicate a functional association of verbal memory functions with the left temporal lobe similar to findings in adult patients. Declines after left-sided temporal resections seem to be reversible at least for part of the children, perhaps due to the greater plasticity of the immature brain.

Adolescent↗

Dynorphin and the kappa 1 ligand [3H]U69,593 binding in the human epileptogenic hippocampus.

The distribution of dynorphin (DYN), one of its binding sites (kappa 1 receptor) and their relationship to neuronal loss and granule cell hyperexcitability was examined in hippocampi from patients with temporal lobe epilepsy (TLE). In hippocampi that were not the seizure focus (mass associated temporal lobe epilepsy, MaTLE; and paradoxical temporal lobe epilepsy, PTLE) DYN-like immunoreactivity was localized in the dentate granule cells and their mossy fiber terminals within the hilus and area CA3. In hippocampi that were the seizure focus (MTLE), 89% showed an additional band of immunoreactivity confined to the inner molecular layer (IML) of the dentate gyrus, representing recurrent mossy fiber collaterals. In 11% of MTLE patients no staining was found in the IML (MTLE/DYN-). The MTLE/DYN- hippocampi were also characterized by a significantly lower degree of cell loss than in MTLE hippocampi in the dentate granule cell layer, the hilus and CA3. Both MTLE and MTLE/DYN- hippocampi showed evoked epileptiform bursting in granule cells while MTLE showed greater polysynaptic EPSPs and spontaneous excitatory activity. Thus granule cell recurrent collateral sprouting may account for only some aspects of hyperexcitability. In 30% of the MTLE group, hilar neurons of a variety of morphological types expressed DYN immunoreactivity in their somata and dendrites. The density of [3H]U69,593 binding sites in MaTLE and PTLE patients was highest in areas CA1 and the subiculum-regions having little or no DYN-staining. In the dentate molecular layer, hilus and CA3--regions with the most DYN immunoreactivity--there was a low density of ligand binding. The significance of this transmitter/receptor mismatch is yet unknown.

Adolescent↗

Disrupted development of the cerebral hemispheres in transgenic mice expressing the mammalian Groucho homologue transducin-like-enhancer of split 1 in postmitotic neurons.

Transducin-like Enhancer of split (TLE) 1 is a mammalian transcriptional corepressor homologous to Drosophila Groucho. In Drosophila, Groucho acts together with bHLH proteins of the Hairy/Enhancer of split (HES) family to negatively regulate neuronal differentiation. Loss of the functions of Groucho or HES proteins results in supernumerary central and peripheral neurons. This suggests that mammalian TLE/Groucho family members may also be involved in the regulation of neuronal differentiation. Consistent with this possibility, TLE1 is expressed in proliferating neural progenitor cells of the central nervous system, but its expression is transiently down-regulated in newly generated postmitotic neurons. Based on these observations, we investigated whether persistent TLE1 expression in postmitotic neurons would perturb the normal course of neuronal development. Transgenic mice were derived in which the human TLE1 gene is regulated by the promoter of the Talpha1 alpha-tubulin gene, which is exclusively expressed in postmitotic neurons. In these mice, constitutive expression of TLE1 inhibits neuronal development in the embryonic forebrain leading to increased apoptosis and neuronal loss in the ventral and dorsal telencephalon. These results provide the first direct evidence that TLE1 is an important negative regulator of postmitotic neuronal differentiation in the mammalian central nervous system.

Animals↗

Preoperative evaluation for temporal lobe surgery.

Temporal lobe epilepsy (TLE), the most common form of partial epilepsy in adults is often refractory to medical treatment and in these patients epilepsy surgery is considered. Successful surgery is dependent on accurate localisation and lateralisation of the epileptogenic zone. The preoperative evaluation involves a series of assessments and investigations including detailed clinical history, interictal EEG, video-EEG monitoring, MRI, PET, SPECT, and neuropsychology and neuropsychiatric assessment. The role of each of these investigations and assessments in the preoperative evaluation is discussed. Advanced MR techniques including magnetic resonance spectroscopy, MR diffusion and MR perfusion have recently been assessed and are likely to enhance the pre-surgical evaluation of patients with TLE.The surgical outcome and preoperative investigations performed of 80 consecutive patients who underwent temporal lobe surgery between 1993 and 2002 at Royal Melbourne Hospital were reviewed. All patients had MRI, video-EEG monitoring and neuropsychology assessment and 56% a PET scan. During a mean follow-up of 5.9 years 75% had Class 1 outcome, 22% non-Class 1 outcome and 3% were lost to follow-up. The results of preoperative investigations were correlated with outcome. For interictal EEG, seizure semiology, ictal EEG, PET and neuropsychology assessment the surgical outcome of patients in whom results were concordant to side of surgery was compared with those discordant or non-lateralising. There was no significant difference. In 78 of 80 patients MRI revealed mesial temporal sclerosis or a foreign tissue lesion. The outcome was no different between these two groups. Results suggest that in patients with unilateral temporal lobe lesion on MRI and where ictal EEG is either concordant or non-lateralising, other investigations including PET, provide little additional prognostic information.

Electroencephalography↗

Discovery and structure--activity relationship studies of a novel and specific peptide motif, Pro-X-X-X-Asp-X, as a platelet fibrinogen receptor antagonist.

A novel hexapeptide, H-Pro-Ser-Nva-Gly-Asp-Trp-OH 6, a specific antagonist of platelet fibrinogen receptor (GpIIb/IIIa), was discovered in a structure-activity relationship (SAR) study where the role of the N-terminal Pro moiety of an RGD-containing peptide, H-Pro-Ser-Arg-Gly-Asp-Trp-OH 1, which is a potent but not specific antagonist toward GpIIb/IIIa integrin, was investigated. This novel peptide 6 exhibits very high activity as a human platelet aggregation inhibitor (IC50 0.59 microM, human PRP/collagen) as well as marked specificity for GpIIb/IIIa. A series of substitutions at the third position (Nva residue) in this hexapeptide, focused on the conformational rigidity, led to compounds which are superior to the original novel peptide 6 with regard to anti-platelet activity. The peptides, H-Pro-Ser-Hyp-Gly-Asp-Trp-OH 17 and H-Pro-Ser-delta Pro-Gly-Asp-Trp-OH 18 with the 5-membered ring structure, which restricted the conformation of the peptide backbone at the third position, inhibited the aggregation of human platelets at submicromolar concentrations (IC50 0.39 and 0.30 microM, respectively). Further structure-activity relationship studies at each position of the peptide sequence suggest a novel motif sequence, Pro-X1-X2-X3-Asp-X4, for specific GpIIb/IIIa integrin recognition, in which the N-terminal free Pro residue and the Asp residue at the fifth position are essential to the activity. This motif sequence is summarized as follows: (1) a small amino acid such as Ser, Ala or Gly is preferable at X1 position; (2) X2 may be any amino acid, preferably a bulky amino acid such as Tle or a cyclic amino acid such as Pro; (3) X3 must be a small amino acid such as Gly; and (4) X4 is preferably an amino acid with an aromatic side chain.

Amino Acid Sequence↗

Biodistribution and catabolism of (18)F-labeled neurotensin(8-13) analogs.

4-([(18)F]fluoro)benzoyl-neurotensin(8-13) ((18)FB-Arg(8)-Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 1) and two analogs stabilized in one and two positions ((18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 2, (18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)-Tle(12)-Leu(13)-OH, 3) were synthesized in a radiochemical yield of 25-36% and a specific activity of 5-15 GBq/mmol. The peptides were evaluated in vitro and in vivo for their potential to image tumors overexpressing neurotensin receptor 1 (NTR1) by positron emission tomography (PET). All analogs exhibited in vitro binding affinity in the low nanomolar range to NTR1-expressing human tumors, measured by quantitative receptor autoradiography, HT-29 and WiDr cells, and to sections of tumors derived from these cell lines in mice. The radiotracers were internalized in the cells in vitro, and the fluorinated peptides were able to mobilize intracellular Ca(2+) of WiDr cells. In in vivo studies in rats and in mice bearing HT-29 cell tumors, only a moderate uptake of the radioligands into the studied tumors was observed, presumed to be due to degradation in vivo and fast elimination by the kidneys. In comparison with the other analogs, the specific tumor uptake expressed as tumor-to-muscle relation was highest for the radioligand 3. The blood clearance of 3 was reduced by co-injection of peptidase inhibitors. The catabolic pathways of the radiofluorinated peptides were elucidated. The results suggest that the high binding affinity to NTR1 and the stabilization against proteolytic degradation are not yet sufficient for tumor imaging by PET.

Animals↗

Stabilization of neurotensin analogues: effect on peptide catabolism, biodistribution and tumor binding.

Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [99mTc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (NalphaHis)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH2NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.

Animals↗

Automatisms with preserved responsiveness and ictal aphasia: contradictory lateralising signs during a dominant temporal lobe seizure.

The 25-year-old right-handed woman suffering from temporal lobe epilepsy (TLE) was referred to our centre for presurgical evaluation. MRI showed a right-sided hippocampal sclerosis. During video-EEG-recorded seizures, abdominal aura was followed by oral automatisms, during which she was completely reactive to external stimuli, although she was unable to speak. Ictal EEG showed right temporal seizure pattern, without contralateral propagation. She had abnormal speech postictally. Speech-activated functional transcranial Doppler sonography revealed right-sided speech dominance. She has become seizure free after a right-sided amygdalo-hippocampectomy. In our patient, contradictory clinical ictal lateralising signs (automatisms with preserved responsiveness vs. ictal and postictal dysphasia) occurred during right-, speech-dominant-sided seizures. This is the first report when automatisms with preserved consciousness occurred during a seizure originating and involving the speech-dominant hemisphere.

Adult↗

A retrospective analysis of patients with febrile seizures followed by epilepsy.

This study was performed to investigate some clinical parameters of febrile seizures (FSs) in patients with epilepsy, testing any possible correlation between those parameters and the type of subsequent epilepsy. One hundred and nine patients with epilepsy having a history of FSs were evaluated for age at onset of FSs, interval between first FS and first afebrile seizure, recurrence rate, type of FSs, incidence of febrile status, family history for epilepsy and for FSs and the neurological status of the patient. The epilepsy that developed subsequently, were classified as generalised versus partial and also according to their syndromic subgroups. In temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS), statistical analyses revealed a younger age at onset of FSs, and a high incidence of episodes of febrile status and of complex FSs. Clinical characteristics of FSs followed by partial epilepsies were younger age at onset, presence of focal features and of febrile status, longer interval between the first FS and the first afebrile seizure, and a high incidence of FSs in the family history. In generalised epilepsies, however, a shorter interval between the first FS and the first afebrile seizure, a high incidence of single FS and of a family history of epilepsy were predominating characteristics. Results suggest that certain features of FSs may be predictive of a particular type of subsequent epilepsy.

Adolescent↗

Intraoperative electrocorticography in epilepsy surgery: useful or not?

Intraoperative electrocorticography (ECoG) has been traditionally used in the surgical management of medically refractory partial epilepsies to identify the location and limits of the epileptogenic area, to guide the extent of resection, and to assess its completeness. Although in clinical use for many years, the basic questions regarding indications and limitations of this method has remained unanswered. ECoG plays a major role in tailored temporal lobectomies, whereas, it serves no practical purpose in standard resection of medial temporal lobe epilepsy (TLE) with magnetic resonance imaging (MRI) evidence of mesial temporal sclerosis (MTS). Residual hippocampal spikes, unaltered by resection, correlate with a greater proportion of seizure recurrence. Intraoperative hippocampal ECoG can allow sparing of functionally important hippocampus, thus minimising postoperative memory decline. ECoG eminently aids removal of developmental malformations of brain, and most importantly, the excision of highly epileptogenic cortical dysplasias (CDs) for deciding the extent of resection for best seizure control. The ECoG can be a valuable tool during multiple subpial transections (MST).

Anesthesia↗

Changes of central benzodiazepine receptor density in the course of anticonvulsant treatment in temporal lobe epilepsy.

The first investigation of the central-type benzodiazepine (BZ) receptor density before and following 2 months successful treatment with carbamazepine (CBZ) in a patient with temporal lobe epilepsy (TLE) using 123I-labelled Iomazenil (a specific lipophile central BZ receptor compound) and single photon emission tomography (SPET) is reported. First, a focal slowing of the EEG in the left temporal area was noted and a corresponding reduction of the central BZ density of the left temporal lobe was found. After 2 months of treatment the patient was symptom-free, and a normal BZ receptor density and no pathological EEG signs were found. The increase in central BZ receptor binding sites might be related to the anticonvulsant effects of CBZ mediated by the so-called peripheral BZ receptor sites.

Adult↗

Neural networks involving the medial temporal structures in temporal lobe epilepsy.

OBJECTIVES: In a previous study using the averaged coherence technique to study interactions between medial/limbic and lateral/neocortical regions, we observed that epileptogenic networks in temporal lobe epilepsy seizures (TLES) could be divided into 4 subtypes, i.e. medial (M), medial-lateral (ML), lateral-medial (LM), and lateral (L). In the ML and LM subtypes, medial structures and the anterior temporal neocortex are co-activated at the onset of seizures. However, using this approach, we were unable to determine the direction of coupling and may have overlooked non-linear variations in interdependency. The purpose of the present study using non-linear regression for analysis of stereoelectroencephalographic (SEEG) signal pairs was to measure the degree and direction of coupling between medial and neocortical areas during TLES in patients with the M, ML, and LM subtypes. METHODS: Eighteen patients with drug-resistant TLEs who underwent SEEG recording were studied. We used a non-linear correlation method as a measure of the degree and the direction of coupling on SEEG signal pairs. Patients with pure lateral TLEs were not studied. We analyzed the functional coupling between 3 regions of the temporal lobe: the anterior temporal neocortex, the amygdala, and the anterior hippocampus. A physiological model of EEG generation was used to validate the non-linear quantification method and assess its applicability to real SEEG signals. RESULTS: Results are first based on a physiological model of EEG data in which both degree and direction of coupling are explicitly represented, thus allowing construction of the neural systems inside which causality relationships are controlled and generation of multichannel EEG signals from these systems. These signals provide an objective way of studying the performance of non-linear regression analysis on real signals. In medial networks (10 patients), the ictal discharge is limited to the medial limbic structures and may propagate secondarily to the cortex. Quantified results demonstrated no significant coupling between medial and lateral structures at the beginning of the seizures. Conversely, almost constant unidirectional or bidirectional coupling was observed between hippocampus and amygdala. In medial-lateral (5 patients) and lateral-medial (3 patients) networks, the initial ictal discharge includes both limbic and neocortical regions. A rapid "tonic" discharge is observed over the temporal neocortex at the onset of seizure. Quantitative analysis showed an initial increase in the non-linear correlation coefficient between neocortex and medial structures. Quantification of the coupling direction demonstrated influence of medial over lateral structures (medial-lateral) or of the lateral neocortex over medial structures (lateral-medial). CONCLUSIONS: These results confirm the existence of several generic and organized networks involving the medial structures during TLE seizures.

Amygdala↗