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Biomedical subjects

C E Elger

Publications and source records attributed to C E Elger.

At least 199 records · Page 11Linked to original sources

Aggravation of focal epileptic seizures by antiepileptic drugs.

Aggravation of focal epileptic seizures in adults is common after the antiepileptic drug (AED) therapy is initiated. Sometimes aggravation is mimicked by clustering of the seizures. Therefore, it is always necessary to analyze the patient's history and therapy carefully before drawing any conclusions. It is likely that a paradoxical aggravation of epileptic seizures can be attributed to the given AED and is sometimes, but only rarely, due to drug interactions.

Acetates↗

Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy.

OBJECTIVES: Existing speculations regarding the cognitive functions of the right hippocampus suggest a special involvement in non-verbal memory functions. However, all supporting evidence in epileptic patients came from postoperative studies that did not consider the preoperative functioning level. The present study investigates in patients with right temporal lobe epilepsy (RTLE), both preoperatively and postoperatively, the role of the right hippocampus for visual memory, visuoconstruction, and spatial visualisation. METHODS: Two groups of patients with RTLE with and without right hippocampal damage (HC+/n=15 v HC-/n=13) were set up retrospectively thereby taking into account the surgical treatment (selective amygdalohippocampectomy v temporal resections sparing the hippocampus), the postoperative pathological findings (hippocampal sclerosis in the HC+ group) and the seizure outcome (all seizure free). The two groups were compared with regard to their neuropsychological performance preoperatively and 3 months after temporal lobe surgery. RESULTS: The preoperative results indicated impaired visual memory performance only for the HC+ patients, whereas the HC- patients exhibited no deficiencies in any of the assessed functions. Postoperatively, both groups exhibited partially improved performances. The type of surgical treatment had no different effects on the postoperative performance changes. CONCLUSIONS: The results suggest that hippocampal damage is the major cause of non-verbal memory deficiencies in preoperative patients with right temporal lobe epilepsy. Hence the results support and extend findings from previous postoperative studies. Right hippocampal resections did not increase the preoperative visual memory deficiencies, thus supporting the view that right temporal lobe resection in general bears only small risks for cognitive deteriorations.

Adult↗

New antiepileptic drugs in epileptology.

New antiepileptic drugs have been developed and released for the treatment of chronic focal and secondarily generalized epileptic seizures. The anticonvulsant efficacy of these drugs (vigabatrin, lamotrigine, gabapentin, felbamate, tiagabine, topiramate and oxcarbazepine) does not seem to be superior to that of traditional anticonvulsants. The main advantage of these newly developed drugs is a different spectrum of possible adverse events (i.e. these drugs usually do not induce sedation). Moreover, interactions with traditional anticonvulsants are less common, therefore, comedication with these drugs shows an improved tolerability. The availability of new antiepileptic drugs enables us to establish an individually tailored anticonvulsant strategy for each patient.

Anticonvulsants↗

Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis.

OBJECTIVE: One hypothesis proposes that a pre-existing alteration of medial temporal lobe structures contributes to febrile convulsions and subsequent hippocampal sclerosis (HS) in patients with temporal lobe epilepsy (TLE) and antecedent febrile convulsions. It is possible that such a structural alteration does not always lead to convulsions and may also be present in clinically unaffected relatives. METHODS: We tested this hypothesis by MRI investigation of 23 members of two families, of whom 13 had experienced febrile convulsions and 10 had not. One member of each family with febrile convulsions subsequently developed TLE. We compared the right/left ratios of hippocampal volumes (RHV) with 23 age- and sex-matched controls. Additionally, two independent raters assessed hippocampal signal intensity and pattern in T2- and fluid-attenuated inversion recovery images. RESULTS: Both TLE patients showed left HS. All subjects with febrile convulsions who did not develop epilepsy and six clinically unaffected relatives also showed asymmetric RHV (>3 standard deviation) but a normal hippocampal signal intensity. In all of these subjects, the left hippocampus was smaller. Visual inspection of these smaller hippocampi revealed blurred internal pattern or flat hippocampal bodies or both in one family and smaller hippocampal heads in the other. The pattern of HS in TLE patients showed a structural correlation with the abnormalities seen in their relatives. One subject with febrile convulsions had additional subcortical heterotopias. CONCLUSION: These findings suggest a subtle, pre-existing hippocampal malformation that may facilitate febrile convulsions and contribute to the development of subsequent HS.

Adolescent↗

Automatic detection of epileptiform spikes in the electrocorticogram: a comparison of two algorithms.

The detection and analysis of epileptiform spikes is of major importance for the presurgical evaluation of epilepsy patients concerning the localization of the epileptogenic zone. To examine the reliability of automatic spike detection software for intracranial subdural strip and intrahippocampal depth recordings, the results of two algorithms were compared with those of two human reviewers. The first is a newly developed two-stage algorithm whose first stage uses the enhanced prediction error of an updating linear predictor of the electrocorticogram (ECoG) to select candidates for the following mimetic rule-based system. The second system is the well-known rule-based algorithm developed by Gotman. Both systems achieved only a surprisingly small number of common detections (32 and 24%) accompanied by a high number of false detections (65 and 78%). Though the results were better for the first system, the clinical use of the automatic spike detection systems should be limited to the following purposes. 1. To achieve data reduction before visual inspection of the spike candidates. 2. To get an overview of the spatial distribution of spike counts. 3. To obtain a data basis for the analysis of quantitative spike parameters.

Adult↗

Inhibitory effects of mesial temporal partial seizures onto frontal neocortical structures.

PURPOSE: A retrospective evaluation of the ictal temporal tracer uptake and the perfusion pattern in other neo- and subcortical structures was performed to define typical extratemporal changes of rCBF that might further aid the differentiation of temporal and extratemporal seizures. METHOD: Ictal and interictal rCBF brain SPECT studies were done in 17 patients with seizures of mesial temporal onset according to scalp electroencephalography (EEG) and electrocorticography (ECoG) using 99mTc-ECD. Except for hippocampal sclerosis/atrophy, which was found in 11/17 patients, no morphologic anomalies were detected by MRI. Ictal tracer injections were given immediately after the onset of the seizure according to continuous video-EEG monitoring. The injection latency was two to twenty seconds. The data acquisition was done 45 minutes after the tracer injection using an annular crystal system (Ceraspect, DSI). In 15 patients a semiquantitative ROI-analysis of the tracer uptake in temporal and frontal regions could be obtained. RESULTS: All ictal studies correctly localised the affected temporal lobe. A detection of the epileptogenic focus itself was successful in 59% of patients while in the remaining patients the maximum of tracer uptake was not found to be located in the mesial temporal lobe only. In contrast to all other cerebral structures, only within the ipsilateral basal frontal cortex a frequent reaction to the temporal seizure was found. The basal frontal cortex ipsilateral to the affected temporal lobe showed a reduction of tracer uptake between the ictal and interictal study in 82% of patients which was semiquantitatively significant using a paired t-test (p < 0.05). Other neo- or subcortical structures showed inconsistent results. CONCLUSION: Secondary involvement of neocortical temporal structures in ictal rCBF-SPECT with 99mTc-ECD occurs early and focal maxima of tracer uptake within the temporal lobe do not necessarily represent the epileptogenic focus itself. Seizures of mesial temporal origin did not activate but frequently depressed the ipsilateral basal frontal tracer uptake during the early ictal phase. This phenomenon may account for some aspects of the clinical appearance of mesial temporal seizures.

Adolescent↗

Evidence of very fast memory consolidation: an intracarotid amytal study.

This study provides evidence from intracarotid amobarbital tests (IAT) in patients with epilepsy that complete suppression of the electrophysiological activity of the left language-dominant hemisphere through left IAT does not impair memory for verbal information given 1 min or immediately before the injection of the barbiturate. Although language functions were completely disrupted and patients were unable to encode new information during the left IAT, pre/post memory was as good as in the right IAT. This lack of retrograde amnesia leads to the conclusion that a relatively stable representation of events is achieved within seconds after encoding. The results contradict models which assume that short-term memory is based on purely electrophysiological processes.

Amobarbital↗

Metabotropic glutamate receptors modulate synaptic transmission in the perforant path: pharmacology and localization of two distinct receptors.

Metabotropic glutamate receptors (mGluRs) have emerged as an interesting family of eight different receptor subtypes that can be divided into three groups according to their pharmacology and sequence similarity. In the present study, the specific mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed field excitatory postsynaptic potentials (fEPSPs) in the rat dentate gyrus evoked by perforant path stimulation in a concentration-dependent, rapid and reversible manner (EC50: L-AP4 5.9 +/- 1.6 microM, (1S,3R)-ACPD 80 +/- 34 microM). In a 'paired-pulse' stimulation protocol, the first fEPSP showed a stronger reduction, resulting in 'paired-pulse' facilitation. The effects of L-AP4 but not of (1S,3R)-ACPD could be antagonized by the group III mGluR antagonists (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4) and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG). Moreover, (1S,3R)-ACPD was still potently depressing fEPSPs after preperfusion of near saturating concentrations of L-AP4. Together, the results suggest that both substances act on different mGluRs. The effects of (1S,3R)-ACPD could not be further differentiated by selective group I or group II mGluR agonists. Although (2S,1'S,2'S)-2-carboxycyclopropylglycine (L-CCG-I) blocked fEPSPs at concentrations >> 1 microM, these effects, as well as L-AP4 effects, were potently antagonized by MAP4. This suggests that mGluR8 might be responsible for the actions of L-AP4 and L-CCG-I. The two different mGluRs showed a distinct distribution when fEPSPs were recorded simultaneously in the outer and middle molecular layer (OML/MML): The L-AP4 sensitive receptor, possibly mGluR8, seems to be located in the OML while (1S,3R)-ACPD showed its main effect in the MML.

Aminobutyrates↗

The apolipoprotein E epsilon 4 allele is not associated with early onset temporal lobe epilepsy.

A polymorphism of the apolipoprotein E gene, in particular the epsilon 4 allele (ApoE4), has been associated with impaired neuronal phospholipid metabolism and synapse reorganization and has been implicated in several neurodegenerative disorders. Since selective neuronal cell lose and aberrant axonal reorganization represent hall-marks of Ammon's horn sclerosis (AHS) in patients with chronic temporal lobe epilepsy (TLE), the ApoE polymorphism was studied in 125 patients with TLE. The genotype analysis revealed a frequency of 15.5% for epsilon 4, and 74.8% and 9.8% for epsilon 3 and epsilon 2, respectively. These figures were not significantly different from those reported in the normal European population. In addition, no correlation was found between the ApoE4 allelotype and the age of epilepsy onset, seizure type, febrile seizures, family history of epilepsy, surgical outcome and neuropathological findings in patients with TLE. These data virtually exclude ApoE as a susceptibility gene involved in the pathogenesis of early onset TLE or AHS.

Adolescent↗

Potassium currents in acutely isolated human hippocampal dentate granule cells.

1. Properties of voltage- and Ca(2+)-dependent K+ currents were investigated in thirty-four dentate granule cells acutely isolated from the resected hippocampus of eleven patients with therapy-refractory temporal lobe epilepsy (TLE). 2. When intracellular Ca2+ was strongly buffered with 11.5 mM EGTA-1 mM Ca2+ in the recording pipette, K+ currents (IK) with a slow activation and biexponential time-dependent decay could be elicited, which showed a threshold for activation around -30 mV. 3. A contribution of Ca(2+)-dependent K+ currents became apparent with intracellular solution containing 1 mM BAPTA-0.1 mM Ca2+. Superfusion of low-Ca2+ extracellular solution blocked 43% of outward currents in this recording configuration. Outward current components could also be blocked by substituting 5 mM Ba2+ for extracellular Ca2+ (78%), or by application of 100 microM Cd2+ (25%). 4. The Ca(2+)-dependent K+ currents could be pharmacologically subdivided into two components. One component was sensitive to 500 microM tetraethylammmonium (TEA; 41%) and 10 nM charybdotoxin (CTX; 47.2%). The blocking effects of 10 nM CTX and 500 microM TEA were not additive, suggesting that both agents block the same conductance. A second, smaller outward current component was blocked by 50 nM apamin (13%). 5. A transient A-type K+ current could be observed in six neurones and showed a fast monoexponential time-dependent inactivation with a steady-state voltage dependence that was distinct from that of IK. The A-type current was blocked by 4-aminopyridine (4-AP) but not by TEA or low-Ca2+ solution. 6. We conclude that outward currents in human hippocampal dentate granule cells can be separated into at least four types by their kinetic and pharmacological properties. These include at least one voltage-dependent current similar to those observed in mammalian hippocampal neurones, and two Ca(2+)-dependent K+ currents that most probably correspond to SK- and BK-type currents. A classical A-type current could be detected in some patients with Ammon's horn sclerosis (AHS) but not in patients with lesion-associated TLE.

Epilepsy, Temporal Lobe↗

Rey Auditory-Verbal Learning Test: structure of a modified German version.

The Auditory Verbal Learning Test (AVLT) is widely used in scientific research as well as in clinical practice. But there exists little research on the structure of the AVLT. We investigated the structure of a German version of the AVLT and VLMT, in 232 patients of a psychiatric clinic and in 872 patients of an epileptologic clinic. First we stated a theoretical LISREL model relating the observed variables of the VLMT to short-term memory (STM) and long-term memory (LTM) as latent variables. Then we estimated the postulated LISREL model in the two samples. The proposed model showed excellent fit in both samples, and there were no significant deviations between the estimated and the observed covariance matrices. Thus, STM and LTM suffice to explain the structure of the VLMT, and the proposed structural equations model can be used to estimate STM and LTM capacity from VLMT data.

Adult↗

Patterns of language dominance in focal left and right hemisphere epilepsies: relation to MRI findings, EEG, sex, and age at onset of epilepsy.

The present study evaluates results of language testing during intracarotid amobarbital procedures in 167 patients with either left (LHE, n = 81) or right hemisphere epilepsies (RHE, n = 86). In both groups there was a high rate of deviance from complete left hemisphere dominance of 24 and 31%, respectively. Whilst complete right hemisphere or incomplete left hemisphere language dominance were the prominent atypical patterns in LHE, RHE was associated with either bilateral dominance or incomplete left dominance. In LHE, atypical language dominance was frequently associated with an extratemporal localization of lesions or epileptic foci. The age at onset of epilepsy and the degree of right hemisphere language dominance correlated significantly in LHE but not in RHE. Finally, atypical dominance in LHE but not in RHE was associated with poorer language and nonlanguage functions, the latter being negatively correlated with the degree of right hemisphere language dominance. Conclusions are: (1) The data contradict the assumption of equipotentiality and favor the supposition of a predetermined left hemisphere superiority in language processing. (2) Atypical language dominance in LHE can largely be explained in terms of a plasticity dependent language shift as a consequence of early left hemisphere epilepsies and lesions. (3) Atypical dominance patterns in RHE appear to reflect the prevalence of genetically determined variants and the possibility of a language transfer from the right to the left hemisphere.

Age of Onset↗

Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy.

A wealth of animal and human research has pointed to a significant involvement of the temporal lobes in memory processing, and yet the different functional roles of temporal cortical vs. mesial structures remain unclear. We studied verbal declarative memory, by using a word list paradigm that differentiates among learning (immediate recall), memory (delayed recall), and recognition, in epilepsy patients being considered for surgical resection of the left temporal lobe. Verbal memory was evaluated preoperatively and during the recording of intracranial event related potentials and postoperatively after selective hippocampectomy, temporal cortical lesionectomy, or anterior two-thirds en bloc temporal lobe resection procedures. Preoperative differences in verbal memory performance as a function of differences in underlying neuropathology, concurrent event-related potentials, and specific patterns of postoperative memory impairments lead to converging evidence that verbal declarative memory relies on a synergistic interaction of at least two functionally distinct brain systems. Material-specific data acquisition, or working memory, is mediated by neocortical temporal structures, whereas long-term consolidation/retrieval is particularly mediated by temporomesial structures. In contrast to the left temporal neocortex, the function of the temporomesial system appears to be material nonspecific. Apparently, its preferential involvement in verbal memory is due to its close interaction with overlying neocortical structures that are specialized for language processing.

Adult↗

Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy.

Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.

Adult↗

Relational verbal memory processing in patients with temporal lobe epilepsy.

Patients with left temporal lobe epilepsy (LTLE) have been shown to demonstrate impaired categorization in semantic memory tasks leaving open the question whether this is due to problems with active categorization or to problems with consolidation/retrieval of relations. 35 patients with left or right temporal lobe epilepsy (LTLE, RTLE) and 20 healthy controls performed three verbal learning and memory tests differing in the relational distance between the items to be learned (unrelated, low associative, high associative). In order to separate the memory component in relational memory processing, we avoided problems in active categorization and perception of semantic relations by presenting category members already clustered in the order of category membership, and by checking whether the patients had actually noticed the categories. In controls and in patients with RTLE, both semantic conditions significantly improved the test performance. LTLE-patients showed the worst test performance independent of the test condition. Their performance improved under the high associative condition, but they did not at all profit from the low associative condition. Although the semantic tasks had no demand on active clustering and although all LTLE-patients noticed the relational properties very well, they could not make use of the offered clusters. They demonstrated significantly more "item specific" than "relational" encoding than the other groups. This was pronounced in the low associative condition but became evident also in the high associative condition. In contrast to the other groups, the order in recall (clustering) deteriorated with passing time in LTLE-patients. In conclusion the data provide evidence of impaired semantic relational processing in LTLE. The impairment depends on the relational properties of the material to be learned, in that it increases with the relational distance between the memory contents. Because the tasks did not demand active clustering, we can attribute this impairment to deficits in relational encoding/retrieval which would be consistent with current opinions of the role of temporolimbic structures in relational memory processing.

Adult↗

Neuronal complexity loss in temporal lobe epilepsy: effects of carbamazepine on the dynamics of the epileptogenic focus.

Analysis methods derived from the theory of non-linear dynamics have been shown to provide new information about the complex spatio-temporal behaviour of neuronal networks involved in temporal lobe epilepsy. To test whether day to day alterations in neuronal complexity are influenced by changes in serum level of carbamazepine (CBZ), a moving-window correlation dimension analysis was applied to electrocorticographic and stereoelectroencephalographic recordings of 10 patients with unilateral temporal lobe epilepsy. Data sets (n = 78) were obtained from interictal states at subsequent days during the presurgical evaluation with strongly variant CBZ serum levels. The so-called neuronal complexity loss L* was used to quantify the change of dimensionality in brain electrical activity recorded under different levels of medication. We found a significant inverse relationship between L* and CBZ serum level spatially restricted to the primary epileptogenic area. This finding can be assumed to reflect the mechanism of action of CBZ attributed to an inhibition of sustained high-frequency firing of bursting neurons.

Adult↗