PubMed Health⌕ Search

Biomedical subjects

C E Elger

Publications and source records attributed to C E Elger.

At least 163 records · Page 9Linked to original sources
PubMed1999

Sex differences in material-specific cognitive functions related to language dominance: an intracarotid amobarbital study in left temporal lobe epilepsy.

Population-based studies of material-specific cognitive functions yield evidence of sex differences: women are superior on verbal tasks whereas men are superior on figural and visuo-spatial tasks. Although there is still no direct evidence, these sex differences have been assumed to be related to a different cerebral organisation of language and nonlanguage functions, i.e. language in women is suggested to be more bilaterally organised than in men. We investigated this issue with respect to verbal/nonverbal memory functions in 42 men and 43 women with left temporal lobe epilepsies who all underwent intracarotid amobarbital testing for language dominance. The results indicate that atypical language dominance is not significantly more frequent in women than in men (44% vs 33%). Atypical dominance was related to an onset of epilepsy before puberty and appeared to be a consequence of the left hemisphere pathology rather than being naturally predisposed. Furthermore, women indeed showed the expected advantage with respect to verbal memory, and men showed an advantage in figural memory. With consideration of language dominance, however, the sex difference in verbal memory was observed particularly with atypical dominance, whereas the sex difference in figural memory was observed with left dominance.

Journal Article↗
PubMed1999

5'-Nucleotidase activity indicates sites of synaptic plasticity and reactive synaptogenesis in the human brain.

The localization and morphological assessment of plastic or newly formed synapses in the human brain remains difficult due to the lack of specific markers. The ectoenzyme 5'-nucleotidase may represent a useful marker of these structures, since in adult rodents synaptic 5'-nucleotidase activity is restricted to sites of spontaneous synaptic turnover and induced reactive synaptogenesis. However, it is unclear to what extent synaptic 5'-nucleotidase activity occurs in the normal human brain, and whether reactive synaptogenesis, as seen e.g. in temporal lobe epilepsy (TLE), is associated with this ectoenzyme. Therefore, we have investigated the histochemical distribution of 5'-nucleotidase in hippocampal control specimens (n = 3) and in the hippocampus of TLE patients (n = 13). In controls, 5'-nucleotidase activity was present in the dentate gyrus molecular layer (DG-ML) and the mossy fiber termination field within the CA4 and CA3 subfields. Compared with controls, TLE specimens revealed markedly increased 5'-nucleotidase labeling in the DG-ML, implying TLE-associated reactive synaptogenesis in this hippocampal region. In contrast to GAP-43, synaptophysin, and dynorphin A, synaptic 5'-nucleotidase activity may serve as a potential specific indicator of plastic synapses or newly formed terminals in the human brain and prove useful for the study of diseases involving aberrant sprouting or altered synaptic plasticity.

5'-Nucleotidase↗
PubMed1999

Visual and automatic investigation of epileptiform spikes in intracranial EEG recordings.

PURPOSE: Performance of automatic spike-detection algorithms and interrater reliability of human EEG reviewers were investigated previously by using scalp EEG recordings. However, it is not known, whether the findings of these studies hold for intracranial recordings. To address this question, we analyzed spike detection in intracranial recordings by two human reviewers and three automatic systems covering major lines in the development of automatic spike-detection systems. METHODS: Intracranial recordings from subdural and intrahippocampal depth electrode contacts in seven patients were analyzed by two reviewers and three spike-detection systems: (a) The rule-based system by Gotman, (b) a two-stage system consisting of a linear predictor and a second rule-based stage, and (c) a system using wavelet coefficients of the intracranial EEG data. RESULTS: Agreement between the two human reviewers with respect to spike identification was <50%. The automatic systems achieved agreements of 24% (Gotman), 26% (wavelet detector), and 32% (two-stage system) with the individual human reviewers. In spite of the small proportion of agreements, the same anatomic regions were identified by human and automatic EEG analysis as generators for the majority of spikes. CONCLUSIONS: The poor agreement between the human EEG reviewers suggests that the definition of spikes and spike-like episodes in intracranial electrodes is far from unequivocal. Nevertheless, localizing information is highly consistent by either visual or automatic spike detection, independent of the algorithm used for automatic spike detection.

Adult↗
PubMed1999

Prediction of postoperative seizure control by hippocampal event-related potentials.

PURPOSE: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control. METHODS: We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after temporal lobe surgery. RESULTS: Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of postoperative seizure control in 94% of all patients. CONCLUSIONS: Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral epileptogenicity.

Adolescent↗
PubMed1999

Carbamazepine effects on Na+ currents in human dentate granule cells from epileptogenic tissue.

PURPOSE: Carbamazepine (CBZ) is a well-established drug in the therapy of temporal lobe epilepsy (TLE). The anticonvulsant action of CBZ has been explained mainly by use-dependent effects on voltage-dependent Na+ channels in various nonhuman cell type. However, it is unclear whether Na+ currents in neurons within the focal epileptogenic area of patients with medically intractable TLE show similar characteristics. METHODS: Therefore we used the whole-cell patch-clamp technique to investigate the effects of CBZ on voltage-dependent Na+ currents in 23 acutely isolated dentate granule cells (DGCs) from the resected hippocampus of eight patients with medically intractable TLE. RESULTS: As in findings in animal preparations, CBZ significantly reduced the amplitude of the Na+ current and significantly shifted the current-voltage dependence of the steady-state inactivation in the hyperpolarizing direction. In contrast, the rapid component of the recovery from inactivation of the Na+ currents was not affected by CBZ. In addition, the reduction of the Na+ current amplitude observed during repetitive stimulation with depolarizing pulses was not significantly altered by CBZ. CONCLUSIONS: In summary, CBZ strongly affects the voltage-dependent steady-state inactivation, with no effects on the removal of inactivation in Na+ currents of human DGCs. In spite of the lack of suitable control material, the CBZ insensitivity of the removal of inactivation may be an interesting concept to explain the medically intractable TLE in these patients.

Action Potentials↗
PubMed1999

Increased high-density lipoprotein cholesterol in patients with epilepsy treated with carbamazepine: a gender-related study.

PURPOSE: Long-term treatment with carbamazepine (CBZ) may alter serum lipoprotein concentrations. Gender-related examinations, however, are rare and inconsistent in their results. METHODS: To examine possible sex differences, serum lipoproteins were analyzed in 127 clinic outpatients (56 women and 71 men) with epilepsies with focal or secondarily generalized tonic-clonic seizures (or both) treated with a CBZ monotherapy. Results were compared with a control group of 177 blood donors (67 women and 110 men) matched for age and weight. RESULTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were higher in both male and female patients treated with CBZ compared with controls. The known sex difference in serum lipoprotein concentrations (i.e., higher LDL cholesterol and triglycerides but lower HDL cholesterol in men) was confirmed in controls and patients treated with CBZ, with the exception of LDL cholesterol. The HDL as well as the LDL differences were significantly more pronounced in women treated with CBZ than in men when compared with their controls. These results were independent of the dose of CBZ and plasma concentrations. Lathosterol, a cholesterol precursor, and its ratio to cholesterol, an indicator of cholesterol synthesis, were not different, when compared between gender and different HDL groups. CONCLUSIONS: The observed increase in HDL cholesterol in patients with CBZ, especially in women, might correlate with the previously reported diminished rate of death from coronary heart disease in patients with epilepsy as HDL exerts an antiatherogenic effect.

Adult↗
PubMed1999

Options after the first antiepileptic drug has failed.

Long-term antiepileptic drug (AED) treatment is the standard therapy for epilepsies. In about 60% of patients, the first AED tried usually leads to seizure control. After failure of the first AED, it is important to achieve seizure control rapidly and without side effects. Combining the first drug with an add-on drug appears to be more effective than a second monotherapy. However, no scientifically based data are available that favor any particular drug combination. Along with pharmacokinetic considerations, clinical experience is an important determinant in choosing a second AED for use as an add-on. The time needed to introduce a particular AED is a further consideration. The simultaneous introduction of two add-on drugs, one requiring slow titration and one permitting rapid introduction, may be a useful strategy. If the quickly introduced drug is effective as an add-on, introduction of a slowly titrated second add-on can be obviated. If the quickly introduced drug reduces seizure frequency, the patient's quality of life is improved during titration of the second add-on. If the second, slowly titrated drug is more effective than the quickly introduced one, the less-effective drug can be withdrawn. This strategy also allows a direct comparison between two add-on drugs at the same time.

Acetates↗
PubMed1999

Pre- and postoperative neuropsychological profiles in children and adolescents with temporal lobe epilepsy.

PURPOSE: To evaluate the neuropsychological performance of children before and after temporal lobe resection (TLR). METHODS: Memory, attention, language, and visuoconstructive abilities were examined in 20 children (age 10-16 years) before, and 3 and 12 months after TLR (right, n = 10; left, n = 10; two-thirds anterior resection, n = 16; amygdalohippocampectomy, n = 4). Preoperative performance was compared with data of 30 age-matched healthy children; changes in performance after surgery were determined by repeated-measurement multivariate analysis of variance (MANOVA) and by use of reliable change indices (RCI). RESULTS: Preoperatively, no differences were observed between patients and controls in verbal and figural memory performance. Children with temporal lobe epilepsy (TLE), however, and particularly those with a left temporal focus, showed significantly reduced language performance. Repeated-measurement statistics indicated that memory performance did not change after surgery, whereas language performance and attention significantly improved 3 months and 1 year after surgery, respectively. Individual evaluations of memory showed gains in five children and deterioration in four children. Poor seizure control appeared the decisive variable characterizing children with losses in memory. CONCLUSIONS: Compared with adults, pre- and postoperative memory data suggest less pronounced hemispheric differences in school-age children with TLE. The results raise the possibility that children have a lower risk of memory deterioration after TLR, which may be due to their larger potential for cerebral plasticity.

Adolescent↗
PubMed1999

Surgical outcome in a group of low-IQ patients with focal epilepsy.

PURPOSE: Because a low IQ score indicates global brain damage, several authors consider it a contraindication for resective epilepsy surgery. This study reports the postoperative results of a small group of subaverage-intelligence patients with epilepsy who underwent focal resections. METHODS: We report on 16 patients who underwent focal resections (no callosotomy or hemispherectomy). All had IQ's <85 and were >13 years of age at the time of surgery. Low IQ was psychometrically assessed (mean IQ = 70) and confirmed by the patients' educational/occupational status. Clinical characteristics, findings from the preoperative workup, and the surgical treatment are described in detail. Postoperative outcome was evaluated with respect to seizure relief and cognitive/ socioeconomic development. RESULTS: Three months after surgery, 14 (87%) of 16 patients were completely seizure free, and nine (64%) of 14 were seizure free at the 1-year follow-up. Patients' cognitive abilities and socioeconomic status were mostly unchanged and in some cases improved. Seizure outcome was not related to IQ level, and there was no evidence of multiple epileptic foci in the patients with continued seizures. CONCLUSIONS: A low IQ level does not entail the presence of extended epileptogenic regions or multiple epileptic foci. Seizure-relief rates in our group concurred with the rates in patients of average intelligence, and the cognitive/socioeconomic outcome was favorable. We conclude that focal surgery in intellectually impaired patients can be recommended if the preoperative diagnostics confirm a circumscribed seizure onset.

Adolescent↗
PubMed1999

Gabapentin add-on treatment: how many patients become seizure-free? An open-label multicenter study.

The aim of the study was to find out the percentage of patients with localization-related epilepsy achieving complete seizure control with gabapentin (GBP) add-on therapy. Patients under anti-epileptic drug monotherapy during 8 weeks baseline (BSL) with 6 or more seizures were treated with GBP for 26 weeks up to 2400 mg/day. Patients obtaining complete seizure control of all seizures or any partial seizure type during the last 8 weeks were calculated. Seizure frequency was compared between BSL and last 8 weeks. In all, 110 patients were enrolled (92 completed, 18 discontinued): mean age of the completers: 37.6 years (range 16-72), median seizure frequency per 28 days at BSL: 6.8 (2.5-24.5), mean duration of epilepsy: 17.6 years (0.2-51.4), mean duration with GBP for completers: 182.8 days (144-187). Complete seizure control of all seizures was achieved in 8.7% of patients (simple partial seizures: 13.3%, complex partial seizures 24.3%, secondarily generalized seizures: 61.5%): 38% of the patients became seizure-free in at least 1 seizure-type; 40% experienced adverse events. Assessment for quality of life (QoL) and trough plasma levels of GBP did not correlate with the good effect of GBP.

Acetates↗
PubMed1999

Ca(2+)-dependent inactivation of high-threshold Ca(2+) currents in hippocampal granule cells of patients with chronic temporal lobe epilepsy.

Intracellular Ca(2+) represents an important trigger for various second-messenger mediated effects. Therefore a stringent control of the intracellular Ca(2+) concentration is necessary to avoid excessive activation of Ca(2+)-dependent processes. Ca(2+)-dependent inactivation of voltage-dependent calcium currents (VCCs) represents an important negative feedback mechanism to limit the influx of Ca(2+) that has been shown to be altered in the kindling model of epilepsy. We therefore investigated the Ca(2+)-dependent inactivation of high-threshold VCCs in dentate granule cells (DGCs) isolated from the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE) using the patch-clamp method. Ca(2+) currents showed pronounced time-dependent inactivation when no extrinsic Ca(2+) buffer was present in the patch pipette. In addition, in double-pulse experiments, Ca(2+) entry during conditioning prepulses caused a reduction of VCC amplitudes elicited during a subsequent test pulse. Recovery from Ca(2+)-dependent inactivation was slow and only complete after 1 s. Ca(2+)-dependent inactivation could be blocked either by using Ba(2+) as a charge carrier or by including bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) or EGTA in the intracellular solution. The influence of the cytoskeleton on Ca(2+)-dependent inactivation was investigated with agents that stabilize and destabilize microfilaments or microtubules, respectively. From these experiments, we conclude that Ca(2+)-dependent inactivation in human DGCs involves Ca(2+)-dependent destabilization of both microfilaments and microtubules. In addition, the microtubule-dependent pathway is modulated by the intracellular concentration of GTP, with lower concentrations of guanosine triphosphate (GTP) causing increased Ca(2+)-dependent inactivation. Under low-GTP conditions, the amount of Ca(2+)-dependent inactivation was similar to that observed in the kindling model. In summary, Ca(2+)-dependent inactivation was present in patients with TLE and Ammon's horn sclerosis (AHS) and is mediated by the cytoskeleton similar to rat pyramidal neurons. The similarity to the kindling model of epilepsy may suggest the possibility of altered Ca(2+)-dependent inactivation in patients with AHS.

Adult↗
PubMed1999

Clinical relevance of amygdala sclerosis in temporal lobe epilepsy.

OBJECT: The goal of this study was to define the incidence and clinical significance of amygdala sclerosis (AS) in patients with temporal lobe epilepsy (TLE). METHODS: Surgical specimens of the lateral amygdaloid nucleus and the hippocampus excised from 71 patients who were treated for medically intractable TLE were quantitatively evaluated using a computer-assisted image-analysis system and compared with 10 normal autopsy specimens. Densities of neurons and reactive astrocytes in the patients with TLE were correlated with clinical, neuropsychological, and depth-electroencephalography data. The neuron counts of the lateral amygdaloid nucleus did not correlate with various presumed etiological factors of TLE including hereditary seizures, birth complications, febrile convulsions, traumatic brain injury, infections, seizure semiology, and epileptological outcome. However, patient age at surgery was significantly higher (mean difference 10 years) when AS was present, as compared with patients without AS (p < 0.01). Seizure origin, as determined by using amygdalohippocampal depth electrodes, did not correlate with the presence or absence of AS. Neuropsychologically, there was a significant correlation between the neuronal densities of the lateral amygdaloid nucleus and both preoperative visual recognition and postoperative deterioration of short-term verbal memory performance (p < 0.05). CONCLUSIONS: Except for the relatively long history of epilepsy, the presence of AS is not associated with specific clinical or electrocorticographic features of mesial TLE. However, patients without AS are particularly at risk for deterioration of short-term verbal memory following amygdalohippocampectomy.

Adolescent↗
PubMed1999

Is it possible to anticipate seizure onset by non-linear analysis of intracerebral EEG in human partial epilepsies?

Detection of electrophysiological features preceding and indicative of imminent seizures in patients with epilepsy would be a major breakthrough with immense scientific and clinical implications. The definition of a "pre-ictal state" several minutes prior to seizure onset would open a new time window for studying mechanisms of seizure generation as well as for possible therapeutic interventions. In this review we present recent findings from nonlinear time series analysis of intracranially recorded EEG that may allow to forecast seizure onset in patients with partial epilepsy.

Animals↗
PubMed1998

Limbic ERPs predict verbal memory after left-sided hippocampectomy.

Surgical removal of the dominant medial temporal lobe regions runs a considerable risk of verbal memory deficits which may be compensated for postoperatively by corresponding regions in the non-dominant medial temporal lobe. We examined this possibility by recording event-related potentials (ERPs) to words from the medial temporal lobes of patients with left-sided temporal lobe epilepsy (TLE) undergoing presurgical evaluation. N400 amplitudes in the right anterior medial temporal lobe predicted the postoperative verbal recall performance of individual patients with surprising accuracy, indicating that intracranial recordings can be used to quantify the functional capacities of the right hemisphere that can compensate for the verbal memory deficits after loss of medial temporal lobe structures in the left hemisphere.

Adolescent↗
PubMed1998

Microcutting of living brain slices by a pulsed ultrafine water jet which allows simultaneous electrophysiological recordings (micromingotome).

Up to now microsurgical dissections in living nervous tissue (e.g. in slices or cell cultures) are performed either by micro-scalpels or by laser beams. As an alternative technique, a device for cutting with an ultrafine pulsed water jet was developed to allow precise, visually controled dissections in neuronal circuits even during electrophysiological recordings. Water is ejected by pressure (20-30 bar) from patch pipettes with tip diameters of 10-12 microm. By means of a piezo-element the pipette and the water jet are forced to oscillate vertically with a frequency of 200-400 Hz with an adjustable amplitude. These oscillations facilitate the transsection of neuronal connections even in thick slice preparations. Best results were obtained when the tip of the pipette was about 500 microm above the surface of the submerged slice tissue. This micromingotome offers the following advantages: (i) histological studies show that the water jet cleans the cutting surface, thus avoiding debris and its uncontrolable effects on cells underneath; (ii) the arrangement enables ongoing electrophysiological recordings from hippocampal slices during the cutting procedure and thus facilitates studies of the functions of neuronal connections; (iii) the device allows even disconnection in cultured nervous tissue overgrowing polyamid grids with 50 microm wide meshes.

Animals↗
PubMed1998

Electrophysiological characterization of Na+ currents in acutely isolated human hippocampal dentate granule cells.

1. Properties of voltage-dependent Na+ currents were investigated in forty-two dentate granule cells (DGCs) acutely isolated from the resected hippocampus of twenty patients with therapy-refractory temporal lobe epilepsy (TLE) using the whole-cell patch-clamp technique. 2. Depolarizing voltage commands elicited large, rapidly activating and inactivating Na+ currents (140 pS microm-2; 163 mM extracellular Na+) that were reduced in amplitude by lowering the Na+ gradient (43 mM extracellular Na+). At low temperatures (8-12 C), the time course of Na+ currents slowed and could be well described by the model of Hodgkin & Huxley. 3. Na+ currents were reversibly blocked by tetrodotoxin (TTX) and saxitoxin (STX) with a half-maximal block of 4.7 and 2.6 nM, respectively. In order to reduce series resistance errors, the Na+ current was partially blocked by low toxin concentrations (10-15 nM) in the experiments described below. Under these conditions, Na+ currents showed a threshold of activation of about -50 mV, and the voltages of half-maximal activation and inactivation were -29 and -55 mV, respectively. 4. The time course of recovery from inactivation could be described with a double-exponential function (time constants, 3-20 and 60-200 ms). The rapid and slow time constants showed a distinct voltage dependence with maximal values around -55 and -80 mV, respectively. These properties contributed to a reduction of the Na+ currents during repetitive stimulation that was more pronounced with higher stimulation frequencies and also showed a dependence on the holding potential. 5. In summary, the most striking features of DGC Na+ currents were the large current density and the presence of a current component showing a slow recovery from inactivation. Our data provide a basis for comparison with properties of Na+ currents in animal models of epilepsy, and for the study of drug actions in therapy-refractory epilepsy.

Adult↗
PubMed1998

Verbal novelty detection within the human hippocampus proper.

Animal studies and neuropsychological tests of patients with temporal lobe epilepsy have demonstrated the importance of human medial temporal lobes for memory formation. In addition, more recent studies have shown that the human hippocampal region is also involved in novelty detection. However, the exact contribution of the hippocampus proper to these processes is still unknown. To examine further its role we compared event-related potentials recorded within the medial temporal lobes in 29 temporal lobe epilepsy patients with and 21 without hippocampal sclerosis. While in patients with extrahippocampal lesions but without hippocampal sclerosis event-related potentials to first presentations and repetitions of words were reduced on the side of the epileptogenic focus, in patients with hippocampal sclerosis only those to first presentations but not to repetitions were affected. Because sclerosis of the hippocampus proper selectively reduced event-related potentials to new but not old verbal stimuli, it can be concluded that the human hippocampus proper contributes to verbal novelty detection.

Adolescent↗