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C E Elger

Publications and source records attributed to C E Elger.

At least 181 records · Page 10Linked to original sources

Successful verbal encoding into episodic memory engages the posterior hippocampus: a parametrically analyzed functional magnetic resonance imaging study.

The medial temporal lobe (MTL) is essential for episodic memory encoding, as evidenced by memory deficits in patients with MTL damage. However, previous functional neuroimaging studies have either failed to show MTL activation during encoding or they did not differentiate between two MTL related processes: novelty assessment and episodic memory encoding. Furthermore, there is evidence that the MTL can be subdivided into subcomponents serving different memory processes, but the extent of this functional subdivision remains unknown. The aim of the present functional magnetic resonance imaging (fMRI) study was to investigate the role of the MTL in episodic encoding and to determine whether this function might be restricted to anatomical subdivisions of the MTL. Thirteen healthy volunteers performed a word list learning paradigm with free recall after distraction. Functional images acquired during encoding were analyzed separately for each participant by a voxel-wise correlation (Kendall's tau) between the time series of the T2*-signal intensity and the number of subsequently recalled words encoded during each particular scan. Of the 13 participants, 11 showed voxel clusters with statistically significant, positive correlations in the posterior part of the hippocampus. Across participants, an ANOVA on the number of voxels with significant, positive correlations within individually defined volumes of interest confirmed a statistically significant difference in activation for anterior versus posterior regions of the hippocampus. However, no differences between left and right hippocampal activation were revealed. Thus, these findings demonstrate that successful encoding into episodic memory engages neural circuits in the posterior part of the hippocampus.

Adolescent↗

[Asystolic seizures].

Epileptic seizures may alter autonomic functions. This is especially the case with complex focal seizures (of temporal lobe origin) and grand mal. Most frequently, such seizures cause ictal tachycardia, sometimes tachypnea, probably caused by the propagation of epileptic discharges to autonomic cerebral structures. Ictal bradycardia and asystole are rare phenomena. However, they may be life threatening. Their differentiation from primary cardiac arrest is possible by the use of ictal EEG and ECG registration. Postictal serum prolactin measurement does not differentiate syncope from seizure. However, a postictal increase of creatine kinase is only measured after epileptic seizures and not after syncope. Treatment of such epileptic seizures includes an optimization of anticonvulsant drug therapy and the implantation of a cardiac demand stimulator. There is growing evidence that ictal asystole is a cofactor in sudden unexplained death in epileptic patients.

Adult↗

[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin].

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being. Isolated changes of standard laboratory liver parameters are not reliable early indicators. Thus, according to the knowledge of today, prophylactic blood screening cannot predict complications. On the contrary, clinical symptoms are the most relevant indicators of impending complications, eventually supported by laboratory findings. An abrupt withdrawal of valproate and administering carnitin in parallel can interrupt the otherwise fatal course of the complication and induce a subsequent recovery. At a Consensus Conference the current knowledge about early detection and therapy of the valproate-induced serious hepatotoxicity was discussed. The results regarding recommended laboratory screening, as well as diagnostic and therapeutic strategies are reported.

Adolescent↗

Plectin in the human central nervous system: predominant expression at pia/glia and endothelia/glia interfaces.

Plectin is a high molecular weight protein that serves as a versatile cytoskeletal cross-linker molecule. Mutations of the human plectin gene have recently been identified to cause the autosomal recessive disorder epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). A subgroup of EBS-MD patients display signs of a neurodegenerative disorder suggesting that the expression of defective plectin may also interfere with the structural and functional integrity of the human central nervous system. However, the expression pattern of plectin in the human brain is still unknown. We therefore analyzed the immunohistochemical distribution of plectin in normal hippocampal specimens obtained at autopsy and in neocortical and hippocampal tissue of patients who had undergone epilepsy surgery. In general, plectin-immunoreactive cells were identified as capillary endothelia and astrocytes. A striking feature seen in all specimens was the accentuated plectin immunoreactivity of astrocytic end feet abutting on blood vessels and on the pial surface. Furthermore, the analysis of hippocampal tissue of epilepsy patients with Ammon's horn sclerosis (AHS) revealed a strong plectin labeling of reactive astrocytes. The latter finding suggests that the up-regulation of plectin, which parallels the increase of glial fibrillary acidic protein, may be a general feature of reactive astroglia. The predominant expression of plectin at pia/glia and endothelia/glia interfaces in the human brain indicates that plectin may have an integral role in the structural organization of the blood-brain barrier and the leptomeninges.

Animals↗

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs. resections plus multiple subpial transections; MST), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short-term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the 3 month follow-up examination, patients with temporal lobectomy had improved frontal functions, whereas patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure-free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MSTs of the precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favourable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short-term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated with frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adult↗

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs resections plus Multiple Subpial Transections), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the three month follow-up examination, patients with temporal lobectomy had improved frontal functions, while patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MST's of precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favorable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated to frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adolescent↗

Voltage-dependent Ca2+ currents in epilepsy.

Voltage-dependent Ca2+ channels (VCCs) represent one of the main routes of Ca2+ entry into neuronal cells. Changes in intracellular Ca2+ dynamics and homeostasis can cause long-lasting cellular changes via activation of different Ca2+ dependent signalling pathways. We have investigated the properties of VCCs in human hippocampal dentate granule cells (DGCs) using the whole-cell configuration of the patch-clamp method. Classical high-threshold Ca2+ currents were composed mainly of omega-CgTx-sensitive N-type and nifedipine-sensitive L-type currents that were present in similar proportions. In addition, a Ca2+ current component that was sensitive to low concentrations of Ni2+, but not to nifedipine or omega-conotoxin GVIA (omega-CgTx GVIA) was present. This latter component showed a half-maximal inactivation at more hyperpolarized potentials than high-threshold currents and a more rapid time-dependent inactivation. This current was termed T-type Ca2+ current. Current components with similar pharmacological and kinetic characteristics could be elicited in acutely isolated control rat DGCs. The current density of high threshold and T-type Ca2+ components was significantly larger in human DGCs and in the kainate model compared to DGCs isolated from adult control rats. These differences in current density were not accompanied by parallel differences in the voltage-dependence of VCCs. Taken together, these data suggest that an up-regulation of Ca2+ current density may occur in hippocampal epileptogenesis without consistent changes in Ca2+ current properties.

Adult↗

The performance-complaint relationship in patients with epilepsy: a matter of daily demands?

Weak relationships have been reported between subjective complaints of memory deficits and memory performance in neuropsychological tests in patients with temporal lobe epilepsy (TLE). This study investigated whether the individual exposure to cognitive demands in daily life contributes to cancel out the performance-complaint relationship in such a way that cognitive deficits are more likely experienced by patients in 'high demand' than in 'low demand' situations. Neuropsychological performance, subjective complaints and daily demands were assessed in 57 TLE-patients 1 year after a temporal lobe surgery. Data were analyzed using non-parametric statistical techniques. Results indicated surprisingly close relationships between subjective complaints and memory performance in standardized tests. The highest correlations were found for the non-verbal memory test. Cognitive demands did not counteract this result. Contrary to our expectation, lower demands were associated with stronger subjective complaints. Cognitive demands thus appeared not as a modulating factor that weakens the relationship between test deficits and subjective complaints in patients with TLE.

Activities of Daily Living↗

Seizure prediction by non-linear time series analysis of brain electrical activity.

Brain electrical activity of 16 patients with temporal lobe epilepsy, recorded intracranially during seizure-free intervals as well as during transitions to the seizure state, was analysed using methods derived from the theory of non-linear dynamics. Long-lasting and marked changes towards low-dimensional system states were found to occur specifically up to 25 min prior to epileptic seizures and allow to predict the occurrence of individual seizures in time. These findings reflect a continuous increase in the degree of synchronicity, and thus open a window for the study of mechanisms generating seizures in humans. This offers new possibilities for therapeutic interventions.

Adolescent↗

Ecological validity of list-learning tests and self-reported memory in healthy individuals and those with temporal lobe epilepsy.

We evaluated in patients with temporal lobe epilepsy (TLE) and healthy volunteers whether list-learning tests of episodic verbal/figural memory and subjective self-reports reliably indicate "Memory in Reality" (MIR). MIR was assessed by the incidental memory of the neuropsychological test event one week after testing. Subjective Memory was assessed by a questionnaire (SMQ). Patients achieved poorer results than controls in all measures of memory. Correlation and multiple regression analysis indicates that list-learning is highly predictive regarding performance in MIR. MIR predominantly relied on verbal memory in patients and on visual/figural memory in controls. Subjective memory differentiated patients and controls but it correlated to MIR only in subjects with unimpaired memory. In conclusion, the data indicate a high ecological validity of list-learning paradigms and they seriously question the diagnostic value of self-reported memory. They also indicate that incidentally acquired knowledge might be differentially represented in patients with a memory disorder and healthy persons.

Adult↗

Altered patterns of Ca2+/calmodulin-dependent protein kinase II and calcineurin immunoreactivity in the hippocampus of patients with temporal lobe epilepsy.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin represent neuronal Ca2+-dependent enzymes which dynamically modify several common substrates in the mammalian brain via phosphorylation/dephosphorylation cycles. Studies in animal models indicate that altered expression and activity of these enzymes may be involved in epilepsy. We have analyzed their immunohistochemical distribution in hippocampi of 28 temporal lobe epilepsy (TLE) patients and 13 controls. TLE specimens were classified as Ammon's horn sclerosis (AHS) or focal lesions without alteration of hippocampal cytoarchitecture. Compared to control and lesion-associated TLE specimens, striking changes in the distribution pattern of both enzymes were found in the dentate gyrus (DG) of AHS specimens: Whereas CaMKII labeling was significantly increased in the granule cell somata and their proximal dendrites, calcineurin immunoreactivity was significantly reduced in the granule cell somata. Furthermore, calcineurin staining in controls showed high levels in the inner molecular layer with a sharp demarcation towards the outer molecular layer. In AHS, calcineurin staining was reduced in the inner molecular layer, with partial loss of this demarcation. These findings raise the possibility, that an up-regulation of CaMKII with a concomitant down-regulation of calcineurin in the DG of AHS specimens may cause a pathogenetically relevant imbalance of neuronal Ca2+/calmodulin-dependent phosphorylation/dephosphorylation systems.

Adult↗

Depth electrode implantation in the length axis of the hippocampus for the presurgical evaluation of medial temporal lobe epilepsy: a computed tomography-based stereotactic insertion technique and its accuracy.

OBJECTIVE: An individualized computed tomography-based stereotactic technique for the longitudinal insertion of intrahippocampal electrodes is presented and its accuracy described. METHODS: The technique makes use of one well reproducible target in the hippocampal head and of the approximate inclination of the anteroposterior length axis of the hippocampus, for which the orbital floor is taken as an auxiliary landmark. It was used in 141 patients with medically intractable complex partial seizures. In 106 patients, magnetic resonance imaging (MRI) was available for assessment of implantation accuracy. Each of the 212 electrodes was plotted on topographic drawings and its goodness of fit rated. RESULTS: Whereas hippocampal head and body were hit by 97 and 96% of the electrodes, respectively, the amygdala was hit by only 75% of the electrodes and mainly at its basal margin. For 93% of the electrodes, the inclination in a sagittal plane corresponded exactly to that of the hippocampus. The implantation morbidity amounted to 5.7%, whereas permanent neurological deficit occurred in one (0.7%) of the 141 patients. CONCLUSION: This computed tomography-based protocol proved to be reliable and hence can be considered as an adequate alternative to MRI-based stereotactic implantation if MRI is not available or if a single MRI-based stereotactic set-up is unreliable because of intolerable distortions.

Amygdala↗

Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication.

PURPOSE: To evaluate the changes in serum sex hormones of gonadal or adrenal origin, the gonadotropic hormones, and sex hormone-binding globulin (SHBG) in men and women with chronic temporal lobe epilepsy (TLE), who are undergoing monotherapy with carbamazepine or receiving carbamazepine in combination with other anticonvulsant drugs. METHODS: Gonadal hormones (estradiol, testosterone, free testosterone, and inhibin B), adrenal hormones [cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17alpha-hydroxyprogesterone], and gonadotropic hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) were measured in 22 women and 26 men with TLE. The study also measured prolactin; human growth hormone and its major mediator, insulin-like growth factor-I; thyroid hormones (free thyroxine and free triiodothyronine); thyroid-stimulating hormone (TSH); and SHBG. The results were compared with those obtained from 60 healthy women and 106 healthy men. RESULTS: In the female patients, TSH, DHEAS, follicular-phase LH, and luteal-phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17alpha-hydroxyprogesterone, free testosterone, inhibin B, and the testosterone/LH ratio were significantly lower than in the control group, with LH, FSH, and SHBG significantly higher. Increased FSH in 31% of the men indicates an impairment of spermatogenesis; lowered inhibin B in 12% indicates an impaired Sertoli's cell function; and the decreased testosterone/LH ratio in 50% indicates an impaired Leydig's cell function. CONCLUSIONS: The case patients had endocrine disorders, mainly concerning the gonadotropic and gonadal functions in both sexes; the adrenal function, with lowered DHEAS levels in both sexes; and lowered 17alpha-hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.

Adult↗

Effects of phenytoin, carbamazepine, and gabapentin on calcium channels in hippocampal granule cells from patients with temporal lobe epilepsy.

PURPOSE: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current modulation has been proposed to contribute to the antiepileptic activity of these drugs. The purpose of this study was to determine the effects of these anticonvulsants on voltage-dependent calcium channels in pathologically altered neurons from patients with chronic temporal lobe epilepsy. METHODS: Acutely isolated human hippocampal granule cells were examined by using the whole-cell configuration of the patch-clamp technique. RESULTS: PHT and CBZ produced a reversible, concentration-dependent inhibition of high-voltage-activated (HVA) Ca2+ currents without affecting voltage-dependent activation. The concentration-response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%, respectively, with half-maximal inhibition being obtained at 89 and 244 microM, respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ showed a reduction of HVA currents of 16% at a therapeutic whole-brain concentration of 80 microM. In contrast to CBZ, PHT produced a small hyperpolarizing shift in the voltage dependence of steady-state inactivation. PHT, 80 microM, shifted the potential of half-maximal inactivation by -3.1 +/- 0.5 mV (p < 0.05). GBP, which was recently found to bind to the alpha2delta subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances. CONCLUSIONS: These results suggest that, in contrast to GBP and CBZ, modulation of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT in human hippocampal granule cells.

Acetates↗

Functional plasticity after left anterior temporal lobectomy: reconstitution and compensation of verbal memory functions.

PURPOSE: This study investigated the functional plasticity of the brain to reconstitute and compensate for verbal memory functions after epilepsy surgery of left temporocortical and temporomesial structures. We hypothesized that memory outcome would be best when surgery is performed within the period of cerebral plasticity, and that the outcome should be worst when fluid intelligence starts to decrease with physiologic aging. We also raised the question of different plasticity and compensation mechanisms for temporomesial and temporocortical memory functions. METHODS: We evaluated preoperative and 1-year-postoperative memory data and other verbal functions in 104 patients with epilepsy, who underwent a standard left anterior temporal lobe resection. We used memory measures that had been previously shown to be most selective for mesial and lateral functions, respectively. Determinants of postoperative memory outcome were evaluated by multiple regression analysis. Group statistics were calculated on the basis of the periods that are usually assumed to be significant for plasticity and behavioral compensation. Individual postoperative changes in memory functions were evaluated on the basis of test-retest data obtained in a group of 100 nonsurgical patients with localization-related epilepsies (mean retest interval >12 months). RESULTS: Only changes in cortically represented learning and data acquisition were related to age, plasticity, and capacities for behavioral compensation. No patient in the youngest group (younger than 15 years), 33% of patients who had surgery between the ages of 15 and 30 years, and 61% of the patients undergoing surgery older than age 30 years had significant deterioration in verbal learning. In contrast, postoperative changes in temporomesial consolidation/retrieval processes were independent of age at the time of surgery, plasticity, and capacities for behavioral compensation. CONCLUSIONS: Our data indicate different time windows for the reconstitution and compensation of mesial and cortical aspects of memory. Whereas the reconstitution of and compensation for cortical functions appear restricted by decreasing plasticity and physiological aging, mesial functions seem to be reconstituted by contralateral mesial structures over a much longer period. Concerning drug-resistant localization-related epilepsies, our results justify early consideration of surgery, especially when cortical structures are affected.

Adolescent↗

Neuronal complexity loss in interictal EEG recorded with foramen ovale electrodes predicts side of primary epileptogenic area in temporal lobe epilepsy: a replication study.

PURPOSE: To investigate whether a correct lateralization of the primary epileptogenic area by means of neuronal complexity loss analysis can be obtained from interictal EEG recordings using semi-invasive foramen ovale electrodes. In a previous study with recordings from intrahippocampal depth and subdural strip electrodes it was shown that the dynamics of the primary epileptogenic area can be characterized by an increased loss of neuronal complexity in patients with unilateral temporal lobe epilepsy (TLE). METHODS: Neuronal complexity loss analysis was applied. This analysis method is derived from the theory of nonlinear dynamics and provides a topological diagnosis even in cases where no actual seizure activity can be recorded. We examined interictal EEG recorded intracranially from multipolar foramen ovale electrodes in 19 patients with unilateral TLE undergoing presurgical evaluation. RESULTS: The primary epileptogenic area was correctly lateralized in 16 of the 19 investigated patients. The misclassification of the side of seizure onset in three patients might be attributed to the larger distance between the foramen ovale electrodes and the mesial temporal structures as compared to intrahippocampal depth electrodes. CONCLUSIONS: Our results confirm the previous findings and provide further evidence for the usefulness of nonlinear time-series analysis for the characterization of the spatiotemporal dynamics of the primary epileptogenic area in mesial temporal lobe epilepsy.

Adult↗