Search PubMed⌕ Search

Biomedical subjects

Christian E Elger

Publications and source records attributed to Christian E Elger.

At least 19 recordsLinked to original sources
PubMed2003

Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.

Adult↗
PubMed2003

Neuronal substrates of sensory gating within the human brain.

BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the second of two paired clicks but not in schizophrenia patients. To identify its neural correlates, we recorded electrical traces of sensory gating directly from the human hippocampus and neocortex. METHODS: Intracranial evoked potentials were recorded using hippocampal depth electrodes and subdural strip and grid electrodes in 32 epilepsy patients undergoing invasive presurgical evaluation. RESULTS: We found evidence of sensory gating only in the hippocampus, the temporo-parietal region (Brodmann's areas 22 and 2), and the prefrontal cortex (Brodmann's areas 6 and 24); however, whereas neocortical habituating responses to paired clicks were peaking around 50 msec, responses within the hippocampus proper had a latency of about 250 msec. CONCLUSIONS: Consistent with data from animal studies, our findings show that the hippocampus proper contributes to sensory gating, albeit during a time window following neocortical habituation processes. Thus, sensory gating may be a multistep process, with an early phase subserved by the temporo-parietal and prefrontal cortex and a later phase mediated by the hippocampus.

Adult↗
PubMed2003

Heterotopias, cortical dysplasias and glioneural tumors participate in cognitive processing in patients with temporal lobe epilepsy.

Focal brain lesions such as cortical dysplasia and glioneural tumors generate epileptic activity and thus may be synaptically connected with normal cortex. To test this hypothesis, we compared event-related potentials recorded directly from the medial temporal lobe (MTL) and a dysplastic lesion in eight patients with intractable temporal lobe epilepsy. The P3 component, related to visual target detection, showed different peak latencies in four patients and a larger intralesional amplitude compared to established anterior-MTL-generators in two patients. Semantic processing was identified by the N400 component and showed a different latency in four patients and larger intralesional amplitudes in two patients. These results are compatible with the hypothesis that cortical lesions interact with synaptic pathways related to cognitive functions such as visual target detection, and verbal processing.

Adult↗
PubMed2003

Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies.

Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a gene associated with the four most common IGE subtypes: childhood and juvenile absence epilepsy (CAE and JAE), juvenile myoclonic epilepsy (JME), and epilepsy with grand mal seizures on awakening (EGMA; ref. 8). We identified three different heterozygous mutations in the chloride-channel gene CLCN2 in three unrelated families with IGE. These mutations result in (i) a premature stop codon (M200fsX231), (ii) an atypical splicing (del74-117) and (iii) a single amino-acid substitution (G715E). All mutations produce functional alterations that provide distinct explanations for their pathogenic phenotypes. M200fsX231 and del74-117 cause a loss of function of ClC-2 channels and are expected to lower the transmembrane chloride gradient essential for GABAergic inhibition. G715E alters voltage-dependent gating, which may cause membrane depolarization and hyperexcitability.

Adolescent↗
PubMed2003

Automated detection of a preseizure state based on a decrease in synchronization in intracranial electroencephalogram recordings from epilepsy patients.

The question whether information extracted from the electroencephalogram (EEG) of epilepsy patients can be used for the prediction of seizures has recently attracted much attention. Several studies have reported evidence for the existence of a preseizure state that can be detected using different measures derived from the theory of dynamical systems. Most of these studies, however, have neglected to sufficiently investigate the specificity of the observed effects or suffer from other methodological shortcomings. In this paper we present an automated technique for the detection of a preseizure state from EEG recordings using two different measures for synchronization between recording sites, namely, the mean phase coherence as a measure for phase synchronization and the maximum linear cross correlation as a measure for lag synchronization. Based on the observation of characteristic drops in synchronization prior to seizure onset, we used this phenomenon for the characterization of a preseizure state and its distinction from the remaining seizure-free interval. After optimizing our technique on a group of 10 patients with temporal lobe epilepsy we obtained a successful detection of a preseizure state prior to 12 out of 14 analyzed seizures for both measures at a very high specificity as tested on recordings from the seizure-free interval. After checking for in-sample overtraining via cross validation, we applied a surrogate test to validate the observed predictability. Based on our results, we discuss the differences of the two synchronization measures in terms of the dynamics underlying seizure generation in focal epilepsies.

Journal Article↗
PubMed2003

Testing the null hypothesis of the nonexistence of a preseizure state.

A rapidly growing number of studies deals with the prediction of epileptic seizures. For this purpose, various techniques derived from linear and nonlinear time series analysis have been applied to the electroencephalogram of epilepsy patients. In none of these works, however, the performance of the seizure prediction statistics is tested against a null hypothesis, an otherwise ubiquitous concept in science. In consequence, the evaluation of the reported performance values is problematic. Here, we propose the technique of seizure time surrogates based on a Monte Carlo simulation to remedy this deficit.

Biophysical Phenomena↗
PubMed2003

A novel mechanism underlying drug resistance in chronic epilepsy.

The development of resistance to pharmacological treatment is common to many human diseases. In chronic epilepsy, many patients develop resistance to anticonvulsant drug treatment during the course of their disease, with the underlying mechanisms remaining unclear. We have studied cellular mechanisms underlying drug resistance in resected hippocampal tissue from patients with temporal lobe epilepsy by comparing two groups of patients, the first displaying a clinical response to the anticonvulsant carbamazepine and a second group with therapy-resistant seizures. Using patch-clamp recordings, we show that the mechanism of action of carbamazepine, use-dependent block of voltage-dependent Na(+) channels, is completely lost in carbamazepine-resistant patients. Likewise, seizure activity elicited in human hippocampal slices is insensitive to carbamazepine. In marked contrast, carbamazepine-induced use-dependent block of Na(+) channels and blocked seizure activity in vitro in patients clinically responsive to this drug. Consistent with these results in human patients, we also show that use-dependent block of Na(+) channels by carbamazepine is absent in chronic experimental epilepsy. Taken together, these data suggest that a loss of Na(+) channel drug sensitivity may constitute a novel mechanism underlying the development of drug-resistant epilepsy.

Adult↗
PubMed2003

Is synchronized neuronal gamma activity relevant for selective attention?

Today, much evidence exists that sensory feature binding is accomplished by phase synchronization of induced neuronal gamma activity (30-80 Hz). Recent studies furthermore suggest that phase synchronization of induced gamma activity may represent a general mechanism enabling transient associations of neural assemblies and thus may play a central role in cortical information processing. Here, we describe findings indicating that synchronized gamma activity is moreover specifically involved in selective attention. While feature binding appears to depend primarily on induced gamma synchronization, attentional processes seem to involve both induced and evoked gamma oscillations. Yet it is still an open question, as to which top-down and bottom-up processes are associated with attentional modulation of gamma activity. A possible mechanism to project influences from attentional control structures to areas concerned with stimulus representation and vice versa, may be neuronal synchronization and the resulting firing rate changes of coincidence-detecting neurons in target areas.

Animals↗
PubMed2003

More than synchrony: EEG chaoticity may be necessary for conscious brain functioning.

Transient phase synchronization of EEG oscillations was reported to be essential for conscious brain activity. However, it has been argued that EEG synchrony is not the only necessary factor, but at least must be accompanied by a sufficient complexity of brain dynamics. Here, we propose that, besides complexity, EEG chaoticity may be another necessary condition for conscious brain functioning.

Brain↗
PubMed2003

Epileptic seizures are preceded by a decrease in synchronization.

The exact mechanisms leading to the occurrence of epileptic seizures in humans are still poorly understood. It is widely accepted, however, that the process of seizure generation is closely associated with an abnormal synchronization of neurons. In order to investigate this process, we here measure phase synchronization between different regions of the brain using intracranial EEG recordings. Based on our preliminary finding of a preictal drop in synchronization, we investigate whether this phenomenon can be used as a sensitive and specific criterion to characterize a preseizure state and to distinguish this state from the interictal interval. Applying an automated technique for detecting decreased synchronization to EEG recordings from a group of 18 patients with focal epilepsy comprising a total of 117 h, we observe a characteristic decrease in synchronization prior to 26 out of 32 analyzed seizures at a very high specificity as tested on interictal recordings. The duration of this preictal state is found to range from several minutes up to a few hours. Investigation of the spatial distribution of preictal desynchronization indicates that the process of seizure generation in focal epilepsy is not necessarily confined to the focus itself but may instead involve more distant, even contralateral areas of the brain. Finally, we demonstrate an intrahemispheric asymmetry in the spatial dynamics of preictal desynchronization that is found in the majority of seizures and appears to be an immanent part of the mechanisms underlying the initiation of seizures in humans.

Adult↗
PubMed2003

Allopregnanolone serum levels and expression of 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase isoforms in hippocampal and temporal cortex of patients with epilepsy.

In the human central nervous system, progesterone is rapidly metabolised to 5 alpha-dihydroprogesterone which subsequently is further reduced to allopregnanolone (AP). These conversions are catalysed by 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD). Although different isoforms of both enzymes have been identified in the brain, our knowledge of their expression in the human brain remains limited. The aim of the present study was to investigate the mRNA expression of 5 alpha-reductase 1 as well as 3 alpha-HSD 1, 2, 3 and 20 alpha-HSD in brain tissue from patients with pharmacoresistant temporal lobe epilepsy (TLE). Specimens were derived from either the hippocampus or the temporal lobe cortex and from the tumor-free approach corridor tissue of patients with brain tumors. Quantification of different mRNAs was achieved by real time PCR. In addition, we provide data on simultaneous evaluation of serum AP concentrations. We could demonstrate that 3 alpha-HSD 1 was not expressed in the hippocampus and temporal lobe of patients with TLE. In the hippocampus and temporal lobe, the expression levels of 3 alpha-HSD 2 were about 20% of that in liver tissue, those of 3 alpha-HSD 3 about 7% and those of 20 alpha-HSD about 2%, respectively. In patients with TLE, expression of 3 alpha-HSD 2 was significantly higher in the hippocampus than in temporal lobe cortex tissue (P<0.006). AP concentrations did not correlate significantly with the mRNA expression levels of 5 alpha-reductase 1, 3 alpha-HSD 2 and 3 and 20 alpha-HSD in any of the patient groups under investigation. In conclusion, the present study demonstrates mRNA expression of 5 alpha-reductase 1 and 3 alpha-HSD 2 and 3 and 20 alpha-HSD in the hippocampus and temporal lobe of epileptic patients. These findings provide further molecular biological evidence for the formation and metabolism of neuroactive steroids in the human brain.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Significant improvement in frontal lobe associated neuropsychological functions after withdrawal of topiramate in epilepsy patients.

RATIONALE: Topiramate (TPM) is a highly effective anticonvulsant drug, but a comparably high rate of cognitive adverse effects have been reported. In this study, we investigated changes in frontal lobe associated cognitive measures after TPM withdrawal in epilepsy patients hospitalized for presurgical evaluation. METHODS: Twenty epilepsy patients were administered a brief neuropsychological test battery before and after withdrawal of TPM. Neuropsychological evaluation included a verbal fluency task, verbal (Wechsler's digits) and spatial spans (Corsi block-tapping) and Trail Making Test (TMT, parts A and B). Median baseline dosage of TPM was 237.5mg/d, the median retest-interval was 8 days. Results were compared to a matched group of patients, who had been tested and retested before and after reduction of AEDs other than TPM at comparable time intervals. RESULTS: After TPM withdrawal, group performance appeared significantly improved in five of six tests administered. The scores of the control patients remained largely unchanged after drug reduction. After withdrawal, the scores of the TPM group did not differ significantly from the results of the control group whereas pronounced differences had been observed before. Individual improvement became apparent in the majority of patients. Cognitive performance was not correlated to current daily dosages/current blood serum levels of TPM. CONCLUSION: Withdrawal of TPM causes significant improvement in frontal lobe associated measures like verbal fluency and working memory. As withdrawal was part of the preoperative work-up, and not initiated because of patients' complaints or hints of intoxication, cognitive impairment due to TPM appears to be easily overlooked and underestimated.

Adult↗
PubMed2003

Psychogenic nonepileptic seizures: review and update.

The population incidence of psychogenic nonepileptic seizures (PNES) may be only 4% that of epilepsy, but many patients with PNES have a tendency to seek medical attention, and PNES make up a larger share of the workload of neurologists and emergency and general physicians. Although a great number of publications describe how PNES can be distinguished from epileptic seizures, it usually takes several years to arrive at this diagnosis, and three-quarters of patients (with no additional epilepsy) are treated with anticonvulsants initially. However, the management of PNES as epileptic seizures can lead to significant iatrogenic harm. Moreover, the failure to recognize the psychological cause of the disorder detracts from addressing associated psychopathology and enhances secondary somatization processes. This review provides an overview of studies of the diagnosis, etiology, treatment, and prognosis of PNES. Physicians should always consider PNES in the differential diagnosis of a seizure disorder. If a diagnosis of PNES is possible, or a diagnosis of epilepsy in doubt, a clear diagnostic categorization should be sought. This should involve the assessment of the patient by a physician versed in the diagnosis of seizure disorders and, in many cases, the documentation of a typical seizure by video-EEG. Outcome may be improved if the diagnosis is more actively sought, made earlier, and communicated more convincingly.

Anticonvulsants↗
PubMed2003

Rhinal-hippocampal theta coherence during declarative memory formation: interaction with gamma synchronization?

The hippocampus and the rhinal cortex, two substructures of the medial temporal lobe, together play a crucial role in human declarative memory formation. To investigate in detail the mechanism connecting these two structures transiently during memory formation we recorded depth EEG in epilepsy patients from within the hippocampus and the rhinal cortex. During this recording, patients performed a single-trial word list-learning paradigm with a free recall memory test following a distraction task. Rhinal-hippocampal EEG coherence and spectral power at both locations in the time interval up to 2 s after onset of word presentation were analysed in the frequency range 1-19 Hz. Successful as opposed to unsuccessful memory formation was associated with a general rhinal-hippocampal coherence enhancement, but without alterations in spectral power. Coherence increases in the theta range were correlated with the previously reported memory-related changes in rhinal-hippocampal gamma phase synchronization. This correlation may suggest an interaction of the two mechanisms during declarative memory formation. While theta coherence might be associated with slowly modulated coupling related to an encoding state, rhinal-hippocampal gamma synchronization may be more closely related to actual memory processes by enabling fast coupling and decoupling of the two structures.

Adult↗
PubMed2003

Anticonvulsant pharmacology of voltage-gated Na+ channels in hippocampal neurons of control and chronically epileptic rats.

Voltage-gated Na+ channels are a main target of many first-line anticonvulsant drugs and their mechanism of action has been extensively investigated in cell lines and native neurons. Nevertheless, it is unknown whether the efficacy of these drugs might be altered following chronic epileptogenesis. We have, therefore, analysed the effects of phenytoin (100 micro m), lamotrigine (100 micro m) and valproate (600 micro m) on Na+ currents in dissociated rat hippocampal granule neurons in the pilocarpine model of chronic epilepsy. In control animals, all three substances exhibited modest tonic blocking effects on Na+ channels in their resting state. These effects of phenytoin and lamotrigine were reduced (by 77 and 64%) in epileptic compared with control animals. Phenytoin and valproate caused a shift in the voltage dependence of fast inactivation in a hyperpolarizing direction, while all three substances shifted the voltage dependence of activation in a depolarizing direction. The anticonvulsant effects on Na+ channel voltage dependence proved to be similar in control and epileptic animals. The time course of fast recovery from inactivation was potently slowed by lamotrigine and phenytoin in control animals, while valproate had no effect. Interestingly, the effects of phenytoin on fast recovery from inactivation were significantly reduced in chronic epilepsy. Taken together, these results reveal that different anticonvulsant drugs may exert a distinct pattern of effects on native Na+ channels. Furthermore, the reduction of phenytoin and, to a less pronounced extent, lamotrigine effects in chronic epilepsy raises the possibility that reduced pharmacosensitivity of Na+ channels may contribute to the development of drug resistance.

Animals↗
PubMed2003

Correlation of hippocampal glucose oxidation capacity and interictal FDG-PET in temporal lobe epilepsy.

PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60-90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity. METHODS: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-microm-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus. RESULTS: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (rp = 0.7, p = 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found. CONCLUSIONS: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism.

Adolescent↗
PubMed2003

The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects.

PURPOSE: To describe the histologic spectrum and clinical characteristics of patients with neuroepithelial tumors and drug-resistant epilepsy and to analyze clinical data and treatment related to seizure outcome and survival. METHODS: Data were analyzed from 207 consecutive patients with intractable epilepsy (aged 2-54 years), who between 1988 and 1999 had >or=50% resection of supratentorial, neuroepithelial tumors. Extent of resection was assessed on postoperative magnetic resonance imaging (MRI); seizure outcome was classified according to Engel's outcome scale; and follow-up data were prospectively updated. RESULTS: Median follow-up was eight years (range, 2-14 years). Histologic examination revealed 154 classic epilepsy-associated tumors (ganglioglioma, dysembryoplastic neuroepithelial tumor, pleomorphic xanthoastrocytoma, and pilocytic astrocytomas) and 53 others (astrocytomas and oligodendrogliomas). Four World Health Organization (WHO) grade III tumors were found (astrocytoma, n = 3; ganglioglioma, n = 1). After surgery, 82% of the patients were seizure free (class I). The following factors were associated with improved seizure outcome: Short duration of epilepsy before surgery, single EEG focus, absence of additional hippocampal sclerosis or cortical dysplasia, transsylvian approach, other than astrocytomas, and complete tumor resection. After 5 years, only nine (4%) patients had tumor recurrence, four (2%) with malignant transformation and death. None of the four patients with anaplastic tumors died. Even patients with astrocytomas of WHO grade II or III showed 10-year recurrence of only 25% and 10-year survival of 90%. CONCLUSIONS: Tumors associated with long-term epilepsy should be removed early for two different reasons: high rate of seizure freedom and rare but potential risk of malignant tumor progression. The unexpected long survival of these astrocytomas should be investigated by using immunohistochemistry and molecular biology.

Adolescent↗