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C E Elger

Publications and source records attributed to C E Elger.

At least 145 records · Page 8Linked to original sources
PubMed2000

Time adaptive denoising of single trial event-related potentials in the wavelet domain.

We present a new wavelet-based method for single trial analysis of transient and time variant event-related potentials (ERPs). Expecting more accurate filter settings than achieved by other techniques (low-pass filter, a posteriori Wiener filter, time invariant wavelet filter), ERPs were initially balanced in time. By simulation, better filter performance could be established for test signals contaminated with either white noise or isospectral noise. To provide an example of real application, the method was applied to limbic P300 potentials (MTL-P300). As a result, variance of single trial MTL-P300s decreased, without restricting the corresponding mean. The proposed method can be regarded as an alternative for single-trial ERP analysis.

Artifacts↗
PubMed1999

Cellular pathology of hilar neurons in Ammon's horn sclerosis.

In addition to functionally affected neuronal signaling pathways, altered axonal, dendritic, and synaptic morphology may contribute to hippocampal hyperexcitability in chronic mesial temporal lobe epilepsies (MTLE). The sclerotic hippocampus in Ammon's horn sclerosis (AHS)-associated MTLE, which shows segmental neuronal cell loss, axonal reorganization, and astrogliosis, would appear particularly susceptible to such changes. To characterize the cellular hippocampal pathology in MTLE, we have analyzed hilar neurons in surgical hippocampus specimens from patients with MTLE. Anatomically well-preserved hippocampal specimens from patients with AHS (n = 44) and from patients with focal temporal lesions (non-AHS; n = 20) were studied using confocal laser scanning microscopy (CFLSM) and electron microscopy (EM). Hippocampal samples from three tumor patients without chronic epilepsies and autopsy samples were used as controls. Using intracellular Lucifer Yellow injection and CFLSM, spiny pyramidal, multipolar, and mossy cells as well as non-spiny multipolar neurons have been identified as major hilar cell types in controls and lesion-associated MTLE specimens. In contrast, none of the hilar neurons from AHS specimens displayed a morphology reminiscent of mossy cells. In AHS, a major portion of the pyramidal and multipolar neurons showed extensive dendritic ramification and periodic nodular swellings of dendritic shafts. EM analysis confirmed the altered cellular morphology, with an accumulation of cytoskeletal filaments and increased numbers of mitochondria as the most prominent findings. To characterize cytoskeletal alterations in hilar neurons further, immunohistochemical reactions for neurofilament proteins (NFP), microtubule-associated proteins, and tau were performed. This analysis specifically identified large and atypical hilar neurons with an accumulation of low weight NFP. Our data demonstrate striking structural alterations in hilar neurons of patients with AHS compared with controls and non-sclerotic MTLE specimens. Such changes may develop during cellular reorganization in the epileptogenic hippocampus and are likely to contribute to the pathogenesis or maintenance of temporal lobe epilepsy.

Aged↗
PubMed1999

Visualization of defective mitochondrial function in skeletal muscle fibers of patients with sporadic amyotrophic lateral sclerosis.

The mitochondrial function in skeletal muscle was investigated in skeletal muscle biopsies of 26 patients with sporadic amyotrophic lateral sclerosis (ALS) and compared with investigations of 28 age-matched control muscle samples and biopsies of 6 patients with spinal muscular atrophy (SMA) and two patients with Tay-Sachs disease. In comparison to the control, SMA and Tay-Sachs biopsies, we observed in the ALS samples a significant about two-fold lower activity of complex I of mitochondrial respiratory chain. To visualise the distribution of the mitochondrial defect in skeletal muscle fibers we applied confocal laser-scanning microscopy and video fluorescence microscopy of NAD(P)H and fluorescent flavoproteins. The redox change of mitochondrial NAD(P)H and flavoproteins on addition of mitochondrial substrates, ADP, or cyanide were determined by measurement of fluorescence intensities with dual-photon UV-excitation and single-photon blue excitation. In skeletal muscle fibers of ALS patients with abnormalities of mitochondrial DNA (multiple deletions, n=1, or lower mtDNA levels, n=14) we observed a heterogeneous distribution of the mitochondrial defects among individual fibers and even within single fibers. In some patients (n=3) a mitochondrial defect was also detectable in cultivated skin fibroblasts. These findings support the viewpoint that the observed impairment of mitochondrial function in muscle of certain ALS patients is caused by an intrinsic mitochondrial defect which may be of pathophysiological significance in the etiology of this neurodegenerative disease.

Adult↗
PubMed1999

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors.

Studies in rodents and nonhuman primates have linked the activity of N-methyl-D-aspartate (NMDA) receptors within the hippocampus to animals' performance on memory-related tasks. However, whether these receptors are similarly essential for human memory is still an open question. Here we present evidence suggesting that hippocampal NMDA receptors, most likely within the CA1 region, do participate in human verbal memory processes. Words elicit a negative event-related potential (ERP) peaking around 400 ms within the anterior mesial temporal lobe (AMTL-N400). Ketamine, an NMDA-receptor antagonist, reduces the amplitude of the AMTL-N400 (in contrast to other hippocampal potentials) on initial presentation, eliminates the typical AMTL-N400 amplitude reduction with repetition, and leads to significant memory impairment. Of the various hippocampal subfields, only the density of CA1 neurons correlates with the word-related ERPs that are reduced by ketamine. Altogether, our behavioral, anatomical, and electrophysiological results indicate that hippocampal NMDA receptors are involved in human memory.

Adult↗
PubMed1999

Expression of cytochrome P450scc mRNA in the hippocampus of patients with temporal lobe epilepsy.

The hippocampus is one of the target areas of neurosteroidal action. Expression of cytochrome P450scc (P450scc, CYP11A1), one of the key enzymes in steroid metabolism, results in de novo synthesis of the neurosteroid pregnenolone. We used a competitive RT-PCR assay to quantify the amount of P450scc mRNA in hippocampal tissue specimens obtained at neurosurgery from patients with temporal lobe epilepsy (TLE). P450scc mRNA is expressed approximately 200 times lower in the hippocampus than in adrenal tissue known for high P450scc expression. P450scc mRNA concentrations were significantly higher in the hippocampus of women (1.72 +/- 0.36 aU, arbitrary units; mean +/- s.e.m.) than of men (0.92 +/- 0.15 aU, p < 0.004). Our data show for the first time the sex-dependent expression of P450scc mRNA in the hippocampus of patients with TLE.

Adrenal Glands↗
PubMed1999

Real-time tracking of memory formation in the human rhinal cortex and hippocampus.

A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes implanted in the brains of patients with temporal lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the medial temporal lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.

Adult↗
PubMed1999

Reduced signal complexity of intracellular recordings: a precursor for epileptiform activity?

Recent studies have shown that time windowed extraction of nonlinear parameters like an effective correlation dimension from intracranially recorded EEG of epileptic patients often allows to detect and identify an unequivocal "pre-ictal phase" preceding an epileptic seizure. In another study, however, such an anticipation could not be made. These conflicting findings may indicate that observed changes in nonlinear parameters probably depend on the type of elementary mechanisms underlying epileptic processes and/or the spatial distribution of neurons primarily involved in generation of epileptiform discharges. To test the existence of such dependencies, the transition from normal to epileptiform activity (EA) of CA3-neurons in hippocampal slices was analyzed in four epilepsy models, using a time windowed computation of an effective correlation dimension. Indeed, in xanthine and penicillin models, signal complexity in intracellular recordings was reduced before manifestation of paroxysmal depolarization shifts (PDS), whereas a preceding loss of complexity was missing in low-magnesium and veratridine models. These findings indicate that interictal-like EA is predictable only in some epilepsy models.

Electroencephalography↗
PubMed1999

Amobarbital effects on the posterior hippocampus during the intracarotid amobarbital test.

OBJECTIVE: To relate functional effects on the hippocampus during the intracarotid amobarbital test (IAT) to its direct perfusion with amobarbital. METHODS: In 17 patients with intractable temporal lobe epilepsy, 28 hemispheres were perfused with 2.3 mL of 10% solution of 200 mg amobarbital and 37 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO). For evaluation of amobarbital effects, data were combined from stereo-EEG (S-EEG) recordings from intrahippocampal depth electrodes and high-resolution SPECT after intracarotid injection of HMPAO. RESULTS: Perfusion of the entire hippocampus was observed only in hemispheres with a fetal origin of the posterior cerebral artery (PCA). In 10 hemispheres, S-EEG recordings could not unequivocally be assigned to either the anterior or the posterior part of the hippocampus. In the remaining 18 hemispheres, only the two with a fetal type of PCA showed perfusion of the entire hippocampus. In both, hippocampal electrical activity changed under the influence of amobarbital but did not differ in anterior and posterior contacts. In 15 of 16 hemispheres in which SPECT demonstrated perfusion of the anterior hippocampus only, amobarbital injection resulted in significant S-EEG activity change in both the anterior and the posterior parts of the hippocampus. CONCLUSION: S-EEG effects on the posterior hippocampus during the IAT can occur without direct perfusion of those brain areas.

Adolescent↗
PubMed1999

Altered mitochondrial oxidative phosphorylation in hippocampal slices of kainate-treated rats.

Mitochondria provide the main neuronal energy supply and are important organelles for the sequestration of intracellular Ca2+. This indicates a possible important role for mitochondria in modulating neuronal excitability in normal function as well as in disease. Therefore, we have investigated mitochondrial oxidative phosphorylation in the kainate model of epilepsy. We measured the oxygen consumption of single 400-micron rat hippocampal slices applying high resolution respirometry and determined mitochondrial NAD(P)H autofluorescence signal changes in single slices by laser-excited fluorescence spectroscopy. We observed an about 2-fold higher (p<0.001) basal glucose oxidation rate in slices from kainate-treated animals. This increased endogenous energy consumption was found to be unrelated to spontaneous activity since it was not sensitive to the inhibitors of the sodium-potassium ATPase ouabain and of the mitochondrial adenine nucleotide translocator atractyloside. This finding suggested an increased mitochondrial energy turnover in kainate-induced epilepsy. Furthermore, the uncoupler-stimulated oxygen consumption of the slices was approximately 1.3-fold higher (p<0.01) in the kainate model. In accordance with the respirometric data, fluorescence spectroscopy showed decreased reduction levels of the mitochondrial NAD-system in glucose oxidizing slices from kainate-treated rats. The preincubation of epileptic hippocampal slices with either BAPTA AM, ruthenium red or TPP+ increased the atractyloside sensitivity of glucose oxidation to about 1.4-fold (p<0.01). These observations indicate that the increased mitochondrial energy turnover in hippocampal slices from kainate-treated rats is most possibly caused by futile Ca2+-cycling.

Animals↗
PubMed1999

An increase of hippocampal calretinin-immunoreactive neurons correlates with early febrile seizures in temporal lobe epilepsy.

Numerous studies indicate that initial precipitating injuries (IPI) such as febrile seizures during early childhood may play a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS). Previous data demonstrate an increase of horizontally oriented neurons in molecular layers of hippocampal subfields, which are immunoreactive for calretinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells are transiently expressed in the murine developing hippocampus and are critically involved in neuronal pattern formation. Here we investigated a potential relationship between the distribution of horizontally oriented calretinin-immunoreactive neurons and the clinical history of TLE patients with AHS. Horizontally oriented neurons in the molecular layer of the hippocampal formation have been visualized by antibodies against the calcium-binding proteins calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients with AHS were compared with autopsy specimens from developing and adult normal human hippocampus (n = 26). During ontogeny, CR-ir cells showed a marked perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML) followed by a gradual postnatal decline. In hippocampal specimens from TLE patients with AHS and seizure onset before the age of 4 years, significantly higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P < 0.05) were encountered than in AHS patients without precipitating seizures or with an uneventful early medical history. However, all three groups had higher levels of CR-ir neurons compared to adult controls obtained at autopsy (P < 0.01). In addition, AHS specimens showed increased CR-ir neuropil staining throughout the DG-ML compared with the restricted distribution of CR-ir fibers within the superficial granule cell layer visible in controls. These findings suggest that a considerable number of TLE patients with AHS display signs of impaired hippocampal maturation and circuitry formation as indicated by increased numbers of Cajal-Retzius like cells. It remains to be elucidated, how these changes contribute to the pathogenesis of TLE.

Adolescent↗
PubMed1999

The CD34 epitope is expressed in neoplastic and malformative lesions associated with chronic, focal epilepsies.

The etiology and pathogenesis of complex focal lesions associated with chronic, intractable epilepsy are largely unknown. Some data indicate that malformative changes of the central nervous system may precede the development of gangliogliomas and other epilepsy-associated neoplasms. In the present immunhistochemical study, we have examined epilepsy-associated lesions for CD34, a stem cell marker transiently expressed during early neurulation. Surprisingly, most tissue samples from patients with chronic epilepsy (n = 262) revealed neural cells immunoreactive for CD34. Prominent immunoreactivity was detected in gangliogliomas (74%), low-grade astrocytomas (62%) and oligodendrogliomas (59%). Only 52% of non-neoplastic, malformative pathologies, such as glio-neuronal hamartias or hamartomas showed solitary or small clusters of CD34-immunoreactive cells. None of the adult control tissues (n = 22), none of the specimens obtained from the developing human brain (n = 44) and none of those tumor samples from patients without epilepsy (n = 63) contained CD34-immunoreactive neural cells. However, a malignant teratoma with microscopic features of early neural differentiation displayed a focal CD34-immunoreactive staining pattern. The majority of CD34-immunoreactive cells co-localized with S-100 protein and a small subpopulation was also immunoreactive for neuronal antigens. CD34 may, thus, represent a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathological changes in epilepsy patients. The CD34 immunoreactivity of these lesions indicates an origin from dysplastic or atypically differentiated neural precursors. Further studies may elucidate the functional significance of CD34 expression during the pathogenesis of epilepsy-related focal lesions as well as during neurogenesis.

Adolescent↗
PubMed1999

Safety of single and repetitive focal transcranial magnetic stimuli as assessed by intracranial EEG recordings in patients with partial epilepsy.

The safety of single and repetitive (paired and quadruple) focal transcranial magnetic stimuli as possible inducers of epileptic discharges or clinically manifest seizures was investigated in 21 patients with intractable epilepsy during invasive presurgical monitoring. Subdural and/or intracerebral depth electrodes had been implanted in close proximity to the suspected epileptogenic zone, and the anticonvulsant medication had been reduced. Focal transcranial magnetic stimuli were applied by a Magstim QuadroPulse magnetic stimulator over the hand area of the motor cortex ipsilateral to the epileptogenic focus at intensities of 120% and 150% of motor threshold and additionally as close as possible to the suspected epileptogenic zone at 40-100% of maximal stimulator output. Stimulation did not induce any complex partial or secondary generalized tonic-clonic seizures. One patient with hippocampal sclerosis experienced an aura associated with rhythmic electroencephalographic discharges restricted to the ipsilateral intrahippocampal depth electrode after stimulation over his left temporal lobe. This patient, however, also had frequent spontaneously occurring auras with focal ictal discharges originating from this hippocampus. Interictal discharges were not influenced significantly by single or repetitive magnetic stimuli. In conclusion, from this study there is no evidence that single or serial focal transcranial magnetic stimuli activate epileptogenic foci. At least four high-frequency repetitive stimuli of high intensity may thus be applied with a low risk of seizure induction even in patients with low seizure threshold.

Adolescent↗
PubMed1999

Distribution of voltage-dependent calcium channel beta subunits in the hippocampus of patients with temporal lobe epilepsy.

Voltage-dependent Ca2+ channels constitute a major class of plasma membrane channels through which a significant amount of extracellular Ca2+ enters neuronal cells. Their pore-forming alpha1 subunits are associated with cytoplasmic regulatory beta subunits, which modify the distinct biophysical and pharmacological properties of the alpha1 subunits. Studies in animal models indicate altered expression of alpha1 and/or beta subunits in epilepsy. We have focused on the regulatory beta subunits and have analysed the immunoreactivity patterns of the beta1, beta2, beta3 and beta4 subunits in the hippocampus of patients with temporal lobe epilepsy (n = 18) compared to control specimens (n = 2). Temporal lobe epilepsy specimens were classified as Ammon's horn sclerosis (n = 9) or focal lesions without alteration of hippocampal cytoarchitecture (n = 9). Immunoreactivity for the beta subunits was observed in neuronal cell bodies, dendrites and neuropil. The beta1, beta2 and beta3 subunits were found mainly in cell bodies while the beta4 subunit was primarily localized to dendrites. Compared to the control specimens, epilepsy specimens of the Ammon's horn sclerosis and of the lesion group showed a similar beta subunit distribution, except for beta1 and beta2 staining in the Ammon's horn sclerosis group: in the severely sclerotic hippocampal subfields of these specimens, beta1 and beta2 immunoreactivity was enhanced in some of the remaining neuronal cell bodies and, in addition, strongly marked dendrites. Thus, hippocampal neurons apparently express multiple classes of beta subunits which segregate into particular subcellular domains. In addition, the enhancement of beta1 and beta2 immunoreactivity in neuronal cell bodies and the additional shift of the beta1 and beta2 subunits into the dendritic compartment in severely sclerotic hippocampal regions indicate specific changes in Ammon's horn sclerosis. Altered expression of these beta subunits may lead to increased currents carried by voltage-dependent calcium channels and to enhanced synaptic excitability.

Adult↗
PubMed1999

Loss of dynorphin-mediated inhibition of voltage-dependent Ca2+ currents in hippocampal granule cells isolated from epilepsy patients is associated with mossy fiber sprouting.

The endogenous kappa receptor selective opioid peptide dynorphin has been shown to inhibit glutamate receptor-mediated neurotransmission and voltage-dependent Ca2+ channels. It is thought that dynorphin can be released from hippocampal dentate granule cells in an activity-dependent manner. Since actions of dynorphin may be important in limiting excitability in human epilepsy, we have investigated its effects on voltage-dependent Ca2+ channels in dentate granule cells isolated from hippocampi removed during epilepsy surgery. One group of patients showed classical Ammon's horn sclerosis characterized by segmental neuronal cell loss and astrogliosis. Prominent dynorphin-immunoreactive axon terminals were present in the inner molecular layer of the dentate gyrus, indicating pronounced recurrent mossy fiber sprouting. A second group displayed lesions in the temporal lobe that did not involve the hippocampus proper. All except one of these specimens showed a normal pattern of dynorphin immunoreactivity confined to dentate granule cell somata and their mossy fiber terminals in the hilus and CA3 region. In patients without mossy fiber sprouting the application of the kappa receptor selective opioid agonist dynorphin A ([D-Arg6]1-13, 1 microM) caused a reversible and dose-dependent depression of voltage-dependent Ca2+ channels in most granule cells. These effects could be antagonized by the non-selective opioid antagonist naloxone (1 microM). In contrast, significantly less dentate granule cells displayed inhibition of Ca2+ channels by dynorphin A in patients with mossy fiber sprouting (Chi-square test, P < 0.0005). The lack of dynorphin A effects in patients showing mossy fiber sprouting compares well to the loss of kappa receptors on granule cells in Ammon's horn sclerosis but not lesion-associated epilepsy. Our data suggest that a protective mechanism exerted by dynorphin release and activation of kappa receptors may be lost in hippocampi with recurrent mossy fiber sprouting.

Adolescent↗
PubMed1999

Quantitative investigation of mitochondrial function in single rat hippocampal slices: a novel application of high-resolution respirometry and laser-excited fluorescence spectroscopy.

Highly sensitive techniques are needed for the quantitative determination of mitochondrial oxidative phosphorylation function in single rat hippocampal slices or isolated hippocampal subfields. We determined the oxygen consumption of single hippocampal slices or subfields applying high-resolution respirometry adapted for slice measurements and measured the redox state of mitochondrial NAD(P)H in single hippocampal slices by laser-excited fluorimetry. These methods allow the sensitive detection of two parameters of mitochondrial oxidative phosphorylation which depend on supply of substrates and respiratory chain function.

Animals↗
PubMed1999

Limbic P300s in temporal lobe epilepsy with and without Ammon's horn sclerosis.

Limbic P300 potentials can be recorded within the mesial temporal lobes of patients with temporal lobe epilepsy (TLE). To delineate possible mechanisms of their generation and pathological alteration, we analysed limbic P300s in 55 TLE patients with and 29 without Ammon's horn sclerosis (AHS) and correlated their amplitudes with neuronal cell counts in 30 histopathological specimens. Limbic P300 amplitudes were reduced on the side of the epileptogenic focus only in patients with AHS. Moreover, in AHS patients, limbic P300 latencies were prolonged bilaterally; and in patients with left-sided AHS, amplitudes were reduced bilaterally. Both findings suggest bilateral functional deficits in TLE with unilateral AHS. Limbic P300 areas correlated significantly with neuronal densities of dentate gyrus granule cells but not hippocampal pyramidal cells in the CA1-4 (cornu ammonis) subfields. This finding points to a potential mechanism for the bilateral effects of unilateral AHS as both dentate gyri exhibit strong reciprocal contralateral connectivity.

Adolescent↗
PubMed1999

Metabolic consequences of the cytochrome c oxidase deficiency in brain of copper-deficient Mo(vbr) mice.

Biochemical micromethods were used for the investigation of changes in mitochondrial oxidative phosphorylation associated with cytochrome c oxidase deficiency in brain cortex from Mo(vbr) (mottled viable brindled) mice, an animal model of Menkes' copper deficiency syndrome. Enzymatic analysis of cortex homogenates from Mo(vbr) mice showed an approximately twofold decrease in cytochrome c oxidase and a 1.4-fold decrease in NADH:cytochrome c reductase activities as compared with controls. Assessment of mitochondrial respiratory function was performed using digitonin-treated homogenates of the cortex, which exhibited the main characteristics of isolated brain mitochondria. Despite the substantial changes in respiratory chain enzyme activities, no significant differences were found in maximal pyruvate or succinate oxidation rates of brain cortex homogenates from Mo(vbr) and control mice. Inhibitor titrations were used to determine flux control coefficients of NADH:CoQ oxidoreductase and cytochrome c oxidase on the rate of mitochondrial respiration. Application of amobarbital to titrate the activity of NADH:CoQ oxidoreductase showed very similar flux control coefficients for control and mutant animals. Alternately, titration of respiration with azide revealed for Mo(vbr) mice significantly sharper inhibition curves than for controls, indicating a more than twofold elevated flux control coefficient of cytochrome c oxidase. Owing to the reserve capacity of respiratory chain enzymes, the reported changes in activities do not seem to affect whole-brain high-energy phosphates, as observed in a previous study using 31P NMR.

Animals↗