Biomedical subjects

C E Elger

Publications and source records attributed to C E Elger.

At least 73 records · Page 4Linked to original sources

PubMed2001

Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy.

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE.

Adolescent↗

PubMed2001

A fast FLAIR dual-echo technique for hippocampal T2 relaxometry: first experiences in patients with temporal lobe epilepsy.

To evaluate the use of cerebrospinal fluid (CSF) signal nulling in MR T2 measurements of the hippocampus in normal control subjects and patients with temporal lobe epilepsy (TLE), dual-echo acquisitions covering the whole brain were used. T2 relaxation times were estimated in 12 standard Eurospin II MR test objects and in the hippocampi of 10 control subjects, using T2 maps constructed from conventional spin-echo (CSE), fast spin-echo (FSE), and fast FLAIR (FF) dual-echo sequences on a 1.5-T MR scanner. Hippocampal T2 values (HCT2) were measured on contiguous coronal 5-mm slices throughout the antero-posterior extent of each hippocampus in the 10 controls and 12 TLE patients, using both CSE and FF. Scan-rescan reproducibility in Eurospin II standard MR test objects was high for all sequences. There was a good correlation between T2 values from CSE, FF, and FSE sequences in test objects and in control hippocampi. In controls, the coefficient of variation of mean HCT2 values differed between slice positions, but was lowest for FF, followed by CSE data. The intrarater coefficient of reliability between repeated measurements in control subjects was lowest for FF HCT2, at 2.3%. The interrater coefficient of reliability for CSE HCT2 measurements in controls (4.8%) was slightly lower than the interrater coefficient for FF HCT2 (5.4%). HCT2 measurement with both CSE and FF identified abnormal values in the same 10 hippocampi of 12 patients. Hippocampal dual-echo T2 relaxometry using CSF nulling is reliable in control subjects, and identifies the abnormal hippocampi in patients with TLE. The increases in hippocampal T2 signal demonstrated using FF HCT2 measurements are unlikely to be partial volume effects from CSF.

Adult↗

PubMed2001

Self-Reported Mood Changes following 6 Months of Vagus Nerve Stimulation in Epilepsy Patients.

Vagus nerve stimulation (VNS) for treatment of drug-resistant epileptic seizures has been reported to have additional positive mood effects as obtained by psychiatric ratings. To avoid rater bias effects, this study used self-report questionnaires and examined changes in self-reported mood and health-related quality of life following 6 months of VNS treatment. From 40 adult patients treated with VNS since the beginning of the study, 28 patients (mean age: 35.4 years) with unchanged medication were included. Repeated-measures MANOVA revealed a significant general mood improvement. Post hoc univariate tests obtained improvements of tenseness and dysphoria but not of depression, level of activity, or health-related quality of life. Mood and seizure outcome were correlated. VNS may improve unspecific states of indisposition and dysphoria. Absolute seizure reduction contributes to this antidysphoric effect. Since baseline depression scores were low, findings do not contradict but complement earlier reports of an antidepressive effect of VNS.

Journal Article↗

PubMed2001

No evidence for cognitive side effects after 6 months of vagus nerve stimulation in epilepsy patients.

Vagus nerve stimulation (VNS) can reduce seizure frequency in epilepsy patients and may affect central mechanisms of brain functioning. Experimental studies have provided evidence of cognitive alterations during VNS on phases. This single-arm follow-up study evaluates the potential of VNS to affect cognitive performance following long-term treatment. Thirty-six adult patients with medication-resistant epilepsies enrolled. Cognition was assessed before and at least 6 months after implantation of the stimulation device by a comprehensive neuropsychological assessment battery comprising tests on attention, motor functioning, short-term memory, learning and memory, and executive functions. Neither multiple testing of single score changes nor multivariate testing of cognitive domains revealed significant pre-post changes. Improvements in attentional performance were completely explained by practice effects as is usually expected. In particular, no negative side effects were revealed. These findings are in line with the clinical impression that VNS does not affect cognitive performance.

Journal Article↗

PubMed2001

Effect of creatine supplementation on metabolite levels in ALS motor cortices.

Mitochondrial pathology is an early observation in motor neurons and skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). To clarify the relevance of this finding, we determined the effects of a 1-month oral administration of creatine on (1)H NMR-visible metabolites in the motor cortices of 15 controls and 15 patients with sporadic ALS, most of whom had mitochondrial pathology in skeletal muscle. In the motor cortex of the ALS group the N-acetylaspartate (NAA)/creatine (Cr(t)) metabolite ratio was lower than in our control group, indicating NAA loss. Upon creatine supplementation we observed in the controls a decline in the NAA/Cr(t), NAA/choline (Cho), glutamate + glutamine (Glx)/Cr(t), and Glx/Cho metabolite ratios. In contrast, in the ALS patient group the NAA/Cr(t) and the NAA/Cho metabolite ratios remained unchanged, while the Glx/Cr(t) and Glx/Cho metabolite ratios decreased. These data are compatible with the interpretation that creatine supplementation causes an increase in the diminished NAA levels in ALS motor cortex as well as an increase of choline levels in both ALS and control motor cortices. Because NAA is synthesized by mitochondria in an energy-dependent manner and the NAA/Cho metabolite ratios in the ALS motor cortices were found to be correlated to the degree of mitochondrial pathology in ALS skeletal muscle, our results can be explained by a deficiency of enzymes of mitochondrial respiratory chain in the ALS motor cortex which might affect motor neuron survival.

Adult↗

PubMed2001

Language mapping in less than 15 minutes: real-time functional MRI during routine clinical investigation.

Neurosurgical interventions often require the presurgical determination of language dominance or mapping of language areas. Results obtained by fMRI are closely correlated with invasive procedures such as electrical stimulation mapping or the intracarotid amobarbital test. However, language fMRI is not used routinely, because postprocessing is time-consuming. We utilized a real-time analysis software installed directly on the MR console computer and SPM99 as reference postprocessing software. We assessed the reliability of the immediate determination of language dominance based on individual activation maps by comparing the results of the visual analysis of images derived from conventional postprocessing with those produced by the real-time tool. All images were rated independently by six senior neurologists blinded to other data. We validated the robustness of the real-time method statistically by comparing global and regional lateralization indices derived from real-time and postprocessing analysis. Functional MRI was performed with a standard 1.5-T whole-body scanner. Brain activity was contrasted between an alternating semantic judgment and letter matching task. Twelve right-handed, healthy control subjects and 12 consecutive patients with drug-resistant, localization-related epilepsy were investigated. The semantic condition induced almost invariably left hemispheric activations in Broca's area, the premotor cortex, the dorsolateral prefrontal cortex, and the temporoparietal region. Although real-time analysis reduced noise less effectively than SPM99, visual ratings and lateralization indices produced highly concordant results with both methods. In conclusion, real-time fMRI, as used here, allowed reliable language lateralization and mapping in less than 15 min during routine clinical MRI investigation with no need for postprocessing.

Adult↗

PubMed2001

Carbamazepine in phenobarbital-nonresponders: experience with ten preterm infants.

UNLABELLED: Carbamazepine is a standard anticonvulsant in children and adults. Until now there is only little information available on its use in neonates. We investigated the oral administration of carbamazepine in refractory neonatal seizures treated with phenobarbital. Ten preterm infants (gestational age 23 + 6-34 + 6 weeks, birth weight 640 g-3080 g) with neonatal seizures were refractory to a primary therapy with phenobarbital. All patients subsequently received carbamazepine exclusively as a second choice anticonvulsant. A daily dose of 7-23 mg/kg carbamazepine was administered orally in two to three aliquots. All patients reached therapeutic plasma drug levels (3-12 mg/l; 13-50 mumol/l). In nine out of ten patients (complete group of small preterms with gestational age under 30 weeks and weight less than 1000 g), therapeutic success was excellent. Carbamazepine was continued for 1-5 months. After termination of therapy no further seizures occurred, also on EEG recordings. Finally, no carbamazepine-induced adverse effects were observed. CONCLUSION: This is the first report on the use of carbamazepine in small preterm infants. Carbamazepine may provide a useful and effective oral maintenance therapy in the management of neonatal seizures in these patients.

Administration, Oral↗

PubMed2001

The hippocampal contribution to verbal fluency in patients with temporal lobe epilepsy.

We report the effects of hippocampal and non-hippocampal temporal-lobe dysfunction on verbal fluency performance. Quantitative aspects of semantic and phonemic fluency performance were examined in 46 patients with right- or left-temporal-lobe epilepsy and 20 healthy controls. A pattern of fewer words generated on semantic rather than phonemic fluency tasks was found among patients with damage to hippocampal structures. This pattern was not obtained in patients with non-hippocampal temporal-lobe damage, suggesting that the hippocampus plays a crucial role in semantic fluency performance. An interesting lateralization effect was obtained. Among patients with left temporal-lobe involvement, fluency performance was impaired regardless of whether the hippocampus was involved. In contrast, among patients with right temporal-lobe involvement, fluency performance was impaired only when the hippocampus was involved.

Adult↗

PubMed2001

Monotherapy trials in antiepileptic drugs: are modified "presurgical studies" a way out of the dilemma?

Monotherapy trials in epilepsy are confronted with a dilemma: either they are in conflict with ethical requirements, or they are scientifically not meaningful. Monotherapy trials, which are performed as controlled studies randomizing patients to ineffective (pseudo)placebo treatment, are incompatible with the Helsinki Declaration. On the other hand, equivalence or noninferiority studies using an active-control design do not permit valid conclusions on the efficacy of the test drug. Therefore, they do not fulfill scientific requirements for trials on new drugs. As an alternative approach, a monotherapy trial design for epilepsy patients undergoing presurgical evaluation was outlined. During presurgical evaluation, antiepileptic drugs are routinely tapered down for seizure recording. This situation is used for a placebo-controlled short-term monotherapy trial. Four trials according to this design have been completed so far. Recently, several points of concern have been raised against this design, especially for matters of ethics and external validity. In the present article, these objections are outlined and discussed. In the proposed modification the randomization and the titration of the test drug or control begins prior to the presurgical investigations. The advantages are: the test drug does not have to be titrated quickly, pure monotherapy conditions are achieved, and the subjects do not have to experience more seizures than are required for the presurgical evaluation.

Anticonvulsants↗

PubMed2001

Neuroactive steroids and seizure susceptibility.

There is increasing clinical and experimental evidence that hormones, in particular sex steroid hormones, influence neuronal excitability and other brain functions. The term 'neuroactive steroids' has been coined for steroids that interact with neurotransmitter receptors. One of the best characterized actions of neuroactive steroids is the allosteric modulation of GABA(A)-receptor function via binding to a putative steroid-binding site. Since neuroactive steroids may interact with a variety of other membrane receptors, excitatory as well as inhibitory, they may have an impact on the excitability of specific brain regions. Neuronal excitability is enhanced by estrogen, whereas progesterone and its metabolites exert anticonvulsant effects. Testosterone and corticosteroids have less consistent effects on seizure susceptibility. Apart from these particular properties, neuroactive steroids may regulate gene expression via progesterone receptors. Based on their molecular properties, these compounds appear to have a promising therapeutical profile for the treatment of different neuropsychiatric diseases including epilepsy. This review focuses on the effects of neuroactive steroids on neuronal excitability and their putative impact on the physiology of epileptic disorders.

Adrenal Cortex Hormones↗

PubMed2001

The epileptic process as nonlinear deterministic dynamics in a stochastic environment: an evaluation on mesial temporal lobe epilepsy.

The theory of deterministic chaos addresses simple deterministic dynamics in which nonlinearity gives rise to complex temporal behavior. Although biological neuronal networks such as the brain are highly complicated, a number of studies provide growing evidence that nonlinear time series analysis of brain electrical activity in patients with epilepsy is capable of providing potentially useful diagnostic information. In the present study, this analysis framework was extended by introducing a new measure xi, designed to discriminate between nonlinear deterministic and linear stochastic dynamics. For the evaluation of its discriminative power, xi was extracted from intracranial multi-channel EEGs recorded during the interictal state in 25 patients with unilateral mesial temporal lobe epilepsy. Strong indications of nonlinear determinism were found in recordings from within the epileptogenic zone, while EEG signals from other sites mainly resembled linear stochastic dynamics. In all investigated cases, this differentiation allowed to retrospectively determine the side of the epileptogenic zone in full agreement with results of the presurgical workup.

Adolescent↗

PubMed2001

Memory alterations during acute high-intensity vagus nerve stimulation.

Left cervical vagus nerve stimulation (VNS) is an accepted add-on treatment for pharmacoresistant epilepsy. However, it also allows the investigation of the effects of peripheral nerve stimulation on central nervous functions. The impact of 4.5 min high intensity VNS (>1 mA) on material-specific memory and decision times was evaluated in an experimental 'box car' design in 11 patients with pharmacoresistant epilepsy. Results indicate reversible deterioration of figural but not verbal memory and a trend of accelerated decision times during VNS. Thus, further support of cognitive effects of VNS is provided. There are indications of a major projection of VNS to activating brain structures of and the right hemisphere. Significant cognitive side effects in clinical application are unlikely because of the reversibility of the effect and differences between experimental and therapeutic stimulation conditions. However, since the effectors and the direction of the cognitive effects of VNS seem to depend strongly on stimulation conditions, we recommend future experimental research covering a larger range of stimulation conditions.

Adolescent↗

PubMed2001

The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy.

We tested the hypothesis that genetic variation in the human sodium channel gene SCN2A confers liability to idiopathic generalized epilepsy (IGE). We performed a systematic search for mutations in 46 familial IGE cases and detected three novel polymorphisms, however, allele frequencies did not differ significantly between patients and controls. A rare mutation (R1918H) was identified in one patient but was absent in one further affected family member. Thus, our results do not suggest a major role of SCN2A in the etiology of IGE.

Alleles↗

PubMed2001

Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling.

In humans, distinct processes within the hippocampus and rhinal cortex support declarative memory formation. But do these medial temporal lobe (MTL) substructures directly cooperate in encoding new memories? Phase synchronization of gamma-band electroencephalogram (EEG) oscillations (around 40 Hz) is a general mechanism of transiently connecting neural assemblies. We recorded depth-EEG from within the MTL of epilepsy patients performing a memorization task. Successful as opposed to unsuccessful memory formation was accompanied by an initial elevation of rhinal-hippocampal gamma synchronization followed by a later desynchronization, suggesting that effective declarative memory formation is accompanied by a direct and temporarily limited cooperation between both MTL substructures.

Action Potentials↗

PubMed2001

Mutational analysis of TSC1 and TSC2 genes in gangliogliomas.

Gangliogliomas constitute the most frequent tumour entity in patients with temporal lobe epilepsy. The characteristic histopathological admixture of glial and neuronal elements, the focal nature and their differentiated phenotype and benign biological behaviour suggest an origin from a developmentally compromised or dysplastic precursor lesion. The present study analysed TSC1 and TSC2 genes as potential candidates involved in the pathogenesis of this intriguing neoplasm. Recent data suggest that both genes play a role in cortical differentiation and growth control. DNA sequence analysis of TSC1 and TSC2 was studied in 20 patients with gangliogliomas. Fifteen of these tumours (75%) carried polymorphisms in the TSC2 gene. The frequency of these polymorphisms was significantly increased in intron 4 (12.5%) and exon 41 (15%) compared to control individuals (8.1 and 6.5%, respectively, n = 100). A somatic mutation in intron 32 of the TSC2 gene was encountered in one patient. In the TSC1 gene, seven polymorphisms occurred as a combination of base exchanges in exon 14 and intron 13. No mutations were observed in this gene. Laser microdissection and harvesting of individual neuronal and glial elements identified the intron 32 mutation within the glial portion but not in dysplastic neurones of the tumour. The data demonstrate numerous polymorphisms as well as a novel TSC2 mutation in gangliogliomas from patients with chronic epilepsies. The selective detection of the TSC2 mutation within the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.

Brain Neoplasms↗

PubMed2001

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study.

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.

Adult↗

PubMed2001

Psychogenic seizures mimicking juvenile myoclonic epilepsy: case reports.

We describe two patients with psychogenic seizures of rare semiology. Both patients (a 23-year-old man and a 26-year-old woman) attended the emergency department because status epilepticus with myoclonic seizures had been diagnosed. Seizures were documented with video-electroencephalography. Semiology of seizures were brief myoclonia of both arms resulting in a short elevation of both arms without impairment of consciousness. Ictal EEG registration was without abnormal finding. Psychiatric diagnostic assessment suggested a dissociative disorder and mild depression, respectively. During psychiatric treatment seizures occurred only rarely within a 3-5 months follow-up. One should be aware that juvenile myoclonic epilepsy may be mimicked by psychogenic seizures

Adult↗

PubMed2001

Nonlinear EEG analysis in epilepsy: its possible use for interictal focus localization, seizure anticipation, and prevention.

Several recent studies emphasize the high value of nonlinear EEG analysis particularly for improved characterization of epileptic brain states. In this review the authors report their work to increase insight into the spatial and temporal dynamics of the epileptogenic process. Specifically, they discuss possibilities for seizure anticipation, which is one of the most challenging aspects of epileptology. Although there are numerous studies exploring basic neuronal mechanisms that are likely to be associated with seizures, to date no definite information is available regarding how, when, or why a seizure occurs. Nonlinear EEG analysis now provides strong evidence that the interictal-ictal state transition is not an abrupt phenomenon. Rather, findings indicate that it is indeed possible to detect a preseizure phase. The unequivocal definition of such a state with a sufficient length would enable investigations of basic mechanisms leading to seizure initiation in humans, and development of adequate seizure prevention strategies.

Animals↗