Biomedical subjects

C E Elger

Publications and source records attributed to C E Elger.

At least 109 records · Page 6Linked to original sources

PubMed2000

[Therapy of generalized tonic-clonic status epilepticus in adulthood].

If continuous seizure activity lasts longer than 5 minutes generalized tonic-clonic seizures require prompt treatment, if significant morbidity and mortality are to be avoided. The mortality varies (mean: 20%) depending on patient age and etiology. Control of status epilepticus is achieved by benzodiazepines in about 80% of cases: Lorazepam is recommended due to its longer-acting effects on the central nervous system. To maintain the anticonvulsive effect phenytoin is usually administered intravenously. Fosphenytoin (not approved in Germany) has advantages over phenytoin, because it can be given three times more rapidly and produces fewer side effects. The IV use of valproic acid in status epilepticus seems to be promising, but needs further evaluation. There is no generally accepted treatment protocol for the therapy of persistent seizure activity lasting more than 60 minutes (i.e., refractory status epilepticus). Usually phenobarbital, or general anesthesia with thiopental or pentobarbital are treatment recommendations. In recent reports, the administration of midazolam or propofol proved to be effective and well-tolerated.

Anticonvulsants↗

PubMed2000

[Temporal lobe epilepsy: longitudinal clinical, neuropsychological and psychosocial follow-up of surgically and conservatively managed patients].

Little is known about the differential long-term outcome from surgical and nonsurgical therapy in patients with chronic epilepsy. In the present study, 161 surgically or nonsurgically treated patients with drug-resistant temporal lobe epilepsy (TLE) were re-evaluated according to a detailed clinical, neuropsychological, and psychosocial protocol with a mean follow-up interval of 58 months. Freedom from seizures was achieved in 64% of the surgical group; yet 23% of the nonsurgical patients became seizure-free as a result of modifications in drug therapy. Generally, socioeconomic development was poorer in nonsurgical than in surgical patients. Freedom from seizures, employment, and the absence of depression were significant determinants of better quality of life. As for neuropsychological outcome, verbal memory impairment was common after left-sided temporal resection; however, there was no evidence of a marked progression of cognitive impairment after the first postoperative year. In nonsurgical patients, too, cognitive capacities were surprisingly stable over time, although persisting seizures and good baseline performance predicted a poorer neuropsychological outcome.

Adult↗

PubMed2000

[Oxcarbazepine (Trileptal). An effective and well tolerated new drug as first choice in treatment of focal seizures].

Oxcarbazepin (OXC; 10,11-dihydro-10-oxo-5H-dibenz-[b,f]azepin-5-carboxamid, trade name Trileptal) is a new antiepileptic drug for treatment of mono- and adjunctive therapy of partial seizures with or without secondary generalization for adults and children above 6 years of age. It was developed through structural variation of carbamazepine. Extensive postmarketing use includes more than 200,000 patient years. The mechanism of action mainly involves blockage of sodium currents. The recommended daily starting dose of oxcarbazepin for both mono- and adjunctive treatment is 8-10 mg/kg (600 mg/day for adults) in two doses and can be titrated according to clinical benefit up to 2400 mg/day. Oxcarbazepin undergoes reductive metabolism at its keto moiety to form MHD, which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. Thus, OXC has limited drug interactions and does not require slow titration, allowing for better tolerability. Oxcarbazepin compares favorably to presently available new anticonvulsants of the second generation for two reasons: it is available immediately for both mono- and adjunctive therapy in adults and children, and extensive postmarketing experience from many countries is already available. In addition, OXC has been thoroughly tested in an unusually large clinical development program and been shown to be similarly effective as standard antiepileptic drugs.

Adult↗

PubMed2000

Corticosteroid receptor mRNA expression in the brains of patients with epilepsy.

The effects of corticosteroids in the brain are mediated through the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid/mineralocorticoid receptor expression (liver/kidney). GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain.

Adolescent↗

PubMed2000

Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1, 2, 3 and 4 in epileptic human hippocampus.

Sex steroid hormones exert important influences on neuroendocrine and behavioural brain function. As neuroactive steroids they are able to modify neuronal excitability. Unbalanced synthesis may thus be implicated in pathophysiological conditions, such as epilepsy, migraine, depression and anxiety. In sex steroid metabolism, 17beta-hydroxisteroid dehydrogenases (17beta-HSDs) play a crucial role in catalyzing the final steps of androgen and estrogen biosynthesis. The hippocampus appears to be a major target area of neurosteroidal action. The expression of 17beta-HSD isozymes has not yet been studied in human hippocampus. Therefore, we investigated the expression of 17beta-HSD 1, 2, 3 and 4 mRNAs in hippocampal tissue specimens obtained at neurosurgery from 42 patients with pharmacoresistant temporal lobe epilepsy. A competitive RT-PCR assay was used to quantify the mRNA transcript level. 17beta-HSD 1 mRNA concentrations were 10000 fold lower in the hippocampus compared to placental tissue, whereas 17beta-HSD 3 mRNA concentrations were 50 fold lower than in testis and 17beta-HSD 4 concentrations were in the same order of magnitude as in liver. 17beta-HSD 2 mRNA was not expressed. 17beta-HSD 1, 3 and 4 mRNA concentrations in the hippocampus showed no significant differences between men and women and there were no significant differences in expression levels of these enzymes between patients with Ammon's horn sclerosis (AHS) and those with histopathologically normal hippocampus associated with extrahippocampal lesions. No significant correlation could be detected between duration of epilepsy, individual seizure frequency and expression levels of 17beta-HSDs. In conclusion, the present study is the first to demonstrate mRNA expression of 17beta-HSD 1, 3 and 4 in the epileptic human hippocampus. Together with data on 5alpha-reductase 1, 3alpha-hydroxisteroid oxidoreductase 2 and cytochrome P450scc, previously shown to be expressed in the human hippocampus also, our data provide further evidence for the existence of sex steroid formation and metabolism in this specific brain area.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women.

A prospective cohort analysis of premenopausal women with focal epilepsy was conducted in order to determine whether polycystic ovary syndrome (PCOS) is a common finding in women treated with antiepileptic drugs (AED). This study was carried out in 93 of 150 women (aged between 20 and 53 years; mean, 34.3 years) with chronic focal epilepsy consecutively cared for at the Department of Epileptology, University of Bonn: 38 were receiving one AED (18 valproate, 20 carbamazepine), 36 more than one drug, and 19 were without medication. Patients were followed-up for 6 months. PCOS was defined as hyperandrogenism (testosterone concentration, > 0.7 ng/ml) combined with oligomenorrhoea (cycle length, > 35 days) or amenorrhoea. PCOS was identified in two out of 19 (10.5%) patients receiving no medication; in four of 38 (10.5%) of patients receiving monotherapy, and in none of the patients receiving more than one AED. The incidence of PCOS in patients treated with valproate monotherapy (11.1%) was similar to that in patients treated with carbamazepine (10%) and also to that in patients not treated with AEDs. The results of this study suggest that the manifestation of PCOS in women with focal epilepsy is not related to the administration of valproate or carbamazepine.

Adult↗

PubMed2000

Behavioral markers for self- and other-attribution of memory: a study in patients with temporal lobe epilepsy and healthy volunteers.

OBJECTIVES: The correlation between clinical measures of memory and subjectively reported memory is often poor. Regarding this we investigated in patients with temporal lobe epilepsy (TLE) whether there is evidence that persons mistake other cognitive performances for memory due to subjective memory theories. METHODS: a neuropsychological test battery comprising measures of attention, verbal/figural memory and other visual or language related functions was applied in patients with left (L-TLE, n=24) or right temporal lobe epilepsy (R-TLE, n=21) and healthy volunteers (n=20). In addition, subjective self- and other-reported memories were assessed by the subjective memory questionnaire (SMQ). RESULTS: subjective measures as well as objective measures indicate significant cognitive impairment in TLE and in L-TLE in particular. Self-reports and other-reports are interrelated but only self-reported memory correlates significantly with objective memory performance. Regression analysis indicates that self-reported memory is best predicted by word fluency followed by verbal memory and vocabulary, and other-reported memory is best predicted by word fluency, vocabulary, confrontation naming, and verbal recognition memory. DISCUSSION: The results suggest that attribution of memory refers to a subjective view of memory which is wider than its neuropsychological definition. It furthermore differs dependent on the observer's point of view. Memory is preferentially concluded from verbal behaviors. These reflect language skills and access to vocabulary rather than declarative memory. Consideration of subjective memory theories and associated attribution processes can significantly contribute to our understanding of the often-poor relationship between objective test results and subjective impairment in TLE.

Adolescent↗

PubMed2000

Tiagabine in the treatment of epilepsy--a clinical review with a guide for the prescribing physician.

Tiagabine is currently recommended mainly as add-on therapy in adults and children above 12 years with partial epilepsy not satisfactorily controlled with other antiepileptic drugs. Based on available evidence and our clinical experience, tiagabine should be used preferably in patients sharing one or more of the following additional features, (i) a history of drug-induced cutaneous adverse events; (ii) mild to moderate epilepsy allowing for a slow titration and gradual onset of anticonvulsant action over a few weeks; (iii) patients for whom it is particularly important to avoid a deterioration in cognitive performance; and, (iv) patients who failed to respond to previous treatment with sodium channel blocker agents as they may particularly benefit from the introduction of tiagabine, due to its GABAergic mechanism of action. Tiagabine can also be used successfully in other patients with refractory partial epilepsy. Tiagabine is not indicated for patients with generalized or unclassified epilepsies and for patients with severely impaired liver function.

Adult↗

PubMed2000

No evidence for association between the KCNQ3 gene and susceptibility to idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) comprises a heterogeneous group of disorders, in which a high genetic predisposition and a complex mode of inheritance have been suggested. Recent identification of ion channel gene mutations in Mendelian epileptic disorders suggests genetically driven neuronal hyperexcitability as one important factor in epileptogenesis. Mutations in two neuronal voltage-gated potassium channel genes (KCNQ2 and KCNQ3) have already been shown to cause epilepsy (BFNC), and we now tested the hypothesis that genetic variation in the KCNQ3 gene confers liability to common IGE subtypes. Length variation of two intragenic polymorphic markers (D8S558 and D8S1835) were therefore assessed in 71 nuclear families ascertained for an affected child. However, the transmission-disequilibrium-test did not show significant differences between the transmitted and non-transmitted parental alleles. Thus, our findings do not provide evidence that genetic variation in the KCNQ3 gene exerts a relevant effect in the etiology of common IGE subtypes.

Alleles↗

PubMed2000

Vagus nerve stimulation is associated with mood improvements in epilepsy patients.

Vagus nerve stimulation (VNS) has gained increasing acceptance for treatment of drug-resistant seizures. The aim of this study was to evaluate effects of VNS on depressed mood in epilepsy patients during the first 6 months after implantation of the stimulation device. This study was conducted as an addition to the international multisite randomized and double-blind controlled trial on anti-seizure effects of VNS (EO3). Only adult patients with >4/month medication-resistant complex-partial seizures were included (N=11). During the acute phase of the study (3 months after implantation), patients were randomly assigned to low (stimulation detection) versus high stimulation (maximal tolerability, maximum 1.75 mA). Mood and mood changes were recorded based on standardized psychiatric rating scales and self-report questionnaires. Patients were assessed 4 weeks before (baseline) as well as 3 and 6 months after implantation. Significant positive mood effects were observed in most scales and subscales at the 3-month follow-up (P<0.05). Mood improvements were sustained at the 6-month follow-up and were independent of effects on seizure activity (9/11 mood responders versus 2/11 seizure responders). Mood effects appeared more pronounced in the high stimulation group after the acute study phase, but findings were not significant (P<0.10). VNS is associated with mood improvements in patients with epilepsy, but to confirm VNS dose effects, studies with more statistical power are needed.

Adult↗

PubMed2000

Association analysis between a regulatory-promoter polymorphism of the human monoamine oxidase A gene and idiopathic generalized epilepsy.

Monoaminergic neurotransmission plays an important role in the regulation of neuronal network excitability and seizure activity. Therapeutic inhibition of the mitochondrial enzyme monoamine oxidase A (MAO-A), which is involved in the degradation and inactivation of monoaminergic neurotransmitters, has been shown to confer a potent anticonvulsant effect. These and other findings suggest a possible role of the X-linked MAO-A gene in epileptogenesis. Therefore, our study was designed to test for an association between a novel MAO-A gene promoter polymorphism and common subtypes of idiopathic generalized epilepsy (IGE). The length of a 30-bp repetitive sequence approximately 1.2 kb upstream of the ATG initiation codon was assessed in 126 patients with juvenile myoclonic epilepsy (JME), 122 patients with idiopathic absence epilepsy (IAE), and 248 healthy controls of German descent. Both sexes were analyzed separately. Although we observed a trend towards a lower number of heterozygotes carrying the 3 and 4 copy alleles in female IAE patients (chi2 = 3.813, df = 1, P = 0.053), allele frequencies did not deviate significantly between patients and controls. Thus, our results do not provide evidence for a contribution of the functional MAO-A gene promoter polymorphism to the pathogenesis of common IGE subtypes.

Adult↗

PubMed2000

Depression in patients with temporal lobe epilepsy is related to mesial temporal sclerosis.

Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depression Inventory in 60 patients with temporal lobe epilepsy, with particular consideration of morphological abnormalities within the temporal lobe (mesial temporal sclerosis (MTS) versus neocortical lesions) and lateralization of the lesion. Multivariate analyses indicated significant higher depression scores in MTS independent of the lateralization of the lesion. Depression was a good indicator for MTS but not vice versa. Hence, MTS can be discussed as a predisposing factor for the development of mood disorders in focal epilepsy.

Adult↗

PubMed2000

Single trial analysis of event related potentials: non-linear de-noising with wavelets.

We present and apply a method for single trial analysis of event related potentials (ERPs) that combines techniques from non-linear time series analysis with the wavelet transform. For this method, convincing results have already been achieved for simulated data as well as for intracranially recorded ERPs (Physica D 140 (2000) 257). However, ERPs are affected by a variety of external and internal experimental parameters, which makes the appropriate configuration of single trial analysis difficult. Thus, several pitfalls may occur in realistic applications. In this paper, we applied the method of non-linear de-noising with wavelets to both intra- and extracranially recorded ERPs, and show examples of how and where this single trial analysis can be used to obtain additional information on dynamic neural processes.

Brain↗

PubMed2000

Precipitating factors and therapeutic outcome in epilepsy with generalized tonic-clonic seizures.

OBJECTIVES: The aim of the study was to evaluate the influence of precipitating factors and therapy on the outcome of epilepsy with generalized tonic-clonic seizures. PATIENTS AND METHODS: Retrospective analysis of data from 34 patients (mean age at seizure onset 19 years; mean duration of follow-up 9.2 years) suffering from epilepsy of either cryptogenic or remote symptomatic (n = 19), or idiopathic (n = 15) etiology. The total number of seizures in all patients was 146. RESULTS: Without treatment 97 seizures manifested during 90.5 years without treatment (1.07 seizures/year), during treatment with carbamazepine or valproate 49 seizures occurred within 224 years (0.2 seizures/year). The frequency of seizures was significantly lower during treatment. Precipitating factors were found in relation to 31% of seizures in patients with remote symptomatic or cryptogenic epilepsy, and for 51% of seizures in patients with idiopathic epilepsy. CONCLUSIONS: There was a low frequency of seizures in patients with generalized tonic-clonic seizures. Precipitating factors are common. Antiepileptic drug treatment is effective.

Adolescent↗

PubMed2000

Muscle fibres: applications for the study of the metabolic consequences of enzyme deficiencies in skeletal muscle.

Mitochondrial function in saponin-permeabilized muscle fibres can be studied by high-resolution respirometry, laser-excited fluorescence spectroscopy and fluorescence microscopy. We applied these techniques to study metabolic effects of changes in the pattern of mitochondrial enzymes in skeletal muscle of patients with chronic progressive external ophthalmoplegia or Kearns-Sayre syndrome harbouring large-scale deletions of mitchondrial DNA (mtDNA). In all patients combined deficiencies of respiratory chain enzymes containing mitochondrially encoded subunits were observed. The citrate synthase-normalized activity ratios of these enzymes decreased linearly with increasing mtDNA heteroplasmy. This indicates the absence of any well-defined mutation thresholds for mitochondrial enzyme activities in the entire skeletal muscle. We applied metabolic control analysis to perform a quantitative estimation of the metabolic influence of the observed enzyme deficiencies. For patients with degrees of mtDNA heteroplasmy below about 60% we observed at almost normal maximal rates of respiration an increase in flux control coefficients of complexes I and IV. Permeabilized skeletal-muscle fibres of patients with higher degrees of mtDNA heteroplasmy and severe enzyme deficiencies exhibited additionally decreased maximal rates of respiration. This finding indicates the presence of a 'metabolic threshold' which can be assessed by functional studies of muscle fibres providing the link to the phenotypic expression of the mtDNA mutation in skeletal muscle.

Adult↗

PubMed2000

Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances.

Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE. During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.

Adult↗

PubMed2000

Ictal generalized rhythmic alpha activity during non-convulsive status epilepticus.

We investigated the repetitive manifestation of non-convulsive status epilepticus with an uncommon ictal electroencephalographic pattern observed in two patients suffering from epilepsy (aged 29 and 55 years). The patients had suffered from epilepsy since the age of 1 and 40 years, respectively. Interictal and ictal neurological, neuropsychological and electroencephalographic investigations were carried out. Non-convulsive status started and ended abruptly, clinically as well as electroencephalographically. The ictal electroencephalographic pattern was a monomorphic alpha activity with a generalized bilateral distribution. Altered responsiveness, sometimes eyelid myoclonia (in one patient) and amnesia were the most characteristic clinical findings during non-convulsive status. Intellectual development was delayed in the patient with early onset of epilepsy. However, this was not the case in the other patient, who developed memory impairment during the course of the disease. In both patients, lamotrigine added to valproate reduced the frequency of status epileptici significantly. Obviously, these patients suffer(ed) from a type of generalized non-convulsive status epilepticus with an uncommon electroencephalographic pattern.

Adult↗

PubMed2000

The impact of epilepsy surgery on sex hormones and the menstrual cycle in female patients.

We investigated the impact of temporal lobe epilepsy surgery on sex hormones and menstrual cycles. Sixteen female patients with temporal lobe epilepsy were investigated prior to surgery and 3, 6, and 12 months after surgery. The patients received carbamazepine (CBZ) as monotherapy (10 patients) or in combination with other antiepileptic drugs (six patients). Antiepileptic drugs were maintained after surgery. During the 1-year follow-up after surgery eight patients (50%) remained completely free of seizures. In another four patients (25%) only rare disabling seizures occurred. There were no significant differences between pre-surgical and post-surgical serum concentrations of testosterone, free testosterone, prolactin, dehydroepiandrosterone sulfate, growth hormone, cortisol and sex hormone binding globulin. There was, however, a significant increase in serum androstenedione concentration 6 months post-surgically (P < 0.02). Documentation of menstrual cycles in addition to laboratory parameters revealed individual post-surgical changes of the menstrual cycle in eight patients. Four patients had a change in menstrual periodicity: two patients with complete seizure control had regular cycles instead of oligomenorrhoea and two patients with incomplete seizure control had oligomenorrhoea instead of regular cycles. These data indicate that at least in some patients with temporal lobe epilepsy surgical treatment influences menstrual periodicity.

Adult↗