Search PubMed⌕ Search

Biomedical subjects

C E Elger

Publications and source records attributed to C E Elger.

At least 37 records · Page 2Linked to original sources
PubMed2005

Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy.

OBJECTIVE: Whereas the efficacy of the newer antiepileptic drugs (AEDs) is well established, there remain questions regarding their cognitive side effects. Therefore, we performed a comparative open randomized trial with TPM and TGB as add-on therapy, with particular consideration of cognition, mood, and health-related quality of life (HRQOL). METHODS: Forty-one patients with refractory epilepsy were randomly assigned to one of the two treatment groups (TPM vs TGB) and received neuropsychological testing at baseline (T1), after titration (3 months, T2), and during the maintenance phase (another 3 months, T3). Tests included measures of intelligence, attention, working memory, episodic memory, language, and self-report questionnaires regarding mood and HRQOL. Twenty patients (8 TPM, 12 TGB) discontinued the trial for different reasons (no group difference). RESULTS: Seizure outcome (intention-to-treat analysis) was comparably good in both groups (8.1% seizure free, 29.7% seizure reduction>50%). From baseline to after the titration paired sample t tests revealed significant deterioration in verbal fluency, language comprehension, working memory, and visual block tapping under TPM and a deterioration in verbal memory (delayed free recall) in the TGB group. These functions remained stable in the maintenance phase. Self-report measures initially indicated concerns about AED side effects in both groups and concerns about worse cognitive functioning and depression under TPM. In the maintenance phase the TGB group reported feeling a lack of energy, whereas patients on TPM demonstrated improvement on all QOLIE scales on a descriptive level. CONCLUSION: This study demonstrates the comparable efficacy of TPM and TGB. Consistent with previous reports, TPM but not TGB appears to be associated with persistent negative cognitive side effects on frontal lobe-associated functions, the degree of which may be estimated by the fact that this effect was observed with a very small sample size. In contrast, in patients taking TPM, initially negatively affected HRQOL returns to baseline in the long run on a descriptive level. The latter finding may be interpreted in accordance with the observation that objective performance and subjective self-report under TPM can be dissociated.

Adolescent↗
PubMed2004

Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy.

Increased hippocampal excitability constitutes a pathogenetic hallmark of pharmacoresistant human temporal lobe epilepsy (TLE). Metabotropic glutamate receptors (mGluRs) can be subdivided into three classes based on sequence homologies, mechanisms of signal transduction as well as pharmacological characteristics. Generally, class I mGluRs mediate neuronal excitation whereas activation of class II and III mGluRs decreases synaptic transmission. Changes in expression of class I and III mGluR subunits have been described in human TLE. It remains to be determined whether altered mGluR expression relates to differences in seizure susceptibility or hippocampal damage. Here, we examine the transcription levels of mGluRs class I (mGluR1 and 5) and III (mGluR4 and 7) in experimental TLE and correlate differential mGluR subunit expression with mouse-strain-dependent susceptibility to TLE induced by pilocarpine. Expression of mGluRs 1, 4, 5 and 7 was determined in epileptic dentate gyrus granule cells (DG) in CD1, C57BL/6 and FVB/N mice by real time RT-PCR. FVB/N mice appear significantly more vulnerable to pilocarpine-induced seizures than C57BL/6 and CD1 strains. RT-PCR analysis demonstrates an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR 1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6 (p<0.05, n=6 each) but not in the FVB/N strain. These results correlate differential expression of excitatory class mGluR I and inhibitory class mGluR III to seizure susceptibility and hippocampal damage. Our data suggest mGluRs class I and III as interesting potential therapeutic targets to interfere with hippocampal epileptogenesis and hyperexcitability.

Animals↗
PubMed2004

Recognition of famous faces in the medial temporal lobe: an invasive ERP study.

OBJECTIVE: To investigate the involvement of the rhinal cortex and the hippocampus in the processing of famous faces in contrast to nonfamous faces using intracranial event-related potentials (ERPs), and to analyze repetition effects for famous and nonfamous faces. METHODS: ERPs were elicited by pictures of famous and nonfamous faces and recorded from rhinal and hippocampal sites of intracranial electrodes in 10 presurgical patients with unilateral medial temporal lobe epilepsy. Famous and nonfamous faces were presented twice and mixed with distorted faces serving as targets. There was no instruction for an overt discrimination between famous and nonfamous faces. In contrast to nonfamous faces, famous faces stimulate processes related with access and retrieval of semantic memory. RESULTS: All faces evoked anterior medial temporal lobe N400-like (AMTL-N400) potentials in the rhinal cortex and P600-like potentials in the hippocampus. The AMTL-N400 and the hippocampal P600 amplitudes were larger for famous faces than for nonfamous faces. Mean amplitudes of the first and second presentation of famous faces suggest a repetition effect for the rhinal sites; however, they are significant only in the later signal components. No repetition effect was found for nonfamous faces and for potentials from the hippocampus. CONCLUSION: The anterior medial temporal lobe N400 and the hippocampal P600 may be related to the access and retrieval of person-specific semantic memory.

Adult↗
PubMed2004

An open study of tacrolimus therapy in Rasmussen encephalitis.

Seven patients with Rasmussen encephalitis (RE) were treated with the immunosuppressant tacrolimus and followed for a median of 22.4 months. They were compared with 12 historical untreated RE patients (median follow-up 13.9 months). The tacrolimus-treated patients had a superior outcome regarding neurologic function and progression rate of cerebral hemiatrophy but no better seizure outcome. No treated patient, but 7 of 12 control patients, became eligible for hemispherectomy. Tacrolimus did not have any major side effects.

Adolescent↗
PubMed2004

The impact of sex and language dominance on material-specific memory before and after left temporal lobe surgery.

Recent findings raised evidence that in early-onset left temporal lobe epilepsy, women show greater functional plasticity for verbal memory than men. In particular, women with lesion- or epilepsy-driven atypical language dominance show an advantage over men. The question asked in this study was whether there is evidence of sex- and language dominance-dependent late, i.e. adult age, plasticity for verbal memory when epilepsy surgery is performed in these patients. Pre- and 1-year postoperative memory performance was evaluated in 169 patients (94 males and 75 females) who underwent left temporal lobe surgery and who had WADA testing of hemispheric language dominance prior to surgery. Verbal memory and figural memory were assessed by list-learning paradigms. According to the Bonn intracarotid amobarbital test (IAT) protocol, patients were categorized into left dominant or atypically dominant (right, incomplete left or right, and bilateral dominant) groups. Results were controlled for the hypothesized sex differences. Thirty-four percent of men and 47% of women displayed patterns of atypical language dominance. Atypical dominance was related to an early onset of epilepsy. Men showed a larger time window for development of atypical dominance but, differently from women, the pattern of atypical dominance was more strictly determined by the age at onset of epilepsy. Atypically dominant women showed better verbal memory than typically dominant women or men. After surgery, right dominant patients had better verbal memory outcome than patients with bilateral or left language dominance who showed significant memory loss. No effect of sex on verbal memory change was found. Figural memory deteriorated in men and improved in women, when they were not left dominant. Seizure outcome had no effect on performance changes. It was concluded that better preserved verbal memory in atypically dominant women before surgery indicates greater benefit from atypical dominance in women than men with regard to the initial damage associated with left hemisphere epilepsy. Later in life, when epilepsy surgery causes additional damage, no such sex difference is observed, indicating that the women's advantage over men is fixed to an early time window in life. Postoperative changes in figural memory suggest dynamics in crowding and suppression patterns. Whether this reflects late plasticity and compensation needs further demonstration. For clinical practice, it is important to note that incomplete right hemisphere and bilateral language dominance do not protect against verbal memory loss after left-sided temporal lobe surgery.

Adult↗
PubMed2004

Rasmussen encephalitis with active inflammation and delayed seizures onset.

Severe focal epilepsy is regarded as a clinical hallmark of Rasmussen encephalitis (RE). The authors report two children with progressive hemiparesis, contralateral hemispheric atrophy, and pathologic features characteristic for RE. At histologic diagnosis and over several months, neither patient experienced seizures. The report enlarges the clinical spectrum of RE and suggests that seizures are not an obligatory presenting symptom of the disorder.

Age of Onset↗
PubMed2004

Interstitial radiosurgery in the treatment of gelastic epilepsy due to hypothalamic hamartomas.

The authors evaluated a new stereotactic radiosurgical approach in seven patients with gelastic epilepsy due to hypothalamic hamartomas. Stereotactic implantation of 125I-seeds into the hamartoma was feasible in six patients. At follow-up at least 1 year after interstitial radiotherapy, two patients had become seizure-free within 2 months, and two others had only persisting auras. There were no major perioperative or postoperative side effects.

Adolescent↗
PubMed2004

[How is oxcarbazepine different from carbamazpine?].

Oxcarbazepine (OXC, trade names Timox, Trileptal is a new antiepileptic drug (AED) for treatment of mono- and adjunctive therapy of partial seizures with or without secondary generalization for adults and children older than 6 years of age. Although OXC was developed through structural variation of carbamazepine in order to avoid side effects from metabolites, significant differences have emerged between the two drugs. The mechanism of action mainly involves blockade of sodium currents but differs from CBZ by modulating different types of calcium channels. In contrast to CBZ, which is oxidized by the cytochrome P-450 system, OXC undergoes reductive metabolism at its ketomoiety to form MHD, which is glucuronidated and excreted in the urine. Involvement of the hepatic cytochrome P450-dependent enzymes in the metabolism of OXC is minimal. This allows for better combining of OXC with other AEDs such as valproate. In postmarketing experience of over 800,000 patient-years, OXC also showed an advantageous risk-benefit ratio. Oxcarbazepine should be preferred over CBZ and other older AEDs due to its very good efficacy and better side effect profile in children, adolescents, and adults with partial seizures.

Adolescent↗
PubMed2004

The reelin pathway components disabled-1 and p35 in gangliogliomas--a mutation and expression analysis.

Focal epilepsies in young patients are frequently associated with differentiated glioneuronal tumours. Dysplastic neurones represent a characteristic neuropathological feature of gangliogliomas, the most common entity encountered in this group. Here, we have analysed two major components of the reelin pathway involved in neuronal migration and cortical development, that is, p35 and disabled-1 (dab1), in gangliogliomas. Genomic structures of human dab1 and p35 were identified 'in silico' using the HTGS databank, NCBI BLAST 2.1. DNA sequence analysis was carried out in gangliogliomas obtained from 29 epilepsy patients vs. peripheral blood DNA from non-affected control individuals (n = 100). Gene expression of dab1 and p35 was determined by real-time RT-PCR (reverse transcriptase polymerase chain reaction) in gangliogliomas (n = 14) vs. non-neoplastic central nervous system tissue (n = 20). The human dab1 gene contains 13 coding exons and is located on chromosome 1p31-32. A single coding exon constitutes the human p35 gene, which is located on chromosome 17q11.2. A novel homologueous genomic region on chromosome 2 has to be taken into account for future studies on p35. One ganglioglioma patient showed a unique polymorphism in the p35 gene. The single base exchange (C to A) at nucleotide 904 of the p35 cDNA (GenBank X80343, start ATG, codon 302) results in a leucine-isoleucine amino acid substitution. No mutations of the dab1 and p35 genes in gangliogliomas were observed. However, significantly lower levels of dab1 and p35 gene transcripts were detected in gangliogliomas compared to controls (dab1 28.24%, t-test P < 0.001; p35 21.28%, t-test P < 0.001, in gangliogliomas vs. controls). Our data suggest that mutational events of dab1 and p35 are not involved in the molecular pathogenesis of gangliogliomas. A potential functional role of these developmentally regulated genes for the formation of epileptogenic glioneuronal lesions remains to be elucidated.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Multidimensional assessment of personality in patients with psychogenic non-epileptic seizures.

OBJECTIVES: To determine whether patients with psychogenic non-epileptic seizures (PNES) have evidence of maladaptive personality, and whether they have a single or several different typical pathological personality profiles. METHODS: Patients were recruited from the department of epileptology, Bonn, Germany. In all, 85 patients with PNES and 63 with epilepsy completed a postal questionnaire including the dimensional assessment of personality pathology - basic questionnaire (DAPP-BQ). The DAPP-BQ was also completed by 100 healthy volunteers. The groups were compared and the PNES group was subjected to cluster analysis. RESULTS: Patients with PNES had a greater degree of personality abnormality than clinical and non-clinical controls. There were several clusters of personality pathology. The profile of the largest cluster (n = 43) resembled that found in borderline personality disorder, that of the second largest (n = 37) was characterised by an overly controlled personality, that of the third (n = 4) was similar to the profile in avoidant personality disorder. Outcome differed between clusters. CONCLUSIONS: Maladaptive personality is common in patients with PNES. PNES are associated with several distinct profiles of pathological personality. This is relevant because outcome differed between profiles.

Adult↗
PubMed2004

Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy.

BACKGROUND: Highly selective epilepsy surgery in temporal lobe epilepsy is intended to achieve seizure freedom at a lower cognitive risk than standard en bloc resections, but bears the risk of collateral cortical damage resulting from the surgical approach. OBJECTIVE: To investigate cortical damage associated with selective amygdalo-hippocampectomy (SAH). METHODS: 34 epileptic patients were evaluated. They were randomly assigned to SAH using either a sylvian (9 left/10 right) or a transcortical surgical approach (5 left/10 right). Postoperative MRI signal intensity changes adjacent to the approach were correlated with performance changes in serial word and design list learning. RESULTS: Losses in verbal learning and recognition memory were positively related to signal intensity changes, independent of the side of the resection, the surgical approach, or the extent of the mesial resection. Losses in consolidation/retrieval (memory) were greater after left sided surgery. Losses in design learning were related to right sided surgery and signal intensity changes. Seizure outcome (85% seizure-free) did not differ depending on the side or type of surgery. CONCLUSIONS: Collateral damage to cortical tissues adjacent to the surgical approach contributes to postoperative verbal and figural memory outcome after SAH. Controlling for collateral damage may clarify the controversial memory outcomes after SAH reported by different surgical centres.

Amygdala↗
PubMed2003

Hippocampal function and visual object processing in temporal lobe epilepsy.

Limbic event-related potentials related to verbal but not to visual recognition memory have been found to be attenuated within the epileptic hippocampus of patients with temporal lobe epilepsy (TLE). To identify hippocampal contributions to visual processing and memory we recorded intracranial ERPs directly from within the epileptic and the non-epileptic hippocampus in 12 patients with unilateral TLE during a visual object decision and naming task. While the non-epileptic hippocampus differentiated reliably between real and nonsense objects, this effect was completely eliminated within the epileptic mesial temporal lobe. This finding suggests that the hippocampus proper contributes to the semantic processing of visual objects and may help to explain visual memory deficits in TLE.

Adult↗
PubMed2003

Distribution of alpha and beta integrin subunits in the adult rat hippocampus after pilocarpine-induced neuronal cell loss, axonal reorganization and reactive astrogliosis.

Integrins are alphabeta-heterodimers that act as cell-extracellular matrix (ECM) and cell-cell adhesion molecules. During development, they are involved in axonal guidance, synaptogenesis, and in astrocytic maturation and migration. Here, we have examined the potential role of the integrin subunits alpha1-alpha5 and beta1-beta5 in axonal sprouting, synaptogenesis and reactive astrogliosis in the adult rat brain caused by pilocarpine-induced status epilepticus (SE). Strong hippocampal immunoreactivity of alpha1-alpha5, beta1, beta3, beta4, and beta5 was observed in the pia mater, in vascular endothelia, and in astrocytes at the pial surface. beta2 immunoreactivity was found exclusively in vascular endothelia. Pyramidal cells and interneurons of CA3-CA1, as well as hilar neurons revealed moderate alpha5 labeling in their cell bodies. Mossy fibers were immunoreactive for alpha2, beta4, and beta5. After pilocarpine-induced SE, strong immunoreactivity for alpha1, alpha2, alpha4, alpha5, beta1, beta3, and beta4 was observed in reactive astrocytes. Our results show that members of the integrin family are differently distributed in cellular and subcellular compartments of the hippocampus and undergo specific patterns of regulation, which may be important for lesion-induced reactive changes in the adult brain.

Animals↗
PubMed2003

Intrasubject reproducibility of presurgical language lateralization and mapping using fMRI.

BACKGROUND: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. OBJECTIVE: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. METHODS: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). RESULTS: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. CONCLUSION: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

Adolescent↗
PubMed2003

Dissecting out conscious and unconscious memory (sub)processes within the human medial temporal lobe.

The human medial temporal lobe (MTL) system mediates memories that can be consciously recollected. However, the specific natures of the individual contributions of its various subregions to conscious memory processes remain equivocal. Here we show a functional dissociation between the hippocampus proper and the parahippocampal region in conscious and unconscious memory as revealed by invasive recordings of limbic event-related brain potentials recorded during explicit and implicit word recognition: Only hippocampal and not parahippocampal neural activity exhibits a sensitivity to the implicit versus explicit nature of the recognition memory task. Moreover, only within the hippocampus proper do the neural responses to repeated words differ not only from those to new words but also from each other as a function of recognition success. By contrast parahippocampal (rhinal) responses are sensitive to repetition independent of conscious recognition. These findings thus demonstrate that it is the hippocampus proper among the MTL structures that is specifically engaged during conscious memory processes.

Brain Mapping↗
PubMed2003

Clinical and neuropsychological characteristics of pediatric epilepsy patients with atypical language dominance.

Studies on intracarotid amobarbital procedures (IAP) in pediatric patients are rare and mainly focus on practicability aspects. Very few studies have reported characteristics of children with atypical language dominance. We compared children with left-sided focal epilepsy and atypical (i.e., right or bilateral) versus left-sided language representation (n=12 versus 17). Our results indicate a higher incidence of left handedness, extratemporal lesions, an earlier onset of epilepsy, and a neuropsychological "crowding effect" with distinct nonverbal memory deficits in the atypical group. We conclude that atypical language representation in children with left-sided epilepsy is associated with similar characteristics as in adults. It is recommended that the possibility of a language shift in the presurgical workup of pediatric patients be considered, particularly if a left-hemispheric epileptic focus is suspected.

Adolescent↗
PubMed2003

Molecular and functional changes in voltage-dependent Na(+) channels following pilocarpine-induced status epilepticus in rat dentate granule cells.

Status epilepticus (S.E.) is known to lead to a large number of changes in the expression of voltage-dependent ion channels and neurotransmitter receptors. In the present study, we examined whether an episode of S.E. induced by pilocarpine in vivo alters functional properties and expression of voltage-gated Na(+) channels in dentate granule cells (DGCs) of the rat hippocampus. Using patch-clamp recordings in isolated DGCs, we show that the voltage-dependent inactivation curve is significantly shifted toward depolarizing potentials following S.E. (half-maximal inactivation at -43.2+/-0.6 mV) when compared with control rats (-48.2+/-0.8 mV, P<0.0001). The voltage-dependent activation curve is significantly shifted to more negative potentials following S.E., with half-maximal activation at -28.6+/-0.8 mV compared with -25.8+/-0.9 mV in control animals (P<0.05). The changes in voltage dependence resulted in an augmented window current due to increased overlap between the activation and inactivation curve. In contrast to Na(+) channel voltage-dependence, S.E. caused no changes in the kinetics of fast or slow recovery from inactivation. The functional changes were accompanied by altered expression of Na(+) channel subunits measured by real-time reverse transcription-polymerase chain reaction in dentate gyrus microslices. We investigated expression of the pore-forming alpha subunits Na(v)1.1-Na(v)1.3 and Na(v)1.5-Na(v)1.6, in addition to the accessory subunits beta(1) and beta(2). The Na(v)1.2 and Na(v)1.6 subunit as well as the beta(1) subunit were persistently down-regulated up to 30 days following S.E. The beta(2) subunit was transiently down-regulated on the first and third day following S.E. These results indicate that differential changes in Na(+) channel subunit expression occur in concert with functional changes. Because coexpression of beta subunits is known to robustly shift the voltage dependence of inactivation in a hyperpolarizing direction, we speculate that a down-regulation of beta-subunit expression may contribute to the depolarizing shift in the inactivation curve following S.E.

Animals↗