C Elger

Publications (10)32.01 Total impact

• Article: Neue Entwicklungen der Epileptogenese und therapeutische Perspektiven

  H. Lerche, A. Vezzani, H. Beck, I. Blümcke, Y. Weber, C. Elger
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  ABSTRACT: Die Epileptogenese beschreibt die Entstehungsmechanismen von Epilepsien. Wir haben 4Gebiete ausgewählt, auf denen entscheidende Fortschritte für das Verständnis der Epileptogenese erzielt wurden. Dies betrifft im Einzelnen (1) inflammatorische Prozesse, denen bei der Entstehung von Temporallappenepilepsien mit Hippokampussklerose (TLE mit HS) eine zunehmende Bedeutung zukommt, (2) Störungen intrinsischer Eigenschaften von neuronalen Kompartimenten, v.a. erworbene Störungen von Ionenkanälen, von denen hier bei der TLE mit HS solche in Dendriten beschrieben werden sollen, (3) epigenetische Effekte, die z.B. die Methylierung von Promotoren betreffen und dadurch sekundär die Expression bestimmter Gene verändern und die auch bei der TLE mit HS gefunden werden, und schließlich (4) die Epileptogenese der idiopathischen Epilepsien, die durch angeborene genetische Veränderungen verursacht werden und überwiegend Ionenkanäle betreffen. Neben grundlagenwissenschaftlichen Aspekten wird auf klinische Konsequenzen und therapeutische Perspektiven eingegangen. Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical consequences and therapeutic perspectives. SchlüsselwörterEpilepsie–Inflammation–Ionenkanal–Epigenetik–Genetik KeywordsEpilepsy–Inflammation–Ion channel–Epigenetics–Genetics
  Der Nervenarzt 04/2012; 82(8):978-985. · 0.68 Impact Factor
• Article: [New developments in epileptogenesis and therapeutic perspectives].

  H Lerche, A Vezzani, H Beck, I Blümcke, Y Weber, C Elger
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  ABSTRACT: Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical consequences and therapeutic perspectives.
  Der Nervenarzt 08/2011; 82(8):978-85. · 0.68 Impact Factor
• Article: Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy.

  M J Brodie, H Lerche, A Gil-Nagel, C Elger, S Hall, P Shin, V Nohria, H Mansbach
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  ABSTRACT: This study assessed the efficacy and safety of the neuronal potassium channel opener ezogabine (US adopted name; EZG)/retigabine (international nonproprietary name; RTG) as adjunctive therapy for refractory partial-onset seizures. This was a multicenter, randomized, double-blind, placebo-controlled trial in adults with ≥4 partial-onset seizures per month receiving 1 to 3 antiepileptic drugs. EZG (RTG) or placebo, 3 times daily, was titrated to 600 or 900 mg/d over 4 weeks, and continued during a 12-week maintenance phase. Median percentage seizure reductions from baseline and responder rates (≥50% reduction in baseline seizure frequency) were assessed. The intention-to-treat population comprised 538 patients (placebo, n = 179; 600 mg, n = 181; 900 mg, n = 178), 471 of whom (placebo, n = 164; 600 mg, n = 158; 900 mg, n = 149) entered the maintenance phase. Median percentage seizure reductions were greater in EZG (RTG)-treated patients (600 mg, 27.9%, p = 0.007; 900 mg, 39.9%, p < 0.001) compared with placebo (15.9%). Responder rates were higher in EZG (RTG)-treated patients (600 mg, 38.6%, p < 0.001; 900 mg, 47.0%, p < 0.001) than with placebo (18.9%). Treatment discontinuations due to adverse events (AEs) were more likely with EZG (RTG) than with placebo (placebo, 8%; 600 mg, 17%, 900 mg, 26%). The most commonly reported (>10%) AEs in the placebo, EZG (RTG) 600 mg/d, and EZG (RTG) 900 mg/d groups were dizziness (7%, 17%, 26%), somnolence (10%, 14%, 26%), headache (15%, 11%, 17%), and fatigue (3%, 15%, 17%). In this dose-ranging, placebo-controlled trial, adjunctive EZG (RTG) was effective and generally well tolerated in adults with refractory partial-onset seizures. This study provides Class II evidence that adjunctive EZG/RTG reduces the occurrence of partial-onset seizures.
  Neurology 10/2010; 75(20):1817-24. · 8.31 Impact Factor
• Article: The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression.

  C Montag, B Weber, K Fliessbach, C Elger, M Reuter
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  ABSTRACT: The role of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of affective disorders such as depression has been controversial. Mounting evidence comes from structural imaging, that the functional BDNF Val66Met polymorphism influences the hippocampal volume with carriers of the 66Met allele (Val/Met and Met/Met group) having smaller hippocampi. Given that stress-induced atrophy of the hippocampus is associated with the pathogenesis of affective disorders, the functional BDNF Val66Met polymorphism could be an incremental risk factor. Eighty-seven healthy Caucasian participants underwent structural imaging and were genotyped for the BDNF Val66Met polymorphism. Data were analysed by means of voxel-based morphometry (VBM). Region of interest (ROI) analyses revealed an association between the 66Met allele and smaller parahippocampal volumes and a smaller right amygdala. In addition, the whole-brain analysis showed that the thalamus, fusiformus gyrus and several parts of the frontal gyrus were smaller in 66Met allele carriers. This study demonstrates that the impact of the BDNF Val66Met polymorphism is not confined to the hippocampus but also extends to the parahippocampal gyrus and the amygdala.
  Psychological Medicine 05/2009; 39(11):1831-9. · 6.16 Impact Factor
• Article: Sexuality in male psychiatric inpatients. a descriptive comparison of psychiatric patients, patients with epilepsy and healthy volunteers.

  J Westheide, C Helmstaedter, C Elger, D Cooper-Mahkorn, B Sträter, W Maier, K U Kühn
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  ABSTRACT: The majority of psychiatric patients suffer from sexual dysfunction. Although sexual impairment is a major cause for non-compliance in psychiatric patients, it remains underdiagnosed by the attending physician. Therefore, the aim of the following study was to examine sexual behaviour and sexual dysfunction in a large sample of psychiatric patients. Male psychiatric inpatients received a questionnaire for sexuality ("Sexualitätsfragebogen für Männer", SFM) examining various aspects of sexual behaviour (e.g., value of sexuality, sexual dysfunction). Questionnaires from 351 patients were analysed. Additionally, 55 male healthy controls and 52 male patients with epilepsy were recruited. Psychiatric patients demonstrated more severe sexual dysfunction in the acute phase of their illness as well as in the premorbid time period compared with healthy controls. Patients with epilepsy showed only mild current sexual dysfunction (in the acute phase of the illness), with the exception of persisting erectile dysfunction. When comparing the two groups of patients, the psychiatric patients reported more current sexual impairments. Sexual dysfunction is not limited to the acute phase of psychiatric illnesses. Hence, treatment and follow-up must be geared towards such aspects of the quality of life while focussing on coping strategies.
  Pharmacopsychiatry 10/2007; 40(5):183-90. · 2.07 Impact Factor
• Article: Evidence of brain abnormality in patients with psychogenic nonepileptic seizures.

  M Reuber, G Fernández, C Helmstaedter, A Qurishi, C E. Elger
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  ABSTRACT: Markers of brain abnormalities in patients with psychogenic nonepileptic seizures (PNES) were studied to explore whether physical brain disorder is associated with an increased risk of PNES. Evidence of epileptiform EEG changes, MRI abnormalities, and neuropsychological (NPS) deficits was obtained from the records of 329 consecutive patients in whom the diagnosis of PNES was established at our center between 1991 and 2001. Two hundred six patients had PNES alone, and 123 PNES and epilepsy (PNES+E). In the PNES-only group, at least one marker of brain disorder was detected in 22.3% of patients (epileptiform potentials in 8.7%, MRI changes in 9.7%, NPS deficits in 9.7%). The actual prevalence of abnormalities is likely to be higher because 54.9% of the patients with only psychogenic seizures did not undergo MRI or neuropsychological testing. Evidence of brain abnormality was found more frequently in the PNES+E group (epileptiform potentials in 70.7%, MRI changes in 60.2%, NPS deficits in 52.8%). Although markers of brain abnormality were detected much less commonly in the PNES than in the PNES+E group, they were still found in a substantial proportion of patients with PNES alone. This suggests that physical brain disease plays a role in the development of PNES. Markers of physical abnormality were not more common in the right hemisphere.
  Epilepsy & Behavior 07/2002; 3(3):249-254. · 2.34 Impact Factor
• Article: Neuropsychological Outcome in Children after Frontal Lobe Epilepsy Surgery.

  M Lendt, U Gleissner, C Helmstaedter, R Sassen, H Clusmann, C E. Elger
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  ABSTRACT: We investigated the neuropsychological performance of children with frontal lobe epilepsy (FLE, n = 12) before and 1 year after surgery. Children with temporal lobe epilepsy (TLE, n = 12) were included as control group. Preoperatively, children with FLE had a significantly higher IQ than children with TLE, but were significantly more often impaired in manual motor coordination. Postoperatively, both groups improved in attention, short-term and long-term memory, and manual coordination, although the latter was not significant. Neuropsychological outcome in FLE patients was not better in seizure-free patients than in patients with continuing seizures. To avoid deterioration in language functions of patients in whom surgery involved left area 44, correspondence of results in cortical stimulation and intracarotid amytal test may be essential. All in all, our data indicate a favorable cognitive outcome in children 1 year after frontal lobe surgery.
  Epilepsy & Behavior 03/2002; 3(1):51-59. · 2.34 Impact Factor
• Article: Postsurgical outcome of children and adolescents with medically refractory frontal lobe epilepsies.

  T Kral, S Kuczaty, I Blümcke, H Urbach, H Clusmann, O D Wiestler, C Elger, J Schramm
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  ABSTRACT: In the adult population surgical treatment is generally less favorable for refractory frontal lobe epilepsy (FLE) than for temporal lobe epilepsy (TLE). Predictive factors and outcome of FLE surgery had not previously been described for the pediatric and adolescent population. Therefore, 32 children and adolescents who underwent FLE surgery were analyzed in this study. Medical records were reviewed for demographic data, presurgical evaluation procedures, surgical procedures, pathological findings and follow-up. Mean age at operation was 10.8 years, with seizure onset at 4.6 years. Excellent outcomes were observed in 21 of the 32 patients following evaluation a mean of 34.5 months after surgery. Nineteen of 22 patients became seizure free after tailored resections, versus 2 out of 10 after lobectomy. Transient neurological and surgical complications occurred in 4 patients. Focal neoplastic lesions detectable by MRI were associated with a favorable outcome. As seen in adult FLE series, the detection of a resectable ictal neoplastic lesion on preoperative MRI is associated with an excellent outcome comparable to that of TLE surgery.
  Child s Nervous System 11/2001; 17(10):595-601. · 1.54 Impact Factor
• Article: Temporal lobe epilepsy associated up-regulation of metabotropic glutamate receptors: correlated changes in mGluR1 mRNA and protein expression in experimental animals and human patients.

  I Blümcke, A J Becker, C Klein, C Scheiwe, A A Lie, H Beck, A Waha, M G Friedl, R Kuhn, P Emson, C Elger, O D Wiestler
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  ABSTRACT: Aberrant axonal reorganization and altered distribution of neurotransmitter receptor subtypes have been proposed as major pathogenic mechanisms for hippocampal hyperexcitability in chronic temporal lobe epilepsies (TLE). Recent data point to excitatory class I metabotropic glutamate receptors (mGluR1 and mGluR5) as interesting candidates. Here, we have analyzed the hippocampal distribution and mRNA expression of mGluR1 and mGluR5 in two rat models of limbic seizures, i.e. electrical kindling and intraperitoneal kainate injections, as well as in human TLE. Quantitative RT-PCR analysis detected a significant increase of hippocampal mGluR1 gene transcript levels in kainate treated and kindled rats. In addition, microdissected hippocampal tissue samples localized this increase to the dentate gyrus. Using immunohistochemistry with mGluR1alpha subtype specific antibodies, increased labeling was observed within the dentate gyrus molecular layer (DG-ML). A similar pattern of increased mGluR1alpha neuropil staining was found within the DG-ML of epilepsy patients (n = 42) compared with peritumoral hippocampus specimens obtained from nonepileptic patients (biopsy controls, n = 3). This increase was detected in TLE patients with segmental hippocampal cell loss, as well as in TLE patients with focal lesions but no histopathological alterations of the hippocampus. In contrast, mGluR5 immunoreactivity and mRNA expression were not significantly altered in the DG-ML. Our data demonstrate a striking regional induction of mGluR1alpha in the hippocampal dentate gyrus of experimental animals with limbic seizures as well as in human patients with chronic, intractable TLE. This increase corresponds to functional alterations of class I mGluRs observed in seizure models and may significantly contribute to hippocampal hyperexcitability in focal human epilepsies.
  Journal of Neuropathology and Experimental Neurology 02/2000; 59(1):1-10. · 4.26 Impact Factor
• Article: Verbal working memory components can be selectively influenced by transcranial magnetic stimulation in patients with left temporal lobe epilepsy.

  E Düzel, A Hufnagel, C Helmstaedter, C Elger
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  ABSTRACT: The aim of this study was to investigate whether transcranial magnetic stimulation (TMS) can be used for a lateralization of verbal and non-verbal memory functions in candidates for epilepsy surgery by inducing focal, material-specific memory deficits. Twenty patients who underwent presurgical epilepsy evaluation with chronically implanted subdural strip electrodes were submitted to focal TMS over the temporal lobes and the vertex while sequences of items of the Digit Span and the Corsi Block test were presented on a computer screen. TMS was applied synchronously or 200 msec following presentation of each item. The effects of TMS on the memory span and the serial position curve were analysed in comparison to baseline levels. The following results were obtained: the quantitative effects on the verbal (Digit Span) and non-verbal (Corsi Block) memory span were not significant, but there were significant qualitative changes of serial position effects. In the group of six patients with left temporal epilepsy, TMS over the left temporal lobe induced a significant recency effect in the Digit Span test, while TMS over the vertex significantly increased the recency errors. The absolute number of errors remained unchanged. No such effects were observed in the group of nine patients with right temporal lobe epilepsy. These results suggest that in the presence of a left temporal lobe focus TMS can induce qualitative, material specific changes in verbal working memory (phonological loop) which become apparent in the serial position curve. The dissociation of TMS effects for temporal and vertex stimulation imply that TMS can selectively influence specific phonological loop components and that the phonological loop has a functionally and neuroanatomically multimodular structure.
  Neuropsychologia 09/1996; 34(8):775-83. · 3.64 Impact Factor