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Christoph Baumgartner

Publications and source records attributed to Christoph Baumgartner.

At least 19 recordsLinked to original sources
PubMed2006

In vitro responsiveness of human-drug-resistant tissue to antiepileptic drugs: insights into the mechanisms of pharmacoresistance.

Pharmacoresistance in epileptic patients may be ascribed to at least two, not mutually exclusive, mechanisms: a pharmacokinetic mechanism and a decreased sensitivity or availability of targets to antiepileptic drugs (AEDs; i.e., carbamazepine and phenytoin (CBZ, PHT)). Brain:plasma drug concentration ratios were determined intraoperatively during lobectomies performed to alleviate drug-resistant seizures. The brain:plasma ratio of CBZ was 1.48 when therapeutic serum levels (15-34 microM) were achieved. When concentrations of CBZ found in multiple-drug-resistant brain were directly applied to human cortical slices from drug-resistant patients made hyperexcitable and hypersynchronous by Mg(2+)-free media, bursting frequency was not significantly affected and overall excitability was reduced by 40%. Similar results were obtained for PHT. At higher AED concentrations (60-200 microM), a dose-dependent decrease of bursting frequency and amplitude was observed. Slices from drug-resistant epileptic patients made hypersynchronous/hyperexcitable by elevated potassium or inhibition of GABA-A receptors behaved similarly. Of note is the response of slices from human multiple-drug-resistant brain, which was greater than in rodent cortex from naive animals. Taken together, our results support the hypothesis that multiple drug resistance to AEDs involves cerebrovascular changes that impede the achievement of appropriate drug levels in the central nervous system.

Adolescent↗
PubMed2006

Panic attacks in an individual with bilateral selective lesions of the amygdala.

OBJECTIVE: To describe the unique case of a patient with panic attacks and bilateral selective amygdala lesions due to Urbach-Wiethe disease. DESIGN: Case report. SETTING: Epilepsy Monitoring Unit, Medical University of Vienna. Patient A 38-year-old man with Urbach-Wiethe disease developed spontaneous panic attacks and depressive mood, which ceased after antidepressive treatment. INTERVENTIONS: Video electroencephalography monitoring, magnetic resonance imaging, and neuropsychological testing. RESULTS: Extended video electroencephalography monitoring excluded an epileptic etiology of the panic attacks. Results of cranial magnetic resonance imaging showed bilateral selective calcifications of the whole amygdaloid complex. Neuropsychological testing revealed selective memory impairment of autobiographic episodes with preserved memory for autobiographic facts. CONCLUSIONS: Our findings indicate that the occurrence of panic attacks does not critically depend on the integrity of the amygdala. Furthermore, the neuropsychological findings in our patient suggest that the amygdala represents an essential neural substrate for the processing of episodic autobiographic memories.

Adult↗
PubMed2006

1H magnetic resonance spectroscopy at 3 T in cryptogenic and mesial temporal lobe epilepsy.

The objectives of this work were to compare concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), Glx (=Glu + Gln), myo-inositol (mI), total creatine (Cre) and other metabolites in the temporal lobes of patients with mesial temporal lobe epilepsy (mTLE), cryptogenic TLE (cTLE), who show no abnormalities in high-resolution MRI, and healthy controls using single voxel (1)H MRS at 3 T. Twelve patients with mTLE, nine with cTLE and 22 controls were investigated using a short echo time STEAM protocol. Voxels were positioned bilaterally in the medial and lateral temporal lobes. Spectra were processed with LCModel. Significantly lower mean NAA were detected in mTLE patients (P < 0.001) and a trend towards lower NAA in cTLE patients compared to controls (P = 0.053). Glx was not different between groups. Estimates of Glu showed a different metabolic pattern in mTLE with elevated Glu in lateral compared with medial voxels on the ipsilateral side to seizure onset (P = 0.019). MI concentrations were significantly lower in cTLE (P < 0.001) and in mTLE patients (P = 0.005) compared with healthy controls. MI/Cre was significantly reduced in cTLE patients only (P = 0.004). The results confirm low NAA in mTLE and to a lesser extent in cTLE patients. MI and mI/Cre were identified as potential metabolic indicators of the epileptogenic area in cTLE.

Adult↗
PubMed2006

Revisiting the role of magnetoencephalography in epilepsy.

PURPOSE OF REVIEW: This review considers the current role of magnetoencephalography in clinical epileptology. RECENT FINDINGS: While magnetoencephalography and electroencephalography complement each other for interictal spike detection, magnetoencephalography is more sensitive in neocortical epilepsy. In temporal lobe epilepsy, magnetoencephalography can attribute epileptic activity to subcompartments of the temporal lobe and differentiate between patients with mesial, lateral and diffuse seizure onsets. In extratemporal epilepsy, magnetoencephalography provides unique information in nonlesional cases and helps to define the relationship of epileptic activity with respect to lesions and eloquent cortex. Magnetoencephalography also contributes to the clinical decision process in patients with cortical dysplasias, Landau-Kleffner syndrome and recurrent seizures after prior epilepsy surgery. Magnetoencephalography-guided re-evaluation of magnetic resonance imaging helps to reveal previously unrecognized lesions. In a presurgical setting interictal magnetoencephalography was superior to scalp electroencephalography. Complete resection of the magnetoencephalography-defined irritative zone has prognostic implications on postoperative seizure control. Magnetoencephalography can reliably localize sensorimotor and language cortex. Disadvantages of this technique include the difficulties in obtaining ictal recordings and the considerable costs involved. SUMMARY: Magnetoencephalography has been developed to a valuable noninvasive tool in clinical epileptology. The development of approaches which take into account both magnetoencephalography and electroencephalography simultaneously should provide more useful information in the future.

Brain Mapping↗
PubMed2006

Lack of association between a GABA receptor 1 gene polymorphism and temporal lobe epilepsy.

PURPOSE: Recently a coding nonsynonymous single-nucleotide polymorphism (SNP; G1465A) in the GABBR1 gene was reported to be associated with the incidence and severity of temporal lobe epilepsy (TLE). To clarify the role of this polymorphism in TLE, we attempted to replicate this study. METHODS: We genotyped 188 unrelated patients with TLE (110 women, 78 men) and 259 controls of middle European descent by a restriction-length polymerase chain reaction (PCR) assay. RESULTS: Only two (0.5%) patients and none of the controls exhibited the heterozygous A/G genotype, which was previously reported to be overrepresented among patients as compared with controls. CONCLUSIONS: Although our study was sufficiently powered, we could not replicate the original association. Potential reasons for this failure could lie in subtle genetic differences between the studied populations or differences in the TLE phenotypes.

Adolescent↗
PubMed2005

Combined MEG/EEG analysis of the interictal spike complex in mesial temporal lobe epilepsy.

We studied the functional organization of the interictal spike complex in 30 patients with mesial temporal lobe epilepsy (MTLE) using combined magnetoencephalography (MEG)/electroencephalography (EEG) recordings. Spikes could be recorded in 14 patients (47%) during the 2- to 3-h MEG/EEG recording session. The MEG and EEG spikes were subjected to separate dipole analyses; the MEG spike dipole localizations were superimposed on MRI scans. All spike dipoles could be localized to the temporal lobe with a clear preponderance in the medial region. Based on dipole orientations in MEG, patients could be classified into two groups: patients with anterior medial vertical (AMV) dipoles, suggesting epileptic activity in the mediobasal temporal lobe and patients with anterior medial horizontal (AMH) dipoles, indicating involvement of the temporal pole and the anterior parts of the lateral temporal lobe. Whereas patients with AMV dipoles had strictly unitemporal interictal and ictal EEG changes during prolonged video-EEG monitoring, 50% of patients with AMH dipoles showed evidence of bitemporal affection on interictal and ictal EEG. Nine patients underwent epilepsy surgery so far. Whereas all five patients with AMV dipoles became completely seizure-free postoperatively (Class Ia), two out of four patients with AMH dipoles experienced persistent auras (Class Ib). This difference, however, was not statistically significant. We therefore conclude that combined MEG/EEG dipole modeling can identify subcompartments of the temporal lobe involved in epileptic activity and may be helpful to differentiate between subtypes of mesial temporal lobe epilepsy noninvasively.

Adult↗
PubMed2005

FMRI reveals functional cortex in a case of inconclusive Wada testing.

OBJECTIVES: The intracarotid amobarbital test (Wada test) currently represents the gold standard for preoperative lateralization of hemispheric dominance. Here, we report an epileptic patient with a longstanding extended lesion of the left hemisphere showing absence of motor and speech dysfunction with left carotid amobarbital injection, but tetraplegia and speech arrest with right carotid injection interpreted as a neuroplastic shift of motor and language functions to the right hemisphere. In contrast to the Wada results, motor functional magnetic resonance imaging (fMRI) showed a strong left hemispheric activation with right hand movements. METHODS: Right and left hand motor fMRI was performed. FMRI results and neurophysiological information obtained by motor and sensory evoked potential measurements were compared with the Wada test results. RESULTS: Initial interpretation of neuroplastic shifts of intrinsic left hemisphere functions to the right brain was revised after fMRI results which were confirmed by motor and sensory evoked potentials. CONCLUSION: As motor inactivation usually is thought to be the most robust feature of the Wada test, this case demonstrates that fMRI may reveal residual functional cortex in cases of inconclusive Wada results.

Adult↗
PubMed2005

Influence of functional haplotypes in the drug transporter gene ABCB1 on central nervous system drug distribution in humans.

BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms in the human multidrug-resistance gene ABCB1 have been reported to be associated with altered expression and function of P-glycoprotein, an efflux transporter, expressed at the blood-brain barrier. To test whether certain ABCB1 haplotypes contribute to interindividual differences in central nervous system drug distribution, brain distribution of a model P-glycoprotein substrate, the calcium channel inhibitor verapamil, was measured by positron emission tomography (PET) in 2 groups of healthy volunteers. METHODS: Ten homozygous carriers (cases) of the TTT haplotype (3435T, 1236T, and 2677T) and 10 controls homozygous for the wild-type CGC haplotype (3435C, 2677G, and 1236C) were administered a mean intravenous bolus of 412 +/- 114 MBq carbon 11-labeled verapamil containing less than 15 nmol of unlabeled verapamil. PET imaging of brain tissue and venous blood sampling were performed for 1 hour after dosing. RESULTS: As a measure of brain penetration, the ratio of PET area under the time-radioactivity curve (AUC) to plasma AUC was calculated from time-radioactivity curves, with a mean ratio of 1.1 +/- 0.3 (SD) (95% confidence interval, 0.9-1.3) for cases and 1.1 +/- 0.2 (95% confidence interval, 0.9-1.2) for controls, respectively (P = .96). Mean brain AUC values were 31.2 +/- 3.9 and 35.7 +/- 5.7 for the TTT and CGC haplotype, respectively (P = .11). Plasma AUCs were not significantly different. CONCLUSION: No difference in the brain distribution of [(11)C]verapamil could be detected in healthy volunteers differing in ABCB1 haplotypes.

Adult↗
PubMed2005

Somatostatin receptor type 2 undergoes plastic changes in the human epileptic dentate gyrus.

Temporal lobe epilepsy (TLE) is characterized by hippocampal sclerosis together with profound losses and phenotypic changes of different classes of interneurons, including those expressing somatostatin (SRIF). To understand the functional significance of the plasticity of SRIF transmission in TLE, unraveling the status of SRIF receptors is, however, a prerequisite. To address this issue, we characterized expression and distribution of the major SRIF receptor, the sst2 subtype, in hippocampal tissue resected in patients with TLE using complementary neuroanatomic approaches. In patients with hippocampal sclerosis, the number of cells expressing sst2 receptor mRNA as well as sst2 receptor-binding sites and immunoreactivity decreased significantly in the CA1-3, reflecting neuronal loss. By contrast, in the dentate gyrus, sst2 receptor mRNA expression was strongly increased in the granule cell layer, and sst2 receptor-binding sites and immunoreactivity was preserved in the inner but decreased significantly in the outer molecular layer. In this latter region, pronounced changes in SRIF terminal fields were observed. Decreased receptor density in the distal dendrites of granule cells is likely to reflect downregulation of sst2 receptors in response to physiopathologic release of SRIF. Because sst2 receptors have anticonvulsant and antiepileptogenic properties, this phenomenon may contribute to the etiology of TLE seizures.

Adolescent↗
PubMed2005

A pilot study on brain-to-plasma partition of 10,11-dyhydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide and MDR1 brain expression in epilepsy patients not responding to oxcarbazepine.

PURPOSE: We measured the brain-to-plasma partition of 10,11-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide (10-OHCBZ) in epilepsy patients undergoing surgery to alleviate drug-resistant seizures and administered with different oral doses of oxcarbazepine (OXC). We addressed the possible contribution of the multidrug transporter P-glycoprotein (P-gp or MDR1) in determining 10-OHCBZ brain levels by measuring whether this active metabolite is a substrate of P-gp and the relation between the level of expression of MDR1 and the drug concentration in the same brain tissue specimens. METHODS: Steady-state plasma and brain concentrations (C(ss)) of 10-OHCBZ were determined intraoperatively in 11 patients by high-performance liquid chromatography (HPLC) with UV detection. The level of expression of MDR1 mRNA was measured in surgically resected brain tissue by reverse transcriptase polymerase chain reaction (RT-PCR). The ability of 10-OHCBZ to act as substate of P-gp was evaluated by measuring its uptake in cell lines expressing different levels of P-gp, in the presence or absence of a selective P-gp inhibitor. RESULTS: OXC was converted to 10-OHCBZ and to Di-OHCBZ, the two main metabolites measured in plasma. The brain concentrations of the active metabolite 10-OHCBZ did not reflect plasma C(ss). A significant inverse linear correlation was found between 10-OHCBZ brain-to-plasma concentration ratio and the level of brain expression of MDR1 mRNA. In vitro uptake studies demonstrated lower intracellular 10-OHCBZ levels in cells with higher P-gp expression. Intracellular drug concentration was increased by XR9576, a specific P-gp blocker. CONCLUSIONS: Pharmacologic failure of OXC in pharmacoresistant epilepsy is unlikely to be due to alterations in drug metabolism. 10-OHCBZ does not appear to cross the blood-brain barrier by simple diffusion, and it acts as a substrate of P-gp. The level of expression of MDR1 is inversely correlated with 10-OHCBZ concentration in the epileptic tissue. P-gp may play a role in the pharmacoresistance to OXC by determining the attainment of insufficient concentrations of its active metabolite at neuronal targets.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Predictors for negative attitudes toward subjects with epilepsy: a representative survey in the general public in Austria.

PURPOSE: To assess knowledge of and attitudes toward epilepsy in the Austrian general public and to identify independent predictors of negative attitudes. METHODS: A survey consisting of a representative sample of 2,128 Austrian adults was commissioned. A questionnaire similar to the ones used in earlier studies in other countries was used. The independent influence of socioeconomic variables and of knowledge and concepts about epilepsy on attitudes were analyzed by using logistic stepwise regression procedure. RESULTS: Nearly 10% of respondents expressed negative attitudes toward people with epilepsy. These figures are similar to those of other studies performed in comparable societies. In addition to being male and of low socioeconomic background, having little theoretical knowledge about epilepsy, misconceptions of epilepsy as a form of insanity, and no personal acquaintance with someone with epilepsy independently predispose to unfavorable attitudes toward epilepsy. CONCLUSIONS: Information campaigns on epilepsy are likely to improve attitudes toward epilepsy when they target misconceptions about epilepsy and when they offer opportunities for personal acquaintance with people with epilepsy.

Adult↗
PubMed2004

Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy.

Although the syndrome of mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis has been elaborated in recent years, pathogenesis and pathomechanisms are still elusive. Performing protein hunting in hippocampus of patients with MTLE we detected derangement of collapsin response mediated protein-2 (CRMP-2). Hippocampal tissue from controls and MTLEs was taken and two-dimensional gel electrophoresis with subsequent MALDI-MS-characterisation was applied. The proteomic approach identified 13 spots unambiguously assigned to CRMP-2. Three spots at molecular weight 55 kDa showed a significant decrease in MTLE and other 3 spots at 65 kDa showed deranged in MTLE. Immunoblotting revealed two bands at 65 and 55 kDa in the control group whereas the 55 kDa band was extremely low expressed in MTLE. CRMP-2 is required to induce axonal outgrowth and maintaining neuronal polarity in hippocampal neurons and the significant decrease of this protein may represent or underlie impaired neuronal plasticity, neurodegeneration, wiring of the brain in MTLE and may explain abnormal migration. Therefore, the decrease of CRMP-2 may well contribute to the understanding of the still unclear pathomechanisms involved in MTLE.

Adult↗
PubMed2004

Controversies in clinical neurophysiology. MEG is superior to EEG in the localization of interictal epileptiform activity: Con.

OBJECTIVE: To assess whether MEG is superior to scalp-EEG in the localization of interictal epileptiform activity and to stress the 'con' part in this controversy. METHODS: Advantages and disadvantages of the two techniques were systematically reviewed. RESULTS: While MEG and EEG complement each other for the detection of interictal epileptiform discharges, EEG offers the advantage of long-term recording significantly increasing its diagnostic yield which is not feasible with MEG. Localization accuracies of EEG and MEG are comparable once inaccuracies for the solution of the forward problem are eliminated. MEG may be more sensitive for the detection of neocortical spike sources. EEG and MEG source localizations show comparable agreement with invasive electrical recordings, can clarify the spatial relationship between the irritative zone and structural lesions, guide the placement of invasive electrodes and attribute epileptic activity to lobar subcompartments in temporal lobe epilepsy and to a lesser extent in extratemporal epilepsy. CONCLUSIONS: A clear superiority of MEG over EEG for the localization of interictal epileptiform activity cannot be derived from the studies presently available. SIGNIFICANCE: The combination of EEG and MEG provides information for the localization of interictal epileptiform activity which cannot be obtained with either technique alone.

Electroencephalography↗
PubMed2004

Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience.

PURPOSE: Although epilepsy surgery, especially temporal lobe epilepsy surgery, is well established to control seizures in patients remaining on antiepileptic drug (AED) treatment, less information is available about how many seizure-free surgical patients will relapse after discontinuation of AEDs under medical supervision. METHODS: A literature review yielded six retrospective clinical observations. RESULTS: After planned discontinuation of AEDs in patients rendered seizure free after epilepsy surgery, most often various forms of temporal lobe surgery, the mean percentage recurrence rate in adults in four studies was 33.8%[95% confidence interval (CI), 32.4-35.2%], with maximum follow-up ranging from 1 to 5 years. Seizure recurrence increased during the follow-up of 1 to 3 years and occurred within 3 years of AED discontinuation. In one study of children with temporal lobe epilepsy, the recurrence rate was 20%. More than 90% of adult patients with seizure recurrence regained seizure control with reinstitution of previous AED therapy. Seizure recurrence was unaffected by the duration of postoperative AED treatment; as a consequence, delaying discontinuation beyond 1 to 2 years of complete postoperative seizure control seems to have no added benefit. The occurrence of rare seizures or auras after surgery did not eliminate the possibility of eventual successful AED discontinuation. CONCLUSIONS: AED discontinuation is associated with a seizure recurrence in one in three patients rendered seizure free by epilepsy surgery. These results will be useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.

Anticonvulsants↗
PubMed2004

Increased expression of Nogo-A in hippocampal neurons of patients with temporal lobe epilepsy.

Mesial temporal lobe epilepsy (TLE) is associated with pronounced anatomical and biochemical changes in the hippocampal formation including extensive neurodegeneration, reorganization of mossy fibres and sprouting of interneurons. Although the anatomical features and some of the physiological consequences of hippocampal remodeling have been well documented, the molecular mechanisms underlying the profound and orientated outgrowth of hippocampal neurons in TLE are not yet understood. The reticulon protein Nogo-A has been associated with an inhibitory action on axon growth and plasticity. Using immunohistochemistry and in situ hybridization, we investigated the expression of Nogo-A in specimens obtained at surgery from patients with TLE compared with those obtained from autopsy controls. In control specimens, Nogo-A immunoreactivity and mRNA were mainly confined to oligodendrocytes. Only approximately 40% of the specimens revealed low expression of Nogo-A mRNA in neurons. In contrast, in TLE patients with and without Ammon's horn sclerosis, Nogo-A mRNA and immunoreactivity were markedly up-regulated in most neurons (3.6- and 4.4-fold increases in Nogo-A mRNA in granule cells of sclerotic and nonsclerotic specimens) and their processes throughout the hippocampal formation. Similar elevations in Nogo-A mRNA and protein levels were determined by quantitative RT-PCR and Western blotting. Since Nogo-A expression was also up-regulated in specimens without hippocampal sclerosis, it may be induced by seizures prior to progressing neurodegeneration.

Adolescent↗
PubMed2003

Increased expression of gamma-aminobutyric acid type B receptors in the hippocampus of patients with temporal lobe epilepsy.

Malfunctioning of the GABA-ergic system has been postulated as a possible cause of epilepsy. We investigated changes in the mRNA expression of the GABA(B) receptor subtypes GABA(B)-R1 and GABA(B)-R2 and of GABA(B) receptor binding in the hippocampus of patients with temporal lobe epilepsy (TLE) compared with post-mortem controls. In patients with Ammon's horn sclerosis, significant decreases in [3H]CG54626A binding were observed in subfields CA1 and CA3 of the hippocampus proper and the dentate hilus. On the other hand, both GABA(B) receptor mRNAs and receptor binding were enhanced after correction for neuronal loss in dentate granule cells and in the molecular layer, respectively, and the subiculum of patients with and without hippocampal sclerosis. These increases were even more pronounced when correcting the values for cell losses in the respective areas and indicated also increased expression of GABA(B)-R in the dentate hilus. Increased expression of both subtypes of GABA(B) receptors indicates augmented presynaptic inhibition of glutamate release as a possible protective mechanism in TLE.

Adolescent↗
PubMed2003

Postictal psychosis in temporal lobe epilepsy.

PURPOSE: Postictal psychosis is a well-known complication, occurring especially in patients with temporal lobe epilepsy. It usually runs a benign course. The literature on this topic is sparse, and the underlying pathogenic mechanisms are not known. METHODS: We report five patients with temporal lobe epilepsy in whom postictal psychosis developed during the course of video-EEG monitoring; they were studied with hexamethyl-propyleneamine-oxime single-photon emission computed tomography (HMPAO-SPECT) during and after the psychotic event. RESULTS: In comparison to the interictal state, all SPECT scans obtained during postictal psychosis were remarkable for bifrontal and bitemporal hyperperfusion patterns. Some studies also demonstrated unilateral left lateral frontal hyperperfusion. These cortical blood-flow patterns appeared to be distinct from those obtained during complex partial seizures. CONCLUSIONS: Our data suggest that postictal psychoses in patients with temporal lobe epilepsy are associated with hyperactivation of both temporal and frontal lobe structures. This hyperperfusion may reflect ongoing (subcortical) discharges, active inhibitory mechanisms that terminate the seizure, or simply a dysregulation of cerebral blood flow.

Adult↗