Biomedical subjects

H Stefan

Publications and source records attributed to H Stefan.

At least 19 recordsLinked to original sources

PubMed2006

Spatial intralobar correlation of spike and slow wave activity localisations in focal epilepsies: a MEG analysis.

12 patients with focal epilepsy were examined by magnetoencephalography (MEG). Source localisations of interictal epileptiform activity (spikes) yielded clear results. Slow wave dipole density in the frequency range from 2 to 6 Hz, using time selections from an automatic principal component analysis (PCA), was calculated. Results of spike and slow wave dipole density localisations were superimposed on MR-images of each patient. Slow wave dipole densities were increased close to spike localisations. Distances between spike center of mass and slow wave maxima were calculated, average mean distance was 2.0 cm. Independant of the localisation in either TLE or ETLE a concordance of slow wave and spike localisations were found. Slow wave localisations were found in patients with lesions in MRI and patients with no abnormalities on the MRI. In comparison to healthy subjects, slow wave dipole density in patients with epilepsy was clearly increased. The localisation of slow wave dipole density yielded additional important information and may contribute to defining the irritative zone.

Adolescent↗

PubMed2006

Periventricular nodular heterotopia: A challenge for epilepsy surgery.

Pharmacoresistant focal epilepsies due to periventricular nodular heterotopia are a diagnostic and therapeutic challenge because of the need of invasive presurgical diagnostics and the selection of an optimal surgical approach. Invasive investigations in previous studies showed that focal epileptic activity can be correlated predominantly either with one of the nodular heterotopia or with neocortical epileptogenic zones distant to the periventricular nodules. Up to now, invasive recordings were required for localization of epileptic activity and its correlation to heterotopia. The following case presentation reports on a non-invasive approach using magnetic source imaging (MSI) combined with intraoperative ECoG. MSI combines preoperative data from magnetic resonance imaging (MRI) with magnetoencephalography (MEG). The MSI data for definition of the localization of the epileptic activity and functional important areas were coregistered with the intraoperative high-field-MRI and diffusion tensor imaging-based fiber tracking (DTI) of the visual pathway using a neuronavigational system. A neuronavigation-guided surgical resection of the epileptogenic area was performed leaving the heterotopia and the visual tract fibers intact. Postoperatively preservation of the visual fields was documented and the frequency of seizures was markedly reduced.

Brain Diseases↗

PubMed2006

Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss.

BACKGROUND: The hippocampal formation is essentially involved in the formation of conscious memories for facts and events and neurologic diseases affecting the hippocampus associate with severe memory deficits, i.e., temporal lobe epilepsies. METHODS: We studied the degree of declarative memory dysfunction in 24 human subjects with unilateral mesial temporal lobe epilepsy, using the unique possibility to access memory performance of each isolated hippocampus by intracarotid amobarbital anesthesia. Subsequently, hippocampal specimens from the same patients were available for neuropathologic analysis following surgical treatment of intractable seizures. RESULTS: Neuronal cell loss in the dentate gyrus and all hippocampal subfields correlated with memory performance with the exception of CA2. Moreover, multiple regression and partial correlation analyses identified neuronal cell loss within the internal limb of the dentate gyrus, a developmentally distinct subregion of the hippocampal formation known to generate new neurons throughout life, as highly significant predictor for the patient's ability to learn and recall memories. CONCLUSIONS: In accordance with animal studies, the dentate gyrus may play a critical role in the neuronal network associated with memory formation.

Adult↗

PubMed2006

Novel anticonvulsant drugs.

Principles of complex mechanisms of action of anticonvulsants including latest reports concerning new antiepileptic drugs (AED) are considered. Different aspects of new anticonvulsant drugs (2nd generation) from preclinical and clinical testing, pharmacokinetics, and mono or combination therapy in children and adults are summarized. In the following condensed synopsis pharmacological and clinical characteristics of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB) and tiagabine (TGB) as well as topiramate (TPM) and zonisamide (ZNS) are discussed. In addition to the mechanisms of action, pharmacokinetics, interactions, indications and dosages as well as side effects are considered. Important data concerning the effect and tolerability of anticonvulsant drugs can be obtained from controlled studies. In comparison to drugs of the first generation (phenobarbital [PB], primidon [PRD], phenytoin [PHT], carbamazepine [CBZ] and valproic acid [VPA]) the potential for interactions and side effects due to enzyme induction or inhibition is reduced by most of the anticonvulsant drugs of the second generation. New anticonvulsant drugs increase the spectrum of treatment and represent further steps with regard to the optimization of an individual therapy of the epilepsies.

Amines↗

PubMed2006

Fast activity as a surrogate marker of epileptic network function?

The detection of epileptiform discharges in electroencephalography recordings is a crucial part in diagnosing epilepsy. Thorough electrophysiologic evaluation yields information that allows for tailored surgical therapy in many cases, and thus improves treatment outcome. In recent years, fast activity (>60-80Hz) has been investigated for its diagnostic value in addition to well-known patterns such as epileptic transients. It was shown that these high frequency oscillations are highly specific for epileptic network function and might provide valuable information for localization of epileptic networks and understanding of their mechanisms. In this review, an overview of the electrophysiologic characteristics, putative cellular and network mechanisms in epilepsy is given. Recent studies are reviewed and interpreted in the context of a common hypothetical model.

Brain↗

PubMed2006

Identifying the affected hemisphere by (1)H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI.

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.

Adult↗

PubMed2006

Influence of levetiracetame on ictal and postictal EEG in patients with partial seizures.

To investigate the influence of levetiracetame (LEV) treatment on the interhemispheric seizure pattern propagation and postictal recovery of electroencephalography (EEG) background activity. Twenty-three adult patients (age > 16 years) with pharmacoresistant focal epilepsies presenting at the Epilepsy Center Erlangen for pre-surgical evaluation were enrolled in the study. Those eligible patients receiving only one antiepileptic drugs were recruited to the 48-h baseline phase and, after at least two seizures, were randomized to the 7-day treatment phase with either LEV (n = 11) or placebo (n = 12). All participants were submitted to continuous day-and-night video-EEG monitoring. The daily dose of LEV was 1000 mg (500 mg bid.) on the first treatment day and was increased to 2000 mg (1000 mg bid.) from the second day onward. The EEG changes relating to the time delay of the interhemispheric seizure pattern propagation and to the postictal recovery of the background activity were analysed by computerized video-EEG recording and compared using the non-parameter Mann-Whitney U-exact test (alpha = 0.05). A prolonged latency of the contralateral seizure pattern propagation was observed in the LEV group, whereas a more rapid propagation was observed in the placebo group (P = 0.009). Postictal generalized slowing of the background activity was recorded in 21 patients during the baseline phase. More rapid postictal recovery of the EEG background activity was observed in the LEV, but not in the placebo group (P = 0.03). This study demonstrated that LEV not only prevented the seizure pattern propagation but also helped the speedy recovery of the postictal background activity in the EEG.

Adult↗

PubMed2006

Epileptogenesis and rational therapeutic strategies.

The understanding of neurobiological mechanisms of epileptogenesis is essential for rational approaches for a possible disease modification as well as treatment of underlying causes of the epilepsies. More effort is necessary to translate results from basic investigations into new approaches for clinical research and to better understand a relationship with findings from clinical studies. The following report is a condensed synapsis in which molecular mechanisms of epileptogenesis, pharmacological modulation of epileptogenesis, evidence based therapy, refractoriness and prediction of outcome is provided in order to stimulate further collaborative international research.

Anticonvulsants↗

PubMed2005

Short TE single-voxel 1H-MR spectroscopy of hippocampal structures in healthy adults at 1.5 Tesla--how reproducible are the results?

The purpose of our study was to evaluate inter- and intra-subject variability and scan-rescan reproducibility of single-voxel 1H-MR spectroscopy (1H-MRS) in hippocampal structures at 1.5 T field strength. Thirty healthy adults were studied bilaterally by optimized, standardized short echo time single-voxel 1H-MRS (PRESS, TE=30 ms, TR=3000 ms, oblique voxel orientation, voxel size 2 cm3). Spectral analysis and absolute metabolite quantitation of N-acetylaspartate+N-acetylaspartyl-glutamate (tNAA), choline (Cho), creatine (Cr), total glutamate plus glutamine (Glu+Gln) and myo-inositol (Ins) were carried out by LCModel. Inter- and intra-individual reproducibility of these metabolite values were investigated by calculation of mean, standard deviation, coefficient of variation (CV), and by analysis of variance for repeated measurements. The smallest CV in intersubject variability was obtained for tNAA, followed by Cr, Cho, Ins and Glu+Gln. The results of the analysis of variance for repeated measures in inter-subject variability showed a marginal effect of scan repetition for Cr (p=0.063) and Glu+Gln (p=0.082); the rescan of both metabolites showed slightly higher concentrations. No statistical significant effect of scan repetition was seen for tNAA (p=0.913), Cho (p=0.857), and Ins (p=0.826). Rescan led to the same results and gave proof of good reproducibility. Scan-rescan testing in one subject showed comparable results: tNAA (CV=4.8%), followed by Cr, Ins, Glu+Gln and Cho (all CV above 10%).

Adult↗

PubMed2005

[Familial cavernous malformations of the central nervous system. A clinical and genetic study of 15 German families].

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Adult↗

PubMed2005

[Brain tumors and epilepsy].

Improved tumor and epilepsy treatment requires long-term care of patients with symptomatic epilepsies caused by tumors. Pathophysiology, epidemiology, prognosis, drugs, and surgical treatment are discussed with special emphasis on seizure control, side effects, and quality of life. Because of the long-term course -- often 10 to 20 years -- optimal treatment strategies have to be selected individually. These should consider possibilities of new techniques of co-registering imaging and electrophysiology, surgery, and the interaction of anticonvulsive and chemotherapeutic drugs, cognition, and mood.

Anticonvulsants↗

PubMed2005

Ictal dystonic posturing in mesial versus neocortical temporal lobe seizures.

PURPOSE: Ictal contralateral dystonic posturing is a frequently observed clinical feature in temporal lobe seizures. It is generally interpreted as the result of spread of the ictal discharge into basal ganglia structure. In previous reports, analysing ictal behavior, a precise definition and description of the upper limb ictal dystonia is often lacking or contradictory. In our study we aimed to determine whether different subtypes of dystonia and their latency from the clinical onset of seizure might be of value for the differentiation between mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE). METHODS: Eighty seizures (51 MTLE and 29 NTLE) and 30 patients (20 MTLE and 10 NTLE) were analyzed with regard to dystonic posturing of the upper limb. Ictal dystonia was subdivided into different subtypes according to distinct clinical features. Their frequency and latency from the clinical onset of seizure were assessed. RESULTS: Frequencies of all subtypes were similar in MTLE and NTLE. Concerning the latencies contralateral dystonic posturing characterized by sustained muscle contractions with flexion of the wrist and fist closure, a frequently appearing feature, occurred significantly earlier in NTLE than in MTLE seizures. CONCLUSIONS: This difference between the two groups may provide a differentiation between an epileptic focus of mesial from neocortical temporal lobe origin.

Adult↗

PubMed2005

[Valproate sustained release in the treatment of epilepsy].

In an observational study under routine clinical setting data after administration of once daily evening dosing of valproate sustained release minitablets were recorded in 359 patients with epilepsy aged between 12 and 86 years. Patients were either newly treated with valproate sustained release minitablets (N = 58) or switched from conventional valproate (N = 124) or from sustained release valproate (N = 138) to the once daily evening dosing. In 39 patients other antiepileptic drugs were replaced. At the end of the 7-week observational period most patients (65.4 %) received a daily dose of 10 to less than 18 mg/kg body weight followed by 17.4 % receiving doses in the therapeutically recommended range of 18 - 24 mg/kg. 8.6 % and 7.4 % of patients received more than 24 mg/kg or less than 10 mg/kg body weight, respectively. As expected, in both groups with valproate pre-treatment the mean morning valproate plasma levels increased by approximately 10 microg/ml after switch to once evening dosing with sustained release minitablets. The mean seizure frequency decreased from 2.1 to 0.5 in the 318 patients with data before the beginning and at the end of the investigation. At the final examination 137 patients (62.3 %) were seizure free, and further 60 patients (27.3 %) experienced a seizure reduction of more than 50 % (responder) of those 220 patients who experienced seizures in the last 7 weeks before the study. The efficacy and tolerability was rated in more than 95 % of the cases by the patient and the investigator as good or very good. The compliance/acceptance of the valproate sustained release minitablets was rated as good or very good in almost all patients. These results confirm the excellent benefit-risk ratio of the valproate sustained release minitablets and underline the importance of a simple compliance-improving dose regimen for effective seizure control.

Adolescent↗

PubMed2005

Changes of seizures activity during rapid withdrawal of lamotrigine.

Quantitatively evaluating the rapid withdrawal effects of lamotrigine (LTG) and carbamazepine (CBZ) on seizure activity during pre-surgical evaluation in patients with pharmacoresistant complex partial epilepsy. The duration and frequency of seizure activities and electrographic seizure onset of 41 patients totally withdrawing from CBZ monotherapy (n = 20), LTG monotherapy (n = 10) and CBZ + LTG combined therapy (n = 11) were intensively studied by therapeutic intensive seizure analysis (TISA) method. Study phases ran from the baseline phase to the antiepileptic drug (AED) withdrawal phase until the AED free phase, 3 days for each phase. Seizure duration and frequency obviously increased during the withdrawal process in each group (P < 0.05). The duration of secondarily generalized clonic signs markedly increased with the tapering of each drug; tonic signs, however, only in the AED free phase (P < 0.05). The frequency of secondary tonic and clonic signs only increased in the CBZ and CBZ + LTG group. Intergroup comparisons of all variables were insignificant (P > 0.05). There was no change of ictal EEG localization during all withdrawal protocols. All patients experienced more severe seizures during the withdrawal processes. An earlier aggravation of the clonic signs than the tonic signs was observed in each group. Difference between the withdrawal effects of LTG and CBZ monotherapy and LTG + CBZ polytherapy was mainly in the frequency change of ictal signs. The withdrawal process did not influence the ictal EEG localization. This study justified the withdrawal in pre-surgical localization, rationalized precautions for possible accompanying risks, and also aroused attentions in clinical anticonvulsant trials and substitutions involving withdrawal process.

Adolescent↗

PubMed2004

Comparison of clonidine to sleep deprivation in the potential to induce spike or sharp-wave activity.

OBJECTIVE: This study aimed to investigate previously observed side effects, i.e. increased epileptic activity during clonidine medication. The safety and effectiveness of clonidine as spike inducing agent compared to sleep deprivation were tested. METHODS: Patients suffering from drug-resistant localization related epilepsy took part in 3 magnetoencephalography (MEG) sessions. One session was recorded without any activating measures. The other two sessions were either performed after sleep deprivation or after medication with clonidine. Target parameter was the number of spikes or sharp-waves during a 30 min recording period. RESULTS: About 67% of the patients showed increased spike activity after clonidine, whereas sleep deprivation increased the number of spikes in 33%, and 29% of the patients did not show any activation at all. Clonidine was most effective in temporal lobe epilepsy, when the focus was located in the right hemisphere, and when clonidine serum concentrations were ranging between 0.6 and 1.0 ng/ml. CONCLUSIONS: This study showed for the first time that clonidine can be considered an effective spike or sharp-wave inducing drug that is superior to the potency of sleep deprivation. SIGNIFICANCE: The administration of clonidine increases the probability of recording ictal and interictal epileptic activity during limited acquisition time.

Action Potentials↗

PubMed2004

[How to diagnose and treat epilepsy].

The mainstay for the diagnosis of epilepsy is a comprehensive history and eyewitness descriptions. For further diagnostic evaluation electroencephalography (EEG) and magnetic resonance imaging (MRI) are employed, but also such newer methods as positron emission tomography (PET), single photon emission tomography (SPECT) and Magnetoencephalography (MEG). Treatment of epilepsy is in the first instance medical. The choice of anticonvulsant is based on effectiveness, the spectrum of side effects and patient comorbidity. Difficult-to-treat and drug-resistant epilepsy should be treated surgically and the patients should be referred to an epilepsy center for a pre-operative diagnostic work-up.

Anticonvulsants↗

PubMed2004

[Supratentorial cavernoma and epileptic seizures. Are there predictors for postoperative seizure control?].

For cavernous haemangiomas, it is the aim of surgical treatment to control epilepsy and eliminate potential sources of intracerebral haematomas. In the following investigation, it was attempted to find indicators for seizure freedom after surgery. Success of therapy was assessed according to three patterns of classification. Thirty patients underwent tailored resection based on findings from preoperative investigations and intraoperative electrocorticography. Follow-up averaged 4 years. Lesionectomy, extended lesionectomy, and modified lobe resection were carried out in 13, 11, and six patients, respectively. For all procedures, including microsurgical lesionectomy, the firm gliotic layer unequivocally differed in colour and consistency from normal brain and was removed. Further tissue resection was carried out only if the electrocortical course suggested persistent spike activity around the resection cavity or if presurgical MRI evaluation (e.g. hippocampal atrophy) or electrophysiology also pointed to pathology distant from the lesion. Of the patients, 53.3% became completely seizure-free (Engel I), and one additional patient had only occasional isolated auras. Dramatic reductions in seizure frequency and severity were exhibited by 26.7%. Outcome in respect to seizure control was not associated with resection procedure, comparing pure lesionectomy with lesionectomy plus cortectomy. In the group of patients with epilepsy surgery, those with hippocampectomy had significantly better outcome than those without. Important prognostic factors were early operation after seizure manifestation (91.7% operated upon within 2 years of seizure onset became seizure-free). Another prognostic factor was unifocal seizure onset (bilateral or multifocal seizure onset was found in care of the ten patients with unfavourable outcome). None of the four patients harbouring multiple cavernomas became seizure-free after resection of one lesion, which was believed to be mostly attributable to the epileptic focus that was removed.

Adult↗

PubMed2004

[(1)H MR spectroscopy. Methods and applications in diagnosis and assessment of surgical and conservative treatment strategies in epilepsies].

Techniques and methods of clinical (1)H-MR spectroscopy are described in this manuscript. The role of (1)H-MRS in the multimodal focus analysis of temporal lobe epilepsy (TLE) is illustrated with special respect to focus lateralization and differentiation between mesial and lateral (neocortical) TLE. Additionally the application of (1)H-MRS for evaluating postoperative outcome and monitoring conservative antiepileptic treatment schedules is summarized.

Algorithms↗