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Hermann Stefan

Publications and source records attributed to Hermann Stefan.

At least 19 recordsLinked to original sources
PubMed2007

A new clinico-pathological classification system for mesial temporal sclerosis.

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Adult↗
PubMed2007

Spatial relationship of source localizations in patients with focal epilepsy: Comparison of MEG and EEG with a three spherical shells and a boundary element volume conductor model.

Epilepsy surgery is an option for patients with pharmacoresistant focal epilepsies, but it requires a precise focus localization procedure. Magnetoencephalography (MEG) and electroencephalography (EEG) can be used for analysis of interictal activity. The aim of this prospective study was to compare clusters of source localization results with MEG and EEG using a three spherical shells (3SS) and a boundary element method (BEM) volume conductor model. The study was closed when 100 patients met the inclusion criteria. Simultaneous MEG and EEG were recorded during presurgical evaluation. Epileptiform signals were analyzed using an equivalent current dipole model. Centroids of source localizations from MEG, EEG, 3SS, and BEM in their respective combinations were compared. In a 3SS model, MEG source localizations were 5.6 mm inferior to those obtained by EEG, while in a BEM model MEG source localizations were 6.3 mm anterior and 4.8 mm superior. The mean scattering of source localizations between both volume conductor models was 19.5 mm for EEG and 9.6 mm for MEG. For MEG no systematic difference between BEM and 3SS source localizations was found. For EEG, source localizations with BEM were 5.9 mm posterior and 11.7 mm inferior to those determined using 3SS. No differences were found between the 46 temporal and the 54 extratemporal lobe epilepsy patients. The observed systematic differences of source localizations of epileptic spikes due to the applied source signal modality and volume conductor model should be considered in presurgical evaluation when only one source signal and volume conductor model is available.

Adult↗
PubMed2006

When do patients forget their seizures? An electroclinical study.

Accurate knowledge of the frequency of epileptic seizures is a precondition for evaluating the efficacy of pharmacotherapy. It is a well-known fact that the information provided by epilepsy patients about the number of seizures they experience is often unreliable. In the present study, we aimed to identify predictors of a higher risk of unrecognized events. Thirty patients who underwent presurgical evaluation in a video/EEG monitoring unit were recruited. As soon as the patient became aware of a seizure, he or she completed a standardized questionnaire on the subjective perception of the seizure, which was then compared with the video/EEG findings. Of the 138 seizures recorded, 49.3% were reliably detected by the patient, whereas 44.2% went unnoticed; the remainder were incompletely or uncertainly perceived. Subjects in whom events occurred during sleep or originated in (or propagated to) the left temporal lobe had a significantly higher percentage of unrecognized events.

Adult↗
PubMed2006

Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy.

PURPOSE: Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue from Coriaria lactone (CL)-kindled Sprague-Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA). METHODS: Twenty-five CL-kindled SD rats were randomized into five groups (n = 5 for each group) to receive once-daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage, or normal saline (NS control) for 1 month. The expression of P-gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro-plus 4.0). Mean area and mean integrated optical density (mean IOD) of P-gp expression were calculated. In addition, the changes in seizure severity were analyzed via video-camera monitoring. RESULTS: A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P-gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05). CONCLUSIONS: TPM and LTG significantly inhibited seizures in this CL model. The expression of P-gp was not significantly increased by TPM or LTG treatment in this study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Onset of action of levetiracetam: a RCT trial using therapeutic intensive seizure analysis (TISA).

OBJECTIVES: To correlate the onset of clinical effects of add-on levetiracetam (LEV) therapy with daily serum LEV concentration, in pharmaco-resistant focal epilepsies, using the TISA method. METHODS: 25 adult patients (aged>6 years) with pharmaco-resistant focal epilepsies undergoing presurgical evaluation at the Epilepsy Center Erlangen were enrolled in the study. Eligible patients on a maximum of one other antiepileptic drug (AED) were recruited into the 48-hour baseline phase. Those who had at least two seizures during this phase were randomized into the seven-day treatment phase, when they received either LEV or placebo, under continuous day-and-night video-EEG monitoring. The starting daily dose of LEV was 500 mg bid, titrated from the second treatment day to 1,000 mg bid. The peak serum concentration of LEV was monitored daily at 8:00 am (one hour after drug administration) for every patient. The number and duration of seizures per 24h (N/24h and D/24h respectively) were investigated. RESULTS: 23 patients completed the study (LEV group n=11 and placebo group n=12). Seven patients in the LEV group and two patients in the placebo group achieved seizure-freedom during the treatment phase. The intergroup comparison of the decrease in N/24h and D/24h from the baseline phase to the treatment phase was in favor of the LEV group (p<0.05). A significant effect of LEV on D/24h was seen as early as the second treatment day (p=0.013), becoming more apparent on the third treatment day (p=0.009). CONCLUSION: The present study objectively quantified the correlation between the anticonvulsant effects of LEV in focal epilepsies and the peak serum concentration of the drug. For the first time, direct measurement was used to demonstrate the onset of action of LEV to be two days after drug initiation.

Adult↗
PubMed2005

Model based prognosis of postoperative object naming in left temporal lobe epilepsy.

Epilepsy surgery in the left temporal lobe is associated with a high risk of naming decline. In the present study, in 45 patients with left temporal lobe epilepsy (TLE) and confirmed left hemisphere language dominance, 13 (29%) patients demonstrated postoperative decrement >or=5 naming failures in the Boston Naming Test (BNT). Multivariate discriminant analysis with age at onset of epilepsy, age at first risk, age at operation and preoperative naming performance as predictors indicated that 12 (92%) patients with later naming decline could be identified preoperatively. Univariate group comparisons revealed that specifically patients with seizure onset later than 14 years without preceding risk factors (e.g., febrile seizures) are in danger of postoperative dysnomia. It is hypothesized, that there is a strong connection between stable naming performance and deviant intrahemispheric speech representation as a result of early brain damage and/or chronic seizures.

Adult↗
PubMed2005

Vagus nerve stimulation suppresses pain but has limited effects on neurogenic inflammation in humans.

Left vagus nerve stimulation reduces pain perception in humans. In animal studies it has been shown that beyond the inhibitory effect, which the vagus nerve exerts via its widespread central connections, there might be also a peripheral effect on nociceptors. In humans, the exact mechanisms of VNS-mediated analgesia are still unclear. To test whether VNS also affects activation of primary nociceptive afferents in humans, we investigated 11 patients before and after implantation of a vagus nerve stimulator by using tonic pressure as pain stimulus. Vasodilator axon reflexes ("neurogenic" inflammation) were quantified by laser-Doppler-imaging and served as surrogates for primary afferent activation. Pain was measured on a visual analogue scale (VAS). The squeezing experiment was performed three times at 15 min intervals in each session. As controls 9 healthy age- and gender-matched subjects were studied. As shown in our previous study, VNS significantly reduces pain to tonic pressure. Likewise, there was a moderate reduction of the blood flow within the area of the axon reflex, which indicates a possible but limited inhibitory effect of VNS on peripheral nociceptors. Our data suggests that VNS might affect peripheral nociceptor function in humans. Since VNS has been shown to be more effective in experimental procedures in which pain magnitude is amplified by central processing, further studies are warranted to elucidate whether the central or peripheral effect is most important for VNS-mediated analgesia.

Adult↗
PubMed2004

Utilization of magnetoencephalography results to obtain favourable outcomes in epilepsy surgery.

Magnetoencephalography (MEG) is a well-known technique in the presurgical evaluation of epilepsy patients. Like EEG, it can detect and localize epileptic activity. Epilepsy surgery can be used to evaluate MEG source localizations. Resection volumes were determined in 33 epilepsy surgery patients. The resection volume, taken together with the post-operative outcome, was used to evaluate MEG results. The scattering MEG localizations of interictal epileptic activity were represented by an ellipsoidal volume. Using this MEG results ellipsoid, it was demonstrated that a high coverage by the resection volume and a small distance to the resection volume are both correlated to a favourable outcome; in addition, a homogeneous distribution of MEG localizations is correlated to a favourable outcome. This study shows that MEG source localization can help to delineate epileptic activity and, along with other techniques, should be taken into account for epilepsy surgery.

Adolescent↗
PubMed2004

Ictal pleasant sensations: cerebral localization and lateralization.

Ictal pleasant feelings are a rare sign of focal epilepsies. The most popular description was performed by Dostojevskij, who reported an aura by Myshken in one of his books. No convincing evidence has been published concerning the cerebral localization of ictal happiness. In this study, the findings of 11 patients with ictal pleasant feelings are described. In eight patients, the origin of the focal epileptic activity was found in the temporal lobe (most often temporal inferior basal); in three patients, frontal or parietal lobe in addition to temporal lobe involvement was found. According to our findings ictal happiness is a localizing sign pointing to the ictal involvement of temporal mesiobasal areas. Lateralization to the right temporal lobe was found in seven and to the left temporal lobe in four patients.

Adolescent↗
PubMed2003

Outcome of epilepsy surgery correlates with sympathetic modulation and neuroimaging of the heart.

Temporal lobe epilepsy (TLE) is frequently associated with sympathetic over-activity. Single photon emission computed tomography (SPECT) with 123iodine-meta-iodobenzylguanidine (MIBG), a norepinephrine analogue, showed reduced tracer uptake in cardiac sympathetic nerve endings, indicating myocardial catecholamine disturbance. We investigated whether outcome of epilepsy surgery correlates with cardiac autonomic function in TLE patients. We studied 16 TLE patients before and after epilepsy surgery. We recorded heart rate (HR) and determined sympathetic and parasympathetic cardiac modulation as powers of low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) heart rate oscillations. The LF/HF-ratio was calculated as index of sympathovagal balance. Cardiac MIBG uptake was assessed with MIBG-SPECT and compared to control data. After surgery, eight patients were seizure-free and eight had persistent seizures. Sympathetic LF-power and LF/HF-ratio were higher in patients who had persistent seizures than in patients who became seizure-free. After surgery, both parameters decreased in seizure-free patients but increased in patients with persistent seizures. MIBG uptake was lower in patients than controls and even lower in the patient subgroup who had persistent seizures. In this subgroup, MIBG uptake further decreased after surgery (P<0.05). Sympathetic cardiac modulation decreased in TLE patients after successful surgery, but further increased if seizures persisted. Reduction of cardiac MIBG uptake progressed after surgery in patients with persistent seizures. Interference of epileptogenic discharges with autonomic neuronal transmission might account for sympathetic cardiac over-stimulation and reduced MIBG uptake. Both findings are possible risk factors for sudden unexplained death and might be relevant for risk stratification in epilepsy patients.

3-Iodobenzylguanidine↗
PubMed2003

Cortical processing of brush-evoked allodynia.

The cortical processing of allodynia (touch-evoked pain) resulting from neuralgia of the lateral cutaneous femoral nerve was investigated with a newly designed pneumatically driven brush by means of magnetoencephalography. Brushing the unaffected thigh produced subsequent activation of the contralateral primary somatosensory cortex (S1) with peak latencies of 37 and 56 ms. Brushing the affected side led to comparable activation of the contralateral S1 cortex. In addition, the magnetic fields were stronger, and the corresponding equivalent current dipoles were located more laterally, consistent with the presence of cortical reorganisation. Allodynia was also accompanied by an activation of the cingulate cortex, occurring only 92 ms. after stimulus onset, an observation suggesting an Abeta-fiber-mediated neuronal pathway involved in dynamic mechanical allodynia. This study corroborates the concept of cortical reorganisation underlying chronic pain. Furthermore, it demonstrates that a remarkable early activation of the cingulate cortex may be involved in the cortical processing of allodynia.

Cerebral Cortex↗
PubMed2003

Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study.

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.

Adult↗
PubMed2003

[Fractionated stereotactically guided radiotherapy for pharmacoresistant epilepsy].

AIM: This prospective study evaluated the efficiency of fractionated stereotactically guided radiotherapy as a treatment of pharmacoresistant temporal lobe epilepsy. PATIENTS AND METHODS: Inclusion criteria were patients aged between 17 and 65 years with one-sided temporally located focus, without sufficient epilepsy control by antiepileptic drugs or neurosurgery. Between 1997 and 1999, two groups of six patients each were treated with 21 Gy (7 times 3 Gy) and 30 Gy (15 times 2 Gy). Study end points were seizure frequency, intensity, seizure length and neuropsychological parameters. RESULTS: All patients experienced a marked reduction in seizure frequency. The mean reduction of seizures was 37% (range 9-77%, i. e. seizures reduced from a monthly mean number of 11.75 to 7.52) at 18 months following radiation treatment and 46% (23-94%, i. e. 0.2-23 seizures per month) during the whole follow-up time. Seizure length was reduced in five out of eleven patients and intensity of seizures in seven out of eleven patients. CONCLUSION: Radiotherapy was identified as safe and effective for pharmacoresistant epilepsy since a very good reduction of seizure frequency was observed. It is no substitute for regular use of antiepileptic drugs, but means an appropriate alternative for patients with contraindication against neurosurgery or insufficient seizure reduction after neurosurgery.

Adolescent↗
PubMed2003

Autonomic phenomena of temperature regulation in temporal lobe epilepsy.

Cold shiver and piloerection are rare ictal signs in focal epilepsies. They are often associated with an epileptic seizure focus within the temporal lobe. In rare cases the phenomenon of piloerection has been reported to be confined to body parts ipsilateral to the seizure focus. In this multicentric study epilepsy patients with ictal cold shiver and/or piloerection were retrospectively asked to describe exactly location and spreading patterns of these signs as well as their temporal sequence in relation to other ictal signs. Clinical data, etiology of epilepsy, and seizure focus location were also assessed. In our patient group there was a high relationship to an epileptic focus within the left temporal lobe. Distinct spreading patterns or unilateral piloerection was not indicative of a focus in the ipsilateral temporal lobe as described previously. Our results suggest that phenomena of temperature dysregulation during epileptic seizures may be of value in the presurgical evaluation as they may be indicative of a left temporal lobe seizure focus.

Adult↗
PubMed2003

A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague-Dawley rats induced by Coriaria lactone and its possible mechanism.

PURPOSE: The aim of this study was to develop a new animal model of pharmacoresistant temporal lobe epilepsy (TLE) by repeated intramuscular injection of Coriaria lactone (CL) at subthreshold dosages and to explore the mechanisms that might be involved. METHODS: Healthy male Sprague-Dawley rats (n = 160) were randomized into four groups during the kindling process: three groups (n = 50 for each group) received CL injection at subthreshold dosages (1.25, 1.5, and 1.75 mg/kg, respectively), and ten received normal saline (NS) injection as a control group. The maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) was administered as monotherapy to different groups of kindled rats for 1 month (n = 20 for each group). Changes in EEG recording, seizure number, intensity (expressed as grade 1-5 according to Racine stage), and duration, including spontaneous seizures during different interventions, were compared. The expression of P-170, a multiple drug resistance gene (MDR1) encoding P-glycoprotein, was measured in brain samples from different groups of experimental rats by using an image analysis and measurement system (ImagePro-Plus 4.0). RESULTS: A total of 70 (46.7%) rats were fully kindled with a median of 15 (seven to 20) CL injections. Electrocorticogram (ECoG) including hippocampal (EHG) monitoring revealed the temporal lobe origins of epileptiform potentials, which were consistent with the behavioral changes observed. Spontaneous seizures occurred with frequency and diurnal patterns similar to those of human TLE. The antiepileptic drugs (AEDs) tested lacked a satisfactory seizure control. The maximal P-170 expression was in the kindled rats with AED treatment; the next highest was in the kindled rats without AED intervention. Nonkindled SD rats with CL injection also had increased P-170 expression compared with control SD rats. CONCLUSIONS: The study provided a simple and stable animal TLE kindling model with pharmacoresistant properties. The pharmacoresistance observed in the kindled rats to CBZ, VPA, and PHT at maximal human adult dosages together with the increased P-170 expression was a distinct feature of this model. This model might be used in further investigations of the mechanisms involved in pharmacoresistant TLE and for developing new AEDs.

ATP Binding Cassette Transporter, Subfamily B↗