Publications by authors named "Rainer Surges"

149 Publications

Predictors of postoperative long-term seizure outcome in pediatric patients with focal cortical dysplasia type II at a German tertiary epilepsy center.

J Neurosurg Pediatr 2021 Oct 15:1-9. Epub 2021 Oct 15.

1Department of Neurosurgery, University of Bonn.

Objective: Focal cortical dysplasia (FCD) is a common cause of early-onset intractable epilepsy, and resection is a highly sufficient treatment option. In this study, the authors aimed to provide a retrospective analysis of pre- and postoperative factors and their impact on postoperative long-term seizure outcome.

Methods: The postoperative seizure outcomes of 50 patients with a mean age of 8 ± 4.49 years and histologically proven FCD type II were retrospectively analyzed. Furthermore, pre- and postoperative predictors of long-term seizure freedom were assessed. The seizure outcome was evaluated based on the International League Against Epilepsy (ILAE) classification.

Results: Complete resection of FCD according to MRI criteria was achieved in 74% (n = 37) of patients. ILAE class 1 at the last follow-up was achieved in 76% (n = 38) of patients. A reduction of antiepileptic drugs (AEDs) to monotherapy or complete withdrawal was achieved in 60% (n = 30) of patients. Twelve patients (24%) had a late seizure recurrence, 50% (n = 6) of which occurred after reduction of AEDs. A lower number of AEDs prior to surgery significantly predicted a favorable seizure outcome (p = 0.013, HR 7.63). Furthermore, younger age at the time of surgery, shorter duration of epilepsy prior to surgery, and complete resection were positive predictors for long-term seizure freedom.

Conclusions: The duration of epilepsy, completeness of resection, number of AEDs prior to surgery, and younger age at the time of surgery served as predictors of postoperative long-term seizure outcome, and, as such, may improve clinical practice when selecting and counseling appropriate candidates for resective epilepsy surgery. The study results also underscored that epilepsy surgery should be considered early in the disease course of pediatric patients with FCD type II.
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http://dx.doi.org/10.3171/2021.7.PEDS21219DOI Listing
October 2021

Outcome after resective epilepsy surgery in the elderly.

J Neurosurg 2021 Oct 8:1-10. Epub 2021 Oct 8.

Departments of1Epileptology and.

Objective: The objective of this study was to compare complications, seizures, and neuropsychological outcomes after resective epilepsy surgery in patients ≥ 60 years of age who underwent operations to younger and matched controls.

Methods: Charts of 2243 patients were screened for operated patients in the authors' center between 2000 and 2015. Patients with available postsurgical follow-up data who were operated on at the age of 60 years or older and matched (by gender, histopathology, and side of surgery) controls who were between 20 and 40 years of age at the time of surgery were included. Outcomes regarding postoperative seizure control were scored according to the Engel classification and group comparisons were performed by using chi-square statistics.

Results: Data of 20 older patients were compared to those of 60 younger controls. Postoperative seizure control was favorable in the majority of the elderly patients (Engel classes I and II: 75% at 12 months, 65% at last follow-up), but the proportion of patients with favorable outcome tended to be larger in the control group (Engel classes I and II: 90% at 12 months, p = 0.092; 87% at last follow-up, p = 0.032, chi-square test). The surgical complication rate was higher in the elderly population (65% vs 27%, p = 0.002), but relevant persistent deficits occurred in 2 patients of each group only. Neuropsychological and behavioral assessments displayed considerable preoperative impairment and additional postoperative worsening, particularly of verbal skills, memory (p < 0.05), and mood in the elderly.

Conclusions: The overall favorable postsurgical outcome regarding seizure control and the moderate risk of disabling persistent neurological deficits in elderly patients supports the view that advanced age should not be a barrier per se for resective epilepsy surgery and underscores the importance of an adequate presurgical evaluation and of referral of elderly patients to presurgical assessment.
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http://dx.doi.org/10.3171/2021.4.JNS204013DOI Listing
October 2021

Timing of syncope in ictal asystole as a guide when considering pacemaker implantation.

J Cardiovasc Electrophysiol 2021 Sep 12. Epub 2021 Sep 12.

Stichting Epilepsie Instellingen Nederland (SEIN), Zwolle, The Netherlands.

Introduction: In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk.

Methods: In this retrospective cohort study, we searched video-EEG databases for individuals with focal seizures and IA (asystole ≥ 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting ≤3 s before syncope onset, or after syncope began, could not have been the dominant cause.

Results: We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5-32] vs. 5 [range: 3-9] s; p < .001) and those with the patient seated vs. supine (79% vs. 46%; p = .049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism.

Conclusions: In IA, cardioinhibition played an important role in most seizure-induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA.
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http://dx.doi.org/10.1111/jce.15239DOI Listing
September 2021

Infratentorial MRI Findings in Rasmussen Encephalitis Suggest Primary Cerebellar Involvement.

Neurol Neuroimmunol Neuroinflamm 2021 11 13;8(6). Epub 2021 Aug 13.

From the Department of Epileptology (J.T.R., B.D., S.E., C.C.P., T.B., C.E.E., R.S., T.R.), University Hospital Bonn; Charité-Universitätsmedizin Berlin (D.A., A.M.K.), Department of Pediatric Neurology; Charité-Universitätsmedizin Berlin (D.A., A.M.K.), Center for Chronically Sick Children; Charité-Universitätsmedizin Berlin (A.T.), Institute of Neuroradiology; Charité-Universitätsmedizin Berlin (A.M.K.), Institute for Cell Biology and Neurobiology; Department of Neuroradiology (V.K., A.R.), University Hospital Bonn; Department of Radiology and Nuclear Medicine (V.K.), Vrije Universiteit Amsterdam Medisch Centrum, The Netherlands; Institute of Experimental Epileptology and Cognition Research (B.W.), University Hospital Bonn; and Section for Translational Epilepsy Research (A.J.B.), Department of Neuropathology, University Hospital Bonn, Germany.

Background And Objective: Rasmussen encephalitis (RE) is characterized by its unilateral cerebral involvement. However, both ipsi- and contralesional cerebellar atrophy have been anecdotally reported raising questions about the nature and extent of infratentorial findings. Using MRI, we morphometrically investigated the cerebellum and hypothesized abnormalities beyond the effects of secondary atrophy, implicating a primary involvement of the cerebellum by RE.

Methods: Voxel-based morphometry of the cerebellum and brainstem was conducted in 57 patients with RE and in 57 matched controls. Furthermore, patient-specific asymmetry indices (AIs) of cerebellar morphometry and fluid-attenuated inversion recovery (FLAIR) intensity were calculated. Using diffusion tensor imaging, the integrity of the cortico-ponto-cerebellar (CPC) tract was assessed. Finally, a spatial independent component analysis (ICA) was used to compare atrophy patterns between groups.

Results: Patients with RE showed bilateral cerebellar and predominantly ipsilesional mesencephalic atrophy ( < 0.01). Morphometric AIs revealed ipsilesional < contralesional asymmetry in 27 and ipsilesional > contralesional asymmetry in 30 patients. In patients with predominant ipsilesional atrophy, morphometric AIs strongly correlated with FLAIR intensity AIs ( = 0.86, < 0.0001). Fractional anisotropy was lower for ipsilesional-to-contralesional CPC tracts than opposite tracts ( = 2.30, < 0.05). ICA revealed bilateral and strictly ipsi- and contralesional atrophy components in patients with RE ( < 0.05).

Discussion: We demonstrated atrophy of the ipsilesional-to-contralesional CPC pathway and, consequently, interpret the loss of contralesional gray matter as secondary crossed cerebellar atrophy. The ipsilesional cerebellar atrophy, however, defies this explanation. Based on FLAIR hyperintensities, we interpret ipsilesional atrophy to be due to inflammation in the scope of a primary involvement of the cerebellum by RE.
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http://dx.doi.org/10.1212/NXI.0000000000001058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382488PMC
November 2021

Functional redundancy of the premotor network in hemispherotomy patients.

Ann Clin Transl Neurol 2021 Sep 4;8(9):1796-1808. Epub 2021 Aug 4.

Department of Epileptology, University of Bonn Medical Center, Bonn, Germany.

Objective: Using multimodal imaging, we tested the hypothesis that patients after hemispherotomy recruit non-primary motor areas and non-pyramidal descending motor fibers to restore motor function of the impaired limb.

Methods: Functional and structural MRI data were acquired in a group of 25 patients who had undergone hemispherotomy and in a matched group of healthy controls. Patients' motor impairment was measured using the Fugl-Meyer Motor Assessment. Cortical areas governing upper extremity motor-control were identified by task-based functional MRI. The resulting areas were used as nodes for functional and structural connectivity analyses.

Results: In hemispherotomy patients, movement of the impaired upper extremity was associated to widespread activation of non-primary premotor areas, whereas movement of the unimpaired one and of the control group related to activations prevalently located in the primary motor cortex (all p ≤ 0.05, FWE-corrected). Non-pyramidal tracts originating in premotor/supplementary motor areas and descending through the pontine tegmentum showed relatively higher structural connectivity in patients (p < 0.001, FWE-corrected). Significant correlations between structural connectivity and motor impairment were found for non-pyramidal (p = 0.023, FWE-corrected), but not for pyramidal connections.

Interpretation: A premotor/supplementary motor network and non-pyramidal fibers seem to mediate motor function in patients after hemispherotomy. In case of hemispheric lesion, the homologous regions in the contralesional hemisphere may not compensate the resulting motor deficit, but the functionally redundant premotor network.
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http://dx.doi.org/10.1002/acn3.51427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419409PMC
September 2021

Seizure-mediated iron accumulation and dysregulated iron metabolism after status epilepticus and in temporal lobe epilepsy.

Acta Neuropathol 2021 10 22;142(4):729-759. Epub 2021 Jul 22.

Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Neuronal dysfunction due to iron accumulation in conjunction with reactive oxygen species (ROS) could represent an important, yet underappreciated, component of the epileptogenic process. However, to date, alterations in iron metabolism in the epileptogenic brain have not been addressed in detail. Iron-related neuropathology and antioxidant metabolic processes were investigated in resected brain tissue from patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), post-mortem brain tissue from patients who died after status epilepticus (SE) as well as brain tissue from the electrically induced SE rat model of TLE. Magnetic susceptibility of the presumed seizure-onset zone from three patients with focal epilepsy was compared during and after seizure activity. Finally, the cellular effects of iron overload were studied in vitro using an acute mouse hippocampal slice preparation and cultured human fetal astrocytes. While iron-accumulating neurons had a pyknotic morphology, astrocytes appeared to acquire iron-sequestrating capacity as indicated by prominent ferritin expression and iron retention in the hippocampus of patients with SE or TLE. Interictal to postictal comparison revealed increased magnetic susceptibility in the seizure-onset zone of epilepsy patients. Post-SE rats had consistently higher hippocampal iron levels during the acute and chronic phase (when spontaneous recurrent seizures are evident). In vitro, in acute slices that were exposed to iron, neurons readily took up iron, which was exacerbated by induced epileptiform activity. Human astrocyte cultures challenged with iron and ROS increased their antioxidant and iron-binding capacity, but simultaneously developed a pro-inflammatory phenotype upon chronic exposure. These data suggest that seizure-mediated, chronic neuronal iron uptake might play a role in neuronal dysfunction/loss in TLE-HS. On the other hand, astrocytes sequester iron, specifically in chronic epilepsy. This function might transform astrocytes into a highly resistant, pro-inflammatory phenotype potentially contributing to pro-epileptogenic inflammatory processes.
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http://dx.doi.org/10.1007/s00401-021-02348-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423709PMC
October 2021

Performance of ECG-based seizure detection algorithms strongly depends on training and test conditions.

Epilepsia Open 2021 Sep 20;6(3):597-606. Epub 2021 Jul 20.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Objective: To identify non-EEG-based signals and algorithms for detection of motor and non-motor seizures in people lying in bed during video-EEG (VEEG) monitoring and to test whether these algorithms work in freely moving people during mobile EEG recordings.

Methods: Data of three groups of adult people with epilepsy (PwE) were analyzed. Group 1 underwent VEEG with additional devices (accelerometry, ECG, electrodermal activity); group 2 underwent VEEG; and group 3 underwent mobile EEG recordings both including one-lead ECG. All seizure types were analyzed. Feature extraction and machine-learning techniques were applied to develop seizure detection algorithms. Performance was expressed as sensitivity, precision, F score, and false positives per 24 hours.

Results: The algorithms were developed in group 1 (35 PwE, 33 seizures) and achieved best results (F score 56%, sensitivity 67%, precision 45%, false positives 0.7/24 hours) when ECG features alone were used, with no improvement by including accelerometry and electrodermal activity. In group 2 (97 PwE, 255 seizures), this ECG-based algorithm largely achieved the same performance (F score 51%, sensitivity 39%, precision 73%, false positives 0.4/24 hours). In group 3 (30 PwE, 51 seizures), the same ECG-based algorithm failed to meet up with the performance in groups 1 and 2 (F score 27%, sensitivity 31%, precision 23%, false positives 1.2/24 hours). ECG-based algorithms were also separately trained on data of groups 2 and 3 and tested on the data of the other groups, yielding maximal F scores between 8% and 26%.

Significance: Our results suggest that algorithms based on ECG features alone can provide clinically meaningful performance for automatic detection of all seizure types. Our study also underscores that the circumstances under which such algorithms were developed, and the selection of the training and test data sets need to be considered and limit the application of such systems to unseen patient groups behaving in different conditions.
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http://dx.doi.org/10.1002/epi4.12520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408591PMC
September 2021

Transcutaneous vagus nerve stimulation in the treatment of drug-resistant epilepsy.

Auton Neurosci 2021 11 30;235:102840. Epub 2021 Jun 30.

Department of Epileptology, University Hospital Bonn, Venusberg Campus 1, 53127 Bonn, Germany.

Epilepsy is a common chronic neurological disease with a high burden of illness. Invasive vagus nerve stimulation (iVNS) is a well-established treatment option in patients with epilepsy (PWE). More recently, transcutaneous vagus nerve stimulation (tVNS) was introduced, an alternative option which is particularly interesting because it does not require surgery and is instantaneously removable. Here, we thoroughly reviewed clinical data on efficacy and safety of tVNS in epilepsies. Five prospective trials in 118 patients with drug-resistant epilepsies and 3 randomized controlled trials in 280 patients with drug-resistant epilepsies were carried out. Study protocols were heterogeneous in terms of patients' characteristics, used device, stimulation parameters, study duration and endpoints. Seizure reduction amounted up to 64%, with responder rates (seizure reduction ≥50%) up to 65%. Seizure freedom was reached in up to 24%, and even to 31% in a small pediatric study group. Seizure severity scores were provided in 4 studies, showing significant improvement in two of them. Adverse side effects were mostly headache, ear pain and skin alteration and rated as mild to moderate. Drowsiness might be depend on stimulation intensity. Quality of life scores reflecting burden of illness showed significant improvement in two studies. Efficacy and safety of tVNS in PWE has to be interpreted as promising. Multicenter randomized double-blind clinical trials with standardized stimulation protocols and long-term follow-up studies are necessary to finally assess tVNS treatment outcome in drug-resistant epilepsies.
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http://dx.doi.org/10.1016/j.autneu.2021.102840DOI Listing
November 2021

Analysis of autoantibody spectrum and human herpesvirus 6 in adult patients with 'early' versus 'late' diagnosis of 'possible limbic encephalitis'.

Epilepsy Res 2021 Oct 23;176:106698. Epub 2021 Jun 23.

Section for Translational Epilepsy Research, Dept. of Neuropathology, University Hospital Bonn, Germany; Dept. of Epileptology, University Hospital Bonn, Germany. Electronic address:

New onset temporal seizures are increasingly encountered in adult patients. Many of those fulfill diagnostic criteria for possible or definite limbic encephalitis (LE). LE is associated with autoantibodies (autoABs) against neuronal surface structures ('neuronal' autoABs), 'onconeuronal' or GAD65. AutoABs can emerge in a paraneoplastic setting. However, by far not all patients with possible/definite LE have an oncological history. AutoABs have also found to arise in the context of viral encephalitis. Rare associations between autoAB-positive LE and human herpes virus 6 (HHV-6) infection have been as well reported. Our present analysis was dedicated to learn about potentially different autoAB spectra and HHV-6 detection rates in adult-onset temporal seizure patients with possible LE and largely different time spans between first seizure events and referral to a tertiary epileptological center due to pharmacoresistent seizures. We scrutinized serum/CSF samples obtained from adults with 'early diagnosis' of possible LE (≤ 30 months after first seizure event; n = 94) versus a patient group with 'late diagnosis' of possible LE (≥ 97 months; n = 45) for the presence of autoABs and HHV-6 DNA. AutoABs were detected in CSF and/or serum samples (n = 20) in 21.3 % of the early diagnosis patients with the highest abundance of anti-LGI1 (n = 8), significantly more frequent than in the late diagnosis group (autoAB positive: n = 4 (8.9 %); *p < 0.05, Fisher's Exact Test). Quantitative PCR revealed viral HHV-6 DNA in only one serum sample of the early diagnosis cohort but no evidence in corresponding CSF samples or in any sample of the late diagnosis group. The present data demonstrate a higher incidence of distinct autoABs in adults with early diagnosis of possible LE. The distinct spectra of autoABs have to be taken into account in the differential diagnosis of possible LE patients with short versus more sustained duration of temporal seizure activity.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106698DOI Listing
October 2021

Duplicate Detection of Spike Events: A Relevant Problem in Human Single-Unit Recordings.

Brain Sci 2021 Jun 8;11(6). Epub 2021 Jun 8.

Department of Epileptology, University of Bonn Medical Center, Venusberg-Campus 1, 53127 Bonn, Germany.

Single-unit recordings in the brain of behaving human subjects provide a unique opportunity to advance our understanding of neural mechanisms of cognition. These recordings are exclusively performed in medical centers during diagnostic or therapeutic procedures. The presence of medical instruments along with other aspects of the hospital environment limit the control of electrical noise compared to animal laboratory environments. Here, we highlight the problem of an increased occurrence of simultaneous spike events on different recording channels in human single-unit recordings. Most of these simultaneous events were detected in clusters previously labeled as artifacts and showed similar waveforms. These events may result from common external noise sources or from different micro-electrodes recording activity from the same neuron. To address the problem of duplicate recorded events, we introduce an open-source algorithm to identify these artificial spike events based on their synchronicity and waveform similarity. Applying our method to a comprehensive dataset of human single-unit recordings, we demonstrate that our algorithm can substantially increase the data quality of these recordings. Given our findings, we argue that future studies of single-unit activity recorded under noisy conditions should employ algorithms of this kind to improve data quality.
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http://dx.doi.org/10.3390/brainsci11060761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228483PMC
June 2021

Post-Surgical Outcome and Its Determining Factors in Patients Operated on With Focal Cortical Dysplasia Type II-A Retrospective Monocenter Study.

Front Neurol 2021 9;12:666056. Epub 2021 Jun 9.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy. Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews. Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic-clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only. Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome.
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http://dx.doi.org/10.3389/fneur.2021.666056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220082PMC
June 2021

COVID-19 vaccination in patients with epilepsy: First experiences in a German tertiary epilepsy center.

Epilepsy Behav 2021 09 21;122:108160. Epub 2021 Jun 21.

Department of Epileptology, University Hospital of Bonn, Bonn, Germany.

Introduction: Due to the high demand for information regarding COVID-19 vaccination in people with epilepsy (PWE), we assessed the symptoms and seizure control of PWE following their COVID-19 vaccination.

Methods: All adult patients who were treated at our center were asked to report on their vaccination status and, if vaccinated, about their experiences following their first COVID-19 vaccination with regard to adverse effects and seizure control.

Results: Fifty-four PWE have already received their first vaccination against COVID-19 (27 female, 20% seizure free, 96<% on antiseizure medication) and were included in the study. Two-thirds tolerated the vaccines generally either very well or well. Thirty-three percent reported general vaccination adverse effects. The most frequently reported general adverse effects were, in descending order, headache, fatigue and fever, and shivering. With regard to epilepsy-related adverse effects, one patient reported increased seizure frequency one day after the first COVID-19 vaccination was administered, and one reported the occurrence of a new seizure type. None of the patients reported a status epilepticus or aggravation of preexisting adverse effects.

Conclusions: Our data suggest that vaccination against COVID-19 appears to be well tolerated in PWE, supporting the recommendation of vaccination to PWE.
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http://dx.doi.org/10.1016/j.yebeh.2021.108160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216683PMC
September 2021

Satisfaction with and reliability of in-hospital video-EEG monitoring systems in epilepsy diagnosis - A German multicenter experience.

Clin Neurophysiol 2021 Sep 1;132(9):2317-2322. Epub 2021 Jun 1.

Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University, Frankfurt am Main, Germany. Electronic address:

Objective: To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics.

Methods: A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics.

Results: Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service.

Conclusion: Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management.

Significance: This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement.
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http://dx.doi.org/10.1016/j.clinph.2021.04.020DOI Listing
September 2021

Permanent loss of independence in adult febrile-infection-related epilepsy syndrome survivors: an underestimated and unsolved challenge.

Eur J Neurol 2021 09 2;28(9):3061-3071. Epub 2021 Jul 2.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Background And Purpose: Febrile-infection-related epilepsy syndrome (FIRES) is an exceedingly rare and devastating subtype of new-onset refractory status epilepticus, which causes refractory epilepsy and permanent neurocognitive impairment.

Methods: This was a long-term follow-up of adult FIRES survivors treated between 2005 and 2018 as part of the EpiCARE initiative, a European Reference Network for rare and complex epilepsies. Clinical, electroencephalography, imaging and functional outcome measures are described using the Scores of Independence for Neurologic and Geriatric Rehabilitation, the modified Rankin Scale and the Global Assessment of Severity of Epilepsy Scale.

Results: Six patients with refractory epilepsy following FIRES were evaluated. Despite general improvement after intensive care unit discharge, disease severity was still high at follow-up in all patients. The functional outcome, as assessed by the modified Rankin Scale, was moderately impaired in 2/6 patients. In contrast, the Scores of Independence for Neurologic and Geriatric Rehabilitation indicated a loss of independence in 5/6, serious problems in memory and planning/problem-solving in 4/6 and serious attentional problems in 3/6 patients.

Conclusions: Febrile-infection-related epilepsy syndrome survivors may regain vital functions and mobility but experience a significant loss of independence and participation due to recurring seizures, structural brain damage and neurocognitive decline. Minimization of disastrous outcomes through the systematic evaluation of rescue therapies within a network of specialized centres is crucial.
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http://dx.doi.org/10.1111/ene.14958DOI Listing
September 2021

Visual surround suppression in people with epilepsy correlates with attentional-executive functioning, but not with epilepsy or seizure types.

Epilepsy Behav 2021 08 31;121(Pt A):108080. Epub 2021 May 31.

Department of Epileptology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

Purpose: Following reports that an index of visual surround suppression (SI) may serve as a biomarker for an imbalance of cortical excitation and inhibition in different psychiatric and neurological disorders including epilepsy, we evaluated whether SI is associated with seizure susceptibility, seizure spread, and inhibitory effects of antiseizure medication (ASM).

Methods: In this prospective controlled study, we examined SI with a motion discrimination task in people with genetic generalized epilepsy (GGE) and focal epilepsy with and without focal to bilateral tonic-clonic seizures. Cofactors such as GABAergic ASM, attentional-executive functioning, and depression were taken into account.

Results: Data of 45 patients were included in the final analysis. Suppression index was not related to epilepsy or seizure type, GABAergic ASM treatment or mood. However, SI correlated with attentional-executive functioning (r = 0.32), which in turn was associated with ASM load (r = -0.38). Repeated task administration (N = 7) proved a high stability over a one-week interval (r = 0.89).

Conclusions: Our results do not support the hypothesis that SI is a reliable biomarker for mechanisms related to inhibition of seizure spread or seizure frequency, i.e., it does not seem to reflect inhibitory capacities in epilepsy. Likewise, SI did not differentiate GGE from focal epilepsy, nor was it influenced by ASM load or mode of action. Thus, in epilepsy, no added value of including SI to routine diagnostics can be concluded.
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http://dx.doi.org/10.1016/j.yebeh.2021.108080DOI Listing
August 2021

Atrioventricular Conduction in Mesial Temporal Lobe Seizures.

Front Neurol 2021 28;12:661391. Epub 2021 Apr 28.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Asymmetric cerebral representation of autonomic function could help to stratify cardiac complications in people with epilepsy, as some seizures are associated with potentially deleterious arrhythmias including bradycardia and atrioventricular (AV) conduction block. We investigated seizure-related changes in AV conduction and ascertained whether these alterations depend on the hemisphere in mesial temporal lobe epilepsy (mTLE). EEG and ECG data of people with pharmacoresistant mTLE undergoing pre-surgical video-EEG telemetry with seizures independently arising from both hippocampi, as determined by intracranial depths electrodes were reviewed. RR and PR intervals were measured using one-lead ECG. Statistics were done with paired student's -tests and linear regression analysis. Data are given as mean ± SD. Fifty-six seizures of 14 patients (5 men, age 34.7 ± 9.8 years) were included (2 seizures per hemisphere and patient). There were no differences of absolute PR intervals and HR before and during unilateral ictal activity between left- and right-sided hippocampal seizures. Peri-ictal modulation of AV conduction, however, appeared greater with left-sided seizures, as the slope of the PR/HR correlations was significantly steeper with seizures originating in the left hippocampus. PR lengthening >200 ms or full block did not occur in any seizure. Our data show that on average, PR intervals shortens with mesial temporal lobe seizures with more prominent effects in seizures with left-sided onset, supporting the notion of lateralized cerebral control of cardiac function. The clinical relevance of this subtle finding is unclear but may indicate a lateralized susceptibility to seizure-related AV node dysfunction in mTLE.
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http://dx.doi.org/10.3389/fneur.2021.661391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115552PMC
April 2021

Tumor-associated epilepsy in patients with brain metastases: necrosis-to-tumor ratio forecasts postoperative seizure freedom.

Neurosurg Rev 2021 May 14. Epub 2021 May 14.

Department of Neurosurgery, Center of Integrated Oncology (CIO) Bonn, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Surgical resection is highly effective in the treatment of tumor-related epilepsy (TRE) in patients with brain metastases (BM). Nevertheless, some patients suffer from postoperative persistent epilepsy which negatively impacts health-related quality of life. Therefore, early identification of patients with potentially unfavorable seizure outcome after BM resection is important. Patients with TRE that had undergone surgery for BM at the authors' institution between 2013 and 2018 were analyzed with regard to preoperatively identifiable risk factors for unfavorable seizure outcome. Tumor tissue and tumor necrosis ratios were assessed volumetrically. According to the classification of the International League Against Epilepsy (ILAE), seizure outcome was categorized as favorable (ILAE 1) and unfavorable (ILAE 2-6) after 3 months in order to avoid potential interference with adjuvant cancer treatment. Among all 38 patients undergoing neurosurgical treatment for BM with concomitant TRE, 34 patients achieved a favorable seizure outcome (90%). Unfavorable seizure outcome was significantly associated with larger tumor volumes (p = 0.012), a midline shift > 7 mm (p = 0.025), and a necrosis/tumor volume ratio > 0.2 (p = 0.047). The present study identifies preoperatively collectable risk factors for unfavorable seizure outcome in patients with BM and TRE. This might enable to preselect for highly vulnerable patients with postoperative persistent epilepsy who might benefit from accompanying neuro-oncological expertise during further systemical treatment regimes.
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http://dx.doi.org/10.1007/s10143-021-01560-yDOI Listing
May 2021

CSF and Serum Biomarkers of Cerebral Damage in Autoimmune Epilepsy.

Front Neurol 2021 16;12:647428. Epub 2021 Apr 16.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Our goal was to investigate whether biomarkers of cerebral damage are found in autoimmune-mediated epilepsy (AIE) and whether these can differentiate AIE from other seizure disorders. We retrospectively searched our cerebrospinal fluid (CSF) database for patients with definite AIE, hippocampal sclerosis due to other causes (HS), genetic generalized epilepsy (GGE), and psychogenic, non-epileptic seizures (PNES). We measured serum and CSF tau, neurofilament 1 (NFL), glial fibrillary acid protein (GFAP), and ubiquitin-carboxy-terminal hydrolase L1 with a single-molecule array. We identified suitable samples from patients with AIE ( = 13) with different antibodies and compared them to HS ( = 13), GGE ( = 7), and PNES ( = 8). The NFL levels were significantly elevated in the serum ( = 0.0009) and CSF ( < 0.0019) of AIE patients. The AIE group was significantly older, while the disease duration was significantly shorter than in the control groups. NFL correlated significantly with age in all groups, and the NFL levels of AIE patients were hardly higher than those of healthy elderly people published elsewhere. Our data indicate that the elevated NFL levels in AIE patients are most likely due to the higher age in this group and not due to the underlying inflammation. Unless larger prospective studies with intra-individual, longitudinal analyses and treatment responses would contradict our findings, NFL in serum might yet become a biomarker for disease activity and differential diagnosis.
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http://dx.doi.org/10.3389/fneur.2021.647428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085401PMC
April 2021

Auditory Beat Stimulation Modulates Memory-Related Single-Neuron Activity in the Human Medial Temporal Lobe.

Brain Sci 2021 Mar 12;11(3). Epub 2021 Mar 12.

Department of Epileptology, Venusberg-Campus 1, University Hospital Bonn, 53127 Bonn, Germany.

Auditory beats are amplitude-modulated signals (monaural beats) or signals that subjectively cause the perception of an amplitude modulation (binaural beats). We investigated the effects of monaural and binaural 5 Hz beat stimulation on neural activity and memory performance in neurosurgical patients performing an associative recognition task. Previously, we had reported that these beat stimulation conditions modulated memory performance in opposite directions. Here, we analyzed data from a patient subgroup, in which microwires were implanted in the amygdala, hippocampus, entorhinal cortex and parahippocampal cortex. We identified neurons responding with firing rate changes to binaural versus monaural 5 Hz beat stimulation. In these neurons, we correlated the differences in firing rates for binaural versus monaural beats to the memory-related differences for remembered versus forgotten items and associations. In the left hemisphere, we detected statistically significant negative correlations between firing rate differences for binaural versus monaural beats and remembered versus forgotten items/associations. Importantly, such negative correlations were also observed between beat stimulation-related firing rate differences in the pre-stimulus window and memory-related firing rate differences in the post-stimulus windows. In line with concepts of homeostatic plasticity, our findings suggest that beat stimulation is linked to memory performance via shifting baseline firing levels.
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http://dx.doi.org/10.3390/brainsci11030364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000797PMC
March 2021

A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies.

Epilepsia Open 2021 03 13;6(1):160-170. Epub 2021 Jan 13.

IRCCS Mondino Foundation Pavia Italy.

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies.

Methods: Members of the ( were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease.

Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers.

Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.
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http://dx.doi.org/10.1002/epi4.12459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918306PMC
March 2021

Identifying patients with epilepsy at high risk of cardiac death: signs, risk factors and initial management of high risk of cardiac death.

Epileptic Disord 2021 Feb;23(1):17-39

Stichting Epilepsie Instellingen Nederland - SEIN, Achterweg 5, 2103 SW, Heemstede, The Netherlands, NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK, Department of Neurology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

People with epilepsy have a three-fold increased risk of dying prematurely, and a significant proportion is due to sudden cardiac death or acute myocardial infarctions. The causes of increased cardiovascular morbidity and mortality in epilepsy are manifold and include acute or remote effects of epileptic seizures, the longstanding epilepsy itself or antiseizure treatments. Seizure-related cardiac arrhythmias are common and comprise bradyarrhythmia and asystole, atrial fibrillation and ventricular tachycardia. The most frequent clinically relevant seizure-related arrhythmia is ictal asystole that may require implantation of a cardiac pacemaker, whereas seizure-related ventricular tachycardias are only rarely reported. Takotsubo cardiomyopathy and myocardial infarction are rare complications and predominantly described in association with tonic-clonic seizures. Epilepsy-related cardiac complications include a disturbed cardiac autonomic nervous system and acquired dysfunction of the heart (recently defined as 'epileptic heart'), probably contributing to the abnormalities of cardiac repolarisation and elevated risk of sudden cardiac death in people with epilepsy. If successful, the use of antiseizure medication prevents seizure-related cardiac arrhythmias and remote cardiac complications. However, enzyme-inducing antiseizure medications have a negative impact on cardiovascular risk factors, which may further be aggravated by weight gain linked to specific antiseizure drugs. Given the severe consequences of cardiac risks, the aim of this educational review is to explain the many facets of cardiac complications and their underlying causes, and to enable the reader to recognize and manage these risks with the goal to mitigate the cardiac risks in people with epilepsy. Features of syncope are explained in detail, as syncope of all origins can be mistaken as epileptic seizures in people with or without epilepsy, and ictal syncope (i.e. seizure-induced syncope) can easily be ignored.
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http://dx.doi.org/10.1684/epd.2021.1254DOI Listing
February 2021

External validation of automated focal cortical dysplasia detection using morphometric analysis.

Epilepsia 2021 04 27;62(4):1005-1021. Epub 2021 Feb 27.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Objective: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set.

Methods: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years).

Results: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%.

Significance: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy.
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http://dx.doi.org/10.1111/epi.16853DOI Listing
April 2021

[SUDEP in brief - knowledge and practice recommendations on sudden unexpected death in epilepsy].

Nervenarzt 2021 Aug 16;92(8):809-815. Epub 2021 Feb 16.

Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Centre for Cognitive Neuroscience, Salzburg, Österreich.

Sudden unexpected death in epilepsy (SUDEP) is the sudden and unexpected death of an epilepsy patient, which occurs under benign circumstances without evidence of typical causes of death. SUDEP concerns all epilepsy patients. The individual risk depends on the characteristics of the epilepsy and seizures as well as on living conditions. Focal to bilateral and generalized tonic-clonic seizures (TCS), nocturnal seizures and lack of nocturnal supervision increase the risk. Most SUDEP cases are due to a fatal cascade of apnea, hypoxemia and asystole in the aftermath of a TCS. Two thirds of SUDEP cases in unsupervised epilepsy patients with TCS could probably be prevented. Wearables can detect TCS and alert caregivers. SUDEP information is desired by most patients and relatives, has a favorable impact on treatment adherence and behavior and has no negative effects on mood and quality of life.Recommendations of the committee on patient safety of the German Society of Epileptology: the ultimate treatment goal is seizure freedom. If this cannot be achieved, control of TCS should be sought. All epilepsy patients and their relatives should be informed about SUDEP and risk factors. Patients and relatives should be informed about measures to counteract the elevated risk and imminent SUDEP. The counselling should be performed during a face-to-face discussion, at the time of first diagnosis or during follow-up visits. The counselling should be documented. Wearables for TCS detection can be recommended. If TCS persist, therapeutic efforts should be continued. The bereaved should be contacted after a SUDEP.
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http://dx.doi.org/10.1007/s00115-021-01075-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342364PMC
August 2021

Cannabidiol in the Treatment of Epilepsy.

Clin Drug Investig 2021 Mar 9;41(3):211-220. Epub 2021 Feb 9.

Department of Epileptology, University Hospital Bonn (UKB), Venusberg Campus 1, 53127, Bonn, Germany.

Anecdotal reports addressing the successful seizure treatment of severe epilepsies with cannabidiol (CBD) have increased both public interest and academic research. Placebo-controlled, randomized, controlled trials proved the efficacy of pharmaceutical-grade CBD in epilepsy treatment, thus leading to pharmaceutical-grade CBD approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of seizures in Dravet syndrome and Lennox-Gastaut syndrome as well as for tuberous complex syndrome by the Food and Drug Administration only. However, the CBD market is confusing because an array of products of different origins, purity, and concentration is available. Additionally, the results from the pivotal studies with plant-derived, pharmaceutical-grade CBD cannot simply be transferred to other epilepsy types or CBD of any origin. Because of the high demands and expectations that patients with epilepsy and their caregivers have regarding CBD, information outlining the proven facts and potential risks is essential. The aim of this article is to thoroughly review available research data and practical recommendations to provide the treating physician with the necessary information for counseling patients with epilepsy.
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http://dx.doi.org/10.1007/s40261-021-01003-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946683PMC
March 2021

Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection.

J Neurooncol 2021 Apr 7;152(2):339-346. Epub 2021 Feb 7.

Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Introduction: The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures.

Methods: Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors' institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2-6).

Results: Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4-515.9).

Conclusions: ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.
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http://dx.doi.org/10.1007/s11060-021-03705-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997820PMC
April 2021

Novel Mutations Associated with Epilepsy: Broadening the Phenotypic Spectrum of -Associated Diseases.

Genes (Basel) 2021 01 21;12(2). Epub 2021 Jan 21.

Department of Epileptology, University Hospital Bonn, 53127 Bonn, Germany.

Here, we describe four patients suffering from a rather broad spectrum of epilepsy-related disorders, ranging from developmental and epileptic encephalopathy with intellectual disability (DEE) to genetic generalized epilepsy (GGE), which all harbor novel mutations. In one family, we found a weak association of a novel nonsense mutation with epilepsy, suggesting reduced penetrance, and which shows, in agreement with previous findings, that gain-of-function effects rather than haploinsufficiency are important for the pathogenicity of mutations. De novo missense variants in the pore region of the channel result in severe phenotypes presenting usually with DEE with various malformations. The potential pathogenicity of a novel germline mutation located outside of the critical pore domain observed in a GGE patient with a milder phenotype is supported by the fact that the very same amino acid exchange was detected as a somatic mutation in the resected brain tissue of a patient suffering from a focal cortical dysplasia type IIb. Thus, our case series broadens the phenotypic spectrum of -associated diseases.
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http://dx.doi.org/10.3390/genes12020132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909785PMC
January 2021

Multi-scale image analysis and prediction of visual field defects after selective amygdalohippocampectomy.

Sci Rep 2021 01 14;11(1):1444. Epub 2021 Jan 14.

Department of Epileptology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.

Selective amygdalohippocampectomy is an effective treatment for patients with therapy-refractory temporal lobe epilepsy but may cause visual field defect (VFD). Here, we aimed to describe tissue-specific pre- and postoperative imaging correlates of the VFD severity using whole-brain analyses from voxel- to network-level. Twenty-eight patients with temporal lobe epilepsy underwent pre- and postoperative MRI (T1-MPRAGE and Diffusion Tensor Imaging) as well as kinetic perimetry according to Goldmann standard. We probed for whole-brain gray matter (GM) and white matter (WM) correlates of VFD using voxel-based morphometry and tract-based spatial statistics, respectively. We furthermore reconstructed individual structural connectomes and conducted local and global network analyses. Two clusters in the bihemispheric middle temporal gyri indicated a postsurgical GM volume decrease with increasing VFD severity (FWE-corrected p < 0.05). A single WM cluster showed a fractional anisotropy decrease with increasing severity of VFD in the ipsilesional optic radiation (FWE-corrected p < 0.05). Furthermore, patients with (vs. without) VFD showed a higher number of postoperative local connectivity changes. Neither in the GM, WM, nor in network metrics we found preoperative correlates of VFD severity. Still, in an explorative analysis, an artificial neural network meta-classifier could predict the occurrence of VFD based on presurgical connectomes above chance level.
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http://dx.doi.org/10.1038/s41598-020-80751-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809286PMC
January 2021

CD8 T-Lymphocyte-Driven Limbic Encephalitis Results in Temporal Lobe Epilepsy.

Ann Neurol 2021 04 15;89(4):666-685. Epub 2021 Jan 15.

Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, Bonn, Germany.

Objective: Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence of autoantibodies and lymphoid cells. However, the potential of distinct lymphocyte subsets alone to elicit key clinicopathological sequelae of LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures and hippocampal sclerosis (HS) is unresolved.

Methods: Here, we scrutinized pathogenic consequences emerging from CD8 T cells targeting hippocampal neurons by recombinant adeno-associated virus-mediated expression of the model-autoantigen ovalbumin (OVA) in CA1 neurons of OT-I/RAG1 mice (termed "OVA-CD8 LE model").

Results: Viral-mediated antigen transfer caused dense CD8 T cell infiltrates confined to the hippocampal formation starting on day 5 after virus transduction. Flow cytometry indicated priming of CD8 T cells in brain-draining lymph nodes preceding hippocampal invasion. At the acute model stage, the inflammatory process was accompanied by frequent seizure activity and impairment of hippocampal memory skills. Magnetic resonance imaging scans at day 7 of the OVA-CD8 LE model revealed hippocampal edema and blood-brain barrier disruption that converted into atrophy until day 40. CD8 T cells specifically targeted OVA-expressing, SIINFEKL-H-2K -positive CA1 neurons and caused segmental apoptotic neurodegeneration, astrogliosis, and microglial activation. At the chronic model stage, mice exhibited spontaneous recurrent seizures and persisting memory deficits, and the sclerotic hippocampus was populated with CD8 T cells escorted by NK cells.

Interpretation: These data indicate that a CD8 T-cell-initiated attack of distinct hippocampal neurons is sufficient to induce LE converting into TLE-HS. Intriguingly, the role of CD8 T cells exceeds neurotoxic effects and points to their major pathogenic role in TLE following LE. ANN NEUROL 2021;89:666-685.
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http://dx.doi.org/10.1002/ana.26000DOI Listing
April 2021

Serum biomarkers of cerebral cellular stress after self-limiting tonic clonic seizures: An exploratory study.

Seizure 2021 Feb 17;85:1-5. Epub 2020 Dec 17.

Center of Clinical Neuroscience, Department of Neurology, Carl Gustav Carus University Hospital, Dresden, Germany.

Objective: It has been debated for decades whether single, self-limited seizures damage cerebral cells. Meanwhile, very sensitive measurements of biomarkers have become available, i.e. tau, neurofilament protein light (NFL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminate hydrolase L1 (UCHL-1), which we explored in this study.

Methods: Adult patients of the epilepsy monitoring unit were admitted to the study after written consent. Blood samples were drawn at baseline, immediately after a TCS and after two, six and 24 h. The markers were measured from frozen samples with a single-molecule array (SIMOA).

Results: 20 patients and 20 seizures were included. All markers showed subtle but significant postictal increases and returned to normal within the next few hours (p < 0.05). An increase of at least 100 % from baseline was noted in 30 % of patients for tau, 25 % for UCHL-1 and 15 % for GFAP, while NFL levels never increased above 100 %. Lactate was slightly correlated with the tau increase (r = 0.47, p = 0.037), leukocytes were correlated with postictal changes of GFAP (r = 0.68 p = 0.001).

Conclusion: Our data supports the assumption that significant cerebral stress occurs in some but not all self-limited TCS. The postictal inflammatory response in particular seems to play an important role.
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http://dx.doi.org/10.1016/j.seizure.2020.12.009DOI Listing
February 2021
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