Publications by authors named "Christian E Elger"

402 Publications

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

Epilepsia Open 2021 Jul 12. Epub 2021 Jul 12.

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
July 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

Occurrence of status epilepticus in persons with epilepsy is determined by sex, epilepsy classification, and etiology: a single center cohort study.

J Neurol 2021 May 21. Epub 2021 May 21.

Department of Neurology with Institute of Translational Neurology, University of Münster, University Hospital Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Germany.

Background: Status epilepticus (SE) can occur in persons with or without epilepsy and is associated with high morbidity and mortality.

Methods: This survey aimed to record self-reported frequency of SE in persons with epilepsy, its association with clinical characteristics and patient level of information on SE and rescue medication. 251 persons with epilepsy at a tertiary epilepsy center were included in the study.

Results: 87 (35%) had a history of SE defined as seizure duration of more than 5 min. These patients were less likely to be seizure-free, and had a higher number of present and past anti-seizure medication. Female sex, cognitive disability, younger age at epilepsy onset, defined epilepsy etiology, and focal epilepsy were associated with a history of SE. On Cox regression analysis, female sex, defined etiology and focal classification remained significant. 67% stated that they had information about prolonged seizures, and 75% knew about rescue medication. 85% found it desirable to receive information about SE at the time of initial diagnosis of epilepsy, but only 16% had been offered such information at the time.

Conclusion: SE is frequent among persons with epilepsy and there remain unmet needs regarding patient education.
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http://dx.doi.org/10.1007/s00415-021-10600-yDOI Listing
May 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 Jan 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

Resection of piriform cortex predicts seizure freedom in temporal lobe epilepsy.

Ann Clin Transl Neurol 2021 01 2;8(1):177-189. Epub 2020 Dec 2.

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

Objective: Transsylvian selective amygdalo-hippocampectomy (tsSAHE) represents a generally recognized surgical procedure for drug-resistant mesial temporal lobe epilepsy (mTLE). Although postoperative seizure freedom can be achieved in about 70% of tsSAHE, there is a considerable amount of patients with persisting postoperative seizures. This might partly be explained by differing extents of resection of various tsSAHE target volumes. In this study we analyzed the resected proportions of hippocampus, amygdala as well as piriform cortex in regard of postoperative seizure outcome.

Methods: Between 2012 and 2017, 82 of 103 patients with mTLE who underwent tsSAHE at the authors' institution were included in the analysis. Resected proportions of hippocampus, amygdala and temporal piriform cortex as target structures of tsSAHE were volumetrically assessed and stratified according to favorable (International League Against Epilepsy (ILAE) class 1) and unfavorable (ILAE class 2-6) seizure outcome.

Results: Patients with favorable seizure outcome revealed a significantly larger proportion of resected temporal piriform cortex volumes compared to patients with unfavorable seizure outcome (median resected proportional volumes were 51% (IQR 42-61) versus (vs.) 13 (IQR 11-18), P = 0.0001). Resected proportions of hippocampus and amygdala did not significantly differ for these groups (hippocampus: 81% (IQR 73-88) vs. 80% (IQR 74-92) (P = 0.7); amygdala: 100% (IQR 100-100) vs. 100% (IQR 100-100) (P = 0.7)).

Interpretation: These results strongly suggest temporal piriform cortex to constitute a key target resection volume to achieve seizure freedom following tsSAHE.
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http://dx.doi.org/10.1002/acn3.51263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818082PMC
January 2021

Adult-onset temporal lobe epilepsy suspicious for autoimmune pathogenesis: Autoantibody prevalence and clinical correlates.

PLoS One 2020 29;15(10):e0241289. Epub 2020 Oct 29.

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

Temporal lobe adult-onset seizures (TAOS) related to autoimmunity represent an increasingly recognized disease syndrome within the spectrum of epilepsies. In this context, certain autoantibodies (autoABs) were often associated with limbic encephalitis (LE). Here, we aimed to gain insights into (a) the distribution of 'neurological' autoABs (neuroABs, defined as autoABs targeting neuronal surface structures or 'onconeuronal' ABs or anti-glutamate acid decarboxylase 65 (GAD65) autoABs) in a large consecutive TAOS patient cohort, to characterize (b) clinical profiles of seropositive versus seronegative individuals and to find (c) potential evidence for other autoABs. Blood sera/cerebrospinal fluid (CSF) of TAOS patients (n = 800) and healthy donors (n = 27) were analyzed for neuroABs and screened for other autoABs by indirect immunofluorescence on hippocampal/cerebellar sections and immunoblots of whole brain and synaptosome lysates. Serological results were correlated with clinico-neuropsychological features. 13% of TAOS patients (n = 105) were neuroAB+, with anti-GAD65 and anti-N-methyl-D-aspartate receptors (NMDAR) as most frequent autoABs in this group. In our screening tests 25% of neuroAB- patients (n = 199) were positive (screening+), whereas all control samples were negative (n = 27). Intriguingly, key clinico-neuropsychological characteristics including magnetic resonance imaging (MRI) findings, epileptiform electroencephalographic (EEG) activity, and inflammatory cellular infiltrates in CSF were shared to a greater extent by neuroAB+ with neuroAB-/screening+ patients than with neuroAB-/screening- patients. Serological testing in a large consecutive TAOS patient series revealed seropositivity for anti-GAD65 autoABs as the most frequent neuroAB. Intriguingly, neuroAB+ individuals were virtually indistinguishable from neuroAB-/screening+ patients in several major clinical features. In contrast, neuroAB-/screening- TAOS patients differed in many parameters. These data support the potential presence of so far unrecognized autoABs in patients with TAOS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241289PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595292PMC
December 2020

Does the accumulated antiepileptic drug load in chronic epilepsy reflect disease severity?

Epilepsia 2020 12 15;61(12):2685-2695. Epub 2020 Oct 15.

Department of Epileptology, University Hospital Bonn (UKB), Bonn, Germany.

Objective: To ascertain factors that are related to the antiepileptic drug load in epilepsy.

Methods: In this cross-sectional study, we analyzed a large cohort of conservatively treated patients with epilepsy (n = 1135) and a smaller homogeneous group of presurgical patients with neuropathologically confirmed unilateral hippocampal sclerosis (n = 91). Considered clinical variables comprised (1) presence of an underlying cerebral lesion, (2) onset and (3) duration of epilepsy, (4) seizure frequency, (5) generalized or focal to bilateral tonic-clonic seizures, (6) ictal impairment of awareness, and (7) a history of convulsive status epilepticus. In the presurgical sample, we additionally considered (8) the degree of pathology (hippocampal neuronal cell densities) instead of (1) presence of a cerebral lesion and (9) an overall rating of epilepsy severity (GASE scale). Drug load was quantified as (a) the number of concomitant antiepileptic drugs (AEDs) and (b) the total defined daily dose (DDD).

Results: Analyses disclosed only small correlations between clinical variables and drug load indices. In the conservatively treated cohort, the multiple regression analyses revealed that epilepsy onset, cerebral lesion, history of convulsive status epilepticus, and seizure frequency combined explained only 6%-10% of variance in drug load. Nearly the same variance (5%-8%) could be explained by duration of epilepsy alone. Degree of hippocampal pathology and the epilepsy severity ratings were not related to drug load indices.

Significance: Clinical markers of epilepsy severity were only marginally associated with drug load. Findings rather indicate that patients seem to accumulate drugs due to the chronicity of epilepsy. Overall, the drug load remained largely unexplained. The findings nevertheless call for scrutinizing multidrug therapies in patients with long-lasting epilepsies.
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http://dx.doi.org/10.1111/epi.16720DOI Listing
December 2020

Single-Neuron Correlates of Decision Confidence in the Human Medial Temporal Lobe.

Curr Biol 2020 12 8;30(23):4722-4732.e5. Epub 2020 Oct 8.

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

The human medial temporal lobe (MTL) has been suggested to play a role in valuation. However, little is known about its role in binary decisions and metacognition. We performed two decision-making tasks while recording from neurons in the human MTL. During a break, subjects consumed their preferred food item to satiation and subsequently repeated both tasks. We identified both a persistent and a transient modulation of the neural activity. Two independent subpopulations of neurons showed a persistent correlation of their firing rates with either decision confidence or reaction times. Importantly, the changes in confidence and reaction time between experimental sets were accompanied by a correlated change in the neural activity, and this correlation lasted as long as it was relevant for the behavioral task. Previous studies have suggested a transient modulation of the neural activity in the human MTL correlated with subjective value. However, in our study, neither subjective value nor unsigned value could explain this transient activity better than the nutritional features of the stimuli, calling into question the role of the human MTL in valuation.
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http://dx.doi.org/10.1016/j.cub.2020.09.021DOI Listing
December 2020

Structural network topology in limbic encephalitis is associated with amygdala enlargement, memory performance and serostatus.

Epilepsia 2020 10 17;61(10):e140-e145. Epub 2020 Sep 17.

Department of Epileptology, University Hospital Bonn, Germany.

Limbic encephalitis (LE) forms a spectrum of autoimmune diseases involving temporal lobe epilepsy and memory impairment. Imaging features of LE are known to depend on the associated antibody and to occur on the brain network level. However, first studies investigating brain networks in LE have either focused on one distinct antibody subgroup or on distinct anatomical regions. In this study, brain graphs of 17 LE patients with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE), four LE patients with autoantibodies against leucine-rich glioma-inactivated 1, five LE patients with autoantibodies against contactin-associated protein-like 2, 26 age- and gender-matched healthy control subjects, and 20 epilepsy control patients with hippocampal sclerosis were constructed based on T1-weighted structural magnetic resonance imaging scans and diffusion tensor imaging. GAD-LE showed significantly altered global network topology in terms of integration and segregation as compared to healthy controls and patients with hippocampal sclerosis (P < .01, analysis of variance with Tukey-Kramer post hoc tests). Linear regression linked global network measures with amygdala volume and verbal memory performance (P < .05). Alterations of local network topology show serotype dependence in hippocampus, amygdala, insula, and various cortical regions. Our findings reveal serotype-dependent patterns of structural connectivity and prove the relevance of in silico network measures on clinical grounds.
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http://dx.doi.org/10.1111/epi.16691DOI Listing
October 2020

Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies.

Epilepsia 2020 10 7;61(10):e153-e158. Epub 2020 Sep 7.

Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.

Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen-DR isotype (HLA-DR)-expressing CD4 T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14 CD16 cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR-expressing CD8 T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.
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http://dx.doi.org/10.1111/epi.16688DOI Listing
October 2020

Contralesional White Matter Alterations in Patients After Hemispherotomy.

Front Hum Neurosci 2020 7;14:262. Epub 2020 Jul 7.

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

Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A -test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values ( < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls ( < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.
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http://dx.doi.org/10.3389/fnhum.2020.00262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358777PMC
July 2020

Predictive value of electrically induced seizures for postsurgical seizure outcome.

Clin Neurophysiol 2020 09 30;131(9):2289-2297. Epub 2020 Jun 30.

Department of Epileptology, University Hospital Bonn, Bonn, Germany. Electronic address:

Objective: To determine whether semiological similarity of electrically induced seizures (EIS) and spontaneously occurring habitual seizures (SHS) is associated with postsurgical seizure outcome in patients undergoing invasive video-EEG monitoring (VEM) before resective epilepsy surgery.

Methods: Data of patients undergoing invasive VEM were retrospectively reviewed and included if at least one EIS and SHS during VEM occurred and the brain region in which EIS were elicited was resected. Seizure outcome was evaluated at three follow-up (FU) visits after surgery (1, 2 years and last available FU) according to the classification by Engel and the International League Against Epilepsy (ILAE). The level of semiological similarity of EIS and SHS was rated blinded to the surgical outcome. Statistics were done using Fisher's exact test and a mixed linear-logistic regression model.

Results: 65 patients were included. Postsurgical seizure freedom was achieved in 51% (ILAE class 1) and 58% (Engel class I) at last FU (median 36 months). Patients with identical EIS and SHS displayed significantly better postsurgical seizure outcomes (ILAE class 1 at last FU: 76% vs. 31%, p < 0.001; Engel class I: 83% vs. 39%, p < 0.001).

Conclusion: EIS are useful to confirm the location of the epileptogenic zone. A high level of similarity between EIS and SHS is associated with a favorable postsurgical seizure outcome.

Significance: EIS may be used as an additional predictor of postsurgical outcome when counselling patients to proceed to resective epilepsy surgery.
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http://dx.doi.org/10.1016/j.clinph.2020.06.013DOI Listing
September 2020

Fixel-based analysis links white matter characteristics, serostatus and clinical features in limbic encephalitis.

Neuroimage Clin 2020 26;27:102289. Epub 2020 May 26.

Department of Epileptology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University Frankfurt, Schleusenweg 2, 60528 Frankfurt, Germany; Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Schleusenweg 2, 60528 Frankfurt, Germany. Electronic address:

Limbic encephalitis (LE) is an autoimmune syndrome often associated with temporal lobe epilepsy. Recent research suggests that particular structural changes in LE depend on the type of the associated antibody and occur in both mesiotemporal gray matter and white matter regions. However, it remains questionable to what degree conventional diffusion tensor imaging (DTI)-methods reflect alterations in white matter microstructure, since these methods do not account for crossing fibers. To address this methodological shortcoming, we applied fixel-based analysis as a novel technique modeling distinct fiber populations. For our study, 19 patients with LE associated with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE, mean age = 35.9 years, 11 females), 4 patients with LE associated with autoantibodies against leucine-rich glioma-inactivated 1 (LGI1-LE, mean age = 63.3 years, 2 females), 5 patients with LE associated with contactin-associated protein-like 2 (CASPR2, mean age = 57.4, 0 females), 20 age- and gender-matched control patients with hippocampal sclerosis (19 GAD-LE control patients: mean age = 35.1 years, 11 females; 4 LGI1-LE control patients: mean age = 52.6 years, 2 females; 5 CASPR2-LE control patients: mean age = 42.7 years, 0 females; 10 patients are included in more than one group) and 33 age- and gender-matched healthy control subjects (19 GAD-LE healthy controls: mean age = 34.6 years, 11 females; 8 LGI1-LE healthy controls: mean age = 57.0 years, 4 females, 10 CASPR2-LE healthy controls: mean age = 57.2 years, 0 females; 4 subjects are included in more than one group) underwent structural imaging and DTI at 3 T and neuropsychological testing. Patient images were oriented according to lateralization in EEG resulting in an affected and unaffected hemisphere. Fixel-based metrics fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC = FD · FC) were calculated to retrieve information about white matter integrity both on the micro- and the macroscale. As compared to healthy controls, patients with GAD-LE showed significantly (family-wise error-corrected, p < 0.05) lower FDC in the superior longitudinal fascicle bilaterally and in the isthmus of the corpus callosum. In CASPR2-LE, lower FDC in the superior longitudinal fascicle was only present in the affected hemisphere. In LGI1-LE, we did not find any white matter alteration of the superior longitudinal fascicle. In an explorative tract-based correlation analysis within the GAD-LE group, only a correlation between the left/right ratio of FC values of the superior longitudinal fascicle and verbal memory performance (R = 0.64, Holm-Bonferroni corrected p < 0.048) remained significant after correcting for multiple comparisons. Our results underscore the concept of LE as a disease comprising a broad and heterogeneous group of entities and contribute novel aspects to the pathomechanistic understanding of this disease that may strengthen the role of MRI in the diagnosis of LE.
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http://dx.doi.org/10.1016/j.nicl.2020.102289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334603PMC
March 2021

CD19+ B-cells in autoantibody-negative limbic encephalitis.

Epilepsy Behav 2020 05 18;106:107016. Epub 2020 Mar 18.

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

Purpose: Flow cytometry helps to elucidate the cellular immune repertoire's mechanisms in patients with temporal lobe epilepsy (TLE) due to limbic encephalitis (LE) subcategories and carries potential significance for subtype-specific treatment.

Methods: We enrolled 62 patients with TLE due to LE associated with no autoantibodies (n = 40), neural autoantibodies (n = 22), as well as autoantibodies against intracellular antigens (n = 15/22). All patients underwent neuropsychological testing, brain magnetic resonance imaging (MRI), electroencephalography (EEG) recordings, and peripheral blood (PB) and cerebrospinal fluid (CSF) investigations including flow cytometry.

Results: CD19+ B-cells were increased in the PB and CSF of patients with antibody-negative LE compared with those associated with antibodies against intracellular antigens (Kruskal-Wallis one way analysis of variance (ANOVA) on ranks with Dunn's test, p < 0.05). There were no differences in CD138+ B-cells, CD4+ T-cells, human leukocyte antigen - DR isotype (HLA-DR+) CD4+ T-cells, CD8+ T-cells, and HLA-DR+ CD8+ T-cells in the CSF between groups with LE. The blood-brain barrier is more often impaired in patients with antibody-negative LE than in LE with antibodies against intracellular antigens (chi-square test, p < 0.05). In addition, we detected no correlations between immune cell subsets and clinical or paraclinical parameters in patients with antibody-negative and intracellular antibody-positive LE.

Conclusions: The increase of CD19+ B-cells in the CSF and frequent signs of dysfunctional blood-brain barrier in patients with antibody-negative rather than intracellular antibody-positive LE suggest that CD19+ B-cells play a role in antibody-negative encephalitis although their pathogenic role in the central nervous system (CNS) immunity because of missing correlations between immune cells and clinical and paraclinical parameters remains unknown. Further studies are required to evaluate the usefulness of these B-cells as a biomarker for the stratification of treatment strategies.
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http://dx.doi.org/10.1016/j.yebeh.2020.107016DOI Listing
May 2020

Drebrin Autoantibodies in Patients with Seizures and Suspected Encephalitis.

Ann Neurol 2020 06 10;87(6):869-884. Epub 2020 Apr 10.

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

Objective: Assess occurrence of the dendritic spine scaffolding protein Drebrin as a pathophysiologically relevant autoantibody target in patients with recurrent seizures and suspected encephalitis as leading symptoms.

Methods: Sera of 4 patients with adult onset epilepsy and suspected encephalitis of unresolved etiology and equivalent results in autoantibody screening were subjected to epitope identification. We combined a wide array of approaches, ranging from immunoblotting, immunoprecipitation, mass spectrometry, subcellular binding pattern analyses in primary neuronal cultures, and immunohistochemistry in brains of wild-type and Drebrin knockout mice to in vitro analyses of impaired synapse formation, morphology, and aberrant neuronal excitability by antibody exposure.

Results: In the serum of a patient with adult onset epilepsy and suspected encephalitis, a strong signal at ∼70kDa was detected by immunoblotting, for which mass spectrometry revealed Drebrin as the putative antigen. Three other patients whose sera also showed strong immunoreactivity around 70kDa on Western blotting were also anti-Drebrin-positive. Seizures, memory impairment, and increased protein content in cerebrospinal fluid occurred in anti-Drebrin-seropositive patients. Alterations in cerebral magnetic resonance imaging comprised amygdalohippocampal T2-signal increase and hippocampal sclerosis. Diagnostic biopsy revealed T-lymphocytic encephalitis in an anti-Drebrin-seropositive patient. Exposure of primary hippocampal neurons to anti-Drebrin autoantibodies resulted in aberrant synapse composition and Drebrin distribution as well as increased spike rates and the emergence of burst discharges reflecting network hyperexcitability.

Interpretation: Anti-Drebrin autoantibodies define a chronic syndrome of recurrent seizures and neuropsychiatric impairment as well as inflammation of limbic and occasionally cortical structures. Immunosuppressant therapies should be considered in this disorder. ANN NEUROL 2020;87:869-884.
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http://dx.doi.org/10.1002/ana.25720DOI Listing
June 2020

Predictors of focal to bilateral tonic-clonic seizures during long-term video-EEG monitoring.

Epilepsia 2020 03 18;61(3):489-497. Epub 2020 Feb 18.

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

Objective: To determine predictors of focal to bilateral tonic-clonic seizures (FBTCS) during video-electroencephalography (EEG) monitoring (VEM).

Methods: All adult patients undergoing presurgical VEM from 2014 to 2015 in the department of epileptology were eligible (N = 229). Those with refractory focal epilepsy and epileptic seizures recorded during VEM were analyzed (N = 188, Group 1). To assess the effects of antiepileptic drug (AED) taper, the total AED load was calculated as the sum of the ratios of prescribed daily dose and defined daily dose of all AEDs per VEM day and was correlated with the occurrence of focal seizures without bilateral tonic-clonic seizures (FwoBTCS) and FBTCS. To validate the findings, data of patients undergoing VEM in 2004 and 2005 (Group 2, eligible N = 243, analyzed N = 203) were also investigated.

Results: In Group 1, 53 patients had FBTCS and 135 patients had exclusively FwoBTCS during VEM. Reduced AED load at seizure onset was the most important modifiable risk factor for FBTCS (receiver-operating characteristic [ROC]: area under the curve [AUC] = 0.78). Furthermore, the risk of FBTCS varied with the history and frequency of FBTCS prior to VEM. For instance, patients had a 50% risk of FBTCS by reducing the AED load to ~20% when no information about history of FBTCS was taken into account, to ~30% when a positive history of FBTCS was taken into account, and to ~50% when a high frequency of FBTCS prior to VEM was taken into account. These findings were largely replicated in Group 2 (59 patients with FBTCS and 144 exclusively with FwoBTCS).

Significance: The risk of FTBCS during VEM depends on the history and frequency of FTBCS prior to VEM and is particularly associated with the extent of AED reduction. Our data underscore the need for appropriate tapering regimens in VEM units.
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http://dx.doi.org/10.1111/epi.16454DOI Listing
March 2020

Pyramidal tract and alternate motor fibers complementarily mediate motor compensation in patients after hemispherotomy.

Sci Rep 2020 01 23;10(1):1010. Epub 2020 Jan 23.

Department of Epileptology, University of Bonn Medical Center, Bonn, 53127, Germany.

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
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http://dx.doi.org/10.1038/s41598-020-57504-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978326PMC
January 2020

18F-FDG-PET/MRI in the diagnostic work-up of limbic encephalitis.

PLoS One 2020 17;15(1):e0227906. Epub 2020 Jan 17.

Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Introduction: Limbic encephalitis (LE) is an immune-related, sometimes paraneoplastic process of the central nervous system. Initial diagnosis and treatment are based on the clinical presentation as well as antibody profiles and MRI. This study investigated the diagnostic value of integrated 18F-FDG-PET/MRI in the diagnostic work-up of patients with LE for a cerebral and whole-body imaging concept.

Material And Methods: Twenty patients with suspected LE were enrolled in this prospective study. All patients underwent a dedicated PET/MRI protocol of the brain as well as the whole-body. Two neuroradiologists, one body radiologist and one nuclear medicine physician performed blinded consensus readings of each corresponding MRI and PET/MRI dataset of the brain and whole-body. Diagnostic confidence was evaluated on a Likert scale.

Results: Based on integrated PET/MRI 19 / 20 patients were found to show morphologic and / or metabolic changes indicative of LE, whereas sole MRI enabled correct identification in 16 / 20 patients. Three patients with negative MRI showed metabolic changes of the limbic system or extra-limbic regions, shifting the diagnosis from (negative) MRI to positive for LE in PET/MRI. Whole-body staging revealed suspected lesions in 2/20 patients, identified by MRI and PET, one confirmed as malignant and one false positive. Diagnostic confidence for cerebral and whole-body imaging reached higher scores for PET/MRI (cerebral: 2.7 and whole body: 4.8) compared to MRI alone (cerebral: 2.4 and whole body: 4.5).

Conclusion: LE diagnosis remains challenging for imaging as it shows only subtle imaging findings in most patients. Nevertheless, based on the simultaneous and combined analysis of morphologic and metabolic data, integrated PET/MRI may enable a dual platform for improved diagnostic confidence and overall detection of LE as well as whole-body imaging for exclusion of paraneoplastic LE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227906PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968877PMC
April 2020

Low CSF CD4/CD8+ T-cell proportions are associated with blood-CSF barrier dysfunction in limbic encephalitis.

Epilepsy Behav 2020 01 14;102:106682. Epub 2019 Dec 14.

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

Purpose: Investigating immune cells in autoimmune limbic encephalitis (LE) will contribute to our understanding of its pathophysiology and may help to develop appropriate therapies. The aim of the present study was to analyze immune cells to reveal underlying immune signatures in patients with temporal lobe epilepsy (TLE) with LE.

Methods: We investigated 68 patients with TLE with LE compared with 7 control patients with TLE with no signs of LE screened from 154 patients with suspected LE. From the patients with TLE-LE, we differentiated early seizure onset (<20 years, n = 9) and late seizure onset group (≥20 years, n = 59) of patients. Patients underwent neuropsychological assessment, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and peripheral blood (PB) and cerebrospinal fluid (CSF) analysis including flow cytometry.

Results: We identified a higher CD4/8+ T-cell ratio in the PB in all patients with TLE-LE and in patients with late-onset TLE-LE each compared with controls (Kruskal-Wallis one-way ANOVA (analysis of variance) with Dunn's test, p < 0.05). Moreover, a lower CD4/CD8+ T-cell ratio is detected in all patients with TLE-LE with blood-CSF barrier dysfunction, unlike in those with none (Kruskal-Wallis one-way ANOVA with Dunn's test, p < 0.05).

Conclusions: These findings suggest that the proportion of CD4+ and CD8+ T-cells in the CSF of patients with LE associated with blood-CSF barrier dysfunction plays a potential role in CNS (central nervous system) inflammation in these patients. Thus, flow cytometry as a methodology reveals novel insights into LE's genesis and symptomatology. The CD4/8+ T-cell ratio in PB as a biomarker for LE requires further investigation.
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http://dx.doi.org/10.1016/j.yebeh.2019.106682DOI Listing
January 2020

Acute metabolic effects of tonic-clonic seizures.

Epilepsia Open 2019 Dec 22;4(4):599-608. Epub 2019 Oct 22.

Department of Epileptology University of Bonn Medical Center Bonn Germany.

Objective: Tonic-clonic seizures (TCS) lead to metabolic stress and changes in related blood markers. Such markers may indicate harmful conditions but can also help to identify TCS as a cause of transient loss of consciousness. In this study, we hypothesized that the alterations of circulating markers of metabolic stress depend on the clinical features of TCS.

Methods: Ninety-one adults undergoing video-EEG monitoring participated in this prospective study. Electrolytes, renal parameters, creatine kinase (CK), prolactin (PRL), lactate, ammonia, glucose, and other parameters were measured at inclusion and different time points after TCS.

Results: A total of 39 TCS were recorded in 32 patients (six generalized onset tonic-clonic seizures in 6 and 33 focal to bilateral tonic-clonic seizures in 26 patients). Shortly after TCS, mean lactate, ammonia, and PRL levels were significantly increased 8.7-fold, 2.6-fold, and 5.1-fold, respectively, with levels of more than twofold above the upper limits of the normal (ULN) in 90%, 71%, and 70% of the TCS and returned to baseline levels within 2 hours. Only postictal lactate levels were significantly correlated with the total duration of the tonic-clonic phase. In contrast, CK elevations above the ULN were found in three TCS (~10%) only with a peak after 48 hours. Immediately after the TCS, hyperphosphatemia occurred in one third of the patients, whereas hypophosphatemia was observed in one third 2 hours later. TCS led to subtle but significant alterations of other electrolytes, creatinine, and uric acid, whereas glucose levels were moderately increased.

Significance: Lactate is a robust metabolic marker of TCS with elevations found in ~90% of cases within 30 minutes after seizure termination, whereas ammonia rises in ~ 70%, similarly to PRL. Phosphate levels show an early increase and a decrease 2 hours after TCS in a third of patients. CK elevations are rare after video-EEG-documented TCS, challenging its value as a diagnostic marker.
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http://dx.doi.org/10.1002/epi4.12364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885665PMC
December 2019

Parents' view of the cognitive outcome one year after pediatric epilepsy surgery.

Epilepsy Behav 2019 12 5;101(Pt A):106552. Epub 2019 Nov 5.

Department of Epileptology, University of Bonn Medical Centre, Venusberg-Campus 1, FRG-53127 Bonn, Germany; St. Mauritius Therapieklinik, Strümper Str. 111, FRG-40670 Meerbusch, Germany.

Objectives: The cognitive outcome of pediatric epilepsy surgery has mainly been examined on the basis of standardized tests. Here, we analyzed the outcome in six cognitive domains from the parents' view.

Methods: Included were consecutive surgical pediatric patients whose parents filled-in a comprehensive questionnaire on cognitive problems in children and adolescents (Kognitive Probleme bei Kindern und Jugendlichen (KOPKIJ); Gleissner et al. 2006) at the preoperative baseline (T1) as well as twelve months thereafter (T2). All children also underwent standard neuropsychological assessments at T1 and T2.

Results: Parents of 96 patients provided pre- and postoperative KOPKIJ data. Overall, 80% of the children became seizure-free at the follow-up. Group means indicated a strong positive effect of time on KOPKIJ and neuropsychological performance. We found postoperative improvements in five out of six cognitive domains (language, memory, executive functions, attention, school; unchanged: visuospatial abilities). Individually, improvements were twice as likely as declines. However, 33 patients (35%) experienced significant decline in at least one cognitive domain. Later onset of epilepsy resulted in better performance but had no effect on change scores. Seizure-free status, lower antiseizure drug load, and stronger drug reduction after surgery contributed to postoperative cognitive improvements as perceived by the parents; no other effects of clinical factors were obtained (e.g., localization/lateralization). Despite their similar outcome patterns, change scores as derived from parental ratings and neuropsychological assessment were not correlated.

Conclusions: Parents acknowledged the overall positive neurocognitive development after pediatric epilepsy surgery as previously shown by standardized tests. Seizure freedom and lower antiseizure drug load contributed to the beneficial cognitive outcome. Even if cognitive improvements outweighed declines, a risk for cognitive decline with impact on everyday functioning does exist.
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http://dx.doi.org/10.1016/j.yebeh.2019.106552DOI Listing
December 2019

Accuracy of expert predictions of seizure freedom after epilepsy surgery.

Seizure 2019 Aug 30;70:59-62. Epub 2019 Jun 30.

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

Purpose: To evaluate the accuracy of expert estimations of achieving seizure freedom after epilepsy surgery in the context of presurgical patient counseling.

Method: The retrospective study comprised a random sample of 200 patients who underwent any type of resective epilepsy surgery at the University of Bonn Epilepsy Center and the routine 1-year postoperative control visit in the years from 2008-2016. The prediction by a team of epileptologists and the actual seizure outcome were extracted from the pre- and postsurgical medical files, respectively. A deviation of >10% was a priori defined as a relevant discrepancy.

Results: Estimated chances of achieving seizure freedom ranged from 30 to 90% (mean: 67%). The actual seizure freedom rate was 66% (Engel Ia/ ILAE 1a). Nine of 12 estimation categories showed a tolerable deviation of ≤10%, none of these with a worse than expected outcome. Two estimation categories (40-50%, and 80%) showed a worse actual seizure outcome with deviations of -40% (n = 3); and -17% (n = 30), respectively. All in all, for 83% of the patients a correct prediction was provided.

Conclusions: For the vast majority of surgical patients, the expert prediction of postsurgical seizure freedom at the 1-year follow-up was accurate despite the heterogeneity of patients and surgical procedures.
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http://dx.doi.org/10.1016/j.seizure.2019.06.030DOI Listing
August 2019

Seizure-induced shoulder dislocations - Case series and review of the literature.

Seizure 2019 Aug 20;70:38-42. Epub 2019 Jun 20.

Department of Neurology, University of Münster, Münster, Germany. Electronic address:

Purpose: We aimed to identify clinical characteristics of patients with shoulder dislocations caused by an epileptic seizure.

Methods: In our retrospective analysis, we identified 15 patients, recorded over an 8-year period, who were diagnosed with shoulder dislocations in the setting of a bilateral tonic-clonic seizure.

Results: Patients were almost exclusively male (13/15) and drug-naïve patients suffering their first or second seizure (14/15). Epilepsy was diagnosed in five of these 14 patients after further diagnostic tests, four patients were diagnosed with a provoked or acute symptomatic seizure and five patients with an unprovoked seizure. Treatment with anticonvulsant drugs (AED) was initiated in 10/15 patients after the first seizure, without recommendation for tapering, although long-term treatment was retrospectively judged to be appropriate for only four of those cases. Posterior dislocations - usually rare - were seen in 12/15 patients and often required complex orthopedic interventions.

Conclusions: We conclude that in particular posterior shoulder dislocations are often caused by a first seizure and should always raise the suspicion of an epileptic seizure even in the absence of a clear history. AED treatment likely has a protective effect against this type of injury, even if seizure-freedom is not achieved.
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http://dx.doi.org/10.1016/j.seizure.2019.06.025DOI Listing
August 2019

Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe.

PLoS Biol 2019 06 3;17(6):e3000290. Epub 2019 Jun 3.

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

Sensory experience elicits complex activity patterns throughout the neocortex. Projections from the neocortex converge onto the medial temporal lobe (MTL), in which distributed neocortical firing patterns are distilled into sparse representations. The precise nature of these neuronal representations is still unknown. Here, we show that population activity patterns in the MTL are governed by high levels of semantic abstraction. We recorded human single-unit activity in the MTL (4,917 units, 25 patients) while subjects viewed 100 images grouped into 10 semantic categories of 10 exemplars each. High levels of semantic abstraction were indicated by representational similarity analyses (RSAs) of patterns elicited by individual stimuli. Moreover, pattern classifiers trained to decode semantic categories generalised successfully to unseen exemplars, and classifiers trained to decode exemplar identity more often confused exemplars of the same versus different categories. Semantic abstraction and generalisation may thus be key to efficiently distill the essence of an experience into sparse representations in the human MTL. Although semantic abstraction is efficient and may facilitate generalisation of knowledge to novel situations, it comes at the cost of a loss of detail and may be central to the generation of false memories.
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http://dx.doi.org/10.1371/journal.pbio.3000290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564037PMC
June 2019

Blood Pressure in Seizures and Epilepsy.

Front Neurol 2019 14;10:501. Epub 2019 May 14.

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

In this narrative review, we summarize the current knowledge of neurally mediated blood pressure (BP) control and discuss how recently described epilepsy- and seizure-related BP alterations may contribute to premature mortality and sudden unexpected death in epilepsy (SUDEP). Although people with epilepsy display disturbed interictal autonomic function with a shift toward predominant sympathetic activity, prevalence of arterial hypertension is similar in people with and without epilepsy. BP is transiently increased in association with most types of epileptic seizures but may also decrease in some, illustrating that seizure activity can cause both a decrease and increase of BP, probably because of stimulation or inhibition of distinct central autonomic function by epileptic activity that propagates into different neuronal networks of the central autonomic nervous system. The principal regulatory neural loop for short-term BP control is termed baroreflex, mainly involving peripheral sensors and brain stem nuclei. The baroreflex sensitivity (BRS, expressed as change of interbeat interval per change in BP) is intact after focal seizures, whereas BRS is markedly impaired in the early postictal period following generalized convulsive seizures (GCS), possibly due to metabolically mediated muscular hyperemia in skeletal muscles, a massive release of catecholamines and compromised brain stem function. Whilst most SUDEP cases are probably caused by a cardiorespiratory failure during the early postictal period following GCS, a profoundly disturbed BRS may allow a life-threatening drop of systemic BP in the aftermath of GCS, as recently reported in a patient as a plausible cause of SUDEP in a few patients.
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http://dx.doi.org/10.3389/fneur.2019.00501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527757PMC
May 2019

Seizures and epilepsy in multiple sclerosis: epidemiology and prognosis in a large tertiary referral center.

J Neurol 2019 Jul 8;266(7):1789-1795. Epub 2019 May 8.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Germany.

Background: Seizures and epilepsy may substantially add to the burden of disease in multiple sclerosis (MS), whereas the exact prevalence and prognosis of seizures and epilepsy in patients with MS remains largely unknown.

Objectives: We aimed to investigate the epidemiology and prognosis of seizures and epilepsy in MS.

Methods: We retrospectively analyzed a cohort of 4078 MS patients from a single tertiary referral clinic.

Results: After excluding 37 patients with unconfirmed MS and alternative seizure etiologies, we found seizures attributable to MS in 1.5% and epilepsy in 0.9% of patients. 40.4% of patients with a follow-up of at least twelve months experienced only a single seizure and 59.6% had recurring seizures. 39% of patients with recurrent seizures were considered drug-resistant, with 9.7% experiencing status epilepticus. Seizure recurrence after a first seizure depended significantly on the MS subtype and was seen more often if the first seizure occurred simultaneously with a MS relapse than in the absence of a relapse.

Conclusion: Our study shows a lower number of seizures and epilepsy in MS than previously reported. While a single seizure in MS usually has a good prognosis, relapse-associated seizures and established epilepsy in MS may not be as benign as previously assumed.
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http://dx.doi.org/10.1007/s00415-019-09332-xDOI Listing
July 2019

Morphometric MRI findings challenge the concept of the "unaffected" hemisphere in Rasmussen encephalitis.

Epilepsia 2019 05 8;60(5):e40-e46. Epub 2019 Apr 8.

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

Rasmussen encephalitis (RE) is an immune-mediated brain disease with progressive unihemispheric atrophy. Although it is regarded as a strictly one-sided pathology, volumetric magnetic resonance imaging (MRI) studies have revealed atrophy in the so-called unaffected hemisphere. In contrast to previous studies, we hypothesized that the contralesional hemisphere would show increased gray matter volume in response to the ipsilesional atrophy. We assessed the gray matter volume differences among 21 patients with chronic, late-stage RE and 89 age- and gender-matched healthy controls using voxel-based morphometry. In addition, 11 patients with more than one scan were tested longitudinally. Compared to controls, the contralesional hemisphere of the patients revealed a higher cortical volume but a lower subcortical gray matter volume (all P < 0.001, unpaired t test). Progressive gray matter volume losses in bilateral subcortical gray matter structures were observed (P < 0.05, paired t test). The comparatively higher cortical volume in the contralesional hemisphere can be interpreted as a result of compensatory structural remodeling in response to atrophy of the ipsilesional hemisphere. Contralesional subcortical gray matter volume loss may be due to the pathology or its treatment. Because MRI provides the best marker for determining the progression of RE, an accurate description of its MRI features is clinically relevant.
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http://dx.doi.org/10.1111/epi.14702DOI Listing
May 2019

Recollection in the human hippocampal-entorhinal cell circuitry.

Nat Commun 2019 04 3;10(1):1503. Epub 2019 Apr 3.

Deptartment of Epileptology, University of Bonn Medical Centre, Bonn, D- 53175, Germany.

Imagine how flicking through your photo album and seeing a picture of a beach sunset brings back fond memories of a tasty cocktail you had that night. Computational models suggest that upon receiving a partial memory cue ('beach'), neurons in the hippocampus coordinate reinstatement of associated memories ('cocktail') in cortical target sites. Here, using human single neuron recordings, we show that hippocampal firing rates are elevated from ~ 500-1500 ms after cue onset during successful associative retrieval. Concurrently, the retrieved target object can be decoded from population spike patterns in adjacent entorhinal cortex (EC), with hippocampal firing preceding EC spikes and predicting the fidelity of EC object reinstatement. Prior to orchestrating reinstatement, a separate population of hippocampal neurons distinguishes different scene cues (buildings vs. landscapes). These results elucidate the hippocampal-entorhinal circuit dynamics for memory recall and reconcile disparate views on the role of the hippocampus in scene processing vs. associative memory.
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http://dx.doi.org/10.1038/s41467-019-09558-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447634PMC
April 2019
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