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Markus Reuber, Christoph Helmstaedter, Weiping Liao, Tobias Loddenkemper, Rhys Thomas, Reetta Kälviäinen, Michael Mann
No abstract text is available yet for this article.
October 2016: Seizure: the Journal of the British Epilepsy Association
Michael P Malter, Guido Widman, Norbert Galldiks, Winfried Stoecker, Christoph Helmstaedter, Christian E Elger, Jan Wagner
OBJECTIVE: Recent reports define temporal lobe epilepsy with amygdala enlargement (TLE-AE) as a distinct electroclinical syndrome comparable to TLE with hippocampal sclerosis. In this retrospective observational study, we present the largest consecutive series of patients with new-onset TLE-AE to date and describe clinical characteristics and seizure outcome, and we aim to explore underlying autoimmune mechanisms within this syndrome. METHODS: We reviewed all consecutive patients between 2004 and 2014 at our tertiary epilepsy center at the University of Bonn, Germany, with new-onset (<5 years) TLE-AE, negative serum antibody (ab) test results, and with available follow-up data for at least 12 months...
September 2016: Epilepsia
Felix Rosenow, Thomas Bast, Thomas Czech, Martha Feucht, Volkmar H Hans, Christoph Helmstaedter, Hans-Jürgen Huppertz, Soheyl Noachtar, Frank Oltmanns, Tilman Polster, Margitta Seeck, Eugen Trinka, Kathrin Wagner, Adam Strzelczyk
The definition of minimal standards remains pivotal as a basis for a high standard of care and as a basis for staff allocation or reimbursement. Only limited publications are available regarding the required staffing or methodologic expertise in epilepsy centers. The executive board of the working group (WG) on presurgical epilepsy diagnosis and operative epilepsy treatment published the first guidelines in 2000 for Austria, Germany, and Switzerland. In 2014, revised guidelines were published and the WG decided to publish an unaltered English translation in this report...
August 2016: Epilepsia
Florian Grahammer, Suresh K Ramakrishnan, Markus M Rinschen, Alexey A Larionov, Maryam Syed, Hazim Khatib, Malte Roerden, Jörn Oliver Sass, Martin Helmstaedter, Dorothea Osenberg, Lucas Kühne, Oliver Kretz, Nicola Wanner, Francois Jouret, Thomas Benzing, Ferruh Artunc, Tobias B Huber, Franziska Theilig
Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria...
June 13, 2016: Journal of the American Society of Nephrology: JASN
Teia Kobulashvili, Julia Höfler, Judith Dobesberger, Florian Ernst, Philippe Ryvlin, J Helen Cross, Kees Braun, Petia Dimova, Stefano Francione, Hrvoje Hecimovic, Christoph Helmstaedter, Vasilios K Kimiskidis, Morten Ingvar Lossius, Kristina Malmgren, Petr Marusic, Bernhard J Steinhoff, Paul Boon, Dana Craiu, Norman Delanty, Daniel Fabo, Antonio Gil-Nagel, Alla Guekht, Edouard Hirsch, Reetta Kalviainen, Ruta Mameniskiené, Çiğdem Özkara, Margitta Seeck, Guido Rubboli, Pavel Krsek, Sylvain Rheims, Eugen Trinka
PURPOSE: The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. METHOD: A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement...
May 2016: Seizure: the Journal of the British Epilepsy Association
Klaus Lehnertz, Henning Dickten, Stephan Porz, Christoph Helmstaedter, Christian E Elger
Drug-resistant, multifocal, non-resectable epilepsies are among the most difficult epileptic disorders to manage. An approach to control previously uncontrollable seizures in epilepsy patients would consist of identifying seizure precursors in critical brain areas combined with delivering a counteracting influence to prevent seizure generation. Predictability of seizures with acceptable levels of sensitivity and specificity, even in an ambulatory setting, has been repeatedly shown, however, in patients with a single seizure focus only...
2016: Scientific Reports
Brian E Mouthaan, Matea Rados, Péter Barsi, Paul Boon, David W Carmichael, Evelien Carrette, Dana Craiu, J Helen Cross, Beate Diehl, Petia Dimova, Daniel Fabo, Stefano Francione, Vladislav Gaskin, Antonio Gil-Nagel, Elena Grigoreva, Alla Guekht, Edouard Hirsch, Hrvoje Hecimovic, Christoph Helmstaedter, Julien Jung, Reetta Kalviainen, Anna Kelemen, Vasilios Kimiskidis, Teia Kobulashvili, Pavel Krsek, Giorgi Kuchukhidze, Pål G Larsson, Markus Leitinger, Morten I Lossius, Roman Luzin, Kristina Malmgren, Ruta Mameniskiene, Petr Marusic, Baris Metin, Cigdem Özkara, Hrvoje Pecina, Carlos M Quesada, Fergus Rugg-Gunn, Bertil Rydenhag, Philippe Ryvlin, Julia Scholly, Margitta Seeck, Anke M Staack, Bernhard J Steinhoff, Valentin Stepanov, Oana Tarta-Arsene, Eugen Trinka, Mustafa Uzan, Viola L Vogt, Sjoerd B Vos, Serge Vulliémoz, Geertjan Huiskamp, Frans S S Leijten, Pieter Van Eijsden, Kees P J Braun
OBJECTIVE: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers. METHODS: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium...
May 2016: Epilepsia
Ido Amit, David Baker, Roger Barker, Bonnie Berger, Carolyn Bertozzi, Sangeeta Bhatia, Alessandra Biffi, Francesca Demichelis, Jennifer Doudna, Steven F Dowdy, Drew Endy, Moritz Helmstaedter, Howard Junca, Carl June, Sasha Kamb, Anastasia Khvorova, Dae-Hyeong Kim, Jin-Soo Kim, Yamuna Krishnan, Melike Lakadamyali, Tuuli Lappalainen, Sharon Lewin, James Liao, Nick Loman, Emma Lundberg, Lee Lynd, Cathie Martin, Ira Mellman, Atsushi Miyawaki, Christine Mummery, Karen Nelson, Jeanne Paz, Pamela Peralta-Yahya, Paola Picotti, Kornelia Polyak, Kristala Prather, Jun Qin, Stephen Quake, Aviv Regev, John A Rogers, Reshma Shetty, Morten Sommer, Molly Stevens, Gustavo Stolovitzky, Masayo Takahashi, Fuchou Tang, Sarah Teichmann, Maria-Elena Torres-Padilla, Leena Tripathi, Praveen Vemula, Greg Verdine, Frank Vollmer, Jun Wang, Jackie Y Ying, Feng Zhang, Tian Zhang
No abstract text is available yet for this article.
March 2016: Nature Biotechnology
Christoph Helmstaedter, Christian Erich Elger, Juri-Alexander Witt
PURPOSE: Epilepsy surgery is associated with a risk of cognitive deterioration, but improvement has also been reported. Improvements have mostly been attributed to seizure control, neglecting changes in drug treatment during the observation period. We evaluated whether changes of antiepileptic treatment affect cognitive outcome one year after epilepsy surgery. METHODS: This retrospective study evaluated the impact of quantitative and qualitative antiepileptic drug changes on postoperative outcome on cognition (executive functions, episodic memory) and mood in 116 epilepsy surgery patients, controlling the results for seizure outcome (seizure free yes/no) and site of surgery (87 temporal lobe, 29 extratemporal lobe resections)...
March 2016: Seizure: the Journal of the British Epilepsy Association
B von Rhein, J Wagner, G Widman, M P Malter, C E Elger, C Helmstaedter
OBJECTIVES: Whether and when to immunologically treat epilepsy patients with suggested autoantibody (AB)-negative limbic encephalitis (LE) is clinically challenging. Therefore, we evaluated the clinical outcome and eventual outcome predictors of immunotherapy in a group of AB-negative patients with recent-onset temporal lobe epilepsy (TLE), magnetic resonance imaging (MRI) indicators of LE, subjective cognitive decline, and/or psychiatric symptoms. METHODS: This retrospective, observational, uncontrolled study monitored 28 TLE patients with suggested AB-negative LE along with methylprednisolone immunotherapy...
March 4, 2016: Acta Neurologica Scandinavica
Jan Wagner, Jan-Christoph Schoene-Bake, Juri-Alexander Witt, Christoph Helmstaedter, Michael P Malter, Winfried Stoecker, Christian Probst, Bernd Weber, Christian E Elger
OBJECTIVE: Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). METHODS: Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups...
March 2016: Epilepsia
Michael R Johnson, Kirill Shkura, Sarah R Langley, Andree Delahaye-Duriez, Prashant Srivastava, W David Hill, Owen J L Rackham, Gail Davies, Sarah E Harris, Aida Moreno-Moral, Maxime Rotival, Doug Speed, Slavé Petrovski, Anaïs Katz, Caroline Hayward, David J Porteous, Blair H Smith, Sandosh Padmanabhan, Lynne J Hocking, John M Starr, David C Liewald, Alessia Visconti, Mario Falchi, Leonardo Bottolo, Tiziana Rossetti, Bénédicte Danis, Manuela Mazzuferi, Patrik Foerch, Alexander Grote, Christoph Helmstaedter, Albert J Becker, Rafal M Kaminski, Ian J Deary, Enrico Petretto
Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular...
February 2016: Nature Neuroscience
Julia Bungenberg, Natascha Surano, Alexander Grote, Rainer Surges, Katharina Pernhorst, Andrea Hofmann, Susanne Schoch, Christoph Helmstaedter, Albert J Becker
Temporal lobe epilepsy (TLE) is a severe brain disorder affecting particularly young adults. TLE is frequently associated with memory deterioration and neuronal damage of the hippocampal formation. It thereby reveals striking parallels to neurodegenerative disorders including Alzheimer's disease (AD). TLE patients differ with respect to their cognitive performance, but currently little is known about relevant molecular-genetic factors. Here, we correlated differential memory performance of pharmacoresistant TLE patients undergoing neurosurgery for seizure control with in-vitro findings of their hippocampal tissues...
February 2016: Neurobiology of Disease
Manuel Berning, Kevin M Boergens, Moritz Helmstaedter
Progress in electron microscopy-based high-resolution connectomics is limited by data analysis throughput. Here, we present SegEM, a toolset for efficient semi-automated analysis of large-scale fully stained 3D-EM datasets for the reconstruction of neuronal circuits. By combining skeleton reconstructions of neurons with automated volume segmentations, SegEM allows the reconstruction of neuronal circuits at a work hour consumption rate of about 100-fold less than manual analysis and about 10-fold less than existing segmentation tools...
September 23, 2015: Neuron
Shanika R Samarasekera, Christoph Helmstaedter, Markus Reuber
AIM: This study aimed to assess the relationship between objective measures of cognition and subjective perception of cognitive functioning reported by patients with epilepsy and their caregivers. METHODS: One hundred patients with epilepsy attending hospital neurology outpatient clinics and their caregivers were enrolled in this study. The EpiTrack (version 1) brief cognitive screening tool was used to measure objective impairment, the ABNAS questionnaire (A-B Neuropsychological Assessment Schedule) to assess subjective cognitive performance, and a version of the ABNAS designed to be completed by caregivers (C-ABNAS) to document caregivers' views...
November 2015: Epilepsy & Behavior: E&B
Christian Hoppe, Mieke Feldmann, Barbara Blachut, Rainer Surges, Christian E Elger, Christoph Helmstaedter
OBJECTIVES: Patient-reported seizure frequency is essential for therapy management and clinical research but lacks validity mainly due to seizure-induced seizure unawareness. Automated seizure detection by mobile monitoring devices promises to settle this serious methodological issue. Here, we explored attitudes and preferences towards future devices for seizure detection in adult patients with therapy-refractory epilepsies. METHODS: A total of 102 inpatients enrolled and underwent a newly constructed semistructured 30-minute interview on automated seizure registration...
November 2015: Epilepsy & Behavior: E&B
Juri-Alexander Witt, Christian E Elger, Christoph Helmstaedter
The study was set up to evaluate the impact of the total drug load of antiepileptic pharmacotherapy on cognition. Retrospective analyses were based on 834 patients with epilepsy who underwent a brief routine assessment of executive function and verbal memory (EpiTrack Plus) at our department. The total drug load was quantified in two ways: (1) number of concurrent antiepileptic drugs (AEDs) and (2) total drug load according to the defined daily dose (DDD) provided by the World Health Organization. The cognitive measures showed higher inverse correlations with the number of AEDs (executive function: r=-0...
November 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
B Pohlmann-Eden, A Aldenkamp, G A Baker, C Brandt, F Cendes, R Coras, C E Crocker, C Helmstaedter, M Jones-Gotman, A M Kanner, A Mazarati, M Mula, M L Smith, A Omisade, J Tellez-Zenteno, B P Hermann
Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most research studies to date have not adequately addressed the precise nature of the relationship between these comorbidities and seizures. To address this complex issue and to facilitate collaborative, innovative research in the rising field of neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy, international epilepsy experts met at the 3rd Halifax International Epilepsy Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from September 18 to 20, 2014...
October 2015: Epilepsy & Behavior: E&B
Guido Widman, Kristin Golombeck, Hubertus Hautzel, Catharina C Gross, Carlos M Quesada, Juri-Alexander Witt, Elena Rota-Kops, Johannes Ermert, Susanne Greschus, Rainer Surges, Christoph Helmstaedter, Heinz Wiendl, Nico Melzer, Christian E Elger
BACKGROUND: Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab...
2015: Frontiers in Neurology
Yunfeng Hua, Philip Laserstein, Moritz Helmstaedter
Large-scale connectomics requires dense staining of neuronal tissue blocks for electron microscopy (EM). Here we report a large-volume dense en-bloc EM staining protocol that overcomes the staining gradients, which so far substantially limited the reconstructable volumes in three-dimensional (3D) EM. Our protocol provides densely reconstructable tissue blocks from mouse neocortex sized at least 1 mm in diameter. By relaxing the constraints on precise topographic sample targeting, it makes the correlated functional and structural analysis of neuronal circuits realistic...
2015: Nature Communications
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