DOCSLIB.ORG

A Computational Biomarker of Idiopathic Generalized

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Computational Biomarker of Idiopathic Generalized University of Birmingham A computational biomarker of idiopathic generalized epilepsy from resting state EEG Schmidt, H.; Woldman, W.; Goodfellow, M.; Chowdhury, F.A.; Koutroumanidis, M.; Jewell, S.; Richardson, M.P.; Terry, J.R. DOI: 10.1111/epi.13481 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Schmidt, H, Woldman, W, Goodfellow, M, Chowdhury, FA, Koutroumanidis, M, Jewell, S, Richardson, MP & Terry, JR 2016, 'A computational biomarker of idiopathic generalized epilepsy from resting state EEG', Epilepsia, vol. 57, pp. e200-e204. https://doi.org/10.1111/epi.13481 Link to publication on Research at Birmingham portal Publisher Rights Statement: Schmidt, H. , Woldman, W. , Goodfellow, M. , Chowdhury, F. A., Koutroumanidis, M. , Jewell, S. , Richardson, M. P. and Terry, J. R. (2016), A computational biomarker of idiopathic generalized epilepsy from resting state EEG. Epilepsia, 57: e200-e204. doi:10.1111/epi.13481 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive. If you believe that this is the case for this document, please contact [email protected] providing details and we will remove access to the work immediately and investigate. Download date: 25. Sep. 2021 BRIEF COMMUNICATION A computational biomarker of idiopathic generalized epilepsy from resting state EEG *†‡1Helmut Schmidt, *†‡1Wessel Woldman, *†‡Marc Goodfellow, §Fahmida A. Chowdhury, §¶Michalis Koutroumanidis, §Sharon Jewell, ‡§2Mark P. Richardson, and *†‡2John R. Terry Epilepsia, 57(10):e200–e204, 2016 doi: 10.1111/epi.13481 SUMMARY Epilepsy is one of the most common serious neurologic conditions. It is characterized by the tendency to have recurrent seizures, which arise against a backdrop of appar- ently normal brain activity. At present, clinical diagnosis relies on the following: (1) case history, which can be unreliable; (2) observation of transient abnormal activity during electroencephalography (EEG), which may not be present during clinical evalu- ation; and (3) if diagnostic uncertainty occurs, undertaking prolonged monitoring in an attempt to observe EEG abnormalities, which is costly. Herein, we describe the discov- ery and validation of an epilepsy biomarker based on computational analysis of a short segment of resting-state (interictal) EEG. Our method utilizes a computer model of Helmut Schmidt is an dynamic networks, where the network is inferred from the extent of synchrony applied mathematician between EEG channels (functional networks) and the normalized power spectrum of working in the field of the clinical data. We optimize model parameters using a leave-one-out classification computational on a dataset comprising 30 people with idiopathic generalized epilepsy (IGE) and 38 neuroscience. normal controls. Applying this scheme to all 68 subjects we find 100% specificity at 56.7% sensitivity, and 100% sensitivity at 65.8% specificity. We believe this biomarker could readily provide additional support to the diagnostic process. KEY WORDS: Biomarker, Diagnosis, Resting-state EEG, Computational model, IGE. Wessel Woldman is an MRC Research Fellow working on mathematical models of seizure generation. Accepted July 5, 2016; Early View publication August 8, 2016. *College of Engineering, Mathematics & Physical Sciences, University of Exeter, Exeter, United Kingdom; †Wellcome Trust ISSF Centre for Biomedical Modelling and Analysis, University of Exeter, Exeter, United Kingdom; ‡EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter, United Kingdom; §Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom; and ¶Department of EEG and Epilepsy, St. Thomas’s Hospital, Guy’s and St. Thomas’s NHS Foundation Trust, London, United Kingdom Address correspondence to John R. Terry, College of Engineering, Mathematics & Physical Sciences, University of Exeter, Exeter EX4 4QJ, U.K. E-mail: [email protected] 1Denotes equal contribution as first author. 2Denotes equal contribution as last author. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. e200 e201 A Computational Biomarker of IGE At present, a confirmed diagnosis of epilepsy is made state” EEG activity from the initial stage of the recordings through a case history and a positive electroencephalogra- from each participant. These data were band-pass filtered phy (EEG), confirming the presence of epileptiform dis- using a Butterworth filter between 0.5 and 70 Hz, and band- charges. However, a positive EEG occurs at best in only stop filtered between 48 and 52 Hz to remove power-line 60% of cases, resulting in diagnostic uncertainty for many artifacts. Because signal amplitude may vary between indi- people,1 with significant associated costs.2 These costs pre- viduals due to different anatomic features (such as the size dominantly result from additional longer-term EEG moni- and shape of the cranium) the data were normalized by toring, repeated hospital admissions, as well as unnecessary dividing the power spectrum in each channel by the total prescription of antiepileptic drugs (AEDs). power in the spectrum averaged across all channels. This Idiopathic generalized epilepsy (IGE) is one of the main normalized power preserves relative differences in power classes of epilepsy. In recent years, studies comparing between channels. We then band-pass filtered the EEG seg- cohorts of people with IGE and cohorts of healthy controls ments into either the alpha (8–13 Hz) or low alpha bands7 have shown statistically significant alterations at the group (6–9 Hz). For segments band-pass filtered in the low alpha level when examining resting-state features of the EEG band, we further inferred functional networks using the using power spectrum,3 functional networks,4 and a model- Phase-Locking Factor8 (PLF) and phase-lags (as described driven analysis of functional networks.5 However, substan- previously).5 tial overlap of these markers between groups may render the For the purpose of biomarker discovery, we consider measurement unsuitable as a diagnostic test or biomarker6 measures that have demonstrated group-level differences for any one individual. Our aim therefore is to assess the between people with IGE and healthy controls using rest- performance of each of these methods as a classifier that has ing-state EEG. First, the peak in alpha power across occipi- three outcomes for each individual: unequivocally IGE, tal EEG channels, which is known to shift toward lower unequivocally normal, or uncertain. Such a classifier could frequencies in people with IGE.3 Second, the mean degree be used as a screening test in a nonspecialist primary care of the PLF-inferred low alpha functional network, which is setting, as well as a diagnostic validation test in a specialist elevated in people with IGE.4 Third, a model-driven analy- epilepsy setting. This would focus further medical investi- sis where the low alpha functional network inferred from gation and resources on a smaller subgroup, producing effi- the EEG of each individual is integrated within a phase ciency gains and cost savings. oscillator model (of Kuramoto type).5 Here the local cou- pling constant within each node of the network is inferred Methods by multiplying the variance of the signal in the correspond- ing EEG channel by a uniform parameter K, to give a sub- We studied data from 38 healthy controls and 30 people ject-specific dynamic network model of the brain. The with IGE between the ages of 16 and 59 years. The individu- seizure-generating capability of each region within this als with IGE were drug naive and recruited through clinics model is then evaluated computationally, as the average at St Thomas’s Hospital. A diagnosis of epilepsy was con- level of emergent seizure activity across the whole network firmed in each case by an experienced epilepsy specialist driven by the region of interest (see Fig. 1A). through observation of typical generalized spike-wave The performance of all three candidate biomarkers was (GSW) activity on EEG either spontaneously or following evaluated
Load more

Recommended publications
  • 1 ILAE Classification & Definition of Epilepsy Syndromes in the Neonate
    ILAE Classification & Definition of Epilepsy Syndromes in the Neonate and Infant: Position Statement by the ILAE Task Force on Nosology and Definitions Authors: Sameer M Zuberi1, Elaine Wirrell2, Elissa Yozawitz3, Jo M Wilmshurst4, Nicola Specchio5, Kate Riney6, Ronit Pressler7, Stephane Auvin8, Pauline Samia9, Edouard Hirsch10, O Carter Snead11, Samuel Wiebe12, J Helen Cross13, Paolo Tinuper14,15, Ingrid E Scheffer16, Rima Nabbout17 1. Paediatric Neurosciences Research Group, Royal Hospital for Children & Institute of Health & Wellbeing, University of Glasgow, Member of European Reference Network EpiCARE, Glasgow, UK. 2. Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester MN, USA. 3. Isabelle Rapin Division of Child Neurology of the Saul R Korey Department of Neurology, Montefiore Medical Center, Bronx, NY USA. 4. Department of Paediatric Neurology, Red Cross War Memorial Children’s Hospital, Neuroscience Institute, University of Cape Town, South Africa. 5. Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu’ Children’s Hospital, IRCCS, Member of European Reference Network EpiCARE, Rome, Italy 6. Neurosciences Unit, Queensland Children's Hospital, South Brisbane, Queensland, Australia. Faculty of Medicine, University of Queensland, Queensland, Australia. 7. Clinical Neuroscience, UCL- Great Ormond Street Institute of Child Health, London, UK. Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, Member of European Reference Network EpiCARE London, UK 8. Université de Paris, AP-HP, Hôpital Robert-Debré, INSERM NeuroDiderot, DMU Innov-RDB, Neurologie Pédiatrique, Member of European Reference Network EpiCARE, Paris, France. 9. Department of Paediatrics and Child Health, Aga Khan University, East Africa. 1 10. Neurology Epilepsy Unit “Francis Rohmer”, INSERM 1258, FMTS, Strasbourg University, France.
    [Show full text]
  • Focus on Pregnancy: Vitamin K, Folic Acid
    Practice Parameter update: Management issues for women with epilepsy−−Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society C. L. Harden, P. B. Pennell, B. S. Koppel, et al. Neurology 2009;73;142-149 Published Online before print April 27, 2009 DOI 10.1212/WNL.0b013e3181a6b325 This information is current as of April 27, 2009 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.neurology.org/content/73/2/142.full.html Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright . All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X. SPECIAL ARTICLE Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society C.L. Harden, MD ABSTRACT P.B. Pennell, MD Objective: To reassess the evidence for management issues related to the care of women with B.S. Koppel, MD epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K C.A. Hovinga, PharmD use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast B. Gidal, PharmD milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels K.J.
    [Show full text]
  • ICTALS2019 the Epilepsy Journey
    ICTALS2019 The Epilepsy Journey 2-5 September In partnership with Abstract book This conference is supported by a grant from the American Epilepsy Society ICTALS2019 The Epilepsy Journey Foreword The International Conference for Technology and Analysis of Seizures, 2019 (ICTALS2019) aims to bring together neurologists, neuroscientists, researchers from quantitative disciplines and people with lived experience of epilepsy in order to work as a community to advance our understanding of epilepsy and develop practical ways to improve diagnosis and treatment. The theme for this year’s conference is: The Epilepsy Journey: from first seizure to treatment and beyond. We will emphasise how advances in our understanding of the dynamics of brain networks can be used to make a difference to people with epilepsy at all points of their journey: from elucidating the causes of the first seizure to diagnosing epilepsy, understanding how ictogenic networks give rise to recurrent seizures and how this insight can inform personalised treatment. To encourage this focus on the whole epilepsy journey we seek to include all relevant communities. In addition to discussions on current scientific, clinical and technological advances, we will take steps to increase accessibility for people with lived experience of epilepsy. Dates: Monday 2 September 2019 - Thursday 5 September 2019 Venue: University of Exeter, Streatham Campus, Xfi Building Conference website: http://ex.ac.uk/ictals2019 Contact the organisers: [email protected] ICTALS2019 The Epilepsy Journey Partners We are partnering with charities Epilepsy Research UK and Epilepsy Action and Alliance for Epilepsy Research. Sponsors This event would not be possible without the generous contributions from our generous sponsors UCB, the Epilepsy Foundation, NeuraLynx, and Liva Nova.
    [Show full text]
  • Fundraising Financial Summar
    Chairman’s Report research arena. In March 2012, I would like to take this opportunity we organised our ninth international to thank Samantha Cameron for MY FIRST 12 MONTHS AS CHAIR It was always our ambition to mark workshop entitled ‘Why do some graciously hosting the Epilepsy OF EPILEPSY RESEARCH UK HAVE the 20th anniversary of Epilepsy brains seize? Molecular, cellular and Research UK reception at 10 Downing COINCIDED WITH OUR 20TH Research UK with a grant round of network mechanisms’ where fifty Street in May 2012 that rounded off our ANNIVERSARY AND OUR MOST this magnitude, but to have realised experts from around the world anniversary year. This event, together SUCCESSFUL YEAR TO DATE. it in the current economic climate is a gathered to consider the key with the Gala Ball in October 2011, Credit for that goes to my tremendous achievement. This success differences between normal were highlights of a momentous twelve predecessor as Chair, Professor Helen allowed us to fund five new project functioning brains and those that months for Epilepsy Research UK, with Cross, for her excellent stewardship grants, two fellowship grants and one periodically exhibit spontaneous both well attended by our loyal and of the charity over the past six years, project grant extension at a total cost of seizures. The proceedings of the committed supporters. We owe a huge the staff of Epilepsy Research UK for £1,189,332. As always, these awards workshop will be published in debt of gratitude to our supporters for a continuing dedication to the cause their continuing hard work, and the covered a broad spectrum of research the highly prestigious Journal of of epilepsy research that has enabled remarkable efforts of our donors and focused on the causes, prevention and Physiology later in the year.
    [Show full text]
  • Paediatric Epilepsy Research Report 2019
    Paediatric Epilepsy 2019 Research Report Inside Who we are The organisations and experts behind our research programme What we do Our strategy, projects and impact youngepilepsy.org.uk Contents Introduction 1 Who we are 2 Research Partners 2 Research Funding 4 Research Team 5 What we do 10 Programme Strategy 10 The MEG Project 12 New Research Projects 14 Research Project Update 21 Completed Projects 32 Awarded PhDs 36 Paediatric Epilepsy Masterclass 2018 37 Paediatric Epilepsy Research Retreat 2019 38 Research Publications 40 Unit Roles 47 Unit Roles in Education 49 Professional Recognition and Awards 50 Paediatric Epilepsy Research Report 2019 Introduction I am delighted to present our annual research report for the period July 2018 to June 2019 for the paediatric epilepsy research unit across Young Epilepsy, UCL GOS - Institute of Child Health and Great Ormond Street Hospital for Children. We have initiated 13 new research projects, adding to 20 active projects spanning the clinical, educational and social elements of paediatric epilepsy. We have published 110 peer-reviewed items of primary research and a further 54 chapters in books, reviews and commentaries of expert opinion. During this period, Young Epilepsy Chief Executive Carol Long caught the research bug and moved on to begin her PhD at Durham University. We welcomed our new Chief Executive, Mark Devlin at our Paediatric Epilepsy Research Retreat in January 2019. As an organisation, we are launching a new strategy This report features a spotlight on a truly which sets our research programme as one of innovative project which will change the UK’s the four key offers at Young Epilepsy, and we diagnostic and surgical evaluation imaging suite look forward to sharing our research more widely for childhood epilepsy.
    [Show full text]
  • Clinical Spectrum Ofstx1b-Related Epileptic Disorders
    ARTICLE OPEN ACCESS Clinical spectrum of STX1B-related epileptic disorders Stefan Wolking, MD, Patrick May, PhD, Davide Mei, PhD, Rikke S. Møller, PhD, Simona Balestrini, PhD, Correspondence Katherine L. Helbig, MS, Cecilia Desmettre Altuzarra, MD, Nicolas Chatron, PhD, Charu Kaiwar, MD, Dr. Lerche Katharina Stohr,¨ MD, Peter Widdess-Walsh, MB, Bryce A. Mendelsohn, PhD, Adam Numis, MD, holger.lerche@ Maria R. Cilio, PhD, Wim Van Paesschen, MD, Lene L. Svendsen, MD, Stephanie Oates, MD, Elaine Hughes, MD, uni-tuebingen.de Sushma Goyal, MD, Kathleen Brown, MS, Margarita Sifuentes Saenz, MD, Thomas Dorn, MD, Hiltrud Muhle, MD, Alistair T. Pagnamenta, PhD, Dimitris V. Vavoulis, PhD, Samantha J.L. Knight, PhD, Jenny C. Taylor, PhD, Maria Paola Canevini, MD, Francesca Darra, MD, Ralitza H. Gavrilova, MD, Zoe¨ Powis, MS, Shan Tang, PhD, Justus Marquetand, MD, Martin Armstrong, PhD, Duncan McHale, PhD, Eric W. Klee, PhD, Gerhard J. Kluger, MD, Daniel H. Lowenstein, MD, Sarah Weckhuysen, PhD, Deb K. Pal, PhD, Ingo Helbig, MD, Renzo Guerrini, MD, Rhys H. Thomas, PhD, Mark I. Rees, PhD, Gaetan Lesca, PhD, Sanjay M. Sisodiya, PhD, Yvonne G. Weber, MD, Dennis Lal, PhD, Carla Marini, PhD, Holger Lerche, MD, and Julian Schubert, PhD Neurology® 2019;92:e1238-e1249. doi:10.1212/WNL.0000000000007089 Abstract Objective The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease- related variants. Methods We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases.
    [Show full text]
  • Seizure: European Journal of Epilepsy 83 (2020) 70–75
    Seizure: European Journal of Epilepsy 83 (2020) 70–75 Contents lists available at ScienceDirect Seizure: European Journal of Epilepsy journal homepage: www.elsevier.com/locate/seizure Review Redefining the role of Magnetoencephalography in refractory epilepsy Umesh Vivekananda 1 Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, UCL, WC1N 3BG, United Kingdom ARTICLE INFO ABSTRACT Keywords: Magnetoencephalography (MEG) possesses a number of features, including excellent spatiotemporal resolution, magnetoencephalography that lend itself to the functional imaging of epileptic activity. However its current use is restricted to specific electroencephalograph scenarios, namely in the diagnosis refractory focal epilepsies where electroencephalography (EEG) has been source localisation inconclusive. This review highlights the recent progress of MEG within epilepsy, including advances in the OPMs technique itself such as simultaneous EEG/MEG and intracranial EEG/MEG recording and room temperature MEG recording using optically pumped magnetometers, as well as improved post processing of the data during interictal and ictal activity for accurate source localisation of the epileptogenic focus. These advances should broaden the scope of MEG as an important part of epilepsy diagnostics in the future. 1. Introduction one large study of 1000 consecutive cases of refractory focal epilepsy demonstrated that MEG provided additional information to existing pre- A mainstay in epilepsy diagnostics over the last century has been the surgical methods (including scalp EEG, single photon emission electroencephalogram or EEG. Simply explained, EEG records electrical computed tomography (SPECT) and MRI) in 32% of cases, and complete currents reflecting synchronous neuronal activity attributable to the magnetoencephalography resection was associated with significantly brain surface, and can identify abnormal activity related to epilepsy with higher chances to achieve seizure freedom in the short and long-term good temporal resolution.
    [Show full text]
  • Download of the Event Diaries Database for Future Research
    JMIR RESEARCH PROTOCOLS Biondi et al Protocol Remote and Long-Term Self-Monitoring of Electroencephalographic and Noninvasive Measurable Variables at Home in Patients With Epilepsy (EEG@HOME): Protocol for an Observational Study Andrea Biondi1, MSc; Petroula Laiou1, PhD; Elisa Bruno1, MD, PhD; Pedro F Viana1,2, MSc, MD; Martijn Schreuder3, PhD; William Hart4, PhD; Ewan Nurse4,5, PhD; Deb K Pal1, PhD; Mark P Richardson1, BMBCh, PhD 1Institute of Psychiatry, Psychology & Neuroscience, King©s College London, London, United Kingdom 2Faculty of Medicine, University of Lisbon, Hospital de Santa Maria, Lisbon, Portugal 3ANT Neuro UK, Ltd, Stevenage, United Kingdom 4Seer Medical Inc, Melbourne, Australia 5Department of Medicine, St. Vincent's Hospital Melbourne, The University of Melbourne, Melbourne, Australia Corresponding Author: Andrea Biondi, MSc Institute of Psychiatry, Psychology & Neuroscience King©s College London 5 Cutcombe Rd London, SE5 9RT United Kingdom Phone: 44 7753986485 Email: [email protected] Abstract Background: Epileptic seizures are spontaneous events that severely affect the lives of patients due to their recurrence and unpredictability. The integration of new wearable and mobile technologies to collect electroencephalographic (EEG) and extracerebral signals in a portable system might be the solution to prospectively identify times of seizure occurrence or propensity. The performances of several seizure detection devices have been assessed by validated studies, and patient perspectives on wearables have been explored to better match their needs. Despite this, there is a major gap in the literature on long-term, real-life acceptability and performance of mobile technology essential to managing chronic disorders such as epilepsy. Objective: EEG@HOME is an observational, nonrandomized, noninterventional study that aims to develop a new feasible procedure that allows people with epilepsy to independently, continuously, and safely acquire noninvasive variables at home.
    [Show full text]
  • Estimation of Brain Network Ictogenicity Predicts Outcome from Epilepsy Surgery Goodfellow, M; Rummel, C; Abela, E; Richardson, MP; Schindler, K; Terry, JR
    University of Birmingham Estimation of brain network ictogenicity predicts outcome from epilepsy surgery Goodfellow, M; Rummel, C; Abela, E; Richardson, MP; Schindler, K; Terry, JR DOI: 10.1038/srep29215 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Goodfellow, M, Rummel, C, Abela, E, Richardson, MP, Schindler, K & Terry, JR 2016, 'Estimation of brain network ictogenicity predicts outcome from epilepsy surgery', Scientific Reports, vol. 6, no. 1, 29215. https://doi.org/10.1038/srep29215 Link to publication on Research at Birmingham portal Publisher Rights Statement: Goodfellow, M. et al (2016) Estimation of brain network ictogenicity predicts outcome from epilepsy surgery, Scientific Reports volume 6, Article number: 29215; https://doi.org/10.1038/srep29215 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.
    [Show full text]
  • Neurologic Phenotypes Associated with COL4A1/2 Mutations Expanding the Spectrum of Disease
    ARTICLE OPEN ACCESS Neurologic phenotypes associated with COL4A1/2 mutations Expanding the spectrum of disease Sara Zagaglia, MD, Christina Selch, MD, Jelena Radic Nisevic, MD, Davide Mei, MD, Zuzanna Michalak, PhD, Correspondence Laura Hernandez-Hernandez, PhD, S. Krithika, PhD, Katharina Vezyroglou, MD, Sophia M. Varadkar, MRCPI, PhD, Dr. Sisodiya Alexander Pepler, MBiol, Saskia Biskup, MD, PhD, Miguel Leão, MD, PhD, Jutta G¨artner, MD, Andreas Merkenschlager, MD, [email protected] Michaela Jaksch, MD, Rikke S. Møller, MsC, PhD, Elena Gardella, MD, PhD, Britta Schlott Kristiansen, MD, Lars Kjærsgaard Hansen, MD, Maria Stella Vari, MD, Katherine L. Helbig, MSc, Sonal Desai, MD, Constance L. Smith-Hicks, MD, PhD, Naomi Hino-Fukuyo, MD, PhD, Tiina Talvik, DrMed, Rael Laugesaar, MD, Pilvi Ilves, MD, PhD, Katrin Õunap, DrMed, Ingrid Korber,¨ BSc, Till Hartlieb, MD, Manfred Kudernatsch,MD,PeterWinkler,MD, MareikeSchimmel,MD,AnetteHasse,MD,MarkusKnuf,MD,JanHeinemeyer,MD,ChristineMakowski,MD, Sondhya Ghedia, MBBS, FRACP, Gopinath M. Subramanian, FRACP, Pasquale Striano, MD, PhD, Rhys H. Thomas, MBChB, PhD, Caroline Micallef, FRCR,MariaThom,FRCPath,DavidJ.Werring,PhD,FRCP, Gerhard Josef Kluger, MD, PhD, J. Helen Cross, PhD, FRCPCH, Renzo Guerrini, MD, PhD, Simona Balestrini, MD, PhD, and Sanjay M. Sisodiya, PhD, FRCP Neurology® 2018;91:e2078-e2088. doi:10.1212/WNL.0000000000006567 Abstract Objective To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype–phenotype correlation. Methods We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. Results Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype.
    [Show full text]
  • Onset Genetic Generalized Epilepsy
    Accepted: 19 October 2017 DOI: 10.1111/epi.13955 FULL-LENGTH ORIGINAL RESEARCH Thalamic volume reduction in drug-naive patients with new-onset genetic generalized epilepsy Suejen Perani1,2 | Tim M. Tierney2 | Maria Centeno2 | Elhum A. Shamshiri2 | Siti N. Yaakub1 | Jonathan O’Muircheartaigh3,4 | David W. Carmichael2 | Mark P. Richardson1 1Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Summary Psychology and Neuroscience, King’s Objective: Patients with genetic generalized epilepsy (GGE) have subtle morpho- College London, London, United logic abnormalities of the brain revealed with magnetic resonance imaging (MRI), Kingdom particularly in the thalamus. However, it is unclear whether morphologic abnor- 2Developmental Imaging and Biophysics Section, Developmental Neurosciences malities of the brain in GGE are a consequence of repeated seizures over the Program, UCL Great Ormond Street duration of the disease, or are a consequence of treatment with antiepileptic drugs Institute of Child Health, London, United (AEDs), or are independent of these factors. Therefore, we measured brain mor- Kingdom 3Department of Neuroimaging, Institute of phometry in a cohort of AED-naive patients with GGE at disease onset. We Psychiatry, Psychology and Neuroscience, hypothesize that drug-naive patients at disease onset have gray matter changes ’ King s College London, London, United compared to age-matched healthy controls. Kingdom Methods: We performed quantitative measures of gray matter volume in the tha- 4Centre for the Developing Brain, Division of Imaging Sciences and lamus, putamen, caudate, pallidum, hippocampus, precuneus, prefrontal cortex, Biomedical Engineering, King’s College precentral cortex, and cingulate in 29 AED-naive patients with new-onset GGE London, London, United Kingdom and compared them to 32 age-matched healthy controls.
    [Show full text]
  • ILAE Definition of the Idiopathic Generalized Epilepsy Syndromes: Position Statement by the ILAE Task Force on Nosology and Definitions
    1 ILAE Definition of the Idiopathic Generalized Epilepsy Syndromes: Position Statement by the ILAE Task Force on Nosology and Definitions E Hirsch1, J French2, IE Scheffer3, SM Zuberi4, E Trinka5,6, N Specchio7, E Somerville8, P Samia9, K Riney10, R Nabbout11, S Jain12, A Bogacz13, T Alsaadi14, JM Wilmshurst15, S Auvin16, S Wiebe17, P Tinuper18,19*, E Wirrell20* *Co senior authors 1. Neurology Epilepsy Units “Francis Rohmer”, INSERM 1258, FMTS, Strasbourg University, France. 2. NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA. 3. University of Melbourne, Austin Health and Royal Children’s Hospital, Florey Institute, Murdoch Children’s Research Institute, Melbourne, Australia. 4. Paediatric Neurosciences Research Group, Royal Hospital for Children & Institute of Health & Wellbeing, University of Glasgow, Member of European Reference Network EpiCARE, Glasgow, UK. 5. Department of Neurology and Neuroscience Institute, Christian Doppler University Hospital, Paracelsus Medical University, and Centre for Cognitive Neuroscience, Affiliated Member of EpiCARE, Salzburg, Austria. 6. Department of Public Health, Health Services Research and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria. 7. Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu’ Children’s Hospital, IRCCS, Member of European Reference Network EpiCARE, Rome, Italy 8. Prince of Wales Hospital and University of New South Wales, Sydney, Australia. 9. Department of Paediatrics and Child Health, Aga Khan University, East Africa. 10. Neurosciences Unit, Queensland Children's Hospital, South Brisbane, Queensland, Australia. Faculty of Medicine, University of Queensland, Queensland, Australia. 11. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker–Enfants Malades Hospital, APHP, Member of European Reference Network EpiCARE, Institut Imagine, INSERM, UMR 1163, Université de Paris, Paris, France.
    [Show full text]