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Epilepsy: HELP
Articles by Judith Helen Cross
Based on 140 articles published since 2010
(Why 140 articles?)
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Between 2010 and 2020, J. H. Cross wrote the following 140 articles about Epilepsy.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Guideline Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. 2017

Harden, Cynthia / Tomson, Torbjörn / Gloss, David / Buchhalter, Jeffrey / Cross, J Helen / Donner, Elizabeth / French, Jacqueline A / Gil-Nagel, Anthony / Hesdorffer, Dale C / Smithson, W Henry / Spitz, Mark C / Walczak, Thaddeus S / Sander, Josemir W / Ryvlin, Philippe. ·From the Department of Neurology (C.H.), Mount Sinai Health System, New York, NY · Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden · Department of Neurology (D.G.), CAMC Physicians, Charleston, WV · Departments of Pediatrics and Clinical Neurosciences (J.B.), Alberta Children's Hospital, University of Calgary, Canada · Department of Clinical Neurosciences, Institute of Child Health (J.H.C.), and Institute of Neurology (J.W.S.), University College London · Great Ormond Street Hospital for Children NHS Foundation Trust (J.H.C.), London, UK · Department of Paediatrics (E.D.), Division of Neurology, The Hospital for Sick Children, University of Toronto, Canada · Department of Neurology (J.A.F.), New York University Langone Comprehensive Epilepsy Center, New York · Department of Neurology (A.G.-N.), Hospital Ruber Internacional, Madrid, Spain · Gertrude H. Sergievsky Center and Department of Epidemiology (D.C.H.), Columbia University Medical Center, New York, NY · Department of General Practice (W.H.S.), University College Cork, Ireland · Anschutz Outpatient Pavilion (M.C.S.), University of Colorado Health, Aurora · Neurology Clinic (T.S.W.), University of Minnesota, Minneapolis · Stichting Epilepsie Instellingen Nederland (SEIN) (J.W.S.), Heemstede, the Netherlands · and the Department of Clinical Neurosciences (P.R.), CHUV, Lausanne, Switzerland. ·Neurology · Pubmed #28438841.

ABSTRACT: OBJECTIVE: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. METHODS: Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus. RESULTS: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16-0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). RECOMMENDATIONS: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

2 Guideline Diagnosis and management of the epilepsies in children: a summary of the partial update of the 2012 NICE epilepsy guideline. 2012

Appleton, Richard E / Freeman, Amanda / Cross, J Helen. ·Department of Neurology, The Roald Dahl EEG Unit, Paediatric Neurosciences Foundation, Alder Hey Children's NHS Foundation Trust, Liverpool, UK. Richard.appleton@alderhey.nhs.uk ·Arch Dis Child · Pubmed #23042803.

ABSTRACT: The epilepsies of childhood are a heterogeneous group of disorders with different causes, treatments and outcomes. The choice of anti-epileptic drug is largely determined by its effectiveness in a specific epilepsy syndrome, or seizure type(s) if a syndrome cannot be readily identified, and the drug's safety profile. There are minimal randomised controlled trial data to help inform this decision. In January 2012, the National Institute for Health and Clinical Excellence (NICE) published its partially revised and updated clinical guideline on the pharmacological treatment of the epilepsies in children and adults. This partial update provides additional data and also specific recommendations that improve the evidence base for the use of specific anti-epileptic drugs in treating the epilepsies of childhood.

3 Editorial Pediatric epilepsy surgery: the earlier the better. 2018

Braun, Kees P J / Cross, J Helen. ·a Department of Child Neurology. Brain Center Rudolf Magnus , University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands. · b Clinical Neurosciences Unit , UCL-Great Ormond Street Institute of Child Health , London , UK. · c Young Epilepsy , Lingfield , UK. ·Expert Rev Neurother · Pubmed #29560752.

ABSTRACT: -- No abstract --

4 Editorial Epilepsy surgery in children--no longer a last resort. 2010

Cross, J Helen. · ·Dev Med Child Neurol · Pubmed #20412249.

ABSTRACT: -- No abstract --

5 Review Optimising Evidence-Based Psychological Treatment for the Mental Health Needs of Children with Epilepsy: Principles and Methods. 2020

Shafran, Roz / Bennett, Sophie / Coughtrey, Anna / Welch, Alice / Walji, Fahreen / Cross, J Helen / Heyman, Isobel / Sibelli, Alice / Smith, Jessica / Ross, Jamie / Dalrymple, Emma / Varadkar, Sophia / Anonymous5341122 / Moss-Morris, Rona. ·Population, Policy and Practice Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. r.shafran@ucl.ac.uk. · Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK. r.shafran@ucl.ac.uk. · Population, Policy and Practice Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. · Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK. · Health Psychology, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE1 9RT, UK. · King's College London, Strand, London, WC2R 2LS, UK. · Department of Primary Care and Population Health, UCL Medical School (Royal Free Campus), University College London, Rowland Hill Street, London, NW3 2PF, UK. ·Clin Child Fam Psychol Rev · Pubmed #31965422.

ABSTRACT: There are potent evidence-based psychological treatments for youth with mental health needs, yet they are rarely implemented in clinical practice, especially for youth with mental health disorders in the context of chronic physical illness such as epilepsy. Implementation science, the study of the translation of research into practice, can promote the uptake of existing effective interventions in routine clinical practice and aid the sustainable integration of psychological treatments with routine health care. The aim of this report was to use four implementation science methods to develop a version of an existing effective psychological treatment for mental health disorders [the Modular Approach to Treatment of Children with Anxiety, Depression or Conduct Problems (MATCH-ADTC)] for use within paediatric epilepsy services: (a) literature search; (b) iterative focus groups underpinned by normalisation process theory; (c) Plan-Do-Study-Act methods; and (d) qualitative patient interviews. Findings: Three modifications were deemed necessary to facilitate implementation in children with both mental health disorders and epilepsy. These were (a) a universal brief psychoeducational component addressing the relationship between epilepsy and mental health; (b) supplementary, conditionally activated interventions addressing stigma, parental mental health and the transition to adulthood; and (c) additional training and supervision. The intervention needed relatively little alteration for implementation in paediatric epilepsy services. The modified treatment reflected the scientific literature and the views of clinicians and service users. The multi-method approach used in this report can serve as a model for implementation of evidence-based psychological treatments for children with mental health needs in the context of other chronic illnesses.

6 Review The concept of disease modification. 2020

Cross, J Helen / Lagae, Lieven. ·UCL NIHR BRC Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK. Electronic address: h.cross@ucl.ac.uk. · Paediatric Neurology, University Hospitals Leuven, Herestraat 49, Leuven, BE B-3000, Belgium. ·Eur J Paediatr Neurol · Pubmed #31879224.

ABSTRACT: Traditionally treatment of epileptic seizures has been symptomatic, namely medication has been targeted at raising the threshold to the occurrence of epileptic seizures. This has had little impact on the rate of drug resistance over time, or impact on comorbidities such as learning and behaviour particularly in the early onset epilepsies. The advent of advanced neuroimaging and genomics has revealed the cause of the epilepsy in a much higher percentage, and advanced our knowledge as to the underlying pathophysiology. This has given us the opportunity to turn to the possibility of interventional treatment, targeting the underlying cause, and consequently the possibility of changing the natural history of disease. Here we review the options open to us, and the evidence to date.

7 Review A perspective on cannabinoids for treating epilepsy: Do they really change the landscape? 2019

Cross, J Helen / Cock, Hannah. ·UCL NIHR BRC Great Ormond Street Institute of Child Health, Guilford St, London, WC1N 1EH, UK; Great Ormond Street for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK; Young Epilepsy, Lingfield, Surrey, UK. · Institute of Molecular and Clinical Sciences, St George's University of London, SW17 0RE, UK; Atkinson Morley Regional Epilepsy Network, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW17 0QT, UK. Electronic address: hannahrc@sgul.ac.uk. ·Neuropharmacology · Pubmed #31770546.

ABSTRACT: With the licensing of cannabidiol for drug resistant seizures in Dravet and Lennox Gastaut syndromes in the United states in 2018, interest in the potential for cannabis-based-medicinal products to meet currently unmet needs for people with epilepsy continues to grow. This review summarizes current knowledge and discusses the implications for future research and practice. Both cannabidiol and tetrahydrocannabinol, the main components, have been extensively studied in animal models, with multimodal mechanisms of action proposed. Only pure cannabidiol formulations have been rigorously evaluated in controlled trials thus far, with modest but significant improvements in motor seizures. Adverse effects include diarrhoea, somnolence and reduced appetite, with mostly acceptable tolerability, but a not insignificant (up to 1 in 23) risk of serious adverse events. Recognized drug interactions include with valproate (increased risk of hepatotoxicity) and clobazam (contributing to somnolence, increased secretions, probably chest infections, and potentially efficacy). Whilst there is public (and producer) interest in products also containing tetrahydrocannabinol, clinicians have justifiable concerns about exposing a group already vulnerable to mental health and neurobehavioural comorbidities to the associated additional risks in these domains. Artisanal preparations, with often inconsistent/unknown constituents are frequently used but not recommended. A gulf exists between the actual evidence, including a lack of comparative studies and public beliefs, fuelled by media and anecdote. Continued education of the public, policymakers, researchers and healthcare providers about what is and isn't yet known, together with on-going good quality research is essential to mitigate against future potential risks, particularly in relation to vulnerable populations. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.

8 Review Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review. 2019

Olson, Heather E / Demarest, Scott T / Pestana-Knight, Elia M / Swanson, Lindsay C / Iqbal, Sumaiya / Lal, Dennis / Leonard, Helen / Cross, J Helen / Devinsky, Orrin / Benke, Tim A. ·Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts. Electronic address: Heather.Olson@childrens.harvard.edu. · Children's Hospital Colorado, University of Colorado, School of Medicine, Aurora, Colorado; Department of Pediatrics, University of Colorado, School of Medicine, Aurora, Colorado. · Cleveland Clinic Neurological Institute Epilepsy Center, Cleveland Clinic Neurological Institute Pediatric Neurology Department, Neurogenetics, Cleveland Clinic Children's, Cleveland, Ohio. · Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio; Neurological Institute, Cleveland Clinic, Cleveland, Ohio. · Telethon Kids Institute, University of Western Australia, Perth, WA, Australia. · UCL Great Ormond Street NIHR BRC Institute of Child Health, London, UK. · Department of Neurology, NYU Langone Health, New York, New York. · Children's Hospital Colorado, University of Colorado, School of Medicine, Aurora, Colorado; Department of Pediatrics, University of Colorado, School of Medicine, Aurora, Colorado; Department of Pharmacology, University of Colorado, School of Medicine, Aurora, Colorado; Department of Neurology, University of Colorado, School of Medicine, Aurora, Colorado; Department of Otolaryngology, University of Colorado, School of Medicine, Aurora, Colorado. ·Pediatr Neurol · Pubmed #30928302.

ABSTRACT: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene CDKL5. This unique disorder includes early infantile onset refractory epilepsy, hypotonia, developmental intellectual and motor disabilities, and cortical visual impairment. We review the clinical presentations and genetic variations in CDD based on a systematic literature review and experience in the CDKL5 Centers of Excellence. We propose minimum diagnostic criteria. Pathogenic variants include deletions, truncations, splice variants, and missense variants. Pathogenic missense variants occur exclusively within the kinase domain or affect splice sites. The CDKL5 protein is widely expressed in the brain, predominantly in neurons, with roles in cell proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis, and synapse development. The molecular biology of CDD is revealing opportunities in precision therapy, with phase 2 and 3 clinical trials underway or planned to assess disease specific and disease modifying treatments.

9 Review A web-based diagnostic reference centre for the European Reference Network "EpiCare": recommendations of the eNeuropathology working group. 2018

Kölble, Konrad / Cross, J Helen / Becker, Albert / Blümcke, Ingmar. ·Neuropathologisches Institut, Universitätsklinikum Erlangen, Schwabachanlage 6, D-91054 Erlangen, Germany. · UCL-Institute of Child Health, Great Ormond Street Hospital for Children, London & Young Epilepsy, Lingfield, UK. · Neuropathologisches Institut, Universitätsklinikum Bonn, Sigmund-Freud Str. 25, D-53105 Bonn, Germany. ·Epileptic Disord · Pubmed #30361181.

ABSTRACT: Epilepsy surgery is a valuable treatment strategy for a selected group of patients with drug-resistant focal epilepsy. While reliable disease classification is essential for the optimal management of patients in general and crucial for the development of more personalized therapies in the future, arriving at a precise diagnosis often poses considerable difficulties due to the broad and variant-rich spectrum of epilepsy-associated brain lesions. Given the scarcity of European institutions diagnostically focusing on the histopathology of epilepsy surgery cases, the provision of subspecialty expertise as well as training opportunities remains logistically and financially challenging. To improve this situation, the European Reference Network's (ERN) epilepsy care program (EpiCare, http://epi-care.eu) has set out to develop a web-based microscopy referral and teaching framework. This paper reviews the aspects of digital microscopy, data storage, and image analysis technology relevant to the practice of neuropathology. Cognizant of the European data security requirements and regulations, we propose a collaborative, diagnostic network initiative (the eNeuropathology reference centre) and delineate a roadmap for its implementation favouring open-source, vendor-independent browser platforms.

10 Review The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology-related and developmental encephalopathies. 2018

Kalser, Judith / Cross, J Helen. ·UCL-Great Ormond Street Institute of Child Health, Great Ormond Street Hospital for Children NHS Trust, London, UK. ·Curr Opin Neurol · Pubmed #29356691.

ABSTRACT: PURPOSE OF REVIEW: We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. RECENT FINDINGS: The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of 'developmental encephalopathy' which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful. SUMMARY: The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.

11 Review Prevalence and risk factors for autism spectrum disorder in epilepsy: a systematic review and meta-analysis. 2018

Strasser, Lauren / Downes, Michelle / Kung, Jane / Cross, J Helen / De Haan, Michelle. ·UCL Great Ormond Street Institute of Child Health, London, UK. ·Dev Med Child Neurol · Pubmed #29119560.

ABSTRACT: AIM: To assess the prevalence and risk factors for autism spectrum disorder (ASD) in epilepsy, and to better understand the relationship and comorbidity between these disorders. METHOD: PsychINFO and PubMed were searched for articles published in the past 15 years that examined the prevalence of ASD in individuals with epilepsy. RESULTS: A total of 19 studies were found with a pooled ASD prevalence of 6.3% in epilepsy. When divided by type, the risks of ASD for general epilepsy, infantile spasms, focal seizures, and Dravet syndrome were 4.7%, 19.9%, 41.9%, and 47.4% respectively. Studies with populations under 18 years showed a 13.2 times greater risk of ASD than study populations over 18 years, and samples with most (>50%) individuals with intellectual disability showed a greater risk 4.9 times higher than study populations with a minority of individuals with intellectual disability. The main risk factors for ASD reported in the 19 studies included presence of intellectual disability, sex, age, and symptomatic aetiology of epilepsy. INTERPRETATION: Current research supports a high prevalence of ASD in epilepsy. This study helps to define the clinical profile of patients with epilepsy who are at risk for ASD, which may help clinicians in early screening and diagnosis of ASD in this population. WHAT THIS PAPER ADDS: Critical evaluation of previous studies examining the prevalence of autism spectrum disorder (ASD) in individuals with epilepsy. A meta-analysis of 19 studies showed a pooled ASD prevalence of 6.3% in individuals with epilepsy. Studies that included a majority of individuals with intellectual disability or younger population age had a higher prevalence of autism. Risk factors reported in studies included presence of intellectual disability, sex, age, and symptomatic epilepsy origin.

12 Review Expert Opinion on the Management of Lennox-Gastaut Syndrome: Treatment Algorithms and Practical Considerations. 2017

Cross, J Helen / Auvin, Stéphane / Falip, Mercè / Striano, Pasquale / Arzimanoglou, Alexis. ·Clinical Neurosciences Section, UCL Institute of Child Health, ERN EpiCARE, London, United Kingdom. · APHP, Robert Debré University Hospital, Paris, France. · Epilepsy Unit, Neurology Service, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. · Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, G. Gaslini Institute, Genoa, Italy. · Epilepsy Unit, Child Neurology Department, Hospital San Juan de Déu, ERN EpiCARE, Barcelona, Spain. · Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, ERN EpiCARE, University Hospitals of Lyon (HCL), Lyon, France. ·Front Neurol · Pubmed #29085326.

ABSTRACT: Lennox-Gastaut syndrome (LGS) is a severe epileptic and developmental encephalopathy that is associated with a high rate of morbidity and mortality. It is characterized by multiple seizure types, abnormal electroencephalographic features, and intellectual disability. Although intellectual disability and associated behavioral problems are characteristic of LGS, they are not necessarily present at its outset and are therefore not part of its diagnostic criteria. LGS is typically treated with a variety of pharmacological and non-pharmacological therapies, often in combination. Management and treatment decisions can be challenging, due to the multiple seizure types and comorbidities associated with the condition. A panel of five epileptologists met to discuss consensus recommendations for LGS management, based on the latest available evidence from literature review and clinical experience. Treatment algorithms were formulated. Current evidence favors the continued use of sodium valproate (VPA) as the first-line treatment for patients with newly diagnosed

13 Review Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI. 2017

Adler, Sophie / Lorio, Sara / Jacques, Thomas S / Benova, Barbora / Gunny, Roxana / Cross, J Helen / Baldeweg, Torsten / Carmichael, David W. ·Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, University College London, London, UK. · Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, University College London, London, UK. Electronic address: s.lorio@ucl.ac.uk. · Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, UK. · Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, UK; Department of Paediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic; 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Department of Radiology, Great Ormond Street Hospital for Children, London, UK. ·Neuroimage Clin · Pubmed #28491496.

ABSTRACT: Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment of standard structural MRI is useful for the localization of lesions but is unable to accurately predict the histopathological features. Quantitative MRI offers the possibility to probe tissue biophysical properties in vivo and may bridge the gap between radiological assessment and ex-vivo histology. This review will cover histological, genetic and radiological features of FCD following the ILAE classification and will explain how quantitative voxel- and surface-based techniques can characterise these features. We will provide an overview of the quantitative MRI measures available, their link with biophysical properties and finally the potential application of quantitative MRI to the problem of FCD subtyping. Future research linking quantitative MRI to FCD histological properties should improve clinical protocols, allow better characterisation of lesions in vivo and tailored surgical planning to the individual.

14 Review Clinical Drug Development in Epilepsy Revisited: A Proposal for a New Paradigm Streamlined Using Extrapolation. 2016

Wadsworth, Ian / Jaki, Thomas / Sills, Graeme J / Appleton, Richard / Cross, J Helen / Marson, Anthony G / Martland, Tim / McLellan, Ailsa / Smith, Philip E M / Pellock, John M / Hampson, Lisa V. ·MRC North-West Hub for Trials Methodology Research, Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster, LA1 4YF, UK. · Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · The Roald Dahl EEG Unit, Paediatric Neurosciences Foundation, Alder Hey Children's Hospital, Liverpool, UK. · University College London-Institute of Child Health, Great Ormond Street Hospital for Children, London, UK. · The Walton Centre NHS Foundation Trust, Liverpool, UK. · Department of Paediatric Neurology, Royal Manchester Children's Hospital, Manchester, UK. · Department of Paediatric Neurosciences, Royal Hospital for Sick Children, Edinburgh, UK. · Department of Neurology, University Hospital of Wales, Cardiff, UK. · Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA. · MRC North-West Hub for Trials Methodology Research, Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster, LA1 4YF, UK. l.v.hampson@lancaster.ac.uk. ·CNS Drugs · Pubmed #27623676.

ABSTRACT: Data from clinical trials in adults, extrapolated to predict benefits in paediatric patients, could result in fewer or smaller trials being required to obtain a new drug licence for paediatrics. This article outlines the place of such extrapolation in the development of drugs for use in paediatric epilepsies. Based on consensus expert opinion, a proposal is presented for a new paradigm for the clinical development of drugs for focal epilepsies. Phase I data should continue to be collected in adults, and phase II and III trials should simultaneously recruit adults and paediatric patients aged above 2 years. Drugs would be provisionally licensed for children subject to phase IV collection of neurodevelopmental safety data in this age group. A single programme of trials would suffice to license the drug for use as either adjunctive therapy or monotherapy. Patients, clinicians and sponsors would all benefit from this new structure through cost reduction and earlier access to novel treatments. Further work is needed to elicit the views of patients, their parents and guardians as appropriate, regulatory authorities and bodies such as the National Institute for Health and Care Excellence (UK).

15 Review Ketogenic diet guidelines for infants with refractory epilepsy. 2016

van der Louw, Elles / van den Hurk, Dorine / Neal, Elizabeth / Leiendecker, Bärbel / Fitzsimmon, Georgiana / Dority, Laura / Thompson, Lindsey / Marchió, Maddelena / Dudzińska, Magdalena / Dressler, Anastasia / Klepper, Joerg / Auvin, Stéphane / Cross, J Helen. ·Erasmus Medical Center Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. Electronic address: e.vanderlouw@erasmusmc.nl. · Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands. Electronic address: t.vandenhurk@umcutrecht.nl. · Matthews Friends Clinics, Lingfield, UK. Electronic address: e.neal@mfclinics.com. · University of Essen, Children's Hospital, Germany. Electronic address: baerbel.Leiendecker@uk-essen.de. · Great Ormond Street Hospital for Children, London, UK. Electronic address: Georgiana.Fitzsimmons@gosh.nhs.uk. · Medical University of South Carolina, USA. Electronic address: kenla@musc.edu. · Children's Mercy Hospital and Clinics, Overland Park, KS, USA. Electronic address: lmthompson@cmh.edu. · University of Modena and Reggio Emilia, Italy. Electronic address: maddalena.marchio@unimore.it. · Center of Pediatrics and Oncology, Chorzow, Poland. Electronic address: mdudzinskapl@yahoo.com. · Medical University Vienna, Austria. Electronic address: anastasia.dressler@meduniwien.ac.at. · Klinikum Aschaffenburg-Alzenau, Germany. Electronic address: Jorg.Klepper@klinikum-ab-alz.de. · Pediatric Epilepsy & Child Neurology Paris-Diderot University, France. Electronic address: stephane.auvin@aphp.fr. · UCL Institute of Child Health, Great Ormond Street Hospital for Children NHS Trust, London, UK. Electronic address: h.cross@ucl.ac.uk. ·Eur J Paediatr Neurol · Pubmed #27470655.

ABSTRACT: BACKGROUND: The ketogenic diet (KD) is an established, effective non-pharmacologic treatment for drug resistant childhood epilepsy. For a long time, the KD was not recommended for use in infancy (under the age of 2 years) because this is such a crucial period in development and the perceived high risk of nutritional inadequacies. Indeed, infants are a vulnerable population with specific nutritional requirements. But current research shows that the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is often achieved and maintained in this specific patient group. There is a need for standardised protocols and management recommendations for clinical use. METHOD: In April 2015, a project group of 5 experts was established in order to create a consensus statement regarding the clinical management of the KD in infants. The manuscript was reviewed and amended by a larger group of 10 international experts in the KD field. Consensus was reached with regard to guidance on how the diet should be administered and in whom. RESULTS: The resulting recommendations include patient selection, pre-KD counseling and evaluation, specific nutritional requirements, preferred initiation, monitoring of adverse effects at initiation and follow-up, evaluation and KD discontinuation. CONCLUSION: This paper highlights recommendations based on best evidence, combined with expert opinions and gives directions for future research.

16 Review Integrated care for childhood epilepsy: ongoing challenges and lessons for other long-term conditions. 2016

Bali, Amit / Hargreaves, Dougal S / Cowman, John / Lakhanpaul, Monica / Dunkley, Colin / Power, Millie / Cross, J Helen. ·Young Epilepsy, Lingfield, Surrey, UK. · PPP Programme, UCL Institute of Child Health, London, UK. · Integrated Children, Young People and Maternal Health Programme, UCL Partners, London, UK. · Sherwood Forest Hospitals NHS Foundation Trust, King's Mill Hospital, Nottinghamshire, UK. · Service User, London, UK. · The Prince of Wales's Chair of Childhood Epilepsy and Honorary Consultant in Paediatric Neurology, UCL - Institute of Child Health, Great Ormond Street Hospital, London & Young Epilepsy, Lingfield, Surrey, UK. ·Arch Dis Child · Pubmed #27221818.

ABSTRACT: Epilepsy care has been identified as a major global issue-and there are many recognised concerns in the UK for children and young people with the condition. A proposed new model could help to increase multisector integration, facilitate better outcomes and offer lessons for improving care of other long-term conditions.

17 Review Definition and diagnostic criteria of sleep-related hypermotor epilepsy. 2016

Tinuper, Paolo / Bisulli, Francesca / Cross, J H / Hesdorffer, Dale / Kahane, Philippe / Nobili, Lino / Provini, Federica / Scheffer, Ingrid E / Tassi, Laura / Vignatelli, Luca / Bassetti, Claudio / Cirignotta, Fabio / Derry, Christopher / Gambardella, Antonio / Guerrini, Renzo / Halasz, Peter / Licchetta, Laura / Mahowald, Mark / Manni, Raffaele / Marini, Carla / Mostacci, Barbara / Naldi, Ilaria / Parrino, Liborio / Picard, Fabienne / Pugliatti, Maura / Ryvlin, Philippe / Vigevano, Federico / Zucconi, Marco / Berkovic, Samuel / Ottman, Ruth. ·From IRCCS Istituto delle Scienze Neurologiche (P.T., F.B., F. Provini, L.V., L.L., B.M., I.N.), Bologna · Department of Biomedical and Neuromotor Sciences (P.T., F.B., F. Provini, L.L.), University of Bologna, Italy · University College London-Institute of Child Health (J.H.C.), Great Ormond Street Hospital for Children NHS Foundation Trust, London and Young Epilepsy, Lingfield, UK · Department of Epidemiology (D.H., R.O.), Mailman School of Public Health, and G.H. Sergievsky Center, College of Physicians & Surgeons, Columbia University, New York, NY · Unité Médicale Epilepsie et Malaises (P.K.), Pôle de Neurologie et Psychiatrie, CHU de Grenoble, France · "C. Munari" Center for Epilepsy Surgery (L.N., L.T.), Niguarda Hospital, Milan, Italy · Epilepsy Research Centre (I.E.S.), Department of Medicine, University of Melbourne, Austin Health, Australia · Department of Neurology (C.B.), University of Bern, Switzerland · Unit of Neurology (F.C.), S. Orsola-Malpighi Hospital, University of Bologna, Italy · Department of Clinical Neurosciences (C.D.), Western General Hospital, Edinburgh, UK · Department of Medical and Surgical Sciences (A.G.), Institute of Neurology, University Magna Græcia, Catanzaro, Italy · Neurology Unit and Laboratories (R.G., C.M.), A. Meyer Children's Hospital, Florence, Italy · National Institute of Clinical Neuroscience (P.H.), Budapest, Hungary · Department of Neurology (M.M.), University of Minnesota Medical School, Minneapolis · Institute of Neurology Mondino (R.M.), University of Pavia · Sleep Disorders Center (L.P.), Department of Neurology, University of Parma, Italy · Department of Neurology (F. Picard), University Hospital and Medical School of Geneva, Switzerland · Department of Biomedical and Surgical Sciences (M.P.), University of Ferrara, Italy · Department of Clinical Neurosciences (P.R.), CHUV, Lausanne, Switzerland · Functional Neurology and Epileptology (P.R.), Hospices Civils de Lyon and CRNL, Lyon · Epilepsy Institute (P.R.), IDEE, Lyon, France ·Neurology · Pubmed #27164717.

ABSTRACT: The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis.

18 Review Targeted Treatment in Childhood Epilepsy Syndromes. 2016

Vezyroglou, Katharina / Cross, J Helen. ·Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK. · Clinical Neurosciences, 30 Guilford St, London, WC1N 1EH, UK. h.cross@ucl.ac.uk. · Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK. h.cross@ucl.ac.uk. ·Curr Treat Options Neurol · Pubmed #27154366.

ABSTRACT: OPINION STATEMENT: The mainstay of treatment of epilepsy has been antiepileptic drugs; however, despite the emergence of new agents, a consistent proportion remain drug-resistant. Newer AEDs show promise. However, as it becomes clear that the epilepsies are a group of diseases rather than a single disorder the prospect of targeted treatment in some may become a reality.

19 Review Ketogenic dietary therapies in adults with epilepsy: a practical guide. 2016

Schoeler, Natasha E / Cross, J Helen. ·Clinical Neurosciences Section, Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK. · Clinical Neurosciences Section, Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK Young Epilepsy, Lingfield, UK. ·Pract Neurol · Pubmed #26908897.

ABSTRACT: Ketogenic dietary therapies are an effective treatment option for children with drug-resistant epilepsy. There is an increasing worldwide interest in using these diets to manage adult epilepsy; uncontrolled studies show similar response rates to those in children. Despite this, there are only a few centres with dedicated services for adults. We clearly need controlled studies of this treatment in adults. Here, we aim to familiarise adult neurologists with the evidence base for these diets and give practical advice on starting and maintaining them in adults.

20 Review The genetic landscape of the epileptic encephalopathies of infancy and childhood. 2016

McTague, Amy / Howell, Katherine B / Cross, J Helen / Kurian, Manju A / Scheffer, Ingrid E. ·Molecular Neurosciences, Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK; Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. · Department of Neurology, Royal Children's Hospital, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Neurosciences Group, Murdoch Childrens Research Institute, Melbourne, VIC, Australia. · Clinical Neurosciences, Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK; Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. · Department of Neurology, Royal Children's Hospital, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Department of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, VIC, Australia; Florey Institute of Neurosciences and Mental Health, Melbourne, VIC, Australia. Electronic address: scheffer@unimelb.edu.au. ·Lancet Neurol · Pubmed #26597089.

ABSTRACT: Epileptic encephalopathies of infancy and childhood comprise a large, heterogeneous group of severe epilepsies characterised by several seizure types, frequent epileptiform activity on EEG, and developmental slowing or regression. The encephalopathies include many age-related electroclinical syndromes with specific seizure types and EEG features. With the molecular revolution, the number of known monogenic determinants underlying the epileptic encephalopathies has grown rapidly. De-novo dominant mutations are frequently identified; somatic mosaicism and recessive disorders are also seen. Several genes can cause one electroclinical syndrome, and, conversely, one gene might be associated with phenotypic pleiotropy. Diverse genetic causes and molecular pathways have been implicated, involving ion channels, and proteins needed for synaptic, regulatory, and developmental functions. Gene discovery provides the basis for neurobiological insights, often showing convergence of mechanistic pathways. These findings underpin the development of targeted therapies, which are essential to improve the outcome of these devastating disorders.

21 Review Diagnostic methods and treatment options for focal cortical dysplasia. 2015

Guerrini, Renzo / Duchowny, Michael / Jayakar, Prasanna / Krsek, Pavel / Kahane, Philippe / Tassi, Laura / Melani, Federico / Polster, Tilman / Andre, Véronique M / Cepeda, Carlos / Krueger, Darcy A / Cross, J Helen / Spreafico, Roberto / Cosottini, Mirco / Gotman, Jean / Chassoux, Francine / Ryvlin, Philippe / Bartolomei, Fabrice / Bernasconi, Andrea / Stefan, Hermann / Miller, Ian / Devaux, Bertrand / Najm, Imad / Giordano, Flavio / Vonck, Kristl / Barba, Carmen / Blumcke, Ingmar. ·Pediatric Neurology and Neurogenetics Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy. · IRCCS Stella Maris Foundation, Pisa, Italy. · Neuroscience Program and the Comprehensive Epilepsy Center, Miami Children's Hospital, Miami, Florida, U.S.A. · Department of Neurology, Miami Children's Hospital, Miami, Florida, U.S.A. · Department of Pediatric Neurology, 2nd Faculty of Medicine, Motol University Hospital, Charles University, Prague, Czech Republic. · INSERM U836, University of Grenoble Alpes, GIN, Grenoble, France. · Epilepsy Unit, Michallon Hospital, Grenoble, France. · Epilepsy Surgery Center, Niguarda Hospital, Milan, Italy. · Department of Child Neurology, Bethel Epilepsy Center, Bielefeld, Germany. · UCB Pharma, Neurosciences Therapeutic Area, Braine-l'Alleud, Belgium. · Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, U.S.A. · Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, U.S.A. · UCL-Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. · Young Epilepsy, Lingfield, United Kingdom. · Clinical Epileptology and Experimental Neurophysiology Unit, Neurological InstituteC. Besta", Milan, Italy. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada. · Epilepsy Unit, Sainte-Anne Hospital, Paris, France. · Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland. · Translational and Integrative Group in Epilepsy Research (TIGER) and Institute for Epilepsies (IDEE), Lyon's Neuroscience Center, INSERM U1028, CNRS 5292, UCBL, Le Vinatier Hospital, Bron, Lyon, France. · Faculty of Medicine, INSERM, U1106, Institute of Neurosciences of Systems, Marseille, France. · Faculty of Medicine, Aix Marseille University, Marseille, France. · Clinical Neurophysiology Unit, Department of Clinical Neurosciences, CHU Timone, Marseille, France. · Henri-Gastaut Hospital, Saint-Paul Center, Marseille, France. · Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada. · Epilepsy Center Erlangen (ZEE), University Erlangen-Nürnberg, Erlangen, Germany. · Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children's Hospital, Miami, Florida, U.S.A. · Neurosurgery Department, Sainte-Anne Hospital, Paris, France. · Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, U.S.A. · Pediatric Neurosurgery Unit, Children's Hospital Meyer-University of Florence, Florence, Italy. · Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent, Belgium. · Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany. ·Epilepsia · Pubmed #26434565.

ABSTRACT: Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.

22 Review Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. 2015

Wilmshurst, Jo M / Gaillard, William D / Vinayan, Kollencheri Puthenveettil / Tsuchida, Tammy N / Plouin, Perrine / Van Bogaert, Patrick / Carrizosa, Jaime / Elia, Maurizio / Craiu, Dana / Jovic, Nebojsa J / Nordli, Doug / Hirtz, Deborah / Wong, Virginia / Glauser, Tracy / Mizrahi, Eli M / Cross, J Helen. ·Paediatric Neurology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa. · Pediatrics and Neurology, Division Epilepsy and Neurophysiology, Comprehensive Pediatric Epilepsy Program, George Washington University, Washington, District of Columbia, U.S.A. · Division of Pediatric Neurology, Department of Neurology, Amrita Institute of Medical Sciences, Cochin, Kerala, India. · Department of Neurology, Children's National Medical Center, Washington, District of Columbia, U.S.A. · Clinical Neurophysiology Department, INSERM U663, Hospital for Sick Children, Paris, France. · Paediatric Neurology, Department of Pediatrics, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Pediatric Department Child Neurology Service, University of Antioquia, Medellín, Colombia. · Unit of Neurology and Clinical Neurophysiopathology, IRCCS Italy Oasi Institute for Research on Mental Retardation and Brain Aging, Troina, EN, Italy. · Department of Neurology, Pediatric Neurology, Psychiatry, Neurosurgery, "Carol Davila" University of Medicine Bucharest, Bucharest, Romania. · "Alexandru Obregia" Clinical Hospital, Bucharest, Romania. · Neurology, Clinic of Neurology and Psychiatry for Children and Youth, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. · Epilepsy Center, Children's Memorial Hospital, Chicago, Illinois, U.S.A. · Office of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, Maryland, U.S.A. · Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong. · Division of Paediatric Neurology/Developmental Behavioural Paediatrics/NeuroHabilitation, Duchess of Kent Children Hospital, Queen Mary Hospital, Hong Kong, Hong Kong. · Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A. · Peter Kellaway Section of Neurophysiology, Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A. · Section of Pediatric Neurology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, U.S.A. · Childhood Epilepsy, Paediatric Neurology, UCL-Institute of Child Health, Great Ormond Street Hospital for Children NHS Trust, NHS Foundation Trust, London, United Kingdom. ·Epilepsia · Pubmed #26122601.

ABSTRACT: Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2 years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.

23 Review Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms. 2015

Mehta, Vishal / Ferrie, Colin D / Cross, J Helen / Vadlamani, Gayatri. ·Department of Paediatrics, Hull and East Yorkshire Hospitals NHS Trust, Anlaby Road, Hull, West Yorkshire, UK, HU3 2JZ. ·Cochrane Database Syst Rev · Pubmed #26086765.

ABSTRACT: BACKGROUND: This is an updated version of the original Cochrane review published in Issue 1, 2007.Epilepsy is a disorder with recurrent epileptic seizures. Corticosteroids have been used in the treatment of children with epilepsy and have significant adverse effects. Their efficacy and tolerability have not been clearly established. OBJECTIVES: To determine the efficacy, in terms of seizure control, improvements in cognition and in quality of life and tolerability of steroids compared to placebo or other antiepileptic drugs in children with epilepsy, excluding epileptic spasms. SEARCH METHODS: We searched the following databases: The Cochrane Epilepsy Group Specialized Register (1 August 2014); CENTRAL, (The Cochrane Library Issue 7, July 2014); MEDLINE (1946 to 1 August 2014); EMBASE (1966 to December 2004); Database of Abstracts of Reviews of Effectiveness (DARE; Issue 3 of the database published in The Cochrane Library Issue 7, July 2014); ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform ICTRP (1 August 2014).We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: All randomised controlled trials of administration of corticosteroids to children (less than 16 years) with epilepsy. DATA COLLECTION AND ANALYSIS: For this update two review authors independently selected trials for inclusion and extracted data. Outcomes included cessation of seizures, reduction in seizure frequency, improvement in cognition, quality of life and adverse effects of steroids. MAIN RESULTS: A single RCT was included that recruited five children in a double blind cross-over trial. One child was withdrawn prematurely from the study and another had infantile spasms and hence was excluded from further analysis. Adrenocorticotrophin hormone (ACTH 4-9) was administered. Of the three children analysed, one showed a reduction in seizures of 25% to 50% at both the low and higher doses of corticosteroids compared to placebo; one child showed a reduction in seizures at the higher dose only and one child showed no reduction in seizures at either dose. No adverse effects were reported. AUTHORS' CONCLUSIONS: Since the last version of this review no new evidence has been found for the efficacy of corticosteroids in treating childhood epilepsies. Clinicians using steroids in childhood epilepsies, other than for epileptic spasms, should take this into account before using these agents.

24 Review Rasmussen Syndrome and Other Inflammatory Epilepsies. 2015

Varadkar, Sophia / Cross, J Helen. ·Epilepsy Unit, Great Ormond Street Hospital for Children NHS Foundation Trust and UCL Institute of Child Health, London, United Kingdom. · Department of Clinical Neurosciences, UCL-Institute of Child Health, Great Ormond Street for Children NHS Foundation Trust, London and Young Epilepsy, Lingfield, United Kingdom. ·Semin Neurol · Pubmed #26060905.

ABSTRACT: An underlying immune basis is emerging in an increasing number of epileptic and encephalopathic syndromes. The immunopathological mechanisms may be categorized into antibody-mediated, T-cell cytotoxicity, and microglia-induced degeneration. The immune basis in Rasmussen syndrome is thought to be T-cell mediated. Antibodies to extracellular and intracellular epitopes are implicated in limbic and other encephalitides, characterized by seizures, movement disorder, sleep disorder, obtundation, psychosis, mutism, and other psychiatric symptoms. Extracellular antibodies are directed at cell-surface-expressed neuronal or glial proteins: glutamate receptors (N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid), voltage-gated potassium channel complex (contactin-associated-protein 2 [CASPR2], contactin-2 and leucin-rich, glioma-inactivated 1 [LGI1]), and γ-aminobutyric acid (GABA) receptors (GABABR and GABAAR). Antibodies to intracellular antigens are less commonly seen (for example, glutamic acid decarboxylase). Diseases caused by antibodies to cell-surface-expressed antigens are better expected to respond to immune treatments than to those where the presumed mechanism is T-cell driven. Antibodies to the folate receptor FR1 are a cause of primary cerebral folate deficiency. Febrile infection-related epilepsy syndrome (FIRES) may also have an immune basis, although this is yet to be proven. For all these epilepsies, the best treatment and the long-term outcomes are not yet clear.

25 Review Epilepsy surgery in children and adults. 2014

Ryvlin, Philippe / Cross, J Helen / Rheims, Sylvain. ·Department of Functional Neurology and Epileptology, Hospices Civils de Lyon, Lyon, France; Lyon's Research Neuroscience Center, Institut National de la Santé et de la Recherche Médicale U1028, Centre National de la Recherche Scientifique 5292, Lyon, France; Department of Clinical Neurosciences, Centre Hospitalio-Universitaire Vaudois, Lausanne, Switzerland. Electronic address: philippe.ryvlin@chu-lyon.fr. · Clinical Neurosciences, UCL Institute of Child Health, Great Ormond Street Hospital for Children NHS Trust, London, UK, and Young Epilepsy, Surrey, UK; Young Epilepsy, Surrey, UK. · Department of Functional Neurology and Epileptology, Hospices Civils de Lyon, Lyon, France; Lyon's Research Neuroscience Center, Institut National de la Santé et de la Recherche Médicale U1028, Centre National de la Recherche Scientifique 5292, Lyon, France. ·Lancet Neurol · Pubmed #25316018.

ABSTRACT: Epilepsy surgery is the most effective way to control seizures in patients with drug-resistant focal epilepsy, often leading to improvements in cognition, behaviour, and quality of life. Risks of serious adverse events and deterioration of clinical status can be minimised in carefully selected patients. Accordingly, guidelines recommend earlier and more systematic assessment of patients' eligibility for surgery than is seen at present. The effectiveness of surgical treatment depends on epilepsy type, underlying pathology, and accurate localisation of the epileptogenic brain region by various clinical, neuroimaging, and neurophysiological investigations. Substantial progress has been made in the methods of presurgical assessment, particularly in patients with normal features on MRI, but evidence is scarce for the indication and effect of most presurgical investigations, with no biomarker precisely delineating the epileptogenic zone. A priority for the development of epilepsy surgery is the generation of high-level evidence to promote the harmonisation and dissemination of best practices.

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