Elena Gardella1, Carla Marini2, Marina Trivisano2, Mark P Fitzgerald2, Michael Alber2, Katherine B Howell2, Francesca Darra2, Sabrina Siliquini2, Bigna K Bölsterli2, Silva Masnada2, Anna Pichiecchio2, Katrine M Johannesen2, Birgit Jepsen2, Elena Fontana2, Gaia Anibaldi2, Silvia Russo2, Francesca Cogliati2, Martino Montomoli2, Nicola Specchio2, Guido Rubboli2, Pierangelo Veggiotti2, Sandor Beniczky2, Markus Wolff2, Ingo Helbig2, Federico Vigevano2, Ingrid E Scheffer2, Renzo Guerrini2, Rikke S Møller2. 1. From the Department of Clinical Neurophysiology (E.G., S.B.), Danish Epilepsy Centre, Dianalund; Institute for Regional Health Services (E.G., K.M.J., R.S.M.), University of Southern Denmark, Odense, Denmark; Neuroscience Department (C.M., R.G., M.M.), Children's Hospital A. Meyer, University of Florence; Department of Neuroscience (M.T., N.S., F.V.), Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Division of Neurology (M.P.F., I.H.), The Children's Hospital of Philadelphia; Departments of Pediatrics and Neurology (M.P.F., I.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Universitätskinderklinik Tübingen (M.A., M.W.), Germany; Department of Neurology (K.H.), Royal Children's Hospital Melbourne; Department of Paediatrics (K.H.), University of Melbourne; Australia Neurosciences Group (K.H.), Murdoch Children's Research Institute, Melbourne, Australia; Servizio di Neuropsichiatria Infantile (F.D., E.F.), Policlinico G.B. Rossi, Universita Degli Studi di Verona; Department of Child Neurology (S.S., G.A.), Ospedale Pediatrico G. Salesi-Ospedali Riuniti, Ancona, Italy; Division of Clinical Neurophysiology (B.B.), Children's Research Center, University Children's Hospital Zurich, Switzerland; Brain and Behaviour Department (S.M.), University of Pavia; Department of Pediatric Neuroradiology (A.P.), IRCCS "C. Mondino" National Neurological Institute, Pavia, Italy; Department of Epilepsy Genetics (K.J., R.S.M.), Danish Epilepsy Centre Dianalund; Department of Child Neurology (B.J.), Danish Epilepsy Centre, Dianalund, Denmark; Cytogenetic and Molecular Genetic Laboratory (S.R., F.C.), Istituto Auxologico Italiano, IRCCS, Milano, Italy; Department of Adult Neurology (G.R.), Danish Epilepsy Centre, Dianalund; University of Copenhagen (G.R.), Denmark; Struttura Complessa di Neurologia Pediatrica Ospedale Vittore Buzzi (P.V.), Milano; Dipartimento di Scienze Biomediche e Cliniche L. Sacco (P.V.), Università di Milano, Italy; Århus University (S.B.), Denmark; Department of Child Neurology (I.E.S.), University of Melbourne, Austin Health, Florey Institute; and Department of Child Neurology (I.E.S.), The Royal Children's Hospital, Melbourne, Australia. elga@filadelfia.dk. 2. From the Department of Clinical Neurophysiology (E.G., S.B.), Danish Epilepsy Centre, Dianalund; Institute for Regional Health Services (E.G., K.M.J., R.S.M.), University of Southern Denmark, Odense, Denmark; Neuroscience Department (C.M., R.G., M.M.), Children's Hospital A. Meyer, University of Florence; Department of Neuroscience (M.T., N.S., F.V.), Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Division of Neurology (M.P.F., I.H.), The Children's Hospital of Philadelphia; Departments of Pediatrics and Neurology (M.P.F., I.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Universitätskinderklinik Tübingen (M.A., M.W.), Germany; Department of Neurology (K.H.), Royal Children's Hospital Melbourne; Department of Paediatrics (K.H.), University of Melbourne; Australia Neurosciences Group (K.H.), Murdoch Children's Research Institute, Melbourne, Australia; Servizio di Neuropsichiatria Infantile (F.D., E.F.), Policlinico G.B. Rossi, Universita Degli Studi di Verona; Department of Child Neurology (S.S., G.A.), Ospedale Pediatrico G. Salesi-Ospedali Riuniti, Ancona, Italy; Division of Clinical Neurophysiology (B.B.), Children's Research Center, University Children's Hospital Zurich, Switzerland; Brain and Behaviour Department (S.M.), University of Pavia; Department of Pediatric Neuroradiology (A.P.), IRCCS "C. Mondino" National Neurological Institute, Pavia, Italy; Department of Epilepsy Genetics (K.J., R.S.M.), Danish Epilepsy Centre Dianalund; Department of Child Neurology (B.J.), Danish Epilepsy Centre, Dianalund, Denmark; Cytogenetic and Molecular Genetic Laboratory (S.R., F.C.), Istituto Auxologico Italiano, IRCCS, Milano, Italy; Department of Adult Neurology (G.R.), Danish Epilepsy Centre, Dianalund; University of Copenhagen (G.R.), Denmark; Struttura Complessa di Neurologia Pediatrica Ospedale Vittore Buzzi (P.V.), Milano; Dipartimento di Scienze Biomediche e Cliniche L. Sacco (P.V.), Università di Milano, Italy; Århus University (S.B.), Denmark; Department of Child Neurology (I.E.S.), University of Melbourne, Austin Health, Florey Institute; and Department of Child Neurology (I.E.S.), The Royal Children's Hospital, Melbourne, Australia.
Abstract
OBJECTIVE: To delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558). METHODS: Twenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment. RESULTS: Sixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at a median age of 4 months, followed by developmental slowing, pyramidal/extrapyramidal signs (22/22), movement disorders (12/22), cortical blindness (17/22), sialorrhea, and severe gastrointestinal symptoms (15/22), worsening during early childhood and plateauing at age 5 to 9 years. Death occurred in 4 children, following extreme neurologic deterioration, at 22 months to 5.5 years. Nonconvulsive status epilepticus recurred in 14 of 22 patients. The most effective antiepileptic drugs were oxcarbazepine, carbamazepine, phenytoin, and benzodiazepines. EEG showed background deterioration, epileptiform abnormalities with a temporo-occipital predominance, and posterior delta/beta activity correlating with visual impairment. Video-EEG documented focal seizures (FS) (22/22), spasm-like episodes (8/22), cortical myoclonus (8/22), and myoclonic absences (1/22). FS typically clustered and were prolonged (<20 minutes) with (1) cyanosis, hypomotor, and vegetative semiology, sometimes unnoticed, followed by (2) tonic-vibratory and (3) (hemi)-clonic manifestations ± evolution to a bilateral tonic-clonic seizure. FS had posterior-temporal/occipital onset, slowly spreading and sometimes migrating between hemispheres. Brain MRI showed progressive parenchymal atrophy and restriction of the optic radiations. CONCLUSIONS: SCN8A developmental and epileptic encephalopathy has strikingly consistent electroclinical features, suggesting a global progressive brain dysfunction primarily affecting the temporo-occipital regions. Both uncontrolled epilepsy and developmental compromise contribute to the profound impairment (increasing risk of death) during early childhood, but stabilization occurs in late childhood.
OBJECTIVE: To delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558). METHODS: Twenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment. RESULTS: Sixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at a median age of 4 months, followed by developmental slowing, pyramidal/extrapyramidal signs (22/22), movement disorders (12/22), cortical blindness (17/22), sialorrhea, and severe gastrointestinal symptoms (15/22), worsening during early childhood and plateauing at age 5 to 9 years. Death occurred in 4 children, following extreme neurologic deterioration, at 22 months to 5.5 years. Nonconvulsive status epilepticus recurred in 14 of 22 patients. The most effective antiepileptic drugs were oxcarbazepine, carbamazepine, phenytoin, and benzodiazepines. EEG showed background deterioration, epileptiform abnormalities with a temporo-occipital predominance, and posterior delta/beta activity correlating with visual impairment. Video-EEG documented focal seizures (FS) (22/22), spasm-like episodes (8/22), cortical myoclonus (8/22), and myoclonic absences (1/22). FS typically clustered and were prolonged (<20 minutes) with (1) cyanosis, hypomotor, and vegetative semiology, sometimes unnoticed, followed by (2) tonic-vibratory and (3) (hemi)-clonic manifestations ± evolution to a bilateral tonic-clonic seizure. FS had posterior-temporal/occipital onset, slowly spreading and sometimes migrating between hemispheres. Brain MRI showed progressive parenchymal atrophy and restriction of the optic radiations. CONCLUSIONS:SCN8A developmental and epileptic encephalopathy has strikingly consistent electroclinical features, suggesting a global progressive brain dysfunction primarily affecting the temporo-occipital regions. Both uncontrolled epilepsy and developmental compromise contribute to the profound impairment (increasing risk of death) during early childhood, but stabilization occurs in late childhood.
Authors: Marina Trivisano; Alessandro Ferretti; Elizabeth Bebin; Linda Huh; Gaetan Lesca; Aleksandra Siekierska; Ryo Takeguchi; Maryline Carneiro; Luca De Palma; Ilaria Guella; Kazuhiro Haginoya; Ruo Ming Shi; Atsuo Kikuchi; Tomoko Kobayashi; Julien Jung; Lieven Lagae; Mathieu Milh; Marie L Mathieu; Berge A Minassian; Antonio Novelli; Nicola Pietrafusa; Eri Takeshita; Marco Tartaglia; Alessandra Terracciano; Michelle L Thompson; Gregory M Cooper; Federico Vigevano; Laurent Villard; Nathalie Villeneuve; Gunnar M Buyse; Michelle Demos; Ingrid E Scheffer; Nicola Specchio Journal: Epilepsia Date: 2020-07-09 Impact factor: 5.864
Authors: Rosie K A Bunton-Stasyshyn; Jacy L Wagnon; Eric R Wengert; Bryan S Barker; Alexa Faulkner; Pravin K Wagley; Kritika Bhatia; Julie M Jones; Marissa R Maniaci; Jack M Parent; Howard P Goodkin; Manoj K Patel; Miriam H Meisler Journal: Brain Date: 2019-02-01 Impact factor: 13.501
Authors: Katherine L Helbig; Robert J Lauerer; Jacqueline C Bahr; Ivana A Souza; Candace T Myers; Betül Uysal; Niklas Schwarz; Maria A Gandini; Sun Huang; Boris Keren; Cyril Mignot; Alexandra Afenjar; Thierry Billette de Villemeur; Delphine Héron; Caroline Nava; Stéphanie Valence; Julien Buratti; Christina R Fagerberg; Kristina P Soerensen; Maria Kibaek; Erik-Jan Kamsteeg; David A Koolen; Boudewijn Gunning; H Jurgen Schelhaas; Michael C Kruer; Jordana Fox; Somayeh Bakhtiari; Randa Jarrar; Sergio Padilla-Lopez; Kristin Lindstrom; Sheng Chih Jin; Xue Zeng; Kaya Bilguvar; Antigone Papavasileiou; Qinghe Xing; Changlian Zhu; Katja Boysen; Filippo Vairo; Brendan C Lanpher; Eric W Klee; Jan-Mendelt Tillema; Eric T Payne; Margot A Cousin; Teresa M Kruisselbrink; Myra J Wick; Joshua Baker; Eric Haan; Nicholas Smith; Azita Sadeghpour; Erica E Davis; Nicholas Katsanis; Mark A Corbett; Alastair H MacLennan; Jozef Gecz; Saskia Biskup; Eva Goldmann; Lance H Rodan; Elizabeth Kichula; Eric Segal; Kelly E Jackson; Alexander Asamoah; David Dimmock; Julie McCarrier; Lorenzo D Botto; Francis Filloux; Tatiana Tvrdik; Gregory D Cascino; Sherry Klingerman; Catherine Neumann; Raymond Wang; Jessie C Jacobsen; Melinda A Nolan; Russell G Snell; Klaus Lehnert; Lynette G Sadleir; Britt-Marie Anderlid; Malin Kvarnung; Renzo Guerrini; Michael J Friez; Michael J Lyons; Jennifer Leonhard; Gabriel Kringlen; Kari Casas; Christelle M El Achkar; Lacey A Smith; Alexander Rotenberg; Annapurna Poduri; Alba Sanchis-Juan; Keren J Carss; Julia Rankin; Adam Zeman; F Lucy Raymond; Moira Blyth; Bronwyn Kerr; Karla Ruiz; Jill Urquhart; Imelda Hughes; Siddharth Banka; Ulrike B S Hedrich; Ingrid E Scheffer; Ingo Helbig; Gerald W Zamponi; Holger Lerche; Heather C Mefford Journal: Am J Hum Genet Date: 2018-10-18 Impact factor: 11.025
Authors: Eric R Wengert; Cathrine E Tronhjem; Jacy L Wagnon; Katrine M Johannesen; Hayley Petit; Ilona Krey; Anusha U Saga; Payal S Panchal; Samantha M Strohm; Jörn Lange; Susanne B Kamphausen; Guido Rubboli; Johannes R Lemke; Elena Gardella; Manoj K Patel; Miriam H Meisler; Rikke S Møller Journal: Epilepsia Date: 2019-10-17 Impact factor: 5.864