Georgia Ramantani1, Louis G Maillard2, Thomas Bast3, Ralf A Husain4, Pascal Niggemann5, Jürgen Kohlhase6, Christoph Hertzberg7, Kristina Ungerath8, Micheil A Innes9, Hartmut Walkenhorst10, Andrea Bevot11, Celina von Stülpnagel12, Kara Thomas13, Frank Niemann14, Mehmet Ali Ergun15, Uta Tacke16, Martin Häusler17, Chrysanthy Ikonomidou18, Rudolf Korinthenberg16, Min Ae Lee-Kirsch19. 1. Epilepsy Center, University Hospital Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany. Electronic address: georgia.ramantani@uniklinik-freiburg.de. 2. Department of Neurology, University Hospital Nancy, Lorraine University, Nancy, France. 3. Epilepsy Center Kork, Kehl-Kork, Germany. 4. Department of Neuropediatrics, University Children's Hospital, Jena, Germany. 5. Department of Radiology, University of Bonn, Bonn, Germany. 6. Center of Human Genetics Freiburg, Freiburg, Germany. 7. Diagnose und Behandlungszentrum für Kinder und Jugendliche, Vivantes Klinikum Neukölln, Berlin, Germany. 8. Altonaer Kinderkrankenhaus, Hamburg, Germany. 9. Department of Medical Genetics, Alberta Health Services, University of Calgary, Calgary, Alberta, Canada. 10. Evangelisches Krankenhaus Bethanien, Iserlohn, Germany. 11. Universitätsklinik für Kinder- und Jugendmedizin, Tübingen, Germany. 12. Schön Klinik Vogtareuth, Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany. 13. Children's Hospital of The King's Daughters and Eastern Virginia Medical School, Norfolk, VA, USA. 14. Kinder- und Jugendklinik Gelsenkirchen, Gelsenkirchen, Germany. 15. Gazi University, Faculty of Medicine, Department of Medical Genetics, Besevler-Ankara, Turkey. 16. Division of Neuropediatrics and Muscular Disorders, Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany. 17. Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Aachen, Aachen, Germany. 18. University of Wisconsin, Neurology, Waisman Center, Madison, WI, USA. 19. Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, Dresden, Germany.
Abstract
BACKGROUND: Aicardi-Goutières syndrome (AGS) is a genetically determined early-onset encephalopathy with variable phenotype, including neurologic manifestations such as dystonia, spasticity, epileptic seizures, progressive microcephaly, and severe developmental delay. The aim of our study was the characterization of epilepsy, one of the most frequent and severe AGS manifestations, in molecularly confirmed patients. METHODS: We reviewed the medical records, EEG, and CT/MRI findings in 16 patients aged 1-22 years that carried AGS1-5 mutations. RESULTS: Epilepsy manifested in 12 (75%) patients and took a refractory course in 9 (56%). 4 (25%) patients presented with seizures in the first four weeks and 11 (69%) altogether in the first year of life. Spasms were reported in 3 (19%) patients, focal seizures in 4 (25%), myoclonic in 5 (31%), symmetric or asymmetric tonic in 11 (69%), generalized tonic-clonic in 3 (19%) and status epilepticus in 4 (25%). EEG recordings initially showed a slow and disorganized background, followed by a regional intermittent theta/delta slow, while obvious multifocal or generalized epileptic discharges were only observed at follow-up. None of these EEG features were specific of AGS. There was no discernible correlation between the genotype and epilepsy onset, seizure types and epilepsy evolution. Epilepsy severity did not correspond to neuroimaging pathology. DISCUSSION: Epilepsy constitutes a cardinal feature of AGS, characterized by early onset, predominantly tonic semiology and a refractory course. The early discrimination of epileptic seizures from paroxysmal dystonia poses a challenge for neuropaediatricians, considering the initially inconspicuous or non-specific EEG findings. This study underlines the necessity of a more systematic serial evaluation of AGS patients using long-term video-EEG recordings.
BACKGROUND: Aicardi-Goutières syndrome (AGS) is a genetically determined early-onset encephalopathy with variable phenotype, including neurologic manifestations such as dystonia, spasticity, epilepticseizures, progressive microcephaly, and severe developmental delay. The aim of our study was the characterization of epilepsy, one of the most frequent and severe AGS manifestations, in molecularly confirmed patients. METHODS: We reviewed the medical records, EEG, and CT/MRI findings in 16 patients aged 1-22 years that carried AGS1-5 mutations. RESULTS:Epilepsy manifested in 12 (75%) patients and took a refractory course in 9 (56%). 4 (25%) patients presented with seizures in the first four weeks and 11 (69%) altogether in the first year of life. Spasms were reported in 3 (19%) patients, focal seizures in 4 (25%), myoclonic in 5 (31%), symmetric or asymmetric tonic in 11 (69%), generalized tonic-clonic in 3 (19%) and status epilepticus in 4 (25%). EEG recordings initially showed a slow and disorganized background, followed by a regional intermittent theta/delta slow, while obvious multifocal or generalized epileptic discharges were only observed at follow-up. None of these EEG features were specific of AGS. There was no discernible correlation between the genotype and epilepsy onset, seizure types and epilepsy evolution. Epilepsy severity did not correspond to neuroimaging pathology. DISCUSSION: Epilepsy constitutes a cardinal feature of AGS, characterized by early onset, predominantly tonic semiology and a refractory course. The early discrimination of epilepticseizures from paroxysmal dystonia poses a challenge for neuropaediatricians, considering the initially inconspicuous or non-specific EEG findings. This study underlines the necessity of a more systematic serial evaluation of AGSpatients using long-term video-EEG recordings.
Authors: Kader Cetin Gedik; Lovro Lamot; Micol Romano; Erkan Demirkaya; David Piskin; Sofia Torreggiani; Laura A Adang; Thais Armangue; Kathe Barchus; Devon R Cordova; Yanick J Crow; Russell C Dale; Karen L Durrant; Despina Eleftheriou; Elisa M Fazzi; Marco Gattorno; Francesco Gavazzi; Eric P Hanson; Min Ae Lee-Kirsch; Gina A Montealegre Sanchez; Bénédicte Neven; Simona Orcesi; Seza Ozen; M Cecilia Poli; Elliot Schumacher; Davide Tonduti; Katsiaryna Uss; Daniel Aletaha; Brian M Feldman; Adeline Vanderver; Paul A Brogan; Raphaela Goldbach-Mansky Journal: Ann Rheum Dis Date: 2022-01-27 Impact factor: 27.973
Authors: Luis Rafael Moscote-Salazar; Willem Guillermo Calderon-Miranda; Ray Vicente Deluquez Baute; Amit Agrawal; Guru Dutta Satyarthee; Johana Maraby-Salgado; Huber Said Padilla-Zambrano; Daniela Lopez-Cepeda; Alfonso Pacheco-Hernandez; Andrei F Joaquim Journal: J Pediatr Neurosci Date: 2018 Jan-Mar