title: Epilepsy in Aicardi-Goutières syndrome.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Epilepsy Center, University Hospital Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany. Electronic address: georgia.ramantani@uniklinik-freiburg.de.
authors.forename: Georgia
authors.initials: G
authors.lastname: Ramantani
authors.affiliation: Department of Neurology, University Hospital Nancy, Lorraine University, Nancy, France.
authors.forename: Louis G
authors.initials: LG
authors.lastname: Maillard
authors.affiliation: Epilepsy Center Kork, Kehl-Kork, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bast
authors.affiliation: Department of Neuropediatrics, University Children's Hospital, Jena, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Husain
authors.affiliation: Department of Radiology, University of Bonn, Bonn, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Niggemann
authors.affiliation: Center of Human Genetics Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.affiliation: Diagnose und Behandlungszentrum für Kinder und Jugendliche, Vivantes Klinikum Neukölln, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hertzberg
authors.affiliation: Altonaer Kinderkrankenhaus, Hamburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Ungerath
authors.affiliation: Department of Medical Genetics, Alberta Health Services, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Micheil A
authors.initials: MA
authors.lastname: Innes
authors.affiliation: Evangelisches Krankenhaus Bethanien, Iserlohn, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Walkenhorst
authors.affiliation: Universitätsklinik für Kinder- und Jugendmedizin, Tübingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bevot
authors.affiliation: Schön Klinik Vogtareuth, Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany.
authors.forename: Celina
authors.initials: C
authors.lastname: von Stülpnagel
authors.affiliation: Children's Hospital of The King's Daughters and Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Thomas
authors.affiliation: Kinder- und Jugendklinik Gelsenkirchen, Gelsenkirchen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Niemann
authors.affiliation: Gazi University, Faculty of Medicine, Department of Medical Genetics, Besevler-Ankara, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Ergun
authors.affiliation: Division of Neuropediatrics and Muscular Disorders, Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Tacke
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Aachen, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Häusler
authors.affiliation: University of Wisconsin, Neurology, Waisman Center, Madison, WI, USA.
authors.forename: Chrysanthy
authors.initials: C
authors.lastname: Ikonomidou
authors.affiliation: Division of Neuropediatrics and Muscular Disorders, Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Korinthenberg
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, Dresden, Germany.
authors.forename: Min Ae
authors.initials: MA
authors.lastname: Lee-Kirsch
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020274:Autoimmune Diseases of the Nervous System / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D009421:Nervous System Malformations / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
keywords: Aicardi–Goutières syndrome; Dystonia; Epilepsy; Leukoencephalopathy; Spasms; Status epilepticus