title: Epilepsy in young Tsc1(+/-) mice exhibits age-dependent expression that mimics that of human tuberous sclerosis complex.
abstract: OBJECTIVE
  To describe the epileptic phenotype of Tsc1(+/-) mice pups in comparison with age-related seizures in human tuberous sclerosis complex (TSC).
  
  
  METHODS
  Tsc1(+/-) and control mice underwent intracranial electroencephalography (EEG) recording at postnatal ages (P)8 to P33, with linear silicon probe implanted in the somatosensory cortex of one or both hemispheres for 8-24 h. Ictal events were classified visually by independent analyzers; distinct EEG patterns were related to age and analyzed to quantify field potential characteristics and signal dynamics between hemispheres. We collected retrospectively 20 infants with prenatally diagnosed TSC and EEG before seizure onset, and analyzed the electroclinical course of epilepsy, taking into account a first-line treatment by vigabatrin.
  
  
  RESULTS
  Spontaneous seizures were disclosed in 55% of Tsc1(+/-) mice at P9-18. Three ictal patterns were identified: from P9 to P12 "spike clusters" consisted of recurring large spikes without clinical correlate; "spasm-like" discharges dominated from P13 to P16 consisting of high amplitude large field potential superimposed with or followed by fast activity repeated every 2-10 s for at least 20 s, accompanied by rhythmic limb contractions; from P14 to P18 a "tonic-clonic like" pattern comprised rhythmic spikes of increasing amplitude with tonic-clonic movements. Early onset "spike clusters" were mainly unilateral, whereas "spasm-like" and "tonic-clonic like" patterns were bilateral. Interhemispheric propagation was significantly faster for "tonic-clonic like" than for "spasm-like" events. In infants diagnosed prenatally with TSC, clusters of sharp waves or spikes preceded the first seizure, and vigabatrin prevented the development of seizures. Patients treated after seizure onset developed spasms or focal seizures that were pharmacoresistant in 66.7% of cases.
  
  
  CONCLUSIONS
  Tsc1(+/-) mice pups exhibit an age-dependent seizure pattern sequence mimicking early human TSC epilepsy features. Spike clusters before seizure onset in TSC should be considered as a first stage of epilepsy reinforcing the concept of preventive antiepileptic therapy.
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Neurology Department, Mignot Hospital, CH Versailles, Le Chesnay, France.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gataullina
authors.affiliation: Innovations and Industrial Development, Activsoft, Antony, France.|Adpuerivitam, Antony, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lemaire
authors.affiliation: INSERM, U1099, Rennes, France.|LTSI, Rennes 1 University, Rennes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Wendling
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Clinical Neurophysiology, Necker-Enfants Malades Hospital, APHP, Paris, France.|Reference Center for Rare Epilepsies, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Kaminska
authors.affiliation: INSERM U901, INMED, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Watrin
authors.affiliation: Pediatric Neurology Department and Reference Center for Tuberous Sclerosis and Rare Epilepsies, University Hospital of Lille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Riquet
authors.affiliation: Pediatric Neurology Department and Center of Reference for Rare Intellectual Disorders, Tuberous Sclerosis, and Rare Epileptic Disorders, University Hospital of Lyon, Lyon, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Ville
authors.affiliation: Neuropediatric Department, Developmental Pathology, Trousseau Hospital, APHP, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Moutard
authors.affiliation: Pediatric Neurology, Department of Pediatrics, University Hospital of Strasbourg, Strasbourg, France.|Reference Center for Rare Epilepsies, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: de Saint Martin
authors.affiliation: Pediatric Department, CHU Rennes, Rennes, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Napuri
authors.affiliation: Neuropediatric Department, CHRU, Bordeaux, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pedespan
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Clinical Neurophysiology, Necker-Enfants Malades Hospital, APHP, Paris, France.|Reference Center for Rare Epilepsies, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Monika
authors.initials: M
authors.lastname: Eisermann
authors.affiliation: Pediatric Neurology Department, Necker-Enfants Malades Hospital, APHP, Paris, France.|INSERM UMR1163, Embryology and Genetics of Congenital Malformations, Paris, France.|Paris Descartes University, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Reference Center for Rare Epilepsies, Necker-Enfants Malades Hospital, APHP, Paris, France.|Pediatric Neurology Department, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Reference Center for Rare Epilepsies, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chiron
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Reference Center for Rare Epilepsies, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France.|Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France.|CEA, Gif sur Yvette, France.|Sorbonne University, UPMC University Paris 06, Paris, France.|Neurophysiology Department, UPMC, CHU Pitié-Salpêtrière, APHP, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Huberfeld
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012189:Retrospective Studies; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C000624650:TSC1 protein, human; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins
keywords: Electroencephalogram; Epileptic spasms; Infants; Seizures; Spikes