Svetlana Gataullina1,2,3,4, Eric Lemaire5,6, Fabrice Wendling7,8, Anna Kaminska1,2,3,9,10, Françoise Watrin11, Audrey Riquet12, Dorothée Ville13, Marie-Laure Moutard14, Anne de Saint Martin15,16, Silvia Napuri17, Jean-Michel Pedespan18, Monika Eisermann1,2,3,9,10, Nadia Bahi-Buisson19,20,21, Rima Nabbout1,2,3,10,19, Catherine Chiron1,2,3,10, Olivier Dulac1,2,3,10, Gilles Huberfeld1,2,3,22,23. 1. INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France. 2. Paris Descartes University, PRES Sorbonne Paris Cité, Paris, France. 3. CEA, Gif sur Yvette, France. 4. Neurology Department, Mignot Hospital, CH Versailles, Le Chesnay, France. 5. Innovations and Industrial Development, Activsoft, Antony, France. 6. Adpuerivitam, Antony, France. 7. INSERM, U1099, Rennes, France. 8. LTSI, Rennes 1 University, Rennes, France. 9. Clinical Neurophysiology, Necker-Enfants Malades Hospital, APHP, Paris, France. 10. Reference Center for Rare Epilepsies, Necker-Enfants Malades Hospital, APHP, Paris, France. 11. INSERM U901, INMED, Marseille, France. 12. Pediatric Neurology Department and Reference Center for Tuberous Sclerosis and Rare Epilepsies, University Hospital of Lille, France. 13. Pediatric Neurology Department and Center of Reference for Rare Intellectual Disorders, Tuberous Sclerosis, and Rare Epileptic Disorders, University Hospital of Lyon, Lyon, France. 14. Neuropediatric Department, Developmental Pathology, Trousseau Hospital, APHP, Paris, France. 15. Pediatric Neurology, Department of Pediatrics, University Hospital of Strasbourg, Strasbourg, France. 16. Reference Center for Rare Epilepsies, Strasbourg, France. 17. Pediatric Department, CHU Rennes, Rennes, France. 18. Neuropediatric Department, CHRU, Bordeaux, France. 19. Pediatric Neurology Department, Necker-Enfants Malades Hospital, APHP, Paris, France. 20. INSERM UMR1163, Embryology and Genetics of Congenital Malformations, Paris, France. 21. Paris Descartes University, Paris, France. 22. Sorbonne University, UPMC University Paris 06, Paris, France. 23. Neurophysiology Department, UPMC, CHU Pitié-Salpêtrière, APHP, Paris, France.
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. SIGNIFICANCE: 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. Wiley Periodicals, Inc.
OBJECTIVE: To describe the epileptic phenotype of Tsc1(+/-) mice pups in comparison with age-related seizures in humantuberous 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. SIGNIFICANCE: Tsc1(+/-) mice pups exhibit an age-dependent seizure pattern sequence mimicking early humanTSCepilepsy features. Spike clusters before seizure onset in TSC should be considered as a first stage of epilepsy reinforcing the concept of preventive antiepileptic therapy. Wiley Periodicals, Inc.
Authors: Nicholas Rensing; Kevin J Johnson; Thomas J Foutz; Joseph L Friedman; Rafael Galindo; Michael Wong Journal: Epilepsia Date: 2020-04-10 Impact factor: 6.740