title: Impaired intracortical inhibition demonstrated in vivo in people with Dravet syndrome.
abstract: OBJECTIVE
  Dravet syndrome is a rare neurodevelopmental disorder characterized by seizures and other neurologic problems.SCN1Amutations account for ∼80% of cases. Animal studies have implicated mutation-related dysregulated cortical inhibitory networks in its pathophysiology. We investigated such networks in people with the condition.
  
  
  METHODS
  Transcranial magnetic stimulation using single and paired pulse paradigms was applied to people with Dravet syndrome and to 2 control groups to study motor cortex excitability.
  
  
  RESULTS
  Short interval intracortical inhibition (SICI), which measures GABAergic inhibitory network behavior, was undetectable in Dravet syndrome, but detectable in all controls. Other paradigms, including those testing excitatory networks, showed no difference between Dravet and control groups.
  
  
  CONCLUSIONS
  There were marked differences in inhibitory networks, detected using SICI paradigms, while other inhibitory and excitatory paradigms yielded normal results. These human data showing reduced GABAergic inhibition in vivo in people with Dravet syndrome support established animal models.
authors.affiliation: From the Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre (W.M.S., J.W.S., S.M.S.), and Sobell Department of Motor Neuroscience and Movement Disorders (J.C.R.), UCL Institute of Neurology; Epilepsy Society (W.M.S., J.W.S., S.M.S.), Chalfont St Peter, UK; and Stichting Epilepsie Instellingen Nederland (SEIN) (J.W.S.), Heemstede, the Netherlands.
authors.forename: William M
authors.initials: WM
authors.lastname: Stern
authors.affiliation: From the Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre (W.M.S., J.W.S., S.M.S.), and Sobell Department of Motor Neuroscience and Movement Disorders (J.C.R.), UCL Institute of Neurology; Epilepsy Society (W.M.S., J.W.S., S.M.S.), Chalfont St Peter, UK; and Stichting Epilepsie Instellingen Nederland (SEIN) (J.W.S.), Heemstede, the Netherlands.
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.affiliation: From the Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre (W.M.S., J.W.S., S.M.S.), and Sobell Department of Motor Neuroscience and Movement Disorders (J.C.R.), UCL Institute of Neurology; Epilepsy Society (W.M.S., J.W.S., S.M.S.), Chalfont St Peter, UK; and Stichting Epilepsie Instellingen Nederland (SEIN) (J.W.S.), Heemstede, the Netherlands.
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
authors.affiliation: From the Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre (W.M.S., J.W.S., S.M.S.), and Sobell Department of Motor Neuroscience and Movement Disorders (J.C.R.), UCL Institute of Neurology; Epilepsy Society (W.M.S., J.W.S., S.M.S.), Chalfont St Peter, UK; and Stichting Epilepsie Instellingen Nederland (SEIN) (J.W.S.), Heemstede, the Netherlands. s.sisodiya@ucl.ac.uk.
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004831:Epilepsies, Myoclonic / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009068:Movement / Q000502:physiology; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000503:physiopathology; D011795:Surveys and Questionnaires; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D005680:gamma-Aminobutyric Acid