title: Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology.
abstract: Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20-66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy.
authors: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, UCL, Queen Square, London WC1N 3BG, UK.
authors: Claudia B
authors: CB
authors: Catarino
authors: Joan Y W
authors: JY
authors: Liu
authors: Ioannis
authors: I
authors: Liagkouras
authors: Vaneesha S
authors: VS
authors: Gibbons
authors: Robyn W
authors: RW
authors: Labrum
authors: Rachael
authors: R
authors: Ellis
authors: Cathy
authors: C
authors: Woodward
authors: Mary B
authors: MB
authors: Davis
authors: Shelagh J
authors: SJ
authors: Smith
authors: J Helen
authors: JH
authors: Cross
authors: Richard E
authors: RE
authors: Appleton
authors: Simone C
authors: SC
authors: Yendle
authors: Jacinta M
authors: JM
authors: McMahon
authors: Susannah T
authors: ST
authors: Bellows
authors: Thomas S
authors: TS
authors: Jacques
authors: Sameer M
authors: SM
authors: Zuberi
authors: Matthias J
authors: MJ
authors: Koepp
authors: Lillian
authors: L
authors: Martinian
authors: Ingrid E
authors: IE
authors: Scheffer
authors: Maria
authors: M
authors: Thom
authors: Sanjay M
authors: SM
authors: Sisodiya
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D004831:Epilepsies, Myoclonic / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels