Fatal Cerebral Edema With Status Epilepticus in Children With Dravet Syndrome: Report of 5 Cases.
Dravet syndrome (DS) is a well-recognized developmental and epileptic encephalopathy associated withSCN1Amutations and 15% mortality by 20 years. Although over half of cases succumb to sudden unexpected death in epilepsy, the cause of death in the remainder is poorly defined. We describe the clinical, radiologic, and pathologic characteristics of a cohort of children with DS andSCN1Amutations who developed fatal cerebral edema causing mass effect after fever-associated status epilepticus. Cases were identified from a review of children with DS enrolled in the Epilepsy Genetics Research Program at The University of Melbourne, Austin Health, who died after fever-associated status epilepticus. Five children were identified, all of whom presented with fever-associated convulsive status epilepticus, developed severe brain swelling, and died. All had de novoSCN1Amutations. Fever of 40°C or greater was measured in all cases. Signs of brainstem dysfunction, indicating cerebral herniation, were first noted 3 to 5 days after initial presentation in 4 patients, though were apparent as early as 24 hours in 1 case. When MRI was performed early in a patient's course, focal regions of cortical diffusion restriction were noted. Later MRI studies demonstrated diffuse cytotoxic edema, with severe cerebral herniation. Postmortem studies revealed diffuse brain edema and widespread neuronal damage. Laminar necrosis was seen in 1 case. Cerebral edema leading to fatal brain herniation is an important, previously unreported sequela of status epilepticus in children with DS. This potentially remediable complication may be a significant contributor to the early mortality of DS.
Epilepsy Research Centre, Department of Medicine and.|Alberta Children's Hospital, Cumming School of Medicine, Department of Pediatrics, Section of Neurology, University of Calgary, Calgary, Alberta, Canada.
Kenneth A
KA
Myers
Epilepsy Research Centre, Department of Medicine and.
Jacinta M
JM
McMahon
Departments of Paediatrics and.|Radiology, The University of Melbourne, Parkville, Victoria, Australia.|The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
Simone A
SA
Mandelstam
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.|Department of Neurology, Royal Children's Hospital, Parkville, Victoria, Australia; and.
Mark T
MT
Mackay
Department of Pathology, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
Renate M
RM
Kalnins
Departments of Paediatrics and.|Department of Neurology, Royal Children's Hospital, Parkville, Victoria, Australia; and.|Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
Richard J
RJ
Leventer
Epilepsy Research Centre, Department of Medicine and scheffer@unimelb.edu.au.|Departments of Paediatrics and.|The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.|Department of Neurology, Royal Children's Hospital, Parkville, Victoria, Australia; and.
Ingrid E
IE
Scheffer
D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D004831:Epilepsies, Myoclonic / Q000150:complications* / Q000235:genetics / Q000401:mortality; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D013226:Status Epilepticus / Q000150:complications*
D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human