PMID- 36750385
OWN - NLM
STAT- MEDLINE
DCOM- 20230419
LR  - 20240419
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 100
IP  - 16
DP  - 2023 Apr 18
TI  - Rates of Status Epilepticus and Sudden Unexplained Death in Epilepsy in People 
      With Genetic Developmental and Epileptic Encephalopathies.
PG  - e1712-e1722
LID - 10.1212/WNL.0000000000207080 [doi]
AB  - BACKGROUND AND OBJECTIVES: The genetic developmental and epileptic 
      encephalopathies (DEEs) comprise a large group of severe epilepsy syndromes, with 
      a wide phenotypic spectrum. Currently, the rates of convulsive status epilepticus 
      (CSE), nonconvulsive status epilepticus (NCSE), and sudden unexplained death in 
      epilepsy (SUDEP) in these diseases are not well understood. We aimed to describe 
      the proportions of patients with frequently observed genetic DEEs who developed 
      CSE, NCSE, mortality, and SUDEP. Understanding the risks of these serious 
      presentations in each genetic DEE will enable earlier diagnosis and appropriate 
      management. METHODS: In this retrospective analysis of patients with a genetic 
      DEE, we estimated the proportions with CSE, NCSE, and SUDEP and the overall and 
      SUDEP-specific mortality rates for each genetic diagnosis. We included patients 
      with a pathogenic variant in the genes SCN1A, SCN2A, SCN8A, SYNGAP1, NEXMIF, 
      CHD2, PCDH19, STXBP1, GRIN2A, KCNT1, and KCNQ2 and with Angelman syndrome (AS). 
      RESULTS: The cohort comprised 510 individuals with a genetic DEE, in whom we 
      observed CSE in 47% and NCSE in 19%. The highest proportion of CSE occurred in 
      patients with SCN1A-associated DEEs, including 181/203 (89%; 95% CI 84-93) 
      patients with Dravet syndrome and 8/15 (53%; 95% CI 27-79) non-Dravet SCN1A-DEEs. 
      CSE was also notable in patients with pathogenic variants in KCNT1 (6/10; 60%; 
      95% CI 26-88) and SCN2A (8/15; 53%; 95% CI 27-79). NCSE was common in patients 
      with non-Dravet SCN1A-DEEs (8/15; 53%; 95% CI 27-79) and was notable in patients 
      with CHD2-DEEs (6/14; 43%; 95% CI 18-71) and AS (6/19; 32%; 95% CI 13-57). There 
      were 42/510 (8%) deaths among the cohort, producing a mortality rate of 6.1 per 
      1,000 person-years (95% CI 4.4-8.3). Cases of SUDEP accounted for 19/42 (48%) 
      deaths. Four genes were associated with SUDEP: SCN1A, SCN2A, SCN8A, and STXBP1. 
      The estimated SUDEP rate was 2.8 per 1,000 person-years (95% CI 1.6-4.3). 
      DISCUSSION: We showed that proportions of patients with CSE, NCSE, and SUDEP 
      differ for commonly encountered genetic DEEs. The estimates for each genetic DEE 
      studied will inform early diagnosis and management of status epilepticus and 
      SUDEP and inform disease-specific counseling for patients and families in this 
      high-risk group of conditions.
CI  - (c) 2023 American Academy of Neurology.
FAU - Donnan, Alice M
AU  - Donnan AM
AUID- ORCID: 0000-0003-1745-7982
AD  - From the Epilepsy Research Centre (A.M.D., A.L.S., S.R.-H., I.E.S.), Department 
      of Medicine, The University of Melbourne, Austin Health; Melbourne Medical School 
      (L.C.), Faculty of Medicine, Dentistry and Health Sciences, The University of 
      Melbourne, Parkville; The Florey Institute of Neurosciences and Mental Health 
      (L.C., I.E.S.), Melbourne; and Department of Paediatrics (I.E.S.), The University 
      of Melbourne, Royal Children's Hospital, and Murdoch Children's Research 
      Institute, Victoria, Australia.
FAU - Schneider, Amy L
AU  - Schneider AL
AD  - From the Epilepsy Research Centre (A.M.D., A.L.S., S.R.-H., I.E.S.), Department 
      of Medicine, The University of Melbourne, Austin Health; Melbourne Medical School 
      (L.C.), Faculty of Medicine, Dentistry and Health Sciences, The University of 
      Melbourne, Parkville; The Florey Institute of Neurosciences and Mental Health 
      (L.C., I.E.S.), Melbourne; and Department of Paediatrics (I.E.S.), The University 
      of Melbourne, Royal Children's Hospital, and Murdoch Children's Research 
      Institute, Victoria, Australia.
FAU - Russ-Hall, Sophie
AU  - Russ-Hall S
AD  - From the Epilepsy Research Centre (A.M.D., A.L.S., S.R.-H., I.E.S.), Department 
      of Medicine, The University of Melbourne, Austin Health; Melbourne Medical School 
      (L.C.), Faculty of Medicine, Dentistry and Health Sciences, The University of 
      Melbourne, Parkville; The Florey Institute of Neurosciences and Mental Health 
      (L.C., I.E.S.), Melbourne; and Department of Paediatrics (I.E.S.), The University 
      of Melbourne, Royal Children's Hospital, and Murdoch Children's Research 
      Institute, Victoria, Australia.
FAU - Churilov, Leonid
AU  - Churilov L
AD  - From the Epilepsy Research Centre (A.M.D., A.L.S., S.R.-H., I.E.S.), Department 
      of Medicine, The University of Melbourne, Austin Health; Melbourne Medical School 
      (L.C.), Faculty of Medicine, Dentistry and Health Sciences, The University of 
      Melbourne, Parkville; The Florey Institute of Neurosciences and Mental Health 
      (L.C., I.E.S.), Melbourne; and Department of Paediatrics (I.E.S.), The University 
      of Melbourne, Royal Children's Hospital, and Murdoch Children's Research 
      Institute, Victoria, Australia.
FAU - Scheffer, Ingrid E
AU  - Scheffer IE
AUID- ORCID: 0000-0002-2311-2174
AD  - From the Epilepsy Research Centre (A.M.D., A.L.S., S.R.-H., I.E.S.), Department 
      of Medicine, The University of Melbourne, Austin Health; Melbourne Medical School 
      (L.C.), Faculty of Medicine, Dentistry and Health Sciences, The University of 
      Melbourne, Parkville; The Florey Institute of Neurosciences and Mental Health 
      (L.C., I.E.S.), Melbourne; and Department of Paediatrics (I.E.S.), The University 
      of Melbourne, Royal Children's Hospital, and Murdoch Children's Research 
      Institute, Victoria, Australia. i.scheffer@unimelb.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230207
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (PCDH19 protein, human)
RN  - 0 (Protocadherins)
RN  - 0 (KCNT1 protein, human)
RN  - 0 (Potassium Channels, Sodium-Activated)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
CIN - Epilepsy Curr. 2023 Nov 30;23(6):354-356. PMID: 38269346
MH  - Humans
MH  - Retrospective Studies
MH  - *Sudden Unexpected Death in Epilepsy/epidemiology
MH  - *Status Epilepticus/epidemiology/genetics/diagnosis
MH  - *Epilepsies, Myoclonic/genetics
MH  - *Epileptic Syndromes/genetics
MH  - *Angelman Syndrome
MH  - Death, Sudden/epidemiology
MH  - Protocadherins
MH  - Potassium Channels, Sodium-Activated
MH  - Nerve Tissue Proteins
PMC - PMC10115508
COIS- I.E. Scheffer has served on scientific advisory boards for BioMarin, Chiesi, 
      Eisai, Encoded Therapeutics, GlaxoSmithKline, Knopp Biosciences, Nutricia, 
      Rogcon, Takeda Pharmaceuticals, UCB, and Xenon Pharmaceuticals; has received 
      speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, Chiesi, Liva 
      Nova, Nutricia, Zuellig Pharma, and Eisai; has received funding for travel from 
      UCB, Biocodex, GlaxoSmithKline, Biomarin, and Eisai; has served as an 
      investigator for Anavex Life Sciences, Cerecin Inc, Cerevel Therapeutics, Eisai, 
      Encoded Therapeutics, EpiMinder Inc, Epygenyx, ES-Therapeutics, GW Pharma, 
      Marinus, Neurocrine BioSciences, Ovid Therapeutics, Takeda Pharmaceuticals, UCB, 
      Ultragenyx, Xenon Pharmaceuticals, Zogenix, and Zynerba; has consulted for Care 
      Beyond Diagnosis, Epilepsy Consortium, Atheneum Partners, Ovid Therapeutics, UCB, 
      Zynerba Pharmaceuticals, BioMarin, Encoded Therapeutics, and Biohaven 
      Pharmaceuticals; and is a Nonexecutive Director of Bellberry Ltd and a Director 
      of the Australian Academy of Health and Medical Sciences and the Australian 
      Council of Learned Academies Limited. She may accrue future revenue on pending 
      patent WO61/010176 (filed: 2008): Therapeutic Compound; has a patent for SCN1A 
      testing held by Bionomics Inc and licensed to various diagnostic companies; and 
      has a patent molecular diagnostic/theranostic target for benign familial 
      infantile epilepsy (BFIE) (PRRT2) 2011904493 & 2012900190 and PCT/AU2012/001321 
      (TECH ID:2012-009). The remaining authors do not have any disclosures. Go to 
      Neurology.org/N for full disclosures.
EDAT- 2023/02/08 06:00
MHDA- 2023/04/19 06:41
PMCR- 2024/04/18
CRDT- 2023/02/07 21:42
PHST- 2022/08/06 00:00 [received]
PHST- 2023/01/05 00:00 [accepted]
PHST- 2023/04/19 06:41 [medline]
PHST- 2023/02/08 06:00 [pubmed]
PHST- 2023/02/07 21:42 [entrez]
PHST- 2024/04/18 00:00 [pmc-release]
AID - WNL.0000000000207080 [pii]
AID - WNL-2023-000015 [pii]
AID - 10.1212/WNL.0000000000207080 [doi]
PST - ppublish
SO  - Neurology. 2023 Apr 18;100(16):e1712-e1722. doi: 10.1212/WNL.0000000000207080. 
      Epub 2023 Feb 7.