Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children

Katrina Peariso; Ravindra Arya; Tracy Glauser; Nicholas S Abend; Cristina Barcia Aguilar; Marta Amengual-Gual; Anne Anderson; Brian L Appavu; J Nicholas Brenton; Jessica Carpenter; Kevin E Chapman; Justice Clark; William D Gaillard; Marina Gaínza-Lein; Joshua Goldstein; Howard Goodkin; Zachary Grinspan; Rejean M Guerriero; Paul S Horn; Linda Huh; Robert Kahoud; Sarah A Kelley; Eric H Kossoff; Kush Kapur; Yi-Chen Lai; B Oyinkan Marquis; Tiffani McDonough; Mohamad A Mikati; Lindsey Morgan; Edward Novotny; Adam P Ostendorf; Eric T Payne; Juan Piantino; James Riviello; Tristan Sands; Carl E Stafstrom; Robert C Tasker; Dmitry Tchapyjnikov; Alejandra Vasquez; Mark S Wainwright; Angus Wilfong; Korwyn Williams; Tobias Loddenkemper; for Pediatric Status Epilepticus Research Group (pSERG)

doi:10.1212/WNL.0000000000207472

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children

Neurology. 2023 Aug 1;101(5):e546-e557. doi: 10.1212/WNL.0000000000207472. Epub 2023 Jun 9.

Authors

Katrina Peariso¹, Ravindra Arya², Tracy Glauser², Nicholas S Abend², Cristina Barcia Aguilar², Marta Amengual-Gual², Anne Anderson², Brian L Appavu², J Nicholas Brenton², Jessica Carpenter², Kevin E Chapman², Justice Clark², William D Gaillard², Marina Gaínza-Lein², Joshua Goldstein², Howard Goodkin², Zachary Grinspan², Rejean M Guerriero², Paul S Horn², Linda Huh², Robert Kahoud², Sarah A Kelley², Eric H Kossoff², Kush Kapur², Yi-Chen Lai², B Oyinkan Marquis², Tiffani McDonough², Mohamad A Mikati², Lindsey Morgan², Edward Novotny², Adam P Ostendorf², Eric T Payne², Juan Piantino², James Riviello², Tristan Sands², Carl E Stafstrom², Robert C Tasker², Dmitry Tchapyjnikov², Alejandra Vasquez², Mark S Wainwright², Angus Wilfong², Korwyn Williams², Tobias Loddenkemper²; for Pediatric Status Epilepticus Research Group (pSERG)

Collaborators

for Pediatric Status Epilepticus Research Group (pSERG):
Seema Bansal, Christa Habela, Dalila Lewis, Claudine Sculier, Melissa Sacco, Daniel Santel, Amanda Weber, Asri Yuliati, Azara Singh, Ashley Heath, David Turner, Cecilia Fernandes, Linh Tran, Raquel Farias-Moeller, Kurt Hecox, Kumar Sannagowdara, David Goldstein, Erin Heinzen Cox, Colin Malone, Alexis Topjian, Cecil Hahn, Saptharishi Rishi Lalgudi Ganesan, Steven Weinstein, Nathan Dean, Renee Shellhaas, Guilia Benedetti, Garnett Smith, Olga Selioutski, Inna Hughes, Lurie Seltzer

Affiliations

¹ From the Department of Neurology and Physical Medicine and Rehabilitation (K.P.), University of Cincinnati College of Medicine, OH; Division of Pediatric Neurology (R.A., T.G., P.S.H.), Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, OH; Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania; Division of Epilepsy and Clinical Neurophysiology (C.B.A., Justice Clark, M.G.-L., K.K., T.L.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, MA; Department of Child Neurology (CBA), Hospital Universitario La Paz, Universidad Autonoma de Madrid, Spain; Pediatric Neurology Unit (M.A.-G.), Department of Pediatrics, Hospital Universitari Son Espases, Universitat de Les Illes Balears, Palma, Spain; Section of Neurology and Developmental Neuroscience (A.A., J.R.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Department of Pediatrics (B.L.A., K.E.C., A.W., K.W.), University of Arizona College of Medicine and Barrow's Neurological Institute at Phoenix Children's Hospital; Department of Neurology and Pediatrics (J.N.B., H.G.), University of Virginia Health System, Charlottesville; Division of Pediatric Neurology (Jessica Carpenter), University of Maryland School of Medicine, Baltimore; Center for Neuroscience (W.D.G.), Children's National Hospital, George Washington University School of Medicine and Health Sciences, DC; Instituto de Pediatría (M.G.-L.), Facultad de Medicina, Universidad Austral de Chile, Valdivia; Servicio de Neuropsiquiatría Infantil (M.G.-L.), Hospital Clínico San Borja Arriarán, Universidad de Chile, Santiago; Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program (J.G.), Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric Neurology and Epilepsy (Z.G., B.O.M.), Department of Pediatrics, Weill Cornell Medicine, New York; Division of Pediatric and Developmental Neurology (R.M.G.), Washington University School of Medicine, St. Louis, MO; Department of Pediatrics (L.H.), British Columbia Children's Hospital, the University of British Columbia, Canada; Division of Child and Adolescent Neurology (R.K., A.V.-A.), Department of Neurology, Mayo Clinic, Rochester, MN; Division of Pediatric Neurology (S.A.K., E.H.K., C.E.S.), Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; Section of Pediatric Critical Care Medicine (Y.-C.L.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Department of Pediatrics (T.M.), Division of Neurology and Epilepsy, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, IL; Division of Pediatric Neurology (M.A.M., D.T.), Duke University Medical Center, Duke University, Durham, NC; Department of Neurology (L.M., E.N., M.S.W.), Division of Child Neurology, Seattle Children's Hospital, WA; Department of Pediatrics (A.P.O.), Nationwide Children's Hospital, The Ohio State University, Columbus; Division of Neurology (E.T.P.), Department of Pediatrics, Alberta Children's Hospital, Calgary, Canada; Division of Neurology (J.P.), Doernbecher Children's Hospital, Oregon Health & Science University, Portland; Division of Child Neurology & Institute for Genomic Medicine (T.S.), Columbia University Irving Medical Center, New York Presbyterian Hospital; and Department of Anesthesiology (R.C.T.), Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, MA. peariska@ucmail.uc.edu.
² From the Department of Neurology and Physical Medicine and Rehabilitation (K.P.), University of Cincinnati College of Medicine, OH; Division of Pediatric Neurology (R.A., T.G., P.S.H.), Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, OH; Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania; Division of Epilepsy and Clinical Neurophysiology (C.B.A., Justice Clark, M.G.-L., K.K., T.L.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, MA; Department of Child Neurology (CBA), Hospital Universitario La Paz, Universidad Autonoma de Madrid, Spain; Pediatric Neurology Unit (M.A.-G.), Department of Pediatrics, Hospital Universitari Son Espases, Universitat de Les Illes Balears, Palma, Spain; Section of Neurology and Developmental Neuroscience (A.A., J.R.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Department of Pediatrics (B.L.A., K.E.C., A.W., K.W.), University of Arizona College of Medicine and Barrow's Neurological Institute at Phoenix Children's Hospital; Department of Neurology and Pediatrics (J.N.B., H.G.), University of Virginia Health System, Charlottesville; Division of Pediatric Neurology (Jessica Carpenter), University of Maryland School of Medicine, Baltimore; Center for Neuroscience (W.D.G.), Children's National Hospital, George Washington University School of Medicine and Health Sciences, DC; Instituto de Pediatría (M.G.-L.), Facultad de Medicina, Universidad Austral de Chile, Valdivia; Servicio de Neuropsiquiatría Infantil (M.G.-L.), Hospital Clínico San Borja Arriarán, Universidad de Chile, Santiago; Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program (J.G.), Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric Neurology and Epilepsy (Z.G., B.O.M.), Department of Pediatrics, Weill Cornell Medicine, New York; Division of Pediatric and Developmental Neurology (R.M.G.), Washington University School of Medicine, St. Louis, MO; Department of Pediatrics (L.H.), British Columbia Children's Hospital, the University of British Columbia, Canada; Division of Child and Adolescent Neurology (R.K., A.V.-A.), Department of Neurology, Mayo Clinic, Rochester, MN; Division of Pediatric Neurology (S.A.K., E.H.K., C.E.S.), Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; Section of Pediatric Critical Care Medicine (Y.-C.L.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Department of Pediatrics (T.M.), Division of Neurology and Epilepsy, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, IL; Division of Pediatric Neurology (M.A.M., D.T.), Duke University Medical Center, Duke University, Durham, NC; Department of Neurology (L.M., E.N., M.S.W.), Division of Child Neurology, Seattle Children's Hospital, WA; Department of Pediatrics (A.P.O.), Nationwide Children's Hospital, The Ohio State University, Columbus; Division of Neurology (E.T.P.), Department of Pediatrics, Alberta Children's Hospital, Calgary, Canada; Division of Neurology (J.P.), Doernbecher Children's Hospital, Oregon Health & Science University, Portland; Division of Child Neurology & Institute for Genomic Medicine (T.S.), Columbia University Irving Medical Center, New York Presbyterian Hospital; and Department of Anesthesiology (R.C.T.), Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, MA.

Abstract

Background and objectives: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children.

Methods: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE.

Results: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE.

Discussion: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner.

Classification of evidence: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Publication types

Observational Study
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Anticonvulsants / therapeutic use
Benzodiazepines / therapeutic use
Case-Control Studies
Child
Diazepam / therapeutic use
Drug Resistant Epilepsy* / drug therapy
Humans
Retrospective Studies
Seizures / drug therapy
Status Epilepticus* / drug therapy

Substances

Anticonvulsants
Benzodiazepines
Diazepam

Abstract

Publication types

MeSH terms

Substances

Grants and funding