. 2015 Sep 29;85(13):1108-14.

doi: 10.1212/WNL.0000000000001971. Epub 2015 Aug 26.

Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial

Collaborators, Affiliations

Collaborators

Childhood Absence Epilepsy Study Group:
Harry Abram, Ellen Albers, Samar J Bahna, Karen Ballaban-Gil, Jose Barrera, Tekolla Belaineh, Mary Bertrand, Hal Blumenfeld, Sarah Borror, Charlie Borzy, Susan Brantz, Candace Cardoza, Kevin Chapman, Harry T Chugani, Robert R Clancy, Peggy O Clark, Yong Collins, Terrie Conklin, Joan A Conry, Patricia K Crumrine, Jason Czachor, M Susan Dean, Sandra Dewar, Michael Duchowny, Deborah Dye, Tammy Eaton, Mary Jo Elgie, Michelle Ellis, Roy Elterman, Daniella Escobedo, Andrew Francis, L Matthew Frank, Tracy A Glauser, Hilary Gray, La June Grayson, May L Griebel, Laurie Guidry, Samantha Hagopian, Jennifer Haky, Amelia Halac, Angel Hernandez, Lee Howard, Krisa Hoyle Elgin, Pong Kankirawatana, Kent R Kelley, Juli Kidd, Divya Khurana, Paul M Levisohn, Donna Lowery, Ricardo Luzondo, Mary Lou Maher, Angela Martinez, Karen McEwen, Sarah J McVey, Mary Miceli, Daniel K Miles, Jennifer Monahan, Elena Morales, Dianne Morus, Cyndi Mott, JoAnn Narus, Mark Nespeca, Edward Novotny Jr, Suzanne Oken, Juliann Paolicchi, Bryan Philbrook, Tami Quintero, Amber Reese-Porter, Jong M Rho, Tracee Ridley-Pryor, Angela Riggs, Colin Roberts, Kathy Romine, Veronique Ruppe, Russell P Saneto, Raman Sankar, Mark S Scher, Rebecca Schultz, Michael Schwabe, Dina Schwam, Sagar Shah, Gregory Sharp, Rolla Shbarou, Ruth C Shinnar, Shlomo Shinnar, Marcio Sotero de Menezes, Donovan Stock, Christina Lopez Talley, Susanna Taylor, Mamello Tekateka, Doris A Trauner, Edwin Trevathan, William R Turk, Colin B Van Orman, GeorgAnn Vanderjagt, Mary Warde, Jorge Vidaurre, Arie Weinstock, Nanastasia Welnick, Rhonda Werner, James Wheless, Angus A Wilfong, Korwyn Willliams, Shelley Williams, Teresa Williams, Jennifer Williamson, Khaled Zamel, Mary Zupanc, Peter C Adamson, Brian K Alldredge, Tina Alvarado-Taylor, Anne Berg, Gordon Bernhard, Blaise Bourgeois, Brooke Bintliff-Janisak, Jeffrey Blumer, Jeffrey R Buchhalter, Edmund V Capparelli, Joan A Conry, Jeanine Dahlquist, Kaitlyn Daniels, Mignon Davis, Julie DiStefano-Pappas, Michael Donaghue, Eileen Dorsey, Nakeshia Drummond, Shonda Evans, Brandy E Fureman, Peter R Gilbert, Melanie Gleave, Gregory A Grabowski, Rong Guo, Gregory Grabowski, Melissa Grubb, Marla J Hamberger, Dale Hesdorffer, Emily Hirschfeld, Michael Hoffman, Paula Jackson, Margaret Jacobs, Mehdi Keddache, Sudha K Kessler, Michael Kuhlmann, Denise LaGory, Laura Lawrence, Paul M Levisohn, David Loring, Xianqun Luan, Chunyan Liu, Jonathan Masur, Susan McMahan, Katherine Montefiore, Guriya Nandwani, John Nevy, Virginia Nissen, Valerie O'Brien, Philip Overby, Nicholas Peccina, John M Pellock, John P Pestian, Michael D Reed, John H Rodman, Ellen B Roecker, Julie Schneider, Charles Scott, Mayadah Shabbout, David Shera, Ruth C Shinnar, Sarah Srodulski, Gerri Tangren, Marc Taylor, Nirmala Thevathasan, Tonia Toon, Maria Vasconcelos, Alexander A Vinks, Gretchen Von Allmen, Clare Weiler, Erica F Weiss, Sheila Wolfer

Affiliations

¹ From Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX. sshinnar@aol.com.
² From Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.

PMID: 26311751
PMCID: PMC4603882
DOI: 10.1212/WNL.0000000000001971

Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial

Shlomo Shinnar et al. Neurology. 2015.

. 2015 Sep 29;85(13):1108-14.

doi: 10.1212/WNL.0000000000001971. Epub 2015 Aug 26.

Collaborators

Childhood Absence Epilepsy Study Group:
Harry Abram, Ellen Albers, Samar J Bahna, Karen Ballaban-Gil, Jose Barrera, Tekolla Belaineh, Mary Bertrand, Hal Blumenfeld, Sarah Borror, Charlie Borzy, Susan Brantz, Candace Cardoza, Kevin Chapman, Harry T Chugani, Robert R Clancy, Peggy O Clark, Yong Collins, Terrie Conklin, Joan A Conry, Patricia K Crumrine, Jason Czachor, M Susan Dean, Sandra Dewar, Michael Duchowny, Deborah Dye, Tammy Eaton, Mary Jo Elgie, Michelle Ellis, Roy Elterman, Daniella Escobedo, Andrew Francis, L Matthew Frank, Tracy A Glauser, Hilary Gray, La June Grayson, May L Griebel, Laurie Guidry, Samantha Hagopian, Jennifer Haky, Amelia Halac, Angel Hernandez, Lee Howard, Krisa Hoyle Elgin, Pong Kankirawatana, Kent R Kelley, Juli Kidd, Divya Khurana, Paul M Levisohn, Donna Lowery, Ricardo Luzondo, Mary Lou Maher, Angela Martinez, Karen McEwen, Sarah J McVey, Mary Miceli, Daniel K Miles, Jennifer Monahan, Elena Morales, Dianne Morus, Cyndi Mott, JoAnn Narus, Mark Nespeca, Edward Novotny Jr, Suzanne Oken, Juliann Paolicchi, Bryan Philbrook, Tami Quintero, Amber Reese-Porter, Jong M Rho, Tracee Ridley-Pryor, Angela Riggs, Colin Roberts, Kathy Romine, Veronique Ruppe, Russell P Saneto, Raman Sankar, Mark S Scher, Rebecca Schultz, Michael Schwabe, Dina Schwam, Sagar Shah, Gregory Sharp, Rolla Shbarou, Ruth C Shinnar, Shlomo Shinnar, Marcio Sotero de Menezes, Donovan Stock, Christina Lopez Talley, Susanna Taylor, Mamello Tekateka, Doris A Trauner, Edwin Trevathan, William R Turk, Colin B Van Orman, GeorgAnn Vanderjagt, Mary Warde, Jorge Vidaurre, Arie Weinstock, Nanastasia Welnick, Rhonda Werner, James Wheless, Angus A Wilfong, Korwyn Willliams, Shelley Williams, Teresa Williams, Jennifer Williamson, Khaled Zamel, Mary Zupanc, Peter C Adamson, Brian K Alldredge, Tina Alvarado-Taylor, Anne Berg, Gordon Bernhard, Blaise Bourgeois, Brooke Bintliff-Janisak, Jeffrey Blumer, Jeffrey R Buchhalter, Edmund V Capparelli, Joan A Conry, Jeanine Dahlquist, Kaitlyn Daniels, Mignon Davis, Julie DiStefano-Pappas, Michael Donaghue, Eileen Dorsey, Nakeshia Drummond, Shonda Evans, Brandy E Fureman, Peter R Gilbert, Melanie Gleave, Gregory A Grabowski, Rong Guo, Gregory Grabowski, Melissa Grubb, Marla J Hamberger, Dale Hesdorffer, Emily Hirschfeld, Michael Hoffman, Paula Jackson, Margaret Jacobs, Mehdi Keddache, Sudha K Kessler, Michael Kuhlmann, Denise LaGory, Laura Lawrence, Paul M Levisohn, David Loring, Xianqun Luan, Chunyan Liu, Jonathan Masur, Susan McMahan, Katherine Montefiore, Guriya Nandwani, John Nevy, Virginia Nissen, Valerie O'Brien, Philip Overby, Nicholas Peccina, John M Pellock, John P Pestian, Michael D Reed, John H Rodman, Ellen B Roecker, Julie Schneider, Charles Scott, Mayadah Shabbout, David Shera, Ruth C Shinnar, Sarah Srodulski, Gerri Tangren, Marc Taylor, Nirmala Thevathasan, Tonia Toon, Maria Vasconcelos, Alexander A Vinks, Gretchen Von Allmen, Clare Weiler, Erica F Weiss, Sheila Wolfer

Affiliations

¹ From Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX. sshinnar@aol.com.
² From Montefiore Medical Center (S.S., D.M., S.L.M.), Albert Einstein College of Medicine, New York, NY; Children's National Health System (A.C., F.H.), Washington, DC; Cincinnati Children's Hospital Medical Center (P.C., T.A.G.); the University of Cincinnati College of Medicine (P.C., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; and Baylor College of Medicine (E.M.M.), Houston, TX.

PMID: 26311751
PMCID: PMC4603882
DOI: 10.1212/WNL.0000000000001971

Abstract

Objective: To determine incidence and early predictors of generalized tonic-clonic seizures (GTCs) in children with childhood absence epilepsy (CAE).

Methods: Occurrence of GTCs was determined in 446 children with CAE who participated in a randomized clinical trial comparing ethosuximide, lamotrigine, and valproate as initial therapy for CAE.

Results: As of June 2014, the cohort had been followed for a median of 7.0 years since enrollment and 12% (53) have experienced at least one GTC. The median time to develop GTCs from initial therapy was 4.7 years. The median age at first GTC was 13.1 years. Fifteen (28%) were not on medications at the time of their first GTC. On univariate analysis, older age at enrollment was associated with a higher risk of GTCs (p=-0.0009), as was the duration of the shortest burst on the baseline EEG (p=0.037). Failure to respond to initial treatment (p<0.001) but not treatment assignment was associated with a higher rate of GTCs. Among patients initially assigned to ethosuximide, 94% (15/16) with GTCs experienced initial therapy failure (p<0.0001). A similar but more modest effect was noted in those initially treated with valproate (p=0.017) and not seen in those initially treated with lamotrigine.

Conclusions: The occurrence of GTCs in a well-characterized cohort of children with CAE appears lower than previously reported. GTCs tend to occur late in the course of the disorder. Children initially treated with ethosuximide who are responders have a particularly low risk of developing subsequent GTCs.

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Figures

**Figure 1. Overall cumulative incidence curves and confidence bands**
Overall cumulative incidence curve and confidence band of time to development of generalized tonic-clonic seizures (GTCs) overall (A), by initial drug assignment (log-rank test p = 0.8, B), and by age group (log-rank test p = 0.0009). ETX = ethosuximide; LTG = lamotrigine; VPA = valproic acid.

**Figure 2. Cumulative risk and confidence band of developing generalized tonic-clonic seizures (GTCs) as a function of age without consideration of age at randomization or response to initial therapy**

**Figure 3. Relationship between age at randomization and age at generalized tonic-clonic seizure (GTC) in those patients who had a GTC**

See this image and copyright information in PMC

References

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1. Hirsch E, Panayatopoulos CP. Childhood absence epilepsy and related syndromes. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Epileptic Syndromes in Infancy Childhood and Adolescence, 4th ed Montrouge, France: John Libbey Eurotext; 2005:315–335.
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Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial

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Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial

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