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August 15, 2017; 89 (7) Article

Pretreatment seizure semiology in childhood absence epilepsy

Sudha Kilaru Kessler, Shlomo Shinnar, Avital Cnaan, Dennis Dlugos, Joan Conry, Deborah G. Hirtz, Fengming Hu, Chunyan Liu, Eli M. Mizrahi, Solomon L. Moshé, Peggy Clark, Tracy A. Glauser, For the Childhood Absence Epilepsy Study Group
First published July 19, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004226
Sudha Kilaru Kessler
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Shlomo Shinnar
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Avital Cnaan
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Dennis Dlugos
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Joan Conry
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Deborah G. Hirtz
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Fengming Hu
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Chunyan Liu
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Eli M. Mizrahi
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Solomon L. Moshé
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Peggy Clark
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Tracy A. Glauser
From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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From the Children's Hospital of Philadelphia (S.K.K., D.D.), Perelman School of Medicine, University of Pennsylvania; Montefiore Medical Center (S.S., S.L.M.), Albert Einstein College of Medicine, Bronx, NY; Children's National Health System (A.C., J.C., F.H.), Washington, DC; National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD; Comprehensive Epilepsy Center (C.L., P.C., T.A.G.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH; and Baylor College of Medicine (E.M.M.), Houston, TX.
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Citation
Pretreatment seizure semiology in childhood absence epilepsy
Sudha Kilaru Kessler, Shlomo Shinnar, Avital Cnaan, Dennis Dlugos, Joan Conry, Deborah G. Hirtz, Fengming Hu, Chunyan Liu, Eli M. Mizrahi, Solomon L. Moshé, Peggy Clark, Tracy A. Glauser, For the Childhood Absence Epilepsy Study Group
Neurology Aug 2017, 89 (7) 673-679; DOI: 10.1212/WNL.0000000000004226

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Abstract

Objective: To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes.

Methods: For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit.

Results: Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%–84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern.

Conclusions: Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome.

GLOSSARY

AUC=
area under the curve;
CAE=
childhood absence epilepsy;
IQR=
interquartile range

Footnotes

  • Coinvestigators are listed at Neurology.org.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received August 22, 2016.
  • Accepted in final form May 23, 2017.
  • © 2017 American Academy of Neurology
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