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Cited by 258Autism Spectrum Disorder ResearchEpilepsy research and treatmentGenetics and Neurodevelopmental Disorders

Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders

Lewine, Jeffrey D., Andrews, Richard, Chez, Michael, Patil, Arun-Angelo, Devinsky, Orrin, Smith, Michael, Kanner, Andres, Davis, John T. +8 more·1999·PEDIATRICS
DOI 10.1542/peds.104.3.405
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Abstract

BACKGROUND: One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. OBJECTIVE: To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. DESIGN: Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder-not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical EEG, when available. Multiple-dipole, spatiotemporal modeling was used to identify sites of origin and propagation for epileptiform transients. RESULTS: The MEG of all children with LKS showed primary or secondary epileptiform involvement of the left intra/perisylvian region, with all but 1 child showing additional involvement of the right sylvian region. In all cases of LKS, independent epileptiform activity beyond the sylvian region was absent, although propagation of activity to frontal or parietal regions was seen occasionally. MEG identified epileptiform activity in 41 of the 50 (82%) children with ASDs. In contrast, simultaneous EEG revealed epileptiform activity in only 68%. When epileptiform activity was present in the ASDs, the same intra/perisylvian regions seen to be epileptiform in LKS were active in 85% of the cases. Whereas primary activity outside of the sylvian regions was not seen for any of the children with LKS, 75% of the ASD children with epileptiform activity demonstrated additional nonsylvian zones of independent epileptiform activity. Despite the multifocal nature of the epileptiform activity in the ASDs, neurosurgical intervention aimed at control has lead to a reduction of autistic features and improvement in language skills in 12 of 18 cases. CONCLUSIONS: This study demonstrates that there is a subset of children with ASDs who demonstrate clinically relevant epileptiform activity during slow-wave sleep, and that this activity may be present even in the absence of a clinical seizure disorder. MEG showed significantly greater sensitivity to this epileptiform activity than simultaneous EEG, 1-hour clinical EEG, and 24-hour clinical EEG. The multifocal epileptiform pattern identified by MEG in the ASDs typically includes the same perisylvian brain regions identified as abnormal in LKS. When epileptiform activity is present in the ASDs, therapeutic strategies (antiepileptic drugs, steroids, and even neurosurgery) aimed at its control can lead to a significa

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Authors
Lewine, J. D., Andrews, R., Chez, M., Patil, A.-A., Devinsky, O., Smith, M., Kanner, A., Davis, J. T., Funke, M., Jones, G., Chong, B., Provencal, S., Weisend, M., Lee, R. R., Orrison, W. W., & MD, Jr.
Affiliations
  • University of Utah (US)
  • Ra Neurological, Omaha, Nebraska;
  • Pediatric Neurology, Lake Forest, Illinois; the
  • University of Nebraska Medical Center (US)
  • New York University (US)
  • Rush University Medical Center (US)
  • From the Department of Radiology, University of Utah, Salt Lake City, Utah;
  • United States Department of Veterans Affairs (US)
ORCID
Venue
PEDIATRICS
Publisher
American Academy of Pediatrics (AAP)
Published
1999-09-01
Volume
104
Issue
3
Pages
405-418
ISSN
  • 0031-4005 (ISSN-L)
  • 1098-4275
DOI
10.1542/peds.104.3.405
OpenAlex
W2167694414
Cited by
258
References
37
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 10 · 2015: 16 · 2014: 12 · 2013: 10 · 2012: 11
FWCI
6.49
Type
journal article
Language
en
Open access
closed
Locations
  • PEDIATRICS (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Landau-Kleffner syndrome, epileptiform activity, pervasive developmental disorders, sleep EEG, seizure semiology, children with autism
MeSH terms
Autistic Disorder, Brain, Child, Child Development Disorders, Pervasive, Child, Preschool, Electroencephalography, Epilepsy, Female, Humans, Male, Sleep, Magnetoencephalography, Landau-Kleffner Syndrome

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