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July 12, 2016; 87 (2) Article

Autism and epilepsy

A population-based nationwide cohort study

Heléne E.K. Sundelin, Henrik Larsson, Paul Lichtenstein, Catarina Almqvist, Christina M. Hultman, Torbjörn Tomson, Jonas F. Ludvigsson
First published June 15, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002836
Heléne E.K. Sundelin
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Henrik Larsson
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Paul Lichtenstein
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Catarina Almqvist
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Christina M. Hultman
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Torbjörn Tomson
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Jonas F. Ludvigsson
From the Department of Pediatrics (H.E.K.S.), University Hospital, Linköping; Departments of Medical Epidemiology and Biostatistics (H.L., P.L., C.A., C.M.H., J.F.L.) and Clinical Neuroscience (T.T.), Karolinska Institutet; Astrid Lindgren Children's Hospital (C.A.), Karolinska University Hospital, Stockholm; Department of Pediatrics (J.F.L.), University Hospital, Örebro, Sweden; and Division of Epidemiology and Public Health (J.F.L.), School of Medicine, University of Nottingham, UK.
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Citation
Autism and epilepsy
A population-based nationwide cohort study
Heléne E.K. Sundelin, Henrik Larsson, Paul Lichtenstein, Catarina Almqvist, Christina M. Hultman, Torbjörn Tomson, Jonas F. Ludvigsson
Neurology Jul 2016, 87 (2) 192-197; DOI: 10.1212/WNL.0000000000002836

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Abstract

Objective: To investigate the risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives to determine shared etiology.

Methods: Through the Swedish Patient Register, we identified 85,201 individuals with epilepsy, as well as all their siblings (n = 80,511) and offspring (n = 98,534). Each individual with epilepsy was compared with 5 controls, matched for age, sex, calendar period, and county, while siblings and offspring were compared with siblings and offspring of controls. We excluded siblings and offspring with epilepsy. Using Cox regression, we calculated hazard ratios (HRs) for future diagnosis of ASD. Logistic regression was applied to calculate odds ratios (ORs) for prior diagnosis of ASD.

Results: During follow-up, 1,381 (1.6%) individuals with epilepsy and 700 (0.2%) controls were diagnosed with ASD. Individuals with epilepsy were therefore at increased risk of future ASD (HR 10.49, 95% confidence interval [CI] 9.55–11.53), with the highest risk seen in individuals diagnosed with epilepsy in childhood. Both siblings (HR 1.62, 95% CI 1.43–1.83) and offspring (HR 1.64, 95% CI 1.46–1.84) of epilepsy patients were at increased risk of ASD. The risk in the offspring was particularly high in mothers with epilepsy (HR 1.91; 95% CI 1.63–2.23). Epilepsy was also associated with a prior diagnosis of ASD (OR 4.56, 95% CI 4.02–5.18).

Conclusions: Individuals with epilepsy are at increased risk of ASD, especially if epilepsy appears in childhood. Further, ASD is more common in the siblings and offspring of individuals with epilepsy, suggesting shared etiology.

GLOSSARY

ASD=
autism spectrum disorder;
CI=
confidence interval;
HR=
hazard ratio;
ICD=
International Classification of Diseases;
OR=
odds ratio

Footnotes

  • 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

  • Editorial, page 130

  • Received October 22, 2015.
  • Accepted in final form March 3, 2016.
  • © 2016 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author Response to Dr. Sethi
    • Helene E.K. Sundelin, Department of Pediatrics, University Hospital, Linkoping, Swedenhelene.sundelin@hotmail.com
    • Jonas F. Ludvigsson, Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; and Department of Pediatrics, Orebro University Hospital, Orebro University, Orebro, Sweden
    Submitted August 16, 2016
  • Austism and epilepsy: A "chicken or egg" situation
    • Nitin K. Sethi, Assistant Professor of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center 525 East 68th Street, New York, NY 1006sethinitinmd@hotmail.com
    Submitted July 25, 2016
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