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Original Investigation |

Population-Level Evidence for an Autoimmune Etiology of Epilepsy

Mei-Sing Ong, PhD1,2; Isaac S. Kohane, MD, PhD2,3; Tianxi Cai, PhD4; Mark P. Gorman, MD3,5; Kenneth D. Mandl, MD, MPH2,3
[+] Author Affiliations
1Australian Institute of Health Innovation, University of New South Wales, Sydney, Australia
2Children’s Hospital Informatics Program at Harvard–Massachusetts Institute of Technology Health Sciences and Technology, Boston Children’s Hospital, Boston, Massachusetts
3Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts
4Department of Biostatics, Harvard School of Public Health, Boston, Massachusetts
5Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts
JAMA Neurol. 2014;71(5):569-574. doi:10.1001/jamaneurol.2014.188.
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Importance  Epilepsy is a debilitating condition, often with neither a known etiology nor an effective treatment. Autoimmune mechanisms have been increasingly identified.

Objective  To conduct a population-level study investigating the relationship between epilepsy and several common autoimmune diseases.

Design, Setting, and Participants  A retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. Participants were beneficiaries enrolled between 1999 and 2006 (N = 2 518 034).

Main Outcomes and Measures  We examined the relationship between epilepsy and 12 autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease.

Results  The risk of epilepsy was significantly heightened among patients with autoimmune diseases (odds ratio, 3.8; 95% CI, 3.6-4.0; P < .001) and was especially pronounced in children (5.2; 4.1-6.5; P < .001). Elevated risk was consistently observed across all 12 autoimmune diseases.

Conclusions and Relevance  Epilepsy and autoimmune disease frequently co-occur; patients with either condition should undergo surveillance for the other. The potential role of autoimmunity must be given due consideration in epilepsy so that we are not overlooking a treatable cause.

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Figure 1.
Risk of Epilepsy in Children (<18 Years) and Nonelderly Adults (≤65 Years) With Autoimmune Disease Compared With Individuals Without Autoimmune Disease

Epilepsy susceptibility was consistently heightened in patients with autoimmune diseases (P < .001). Collectively, patients with any of the autoimmune diseases under study constituted 17.5% of the total epilepsy population. OR indicates odds ratio; SLE, systemic lupus erythematosus. Data markers indicate ORs and limit lines, 95% CIs.

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Figure 2.
Risk of Epilepsy in Children (<18 Years) With Autoimmune Disease Compared With Children Without Autoimmune Disease

Overall, children with an autoimmune disease had a 5-fold increased risk of epilepsy (P < .001 in all cases except otherwise indicated). OR indicates odds ratio; SLE, systemic lupus erythematosus. Data markers indicate ORs and limit lines, 95% CIs.aP = .006.bP = .008.

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Figure 3.
Risk of Epilepsy in Nonelderly Adults (≤65 Years) With Autoimmune Disease Compared With Nonelderly Adults Without Autoimmune Disease

Overall, adults with an autoimmune disease had a 4-fold increased risk of epilepsy (P < .001 in all cases). OR indicates odds ratio; SLE, systemic lupus erythematosus. Data markers indicate ORs and limit lines, 95% CIs.

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