Patients with an autoimmune disease have a 3.8-fold increased risk of developing epilepsy, according to a new population-level study based on health insurance claim data.
The study, led by Harvard Medical School investigators at Boston Children’s Hospital and published online March 31 in JAMA Neurology, is the largest to date to look at the association between autoimmune disease and epilepsy without a recognized neurological cause.
Epilepsy affects approximately 470,000 children and 2.3 million adults in the U.S. alone. While medical and surgical treatments can be effective in managing the disease, the results are mixed. Recently, reports based on small clinical or animal model studies have begun to link specific autoimmune diseases to cases of epilepsy of previously unknown cause. Epilepsy therapy is largely directed at the symptoms of disease, and in about two-thirds of patients, the specific underlying cause of the condition is never found.
"Autoimmunity is strongly linked to seizures. We may be overlooking a treatable mechanism in epilepsy patients," said the study’s lead author, Kenneth Mandl, HMS professor of pediatrics at Boston Children's and a member of the affiliated faculty of the Harvard-MIT Division of Health Sciences and Technology. "We need to change how we think about clinical management of these conditions.”
Mandl and first author Mei-Sing Ong, currently a postdoctoral research fellow at the Centre for Health Informatics, Faculty of Medicine, University of New South Wales, Australia, looked at the autoimmunity-epilepsy connection at a population level by analyzing de-identified claims data related to epilepsy and 12 autoimmune diseases from more than 2.5 million subscribers of a nationwide health insurance carrier.
The researchers found that there was a 3.8-fold increase in the risk of epilepsy for patients with an autoimmune disease, and that 17.5 percent of epilepsy patients also had an autoimmune disease.
The increase in risk of epilepsy varied by form of autoimmunity, ranging from 1.9-fold for psoriasis to 9.4-fold for antiphospholipid syndrome.
In addition, the increase in risk was greater among children (5.2-fold) than adults (4.3-fold).
Findings also revealed that autoimmunity patients on select immuno-suppressing medications had a lower risk of developing epilepsy.
"These findings suggest a new approach to treating seizures, one based on quieting the immune system," said Mandl, who also runs the Intelligent Health Laboratory of the Children’s Hospital Informatics Program (CHIP).
According to Mandl and Mark Gorman, HMS assistant professor of neurology at Boston Children’s and a study co-author, the risk association between epilepsy and autoimmunity suggests that both rheumatologists and neurologists should consider screening their patients for signs of the associated condition.
"There are subtle signs of epilepsy that may suggest to an immunologist that a patient should be assessed by a neurologist," said Gorman. "Similarly, if you are a neurologist, a referral to an immunologist may be warranted if a patient shows subtle signs of autoimmunity.”
The team's data did not allow them to explore possible mechanisms behind the association, but they hope to work with collaborators to look for biological links.
"There are many ways in which autoimmunity can affect the brain and cause seizures," said Gorman. "The next step is to find out what they are."
Additional co-authors on the study were Isaac Kohane, HMS Lawrence J. Henderson Professor of Pediatrics at Boston Children’s, director of the Countway Library of Medicine at HMS and associate professor of medicine at Brigham and Women’s Hospital; and Tianxi Cai, professor of biostatistics at the Harvard School of Public Health.
The study was supported by the National Institute for General Medical Sciences (grant number R01GM104303), the National Center for Biomedical Computing (grant number U54LM008748), the Conte Center for Computational System Genomics of Neuropsychiatric Phenotypes (National Institute of Mental Health grant number P50MH94267) and the Australian National Health and Medical Research Council.
Adapted from a Boston Children’s press release.
