Patients with an autoimmune disease have a 3.8-fold increased risk of developing epilepsy, according to a new population-level study from Boston Children's Hospital based on health insurance claim data. The study, published online March 31, 2014 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. A growing number of 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, MD, MPH, runs Boston Children's Informatics Program (CHIP)'s Intelligent Health Laboratory. "We need to change how we think about clinical management of these conditions."
Mandl and Mei-Sing Ong, PhD, first author of the study, 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 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 immunosuppressing medications had a lower risk of developing epilepsy.
"These findings suggest a new approach to treating seizures, one based on quieting the immune system," Mandl said.
According to Mandl and Mark Gorman, MD, a Boston Children's neurologist involved with the study, 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."
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.
Boston Children's Hospital