Support for Autoimmune-Epilepsy Link

Megan Brooks

April 07, 2014

A new study provides evidence at a population level for an autoimmune cause of epilepsy, prompting the research team to suggest that patients with either condition be screened for the other.

"The potential role of autoimmunity must be given due consideration in refractory epilepsy so that we are not overlooking a treatable etiology," the authors conclude.

"We need to expand our thinking when it comes to clinical management of these conditions," lead investigator Kenneth Mandl, MD, MPH, from Intelligent Health Laboratory, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts, said in a statement.

The study was published online March 31 in JAMA Neurology.

Using insurance claims data from more than 2.5 million subscribers to a national health insurance carrier, the researchers assessed the relationship between epilepsy and 12 autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves' disease, Hashimoto's thyroiditis, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease.

The risk for epilepsy was elevated nearly 4-fold in patients with an autoimmune disease (odds ratio [OR], 3.8; 95% confidence interval [CI], 3.6 - 4.0; P < .001) and was especially high in children (OR, 5.2; 95% CI, 4.1 - 6.5; P < .001). Elevated risk was consistently observed across all 12 autoimmune diseases.

Table. Epilepsy Risk With Autoimmune Disease

Autoimmune Disease Epilepsy (%) OR (95% CI)
Antiphospholipid syndrome 3.2 9.0 (7.7 - 10.5)
Systemic lupus erythematosus 2.5 7.4 (6.5 - 8.4)
Type 1 diabetes 1.8 5.2 (4.9 - 5.6)
Myasthenia gravis 1.7 4.9 (3.1 - 7.8)
Celiac disease 1.5 4.5 (3.1 - 6.5)
Sjögren syndrome 1.5 4.3 (3.2 - 5.6)
Rheumatoid arthritis 1.2 3.5 (3.1 - 4.0)
Crohn's disease 1.1 3.1 (2.5 - 3.8)
Ulcerative colitis 0.9 2.5 (2.1 - 3.1)
Hashimoto's thyroiditis 0.8 2.4 (2.0 - 3.0)
Graves' disease 0.8 2.2 (1.8 - 2.8)
Psoriasis 0.7 1.9 (1.6 - 2.3)


According to the researchers, 17.5% of patients with epilepsy in the study population had an autoimmune disease. The onset of epilepsy preceded the diagnosis of an autoimmune disease in 30% of cases. Seizures tended to occur within the first 1 to 2 years after diagnosis of an autoimmune disease.

Adverse immunologic effects of antiepileptics "clearly" do not explain the link, the researchers say, because 70% of the study population with autoimmune disease and epilepsy were not exposed to antiepileptic medications for at least 2 years before diagnosis of autoimmune disease.

What is clear, they say, is that epilepsy and autoimmune disease "frequently co-occur," and they recommend that patients with either condition undergo surveillance for the other.

"There are subtle signs of epilepsy that may suggest to an immunologist that a patient should be assessed by a neurologist," Mark Gorman, MD, study author and neurologist at Boston Children's Hospital, said in a statement. "Similarly, if you are a neurologist, a referral to an immunologist may be warranted if a patient shows subtle signs of autoimmunity."

"There are many ways in which autoimmunity can affect the brain and cause seizures. The next step is to find out what they are," Dr. Gorman said.

The authors say a limitation of the study is the use of claims data, which have "limited resolution and do not permit fine-grained classification of epilepsy type."

Autoimmune Cause of Epilepsy?

Reached for comment, John Stern, MD, professor of neurology and director of UCLA Seizure Disorder Center in Los Angeles, California, said this paper "adds to our understanding of the attraction between the immune system and epilepsy."

"We've known for a long time that certain forms of epilepsy have immune components. What this paper does is go back to some of the well-characterized autoimmune diseases and finds that there is a relationship with epilepsy," he said in an interview with Medscape Medical News.

The fact that this is a large comprehensive paper "makes it interesting," he added. "It shows that having one of these autoimmune diseases raises one's risk of epilepsy, in particular lupus or antiphospholipid syndrome, which is already well-established."

"As a neurologist, what I would be interested in is whether someone with epilepsy has an autoimmune cause for the epilepsy. That's where this is meaningful — what aspect of epilepsy is autoimmune and whether there is an opportunity there for treatment that is overlooked. But there is still a lot to learn," Dr. Stern said.

The study was supported by the National Institute for General Medical Sciences, the National Center for Biomedical Computing, the Conte Center for Computational System Genomics of Neuropsychiatric Phenotypes, and the Australian National Health and Medical Research Council. The authors and Dr. Stern have disclosed no relevant financial relationships.

JAMA Neurol. Published online March 31, 2014. Abstract


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