Epilepsy & Autoimmune Disease: Are They Linked?

September 28, 2016
Veronica Hackethal, MD

To investigate an association between epilepsy and autoimmune disease, researchers reviewed 25 studies, covering patients of various ages.

Epilepsy and autoimmune disease are linked, with the presence of one disorder increasing the risk for the other and vice versa, according to a study published online in Seizure.

The study also found that the risk for epilepsy and autoimmune disease may increase with younger age, though further studies are needed.

“Our meta-analysis suggests that clinicians who specialize in epilepsy should pay close attention to insidious systemic autoimmune disease and try to diagnose it.  Additionally, clinicians who specialize in immune diseases should focus on preventing epilepsy regardless of the patient’s age,” wrote lead author Zou Xiaoyi, MD, of Sichuan University, Chengdu, China, and colleagues.

The study is the first meta-analysis to evaluate the relationship between systemic autoimmune disease and epilepsy.

Recent research has suggested increased risk for epilepsy with systemic autoimmune disease, and indicated a two-way street in which systemic autoimmune disease may also increase the risk for epilepsy. An underlying proinflammatory milieu and autoantibodies may be involved in increased risk for epilepsy. Conversely, seizures may result in the release of pro-inflammatory cytokines, which may aggravate systemic immune disease, according to background information in the article.

In the study, researchers searched Medline and Embase for studies that evaluated the association between systemic autoimmune disease and epilepsy, and were published from inception through February 2016. The analysis included 25 studies, covering 10,972 individuals with epilepsy and 2,618,637 with systemic autoimmune disease. The majority of studies were conducted in Europe.

Key Results:

• Epilepsy linked to 2.5 times increased risk of systemic autoimmune disease (OR 2.58, 95% CI 1.48-4.50, P<0.01)

♦ Celiac disease linked to 2.7 times increased risk of epilepsy (OR=2.77 [95% CI 1.23-6.23], P=0.01)

♦ Bullous pemphigoid linked to 3 times increased risk of epilepsy (OR 3.16, 95% CI 1.57-6.33, P<0.01)

• Systemic autoimmune disease linked to 2.7 times increased risk of epilepsy (OR 2.66, 95% CI 1.88-3.76, P<0.01)

♦ Systemic lupus erythematosus linked to 4.5 times increased risk of epilepsy (OR=4.57, 95% CI 2.40-8.67, P<0.01)

• Risk of systemic autoimmune disease was higher in younger patients with epilepsy:

♦ <20 years: three times increased risk (OR 3.04, 95% CI 1.27-7.27, P=0.01)

♦ >20 years: 42% increased risk (OR 1.42, 95% CI 0.60-3.34, P=0.42)

• Risk of epilepsy was higher in younger patients with systemic autoimmune disease:

♦ <20 years: Three times increased risk (OR 3.15, 95% CI 1.92-5.15, P<0.01)

♦ >20 years: Over twice increased risk (OR 2.27, 95% CI 1.43-3.61, P<.01)

• No obvious publication bias

The authors highlighted the association between increased risk for epilepsy and systemic autoimmune disease (and vice versa) in younger compared to older individuals. However, they pointed out that the association lost significance on further analyses that indirectly compared younger to older patients.

They concluded: “Future studies are needed to further examine the underlying biological mechanisms of this association and to determine the role that young age plays in this increased risk.”

Take-home Points

• A meta-analysis suggests that epilepsy and autoimmune disease are linked: epilepsy was linked to 2.5 times increased risk of systemic autoimmune disease, and systemic autoimmune disease was linked to 2.7 times increased risk of epilepsy.

• Risk of systemic autoimmune disease and epilepsy were higher in younger compared to older patients.

• More studies are needed to evaluate the mechanisms underlying this relationship, and to confirm whether risk increases with younger age.

The authors report no conflicts of interest

Reference: Lin Z, et al. Association between epilepsy and systemic autoimmune diseases: a meta-analysis. Seizure. 2016 Aug 23;41:160-166.