Autism More Likely If Parent, Sibling Have Epilepsy

June 30, 2016

Individuals with epilepsy, as well as their children and siblings, are at an increased risk for autism, a new study has shown.

The Swedish study, the largest so far to look at the link between epilepsy and autism, was published online in Neurology on June 15.

The authors, led by Heléne E.K. Sundelin, MD, University Hospital, Linköping, Sweden, conclude that their findings "have unique implications for the health care of patients with epilepsy."

"This group of patients should be screened for ASD [autism spectrum disorder], and if ASD is suspected, assessed for a diagnosis of the disorder," they state.

The also point out that the finding that autism is also more common in siblings and offspring of individuals with epilepsy suggests shared etiology and an overlapping inheritance.

"The goal is to find out more about how these two diseases may be linked so that treatments may be developed that will target both conditions," Dr Sundelin said.

"The most likely explanation of our findings is shared pathophysiologic, possibly genetic, mechanisms, some influencing the balance between excitation and inhibition," the authors add. "There are most likely different factors influencing the core mechanisms behind epilepsy and ASD (their core mechanisms being close or similar), bringing the patient to a tipping point where one or both disorders develop."

In an accompanying editorial Rod C. Scott, MD, University of Vermont, Burlington, and Roberto Tuchman, MD, Nicklaus Children's Hospital, Miami, Florida, say the study provides "compelling evidence" that individuals with epilepsy are at high risk for developing autism, especially for those in whom epilepsy begins early in life.

They stress that the observation that siblings and offspring of people with epilepsy are at increased risk for autism supports the view that these two conditions have a shared pathophysiology and "strongly argues" against the hypothesis that seizures are the cause of autism in individuals with epilepsy.

The editorialists agree that these latest findings "clearly emphasize the importance of early screening for neurodevelopmental disorders in all children with epilepsy, specifically autism spectra disorder."

They add that "this study highlights that the comprehensive management of epilepsy is more than treating seizures and should include interventions targeted at minimizing the consequences of neurodevelopmental disorders related to epilepsy, such as ASD, with the ultimate goal of maximizing quality of life."

More Than 85,000 Patients With Epilepsy, 100,000 Relatives

The authors used data from the nationwide Swedish Patient Register, which is almost complete for inpatient data and includes hospital-based outpatient data since 2001. The authors note that the register includes most individuals with epilepsy in Sweden.

Through the register, they identified 85,201 individuals with epilepsy, as well as all their siblings (n = 80,511) and offspring (n = 98,534).

Each individual with epilepsy was compared with 5 controls, matched for age, sex, calendar period, and county, while siblings and offspring were compared with siblings and offspring of controls. Siblings and offspring with epilepsy were excluded.

During the average 6-year follow-up, 1381 (1.6%) individuals with epilepsy and 700 (0.2%) controls were diagnosed with autism. Individuals with epilepsy had a 10-fold increased risk of developing autism (hazard ratio, 10.49). The highest risk was seen in individuals diagnosed with epilepsy in childhood, with 5.2% of these patients developing autism.

The risk for autism was also higher in women with epilepsy than in men with epilepsy. Regarding this finding, the authors comment: "ASD more often remains undiagnosed in female patients and we speculate that a diagnosis of epilepsy increases the chances of undiagnosed ASD being detected."

The study found a greater than 60% increased risk of developing autism for siblings and offspring. The hazard ratios were 1.62 for siblings and 1.64 for offspring.

The risk in the offspring was particularly high for those who had mothers with epilepsy (a 91% increased risk) compared with a 38% increased risk in those who had fathers with epilepsy. The authors suggest that this finding may be due to fetal exposure to antiepileptic medication in utero.

The study also showed that epilepsy was also associated with a prior diagnosis of autism (odds ratio, 4.56), suggesting a bidirectional temporal relationship between the two conditions.

Dr Sundelin and her colleagues note that previous studies have suggested a link between epilepsy and autism, but the large sample size of the current study has provided high statistical power and narrower confidence intervals. It has also allowed examination of specific subgroups.

The study was supported by the Swedish Research Council; the Swedish Initiative for Research on Microdata in the Social and Medical Sciences; the Swedish Research Council for Health, Working Life and Welfare; the Swedish Research Council; and the Stockholm County Council. Dr Sundelin reports receiving travel costs for expert meeting from Cyberonics. The editorialists have disclosed no relevant financial relationships.

Neurology. Published online June 15, 2016. Abstract Editorial

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