Autism and Epilepsy Comorbidity: Shared Etiology?

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The results indicate a 10-fold increased risk of future autism in patients diagnosed with epilepsy.
The results indicate a 10-fold increased risk of future autism in patients diagnosed with epilepsy.

Results from a large Swedish study suggest that epilepsy and autism spectrum disorder (ASD) have a shared etiology.

The study, which followed nearly 87 000 individuals with epilepsy over a median of 5.5 years, found that participants with epilepsy were at an increased risk of ASD. That risk also extended to siblings and offspring of individuals with epilepsy.

“In children with early-onset epilepsy, the hypothesis is that epileptic seizures and epileptiform abnormalities in the EEG make a large contribution to cognitive and behavioral comorbidities, over and above that caused by the etiology of the epilepsy,” Rod C. Scott, MD, PhD, and Roberto Tuchman, PhD, wrote in an accompanying editorial.1 “Although this approach may have had modest positive effects on cognition, it has minimally, if at all, reduced the severity or frequency of ASD. This observation strongly suggests that there is at least one other mechanism for children with epilepsy and ASD.”

In this study,2 researchers led by Helene E.K. Sundelin, MD, of University Hospital, Linköping, Sweden, identified 85 201 individuals with epilepsy and their siblings (n= 80 511) and offspring (n= 98 534) through the Swedish Patient Register. Each individual with epilepsy was compared with 5 controls matched for age, sex, calendar period, and county, while siblings and offspring were compared to siblings and offspring of controls.

Over a median follow-up of 5.5 years, 1381 individuals with epilepsy and 700 controls were diagnosed with ASD, demonstrating an increased risk of ASD among people with epilepsy (HR 10.49, 95% confidence interval [CI] 9.55–11.53). The highest risk was observed among those who were diagnosed with epilepsy in childhood. Siblings (HR 1.62, 95% CI 1.43– 1.83) and offspring g (HR 1.64, 95% CI 1.46–1.84) of epilepsy patients were also at an increased risk of ASD, with risk particularly high in offspring whose mothers had epilepsy (HR 1.91; 95% CI 1.63–2.23). Notably, the researchers also found an increased occurrence of ASD prior to epilepsy diagnosis (OR 4.56, 95% CI 4.02–5.18).

Among siblings and offspring, siblings of individuals with epilepsy, including those with epilepsy and ASD, had a 1.62-fold increased risk of ASD (95% CI 1.43–1.83). Offspring of individuals with epilepsy were also at an increased risk of ASD compared to control offspring (HR 1.64, 95% CI 1.46–1.84).

The results indicate a 10-fold increased risk of future ASD in patients with epilepsy, as well as an elevated risk in first-degree relatives.

“The most likely explanation of our findings is shared pathophysiologic, possibly genetic, mechanisms, some influencing the balance between excitation and inhibition,” the authors wrote. “It has been suggested that the 2 diseases share risk factors or heritability, which is consistent with our findings of a bidirectional temporal relationship, reinforcing the suggestion that seizures are not the cause of ASD."

References

1. Scott RC, Tuchman R. Epilepsy and Autism: Relatively Related. Neurology. 2016; doi:10.1212/WNL.0000000000002852.

2. Sundelin HEK, Larsson H, Lichtenstein P, et al. Autism and Epilepsy: A population-based nationwide cohort study. Neurology. 2016; doi: 10.1212/WNL.0000000000002836.

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