Epilepsy and Autism Severity: A Study of 6,975 Children

Abstract

Epilepsy is known to occur in a higher-than-expected proportion of individuals with autism spectrum disorders (ASDs). Prior studies of this heterogeneous disorder have suggested that intelligence quotient (IQ) may drive this relationship. Because intellectual disability (ID) is, independently of ASD, a risk factor for epilepsy, current literature calls into question the long-understood unique relationship between ASD and epilepsy. Second, data have been unclear about whether developmental regression in ASD is associated with epilepsy. Using two cohorts from an online research registry, totaling 6,975 children with ASD, we examined the independent role of four ASD severity measures in driving the relationship with epilepsy: ID, language impairment, core ASD symptom severity, and motor dysfunction, controlling for two known relevant factors: age and sex. We also examined whether developmental regression and epilepsy have an independent statistical link. All four ASD severity factors showed independent statistical associations with epilepsy in one cohort, and three in the other. ID showed the largest relative risk (RR) in both cohorts. Effect sizes were modest. Regression similarly showed an independent statistical association with epilepsy, but with small effect size. Similar to previous work, ID showed the greatest contribution to RR for epilepsy among children with ASD. However, other ASD severity markers showed statistical associations, demonstrating that the ASD-epilepsy association is not reducible to the effect of ID. Inconsistencies in the literature may be due to underpowered studies, yet moving forward with larger-n studies, clinical significance and scientific relevance may be dictated by effect size and not merely statistical significance.Lay Summary: Epilepsy is known to occur more often in individuals with autism spectrum disorders (ASDs) than is the case in the general population. The association between ASD and epilepsy is of interest because studying the two disorders in combination may help advance our understanding of genetic, molecular, and cellular mechanisms-as well as therapies-for both. Recent studies have suggested that intelligence quotient (IQ) alone in individuals with ASD may account for the increased prevalence of epilepsy. However, our approach was to look at a range of severity factors relevant to ASD and to look for correlations between each severity factor and epilepsy, within two large samples of children with ASD. In summary, we found that each severity factor-presence of intellectual disability, presence of language atypicalities, ASD-specific symptoms severity, and presence of motor issues-independently predicted a small increased risk for epilepsy, countering the argument that IQ alone is a risk factor. We also examined whether epilepsy is associated with developmental regression. Although severe epilepsy syndromes such as Landau-Kleffner syndrome are known to cause autistic-like symptoms following developmental regression, there is controversy about whether other forms of epil...

Physical Health of Autistic Girls and Women: A Scoping Review

“…Based on Theme 2, epilepsy is the most studied condition, found to be more prevalent in autistic girls/women than in autistic boys/men in most included studies [23,27,28,31,33,35]. However, the complexity underlying this association remains, with studies highlighting potential confounding factors such as heightened autism symptom, language impairment, motor dysfunction, intellectual disability in autistic girls/women [36,37], or multifactorial etiology and shared neurological abnormalities [59]. On the other hand, barriers experienced by girls/women to receive an autism diagnosis [2,4,10] may result in autistic girls/women without evident developmental disabilities being under-represented in the current literature.…”

“…In addition to studies reporting on general health condition prevalence rates including epilepsy mentioned in Theme 1 [27,34], several studies focused specifically on neurological conditions reported a higher prevalence of epilepsy in autistic girls/women compared to autistic boys/men [35][36][37]. Amiet [39].…”

“…Two studies further characterized epilepsy in autism [36,37]. Ewen et al explored associations between epilepsy and autism severity in two cohorts from a US-based research registry, totalling n=6,975 autistic children (6-18 years) [36].…”

“…Two studies further characterized epilepsy in autism [36,37]. Ewen et al explored associations between epilepsy and autism severity in two cohorts from a US-based research registry, totalling n=6,975 autistic children (6-18 years) [36]. They found a higher risk for epilepsy in autistic girls compared to autistic boys in one cohort, with n=4,801 autistic individuals (RR 1.32 [1.14-1.52], p<0.05) but no statistically significant findings in the other, smaller cohort (n=1,736 autistic individuals).…”

Conceptual, Regulatory and Strategic Imperatives in the Early Days of EEG-Based Biomarker Validation for Neurodevelopmental Disabilities

“…Epilepsy, which has increased in recognized prevalence in ASD (Spence and Schneider, 2009; Ewen et al, 2019) and many other NDDs, presents several confounds. First, frank seizures can affect both consciousness/the ability to make volitional responses as well as the EEG tracing.…”