Relationship Between ASD Symptomology, Intellectual Functioning, and Seizure History in Children with ASD

Background:  Autism Spectrum Disorder (ASD) and epilepsy frequently co-occur, and despite similarly identified genetic contributors, it is unclear how shared etiologies are driving the association and how seizures impact ASD symptomology (Gilby & O’brien, 2013). ASD-epilepsy comorbidity has been associated with greater impairment in adaptive functioning, motor skills, and severity of autism, with severity often defined as level of intellectual functioning (Robinson, 2012; Turk, 2009; Viscindi et al., 2014). Additionally, increased rates of restricted and repetitive behaviors have been reported in individuals with comorbid ASD-epilepsy distinguishing them from individuals with ASD alone even when accounting for intellectual disability (Cuccaro et al., 2012).

Objectives:  First, to explore the ASD symptomology profile associated with ASD and history of seizures or ASD alone in a sample of children ascertained for ASD. Second, to further examine the relation between seizure history, autism symptoms, and cognitive functioning

Methods:  Our preliminary analyses included data from 110 children and young adults with ASD between ages of 4 years and 21 years with no reported history of seizures (n = 81, Male = 81%) and a history of non-febrile seizures (n = 30, Male = 73%). Seizure history was defined by parent interview. ASD symptomology was characterized using the ADOS-2 subdomain totals and ADI-R domain totals. Full Scale IQ Standard Score was derived from the Differential Ability Scale for Children (DAS-II; Elliot, 1990) with subjects stratified into IQ equal or higher than 70 (58%) and IQ lower than 70 (47%). Two MANCOVAs examined the effects of IQ status and seizure history (ASD+No Seizure History vs. ASD + History of Seizures) on parent derived ASD symptom scores (ADI-R subdomain totals) and clinician derived ASD symptom scores (ADOS-2 subdomain totals), controlling for current anti-seizure medication use.

Results:  There were no significant multivariate effects or interactions for parent derived ASD symptoms. Significant main effects were found on the clinician derived ASD symptoms for IQ status, F(3,97) = 14.73, p <.001, Wilk’s Lambda = .687 and seizure history, F(3, 97) = 4.94, p = .003, Wilk’s Lambda = .876. A trend for the interaction between groups was observed, F(3, 97) = 2.67, p = .052, Wilk’s Lambda = .924 (see Figure 1). Post hoc testing indicated this interaction was significant for only the behavioral subdomain, F(1, 98) =6.43, p = .013, such that children with higher IQ and with a positive seizure history showed significantly lower restricted and repetitive behaviors compared to children without a history of seizures or children with a seizure history and IQ below 70.

Conclusions:  Results suggest patterns of autism symptoms are associated with seizure history and intellectual functioning with greater ASD impairment associated with intellectual disability. Findings also reveal independent and interactive effects of intellectual functioning and seizure history on ASD symptomology particularly in the area of restricted and repetitive behaviors. Specifically, children with ASD, seizure history, and without intellectual disability demonstrated significantly less behavioral symptoms, suggesting a protective contribution of cognitive functioning in this group.