Epilepsy and Autism

Epidemiology

Epilepsy and autism are both relatively common diagnoses, often made in childhood. The prevalence of autism is increasing, owing to a combination of factors, including changing definitions, increased access to evaluation, and other unknown variables. In the US, prevalence is currently estimated at 1 in every 54 children age 8 years and is much more common in boys (4:1 male to female).^1-3 Epilepsy prevalence and incidence is more static, at approximately 1 in 147 individuals age 18 years or less.⁴

Comorbidity of epilepsy and autism is frequent; approximately 30% of children with autism have epilepsy and vice versa.^3,5 The high rate of comorbidity is thought to be caused by genetic and microstructural brain differences. Both conditions predispose individuals to abnormalities in neural connectivity, although the exact pathophysiology of both conditions remains unknown. There is evidence for epigenetic factors playing a role in some situations. For example, children who have infantile spasms during critical windows of social and language development (6-18 months) are more likely to later develop autism.⁶ There are also syndromes in which a known single gene mutation confers a high risk for both epilepsy and autism (ie, fragile X syndrome).

Diagnostic Evaluations

Possible Autism in People With Epilepsy

Autism is, in part, defined by the presence of repetitive stereotyped atypical behaviors. These can often raise alarm for seizures in parents and caregivers. For example, the common autistic tendency to stare off, “zone out,” or withdraw into an internal world may look like an absence seizure. Repetitive sensory stimulation or stereotypies may appear similar to focal seizures. Careful history-taking is paramount in differentiating seizures from nonepileptic events and critical both to avoid misdiagnosing seizures and to avoid missing a diagnosis of autism (Box 1). Considering this phenotypic overlap, clinicians should maintain a high index of suspicion for autism in children with epilepsy or those seen for evaluation of events concerning for seizures (Box 2). Children who screen positively for developmental delay or autism should be referred for comprehensive evaluations sooner rather than later, because early identification and intensive remediation are shown to improve outcomes for autistic individuals.^7-9

Individuals with autism and epilepsy are more likely to have intellectual disability, specific learning disabilities, and attention deficit hyperactivity disorder (ADHD). Therefore, educational and neuropsychologic evaluations are critical to inform individual education plans (IEPs) and 504 Plans, which ensure appropriate accommodations are made for those who are of school age. It is important to inform parents the additional diagnosis of epilepsy makes it more likely a neuropsychologic evaluation will be covered by insurance. The presence of both autism and epilepsy may affect the implementation of both educational and medical interventions. For example, periods of high seizure burden or medication changes may introduce dynamic changes in academic functioning that need to be accommodated in individual education planning. For the medical provider, medication changes might be best made during school breaks or periods when changes are not also occurring in the child’s environment.

Possible Epilepsy in People With Autism

Although a high index of suspicion for seizures is important in individuals with autism, it is also important to avoid the pitfall of misdiagnosis based on the presence of EEG abnormalities alone without a convincing clinical history. Baseline EEG abnormalities are even more common than epilepsy in individuals with autism. Some studies have shown that up to 60% of people with autism will have EEG abnormalities,^10,11 even without seizures, making the possibility of false positive EEG results high. The EEG findings in autism might be seen as an epiphenomenon of the underlying pathophysiology of the disorder and a reflection of a difference in neural connectivity, rather than a marker for seizure risk, per se. As in all populations, EEG should be used as a tool in the overall clinical evaluation for epilepsy and taken in the context of a thoughtful clinical history. Use of EEG in an individual with autism is warranted only when there is clinical suspicion for seizure, in which case the EEG may provide supporting evidence for or against a diagnosis of epilepsy. This is especially true for those individuals who have aggression or sensory sensitivities that can make the EEG procedure particularly difficult to tolerate. When EEG is clinically necessary for someone with autism, it is important that caregivers and clinicians prepare them in advance to avoid trauma around the procedure as much as possible.

Treatments

Autism

There is no curative treatment for autism, however behavioral and pharmacologic interventions can considerably ameliorate the burden of symptoms and improve functional status and quality of life for individuals and families. Autistic people may receive educational and other accommodations, such as having a 1:1 support person in regular education classrooms or special education services. All individuals providing care, education, or therapy should receive training for seizure first aid and have access to an individualized safety plan that includes a “seizure action plan” and recommendations for safety around water, driving restrictions if the individual is of driving age, and more. If an individual is at risk for wandering or elopement, is nonverbal, or spends time unsupervised, a medical alert bracelet or similar identification including both diagnoses is appropriate.

Epilepsy

Once there is a confirmed diagnosis of epilepsy in a person with autism, treatment should begin—usually with antiseizure medications (ASMs) with the understanding that individualization of therapy is critical. The mantra of “start low and go slow” for titration of ASMs is even more important than usual for people with autism, who in general, have more sensitivities to the environment, including medications.

It is also important to be mindful of whether or not different formulations of an ASM are available and which formulations will be easiest for the individual to tolerate (and the caregiver to administer if needed). The taste, smell, and mouth feel of an ASM that may not bother most can be very bothersome to autistic individuals. Consider whether liquid formulations are available or if pills can be crushed for individuals, especially children and adolescents, who may have difficulty swallowing pills for a longer time than is seen in people without autism.

Conclusion

Autism and epilepsy are frequently comorbid conditions, and it is important to maintain a high index of suspicion for one when the other is present. Screening for autism is warranted in people with epilepsy. Careful history taking should be used to differentiate potential seizures from other repetitive or stereotyped behaviors. Careful diagnostic evaluations, with thoughtful use of EEG testing, can improve diagnostic accuracy and treatment of both conditions when they co-occur.

1. Baio J, Wiggins L, Christensen DL, et al. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2014 [published correction appears in MMWR Morb Mortal Wkly Rep. 2018;67(19):564] [published correction appears in MMWR Morb Mortal Wkly Rep. 2018;67(45):1280]. MMWR Surveill Summ. 2018;67(6):1-23. doi:10.15585/mmwr.ss6706a1

2. Xu G, Strathearn L, Liu B, Bao W. Prevalence of autism spectrum disorder among US children and adolescents, 2014-2016 [published correction appears in JAMA. 2018;319(5):505] [published correction appears in JAMA. 2018;319(5):505]. JAMA. 2018;319(1):81-82. doi:10.1001/jama.2017.17812

3. Hodges H, Fealko C, Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. 2020;9(Suppl 1):S55-S65. doi: 10.21037/tp.2019.09.09.

4. Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology. 2017;88(3):296–303.

5. Lukmanji S, Manji SA, Kadhim S, Sauro KM, Wirrell EC, Kwon CS, Jetté N. The co-occurrence of epilepsy and autism: A systematic review. Epilepsy Behav. 2019 Sep;98(Pt A):238-248. doi: 10.1016/j.yebeh.2019.07.037.

6. Riikonen R. Infantile spasms: outcome in clinical studies. Pediatr Neurol. 2020;108:54-64. doi: 10.1016/j.pediatrneurol.2020.01.015.

7. Bal VH, Kim SH, Cheong D, Lord C. Daily living skills in individuals with autism spectrum disorder from 2 to 21 years of age. Autism. 2015;19(7):774-84. doi: 10.1177/1362361315575840

8. Soorya LV, Siper PM, Beck T, Soffes S, Halpern D, Gorenstein M, Kolevzon A, Buxbaum J, Wang AT. Randomized comparative trial of a social cognitive skills group for children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2015;54(3):208-216.e1. doi: 10.1016/j.jaac.2014.12.005.

9. Landa RJ. Efficacy of early interventions for infants and young children with, and at risk for, autism spectrum disorders. Int Rev Psychiatry. 2018;30(1):25-39. doi: 10.1080/09540261.2018.1432574.

10. Kim HL, Donnelly JH, Tournay AE, Book TM, Filipek P. Absence of seizures despite high prevalence of epileptiform EEG abnormalities in children with autism monitored in a tertiary care center. Epilepsia. 2006;47(2):394-8.
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11. Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A. Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav. 2006;8(1):267-71. doi: 10.1016/j.yebeh.2005.11.001.