The co-occurrence of epilepsy and autism: A systematic review

doi:10.1016/j.yebeh.2019.07.037

Epilepsy & Behavior

Volume 98, Part A, September 2019, Pages 238-248

https://doi.org/10.1016/j.yebeh.2019.07.037 Get rights and content

Highlights

•
Autism and epilepsy often co-occur, which has implications for patient management and outcomes.
•
This study synthesized data on the incidence and prevalence of autism in epilepsy and vice-versa from 74 studies.
•
The median overall period prevalence of epilepsy in people with autism was 12.1% (range: 1.8-60%).
•
The median overall period prevalence of autism in people with epilepsy was 9.0% (range: 0.60-41.9%).
•
The period prevalence of epilepsy in people with autism, and vice-versa, was higher than estimates in general populations.

Abstract

Objective

We aimed to review the literature to determine the incidence and prevalence of autism in epilepsy and epilepsy in autism, conditions that are often comorbid.

Methods

We adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards, and the protocol was registered with PROSPERO. MEDLINE, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews were searched from inception until July 4, 2016. Studies were included if they reported an incidence or prevalence of autism in epilepsy or epilepsy in autism. These estimates were described using mean, standard deviation, median, and interquartile range.

Results

Seventy-four studies reporting on 283,549 patients were included. The median overall period prevalence of epilepsy in people with autism was 12.1% while the median overall period prevalence of autism in people with epilepsy was 9.0% when including all population types. When excluding studies that investigated patients with syndromic epilepsy or developmental delay, the median overall period prevalence of epilepsy in people with autism was 11.2% while the median overall period prevalence of autism in people with epilepsy was 8.1%. We observed trends for sex as the prevalence of autism in epilepsy was higher in males while the prevalence of epilepsy in autism was higher in females. It is important to interpret these estimates with caution, as there was significant heterogeneity between studies. Meta-regression found no association between study quality and prevalence or incidence estimates (all p-values > 0.05).

Conclusions

The period prevalence of epilepsy in people with autism, and vice versa, was consistently higher than previously reported estimates of the occurrence of these disorders in the general population. These findings highlight the importance of screening for autism in people who have epilepsy and epilepsy in people who have autism and may help shed light on shared pathogenesis between these conditions.

Introduction

Epilepsy and autism often co-occur. This co-occurrence is likely due to underlying components that influence both disease processes. In autism spectrum disorder (ASD), a great amount of etiological heterogeneity has been identified, many of which are also associated with epilepsy [1]. Factors such as genetic and chromosomal abnormalities [2], metabolic conditions [3], environmental factors, e.g., maternal rubella during pregnancy [4], and brain damage via neonatal jaundice [5], are examples that have been recognized as predisposing to both epilepsy and autism.

In 2010, the prevalence of ASD in the general population was estimated at 0.76% and responsible for 7.7 million disability adjusted life years (DALYs) across the globe [6]. Similarly, the active prevalence of epilepsy in the general population is 0.6% [7], and it was the fourth most burdensome (DALY) neurological disorder worldwide in 2015 [8].

Determining the bidirectional prevalence of autism and epilepsy is important to inform interventions and allocation of resources. Further, understanding these comorbidities will have a profound effect on the management of these challenging patient populations. For example, it has been found that autistic symptoms can be minimized when epilepsy is treated in patients with both conditions [9]. While there are two systematic reviews that have examined the prevalence of epilepsy in persons with autism [10], [11], neither examined the epidemiology of autism in epilepsy. In addition, one of the systematic reviews only looked at the relationship between autism and epilepsy in terms of intellectual disability and sex [10]. Therefore, we aimed to systematically review the literature to determine the incidence and prevalence of autism in epilepsy and epilepsy in autism.

Section snippets

Methods

This study was registered with PROSPERO (ID: CRD42016039614). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were adhered to for this study [12].

Study selection and characteristics

The search identified 3857 unique abstracts, of which 193 were selected for full-text review and 60 were included (Fig. e-1). Fourteen additional studies were identified through hand searching and expert consultation, resulting in 74 included studies (Appendix e-2). The Kappa statistic between reviewers for study inclusion at the full-text stage was 0.82.

Characteristics of included population-based and nonpopulation-based studies are listed in Table 1, Table 2, respectively. Detailed versions

Discussion

Out of the 74 eligible studies reporting on 283,549 patients identified in our study, the median period prevalence of epilepsy in autism was 12.1% while the prevalence of autism in epilepsy was 9%. The median period prevalence of epilepsy in people with autism and autism in people with epilepsy was found in this systematic review to be markedly higher than previously reported period prevalence of epilepsy or autism in the general population [6], [7]. The first studies looking at the prevalence

Conclusion

The occurrence of autism in persons with epilepsy and epilepsy in persons with autism is higher than the previously reported independent occurrence of each of these conditions in the general population. This trend demonstrates the importance of screening for autism in persons with epilepsy, and vice versa, to appropriately tailor treatment decisions and improve patient outcomes.

The following are the supplementary data related to this article.

. Autism and epilepsy search strategy.

Funding

This study was in part funded by the Brain and Mental Research Clinics of the Hotchkiss Brain Institute.

We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Declaration of Competing Interest

Sara Lukmanji, Sofiya A. Manji, Sandra Kadhim, Khara M. Sauro, and Churl-Su Kwon report no disclosures.

Elaine C. Wirell receives consulting fees from Sunovion and Biomarin. Nathalie Jetté was the holder of a Canada Research Chair in Neurological Health Services Research during the study and is currently the holder of research funding (paid to her academic institutions) for unrelated work from Alberta Health, NINDS (NIH IU54NS100064) and the University of Calgary.

Acknowledgments

We would like to thank Diane Lorenzetti for her insightful feedback and suggestions on the search strategy.

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¹: These authors contributed equally to the manuscript.

View full text

ReviewThe co-occurrence of epilepsy and autism: A systematic review

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Study selection and characteristics

Discussion

Conclusion

Funding

Declaration of Competing Interest

Acknowledgments

Brain Res

Epilepsy Behav

Brain Dev

Biol Psychol

Brain Dev

Brain Dev

Brain Dev

Brain Dev

Epilepsy Behav

Epilepsy Res

Epilepsy Res

Adolescent Psychiatry;J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Eur J Paediatr Neurol

Autism and phenylketonuria

J Autism Dev Disord

Follow-up report on autism in congenital rubella

J Autism Child Schizophr

Extremely low gestational age newborn study I. Girls and boys born before 28 weeks gestation: risks of cognitive, behavioral, and neurologic outcomes at age 10 years

J Pediatr

The epidemiology and global burden of autism spectrum disorders

Psychol Med

Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies

Neurology

Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Lancet

A systematic review of two outcomes in autism spectrum disorder - epilepsy and mortality

Dev Med Child Neurol

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration

PLoS Med

Critical appraisal of the health research literature prevalence or incidence of a health problem

Chronic Dis Inj Can

Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis

BMJ

Review
The co-occurrence of epilepsy and autism: A systematic review