Epilepsy and Autism Spectrum Disorders

1. Epilepsy and Autism
Ade Wijaya, MD – June 2019

2. Introduction
• Epilepsy and autism: common co-occurrence
• Frequency of epilepsy in autism ranged from 5% to about 40%
• The majority onset of epilepsy in autism is above 10 years old of age
• Intellectual disability greatly increases the risk of epilepsy in people with
autism
Kanner L. Autistic disturbances of affective contact. Nerv Child. 1943;2(3):217–250.
Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol. 2002;1(6):352–358.
Bolton PF, Carcani-Rathwell I, Hutton J, Goode S, Howlin P, Rutter M. Epilepsy in autism: features and correlates. Br J Psychiatry. 2011;198(4):289–294.
Amiet C, Gourfinkel-An I, Bouzamondo A, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry. 2008;64(7):577–582

3. Does Epilepsy Cause Autism ?
• Epilepsy does not cause autism
• Epilepsy syndromes associated with autism:
- Landau–Kleffner syndrome
- West syndrome – tuberous sclerosis
Besag FM. Epilepsy in patients with autism: links, risks and treatment challenges. Neuropsychiatric disease and treatment. 2018;14:1.

4. Epilepsy and Autism
Environtmental
Genetics
Evidence now favors a common underlying cause for both conditions
Besag FM. Epilepsy in patients with autism: links, risks and treatment challenges. Neuropsychiatric disease and treatment. 2018;14:1.

5. Jeste SS, Tuchman R. Autism spectrum disorder and epilepsy: two sides of the same coin?. Journal of child neurology. 2015 Dec;30(14):1963-71.

8. Environtmental Factors
• Air pollution
• Intrauterine infection
• Mother takes the antiepileptic drug sodium valproate during pregnancy
• Brain damage arising during delivery
• Neonatal factors such as severe neonatal jaundice
• Metabolic disorders
Besag FM. Epilepsy in patients with autism: links, risks and treatment challenges. Neuropsychiatric disease and treatment. 2018;14:1.

9. Hashimoto et al. 2001 and Eeg-Olofsson et al. 1971

10. Management
• Both conditions should be managed as they would be when occurring
individually
• Tuberous sclerosis - sirolimus (rapamycin) or everolimus
• Some antiepileptic drugs can have effects on mood, behavior or cognition
(levetiracetam: mood deterioration, lamotrigine: mood leveling, topiramate:
world finding difficulties)
• Immunotherapy
Krueger DA, Northrup H, Group ITSCC Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):255–265.
Aldenkamp A, Besag F, Gobbi G, Caplan R, Dunn DW, Sillanpää M. Psychiatric and behavioural disorders in children with epilepsy (ILAE Task Force Report): adverse cognitive and behavioural effects of antiepileptic drugs in children. Epileptic Disord. 2016;18(s1):S55–S67.
Brodie MJ, Besag F, Ettinger AB, et al. Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev. 2016;68(3):563–602. [PMC free article]
Vincent A, Bien CG, Irani SR, Waters P. Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol. 2011;10(8):759–772.
Irani SR, Gelfand JM, Al-Diwani A, Vincent A. Cell-surface central nervous system autoantibodies: clinical relevance and emerging paradigms. Ann Neurol. 2014;76(2):168–184.

11. Comorbidities
ADHD
Sleep
Problems
Anxiety
Besag FM. Epilepsy in patients with autism: links, risks and treatment challenges. Neuropsychiatric disease and treatment. 2018;14:1.

12. Attention Deficit Hyperactivity Disorder
• ADHD is common in children with epilepsy, children with autism and
children with both conditions together
• Some children with epilepsy present with features of ADHD that are the
result of frequent epileptiform discharges  treat the epilepsy
• As a result of inappropriate antiepileptic medication; for example, treatment
with phenobarbital, benzodiazepines or vigabatrin
• Methylphenidate is safe and effective in children with ADHD and
concomitant active seizures or EEG abnormalities
Sillanpää M, Besag F, Aldenkamp A, Caplan R, Dunn DW, Gobbi G. Psychiatric and behavioural disorders in children with epilepsy (ILAE Task Force Report): epidemiology of psychiatric/behavioural disorder in children with epilepsy. Epileptic Disord. 2016;18(s1):S2–S7.
Besag F, Gobbi G, Caplan R, Sillanpää M, Aldenkamp A, Dunn DW. Psychiatric and behavioural disorders in children with epilepsy (ILAE Task Force Report): epilepsy and ADHD. Epileptic Disord. 2016;18(s1):S8–S15.
Gucuyener K, Erdemoglu AK, Senol S, Serdaroglu A, Soysal S, Kockar AI. Use of methylphenidate for attention-deficit hyperactivity disorder in patients with epilepsy or electroencephalographic abnormalities. J Child Neurol. 2003;18(2):109–112.

13. Anxiety
• Anxiety is common in young people who have both epilepsy and autism
• Cognitive-behavioral therapy and other psychologic interventions (first-line)
and then low dose risperidone
Dunn DW, Besag F, Caplan R, Aldenkamp A, Gobbi G, Sillanpää M. Psychiatric and behavioural disorders in children with epilepsy (ILAE Task Force Report): anxiety, depression and childhood epilepsy. Epileptic Disord. 2016;18(s1):S24–S30.
McDougle CJ, Scahill L, Aman MG, et al. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry. 2005;162(6):1142–1148.
Holzhausen SP, Guerreiro MM, Baccin CE, Montenegro MA. Use of risperidone in children with epilepsy. Epilepsy Behav. 2007;10(3):412–416.

14. Sleep Problems
• Sleep problems are very common in children with autism, with or without
epilepsy
• Nocturnal seizures ?
• Melatonin as a treatment for sleep-onset insomnia in children with epilepsy
and autism
Gail Williams P, Sears LL, Allard A. Sleep problems in children with autism. J Sleep Res. 2004;13(3):265–268.
Malow BA. Sleep disorders, epilepsy, and autism. Ment Retard Dev Disabil Res Rev. 2004;10(2):122–125.
Jain S, Besag FM. Does melatonin affect epileptic seizures? Drug Saf. 2013;36(4):207–215.
Lima E, Cabral FR, Cavalheiro EA, Naffah-Mazzacoratti MG, Amado D. Melatonin administration after pilocarpine-induced status epilepticus: a new way to prevent or attenuate postlesion epilepsy? Epilepsy Behav. 2011;20(4):607–612.
Solmaz I, Gurkanlar D, Gokcil Z, Goksoy C, Ozkan M, Erdogan E. Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol-induced seizures. Neurol Res. 2009;31(9):989–995.

15. Summary
• Epilepsy and autism: common co-occurrence
• In most cases, the link between epilepsy and autism arises from a common
underlying factor, it is essential to ensure that the autistic features are not the
result of inadequately treated epilepsy
• There are multiple genetic and environmental causes for both ASD and
epilepsy
• Good management of autism, epilepsy and comorbidities can greatly
improve the quality of life