Epilepsy in patients with autism: links, risks and treatment challenges

Frank Mc Besag, Frank Mc Besag

Abstract

Autism is more common in people with epilepsy, approximately 20%, and epilepsy is more common in people with autism with reported rates of approximately 20%. However, these figures are likely to be affected by the current broader criteria for autism spectrum disorder (ASD), which have contributed to an increased prevalence of autism, with the result that the rate for ASD in epilepsy is likely to be higher and the figure for epilepsy in ASD is likely to be lower. Some evidence suggests that there are two peaks of epilepsy onset in autism, in infancy and adolescence. The rate of autism in epilepsy is much higher in those with intellectual disability. In conditions such as the Landau-Kleffner syndrome and nonconvulsive status epilepticus, the epilepsy itself may present with autistic features. There is no plausible mechanism for autism causing epilepsy, however. The co-occurrence of autism and epilepsy is almost certainly the result of underlying factors predisposing to both conditions, including both genetic and environmental factors. Conditions such as attention deficit hyperactivity disorder, anxiety and sleep disorders are common in both epilepsy and autism. Epilepsy is generally not a contraindication to treating these conditions with suitable medication, but it is important to take account of relevant drug interactions. One of the greatest challenges in autism is to determine why early childhood regression occurs in perhaps 25%. Further research should focus on finding the cause for such regression. Whether epilepsy plays a role in the regression of a subgroup of children with autism who lose skills remains to be determined.

Keywords: CSWS; Landau-Kleffner; autism; environment; epilepsy; genetics; regression.

Conflict of interest statement

Disclosure The author reports no conflicts of interest in this work.

References

    1. 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.
    1. Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012;129(2):256–264.
    1. Reilly C, Atkinson P, Das KB, et al. Neurobehavioral comorbidities in children with active epilepsy: a population-based study. Pediatrics. 2014;133(6):e1586–e1593.
    1. Kanner L. Autistic disturbances of affective contact. Nerv Child. 1943;2(3):217–250.
    1. Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol. 2002;1(6):352–358.
    1. Besag FM. Current controversies in the relationships between autism and epilepsy. Epilepsy Behav. 2015;47:143–146.
    1. 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.
    1. Lotter V. Epidemiology of autistic conditions in young children. Soc Psychiatry Psychiatric Epidemiol. 1966;1(3):124–135.
    1. Baird G, Simonoff E, Pickles A, et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP) Lancet. 2006;368(9531):210–215.
    1. Fombonne E. Estimated prevalence of autism spectrum conditions in Cambridgeshire is over 1% Evidence Based Mental Health. 2010;13(1):32.
    1. Kim YS, Fombonne E, Koh YJ, Kim SJ, Cheon KA, Leventhal BL. A comparison of DSM-IV pervasive developmental disorder and DSM-5 autism spectrum disorder prevalence in an epidemiologic sample. J Am Acad Child Adolesc Psychiatry. 2014;53(5):500–508.
    1. Gillberg C, Steffenburg S. Outcome and prognostic factors in infantile autism and similar conditions: a population-based study of 46 cases followed through puberty. J Autism Dev Disord. 1987;17(2):273–287.
    1. Volkmar FR, Nelson DS. Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry. 1990;29(1):127–129.
    1. El Achkar CM, Spence SJ. Clinical characteristics of children and young adults with co-occurring autism spectrum disorder and epilepsy. Epilepsy Behav. 2015;47:183–190.
    1. 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.
    1. Davies S, Heyman I, Goodman R. A population survey of mental health problems in children with epilepsy. Dev Med Child Neurol. 2003;45(5):292–295.
    1. Landau WM, Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology. 1957;7:523–530.
    1. Deonna TW. Acquired epileptiform aphasia in children (Landau-Kleffner syndrome) J Neurophysiol. 1991;8(3):288–298.
    1. Roulet Perez E, Davidoff V, Despland PA, Deonna T. Mental and behavioural deterioration of children with epilepsy and CSWS: acquired epileptic frontal syndrome. Dev Med Child Neurol. 1993;35(8):661–674.
    1. Deonna T, Beaumanoir A, Gaillard F, Assal G. Acquired aphasia in childhood with seizure disorder: a heterogeneous syndrome. Neuropadiatrie. 1977;8(3):263–273.
    1. Parr JR, Le Couteur A, Baird G, et al. Early developmental regression in autism spectrum disorder: evidence from an international multiplex sample. J Autism Dev Disord. 2011;41(3):332–340.
    1. Irwin K, Birch V, Lees J, et al. Multiple subpial transection in Landau-Kleffner syndrome. Dev Med Child Neurol. 2001;43(4):248–252.
    1. Deonna T, Roulet E. Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy. Epilepsia. 2006;47(Suppl 2):79–82.
    1. Baird G, Robinson RO, Boyd S, Charman T. Sleep electroencephalograms in young children with autism with and without regression. Dev Med Child Neurol. 2006;48(7):604–608.
    1. Besag FMC. Behavioral aspects of pediatric epilepsy syndromes. Epilepsy Behav. 2004;5(Suppl 1):S3–S13.
    1. Pavone P, Striano P, Falsaperla R, Pavone L, Ruggieri M. Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013. Brain Dev. 2014;36(9):739–751.
    1. Bolton PF, Park RJ, Higgins JN, Griffiths PD, Pickles A. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain. 2002;125(Pt 6):1247–1255.
    1. Jambaque I, Mottron L, Chiron C. Neuropsychological outcome in children with West syndrome. In: Jambaque I, Lassonde M, Dulac O, editors. Neuropsychology of Childhood Epilepsy. New York: Kluwer Academic/Plenum Publishers; 2001. pp. 175–183.
    1. Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2011;1380:42–77.
    1. Szatmari P, Jones MB. IQ and the genetics of autism. J Child Psychol Psychiatry. 1991;32(6):897–908.
    1. Charman T, Pickles A, Simonoff E, Chandler S, Loucas T, Baird G. IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP) Psychol Med. 2011;41(3):619–627.
    1. Forsgren L, Edvinsson SO, Blomquist HK, Heijbel J, Sidenvall R. Epilepsy in a population of mentally retarded children and adults. Epilepsy Res. 1990;6(3):234–248.
    1. Steffenburg U, Hagberg G, Viggedal G, Kyllerman M. Active epilepsy in mentally retarded children. I. Prevalence and additional neuro-impairments. Acta Paediatri. 1995;84(10):1147–1152.
    1. Canpolat M, Per H, Gumus H, et al. Rapamycin has a beneficial effect on controlling epilepsy in children with tuberous sclerosis complex: results of 7 children from a cohort of 86. Childs Nerv Syst. 2014;30(2):227–240.
    1. French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10056):2153–2163.
    1. Paciorkowski AR, Fang M. Chromosomal microarray interpretation: what is a child neurologist to do? Pediatr Neurol. 2009;41(6):391–398.
    1. Lee BH, Smith T, Paciorkowski AR. Autism spectrum disorder and epilepsy: disorders with a shared biology. Epilepsy Behav. 2015;47:191–201.
    1. Blackmon K. Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy. Epilepsy Behav. 2015;47:172–182.
    1. Margari L, Palumbi R, Campa MG, et al. Clinical manifestations in children and adolescents with corpus callosum abnormalities. J Neurol. 2016;263(10):1939–1945.
    1. Sundelin HE, Larsson H, Lichtenstein P, et al. Autism and epilepsy: a population-based nationwide cohort study. Neurology. 2016;87(2):192–197.
    1. Besag FM. Rate of epilepsy in people with autism and the rate of autism in people with epilepsy are high. Evid Based Med. 2016;21(6):230.
    1. Baieli S, Pavone L, Meli C, Fiumara A, Coleman M. Autism and phenylketonuria. J Autism Dev Disord. 2003;33(2):201–204.
    1. Schmidt RJ, Lyall K, Hertz-Picciotto I. Environment and autism: current state of the science. Cut Edge Psychiatry Pract. 2014;1(4):21–38.
    1. Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr. 1977;7(1):69–81.
    1. Meador KJ, Loring DW. Prenatal valproate exposure is associated with autism spectrum disorder and childhood autism. J Pediatr. 2013;163(3):924.
    1. Christensen J, Gronborg TK, Sorensen MJ, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013;309(16):1696–1703.
    1. Kuban KC, Joseph RM, O’shea TM, et al. Girls and boys born before 28 weeks gestation: risks of cognitive, behavioral, and neurologic outcomes at age 10 years. J Pediatr. 2016;173:69–75.e61.
    1. Singh R, Turner RC, Nguyen L, Motwani K, Swatek M, Lucke-Wold BP. Pediatric traumatic brain injury and autism: elucidating shared mechanisms. Behav Neurol. 2016;2016:8781725.
    1. Frye RE. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder. Epilepsy Behav. 2015;47:147–157.
    1. 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.
    1. 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.
    1. Brodie MJ, Besag F, Ettinger AB, et al. Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev. 2016;68(3):563–602.
    1. 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.
    1. 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.
    1. Dalton P, Deacon R, Blamire A, et al. Maternal neuronal antibodies associated with autism and a language disorder. Ann Neurol. 2003;53(4):533–537.
    1. 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.
    1. 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.
    1. Hemmer SA, Pasternak JF, Zecker SG, Trommer BL. Stimulant therapy and seizure risk in children with ADHD. Pediatr Neurol. 2001;24(2):99–102.
    1. 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.
    1. 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.
    1. Holzhausen SP, Guerreiro MM, Baccin CE, Montenegro MA. Use of risperidone in children with epilepsy. Epilepsy Behav. 2007;10(3):412–416.
    1. Spina E, Avenoso A, Facciola G, et al. Plasma concentrations of risperidone and 9-hydroxyrisperidone: effect of comedication with carbamazepine or valproate. Ther Drug Monit. 2000;22(4):481–485.
    1. Gail Williams P, Sears LL, Allard A. Sleep problems in children with autism. J Sleep Res. 2004;13(3):265–268.
    1. Malow BA. Sleep disorders, epilepsy, and autism. Ment Retard Dev Disabil Res Rev. 2004;10(2):122–125.
    1. Jain S, Besag FM. Does melatonin affect epileptic seizures? Drug Saf. 2013;36(4):207–215.
    1. 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.
    1. 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.

Source: PubMed

3
Tilaa