Association between Interictal Epileptiform Discharges and Autistic Spectrum Disorder

Laura Luz-Escamilla, José Antonio Morales-González, Laura Luz-Escamilla, José Antonio Morales-González

Abstract

It has been reported that bioelectric alterations in an electroencephalogram (EEG) may play an etiological role in neurodevelopmental disorders. The clinical impact of interictal epileptiform discharges (IEDs) in association with autistic spectrum disorder (ASD) is unknown. The Autism Diagnostic Interview-Revised (ADI-R) is one of the gold standards for the diagnosis of autistic spectrum disorder. Some studies have indicated high comorbidity of IED and ASD, while other studies have not supported an association between the central symptoms of autism and IED. This review examines the high comorbidity and clinical impact of IED; patients with epilepsy are excluded from the scope of this review. ASD can be disabling and is diagnosed at an average age of 5 years old, at which point the greatest neurological development has occurred. If an association between IED and ASD is identified, a clinical tool that entails an innocuous procedure could enable diagnosis in the first years of life. However, in the absence of reports that prove an association between IED and ASD, patients should not be subjected to expensive treatments, such as the administration of anticonvulsant therapies.

Keywords: ADI-R; EEG; autistic spectrum disorder; interictal epileptiforme discharges.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Rapin I., Tuchman R.F. Autism: Definition, Neurobiology, Screening, Diagnosis. Pediatr. Clin. N. Am. 2008;55:1129–1146. doi: 10.1016/j.pcl.2008.07.005.
    1. Sarah J.S., Mark T.S. The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders. Pediatr. Res. 2009;65:599–606.
    1. Ghacibeh G.A., Fields C. Interictal epileptiform activity and autism. Epilepsy Behav. 2015;47:158–162. doi: 10.1016/j.yebeh.2015.02.025.
    1. Giovanardi R.P., Posar A., Parmeggiani A. Epilepsy in adolescents and young adults with autistic disorder. Brain Dev. 2000;22:102–106. doi: 10.1016/S0387-7604(99)00124-2.
    1. Kawasaki Y., Yokota K., Shinomiya M., Shimizu Y., Niwa S. Brief report: Electroencephalographic paroxysmal activities in the frontal area emerged in middle childhood and during adolescence in a follow-up study of autism. J. Autism Dev. Disord. 1997;27:605–620. doi: 10.1023/A:1025886228387.
    1. Volkmar F.R., Nelson D.S. Seizure disorders in autism. J. Am. Acad. Child Adolesc. Psychiatry. 1990;29:127–129. doi: 10.1097/00004583-199001000-00020.
    1. Akshoomoff N., Farid N., Courchesne E., Haas R. Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders. J. Autism Dev. Disord. 2007;37:887–893. doi: 10.1007/s10803-006-0216-9.
    1. Chez M.G., 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;8:267–271. doi: 10.1016/j.yebeh.2005.11.001.
    1. Kim H.L., Donnelly J.H., Tournay A.E., Book T.M., Filipek P. Absence of seizures despite high prevalence of epileptiform EEG abnormalities in children with autism monitored in a tertiary care center. Epilepsia. 2006;47:394–398. doi: 10.1111/j.1528-1167.2006.00434.x.
    1. McVicar K.A., Ballaban-Gil K., Rapin I., Moshe S.L., Shinnar S. Epileptiform EEG abnormalities in children with language regression. Neurology. 2005;65:129–131. doi: 10.1212/01.wnl.0000167193.53817.0f.
    1. Rossi P.G., Parmeggiani A., Bach V., Santucci M., Visconti P. EEG features and epilepsy in patients with autism. Brain Dev. 1995;17:169–174. doi: 10.1016/0387-7604(95)00019-8.
    1. Viscidi E.W., Triche E.W., Pescosolido M.F., McLean R.L., Joseph R.M., Spence S.J., Morrow E.M. Clinical characteristics of children with autism spectrum disorder and co-occurring epilepsy. PLoS ONE. 2013;8:e67797. doi: 10.1371/journal.pone.0067797.
    1. Hollander E., Soorya L., Wasserman S., Esposito K., Chaplin W., Anagnostou E. Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. Int. J. Neuropsychopharmacol. 2006;9:209–213. doi: 10.1017/S1461145705005791.
    1. Hirota T., Veenstra-Vanderweele J., Hollander E., Kishi T. Antiepileptic medications in autism spectrum disorder: A systematic review and meta-analysis. J. Autism Dev. Disord. 2014;44:948–957. doi: 10.1007/s10803-013-1952-2.
    1. Belsito K.M., Law P.A., Kirk K.S., Landa R.J., Zimmerman A.W. Lamotrigine therapy for autistic disorder: A randomized, double-blind, placebo-controlled trial. J. Autism Dev. Disord. 2001;31:175–181. doi: 10.1023/A:1010799115457.
    1. Wasserman S., Iyengar R., Chaplin W.F., Watner D., Waldoks S.E., Anagnostou E., Soorya L., Hollander E. Levetiracetam versus placebo in childhood and adolescent autism: A double-blind placebocontrolled study. Int. Clin. Psychopharmacol. 2006;21:363–367. doi: 10.1097/01.yic.0000224787.13782.0f.
    1. Tharp B.R. Epileptic encephalopathies and their relationship to developmental disorders: Do spikes cause autism? Dev. Disabil. Res. Rev. 2004;10:132–134. doi: 10.1002/mrdd.20025.
    1. DSM 5 American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; Arlington, VA, USA: 2014.
    1. Boutros N. Standard EEG: A Research Roadmap for Neuropsychiatry. Springer; New York, NY, USA: 2014.
    1. McConachie H., Barry R., Spencer A., Parker L., Le Couteur A., Colver A.D. The Challenge of Developing a Regional database for Autism Spectrum Disorder. Arch. Dis. Child. 2009;94:38–41. doi: 10.1136/adc.2007.126326.
    1. Fombonne E., Marcin C., Manera A.C. Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey. J. Autism Dev. Disord. 2016;46:1669–1685. doi: 10.1007/s10803-016-2696-6.
    1. Mulas F., Etchepareborda M.C., Hernández-Muela S., Abad-Mas L., Téllez de Meneses M., Mattos L. Bases neurobiológicas de los trastornos específicos de la comunicación (espectro autista) Rev. Neurol. 2005;41(Suppl. 1):S149–S153.
    1. Volkmar F.R., Lord C., Bailey A., Schultz R.T., Klin A. Autism and pervasive developmental disorders. J. Child Psychol. Psychiatry. 2004;45:135–170. doi: 10.1046/j.0021-9630.2003.00317.x.
    1. Belger A., Carpenter K.L., Yucel G.H., Cleary K.M., Donkers F.C. The Neural Circuitry of Autism. Neurotox Res. 2011;20:201–214. doi: 10.1007/s12640-010-9234-7.
    1. Parmeggiani A., Barcia G., Posar A., Raimondi E., Santucci M., Scaduto M.C. Epilepsy and EGG paroxysmal abnormalities in autism spectrum disorders. Brain Dev. 2010;32:783–789. doi: 10.1016/j.braindev.2010.07.003.
    1. Wiggins L.D., Baio J., Rice C. Examination of the time between first evaluation and first autism spectrum diagnosis in a population-based sample. J. Dev. Behav. Pediatr. 2006;27(Suppl. 2):S79–S87. doi: 10.1097/00004703-200604002-00005.
    1. Sandra B., Magaña V.S., Morales M., McNamara E. Clinical Validity of the ADI-R in a US-Based Latino Population. J. Autism Dev. Disord. 2016;46:1623–1635.
    1. Scott L.J., Dhillon S. Spotlight on risperidone in irritability associated with autistic disorder in children and adolescents. CNS Drugs. 2008;22:259–262. doi: 10.2165/00023210-200822030-00006.
    1. Jesner O.S., Aref–Adib M., Coren E. Risperidone for autism spectrum disorder. Cochrane Database Syst. Rev. 2007:CD005040. doi: 10.1002/14651858.CD005040.pub2.
    1. Hirosawa T., Kikuchi M., Fukai M., Hino S., Kitamura T., An K.M., Sowman P., Takahashi T., Yoshimura Y., Miyagishi Y., et al. Association Between Magnetoencephalographic Interictal: Epileptiform Discharge and Cognitive Function in Young Children With Typical Development and With Autism Spectrum Disorders. Front. Psychiatry. 2018;9:568. doi: 10.3389/fpsyt.2018.00568.
    1. Drenthen G.S., Barendse E.M., Aldenkamp A.P., Van Veenendaal T.M., Puts N.A., Edden R.A., Zinger S., Thoonen G., Hendriks M.P., Kessels R., et al. Altered neurotransmitter metabolism in adolescents with high-functioning autism. Psychiatry Res. 2016;256:44–49. doi: 10.1016/j.pscychresns.2016.09.007.
    1. Dawson M., Soulieres I., Gernsbacher M.A., Mottron L. The level and nature of autistic intelligence. Psychol. Sci. 2007;18:657–662. doi: 10.1111/j.1467-9280.2007.01954.x.
    1. Nader A.M., Courchesne V., Dawson M., Soulieres I. Does WISC-IV underestimate the intelligence of autistic children? J. Autism Dev. Disord. 2016;46:1582–1589. doi: 10.1007/s10803-014-2270-z.
    1. Glennon J.M., Weiss-Croft L., Harrison S., Cross J.H., Boyd S.G., Baldeweg T. Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy. Epilepsia. 2016;57:1436–1442. doi: 10.1111/epi.13479.
    1. Holmes G., Lenck-Santini P. Role of interictal epileptiform abnormalities in cognitive impairment. Epilepsy Behav. 2006;8:504–515. doi: 10.1016/j.yebeh.2005.11.014.
    1. Shewmon D., Erwin R. Focal spike-induced cerebral dysfunction is related to the after coming slow wave. Ann. Neurol. 1988;23:131–137. doi: 10.1002/ana.410230205.
    1. Hasselmo M. Neuromodulation: Acetylcholine and memory consolidation. Trends Cogn. Sci. 1999;3:351–359. doi: 10.1016/S1364-6613(99)01365-0.
    1. Buzsaki G. Memory consolidation during sleep: A neurophysiological perspective. J. Sleep Res. 1998;7(Suppl. 1):17–23. doi: 10.1046/j.1365-2869.7.s1.3.x.
    1. Louie K., Wilson M. Temporally structured replay of awake hippocampal ensemble activity during no REM sleep. Neuron. 2001;29:145–156. doi: 10.1016/S0896-6273(01)00186-6.
    1. Faught E., Karakis I., Drane D.L. The Impact of Interictal Discharges on Performance. Curr. Neurol. Neurosci. Rep. 2018;18:88. doi: 10.1007/s11910-018-0892-9.
    1. Barkmeier D.T., Senador D., Leclercq K., Pai D., Hua J., Boutros N.N., Kaminski R.M., Loeb J.A. Electrical, molecular and behavioral effects of interictal spiking in the rat. Neurobiol. Dis. 2012;47:92–101. doi: 10.1016/j.nbd.2012.03.026.
    1. Rakhade S.N., Shah A.K., Agarwal R., Yao B., Asano E., Loeb J.A. Activity-dependent gene expression correlates with interictal spiking in human neocortical epilepsy. Epilepsia. 2007;48(Suppl. 5):86–95. doi: 10.1111/j.1528-1167.2007.01294.x. Erratum in Epilepsia2007, 48, 2380.
    1. Aldenkamp A.P., Beitler J., Arends J., van der Linden I., Diepman L. Acute effects of subclinical epileptiform EEG discharges on cognitive activation. Funct. Neurol. 2005;20:23–28.
    1. Stores G. Electroencephalographic parameters in assessing the cognitive function of children with epilepsy. Epilepsia. 1990;31(Suppl. 4):S45–S49. doi: 10.1111/j.1528-1157.1990.tb05870.x.
    1. Ibrahim G.M., Cassel D., Morgan B.R., Smith M.L., Otsubo H., Ochi A., Taylor M., Rutka J.T., Snead O.C., 3rd, Doesburg S. Resilience of developing brain networks to interictal epileptiform discharges is associated with cognitive outcome. Brain. 2014;137:2690–2702. doi: 10.1093/brain/awu214.
    1. Aarts J., Binnie C., Smit A., Wilkins A. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain. 1984;107:293–308. doi: 10.1093/brain/107.1.293.
    1. Provinciali L., Signorino M., Censori B., Ceravolo G., Del Pesce M. Recognition impairment correlated with short bisynchronousepileptic discharges. Epilepsia. 1991;32:684–689. doi: 10.1111/j.1528-1157.1991.tb04710.x.
    1. Aldenkamp A.P., Arends J., De la Parra N.M., Migchelbrink E.J. The cognitive impact of EEG discharges and short epileptic seizures: Relationship to characteristics of the cognitive tasks. Epilepsy Behav. 2010;17:205–209. doi: 10.1016/j.yebeh.2009.11.024.
    1. Hughes J.R., Melyn M. EEG and seizures in autistic children and adolescents: Further findings with therapeutic implications. Clin. EEG Neurosci. 2005;36:15–20. doi: 10.1177/155005940503600105.
    1. Binnie C., Kasteleijn-Nolst D., Smit A., Wilkins A. Interactions of epileptiform EEG discharges and cognition. Epilepsy Res. 1987;1:239–245. doi: 10.1016/0920-1211(87)90031-3.
    1. Binnie C. Cognitive impairment during epileptiform discharges: Is it ever justifiable to treat the EEG? Lancet Neurol. 2003;2:725–730. doi: 10.1016/S1474-4422(03)00584-2.
    1. Brinciotti M., Matricardi M., Paolella A., Porro G., Benedetti P. Neuropsychological correlates of subclinical paroxysmal EEG activity in children with epilepsy: Qualitative features (generalized and focal abnormalities) Funct. Neurol. 1989;4:235–239.
    1. Tuchman R.F., Rapin I. Regression in pervasive developmental disorder: Seizures and epileptiform electroencephalogram correlates. Pediatrics. 1997;99:560–566. doi: 10.1542/peds.99.4.560.
    1. Yasuhara A. Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD) Brain Dev. 2010;32:791–798. doi: 10.1016/j.braindev.2010.08.010.
    1. Baird G., Robinson R.O., Boyd S., Charman T. Sleep electroencephalograms in young children with autism with and without regression. Dev. Med. Child Neurol. 2006;48:604–608. doi: 10.1017/S0012162206001265.
    1. Mulligan C.K., Trauner D.A. Incidence and behavioral correlates of epileptiformabnormalities in autism spectrum disorders. J. Autism Dev. Disord. 2014;44:452–458. doi: 10.1007/s10803-013-1888-6.
    1. Gibbs P.A., Lennox W.G., Gibbs E.L. The electroencephalogram in diagnosis and in localisation of epileptic seizures. Arch. Neurol. Psychiatry. 1936;36:1225–1235. doi: 10.1001/archneurpsyc.1936.02260120072005.
    1. Schwab R.S. A method of measuring consciousness in attacks of petit mal epilepsy. Arch. Neurol. Psychiatry. 1939;41:215–217.
    1. Rausch R., Lieb J.P., Crandall P.H. Neuropsychological correlates of depth spike activity in epileptic patients. Arch. Neurol. 1978;35:6–12. doi: 10.1001/archneur.1978.00500350003002.
    1. Siebelink B.M., Bakker D.J., Binnie C.D., Kasteleijn-Nolst Trenité D.G. Psychological effects of subclinical epileptiform EEG discharges in children. II. General intelligence tests. Epilepsy Res. 1988;2:117–121. doi: 10.1016/0920-1211(88)90028-9.
    1. Kleen J.K., Scott R.C., Holmes G.L., Roberts D.W., Rundle M.M., Testorf M., Lenck-Santini P.P., Jobst B.C. Hippocampal interictal epileptiform activity disrupts cognition in humans. Neurology. 2013;81:18–24. doi: 10.1212/WNL.0b013e318297ee50.
    1. Capdevila O.S., Dayyat E., Kheirandish-Gozal L., Gozal D. Prevalence of epileptiform activity in healthy children during sleep. Sleep Med. 2008;9:303–309. doi: 10.1016/j.sleep.2007.03.024.
    1. El S. Interictal epileptiform discharges in persons without a history of seizures: What do they mean? J. Clin. Neurophysiol. 2010;27:229–238.
    1. Picard A., Cheliout Heraut F., Bouskraoui M., Lemoine M., Lacert P., Delattre J. Sleep EEG and developmental dysphasia. Dev. Med. Child Neurol. 1998;40:595–599. doi: 10.1111/j.1469-8749.1998.tb15424.x.
    1. Sánchez Fernández I., Loddenkemper T., Galanopoulou A.S., Moshé S.L. Should epileptiform discharges be treated? Epilepsia. 2015;56:1492–1504. doi: 10.1111/epi.13108.
    1. Hrdlicka M., Komarek V., Propper L., Kulisek R., Zumrova A., Faladova L., Havlovicova M., Sedlacek Z., Blatny M., Urbanek T. Not EEG abnormalities but epilepsy is associated with autistic regression and mental functioning in childhood autism. Eur. Child Adolesc. Psychiatry. 2004;13:209–213. doi: 10.1007/s00787-004-0353-7.
    1. Hara H. Autism and epilepsy: A retrospective follow-up study. Brain Dev. 2007;29:486–490. doi: 10.1016/j.braindev.2006.12.012.
    1. Parmeggiani A., Posar A., Antolini C., Scaduto M.C., Santucci M., Giovanardi-Rossi P. Epilepsy in patients with pervasive developmental disorder not otherwise specified. J. Child Neurol. 2007;22:1198–1203. doi: 10.1177/0883073807306265.
    1. Shinnar S., Rapin I., Arnold S., Tuchman R.F., Shulman L., Ballaban-Gil K., Maw M., Deuel R.K., Volkmar F.R. Language regression in childhood. Pediatr. Neurol. 2001;24:183–189. doi: 10.1016/S0887-8994(00)00266-6.
    1. Veerappan V.D., Sweetha B. Two-Year Follow-up of Isolated Epileptiform Discharges in Autism: An Endophenotypic Biomarker? Indian J. Psychol. Med. 2018;40:219–224.
    1. Kanemura H., Sano F., Tando T., Sugita K., Aihara M. Can EEG characteristics predict development of epilepsy in autistic children? J. Autism Dev. Disord. 2014;44:948–957. doi: 10.1016/j.ejpn.2012.10.002.
    1. Kagan-Kushnir T., Roberts S.W., Snead O.C. Screening electroencephalograms in autism spectrum disorders: Evidencebased guideline. J. Child Neurol. 2005;20:197–206. doi: 10.1177/08830738050200030601.
    1. Swatzyna R.J., Boutros N.N., Genovese A.C., MacInerney E.K., Roark A.J., Kozlowski G.P. Electroencephalogram (EEG) for children with autism spectrum disorder: Evidential considerations for routine screening. Eur. Child Adolesc. Psychiatry. 2019;28:615–624. doi: 10.1007/s00787-018-1225-x.
    1. Lewine J.D., Andrews R., Chez M., Patil A.A., Devinsky O., Smith M., Kanner A., Davis J.T., Funke M., Jones G., et al. Magnetoencephalographic patterns of epileptiform activity in childrenwith regressive autism spectrum disorders. Pediatrics. 1999;104:405–418. doi: 10.1542/peds.104.3.405.
    1. Milovanovic M., Radivojevic V., Radosavljev-Kircanski J., Grujicic R., Toskovic O., Aleksić-Hil O., Pejovic-Milovancevic M. Epilepsy and interictal epileptiform activity in patients with autism spectrum disorders. Epilepsy Behav. 2019;92:45–52. doi: 10.1016/j.yebeh.2018.12.011.
    1. Pressler R.M., Robinson R.O., Wilson G.A., Binnie C.D. Treatment of interictal epileptiform discharges can improve behavior in children with behavioral problems and epilepsy. J. Pediatr. 2005;146:112–117. doi: 10.1016/j.jpeds.2004.08.084.
    1. Hollander E., Dolgoff-Kaspar R., Cartwright C., Rawitt R., Novotny S. An open trial of divalproex sodium in autism spectrum disorders. J. Clin. Psychiatry. 2001;62:530–534. doi: 10.4088/JCP.v62n07a05.
    1. Rugino T.A., Samsock T.C. Levetiracetam in autistic children: An open-label study. J. Dev. Behav. Pediatr. 2002;23:225–230. doi: 10.1097/00004703-200208000-00006.
    1. Braun K.P. Preventing cognitive impairment in children with epilepsy. Curr. Opin. Neurol. 2017;30:140–147. doi: 10.1097/WCO.0000000000000424.

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