Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2018

Open Access 01-12-2018 | Research

Few individuals with Lennox-Gastaut syndrome have autism spectrum disorder: a comparison with Dravet syndrome

Authors: Na He, Bing-Mei Li, Zhao-Xia Li, Jie Wang, Xiao-Rong Liu, Heng Meng, Bin Tang, Wen-Jun Bian, Yi-Wu Shi, Wei-Ping Liao

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2018

Login to get access

Abstract

Background

Autism spectrum disorder (ASD) in epilepsy has been a topic of increasing interest, which in general occurs in 15–35% of the patients with epilepsy, more frequently in those with intellectual disability (ID). Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are two typical forms of intractable epileptic encephalopathy associated with ID. We previously reported that ASD was diagnosed in 24.3% of patients with DS, higher in those with profound ID. Given the severe epilepsy and high frequency of ID in LGS, it is necessary to know whether ASD is a common psychomotor co-morbidity of LGS. This study evaluated the autistic behaviors and intelligence in patients with LGS and further compared that between LGS and DS, aiming to understand the complex pathogenesis of epilepsy-ASD-ID triad.

Methods

A total of 50 patients with LGS and 45 patients with DS were enrolled and followed up for at least 3 years. The clinical characteristics were analyzed, and evaluations of ASD and ID were performed.

Results

No patients with LGS fully met the diagnostic criteria for ASD, but three of them exhibited more or less autistic behaviors. Majority (86%) of LGS patients presented ID, among which moderate to severe ID was the most common. Early onset age and symptomatic etiology were risk predictors for ID. The prevalence of ASD in LGS was significantly lower than that in DS (0/50 vs. 10/45, p < 0.001), while the prevalence and severity of ID showed no significant difference between the two forms of epileptic encephalopathy.

Conclusions

This study demonstrated a significant difference in the co-morbidity of ASD between LGS and DS, although they had a similar prevalence and severity of ID, refuting the proposal that the prevalence of ASD in epilepsy is accounted for by ID. These findings suggest that the co-morbidity of ASD, ID, and epilepsy may result from multifaceted pathogenic mechanisms.
Literature
1.
Hancock EC, Cross JH. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2013;2:CD003277.
2.
Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8(1):82–93.CrossRefPubMed
3.
Bourgeois BF, Douglass LM, Sankar R. Lennox-Gastaut syndrome: a consensus approach to differential diagnosis. Epilepsia. 2014;55(Suppl 4):4–9.CrossRefPubMed
4.
Ferlazzo E, Nikanorova M, Italiano D, Bureau M, Dravet C, Calarese T, et al. Lennox-Gastaut syndrome in adulthood: clinical and EEG features. Epilepsy Res. 2010;89(2–3):271–7.CrossRefPubMed
5.
Orrico A, Zollino M, Galli L, Buoni S, Marangi G, Sorrentino V. Late-onset Lennox-Gastaut syndrome in a patient with 15q11.2-q13.1 duplication. Am J Med Genet A. 2009;149A(5):1033–5.CrossRefPubMed
6.
Lo-Castro A, Curatolo P. Epilepsy associated with autism and attention deficit hyperactivity disorder: is there a genetic link? Brain and Development. 2014;36(3):185–93.CrossRefPubMed
7.
8.
Li BM, Liu XR, Yi YH, Deng YH, Su T, Zou X, et al. Autism in Dravet syndrome: prevalence, features, and relationship to the clinical characteristics of epilepsy and mental retardation. Epilepsy Behav. 2011;21(3):291–5.CrossRefPubMed
9.
Commission. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981;22(4):489–501.CrossRef
10.
Commission. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1989;30(4):389–99.CrossRef
11.
Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51(4):676–85.CrossRefPubMed
12.
13.
Goldsmith IL, Zupanc ML, Buchhalter JR. Long-term seizure outcome in 74 patients with Lennox-Gastaut syndrome: effects of incorporating MRI head imaging in defining the cryptogenic subgroup. Epilepsia. 2000;41(4):395–9.CrossRefPubMed
14.
Hoffmann-Riem M, Diener W, Benninger C, Rating D, Unnebrink K, Stephani U, et al. Nonconvulsive status epilepticus—a possible cause of mental retardation in patients with Lennox-Gastaut syndrome. Neuropediatrics. 2000;31(4):169–74.CrossRefPubMed
15.
Bennett MR, Hacker PM. Emotion and cortical-subcortical function: conceptual developments. Prog Neurobiol. 2005;75(1):29–52.CrossRefPubMed
16.
Vignoli A, La Briola F, Peron A, Turner K, Vannicola C, Saccani M, et al. Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers. Orphanet J Rare Dis. 2015;10:154.CrossRefPubMedPubMedCentral
17.
Berkvens JJ, Veugen I, Veendrick-Meekes MJ, Snoeijen-Schouwenaars FM, Schelhaas HJ, Willemsen MH, et al. Autism and behavior in adult patients with Dravet syndrome (DS). Epilepsy Behav. 2015;47:11–6.CrossRefPubMed
18.
Saemundsen E, Ludvigsson P, Hilmarsdottir I, Rafnsson V. Autism spectrum disorders in children with seizures in the first year of life—a population-based study. Epilepsia. 2007;48(9):1724–30.CrossRefPubMed
19.
Hara H. Autism and epilepsy: a retrospective follow-up study. Brain and Development. 2007;29(8):486–90.CrossRefPubMed
20.
Matsuo M, Maeda T, Sasaki K, Ishii K, Hamasaki Y. Frequent association of autism spectrum disorder in patients with childhood onset epilepsy. Brain and Development. 2010;32(9):759–63.CrossRefPubMed
21.
Amiet C, Gourfinkel-An I, Bouzamondo A, Tordjman S, Baulac M, Lechat P, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry. 2008;64(7):577–82.CrossRefPubMed
22.
Woolfenden S, Sarkozy V, Ridley G, Coory M, Williams K. A systematic review of two outcomes in autism spectrum disorder—epilepsy and mortality. Dev Med Child Neurol. 2012;54(4):306–12.CrossRefPubMed
23.
Berg AT, Plioplys S, Tuchman R. Risk and correlates of autism spectrum disorder in children with epilepsy: a community-based study. J Child Neurol. 2011;26(5):540–7.CrossRefPubMedPubMedCentral
24.
Tuchman R, Cuccaro M, Alessandri M. Autism and epilepsy: historical perspective. Brain and Development. 2010;32(9):709–18.CrossRefPubMed
25.
Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, et al. A structural MRI study of human brain development from birth to 2 years. J Neurosci. 2008;28(47):12176–82.CrossRefPubMedPubMedCentral
26.
Kurokawa T, Yokomizo Y, Lee S, Kusuda T. Clinical features of epilepsy with pervasive developmental disorder. Brain and Development. 2010;32(9):764–8.CrossRefPubMed
27.
Meng H, Xu HQ, Yu L, Lin GW, He N, Su T, et al. The SCN1A mutation database: updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat. 2015;36(6):573–80.CrossRefPubMed
28.
29.
Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, et al. De novo mutations in epileptic encephalopathies. Nature. 2013;501(7466):217–21.CrossRefPubMed
30.
Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet. 2013;45(7):825–30.CrossRefPubMedPubMedCentral
31.
32.
Chonchaiya W, Au J, Schneider A, Hessl D, Harris SW, Laird M, et al. Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder. Hum Genet. 2012;131(4):581–9.CrossRefPubMed
Metadata
Title
Few individuals with Lennox-Gastaut syndrome have autism spectrum disorder: a comparison with Dravet syndrome
Authors
Na He
Bing-Mei Li
Zhao-Xia Li
Jie Wang
Xiao-Rong Liu
Heng Meng
Bin Tang
Wen-Jun Bian
Yi-Wu Shi
Wei-Ping Liao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2018
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/s11689-018-9229-x

Other articles of this Issue 1/2018

Journal of Neurodevelopmental Disorders 1/2018 Go to the issue

Editorial

Inaugural annual special section of the intellectual and developmental disabilities research centers: developmental cognitive neuroscience and neurodevelopmental disorders

Research

Social skills in children with RASopathies: a comparison of Noonan syndrome and neurofibromatosis type 1

Research

Substance use and nicotine dependence in persistent, remittent, and late-onset ADHD: a 10-year longitudinal study from childhood to young adulthood

Research

Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome

Review

Cerebrospinal fluid and the early brain development of autism

Research

Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome