title: Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.
abstract: The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, New York University, New York, New York.
authors.forename: Karen
authors.identifier: http://orcid.org/0000-0002-2665-7807
authors.initials: K
authors.lastname: Blackmon
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, New York University, New York, New York.
authors.forename: Judith
authors.initials: J
authors.lastname: Bluvstein
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, New York University, New York, New York.
authors.forename: William S
authors.initials: WS
authors.lastname: MacAllister
authors.affiliation: Institute of Neurology and Neurosurgery at St. Barnabas, Livingston, New Jersey.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Avallone
authors.affiliation: Institute of Neurology and Neurosurgery at St. Barnabas, Livingston, New Jersey.
authors.forename: Jade
authors.initials: J
authors.lastname: Misajon
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, New York University, New York, New York.
authors.forename: Julie
authors.initials: J
authors.lastname: Hedlund
authors.affiliation: Institute of Neurology and Neurosurgery at St. Barnabas, Livingston, New Jersey.
authors.forename: Rina
authors.initials: R
authors.lastname: Goldberg
authors.affiliation: Institute of Neurology and Neurosurgery at St. Barnabas, Livingston, New Jersey.
authors.forename: Aviva
authors.initials: A
authors.lastname: Bojko
authors.affiliation: Woodhull Medical Center, Brooklyn, New York.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Mitra
authors.affiliation: University Hospital of Brooklyn at Long Island College Hospital, Brooklyn, New York.|State University of New York Downstate Medical Center, Brooklyn, New York.
authors.forename: Radha
authors.initials: R
authors.lastname: Giridharan
authors.affiliation: Jersey Shore Neurology Associates, P.A., Neptune, New Jersey.
authors.forename: Richard
authors.initials: R
authors.lastname: Sultan
authors.affiliation: Advocare Neurology of South Jersey, Lumberton, New Jersey.
authors.forename: Seth
authors.initials: S
authors.lastname: Keller
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, New York University, New York, New York.|Institute of Neurology and Neurosurgery at St. Barnabas, Livingston, New Jersey.
authors.forename: Orrin
authors.initials: O
authors.lastname: Devinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D004827:Epilepsy / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012306:Risk; D017678:Sex Distribution; D055815:Young Adult
keywords: autism spectrum disorder; complex autism; copy-number variants; developmental disorders; epilepsy; female protective model; idiopathic autism; sex differences