Review articleAutism spectrum disorders and epilepsy: Moving towards a comprehensive approach to treatment
Introduction
Autism spectrum disorder (ASD) is a broad classification that includes a heterogeneous group of individuals with behaviorally defined impairments in reciprocal social interaction, verbal and non-verbal communication, and restricted and repetitive behaviors. The ASD category includes those with autistic disorder, pervasive developmental disorder not otherwise specified or Asperger syndrome. It excludes two other categories included in the Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision (DSM IV-TR) [1] and the 10th Edition of the International Classification of Diseases (ICD 10), Rett disorder and childhood disintegrative disorder. Epilepsy is another broad diagnostic category and is defined as having more than one seizure. Seizures are the most dramatic aspect of epilepsy although recent definitions of epilepsy have emphasized the neurologic, cognitive, psychological, and social consequences of this group of disorders [2]. Classification systems for seizures [3] and for epilepsy [4] have been developed and are academically useful but how best to classify seizures and define epilepsy remains an evolving and controversial issue [5].
The prevalence of epilepsy in the ASD population is estimated to be approximately 30% although this number is highly variable depending on the study sample [6]. While the prevalence of ASD in children with epilepsy has been studied less, Clark and colleagues [7] found that approximately 30% of children in a tertiary epilepsy clinic met criteria for ASD. Clearly, the association of ASD and epilepsy is higher than one would expect by chance and the co-occurrence of ASD and epilepsy negatively impacts developmental outcomes and quality of life [8].
In children with epilepsy, younger age at seizure onset, cognitive impairment, temporal or frontal lobe onset of seizures, and intractable epilepsy are associated with an increased likelihood of co-existing social-communication and behavioral disorders [9]. In children with ASD, cognitive and motor impairments, severity of receptive language deficits, and genetic and molecular abnormalities are associated with an increased prevalence of epilepsy [10]. In some children with co-occurring ASD and epilepsy there appears to be a common etiology and pathogenesis. However, our understanding of the pathophysiology of co-occurring ASD and epilepsy is still limited. While the ASD and epilepsy categories are useful and practical for classification purposes they are mainly descriptive and do not reflect singular entities with uniform etiologies [11], [12]. It follows that there is no one single treatment or treatment protocol for children with ASD or epilepsy.
How often a common cause accounts for the co-occurrence of ASD and epilepsy is an interesting but as yet unanswered question. The answer to this question and an understanding of the pathogenesis common to both ASD and epilepsy will provide an avenue for novel therapeutics. At present, the known biological and phenotypic heterogeneity of children with ASD–epilepsy phenotypes presents a significant challenge to the development of treatment protocols. Throughout this review of intervention options we highlight therapeutic strategies most likely to improve developmental outcomes for children with ASD and epilepsy.
Section snippets
Children with ASD who develop epilepsy
The aim of treatment in children with epilepsy is to effectively eliminate seizures without compromising cognitive and behavioral functions [13]. This aim applies equally to the treatment of epilepsy in children with an established diagnosis of ASD [14], [15]. Pharmacological interventions for epilepsy that reduce and eliminate seizures have been developed [16] and these medications are effective in reducing or eliminating seizures in children with ASD and epilepsy. As in epilepsy, seizure
Children with epilepsy who develop ASD
In children with epilepsy the highest risk for developing ASD is in those with seizures in the first year of life [80]. Approximately 40% of all epilepsies occurring during the first 3 years of life fit the definition of epileptic encephalopathies [11]. Epileptic encephalopathies are defined as “a condition in which the epileptiform abnormalities themselves are believed to contribute to the progressive disturbance in cerebral function” [81]. The epileptic encephalopathies begin early in life and
Controversies in treatment: regression and epileptiform EEG
There continues to be debate whether epilepsy or the epileptiform EEG could be a causal factor in the development of the ASD phenotype and whether treatment, medical or surgical, can prevent or reverse the cognitive and behavioral manifestations [140]. What we can say is that children with epileptic encephalopathies, especially those with seizures in the first 3 years of life, are at high risk for the development of ASD. What is controversial is whether epileptiform activity can trigger
Conclusions
Advances in our understanding of the molecular biology of ASD and of epilepsy now allow us to conceptualize intervention strategies that may positively change the developmental trajectory of both ASD and epilepsy. An emerging approach to target more specifically the ASD–epilepsy phenotype is based on our understanding that abnormalities of synaptic structure and function are central to the brain basis of ASD [178] and of epilepsy [179]. Translation of basic science and mouse model data will be
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