Autism and social cognition in epilepsy: implications for comprehensive epilepsy care.

PURPOSE OF REVIEW: The association of epilepsy, autism spectrum disorders (ASD) and social cognition is now well recognized. The overlap of these disorders is generating increasing scientific and clinical interest as the comprehensive management of epilepsy has expanded to include the cognitive and social consequences commonly being recognized as an integral part of epilepsy disorders. RECENT FINDINGS: Recent studies have shown that in individuals with ASD and intellectual disability the rate of epilepsy is as high as 20%. In those with ASD and no intellectual disability the rates of epilepsy are approximately 8%. In epilepsy those most likely to have ASD are those with intellectual disability. There is limited information regarding how often ASD impacts epilepsy and less data on the effect of epilepsy on social cognition. There is a convergence of evidence that when epilepsy coexists with ASD and intellectual disability they share etiopathogenic mechanisms. SUMMARY: There is a significant and important overlap between epilepsy and ASD and this has important implications for comprehensive care of all individuals with epilepsy. Early recognition of social deficits is essential. Treating the seizures in individuals with epilepsy and ASD is not enough. Clinicians need to be aware of and implement interventions that address the social-cognitive deficits.

Epilepsy, cognition, and neuropsychiatry (Epilepsy, Brain, and Mind, part 2).

Epilepsy is, of course, not one disease but rather a huge number of disorders that can present with seizures. In common, they all reflect brain dysfunction. Moreover, they can affect the mind and, of course, behavior. While animals too may suffer from epilepsy, as far as we know, the electrical discharges are less likely to affect the mind and behavior, which is not surprising. While the epileptic seizures themselves are episodic, the mental and behavioral changes continue, in many cases, interictally. The episodic mental and behavioral manifestations are more dramatic, while the interictal ones are easier to study with anatomical and functional studies. The following extended summaries complement those presented in Part 1.

Epilepsy and autism: neurodevelopmental perspective.

Epilepsy and autism coexist in up to 20% of children with either disorder. Current studies suggest that a frequent co-occurring condition in epilepsy and autism is intellectual disability, which shows a very high prevalence in those with both autism and epilepsy. In addition, these recent studies suggest that early-onset seizures may index a group of infants at high risk for developing autism, usually with associated intellectual deficits. In this review we discuss recent advances in the conceptualization of shared anatomical and molecular mechanisms that may account for the coexistence of epilepsy, autism, and intellectual disability. A major contribution to our improved understanding of the relationship among these three phenotypes is the discovery of multiple genomic variants that cut across them as well as other neurobehavioral phenotypes. As these discoveries continue they are very likely to elucidate causal mechanisms for the various phenotypes and pinpoint biologic pathways that may be amenable to therapeutic interventions for this group of neurodevelopmental disorders.

Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review pharmacologic and nonpharmacologic strategies for treating sleep disturbances in children and adolescents with autism spectrum disorder (ASD) and to develop recommendations for addressing sleep disturbance in this population. METHODS: The guideline panel followed the American Academy of Neurology 2011 guideline development process, as amended. The systematic review included studies through December 2017. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS LEVEL B: For children and adolescents with ASD and sleep disturbance, clinicians should assess for medications and coexisting conditions that could contribute to the sleep disturbance and should address identified issues. Clinicians should counsel parents regarding strategies for improved sleep habits with behavioral strategies as a first-line treatment approach for sleep disturbance either alone or in combination with pharmacologic or nutraceutical approaches. Clinicians should offer melatonin if behavioral strategies have not been helpful and contributing coexisting conditions and use of concomitant medications have been addressed, starting with a low dose. Clinicians should recommend using pharmaceutical-grade melatonin if available. Clinicians should counsel children, adolescents, and parents regarding potential adverse effects of melatonin use and the lack of long-term safety data. Clinicians should counsel that there is currently no evidence to support the routine use of weighted blankets or specialized mattress technology for improving disrupted sleep. If asked about weighted blankets, clinicians should counsel that the trial reported no serious adverse events with blanket use and that blankets could be a reasonable nonpharmacologic approach for some individuals.

CSWS-related autistic regression versus autistic regression without CSWS.

Continuous spike-waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.

Autism: definition, neurobiology, screening, diagnosis.

Autism (ie, the autism spectrum disorders) is now recognized in 1 in 150 children. This article highlights the definition, neurobiology, screening, and diagnosis of autism. The genetics, immunology, imaging, and neurophysiology of autism are reviewed, with particular emphasis on areas that impact pediatricians. Early recognition of the social deficits that characterize autism is key to maximizing the potential of these children.

What is the Relationship Between Autism Spectrum Disorders and Epilepsy?

The association of epilepsy and autism spectrum disorders (ASD) is best understood by examining the relationship between social cognition, nonsocial cognition, and epilepsy. The relationship between ASD and epilepsy is bidirectional and is strongly linked to intellectual disability (ID). The risk of developing ASD in children with epilepsy is highest in children with early onset seizures, with a high prevalence in children with infantile spasms. The risk of developing epilepsy in children first diagnosed with ASD is highest in those with ID. The prevalence of seizures in ASD increases with age. When epilepsy and ASD coexist, they share common pathophysiological mechanisms. In epilepsy with and without ID, social-cognitive deficits are an important determinant of neurodevelopmental outcomes. Early recognition of social deficits is an important aspect of the comprehensive management of children with epilepsy. Treating the seizures in individuals with epilepsy and ASD is crucial but interventions that address social-cognitive deficits are necessary to maximize neurodevelopmental outcomes.

Autism and Cognition Within Epilepsy: Social Matters.

The association of epilepsy, autism spectrum disorders (ASD), and intellectual disability (ID) is well recognized. There is a wide range of social-cognitive deficits that can be identified in epilepsy over the life-span, from ASD in infants with an epileptic encephalopathy, to social-cognitive impairments affecting social interaction and comprehension in those with normal nonsocial cognitive function. Identifying ASD and social-cognitive deficits is an important aspect of comprehensive epilepsy care. There are behavioral and educational interventions that exist to treat ASD and social-cognitive deficits. These behavioral, communication, and educational interventions, in conjunction with medications to treat the seizures, should be considered an integral part of the comprehensive management of epilepsy throughout the life-span. The following are the key points of this review: Autism spectrum disorders and social-cognitive deficits are associated with epilepsy throughout the life-span, and identification of these deficits is an important part of epilepsy care.Children with an epileptic encephalopathy such as infantile spasms are at high risk for developing ASD, and the social-cognitive deficits that precede ASD may be recognized in the first year of life.In epilepsy, the likelihood of developing autism spectrum disorders is highest in those with ID, but there is a wide spectrum of manifestations, from ASD in children with epilepsy and ID, to social-cognitive impairments affecting social interaction and comprehension in those with normal nonsocial cognitive function.Implementation of behavioral, communication, and educational interventions that exist to treat ASD and social-cognitive deficits, along with medications to treat the seizures, should be considered an important part of the comprehensive management of epilepsy throughout the life-span.

Autism Spectrum Disorder and Epilepsy: Two Sides of the Same Coin?

Autism spectrum disorders and epilepsy commonly co-occur. In this review, we consider some unresolved questions regarding the temporal relationship, causal mechanisms, and clinical stratification of this comorbidity, highlighting throughout the interplay between autism spectrum disorder, epilepsy, and intellectual disability. We present data on the clinical characterization of children with autism spectrum disorder and epilepsy, discussing distinctive phenotypes in children with this comorbidity. Although some distinctive clinical features emerge, this comorbidity also informs convergent pathways in genetic variants that cause synaptic dysfunction. We then move beyond diagnostic categorization and consider the extent to which electrophysiology as a quantitative biomarker may help guide efforts in clinical stratification and outcome prediction. Epilepsy, and atypical electrophysiological patterns, in autism spectrum disorder may inform the definition of biologically meaningful subgroups within the spectrum that, in turn, can shed light on potential targets for intervention.

Epilepsy in autism.

There is an increased but variable risk of epilepsy in autism. Three main factors--age, cognitive level, and type of language disorder--account for variability in the reported prevalence of epilepsy. The prevalence is highest in studies that have included adolescents and young adults, individuals with moderate to severe mental retardation and those with motor deficits, and individuals with severe receptive language deficits. The association of autism with clinical or subclinical epilepsy might denote common genetic factors in some cases. Whether subclinical epilepsy has adverse effects on cognition, language, and behaviour is debated, as is the relation of autistic regression with an epileptiform electroencephalogram to Landau-Kleffner syndrome. There is no evidence-based treatment recommendation for individuals with autism, regression, and subclinical epilepsy. Double-blind studies with sufficient power to resolve this issue are urgently needed.

DOOR syndrome: deficiency of E1 component of the 2-oxoglutarate dehydrogenase complex.

Four patients from three families with the clinical features of DOOR syndrome (onycho-osteodystrophy, dystrophic thumbs, sensorineural deafness, and increased urinary levels of 2-oxoglutarate) are the subjects of this report. Our report deals with the autosomal recessive form of the disease, wherein the activity of 2-oxoglutarate decarboxylase (E1(0)) in fibroblasts and white blood cells of the patients is decreased. The activity of E1(0) in all patients' fibroblasts and white blood cells was significantly lower compared to the controls. This study demonstrates for the first time that E1(0) deficiency is an important biochemical marker for the autosomal recessive form of DOOR syndrome.

Autism.

Autism is a neurologic disorder with impairments in language, social communication, and behavior, which may improve over time, but which persist throughout the lifetime. The evaluation of autism requires a separation of clinical and research objectives and is done best in close cooperation with professionals in the fields of communication, education, and psychology. There are no biologic markers of autism. Regression in language and social communication is present in approximately 30% of children with autism and is most likely to occur between 18 and 24 months of age. Early deficits in social communication can be identified by the assessment of joint attention, affective reciprocity, and metacognition. Current evidence suggests that deficits in social cognition and communication in autism may be related to dysfunction in the amygdala, hippocampus, and related limbic and cortical structures. Other neuroanatomic structures, such as the cerebellum, also may form part of a distributed neuronal network responsible for social cognition and communication. Genetics play a major role in autism, but what is inherited and how broad the inheritable phenotype is remain unclear. At a neurochemical level, the principal neurotransmitter implicated in autism is serotonin. Seizures and epileptiform discharges are common in autism and are linked to cognitive dysfunction. The role of medication is to target specific symptoms and open windows of opportunity that allow implementation of a multimodal individualized educational plan.

[Autism and pervasive developmental disorders]. / Autismo e doenças invasivas de desenvolvimento.

OBJECTIVE: To review the current knowledge on neurobiological aspects of autism and pervasive developmental disorders, as well as to provide pediatricians with up to date information on diagnosis and treatment of autism. SOURCES OF DATA: Review of MEDLINE and Internet. SUMMARY OF THE FINDINGS: Autism is the 3rd developmental disorder, with an incidence of 40 to 130/100,000 individuals. Diagnosis is based on clinical findings, following DSM IV criteria. Neuroimaging, investigation of fetal neurological status, and genetic investigation contribute towards a better understanding of the neurobiology of autism. CONCLUSION: Pediatricians are the first health professional to come in contact with patients with autism. Thus, they should be able to diagnose and to coordinate the multidisciplinary treatment of these patients.

Deconstructing autism spectrum disorders: clinical perspective.

Autism spectrum disorder (ASD) is a term used to describe a heterogeneous group of children whose behaviorally defined characteristics overlap with the clinical manifestations of a variety of distinct behaviorally defined developmental disorders. ASD has many etiologies and strong but complex genetic and molecular underpinnings supporting genetic and phenotypic heterogeneity. Clinical and biological heterogeneity in ASD is consistent with the view of autism spectrum disorders as the expression of atypical brain development resulting in variable clinical manifestations that reflect differences in specific genetic and molecular pathways. It is likely that there are risk genes and early environmental risk factors for ASD that contribute to an altered trajectory of brain and behavioral development. These alterations are hypothesized to lead to altered social interaction and consequently to abnormal development of the neural networks critical for social and communicative interaction. This amplifies the abnormal socio-communicative developmental process leading to the full ASD syndrome. The hope is that interventions can alter these early developmental processes and put an infant back on a more typical developmental trajectory. In this discussion an overview of the limitations of the triad of behaviors used to diagnose ASD, specifically from the perspective of how these issues impact diagnosis and treatment of children with ASD will be presented and the clinical boundaries of the autism spectrum will be explored.

NINDS epilepsy and autism spectrum disorders workshop report.

The association of epilepsy and autism spectrum disorders (ASD), although well-recognized, is poorly understood. The purpose of this report is to summarize the discussion of a workshop sponsored by the National Institute of Neurological Disorders and Stroke, with support from the National Institute of Child Health and Human Development, Autism Speaks, and Citizens United for Research in Epilepsy, that took place in Bethesda, Maryland, on May 29 and 30, 2012. The goals of this workshop were to highlight the clinical and biological relationships between ASD and epilepsy, to determine both short- and long-term goals that address research and treatment conundrums in individuals with both ASD and epilepsy, and to identify resources that can further both clinical and basic research. Topics discussed included epidemiology, genetics, environmental factors, common mechanisms, neuroimaging, neuropathology, neurophysiology, treatment, and research gaps and challenges in this unique population.

Exploring the relationship between autism spectrum disorder and epilepsy using latent class cluster analysis.

Epilepsy co-occurs frequently in autism spectrum disorders (ASD). Understanding this co-occurrence requires a better understanding of the ASD-epilepsy phenotype (or phenotypes). To address this, we conducted latent class cluster analysis (LCCA) on an ASD dataset (N = 577) which included 64 individuals with epilepsy. We identified a 5-cluster solution with one cluster showing a high rate of epilepsy (29%), earlier age at first recognition, and high rates of repetitive object use and unusual sensory interests. We also conducted LCCA on an ASD-epilepsy subset from the overall dataset (N = 64) which yielded three clusters, the largest of which had impairments in language and motor development; the remaining clusters, while not as developmentally impaired were characterized by different levels of repetitive and sensory behaviors.