1. Abdel Razek A, Mazroa J, Baz H. {{Assessment of white matter integrity of autistic preschool children with diffusion weighted MR imaging}}. {Brain Dev};2013 (Feb 8)
The purpose was to assess white matter integrity of autistic preschool children with diffusion weighted MR imaging. Prospective study was carried on 19 autistic children (mean age 55.2ms, IQ of 86.5) and 10 sex, age and IQ matched control (mean age 53.2ms, IQ 84.5). The childhood Autism Rating Scale (CARS), social age and language age were calculated. Patients and controls underwent diffusion weighted MR imaging of the brain with b factor of 0, 500 and 1000s/mm(2). The apparent diffusion coefficient (ADC) value at different regions of the white matter were calculated and correlated with CARS, social age and language age. There were significant differences at the ADC value of the white matter between autistic and control children at genu (P=0.043), splenium (P=0.003) of the corpus callosum, frontal white matter (P=0.015) and temporal white matter (P=0.020). There was positive correlation of CARS score with ADC value of the genu (r=0.63, P=0.001), splenium (r=0.59, P=0.005), frontal white matter (r=0.81, P=0.001) and temporal white matter (r=0.74, P=0.001). The social age well correlated with ADC value of the frontal white matter (r=0.81, P=0.001) and language age well correlated with ADC value of the temporal white matter (r=0.78, P=0.001). We concluded that ADC value can be helpful in assessment of integrity of the white matter in autistic preschool children and well correlated with CARS score, social age and language age.
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2. Berry RJ, Crider KS, Yeargin-Allsopp M. {{Periconceptional folic acid and risk of autism spectrum disorders}}. {JAMA};2013 (Feb 13);309(6):611-613.
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3. Blaucok-Busch E, Amin OR, Dessoki HH, Rabah T. {{Efficacy of DMSA Therapy in a Sample of Arab Children with Autistic Spectrum Disorder}}. {Maedica (Buchar)};2012 (Sep);7(3):214-221.
Objective: the aim of this study was to provide evidence that DMSA detoxification treatments cause a reduction of the heavy metal burden in the autistic, and that this reduction lessens neurological symptoms associated with ASD (Autistic Spectrum Disorder).Method: The participants were 44 children, age 3 to 9 years of age, with Autistic Spectrum Disorder (ASD) according to Diagnostic and Statistical Manual of Mental Disorders 4t Edition, (DMS-IV). The severity of the autistics symptomatologiy had been measured by the Childhood Autism Rating Scale (SCARS). We collected urine samples before and after the DMSA challenge test, comparing urine metal output. We also compared the results of the DMSA detoxification(=the urine challenge test) with behavioral effects, typical for ASD.Results: The DMSA challenge test increased the urine metal output for a number of potentially toxic metals. Statistically significant difference were noted between the baseline urine and DMSA challenge test regarding the level of cadmium, mercury, and lead (P=0.006, P=0.049, and P=0.008 respectively). We also noted that behavioral effects, typical for ASD (autism spectrum disorders) were reduced with this method of detoxification. A comparison between CARS Subscales and Total Score before and after a 6-month chelation program showed greatest improvements for Verbal and nonverbal communication (P <0.001), Taste, Smell and Touch (P 0.001) and Relating to People (P 0.005). Other improvements were noted for Adaptation to Change and Improvement. Conclusion: DMSA chelation increased the urinary output of toxic and neurotoxic metals. Our data supports evidence that detoxification treatment with oral DMSA has beneficial effect on ASD patients.
4. Cheak-Zamora NC, Yang X, Farmer JE, Clark M. {{Disparities in Transition Planning for Youth With Autism Spectrum Disorder}}. {Pediatrics};2013 (Feb 11)
OBJECTIVE:Little is known about accessibility to health care transition (HCT) services for youth with autism spectrum disorder (ASD). This study expands our understanding by examining the receipt of HCT services in youth with ASD compared with youth with other special health care needs (OSHCN).METHODS:We used the 2005-2006 National Survey of Children with Special Health Care Needs to examine receipt of HCT services for youth (aged 12-17 years) with ASD and youth with OSHCN. Logistic regression analyses explored whether individual, family, or health system factors were associated with receipt of HCT services for youth with ASD.RESULTS:Whereas half of youth with OSHCN received HCT services, less than a quarter of youth with ASD did. Only 14% of youth with ASD had a discussion with their pediatrician about transitioning to an adult provider, less than a quarter had a discussion about health insurance retention, and just under half discussed adult health care needs or were encouraged to take on appropriate responsibility. Logistic regression analyses indicated that having a developmental disability or multiple health conditions in addition to ASD and quality of health care were strong predictors of HCT, whereas demographic and family variables accounted for little variance.CONCLUSIONS:Youth with ASD experience disparities in access to HCT services. Youth with comorbid conditions are at greatest risk for poor access to HCT services and increased quality of care has a positive effect. Research is needed to understand barriers to care and develop policy and practice guidelines tailored for youth with ASD.
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5. Das DK, Udani V, Sanghavi D, Adhia R, Maitra A. {{Mutational Analysis of Methyl-CpG Binding Protein 2 (MECP2) Gene in Indian Cases of Rett Syndrome}}. {J Clin Lab Anal};2013 (Feb 11)
Rett syndrome (RTT) is an X-linked postnatal neurological disorder, primarily affecting females and characterized by regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. RTT is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 200 individual nucleotide changes in the gene, which cause pathogenic mutations, have been reported; however, eight most commonly occurring missense and nonsense mutations account for almost 70% of all mutations. RTT cases have also been reported from India. The phenotype (classical and atypical inclusive) has many differentials. However, a genetically based confirmed diagnosis would help in management and counseling. In this pilot study we have analyzed MECP2 mutations in ten Indian sporadic patients diagnosed clinically as having RTT. Two mutations and one novel variant in MECP2 have been detected. Missense mutations p.R133C and c.806delG have been detected. The missence mutation p.R133C was the part of eight hotspots reported in Rett patients. This patient met all the essential criteria except delayed onset of regression. The other c.806delG mutation positive patient also fulfilled all the obligatory criteria of classical RTT. Another clinically atypical Rett patient showed a novel mutation p.C339S in MECP2 gene. The preliminary result necessitates a large-scale study of RTT patients to determine more precisely the influence of MECP2 mutations in Indian patients and their correlation with clinical phenotypes.
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6. Ferder I, Parborell F, Sundblad V, Chiauzzi V, Gomez K, Charreau E, Tesone M, Dain L. {{Expression of fragile X mental retardation protein (FMRP) and Fmr1 mRNA during folliculogenesis in the rat}}. {Reproduction};2013 (Feb 11)
Fragile X mental retardation protein belongs to a small family of RNA-binding proteins. Its absence or inactivity is responsible for Fragile X Syndrome, the most common cause of inherited mental retardation. Despite its ubiquitous expression, FMRP function and expression remain almost understudied in non-neuronal tissues, though previous studies on germline development during oogenesis may suggest a special function of this protein also in ovarian tissue. In addition, the well documented association of FMR1 premutation state with Fragile X-related Premature Ovarian Insufficiency adds interest to the role of FMRP in ovarian physiology. The aim of the present work was to investigate the expression of Fmr1 mRNA and its protein, FMRP, at different stages of rat follicular development. By immnuhistochemical studies, we demonstrated FMRP expression in granulosa, theca and the germ cell in all stages of follicular development. In addition, changes in Fmr1 expression, both at the protein and mRNA levels, were observed. FMRP levels increased upon follicular development, while preantral and early antral follicles presented similar levels of Fmr1 transcripts, with decreased expression in preovulatory follicles. These observations suggest that Fmr1 expression in the ovary is regulated at different and perhaps independent levels. In addition, our results also show expression of at least four different isoforms of FMRP during all stages of follicular growth, with expression patterns which differ from those observed in brain and testis. Our study shows a regulated expression of Fmr1, both at mRNA and protein levels, during rat follicular development.
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7. Flight MH. {{Neurodevelopmental disorders: Lovastatin as fragile X therapy}}. {Nat Rev Neurosci};2013 (Feb 13)
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8. Flintoft L. {{Disease genetics: Rare inherited mutations in autism}}. {Nat Rev Genet};2013 (Feb 12)
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9. Geier DA, Kern JK, Geier MR. {{A prospective Cross-sectional Cohort Assessment of Health, Physical, and Behavioral Problems in Autism Spectrum Disorders}}. {Maedica (Buchar)};2012 (Sep);7(3):193-200.
Objectives: Autism spectrum disorder (ASD) is diagnostically defined by impaired socialization/communication and stereotypical behaviors. Health, physical, and behavioral problems have also been described in subjects diagnosed with an ASD, but have usually been examined in isolation. The purpose of the present study was to for the first time, systematically and quantitatively, examines health, physical and behavioral problems in a cohort of subjects diagnosed with an ASD.Materials and Methods: A prospective cross-sectional ASD cohort (n=54) was evaluated for health, physical, and behavioral symptoms derived from parentally completed Autism Treatment Evaluation Checklist (ATEC) forms. The study protocol received Institutional Review Board (IRB) approval from Liberty IRB, Inc (Deland, FL).Outcomes: The results showed the following occurrence of symptoms among study participants: gastrointestinal disturbances=48%, incontinence=57%, sleep problems=57%, eating disorders=94%, hyperactivity=67%, lethargy=26%, sensory processing problems=85%, anxiety/fear=74%, behavioral problems=89%, and obsessive-compulsive behaviors=92%. Of all of the areas examined, eating problems, behavioral problems, and obsessive-compulsive behaviors, were reported by the parents to be the most serious and problematic.Conclusions: The present findings, taken together with previous research, suggest that subjects diagnosed with an ASD have significant health, physical, and behavioral problems beyond the symptoms evaluated in the diagnostic criteria used to diagnosis an ASD. The present findings also suggest the ATEC provides an economical means for healthcare providers to identify health, physical, and behavioral problems in subjects diagnosed with an ASD.
10. Gunji A, Goto T, Kita Y, Sakuma R, Kokubo N, Koike T, Sakihara K, Kaga M, Inagaki M. {{Facial identity recognition in children with autism spectrum disorders revealed by P300 analysis: A preliminary study}}. {Brain Dev};2013 (Feb 8)
Background: To reveal the neural substrate of communication difficulties in children with autism spectrum disorders (ASDs), we investigated the P300 component of event-related potentials (ERPs) as represented by the average of electroencephalography findings time-locked to events and behavior. Because the P300 amplitude influences attentional resource allocation during discrimination, the component elicited during perception of known and unknown faces should indicate familiarity processing. Methods and results: Nine typically developing children (TD) and nine children with ASDs participated in this study (Experiment 1). The P300 amplitude in TD children was significantly larger during familiar face perception than during unfamiliar face perception (p<0.01). However, there was no evidence of familiarity effect in children with ASDs. In three children with ASDs, we also assessed the P300 amplitude during perception of a therapist’s face one month before (baseline), a few days before and after social skills training (SST) sessions (Experiment 2). To evaluate the effect of familiarity on facial identity processing, we analyzed the therapist/unknown ratio of P300 amplitudes related to the face discrimination task as an index. The ratio was larger after SST sessions than before, but there was no difference in the ratio between baseline and before SST assessments. Conclusion: The P300 might be influenced by attentional resource allocation depending on the stage of learning face identification in children with ASDs. We speculate that this approach to evaluating brain responses during facial identity recognition could be used as a tool to clarify children’s communication difficulties.
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11. Guo X, Tu WJ, Shi XD. {{Tuberous sclerosis complex in autism}}. {Iran J Pediatr};2012 (Sep);22(3):408-411.
OBJECTIVE: To study the prevalence rate of tuberous sclerosis complex in autistic disorder. METHODS: We studied one cohort of children followed up since 2005 until 2009, with autistic disorder, to determine the incidence of tuberous sclerosis complex. We established an autistic disorder registry in 2005 at China Rehabilitation Research Center. During the 4-year period (2005-2009), we collected a database of 429 children (390 boys and 39 girls; male to female ratio 10:1) with autistic disorder and pervasive developmental disorders. We routinely examined all children with autistic disorder for any features of tuberous sclerosis complex by looking for neurocutaneous markers such as depigmented spots. In those with infantile spasm or epilepsy, the clinical features of tuberous sclerosis complex were monitored regularly during follow-up. FINDINGS: Of these, five had tuberous sclerosis complex. Thus, the prevalence rate of tuberous sclerosis complex in autistic disorder is 1.17%. All of these children were mentally retarded with moderate to severe grades. Their IQ or developmental quotient was less than 70. CONCLUSION: The prevalence rate of tuberous sclerosis complex in autistic disorder was 1.17% in our region; autism spectrum disorder is a condition that might be associated with development of tuberous sclerosis complex.
12. Hallett V, Lecavalier L, Sukhodolsky DG, Cipriano N, Aman MG, McCracken JT, McDougle CJ, Tierney E, King BH, Hollander E, Sikich L, Bregman J, Anagnostou E, Donnelly C, Katsovich L, Dukes K, Vitiello B, Gadow K, Scahill L. {{Exploring the Manifestations of Anxiety in Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2013 (Feb 12)
This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.
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13. Hinckson EA, Dickinson A, Water T, Sands M, Penman L. {{Physical activity, dietary habits and overall health in overweight and obese children and youth with intellectual disability or autism}}. {Res Dev Disabil};2013 (Feb 6);34(4):1170-1178.
In children and youth with disability, the risk of obesity is higher and is associated with lower levels of physical activity, inappropriate eating behaviors, and chronic health conditions. We determined the effectiveness of a program in managing weight, through changes in physical activity and nutrition behaviors in overweight and obese New Zealand children and youth with intellectual disability or autism. Twenty-two children and youth 14+/-4 y (mean+/-SD) and their families participated in a 10-week school-based program. The program consisted of 18 sessions focusing on physical activity and nutrition. Changes were measured immediately after completion of the program (post 1) and at 24 weeks (follow up). Fitness was assessed with the six-minute walk-test (6MWT) and body fatness via waist circumference and BMI. Physical activity and nutrition changes were measured by means of proxy reporting and interviews with parents. Individual interviews were conducted with school teachers and program leaders at 24 weeks to gain feedback regarding the program. Most quantitative outcomes were either unclear or trivial. The only possible change was observed in the six-minute walk-test where 24 weeks post program where participants walked 51m further. There was however, a substantial reduction in the consumption of confectionery and chocolate at the two measurement points. Parents commented that during the program there were less hospital visits and absences from school related to illness. The program assisted in the development of a supportive community network and participants’ abilities to partake in family and community activities. This the first study to report on the results of a physical activity and nutrition program targeted in children and youth with intellectual disability and autism. The results of this study may support and inform future developments of an integrated weight management and prevention program to enhance the health and well being in children and youth with disabilities.
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14. Hoerder-Suabedissen A, Oeschger FM, Krishnan ML, Belgard TG, Wang WZ, Lee S, Webber C, Petretto E, Edwards AD, Molnar Z. {{Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia}}. {Proc Natl Acad Sci U S A};2013 (Feb 11)
The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as in the development of inhibitory cortical circuits in sensory areas. So far no role has been identified for cells in the subplate in the mature brain and disease association of the subplate-specific genes has not been analyzed systematically. Here we present gene expression evidence for distinct roles of the mouse subplate across development as well as unique molecular markers to extend the repertoire of subplate labels. Performing systematic comparisons between different ages (embryonic days 15 and 18, postnatal day 8, and adult), we reveal the dynamic and constant features of the markers labeling subplate cells during embryonic and early postnatal development and in the adult. This can be visualized using the online database of subplate gene expression at https://molnar.dpag.ox.ac.uk/subplate/. We also identify embryonic similarities in gene expression between the ventricular zones, intermediate zone, and subplate, and distinct postnatal similarities between subplate, layer 5, and layers 2/3. The genes expressed in a subplate-specific manner at some point during development show a statistically significant enrichment for association with autism spectrum disorders and schizophrenia. Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders.
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15. Kilsby AJ, Cruwys M, Kukendrajah C, Russell-Eggitt I, Raglan E, Rajput K, Loshe P, Brady AF. {{Homozygosity for piebaldism with a proven KIT mutation resulting in depigmentation of the skin and hair, deafness, developmental delay and autism spectrum disorder}}. {Clin Dysmorphol};2013 (Feb 7)
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16. Lauritsen MB. {{Autism spectrum disorders}}. {Eur Child Adolesc Psychiatry};2013 (Feb);22 Suppl 1:37-42.
The revision of the diagnostic criteria for ASD has been widely anticipated and is expected to be an important contribution to the refinement of the definition of ASD. In the upcoming DSM-5, several changes have been made compared to the previous diagnostic criteria. They include no emphasis on language delay and age of onset except that ASD is defined as a neurodevelopmental disorder with symptoms in early childhood although the disorder may first be diagnosed later in life. The three areas of impairments in ASD are reduced to two areas, namely a social-communication domain and a behavioral domain including fixated interests and repetitive behaviors. In addition, the clinical presentation of ASD in the individual is described in more detail in terms of clinical specifiers. In addition to reporting these changes in the classification, the major international guidelines are introduced and a brief description of good clinical practice of assessment and the overall principles of intervention is provided.
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17. Lemcke S, Juul S, Parner ET, Lauritsen MB, Thorsen P. {{Early Signs of Autism in Toddlers: A Follow-Up Study in the Danish National Birth Cohort}}. {J Autism Dev Disord};2013 (Feb 13)
To identify possible early signs of autism spectrum disorder (ASD) within the Danish National Birth Cohort, we studied prospectively collected interviews from 76,441 mothers about their children’s development and behaviour at 6 and 18 months. In Danish national registries, 720 children with ASD and 231 children with intellectual disability (ID) were identified. At 6 months, associations between early signs and ASD or ID were found only in few areas. At 18 months social, language, and motor skills were delayed, and suspicion of vision and hearing problems were increased for both groups. Signs distinguishing ASD from ID were unclear, and the positive predictive values regarding ASD were below 10 % for individual predictors and aggregated risk scores.
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18. Marschik PB, Kaufmann WE, Sigafoos J, Wolin T, Zhang D, Bartl-Pokorny KD, Pini G, Zappella M, Tager-Flusberg H, Einspieler C, Johnston MV. {{Changing the perspective on early development of Rett syndrome}}. {Res Dev Disabil};2013 (Feb 8);34(4):1236-1239.
We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome (MECP2 positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of speech-language capacities, suggesting a paradigm shift in the pathogenesis of Rett syndrome and a possible approach to its early detection.
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19. Stagg SD, Davis R, Heaton P. {{Associations Between Language Development and Skin Conductance Responses to Faces and Eye Gaze in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2013 (Feb 12)
Attention to social stimuli is associated with language development, and arousal is associated with the increased viewing of stimuli. We investigated whether skin conductance responses (SCRs) are associated with language development in autism spectrum disorder (ASD): a population that shows abnormalities in both attention to others and language development. A sample of 32 children with ASD (7-15 year; M = 9 year) was divided into two groups, based on language onset histories. A typically developing comparison group consisted of 18 age and IQ matched children. SCRs were taken as the participants viewed faces. SCRs differentiated the ASD group based on language onset and were associated with abnormal attention to gaze in infancy and subsequent language development.
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20. Suren P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjolberg S, Davey Smith G, Oyen AS, Susser E, Stoltenberg C. {{Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children}}. {JAMA};2013 (Feb 13);309(6):570-577.
IMPORTANCE: Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. OBJECTIVE: To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. DESIGN, SETTING, AND PATIENTS: The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE: Specialist-confirmed diagnosis of ASDs. RESULTS: At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE: Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
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21. Tuchman R. {{Autism and social cognition in epilepsy: implications for comprehensive epilepsy care}}. {Curr Opin Neurol};2013 (Feb 8)
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.
