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The incidence of seizures among children with autistic symptoms.American Journal of Psychiatry, 136, 1310-1312
Abstract
The authors examined 183 children with autistic symptoms and found that the age-specific incidence rates of seizures in this sample were between 3 and 28 times the rates for children in the general population. The subjects classified as totally autistic were at high risk of developing seizure from early childhood well into adolescence, but especially so at puberty. The partially autistic children had an increased risk of seizures only up to age 10. The authors suggest that the high incidence of seizures at puberty observed in this study may be specific to children with total autistic symptomatology and may represent a distinct pathological process associated with autism.
... Autism spectrum disorder (ASD) affects approximately 1 in 59 children and is characterized by impairments in social communication, along with restrictive interests and repetitive behaviors, that emerges early in development [1,2]. An association between ASD and epilepsy has been well-established with approximately one-third of children with ASD developing epilepsy [3][4][5][6]. However, abnormalities on EEG results are frequently seen in patients with ASD who never had seizures, with rates varying from 8% to as high as 60% [7][8][9]. ...
... Another question that has yet to be answered is whether or not the presence of abnormalities on EEG results, as well as location and frequency, in patients with ASD indicate increased risk for later development of epilepsy. In patients with ASD, it has been historically reported that epilepsy onset occurs in a bimodal distribution, with the initial peak in early childhood and the second peak occurring in adolescence [4]. Many studies have found that epilepsy onset more frequently occurs during adolescence [18,19], but when attempting to determine whether earlier abnormalities on EEG results are predictive of later epilepsy, results are conflicting. ...
Objectives
The association between autism spectrum disorder (ASD) and epilepsy is well-known. Abnormalities on electroencephalography (EEG) results have been reported in patients with ASD without a history of seizures. However, little is known about the relationship between abnormalities on EEG results and the core features of ASD. The purpose of the study was to determine the relationship between the presence of epilepsy and/or abnormalities on EEG results and disease-associated impairments in young children with ASD.
Methods
Data were collected from medical records at Cincinnati Children's Hospital Medical Center (CCHMC) of patients with well-characterized ASD. Patients were subdivided into three groups: ASD without epilepsy but with abnormal EEG results, ASD without epilepsy and normal EEG results, and ASD with epilepsy. Developmental (Mullen Scales of Early Learning (MSEL)), adaptive (Vineland Adaptive Behavior Scales (VABS)), behavioral (Child Behavior Checklist), and language (Preschool Language Scales (PLS)) assessments, along with birth and developmental histories, medications, and medical comorbidities were collected. Electroencephalography data were abstracted from reports and included presence, characterization, and location of abnormalities.
Results
Analysis was performed on 443 patients with ASD. Seventy patients (15.8%) had epilepsy at the time of ASD diagnosis. Out of 372 patients with ASD and no epilepsy, 95 (25.5%) had an abnormal EEG result (67.4% epileptiform, 36.8% other abnormalities). Majority of epileptiform discharges were focal (83%) and most commonly seen in the left temporal region. The group with abnormal EEG results exhibited more impaired adaptive functioning when compared with the group with normal EEG results (p < 0.05). The group with abnormal EEG results was more similar to the group with epilepsy, differing only in expressive language (p < 0.01) and fine motor (p < 0.05) skills on the Mullen Scales. The group with epilepsy exhibited lower scores in all areas of developmental and adaptive functioning compared with the group with normal EEG results (p < 0.05). At the time of analysis, 13 patients (8 in the group with abnormal EEG results, 5 in the group with normal EEG results) developed epilepsy at a mean age of 10.5 years ± 3.3 years.
Conclusions
The presence of an abnormal EEG result or epilepsy in the setting of ASD suggests worse developmental and adaptive functioning. Further analysis will help to clarify associations and offer insight into treatment for this subpopulation without epilepsy but with abnormal EEG results.
... Depakote is capable of reducing vitamin D values (53). Seizures are popular in children with autism (54). Stabilization of plasma vitamin D value has an anticonvulsant influence (55). ...
... This hormone presents immunomodulation, neuroprotection and antiepileptic properties (47). Prenatal, postnatal and even and neonatal vitamin D supplementation is imperative for ordinary brain activities (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). The noticeable rise in the frequency of autism across the last 20 years is due to an increase in medical cautions to avoid the sun exposure because of its increasing of skin cancers. ...
Abstract
Autism is a group of lifelong developmental disabilities with various genetic and environmental risk factors which is generally not curable. The proportion of children with autism spectrum disorders (ASDs) has risen over the past decade. Few studies have focused on vitamin D status of patients with autism. Therefore, this study was aimed to further investigate the relationship between vitamin D deficiency and autism. In this short review, we discuss the relationship between vitamin D deficiency and ASDs. Our literature review yielded over 80 articles published since 2006 in the electronic databases of the Web of Knowledge, EBSCO, OVID and PubMed. As the results showed, no significant difference between children with and without autism regarding vitamin D serum levels was obtained. According to the controversial results on the correlation of vitamin D serum value and autism in children with ASD, it is necessary to conduct further studies in this field.
... Recent estimates indicate that its prevalence may be as high as one in 68 children. 9 An association of ASD with epilepsy has long been noted, [10][11][12] and recent reports, although highly variable, indicate that anywhere from 5% to 40% of individuals with ASD may have epilepsy, 13,14 representing an eight-to 20-fold 3,15 increased odds compared to controls. Some reports indicate that up to two thirds of individuals with ASD may have abnormal EEG activity. ...
... Some reports indicate that up to two thirds of individuals with ASD may have abnormal EEG activity. 12,16,17 There is a large body of literature including many excellent reviews on the subject of epilepsy and ASD, and this brief review is not meant to encompass this body of literature. Rather, a brief overview of salient points is presented to give the reader sufficient background to understand the focus of this article, which is on the contribution of inflammation, especially early life inflammation, to these conditions. ...
Epilepsy is associated with a high incidence of comorbid neurologic and psychiatric disorders. This review focuses on the association of epilepsy with autism spectrum disorder (ASD) and depression. There is high concordance of these behavioral pathologies with epilepsy. We review data that unambiguously reveal that epilepsy, ASD, and depression are associated with elevated brain inflammatory markers and that these may interact with serotoninergic pathways. Interference with inflammatory pathways or actions can reduce the severity of seizures, depression, and ASD-like behavior. Inflammation in the brain can be induced by seizure activity as well as by behavioral, environmental, and physiologic stressors. Furthermore, induction of inflammation at an early time point during gestation and in early neonatal life can precipitate both an ASD-like phenotype as well as a more excitable brain. It appears likely that priming of the brain due to early inflammation could provide a means by which subsequent inflammatory processes associated with epilepsy, ASD, and depression may lead to comorbidity.
... Since Chess reported a higher incidence of autism in those with congenital rubella, Deykin and MacMahon [47] have reported an association with prenatal influenza or rubella in 5% of autism cases. In addition, decreased activity of natural killer cells and inhibition of giant cell migration have been reported in autism [48,49]. ...
Autism spectrum disorder (ASD) is a heterogeneous developmental disorder characterized by impairments in two core areas: 1) social communication and interaction and 2) restricted and repetitive patterns of behaviors and interests. In general, ASD is known to be a lifelong disorder. Follow-up studies from childhood to adulthood have reported that the severity of the key symptoms ASD decreases over time. However, chronic health problems including mental health occur in many patients with ASD. The prevalence of ASD has increased from around 0.04% in the 1970s to 2.8% at present. The average age of diagnosis in developed countries is 38–120 months of age. Recent evidence suggests that biological factors which include genetic, congenital, immunological, neuroanatomical, biochemical, and environmental ones are important in causing autism. Until now, early signs and various risk factors of ASD have been suggested.
... Although data are few, the rates of seizure disorder and EEG abnormality appear to be similar to those observed in autism and suggest EEG should routinely indicated in clinical assessment [1,43,47]. EEG data in recent reports of 45 cases shows abnormalities [18,31,48]. Onset of seizures correlated temporally with onset of developmental deterioration [31]. ...
... 9,10 Bimodal age peaks of seizure onset are apparent for autistic individuals, occurring either before age 5 years or after age 11 years. [11][12][13] However, most information available uses cross-sectional samples rather than the same individuals from childhood to adulthood. ...
Background:
Physical and psychiatric health conditions affect the lives of many autistic adults. However, relatively little is known about individual trajectories in autistic individuals' physical and mental health from adolescence to adulthood.
Methods:
This study uses a well-characterized longitudinal sample (n = 253) to investigate rates of seizures, medication use, and obesity, from early adolescence (age 10 years) into adulthood (age 30 years). Within this sample, 196 participants were diagnosed with autism spectrum disorder (ASD), whereas the remaining 57 participants never received an ASD diagnosis, but, rather, were diagnosed with other neurodevelopmental conditions. Data were collected through parent report questionnaires and in-person interviews and assessments.
Results:
Seizure onset continued well into adulthood, with two individuals experiencing their first seizure at the age of 25 years. Seizures and neuropsychiatric medication use were both higher for those with lower intelligence quotient (IQs). In addition, medication use increased over time for these individuals, whereas those with higher IQs saw a reduction in medication use with age. Between the ages of 15 to 30 years, the predicted probability of medication use increased from 82% to 88% for those with lower IQs and decreased from 37% to 13% for those with higher IQs. Collectively, almost 70% of all participants in this study were classified as either overweight or obese. Body mass index (BMI) increased throughout adulthood, especially for those with higher IQs. The steepest increase in BMI over time occurred for those with higher IQs who also took antipsychotic medications.
Conclusion:
Overall, continued risk for developing seizures, high rates of neuropsychiatric medication use, and significant and increasing rates of obesity from adolescence to adulthood underscore the importance of monitoring health issues in autistic individuals and those diagnosed with other neurodevelopmental conditions throughout the lifespan.
... Specifically, early EEG studies identified abnormalities in epileptic spike activity and alpha and mu oscillations (Small, 1975;White et al. 1964), early differences in visual and auditory discrimination (Hermelin & O'Connor, 1968;Novick et al. 1979), and neural desynchronization (Hutt et al. 1965). EEG abnormalities were also associated with indications of brain damage (Deykin & MacMahon, 1979;Ritvo et al. 1970) and were applied to attempt to predict the emergence of ASD (Taft & Cohen, 1971) and to subgroup individuals with ASD (Small et al. 1977). ...
During the last 40 years, neuroscience has become one of the most central and most productive approaches to investigating autism. In this commentary, we assemble a group of established investigators and trainees to review key advances and anticipated developments in neuroscience research across five modalities most commonly employed in autism research: magnetic resonance imaging, functional near infrared spectroscopy, positron emission tomography, electroencephalography, and transcranial magnetic stimulation. Broadly, neuroscience research has provided important insights into brain systems involved in autism but not yet mechanistic understanding. Methodological advancements are expected to proffer deeper understanding of neural circuitry associated with function and dysfunction during the next 40 years.
... Other significant predictors of incident seizures in depression include being underweight, a current smoker, having alcoholism or drug abuse, and concurrent use of cephalosporins and antiarrhythmics (particularly propranolol) (Bloechliger et al., 2016). An elevated risk of developing seizures has also been reported in other neuropsychiatric diseases such as schizophrenia or autism (Deykin and MacMahon, 1979;Bolton et al., 2011), bipolar disorder (Wotton and Goldacre, 2014;Sucksdorff et al., 2015) and alcohol abuse (Samokhvalov et al., 2010). ...
This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects.
New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy).
An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
... First, longitudinal studies across the lifespan are needed to better understand the clinical profiles and trajectories of neurological disorders in autistic individuals. For example, it has been reported that the age distribution of epilepsy incidence in autism is bimodal, with peaks in early childhood and adolescence (Deykin & Macmahon, 1979;Volkmar & Nelson, 1990). However, most of the currently available studies are cross-sectional, and thus not informative to examine age effects on neurological complications in autism. ...
Lay abstract:
Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.
... Patients diagnosed with epilepsy not only suffer from ictal events (seizures), but also from cognitive deficits and other behavioral symptoms in the periods between seizures [1][2][3][4] . These non-ictal symptoms represent a major challenge for the treatment of epilepsy, as they can persist even after seizures are controlled. ...
Mutations in the astrocyte-enriched enzyme aldehyde dehydrogenase 7a1 (ALDH7A1) cause a neonatal epilepsy accompanied by treatment-resistant, inter-ictal neuropsychiatric symptoms. Nevertheless, the mechanistic impact of ALDH7A1 dysfunction in the brain remains elusive. We generated ALDH7A1 knockout mice and report that constitutive global ALDH7A1 depletion increases chemoconvulsant sensitivity and altered mood-associated behaviors. However, contrary to our expectation, astrocyte-specific ALDH7A1 depletion only affects mood-associated behaviors. Accordingly, in astrocyte-specific ALDH7A1 knockout mice, we show enhanced redox-sensitive microdomain Ca ²⁺ signaling in astrocytes and both elevated synaptic inhibitory tone and increased dendritic spine density in prelimbic pyramidal neurons. Sulforaphane (SFN), an indirect antioxidant and dietary supplement, has been explored as a possible treatment to ameliorate neuropsychiatric manifestations in autism and schizophrenia, at least at the clinical levels, but its mechanism in the brain is unclear. Here we show that SFN rescues both the physiological and behavioral changes by targeting astrocytic redox imbalance in ALDH7A1 knockout mice, implicating astrocyte redox changes in creating cortical excitatory-inhibitory imbalance and mood alteration.
... These disorders are associated with neurodevelopmental complications, and autism spectrum disorders (ASD)-like features are common in patients with both syndromes, suggesting a link between epilepsy and ASD (Ali Rodriguez et al., 2018). In fact, epilepsy is quite common in patients with ASD and therefore the association between epilepsy and autism is receiving growing interest (Deykin and MacMahon, 1979;Olsson et al., 1988; Galanopoulou et al., 2000;Giovanardi Rossi et al., 2000;Besag, 2004;Hughes and Melyn, 2005;Kosinovsky et al., 2005). In addition to the most common mutation in the SCN1A gene affecting the α1 subunit of voltage-gated sodium channels ( Wu et al., 2015), Dravet syndrome may also result from mutations in genes that alter GABAergic transmission, such as GABRA1, GABRB2, GABRB3, and GABRG2, encoding the corresponding subunits of GABA A R (α1, β1, β2 and γ2 subunits, respectively). ...
GABAA receptors (GABAAR) are the major players in fast inhibitory neurotransmission in the central nervous system (CNS). Regulation of GABAAR trafficking and the control of their surface expression play important roles in the modulation of the strength of synaptic inhibition. Different pieces of evidence show that alterations in the surface distribution of GABAAR and dysregulation of their turnover impair the activity of inhibitory synapses. A diminished efficacy of inhibitory neurotransmission affects the excitatory/inhibitory balance and is a common feature of various disorders of the CNS characterized by an increased excitability of neuronal networks. The synaptic pool of GABAAR is mainly controlled through regulation of internalization, recycling and lateral diffusion of the receptors. Under physiological condition these mechanisms are finely coordinated to define the strength of GABAergic synapses. In this review article, we focus on the alteration in GABAAR trafficking with an impact on the function of inhibitory synapses in various disorders of the CNS. In particular we discuss how similar molecular mechanisms affecting the synaptic distribution of GABAAR and consequently the excitatory/inhibitory balance may be associated with a wide diversity of pathologies of the CNS, from psychiatric disorders to acute alterations leading to neuronal death. A better understanding of the cellular and molecular mechanisms that contribute to the impairment of GABAergic neurotransmission in these disorders, in particular the alterations in GABAAR trafficking and surface distribution, may lead to the identification of new pharmacological targets and to the development of novel therapeutic strategies.
... 19 The concept that ASD might be a neurologic disorder is rooted in observations from the 1970s that persons with ASD had abnormal electroencephalogram recordings and increased incidence of seizures. 20,21 Furthermore, it was proposed rather early in the history of ASD that this condition arises from lesions or dysfunction in brainstem centers. 22 This suspicion was supported by an anatomical study that revealed dysmorphology in the cerebellum, though abnormalities were also identified in the forebrain. ...
Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with difficulties in the social, communicative, and behavioral domains. Most cases of ASD arise from an unknown etiologic process, but there are numerous risk factors, including comorbidities and maternal exposures. Although it is not part of the diagnostic criteria, hearing difficulties ranging from deafness to hyperacusis are present in the majority of persons with ASD. High-functioning children with ASD have been found to have significantly slower and asymmetric auditory brainstem reflexes. Additionally, histopathological studies of postmortem brainstems in decedents who had ASD have consistently revealed significantly fewer neurons in auditory nuclei compared with those in people who did not have ASD. The authors review the literature implicating auditory dysfunction in ASD along with results from human study participants and postmortem human brain tissue. Together, these results implicate significant structural and functional abnormalities in the auditory brainstem in ASD and support the utility of auditory testing to screen for ASD.
... 4,5 Moreover, depending on cohort, 5%-30% of individuals with ASD concurrently have epilepsy and >60% exhibit some degree of abnormal brain activity on a scalp electroencephalogram (EEG). 6,7 Although there are many limitations to determining the current prevalence of these disorders, particularly in the context of a comorbidity, the high co-occurrence of ASD and epilepsy suggests that common mechanisms may lead to the copresentation of these clinical conditions. To date, the underlying pathophysiology remains largely unknown; however, both disorders are considered to be multifactorial and involve genetic and environmental contributions. ...
Objective
In different cohorts, 5%‐30% of individuals with autism spectrum disorder (ASD) also have epilepsy. The high co‐occurrence of these disorders suggests that a common mechanistic link may exist. The underlying pathophysiology of this comorbidity remains unknown. To investigate the mechanism(s) involved in the pathogenesis of ASD and epilepsy, we developed and validated a novel mouse model that concurrently exhibits hallmark features of both disorders.
Methods
We utilized inbred BTBR T+ Itpr3tf/J (BTBR) mice that exhibit the core behavioral characteristics of ASD (ie, impaired sociability, altered vocalizations, and restricted interests). BTBR mice received a lipopolysaccharide (LPS) or sterile saline injection at postnatal day (P)7, P14, or P21. Cytokine expression was analyzed for interleukin (IL)‐1β, IL‐10, IL‐6, and tumor necrosis factor α in brain tissue of P7 and adult BTBR mice. Adult BTBR mice were behaviorally analyzed for seizure susceptibility, sociability, communication deficits, and motor stereotypies, and monitored using chronic video‐electroencephalography (EEG).
Results
Adult male and female BTBR mice treated at P7‐P14 with LPS were more sensitive to pentylenetetrazol‐induced seizures than saline‐treated controls. ASD‐like behaviors and hippocampal cytokine levels were unchanged between P7 LPS‐treated BTBR mice and controls. EEG recordings from the dorsal hippocampus revealed a significant increase in number and frequency of seizures over the 4‐week recording period (P60‐P88) in BTBR mice postnatally treated with LPS at P7. These results indicate the presence of a comorbid epileptic phenotype in BTBR mice.
Significance
These findings suggest that an early postnatal immune challenge can increase brain excitability in adult BTBR mice and reveal an underlying epilepsy phenotype. This novel animal model may enable the elucidation of specific molecular alterations that are associated with the concurrent presentation of ASD and epilepsy, which could facilitate the development of targeted therapies for individuals affected by this comorbidity.
... If cognitive deficits in psychiatric disorders reflect a failure of rate coded computation, then our analysis predicts that a change in noise within a circuit, in addition to synaptic modification, may be necessary for deficits to emerge. From this perspective it is intriguing that seizure phenotypes are often associated with disorders such as autism (Deykin and MacMahon, 1979). Alternatively, cognitive deficits may result from a failure to coordinate gamma frequency synchronization of circuits that converge on downstream targets. ...
Neural computations underlying cognitive functions require calibration of the strength of excitatory and inhibitory synaptic connections and are associated with modulation of gamma frequency oscillations in network activity. However, principles relating gamma oscillations, synaptic strength and circuit computations are unclear. We address this in attractor network models that account for grid firing and theta-nested gamma oscillations in the medial entorhinal cortex. We show that moderate intrinsic noise massively increases the range of synaptic strengths supporting gamma oscillations and grid computation. With moderate noise, variation in excitatory or inhibitory synaptic strength tunes the amplitude and frequency of gamma activity without disrupting grid firing. This beneficial role for noise results from disruption of epileptic-like network states. Thus, moderate noise promotes independent control of multiplexed firing rate- and gamma-based computational mechanisms. Our results have implications for tuning of normal circuit function and for disorders associated with changes in gamma oscillations and synaptic strength.
... Increased activity of this pathway in glial cells can also have negative effects on neurobiology, such as aberrant neuronal organization and seizures in astrocyte-specific TSC1 conditional knockout mice (56). Lack of social interactions is a central symptom of ASD (1), and seizures are a common comorbidity in the disorder (57). Together these data suggest that these ASD symptoms could be potentially related to the high Akt/mTOR signaling as described in this study in ASD cells (53,56,58). ...
Autism spectrum disorder (ASD) is a behaviorally defined disorder affecting 1 in 68 children. Currently, there is no known cause for the majority of ASD cases nor are there physiological diagnostic tools or biomarkers to aid behavioral diagnosis. Whole-genome linkage studies, genome-wide association studies, copy number variation screening, and SNP analyses have identified several ASD candidate genes, but which vary greatly among individuals and family clusters, suggesting that a variety of genetic mutations may result in a common pathology or alter a common mechanistic pathway. The Akt/mammalian target of rapamycin (mTOR) pathway is involved in many cellular processes including synaptic plasticity and immune function that can alter neurodevelopment. In this study, we examined the activity of the Akt/mTOR pathway in cells isolated from children with ASD and typically developing controls. We observed higher activity of mTOR, extracellular receptor kinase, and p70S6 kinase and lower activity of glycogen synthase kinase 3 (GSK3)α and tuberin (TSC2) in cells from children with ASD. These data suggest a phosphorylation pattern indicative of higher activity in the Akt/mTOR pathway in children with general/idiopathic ASD and may suggest a common pathological pathway of interest for ASD.
... Ten percent to 30% of children with ASD develop epilepsy at some point in their lives, and up to 80% show epileptiform activity on EEG recordings. 51 Conversely, ASD is diagnosed in up to 8% of the patients with epilepsy, with its prevalence elevated in selected populations such as tuberous sclerosis complex (TSC). 52 TSC is a neurocutaneous disorder characterized by hamartomatous growths in multiple body regions, particularly the central nervous system. ...
Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate with epilepsy-associated comorbidities. A reliable biomarker will allow a more accurate diagnosis and improved treatment of epilepsy-associated comorbidities.
... Although, ASD is defined by behavioral features, it is associated with co-occurring medical conditions. For example, epilepsy is more prevalent in ASD than in the typically developing children with a prevalence ranging from 5 to 38% (Deykin and Macmahon, 1979;Volkmar and Nelson, 1990;Tuchman and Rapin, 2002;Danielsson et al., 2005;Hara, 2007). Data from surveys performed by the Autism Research Institute on over 1200 participants suggests that the prevalence is between 15 and 19%. ...
This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and γ-aminobutyric acid (GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and epilepsy are associated with inhibitory GABA neurotransmission abnormalities including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increase the risk of seizures. Medical abnormalities associated with both epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and GABA and glutamate neurotransmission, mineral and vitamin deficiencies, heavy metal exposures and immune dysfunction. Many of these medical abnormalities can result in an elevation of the excitatory-to-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABAA receptor expression. Defects in energy metabolism can reduce GABA interneuron function. Both pyridoxine dependent seizures and succinic semialdehyde dehydrogenase deficiency cause GABA deficiencies while urea cycle defects and phenylketonuria cause abnormalities in glutamate neurotransmission. Mineral deficiencies can cause glutamate and GABA neurotransmission abnormalities and heavy metals can cause mitochondrial dysfunction which disrupts GABA metabolism. Thus, both ASD and epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of epilepsy in ASD and the elevated prevalence of ASD features in individuals with epilepsy.
... Two participants had single unprovoked seizures: one after 3 wk on sulforaphane, with an undisclosed history of recent seizures; the other 3 wk after discontinuing treatment and a past (more than 1 y) history of seizures well-controlled with antiepileptic drugs. Although patients with autism are predisposed to seizures (31,32), we cannot rule out the possibility of seizures as an adverse effect of sulforaphane in ASD. ...
Autism spectrum disorder (ASD) is a complex, life-long neurodevelopmental disorder currently affecting an estimated 1 out of 68 among children aged 8 y in the United States. ASD has complex genetic and epigenetic features that lead to the phenotype and there is no single genetic marker for the diagnosis. Therefore, the diagnosis for ASD is phenotype-based with no validated or credible laboratory tests available. Evidence-based treatments for ASD are limited. There is no FDA approved medical therapy that addresses either core ASD symptoms or pathophysiological processes associated with ASD. We outline herein, several ASD-associated basic physiological pathways that can be regulated by the small molecule phytochemical sulforaphane, as an example of a druggable small molecule target for which much in vitro, pre-clinical, and clinical evidence already exists: (1) redox metabolism/oxidative stress, (2) mitochondrial dysfunction, (3) immune dysregulation/neuroinflammation, (4) febrile illness and the heat shock response, (5) synaptic dysfunction. Furthermore, we identify the biomarkers that can be used to assess the functioning of these pathways as well suggest how these biomarkers could guide novel treatment strategies to correct these biochemical abnormalities in order to improve core and associated symptoms of ASD.
... It is interesting to note that seizures are often comorbid with several of the disorders discussed above, including autism, schizophrenia, Fragile-X, and Rett syndrome, each presenting with ECM abnormalities. Particularly frequent in these disorders are altered levels of MMP-9 and PNN numbers [369][370][371][372][373][374][375][376][377][378]. Given the compelling relationship between ECM molecules and seizures, such comorbidity may not be surprising and, on a speculative level, may point to partially shared mechanisms. ...
Rapidly emerging evidence implicates perineuronal nets (PNNs) and extracellular matrix (ECM) molecules that compose or interact with PNNs, in the pathophysiology of several psychiatric disorders. Studies on schizophrenia, autism spectrum disorders, mood disorders, Alzheimer's disease, and epilepsy point to the involvement of ECM molecules such as chondroitin sulfate proteoglycans, Reelin, and matrix metalloproteases, as well as their cell surface receptors. In many of these disorders, PNN abnormalities have also been reported. In the context of the "quadripartite" synapse concept, that is, the functional unit composed of the pre- and postsynaptic terminals, glial processes, and ECM, and of the role that PNNs and ECM molecules play in regulating synaptic functions and plasticity, these findings resonate with one of the most well-replicated aspects of the pathology of psychiatric disorders, that is, synaptic abnormalities. Here we review the evidence for PNN/ECM-related pathology in these disorders, with particular emphasis on schizophrenia, and discuss the hypothesis that such pathology may significantly contribute to synaptic dysfunction.
Over the last decade, the comorbidity between Autism Spectrum Disorder (ASD) and epilepsy has been widely demonstrated, and many hypotheses regarding the common neurobiological bases of these disorders have been put forward. A variable, but significant, prevalence of abnormalities on electroencephalogram (EEG) has been documented in non-epileptic children with ASD; therefore, several scientific studies have recently tried to demonstrate the role of these abnormalities as a possible biomarker of altered neural connectivity in ASD individuals. This narrative review intends to summarize the main findings of the recent scientific literature regarding abnormalities detected with standard EEG in children/adolescents with idiopathic ASD. Research using three different databases (PubMed, Scopus and Google Scholar) was conducted, resulting in the selection of 10 original articles. Despite an important lack of studies on preschoolers and a deep heterogeneity in results, some authors speculated on a possible association between EEG abnormalities and ASD characteristics, in particular, the severity of symptoms. Although this correlation needs to be more strongly elucidated, these findings may encourage future studies aimed at demonstrating the role of electrical brain abnormalities as an early biomarker of neural circuit alterations in ASD, highlighting the potential diagnostic, prognostic and therapeutic value of EEG in this field.
Introduction
Sleep is an incredibly complex process that goes beyond relaxing and body resting. Disturbance in sleep leads to several short-term and long-term consequences. Neurodevelopmental diseases such as “autism spectrum disorder” (ASDs), Attention-deficit hyperactivity disorder (ADHD), and intellectual disability commonly experience sleep disorders that affect their clinical presentation, daily function, and quality of life.
Discussion
The incidence of sleep problems in ASD patients ranges from 32 to 71.5%, especially insomnia, while an estimated 25–50% of people with ADHD report having sleep issues in clinical settings. The incidence of sleep issues is widespread in persons with intellectual disabilities, reaching up to 86%. This article is a literature review covering the neurodevelopmental disorder interaction with sleep disorder and different management.
Conclusion
Disorders of sleep are key concerns in children with neurodevelopmental disorders. In this group of patients, sleep disorders are common and tend to be chronic. Recognizing and diagnosis of sleep disorders will enhance their function, response to treatment, and quality of life.
Although Autism (more recently, Autism Spectrum Disorder; ASD) has been characterized as a distinct condition only since the 1940s, individuals with features of ASD are found within historical texts, as well as oral histories across regions and cultures. These core features have persisted throughout the evolution of our understanding of the condition. In a medical model, autism was first conceptualized in the early twentieth century within the field of childhood psychosis/schizophrenia, which was itself understood within a framework of psychoanalytical theory. Therein researchers and clinicians attributed children’s behaviour to unconscious thought and explored the effect of family and the environment on behaviour. Gradually, ASD was identified as a unique entity among developmental–behavioural presentations, as clinicians stratified children based on age of onset, acuity of presentation and social and family history. In the 1960s–70s, researchers classified children by clusters of quantifiable and observable behaviours, establishing an evidence-informed understanding of ASD. Since the 1980s, clinicians and researchers have explored biologic associations, such as seizure disorders and differences in brain structure and function. The effects of genetic and environmental influences on ASD have been investigated, and this cumulative knowledge has led to our current view of ASD as a neurobiologic condition. Additionally, parent and Autistic advocates have enriched our knowledge of ASD, and its intersection with individual experiences as well as societal systems.
To assess the role of clinical features in diagnosing seizures in children with autism spectrum disorder who present with staring spells. A 10-year retrospective chart analysis of autism spectrum disorder patients aged 3–14 years was performed at a tertiary care children’s hospital. Patient demographics, clinical presentation, and epileptic seizure versus non-epileptic spell diagnosis were assessed. Target episodes of staring spells were captured during a long-term electroencephalogram monitoring record. Multilevel likelihood ratios and a receiver operating characteristic curve were determined using 8 of the 11 clinical variables. Among the cohort of 140 patients with autism spectrum disorder, 16% were diagnosed with epileptic seizures with the most common seizure being atypical absence seizures (64%). Clinical semiology differed between those diagnosed with epileptic seizures versus those diagnosed with non-epileptic spells in the average duration of episodes (42 s vs 87 s), frequency of spells per week (6 vs 11.5 spells), increase in frequency of staring spells over time (100% vs 40%), and response to verbal stimulation (0% vs 100%), respectively. Multilevel likelihood ratios based on the receiver operating characteristic curves and clinical semiology features may be helpful in differentiating epileptic seizures from non-epileptic spells in children with autism spectrum disorder.
Lay Abstract
It is a common occurrence for children with autism spectrum disorder to be diagnosed with staring spells. Staring spells are defined as periods of time when children “space out” and are subcategorized as either “absence seizures” (brain activity resembling a seizure but with no physical seizure symptoms) or “non-epileptic spells” (inattentiveness or daydreaming). Due to the subtle characteristics of staring spells, they are usually diagnosed via long-term video electroencephalogram. The child is monitored for 3–5 days with an electroencephalogram which records brain waves. An electroencephalogram may be difficult to perform in children with autism spectrum disorder due to behavior, cognitive, or sensory concerns. Therefore, we wanted to investigate other clinical characteristics that may help us differentiate between epileptic seizures versus non-epileptic spells in children with autism spectrum disorder presenting with staring spells. We reviewed 140 charts retrospectively from the years of 2010–2021. We abstracted demographic and clinical information from the electronic medical record system and reviewed electroencephalogram videos to group the 140 children into epileptic seizure diagnosis group versus non-epileptic spell group. Of the 140 children in this study, 22 were diagnosed with epileptic seizures and the remaining were diagnosed with non-epileptic spells. We found that the two groups differed in certain clinical characteristics such as how long the staring spells lasted, how many staring spells the child had in 1 week, and whether they responded to verbal commands. We believe that clinical features may be helpful in differentiating epileptic seizures from non-epileptic spells in children with autism spectrum disorder.
The literature from inception to 2020 on the prevalence of epilepsy in autistic individuals was systematically reviewed and further explored by subgroup analyses and meta-regression models. This systematic review is registered with PROSPERO (CRD42020179725). A total of 66 studies from 53 articles were included. The updated pooled prevalence of epilepsy in autistic individuals was 10% (95% CI: 6–14). The respective prevalence estimate of epilepsy was 19% (95% CI: 6–35) in the clinical sample-based cross-sectional study, 7% (95% CI: 3–11) in the cohort study, and 9% (95% CI: 5–15) in the population-based cross-sectional study. The pooled prevalence of epilepsy was 7% (95% CI: 4–11) in autistic children and 19% (95% CI: 14–24) in autistic adults. Compared to the school-aged group, the adolescence group (OR: 1.15, 95% CI: 1.06–1.25) and the pre-school group (OR: 1.06, 95% CI: 0.94–1.19) were positively associated with the prevalence of epilepsy. The moderators of age, human development index of the country, gender, and intellectual function accounted for most of the heterogeneity. The prevalence estimates were associated with age, female gender, intellectual disability rate, and the human development index of countries. About 1/10 autistic individuals co-occurred with epilepsy, which was common in the clinical setting, adolescents, adults, females, or patients with intellectual disability, and less common in the country with high human development index.
Lay abstract
Autistic individuals experience higher co-occurring medical conditions than the general population, and yet the estimates of autistic individuals with epilepsy are not updated. Co-occurrence of epilepsy in autistic individuals often aggravated cognitive impairment and increased the risk of poor long-term prognosis. Thus, an updated systematic review and meta-analysis was conducted to study the relevant articles published from inception to 2020, evaluate the prevalence of epilepsy in autistic individuals, and further explore the putative factors influencing the prevalence. A total of 66 studies from 53 articles were included in this study. The results showed that epilepsy is more common in autistic individuals than in the general population. The prevalence of epilepsy in autistic individuals in the clinical sample-based studies was higher than that in the population-based based cross-sectional or cohort studies. The prevalence of epilepsy in autistic adults was higher than that in autistic children. A significantly increased prevalence of epilepsy was detected in the autistic adolescent group (11–17 years old), and a higher trend of prevalence of epilepsy was observed in the autistic pre-school group (⩽ 6 -years-old) than that of the autistic school-aged group (7–10 years-old). The prevalence of epilepsy increased with age, female rate, and low intellectual function rate of autistic individuals. However, the human development index of countries was negatively associated with the pooled prevalence, which could be attributed to the different levels of awareness, diagnostic technologies, and autism-service support worldwide. About 1/10 autistic individuals also had epilepsy, which was common in the clinical setting, adolescents, adults, females, or patients with intellectual disability and less common in the country with high human development index. Thus, these findings provided critical and innovative views on the prevalence of epilepsy in autistic individuals and contributed to the targeted clinical management and preventive measures.
Spektroavtistične motnje (SAM) so kompleksne razvojne motnje, ki se kažejo predvsem kot kakovostno spremenjeno vedenje na področju socialnih interakcij, besedne in nebesedne komunikacije ter imaginacije. Pogostost SAM se v zadnjih letih izrazito povečuje. Vzroka še niso opredelili, najverjetnejši etiološki vzrok pa je interakcija med genetskimi dejavniki in okoljskimi vplivi. Med genetske vzroke za avtizem sodijo tudi prirojene presnovne bolezni (PPB), ki so dokazane pri 2−5 % otrok s SAM. Na PPB kot vzrok za spektroavtistično motnjo pomislimo predvsem ob anamnes-tičnem podatku o regresiji v razvoju in pridruženih dodatnih kliničnih znakih. Diagnostična potrditev zahteva individualno obravnavo in usmerjene presnovne in genetske preiskave. V prihodnosti bodo pri diagnosticiranju SAM v ospredju genetske analize, usmerjene predvsem v potrditev monogenskih vzrokov SAM, med katere uvrščamo tudi PPB. Cilj bo čimprejšnje diagnosticiranje, morda že prenatalno, zlasti če bo z razvojem zdravil dostopno vzročno gensko zdravljenje. V preglednem prispevku povzemamo priporočila za diagnosticiranje prirojenih presnovnih bolezni pri bolnikih s sindromskim avtizmom in s prikazom primera otroka z lizosomsko boleznijo kopičenja in SAM opozarjamo na pomen pravočasne in pravilno postavljene diagnoze.
Progress in addressing the origins of intellectual and developmental disabilities accelerated with the establishment 50 years ago of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health and associated Intellectual and Developmental Disabilities Research Centers. Investigators at these Centers have made seminal contributions to understand human brain and behavioral development, and to define mechanisms and treatments of disorders of the developing brain. This article is protected by copyright. All rights reserved.
Autism, originally described by Kanner in 1943, is among the most severe of all neurodevelopmental disorders. It is a pervasive disorder associated with substantial deficits in reciprocal social interaction and communication, and the presence of repetitive and stereotyped behaviors and unusual interests (1). These classic features of autism typically appear in infancy, and the syndrome, by definition, is always present by the age of 3 years. Its manifestations and course often change throughout development, yet autism remains a chronic, lifelong, and disabling condition.
Autism spectrum disorder (ASD) is the name for a group of developmental disorders including a wide range of signs, symptoms and disability. Landau Kleffner syndrome (LKS) or acquired epileptic aphasia is a pediatric disorder characterized by the association of epileptiform electroencephalographic (EEG) abnormalities and acquired aphasia. The early stages of the LKS may be manifested by the symptoms of the autism leading to misdiagnosis. Since LKS is a progressive disease, its misdiagnosis leads to a greater neurocognitive deterioration which may result in seizure in the final stages. The purpose of this review was to provide an overview of available researches on ASD population and patients with LKS and relationship between these 2 diseases
This chapter lists different medical conditions and problems of autism. Seizure disorders are the most frequently encountered medical complications associated with autism spectrum disorder (ASD). The most common sensory sensitivities reported among children with ASDs are probably those that involve sensitivity to sounds and noises. Children with visual difficulties sometimes exhibit unusual body movements that may be mistaken for those seen in autism. Issues of diagnosis can be most complicated in children who are blind and deaf; fortunately, such cases are rare. Eating nonfood substances (pica) is noted in individuals with intellectual disability as well as with autism. Items eaten can include dirt, paint chips, string, or even clothing. Being bullied can be a major problem for individuals with ASDs. It can begin in the elementary school years and tends to increase in frequency as children become older—particularly for more cognitively able students.
Design of Epidemiological Studies Characteristics of Autistic Samples Rates of Other Pervasive Developmental Disorders Time Trends Immigrant Status, Ethnicity, Social Class, and Other Correlates Conclusion
RICHARD, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX–XXX, 2016.- To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N = 1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p < 0.001), but only reduced ToM in ASD-relatives (p < 0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability.
Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. In this paper we review some of the pathophysiological abnormalities associated with ASD and their potential associated treatments. Overall, there is evidence for some children with ASD being affected by seizure and epilepsy, neurotransmitter dysfunction, sleep disorders, metabolic abnormalities, including abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, redox and mitochondrial metabolism, and immune and gastrointestinal disorders. Although evidence for an association between these pathophysiological abnormalities and ASD exists, the exact relationship to the etiology of ASD and its associated symptoms remains to be further defined in many cases. Despite these limitations, treatments targeting some of these pathophysiological abnormalities have been studied in some cases with high-quality studies, whereas treatments for other pathophysiological abnormalities have not been well studied in many cases. There are some areas of more promising treatments specific for ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. Clearly, there are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future, but more research is needed to better define subgroups of children with ASD who are affected by specific pathophysiological abnormalities and the optimal treatments for these abnormalities.
Epilepsy is a major risk factor for autism spectrum disorder (ASD) and complicates clinical manifestations and management of ASD significantly. Tuberous sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical conditions most commonly associated with ASD and has become an important model to examine molecular pathways associated with ASD. Previous research showed reversal of autism-like social deficits in Tsc1
+/− and Tsc2
+/− mouse models by mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of individuals with TSC also have epilepsy, known to complicate the severity and treatment responsiveness of the behavioural phenotype. No previous study has examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. Adult Tsc2
+/− (Eker)-rats express social deficits similar to Tsc2
+/− mice, with additive social deficits from developmental status epilepticus (DSE). DSE was induced by intraperitoneal injection with kainic acid at post-natal days P7 and P14 (n = 12). The experimental group that modelled TSC pathology carried the Tsc2
+/− (Eker)-mutation and was challenged with DSE. The wild-type controls had not received DSE (n = 10). Four-month-old animals were analysed for social behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus and finally retested in the post-treatment behavioural analysis (T2). In the experimental group, both social interaction and social cognition were impaired at T1. After treatment at T2, behaviour in the experimental group was indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to control levels.
In 1943, Kanner published a report on 11 children who displayed such symptoms as extreme social withdrawal, idiosyncratic and delayed use of language, restriction of interests, and insistence on sameness which he believed constituted a specific syndrome to which he gave the name “autistic disturbances of affective contact.” Although Kanner was not the first researcher to describe severe distortions of developmental processes occurring in very young children (DeSanctis, 1906; Heller, 1930; Maudsley, 1867; Potter, 1933), his particularly clear and incisive clinical report has shaped the direction of clinical investigative activity for close to half a century.
Over 40 years of research on the behavioral syndrome of autism have yielded significant advances in our understanding of this perplexing disorder. As with most disciplines, the conceptualization of autism has been characterized by a series of reorganizations with adaptation (accommodation) to changes as new developments occur. For example, Kanner’s (1943) assertion of good cognitive potential in autistic persons was refuted by studies suggesting that as many as 70% to 80% were mentally retarded, with most of these individuals scoring in the moderate to severe ranges of intelligence (e. g., DeMyer et al., 1974; Wing & Gould, 1978). Accordingly, the American Psychiatric Association now includes Mental Retardation among its associated diagnostic features (DSM-II.1980). In fact, cognitive deficiency is now viewed by some as central to the pathogenesis of autistic disturbance (Rutter, 1983).
Pervasive developmental disorders, or major disorders in childhood, used to be classified as childhood psychoses. The term psychosis has no precise meaning but was used to describe severe conditions in which the child had a severely impaired sense of reality with little insight into his or her own behavior. That behavior is frequently different from normal behavior.
Taylor (1977), among others, has proposed that in spite of the seemingly excellent compensatory mechanisms of the central nervous system, clinical neuropsychiatric development may be compromised in the long run by brain damage occurring in the fetal or perinatal period. Regression or stagnation in the development of skills could occur years later when, for one or other reason, demands for accelerating development are made. Such demands are made, for instance, around the time of physical puberty. Puberty, of course, also marks the onset of major neurochemical changes, which could affect abnormal brain functions negatively. Other, as yet unidentified factors around the time of puberty could enter into the picture also. For all these reasons, the adolescent period in autism should be of particular interest from both the research and clinical points of view.
Behavioral assessment is a multimethod approach for gathering information about behavior using procedures that are both empirically validated and developmentally sensitive (Ollendick & Hersen, 1984). In contrast to traditional assessment methods, behavioral assessment emphasizes environmental and organismic control over behavior, reliance on the direct observation of behavior and subsequent deemphasis on inference, consideration of temporal and contextual bases within which the target behavior is embedded (Mash & Terdal, 1981), and the use of multiple assessment methods. The purposes of behavioral assessment are twofold: (1) to aid treatment plnning by providing predictive information with respect to the potential efficacy of one intervention over another, and (2) to monitor and evaluate the effects of the intervention, once implemented.
Ten years ago, we presented a review of the growing body of research developing on the diagnosis, understanding, and treatment of autism (Rutter, 1978; Schopler, 1978). The definition of autism developed by the National Society for Autistic Children was published along with that review. Although informed by scientific research, the NSAC definition was developed to shape favorable social policy rather than scientific synthesis, and so some anticipated differences between the two definitions arose. Since that time research has continued to accelerate. While these past 7 years have brought new information, they have also generated some new confusion and disputes. This review presents our synthesis of the accumulated research and provides our best assessment of the evidence for resolving some of these disputes.1
Despite the importance of the problem, comorbidity has received relatively little specific attention in autism spectrum disorder (ASD) research until recent years. This chapter explores historical perspectives on comorbidity in ASD, and considers how changes in diagnostic practices have affected the study of co-occurring conditions over time.
Anatomic Studies Behavioral Studies Classification Issues: Autism as a Spectrum with Fuzzy Borders and Overlaps Parent Advocacy Progress in Genetics Intervention Where We Need to Go Conclusion
Hippocampal area CA2 has several features that distinguish it from CA1 and CA3, including a unique gene expression profile, failure to display long-term potentiation and relative resistance to cell death. A recent increase in interest in the CA2 region, combined with the development of new methods to define and manipulate its neurons, has led to some exciting new discoveries on the properties of CA2 neurons and their role in behaviour. Here, we review these findings and call attention to the idea that the definition of area CA2 ought to be revised in light of gene expression data.
This study aimed to assess whether there is a bidirectional association between autism spectrum disorder (ASD) and epilepsy in child and adolescent patients. The National Health Insurance Research Database of Taiwan was used to conduct two cohort studies of patients who were under 18 years of age during the period 1997–2008. Cohort 1 comprised patients with newly diagnosed ASD but excluded those diagnosed with epilepsy prior to ASD. A non-ASD comparison group was matched to each case in terms of age and sex. Cohort 2 comprised patients with newly diagnosed epilepsy but excluded those diagnosed with ASD prior to epilepsy. A non-epilepsy comparison group was matched to each case in terms of age and sex. We calculated the incidence of epilepsy in patients with ASD and hazard ratio (HR) to estimate the risk of epilepsy in association with ASD in cohort 1, and the reverse in cohort 2. In cohort 1, the incidence of epilepsy was 13.7 in the ASD group and 1.3 in the non-ASD group (per 1000 person-years). The adjusted HR for epilepsy was 8.4 (95 % CI 5.5–12.7) in the ASD group when compared with the non-ASD group. In cohort 2, the incidence of ASD was 3.4 in the epilepsy group and 0.3 in the non-epilepsy group (per 1000 person-years). The adjusted HR for ASD was 8.4 (95 % CI 6.2–11.4) in the epilepsy group when compared with the non-epilepsy group. A bidirectional association was, therefore, found to exist between ASD and epilepsy. These findings implicate that ASD and epilepsy probably share common risk factors. However, further studies are required to reveal more detail on the mechanism of this bidirectional association.
Our understanding of “normal adolescence” is full of unknowns and speculation; the study of the exceptional adolescent is just beginning. It is the aim of this chapter to give an overview of what is known of normal adolescence so we might better understand the issues faced by the autistic teenager and his family in terms of developmental changes and behavioral expectations. After a brief historical perspective we will focus on three major aspects which define adolescence: physical development, cognitive development, and social-emotional development. At the end of each of these sections some comments will be made concerning what is known about the autistic adolescent within each of these three major areas of development. At the end of the chapter additional comments will be made as to the challenge which awaits parents, researchers, and the autistic adolescent himself.
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