Sleep disorders, epilepsy, and autism

The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum disorders. Epilepsy and sleep have reciprocal relationships, with sleep facilitating seizures and seizures adversely affecting sleep architecture. The hypothesis put forth is that identifying and treating sleep disorders, which are potentially caused by or contributed to by autism, may impact favorably on seizure control and on daytime behavior. The article concludes with some practical suggestions for the evaluation and treatment of sleep disorders in this population of children with autism.     

Treatment of epilepsy in the multiply handicapped

The medical management of epilepsy in the multi-handicapped patient requires careful evaluation, classification, and pharmacologic treatment. It is estimated that 20-40% of patients with mental retardation and cerebral palsy have epilepsy. This review reports the clinical trial data and personal experience related to the use of newer AEDs in the chronic management of epilepsy syndromes in children and adults, as well as information available on the treatment of seizures in individuals with mental retardation and associated handicaps. Furthermore, clusters of seizures, prolonged seizures and status epilepticus are more commonly seen in the multiply handicapped and mentally retarded population and require special attention. The new antiepileptic drugs felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide show specific advantage in some multiply handicapped patients, be it for seizure control or medication tolerance. Furthermore, new modalities of treatment for prolonged seizures allow better efficacy both outside of hospital and within hospital facilities. The treatment of epilepsy in multi-handicapped and retarded adults and children has significantly advanced in the past few years, and much of this improvement can be attributed to improved knowledge and monitoring of new antiepileptic drugs. Conventional anticonvulsants remain first line therapy for most clinicians, but newer AEDs must broaden the therapeutic option and do allow improved therapy for some multiply handicapped patients.     

Noncontingent reinforcement and competing stimuli in the treatment of pseudoseizures and destructive behaviors

Individuals diagnosed with epilepsy have sometimes also been observed to display ‘pseudoseizures’, or clinical events that mimic those observed during epileptic seizures, but are not associated with abnormal cortical electrical discharges. Several investigators have hypothesized that pseudoseizures, in some proportion of those individuals that display them, may be maintained through operant contingencies. In the present study, this sort of hypothesis was tested in a 10‐year‐old boy with severe mental retardation and a seizure disorder. Informal observations, and later, response‐reinforcer contingencies, revealed that the pseudoseizures, as well as other destructive behaviors, occurred at high rates when they resulted in attention from caregivers. Subsequently, a treatment package consisting of noncontingent reinforcement (NCR) and competing stimuli was used to decrease levels of seizure‐like activity and other problem behaviors. This study adds to the literature that suggests that seizure‐like activity may come under operant control and extends the use of NCR and competing stimuli to a novel target behavior. Copyright © 2005 John Wiley & Sons, Ltd.     

Epileptic encephalopathies and their relationship to developmental disorders: do spikes cause autism?

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without seizures. Thirty percent of children with PDD have regression of social behavior and language at 2-3 years of age. Some authors speculate that the regression is caused by epileptiform activity even in the absence of overt clinical seizures ("autism with epileptic regression") and suggest that elimination of the epileptiform activity, either medically or surgically, should lead to improvement in behavior. This review examines the data showing that interictal epileptiform discharges are associated with transient clinical dysfunction and discusses the implications of these observations for autistic behavioral abnormalities. The results of resective surgery, vagal nerve stimulation, and multiple subpial transaction on children with autism and epileptiform EEG abnormalities are also discussed. I conclude that there is no evidence that interictal discharges per se cause (or contribute to) the complex behavioral phenotype of autism. There is no justification to support the use of anticonvulsant medication or surgery in children with PDD without seizures; that is, there is no evidence that treatment to eliminate EEG spikes will have a therapeutic effect on the behavioral abnormalities of PDD and autism.     

Serotonin in autism and pediatric epilepsies

Serotonergic abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development--and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This review explores the hypothesis that an early disturbance in the serotonin system affects cortical development and the development of thalamocortical innervation, and is a potential mechanism, common to autism and pediatric epilepsies associated with cortical dysplasia. An argument is made that cortical malformation leads to abnormalities of thalamocortical connectivity, and that serotonin plays a critical role in this process. Finally, a role for altered metabolism of the serotonin precursur, tryptophan, in both epilepsy and autism is discussed.     

Lennox-Gastaut syndrome: potential mechanisms of cognitive regression

Lennox-Gastaut (L-G) syndrome is an intractable generalized epilepsy of childhood onset, associated with spike waves at a slow rate and paroxysmal fast activity. These epileptiform discharge patterns are thought to reflect excessive neocortical excitability and arise from neuronal and synaptic features peculiar to the immature central nervous system. The epileptic processes associated with L-G syndrome may lead to enduring patterns of abnormal activity and connectivity. These abnormal patterns compete with normal developmental mechanisms and may result in subsequent impairment and/or regression of cognition. Recurring or prolonged seizures themselves may also damage the brain. We hypothesize that the presence of slow spike waves diverts the brain from normal developmental processes toward seizure-preventing mechanisms. Adding to this burden, antiepileptic medications, sleep disruption, and social isolation all retard cognitive development and the learning process at a crucial time of brain maturation.     

Brain development in autism: early overgrowth followed by premature arrest of growth

Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies have now shown that abnormal brain overgrowth occurs during the first 2 years of life in children with autism. By 2-4 years of age, the most deviant overgrowth is in cerebral, cerebellar, and limbic structures that underlie higher-order cognitive, social, emotional, and language functions. Excessive growth is followed by abnormally slow or arrested growth. Deviant brain growth in autism occurs at the very time when the formation of cerebral circuitry is at its most exuberant and vulnerable stage, and it may signal disruption of this process of circuit formation. The resulting aberrant connectivity and dysfunction may lead to the development of autistic behaviors. To discover the causes, neural substrates, early-warning signs and effective treatments of autism, future research should focus on elucidating the neurobiological defects that underlie brain growth abnormalities in autism that appear during these critical first years of life.     

The epidemiology of the epilepsies in children

The epilepsies are a heterogeneous collection of neurological conditions and syndromes characterized by recurrent, unprovoked, paroxysmal seizure activity. There are several types of epileptic seizures and syndromes that are unique to children, including infantile spasms, Lennox-Gastaut syndrome and absence seizures. Febrile seizures and neonatal seizures, while not epilepsy, are relatively common types of seizures in infants and children and are likely markers of risk of later epilepsy. Thus, it is important to consider the epidemiological features of the epilepsies as they occur specifically in infants and children. The purpose of this review is to summarize what is currently known about the epidemiology of the childhood epilepsies and to identify promising areas for further population-based studies. The epilepsies are an important cause of neurological morbidity in children. The average annual rate of new cases (incidence) of epilepsy is approximately 5-7 cases per 10,000 children from birth to age 15 years, and in any given year, about 5 of every 1,000 children will have epilepsy. There is evidence that the incidence of the epilepsies in some populations of children may be decreasing over time, and this possibility merits further investigation. Factors that are known to increase risk of the epilepsies in children include congenital malformations of the central nervous system (CNS), moderate or severe head trauma, CNS infections, certain inherited metabolic conditions, and genetic factors. However, these account for only 25% to 45% of cases, and thus, the etiology of most cases of the epilepsies remains obscure. The paucity of well-controlled etiological studies is due largely to formidable methodological problems in conducting epidemiological studies of the epilepsies. The prognosis for seizure control is generally good, although children with remote symptomatic seizures and those with additional neurological disabilities do less well.     

Interictal and postictal performances on dichotic listening test in children with focal epilepsy

Dichotic listening test (DL) is an important tool to disclose speech dominance in healthy subjects and in clinical cases. The aim of this study was to probe if focal epilepsy in children reveals a corresponding suppression of the ear reports contralateral to seizure onset site. Thus, 15 children and adolescents with clinically and electroencephalographically diagnosed focal epilepsy selected for left-hemisphere speech dominance without mental retardation were compared to matched controls according to age, gender, IQ and handedness. All children were assessed with DL for three times: Interictally (t(0)), postictally 5' (t(1)) and 1h (t(2)). At t(0), all groups revealed a right ear advantage (REA), indicating a left-hemisphere speech dominance. There was a continuous increase in right correct score (REC) over the trials for normal controls. Five minutes postictally, there was an abrupt decrease in REC with a sustained left ear correct score (LEC) for children with epilepsy, independent of which side suffered from seizures. This effect was maintained even after 1h. Thus, in children with left-hemisphere speech dominance the epileptic discharges caused a suppression of REC regardless of origin. The seizures may have a prolonged impact on attention and auditory perception for a considerable time after consciousness has been regained.     

Structural and functional imaging in children with partial epilepsy

Imaging plays an increasingly important role in the evaluation of children with complex partial seizures. Most partial epilepsy, especially of temporal lobe origin, begins during childhood. Structural imaging with high-resolution MRI can help identify the etiology of partial seizure disorders in many children. MRI studies also show the more widespread effect of seizures on brain structure. Progressive volume loss of the hippocampal formation in some patients with temporal lobe epilepsy provides evidence that continued seizures may be associated with progressive neuronal injury. FDG-PET studies show regional decreases in glucose consumption in the cortical zone from which seizures arise. Functional abnormalities often are more extensive than the seizure focus. Studies in children with recent-onset epilepsy show that metabolic abnormalities are considerably less common than in adults with partial epilepsy, supporting the notion that in some patients there may be progressive metabolic changes that occur with continued seizures. Functional MRI may be used to identify language areas in children with partial epilepsy. fMRI language tasks reliably identify the dominant hemisphere for language dominance when compared to the intracarotid amytal procedure. Tests of verbal fluency and semantic decision identify frontal lobe language areas, while reading text paradigms and auditory passage paradigms are better for identifying temporal language areas. A panel of paradigms is best used to identify language areas in children being considered for epilepsy surgery. fMRI is a valuable tool for elucidating the impact of chronic neurologic disease states on the functional organization of language networks during development.     

Examining the Efficacy of Parent–Child Interaction Therapy with Children on the Autism Spectrum

Externalizing behaviors are a common component of the clinical presentation of autism spectrum disorders. Although traditionally used with typically-developing children, parent–child interaction therapy (PCIT) is one behaviorally-based parent training program that has demonstrated success in increasing child compliance, reducing problem behavior, and improving parent–child communication. The study examined the efficacy of PCIT as a treatment for children with autism spectrum disorders by employing a single subject, non-concurrent multiple baseline design across three subjects. Primary findings revealed increases in child compliance, reductions in child disruptive behavior, and improved parenting skills across participants. In addition, each caregiver reported high levels of satisfaction with the intervention. Results suggested that PCIT may be a treatment option for children on the autism spectrum with co-occurring behavioral difficulties. Although the non-concurrent nature of the multiple baseline design is a limitation, this study replicates and extends previous research investigating the efficacy of PCIT with children with autism and their parents.     

自闭症儿童依恋研究述评

摘要　　研究者曾一度认为自闭症儿童无法建立起依恋关系。本文系统回顾了自闭症儿童依恋研究的最新进展,将自闭症儿童是否存在依恋行为（尤其是安全型依恋行为）、依恋发展解释理论、研究方法、类型分布以及影响因素等问题进行了详细梳理,并结合研究分析,提出有关自闭症儿童依恋研究的几点启示,以供参考。     

Developmental regression in autism spectrum disorders

The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences. Counter to clinical intuition, the earlier development of social, language, and attachment behaviors followed by regression does not seem to support later recovery of skills or better developmental outcomes compared to children who never had speech or typical social responsivity. In fact, this regressive group may have somewhat greater developmental impairment than the nonregressive group, though the two groups do not appear to present different behavioral phenotypes. Although autism is not the only condition in which regression occurs, it appears to be the most frequent condition. Other disorders that demonstrate an early regression with no known etiology include total blindness from birth and childhood disintegrative disorder, both of which demonstrate behavioral relations to autism. In addition, two biological conditions with known etiologies also involve regression with some behaviors resembling autism behavioral phenotype: Rett syndrome (a genetic disorder; see Glaze, this issue) and Landau-Kleffner syndrome (see McVicar and Shinnar, this issue), which involves a seizure disorder.     

Assessment of social communication skills in preschoolers

This paper orients the reader to social communication assessment and reviews methods for assessing social communication behavior in children from toddlerhood through the preschool years. Most standardized, normed tests of language in this age range focus on morpho-syntactic and semantic comprehension and production abilities. While social communication is perhaps one of the most important skills for peer acceptance, these skills are often overlooked in language evaluation with children. However, there are a number of caregiver questionnaires, interviews, or direct social-communication sampling methods that are available to assist clinicians or researchers in documenting social-communication skills or behaviors. Since assessment of social communication is essential in clinical work with children with an autism spectrum disorder, some of the tools described below are outgrowths of autism research or provide autism-related scores. While many children receiving social communication assessments do not have autism, the need to assess social communication skills in children with language impairment is highlighted by the growing literature documenting social and pragmatic difficulties in this population (Bishop 2000 Causes, Characteristics, Intervention, and Outcome. Hove, UK: Psychology press). Regardless of whether the measures presented herein were initially designed for children with autism or not, they will provide insights into the social communicative behaviors or tendencies in young children.     

A clinical comparative study evaluating the effect of epilepsy versus ADHD on timed cognitive tasks in children.

Both children with epilepsy and children with ADHD may be characterized by slowing on reaction-time measurement. This is of particular interest, as neuropsychological assessment is often requested in the differential diagnosis between children with short non-convulsive epileptic seizures and children with ADHD. In this study we attempt to identify patterns of impairment on timed tasks that are specific for epilepsy, relative to ADHD. This study was an open, controlled parallel-group clinical investigation which included two groups of patients: 60 children with ADHD and 60 children with epilepsy. These children were compared with a control group (n=30) on two types of timed cognitive tasks: tasks with low information load (simple reaction-time measurement) and tasks with high information load (multiple decision reaction-time measurement). The simple reaction-time measurements show significant differences between ADHD and controls (all except for visual RT non-dominant hand) and between epilepsy and controls (only one test). No significant differences were found between epilepsy and ADHD. The two tests with high information load show significant slowing compared with the controls for epilepsy on the Binary Choice Reaction-Time Test and for ADHD on the Visual Searching Test. On both tests also the differences between epilepsy and ADHD are significant. The two tests in combination have a relatively satisfactory potential to classify the children with ADHD (75% correct classification) and the children with epilepsy (55% correct classification). We may conclude that complex reaction-time tests (i.e., timed tasks with high information load) have potential for assessing the differential impact of ADHD and epilepsy on attentional function. These tasks specifically reveal general slowing for children with epilepsy and slowing as an effect of failures of inhibitory self control on unstructured tasks for ADHD.     

A Clinical Comparative Study Evaluating the Effect of Epilepsy Versus Adhd on Timed Cognitive Tasks in Children

Both children with epilepsy and children with ADHD may be characterized by slowing on reaction-time measurement. This is of particular interest, as neuropsychological assessment is often requested in the differential diagnosis between children with short non-convulsive epileptic seizures and children with ADHD. In this study we attempt to identify patterns of impairment on timed tasks that are specific for epilepsy, relative to ADHD. This study was an open, controlled parallel-group clinical investigation which included two groups of patients: 60 children with ADHD and 60 children with epilepsy. These children were compared with a control group (n =30) on two types of timed cognitive tasks: tasks with low information load (simple reaction-time measurement) and tasks with high information load (multiple decision reaction-time measurement). The simple reaction-time measurements show significant differences between ADHD and controls (all except for visual RT non-dominant hand) and between epilepsy and controls (only one test). No significant differences were found between epilepsy and ADHD. The two tests with high information load show significant slowing compared with the controls for epilepsy on the Binary Choice Reaction-Time Test and for ADHD on the Visual Searching Test. On both tests also the differences between epilepsy and ADHD are significant. The two tests in combination have a relatively satisfactory potential to classify the children with ADHD (75% correct classification) and the children with epilepsy (55% correct classification). We may conclude that complex reaction-time tests (i.e., timed tasks with high information load) have potential for assessing the differential impact of ADHD and epilepsy on attentional function. These tasks specifically reveal general slowing for children with epilepsy and slowing as an effect of failures of inhibitory self control on unstructured tasks for ADHD.     

儿童的人际运动同步

人际运动同步是一种“社会胶粘剂”, 能促进儿童产生更多的亲社会行为。儿童的人际运动同步能力随着年龄的增长不断提升, 其同步表现受到运动方式、节奏刺激类型、同步对象等因素影响。在人际运动同步过程中, 时间感知、运动计划和运动执行三大认知因素参与其中, 既制约着个体同步能力的发展, 也影响个体同步的表现。孤独症作为一种神经发育性障碍, 孤独症儿童表现出异常的人际运动同步。未来的研究不仅要探讨孤独症儿童人际运动同步的异常机制, 还要更多关注人际运动同步训练在孤独症群体中的实际应用和干预效果。     

The effect of alterations in consciousness on quality of life (QoL) in epilepsy: searching for evidence

The impact of epilepsy on quality of life (QoL) is well-documented. The ability of epileptic seizures to alter the conscious states of patients is also well established. Although there is much research on the QoL of people with epilepsy, few researchers have looked specifically at the effect of sudden, unanticipated alterations of consciousness on QoL. This lack of systematic studies of consciousness alterations and QoL in epilepsy limits our ability to shed light on this interrelation. In this article, with these limitations in mind, we focus on studies of newer AEDs. We review the evidence as to whether a significant reduction (typically more than 50%) in seizures that induce alterations of consciousness, as a result of switching to one of the newer AEDs, leads to improvements in QoL. We draw on this literature to speculate on the relationship between ictal consciousness alterations and poor QoL in epilepsy, to identify contributory and confounding factors and to highlight implications for future research. We suggest that an understanding of how factors associated with consciousness impairment affect QoL could help the treatment and management of these patients.     

Patterns of Memory Performance in Children with Controlled Epilepsy on the CVLT-C

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Children's Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.     

Patterns of memory performance in children with controlled epilepsy on the CVLT-C.

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Children's Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.