AEDs and psychotropic drugs in children with autism and epilepsy

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.     

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.     

Drug treatment of epilepsy: when does it fail and how to optimize its use?

Although modern community-based studies have shown that a majority of people with newly diagnosed epilepsy will enter long-term remission, seizures remain refractory to treatment in a substantial proportion of this population--perhaps as much as 40%. A consensus is being reached that, for operational purposes, pharmacoresistance can be suspected when two appropriately chosen, well-tolerated, first-line antiepileptic drugs (AEDs) or one monotherapy and one combination regimen have failed due to lack of efficacy. Poor prognostic factors include lack of response to the first AED, specific syndromes, symptomatic etiology, family history of epilepsy, psychiatric comorbidity, and high frequency of seizures. These observations suggest that prognosis can often be determined early in the course of the disorder. We propose a management paradigm that aims to maximize the chance of successful AED therapy, including the early use of "rational polytherapy" for patients not responding to monotherapy, and to identify efficiently patients suitable for "curative" resective surgery, in particular those with mesial temporal lobe epilepsy. An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life.     

The WISC-V in children and adolescents with epilepsy

Despite its popularity in the neuropsychological evaluation of children, the utility of the Wechsler Intelligence Scale for Children – Fifth Edition (WISC-V) has not yet been investigated in children with epilepsy. Eighty clinically referred children and adolescents with epilepsy were administered the WISC-V as part of a comprehensive assessment and scores were compared to matched controls from the WISC-V standardization sample. T tests compared WISC-V indices and subtests between patients and controls and Chi-square analyses compared the rates of low scores. Correlational analyses assessed the relationships between epilepsy severity variables (e.g., age of onset, duration of epilepsy, number of antiepileptic drugs, seizure frequency). All WISC-V composites and subtests were significantly lower in patients versus controls and the rate of low scores was higher in patients than controls for all composites and subtests with the exception of Figure Weights. The Working Memory Index and Processing Speed Index were most sensitive to impairment, while the Verbal Comprehension Index and Fluid Reasoning Index were least sensitive. Of the epilepsy severity variables, age of seizure onset and number of antiepileptic drugs were strong predictors of deficits, whereas seizure frequency was the weakest predictor. Importantly, no significant differences were seen in children with right hemisphere epilepsy versus left on the five WISC-V composites, though a trend was seen towards a lower Visual-Spatial Index in those with right-sided focal seizures.     

Reproductive dysfunction in women with epilepsy: antiepileptic drug effects on sex-steroid hormones

Women with epilepsy are at risk for reproductive health dysfunction. Sex-steroid hormone abnormalities have been reported in women with epilepsy, but it has been difficult to determine whether these abnormalities are due to epilepsy-related hypothalamic-pituitary axis dysfunction, or to pharmacokinetic actions of antiepileptic drugs (AEDs). Sex-steroid hormones were evaluated in 84 reproductive-aged women with epilepsy receiving an AED in monotherapy, and in 20 nonepileptic controls. Estrone, free testosterone, and androstenedione were significantly lower in subjects receiving enzyme-inducing AEDs than in nonepileptic controls. Free testosterone was significantly elevated in subjects receiving valproate compared to nonepileptic controls. Subjects with epilepsy receiving gabapentin or lamotrigine were no different from the nonepileptic controls in any of the endocrine variables. Subjects with epilepsy who are receiving AEDs that alter cytochrome P450 enzymes are at risk for significant abnormalities in sex-steroid hormones. In contrast, subjects receiving AEDs that do not alter cytochrome P450 enzymes show no differences in sex-steroid hormones compared with nonepileptic controls. With new AEDs available that do not alter cytochrome P450 enzymes, physician selection of therapy should consider not only seizure control, but also potential effects on reproductive physiology.     

The role of neuropsychology in the assessment and treatment of persons with epilepsy.

Several areas of current interest in the neuropsychology of epilepsy are briefly reviewed in this article. These include variables pertaining to seizures, seizure history, antiepileptic drugs, and methods of neuropsychological evaluation. It is apparent that epilepsy is a multifaceted area: Psychologists not only can be of great assistance to patients with this condition, but may also learn a great deal from this complex disorder.     

Theory of Mind in Patients with Epilepsy: a Systematic Review and Meta-analysis

The ability to understand our own thoughts, intentions, beliefs and emotions and those of others (Theory of Mind; ToM) is a high-order social cognitive skill that is vital for social interaction and which has been found to be impaired in patients with epilepsy. Studies examining ToM in patients with epilepsy, however, have yielded inconsistent findings. The main aim of this study is to determine whether the magnitude of ToM deficits varies as a function of the site of epilepsy focus and/or the type of ToM task used. Electronic databases searches included Psychinfo, Medline/PubMed and EMBASE. Studies were included if they examined a group of patients with epilepsy and a group of healthy controls, reported original research, were published in the English language in peer reviewed journals, and used one of five empirically validated measures of ToM: False Belief, Reading the Mind in the Eyes Task (RMET), Faux-pas, Strange Stories, Cartoon ToM vignettes. Twelve studies were identified, ten included adults and two included children with epilepsy. Findings revealed marked ToM deficits in adults with focal seizures emanating from core brain regions underpinning ToM: temporal and frontal lobes (frontal lobe epilepsy, FLE; temporal lobe epilepsy, TLE), but not in adults with focal seizures outside the temporal and frontal lobes (extra-TLE/FLE). ToM deficits were also observed in children with generalised seizures (idiopathic generalised epilepsy, IGE). ToM deficits were documented across ToM tasks. In conclusion, ToM deficits represent a robust finding in adults with frontal and temporal epilepsy, but are also found in children with generalised seizures. Further research into ToM is needed, especially in children with epilepsy as early ToM may have cumulative, negative effects on development of social skills that continues into adulthood.     

从不规范联合用药转变为单药治疗过程分析抗癫痫药物的选择策略

单药治疗或合理的联合用药是癫痫治疗的重要原则,本文运用抗癫痫药物的药代动力学知识,分析了1例复杂不规范的联合用药导致治疗失败的原因,系统讲解了将其转变为有效的传统或新型抗癫痫药物单药治疗的理论和实践过程,并以此展示抗癫痫药物的选择策略。     

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.     

The Portland Neurotoxicity Scale: validation of a brief self-report measure of antiepileptic-drug-related neurotoxicity

The Portland Neurotoxicity Scale (PNS) is a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs (AEDs). The authors present data on the validity of this scale, particularly when used in longitudinal studies. Participants included 55 healthy controls, 23 epilepsy patient controls, and 86 healthy volunteers who took various AEDs or placebos for 12 weeks as part of randomized, double-blind studies of AED effects on cognitive abilities. Test-retest reliability in the control groups averaged .80 (total score). Test-retest changes in the PNS were sensitive to AED usage in general (p < .001) and to each of the five AEDs tested but not to placebo. Test-retest changes in the PNS were strongly correlated with several scales of the Profile of Mood States but only weakly correlated with objective cognitive test measures. The PNS has satisfactory psychometric properties and is sensitive to AED usage in test-retest studies.     

Epilepsie – eine potenziell chirurgisch behandelbare Erkrankung

Epilepsy is one of the most frequent neurological diseases in adults. First line therapy consists of antiepileptic drugs. However, up to 50?% of patients with focal epilepsy do not adequately respond to medical therapy. After failure of two first-line drugs, patients should be referred to a comprehensive epilepsy center for evaluation of the possibility for epilepsy surgery. The noninvasive phase 1 includes history with eye witness report, clinical examination, structural and functional imaging techniques, simultaneous video-EEG monitoring as well as a neuropsychological examination. An invasive phase 2 can be added in cases with incongruent results. Subdural strip and grid electrodes as well as stereotactically implanted depth electrodes give more detailed information on seizure origin and spread. Detailed planning of the surgical approach is of utmost importance. In patients with temporal lobe epilepsy, seizure freedom can be achieved in 60–80?% of cases after epilepsy surgery.     

Speech-Language Outcomes of Hemispherectomy in Children and Young Adults

Children and young adults who had undergone right or left hemispherectomy for intractable seizures after a period of normal language acquisition were compared with respect to scores on speech and language tests. The majority of the subjects had full scale IQs in the borderline to mentally retarded range. Language scores were computed in relation to estimated mental age, not chronological age. On this basis, the left hemispherectomized children were more likely to show syntactic comprehension and rapid-rate auditory processing deficits than the right hemispherectomized. The two groups were similar to one another and to normal children in speech production. The findings are discussed in relation to developmental language disorders.     

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.     

Stimulus overselectivity in autistic,trainable mentally retarded,and non-handicapped children: Comparative research controlling chronological (rather than mental) age

Much of the comparative research on stimulus overselectivity has been flawed by either failure to control for chronological age and language ability of the subjects or reliance on the controversial technique of matching on mental age. The present study investigated the prevalence of overselectivity in autistic, trainable mentally retarded, and non-handicapped children demonstrating some expressive speech. The ages of the children were between 6 years-6 months and 9 years-3 months. Thus, chronological age and language ability were controlled, rather than allowed to vary unsystematically. Results indicated no significant differences between the autistic and TMR samples, but significant differences between the handicapped samples and the non-handicapped group. Some, but not all, of the handicapped children displayed overselectivity.     

视觉障碍儿童人格特征的比较研究

以《缺陷儿童人格诊断量表》为工具对视觉障碍儿童进行人格评定,并将其测验分数与先前有关其他特殊儿童和正常儿童的同一量表测验结果加以比较。比较结果表明．视觉障碍儿童与正常儿童、智力落后儿童的人格特性有明显差异,而与听觉障碍儿童的人格差异相对要小一些。随年龄、障碍程度的不同．视觉障碍儿童的人格特性也有明显差异。     

Using the ADI-R to diagnose autism in preschool children

The use of an investigator-based interview (Autism Diagnostic Interview—Revised; ADI-R) in the diagnosis of 51 autistic and 43 nonautistic mentally handicapped preschool children of equivalent mental and chronological age is described. Significant differences occurred between the groups on every diagnostic subdomain from the DSM-IV/ICD-10 draft criteria, except specific aspects of stereotyped language, still relatively rare in these young children. All but one of the 51 children judged to be autistic by clinical observation and only two of the 30 nonautistic mentally handicapped children with mental ages of 18 months or higher met criteria for autism on an algorithm to DSM-IV/ICD-10 draft criteria. However, discrimination using domain totals between autistic and the 13 nonautistic, nonverbal mentally handicapped children with mental ages under 18 months was poor. Quality of social overtures to adults and peers, play, and unusual sensory behaviors and mannerisms continued to differentiate these two groups. The relevance of these findings to the diagnosis of autism in preschool children is discussed.     

癫痫的诊治与人文思想

癫痫是神经科常见的疾病之一,对于患者的学习、生活和工作均有不同程度影响。它的发病机制尚不十分清楚,主要是以药物治疗为主。在癫痫的诊断中要根据病情和患者的实际情况选择合适的检查;在癫痫的治疗中须按照最优化的医疗原则选择最佳的治疗方案。在治疗中要注意结合人文思想来提高癫痫的治疗效果。     

Intelligence and age as predictors of motor performance

The Yule-Oseretsky test of motor performance was administered to 10 ‘undifferentiated’ mentally-retarded adults, 10 normal children and 10 normal adults. In accordance with Denny's (1964) 3-group design, the children were matched on mental age with the retardates, the normal adults were matched on chronological age with the retardates, and the children and normal adults were matched on intelligence quotient. The results showed that mental age predicted performance on both fine and gross motor tasks, with the children and retarded adults both obtaining similar relatively-low scores.     

Young children's social networks as a function of age and dysfunction

Social networks provide a larger context than that of the nuclear family in which the child develops. In order to examine the networks of young children, mothers of 75 handicapped children, aged 3 to 6 years, and a matched sample of normal children were surveyed in terms of people in the child's network and frequency of daily contact. The effects of age of subject and handicapping condition on social network composition and contact were of interest. Handicapping condition played a much greater role in the network composition than did chronological age. Handicapped children had larger networks, although they did not have daily contact with network members compared to normal children. Handicapped children thus were not isolated, but appeared to have a large network composed of relatives and adults and, to a lesser extent, peers. Normal children showed a developmental shift, in terms of an increase in the proportion of peers to adults, from 3 to 6 years, whereas handicapped children did not show this change. It is suggested that the handicapped child's developmental delay and caregiving demands may necessitate greater and more prolonged adult contact, which, consequently, constrains the nature of the social network in terms of adult and peer composition. Insufficient peer contact may restrict the handicapped child's opportunity to learn important social skills.     

Coincidence anticipation of young normal and handicapped children

Two coincident-timing experiments examined the role of three different target velocities and display extents and three age levels of normal and retarded children. Subjects made a ballistic response to a target moving horizontally across their visual field. In the first experiment there were generally no clear differences between normal and retarded children on the task, with subjects having difficulty for both the slow and fast target speeds. In the second experiment, with target velocity held constant, no significant differences were reported between normal and handicapped children, although the longer the subjects were allowed to view the target the more accurate they were. The data were discussed in terms of the response strategies to perform anticipatory ballistic movements. An ecological issue was raised which suggested that children as well as adults make their most accurate anticipations when confronted with velocity problems that have been experienced in their everyday world.