The Relationship Between Experience and Attitudes Concerning Epilepsy1

Research indicates that epilepsy is a misunderstood and stigmatizing disorder. The present study examined whether various levels and types of experience with epilepsy are related to attitudes about the disorder. It was hypothesized that certain types of direct experience with epilepsy (e.g., knowing people with epilepsy) are related to positive attitudes about the disorder, whereas other types of direct experience (e.g., witnessing seizures) are related to negative beliefs. As predicted, data from telephone interviews with 271 subjects indicate that individuals knowing someone with epilepsy held significantly more accepting attitudes than respondents who had never known an epileptic. The findings also suggest that witnessing epileptic seizures is an emotionally charged event, and, in the absence of other types of experience, this emotional impact might have a negative effect on attitudes toward people with epilepsy. The findings from this study have implications for the development of educational programs aimed at the general public, medical personnel, and people with epilepsy.     

自由基在癫痫发生及其治疗中的研究现状与进展

癫痫是一组包括许多不同症状的综合征,其主要特征是对反复出现的无明显诱因的发作的易感性。无论动物实验还是临床观察均表明癫痫时伴有活跃的自由基反应,自由基与癫痫的发生发展有着密切的联系。清除自由基,阻断自由基反应无疑为癫痫的治疗开辟了新的途径。本文就自由基在癫痫发生及其治疗中的研究现状与进展作一概述。目前应用自由基清除剂治疗癫痫尚处于临床试验阶段,但我们可以预见,进一步探索癫痫发生的自由基病理机制,开发有效清除自由基的药物具有广阔的前景,并将为人类最终战胜癫痫提供有力的帮助。     

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.     

Review of Commercially Available Epilepsy Genetic Panels

Next generation sequencing panels have revolutionized the diagnostic approach to patients with epilepsy. There are several commercial epilepsy panels available. We assessed the list of genes tested and consent forms for epilepsy panels available at seven laboratories. The panels varied in the number of genes included (70–465 genes). In some panels, genes not currently associated with epilepsy were included (up to 4 % of panel content). The panels also included genes for lysosomal storage disorders (6–12 %), congenital disorders of glycosylation (0–8.5 %), metabolic disorders (3.5–34 %), neurological syndromes (18–43 %) and multisystemic genetic syndromes (6.4–21 %). Informed consents differed significantly between laboratories ranging from basic information about genetic testing and possible results to information about insurance, genetic counseling and familial testing, and incidental findings.Our findings suggest that it is important to consider the range of genes offered on epilepsy panels and their predicted phenotypes in an effort toward improving the informed consent process.     

Language Organization and Reorganization in Epilepsy

The vast majority of healthy individuals are left hemisphere dominant for language; however, individuals with left hemisphere epilepsy have a higher likelihood of atypical language organization. The cerebral organization of language in epilepsy has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping (ESM), and more recently, with noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI). Investigators have used these techniques to explore the influence of unique clinical features inherent in epilepsy that might contribute to the reorganization of language, such as location of seizure onset, age of seizure onset, and extent of interictal epileptiform activity. In this paper, we review the contribution of these and other clinical variables to the lateralization and localization of language in epilepsy, and how these patient-related variables affect the results from these three different, yet complementary methodologies. Unlike the abrupt language changes that occur following acute brain injury with disruption of established language circuits, converging evidence suggests that the chronic nature of epileptic activity can result in a developmental shift of language from the left to the right hemisphere or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. Clinical variables have been shown to contribute to cerebral language reorganization in the setting of chronic seizure disorders, yet such factors have not been reliable predictors of altered language networks in individual patients, underscoring the need for language lateralization and localization procedures when definitive identification of language cortex is necessary for clinical care.     

Barriers to the management of patients with surgically remediable intractable epilepsy

It is estimated that only a small proportion of patients with surgically remediable intractable epilepsy receive surgical treatment. There are multiple reasons why this is the case. Patients with intractable epilepsy are sometimes severely disabled and disability can create barriers to getting recommended care. Patients with epilepsy are not well informed about their condition and the available treatments. The incidence of epilepsy is similar in minority populations, and surgically remediable epilepsy frequently presents in adolescence. Nevertheless, these vulnerable populations have specific barriers to receiving epilepsy care, which are often not addressed. In addition, despite scientific evidence for the benefits of the surgical treatment of epilepsy, many healthcare providers do not recommend or adequately discuss surgery with patients. Solutions to these barriers will require interventions that result in informed and capable patients who actively participate in their care and healthcare providers who practice culturally sensitive, recommended care.     

Understanding the delay before epilepsy surgery: who develops intractable focal epilepsy and when?

Intractable temporal lobe epilepsy that is surgically treated in adulthood is a disorder whose onset frequently occurs during childhood and early adolescence. The average duration of epilepsy prior to surgery is on the order of 20 years. The long delay between onset and surgery has at least two components: time from onset to intractability and time from evidence of intractability to surgery. The first interval is prolonged >10 years especially if the onset is during childhood. This suggests a complex natural history that we have not fully appreciated as well as a potential window of opportunity for early secondary intervention. The second interval is also prolonged, especially if onset was during childhood. Reasons for this are not fully clear but may include a reluctance to consider surgery and perhaps difficulty deciding whether seizures are sufficiently intractable to warrant surgery especially after what may have been a relatively benign initial course. Factors involved in the second delay need to be better understood so that surgical interventions can be appropriately targeted early rather than late, thereby reducing serious social, psychological, and educational consequences associated with uncontrolled seizures.     

Epilepsy genes: the link between molecular dysfunction and pathophysiology

Our understanding of the genetic basis of epilepsy is progressing at a rapid pace. Gene mutations causing several of the inherited epilepsies have been mapped, and several more are likely to be added in coming years. In this review, we summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability. Mutations leading to epilepsy have been identified in genes encoding voltage- and ligand-gated ion channels (benign familial neonatal convulsions, autosomal dominant nocturnal frontal lobe epilepsy, generalized epilepsy with febrile seizures "plus"), neurotransmitter receptors (Angelman syndrome), the molecular cascade of cellular energy production (myoclonic epilepsy with ragged red fibers), and proteins without a known role in neuronal excitability (Unverricht-Lundborg disease). Gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.     

Executive Function and Emotional,Behavioral, and Social Competence Problems in Children with Epilepsy

Many researchers have reported elevated rates of emotional, behavioral, and social competence problems (EBSP) in children with epilepsy. Although executive function has been found to be associated with EBSP in children with typical development, almost no research has looked at the individual components of executive function as potential predictors of EBSP in children with epilepsy. This is surprising given the deficits in executive function in children with epilepsy. We investigated EBSP and executive function in 42 children with epilepsy, aged 6.0 to 18.1 years and found, as expected, that EBSP were associated with executive function in these children even after epilepsy-related variables, such as seizure type, were accounted for. However, different components of executive function were related to different emotional, behavioral, and social competence problems in these children. Shifting of mental sets was a significant predictor of emotional, behavioral, and social competence problems whereas inhibition was a significant predictor of behavioral problems. This suggests that different executive function profiles in children with epilepsy may place them at-risk for developing different types of emotional, behavioral, and social competence problems. These results may help researchers and clinicians develop new techniques to identify and treat emotional, behavioral, and social competence problems in children with epilepsy.     

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.     

Factors Involved in Learning Problems and Educational Delay in Children with Epilepsy

Educational delay was assessed in a group of children with epilepsy and co-morbid learning problems, and compared with a matched group of children with learning problems, but without epilepsy. In addition, delay in the academic skills reading/spelling and arithmetic was compared for the two groups. Moreover, the differential contribution for the development of learning problems of each of the following epileptic factors was inspected: type of epilepsy, seizure type, seizure frequency and type of AED-treatment. The ‘Groninger School Onderzoek’ (G.S.O.) was used to yield an objective measurement of school achievement. The first 24 children with a reconfirmed diagnosis of epilepsy and with co-morbid learning problems who were referred to our outpatient department for ‘epilepsy and learning disabilities’ were included in the study. Each child was matched to a control subject (children with learning problems, but without epilepsy). Matching was carried out for the potential confounding factors age, school-type, school-grade and intelligence. The measure for school achievement showed no significant differences between the two groups with a delay in both groups of approximately a half year. Also, no statistically significant difference was found with respect to achievement on the academic skills reading/spelling and arithmetic. The impact of several epileptic factors on the measurement of school achievement were analyzed. The analysis of type of epilepsy showed significant lower school achievement scores for the patients with idiopathic generalized epilepsy compared to the patients with localisation-related epilepsy. Further evaluation of this result shows that most of the patients, classified as idiopathic generalized epilepsy have a recent onset epilepsy, a high seizure frequency and are not yet satisfactorily controlled with antiepileptic therapy. The key factor contributing to learning problems in children with epilepsy is an ‘uncontrolled’ epilepsy, i.e., an epilepsy with high seizure frequency.     

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.     

A Comparison of Children with Epilepsy to an Age- and IQ-Matched Control Group on the Children's Memory Scale

Past research has found that children with epilepsy exhibit decreased memory skills. In addition, some studies have found that children with epilepsy obtain significantly lower IQ scores than controls. In an effort to examine whether children with epilepsy have specific memory weaknesses versus global cognitive difficulties, the present study compared the performance of 62 children (age range = 6–16 years). Thirty-one children with epilepsy were compared to 31 age- and IQ-matched controls on the Children's Memory Scale (CMS) to determine whether differences in memory skills persist when IQ is matched. An independent t-test comparing index and scaled scores was performed. The results indicated that with the exception of the Word Pairs subtest (p < .01), children with epilepsy did not differ significantly on the CMS subtests when IQ was matched. This suggests that list-learning paradigms may be particularly sensitive to memory impairments in children with epilepsy and/or that children with epilepsy have more global cognitive impairments.     

A comparison of children with epilepsy to an age- and IQ-matched control group on the Children's Memory Scale.

Past research has found that children with epilepsy exhibit decreased memory skills. In addition, some studies have found that children with epilepsy obtain significantly lower IQ scores than controls. In an effort to examine whether children with epilepsy have specific memory weaknesses versus global cognitive difficulties, the present study compared the performance of 62 children (age range = 6-16 years). Thirty-one children with epilepsy were compared to 31 age- and IQ-matched controls on the Children's Memory Scale (CMS) to determine whether differences in memory skills persist when IQ is matched. An independent t-test comparing index and scaled scores was performed. The results indicated that with the exception of the Word Pairs subtest (p < .01), children with epilepsy did not differ significantly on the CMS subtests when IQ was matched. This suggests that list-learning paradigms may be particularly sensitive to memory impairments in children with epilepsy and/or that children with epilepsy have more global cognitive impairments.     

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.     

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.     

Neuropsychological profile of children with cryptogenic localization related epilepsy.

Up to one third of the epilepsy population consists of children with cryptogenic localization related epilepsy (CLRE). Unfortunately, the effect of CLRE on the development is still unclear. Behavioral and academic problems have been reported, but no conclusive study concerning the impact of CLRE on neuropsychological functioning is yet published. This study was a systematic cross-sectional open clinical and nonrandomized investigation, which included 68 children with CLRE. Several neuropsychological tests were analyzed and age-related normative values were used as reference. Differences between CLRE and reference values were tested with Paired-Samples t-tests. Z scores were computed to compare the different neuropsychological tests and to inspect whether a characteristic neuropsychological profile exists for CLRE. The Independent-Samples t-test was used to explore which epilepsy factors (seizure type, seizure frequency, age at onset, duration of epilepsy, and drug load) were influencing the cognitive profile of CLRE. There seems to be a characteristic cognitive profile for children with CLRE; children with CLRE experience cognitive difficulties on a wide range of areas-in particular, alertness, mental speed, and memory. Seizure type, seizure frequency, duration of epilepsy, and drug load do not influence this neuropsychological profile. Age at onset was an important risk factor; the earlier the age at onset, the worse the cognitive performance. In spite of the influence of age at onset, the revealed profile can be seen as a stable, independent of temporary factors, neuropsychological profile for children with CLRE.     

Contents

Up to one third of the epilepsy population consists of children with cryptogenic localization related epilepsy (CLRE). Unfortunately, the effect of CLRE on the development is still unclear. Behavioral and academic problems have been reported, but no conclusive study concerning the impact of CLRE on neuropsychological functioning is yet published.

This study was a systematic cross-sectional open clinical and nonrandomized investigation, which included 68 children with CLRE. Several neuropsychological tests were analyzed and age-related normative values were used as reference. Differences between CLRE and reference values were tested with Paired-Samples t-tests. Z scores were computed to compare the different neuropsychological tests and to inspect whether a characteristic neuropsychological profile exists for CLRE. The Independent-Samples t-test was used to explore which epilepsy factors (seizure type, seizure frequency, age at onset, duration of epilepsy, and drug load) were influencing the cognitive profile of CLRE.

There seems to be a characteristic cognitive profile for children with CLRE; children with CLRE experience cognitive difficulties on a wide range of areas—in particular, alertness, mental speed, and memory. Seizure type, seizure frequency, duration of epilepsy, and drug load do not influence this neuropsychological profile. Age at onset was an important risk factor; the earlier the age at onset, the worse the cognitive performance. In spite of the influence of age at onset, the revealed profile can be seen as a stable, independent of temporary factors, neuropsychological profile for children with CLRE.