The effect of seizure type and medication on cognitive and behavioral functioning in children with idiopathic epilepsy

Antiepileptic drugs have been reported to have a variety of adverse effects on behavior and performance in children with epilepsy. Previous studies investigating these side effects, however, have not controlled for the baseline status of the child (e.g. underlying neurological condition, seizure type, socioeconomic status, family variables), making it difficult to determine whether changes in function are attributable to the use of medication. We investigated the cognitive and behavioral profiles of 43 children, aged from 4 to 16 years, with new onset, idiopathic seizures. Twenty-six of these children participated in a 6-month follow-up study, and 12 in a 12-month follow-up study, investigating the effects of antiepileptic medications on psychological functioning. The children were of average intelligence (mean 1Q108) and had not previously been treated with antiepileptic medication. Children were classified as having either generalized convulsive, generalized non-convulsive (absence), simple partial, or complex partial seizures. Prior to the initiation of treatment, children with partial seizures were found to perform better than children with generalized seizures on measures of cognitive functioning. Children with convulsive seizures obtained significantly higher cognitive scores than those with non-convulsive seizures. Children with generalized non-convulsive seizures had lower cognitive scores than subjects with other types of seizure. No differences were found between groups at baseline prior to the initiation of antiepileptic medications. Analysis of subjects' performance after 6 and 12 months of antiepileptic therapy showed no significant deterioration attributable to medication. The differences in cognitive performance of the four seizure groups at baseline were not apparent at the time of follow-up. These results indicate that intrinsic and environmental variables may play a more significant role in predisposing certain children to cognitive and learning problems than do antiepileptic medications.     

Social competence in pediatric epilepsy: insights into underlying mechanisms

This study compared parent-based Child Behavior Checklist (CBCL) social competence scores of 90 children with complex partial seizures (CPS) and 62 with absence epilepsy (CAE) of average intelligence with scores of 91 healthy children. It also examined the role of seizure-related, cognitive, behavioral, linguistic, social communication, and demographic variables on these measures. When differences in cognitive, linguistic, and demographic variables were controlled for, the CPS and CAE groups had significantly lower scores in the school, but not in the social interaction and activities domains compared with the healthy control group. Among the patients, lower Full Scale IQ externalizing behaviors, disruptive disorders, minority status, and impaired social communication, but not seizure variables, predicted lower social competence scores. These findings demonstrate the importance of controlling for cognitive, behavioral, and demographic variables in social competence studies of children with CPS and CAE and the need to assess cognition and behavior when parents report school and social problems in these children.     

The behavioral and emotional correlates of epilepsy in adolescence: a 7-year follow-up study

This 7-year follow-up study examined the behavioral and emotional adjustment of 29 adolescents who experienced regular moderate seizures during middle childhood. Compared with national nonreferred norms on Achenbach checklists, both mothers and adolescents reported clinically significant difficulties in multiple areas regardless of current seizure status. Adolescents who currently experience regular seizures (N=10) reported no differences on psychological outcomes compared with nonseizing counterparts; in contrast, current seizure status was a strong predictor of mother-reported externalizing problems. Hierarchical regression analyses indicated that feelings about having or having had a seizure disorder and mother-adolescent relationship factors were significant predictors of current adjustment over and above current seizure status. Early mother-child relationship process variables and early medical risk were not associated with current adolescent outcomes. The findings are discussed in terms of the multidetermined nature of psychological adjustment to chronic medical illness and factors that may produce versus maintain behavioral and emotional problems in children and adolescents with seizure disorders.     

The impact of childhood epilepsy on neurocognitive and behavioral performance: a prospective longitudinal study

PURPOSE: To assess neurocognitive and behavioral performance in children with idiopathic epilepsy (CWE, n = 74), their siblings without epilepsy (control, n = 23), and children with migraine (CWM, n = 13), and to identify medical factors related to learning or behavioral problems in CWE. METHODS: Subjects, ages 8-13 years with IQs of >/=80, completed a neurocognitive test battery annually for 相似文献   

Effects of age of onset of partial and generalized seizures on neuropsychological performance in children

Neuropsychological performance data from 106 children with epilepsy were evaluated to determine the effects of seizure type and age of onset. The performance of children with partial seizures (N = 49) was similar to that of children with generalized seizures (N = 57). Only one of 13 tests showed a significant difference between groups, with children with partial seizures performing better on that test. The effects of age of onset were also similar in the two seizure groups. Children whose seizures began before the age of 5 years performed significantly worse than children whose seizures began later on four measures (Verbal IQ, Performance IQ, Trails A, and Trails B) and performed more poorly, but not significantly so, on the other nine measures in the battery. A breakdown of the partial group into simple partial, complex partial, and secondarily generalized partial seizure groups found a significant difference between the groups on only one variable, but there were suggestions in the data that the performance of the partial secondarily generalized group was worse than the other two groups. These results indicate that variables associated with an early onset of seizures, regardless of type, place a child at risk for cognitive dysfunction.     

Thought disorder: A developmental disability in pediatric epilepsy

This study compared thought disorder (i.e., impaired use of language to formulate and organize thoughts) in 93 children with complex partial seizures (CPSs) and 56 children with primary generalized epilepsy with absence (PGE) and its relationship to age, seizure, cognitive, and linguistic variables. By the use of psychopathology, social competence, academic achievement, and school problem measures, the functional implications of thought disorder in these two groups were compared. When demographic variables were controlled for, there were no significant differences in thought disorder scores between the CPS and PGE groups. However, the profile of age, gender, seizure, and cognitive variables related to thought disorder differed in the CPS and PGE groups. Within each group, different aspects of thought disorder were associated with different seizure variables. Thought disorder was related to psychopathology, school problems, decreased academic achievement, and poor peer interaction in the CPS group, but with school problems in the PGE group. These findings suggest that CPS and PGE affect the normal maturation of children's discourse skills, albeit through different mechanisms. The relationship of thought disorder to behavioral, academic, and social problems implies that these discourse deficits are one component of the developmental disabilities or comorbidities associated with pediatric CPS and PGE.     

Psychopathology and pediatric complex partial seizures: seizure-related, cognitive, and linguistic variables

PURPOSE: This study examined the role of cognition, language, seizure-related, and demographic variables in the psychopathology of children with complex partial seizure disorder (CPS) of average intelligence. METHODS: One-hundred one CPS and 102 normal children, aged 5.1 to 16.9 years, had a structured psychiatric interview and cognitive and language testing. Parents provided demographic, perinatal, and seizure-related information, as well as behavioral information through the Child Behavior Checklist (CBCL) and a structured psychiatric interview about the child. RESULTS: Significantly more CPS patients had psychopathology, cognitive deficits, and linguistic deficits than did those in the normal group. Among the patients, Verbal IQ predicted the presence of a psychiatric diagnosis, as well as CBCL scores in the borderline/clinical range. Seizure, linguistic, and demographic variables were unrelated to psychopathology. The cognitive and linguistic deficits of the CPS group, however, were predicted by seizure factors (e.g., prolonged seizures/febrile convulsions; seizure frequency/number of antiepileptic drugs) and demographic factors (e.g., minority status). CONCLUSIONS: Because subtle verbal cognitive deficits predict behavioral disturbances in pediatric CPSs, the study's findings highlight the importance of assessing behavior, cognition, and language in these children. They also underscore the negative impact of prolonged seizures, febrile convulsions, seizure frequency, and antiepileptic drug polytherapy on cognition and language in pediatric CPSs.     

Impact of epilepsy characteristics and behavioral problems on school placement in children

Children with epilepsy are known to be prone to educational underachievement as a result of learning and behavioral problems. This cross-sectional study evaluated the effects of the characteristics of epilepsy and behavioral problems on school placement. One hundred eighty-five children aged between 3 and 16 years with nonoccasional epileptic seizures were included; 82 were mainstreamed in regular schools and 103 were in specialized medical and educational institutions for children with epilepsy. Gender distribution and age were comparable for the two groups. Logistic regression analysis indicated a statistically significant effect for age at onset, generalized nonidiopathic epileptic syndromes, number of antiepileptic drugs and behavioral problems, as dominant factors explaining the type of school placement. No significant effect was found for the state of seizure control. By use of a parent-rated behavior questionnaire, children in special institutions were shown to have significantly more problems in the hyperactivity/attention deficit and sociability domains. Later age at onset of epilepsy was related to more depression/anxiety.     

The effect of temperament and neuropsychological functioning on behavior problems in children with new-onset seizures

The present study is part of a larger project that seeks to identify factors that predict children’s behavioral, social, and cognitive adaptation to epilepsy. Children with seizures are more likely to have internalizing and externalizing behavior problems than either healthy children or children with other chronic illnesses. The present research examines risk factors for behavior problems. Early temperament and neuropsychological functioning, specifically executive function and language abilities, are evaluated as unique and moderating predictors of adverse behavioral outcomes in 229 children with a first recognized seizure. Parents assessed temperament, children were administered neuropsychological tests, and teachers evaluated behavior 36 months after seizure onset. Results revealed that early temperament and neuropsychological functioning, specifically executive function, predicted behavioral outcomes 3 years after seizure onset.     

Frontal and temporal volumes in children with epilepsy

This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have smaller total brain, frontal, and temporal lobe volumes than normal children and how this is related to seizure, cognitive, psychiatric, and demographic variables. Forty-four children with CPS and 38 normal children, aged 5-16 years, underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, frontal parcellation, and temporal lobe volumes were computed. Other than significantly larger temporal lobe white matter volumes in the CPS group, there were no significant differences in brain volumes between the CPS and normal groups. Earlier onset, longer duration of illness, younger chronological age, and presence of a psychiatric diagnosis were significantly related to smaller frontotemporal volumes in subjects with CPS. Although these findings suggest that CPS might affect development of the temporal and frontal regions, we are unable to rule out the possibility that smaller frontotemporal volumes might predispose children to CPS. These findings highlight the need to control for seizure, cognitive, psychiatric, and demographic variables in studies of frontotemporal volumes in pediatric CPS.     

Mental retardation subsequent to refractory partial seizures in infancy

Whether seizures are the direct cause of cognitive deterioration in epileptic children is undetermined. This retrospective study aimed to delineate a subgroup of pediatric patients with cognitive deterioration and refractory seizures in the absence of recognized causes for mental retardation. Of the 80 children identified as having mental retardation and refractory seizure disorder, seven (8.7%) had normal cognitive development until at least 1 year of age. Their metabolic status was normal. Five of them suffered repeated frequent partial seizures with onset in the first year of life and two had repeated episodes of status epilepticus. All seven had similar characteristics of early onset partial seizures, six of them had partial seizures secondarily generalized and one had complex partial seizures. The time of peak cognitive deterioration correlated with increases in seizure frequency during that period. Evaluation revealed a well-defined epileptic focus in the absence of neuroimaging abnormality except for hippocampal atrophy in the two children with complex partial seizures and a small vascular malformation in one child. Uncontrolled partial seizures in the first months of life may result in cognitive deterioration.     

Neuropsychological aspects of epilepsy.

Brain dysfunction between seizures is common in epilepsy and a systematic assessment of it assists in planning directed programs of remediation. A battery of well-validated neuropsychological tests formulated with the needs of persons with epilepsy in mind can be of particular help in this regard. Increasing impairment in brain functions is shown to be associated with increasing emotional problems. Medical variables pertaining to seizure history include seizure type, cause, age at onset of seizures, duration of disorder, and seizure frequency. An exploration of relationships between these variables and measures of abilities and adjustment reveals a number of findings, some of which are complex. A review of the cognitive effects of antiepileptic drugs shows that the barbiturates have at least slightly greater adverse cognitive and behavioral effects than other drugs including carbamazepine, phenytoin, and sodium valproate. Whether cognitive differences exist among these latter medications is currently in question. Carbamazepine has the best-established favorable psychiatric effect.     

Carbamazepine Versus Phenobarbital for Partial Onset Seizures in Children

Thirty-nine children were treated with either phenobarbital (PB) or carbamazepine (CBZ) for newly diagnosed partial onset seizures. Drug selection was randomized in 33 subjects. Parents and the psychologist evaluating the child were blind to drug identity. Psychometric and behavioral evaluations were done at intake and at 6- and 12-month follow-ups. There were no significant differences between drugs in effect on behavior or cognitive function. CBZ caused more systemic problems. There was a trend toward better seizure control with CBZ, but this was not statistically significant. Although individual children in each group had changes in behavior or cognitive status, neither group changed significantly, in either acute or chronic follow-up.     

Cognitive skills in children with intractable epilepsy: comparison of surgical and nonsurgical candidates

PURPOSE: To compare neuropsychological performance of two groups of children with intractable epilepsy: those who are surgical candidates, and those who are not. METHODS: Intelligence, verbal memory, visual memory, academic skills, and sustained attention were measured in children aged 6-18 years. The effects of number of antiepileptic drugs (AEDs), seizure frequency, age at seizure onset, and duration of seizure disorder were examined. RESULTS: Both groups had high rates of impairment. Group differences were found only on the verbal memory task. Children who experienced seizures in clusters had higher IQ, reading comprehension, and arithmetic scores. Age at seizure onset and proportion of life with seizures were related to IQ. Performance did not vary with AED monotherapy versus polytherapy. CONCLUSIONS: Few differences exist in cognitive performance between children with intractable seizures who are and those who are not surgical candidates. These findings suggest that children who are not surgical candidates can serve as good controls in studies on cognitive outcome of surgery.     

Complex partial seizures of childhood onset. A five-year follow-up study

Few detailed studies have examined the long-term outcome of complex partial seizures (CPS) in children and adolescents. Previous studies have selected patients on clinical criteria only or have included those with benign focal epileptiform discharges of childhood, nonepileptiform sharp transients, and generalized epileptiform discharges. We have followed up 29 patients with clinically and electroencephalographically defined CPS of childhood onset for five years or more. Twelve patients are seizure free, eight of them after having epilepsy surgery. Of the remaining, eight patients have intractable seizures. Only one patient was able to discontinue anticonvulsant therapy after epilepsy surgery. No patient had spontaneous remission of seizures without anticonvulsant medications. School difficulties, behavior problems, and unemployment were seen in half the group. We believe CPS in this age group are difficult to control and need aggressive management. In selected patients, epilepsy surgery offers a good chance of seizure control and improvement of educational, social, and vocational potential.     

Complex Partial Seizures of Temporal Lobe Origin in Children of Different Age Groups

Summary: The semiology of complex partial seizures(CPS) of temporal lobe origin in adults is well known and is important in establishing seizure localization in patients considered for epilepsy surgery. In contrast, the behavioral features of temporal lobe seizures (TLS) in children described in the literature have not been consistent. In the present study, we investigated children with TLS to compare their attacks to TLS occurring in adults. The study was based on video recordings of 29 children with TLS aged 18 months to 16 years. Children were included, if they became seizure-free after temporal lobectomy (except 4 children with a marked reduction in seizure frequency and 1 with isolated auras), and if clear unitemporal seizure onset in ictal EEG-recordings, unilateral radiological lesions, and corresponding histopathological findings were detected. Children aged >6 years had TLS with features similar to those of adults. In younger children, typical semiology included symmetric motor phenomena of the limbs, postures similar to frontal lobe seizures in adults, and head nodding as in infantile spasms. We concluded that the clinical features of TLS in younger children can be misleading and should therefore be considered with caution in selecting patients for surgical procedures on the temporal lobe.     

Cognitive decline in severe intractable epilepsy

PURPOSE: To explore the relation between seizure-related variables and cognitive change in patients with severe intractable epilepsy. METHODS: A retrospective analysis of data from 136 patients who had undergone a cognitive assessment on two occasions at an interval of > or =10 years. Cognitive measures included tests of memory and executive skills in addition to intelligence quotients (IQ). Details were available regarding seizure type and frequency in the intertest interval. RESULTS: Cognitive decline was severe and occurred across a wide range of cognitive functions. The frequency of generalised tonic-clonic seizures was the strongest predictor of decline. Complex partial seizure frequency was associated with a decline in memory and executive skills but not in IQ. Seizure-related head injuries and advancing age carried a poor cognitive prognosis, whereas periods of remission were associated with a better cognitive outcome. Early age at onset was not implicated, and duration of epilepsy was a much less potent predictor of cognitive decline than has been reported in cross-sectional studies. No evidence indicated that a higher level of cognitive function protected against cognitive decline. CONCLUSIONS: Our findings, together with those from animal studies and surgically treated patients, suggest that seizures can have a direct adverse effect on cognition and that good seizure control even after years of intractability can have a beneficial impact on cognitive prognosis. This study was based on individuals who merited two cognitive assessments > or =10 years apart and hence is biased in favor of those with the most severe forms of refractory epilepsy and those with decline.     

Anterior Temporal Lobectomy and Medically Refractory Temporal Lobe Epilepsy of Childhood

The evaluation and outcome of 22 patients who had onset of complex partial seizures (CPS) of temporal lobe origin in childhood and subsequently underwent anterior temporal lobectomy are described. All patients showed improved seizure control; 81.8% had a reduction greater than or equal to 95% in seizure frequency. However, many patients had difficulty adjusting to a seizure-free life. Psychosocial, behavioral, and educational problems occurred more frequently in patients whose surgery was delayed until adult life. We conclude that attempts should be made early in the course of CPS of childhood to determine whether the seizures are truly intractable to medical management so that surgical intervention can be expedited.     

Age at onset of seizures in young children

Age at onset of seizures in young children and its relationship to factors such as prior neurological status and neurological outcome were examined. Of 52,360 children, 39,270 of whom were followed for the full 7 years, a total of 2,635 experienced one or more seizures between birth and 7 years of age. The incidence of nonfebrile convulsions was highest in the first year of life, especially in the first month. Children with neonatal seizures who later developed nonfebrile seizures did so early, two-thirds by 6 months and three-quarters by 1 year of age. Children with neurological or developmental abnormality assessed in the first year of life did not have their first seizure earlier than children without abnormality. Neurological abnormality in the first year of life before any seizure, and the presence of minor motor seizures, were associated with an increased rate of mental retardation and cerebral palsy at age 7, but early age at onset appeared to have little prognostic value regarding intellectual function, cerebral palsy, and epilepsy.     

Predictors of neuropsychological impairment in seizure-free epilepsy patients

Persons with epilepsy are at increased risk of cognitive deficits as a result of various factors like etiology, structural brain lesions, seizure frequency, seizure type, age at onset of epilepsy, hereditary factors, psychosocial factors, and possible adverse effects of antiepileptic drugs (AEDs). Despite the fact that the majority of epilepsy patients are seizure-free, previous studies on the relationship between epilepsy-related variables and cognitive function have mainly been conducted on patients with persisting seizures. In this study 158 adults with epilepsy on AED monotherapy and without epileptic seizures for at least 2 years were investigated with a neuropsychological test battery in addition to a neurological examination, MRI and EEG. The major findings were that the group had education and employment status similar to the population mean and neuropsychological function in the normal range. In the patient group without idiopathic generalized epilepsy known cerebral etiology was found to be a highly significant predictor of neuropsychological deficit. For patients with idiopathic generalized epilepsy, early seizure debut at < or =18 years was a powerful predictor of neuropsychological impairment.