Neurocognitive development of children with congenital unilateral brain lesion and epilepsy

The aim of this study was to specify the neuropsychological deficits characteristic of children with unilateral non-progressive brain lesion. In order to assess these specific functions, we used a comprehensive model of congenital hemiparesis with partial epilepsy and newly diagnosed partial epilepsy without hemiparesis. The neuropsychological examination was performed using the NEPSY test battery on 44 children aged from 4 to 9 years. The children were divided into three groups: 18 children suffering from congenital hemiparesis with chronic partial epilepsy, 12 children with newly diagnosed partial epilepsy prior to anti-epileptic treatment, and 14 healthy controls matched by sex, age, and socioeconomic status. Children with congenital hemiparesis and epilepsy had a more clearly expressed cognitive dysfunction, especially in language, visuo-perceptual and memory tasks, than children with newly diagnosed partial epilepsy. The profile of cognitive weakness appears to be diffuse and quite similar in both groups, and it did not demonstrate a clear effect of lateralization, according to the side of epileptic electroencephalogram discharges. Children within both groups are likely to have a high risk of developing attention, phonological, visuo-perceptual, and memory deficits in their life. Especially interesting and surprising was the fact that the newly diagnosed epilepsy group demonstrated impairment not only in attention, visuo-perceptual and short-term memory skills, but also in auditory perception, lexical function, and the comprehension of speech. Therefore, it is recommended that children with epilepsy would undergo neuropsychological examination in order to assess their cognitive abilities.     

Antiepileptic drugs in pregnancy: late effects on the children's cognitive abilities. Preliminary data.

The authors report preliminary data on cognitive development of 57 children, perspectively followed, who were exposed to antiepileptic drugs in utero for maternal epilepsy. Cognitive impairments are associated with other risk factors in 5 cases, so that a direct AEDs responsibility is not easy to prove.     

Beneficial effects of antiepileptic medication on absence seizures and cognitive functioning in children

In this prospective clinical study, the effects on cognitive functioning of absence seizures, epileptiform EEG discharges, and their abolishment by antiepileptic medication were evaluated in patients newly diagnosed with childhood absence epilepsy or juvenile absence epilepsy. Eleven children in the study group and ten age- and gender-matched controls with mild asthma underwent combined video/EEG and neurocognitive assessment (IQ, fine-motor fluency, attention, visual and spatial memory). The neuropsychological assessment was repeated after the introduction of antiepileptic medication. Ten children with absence epilepsy became clinically seizure free. The study group improved in attention, fine-motor fluency, and visual memory. The controls improved only in fine-motor and attention skills. Duration of generalized 3-Hz spike-wave discharges and clinical absence seizures was negatively correlated with performance on the visual memory task. Cessation of seizures induced by antiepileptic medication may support neurocognitive functioning in children.     

Neurocognitive profiles in children with epilepsy

Purpose: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization‐related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles. Methods: Fifty‐one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within‐group analyses were also conducted to examine seizure‐related factors that may be related to neuropsychological test performance. Key Findings: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another. Significance: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE.     

Early cognitive development in children born to women with epilepsy: A prospective report

Purpose: In this prospective study the early cognitive development of children born to women with epilepsy (n = 198) was assessed and compared to a group of children representative of the general population (n = 230). Methods: The children were assessed when younger than the age of 2 years using the Griffiths Mental Development Scales, either in their local participating hospital or in their home. The assessments were completed by an assessor who was blinded to whether the child’s mother had epilepsy and to antiepileptic drug type. Results: Children exposed to sodium valproate had a statistically significant increased risk of delayed early development in comparison to the control children. Linear regression analysis showed a statistically significant effect of sodium valproate exposure on the child’s overall developmental level that was not accounted for by confounding variables. Delayed early development is also noted for children within an ad hoc group of less commonly utilized antiepileptic drugs, although conclusions cannot be drawn due to the size of this group (n = 13). Children exposed to either carbamazepine or lamotrigine in utero did not differ significantly in their overall developmental ability. Differences noted in specific developmental areas for these two groups were not statistically significant after the control for confounders such as socioeconomic status and maternal IQ. Discussion: Women with epilepsy should be informed of the risks posed to their potential offspring prior to pregnancy to allow for informed decisions regarding treatment. Children exposed in utero to antiepileptic drugs should be monitored throughout childhood to allow for early intervention when necessary.     

Evaluating cognitive functions with visual and auditory number assays and P300 in children with epilepsy

This study was planned to evaluate cognitive functions, especially attention and immediate recall, in children with epilepsy by using P300 and neuropsychological tests, which included visual and auditory number assays. Fifty five patients with partial seizures, 45 patients with generalized seizures and 20 patients with intractable seizures were enrolled in the study. Twenty five healthy children were taken as the control group. The results were as follows: 1. P300 latencies were significantly longer in the intractable and partial groups when compared with the control subjects. 2. The duration of epilepsy, seizure frequency, cerebral imaging pathologies were not significantly correlated with delayed P300 latencies. 3. The results of the visual and auditory number assays test showed significant abnormalities when each of the three groups were compared with the normal controls. 4. Though some subgroups of the neuropsychological tests were correlated with the P300 latencies, an overall significant correlation was not present between them. So, we suggest that neuropsychological tests are more convenient for the assessment of cognitive functions in children with epilepsy than the P300 recordings.     

Identification of functional domains affected by developmental exposure to methylmercury: Faroe islands and related studies

The Faroe Islands study is a prospective study designed to assess the neurological and behavioral consequences of in utero exposure to methylmercury (meHg). Maternal exposure to meHg was through consumption of fish and intermittent higher-level exposure through pilot whale meat, while consumption of pilot whale blubber resulted in maternal exposure to PCBs. Analysis of the neurobehavioral domains affected revealed impairment in attention, memory, and auditory processing, impairment in primary auditory function, and to a lesser extent motor impairment. For four of the eight endpoints affected by meHg exposure atp < .10, impairment was also correlated (p < .10) with in utero PCB exposure as measured by cord tissue PCB levels. Further analyses provide evidence for an independent effect of PCBs and meHg on these endpoints. Cross-sectional studies in a smaller number of children in the Amazon and Madeira by the same group of investigators, in which average meHg maternal hair levels were about twice as high those in the Faroe Islands, identified auditory, visual, and/or motor deficits, with little or no evidence of deficits in attention or memory. However, the results of the cross-sectional studies must be interpreted with caution, due to limited statistical power as well as a lack of opportunity to correlate effects to in utero exposure.     

Cognitive function in Nigerians with newly diagnosed epilepsy

OBJECTIVE: The objective of this study was to evaluate the pattern of cognitive disturbances in Nigerian Africans with newly diagnosed epilepsy, prior to onset of drug therapy. METHODS: A total of 60 consecutive patients (mean age 31.6 +/- 17.4, range 14-55 years) presenting with a clinical diagnosis of epilepsy were recruited for the study. Sixty healthy volunteers without a history of epilepsy and who were age-, sex- and level of education matched with the epileptic patients, were recruited as controls. The administration of cognitive tests was done with the FePsy computerized neuropsychological test battery. The tests administered were the visual and auditory reaction times, the continuous performance test and the recognition memory tests to assess mental speed, attention and memory respectively. The means of the cognitive performances of the epileptic patients and controls were statistically compared. RESULTS: Epileptic patients performed worse than the controls across the spectrum of cognitive tasks assessed (P = 0.00001; P < 0.025), with the exception of the beta parameter (response bias) of the vigilance test (P = 0.488; P > 0.025). CONCLUSIONS: The cognitive impairments of short-term memory, psychomotor speed and sustained attention observed in this study are similar to those reported in the literature for patients with epilepsy. The results of this study will be useful in the counseling of patients on their educational, social and vocational needs.     

Spatial memory alterations in children with epilepsy of genetic origin or unknown cause

Genetic generalised epilepsy or epilepsy of unknown cause can remit before adolescence. In many children, the disease does not interfere with their academic achievement. Although there are neuropsychological studies characterising the cognitive profile, there are no studies in this population focused on spatial orientation abilities. In this study, we compared children with genetic generalised epilepsy or epilepsy of unknown cause with a control group using a virtual spatial learning task. Children with epilepsy showed worse performance on the spatial orientation task, although their visuo‐spatial memory, attention, and working memory were normal. These results confirm that genetic generalised epilepsy or epilepsy of unknown cause is associated with more cognitive deficits. Virtual reality technologies can complement clinical assessment.     

Factors Associated with Academic Achievement in Children with Controlled Epilepsy

Children with epilepsy are at risk for academic underachievement. Multiple etiologies for this academic vulnerability have been suggested by past research including lower self-esteem, inattention, memory inefficiency, and lower socioeconomic status. The present study assessed 65 children (mean age = 10 years, 5 months) with well-controlled epilepsy on the four primary factors, as well as academic achievement and intelligence. A stepwise regression analysis was employed with academic achievement as the dependent variable and measures of self-esteem, attention, memory, and socioeconomic status as independent variables. When intelligence was controlled, attention was the only variable associated with achievement scores. Seizure variables including seizure type and duration of epilepsy were not associated with differences in academic performance. Findings support the importance of measuring attention skills in children with epilepsy and suggest that reduced auditory attention skills may be associated with decreased academic performance in these children.     

Motor and cognitive functions in newly diagnosed adult seizure patients before antiepileptic medication

OBJECTIVE: Motor and cognitive functions in patients with partial or generalized onset of seizures were evaluated prior to the administration of antiepileptic medication. MATERIAL AND METHODS: Motor function, attention and memory of 52 consecutive newly diagnosed adult patients with partial or generalized seizures were assessed with neuropsychological tests. RESULTS: Patients with partial onset of seizures did not differ from patients with generalized seizures in tests of motor function or attention, nor in tests of learning and memory. Compared to controls patients with epilepsy performed significantly worse on visual motor tasks, mental flexibility and in delayed visual memory. Within the patient group as a whole lower education, higher age and symptomatic epilepsy with more abnormal CT scan findings tended to associate with worse performance in tests of concentration and mental flexibility and tests of memory. CONCLUSION: These findings indicate that newly diagnosed adult patients with partial or generalized onset of seizures prior to treatment with antiepileptic medication experience some problems in visual motor tasks, mental flexibility and memory even without the numerous risk factors for cognitive deficits in epilepsy. In newly diagnosed patients with epilepsy as a whole symptomatic etiology was associated with somewhat more pronounced cognitive problems.     

Auditory verbal memory and psychosocial symptoms are related in children with idiopathic epilepsy

ObjectiveIdiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires.MethodsCognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9–14 years, were assessed and compared with 27 age- and education-matched healthy controls.ResultsCompared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p < 0.0001), working memory deficits (p < 0.003), auditory verbal long-term memory deficits (p < 0.0021), and more frequent psychosocial symptoms (p < 0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls.SignificanceResults suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms.     

Pregnancy outcome and neurodevelopment of children exposed in utero to psychoactive drugs: the Motherisk experience.

This paper presents an overview of the Motherisk Program data on pregnancy outcome and neurodevelopment of children exposed in utero to selected psychoactive drugs. First, the use of cocaine during pregnancy has been associated with increased risk of spontaneous abortions, abruptio placenta, premature labor, and stillbirth. Twenty-three adopted children exposed in utero to cocaine demonstrated an 8-fold increase in risk for microcephaly compared with controls. Global intelligence quotients (IQ) did not differ between the 2 groups, but the cocaine-exposed children achieved significantly lower scores on the Reynell language test. Second, the long-term neurobehavioral effects of fetal alcohol syndrome (FAS) were studied in 384 children to show that alcohol-induced brain insults, which consist of attention and memory deficits together, and poor adaptability and organization are not attenuated with age. Third, the rates of major malformations in children exposed in utero to fluoxetine, tricyclic antidepressants, and nonteratogenic drugs did not differ or exceed the expected rates in the general population. A 2nd phase of this study established the safety of antidepressants during pregnancy by demonstrating that the mean IQ and language scores are comparable in the 3 groups. A level 2 ultrasonography is recommended in cases of in utero exposure to lithium and carbamazepine because of an increased risk of cardiac malformations and spina bifida, respectively.     

Neuropsychological assessment in children with absence epilepsy

OBJECTIVE: To define cognitive deficits in children with absence epilepsy. BACKGROUND: Cognitive deficits have often been reported in children with epilepsy, but have rarely been characterized in patients with a specific epileptic syndrome. METHODS: Detailed neuropsychological testing was carried out on 16 right-handed children with absence epilepsy with similar clinical and EEG findings, and the findings were compared to 16 well-matched right-handed children without absence epilepsy. RESULTS: The authors found lower scores of measures of general cognitive functioning and visuospatial skills in patients with absence epilepsy, as compared to controls. Memory disturbances were also detected in absence epilepsy patients, with selective involvement of nonverbal memory and delayed recall. In contrast, verbal memory and language skills were relatively preserved. Patients whose seizures began at an earlier age seemed to have more severe cognitive deficits. CONCLUSION: Language skills tend to be relatively well preserved in children with generalized epilepsy, with more dysfunction seen in global terms rather than specific lateralizing deficits. Patients with absence epilepsy seem to show a similar neurocognitive profile that may be a reflection of the underlying epilepsy syndrome.     

Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event

Autobiographical memory (AM) is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO) exposed during gestation to insufficient maternal thyroid hormone (TH), a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH), who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval.     

Neuropsychological profile of patients with juvenile myoclonic epilepsy: a controlled study of 50 patients

The purpose of this study was to verify possible cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and its relationship to factors related to epilepsy and schooling. Fifty subjects diagnosed with JME and 50 controls underwent neuropsychological assessment evaluating intellectual functions, attention, memory, executive functions, and language. The patients were further divided into two subgroups on the basis of educational level: < or = 11 and >11 years of formal education. Participants diagnosed with JME scored significantly below age-, education-, and gender-matched controls on neuropsychological measures of attention, immediate verbal memory, mental flexibility, control of inhibition, working memory, processing speed, verbal delayed memory, visual delayed memory, naming, and verbal fluency. A positive correlation was observed between duration of epilepsy and cognitive decline. However, in the group of patients with >11 years of education, this correlation was not significant. In this series of patients with JME, neuropsychological evaluation suggests widespread cognitive dysfunction outside the limits of the frontal lobes. The duration of epilepsy correlated with cognitive decline, and patients with higher education manifested less progression of deficits.     

Educational underachievement in children with epilepsy: a model to predict the effects of epilepsy on educational achievement

In this study, we evaluated the impact on educational achievement of four characteristics of epilepsy individually and combined: epilepsy syndrome (type of epilepsy), seizure type, the frequency of epileptiform electroencephalographic (EEG) discharges, and the effect of antiepileptic treatment. Simultaneously, the effect on cognitive function and the relationship between educational underachievement and cognitive impairment were evaluated, focusing on memory, attention, speed of information processing, and intelligence level. This study was an open, controlled, parallel-group, nonrandomized clinical investigation. Eligible patients were selected when referred to our center for assessment of relationships between epilepsy and learning impairment in the years 1997 to 2001. Separately, children without neurologic deficit and without educational delay were assessed with the same tests as the children with epilepsy. This latter group is used in this study as a control group. One hundred seventy-six children with epilepsy and 113 controls were included. Gender distribution and age were comparable for the two groups. All children were in regular primary education. The children were assessed with a test battery consisting of tests for educational achievement, cognitive tests and tests for reaction time, and tests for memory and intelligence. Multivariate analysis of variance for tests of educational achievement showed a statistically significant effect for type of epilepsy (F = 4.386; P = .04), caused by the statistically lower scores for patients with localized epilepsy and symptomatic generalized epilepsy. For the reaction-time tests, a statistically significant effect for epileptiform EEG discharges (F = 3.165; P = .01) and treatment (F = 4.472; P = .001) on both vigilance tests was found, caused by patients with frequent epileptiform EEG discharges and polytherapy. Two-way interactions showed an interaction with type of epilepsy, with more patients with symptomatic generalized epilepsy having frequent epileptiform EEG discharges and polytherapy. For memory, none of the analyses showed statistically significant effects. For intelligence only for type of epilepsy, a statistically significant effect was found (F = 10.174; P = < .001). We propose a model with the type of epilepsy (epilepsy syndrome) as the dominant factor explaining educational underachievement in children with epilepsy. Such educational underachievement is most prominent for the localized and symptomatic generalized epilepsies, which suggests a dominant impact of underlying etiology (brain dysfunction or damage). These epilepsies are characterized specifically by a lower intelligence; hence, this could be the primary cognitive factor mediating between the type of epilepsy and educational underachievement. From the other factors, treatment (the use of polytherapy) and frequent epileptiform EEG discharges are associated with impaired vigilance, which could have an additional influence on educational achievement. These factors are, however, not independent of the type of epilepsy.     

Baseline cognition, behavior, and motor skills in children with new-onset, idiopathic epilepsy

Aim  Epilepsy is associated with difficulties in cognition and behavior in children. These problems have been attributed to genetics, ongoing seizures, psychosocial issues, underlying abnormality of the brain, and/or antiepileptic drugs. In a previous study, we found baseline cognitive differences between children with partial versus generalized and convulsive versus non-convulsive seizures. Measures in that study focused primarily on IQ scores. In the present study, we assessed baseline function with respect to new learning, attention, and memory, thus providing a more comprehensive profile than our previous study.
Method  We examined 57 children (42 females, 15 males), aged 6 to 17 years (mean 10y 1mo, SD 2y 9mo), with new-onset, idiopathic epilepsy, using tests of cognitive function reflective of new learning, memory, and attention. Seizures were classified as generalized convulsive ( n =5), generalized non-convulsive ( n =18), or focal ( n =34). Focal seizures were divided into unilateral versus bilateral independent foci, and presence versus absence of secondary generalization.
Results  Attention was a particular area of weakness across all groups. The Vocabulary score of an intelligence screen was higher for the focal seizure groups ( p =0.012), primarily because of a difference between the unilateral focal and the primary generalized groups ( p <0.047). Children with generalized, non-convulsive seizures performed significantly worse than the focal group on a measure of short-term auditory memory ( p =0.019). All groups performed poorly on a test of visual–motor speed.
Interpretation  These findings suggest intrinsic abnormalities in children with new-onset, idiopathic epilepsy at baseline.     

Physical and Psychomotor Development in the Offspring Born to Mothers with Epilepsy

Summary:  Psychomotor development of 71 children born to mothers with epilepsy was prospectively studied and compared to those of 99 controls matched for age, maternal educational level and age, and socioeconomic status. Intrauterine growth retardation disappeared before age 3 years. Assessment at age 1.5 years revealed that exposure to seizures, high dose of antiepileptic drugs (AEDs) in utero, and small head circumference at birth affected development quotient (DQ) scores of motor or linguistic abilities or both. DQ scores of motor ability of children of mothers with complex partial seizures were lower than those with simple partial seizures when assessed at age 3 years. Assessments at age 1.5 years revealed that the total daily dose of AEDs correlated negatively with DQ scores of motor ability, and at age 3 years, maternal educational level affected DQ scores of some fields, including linguistic ability. The effects of AED exposure in utero and the occurrence of maternal seizures on the development of offspring were found to matter more at the younger age, but later on, the child care environment and, in particular, maternal ability of child-rearing, became more important. Our findings indicate that careful and regular follow-ups are needed to monitor the developmental stages of children of mothers with epilepsy, and the introduction of a day nursery should be suggested if necessary.     

Sleepiness, on-task behavior and attention in children with epilepsy who visited a school for special education: A comparative study

Children with epilepsy are at risk for problems in daytime functioning. We assessed daytime sleepiness, on-task behavior and attention in 17 children (aged between 7 and 11 years) with epilepsy who visited a school for special education and compared these to 17 children from a control group who visited a regular school. Within the group of children with epilepsy, we explored whether behavioral and cognitive functioning varied across days of the week and times of the day. Data were collected during four consecutive school days. Children with epilepsy had more daytime sleepiness, less on-task behavior and less attention than controls. Furthermore, sleepiness and on-task behavior varied cross days of the week and times of the day, an effect that was not found in controls. Implications for educational practice are discussed.