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.     

Should cognition be screened in new-onset epilepsies? A study in 247 untreated patients

The aim of our study was to assess cognition in newly diagnosed and untreated patients with epilepsy in order to determine the prevalence and the determinants of cognitive deficits at this early stage of the disease. A total of 247 untreated patients with newly diagnosed epilepsy underwent a brief test battery focusing on attention and executive functions (EpiTrack^®) and memory (short form of the VLMT). In addition, the assessment included ratings of self-perceived deficits in attention and memory. Impairments in attention and executive functions were seen in 49.4 % of the patients and memory deficits in 47.8 %. Unimpaired performance in both domains was observed in 27.9 % of the cases. Self-perceived deficits in attention were only reported by 28.7 % of the patients, and 25.1 % of the patients complained of memory impairments. Lower education and a symptomatic, i.e., lesional, cause of epilepsy were associated with worse performance in attention and executive functions, whereas worse memory performance was related to generalized tonic–clonic seizures. Results indicate a high prevalence of cognitive deficits at an early stage of epilepsy, which calls for consideration in the daily clinical care. Patients appear to underreport cognitive deficits. Thus, a routine application of a brief standardized neuropsychological screening before the initiation of a pharmacological treatment would be appreciated to provide a baseline to evaluate subsequent treatment success, to eventually initiate countermeasures, and to monitor the course of the disease.     

The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Canadian Study Group for Childhood Epilepsy

PURPOSE: To compare the cognitive and behavioural effects of clobazam versus standard monotherapy in the treatment of childhood epilepsy. METHODS: A randomized, double-blind, prospective design was carried out at three Canadian pediatric epilepsy centres. This study was part of a larger multi-centre study on the efficacy of clobazam. Children with newly diagnosed epilepsy were assigned randomly to receive clobazam or carbamazepine. Children who had failed previous treatment with carbamazepine were assigned randomly to clobazam or phenytoin. Children who had failed on any other antiepileptic drug were assigned randomly to receive clobazam or carbamazepine. In a subset of patients neuropsychological assessments were carried out at 6 weeks and 12 months after initiation of medication. Intelligence, memory, attention, psychomotor speed, and impulsivity were assessed. RESULTS: There were no differences between the clobazam and standard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months. There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period. CONCLUSION: The cognitive and behavioural effects of clobazam appear to be similar to those of standard monotherapy.     

Reading abilities and cognitive functions of children with epilepsy: influence of epileptic syndrome

Children with epilepsy are at risk of developing learning disorders. To explore the influence of the epileptic syndrome on reading abilities, we have compared the neuropsychological profile of 12 children with benign idiopathic epilepsy with rolandic spikes, 10 with temporal lobe epilepsy and 12 with idiopathic generalized epilepsy. Children underwent a selection of standardised tests designed to assess: oral language, reading, short-term memory, attention and behavioural adjustment. Analysis of variance was adjusted according to age of onset of the epileptic syndrome, duration of the syndrome, and performance IQ for each group. Children with temporal lobe epilepsy (TLE) had significantly lower scores for reading speed and comprehension, but epileptic variables (the age of onset of epilepsy, duration and activity of epilepsy) had influenced academic performances. In the TLE group there was a clear effect of the topography of the epileptic foci (left-side TLE vs. right-side TLE) on reading profile. Furthermore, the effect of epileptic syndromes was found in phonological, semantic and verbal working memory deficits in the TLE group. To a lesser extent children with idiopathic generalized epilepsy (IGE) also exhibit cognitive deficit. The results of the present study lend support to epilepsy-specific patterns of neuropsychological dysfunction in children that should be considered to improve remediation of academic underachievement in these populations.     

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.     

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.     

Benign childhood epilepsy with occipital paroxysms: neuropsychological findings

Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory abilities (p<0.01), visual perception and visual-motor integration global abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01). The presence of cognitive dysfunctions in subjects with EBOS supports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other studies that have documented subtle neuropsychological deficits in benign partial epilepsy, we stress the importance of reconsidering its supposed "cognitive benignity", particularly in occipital types.     

Executive functions in children with frontal and temporal lobe epilepsy.

Even though frontal lobe epilepsy (FLE) is a relatively common seizure type, no formal psychometric studies of children with FLE have been reported. We compared 12 children with FLE and 15 children with temporal lobe epilepsy (TLE) on neuropsychological tests of attention, memory, executive functioning, and adaptive functioning. The results of these tests indicated that the children with FLE had deficits in planning and executive functions, whereas their verbal and nonverbal memory was intact. The opposite pattern was observed in children with TLE. Measures of executive functioning and impulse control were the best predictors of adaptive functioning. The findings suggest that children with FLE have a pattern of cognitive deficits that differs markedly from the pattern seen in children with TLE. Children with FLE have prominent deficits in executive functioning that appear to be related to poor behavioral adaptation.     

癫(癎)患者认知功能特点的研究

目的:研究癫(EP)患者认知功能的特点及其影响因素。方法:采用听觉词语测验、逻辑记忆测验、数字符号转换测验、Stoop字色干扰测验、连线测验、言语流畅性测验、Rey-Osterrieth复杂图片测验及Boston命名测验对166例EP患者进行认知评定。结果:EP患者存在广泛的认知损害,包括言语记忆、情景记忆、视觉空间结构记忆、词语学习能力、注意力、抗干扰能力、精神运动速度及言语命名功能等方面,以词语延迟回忆、注意力及精神运动速度损害最为明显。而未经药物干预的新诊断EP患者已存在除视觉空间记忆、注意力及抗干扰能力外的上述认知功能的损害,以词语延迟回忆最为明显。随访病例与新诊断病例的区别在于,前者在抗干扰能力及精神运动速度方面损害更明显。结论:新诊断EP组以及随访EP组病例在多项神经心理学测验中得分均低于正常对照组,两组之间差异有统计学意义。     

Does Short-Term Antiepileptic Drug Treatment in Children Result in Cognitive or Behavioral Changes?

Summary: Purpose: To determine possible cognitive and behavioral effects of antiepileptic drug (AED) therapy by assessing children with newly diagnosed epilepsy before and after initiation of treatment. A comparison group of children with diabetes mellitus (DM) was included to control for the effects of practice, maturation, and chronic illness.
Methods: Baseline neuropsychological assessments were completed for children with epilepsy (n = 37) and children with DM (n = 26) recruited through outpatient clinics at a regional children's hospital. Children were reevaluated 6 months from baseline testing. At follow-up, children with epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis included a between-group repeated measures ANCOVA with pretest scores serving as the covariate.
Results: Significant differences between groups were not found for any cognitive or behavioral factors, including attention (p < 0.24), immediate memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or behavior problems (p < 0.89).
Conclusions: Changes in performance on cognitive and behavioral measures were not different for children treated with AEDs and controls. Although adverse effects may be associated with prolonged treatment, results would not suggest adverse effects from AED monotherapy during the first 6 months of therapy.     

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.     

Neuropsychological functioning in adolescent children of mothers with a history of bipolar or major depressive disorders.

BACKGROUND: Growing evidence demonstrates an association of neuropsychological deficits with mood disorders, but it is not yet clear whether these deficits are risk factors or are concomitant with the symptoms. This study examines the neuropsychological functioning of a group of adolescent offspring who are at risk for a mood disorder by virtue of being raised by mothers who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BPD). METHODS: Adolescent offspring of mothers with BPD (n = 43) or MDD (n = 72) and of psychiatrically well parents (n = 50) completed a battery of neuropsychological tests to assess executive functioning, memory, and attention. RESULTS: Children of mothers with BPD showed deficits in executive functioning and selective deficits in spatial memory and attention, in comparison with children of well mothers. Deficits were not found for children of MDD mothers. CONCLUSIONS: Knowledge of these neurocognitive processes could aid ultimately in determining whether neurocognitive deficits precede BPD, whether unique profiles are associated with various types of mood disorders, and who may benefit from interventions.     

Neuropsychologic effects of frontal lobe epilepsy in children

Most published neuropsychologic studies on frontal lobe epilepsy have been performed on mixed groups of adults and adolescents with epilepsies of varying etiology. The cognitive profile of frontal lobe epilepsy in children has not been defined. The purpose of this study was to assess neuropsychologic performance in children with frontal lobe epilepsy. Intelligence and executive functions were examined in eight children (age 6 7/12 years to 13 11/12 years) with frontal lobe epilepsy. Performance was related to the focus side, seizure frequency, and age of epilepsy onset. Frontal lobe epilepsy was associated with a range of frontal dysfunctions, but IQ was generally spared. Left focus was associated with deficits in categorization, verbal long-term memory, and detailed visuospatial analysis. Frequent seizures correlated with attention difficulties and inability to inhibit impulsive responses. Children whose epilepsy appeared before age 6 years had reduced ability to change behavioral strategies. Frontal epileptic activity alone can cause selective frontal deficits, the severity and nature of which are related to side, seizure frequency, and age of epilepsy onset. These findings require confirmation on larger series of selected children.     

Cognitive and psychological predictors of everyday memory in children with intractable epilepsy

Children with epilepsy have known deficits on objective measures of learning and memory. Parents and children report that memory deficits have a negative impact on everyday functioning. In adults with epilepsy, self-report of memory is more strongly associated with depression than performance on memory tests. We investigated the cognitive and psychological predictors of everyday memory in 37 children with medically intractable epilepsy, using children's self-report and parent ratings of everyday memory performance and standard tests of attention, intelligence, visual and verbal memory, working memory, and mood/emotional state. Standard multiple regressions demonstrated that only a parent report measure of attention uniquely and significantly (P< or =0.05) predicted estimates of everyday memory performance, accounting for 33% of variance in children's own ratings and 27% of variance in parents' ratings. Findings suggest that everyday memory in children with intractable epilepsy differs from that of adults; attentional problems may underlie everyday memory problems in these children.     

Cerebral lateralization and cognitive deficits after congenital hemiparesis

The purpose of this study was to investigate whether and how handedness is related to the processes of cerebral lateralization and cognitive performance in children with congenital insult. Fifty-six children (31 males and 25 females) with congenital hemiparesis and 14 control subjects were investigated. Of these children, 32 had a left hemisphere lesion, and 24 children had a right hemisphere lesion. There were 30 right-handed, 23 left-handed, and three ambidextrous children in the study group. The neuropsychologic assessment was performed using the NEPSY (a developmental neuropsychological assessment of child development) test battery. We found that 41% of the hemiparetic children and 72% of the children with a left hemisphere lesion were left-handed. In children contralateral to lesion handedness (no evidence of interhemispheric transfer of functions), we found diffuse cognitive deficits with impaired language abilities and poor visuomotor and narrative memory processing. In contrast, children with ipsilateral to brain lesion handedness (interhemispheric transfer of functions) demonstrated minimal or moderate side-specific cognitive dysfunction. Right-handed children with a right hemisphere lesion had attention, spatial, and short-term memory problems; left-handed children with a left hemisphere lesion had receptive language and visuomotor difficulties. Handedness combined with neuropsychologic assessment is a reliable indicator of the processes of cerebral reorganization after early brain insult.     

Brain oscillatory EEG event-related desynchronization (ERD) and -sychronization (ERS) responses during an auditory memory task are altered in children with epilepsy.

PURPOSE: Children with epilepsy are in risk for cognitive impairment, but reliable methods, other than neuropsychological testing, to verify such a decline are few. The purpose of this study was to assess the effect of infrequent seizures on cognitive skills in children with non-symptomatic focal epilepsy taking antiepileptic medication but still having infrequent seizures. METHODS: EEG (electroencephalogram) brain electric oscillatory responses of the 4-6Hz, 6-8Hz, 8-10Hz and 10-12Hz EEG frequency bands were studied. These responses, assessed by means of the event-related desynchronization (ERD) and synchronization (ERS) method, were recorded in 6 children with epilepsy (mean age 11.3 years) and in 11 control children (mean age 12 years) while they performed an auditory memory task. All subjects also underwent a comprehensive neuropsychological test battery. RESULTS: The differences in the 4-6Hz ERD/ERS responses between encoding and recognition were smaller in the children with epilepsy as compared to those of the control children. In the 6-8Hz frequency band, the responses of the two groups dissociated most notably in the frontal electrodes. No statistically significant differences in the alpha frequency range (8-12Hz) were observed between the groups. CONCLUSIONS: Significant alterations in the lower EEG frequency (4-8Hz) ERD/ERS responses in children with epilepsy during auditory memory processing, as compared to age-matched, healthy children may suggest that seizures affect memory and underlying brain processes, indexed also by poorer performance particularly in neuropsychological subtests related to language functions.     

Temporal lobe epilepsy in childhood: comprehensive neuropsychological assessment

The neuropsychological features of children with temporal lobe epilepsy are not yet well defined. The aim of this study was to identify the neuropsychological deficits in children with temporal lobe epilepsy. We evaluated 25 patients and compared them with 25 normal children. All children underwent a comprehensive neuropsychological assessment. We found a significant difference in favor of the control group in the following measures: IQ; forward digit; Trail Making Test for Children B; Wisconsin Card Sorting Test; block design; Boston naming test, verbal fluency; and Wide Range Assessment of Memory and Learning verbal learning, visual learning, verbal memory, visual memory, delayed recall of verbal learning, delayed recall of stories, and recognition of stories. Our findings show that children with temporal lobe epilepsy present with several neuropsychological deficits, despite normal IQ. These findings point to a dysfunction of cerebral areas other than temporal lobe, particularly the frontal lobes.     

Benign partial epilepsy in childhood: selective cognitive deficits are related to the location of focal spikes determined by combined EEG/MEG

Summary:  Purpose: Benign partial epilepsy (BPE) in childhood is characterized by the occurrence of interictal stereotyped focal spikes with variable localization in the EEG. Children with BPE often exhibit neuropsychological deficits. It is unclear whether a correlation exists between these deficits and the localization of spikes, several EEG studies giving inconsistent results. Magnetoencephalography (MEG) improves the accuracy of spike localization. Therefore by using combined MEG/EEG, we investigated the topographic relation between focal spikes and neuropsychological findings in children with BPE.
Methods: Twenty-seven children diagnosed consecutively with BPE were enrolled in the study. All were examined by combined MEG/EEG and magnetic resonance imaging (MRI). Location of spikes was determined by dipole source estimation. A standardized neuropsychological assessment was conducted, including Kaufman ABC battery, language tests, and motor performance series. All children with sufficient MEG data were included in the correlation analysis (N = 20).
Results: Focal spikes were located in the perisylvian region in 13 children, in the occipital region in seven, and in the frontal region in one. Five children had bilateral or multiple foci. Children with left perisylvian spikes did not differ from the others in global IQ, but performed significantly lower in language tests (p = 0.01). Children with occipital spikes performed significantly lower in simultaneous information processing (p = 0.01), especially in visual transformation tasks.
Conclusions: Combined MEG/EEG investigation is a useful tool to examine interictal focal spikes. Our results show a correlation between the location of spikes and selective cognitive deficits in children with BPE. These findings indicate that focal interictal spikes may interfere with complex cognitive functions.     

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.     

Neuropsychological predictors of academic underachievement in pediatric epilepsy: moderating roles of demographic, seizure, and psychosocial variables

PURPOSE: Academic underachievement is common in pediatric epilepsy. Attempts to identify seizure and psychosocial risk factors for underachievement have yielded inconsistent findings, raising the possibility that seizure and psychosocial variables play a complex role in combination with other variables such as neuropsychological functioning. This study cross-validated a neuropsychological measurement model for childhood epilepsy, examined the relation between neuropsychological functioning and academic achievement, and tested the degree to which demographic, seizure, and psychosocial variables moderate that relation. METHODS: Children with chronic epilepsy (N = 173; ages 8 to 15 years; 49% girls; 91% white/non-Hispanic; 79% one seizure type; 79% taking one medication; 69% with active seizures) completed a comprehensive neuropsychological battery. Children diagnosed with mental retardation were excluded. RESULTS: Structural equation modeling identified a three-factor measurement model of neuropsychological function: Verbal/Memory/Executive (VME), Rapid Naming/Working Memory (RN/WM), and Psychomotor (PM). VME and RN/WM were strongly related to reading, math, and writing; PM predicted writing only. Family environment moderated the impact of neuropsychological deficits on writing (p < or = 0.01) and possibly for reading (p = 0.05); neuropsychological deficits had a smaller impact on achievement for children in supportive/organized homes compared with children in unsupportive/disorganized homes. CONCLUSIONS: These findings lend partial support for our theoretical model showing direct effects of neuropsychological function on achievement and the moderating role of family factors. This study suggests that a subgroup of children with epilepsy (those who have not only neuropsychological deficits but also disorganized/unsupportive home environments) are particularly at risk for adverse academic outcomes. Implications for intervention are discussed.