Relative influence of epileptic seizures and of epilepsy syndrome on cognitive function

Cognitive impairment is frequently observed in children with epilepsy. We aimed at addressing to what extent cognitive function is affected by paroxysmal epileptiform activity with or without clinical seizures or by clinical features characteristic of the epilepsy syndrome. To this purpose, combined electroencephalographic (EEG) recording and cognitive testing (IQ and reaction times) were performed in 28 children. Frequent epileptiform EEG discharges significantly reduced reaction time, as did the occurrence of seizures during cognitive testing. Syndrome-related factors tended to affect cognitive functions as well: children with generalized epilepsy and high average seizure frequency obtained lower scores. Linear regression analysis showed that stable aspects of cognitive function, as reflected in intelligence level, are most closely related to the severity of the epilepsy syndrome (average seizure frequency), whereas transient aspects of cognitive function, such as reaction times, are related to the occurrence of epileptiform EEG discharges. This suggests that seizures have a direct effect on transient cognitive aspects, which can accumulate and result in effects on intelligence level.     

Intelligence in childhood epilepsy syndromes

Intellectual deficits play a significant role in the psychosocial comorbidity of children with epilepsy. Early educational intervention is critical. OBJECTIVE: This study aims to determine the intellectual ability of children with common childhood epilepsy syndromes-generalised idiopathic epilepsy (GIE), generalised symptomatic epilepsy (GSE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), central epilepsy (CE) and non-localised partial epilepsy (PE). METHODS: A prospective consecutive series of 169 children were recruited. Epilepsy syndrome was identified by clinical data, seizure semiology, interictal and ictal EEG in each child, using International League Against Epilepsy criteria. Each child had neuropsychology assessment using age-normed and validated instruments. After adjusting for important epilepsy variables, 95% confidence intervals were generated for mean full-scale intelligence quotient (FSIQ) using ANCOVA. RESULTS: Significant differences between epilepsy syndrome groups were found for age of onset (P<0.001), duration of active epilepsy (P=0.027), seizure frequency (P=0.037) and polytherapy (P=0.024). Analysing FSIQ, children with GIE, CE and TLE performed best, and did not differ statistically. Children with GSE had a statistically lower FSIQ than other syndrome groups except PE. FLE functioned significantly better than GSE, but did not differ statistically from other groups. CONCLUSIONS: In childhood epilepsy, delineation of the syndrome has important implications when considering intellectual potential. This information is invaluable in planning educational interventions and supporting the family.     

Effects of epileptiform EEG discharges on cognitive function: is the concept of "transient cognitive impairment" still valid?

In this article we review the existing evidence on the cognitive impact of interictal epileptiform EEG discharges. Such cognitive impairment occurs exclusively in direct relation to episodes of epileptiform EEG discharges and must be distinguished from (post) ictal seizure effects and from the nonperiodic long-term "stable" interictal effects caused by the clinical syndrome or the underlying etiology. Especially in patients with short nonconvulsive seizures, characterized often by difficult-to-detect symptoms, the ictal or postictal effects may be overlooked and the resulting cognitive effects may be erroneously related to the epileptiform EEG discharges. The existing epidemiological data show that the prevalence of cognitive impairment during epileptiform EEG discharges is low. In one study 2.2% of the patients referred to a specialized epilepsy center for EEG recording showed a definite relationship between epileptiform EEG discharges and cognitive impairments ("transient cognitive impairment"). Several studies have sought to analyze to what extent cognitive impairment can be attributed to epileptiform EEG discharges among the other epilepsy factors (such as the effect of the clinical syndrome). These studies show that epileptiform EEG discharges have an additional and independent effect, but this effect is mild and limited to transient mechanistic cognitive processes (alertness, mental speed). This finding concurs with clinical studies that also reported only mild effects. In only exceptional cases are epileptiform EEG discharges the dominant factor explaining cognitive impairment. In addition, some studies have indicated that such mild effects may accumulate over time (when frequent epileptiform EEG discharges persist over years) and consequently result in effects on stable aspects of cognitive function such as educational achievement and intelligence. Hence, the clinical relevance is that early detection of cognitive effects of epileptiform EEG discharges and subsequent treatment may prevent a definite impact on cognitive and educational development. The disruptive effects of epileptiform EEG discharges on long-term potentiation, as established in animal experiments, may be one of the neurophysiological mechanisms underlying this accumulation. In conclusion the concept of "transient cognitive impairment" is still valid, but refinement of methodology has shown that a large proportion of presumed transient cognitive impairment can be attributed to subtle seizures, while interictal epileptic activity accounts for a much smaller part of the cognitive effects than previously thought. In particular cryptogenic partial epilepsies are associated with the risk of cognitive impairment. We hope that increased clinical awareness of this need for early detection will stimulate longitudinal and prospective research that eventually also will provide an answer to the questions of when and how epileptiform discharges that are not part of a seizure need to be treated.     

The relative influence of epileptic EEG discharges, short nonconvulsive seizures, and type of epilepsy on cognitive function

PURPOSE: This study addressed whether cognitive impairment in children with epilepsy is caused by disease-related stable factors, such as the type of epilepsy, or by acute effects of paroxysmal epileptic activity such as epileptic EEG discharges. We studied a nonselected group with short nonconvulsive seizures, as these seizures may elude detection and may therefore persist over a longer period. In this group, the diagnostic issue is to differentiate between the combined effects of several epilepsy-related factors on cognition. METHODS: All children were assessed with 32-channel EEG, synchronized with a computerized cognitive test system and a video-monitoring system. Recording time was 2 h. The primary inclusion criteria were unclear seizures and fluctuations in cognitive performance and/or frequent epileptic EEG discharges in a recent EEG. RESULTS: One hundred fifty-two patients met the inclusion criteria; 31 patients appeared not to have a diagnosis of epilepsy and were used as a nonepilepsy control group. Our results show that type of epilepsy has an impact on stable cognitive functions, such as educational achievement. Paroxysmal epileptic activity (acute effects of seizures and epileptic EEG discharges) affects primarily transient mechanistic cognitive processes (alertness, mental speed). CONCLUSIONS: These results suggest that the effects of paroxysmal epileptic activity on transient cognitive mechanisms may accumulate over time and consequently affect the more stable aspects of cognitive function such as educational achievement. The clinical relevance is that early detection of the cognitive impact of seizure-related activity and subsequent treatment may prevent its detrimental impact on cognitive and educational development.     

Acute effects of subclinical epileptiform EEG discharges on cognitive activation

In this prospective, open, clinical comparative study we analyzed impairments of cognitive activation occurring during, immediately before and immediately after epochs with epileptiform EEG discharges of 3 seconds or longer, in an attempt to establish whether cognitive slowing occurs in direct association with an epoch with epileptiform EEG discharges and whether cognitive impairments precede or follow such an epoch. All children were assessed with EEG/video (Brainlab) simultaneously with computerized neuropsychological testing (FePsy): a test for cognitive activation (simple visual and auditory reaction time measurement). Thirty-seven epochs with epileptiform EEG discharges without clinical signs of a seizure (subclinical epileptiform EEG discharges) were evaluated. The results showed a statistically significant and clinically relevant slowing (35% compared to the overall reaction time), occurring during the epoch with epileptiform EEG discharges (repeated measurement analysis of variance p = < .05; df = 3; F-value: 3.293). No statistically significant slowing was found for the periods 'post-discharge' or 'pre-discharge'. Type of discharge was important and effects on cognitive activation were found exclusively for generalized discharges. This effect was, however, also seen in the remaining period, outside the 'peri-discharge' periods and thus seemed to represent a more general effect of the type of epilepsy on cognitive activation. Our results show that the acute effect of short epileptiform EEG discharges (duration 4.14 sec; sd 1.38) may be impressive, causing impairment (slowing) of cognitive activation. This effect was limited to generalized discharges. This effect was not observed for focal discharges, even during longer periods with discharges. However, it is reassuring that this impact on cognitive activation is limited to the actual period in which the discharges occur and does not have 'post-discharge' effects. The risk of accumulating effects that may have longer-lasting repercussions on higher-order cognitive functions therefore seems to be negligible.     

Effect of epilepsy, seizures and epileptiform EEG discharges on cognitive function

Patients with an established diagnosis of epilepsy were included in three groups on the basis of the absence (Group 2) or presence (Group 3) of epileptiform EEG discharges or subtle seizures (Group 4) during the cognitive assessment procedure. A separate age-matched non-epileptic control group (Group 1) was formed. Twenty-five patients were included in each of the four groups. Thus, a total of 100 patients were investigated. The patients were assessed with continuous 21-channel EEG and video-monitoring, combined with cognitive testing. The results show consistently lower performance on cognitive tests for Group 4, the group with subtle seizures. The difference with the control group was significant for the intelligence subtests and for the complex information processing test (p<0.05). No transient cognitive impairment was found. The results are discussed in the light of possible factors that may be responsible for the lower test-scores in the patients of Group 4: both the ictal effects of the seizures themselves, postictal effects and the effects of the epileptiform EEG discharges may have had an impact on cognitive performance. Finally the absence of evidence for transient cognitive impairment in a group with frequent epileptiform EEG discharges is discussed in detail.     

Differentiating between benign and less benign: epilepsy surgery in symptomatic frontal lobe epilepsy associated with benign focal epileptiform discharges of childhood

Benign focal epileptiform discharges of childhood are a genetically determined electroencephalographic trait. Assessment of their clinical relevance in children with epilepsy may be difficult if imaging reveals a lesion congruent or incongruous with the focus of the benign focal epileptiform discharges of childhood. This article reports a boy with parietooccipital benign focal epileptiform discharges of childhood in whom videoelectroencephalography and magnetic resonance imaging disclosed symptomatic frontal lobe epilepsy. Surgical removal of a focal cortical dysplasia in the left frontal lobe yielded freedom from seizures and positive behavioral and cognitive development. Nocturnal benign focal epileptiform discharges of childhood persisted until puberty (follow-up, 50 months). Early diagnostic differentiation of idiopathic syndromes such as idiopathic benign focal epilepsy of childhood from symptomatic focal epilepsies with a potentially less benign course is important. In symptomatic frontal lobe epilepsy, epilepsy surgery may yield an excellent outcome despite the presence of concurrent benign focal epileptiform discharges of childhood.     

Association between frequency of nocturnal epilepsy and language disturbance in children

In clinical practice, an association is commonly suggested between nocturnal epileptiform activity and language disorders in children. However, this association has not been studied systematically. This study explored the correlation between daily and nocturnal epileptiform discharges ratio, frequency of nocturnal epileptiform discharges, and severity of nocturnal seizures in correlation with the severity of language impairment. A total of 326 children referred to an epilepsy center were included. All children had a 24-hour electroencephalogram (EEG), a neuropsychologic assessment, and a reconfirmed diagnosis of epilepsy. The balance between verbal and performance IQ scores of the Wechsler Intelligence Scale for Children was a focus of the study. A significant correlation between the severity of nocturnal seizures and lower verbal IQ scores compared to performance IQ scores was found (P < 0.05). There was a clinically relevant difference between performance IQ and verbal IQ between the groups of children with only nocturnal epileptiform EEG discharges and only epileptiform EEG discharges during wake (P = 0.033). Children with nocturnal epileptiform EEG discharges have lower verbal than performance IQs when compared to children with only epileptiform EEG discharges during wake. Although a causal relationship is unclear, this indicates an association between the occurrence of nocturnal epileptiform EEG discharges and language disturbance.     

The long-term effect of listening to Mozart K.448 decreases epileptiform discharges in children with epilepsy

Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect. Our previous work revealed that epileptiform discharges in children with epilepsy decrease during and right after listening to Mozart K.448. However, the duration of the effect was not studied. In the study described here, we evaluated the long-term effect of Mozart K.448 on epileptiform discharges in children with epilepsy. Eighteen children with epilepsy whose seizures were clinically well controlled with antiepileptic drugs were included. For each child, EEGs had revealed persistent epileptiform discharges for at least 6 months. These patients listened to Mozart K.448 for 8 minutes once a day before bedtime for 6 months. Epileptiform discharges were recorded and compared before and after 1, 2, and 6 months of listening to Mozart K.448. All of the children remained on the same antiepileptic drug over the 6 months. Relationships between number of epileptiform discharges and foci of discharges, intelligence, epilepsy etiology, age, and gender were analyzed. Epileptiform discharges significantly decreased by 53.2±47.4, 64.4±47.1, and 71.6±45.8%, respectively, after listening to Mozart K.448 for 1, 2, and 6 months. All patients except those with occipital discharges showed a significant decrease in epileptiform discharges. Patients with normal intelligence and idiopathic epilepsy had greater decreases than those with mental retardation and symptomatic epilepsy. Age and gender did not affect the results. We conclude that long-term listening to Mozart K.448 may be effective in decreasing epileptiform discharges in children with epilepsy in a chronologically progressive manner.     

Cognitive and behavioral effects of nocturnal epileptiform discharges in children with benign childhood epilepsy with centrotemporal spikes

This review addresses the effects of subclinical localized epileptiform discharges during sleep in children with benign childhood epilepsy with centrotemporal spikes (BCECTS) on cognition and behavior. A diversity of educational deficits, behavioral impairments, language delay, and neuropsychological test results have been reported in children with BCECTS. The occurrence of atypical seizure characteristics seems to be related to language delay, and several atypical EEG characteristics are related to cognitive or behavioral problems. It remains to be shown whether treatment of nocturnal discharges in children with BCECTS is indicated to improve cognitive and behavioral problems.     

Academic performance in children with rolandic epilepsy

The aim of this study was to investigate the frequency of reading, writing, and calculation disabilities in children with typical rolandic epilepsy (RE) and healthy control children. We also aimed to define the possible electroclinical markers of specific cognitive dysfunctions in RE. School abilities were evaluated and compared in 20 children (eight males, 12 females; mean age 10y 3mo [SD 1y 7mo]; range 7y 9mo-12y 9mo) consecutively diagnosed with typical RE, and a group of 21 healthy controls (nine males, 12 females; mean age 10y 4mo [SD 1y 8mo]; range 7y 6mo-13y 3mo). All the children received standardized neuropsychological tests. For each patient an exhaustive seizure diary was kept and all the sleep electroencephalogram (EEG) recordings were reviewed. Specific difficulties with reading, writing, and calculation (diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition) were found in nine out of 20 children with RE and two out of 21 healthy controls (chi2=0.01). The specific learning disabilities in the RE group were correlated with a marked increase in epileptiform discharges during sleep (chi2=0.02) and an early onset of epilepsy (chi2=0.02). Our findings suggest that seizure onset before age 8 years and epileptiform discharges (more than 50% of the sleep EEG recording) in several tracings over more than a year are relevant markers for identifying patients at risk of developing academic difficulties.     

Continuous epileptiform discharges during sleep as an evolutionary pattern in patients with congenital Zika virus syndrome

Congenital Zika virus syndrome (CZVS) is associated with severe neurological deficits. Clinical characteristics of epilepsy and the electroencephalographic (EEG) pattern in CZVS were documented in infancy. In this study, we aimed to describe the EEG findings observed during the follow-up of children with CZVS. Seventy-six EEGs of 55 children (60% female; mean age = 50 months) with confirmed CZVS were analyzed, considering the background, interictal, and ictal epileptiform discharges. Continuous (or almost continuous) epileptiform discharges during non–rapid eye movement sleep were identified in 22 (40%) patients. In 20 (90.1%) patients, the pattern was symmetrical, with an anterior predominance of the epileptiform activity. All patients with this pattern had epilepsy, which was severe in 15 (68.2%) and demanded polytherapy in 19 (86.4%). Subcortical calcifications (77.3%) and multifocal EEGs (72.8%) in earlier ages occurred more often in patients with this pattern. Other unspecific interictal EEG patterns were focal epileptiform discharges in 23 (41.8%) and multifocal activity in six (10.9%). In CZVS, continuous (or almost continuous) epileptiform discharges during sleep emerge as a pattern after the second year of life. This was associated with severe and drug-resistant epilepsy, but not necessarily with an apparent regression. Subcortical calcifications and multifocal epileptiform discharges in infancy are associated with this pattern.     

Risk for developing epilepsy and epileptiform discharges on EEG in patients with febrile seizures

Purpose: The aim of the present study was to investigate the correlation between epileptiform discharges on EEGs after febrile seizures and the prognosis of patients in terms of the development of epilepsy and recurrence of febrile seizures. This study also evaluated the characteristics of epileptiform discharges and EEG changes on follow-up examination. Methods: This study consisted of 36 children who presented to our hospital with febrile seizures and whose electroencephalograms (EEG) showed epileptiform discharges. The development of epilepsy and the recurrence of febrile seizures were compared between the study group (n = 36) and the control group (n = 87), which included children with febrile seizure but with normal EEG findings. Results: No significant correlation was detected between the recurrence rate of febrile seizures in patients with normal EEG (23 out of 87, 26.4%) findings and that of patients whose EEGs showed epileptiform discharges (12 out of 36, 33.3%) [adjusted OR 0.67 (0.26–1.68)]. However, 9 (25.0%) out of 36 patients with epileptiform discharges on EEG had epilepsy compared to 2 patients (2.3%) in the control group. The correlation was statistically significant [crude OR 10.88 (2.47–47.88) and adjusted OR 8.75 (1.49–51.6)]. Conclusion: Epileptiform discharges on the EEGs of patients with febrile seizures are important predictive risk factors of the development of epilepsy.     

Lateralized effects of subclinical epileptiform EEG discharges on scholastic performance in children

The interaction between lateralization of subclinical epileptiform discharges and cognitive tasks was investigated in 21 children (12 girls and 9 boys, mean age 10.6 years). Seventeen had a diagnosis of epilepsy (partial or secondarily generalized). Testing was by reading, arithmetic, and intelligence subtests during continuous telemetric EEG and video monitoring. Children with left-sided discharges had significantly lower reading performance than children with right-sided discharges. During reading, epileptiform discharges occurred relatively less frequently and with a shorter total duration over the left hemisphere than the right. This supports the view that cognitive tasks suppress epileptiform discharges when they activate a region of the brain within the epileptogenic zone. Discharges from other epileptogenic zones not directly activated by the tasks are increased, however.     

临床下痫样放电对青少年癫痫患者认知功能影响的研究

目的探讨临床下痛样放电对青少年癫痫患者认知功能的影响。方法以全身强直阵挛性发作（GTCS）为临床表现的特发性癫痫患者65例,无临床发作均超过3个月,其中35例动态脑电图或普通脑电图显示有痫样放电,30例患者动态脑电图均正常。65例患者均服用左乙拉西坦治疗,随访6个月,服药前后分别进行基本认知能力测试,分析两组患者6个月前后认知功能的变化。结果63例完成本实验,两组实验前后IQ均在正常范围且差异不明显。但6个月后有痛样放电组认知功能明显下降（P〈0．01）,具体表现在数字鉴别（P〈0．01）、汉字快速比较（P〈0．01）、汉字旋转（P〈0．01）、图形再认（P〈0．01）等方面,而脑电图正常组认知功能无明显变化（P〉0．05）。结论临床下痫样放电可损害患者的认知能力,应受到重视,采取适当的干预措施。     

The cognitive effects of interictal epileptiform EEG discharges and short nonconvulsive epileptic seizures

Purpose: Educational difficulties or even severe cognitive deterioration is seen in many childhood epilepsy syndromes. Many of those cognitive deficits are related directly to the brain disorder underlying the epilepsy syndrome. However, in other types of epilepsy, the epileptic seizures and/or epileptiform activity can be the dominant factor. This is especially unknown for the more “subtle” short nonconvulsive seizure types. For this reason, we analyzed a new cohort of children. Methods: A cross‐sectional study of 188 children with epilepsy. Electroencephalography (EEG)–video recordings and cognitive testing were performed simultaneously. The results of children with short nonconvulsive seizures during a 2‐h testing session were compared with all children with epilepsy without seizures during the 2‐h cognitive testing session and with controls without epilepsy. In a second analysis the cognitive effects of frequency of epileptiform EEG discharges were analyzed. Key Findings: The cognitive effects of short nonconvulsive seizures were large, ranging from 0.5 to 1 standard deviation and concerned global cognitive function, speed of central information processing, and memory function. In children without seizures during cognitive testing, the occurrence of frequent epileptiform discharges showed more subtle effects. These effects were independent from the occurrence of short nonconvulsive seizures. Significance: We concluded that although the effect is less pronounced in number of areas involved and magnitude, the type of association between frequent epileptiform activity (>1% of the time) and cognitive function in children with epilepsy is comparable to the association between short nonconvulsive seizures and cognitive function.     

Psychological effects of subclinical epileptiform EEG discharges in children. II. General intelligence tests

Twenty-one children with suspected or proven epilepsy and subclinical epileptiform EEG discharges in the waking state were studied. The EEG was telemetered and behaviour recorded by closed-circuit television during performance of a general intelligence test (RAKIT, shortened version) which comprised 6 subtests. Mean total IQ was below that of control populations and the subtests profile was abnormal, due particularly to impaired performance on a subtest concerned with verbal short-term memory. This effect was accounted for by that subgroup of children who exhibited discharges during the test; those who did not show discharges at that time were unimpaired. Performance of 3 of the subtests was impaired when discharges occurred during presentation of the test item or between presentation and response. The findings suggest that cognitive impairment found in people with epilepsy may not only represent a more or less static disability, due to drugs, cerebral pathology, etc., but may in part be an intermittent process related to the occurrence of subclinical epileptiform discharges. These preliminary findings need to be amplified but have implications both for interpretation of neuropsychological studies in persons with epilepsy and also for the drug treatment of those who continue to exhibit subclinical EEG discharges when overt seizures have been controlled.     

Variability of epileptiform activity in long-term EEGs with short and long intervals in children with epilepsy.

OBJECTIVE: To evaluate the impact of the time factor on the amount of epileptiform activity in long-term EEG recordings in children with epilepsy. METHODS: Ten children with epilepsy of different types underwent three 24 h EEG examinations during two consecutive days and with a month's interval. The number of epileptiform discharges during selected corresponding periods of time was counted. RESULTS: The number of epileptiform discharges on three repeated examination days showed no significant difference (ANOVA P = 0.88) as intraindividual increases and decreases on different days counterbalanced each other within the group. However the standard deviations of the relative changes were larger between recordings with a month's interval compared to those for consecutive days (86% and 33%). The mean magnitude of change was 55% between days separated by a month compared to 24% on consecutive days. The difference was non-significant but showed a trend towards larger changes with a longer interval (P = 0.07). CONCLUSIONS: The variability of epileptiform activity was larger when the interval between recordings was 1 month compared to consecutive days. The magnitude of the relative changes between intervals of 1 and 30 days showed a trend towards a difference although not statistically significant. When evaluating repeated long-term EEGs in relation to therapy in children, these variations should be considered.     

睡眠性癫癎患者动态脑电图的研究

目的探讨睡眠性癫疒间患者的24h动态脑电图(AEEG)的表现及其诊断价值。方法对91例仅于睡眠中发作癫疒间的患者进行AEEG检查,并对检查结果进行分析。结果AEEG发现疒间性放电71例(78.0%),其中4例出现于清醒状态,41例出现于睡眠状态,26例清醒和睡眠时均有放电;在67例睡眠时有疒间性放电的患者中,34例仅出现在浅睡期,33例整个睡眠中均出现疒间性放电。清醒时有癫疒间波的患者癫疒间发作频率明显高于无异常放电患者和仅睡眠时有疒间性放电的患者(均P<0.05)。结论睡眠中癫疒间发作患者于睡眠中疒间性放电出现率明显高于白天清醒时。AEEG容易发现睡眠性癫疒间患者的发作期和发作间歇期以及自然睡眠状态下的疒间样波。