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Aim: Childhood absence epilepsy (CAE) is a paediatric epilepsy syndrome characterized by typical absence seizures in school age children. Although it is commonly considered to have a good prognosis, with a good response to antiepileptic drugs, recent studies questioned this traditional view of a “benign” disorder, in particular regarding neuropsychological functioning. The aim of this study is to review the neuropsychological involvement in patients affected by CAE., Methods: A literature search was carried out in PubMed's and Medline's databases for all relevant studies published between 1924 and 2014. The keywords used were neuropsychology, absence seizures, and CAE. Specific review articles, systematic reviews, textbooks and case reports were examined for any further publications., Results: In intellectual functioning, CAE patients seem to perform worse than healthy children, even if their IQ scores fall within the normal range. Similarly, CAE seems to affect verbal skills and learning. Executive functions have been reported to be mildly impaired. Data regarding memory are still conflicting., Discussion: Given the neuropsychological deficits in many CAE patients which significantly affect their quality of life, CAE should not be considered entirely “benign”. An early identification of neuropsychological dysfunction in CAE children is essential for appropriate treatment.

Growing numbers of evidence indicate that cognitive impairments are part of clinical profile of childhood absence epilepsy. Little is known on neuropathological changes accompanied by cognitive deficits in absence epilepsy. The aim of the present study was to investigate age-dependent neuropathological changes accompanied by learning and memory impairments in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The learning and memory performances were assessed using passive avoidance paradigm and neuropathological alterations were investigated by the evaluation of the number of dark neurons and apoptotic cells as well as the expression of caspase-3 in the neocortex, the hippocampus, and different regions of the thalamus. Results revealed a decline in learning and spatial memory of 6-month-old WAG/Rij rats compared to age-matched Wistar rats as well as 2-month-old WAG/Rij and Wistar rats. The mean number of dark neurons was significantly higher in the hippocampal CA1 and CA3 areas as well as in the laterodorsal, centromedial, and reticular thalamic nuclei and the somatosensory cortex of 6-month-old WAG/Rij rats. In addition, a higher number of apoptotic cells as well as a higher expression of caspase-3 was observed in the hippocampal CA1 and CA3 regions, the laterodorsal thalamic nucleus, and the somatosensory cortex of 6-month-old WAG/Rij rats compared to other animal groups. These results indicate significant enhancement of neuronal damage and cell death accompanied by memory deficits after seizure attacks in a rat model of absence epilepsy. Seizure-induced neuronal injury and death may underlie cognitive impairments in absence epilepsy., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Dr. Masur and colleagues(1) from the Childhood Absence Epilepsy Study Group tried to answer a few important questions regarding childhood absence epilepsy (CAE) in their article "Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy." First, they wanted to know whether children with absence epilepsy have any problems with thinking before starting medications. If the children have problems with thinking, the authors wanted to identify the specific types of thinking problems the children have. The authors also wanted to assess what effect seizure medications have on attention in these children. In principle, medications could improve or worsen attention. The possible effects of medication on attention may or may not depend on whether the medications control the seizures.

Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine short-term differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine., Methods: Subjects with newly diagnosed CAE entering a double-blind, randomized controlled clinical trial had neuropsychological testing including assessments of general intellectual functioning, attention, memory, executive function, and achievement. Attention was reassessed at the week 16-20 visit., Results: At study entry, 36% of the cohort exhibited attention deficits despite otherwise intact neurocognitive functioning. Structural equation modeling of baseline neuropsychological data revealed a direct sequential effect among attention, memory, executive function, and academic achievement. At the week 16-20 visit, attention deficits persisted even if seizure freedom was attained. More subjects receiving valproic acid (49%) had attention deficits than subjects receiving ethosuximide (32%) or lamotrigine (24%) (p = 0.0006). Parental assessment did not reliably detect attention deficits before or after treatment (p < 0.0001)., Conclusions: Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted., Classification of Evidence: This study provides Class I evidence that valproic acid is associated with more significant attentional dysfunction than ethosuximide or lamotrigine in children with newly diagnosed CAE.

Objective: Our prospective study aimed at the validation of EpiTrack Junior, a neuropsychological screening tool for attention and executive functions in children with epilepsy., Methods: Twenty-two children with absence epilepsy aged 8-17 years underwent comprehensive neuropsychological evaluation including EpiTrack Junior and measures of intelligence, verbal and nonverbal memory, word fluency and visuoconstructive organization. Concurrent and discriminant validity of EpiTrack Junior subtests and total score as well as sensitivity and specificity of the total score were analyzed., Results: EpiTrack Junior total score was impaired in 59% of participants. Concurrent validity was demonstrated in 4/6 subtests and for the total score. Discriminant validity was shown with respect to verbal and nonverbal long-term memory. Sensitivity was higher than specificity and highest for the "working memory index"., Conclusion: EpiTrack Junior is recommended as a sensitive and time-efficient screening tool for attention and executive functions in children with epilepsy. Impaired results should be followed up with detailed evaluation including information from the parents and school as well as counseling where indicated., (© 2013.)

Aripiprazole (APZ) is regarded as a first-line atypical antipsychotic used for the treatment of first and multiple episodes of schizophrenia to improve positive- and negative-symptoms. Its therapeutic indications were extended to acute manic and mixed episodes associated with bipolar disorder. In addition, APZ was approved as an adjunct therapy for major depressive disorder in 2007. Compared to other antipsychotic drugs, APZ has a unique pharmacological profile. It is a partial agonist at D₂ dopamine receptors and serotonin 5-HT(1A) and 5-HT₇ receptors, whereas it is an antagonist at serotonin 5-HT(2A) and 5-HT₆ receptors. Since epilepsy is often accompanied with neurological comorbidities such as depression, anxiety and cognitive deficits caused by both the disease and/or drug treatment, we wished to examine the effects of a sub-chronic treatment (>14 consecutive days) with APZ (0.3, 1 and 3 mg/kg; i.p.) on both absence seizures and WAG/Rij rat's behavior using different standard paradigms: Open field (OF) test, elevated plus maze (EPM) test, forced swimming (FS) test, sucrose consumption (SC) test and Morris water maze (MWM). WAG/Rij rats represent a validated genetic animal model of absence epilepsy with mild-depression comorbidity, also including other behavioral alterations. APZ treatment showed some anti-absence properties and regarding the behavioral comorbidity in this rat strain, we observed that APZ possesses clear antidepressant effects in the FS and SC tests also increasing memory/learning function in the Morris water maze test. In the two anxiety models used, APZ showed only minor effects. In conclusion, our results indicate that APZ might actually have a potential in treating absence seizures or as add-on therapy but more interestingly, these effect might be accompanied by positive modulatory actions on depression, anxiety and memory which might be also beneficial in other epileptic syndromes. This article is part of a Special Issue entitled 'Cognitive Enhancers'., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

In this study, we used surface-based morphometry to examine whether age-related changes in gray matter tissue thickness and depth of sulcal regions at high spatial resolution across the cortex differed in children with childhood absence epilepsy (CAE) compared to healthy control subjects. In addition, the possibility of variable brain-cognition relationships in the CAE compared to the control group was investigated. The main findings of this study are as follows: (1) From the developmental perspective, children with CAE did not demonstrate the normal regional age-related changes involving a decrease in cortical thickness and increase in sulcal depth. (2) None of the seizure variables, including age of onset, seizure frequency, and AEDs had a significant effect on the association between age and cortical morphometry measures in the CAE population. (3) Even though the CAE group had mean VIQ and PIQ scores in the average range, our findings suggest that they use different brain regions to perform these cognitive functions compared to healthy controls. This first study on brain morphometry and cognition in children with childhood absence seizures has important implications for advancing our understanding of brain development and cognitive comorbidity in CAE, as well as for revisiting the clinical notion that CAE is a benign disorder., (Copyright © 2010 Wiley-Liss, Inc.)

The nature and extent of the neuropsychological difficulties associated with childhood absence epilepsy (CAE) remain unclear. Because aberrant thalamocortical rhythms have been implicated in the pathogenesis of CAE, it was hypothesized that children with CAE would show greater difficulties in neuropsychological domains that are thought to be subserved by basal ganglia-thalamocortical circuits. Multivariate analysis of variance was used to compare the neuropsychological functioning of 16 children with CAE with that of 14 children with type 1 diabetes mellitus and 15 healthy children. The CAE group did not perform differently from the other groups on measures of intellectual functioning, memory, academic achievement, fine motor speed, or processing speed. In contrast, significant differences were found in problem solving, letter fluency, complex motor control, attention/behavioral inhibition, and psychosocial functioning. These results suggest that children with CAE show difficulties in neuropsychological functions thought to be subserved by the same regions implicated in the pathogenesis of the disorder., (Copyright 2010 Elsevier Inc. All rights reserved.)

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.

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 IQ 108) 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.

Alterations of consciousness with impaired perception and drive persisting over hours to days can be due to a nonconvulsive status epilepticus. This possibility has to be considered not only in patients with already known epilepsy, but also in those with a negative history for seizure disorders. The immediately recorded electroencephalogram (EEG) provides decisive clues. In the case of petit mal status most frequently appear tiredness, reduced vigilance and lack of drive. The EEG shows a generalized spike-wave activity. In status psychomotoricus, the clinical symptomatology varies from case to case. It can be characterized by anxiety, dreamy states or productive-psychotic states with agitation, automatisms and hallucinations. In the EEG a temporal or temporally-accentuated epileptic activity will be recorded. Transitional and mixed forms of petit mal status and status psychomotoricus can also be found. I.v. injections of benzodiazepines (clonazepam, diazepam) are an appropriate therapy for any type of nonconvulsive status epilepticus. Phenytoin is indicated in status psychomotoricus, but contra-indicated in the case of petit mal status.

Although less often due to seizures than to other conditions, confusional states may be associated with complex partial seizures in adults or absence (petit mal) seizures in younger persons and children. Absence of a metabolic disorder, intoxication, or risk factors for cerebral ischemia increases the probability that seizure caused the confusional state. A computed tomographic scan or magnetic resonance imaging of the brain is essential when the patient is acutely ill or has had several recent confusional episodes. Once a seizure disorder is diagnosed, appropriate drug therapy can be started.