Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.

SUMMARYFrontal lobe epilepsy (FLE) is considered the second most common type of the localization-related epilepsies of childhood. Still, the etiology of FLE in children, its impact on cognitive functioning and behavior, as well as the response to antiepileptic drug treatment in children has not been sufficiently studied. This review focuses on these aspects of FLE in childhood, and reveals that FLE in childhood is most often cryptogenic, and impacts on a broad range of cognitive functions. The nature and severity of cognitive deficits are highly variable, although impaired attention and executive functions are most frequent. Young age at seizure onset is the only potential risk factor for poor cognitive outcome that has been consistently reported. The behavioral disturbances associated with FLE are also highly variable, although attention deficit/ hyperactivity disorder seems most frequent. In 40% of children with FLE satisfactory seizure control could not be achieved. This is a higher percentage than reported for the general population of children with epilepsy. Therefore, pediatric FLE, even if cryptogenic in nature, is frequently complicated by impairment of cognitive function, behavioral disturbances, and therapy-resistance. Given the impact of these complications, there is a need for studies of the etiology of frontal lobe epilepsy-associated cognitive and behavioral disturbances, as well as pharmacotherapy-resistance.

SUMMARYPurpose: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Methods: Thirty-two children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired.Key Findings: Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Significance: Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad-range cognitive impairments in children with FLE.

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Cognition in absence epilepsy (AE) is generally considered undisturbed. However, reports on cognitive deficits in AE in recent years have suggested otherwise. This review systematically assesses current literature on cognitive performance in children with AE. A systematic literature search was performed in Pubmed, Embase, Cochrane and Web of Science. All studies reporting on cognitive performance in children with AE were considered. In total 33 studies were eligible for inclusion. Neuropsychological tests were classified into the following domains: intelligence; executive function; attention; language; motor & sensory-perceptual examinations; visuoperceptual/visuospatial/visuoconstructional function; memory and learning; achievement. Random-effect meta-analyses were conducted by estimating the pooled mean and/or pooling the mean difference in case-control studies. Full-scale IQ in children with AE was estimated at 96.78 (95%CI:94.46–99.10) across all available studies and in case-control studies IQ was on average 8.03 (95%CI:-10.45- -5.61) lower. Verbal IQ was estimated at 97.98 (95%CI:95.80–100.16) for all studies and 9.01 (95%CI:12.11- -5.90) points lower in case-control studies. Performance IQ was estimated at 97.23 (93.24–101.22) for all available studies and 5.32 (95%CI:-8.27–2.36) points lower in case-control studies. Lower performance was most often reported in executive function (cognitive flexibility, planning, and verbal fluency) and attention (sustained, selective and divided attention). Reports on school difficulties, neurodevelopmental problems, and attentional problems were high. In conclusion, in contrast to common beliefs, lower than average neurocognitive performance was noted in multiple cognitive domains, which may influence academic and psychosocial development.Electronic supplementary materialThe online version of this article (10.1007/s11065-019-09419-2) contains supplementary material, which is available to authorized users.