Impaired attention and network connectivity in childhood absence epilepsy.
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ABSTRACT:
SUBMITTER: Killory BD
PROVIDER: S-EPMC3105167 | biostudies-other | 2011 Jun
REPOSITORIES: biostudies-other
Publications
Impaired attention and network connectivity in childhood absence epilepsy.
Killory Brendan D BD Bai Xiaoxiao X Negishi Michiro M Vega Clemente C Spann Marisa N MN Vestal Matthew M Guo Jennifer J Berman Rachel R Danielson Nathan N Trejo Jerry J Shisler David D Novotny Edward J EJ Constable R Todd RT Blumenfeld Hal H
NeuroImage 20110321 4
Patients with childhood absence epilepsy (CAE) often demonstrate impaired interictal attention, even with control of their seizures. No previous study has investigated the brain networks involved in this impairment. We used the continuous performance task (CPT) of attentional vigilance and the repetitive tapping task (RTT), a control motor task, to examine interictal attention in 26 children with CAE and 22 matched healthy controls. Each subject underwent simultaneous 3T functional magnetic reso ...[more]
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Project description:IntroductionChildhood absence epilepsy (CAE) is a well-known pediatric epilepsy syndrome. Recent evidence has shown the presence of a disrupted structural brain network in CAE. However, little is known about the rich-club topology. This study aimed to explore the rich-club alterations in CAE and their association with clinical characteristics.MethodsDiffusion tensor imaging (DTI) datasets were acquired in a sample of 30 CAE patients and 31 healthy controls. A structural network was derived from DTI data for each participant using probabilistic tractography. Then, the rich-club organization was examined, and the network connections were divided into rich-club connections, feeder connections, and local connections.ResultsOur results confirmed a less dense whole-brain structural network in CAE with lower network strength and global efficiency. In addition, the optimal organization of small-worldness was also damaged. A small number of highly connected and central brain regions were identified to form the rich-club organization in both patients and controls. However, patients exhibited a significantly reduced rich-club connectivity, while the other class of feeder and local connections was relatively spared. Moreover, the lower levels of rich-club connectivity strength were statistically correlated with disease duration.DiscussionOur reports suggest that CAE is characterized by abnormal connectivity concentrated to rich-club organizations and might contribute to understanding the pathophysiological mechanism of CAE.
| S-EPMC10213928 | biostudies-literature
Project description:OBJECTIVE: Childhood absence epilepsy (CAE) is a childhood-onset generalized epilepsy. Recent fMRI studies have suggested that frontal cortex activity occurs before thalamic involvement in epileptic discharges suggesting that frontal cortex may play an important role in childhood absence seizures. Neurocognitive deficits can persist after resolution of the epilepsy. We investigate whether structural connectivity changes are present in the brains of CAE patients in young adulthood. METHODS: Cortical thickness measurements were obtained for 30 subjects with CAE (mean age 21 ± 2 years) and 56 healthy controls (mean age 24 ± 4) and regressed for age, sex, and total intracranial volume (TIV). Structural connectivity was evaluated by measuring the correlation between average cortical thicknesses in 915 regions over the brain. Maps of connectivity strength were then obtained for both groups. RESULTS: When compared to controls, the CAE group shows overall increased "connectivity" with focal increased connection strength in anterior regions including; the anterior cingulate and the insula and superior temporal gyrus bilaterally; the right orbito-frontal and supramarginal regions; and the left entorhinal cortex. Decreased connection strength in the CAE group was found in the left occipital lobe, with a similar trend in right occipital lobe. INTERPRETATION: Brains in young adults whose CAE was resolved had abnormal structural connectivity. Our findings suggest that frontal regions correlate most with cortical thickness throughout the brain in CAE patients, whereas occipital regions correlate most in well matched normal controls. We interpret this as evidence of a developmental difference in CAE that emphasizes these frontal lobe regions, perhaps driven by frontal lobe epileptiform activity.
| S-EPMC4435701 | biostudies-other
Project description:ObjectiveThe fundamental mechanisms by which childhood absence epilepsy (CAE) changes neural networks even between seizures remain poorly understood. During seizures, cortical and subcortical networks exhibit bihemspheric synchronous activity based on prior EEG-fMRI studies. Our aim was to investigate whether this abnormal bisynchrony may extend to the interictal period, using a blood oxygen level-dependent (BOLD) resting functional connectivity approach.MethodsEEG-fMRI data were recorded from 16 patients with CAE and 16 age- and gender-matched controls. Three analyses were performed. 1) Using 16 pairs of seizure-related regions of interest (ROI), we compared the between-hemisphere interictal resting functional connectivity of patients and controls. 2) For regions showing significantly increased interhemispheric connectivity in CAE, we then calculated connectivity to the entire brain. 3) A paired-voxel approach was performed to calculate resting functional connectivity between hemispheres without the constraint of predefined ROIs.ResultsWe found significantly increased resting functional connectivity between hemispheres in the lateral orbitofrontal cortex of patients with CAE compared to normal controls. Enhanced between-hemisphere connectivity localized to the lateral orbitofrontal cortex was confirmed by all 3 analysis methods.ConclusionsOur results demonstrate abnormal increased connectivity between the hemispheres in patients with CAE in seizure-related regions, even when seizures were not occurring. These findings suggest that the lateral orbitofrontal cortex may play an important role in CAE pathophysiology, warranting further investigation. In addition, resting functional connectivity analysis may provide a promising biomarker to improve our understanding of altered brain function in CAE during the interictal period.
| S-EPMC3109878 | biostudies-literature
Project description:Background and purposeRecent quantitative neuroimaging studies of childhood absence epilepsy (CAE) have identified various structural abnormalities that might be involved in the onset of absence seizure and associated cognitive and behavioral functions. However, the neuroanatomical alterations specific to CAE remain unclear, and so this study investigated the regional alterations of brain structures associated with newly diagnosed CAE.MethodsSurface and volumetric magnetic resonance imaging data of patients with newly diagnosed CAE (n=18) and age-matched healthy controls (n=18) were analyzed using Free-Surfer software. A group comparison using analysis of covariance was performed with significance criteria of p<0.05 and p<0.01 in global and regional analyses, respectively.ResultsCompared with control subjects, the patients with CAE had smaller total and regional volumes of cortical gray-matter (GM) in the right rostral middle frontal, right lateral orbitofrontal, and left rostral middle frontal regions, as well as in the right precentral, right superior, middle, left middle, and inferior temporal gyri. The cortex in the right posterior cingulate gyrus and left medial occipital region was significantly thicker in patients with CAE than in controls.ConclusionsPatients with CAE showed a reduced bilateral frontotemporal cortical GM volume and an increased posterior medial cortical thickness, which are associated with the default mode network. These structural changes can be suggested as the neural basis of the absence seizures and neuropsychiatric comorbidities in CAE.
| S-EPMC7541981 | biostudies-literature
Project description:ObjectiveTo 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.MethodsSubjects 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.ResultsAt 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).ConclusionsChildren 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 evidenceThis 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.
| S-EPMC3806916 | biostudies-literature
Project description:ObjectiveIn children with newly diagnosed childhood absence epilepsy (CAE), determine pretreatment EEG features and their associations with baseline neuropsychological function and short-term treatment outcome.MethodsIn a multicenter, randomized clinical trial, patients with CAE underwent a pretreatment, 1-hour video-EEG and neuropsychological testing with freedom-from-failure and seizure-freedom (SF) outcome assessed at the 16- to 20-week visit.ResultsDetailed evaluation of the pretreatment EEG was possible for 99.8% of participants (445/446). Median time to first seizure was 6.0 minutes (range 0-59 minutes), median number of seizures was 5 (range 1-60), and median seizure duration was 10.8 seconds (range 3.3-77.6 seconds). Median duration of shortest seizure per EEG was 7.5 seconds (range 3.0-77.6 seconds). Seizure frequency was not associated with baseline measures of attention, executive function, or treatment outcome. Presence of a seizure lasting ≥20 seconds was noted in 29% of subjects (129/440); these children had higher median omissions T score on the Conners Continuous Performance Test (56.3 vs 51.6, p = 0.01). Patients with a shortest seizure of longer duration were more likely to demonstrate treatment success by both freedom-from-failure (p = 0.02) and SF (p = 0.005) criteria, even after controlling for age, treatment group, and number of seizures, with good predictive value (area under the curve 78% for SF).ConclusionsCAE is reliably and quickly confirmed by EEG. Occurrence of a seizure ≥20 seconds, but not overall seizure frequency, was associated with differential baseline measures of attention. Patients whose shortest pretreatment EEG seizure was longer in duration were more likely to achieve SF, regardless of treatment.
| S-EPMC3770172 | biostudies-literature
Project description:While cognitive impairments are not generally considered to be part of the childhood absence epilepsy (CAE) syndrome, some recent studies report cognitive, mainly attentional, deficits. Here we set out to investigate the whole brain functional network of children with CAE and controls. Furthermore, the possible relation of the functional network abnormalities with epilepsy and neurocognitive characteristics is studied. Seventeen children with childhood CAE (aged 9.2 ± 2.1 years) and 15 controls (aged 9.8 ± 1.8 years) were included. Resting state functional MRI was acquired to study the functional network. Using graph theoretical analysis, three global metrics of the functional network were investigated: the characteristic path length, the clustering coefficient, and the small-worldness. A multivariable linear regression model including age, sex, and subject motion as covariates was used to investigate group differences in the graph metrics. Subsequently, relations of the graph metrics with epilepsy and neurocognitive characteristics were assessed. Longer path lengths, weaker clustering and a lower small-world network topology were observed in children with CAE compared to controls. Moreover, longer path lengths were related to a longer duration of CAE and a higher number of absence seizure per hour. Clustering and small-worldness were not significantly related to epilepsy or neurocognitive characteristics. The organization of the functional network of children with CAE is less efficient compared to controls, and is related to disease duration. These preliminary findings suggest that CAE is associated with alterations in the functional network.
| S-EPMC7210592 | biostudies-literature
Project description:PurposeThe electrophysiological characterization of resting state oscillatory functional connectivity within the default mode network (DMN) during interictal periods in childhood absence epilepsy (CAE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in CAE.MethodsUsing a cross-sectional design, we analyzed MEG data from 33 children newly diagnosed with CAE and 26 controls matched for age and sex. The spectral power and functional connectivity of the DMN were estimated using minimum norm estimation combined with the Welch technique and corrected amplitude envelope correlation.ResultsDefault mode network showed stronger activation in the delta band during the ictal period, however, the relative spectral power in other bands was significantly lower than that in the interictal period (p corrected < 0.05 for DMN regions, except bilateral medial frontal cortex, left medial temporal lobe, left posterior cingulate cortex in the theta band, and the bilateral precuneus in the alpha band). It should be noted that the significant power peak in the alpha band was lost compared with the interictal data. Compared with controls, the interictal relative spectral power of DMN regions (except bilateral precuneus) in CAE patients was significantly increased in the delta band (p corrected < 0.01), whereas the values of all DMN regions in the beta-gamma 2 band were significantly decreased (p corrected < 0.01). In the higher frequency band (alpha-gamma1), especially in the beta and gamma1 band, the ictal node strength of DMN regions except the left precuneus was significantly higher than that in the interictal periods (p corrected < 0.01), and the node strength of the right inferior parietal lobe increased most significantly in the beta band (Ictal: 3.8712 vs. Interictal: 0.7503, p corrected < 0.01). Compared with the controls, the interictal node strength of DMN increased in all frequency bands, especially the right medial frontal cortex in the beta band (Controls: 0.1510 vs. Interictal: 3.527, p corrected < 0.01). Comparing relative node strength between groups, the right precuneus in CAE children decreased significantly (β: Controls: 0.1009 vs. Interictal: 0.0475; γ 1: Controls:0.1149 vs. Interictal:0.0587, p corrected < 0.01) such that it was no longer the central hub.ConclusionThese findings indicated DMN abnormalities in CAE patients, even in interictal periods without interictal epileptic discharges. Abnormal functional connectivity in CAE may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction, and prognosis in CAE patients.
| S-EPMC10060817 | biostudies-literature
Project description:To determine optimal second monotherapy for children with childhood absence epilepsy (CAE) experiencing initial treatment failure.Children with CAE experiencing treatment failure during the double-blind phase of a randomized controlled trial comparing ethosuximide, valproic acid, and lamotrigine were randomized to open-label second monotherapy with one of the 2 other study therapies. Primary study outcome was freedom from failure proportion at week 16-20 and month 12 visits after randomization. Secondary study outcome was percentage of participants experiencing attentional dysfunction at these visits.A total of 208 children were enrolled, randomized, and received second therapy. At both week 16-20 visit and month 12 visit, ethosuximide's (63%, 57%) and valproic acid's (65%, 49%) freedom from failure proportions were similar to each other and higher than lamotrigine's (45%, 36%, p = 0.051 and p = 0.062). At both time points, ethosuximide and valproic acid had superior seizure control compared to lamotrigine (p < 0.0001). At both the week 16-20 and month 12 visits, attentional dysfunction was numerically more common with valproic acid than with ethosuximide or lamotrigine. For each medication, second monotherapy freedom from failure proportions demonstrated noninferiority to initial monotherapy freedom from failure proportions.As second monotherapy, ethosuximide and valproic acid, demonstrated higher freedom from failure proportions and greater efficacy than lamotrigine; valproic acid was associated with more attentional dysfunction. Ethosuximide is the optimal second monotherapy for children with CAE not responding to initial therapy with other medications.NCT00088452.This study provides Class III evidence that for children with CAE experiencing initial treatment failure, second monotherapy with ethosuximide or valproic acid is superior to lamotrigine.
| S-EPMC5224720 | biostudies-literature
Project description:ObjectiveTo determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes.MethodsFor participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit.ResultsVideo of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern.ConclusionsAlmost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome.
| S-EPMC5562968 | biostudies-literature