Childhood Absence Epilepsy Group Research Articles

The Challenges of Distinguishing Cognitive Disengagement Syndrome from Childhood Absence Epilepsy in Clinical Settings

ABSTRACT We evaluated clinical parameters distinguishing cognitive disengagement syndrome (CDS) and childhood absence epilepsy (CAE). 40 children with CDS, 27 with CAE, and 41 controls aged 7-12 were compared regarding sleep problems, CDS, and ADHD symptoms. CDS-sluggishness symptoms, but not CDS-daydreaming symptoms, were significantly higher in CDS group than CAE group. CDS scale provided a weak discrimination value between CDS and CAE. Sleep problems and ADHD symptoms were similar between the two clinical entities. These findings highlight that CDS and CAE might have overlapping symptoms. ‘Daydreaming’ symptoms but not ‘sluggishness’ symptoms seem to be main overlapping manifestations between CDS and CAE.

Alterations in white matter integrity and asymmetry in patients with benign childhood epilepsy with centrotemporal spikes and childhood absence epilepsy: An automated fiber quantification tractography study

PurposeTo investigate whether patients with benign childhood epilepsy with centrotemporal spikes (BECTS) and childhood absence epilepsy (CAE) show distinct patterns of white matter (WM) alterations and structural asymmetry compared with healthy controls and the relationship between WM alterations and epilepsy-related clinical variables. MethodsWe used automated fiber quantification to create tract profiles of fractional anisotropy (FA) and mean diffusivity (MD) in twenty-six patients with BECTS, twenty-nine patients with CAE, and twenty-four healthy controls. Group differences in FA and MD were quantified at 100 equidistant nodes along the fiber tract and these alterations and epilepsy-related clinical variables were correlated. A lateralization index (LI) representing the structural asymmetry of the fiber tract was computed and compared between both patient groups and controls. ResultsCompared with healthy controls, the BECTS group showed widespread FA reduction in 43.75% (7/16) and MD elevation in 50% (8/16) of identified fiber tracts, and the CAE group showed regional FA reduction in 31.25% (5/16) and MD elevation in 25% (4/16) of identified fiber tracts. In the BECTS group, FA and MD in the right anterior thalamic radiation positively and negatively correlated with the number of antiepileptic drugs, respectively, and MD in the right arcuate fasciculus (AF) positively correlated with seizure frequency. In the CAE group, the LI values were significantly lower in the inferior fronto-occipital fasciculus and the AF. ConclusionThe two childhood epilepsy syndromes display different patterns of WM alterations and structural asymmetry, suggesting that neuroanatomical differences may underlie the different profiles of BECTS and CAE.

Attention Contributes to Arithmetic Deficits in New-Onset Childhood Absence Epilepsy.

Neuropsychological studies indicate that new-onset childhood absence epilepsy (CAE) is associated with deficits in attention and executive functioning. However, the contribution of these deficits to impaired academic performance remains unclear. We aimed to examine whether attention and executive functioning deficits account for the academic difficulties prevalent in patients with new-onset CAE. We analyzed cognitive performance in several domains, including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention, and executive functioning, in 35 children with new-onset CAE and 33 control participants. Patients with new-onset CAE exhibited deficits in mathematics, general intelligence, attention, and executive functioning. Furthermore, attention deficits, as measured by a visual tracing task, accounted for impaired arithmetic performance in the new-onset CAE group. Therefore, attention deficits, rather than impaired general intelligence or executive functioning, may be responsible for arithmetic performance deficits in patients with new-onset CAE.

Prefrontal Lobe Growth Disturbance in a Patient with Frontal Absence Seizures

Absence seizures sometimes present in patients with frontal lobe epilepsy. Cognitive and behavioral problems in patients with absence seizures may be correlated with frontal lobe dysfunction. We report a 15-year-old female patient with absence seizures. She showed learning and behavioral problems such as inattention and impulsivity. We studied serial changes in frontal and prefrontal lobe volume to clarify such correlations among three-dimensional magnetic resonance imaging (MRI). We compared frontal and prefrontal lobe volumes between this patient, the childhood absence epilepsy group ( n = 4, age 8–11 y), and controls ( n = 10, age 6–15 y). Three-dimensional MRI was performed four times in the case (at worsening of absence seizures and 1, 2, and 4 y later) and three times in the childhood absence epilepsy group (at onset and 1 and 2 y later). Even after the complete cessation of seizures, frontal and prefrontal lobe volumes were lower in the case than in patients with childhood absence epilepsy and control subjects. Also, prefrontal-to-frontal lobe volume ratio increased over time in the childhood absence epilepsy and control subjects, whereas its increase was slight in the case. Patients presenting with frontal absence may show prefrontal lobe growth disturbance, which may manifest as poor frontal lobe function.

Grey matter anomalies in drug-naïve childhood absence epilepsy: A voxel-based morphometry study with MRI at 3.0 T

BackgroundLittle is known, so far, about the cerebral structural abnormalities in drug-naïve patients with childhood absence epilepsy (CAE). We aimed to investigate regional grey matter (GM) volume differences using voxel-based morphometry (VBM) in patients and closely matched healthy control subjects. MethodsTwenty drug-naïve patients diagnosed with CAE and 20 age- and gender-matched healthy subjects were recruited. All participants underwent structural MRI scans with a 3.0T MR system. The differences in regional GM volumes between the two groups were determined by VBM analysis. Additional regression analyses were performed to identify any associations between regional GM volume and clinical seizure variables. ResultsCompared with controls, the patients with CAE showed less GM volume in the bilateral thalami. Furthermore, the GM volume in the bilateral thalami was negatively correlated with disease duration and age of onset in the CAE group. ConclusionsBy excluding the potential effect of medication on brain structures, our study demonstrates less GM volume in the bilateral thalami in drug-naïve patients with idiopathic CAE. Our study further provides structural neuroimaging evidence on the pathophysiology of absence seizures.

Obesity and overweight as CAE comorbidities and differential drug response modifiers.

This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution. Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary intake were standardized for age, sex, and race/ethnicity and compared to age-matched US population from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models tested BMI as a predictor of treatment response. Pharmacokinetic variables were explored as contributors to differential drug response. After standardizing for demographic differences, children with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p < 0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE group than in NHANES controls. With increasing baseline BMI z score, the efficacy and effectiveness of ethosuximide and valproic acid over lamotrigine became more pronounced, despite no significant differences in drug exposure and trough levels. Overweight and obesity are more prevalent in children with newly diagnosed CAE than in age-matched peers, despite lower caloric and carbohydrate intake. Baseline BMI may also predict differential drug response, which cannot be attributed to pharmacokinetic differences.

Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies

To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI–TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29–0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53–0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59–0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06–2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance.

Disrupted Structural Connectivity of Default Mode Network in Childhood Absence Epilepsy

The structural connectivity patterns of human brain are the underlying basis of functional connectivity.Abnormal functional connectivity in default mode network(DMN) has been uncovered in electroencephalography(EEG) and functional magnetic resonance imaging(fMRI) studies,which suggests that the abnormality might be related to the cognitive mental impairment and unconsciousness during absence seizures.However,so far,little is known about the structural connectivity in DMN about childhood absence epilepsy(CAE).In the present study,we hypothesize that the structural connectivity in DMN should be disrupted to respond to the altered brain function in CAE.To test the hypothesis,11 patients with CAE and 12 age-and gender-matched healthy controls were recruited.We utilized diffusion tensor imaging tractography to map the anatomical structural connectivity of DMN.The fiber bundles among regions of DMN were built for each subject.Then,mean length,fractional anisotropic(FA),mean diffusivity(MD) and connection strength on fibers linking two brain regions were calculated.Further,these parameters were executed two-sample t-test between CAE group and health control group.Finally,we used Pearson's correlation coefficient to evaluate the relationship between these parameters and epilepsy duration(year).Both CAE and healthy control groups showed similar structural connectivity patterns in DMN.Among these fiber bundles,three were identified in all subjects,with one linking posterior cingulate cortex/precuneus to medial prefrontal cortex,and another two linking posterior cingulate cortex/precuneus to bilateral medial temporal lobes.Furthermore,the significantly decreased FA and connection strength,and increased MD in fiber bundles linking posterior cingulated cortex/precuneus to medial prefrontal cortex,were found in patients compared with the cases in healthy controls(P 0.05,Bonferroni corrected).Predominantly,the FA values in fiber bundles linking posterior cingulated cortex/precuneus to medial prefrontal cortex were negatively correlated with the epilepsy duration(P=0.006).These findings might reflect the structural basis of the altered functional connectivity in DMN about absence epilepsy.Given that functional connectivity abnormality in our previous work,it is implied that the abnormal fiber connectivity from posterior cingulated cortex/precuneus to medial prefrontal cortex plays an important role in absence epilepsy.This may open up new avenues to understand the pathophysiological mechanisms of absence epilepsy.

Neurocognitive profiles in children with epilepsy

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. 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. 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. 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.

Effects of childhood absence epilepsy on associations between regional cortical morphometry and aging and cognitive abilities

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.

Dysfunction of executive and related processes in childhood absence epilepsy

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.

Frontal and temporal volumes in Childhood Absence Epilepsy

This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child. The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ. These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.

Amygdala volumes in childhood absence epilepsy

Abnormal amygdala volumes in pediatric mood–anxiety disorders and attention deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses in childhood absence epilepsy (CAE), prompted this study of amygdala volume in CAE. Twenty-six children with CAE and 23 normal children, aged 6.6–15.8 years, underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala volumes were obtained by manual tracings. There were no significant amygdala volume differences between the CAE and normal groups. Within the CAE group, however, the children with ADHD had significantly smaller amygdala volumes than the subjects with CAE with no psychopathology and those with mood/anxiety diagnoses. There was also a significant relationship between higher seizure frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing development of the amygdala during late childhood and adolescence, despite the lack of significant group differences in amygdala volumes, the association of amygdala volume abnormalities with ADHD and seizure frequency implies a possible impact of the disorder on amygdala development and CAE-associated comorbidities, such as ADHD.