Changes in background electroencephalographic activity in benign childhood epilepsy with centrotemporal spikes after oxcarbazepine treatment: a standardized low-resolution brain electromagnetic tomography (sLORETA) study.

BACKGROUND: Several neuroimaging studies have reported neurophysiological alterations in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS). However, reported outcomes have been inconsistent, and the progression of these changes in the brain remains unresolved. Moreover, background electroencephalography (EEG) in cases of BCECTS has not been performed often. METHODS: We investigated background EEG activity changes after six months of oxcarbazepine treatment to better understand the neurophysiological alterations and progression that occur in BCECTS. In 18 children with BCECTS, non-parametric statistical analyses using standardized low resolution brain electromagnetic tomography (sLORETA) were performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between untreated and treated conditions. RESULTS: Background EEG activity for the delta frequency band was significantly decreased in the fronto-temporal and limbic regions of the left hemisphere after oxcarbazepine treatment (threshold log-F-ratio = ±2.729, P < 0.01). The maximum current density difference was found in the parahippocampal gyrus of the left limbic lobe (Montreal Neurological Institute coordinate [x, y, z = 25, - 20, - 10], Brodmann area 28) (log-F-ratio = 3.081, P < 0.01). CONCLUSIONS: Our results indicate the involvement of the fronto-temporal and limbic cortices in BCECTS, and limbic lobe involvement, including the parahippocampal gyrus, was noted. In addition to evidence of the involvement of the fronto-temporal and limbic cortices in BCECTS, this study also found that an antiepileptic drug could reduce the delta frequency activity of the background EEG in these regions.

The influence of EEG-detected nocturnal centrotemporal discharges on the expression of core symptoms of ADHD in children with benign childhood epilepsy with centrotemporal spikes (BCECTS): A prospective study in a tertiary referral center.

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most frequent benign focal epilepsy in childhood. Although it is described as a benign epilepsy syndrome, many studies have revealed that a significant number of patients have some degree of neuropsychological impairment. Thirty-two patients with BCECTS aged 6-11years were included in the study. All patients (without any antiepileptic or psychiatric medication) underwent all-night EEG monitoring and complex neuropsychological testing to diagnose the presence of core symptoms of attention-deficit/hyperactivity disorder (ADHD). The spike index (number of spikes per minute) on awake and asleep EEG, age at seizure onset, family history of epilepsy, and perinatal risks were correlated with the results of neuropsychological testing. Of the 32 patients, 21 patients (65.6%) fulfilled the criteria for ADHD diagnosis. Children who were younger at epilepsy onset demonstrated lower IQ and higher attention deficit (P=0.004) and higher impulsivity (P=0.016). The occurence of epileptiform discharges on nocturnal EEG was positively related to higher attention deficit and higher impulsivity. The findings are discussed in terms of how interictal discharges in the centrotemporal region during sleep affect the development of cognitive functions in children during critical epochs of neuropsychological development.

Brain responses to auditory oddball task in children with benign childhood epilepsy with centrotemporal spikes: Quantitative analysis and correlation with neuropsychological assessment scores.

OBJECTIVE: Variable degrees of cognitive dysfunction have been reported in children with benign childhood epilepsy with centrotemporal spikes (BCECTS). Our aim was to perform quantitative analyses of the brain responses to cognitive tasks using event-related desynchronization (ERD) and event-related synchronization (ERS) and correlating the results with the scores of neuropsychological tests in patients with BCECTS. METHODS: This case control study included 30 patients with BCECTS and 20 controls. Clinical assessment, neuropsychological tests, the Positive wave at 300 msec (P300) parameters recording, and quantitative electroencephalography (EEG) analysis were carried out for both groups. Alpha power ERD and ERS were measured in six different brain regions during an auditory oddball paradigm. RESULTS: Children with epilepsy showed a statistically significant poorer performance in verbal intelligence quotient (IQ), performance IQ, and total scale IQ and lower number of correct responses. Moreover, both groups showed diffuse alpha power attenuation in response to the target tones. After summation of the alpha power ERD over all brain regions to get the net diffuse ERD, the patients' group showed a statistically significant smaller net alpha ERD compared with that of the control group (P=0.001). No significant correlations between the alpha ERD percentage, recorded P300 parameters, and neuropsychological tests scores were found. CONCLUSIONS: Children with BCECTS have subtle cognitive dysfunction proved by significantly lower scores of verbal IQ and performance IQ subtests. The significantly smaller net diffuse alpha power ERD detected in children with epilepsy may be an electrophysiological indicator of disruptive brain activation in relation to cognitive attentional tasks; however, its correlation with neuropsychological tests was insignificant.

Behavioral and fMRI responses to fearful faces are altered in benign childhood epilepsy with centrotemporal spikes (BCECTS).

OBJECTIVE: We hypothesized that children with benign childhood epilepsy with centrotemporal spikes (BCECTS) might have altered social cognitive skills and underlying neural networks. METHODS: We studied 13 patients with BCECTS and 11 age-matched controls using event-related functional magnetic resonance imaging (fMRI) with an emotional discrimination task consisting of viewing happy, fearful, scrambled, and neutral faces. Behavioral performance measured during the task was correlated with clinical variables and behavioral ratings. RESULTS: In comparison with age-matched controls, children with BCECTS performing a fearful faces detection task showed significantly reduced bilateral fMRI activation in the insular cortex, caudate, and lentiform nuclei, as well as increased response time. The percentage of errors made by children with BCECTS correlated negatively with age, a finding not observed in controls. In patients, accuracy positively correlated with time since the last seizure. The above abnormalities were not observed during happy faces detection task, except for a slower response in children with BCECTS as compared to controls. SIGNIFICANCE: Our study suggests that BCECTS is associated with altered social cognition network and function, particularly for the identification of fearful faces. The age dependency of some of these findings supports the view that a delayed maturation of spiking cortical regions might underlie the cognitive dysfunction observed in BCECTS.

Depression and anxiety in children with benign childhood epilepsy with centrotemporal spikes (BCECTS).

BACKGROUND: Elevated rates of affective disturbance in children with benign childhood epilepsy with centrotemporal spikes (BCECTS) have been reported. However, it remains unclear how anxiety and depression are related to epilepsy, and it is unknown whether these mood disorders are influenced by the use of antiepileptic drugs. In the present report, we performed a prospective study designed to evaluate affective disorders (anxiety and depression) without the bias of antiepileptic drug treatment in 89 children with BCECTS, based on self-reporting. Furthermore, we sought to determine whether clinical factors, such as age, disease course, seizure frequency, and spike wave index (SWI), were related to the psychological profiles. METHODS: Patients with BCECTS (n = 89) and healthy matched controls (n = 75) were included in this study. The Depression Self-Rating Scale for Children (DSRSC) and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) were completed by the children. RESULTS: None of the children met criteria for clinically significant anxiety or depression. However, the children with BCECTS had significantly higher depression and anxiety scores compared with children in the control group. We found no significant differences in depression or anxiety between the left, right, and bilateral lobe groups. The DSRSC scores were similar between the children with partial seizures and those with secondarily generalized seizures. Similarly, there were no significant differences in the SCARED scores between these two groups. However, the DSRSC and SCARED scores were positively correlated with age, seizure frequency, SWI, and disease course. CONCLUSIONS: The children with BCECTS had an increased likelihood of depression and anxiety, and these higher rates were unrelated to seizure type or epileptic focus, but were positively correlated with age, seizure frequency, SWI, and disease course.

White matter development in children with benign childhood epilepsy with centro-temporal spikes.

Benign childhood epilepsy with centro-temporal spikes (BCECTS) is a unique form of non-lesional age-dependent epilepsy with rare seizures, focal electroencepalographic abnormalities affecting the same well delineated cortical region in most patients, and frequent mild to moderate cognitive dysfunctions. In this condition, it is hypothesized that interictal electroencepalographic discharges might interfere with local brain maturation, resulting in altered cognition. Diffusion tensor imaging allows testing of this hypothesis by investigating the white matter microstructure, and has previously proved sensitive to epilepsy-related alterations of fractional anisotropy and diffusivity. However, no diffusion tensor imaging study has yet been performed with a focus on BCECTS. We investigated 25 children suffering from BCECTS and 25 age-matched control subjects using diffusion tensor imaging, 3D-T1 magnetic resonance imaging, and a battery of neuropsychological tests including Conner's scale and Wechsler Intelligence Scale for Children (fourth revision). Electroencephalography was also performed in all patients within 2 months of the magnetic resonance imaging assessment. Parametric maps of fractional anisotropy, mean-, radial-, and axial diffusivity were extracted from diffusion tensor imaging data. Patients were compared with control subjects using voxel-based statistics and family-wise error correction for multiple comparisons. Each patient was also compared to control subjects. Fractional anisotropy and diffusivity images were correlated to neuropsychological and clinical variables. Group analysis showed significantly reduced fractional anisotropy and increased diffusivity in patients compared with control subjects, predominantly over the left pre- and postcentral gyri and ipsilateral to the electroencephalographic focus. At the individual level, regions of significant differences were observed in 10 patients (40%) for anisotropy (eight reduced fractional anisotropy, one increased fractional anisotropy, one both), and 17 (56%) for diffusivity (13 increased, one reduced, three both). There were significant negative correlations between fractional anisotropy maps and duration of epilepsy in the precentral gyri, bilaterally, and in the left postcentral gyrus. Accordingly, 9 of 12 patients (75%) with duration of epilepsy>12 months showed significantly reduced fractional anisotropy versus none of the 13 patients with duration of epilepsy≤12 months. Diffusivity maps positively correlated with duration of epilepsy in the cuneus. Children with BCECTS demonstrate alterations in the microstructure of the white matter, undetectable with conventional magnetic resonance imaging, predominating over the regions displaying chronic interictal epileptiform discharges. The association observed between diffusion tensor imaging changes, duration of epilepsy and cognitive performance appears compatible with the hypothesis that interictal epileptic activity alters brain maturation, which could in turn lead to cognitive dysfunction. However, such cross-sectional association does not demonstrate causality, and other hitherto unidentified factors could represent the common cause to part or all of the observed findings.

Benign childhood epilepsy with Centro-Temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline--how aggressive should we be?

Since many of the children with BCECTSs display electrical status epilepticus during sleep and many present with different comorbidities, mainly ADHD and behavioral disturbances, clinicians are often confronted with the dilemma of how aggressive they should be with their efforts of normalizing the EEG. We conducted a retrospective study by screening medical records of all consecutive patients with BCECTSs, spike-wave index (SWI) >30%, and ADHD/ADD that were evaluated in our pediatric epilepsy service and were followed up for at least two years. Patients with neurocognitive deterioration detected by formal testing were excluded. A total of 17 patients with mean age of 6.9years at BCECTS diagnosis were identified. The patients' mean SWI was 60% and that dense electrical activity lasted 1.5years on average (range: 1-4.5years). Six children were formally diagnosed with learning disabilities in addition to ADD/ADHD. All of them were treated with an average of three antiepileptic medications, mainly for the purpose of normalizing the EEG, but none of them was treated with steroids or high-dose diazepam. The mean duration of follow-up was 5.5years. A cognitive or behavioral deterioration was not detected in any of them. Our data suggest that when treating a child with BCECTSs, high SWI, and school difficulties, the most critical parameter that determines the necessity of using second-line antiepileptic agents such as steroids or high-dose diazepam is a formal psychological evaluation that proves cognitive (I.Q.) decline. Otherwise, these agents may be avoided.

18 F-FDG PET Brain Findings in a Case of Idiopathic Benign Rolandic Epilepsy of Childhood.

Idiopathic benign rolandic epilepsy, also known as benign childhood epilepsy with centrotemporal spikes (BCECTS), is one of the commonly seen electroclinical epilepsy syndromes of childhood with a generally favorable long-term prognosis. We describe a 5-year-old female child who presented with recurrent focal seizures involving right side of face since the age of 6 months. She had no perinatal or postnatal insults, had normal development, and her neurological examination was unremarkable. Electroencephalogram showed rolandic spikes, suggesting BCETCS. Her seizures remained refractory to two appropriately dosed antiepileptic drugs. Magnetic resonance imaging of the brain did not reveal any structural lesion. Interictal fluorodeoxyglucose 18 F-positron emission tomography brain showed hypometabolism in the left lower rolandic region.

High-Density (HD) Scalp EEG Findings in "Benign" Childhood Epilepsy with Centrotemporal Spikes (BCECTS).

Despite characteristic clinical and scalp EEG findings, BCECTS pathophysiology is unclear regarding involvement of large-scale neuronal networks. Higher number of scalp electrodes with HD-EEG may promote accurate localization of the cortical generators in BCECTS providing additional insight in those with neurocognitive problems. We aimed to determine the value of visual interpretation of topographical maps using 256 channels (when compared to standard 21 channel array) HD-EEG in BCECTS and attempted to source localize interictal discharges (IEDs) using Geosource 2 software. Patient records were reviewed for demographic, seizure, brain magnetic resonance imaging (MRI) details; scalp and HD-EEG findings. HD-EEG software was used to review raw EEG data (21 scalp EEG electrodes were compared to 256 HD-EEG electrodes); select, average, and source localize IEDs.Five BCECTS patients with HD-EEG were identified. Seizure onset age ranged from 5-11 years with 1-18 lifetime seizures; both focal (n = 3) and focal to bilateral tonic-clonic (n = 2). Neurocognitive co-morbidities noted in our cohort included attention deficit hyperactivity disorder, speech/developmental delay and a specific learning disorder. Scalp EEG showed typical findings with IEDs over the centrotemporal regions (bilateral n = 3; unilateral n = 2). Visualization and inspection of expanded coverage topographic maps with HD-EEG showed well-defined islands of maximum negativity and positivity of a dipole compared to conventional channels where boundary delineation was obscured. Further, HD-EEG localized IEDs/"spike-generator" to areas such as the pre-and post-central, middle-frontal and temporal gyrus, and the inferior parietal lobule. In BCECTS, HD-EEG may show affection for a broader neural network and may provide a better insight into the associated neurocognitive morbidities.

Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes.

BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies have identified brain systems underlying different components of working memory (WM) in healthy subjects. The aim of this study was to compare the functional integrity of these neural networks in children with self-limited childhood epilepsy with centro-temporal spikes (ECTS) as compared to healthy controls, using a verbal working memory task (WMT). METHODS: Functional MRI of WM in seventeen 6-to-13 year-old children, diagnosed with ECTS, and 17 sex- and age-matched healthy controls were conducted at 3 T. To estimate BOLD responses during the maintenance of low, medium, and high WMT loads, we used a Sternberg verbal WMT. Neuropsychological testing prior to scanning and behavioral data during scanning were also acquired. RESULTS: Behavioral performances during WMT, in particular accuracy and response time, were poorer in children with ECTS than in controls. Increased WM load was associated with increased BOLD signal in all subjects, with significant clusters detected in frontal and parietal regions, predominantly in the left hemisphere. However, under the high load condition, patients showed reduced activation in the frontal, temporal and parietal regions as compared to controls. In brain regions where WM-triggered BOLD activation differed between groups, this activation correlated with neuropsychological performances in healthy controls but not in patients with ECTS, further suggesting WM network dysfunction in the latter. CONCLUSION: Children with ECTS differ from healthy controls in how they control WM processes during tasks with increasing difficulty level, notably for high WM load where patients demonstrate both reduced BOLD activation and behavioral performances.

Delayed cortical maturation at the centrotemporal brain regions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS).

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is an epilepsy syndrome commonly found in child and adolescent. Although the prognosis is mostly favorable as long as the seizure is well controlled. However, they are often suffering from the cognitive and behavioral problems which might be the consequences of the initial insults. It is still not clear whether the initial epileptiform discharges has long term impact on the resting-state brain activities at later ages. This study investigated the resting-state brain activities in BCECTS patients with clinical seizure remission stage (n = 16; 11 males) and compared with the non-epileptic, age-matched control subjects. Quantitative electroencephalography (qEEG) revealed a significantly higher absolute power of the theta and alpha waves in BCECTS patients with clinical seizure remission as compared with the non-epileptic control subjects. Interestingly, the differences were observed mainly over the centrotemporal electrodes which are the common sites of the initial epileptiform discharges. The differences were more significant in patients with bilateral epileptiform discharges than those with the unilateral epileptic activities. Typically, the brain wave power continuously decreases with increasing ages. Therefore, higher absolute powers of the brain waves indicate more delayed in cortical maturation compared with the non-epileptic control group. These findings indicated that BCECTS patients have delay cortical maturation at the centrotemporal brain regions even at the clinical seizure remission phase.

Distributed source localization of interictal spikes in benign childhood epilepsy with centrotemporal spikes: A standardized low-resolution brain electromagnetic tomography (sLORETA) study.

Benign childhood epilepsy with centrotemporal spikes (BCECTS), also known as Rolandic epilepsy, is the most common benign childhood epilepsy. Centrotemporal spikes are characteristic findings on electroencephalography (EEG). Though the condition is considered benign, many studies have reported some degree of neuropsychological impairment in individuals with BCECTS. There is also growing evidence from neuroimaging studies that BCECTS may affect a larger portion of the brain than originally thought. We performed distributed source localization analysis of interictal spikes in BCECTS. Current-source density (CSD) of the maximal negative peak of the interictal spikes averaged from each of 20 EEG epochs in 11 patients with BCECTS was measured using standardized low-resolution brain electromagnetic tomography (sLORETA). Rolandic area was included in the distribution of the CSD in all of the patients. The significant CSD and its maximal point were distributed in multiple cortical regions over the Rolandic area. It is suggested that the widespread cortical distribution of interictal spikes seen in this study may be associated with atypical presentation and a variety of comorbidities of BCECTS. Our results imply that BCECTS represents a deviation from normal development during a critical period of brain maturation and that children with BECTS might be more likely to need special medical attention.