Dysfunctional white-matter networks in medicated and unmedicated benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECT) is the most common childhood idiopathic focal epilepsy syndrome, which characterized with white-matter abnormalities in the rolandic cortex. Although diffusion tensor imaging research could characterize white-matter structural architecture, it cannot detect neural activity or white-matter functions. Recent studies demonstrated the functional organization of white-matter by using functional magnetic resonance imaging (fMRI), suggesting that it is feasible to investigate white-matter dysfunctions in BECT. Resting-state fMRI data were collected from 24 new-onset drug-naive (unmedicated [NMED]), 21 medicated (MED) BECT patients, and 27 healthy controls (HC). Several white-matter functional networks were obtained using a clustering analysis on voxel-by-voxel correlation profiles. Subsequently, conventional functional connectivity (FC) was calculated in four frequency sub-bands (Slow-5:0.01-0.027, Slow-4:0.027-0.073, Slow-3:0.073-0.198, and Slow-2:0.198-0.25 Hz). We also employed a functional covariance connectivity (FCC) to estimate the covariant relationship between two white-matter networks based on their correlations with multiple gray-matter regions. Compared with HC, the NMED showed increased FC and/or FCC in rolandic network (RN) and precentral/postcentral network, and decreased FC and/or FCC in dorsal frontal network, while these alterations were not observed in the MED group. Moreover, the changes exhibited frequency-specific properties. Specifically, only two alterations were shared in at least two frequency bands. Most of these alterations were observed in the frequency bands of Slow-3 and Slow-4. This study provided further support on the existence of white-matter functional networks which exhibited frequency-specific properties, and extended abnormalities of rolandic area from the perspective of white-matter dysfunction in BECT.

Cortical morphology, epileptiform discharges, and neuropsychological performance in BECTS.

OBJECTIVES: The aim of this study was to understand the relationship between cortical morphology, centrotemporal spike (CTS), and neuropsychological functioning in children with BECTS compared to their typically developing peers. MATERIALS AND METHODS: To examine whole-brain differences in cortical thickness between groups, a general linear model approach was applied to T1-weighted structural magnetic resonance imaging (MRI) in children with BECTS and typically developing children. Further region-of-interest (ROI) analyses were performed to examine the effects of frequency and lateralization of CTS. In addition, the relationship between Processing Speed Index (PSI) and cortical thickness was investigated. RESULTS: Twenty-three patients with BECTS and thirty-two controls were included. There was no statistically significant difference in global cortical thickness between groups. With ROI analyses, we found significantly thinner cortex within right pars opercularis when comparing children with right predominant CTS, and with very frequent right CTS (>10/min) to the control group (P = 0.028 and P = 0.026, respectively). A statistically significant interaction of group (controls vs BECTS) and PSI was seen in bilateral frontal and right superior parietal cortices, indicating a positive relationship between cortical thickness and PSI in healthy controls but not BECTS. CONCLUSION: A region of cortex where right CTS may originate was thinner in BECTS compared to children without BECTS. Typically developing children with faster processing speed had thicker cortices in regions supporting visuomotor integration, motor, and executive function, but this relationship was not observed in BECTS. These results suggest that BECTS is associated with atypical cortical morphology that may underlie poorer neuropsychological performance.

Neuronal networks in epileptic encephalopathies with CSWS.

OBJECTIVE: The aim of our study was to investigate the neuronal networks underlying background oscillations of epileptic encephalopathy with continuous spikes and waves during slow sleep (CSWS). METHODS: Sleep electroencephalography (EEG) studies before and after the treatment were investigated in 15 patients with CSWS. To investigate functional and effective connectivity within the network generating the delta activity in the background sleep EEG, the methods of dynamic imaging of coherent sources (DICS) and renormalized partial directed coherence (RPDC) were applied. RESULTS: Independent of etiology and severity of epilepsy, background EEG pattern in patients with CSWS before treatment is associated with the complex network of coherent sources in medial prefrontal cortex, somatosensory association cortex/posterior cingulate cortex, medial prefrontal cortex, middle temporal gyrus/parahippocampal gyrus/insular cortex, thalamus, and cerebellum. The analysis of information flow within this network revealed that the medial parietal cortex, the precuneus, and the thalamus act as central hubs, driving the information flow to other areas, especially to the temporal and frontal cortex. The described CSWS-specific pattern was no longer observed in patients with normalized sleep EEG. In addition, frequency of spiking showed a strong linear correlations with absolute source power, source coherence strength, and source RPDC strength at both time points: (1) Spike and wave index (SWI) versus absolute source power at EEG1 (r = 0.56; p = 0.008) and at EEG2 (r = 0.45; p = 0.009); (2) SWI versus source coherence strength at EEG1 (r = 0.71; p = 0.005) and at EEG2 (r = 0.52; p = 0.006); and (3) SWI versus source RPDC strength at EEG1 (r = 0.65; p = 0.003) and at EEG2 (r = 0.47; p = 0.009). SIGNIFICANCE: The leading role of the precuneus and thalamus in the hierarchical organization of the network underlying the background EEG points toward the significance of fluctuations of vigilance in the generation of CSWS. This hierarchical network organization appears to be specific for CSWS as it is resolved after successful treatment.

Comparing cortical auditory processing in children with typical and atypical benign epilepsy with centrotemporal spikes: Electrophysiologic evidence of the role of non-rapid eye movement sleep abnormalities.

OBJECTIVE: The mismatch negativity (MMN) is an objective measure of central auditory discrimination. MMN alterations have been shown in children with language and/or developmental disorders. In benign focal epilepsies, neuropsychological disorders are often reported and linked to interictal epileptic discharges (IEDs) during non-rapid eye movement (NREM) sleep. There are few studies reporting MMN in children with benign epilepsy with centrotemporal spikes (BECTS) and sleep IEDs. Moreover, no MMN recording has yet been reported in atypical BECTS children with continuous spike-and-wave during sleep (CSWS). We retrospectively compared MMN in typical and atypical BECTS children, particularly addressing the impact of NREM sleep IEDs on auditory discrimination. Moreover, we attempted a neuropsychological characterization of patients. METHODS: The MMN was recorded in 9 normal controls and 23 patients (14 typical BECTS and 9 atypical BECTS) in an oddball paradigm with syllable stimuli. MMN, sleep electroencephalography (EEG) and neuropsychological evaluation were realized in the same testing session. RESULTS: Measurable MMN responses to speech stimuli were identified in both the control and patient groups. A significant difference between control and atypical BECTS children was found with respect to amplitude (p = 0.0061). Atypical BECTS also showed a lower MMN amplitude with respect to typical BECTS, but this difference did not reach statistical significance (p = 0.0545). Statistical comparisons between groups revealed no differences in latency. Among the neuropsychological variables, academic difficulties were significantly more prominent in the patients with atypical BECTS (p = 0.04). SIGNIFICANCE: CSWS EEG pattern affects auditory discrimination and may have a long-lasting impact on academic skills acquisition, whereas in typical BECTS children with a lower degree of IED NREM sleep, plastic brain reorganization or the preservation of participating networks may prevent such difficulty. Early electrophysiologic identification of auditory discrimination deficits in epileptic children could be used in early rehabilitation, thereby reducing the risk of developing neuropsychological disorders.

Epilepsy surgery of the rolandic and immediate perirolandic cortex: surgical outcome and prognostic factors.

OBJECTIVE: Herein we present a single-center retrospective study of patients who underwent epilepsy surgery for seizures arising from the sensorimotor (rolandic) cortex. The goal was to find prognostic factors associated with better seizure outcome and to evaluate both surgical and neurologic outcomes. PATIENTS, METHODS, AND MATERIALS: A total of 66 patients fulfilled eligibility criteria and were included in the study. Patients were divided into two groups for analysis: patients with resections within rolandic cortex (RO group; n = 46), and patients with resections in immediate perirolandic cortex and simultaneous sensorimotor multiple subpial transections (IPR group; n = 20). RESULTS: Favorable postoperative seizure outcome (International League Against Epilepsy [ILAE]; ILAE1-ILAE3) was achieved in 42 patients (64%), 39 (59%) of whom were completely seizure-free (ILAE1). The favorable seizure outcome in the RO group (72%) was better than in the IPR group (45%) (p = 0.04, relative risk [RR] 0.51 [0.28-0.94, 95% CI]). Eighteen patients (34%) had a postoperative permanent neurologic deficit. Independent predictors for excellent seizure outcome (ILAE1) after multivariate regression analysis were complete resection of the lesion (p < 0.001), pathology (p = 0.009), age at surgery (p = 0.03), and the absence of preoperative simple partial seizures (p = 0.01). SIGNIFICANCE: With a 64% favorable seizure outcome, surgery for intractable epilepsy arising from sensorimotor cortex is possible and can be worthwhile. The increased risk for postoperative neurologic deficits is higher than in other locations, and this must be discussed with patients in detail prior to surgery. Best postoperative results can be achieved in cases in which a complete resection is possible without damaging eloquent cortical areas.

Modify or die?--RNA modification defects in metazoans.

Chemical RNA modifications are present in all kingdoms of life and many of these post-transcriptional modifications are conserved throughout evolution. However, most of the research has been performed on single cell organisms, whereas little is known about how RNA modifications contribute to the development of metazoans. In recent years, the identification of RNA modification genes in genome wide association studies (GWAS) has sparked new interest in previously neglected genes. In this review, we summarize recent findings that connect RNA modification defects and phenotypes in higher eukaryotes. Furthermore, we discuss the implications of aberrant tRNA modification in various human diseases including metabolic defects, mitochondrial dysfunctions, neurological disorders, and cancer. As the molecular mechanisms of these diseases are being elucidated, we will gain first insights into the functions of RNA modifications in higher eukaryotes and finally understand their roles during development.

Connectivity Disturbances in Self-Limited Epilepsy with Centrotemporal Spikes: A Partial Directed Coherence Analysis of Electroencephalogram.

Although the remission of self-limited epilepsy with centrotemporal spikes (SeLECTS) usually occurs by adolescence, deficits in cognition and behavior are not uncommon. Several functional magnetic resonance imaging (fMRI) studies have revealed connectivity disturbances in patients with SeLECTS associated with cognitive impairment. However, the disadvantages of fMRI are expensive, time-consuming, and motion sensitive. In the current study, we used a partial directed coherence (PDC) method to analyze electroencephalogram (EEG) for exploring brain connectivity in patients with SeLECTS. This study enrolled 38 participants (19 patients with SeLECTS and 19 healthy controls) for PDC analysis. Our results demonstrated that the controls had significantly higher PDC inflow connectivity in the F7, T3, FP1, and F8 channels than patients with SeLECTS. By contrast, the patients with SeLECTS demonstrated significantly higher PDC inflow connectivity than did the controls in the T5, Pz, and P4 channels. We also compared the PDC connectivity in different Brodmann areas between the patients with SeLECTS and the controls. The results revealed that the inflow connectivity in the BA9_46_L area was significantly higher in the controls than in the patients with SeLECTS, whereas the inflow connectivity in the MIF_L area 4 was significantly higher in the patients with SeLECTS than in the controls. Our proposed approach of combining EEG with PDC provides a convenient and useful tool for investigating functional connectivity in patients with SeLECTS. This approach is time-saving and inexpensive compared with fMRI, but it achieves similar results to fMRI.

Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes.

PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit. METHODS: We investigated volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus in a group of children with new- and recent-onset BECTS (N = 3) compared to healthy controls (N = 54). We correlated specific subcortical volumes in BECTS that were significantly different from those in healthy controls with performances in executive function. KEY FINDINGS: Children with BECTS demonstrated significantly hypertrophied putamen, which was selective among the subcortical regions examined. Shape analysis showed dorsoventral elongation of the left caudate and bilateral putamen, with subnuclei expansion in ventral and dorsal striatum. Larger putamen volumes were linked to better cognitive performances on two complementary executive function tests. SIGNIFICANCE: Children with BECTS showed aberrant volume and shape in subcortical regions that are critical for both motor processing and executive function. It is of importance to note that the hypertrophy appears to be cognitively adaptive, as enlargement was associated with improved cognitive performances. The anatomic abnormalities and their cognitive effects are evident in a group of children with new- and recent-onset epilepsy, suggesting that the structural brain anomalies occurred before the diagnosis of epilepsy.

Benign childhood focal epilepsies.

The idiopathic focal epilepsies comprise a group of syndromes characterized by focal-onset seizures for which there is no detectable structural brain abnormality and for which there is a proposed functional mechanism for the epilepsy and electroencephalography (EEG) abnormalities. This group includes benign rolandic epilepsy (BRE), benign epilepsy with occipital paroxysms (both early onset and late-onset types), idiopathic photosensitive occipital lobe epilepsy, and some less well-defined syndromes. The limits of the early onset idiopathic occipital epilepsy syndrome are not clear, and perhaps this entity represents part of a larger syndrome group of "autonomic" age-related epilepsies. The term "idiopathic" implies absence of a structural brain lesion and a genetic propensity to seizures. The term "benign" implies that the epileptic seizures are easily treated or require no treatment, show remission without sequelae with ultimate and definitive remission before adulthood, do not have severe or exceedingly disturbing seizures, and have no associated serious intellectual or behavioral disturbances. It may be that a syndrome is benign only when it can be recognized early with reasonable certainty, thereby avoiding unnecessary investigations, overtreatment, and lifestyle restrictions. Although BRE has such characteristic clinical and EEG features to make early recognition possible, this is less constantly so in the other focal idiopathic epilepsy syndromes, where the term "benign" may be inappropriate. Mild and selective neuropsychological impairment may occur even in those with typical syndromes but it is unclear whether such selective deficits outlast the active phase of epilepsy. Sometimes the clinical course may be complicated by obvious cognitive and language impairments. In such cases, the term benign is obviously inappropriate, even when seizures are rare. In most patients with the typical focal idiopathic epilepsy syndromes, medication is not necessary.

Tailored resections for intractable rolandic cortex epilepsy in children: a single-center experience with 48 consecutive cases.

OBJECTIVE: A single-center experience with pediatric patients who underwent surgery for intractable rolandic epilepsy was reviewed with the aim of identifying putative factors that could influence postoperative seizure outcome in this population. METHODS: Clinical data of 48 patients under 18 years of age with diagnosis of intractable rolandic epilepsy who underwent surgery from January 1996 to September 2009 were reviewed. RESULTS: Patients' mean age at surgery was 9.9 ± 5.3 years; mean age at epilepsy onset was 3.9 years; mean seizure duration prior to surgery was 6 years; and mean follow-up was 5.1 years. The most frequent etiologies were cortical dysplasia, astrogliosis, tumors, tuberous sclerosis complex, and Sturge-Weber syndrome, which were observed in 20/48 (41.6%), 10/48 (20.8%), 10/48 (20.8%), 5/48 (10.4%), and 3/48 (6.2%) of the patients, respectively. After surgery, 20 patients (41.6%) showed neurological deficits, which in turn recovered within no longer than 6 months after surgery. Seizure outcome was classified as Engel class I in 29 (60.4%), Engel class II in 10 (20.8%), and Engel class III in 9 (18.8%) of the patients. The factors significantly related with seizure outcome were histological features (tumor versus non-tumor cases, p = 0.04) and lesion site (focal lesions versus non-focal lesions, p = 0.04). CONCLUSIONS: Tailored resection of rolandic cortex for intractable epilepsy can be safely performed in children. Accurate mapping of both functional cortex and epileptogenic areas may lead to improved seizure outcome. Tumor as well as focal lesions in hand and face motor areas are associated with good seizure outcome.

Nonlinear Analysis of Visually Normal EEGs to Differentiate Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS).

Childhood epilepsy with centrotemporal spikes, previously known as Benign Epilepsy with Centro-temporal Spikes (BECTS) or Rolandic Epilepsy, is one of the most common forms of focal childhood epilepsy. Despite its prevalence, BECTS is often misdiagnosed or missed entirely. This is in part due to the nocturnal and brief nature of the seizures, making it difficult to identify during a routine electroencephalogram (EEG). Detecting brain activity that is highly associated with BECTS on a brief, awake EEG has the potential to improve diagnostic screening for BECTS and predict clinical outcomes. For this study, 31 patients with BECTS were retrospectively selected from the BCH Epilepsy Center database along with a contrast group of 31 patients in the database who had no form of epilepsy and a normal EEG based on a clinical chart review. Nonlinear features, including multiscale entropy and recurrence quantitative analysis, were computed from 30-second segments of awake EEG signals. Differences were found between these multiscale nonlinear measures in the two groups at all sensor locations, while visual EEG inspection by a board-certified child neurologist did not reveal any distinguishing features. Moreover, a quantitative difference in the nonlinear measures (sample entropy, trapping time and the Lyapunov exponents) was found in the centrotemporal region of the brain, the area associated with a greater tendency to have unprovoked seizures, versus the rest of the brain in the BECTS patients. This difference was not present in the contrast group. As a result, the epileptic zone in the BECTS patients appears to exhibit lower complexity, and these nonlinear measures may potentially serve as a clinical screening tool for BECTS, if replicated in a larger study population.

Identification of susceptibility variants to benign childhood epilepsy with centro-temporal spikes (BECTS) in Chinese Han population.

BACKGROUND: Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS) is the most common form of idiopathic epilepsy in children, accounting for up to 23% of pediatric epilepsy. The pathogenesis of BECTS is unknown, but it is thought that genetic factors play a role in susceptibility to the disease. METHODS: To investigate the role of common genetic variants in BECTS pathogenesis, a 2-stage genome-wide association study (GWAS) was performed in 1,800 Chinese Han BECTS patients, and 7,090 healthy controls. Genetic findings were used in a Mendelian Randomization study in the UK Biobank dataset to investigate the potential role of smoking in BECTS. FINDINGS: Definitive evidence of a role for common-variant heritability was demonstrated, with heritability of BECTS of >10% observed even with conservative disease prevalence assumptions. Although no individual locus achieved genome-wide significance, twelve loci achieved suggestive evidence of association (5 × 10-8

Speech and school performance in children with benign partial epilepsy with centro-temporal spikes (BCECTS).

PURPOSE: To assess prospectively language and speech ability in children with benign partial epilepsy with centro-temporal spikes (BCECTS). To evaluate academic performance and social competencies both during the active disease and after remission. METHODS: Right-handed school children with typical BCECTS and a control group matched by age, sex, handedness and socioeconomic status were examined. The German version of WISC-R, the "Tübinger Luria Christensen Neuropsychological Test Set for children" (TUKI), the "Verbal Learning Memory Test" (VLMT), the "Heidelberger Speech Development Test-second edition" (HSET), and the "Salzburger reading and writing test" (SLRT) were applied. The Child Behavior Checklist (CBCL) and a semi-structured interview were performed with the children's teachers to gain insight into school performance, behavioral and emotional problems. RESULTS: During the active phase, the patient group - despite normal global intellectual abilities - showed few, but significant impairments both in expressive speech and in receptive and expressive vocabulary. A significant deficit in the ability to recognize and express interpersonal relations was also found. Patients' teachers stated deficits concerning academic performance and complained about disturbing behavior. Parents reported significantly more psycho-pathological features in the subscales "Aggressive Behavior", "Attention Problems" and "Anxious/Depressed" of the CBCL. Results were independent of medication and spike localization. After complete recovery from BCECTS, these problems were not found any more. CONCLUSIONS: Both deficits of speech-related abilities (in both expressive and receptive vocabulary) and behavioral disturbances can be detected in children with typical BCECTS, but are no longer apparent after remission of the seizure disorder.

Cortical thinning in benign epilepsy with centrotemporal spikes (BECTS) with or without attention-deficit/hyperactivity (ADHD).

The aim of this study is to evaluate the abnormal cortical structures associated with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS) patients and assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities. Newly diagnosed BECTS patients (n = 33, 23 males) and age-matched healthy controls (n = 48) were evaluated by surface and volumetric MRI. CAT12 toolbox (HYPERLINK "http://www.neuro.uni-jena.de/cat/"\t"_blank" http://www.neuro.uni-jena.de/cat/, version r1109), SPM12(HYPERLINK"http://www.fil.ion.ucl.ac.uk/spm/software/spm12/"\t"_blank"http://www.fil.ion.ucl.ac.uk/spm/software/spm12/, version 6225) and MATLAB (9.5, Mathworks, Natick, MA) were used to gather CT estimates. An additional comparison was performed between BECTS children with (n = 13) and without ADHD (n = 20). BECTS patients had significantly smaller volume in left postcentral gyrus when compared to healthy controls. BECTS patients with ADHD had significantly thinner superior-inferior frontal cortex, superior temporal cortex, left pericalcarine, lingual and fusiform cortex to healthy controls. Also BECTS without ADHD patients had thinner cortical areas when compared to healthy controls, however the significance was more relevant in the BECTS with ADHD. The left fusiform cortex of BECTS patients with ADHD patients was significantly thinner than BECTS patients without ADHD. Our results showed that BECTS affects frontal, temporal, parietal and occipital lobes by cortical thinning. Our study supports the need for better characterization of patients with BECTS so identification of different phenotypes can occur. Further studies are needed to investigate the relationship between BECTS and ADHD.

Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common focal epilepsy in childhood. To date no hypothesis-free exome-wide mutational screen has been conducted for RE and atypical RE (ARE). Here we report on whole-exome sequencing of 194 unrelated patients with RE/ARE and 567 ethnically matched population controls. We identified an exome-wide significantly enriched burden for deleterious and loss-of-function variants only for the established RE/ARE gene GRIN2A. The statistical significance of the enrichment disappeared after removing ARE patients. For several disease-related gene-sets, an odds ratio >1 was detected for loss-of-function variants.

Identifying neural drivers of benign childhood epilepsy with centrotemporal spikes.

Epilepsy is a neurological disorder characterized by abnormal electrical discharges in a group of brain cells. Benign childhood epilepsy, which affect children under the age of 12 years, has been reported to contribute to the cognitive impairment of these children, even in the absence of structural abnormalities. Functional connectivity models have been applied to provide a deeper understanding of the processes that control and regulate interictal activity of benign childhood epilepsy. These studies have shown regions of increased connectivity and activity, particularly at the epileptic zone, which is usually the central region around the sensorimotor cortex, and in the immediate regions surrounding the zone and reduced activity in distant regions, such as the frontal lobe and temporal regions. The present study was designed to identify the neural drivers involved in the initiation and propagation of epileptic activity and the causal relationships between brain regions with increased and decreased connectivity and functional activity. We used three different models to identify neural drivers and casual connectivity with dynamic causal modelling (DCM) of EEG data. All models showed that the central region, the source of the epileptic activity, is the major driver of the brain network during interictal discharges. Other regions include the temporoparietal junction and temporal pole. The central region also had influence on the frontal and contralateral hemisphere, which might explain the cognitive deficits observed in these patients.

Combined spike-related functional MRI and multiple source analysis in the non-invasive spike localization of benign rolandic epilepsy.

OBJECTIVE: To localize the irritative zone in children by combined spike-related fMRI and EEG multiple source analysis (MSA) in children with benign rolandic epilepsy. METHODS: Interictal spikes were averaged and localized using MSA, and source locations were displayed in the anatomical 3D-MRI in 11 patients (5-12 yrs, median 10). Interictal spikes were additionally recorded during the fMRI acquisition (EEG-fMRI), and the fMRI sequences were correlated off-line with the EEG spikes. RESULTS: MSA revealed an initial central dipole in all patients, including the face or hand area. A second dipolar source was mostly consistent with propagated activity. BOLD activations from EEG-fMRI, consistent with the locations of the initial dipoles, were found in four patients. We found additional large areas of BOLD activations in 3 of these subjects extending into the sylvian fissure and the insula. These were identified as propagated activity by MSA using the short time differences in the source waveforms. CONCLUSIONS: MSA provided reliable localization of the spike onset zone in all children with benign rolandic epilepsy. Using the combination of EEG-fMRI and MSA we were able to discriminate the spike onset zone from propagated epileptiform source activity, using the spatial resolution of the EEG-fMRI technique and the temporal resolution of the MSA. However, the sensitivity of the EEG-fMRI technique was low and further improvements of the technique are warranted. SIGNIFICANCE: This study shows that a combination of EEG-fMRI and MSA may be a powerful tool to describe the irritative zone of patients with idiopathic focal epilepsies. Clinical studies in patients with non-idiopathic focal epilepsies may clarify whether both techniques can be used as complementary clinical tools to localize the onset of interictal epileptic activity in focal epilepsies.

Is Rolandic epilepsy associated with abnormal findings on cranial MRI?

Rolandic epilepsy (RE) is designated an idiopathic epilepsy syndrome, and hence no lesional abnormalities are expected on MRI exam. Recent reports suggest that MRI abnormalities are not only common, but may be specific for temporal lobe epilepsy, and lateralized to the side of EEG discharges. However, no controlled study has been performed to test the hypothesis of association between MRI abnormalities and Rolandic epilepsy. We performed an unmatched case-control study to test the hypothesis of association between MRI abnormalities and Rolandic epilepsy, using 25 typical RE cases and 25 children with migraine. Two independent examiners rated the MRIs for abnormalities. Examiners were blinded to the study hypothesis and identity of case and control exams. Fifty-two percent of RE exams contained at least one abnormality: peri/hippocampal abnormality (one case), non-localized congenital malformation (seven cases), subcortical parenchymal hyperintensities (two cases), periventricular parenchymal hyperintensities (one case), dilated perivascular spaces (six cases). There was no difference between the number or type of abnormalities in cases and controls. No type of abnormality lateralized to the hemisphere from which the EEG spikes emanated. The odds ratio of association between MRI abnormalities and RE was 0.87, 95% CI: 0.18-4.33 after adjusting for potential demographic and technical factors. We conclude that routine cranial MRI abnormalities are common in RE, but no more common than in controls, and not specific for RE.

Sub-cortical brain morphometry and its relationship with cognition in rolandic epilepsy.

PURPOSE: Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated with cognitive difficulties, which can affect children's quality of life. The underlying causes of these cognitive impairments are unclear. The objective of this prospective study is to investigate sub-cortical morphological alterations in RE children with left, right, or bilateral hemispheric focus and its association with cognition. METHODS: Participants include 41 children with rolandic epilepsy and 38 healthy controls (age 8-14 years), recruited from CHU Sainte-Justine Montreal Children Hospital (N=40) and Basel's Children Hospital (N=39). Quantitative volumetric assessment of putamen and caudate structures was performed on T1-weighted MR scans along with the morphological analysis to test for differences between patients and controls. These analyses were performed considering the side of epilepsy focus in all participants. Correlations were investigated between the sub-cortical morphometry and cognitive indices such as intelligence quotient (IQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI). RESULTS: Children with bilateral BECTS showed statistically significant volume reduction in right caudate (p<.05), while no statistically significant putamen volumetric changes were detected in BECTS participants compared to normal controls. According to a spectral-based groupwise shape analysis, regional alterations were found in both putamen and caudate structures of children with BECTS. In particular, children with left BECTS showed significant outward local deformity in left putamen and individuals with bilateral BECTS showed inward local group differences in both right putamen and right caudate. The correlation assessment showed positive association between the volume of the left caudate and cognitive indices in the group containing all BECTS participants. Negative correlation was found between putamen sub-regional shape alterations and cognition in individuals with right BECTS and in all BECTS participants. Negative associations between caudate sub-regional morphologies and cognitive indices were detected in left cohort. SIGNIFICANCE: We have confirmed putamen and caudate shape alterations in children with BECTS. However, our results further suggest that variations in sub-cortical shape affect cognitive functions. Importantly, we have demonstrated that shape alterations and their relation with cognition depend on the side of epilepsy focus. Our results point to different syndromic entities in the BECTS population.

Epileptic Discharge Related Functional Connectivity Within and Between Networks in Benign Epilepsy with Centrotemporal Spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome associated with abnormalities in neurocognitive domains, particularly during interictal epileptiform discharges (IEDs). Here, we investigated the effects of IEDs on brain's intrinsic connectivity networks in 43 BECTS patients and 28 matched healthy controls (HCs). Patients were further divided into IED and non-IED subgroups based on simultaneous EEG-fMRI recordings. Functional connectivity within and between five networks, corresponding to seizure origination and cognitive processes, were analyzed to measure IED effects. We found that patients exhibited increased connectivity within the auditory network (AN) and the somato-motor network (SMN), and decreased connectivity within the basal ganglia network and the dorsal attention network, suggesting that both transient and chronic seizure activity may disturb normal network organization. The IED group showed decreased functional connectivity within the default mode network (DMN) compared with the non-IED group and HCs, implying that the DMN was selectively impaired during epileptiform discharges associated with altered self-referential cognitive functions. Moreover, the IED group exhibited increased positive correlations between the AN and the SMN, which suggests a possible excessive influence of centrotemporal spiking on information processing in the auditory system. The association between epileptic activity and network dysfunctions highlights their importance in investigating the pathological mechanism underlying BECTS.