Auditory stimulation during sleep suppresses spike activity in benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy linked to diverse cognitive abnormalities. The electroencephalogram of patients shows focal interictal epileptic spikes, particularly during non-rapid eye movement (NonREM) sleep. Spike formation involves thalamocortical networks, which also contribute to the generation of sleep slow oscillations (SOs) and spindles. Motivated by evidence that SO-spindle activity can be controlled through closed-loop auditory stimulation, here, we show in seven patients that auditory stimulation also reduces spike rates in BECTS. Stimulation during NonREM sleep decreases spike rates, with most robust reductions when tones are presented 1.5 to 3.5 s after spikes. Stimulation further reduces the amplitude of spikes closely following tones. Sleep spindles are negatively correlated with spike rates, suggesting that tone-evoked spindle activity mediates the spike suppression. We hypothesize spindle-related refractoriness in thalamocortical circuits as a potential mechanism. Our results open an avenue for the non-pharmacological treatment of BECTS.

Measuring the effects of sleep on epileptogenicity with multifrequency entropy.

OBJECTIVE: We demonstrate that multifrequency entropy gives insight into the relationship between epileptogenicity and sleep, and forms the basis for an improved measure of medical assessment of sleep impairment in epilepsy patients. METHODS: Multifrequency entropy was computed from electroencephalography measurements taken from 31 children with Benign Epilepsy with Centrotemporal Spikes and 31 non-epileptic controls while awake and during sleep. Values were compared in the epileptic zone and away from the epileptic zone in various sleep stages. RESULTS: We find that (I) in lower frequencies, multifrequency entropy decreases during non-rapid eye movement sleep stages when compared with wakefulness in a general population of pediatric patients, (II) patients with Benign Epilepsy with Centrotemporal Spikes had lower multifrequency entropy across stages of sleep and wakefulness, and (III) the epileptic regions of the brain exhibit lower multifrequency entropy patterns than the rest of the brain in epilepsy patients. CONCLUSIONS: Our results show that multifrequency entropy decreases during sleep, particularly sleep stage 2, confirming, in a pediatric population, an association between sleep, lower multifrequency entropy, and increased likelihood of seizure. SIGNIFICANCE: We observed a correlation between lowered multifrequency entropy and increased epileptogenicity that lays preliminary groundwork for the detection of a digital biomarker for epileptogenicity.

The attention networks in benign epilepsy with centrotemporal spikes: A long-term follow-up study.

PURPOSE: To evaluate the long-term prognosis of attention deficit in children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS). METHODS: Attention network test (ANT) was performed over a period of 7 years on 42 patients who were newly diagnosed with BECTS, in the Department of Neurology of Anhui Provincial Children's Hospital. RESULTS: In the patients' group, the accuracy of ANT was lower (P = 0.000), the total response time was longer (P = 0.000), and the efficiency of orienting (P = 0.000) and alerting (P = 0.041) networks was lower than that of the control group. Accuracy was positively correlated with age of onset (b = 1.184) and negatively correlated with number of seizures (b = -1.321). After 7 years, there was no significant difference in the accuracy (P = 0.385); total response time (P = 0.661); and alerting (P = 0.797), orienting (P = 0.709), and executive control (P = 0.806) network efficiencies between the patients and controls. Accuracy was positively correlated with age of onset (b = 0.8583) and negatively correlated with number of seizures (b = -1.017) and duration of antiepileptic drugs therapy (b = -3.203). CONCLUSIONS: In our study, the newly diagnosed BECTS patients had impaired attention network, mainly in the alerting and orienting domains. Age of onset, number of seizures, and time of antiepileptic treatment may affect the attention networks. With the remission of BECTS, the attention network dysfunction was reversed.

Differential Clinical Features in Colombian Patients With Rolandic Epilepsy and Suggestion of Unlikely Association With GRIN2A, RBFOX1, or RBFOX3 Gene Variants.

PURPOSE: Our purpose was to describe the phenotypic features and test for association of genes GRIN2A, RBFOX1 and RBFOX3 with rolandic epilepsy in patients from Colombia. METHODS: Thirty patients were enrolled. A structured interview was applied. In addition, saliva samples were collected from the patients and their parents. One polymorphism in each of GRIN2A, RBFOX1 and RBFOX3 genes was tested. RESULTS: The average age at onset was 5.3 years. Almost half the sample presented prolonged seizures (>5 minutes); although the majority of the patients presented their seizures only while asleep, over a quarter presented them only while awake. The most frequent comorbidity was the presence of symptoms compatible with attention-deficit hyperactivity disorder (ADHD). Personal history of febrile seizures and parasomnias were equally frequent (20%). Family history of any type of epilepsy was reported in 80% of the patients, followed by migraine (73.3%) and poor academic performance (63.3%). About half the sample reported sleepwalking in parents or sibs. Most patients had received pharmacologic treatment. We found no association of rolandic epilepsy with the single nucleotide polymorphisms tested. CONCLUSIONS: Our rolandic epilepsy cohort presents clinical features clearly different from other cohorts. For instance, age at onset is much earlier in our set of patients, and personal and family history of febrile seizures as well as parasomnias are highly prevalent in our sample. No association of rolandic epilepsy with variants at the 3 genes tested was found. This lack of association may reflect the high genetic heterogeneity of the epilepsies.

Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes.

BACKGROUND: Most children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance. AIM: To develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors. METHODS: Data were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005-2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared. RESULTS: A subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras. CONCLUSION: Novel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.

Oral language in children with benign childhood epilepsy with centrotemporal spikes.

PURPOSE: Benign childhood epilepsy with centrotemporal spikes is one of the most common childhood disorders. Despite the benignity usually attributed to this epileptic syndrome, several studies have demonstrated that these children have cognitive disabilities. Among these disturbances, language disorders have been the less studied in depth. We aimed to obtain accurate information about the language skills of children with this epileptic syndrome and to explore the correlation between demographic and clinical factors associated with epilepsy and the language skills. METHODS: We assessed 30 children with this epileptic syndrome, followed in three hospitals in Lisbon, and 60 controls, aged between 6 and 12 years, attending the same schools and matched by age, gender, and parents' socioprofessional level. All the included children did not present cognitive impairment (reasoning ability, verbal memory), sensory, or motor limitations. The evaluation tests covered all language areas. RESULTS: Overall, children with this epileptic syndrome had lower skills in the majority of the language areas, when compared with their peers. These children showed greater difficulties in semantics and syntax domains. The atypical evolution of the seizures and a longer duration of epilepsy were the clinical variables that most influence the language skills of our samples. CONCLUSION: The early assessment of these capacities and the possible need for therapeutic intervention should be emphasized, in order to minimize the impact on their academic performance and quality of life.

The feasibility and value of extraoperative and adjuvant intraoperative stereoelectroencephalography in rolandic and perirolandic epilepsies.

OBJECTIVE: The objective of this study was to illustrate the feasibility and value of extra- and intraoperative stereoelectroencephalography (SEEG) in patients who underwent resection in rolandic and perirolandic regions. METHODS: The authors retrospectively reviewed all consecutive patients with at least 1 year of postoperative follow-up who underwent extra- and intraoperative SEEG monitoring between January 2015 and January 2017. RESULTS: Four patients with pharmacoresistant rolandic and perirolandic focal epilepsy were identified, who underwent conventional extraoperative invasive SEEG evaluations followed by adjuvant intraoperative SEEG recordings. Conventional extraoperative SEEG evaluations demonstrated ictal and interictal epileptiform activities involving eloquent rolandic and perirolandic cortical areas in all patients. Following extraoperative monitoring, patients underwent preplanned staged resections guided by simultaneous and continuous adjuvant intraoperative SEEG monitoring. Resections, guided by electrode contacts of interest in 3D boundaries, were performed while continuous real-time electrographic data from SEEG recordings were obtained. Staged approaches of resections were performed until there was intraoperative resolution of synchronous rolandic/perirolandic cortex epileptic activities. All patients in the cohort achieved complete seizure freedom (Engel class IA) during the follow-up period ranging from 18 to 50 months. Resection resulted in minimal neurological deficit; 3 patients experienced transient, distal plantar flexion weakness (mild foot drop). CONCLUSIONS: The seizure and functional outcome results of this highly preselected group of patients testifies to the feasibility and demonstrates the value of the combined benefits of both intra- and extraoperative SEEG recordings when resecting the rolandic and perirolandic areas. The novel hybrid method allows a more refined and precise identification of the epileptogenic zone. Consequently, tailored resections can be performed to minimize morbidity as well as to achieve adequate seizure control.

Persistent abnormalities in Rolandic thalamocortical white matter circuits in childhood epilepsy with centrotemporal spikes.

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) is a common, focal, transient, developmental epilepsy syndrome characterized by unilateral or bilateral, independent epileptiform spikes in the Rolandic regions of unknown etiology. Given that CECTS presents during a period of dramatic white matter maturation and thatspikes in CECTS are activated during non-rapid eye movement (REM) sleep, we hypothesized that children with CECTS would have aberrant development of white matter connectivity between the thalamus and the Rolandic cortex. We further tested whether Rolandic thalamocortical structural connectivity correlates with spike rate during non-REM sleep. METHODS: Twenty-three children with CECTS (age = 8-15 years) and 19 controls (age = 7-15 years) underwent 3-T structural and diffusion-weighted magnetic resonance imaging and 72-electrode electroencephalographic recordings. Thalamocortical structural connectivity to Rolandic and non-Rolandic cortices was quantified using probabilistic tractography. Developmental changes in connectivity were compared between groups using bootstrap analyses. Longitudinal analysis was performed in four subjects with 1-year follow-up data. Spike rate was quantified during non-REM sleep using manual and automated techniques and compared to Rolandic connectivity using regression analyses. RESULTS: Children with CECTS had aberrant development of thalamocortical connectivity to the Rolandic cortex compared to controls (P = .01), where the expected increase in connectivity with age was not observed in CECTS. There was no difference in the development of thalamocortical connectivity to non-Rolandic regions between CECTS subjects and controls (P = .19). Subjects with CECTS observed longitudinally had reductions in thalamocortical connectivity to the Rolandic cortex over time. No definite relationship was found between Rolandic connectivity and non-REM spike rate (P > .05). SIGNIFICANCE: These data provide evidence that abnormal maturation of thalamocortical white matter circuits to the Rolandic cortex is a feature of CECTS. Our data further suggest that the abnormalities in these tracts do not recover, but are increasingly dysmature over time, implicating a permanent but potentially compensatory process contributing to disease resolution.

Cortical and subcortical volume differences between Benign Epilepsy with Centrotemporal Spikes and Childhood Absence Epilepsy.

OBJECTIVE: Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) and Childhood Absence Epilepsy (CAE) are the most common childhood epilepsy syndromes and they share a similar age-dependence. However, the two syndromes clearly differ in seizures and EEG patterns. The aim of this study is to investigate whether children of the same age with BECTS, CAE and typically-developing children have significant differences in grey matter volume that may underlie the different profiles of these syndromes. METHODS: Twenty one patients with newly-diagnosed BECTS and 18 newly diagnosed and drug naïve CAE were included and compared to 31 typically-developing children. Voxel-based morphometry was utilized to investigate grey matter volume differences among BECTS, CAE, and controls. We also examined the effect of age on grey matter volume in all three groups. In addition to the whole brain analysis, we chose regions of interest analysis based on previous literature suggesting the involvement of these regions in BECTS or CAE. The group differences of grey matter volume was tested with 2-sample t-test for between two groups' comparisons and ANOVA for three group comparisons. RESULTS: In the whole brain group comparisons, the grey matter volume in CAE was significantly decreased in the areas of right inferior frontal and anterior temporal compared to BECTS and controls (F2,67 = 27.53, p < 0.001). In the control group, grey matter volume in bifrontal lobes showed a negative correlation with age (r=-0.54, p < 0.05), whereas no correlation was found in either CAE or BECTS. With ROI analyses, the grey matter volume of posterior thalami was increased in CAE compared to other 2 groups (p < 0.05). SIGNIFICANCE: This study shows that there are grey matter volume differences between CAE and BECTS. Our findings of grey matter volume differences may suggest that there may be localized, specific differences in brain structure between these two types of epilepsy.

Clinical and electroencephalographic features of benign childhood epilepsy with centrotemporal spikes comorbidity with attention-deficit hyperactivity disorder in Southwest China.

PURPOSE: This study was conducted to analyze the clinical and electroencephalographic (EEG) features of attention-deficit hyperactivity disorder (ADHD) in children with benign partial epilepsy with centrotemporal spikes (BECTS) in Southwest China, to address the question of what the risk factors are for patients with BECTS who suffer from ADHD. METHODS: Overall 118 right-handed children with BECTS were included from two medical centers. Of them, 29 patients were with diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) at baseline, and the remaining were considered as typical BECTS. Clinical and EEG characteristics were collected at baseline and follow-up endpoint of one year. All the patients completed an eight-hour video-electroencephalogram (VEEG) without sedation at those two time points using a digital system with international 10-20 array electrode placement. At the follow-up endpoint, we also evaluated the intelligence level of all patients using the Wechsler Intelligence Scale for Children-IV (WISC-IV). Multivariate logistical regression model was performed to assess the risk factors of ADHD in BECTS patients. RESULTS: Compared with typical BECTS, patients with BECTS-ADHD had an earlier age of onset, a longer disease course and tended to have lower intelligence quotient (IQ) scores. Their epileptiform discharges were more likely to diffuse to one or both hemispheres, and a higher percentage of patients with BECTS-ADHD patients needed multitherapy to control seizures. Multivariate analysis showed that age of onset, disease course, intelligence score, number of antiepileptic drugs (AEDs), and bilateral or diffusing discharges were independently associated with the occurrence of ADHD in patients with BECTS (p < .05). Additionally, we found that delayed diagnosis (37.3%) and nonadherence to treatment (16.1%) were the main reasons of a long disease course. CONCLUSION: Benign partial epilepsy with centrotemporal spikes with ADHD has the characteristics of early age of onset, long course of disease and low intelligence score. In addition, the epileptiform discharges of BECTS-ADHD were prone to be bilateral or diffuse, and polypharmacological treatment is also common in this group.

Resting state signal latency assesses the propagation of intrinsic activations and estimates anti-epileptic effect of levetiracetam in Rolandic epilepsy.

PURPOSE: We assessed the potential of resting-state fMRI lag analysis (RSLA) in detecting epileptic activation and in estimating anti-epileptic effects of Levetiracetam (LEV) in Rolandic epilepsy. METHODS: Forty-three children with Rolandic epilepsy underwent simultaneous EEG-fMRI. They were grouped into LEV vs drug-naïve groups according to their medication, and into patients who showed or did not show central-temporal spike (CTS) discharges during scans. We calculated the lag structure of rs-fMRI for all patients and assessed interactions with drug (LEV vs. drug-naïve) and CTS status (CTS vs. no-CTS). We furthermore assessed correlations between lag values and number of CTS and medication conditions. RESULTS: RSLA analysis indicated earlier intrinsic activations in bilateral Rolandic areas when CTS occurred. More frequent epileptic discharges were correlated with earlier intrinsic activations (r=-0.46, p = 0.03 left Rolandic). Patients with LEV therapy, on the other hand, displayed delayed intrinsic activity in Rolandic areas compared to drug-naïve patients CONCLUSION: Our RSLA analysis indicated an association between centro-temporal spikes and earlier hemodynamic activations in epileptogenic regions in Rolandic epilepsy, which were counteracted by LEV treatment. As it allows for the mapping of propagation features of intrinsic activity and drug-effects, our findings suggest potential of lag based analyses in detecting focus localization and estimating treatment effects.

Benign epilepsy with centrotemporal spikes: Is there a thalamocortical network dysfunction present?

INTRODUCTION: Benign epilepsy of childhood with centrotemporal spikes (BECTS) is one of the most frequently seen epileptic syndromes in childhood. It is characterized by centrotemporal spikes (CTS) on electroencephalography (EEG) that are typically activated by drowsiness and stage N2 sleep. The location, frequency, and amplitude of the spikes may vary in different EEG records of the same patient, supporting the presence of a global pathology rather than a focal one. Despite the well-known relation between BECTS and stage N2 sleep, the results of sleep studies have been diverse and have mainly focused on sleep cycles. The characteristics of sleep spindles in the interictal periods have not been studied well. METHODS: A retrospective study involving patients with BECTS who were admitted to the Gazi University, Faculty of Medicine, Department of Pediatric Neurology from January 2017 to October 2018 was conducted herein. Patients with BECTS and age-matched controls who had stage N2 sleep records of 10 min were enrolled for spindle amplitude (peak-to-peak difference in spindle voltage), frequency (number of waveforms per second), and duration and density (number of spindle bursts/minute of stage N2 sleep). RESULTS: A total of 30 children with BECTS and 20 age-matched healthy peers were enrolled in the study. There were no significant differences between the age and sex of the patients. Statistically significant lower mean values of the amplitude, and duration and density of the spindle activity were observed in patients with BECTS when compared to the controls (P: 0.034, P: 0.016, and 0.020, respectively). Additionally, the risk of epilepsy was found to increase by 1.9 %, by the decrease of the mean amplitude of the spindles by 1 mV when compared to control group. CONCLUSION: The interictal records of stage N2 sleep differed in the patients with BECTS when compared to the controls. Findings related to the stage N2 sleep of the present study may suggest a network problem involving the thalamus and thalamocortical pathways in patients with BECTS.

Social cognition in childhood epilepsy with centrotemporal spikes.

PURPOSE: Social cognition is involved in the perception, processing, and interpretation of social information. For this reason, social cognition is a crucial domain for successful communication and interpersonal relationships. With this in mind, we aimed to assess social cognition in children with Self-Limited Childhood Epilepsy with Centrotemporal Spikes (CECTS) and its association with traditional executive function tests and clinical variables of epilepsy. METHODS: We evaluated 23 patients with CECTS (65% male, mean age of 10.64 years) and 20 healthy children (75% male, mean age of 10.15 years). We used the Faux-Pas Child Task (FP) to analyze social cognition and a comprehensive battery of neuropsychological tests to evaluate domains of classic executive functions. RESULTS: Patients with CECTS had impairments in FP compared to healthy children [p < 0.001]. Impairments in some areas of traditional executive functions were related to worse social cognition in patients with CECTS. Epilepsy-related factors did not impair the performance on FP, except for the number of antiseizure medication [p = 0.016]. CONCLUSIONS: Social cognition is impaired in children and adolescents with CECTS. The presence of ongoing seizures and frequent epileptiform activity were not correlated with social cognition. Therefore, epilepsy per se was more relevant for social cognition than its severity.

Electrical status epilepticus in sleep affects intrinsically connected networks in patients with benign childhood epilepsy with centrotemporal spikes.

BACKGROUND: Although outcomes of benign childhood epilepsy with centrotemporal spikes (BECTS) are frequently excellent, some atypical forms of BECTS, especially electrical status epilepticus in sleep (ESES), are characterized by worse outcomes and negative impacts on cognitive development. METHODS: To explore specific ESES-related brain networks in patients with BECTS, we used resting-state functional magnetic resonance imaging (fMRI) to scan patients with BECTS with ESES (n = 9), patients with BECTS without ESES (n = 17), and healthy controls (n = 36). Unbiased seed-based whole-brain functional connectivity (FC) was adopted to explore the connectivity mode of three resting-state cerebral networks: the default mode network (DMN), salience network (SN), and central executive network (CEN). RESULTS: Compared with the other two groups, patients with BECTS with ESES showed FC in the SN or in the CEN decreased, but not in the DMN. Moreover, we found the FC in the CEN in patients with BECTS without ESES decreased when compared with controls. Our currently intrinsically defined anticorrelated networks strength was disrupted in BECTS and connote greater deactivation than the results from FC for a seed region in children with BECTS. CONCLUSION: These results indicated that children with BECTS with ESES showed brain activity altered in the CEN and the SN. The difference of impairment in the SN and CEN may lead to improve the understanding of the underlying neuropathophysiology, and to assess the activity of patients with BECTS with ESES, which is crucial for measuring disease activity, improving patient care, and assessing the effect of antiepilepsy therapy.

Cortical Excitability, Synaptic Plasticity, and Cognition in Benign Epilepsy With Centrotemporal Spikes: A Pilot TMS-EMG-EEG Study.

PURPOSE: Children with benign epilepsy with centrotemporal spikes have rare seizures emerging from the motor cortex, which they outgrow in adolescence, and additionally may have language deficits of unclear etiology. We piloted the use of transcranial magnetic stimulation paired with EMG and EEG (TMS-EMG, TMS-EEG) to test the hypotheses that net cortical excitability decreases with age and that use-dependent plasticity predicts learning. METHODS: We assessed language and motor learning in 14 right-handed children with benign epilepsy with centrotemporal spikes. We quantified two TMS metrics of left motor cortex excitability: the resting motor threshold (measure of neuronal membrane excitability) and amplitude of the N100-evoked potential (an EEG measure of GABAergic tone). To test plasticity, we applied 1 Hz repetitive TMS to the motor cortex to induce long-term depression-like changes in EMG- and EEG-evoked potentials. RESULTS: Children with benign epilepsy with centrotemporal spikes tolerate TMS; no seizures were provoked. Resting motor threshold decreases with age but is elevated above maximal stimulator output for half the group. N100 amplitude decreases with age after controlling for resting motor threshold. Motor cortex plasticity correlates significantly with language learning and at a trend level with motor learning. CONCLUSIONS: Transcranial magnetic stimulation is safe and feasible for children with benign epilepsy with centrotemporal spikes, and TMS-EEG provides more reliable outcome measures than TMS-EMG in this group because many children have unmeasurably high resting motor thresholds. Net cortical excitability decreases with age, and motor cortex plasticity predicts not only motor learning but also language learning, suggesting a mechanism by which motor cortex seizures may interact with language development.

Electroencephalographic abnormalities are correlated with cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes: A clinical study of 61 cases.

OBJECTIVE: The objective of this study was to explore the effect of spikes on cognition in patients with benign childhood epilepsy with centrotemporal spikes (BECTS) and to identify electroencephalography (EEG) markers enabling early detection of cognitive impairment. METHODS: Sixty-one children with BECTS diagnoses and 60 age- and education-matched healthy controls were enrolled. Four-hour EEG recordings were analyzed for each patient to check for interictal spikes, high-frequency oscillations (HFOs), nondipole spikes, and other atypical EEG features and to examine the spike-wave index of nonrapid eye movement (NREM) sleep. All 121 children underwent a series of neuropsychological tests to assess cognitive function. RESULTS: Patients with a high NREM sleep discharge index (≥55%) in the first sleep cycle exhibited significantly lower scores for arithmetic calculation, executive function, and attention and memory tests than patients with a low discharge index (<55%). Eight patients with HFOs exhibited even poorer performance than HFO-negative patients for arithmetic calculation, executive function, vocabulary comprehension, visual perception, vocal perception, spatial memory ability, and response ability. Children with bilateral discharge exhibited poorer ability in three-dimensional spatial imaging test, poorer memory, and slower response than did those with unilateral discharge (P < .05). Nondipole spikes, multiple asynchronous discharges, and generalized spike-wave discharges respectively had an impact on calculation ability, memory, and reaction ability respectively (P < .05). CONCLUSIONS: Spike frequencies in stage 3 and 4 sleep varied from those observed in stage 1 and 2 sleep; the highest spike frequency was in stage 2 sleep. High NREM sleep discharge index (i.e., ≥55%) and HFOs were linked to the highest risk for cognitive deficit, while bilateral discharges, nondipole spikes, multiple asynchronous discharges, and generalized spike-wave discharges were less indicative of cognitive impairment.

The natural history of seizures and neuropsychiatric symptoms in childhood epilepsy with centrotemporal spikes (CECTS).

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) (formally benign epilepsy with centrotemporal spikes, BECTS) is a common childhood epilepsy syndrome characterized by psychiatric, behavioral, and cognitive abnormalities and self-limited seizures. Although CECTS is one of the most well-characterized electroclinical epilepsy syndromes, the natural history of neuropsychiatric outcomes is poorly understood. We report the psychiatric, behavioral, and cognitive profiles over the course of disease from a large, prospectively-enrolled, longitudinal cohort of children with CECTS. We further characterize the detailed seizure course and test the relationship between several proposed risk factors and neuropsychiatric and seizure outcomes in these children. METHODS: Patients diagnosed with CECTS were enrolled as part of a community-based study and followed from diagnosis through disease resolution (16.0 ±â€¯3.1 years, N = 60). Twenty sibling controls were also recruited. We report the natural history of premorbid neuropsychiatric concerns, postmorbid neuropsychiatric diagnoses, long-term neuropsychological performance, seizure course, antiseizure medication (ASM) treatment response, and the relationship between duration seizure-free and remission. Age at onset and premorbid neuropsychiatric concerns were tested as predictors of seizure count, epilepsy duration, postmorbid neuropsychiatric diagnoses, and long-term neuropsychological performance. Antiseizure medication treatment duration, seizure count, and epilepsy duration were tested as predictors of postmorbid neuropsychiatric diagnoses and long-term neuropsychological performance. RESULTS: Children with CECTS had a high incidence of ADD/ADHD symptoms (18.3%) or learning difficulties (21.7%) before diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after CECTS diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls. More than two-thirds of treated children experienced at least one seizure during treatment. Most children (61.7%) had entered terminal resolution after 12 months seizure-free. Among all children, for each month seizure-free, there was a 6-7% increase in the probability of achieving terminal remission (p < 1e-10). The presence of a premorbid neurodevelopmental concern predicted a longer epilepsy duration (p = 0.02), higher seizure count (p = 0.02), and a postmorbid psychiatric or neurodevelopmental diagnosis (p = 0.002). None of the tested features predicted long-term neuropsychological performance. SIGNIFICANCE: Children are at high risk of neuropsychiatric symptoms along the course of the disease in CECTS, however, long-term cognitive performance is favorable. The majority of children had a seizure while being treated with ASMs, suggesting that CECTS is not as pharmacoresponsive as assumed or that treatment approaches are not optimized. Among treated and untreated children, future seizure-risk can be estimated from duration seizure-free. The presence of a premorbid neuropsychiatric concern predicted a more severe disease course in CECTS.

Change of centrotemporal spikes from onset to remission in self-limited epilepsy with centrotemporal spikes (SLECTS).

OBJECTIVE: To reveal the changes of centrotemporal spikes that occur during the disease course of self-limited epilepsy with centrotemporal spikes (SLECTS). METHOD: We retrospectively reviewed the serial EEGs of 63 patients with SLECTS from initial diagnosis to remission. There were 32 patients who did not undergo treatment and 31 patients who underwent treatment with oxcarbazepine (OXC). The change of occurrence or abundance, voltage, and location of centrotemporal spikes of serial EEGs were analyzed and compared between the two groups. Clinical seizure evidenced and reported was counted. The time gap between seizure remission and EEG remission was measured in the two groups. RESULT: Changes of occurrence or abundance of the centrotemporal spikes were either abrupt (sudden disappearance of the frequent spikes on following EEG) or gradual (decline in number over 2 or more serial EEGs). Pattern of spike disappearance was not significantly different between the medication naïve group and OXC treated group. The spike voltage or the location of centrotemporal spikes did not change during the disease course in most cases. Delay between seizure remission and EEG normalization was 3.34 ± 1.75 (mean ± standard deviation, range: 0.77-7.97) years in untreated patients and 3.03 ± 1.41 (0.95-6.61) years in OXC-treated group. CONCLUSION: Pattern of spike disappearance in SLECTS was either abrupt or gradual. Treatment with OXC had no effect in the disappearance pattern. Precise data regarding the pattern of disappearance and delay between seizure remission and EEG normalization can help to understand the evolution of spike in SLECTS and to predict the timing of normalization of EEG after seizure remission.

Impact of epilepsy on language and discourse: Two self-limited focal epileptic syndromes of childhood.

Self-limited focal epilepsy with centro-temporal spikes, also known as Rolandic epilepsy (RE), is a well-established focal epilepsy of childhood, characterized with language impairment. To investigate the relationship between language deficits and clinical parameters of self-limited focal epilepsies of childhood (SFEC), 21 patients with RE, 10 patients with childhood occipital epilepsy of Gastaut type (COE-G) (another SFEC that is not typically associated with language impairment), and 31 healthy controls were recruited. A broad panel of language tests also including narration sample was administered, and clinical features were documented. The language was significantly impaired in both RE and COE-G. Patients with COE-G showed worse scores than patients with RE in subtests measuring semantic functions. Clinical parameters were not associated with impaired language domains. Language impairment is experienced in different types of SFEC, emphasizing the broad representation of the language network. In SFEC, recent activity of epilepsy does not affect the severity of language dysfunction.

Benign Rolandic epilepsy: widespread increases in connectivity in a focal epilepsy syndrome.

Benign Rolandic epilepsy (benign epilepsy with centrotemporal spikes; recently renamed self-limited epilepsy with centrotemporal spikes) is associated with widespread deficits in cognition and behavior, suggesting abnormalities in networks that extend beyond the centrotemporal region. To assess functional connectivity in children with benign Rolandic epilepsy, we assessed EEG spectral power and coherence during awake and sleep records in 27 children with centrotemporal spikes. Coherence represents the consistency of the phase difference between two EEG signals when compared over time and serves as a measure of synchronization between two EEG signals based mainly on phase consistency. Epochs of EEG with and without centrotemporal spikes were compared during both waking and sleep. During the spike epochs, there was an increase in spectral power at all frequencies, although statistical significance was seen primarily in the delta, theta and alpha bandwidths. This increase in absolute power was seen at all electrode sites and was similar in left and right-sided electrodes. During centrotemporal spikes, there were significant changes in coherence compared to the EEG segments without spikes. In the theta, alpha and beta bandwidths, there were significant increases in coherence. The increases in coherences were widespread and bilateral, and involved electrode pairs outside the central and temporal regions. To determine if there was a relationship between location of the spikes and coherence values, right-sided, left-sided and bilateral centrotemporal spikes were compared. There was no relationship between location of the centrotemporal spikes and power or coherence values. These findings indicate that benign Rolandic epilepsy results in generalized changes in spectral power and connectivity and raises the suggestion that from a functional standpoint, benign Rolandic epilepsy resembles a generalized rather than focal seizure disorder.