Cognitive impairment in children with benign childhood epilepsy with centrotemporal spikes (BECT) has complex etiologies and is closely associated abnormal neural networks. Multimodal magnetic resonance imaging of brain structure and function is a powerful tool for studying abnormal neural networks of cognitive impairment in epilepsy and can explore the pathogenesis of cognitive impairment in epilepsy at the level of brain structure and function by analyzing the imaging features of brain structure and function. This article reviews the research advances in multimodal magnetic resonance for cognitive impairment in children with BECT.
Brain ; Child ; Cognitive Dysfunction ; complications ; Epilepsy, Rolandic ; complications ; Humans ; Magnetic Resonance Spectroscopy

BACKGROUND AND PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS) is one of the most common pediatric epilepsies, and it generally has a good prognosis. However, recent research has indicated that the epileptic activity of BECTS can cause cognitive defects such as language, visuospatial, and auditory verbal memory deficits. This study assessed language-delivery deficits in BECTS patients using diffusion-tensor magnetic resonance imaging (DTI). METHODS: T1-weighted MRI, DTI, and language tests were conducted in 16 BECTS patients and 16 age-matched controls. DTI data were analyzed using the TRActs Constrained by Underlying Anatomy tool in FreeSurfer 5.3, and 18 major white-matter tracts were extracted, which included 4 language-related tracts: the inferior longitudinal fasciculus, superior longitudinal fasciculus-parietal terminations, superior longitudinal fasciculus-temporal terminations, and uncinate fasciculus (UNC). Language tests included the Korean version of the Receptive and Expressive Vocabulary Test, Test of Problem-Solving Abilities (TOPS), and the mean length of utterance in words. RESULTS: The BECTS group exhibited decreased mean fractional anisotropy and increased mean radial diffusivity, with significant differences in both the superior longitudinal fasciculus and the left UNC (p<0.05), which are the language-related white-matter tracts in the dual-loop model. The TOPS language test scores were significantly lower in the BECTS group than in the control group (p<0.05). CONCLUSIONS: It appears that BECTS patients can exhibit language deficits. Seizure activities of BECTS could alter DTI scalar values in the language-related white-matter tracts.
Anisotropy ; Child ; Cognition Disorders ; Epilepsy ; Epilepsy, Rolandic ; Humans ; Language Tests ; Magnetic Resonance Imaging ; Memory Disorders ; Prognosis ; Retrospective Studies ; Seizures

BACKGROUND AND PURPOSE: This study is to assess the responsiveness of electroencephalography (EEG) abnormalities and their effects on language ability after initiating different types of antiepileptic therapy in children with newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS). METHODS: The records of patients newly diagnosed with BECTS (n=120; 69 males) were reviewed retrospectively. The patients were randomly treated with lamotrigine, oxcarbazepine, or topiramate monotherapy, and underwent at least two EEG and standardized language tests. Effects were compared using Pearson’s chi-square tests and paired t-tests. RESULTS: The recurrence rates for seizures in the lamotrigine, topiramate, and oxcarbazepine groups were 19.4%, 21.7%, and 11.4%, respectively, while complete or partial recovery (as indicated by EEG) occurred in 32%, 39%, and 16% of the patients. Patients in the lamotrigine group showed significant improvements in all parameters assessed by the Test of Language Problem Solving Abilities, except for ‘determining cause.’ Patients in the oxcarbazepine group also showed improvements, except for ‘making inferences’ (p < 0.05). Most linguistic index scores were worse in the topiramate group except for Mean Length of Utterance in Words. Patients in the lamotrigine and oxcarbazepine groups showed significant improvements in the receptive language test (p < 0.05). EEG improvements were not related to language ability. CONCLUSIONS: The improvements in language and problem-solving performance in children with BECTS were greater for lamotrigine and oxcarbazepine than for topiramate. However, EEG remission did not imply that language function would be improved after the treatments.
Anticonvulsants* ; Child ; Electroencephalography ; Epilepsy ; Epilepsy, Rolandic* ; Humans ; Language Tests ; Language* ; Linguistics ; Problem Solving ; Recurrence ; Retrospective Studies ; Seizures

N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2A mutation (c.1341T>A, p.N447K) from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizure-free with a combination of valproate and lamotrigine. Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293T cells revealed that the N447K mutation increased the NMDAR current density by ~1.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg inhibition. These results indicated that N447K is a gain-of-function mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue (N447A and N447E) did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447K as a novel mutation associated with epilepsy and validated its functional consequences in vitro. Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.
Adolescent ; Epilepsy, Rolandic ; genetics ; Humans ; Male ; Mutation ; Receptors, N-Methyl-D-Aspartate ; genetics

PURPOSE: Benign childhood epilepsy with centrotemporal spikes (BECTS) is one of the most common and benign focal epilepsy syndromes during childhood. In this study, we analyzed the clinical features and electroencephalogram (EEG) of BECT patients to determine if there were any predictive factors for seizures or abnormal EEG findings lasting longer than the average. METHODS: We studied 49 patients who were diagnosed with BECTS at the Department of Pediatrics, Chonnam National University Hospital and were 18 years of age or older at the time of the study. Differences in clinical course according to EEG features, treatment duration, abnormal EEG duration, seizure development period, and time to achieving the first normal EEG were analyzed. RESULTS: Average onset age was 8.3±1.9 years and follow-up duration was 4.2±2.4 years. The average seizure-free age was 9.5±2.0 years, and abnormal EEG-free age was 11.6±2.1 years. Younger-onset patients had a longer duration of medication (P=0.04). Patients who needed shorter time to achieving the first normal EEG had a shorter seizure development period (P=0.02). Patients who did not show typical EEG findings consistent with BECTS had a significantly longer duration of medication (P<0.01) and seizure development period (P=0.02), and abnormal EEG duration (P= 0.01). The ratio of abnormal findings in the first three EEGs was significantly correlated with the seizure development period, abnormal EEG duration, and duration of medication (P<0.01). CONCLUSION: Although BECTS is known to take a benign course, the actual clinical course varied from patient to patient, and these variations may be predicted by analyzing clinical factors or EEGs.
Age of Onset ; Child* ; Electroencephalography ; Epilepsies, Partial ; Epilepsy* ; Epilepsy, Rolandic ; Follow-Up Studies ; Humans ; Jeollanam-do ; Pediatrics ; Seizures

Child, Preschool ; Electroencephalography ; Epilepsy, Rolandic ; physiopathology ; Female ; Humans ; Male ; Syndrome

OBJECTIVEBenign epilepsy with centro-temporal spikes (BECTs) is a common idiopathic partial epileptic syndrome in childhood, which often affect the pre-school and school-age children and a considerable proportion have comorbidity including lower academic achievement and cognitive impairment. Few studies involved the psychocognitive assessment in such a drug-treatable epileptic syndrome especially in the newly diagnosed and medications-naive group. This study aimed to investigate the cognitive characteristics of children with newly onset BECTs before treatment.

METHODForty-one outpatients with newly diagnosed BECTs who visited the Clinic during the periods from October 2012 to May 2014 before the medications against epilepsy and 41 healthy controls recruited from regular school in Beijing during the period from July 2013 to March 2014, who matched in age and gender underwent battery testing by computerized cognitive testing in epilepsy (CCTE). The BECTs group included 41 children, 20 boys and 21 girls, mean age (8.2 ± 1.7) years, the age of onset of epilepsy 4.5-11.5 years (the age of onset <8 years in 25 cases, ≥ 8 years in 16 cases). The cognitive characteristics and associated factors were analyzed. The primary data including correct answer numbers and reaction times were analyzed by independent sample t-test between the two groups of children with BECTs and healthy controls based on SPSS 18.0 statistical software.

RESULTRaw data of 9 tasks' scores collected from BECTs and healthy control children were continuous variables in accordance with normal distribution. BECTs children performed significantly worse than controls in choice reaction time ((618+158) vs. (524+254) ms), three-dimensional mental rotation (11 ± 10 vs. 18 ± 12) and visual tracing (10 ± 6 vs.15 ± 6), t=2.01, 3.03 and 3.47, P<0.05, <0.01 and <0.001, respectively.While other 6 tasks showed no significant difference between the two groups (P>0.05 for all comparisons). BECTs boys performed significantly worse than girls on simple substraction tasks compared with standard nine score ((4.7 ± 1.5) vs. (5.6 ± 1.2), t=-2.24, P<0.05). Other 8 tasks showed no significant difference between boys and girls (P>0.05 for all comparisons). Other 9 tasks showed no significant differences between the two groups of BECTs children whose age of onset was before 8 years and those who started seizure ≥ 8 years (P all >0.05). The standard nine scores of simple substraction from the three BECTs groups of dominance sides of spikes and waves during NREM showed significant difference (P<0.05). BECTs children with bilateral discharges performed significantly worse than the other two groups dominantly right or left discharges (4.7 ± 1.2 vs. 6.0 ± 1.2 vs. 4.9 ± 1.4, P all <0.05). There was no significant difference between the two groups with right and left side dominance discharges (P>0.05). Other 8 tasks showed no significant differences among the three groups (P>0.05 for all comparisons).

CONCLUSIONAlthough EEG discharges index below 50% during NREM period, while newly diagnosed BECTs children before treatment with medications against epilepsy performed poorer on tasks of choice reaction time, three-dimensional mental rotation, and visual tracing. The two factors of male and bilateral discharges during NREM period correlate with dysfunction of simple subtraction, the mechanism needs further study and the cognitive function of epilepsy children should be evaluated and followed up, in order to provide psychologic baseline data for persistent cognitive disturbance.

Beijing ; Case-Control Studies ; Child ; Child, Preschool ; Cognition ; Cognition Disorders ; diagnosis ; Comorbidity ; Epilepsy, Rolandic ; physiopathology ; Female ; Humans ; Male ; Reaction Time ; Seizures ; physiopathology

OBJECTIVETo study the efficacy of levetiracetam (LEV) combined with short-term clonazepam (CZP) in the treatment of electrical status epilepticus during sleep (ESES) in children with benign childhood epilepsy with centrotemporal spikes (BECCT).

METHODSFifteen children (9 boys and 6 girls) diagnosed with BECCT with ESES, who had continuous spike-and-wave accounting for over 85% of the non-rapid eye movement sleep as monitored by 24-hours ambulatory EEG or 3-hours video EEG, were enrolled. The clinical manifestations and EEG characteristics of patients were retrospectively analyzed. These children received two months of CZP treatment in addition to oral LEV [20-40 mg/(kg·d)]. All patients were followed up for 6-18 months.

RESULTSThe 15 children were orally given LEV in the early stage, but showed no improvement when reexamined by EEG or had seizures during treatment. Then, they received LEV in combination with short-term CZP. Re-examinations at 1 and 6 months after treatment showed that 14 cases had significantly reduced discharge (only little discharge in the Rolandic area) or no discharge, as well as completely controlled seizure; one case had recurrent ESES and two epileptic seizures during follow-up. The recurrent case received the combination therapy again, and re-examinations 1 and 6 months later revealed normal EEG; no seizure occurred in the 8 months of follow-up.

CONCLUSIONSLEV combined with short-term CZP is effective and has few side effects in treating ESES syndrome among children with BECCT.

Anticonvulsants ; administration & dosage ; Child ; Child, Preschool ; Clonazepam ; administration & dosage ; Drug Therapy, Combination ; Electroencephalography ; Epilepsy, Rolandic ; drug therapy ; physiopathology ; Female ; Humans ; Male ; Piracetam ; administration & dosage ; analogs & derivatives ; Retrospective Studies ; Sleep ; physiology ; Status Epilepticus ; drug therapy ; physiopathology

PURPOSE: Benign childhood epilepsy with centrotemporal spikes (BECTS) is known to have a good prognosis, and is easily controlled with antiepileptic drugs. In this study, we evaluate the efficacy of low-dose topiramate (TPM), once at night time in children with BECTS, and compare with that of oxcarbazepine (OXC). METHODS: OXC was used as a first drug in 58 patients with BECTS at the department of pediatrics, Chonnam National University hospital from Jan. 2003 to Nov. 2010. Their medical records were reviewed, focusing on the onset age of seizure, the dosage of drugs, response to treatment and other clinical features. Since Aug. 2008 through Apr. 2011, some newly diagnosed patients with BECTS were given a low-dose (25mg) of TPM, once at nighttime. The efficacy was reviewed in 14 children, who had been followed up in the outpatient clinic for longer than twelve months. RESULTS: Forty five out of 58 (77.6%) patients were well controlled with OXC. Thirteen out of 58 (22.4%), seizures recurred, on whom TPM (n=9) or lamotrigine (n=4) was added. Nine (64.3%) of the 14 patients who were started with low dose TPM became seizure-free for at least 12 months. However, Two out of 14, the dose of TPM had to be increased up to 100 mg/day and 75 mg/day, respectively. In three, seizure was controlled with OXC. CONCLUSION: A single low-dose TPM would be as effective as the conventional OXC without any adverse effects in children with BECTS.
Age of Onset ; Ambulatory Care Facilities ; Anticonvulsants ; Carbamazepine ; Child ; Epilepsy ; Epilepsy, Rolandic ; Fructose ; Humans ; Medical Records ; Pediatrics ; Prognosis ; Seizures ; Triazines

Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, and it is distinguished from Batter syndrome by hypomagnesemia and hypocalciuria. This disorder is caused by mutation in SLC12A3 gene which encodes thiazide-sensitive Na(+)-Cl(-)cotransporter (NCCT) which is expressed in the apical membrane of cells, lining distal convoluted tubule. A 8-year old boy who presented with Rolandic epilepsy, and horseshoe kidney accidentally showed clinical features of metabolic alkalosis, hypokalemia, hypocalciuria without hypomagnesemia. So we identified a heterozygote mutation and an abnormal splicing in the SLC12A3 gene, encoding NCCT. The mutation was detected in the exon 15 and 22 of SLC12A3 gene.
Alkalosis ; Epilepsy, Rolandic ; Exons ; Gitelman Syndrome ; Heterozygote ; Hypokalemia ; Kidney ; Magnesium ; Membranes