Benign epilepsy with centrotemporal spikes: Correlating spike frequency and neuropsychology.

OBJECTIVES: Neuropsychological sequelae are a feature of benign epilepsy with centrotemporal spikes (BECTS) in children. A correlation between the frequency of interictal EEG discharges and the cognitive as well as behavioral profile of the patients has been suspected but not proven. MATERIALS AND METHODS: Children with BECTS that had not yet been treated were included into a randomized controlled trial. In the initial visit, EEGs were recorded. The frequency of interictal discharges was quantified. Correlations between the discharge frequency and the performance in a neuropsychological test battery were examined. RESULTS: The cognitive test results were within or slightly above normal range (Culture-free intelligence test: 99.4%-confidence interval [CI]: [50.3, 59.9], test standardized to a population mean of 50). Parent-reported behavioral abnormalities were statistically significantly increased (CBCL total score CI: [51.9, 61.9], population mean as above). Correlations between the frequency of interictal epileptic discharges and the test results could not be identified (lowest encountered P-value: 0.034, not significant after correction for multiple testing). CONCLUSION: The data do not support the hypothesis that the frequency of the interictal EEG discharges influences the neurocognitive performance or behavioral parameters of children with BECTS.

The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome.

The first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood-brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of epilepsy including early onset absence epilepsy (EOAE), myoclonic astatic epilepsy (MAE), and genetic generalized epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of epilepsy including MAE and absence epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.

Noninvasive Ventilation and Rapid Enteral Feeding Advances in Preterm Infants-2-Year Follow-Up of the STENA-Cohort.

The importance of nutritional supply for somatic growth and neurodevelopmental outcome in very-low-birthweight infants is an established medical strategy for reducing long-term morbidities. Our cohort study on rapid enteral feeding advances using a standardized protocol (STENA) previously demonstrated a 4-day reduction of parenteral nutrition. STENA did not impede the success of noninvasive ventilations strategies but significantly less infants required mechanical ventilation. Most importantly, STENA resulted in improved somatic growth at 36 weeks of gestation. Here, we evaluated our cohort for psychomotor outcomes and somatic growth at 2 years of age. n = 218 infants of the original cohort were followed-up (74.4%). Z-scores for weight and length did not differ but the benefits of STENA for head circumference persisted until the age of 2 years (p = 0.034). Concerning the psychomotor outcome, we neither found any statistically significant differences in the mental developmental index (MDI) (p = 0.738), norin the psychomotor developmental index (PDI) (p = 0.122). In conclusion, our data adds important insights on the topic of rapid enteral feeding advances and confirms the safety of STENA with respect to somatic growth and psychomotor outcome measures.

Encephalopathy Associated With Neurochondrin Autoantibodies.

We determined the prevalence of autoantibodies against an extended number of established and novel neural antigens in children and adolescents with suspected autoimmune encephalitis, epilepsy, single seizures, or marked epileptiform activity in electroencephalography (EEG). Prospectively, 103 patients were recruited aged between 0 and 18 years and 104 controls. A panel of 35 autoantibodies against neural cell-surface and intracellular antigens was screened. Sixteen of 103 patients (15.5%) showed a positive result for 1 or more autoantibodies, compared to 6 of 104 controls (5.8%, P = .02). Neurochondrin was identified as a possible new target of autoantibodies in 3 patients within this cohort, but none in controls. The patients showed severe behavioral disturbances, memory and cognitive impairment, episodes of reduced responsiveness, but no seizures, and normal MRI. Clinical findings, course, and treatment response of these 3 patients are presented.

Effects of Levetiracetam and Sulthiame on EEG in benign epilepsy with centrotemporal spikes: A randomized controlled trial.

PURPOSE: BECTS (benign childhood epilepsy with centrotemporal spikes) is associated with characteristic EEG findings. This study examines the influence of anti-convulsive treatment on the EEG. METHODS: In a randomized controlled trial including 43 children with BECTS, EEGs were performed prior to treatment with either Sulthiame or Levetiracetam as well as three times under treatment. Using the spike-wave-index, the degree of EEG pathology was quantified. The EEG before and after initiation of treatment was analyzed. Both treatment arms were compared and the EEG of the children that were to develop recurrent seizures was compared with those that were successfully treated. RESULTS: Regardless of the treatment agent, the spike-wave-index was reduced significantly under treatment. There were no differences between the two treatment groups. In an additional analysis, the EEG characteristics of the children with recurrent seizures differed statistically significant from those that did not have any further seizures. CONCLUSION: Both Sulthiame and Levetiracetam influence the EEG of children with BECTS. Persistent EEG pathologies are associated with treatment failures.

Effect of anticonvulsive treatment on neuropsychological performance in children with BECTS.

INTRODUCTION: Benign epilepsy with centrotemporal spikes (BECTS) is a common epilepsy syndrome in childhood. Besides the occurrence of seizures, mild cognitive impairments and behavioral problems affecting language skills, spatial perception, memory, executive function, and academic achievement might be present. There is no international consensus about the decision whether or not to treat affected children. The influence of treatment on cognitive functions is debated. METHODS: Patients diagnosed with BECTS were assessed in short term auditory memory, long-term verbal memory, intelligence and behavior using the "number recall" test from the Kaufman assessment battery for children, the "verbal learning memory test", the "culture free intelligence test" and the "child behavior checklist" prior to a randomized controlled antiepileptic therapy and after a treatment period of 6 months with either sulthiame or levetiracetam. RESULTS: 43 of 44 randomized patients were analyzed. One patient had to be excluded due to protocol violation. Patients who completed the study showed a non-significant improvement in parent-reported behavioral problems under therapy. Cognitive skills were not affected. CONCLUSION: The present data suggest that antiepileptic drug treatment of children with BECTS with either sulthiame or levetiracetam does not affect cognitive performance. Behavior improved in a subset of patients though not reaching statistical significance.

Occipital sharp waves in idiopathic partial epilepsies--clinical and genetic aspects.

In order to gain new insight into the pathogenesis and nosography of benign partial epilepsy with occipital paroxysms (BEOP) we retrospectively analysed cases with benign focal sharp waves (SHW) of different localisations, in which analogous EEG changes had been found in at least one first degree relative. Fifty-six families were evaluated. Nineteen cases with occipital SHW (group A) were compared with 37 cases without (group B). There was a broad spectrum of symptomatology with large overlaps between the two groups. However, a number of striking differences, yielding a characteristic picture of early childhood epilepsy with occipital foci were identified: (1) Age of onset under 5 years; (2) a larger proportion of febrile convulsions (FC 47 vs. 19%); (3) a trend towards a higher rate of typical early childhood occipital seizures (26 vs. 5%); (4) a higher rate of frontal and generalizing SHW foci (32 vs. 5%; 37 vs. 11%); (5) a higher rate of generalized spikes and waves (SW) (46 vs. 14%); (6) a trend towards a higher rate of photoparoxysmal response (PPR) (57 vs. 32%). The high prevalence of independent genetic traits favours a multifactorial pathogenesis. The predisposition to FC with characteristic early seizure onset and varying patterns of generalized genetic EEG traits plays a crucial role within the complex pathogenetic network. The early-onset benign childhood occipital seizure susceptibility syndrome of Panayiotopoulos (Benign Childhood Partial Seizures and Related Epileptic Syndromes, John Libbey & Company Ltd., London (1999)) cannot be regarded as the sole representative of occipital spikes in early childhood but as an important even though rare form of occipital epilepsy.

Levetiracetam vs. sulthiame in benign epilepsy with centrotemporal spikes in childhood: a double-blinded, randomized, controlled trial (German HEAD Study).

OBJECTIVE: To show non-inferiority of levetiracetam to sulthiame with respect to efficacy, tolerability and safety in benign epilepsy with centrotemporal spikes in a prospective, double-blinded randomized controlled trial. METHODS: A sample size of 60 subjects (treatment group) was calculated to show reliable statistical results for non-inferiority. A total of 44 patients could be randomly allocated to either (LEV or STM) treatment group. Explorative data analysis was performed to investigate differences in the number of treatment failure events (occurrence of a seizure during the observation period of 6 months) and total dropouts. In addition, information of the occurrence of adverse events was collected. RESULTS: 43 patients were analyzed. One patient had to be excluded due to protocol violation. Treatment failure events occurred in four patients (19.0%) in the LEV treatment group and in two patients (9.1%) in the STM treatment group, respectively, (p = 0.412). The number of dropouts due to adverse reactions was five in the LEV treatment group and one in STM treatment group (23.8% vs. 4.5%, respectively, p = 0.095). Severe adverse events occurred in patients treated with LEV (n = 2, 9.5%). The total number of dropouts due to either seizure recurrence or adverse events was significantly higher in the LEV group (n = 9, 42.9%) compared to the STM group (n = 3, 13.6%, p = 0.03). INTERPRETATION: The study results concerning non-inferiority were not conclusive, as the calculated sample size was not reached to support sufficient statistical power due to limited recruitment in a 26 months period. The rates of seizure free patients were [relatively] high in both groups. However, the results indicate that termination of drug treatment due to seizure recurrence or adverse events occurred more frequently in the LEV group compared to STM. Behavioral disturbances were the most common adverse event causing study termination.