Effects of antiseizure monotherapy on visuospatial memory in pediatric age

Working memory capacity increases throughout childhood and adolescence, which is important for the development of a wide range of cognitive abilities, including complex reasoning. The spatial-span task, in which subjects retain information about the order and position of a number of objects, is a sensitive task to measure development of spatial working memory. This review considers results from previous neuroimaging studies investigating the neural correlates of this development. Older children and adolescents, with higher capacity, have been found to have higher brain activity in the intraparietal cortex and in the posterior part of the superior frontal sulcus, during the performance of working memory tasks. The structural maturation of white matter has been investigated by diffusion tensor magnetic resonance imaging (DTI). This has revealed several regions in the frontal lobes in which white matter maturation is correlated with the development of working memory. Among these is a superior fronto-parietal white matter region, located close to the grey matter regions that are implicated in the development of working memory. Furthermore, the degree of white matter maturation is positively correlated with the degree of cortical activation in the frontal and parietal regions. This suggests that during childhood and adolescence, there is development of networks related to specific cognitive functions, such as visuo-spatial working memory. These networks not only consist of cortical areas but also the white matter tracts connecting them. For visuo-spatial working memory, this network could consist of the superior frontal and intraparietal cortex.

Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined. In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons. The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03). Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.) 2010 Massachusetts Medical Society