The Association of MRI Findings and Neuropsychological Functioning after the First Recognized Seizure

Structural brain abnormalities of various types can lead to epilepsy, and many are associated with delays in cognitive development or specific cognitive deficits. Genetic cortical malformations (e.g., lissencephaly, schizencephaly, heterotopias, and polymicrogyria) are often characterized by seizure disorders, typically with significant delays in broad cognitive development (Guerrini, 2005). Similarly, tuberous sclerosis is characteristically associated with seizures and developmental delays. More importantly, the degree of intellectual deficit appears to be related to the degree of structural abnormality (i.e., the number of tubers) (Jambaque et al., 1991). Hippocampal sclerosis, a common finding in temporal lobe epilepsy in adults, has been associated with specific deficits in verbal memory and language or spatial memory in a manner consistent with the hemisphere affected (e.g., Baxendale et al., 1998); intelligence and other functions are relatively spared (e.g., Bourgeois et al., 1983; Ellenberg et al., 1986; Martin et al., 1999; Rodin et al., 1986). The degree of neuropsychological deficit is related to hippocampal volumes in adulthood (Baxendale et al., 1998; Hermann et al., 2002). The nature and extent of these neuropsychological deficits appear to be related to age of seizure onset, with lower memory scores and smaller hippocampal volumes observed among individuals with childhood onset (Baxendale et al., 1998). Furthermore, these effects might even be moderated by age of onset, with earlier age of onset being associated with not only hippocampal volume loss but an additional reduction in total brain volume, together with broader neuropsychological deficits that extend outside of the memory domain (Hermann et al., 2002). These findings support an association between the presence of structural brain abnormalities and cognitive deficits in children with epilepsy. For some conditions (e.g. tuberous sclerosis complex), the extent of the structural abnormalities is related to the severity of neuropsychological dysfunction (Jambaque et al., 1991; O’Callaghan et al., 2003; Weber et al., 2000). Moreover, the type and location of the structural abnormalities can be related to the nature of neuropsychological deficits affecting specific cognitive domains (e.g., Hermann et al., 2002). Shinnar and colleagues followed 411 children in New York City after their first unprovoked afebrile seizure (Shinnar et al., 2001). That study helped to characterize a new onset sample with regard to structural brain abnormalities; however, there are potential limitations that could affect the conclusions and generalizability of those findings. First, although the sample was large, only 27% (n = 59) of the children had MRIs; the majority (73%) had CT scans. As would be expected, abnormalities were detected in higher proportions of children using MRI (34%) compared to CT (22%). Therefore, that study likely underestimated the extent of structural brain abnormalities in this population. Second, there was no differentiation between abnormalities that seemed to be related to the seizure disorder versus those that were not related. In addition, imaging data were collected over the course of the children’s disorder in order to use the most sensitive imaging study for each participant that was available at the time of the 2001 publication (Shinnar, 2006). Consequently, many of the children in that sample completed their imaging studies many years after onset. In a subsequent and parallel study, Berg and colleagues followed 613 children in Connecticut following a second unprovoked seizure (Berg et al., 2000). The Connecticut study improved on many of the limitations in the New York City study. The majority of children in the Connecticut study completed MRI studies (vs. CT), and the imaging was obtained in conjunction with the initial evaluation at onset. Consequently, the lower proportion of children showing abnormalities in the Connecticut sample (12.7%, using more sensitive imaging but closer to onset) versus the New York City sample (21%, using less sensitive imaging but more chronic seizures) raises the possibility that some of these abnormalities might develop or become more detectable over the course of the disorder. However, it is possible that differences in exclusion criteria and/or definitions of onset also contributed to the differences in rates of abnormalities. In an effort to start addressing these differences, it would be beneficial to replicate these findings in a new sample with many of the strengths of the Connecticut study. All of these imaging studies have documented the potential for structural abnormalities at the onset of seizures in children. However, it is unclear if these abnormalities are related to cognitive function. Neuropsychological data were not reported for any of these studies. Neuropsychological deficits have been well documented in children with epilepsy (see Fastenau et al., 2003, for brief review), but there have been mixed findings in children at the onset of the disorder. Williams and colleagues (Williams et al., 1998) examined a small cohort (n = 37) of children newly diagnosed with epilepsy prior to initiation of antiepileptic drug therapy and found no differences in neuropsychological performance compared to children newly diagnosed with diabetes. However, others have documented subtle deficits at onset in children. Oostrom and colleagues (Oostrom et al., 2003) compared 51 children with new onset of epilepsy (i.e., at least two seizures) to a group of 48 healthy same age classmates with nearly identical IQ. At baseline they found that children with epilepsy showed deficits in attention and learning compared to the control group. None of these studies examined the relationship between structural abnormalities and neuropsychological deficits at the onset of the disorder. In this study, we explored the relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. In the analyses we separated the MRI abnormalities into those that seemed to be related to the seizure disorder and into those that were not related.