Symptomatic focal epilepsy in childhood: cognitive effects of seizure onset during a critical developmental period

Abstract

It is well recognised that cognitive impairment is a common morbidity of childhood epilepsy. However, not all children are at equal risk for these difficulties. Seizures are a defining characteristic of epilepsy, and animal studies provide insight into detrimental changes including dysfunctional reorganisation of networks, with the developing brain more vulnerable to these effects. Despite this knowledge, human research is mixed as to the precise contribution that seizures make to cognitive outcome, especially since epilepsy is a complex disorder with many intrinsically-related variables contributing to outcome. The ability of previous research to disentangle these factors has been limited by studying refractory epilepsy, where these variables are more strongly enmeshed than at diagnosis. Thus, the first aim of this research was to clarify cognitive effects of seizures and epilepsy on cognitive functioning in children aged three to eight years with new-onset symptomatic focal epilepsy (N = 35). The second and main aim of this research was to elucidate the effects of timing of seizures on cognition during early childhood. There has been considerable debate regarding whether the young brain is more vulnerable or resilient than the mature brain after injury. Recent research on paediatric brain insults indicates that the developing brain is more susceptible to cognitive deficits. Knowledge of the age-related effects of seizures on cognition is comparatively sparse and tends to focus on adult samples. Given that children are undergoing dynamic periods of development when seizures occur, investigating age at seizure onset within childhood allows examination during a critical period. There is accumulating evidence that in children with epilepsy, age at onset independently predicts cognitive outcome. In-depth examination as to why seizures earlier in childhood equate to greater cognitive deficits is lacking. To address these aims, the cognitive abilities of children with symptomatic focal epilepsy (SFE) beginning between three to five years (N = 18) were compared to those with onset between six to eight years (N = 8). Individual cognitive domains were studied (language, attention, memory and visuospatial skills), rather than relying on general ability measures. Given that research to date has lacked consideration of age-specific effects of seizures within a developmental paradigm, the hypotheses were framed according to Dennis’ (1989) heuristic, that is, skills that are emerging at the time of the insult were predicted to be more vulnerable to damage. The findings of this research indicate that children with SFE demonstrate widespread cognitive deficits relative to normative standards. Children with secondarily generalised seizures, and on polytherapy and from families with lower socioeconomic status, were more likely to demonstrate poorer cognitive functioning. From a developmental perspective, skills in an emerging phase were more vulnerable than those that were established at time of diagnosis. The early onset group were more likely to have cognitive deficits relative to normative standards and the late onset group, particularly for visuospatial skills. These findings hold important theoretical and empirical implications. The early vulnerability to seizures argues for consideration of timing of early interventions such as surgery to halt seizures as soon as possible.