Does epilepsy in childhood affect cognitive development?



This commentary is on the original article by Rathouz et al. on pages 635–641 of this issue.

The relationship between epilepsy and cognitive development remains poorly understood despite increased interest in this area in recent years. Rathouz et al. [1] present one of the first prospective studies examining the trajectory of cognitive development in children with a recent diagnosis of epilepsy. While cognitive abnormalities have long been linked to epilepsy diagnosis, there has been considerable debate in the literature regarding the impact of epilepsy on further cognitive development and achievement. The authors have provided an important addition to this growing body of literature. Their study confirms previous findings of cognitive impairment at or near the time of initial epilepsy diagnosis, but also demonstrates that abnormalities present at the time of diagnosis remain static over the 5-year to 6-year follow-up period, even when measured over multiple cognitive domains. Previous studies have proposed that lower IQ can be independently linked to a diagnosis of epilepsy.[2] This study suggests a relatively weak relationship between epilepsy and overall intelligence, instead finding specific domains had more impact than others, namely motor and psychomotor speed, attention and inhibition, and arithmetic computation skills. These findings echo past studies linking higher rates of attention-deficit–hyperactivity disorder and specific learning disorders in children diagnosed with epilepsy.[3]

Utilization of a comprehensive psychometric test battery is a strength of the paper by Rathouz et al., representing a more objective measurement of ability than some past studies relying on grade level retention, inclusion in special education classes, and teacher rating scales as measures of ability and achievement.[3] What remains unclear is whether these objective measures alone relate to academic success. While these findings reflect static changes in cognitive functioning, it is not yet understood whether this will carry forward in regard to long-term achievement.

This study has limitations when generalizing the results to larger populations with epilepsy. The findings are limited to children with normal intelligence, neurological examination, and imaging studies, and with onset of epilepsy during school age (8–18y). The study does not look at children of an early age at seizure onset who may be at increased risk of cognitive difficulties. Many of the epileptic encephalopathies start early in life and have been associated with decline in cognitive function.[4] One small study of children with tuberous sclerosis was able to assess cognition before and after the onset of seizures. They found a decline in intellectual development after onset of infantile spasms but not in children with other seizure types.[5] Other studies have suggested that early onset seizures may have a more negative impact on subsequent academic performance than later onset seizures.[6] However, the evidence for cognitive decline with seizures other than the epileptic encephalopathies is still weak. It is still unknown whether younger children with epilepsy experience a more severely affected trajectory of cognitive development over time.

There is no general consensus in the literature regarding the use of antiepileptic medications and their impact on cognitive development. Antiepileptic drugs such as phenobarbital, topiramate, and valproic acid have adversely affected attention and might secondarily have a negative impact on academic achievement.[7] Although participants in the current study diagnosed with idiopathic/genetic epilepsy were older at seizure onset, they were also more likely to be on antiepileptic medication. When differences in cognitive ability did exist between the groups, those with idiopathic/genetic epilepsy were more severely affected. Questions remain whether pharmacotherapy plays a role in cognitive deficits, and whether this is consistent over time.

Further research is needed to understand premorbid cognitive functioning in children diagnosed with epilepsy, as the majority of current studies point to correlations between epilepsy and cognitive deficits, but fail to establish cause and effect – a difficult task. It remains to be seen whether specific impairments in cognitive domains are linked to different forms of epilepsy – including forms which may be considered more severe, of earlier onset, or requiring antiepileptic medication therapy. Additionally, rates of psychiatric comorbidity are higher in children with epilepsy when compared to healthy controls.[3] Understanding the role of psychiatric comorbidity and subjective reports of cognitive impairment in conjunction with measured cognitive changes will be key when looking at long-term outcomes.

This paper strengthens the argument that routine cognitive screening is important in children with new onset epilepsy, even in cases formerly considered ‘benign’ and without additional neurological, psychiatric, or known developmental/intellectual delays. One could argue that children with epilepsy may benefit from additional support prior to clear academic or psychosocial deficits to promote long-term academic, social, and career success. Questions remain whether interventions initiated at the time of epilepsy diagnosis can affect the trajectory of cognitive development in this population, an area which has the potential to hold numerous implications for our patients and their families.