Cognitive function of idiopathic childhood epilepsy

1) Juvenile myoclonic epilepsy (JME)

Cognitive correlates of JME have received little attention despite the extensive literature on cognition in other types of epilepsy. Neuropsychological studies have shown that subjects with JME are impaired in several frontal functions, including mental flexibility, concept formation, cognitive speed, working memory, verbal fluency, perseveration, and planning13,14). Assessments of frontal lobe function in 15 adults with histories of JME and normal IQ showed that nearly half were impaired on 4 or more of 11 tests of frontal lobe function, although the impact of interictal EEG discharges was unclear15). Impairments in verbal and executive functioning may have important ramifications for the social, occupational, and academic performance of individuals with JME16). Cognitive performance may be independent of EEG activity. Significant executive dysfunction in children with JME has been associated with significantly smaller thalami and increased frontal cerebrospinal fluid17). Children with recent-onset benign childhood epilepsy with centrotemporal spikes (BCECTS), did not display the same pattern. Thus, frontal and thalamic volumes appear to mediate the relationship between executive functioning and brain structure in individuals with JME.

A study comparing the neuropsychological performances of 50 patients with JME with 50 age-, education-, and gender-matched controls found that the former group showed more extensive deficits than observed in other studies8). For example, the JME group showed significantly poorer performance in tests of attention, inhibition, working memory, processing speed, and mental flexibility, in addition to deficits in verbal and visual memory, naming, and verbal fluency.

2) Childhood absence epilepsy (CAE)

Patients with CAE showed slight but statistically significant deficits in global cognitive function, visual spatial function, and visual memory, although their verbal skills and verbal memory were less affected18). Compared with control individuals, patients with CAE have demonstrated higher rates of impaired behavior, emotion, cognition, and language, and lower intervention rates. These impairments particularly affected CAE patients with longer duration of illness, those with controlled seizures, and those treated with AEDs9).

1) BCECTS (benign rolandic epilepsy)

BCECTS is the most common form of epilepsy in childhood, and several clinical studies have assessed the prevalence of cognitive impairments and learning disabilities in these children. Although most children with BCECTS display normal cognitive function and have a very good prognosis with regard to their seizures, several neuropsychological problems have been identified in individuals with active epilepsy and epileptiform discharges.

Because of the topography of discharges in patients with BCECTS, there is considerable interest in assessing language function in these individuals19-22). Deficits in reading, writing, morphosyntax, auditoryverbal learning, and auditory discrimination20) have been reported in children with BCECTS, along with impairments in short-term memory21,22), executive function21,22), visual and perceptive abilities22), and fine motor activity23). Interictal activity was found to cause the laterality of speech perception to be reorganized, resulting in a bilateral representation of auditory and verbal stimuli and a loss of the usual right ear/left hemisphere advantage in processing these stimuli24). A higher spike frequency on EEG was found to correlate with poorer outcomes in visual perception, fine motor performance, short-term memory, and behavioral status, suggesting that focal epileptic activity may alter the cerebral mechanisms underlying cognitive functioning19). The correlation between epileptic events, such as seizures or sharp-wave discharges, and cognitive impairment19), along with findings of transitory cognitive impairment concomitant with sharp-wave discharge on EEG recordings25), strongly indicates that epilepsy has direct effects on cognitive capacities.

However, there have been studies that have assessed children and found no correlation between EEG patterns and cognitive abilities7,26). Although EEG features were minimally associated with cognitive variables, there was no relationship between spike burden and laterality25). Improvements in verbal memory and receptive language, but not in visual memory performance and phonological awareness, were observed27). Epileptiform discharges on EEG in the absence of seizures did not appear to have an independent effect on cognitive function28).

To determine whether the cognitive deficits are transient or chronic, several studies have investigated the long-term cognitive outcomes in patients with BCECTS. For example, a study that followed 22 children with BCECTS from the onset of seizures until remission found an inverse relationship between performance on various subtests of the Wechsler Intelligence Scale for Children and the density of the paroxysmal EEG abnormalities29). After 18 months, children with greater EEG anomalies and a persistent focus scored significantly lower on tasks involving working memory, verbal comprehension, attention, and sequential operations. A 2-year follow-up study showed improvements in visual-motor coordination, short-term non-verbal memory, attention, and flexibility22), and normal attentional abilities and visual-motor performance were observed in a cohort of children with BCECTS who had been in remission for 4 years30). Another prospective study following 19 children with BCECTS and 3 with paroxysmal occipital epilepsy for up to 3 years found that 8 of the children with BCECTS were slow learners and required special education, with 4 of these showing delayed language development26). Eight other children had low scores in specific learning areas, which subsequently improved or became normal with normalization of their EEGs. Improved or normal performance was seen more frequently in patients with complete remission (no seizures or EEG abnormalities). Since there have been few follow-up studies in adults, there is as yet no general consensus as to whether these deficits are transient or chronic.

Although the term "benign" refers to the spontaneous disappearance of seizures or their complete control with AEDs, without relapse after cessation of treatment, care should be taken in describing epilepsy as benign in respect to the cognitive development of children with BCECTS.

2) Childhood epilepsy with occipital paroxysms

Although there have been few studies on this syndrome, several neuropsychological investigations have found cognitive impairments in children with benign epilepsy with occipital paroxysms (BEOP)31-33). In one study, children with BEOP demonstrated significantly lower performance than controls matched for age, sex, and socioeconomic status on measures of intellectual functioning, particularly on performance IQ31). Another study, however, found no betweengroup differences in performance IQ, although verbal IQ was lower in children with BEOP than in controls32). In both studies, the children with epilepsy showed significantly reduced performance across a wide variety of cognitive tasks, including attention, memory, visuospatial skills, language skills, and motor skills. Although another study found that between-group differences remained significant when controlling for intellectual functioning, there were no betweengroup differences in academic achievement, visuomotor skills, or executive functioning33). Thus, to date, there is no consensus about the relationship between cognitive function and BEOP, which suggests the need for further prospective studies.