Rianne P. Reijs

Educational Underachievement in Children With Epilepsy: A Model to Predict the Effects of Epilepsy on Educational Achievement

In this study, we evaluated the impact on educational achievement of four characteristics of epilepsy individually and combined: epilepsy syndrome (type of epilepsy), seizure type, the frequency of epileptiform electroencephalographic (EEG) discharges, and the effect of antiepileptic treatment. Simultaneously, the effect on cognitive function and the relationship between educational underachievement and cognitive impairment were evaluated, focusing on memory, attention, speed of information processing, and intelligence level. This study was an open, controlled, parallel-group, nonrandomized clinical investigation. Eligible patients were selected when referred to our center for assessment of relationships between epilepsy and learning impairment in the years 1997 to 2001. Separately, children without neurologic deficit and without educational delay were assessed with the same tests as the children with epilepsy. This latter group is used in this study as a control group. One hundred seventy-six children with epilepsy and 113 controls were included. Gender distribution and age were comparable for the two groups. All children were in regular primary education. The children were assessed with a test battery consisting of tests for educational achievement, cognitive tests and tests for reaction time, and tests for memory and intelligence. Multivariate analysis of variance for tests of educational achievement showed a statistically significant effect for type of epilepsy (F = 4.386; P = .04), caused by the statistically lower scores for patients with localized epilepsy and symptomatic generalized epilepsy. For the reaction-time tests, a statistically significant effect for epileptiform EEG discharges (F = 3.165; P = .01) and treatment (F = 4.472; P = .001) on both vigilance tests was found, caused by patients with frequent epileptiform EEG discharges and polytherapy. Two-way interactions showed an interaction with type of epilepsy, with more patients with symptomatic generalized epilepsy having frequent epileptiform EEG discharges and polytherapy. For memory, none of the analyses showed statistically significant effects. For intelligence only for type of epilepsy, a statistically significant effect was found (F = 10.174; P = < .001). We propose a model with the type of epilepsy (epilepsy syndrome) as the dominant factor explaining educational underachievement in children with epilepsy. Such educational underachievement is most prominent for the localized and symptomatic generalized epilepsies, which suggests a dominant impact of underlying etiology (brain dysfunction or damage). These epilepsies are characterized specifically by a lower intelligence; hence, this could be the primary cognitive factor mediating between the type of epilepsy and educational underachievement. From the other factors, treatment (the use of polytherapy) and frequent epileptiform EEG discharges are associated with impaired vigilance, which could have an additional influence on educational achievement. These factors are, however, not independent of the type of epilepsy. (J Child Neurol 2005;20:175—180).

Functional MRI reveals declined prefrontal cortex activation in patients with epilepsy on topiramate therapy

Functional magnetic resonance imaging of covert word generation was used to examine brain activation abnormalities associated with topiramate-induced cognitive language impairment in patients with epilepsy. Compared with a control epilepsy group, in the topiramate-treated group, there was significantly less activation in the language-mediating regions of the prefrontal cortex; the topiramate group also had significantly lower neuropsychological language scores. These findings suggest that topiramate has a critical effect on the cerebral neural systems that mediate expressive language.

Cognitive fMRI and neuropsychological assessment in patients with secondarily generalized seizures

OBJECTIVES Cognitive dysfunction is a frequent comorbid disorder in epilepsy which has been associated with high seizure frequency. We examined the effect of secondarily generalized tonic-clonic seizures (SGTCS) on cognitive dysfunction using neuropsychological assessment and fMRI. PATIENTS AND METHODS Sixteen patients with localization-related epilepsy of varying etiologies and SGTCS underwent extensive neuropsychological assessment. Functional MRI was performed probing the frontal and temporal lobes with two paradigms aimed at investigating speed of mental processing and working memory. RESULTS A high number of total lifetime SGTCS was associated with lower intelligence scores. Moreover, a trend towards cognitive decline related to the number of SGTCS was observed. A relatively increased prefrontal activation related to the number of SGTCS was demonstrated, plus a trend towards a decreased activation in the frontotemporal areas. CONCLUSION High numbers of SGTCS are associated with a drop in intelligence scores and altered prefrontal brain activation. A shift from frontotemporal to prefrontal activation seems to have occurred, suggesting that a functional reorganization of working memory is induced by a high number of SGTCS. It remains uncertain if this reorganization reflects a compensation mechanism, or the underlying pathological processes of cognitive dysfunction.

Cryptogenic localization-related epilepsy with childhood onset: The problem of definition and prognosis.

BACKGROUND Up to one-third of children with epilepsy are diagnosed with cryptogenic localization-related epilepsy (CLRE). CLRE is a large nonspecific category within the ILAE classification. For this population no unequivocal prognosis exists. METHODS Twenty-five articles describing aspects of CLRE were included in this review. RESULTS As a result of the progress in epilepsy research, as well as more advanced investigation in individual cases, the population with CLRE constantly changes. Also, disagreement on interpretation of the classification has resulted in striking differences between the populations described. High remission rates are reported, but relapse occurs frequently, leaving the long-term prognosis unforeseeable. This is reflected in academic and psychosocial prognosis, which is described to be problematic in CLRE specifically. Possible prognostic factors of CLRE in children have been identified: age at onset, seizure semiology, seizure frequency, intractability, interictal epileptiform activity on EEG, and premorbid IQ. These factors are explored to define subgroups within the CLRE population. DISCUSSION Prospective studies on well-defined CLRE cohorts are needed to identify factors that distinguish various prognostic subgroups. Specific attention should be focused on course of the epilepsy, scholastic achievement, and psychosocial outcome.

Neuropsychological profile of children with cryptogenic localization related epilepsy.

Up to one third of the epilepsy population consists of children with cryptogenic localization related epilepsy (CLRE). Unfortunately, the effect of CLRE on the development is still unclear. Behavioral and academic problems have been reported, but no conclusive study concerning the impact of CLRE on neuropsychological functioning is yet published. This study was a systematic cross-sectional open clinical and nonrandomized investigation, which included 68 children with CLRE. Several neuropsychological tests were analyzed and age-related normative values were used as reference. Differences between CLRE and reference values were tested with Paired-Samples t-tests. Z scores were computed to compare the different neuropsychological tests and to inspect whether a characteristic neuropsychological profile exists for CLRE. The Independent-Samples t-test was used to explore which epilepsy factors (seizure type, seizure frequency, age at onset, duration of epilepsy, and drug load) were influencing the cognitive profile of CLRE. There seems to be a characteristic cognitive profile for children with CLRE; children with CLRE experience cognitive difficulties on a wide range of areas—in particular, alertness, mental speed, and memory. Seizure type, seizure frequency, duration of epilepsy, and drug load do not influence this neuropsychological profile. Age at onset was an important risk factor; the earlier the age at onset, the worse the cognitive performance. In spite of the influence of age at onset, the revealed profile can be seen as a stable, independent of temporary factors, neuropsychological profile for children with CLRE.

Psychomotor and motor functioning in children with cryptogenic localization related epilepsy

The aim of this study is to investigate psychomotor- and motor functioning in children with cryptogenic localization related epilepsy (CLRE) and to explore possible relationships between these two functions. Eighty-nine children were included. Results of reaction times measurements and motor functioning tasks were compared to age-related normative values. Correlations between the psychomotor and motor tasks were computed. Manual dexterity and balance problems are present in about 35% of CLRE-children. Ball skills are problematic in approximately 55% of the children. Simple reaction time measurements showed significantly slowing for CLRE children relative to the reference values. Also, performance on the m-ABC was significantly lower than the reference values. The better the childs performance on the simple reaction time measurements, the better the performance on the m-ABC.

Behavior in children with cryptogenic localization related epilepsy: a follow-up study.

Using the Child Behavior Checklist, the behavior of 16 children with cryptogenic localization-related epilepsy was assessed at first admission to our epilepsy center, and approximately 2 years later. Behavior improved substantially from t(1) (first assessment, when patients were admitted to our center) to t(2) (reassessment after approximately 2 years) on almost all subscales of the Child Behavior Checklist. At t(2), all subscales scored within normal range. Furthermore, seizure frequency improved considerably in the 2 years between assessments. After a period of approximately 2 years, normalization of behavior in children with cryptogenic localization-related epilepsy occurred.

The effect of duration of epilepsy on IQ in children with CLRE; a comparison to SLRE and IGE

Up to one third of the children with epilepsy are classified as having cryptogenic localization epilepsy (CLRE). Unfortunately, not much is known on the prognosis of CLRE; it is assumed to be somewhere between the benign course of many idiopathic epilepsies and the more malignant course of most symptomatic epilepsies. The risk of cognitive decline over time seems to be increased for children with epilepsy, but no data are available specifically for CLRE. This study was a systematic cross-sectional open clinical and non-randomized investigation, which included 68 children with CLRE, 24 children with symptomatic localization related epilepsy (SLRE) and 21 children with idiopathic generalized epilepsy (IGE). One-way between-groups ANOVAs with Tukey post hoc testing were used to test differences in demographical variables and IQ between CLRE, SLRE and IGE and to test the influence of duration of epilepsy and other epilepsy factors on IQ. To test whether there were IQ differences between the three types of epilepsy regarding duration of epilepsy and other epilepsy factors, the Kruskal-Wallis test was used. In CLRE, intelligence is stable over time; IQ scores do neither improve nor deteriorate. Age at onset, seizure type, seizure frequency and the use of AED appeared to have no influence on intelligence in CLRE. Furthermore, over time, there appeared to be no differentiation regarding IQ between CLRE, SLRE and IGE.

Motor function in children with cryptogenic localization related epilepsy

INTRODUCTION In CLRE specific learning difficulties and motor problems may occur. The aim of this study is to examine whether CLRE or the accompanying specific learning difficulties are associated with the occurring problems in motor function. METHODS Motor functioning in 140 children with CLRE and without epilepsy, as well as with and without specific learning difficulties is compared using Chi-square. RESULTS In the CLRE group 35% score below the 5th percentile (poor motor function). No correlations with epilepsy variables or the occurrence of specific learning difficulties is found. DISCUSSION A subgroup of about one-third of children with CLRE are at risk for poor motor function. Their development is best monitored using a multi-dimensional approach, including cognitive development and motor functioning.

Multimodal MRI Reveals Secondarily Generalized Seizure Related Abnormalities at 1.5 T: Preliminary Findings

Patients with chronic epilepsy, who have suffered a high number of secondarily generalized tonic-clonic seizures (SGTCS) frequently show cognitive comorbidity. It is yet unclear whether a higher number of SGTCS is associated with tissue changes in the brain. We have investigated in patients with chronic epilepsy whether a high number of SGTCS accumulated over life is associated with microstructural changes in brain tissue. Sixteen patients with localization-related epilepsy with SGTCS underwent a multimodal quantitative Magnetic Resonance (MR) examination at 1.5 T, comprising T2 relaxometry, and diffusion weighted imaging to study microstructural changes in the temporal and frontal lobes. Fourteen healthy volunteers were also included to assess the effect of age. Patients with more than 20 SGTCS (n=8) showed a significantly lower IQ (-20%, p<0.05) compared to those with less than 20 SGTCS (n=8). Furthermore, regional combined multimodal analysis revealed that significant quantitative MRI changes, related to the number of SGTCS, were present in the frontal lobe but not in the temporal lobe. Moreover, the left and right frontal lobe generally displayed lower T2 relaxation times, smaller pericortical cerebrospinal fluid fraction and lower apparent diffusion coefficients, in the patients with more than 20 SGTCS. These findings suggest that SGTCS are associated with substantial changes in microstructural brain tissue characteristics within the frontal lobes. These frontal changes possibly explain the cognitive problems which are often observed in patients with many SGTCS. This knowledge may help in the development of treatment aimed at preventing decline in cognitive abilities.