Visual memory after epilepsy surgery in children: a standardized regression-based analysis of group and individual outcomes.

Visual memory is vulnerable to epilepsy surgery in adults, but studies in children suggest no change or small improvements. We investigated visual memory after epilepsy surgery, both group-wise and in individual children, using two techniques to assess change: 1) repeated measures analysis of variance (ANOVA) and 2) an empirically based technique for detecting cognitive change [standardized regression-based (SRB) analysis]. A prospective cohort consisting of 21 children completed comprehensive assessments of memory both before surgery (T0) and 6 (T1), 12 (T2), and 24 months (T3) after surgery. For each patient, two age- and gender-matched controls were assessed with the same tests at the same intervals. Repeated measures ANOVA replicated the results of previous studies reporting no change or minor improvements after surgery. However, group analysis of SRB results eliminated virtually all improvements, indicating that the ANOVA results were confounded by practice effects. Standardized regression-based group results showed that in fact patients scored lower after surgery than would be predicted based on their presurgical performance. Analysis of individual SRB results showed that per visual memory measure, an average of 18% of patients obtained a significantly negative SRB score, whereas, on average, only 2% obtained a significantly positive SRB score. At T3, the number of significantly negative SRB scores outweighed the number of significantly positive SRB scores in 62% of patients. There were no clear associations of clinical variables (including side and site of surgery and postsurgical seizure freedom) with memory outcome. The present analysis revealed that given their individual presurgical functioning, many children obtained disappointing results on some visual memory tests after epilepsy surgery. Comparison of the SRB analysis with ANOVA results emphasizes the importance of empirically based techniques for detecting cognitive effects of epilepsy surgery in childhood.

Recognition memory of serially or simultaneously presented words or figures, of epilepsy patients with or without mesial temporal sclerosis.

Previous studies, examining short-term recognition memory in patients with partial seizures as a consequence of mesial temporal sclerosis (MTS) have reported inconsistent findings. Dependent on the paradigms used for measuring recognition memory, some studies have demonstrated that the mesial temporal structures are not critically involved in short-term recognition memory. In addition, other studies found a lateralization effect that is consistent with the generally accepted association between left temporal lobe lesions and verbal memory deficits, and right temporal lobe lesions and non-verbal memory impairments. In the present study verbal and non-verbal recognition memory was tested in 41 patients with left or right temporal lobe epilepsy with MTS (22 left; 19 right) versus 44 patients with left or right temporal lobe epilepsy but without MTS (28 left; 16 right). Verbal and non-verbal recognition tasks were presented in both a serial and simultaneous condition to test a hypothesized local/global paradigm. Multiple analyses of variance (MANOVA) showed that unilateral MTS has no marked effects on verbal or non-verbal recognition memory of patients with seizures. An interaction effect between MTS and the lateralization of epileptic activity was found on memory performance: MTS only leads to deficits in recognition memory in patients with right-sided epileptiform activity. As hypothesized, patients with left temporal lobe abnormalities, have specific deficits with recognizing serially presented information.

Diagnostic significance of Wada procedure in very young children and children with developmental delay.

Localization of vital components of neurological functioning has to be performed before epilepsy surgery can be considered in children with intractable epilepsy. This study reports the experience with the Wada procedure in very young children and/or developmentally delayed children with an a priori considerable chance of failing the procedure. The aim of this study was to indicate the applicability of this procedure in this patient group. The Wada procedure is described in 16 children under 10 years of age and/or have intelligence quotient scores below 50 and/or are critically ill and/or are behaviourally disturbed. Information on motor, language and memory functioning is obtained in respectively 13/15, 9/13, and 5/11 children. Nine children underwent epilepsy surgery without postoperative impairment of neurological functioning. In five children epilepsy surgery was not performed because of the results of the Wada procedure or the lack of information during the Wada procedure. One child became seizure-free before surgery. Even in very young, developmentally delayed or behaviourally disturbed children, the Wada test can provide important information with respect to the decision pro or contra epilepsy surgery.

The lesioned brain: still a small-world?

The intra-arterial amobarbital procedure (IAP or Wada test) is used to determine language lateralization and contralateral memory functioning in patients eligible for neurosurgery because of pharmaco-resistant epilepsy. During unilateral sedation, functioning of the contralateral hemisphere is assessed by means of neuropsychological tests. We use the IAP as a reversible model for the effect of lesions on brain network topology. Three artifact-free epochs (4096 samples) were selected from each electroencephalogram record before and after amobarbital injection. Functional connectivity was assessed by means of the synchronization likelihood. The resulting functional connectivity matrices were constructed for all six epochs per patient in four frequency bands, and weighted network analysis was performed. The clustering coefficient, average path length, small-world index, and edge weight correlation were calculated. Recordings of 33 patients were available. Network topology changed significantly after amobarbital injection: clustering decreased in all frequency bands, while path length decreased in the theta and lower alpha band, indicating a shift toward a more random network topology. Likewise, the edge weight correlation decreased after injection of amobarbital in the theta and beta bands. Network characteristics after injection of amobarbital were correlated with memory score: higher theta band small-world index and increased upper alpha path length were related to better memory score. The whole-brain network topology in patients eligible for epilepsy surgery becomes more random and less optimally organized after selective sedation of one hemisphere, as has been reported in studies with brain tumor patients. Furthermore, memory functioning after injection seems related to network topology, indicating that functional performance is related to topological network properties of the brain.

The effect of the new antiepileptic drug rufinamide on cognitive functions.

PURPOSE: Rufinamide (RUF 331; 1-(2,6-difluoro-phenyl)methyl-1H-1,2,3-triazole-4-carboxamide) is a structurally novel compound that limits the frequency of sodium-dependent neuronal action potentials. So far no data have been published on the cognitive effects of RUF, except for two animal studies. METHODS: The study used a multicenter, multinational double-blind, randomized, placebo-controlled parallel-study design with four different doses of RUF (based on prior studies): 200 mg/day, 400 mg/day, 800 mg/day, and 1,600 mg/day as add-on to the existing medication. All patients had partial seizures, in the age range of 15-64 years (with an average of 37.5 years). Cognitive assessments were performed at baseline (before the start with RUF treatment) and at end point (after 3 months of treatment). RESULTS: In total, 189 patients were included, divided over the treatment groups: placebo (n = 41), 200 mg/day (n = 33), 400 mg/day (n = 38), 800 mg/day (n = 37), and 1,600 mg/day (n = 40). The most important finding is that for none of the cognitive tests did a statistically significant worsening occur for any of the doses of RUF when the period after 12 weeks of treatment was compared with the baseline before introducing RUF. Also none of the comparisons between dose and placebo showed a statistically significant difference. CONCLUSIONS: RUF is a new AED with no serious cognitive effects even in add-on treatment and even in the higher dose ranges.

The effects on cognitive performance of tailored resection in surgery for nonlesional mesiotemporal lobe epilepsy.

PURPOSE: Mesiotemporal lobe epilepsy (MTLE) can be treated with different surgical approaches. In tailored resections, neocortex is removed beyond "standard" margins when spikes are present in the electrocorticogram. We hypothesized that these larger resections are justified because spiking neocortex is dysfunctional. This would imply that in patients with spikes (a) postoperative cognitive performance is not affected, and (b) preoperative performance is worse than without spikes. METHODS: We studied 80 operated-on MTLE patients with pathologically confirmed nonlesional hippocampal sclerosis. All patients were left-sided language dominant and underwent cognitive tests 6 months pre- and postoperatively. A repeated measures analysis of variance (ANOVA) was performed, looking for within- and between-subjects interactions with presence of intraoperative neocortical spikes. RESULTS: Intraoperatively, neocortical spikes were present in 61% of patients. Improved postoperative cognitive outcome was seen only in left-sided patients with spikes. Their performance IQ (PIQ) increased by 8.1 points (95% confidence interval, 3.8-12.3; p = 0.02), and visual naming latency by 12.8 s (95% CI, 2.1-23.5; p = 0.07). Conversely, in left-sided patients without spikes, naming latency declined by 7.5 s (95% CI, -2.3-17.2; p = 0.07). Preoperative scores were comparable except for a 15.3-point (95% CI, 0.1-30.5; p = 0.02) lower VIQ in left-sided patients without spikes. CONCLUSIONS: Tailoring does not harm cognitive performance and is, in left-sided MTLE, associated with postoperative improvement. Left-sided MTLE without neocortical spikes has lower verbal scores, which tend to decline after standard resection and may represent a special pathophysiologic entity.