W.C.J. Alpherts

fMRI-Determined Language Lateralization in Patients with Unilateral or Mixed Language Dominance According to the Wada Test

Due to the reported variability of the language laterality index (LI) across fMRI studies, reliable distinction between patients with unilateral and mixed language dominance is currently not possible, preventing clinical implementation of fMRI as a replacement for the invasive Wada test. Variability of the LI may be related to differences in experimental and control tasks, and statistical methodology. The goal of this study was to improve detection power of fMRI for hemispheric language dominance by using a combined analysis of four different language tasks (CTA), that has previously shown more reliable and robust Lls in groups of normal volunteers than individual task analyses (see Ramsey et al). The CTA targets brain areas that are common to different language tasks, thereby focusing on areas that are critical for language processing. Further advantage of the CTA is that it is relatively independent of specific task and control conditions. 18 patients with typical (i.e., left-sided, n = 11) and atypical (i.e., right-sided or mixed, respectively, n = 3 and n = 4) language dominance according to the Wada test underwent fMRI (groups respectively denoted as WadaL, WadaR, and WadaM patients). Statistical methodology (including thresholding of activity maps) was fixed to assure a user-independent approach. CTA yielded better results than any of the individual task analyses: it was more robust (on average 2.5 times more brain activity was detected due to its higher statistical power) and more reliable (concordance for WadaL, WadaM and WadaR patients was respectively 10/11 (91%), 3/4 (75%), and 2/3 patients (67%)). Overall, a significant correlation was observed between frontal and temporoparietal LIs. Remarkably, brain activity for WadaM patients was significantly lower than for WadaL or WadaR patients, and a dissociation in lateralization was observed between frontal (right-sided) and temporoparietal (left-sided) activity in three of four patients. Of the individual task analyses, the verb generation task yielded best results for patients with unilateral language dominance (same concordance as CTA). However, in contrast to CTA results, the verb generation task was unable to identify WadaM patients (concordance in one of four patients). In conclusion, the CTA is a promising approach for clinical implementation of fMRI for the prediction of hemispheric language dominance.

Neuropsychological Aspects of Learning Disabilities in Epilepsy

Summary: Cognitive impairment is regarded as the link between epileptic conditions and the inability to learn in school. The neuropsychological approach to learning disabilities in epilepsy, therefore, first concentrates on analyzing the differential effects of epileptic factors on cognitive function. The impact of seizure activity, localization of epileptogenic foci, and antiepileptic treatment on cognitive functioning can be evaluated based upon the results of continuous assessment with a computerized neuropsychological test system. Second, learning disabilities may be evaluated on observations made during classroom performance. Three issues seem to predominate in learning studies among disabled children with epilepsy: test‐retest variability, deterioration, and the supposed specificity of the learning disabilities.

Verbal memory decline after temporal epilepsy surgery?: A 6-year multiple assessments follow-up study.

Objective: To assess the long-term effects of temporal lobe epilepsy surgery on verbal memory. Methods: We assessed verbal memory performance as measured by a verbal learning test (“15 Words Test,” a Dutch adaptation of Reys Auditory Verbal Learning Test) before surgery and at three specific times after surgery: 6 months, 2 years, and 6 years in 85 patients (34 left temporal lobe [LTL] vs. 51 right temporal lobe [RTL]). An amygdalo-hippocampectomy and a neocortical temporal resection between 2.5 and 8 cm were carried out in all patients. Results: LTL patients showed an ongoing memory decline for consolidation and acquisition of verbal material (both 2/3 SDs) for up to 2 years after surgery. RTL patients at first showed a gain in both memory acquisition and consolidation, which vanished in the long term. Breaking the group up into a mesiotemporal (MTS) group and a non-MTS group showed clear differences. The group with pure MTS showed an overall lower verbal memory performance than the group without pure MTS, in the LTL group more pronounced than in the RTL group. After surgery, both pathology groups showed an ongoing decline for up to 2 years, but the degree of decline was greater for the LTL patients with MTS compared with the non-MTS group. Becoming and remaining seizure-free after surgery does not result in a better performance in the long term. Predictors of postoperative verbal memory performance at 6 years after surgery were side of surgery, preoperative memory score, and age. Conclusions: The results provide evidence for a dynamic decline of verbal memory functions up to 2 years after left temporal lobectomy, which then levels off.

Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy

1. A new pyrrolidine derivative (levetiracetam), resembling piracetam, was given as antiepileptic concomitant drug to patients with chronic epilepsy. 2. In a single-blind add-on rising-dose study the cognitive side-effects were investigated twice after one week of administration. 3. The results did not show any significant changes in cognitive performances.

The Effect of the New Antiepileptic Drug Rufinamide on Cognitive Functions

Summary:  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.

Relationships between epilepsy-related factors and memory impairment.

Objectives:  In this study, we will explore the effect of epilepsy‐related factors such as: ‘type of epilepsy, ‘site and side of focus localisation’ and ‘age at onset’, as well as four seizure‐related factors: ‘years with continuing seizures’, ‘seizure type’ and ‘seizure frequency’, and the treatment factor ‘adverse effects of the medication’, on memory impairment. Additionally, we explored whether these epilepsy factors are related to different aspects of memory, i.e. short‐term recall vs long‐term recall, learning, and verbal memory vs non‐verbal memory.

Memory Complaints in Medically Refractory Epilepsy: Relationship to Epilepsy-Related Factors

This study reports the results of a multicenter study on memory complaints in 252 patients with epilepsy who presented with subjective complaints about memory problems in daily life. Memory complaints were measured with a standardized memory questionnaire (GKLE). The main purpose was to analyze the type of memory complaints and to examine the relationship between subjective complaints and several epilepsy-related factors. These include seizure type, lateralization and location of the focus, etiology, duration, age at onset, and antiepileptic medication. As expected patients experienced significantly more memory complaints. In particular, patients of older age and higher intelligence level complained more about their memory functioning. Although the clinical significance is marginal, neuroticism showed a significant relationship to the total complaint score. The total amount of subjective complaints is not related to the localization or lateralization of the epileptic disturbances. Patients with a longer duration of epilepsy complained significantly more about memory problems, especially about retrieving information from memory. All other epilepsy-related factors showed no relationship to memory complaints.

The Wada test: prediction of focus lateralization by asymmetric and symmetric recall

PURPOSE The intracarotid amytal test is commonly used as a predictor of memory dysfunctioning after anterior temporal lobe resection (ATL) for intractable epilepsy. Asymmetry in memory scores can provide focus lateralizing information. In this study the predictive value of a set of Wada test parameters was analyzed, including patients with symmetrical memory scores. METHODS The Wada test was carried out in 226 patients undergoing ATL (94 L, 132 R). Data were collected on item recognition (five items), story recall, amytal dose, presentation time, EEG and arterial filling of amytal. A logistic regression analysis was performed on these data in order to find a set of variables which could best predict the side of seizure onset. RESULTS The analysis yielded four variables, i.e. both memory scores, story recall after right-sided injection and presentation time of stimuli after left-sided injection which could correctly predict seizure lateralization in 85% of the cases. Misclassification was lower for right foci than for left foci. Seizure outcome was four times more favourable in the correctly classified patients. CONCLUSIONS The results suggest that prediction of focus lateralization in temporal lobe epilepsy can be fairly exact even if left/right memory scores are equal. Performing the Wada test with only five memory items keeps the time window of active amytal short enough and gives accurate information about contralateral temporal lobe functioning. The classification scheme can be useful in predicting a lowered chance of seizure freedom.

Long-term effects of temporal lobectomy on intelligence.

Objective: To characterize the long-term effects of anterior temporal resection on intelligence. Methods: Twenty-eight left temporal lobectomy (LTL) and 43 right temporal lobectomy (RTL) patients were followed at standard time points for at least 6 years after surgery. Results: The average gain 6 years after operation was 3.6 Verbal IQ (VIQ) points and 10.3 Performance IQ (PIQ) points in LTL patients and 2.9 VIQ points and 7.7 PIQ points in RTL patients. A seizure-free outcome did not influence the increase in IQ, nor was the extent of resection related to IQ scores at the 6-year follow-up. Patients with exclusively mesial temporal sclerosis did not perform as well as patients with other pathologies, both before and after surgery. Major predictors of improved performance at 6 years were initial higher level of performance and lower age at surgery. Much of the observed improvement may be related to retest effects. Conclusions: The effects of epilepsy surgery on intelligence in the long term are limited. The largest gain in VIQ is seen from 2 to 6 years after surgery.

Test-retest variability in children with epilepsy — a comparison of WISC-R profiles

Reports of test-retest variability appear recurrently in relation to epilepsy. To date, the amount of information available on the stability of cognitive profiles over a number of years is limited. In this study, 45 children were assessed, using the Wechsler Intelligence Test for Children - Revised (WISC-R). The children were retested after a period of at least 2 years. A group of 20 children was tested 3 times. The average follow-up period was 4.2 years. Although most subjects in our sample had a high seizure frequency and continued to have their seizures during the period of follow-up, a marked stability of cognitive profiles is found over a period of time. These profiles show low scores for the subtests Information, Coding, Digit Span, Vocabulary and resemble profiles reported in other studies on subjects with intractable epilepsies.