Biomedical subjects

W C Alpherts

Publications and source records attributed to W C Alpherts.

18 recordsLinked to original sources

PubMed2002

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.

Adult↗

PubMed2000

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.

Adult↗

PubMed1999

[No adverse effects on intelligence 6 years after surgery for epilepsy].

OBJECTIVE: To evaluate the long-term effects of epilepsy surgery on intelligence. DESIGN: Prospective descriptive. METHOD: The group included 20 patients of the Instituut voor Epilepsiebestrijding, Heemstede, and the Epilepsiecentrum Kempenhaeghe, Heeze, the Netherlands, who suffered from medication-resistant epilepsy originating from the temporal lobe, in 9 patients from the left lobe (mean age: 33.1 years), in 11 from the right one (34.6 years). The epilepsy focus was removed surgically (Academic Hospital, Utrecht). The scores on the 'Wechsler adult intelligence scale' (WAIS) were determined before the operation and 6 months, 2 years and 6 years after operation. RESULTS: The mean WAIS IQs before operation were: verbal IQ (VIQ): 111.8 and performance IQ (PIQ): 117.7 in the group treated on the left and VIQ: 113.5 and PIQ: 112.4 in the group treated on the right. The mean gains 6 years after operation were 0.8 and 2.6 VIQ-points and 8.7 and 8.5 PIQ-points respectively. In the patients operated on the left the difference between VIQ and PIQ was significant 2 and 6 years after operation. The increase in IQs remained within what could be expected in retests. Only for the VIQ of patients treated on the left was a smaller retest effect found. CONCLUSION: These figures show that in the long term epilepsy surgery does not have an adverse outcome on the intelligence.

Adult↗

PubMed1998

Antiepileptic drug-related cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation.

The cognitive complaints reported by children and their parents, as subjectively associated with antiepileptic drug (AED) treatment, were evaluated in seizure-free children before and after drug discontinuation. The aim of the design was to isolate the cognitive side effects of AEDs from other factors, such as the effect of seizures. Our inventory explored the following areas: "alertness," "concentration," "activation/ tiredness," "memory," "drowsiness," "depression," "aggressiveness," and "hyperactivity," using a 5-point Likert scaling procedure. One hundred two eligible patients were selected, each matched with a healthy control and assessed when still on antiepileptic medication. All children were seizure free for at least 1 year. The medication was then discontinued gradually over a 3-month period. Four months after the children were completely medication free, a second assessment was carried out, but only in the 83 children who remained seizure free and in their matched controls. The results of the reports made by the children themselves did not show differences with the matched controls, and only showed improvement after drug discontinuation for complaints about "tiredness." Parents of the children with epilepsy reported significant improvement in all areas related to "alertness and activation" after discontinuation of the drugs. The finding that only a limited number of children have cognitive complaints, both when still on AEDs and after discontinuation, may be in line with the reports that the major factor contributing to quality of life is whether patients are seizure free or still have seizures. All patients in this study were seizure free for a period >1 year, which may have caused the favorable pattern of response in our patient group.

Adolescent↗

PubMed1995

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.

Administration, Oral↗

PubMed1994

Withdrawal of antiepileptic medication in children. Correlation of cognitive function and plasma concentration--the multicentre 'Holmfrid' study.

Eighty-three patients with epilepsy and 83 matched controls completed 12 computerized cognitive tests while on antiepileptic drugs and six months later when they had been medication-free for three to four months. All patients had been seizure-free for more than one year and were on monotherapy with carbamazepine (CBZ, n = 56), valproate (VPA, n = 17), or phenytoin (PHT, n = 10). The tests and plasma concentration collection were done at noon. The mean peak plasma concentrations in the CBZ patients were as follows: 31% below 30 mumol/l, 48% between 30 and 42 mumol/l and 21% above 42 mumol/l. No difference in performance could be detected between the groups. One significant correlation between plasma concentration and test results was found. The mean VPA concentration was 625 mumol/l (S.D. 189). A tendency towards a weak negative correlation between test results and plasma concentration was present. The PHT patients' therapeutic range had a mean concentration of 32.0 mumol/l (S.D. 18.5). One significant correlation between a memory test and plasma concentration could be detected. Overall, the patients in the different antiepileptic groups performed less good than the control group and in a few cases the differences were statistically significant when compared either before or after withdrawal. A comparison of the changes after withdrawal showed improvement in the majority of tests, but these changes were also present in the matched control group.

Adolescent↗

PubMed1994

Cognitive side-effects of phenytoin compared with carbamazepine in patients with localization-related epilepsy.

In continuation of an earlier study of our group (Neurology, 43 (1) (1993) 41-51), we present the results of an investigation of the adverse effects of carbamazepine versus phenytoin on cognitive function. Two groups of twenty-five patients are compared in an open, parallel group and non-randomized clinical investigation: a group of patients on carbamazepine (CBZ) monotherapy versus a group of similar size on phenytoin (PHT) monotherapy. The two groups do not show significant differences on variables that could confound the comparison of drug-specific adverse effects: age, gender, intelligence, type of epilepsy, seizure type, seizure frequency, EEG focus and age at onset of the epilepsy. All patients were investigated with a comprehensive neuropsychological test battery ('FePsy'), assessing the cognitive domains of 'speed factors', memory and attention. The results show lower performance in the PHT group compared to the CBZ group on all tests measuring motor speed. Additionally, there is evidence that PHT also affects the speed of central 'higher cortical' processing systems. Our investigation also shows slower performance in tasks that measure speed of information processing ('mental speed'). The other investigated areas, i.e. short-term memory, long-term (verbal and non-verbal) memory and selective attention, do not reveal statistically significant differences between the two groups. These results reconfirm that patients on PHT may suffer from cognitive side-effects even when the medication is sufficiently controlled and the drugs are given within the assumed therapeutical interval.

Adolescent↗

PubMed1994

Cognitive performance in learning disabled children with and without epilepsy.

Cognitive functioning and educational achievement were examined in learning disabled children with epilepsy (n = 65) and without epilepsy (n = 122) in order to explore whether children with epilepsy show unique types of learning problems, different from those in other learning disabled children. The learning disabled children with epilepsy tended to perform better on tests of verbal intelligence, certain achievement-related abilities and were better in one area of academic achievement, i.e. spelling. Despite their superior performance in these areas, the learning disabled children with epilepsy were slower than those without epilepsy and regular education controls (n = 100) on simple auditory and visual reaction tasks as well as on a multiple decision reaction task and a visual searching task. The results obtained with the school achievement tasks provide no clear evidence for specific types of learning impairment in children with epilepsy. Learning disabled children with epilepsy do not appear to have educational needs different from those of other learning disabled children.

Attention↗

PubMed1993

[Results of the neurosurgical treatment of patients with drug-resistant epilepsy: psychosocial aspects].

OBJECTIVE: Evaluation of psychological and social functioning of patients after neurosurgical treatment for pharmacologically intractable epilepsy. DESIGN: Descriptive study. SETTING: University Hospital Utrecht in collaboration with the Institute for Epilepsy in Heemstede, the Netherlands. METHOD: After two years' follow-up, social functioning, vocational adjustment and emotional stability were assessed in a group of 13 adult patients treated surgically between 1985 and 1992 for intractable seizures. RESULTS: The majority of the patients improved or at least maintained their social and employment status. Emotional functioning showed minor changes for anxiety and emotional stability. CONCLUSION: The outlook for improvement in psychosocial functioning for epileptic patients treated neurosurgically is promising. Minor changes were found in emotional stability.

Adaptation, Psychological↗

PubMed1993

Memory complaints in epilepsy: correlations with cognitive performance and neuroticism.

Subjective memory functioning was assessed by a questionnaire in 102 patients with epilepsy. Factor analysis of their responses yielded five factors: (1) Absentmindedness, (2) Retrieval, (3) Memory for Semantic Structures, (4) Childhood Memories and (5) Rote Memory. Scales representing the factors were constructed. On all scales, patients (n = 71) who had been specifically referred for an evaluation of subjective memory problems showed moderate to large differences from normal Controls (n = 111) in complaint scores, indicating adequate sensitivity of the scales to clinically significant complaint levels. By contrast, candidates for epilepsy surgery (n = 31) resembled the Controls in their perceived memory status, showing a moderately elevated complaint level on only one of the factor based scales. Relationships of subjective memory difficulties to performance on objective tests of memory and other relevant cognitive functions as well as neuroticism were examined. The two epilepsy groups were fairly similar in their test performance, but differed markedly in their subjective memory problems. Also, correlational analysis revealed only a single weak correlation between cognitive tests and subjective memory ratings. The present findings indicate that there is no simple relationship between subjective evaluations of memory and test performance. Patients' memory complaints do not accurately predict disturbances that can be measured on standard neuropsychological tests. Such complaints may be related more to neuroticism. Also, psychosocial difficulties which may accompany chronic disorders in general may have to be invoked to account for memory complaints in people with epilepsy. The epilepsy itself does not appear to be a critical factor in producing memory complaints.

Adolescent↗

PubMed1993

Withdrawal of antiepileptic medication in children--effects on cognitive function: The Multicenter Holmfrid Study.

We present 100 children diagnosed with epilepsy who were seizure-free for more than 1 year and still on monotherapy of antiepileptic drugs (AEDs). We matched each child with a healthy classmate and performed neuropsychological testing and EEG before and after complete withdrawal of the AEDs. The withdrawal phase lasted 3 months, but the dose decrease was individualized for each patient. Three to 4 months after complete withdrawal of the drug all patients were reassessed. Patients with seizure relapse are excluded from the study. Seventeen patients are regarded as dropout, 11 because of seizure relapse and six because of protocol violation. The remaining 83 patients were treated with carbamazepine (n = 56), valproic acid (n = 17), or phenytoin (n = 10). Serum concentrations of the AEDs were measured using peak plasma levels that were taken immediately before or after psychological testing. We used neuropsychological tests to assess psychomotor function and "central" cognitive processing such as information processing or memory function. We found significant improvement attributable to drug withdrawal on only one of the cognitive tests, namely, psychomotor speed, suggesting that the impact of AED treatment on higher-order cognitive function is rather limited. In addition, we found group differences between the epilepsy group and the control group at baseline that persisted after drug withdrawal. Subsequent analysis showed some factors that may have contributed to these group differences. First, patients with a former diagnosis of absence seizures show lower scores both at baseline and after drug withdrawal. We may assume that the seizure propensity has not disappeared completely in these patients. Some evidence is found that phenytoin may have a different cognitive profile than carbamazepine, with more impairment on tests that measure motor and mental speed. Again, this impairment persists after drug withdrawal.

Adolescent↗

PubMed1992

Subtest profiles of the WISC-R and WAIS in mentally retarded patients with epilepsy.

In this study, WISC-R and WAIS subtest profiles of mentally retarded patients with epilepsy are analysed with respect to the Verbal-Performance IQ Discrepancy scores and rank order of mean subtest scores. The relative strengths and weaknesses in cognitive patterns of this sample are compared with subtest profiles mentioned in the literature on mentally retarded populations and samples of normal intelligent patients with epilepsy in order to determine the impact of epilepsy factors on cognition. The results indicate that people with mental retardation have problems with the verbal subtests Arithmetic, Vocabulary and Information, while patients with epilepsy have problems with Coding (Digit Symbol), Digit Span and Information. For this sample of mentally retarded patients with epilepsy, the most difficult subtests are Digit Span and Coding. The results concerning subtest profiles in different populations are discussed in light of the deleterious impact of epilepsy on cognition, which may superimpose the general effect of brain damage in mentally retarded patients. It is suggested that especially attentional processes, as measured with the subtest Coding, are vulnerable for epilepsy factors.

Adolescent↗

PubMed1990

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.

Anticonvulsants↗

PubMed1990

Computerized neuropsychological assessment of cognitive functioning in children with epilepsy.

The value of a range of computer-aided tests in the neuropsychological assessment was investigated in 94-177 children with epilepsy, aged 8-18 years, compared with 68-161 controls in the same age group. Children from the age of 8 years could cope with rather complex tests in a wide range of functions: reaction time measurements, motor speed, information processing, and memory. The speed of performance tended to increase with age in both groups, with differences in information processing becoming apparent from the age of 12 years. The precise control of stimulus and response required to define the mainly minor differences between the epilepsy and control groups can only be fulfilled by computerized testing, which should undergo further refinement including voice and language recognition, followed by artificial intelligence.

Adolescent↗

PubMed1990

Neuropsychological aspects of learning disabilities in epilepsy.

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.

Adolescent↗

PubMed1987

CGP 11.952: an experimental benzodiazepine derivative. Effects on cognitive functioning in patients with epilepsy.

1. In two open studies using patients with intractable epilepsy, the effects of CGP 11.952, a triazolyl benzophenone, on cognitive functioning were assessed by means of a computerized neuropsychological battery. 2. In the first study CGP 11.952 turned out to have a positive effect on information processing speed, perceptual sensitivity and preciseness of responses. 3. Negative effects were found on reaction time. 4. In the second study this latter effect was less clear. 5. A striking result was the less negative effect on memory consolidation under influence of CGP 11.952 in comparison with other benzodiazepines.

Adolescent↗

PubMedDate not supplied

Controlled release carbamazepine: cognitive side effects in patients with epilepsy.

The treatment of epilepsy with carbamazepine (CBZ) may be hampered by cognitive side effects. These side effects are thought to be related to pharmacokinetic properties of the drug. The serum concentration of CBZ is characterized by rapid absorption and a short half-life, which may lead to a considerable fluctuation of the level between doses. Cognitive defects may result from peak levels: short periods with high serum concentration. In a single-blind crossover design, cognitive performance was compared in three conditions. All patients were first tested in the steady state of conventional CBZ. The patients were then assigned randomly to either CBZ-controlled release (CR) or a condition in which conventional CBZ was administered in the same tablet form and dose frequency as CR. Psychological tests were administered four times daily, immediately after the serum samples were taken. A nonmedication control group was tested following the same test scheme to obtain standards for the evaluation of changes in performance during the day. A systematic tendency was found toward higher test performance in the CR condition. This is especially evident for tests of memory and accuracy of visual information processing. The results of the repeated test procedure show that the smoothing effect of the CR condition on serum concentration fluctuations results in a more stable pattern of cognitive functioning during the day.

Adolescent↗

PubMedDate not supplied

Double-blind placebo-controlled, neuropsychological and neurophysiological investigations with oxiracetam (CGP 21690E) in memory-impaired patients with epilepsy.

A double-blind placebo-controlled between-patient study was carried out to assess the effects of oxiracetam (CGP 21690E) on memory function in patients with epilepsy. During a 12-week period, either oxiracetam (800 mg t.i.d.) or placebo was given to 30 patients. Twenty-four of the patients had a partial epilepsy. Most patients were on monotherapy carbamazepine. Effect of oxiracetam on memory and related cognitive functions were assessed, using a computerized neuropsychological testing method, while concomitant electrophysiological changes were investigated with routine EEG registration, power spectrum analysis and auditory evoked event-related potentials (P300). Subjective evaluation of well-being was quantified with a mood rating scale. The results did not show any meaningful changes in memory function. This finding is in line with the subjective patient reports and the P300 measures.

Adolescent↗