The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice.

INTRODUCTION: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure. METHOD: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment. RESULTS: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant. CONCLUSION: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.

Acute effects of subclinical epileptiform EEG discharges on cognitive activation.

In this prospective, open, clinical comparative study we analyzed impairments of cognitive activation occurring during, immediately before and immediately after epochs with epileptiform EEG discharges of 3 seconds or longer, in an attempt to establish whether cognitive slowing occurs in direct association with an epoch with epileptiform EEG discharges and whether cognitive impairments precede or follow such an epoch. All children were assessed with EEG/video (Brainlab) simultaneously with computerized neuropsychological testing (FePsy): a test for cognitive activation (simple visual and auditory reaction time measurement). Thirty-seven epochs with epileptiform EEG discharges without clinical signs of a seizure (subclinical epileptiform EEG discharges) were evaluated. The results showed a statistically significant and clinically relevant slowing (35% compared to the overall reaction time), occurring during the epoch with epileptiform EEG discharges (repeated measurement analysis of variance p = < .05; df = 3; F-value: 3.293). No statistically significant slowing was found for the periods 'post-discharge' or 'pre-discharge'. Type of discharge was important and effects on cognitive activation were found exclusively for generalized discharges. This effect was, however, also seen in the remaining period, outside the 'peri-discharge' periods and thus seemed to represent a more general effect of the type of epilepsy on cognitive activation. Our results show that the acute effect of short epileptiform EEG discharges (duration 4.14 sec; sd 1.38) may be impressive, causing impairment (slowing) of cognitive activation. This effect was limited to generalized discharges. This effect was not observed for focal discharges, even during longer periods with discharges. However, it is reassuring that this impact on cognitive activation is limited to the actual period in which the discharges occur and does not have 'post-discharge' effects. The risk of accumulating effects that may have longer-lasting repercussions on higher-order cognitive functions therefore seems to be negligible.

Relative influence of epileptic seizures and of epilepsy syndrome on cognitive function.

Cognitive impairment is frequently observed in children with epilepsy. We aimed at addressing to what extent cognitive function is affected by paroxysmal epileptiform activity with or without clinical seizures or by clinical features characteristic of the epilepsy syndrome. To this purpose, combined electroencephalographic (EEG) recording and cognitive testing (IQ and reaction times) were performed in 28 children. Frequent epileptiform EEG discharges significantly reduced reaction time, as did the occurrence of seizures during cognitive testing. Syndrome-related factors tended to affect cognitive functions as well: children with generalized epilepsy and high average seizure frequency obtained lower scores. Linear regression analysis showed that stable aspects of cognitive function, as reflected in intelligence level, are most closely related to the severity of the epilepsy syndrome (average seizure frequency), whereas transient aspects of cognitive function, such as reaction times, are related to the occurrence of epileptiform EEG discharges. This suggests that seizures have a direct effect on transient cognitive aspects, which can accumulate and result in effects on intelligence level.