Effect of levetiracetam monotherapy on background EEG activity and cognition in drug-naïve epilepsy patients

https://doi.org/10.1016/j.clinph.2011.09.012Get rights and content

Abstract

Objective

To investigate the cognitive effect of levetiracetam (LEV) monotherapy with quantitative electroencephalogram (EEG) analysis and neuropsychological (NP) tests.

Methods

Twenty-two drug-naïve epilepsy patients were enrolled. EEG recordings were performed before and after LEV therapy. Relative power of discrete frequency bands was computed, as well as alpha peak frequency (APF) at occipital electrodes. Eighteen patients performed a battery of NP tests twice across LEV treatment.

Results

LEV therapy decreased the power of delta (1–3 Hz, p < 0.01) and theta (3–7 Hz, p < 0.05) bands and increased that of alpha-2 (10–13 Hz, p < 0.05) and beta-2 (19–24 Hz, p < 0.05) bands. Region-specific spectral change was observed: delta power change was significant in fronto-polar region, theta in anterior region, alpha-2 in broad region, and beta-2 in left fronto-central region. APF change was not significant. Improvement in diverse NP tests requiring attention, working memory, language and executive function was observed. Change in theta, alpha-2, and beta-2 power was correlated with improvement in several NP tests.

Conclusions

Our data suggest LEV is associated with acceleration of background EEG frequencies and improved cognitive function. Change in frequency band power could predict improvement in several cognitive domains across LEV therapy.

Significance

Combined study of quantitative EEG analysis and NP tests can be useful in identifying cognitive effect of antiepileptic drugs.

Highlights

► We evaluated the effect of LEV on background EEG and cognition in epilepsy patients. ► LEV decreases slow frequency power and increases fast frequency power. ► LEV causes improvement in diverse neuropsychological tests. ► Some EEG changes across LEV therapy were correlated with change in cognitive tests.

Introduction

Antiepileptic drugs (AEDs) remain the primary treatment option in epilepsy. Although they can be effective for seizure control, AEDs can also cause neurotoxicity, adversely affecting normal functions of the central nervous system (CNS) (Ortinski and Kimford, 2004). Neuropsychological testing has been the preferred method of examining the impact of AEDs on cognitive functions, but suffers from several limitations, such as test–retest variability and practice effect (Clemens et al., 2006). Inclusion of quantitative EEG measures can provide additional insight in investigating the impact of pharmacological intervention on cognitive function (Gevins et al., 2002, Smith et al., 2006). Quantitative analysis of background EEG frequencies can be a simple and objective method of evaluating the effect of AEDs and disclosing its implication on cognitive function, since background EEG activity represents the functional state of the brain.

Levetiracetam (LEV) is one of the “new” AEDs that have demonstrated its effectiveness in the treatment of symptomatic and idiopathic epilepsy (Rocamora et al., 2006, Gambardella et al., 2008). LEV appears to be as effective as the older AEDs in seizure control, but is more tolerable and has more favorable neuropsychological profile (Berkovic et al., 2007). Neuropsychological examinations on patients with LEV therapy consistently show no negative effect, and even improvement in some studies (Piazzini et al., 2006, Gomer et al., 2007, Meador et al., 2007, Helmstaedter and Witt, 2008, Zhou et al., 2008). However, the effect of LEV on background EEG activity and neurophysiological relevance of these reported favorable neuropsychological findings are largely unexplored.

The primary objective of this study is to analyze the effect of LEV monotherapy on background EEG activity and to relate quantitative EEG findings with neuropsychological outcomes. We have quantified the relative power of discrete frequency bands before and after the LEV treatment, to observe whether LEV monotherapy causes background EEG change globally and/or locally at a certain brain region. Alpha peak frequency in occipital electrodes was also calculated. In parallel, standard neuropsychological tests have been administered to evaluate the effect of LEV on cognitive function. We hypothesized that the cognitive effect of LEV monotherapy on epilepsy patients can be better explored by combined neurophysiological and neuropsychological measures.

Section snippets

Patients

Twenty-two consecutive drug-naïve patients were recruited from an outpatient epilepsy clinic at Samsung Medical Center (SMC), between August 2007 and January 2010. Patients with newly or recently diagnosed epilepsy were included, who had least two unprovoked seizures (>48 h apart) during the last year at the time of study enrollment. The study was approved by the internal review committee in SMC (IRB file No. 2007-08-063-001) and all patients gave their written informed consent to participate in

Patients

Patient information and clinical information are summarized in Table 1. Out of 22 patients enrolled in this study, 13 were female. The mean age of the patients was 32.2 ± 13.0 years (range 16–58 years). The mean duration of the evaluation period (i.e. the interval between baseline and follow-up EEG recordings and neuropsychological tests) was 12.4 ± 3.6 months (range 8–22 months). The mean seizure frequency before first prescription was 3.4 ± 8.8 per month. The mean dose level of LEV at the end of

Discussion

To our knowledge, this is the first study to characterize changes in background EEG activity and NP tests after LEV monotherapy in drug-naïve epilepsy patients. Our study demonstrates that prolonged LEV treatment induced an acceleration of background EEG frequencies: a decrease in the relative power of delta and theta bands and an increase in that of fast frequency bands, specifically at alpha-2 and beta-2 (Fig. 2, Fig. 3). These effects were region-specific: we found decreased slow frequency

Disclosure

The authors report no conflicts of interest.

Acknowledgments

This work was supported by a grant (2010K000817) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and by a Grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (No. A110097).

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