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Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials

OBJECTIVE: Antiepileptic drug (AED) treatment failures may occur because there is insufficient drug in the brain or because of a lack of relevant therapeutic response. Until now it has not been possible to measure these factors. It has been recently shown that the combination of transcranial magneti...

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Autores principales: Premoli, Isabella, Biondi, Andrea, Carlesso, Sara, Rivolta, Davide, Richardson, Mark P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244669/
https://www.ncbi.nlm.nih.gov/pubmed/27808418
http://dx.doi.org/10.1111/epi.13599
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author Premoli, Isabella
Biondi, Andrea
Carlesso, Sara
Rivolta, Davide
Richardson, Mark P.
author_facet Premoli, Isabella
Biondi, Andrea
Carlesso, Sara
Rivolta, Davide
Richardson, Mark P.
author_sort Premoli, Isabella
collection PubMed
description OBJECTIVE: Antiepileptic drug (AED) treatment failures may occur because there is insufficient drug in the brain or because of a lack of relevant therapeutic response. Until now it has not been possible to measure these factors. It has been recently shown that the combination of transcranial magnetic stimulation and electroencephalography (TMS‐EEG) can measure the effects of drugs in healthy volunteers. TMS‐evoked EEG potentials (TEPs) comprise a series of positive and negative deflections that can be specifically modulated by drugs with a well‐known mode of action targeting inhibitory neurotransmission. Therefore, we hypothesized that TMS‐EEG can detect effects of two widely used AEDs, lamotrigine and levetiracetam, in healthy volunteers. METHODS: Fifteen healthy subjects participated in a pseudo‐randomized, placebo‐controlled, double‐blind, crossover design, using a single oral dose of lamotrigine (300 mg) and levetiracetam (3,000 mg). TEPs were recorded before and 120 min after drug intake, and the effects of drugs on the amplitudes of TEP components were statistically evaluated. RESULTS: A nonparametric cluster‐based permutation analysis of TEP amplitudes showed that AEDs both increased the amplitude of the negative potential at 45 msec after stimulation (N45) and suppressed the positive peak at 180 msec (P180). This is the first demonstration of AED‐induced modulation of TMS‐EEG measures. SIGNIFICANCE: Despite the different mechanism of action that lamotrigine and levetiracetam exert at the molecular level, both AEDs impact the TMS‐EEG response in a similar way. These TMS‐EEG fingerprints observed in healthy subjects are candidate predictive markers of treatment response in patients on monotherapy with lamotrigine and levetiracetam.
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spelling pubmed-52446692017-01-25 Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials Premoli, Isabella Biondi, Andrea Carlesso, Sara Rivolta, Davide Richardson, Mark P. Epilepsia Full‐length Original Research OBJECTIVE: Antiepileptic drug (AED) treatment failures may occur because there is insufficient drug in the brain or because of a lack of relevant therapeutic response. Until now it has not been possible to measure these factors. It has been recently shown that the combination of transcranial magnetic stimulation and electroencephalography (TMS‐EEG) can measure the effects of drugs in healthy volunteers. TMS‐evoked EEG potentials (TEPs) comprise a series of positive and negative deflections that can be specifically modulated by drugs with a well‐known mode of action targeting inhibitory neurotransmission. Therefore, we hypothesized that TMS‐EEG can detect effects of two widely used AEDs, lamotrigine and levetiracetam, in healthy volunteers. METHODS: Fifteen healthy subjects participated in a pseudo‐randomized, placebo‐controlled, double‐blind, crossover design, using a single oral dose of lamotrigine (300 mg) and levetiracetam (3,000 mg). TEPs were recorded before and 120 min after drug intake, and the effects of drugs on the amplitudes of TEP components were statistically evaluated. RESULTS: A nonparametric cluster‐based permutation analysis of TEP amplitudes showed that AEDs both increased the amplitude of the negative potential at 45 msec after stimulation (N45) and suppressed the positive peak at 180 msec (P180). This is the first demonstration of AED‐induced modulation of TMS‐EEG measures. SIGNIFICANCE: Despite the different mechanism of action that lamotrigine and levetiracetam exert at the molecular level, both AEDs impact the TMS‐EEG response in a similar way. These TMS‐EEG fingerprints observed in healthy subjects are candidate predictive markers of treatment response in patients on monotherapy with lamotrigine and levetiracetam. John Wiley and Sons Inc. 2016-11-03 2017-01 /pmc/articles/PMC5244669/ /pubmed/27808418 http://dx.doi.org/10.1111/epi.13599 Text en © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full‐length Original Research
Premoli, Isabella
Biondi, Andrea
Carlesso, Sara
Rivolta, Davide
Richardson, Mark P.
Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials
title Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials
title_full Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials
title_fullStr Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials
title_full_unstemmed Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials
title_short Lamotrigine and levetiracetam exert a similar modulation of TMS‐evoked EEG potentials
title_sort lamotrigine and levetiracetam exert a similar modulation of tms‐evoked eeg potentials
topic Full‐length Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244669/
https://www.ncbi.nlm.nih.gov/pubmed/27808418
http://dx.doi.org/10.1111/epi.13599
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