Cortical excitability in epilepsy and the impact of antiepileptic drugs: transcranial magnetic stimulation applications

ABSTRACT

Introduction

Epileptic conditions are characterized by impaired cortical excitation/inhibition balance and interneuronal disinhibition. Transcranial magnetic stimulation (TMS) is a neurophysiological method that assesses brain excitation/inhibition.

Area covered

This review was written after a detailed search in PubMed, EMBASE, ISI web of science, SciELO, Scopus, and Cochrane Controlled Trials databases from 1990 to 2020. It summarizes TMS applications for diagnostic and therapeutic purposes in epilepsy. TMS studies help to distinguish different epilepsy conditions and explore the antiepileptic drugs’ (AEDs’) effects on neuronal microcircuits and plasticity mechanisms. Repetitive TMS studies showed that low-frequency rTMS (0.33–1 Hz) can reduce seizures’ frequency in refractory epilepsy or pause ongoing seizures; however, there is no current approval for its use in such patients as adjunctive treatment to AEDs.

Expert opinion

There are variable and conflicting TMS results which reflect the distinct pathogenic mechanisms of each epilepsy condition, the dynamic epileptogenic process over the long disease course resulting in the development of recurrent spontaneous seizures and/or progression of epilepsy after it is established, and the differential effect of AEDs on cortical excitability. Future epilepsy research should focus on combined TMS/functional connectivity studies that explore the complex cortical excitability circuits and networks using different TMS parameters and techniques.

KEYWORDS:

• Epilepsy
• cortical excitability
• cortical disinhibition
• antiepileptic drugs
• transcranial magnetic stimulation (TMS)
• motor thresholds
• cortical silent period (CSP)
• intracortical inhibition
• intracortical facilitation

Article highlights

• Epileptic conditions are characterized by impaired balance between excitatory and inhibitory influences and interneuronal disinhibition at the cortical level.

• TMS is a neurophysiological method which can be used to assess cortical excitability in epilepsy and guiding AEDs therapy.

• TMS is safe and tolerable and not associated with severe adverse effects.

• TMS can provide information about the differential effect of AEDs on brain microcircuits and cortical plasticity mechanisms.

• Bi-hemispheric disturbances of cortical neuronal excitability and synaptic and interneuronal connectivity occur with generalized epilepsy, whereas in focal epilepsy, changes can spread beyond the epileptic focus but often remained lateralized.

• There are evidences for the therapeutic potential of low-frequency rTMS (0.33–1 Hz) to reduce seizure frequency in refractory epilepsy.

• The conflicting TMS findings reflect the distinct pathophysiology underlying each epilepsy condition, inter- and intra-individual dynamic epileptogenic process and the compensatory phenomena per individual over the long disease course and the changes on cortical excitability induced by AEDs.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.