Biomarkers Obtained by Transcranial Magnetic Stimulation of the Motor Cortex in Epilepsy.

Melissa Tsuboyama,Alexander Rotenberg,Harper Lee Kaye

doi:10.3389/fnint.2019.00057

Abstract

Epilepsy is associated with numerous neurodevelopmental disorders. Transcranial magnetic stimulation (TMS) of the motor cortex coupled with electromyography (EMG) enables biomarkers that provide measures of cortical excitation and inhibition that are particularly relevant to epilepsy and related disorders. The motor threshold (MT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) are among TMS-derived metrics that are modulated by antiepileptic drugs. TMS may have a practical role in optimization of antiepileptic medication regimens, as studies demonstrate dose-dependent relationships between TMS metrics and acute medication administration. A close association between seizure freedom and normalization of cortical excitability with long-term antiepileptic drug use highlights a plausible utility of TMS in measures of anti-epileptic drug efficacy. Finally, TMS-derived biomarkers distinguish patients with various epilepsies from healthy controls and thus may enable development of disorder-specific biomarkers and therapies both within and outside of the epilepsy realm.

Highlights

Transcranial magnetic stimulation (TMS) BASICS AND MEASURES IN EPILEPSYEpilepsy is among the most common neurologic disorders in childhood, and accompanies numerous neurodevelopmental disorders, the autism spectrum disorders (ASDs; Levisohn, 2007; Tuchman and Rapin, 2002; Danielsson et al, 2005)
Epilepsy is associated with numerous neurodevelopmental disorders
The motor threshold (MT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) are among Transcranial magnetic stimulation (TMS)-derived metrics that are modulated by antiepileptic drugs

Summary

TMS BASICS AND MEASURES IN EPILEPSY

Epilepsy is among the most common neurologic disorders in childhood, and accompanies numerous neurodevelopmental disorders, the autism spectrum disorders (ASDs; Levisohn, 2007; Tuchman and Rapin, 2002; Danielsson et al, 2005). When positioned over the motor cortex, TMS by a figure-of-eight coil enables selective activation of intrinsic hand muscles in the limb contralateral to the stimulated hemisphere, without co-activation of more proximal muscle groups Such motor cortex activation can be quantified with skin surface electromyography (EMG) that records a per-stimulus motor evoked potential (MEP) which predictably reflects the magnitude of stimulation and is the main outcome measure in TMS studies of the cortical excitation:inhibition (E:I) ratio (Figure 1; reviewed in Kobayashi and Pascual-Leone, 2003; Frye et al, 2008). Long-interval intracortical inhibition (LICI) is measured using ppTMS with two supra-threshold stimuli applied at long ISIs of 50–300 ms in which the conditioning stimulus inhibits the test MEP Topiramate (TPM), like VPA has several mechanisms of action, including voltage gated sodium channel antagonism, but does not affect rMT while reducing ICF as its anti-epileptic properties stem primarily from inhibition of ligand-gated AMPA subtype

Likely mechanism

Examples of change with medication

No No

DS SSADHD

Findings

CONCLUSION