Transcranial magnetic stimulation‐evoked electroencephalography responses as biomarkers for epilepsy: A review of study design and outcomes

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS‐EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS‐EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti‐seizure medication. We searched the Cochrane Library, Embase, PubMed and Web of Science databases for original TMS‐EEG studies comparing people with epilepsy and healthy controls, and healthy subjects before and after taking anti‐seizure medication. Studies should involve quantitative analyses of TMS‐evoked EEG responses. We evaluated the reporting of study population characteristics and TMS‐EEG protocols (TMS sessions and equipment, TMS trials and EEG protocol), assessed the variation between protocols, and recorded the main TMS‐EEG findings. We identified 20 articles reporting 14 unique study populations and TMS methodologies. The median reporting rate for the group of people with epilepsy parameters was 3.5/7 studies and for the TMS parameters was 13/14 studies. TMS protocols varied between studies. Fifteen out of 28 anti‐seizure medication trials in total were evaluated with time‐domain analyses of single‐pulse TMS‐EEG data. Anti‐seizure medication significantly increased N45, and decreased N100 and P180 component amplitudes but in marginal numbers (N45: 8/15, N100: 7/15, P180: 6/15). Eight articles compared people with epilepsy and controls using different analyses, thus limiting comparability. The reporting quality and methodological uniformity between studies evaluating TMS‐EEG as an epilepsy biomarker is poor. The inconsistent findings question the validity of TMS‐EEG as an epilepsy biomarker. To demonstrate TMS‐EEG clinical applicability, methodology and reporting standards are required.