Case Report of a Syncope Episode in a Healthy Male Adult Participant During Single-Pulse Transcranial Magnetic Stimulation To the Editor; W e report the following syncope epi- sode during a single-pulse transcra- nial magnetic stimulation (TMS) study. A healthy 19-year-old young man was partic- ipating in the first of 5 testing sessions. He consented to participation and using the TMS screening questionnaire reported no neurological or psychological risk factors and no history of head injuries, seizures, or epilepsy. 1 He had not received TMS pre- viously and did not report recent sleep dep- rivation, medication use, or high doses of caffeine or energy drinks. Testing commenced at 12:30 PM at a university, and the incident occurred at ap- proximately 1:00 PM. Single-pulse TMS was delivered via a MagPro R30 stimulator (Magventure, Farum, Denmark) with 70-mm figure-of-8 coil (MC-B70; Magventure) to the dominant (left) primary motor cortex (M1) over the hotspot for the first dorsal interossei (FDI). The subject was seated in an adjustable semireclined treatment chair (Magventure), with the dominant hand resting comfortably on the armrest. Follow- ing preparation of the skin and placement of surface electrodes over the FDI, the C3 scalp region was marked based on the elec- troencephalography international 10-20 sys- tem. The TMS coil was oriented at 45° to the midline and tangential to the scalp so the current flowed posteroanteriorly. The TMS machine was set to 45% of maximal stimu- lator output. To confirm the marked scalp region was the “hotspot” for FDI, the TMS coil was held over the marked region, and single-pulse stimuli were administered with interstimulus interval of 6 seconds. The sub- ject received 8 single-pulse stimuli, and when asked for feedback by the TMS oper- ator, he stated the stimuli felt “weird” and asked to “have a break. ” Testing was ceased immediately, and when asked to describe the sensations he experienced, he became nonre- sponsive. The TMS operator noted the sub- ject ’s head had fallen back toward the chair, his eyes were slightly open, and there were 3 to 4 twitch movements bilaterally in his hands. Because of limited space and equipment surrounding the testing area, the subject was unable to be transferred to a su- pine position. The TMS operator notified the senior team member, and after approxi- mately 20 to 30 seconds, the subject be- came responsive again. The subject had noticeable pallor of his face with systemic perspiration with increased skin tempera- ture. The subject was responsive to com- mands and able to orient himself, but was reporting loss of vision and able to detect only “vague outlines of objects. ” The sub- ject was then provided with a small glass of water, and immediately following 1 to 2 small sips of water, he reported a return of normal vision. The TMS operator noted color had returned to the subject's face, and perspiration and skin temperature had re- duced. It was at this time the subject reported 1 previous episode of syncope while under- going a blood test several years prior, with the same resolution of symptoms from drinking water. Under instruction from the TMS operator, the subject remained seated for the next 10 to 15 minutes and continued to drink small volumes of water. In this time, the TMS operator explained to the subject he may have experienced a syncope episode. The syncope episode self-terminated, and he did not experience any urinary or fecal in- continence, tongue biting, or other physi- cal trauma. As a precautionary measure, the TMS operator and senior team mem- ber escorted the subject approximately 100 m to the university medical clinic for medical examination. The TMS oper- ator provided a brief summary of events to the treating doctor before the subject underwent examination. The TMS operator and senior team member decided that the subject be with- drawn from further participation. The TMS operator kept in contact with the subject over the next 1 to 2 weeks, where he reported complete resolution of symptoms, and the treating doctor had diagnosed it as a syn- cope episode. The specific reasons for fa- voring this choice versus the differential diagnoses of a TMS-related seizure were the history of syncope during a blood test, the brief duration and rapid regaining from loss of consciousness (~20–30 seconds), lack of convulsions during and lack of con- fusion following the event, and previously published cases reporting similar episodes and symptoms. 2 A formal risk management incident report was submitted to the univer- sity occupational health and safety team. Syncope episodes during TMS are rare. While high numbers of TMS pulses can be safely delivered without producing signifi- cant adverse effects, there have been previ- ous reported cases of syncope episodes. 2,3 In addition, as in this case report, it has been reported that 46% of people have in- voluntary twitching movements after loss of consciousness during a syncope epi- sode. 4 These highlight the importance of comprehensive screening for risk factors that may increase the likelihood of a syn- cope episode. Kirton et al 3 discussed the in- volvement that anxiety and stress coupled with mildly noxious stimuli such as TMS pulses can sometimes result in a syncope episode and that adequate hydration and re- cent food intake may assist in minimizing these risks. The subject reported he had not yet had lunch, and therefore it is reason- able to suggest that inadequate food intake prior to participating in this study, with subsequent reduced blood sugar levels, contributed to the syncope episode. Following this event, we recommend the screening process for participation be modified to minimize the risk of future syn- cope episodes. Recognizing that anxiety and stress may contribute to syncope epi- sodes, we recommend systematically mon- itoring levels of anxiety and stress prior to participation via the State-Trait Anxiety Inventory. 5 When stress and anxiety levels are high, further explanations on the safety of TMS should be provided with the op- portunity to withdraw from participation. Furthermore, subjects should be asked if they have had previous syncope epi- sodes while undergoing mildly noxious stimuli such as blood tests. Lastly, we recommend subjects remain adequately hydrated throughout testing sessions and suggest they have adequate food intake prior to participation. While syncope episodes are rare, it is important future researchers report similar cases of adverse effects during TMS use in the continuous endeavor to identify and mini- mize factors contributing to syncope episodes. Michael Pellegrini, BSc (Hons) Non-Invasive Brain Stimulation and Neuroplasticity Laboratory Department of Physiotherapy School of Primary and Allied Health Care Faculty of Medicine Nursing and Health Science Monash University Melbourne, Australia michael.pellegrini@monash.edu Maryam Zoghi, PhD Department of Rehabilitation Nutrition and Sport School of Allied Health Discipline of Physiotherapy La Trobe University Melbourne, Australia Shapour Jaberzadeh, PhD Non-Invasive Brain Stimulation and Neuroplasticity Laboratory Department of Physiotherapy School of Primary and Allied Health Care Faculty of Medicine Nursing and Health Science Monash University Melbourne, Australia Journal of ECT • Volume 35, Number 2, June 2019 Letters to the Editor © 2019 Wolters Kluwer Health, Inc. All rights reserved. www.ectjournal.com e11 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.