Brigham Research Institute Poster Session Site logo-1
Close this search box.

Quinn Rademaker


BWH Job Title:

Research Assistant

Academic Rank:





Quinn J. Rademaker, Jong Woo Lee MD, PhD, Mo Shafi MD, PhD, Michael D Fox MD, PhD, Samuel B Snider MD

Interim Analysis of Epileptiform Discharge Inhibition with TMS (EDIT) Study



Focal epileptiform discharges are frequently encountered in hospitalized patients with acute brain injuries or structural brain abnormalities. They constitute an increased risk for future seizures1-3, show a frequency-dependent association with brain tissue hypoxia4, 5, and are independently associated with poor outcome in patients with and without brain injury6-10. Whether the discharges themselves are causally related to outcome is unknown. Testing this would require a tool capable of reducing epileptiform discharge burden rapidly.

A 1-2 week course of daily Repetitive Transcranial magnetic stimulation (rTMS) is a non-invasive means of focally inhibiting an underlying brain region. One fundamental barrier to testing this intervention is that it takes 1-2 weeks, not a feasible time frame for an acutely needed therapy. rTMS protocols for psychiatric conditions have recently been shown to have equivalent treatment efficacy after consolidation from months-long daily treatments to 10 hourly treatments over several days15, 16. This pilot study aims to assess a similarly accelerated course of rTMS for patients with symptomatic epileptiform discharges.


We conducted an open-label Phase I prospective clinical study of TMS in patients with symptomatic focal epileptiform discharges and seizures. We enrolled adult patients receiving continuous EEG monitoring with focal status epilepticus or focal periodic discharges and (a) symptoms attributable to these discharges including time-locked focal motor activity, encephalopathy or focal deficits, or concomitant clinical or electrographic seizures emanating from the same brain region or (b) electrographic characteristics associated with brain tissue hypoxia. Patients were only enrolled if there was no intention of the treating clinical team at time of enrollment to add an antiseizure medication. Enrolled patients completed two consecutive days of three 30 min sessions of 1 Hz rTMS spaced 1 hour apart at 100% of resting motor threshold, targeting the site of maximal discharge amplitude or focal seizure onset on a full montage scalp EEG montage. We measured epileptic discharge and/or seizure burden for 24 hours preceding and 24 hours following the treatment. Our primary outcome was the proportion of patients able to complete the full protocol and our primary safety outcome was treatment-emergent serious adverse events, as adjudicated by an independent panel. Here, we report an interim analysis of the first 4 patients.


Between November 2022 and March 2024, four patients have been enrolled. The mean +/- SD age was 73 (5.7). 3 of 4 patients (75%) completed the study protocol. One patient had treatment aborted after a single TMS session due to an adverse event (focal electrographic seizure). Independent review concluded this seizure was not clearly caused by the treatment (the patient had been having frequent seizures). Comparing the normalized burden of epileptiform activity 24 hours after compared to before treatment, subject 1 experienced at 42.5% decline in seizures, subject 2 had a 5.9% increase in epileptiform discharges and subject 3 had a 9.1% decline in discharges.

The interim analysis shows that accelerated rTMS treatment may be safe and feasible in patients with refractory focal epileptiform activity.


1. Struck AF, Tabaeizadeh M, Schmitt SE, et al. Assessment of the Validity of the 2HELPS2B Score for Inpatient Seizure Risk Prediction. JAMA Neurol 2020;77:500-507.

1. Struck AF, Osman G, Rampal N, et al. Time-dependent risk of seizures in critically ill patients on continuous electroencephalogram. Ann Neurol 2017;82:177-185.

1. Shafi MM, Westover MB, Cole AJ, Kilbride RD, Hoch DB, Cash SS. Absence of early epileptiform abnormalities predicts lack of seizures on continuous EEG. Neurology 2012;79:1796-1801.

1. Subramaniam T, Jain A, Hall LT, et al. Lateralized periodic discharges frequency correlates with glucose metabolism. Neurology 2019;92:e670-e674.

1. Witsch J, Frey HP, Schmidt JM, et al. Electroencephalographic Periodic Discharges and Frequency-Dependent Brain Tissue Hypoxia in Acute Brain Injury. JAMA Neurol 2017;74:301-309.

1. Zafar SF, Rosenthal ES, Jing J, et al. Automated annotation of epileptiform burden and its association with outcomes. Ann Neurol 2021.

1. Kim JA, Zheng WL, Elmer J, et al. High epileptiform discharge burden predicts delayed cerebral ischemia after subarachnoid hemorrhage. Clin Neurophysiol 2021.

1. Lin L, Al-Faraj A, Ayub N, et al. Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes. Ann Neurol 2021;89:872-883.

1. Lissak IA, Locascio JJ, Zafar SF, et al. Electroencephalography, Hospital Complications, and Longitudinal Outcomes After Subarachnoid Hemorrhage. Neurocrit Care 2021.

1. Tabaeizadeh M, Aboul Nour H, Shoukat M, et al. Burden of Epileptiform Activity Predicts Discharge Neurologic Outcomes in Severe Acute Ischemic Stroke. Neurocrit Care 2020;32:697-706.

1. Fregni F, Otachi PT, Do Valle A, et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol 2006;60:447-455.

1. Cantello R, Rossi S, Varrasi C, et al. Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial. Epilepsia 2007;48:366-374.

1. Sun W, Mao W, Meng X, et al. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study. Epilepsia 2012;53:1782-1789.

1. Tsuboyama M, Kaye HL, Rotenberg A. Review of Transcranial Magnetic Stimulation in Epilepsy. Clin Ther 2020;42:1155-1168.

1. Williams NR, Sudheimer KD, Bentzley BS, et al. High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain 2018;141:e18.

1. Williams NR, Sudheimer KD, Cole EJ, et al. Accelerated neuromodulation therapy for Obsessive-Compulsive Disorder. Brain Stimul 2021;14:435-437.