Seizure Induced by Deep Transcranial Magnetic Stimulation in an Adolescent with Depression

Abstract

Objective: Deep transcranial magnetic stimulation (TMS) with an H-1 coil was recently approved by the U.S. Food and Drug Administration (U.S. FDA) for treatment-resistant depression (TRD) in adults. Studies assessing the safety and effectiveness of deep TMS in adolescent TRD are lacking. The purpose of this brief report is to provide a case history of an adolescent enrolled in an investigational deep TMS protocol. Methods: A case history is described of the first participant of a sham-controlled clinical trial who had a seizure in the course of deep TMS with parameter settings extrapolated from the adult studies that led to US FDA approval (H-1 coil, 120% target stimulation intensity, 18 Hz, 55 trains of 2-second duration, total 1980 pulses). Results: The participant was a 17-year-old unmedicated female, with no significant medical history and no history of seizures or of drug or alcohol use. Brain magnetic resonance imaging showed no structural abnormalities. She initially received sham, which was well tolerated. During active treatment sessions, titration began at 85% of motor threshold (MT) and increased by 5% per day. Her weekly MT measurements were stable. On her first day of 120% MT (8th active treatment), during the 48th train, the participant had a generalized, tonic-clonic seizure that lasted 90 seconds and resolved spontaneously. She had an emergency medicine evaluation and was discharged home without anticonvulsant medications. There were no further seizures reported at a 6-month follow-up. Conclusions: We report a deep TMS-induced generalized tonic-clonic seizure in an adolescent with TRD participating in a clinical trial. Given the demonstrated benefits of deep TMS for adult TRD, research investigating its use in adolescents with TRD is an important area. However, in light of this experience, additional precautions for adolescents should be considered. We propose that further dose-finding investigations are needed to refine adolescent-specific parameters that may be safe and effective for treating adolescents with TRD with deep TMS.

Safety of Transcranial Magnetic Stimulation in Children: A Systematic Review of the Literature

“…However, we did find three reports of new onset seizures 65, 68, 72 that are lacking in similar recent reviews. In two cases, patients were diagnosed and treated for depression with sertraline which has been associated with seizures, albeit rarely 85, 86 .…”

“…The mild adverse events were as follows: headache (n=45) 15, 21, 64, 69-71, 75, 78 , dizziness (n=8) 66, 69, 70 , jaw twitching (n=4) 66 , nausea/vomiting (n=4) 21, 75 , anxiety (n=3) 69 , neck stiffness (n=3) 21 , tingling/dullness (n=3) 69, 75 , scalp pain (n=2) 13, 67 , neck pain (n=2) 70 , restlessness (n=1) 77 , and sleepiness (n=1) 14 . Moderate adverse events include generalized tonic-clonic seizure (n=3) 65, 68, 72 and rapid moodswings (n=1) 77 . The only severe adverse event to occur in rTMS stimulation is 8-9 hours of stimulation-induced hypomania (n=1) 72 .…”

“…With multiple seizure risk factors, it is of crucial importance that TMS investigators carefully screen for medications and other potential seizure precipitants. The most recent case was an unmedicated youth with major depressive disorder treated with deep TMS 68 . Deep TMS uses H-coils that induce an effective field at a wider depth l compared to standard figure-8 TMS coils 91 .…”

Pediatric Neuromodulation Comes of Age

“…Standard localization techniques may identify variable locations for coil placement, but the clinical significance of this in unknown ). Cullen et al (2016) also present a case history of a deep TMSinduced generalized tonic-clonic seizure in an adolescent. This underscores the necessity of further safety and dose finding research in adolescents with major depressive disorder.…”

An Update on Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depressive Disorder

“…One major concern is new‐onset seizures, due to children and adolescents' lower seizure threshold in comparison with adults. However, only a few cases of rTMS‐induced seizures in children and adolescents with rTMS have been reported so far . In fact, a systematic review on the safety of rTMS in children (639 healthy children, 482 children with central nervous system disorders, and 84 children with epilepsy) suggested a similar risk from rTMS in children .…”