Seizure Induced by Deep Transcranial Magnetic Stimulation in an Adolescent with Depression.
ABSTRACT: 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.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).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.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.
Project description:Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Here we combine transcranial magnetic stimulation with electroencephalography (TMS-EEG) to evaluate the effects of MST on connectivity and activation between the DLPFC, the SGC and hippocampus (Hipp) in patients with TRD. The TMS-EEG was collected from 31 TRD patients prior to and after an MST treatment trial. Through TMS-EEG methodology we evaluated significant current scattering (SCS) as an index of effective connectivity between the SGC and left DLPFC. Significant current density (SCD) was used to assess activity at the level of the Hipp. The SCS between the SGC and DLPFC was reduced after the course of MST (p?<?0.036). The DLPFC-SGC effective connectivity reduction correlated with the changes in Hamilton depression score pre-to-post treatment (R?=?0.46; p?<?0.031). The SCD localized to the Hipp was reduced after the course of MST (p?<?0.015), and the SCD change was correlated with montreal cognitive assessment (MOCA) scores pre-post the course of MST (R?=?-0.59; p?<?0.026). Our findings suggest that MST treatment is associated with SGC-DLPFC connectivity reduction and that changes to cognition are associated with Hipp activation reduction. These findings demonstrate two distinct processes which drive efficacy and side effects separately, and might eventually aid in delineating physiological TRD targets in clinical settings.
Project description:Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation (VNS), which continues to develop new technology, is approved for use in the United States. Deep brain stimulation of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to 1 or 2 seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS are split on efficacy, which may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of shake detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of electroencephalography (EEG) is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures, and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience.
Project description:Underage alcohol use is the leading cause of preventable mortality among adolescents in the USA. Moreover, the average age of onset of underage drinking is 13 years. This study examined the feasibility of using a text messaging survey (TMS) to assess adolescent alcohol use. A sample of 29 adolescents, aged 13-17 years, was recruited from two primary care clinics. They completed a 16 question TMS while in the waiting room and a two-question exit TMS. The participation rate was 87%. Two out of 25 (8%) adolescents met the criteria for hazardous drinking and 28% reported alcohol use. It was found that 38% and 25% of adolescents who completed the exit TMS were asked or advised about drinking, respectively. Text messaging to assess adolescent alcohol use in this setting seems feasible, does not disrupt patient workflow, and can assess many health behaviors before a clinical encounter.
Project description:Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical-evoked activity (CEA) and long-interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Results show that 44.4% of patients experienced resolution of suicidal ideation. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p?<?0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p?<?0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p?<?0.05; rho?=?0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC?=?0.9, p?=?0.004). There was no significant finding with motor cortex assessment. Overall, MST produced significant rates of resolution of suicidal ideation. MST also produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition-a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression.
Project description:Introduction:The use of transcranial magnetic stimulation (TMS) has become increasingly prevalent in psychiatry. A growing body of literature supports its use with treatment-resistant depression (TRD), and this indication has gained FDA approval. However, new psychiatry residents often have little exposure to or understanding of TMS. Methods:This animated, fully narrated, self-learning module (SLM) introduces learners to TMS and its use in TRD and can be completed within 30 minutes. The goal is for viewers to be proficient with the basic science, indications, contraindications, side effects, and treatment process for TMS in TRD. Self-assessment questions throughout the module highlight and reinforce key learning points falling under the educational objectives. Results:This SLM was deployed with PGY 1-4 training residents at the University of Minnesota during the 2016-2017 academic year as part of a study aimed at improving TMS education within our residency program. Fourteen residents participated in the study and offered feedback on the SLM's efficacy using 5-point Likert-scale surveys. Prior to the SLM's completion, the percentage of participants who disagreed or strongly disagreed with having met individual educational objectives ranged from 64% to 86%. Following completion, the percentage who agreed or strongly agreed with having met individual objectives ranged from 79% to 93%. Discussion:This SLM provides an introductory curriculum on TMS for TRD to medical students and psychiatry residents who otherwise might not be adequately exposed to this treatment modality. As institutions adopt TMS, the module can serve as a primer for trainees prior to hands-on experience with the technology.
Project description:Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.
Project description:INTRODUCTION:Intraoperative seizures under general anesthesia are rare and our observation is the first to demonstrate a distinct electroencephalogram (EEG) pattern on the Narcotrend monitor. PATIENT CONCERNS:We present the case of a 30-year-old man undergoing craniotomy for glioblastoma resection under general anesthesia who suffered tonic-clonic seizures captured in a specific pattern by the intraoperative EEG. DIAGNOSES:Our depth of anesthesia monitor recorded, before the seizure, a widening of the beta-wave performance in a distinct "triangular-shaped" pattern. This pattern was repeated before the second seizure. The patient had no previous history of seizures and following surgery no further seizures were recorded. INTERVENTIONS:A spectrogram analysis showed a distinct increase in mean absolute beta power immediately prior to the first seizure. The EEG immediately prior to the second seizure was characterized by broadband noise. Both seizures were characterized by increased mean absolute delta, theta, and beta power. OUTCOMES:The increase in EEG beta activity seen before the tonic-clonic movements may represent cortical irritability secondary to surgical manipulation, induced by electrical stimulation, reflecting progressive brain over-arousal. The attentive analysis of the relative beta power may have helped forecast the occurrence of the second seizure. LESSONS:We report the use of a simple, inexpensive, and portable EEG-based monitoring device to assist seizure detection and decision making.
Project description:Importance:Adolescent well care visits provide opportunities for clinicians to facilitate parent-adolescent communication (PAC) to reduce pregnancy, sexually transmitted infections, and alcohol-related harm among adolescents. Objective:To test the effect of brief parent-targeted interventions delivered in primary care settings on PAC about sexual and alcohol use behaviors. Design, Setting, and Participants:Randomized clinical trial conducted at a primary care pediatric practice from January 4, 2016, to April 10, 2017. Adolescents who were scheduled for a well care visit were recruited, along with their parent or guardian. Data analyses continued through April 30, 2018. Interventions:During well care visits, parents in sexual health intervention and alcohol prevention intervention groups received coaching to discuss written intervention materials encouraging PAC about sex or alcohol, respectively, with their adolescent within 2 weeks, followed by a brief clinician endorsement. After 2 weeks, parents received a follow-up telephone call. Control group parents received usual care. Main Outcomes and Measures:Participants were surveyed 4 months after the well care visit. Parent-reported and adolescent-reported quality of PAC was measured using the 20-item Parent-Adolescent Communication Scale, in which a higher score indicates better PAC; and frequency of PAC about sex or alcohol was measured using a 4-point Likert-type scale with 1 indicating not at all or never, and 4 indicating a lot or often. Results:Of 196 parent-adolescent dyads assessed for eligibility, 118 (60.2%) were eligible to participate. These 118 dyads were randomized to 1 of 3 groups: (1) sexual health intervention (n?=?38 [32.2%]); (2) alcohol prevention intervention (n?=?40 [33.9%]); and control (n?=?40 [33.9%]); 104 parents (88.1%) and 99 adolescents (83.9%) completed the study. Parents included 112 women (94.9%) and had a mean (SD) age of 45.8 (6.9) years. Adolescents included 60 girls (50.9%); 67 adolescents (56.8%) were aged 14 years, and 51 adolescents (43.2%) were aged 15 years. Participant race/ethnicity reflected that of the practice (63 black adolescents [53.4%]; 46 white adolescents [38.9%]; 111 non-Hispanic adolescents [94.1%]). At baseline, 15 adolescents (12.7%) reported a history of sexual behavior and 16 adolescents (13.6%) reported a history of alcohol use. Intention-to-treat analyses found that 4 months after the intervention, adolescents in the sexual health intervention group reported a higher mean frequency score for PAC about sex compared with those in the control group (2.32 [95% CI, 1.97-2.66] vs 1.79 [95% CI, 1.50-2.08]; P?=?.02); adolescents in the alcohol prevention intervention group reported a higher mean frequency score for PAC about alcohol compared with those in the control group (2.93 [95% CI, 2.60-3.25] vs 2.40 [95% CI, 2.08-2.72]; P?=?.03). Parent-reported frequency scores for PAC about sex or alcohol did not differ by group. Conclusions and Relevance:Brief parent-targeted interventions in primary care settings increased adolescent-reported frequency of PAC about sexual health and alcohol use and may be an important strategy for parents to influence adolescent behaviors and health outcomes. Trial Registration:ClinicalTrials.gov identifier: NCT02554682.
Project description:Transcranial magnetic stimulation (TMS) is an approved intervention for treatment-resistant depression (TRD), but current targeting approaches are only partially successful. Our objectives were (1) to examine the feasibility of MRI-guided TMS in the clinical setting using a recently published surface-based, multimodal parcellation in patients with TRD who failed standard TMS (sdTMS); (2) to examine the neurobiological mechanisms and clinical outcomes underlying MRI-guided TMS compared to that of sdTMS. We used parcel-guided TMS (pgTMS) to target the left dorsolateral prefrontal cortex parcel 46. Resting-state functional connectivity (rsfc) was assessed between parcel 46 and predefined nodes within the default mode and visual networks, following both pgTMS and sdTMS. All patients (n?=?10) who had previously failed sdTMS responded to pgTMS. Alterations in rsfc between frontal, default mode, and visual networks differed significantly over time between groups. Improvements in symptoms correlated with alterations in rsfc within each treatment group. The outcome of our study supports the feasibility of pgTMS within the clinical setting. Future prospective, double-blind studies of pgTMS vs. sdTMS appear warranted.
Project description:BACKGROUND:Suicide is a leading cause of death among youth. Prior research using transcranial magnetic stimulation (TMS) has implicated deficits in GABAergic cortical inhibition in adolescent suicidal behavior, yet no studies have assessed whether cortical inhibition varies over time in conjunction with changes in suicidal ideation (SI). This study examined dynamic changes in long-interval intracortical inhibition (LICI), a TMS measure of GABAB-mediated inhibition, and their relationship with changes in SI in a small sample of adolescents undergoing pharmacologic treatment for depression. METHODS:Ten depressed adolescents (aged 13-17) underwent clinical assessment and TMS testing at baseline and again at follow-up. All were treated with antidepressant medication in the interim. SI was measured with the Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of Ideation subscale. LICI was measured at interstimulus intervals of 100 and 150?ms. RESULTS:There was a significant partial correlation, controlling for change in depression severity, between ?LICI-100 and change in SI as measured by ?C-SSRS (??=?.746, df?=?7, p?=?.021), which remained after also controlling for time to follow-up assessment (??=?.752, df?=?6, p?=?.032). No significant correlation was observed between ?LICI-150 and change in SI. LIMITATIONS:Sample size; variable follow-up interval; inability to control for age, sex, and potential treatment effects. CONCLUSIONS:These data offer preliminary signal of an association between increases in GABAB-mediated cortical inhibition and reduction in SI over time in adolescents treated for depression. Further studies are warranted to explore the role of cortical inhibition in adolescent suicidal ideation and behavior.