Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

A novel technique for intraoperative mapping of the somatosensory cortex.

OBJECTIVE: Intraoperative mapping of the nervous system is used to identify "eloquent" cortical areas. In this technical report, we describe a novel way of mapping the somatosensory cortex so that injury to those critical pathways can be avoided. METHODS: An 8 year old female with drug resistant epilepsy presented for resection of a right posterior parietal focal cortical dysplasia. Left median nerve stimulation was used to record somatosensory evoked potentials (SEP) directly from the somatosensory cortex with a strip electrode. A handheld monopolar electrode was also used to record both the median and tibial SEP. Total intravenous anesthesia with propofol and remifentanil was used. RESULTS: SEP recordings were obtained from a 4-contact strip electrode placed across the central sulcus. A phase reversal was identified and the most likely post central gyrus was noted. With the strip electrode left in place, a monopolar handheld electrode was used to record the median nerve SEPs from different locations on the post central gyrus. The tibial nerve was also stimulated to record where the highest amplitude tibial nerve SEP was present. This map was used delineate functionally "eloquent" areas to avoid during surgery. During resection, the median nerve SEP was recorded from the strip electrode continuously. No significant change in the SEP was noted, and the patient awoke without any sensory deficits. CONCLUSIONS: Sensory mapping of the cortex is possible with a handheld monopolar electrode. This technique is easy to perform and can help reduce neurological morbidity.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Facilitation of motor evoked potentials after tetanic peripheral nerve stimulation.

OBJECTIVE: Tetanic stimulation of a peripheral nerve prior to transcranial electrical stimulation (TES) may enhance motor evoked potential (MEP) amplitudes. The purpose of this study was to investigate the post-tetanic MEP (p-MEP) technique in improving MEP amplitudes. METHODS: Conventional TES MEPs (c-MEP) and p-MEPs with left upper limb stimulation (p-MEPUL) or left lower limb stimulation (p-MEPLL) were performed in 26 patients. Bilateral hand and foot MEP amplitudes obtained with each protocol were compared. Subgroup comparisons were performed for myelopathy and peripheral neuropathy patients. Within-subject amplitude differences between c-MEP and each p-MEP technique were compared using a Wilcoxon test. RESULTS: The mean age of the patients was 52.7 years (range, 12-79 years). Overall, p-MEPUL resulted in MEP improvement in 25 of 26 (96%) patients, and p-MEPLL improved MEPs in 19 of 26 (73%) patients. The increase in MEP amplitudes were statistically significant in all muscle groups except left foot. Similar improvements were seen in the myelopathy group; in the neuropathy group, p-MEPUL produced similar results, but p-MEPLL did not. CONCLUSIONS: The p-MEP technique can improve MEP amplitudes, including in patients with myelopathy. In patients with peripheral neuropathy, the results were mixed. SIGNIFICANCE: Tetanic stimulation can enhance intraoperative MEP amplitudes.

Dosing and transition characteristics in people with narcolepsy transitioning from sodium oxybate to low-sodium oxybate: Data from the real-world TENOR study.

OBJECTIVE: The Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR) study assessed the real-world experience of people with narcolepsy switching from sodium oxybate (SXB) to low-sodium oxybate (LXB; 92 % less sodium than SXB). METHODS: TENOR is a patient-centric, prospective, observational, virtual-format study. Eligible participants included US adults with narcolepsy transitioning from SXB to LXB (±7 days from LXB initiation). Longitudinal data were collected from baseline (taking SXB) through 21 weeks post-transition. RESULTS: TENOR included 85 participants with narcolepsy (type 1, n = 45; type 2, n = 40). Mean (SD) age was 40.3 (13.0) years; the majority (73 %) were female and White (87 %). At study completion, wake-promoting agents were the most common concomitant medications (47 %). Mean (SD) SXB treatment duration was 57.8 (52.1) months; 96 % took SXB twice nightly. After transitioning, 97 % continued on twice-nightly regimens. Mean (SD) dose of both total nightly SXB (n = 85) and baseline LXB (n = 84) was 7.7 (1.5) g; SXB-LXB dose conversions at baseline were gram-for-gram in 87 % of participants. The mean final total nightly dose of LXB was 7.9 g. The most common participant-reported reasons for transitioning included lower sodium content for improved long-term health (93 %), physician recommendation (47 %), to avoid cardiovascular issues (39 %), to avoid side effects (31 %), and to improve control of narcolepsy symptoms (18 %). CONCLUSION: Most participants transitioned from SXB to LXB using a gram-for-gram strategy. The most commonly cited reason for transition was long-term health benefits due to lower sodium.

Impairment in Functioning and Quality of Life in Patients with Idiopathic Hypersomnia: The Real World Idiopathic Hypersomnia Outcomes Study (ARISE).

Purpose: Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness, sleep inertia, and prolonged sleep. Its impact on patients' quality of life and daily functioning has not been fully elucidated. The Real World Idiopathic Hypersomnia Outcomes Study (ARISE) evaluated the daily functioning, relationships, cognition, emotional well-being, and productivity/employment of participants with idiopathic hypersomnia. Patients and Methods: ARISE was a US-based virtual cross-sectional survey comprising multiple patient-reported outcome measures (Functional Outcomes of Sleep Questionnaire, short version [FOSQ-10], Quality of Life in Neurological Disorders [Neuro-QoL] Social Roles and Stigma domains, British Columbia Cognitive Complaints Inventory [BC-CCI], Patient Health Questionnaire [PHQ-9], and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP]). Participants were adults 21-65 years of age with idiopathic hypersomnia. Data were analyzed for all participants and for subgroups with/without long sleep time (LST; self-reported sleep ≥11 hours in 24 hours). Results: Of 75 participants enrolled, most were female (81.3%) and the mean (SD) age was 34.1 (10.7) years. Participants' scores on the FOSQ-10 (mean [SD] score: 10.7 [2.8]) and the Neuro-QoL Social Roles (43.4 [4.2]) and Stigma (57.3 [5.9]) domains reflected impairments in daily functioning and quality of life. More than half of participants reported moderate to severe cognitive complaints (BC-CCI; 62.7%) and moderate to severe depressive symptoms (PHQ-9; 66.7%). Scores on the WPAI:SHP showed substantial impairments in absenteeism, presenteeism, overall work productivity, and overall regular daily activity (mean percent [SD]: 12.3 [23.6], 47.6 [22.7], 51.4 [24.7], and 64.0 [21.9], respectively). These considerable impairments were found in participants with and without LST. Conclusion: ARISE participants with idiopathic hypersomnia demonstrated poor quality of life and impaired functioning across multiple symptom domains.

Effectiveness and tolerability in people with narcolepsy transitioning from sodium oxybate to low-sodium oxybate: Data from the real-world TENOR study.

OBJECTIVES: The Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR) study was conducted to provide real-world insight into the experience of people with narcolepsy switching from sodium oxybate (SXB) to low-sodium oxybate (LXB; 92% less sodium than SXB). METHODS: TENOR is a patient-centric, prospective, observational, virtual-format study. Participants were adults with narcolepsy (type 1 or 2) who were transitioning from SXB to LXB treatment (±7 days from LXB initiation). Effectiveness and tolerability data were collected online from baseline (taking SXB) through 21 weeks (taking LXB) via daily and weekly diaries and questionnaires, including the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire, short version (FOSQ-10), and the British Columbia Cognitive Complaints Inventory (BC-CCI). RESULTS: TENOR participants (N = 85) were 73% female with a mean (SD) age of 40.3 (13.0) years. Mean (SD) ESS scores decreased numerically throughout the transition from SXB to LXB (baseline: 9.9 [5.2]; week 21: 7.5 [4.7]), with 59.5% and 75.0% of participants having scores in the normal range (≤10) at baseline and week 21, respectively. Mean (SD) FOSQ-10 scores (baseline: 14.4 [3.4]; week 21: 15.2 [3.2]) and BC-CCI scores (baseline: 6.1 [4.4]; week 21: 5.0 [4.3]) also remained stable. The most common symptoms related to tolerability reported by participants at baseline were sleep inertia, hyperhidrosis, and dizziness (45.2%, 40.5%, and 27.4%, respectively), which decreased in prevalence by week 21 (33.8%, 13.2%, and 8.8%, respectively). CONCLUSIONS: Findings from TENOR confirm maintenance of effectiveness and tolerability when transitioning from SXB to LXB treatment.

Automated Interpretation of Clinical Electroencephalograms Using Artificial Intelligence.

Importance: Electroencephalograms (EEGs) are a fundamental evaluation in neurology but require special expertise unavailable in many regions of the world. Artificial intelligence (AI) has a potential for addressing these unmet needs. Previous AI models address only limited aspects of EEG interpretation such as distinguishing abnormal from normal or identifying epileptiform activity. A comprehensive, fully automated interpretation of routine EEG based on AI suitable for clinical practice is needed. Objective: To develop and validate an AI model (Standardized Computer-based Organized Reporting of EEG-Artificial Intelligence [SCORE-AI]) with the ability to distinguish abnormal from normal EEG recordings and to classify abnormal EEG recordings into categories relevant for clinical decision-making: epileptiform-focal, epileptiform-generalized, nonepileptiform-focal, and nonepileptiform-diffuse. Design, Setting, and Participants: In this multicenter diagnostic accuracy study, a convolutional neural network model, SCORE-AI, was developed and validated using EEGs recorded between 2014 and 2020. Data were analyzed from January 17, 2022, until November 14, 2022. A total of 30 493 recordings of patients referred for EEG were included into the development data set annotated by 17 experts. Patients aged more than 3 months and not critically ill were eligible. The SCORE-AI was validated using 3 independent test data sets: a multicenter data set of 100 representative EEGs evaluated by 11 experts, a single-center data set of 9785 EEGs evaluated by 14 experts, and for benchmarking with previously published AI models, a data set of 60 EEGs with external reference standard. No patients who met eligibility criteria were excluded. Main Outcomes and Measures: Diagnostic accuracy, sensitivity, and specificity compared with the experts and the external reference standard of patients' habitual clinical episodes obtained during video-EEG recording. Results: The characteristics of the EEG data sets include development data set (N = 30 493; 14 980 men; median age, 25.3 years [95% CI, 1.3-76.2 years]), multicenter test data set (N = 100; 61 men, median age, 25.8 years [95% CI, 4.1-85.5 years]), single-center test data set (N = 9785; 5168 men; median age, 35.4 years [95% CI, 0.6-87.4 years]), and test data set with external reference standard (N = 60; 27 men; median age, 36 years [95% CI, 3-75 years]). The SCORE-AI achieved high accuracy, with an area under the receiver operating characteristic curve between 0.89 and 0.96 for the different categories of EEG abnormalities, and performance similar to human experts. Benchmarking against 3 previously published AI models was limited to comparing detection of epileptiform abnormalities. The accuracy of SCORE-AI (88.3%; 95% CI, 79.2%-94.9%) was significantly higher than the 3 previously published models (P < .001) and similar to human experts. Conclusions and Relevance: In this study, SCORE-AI achieved human expert level performance in fully automated interpretation of routine EEGs. Application of SCORE-AI may improve diagnosis and patient care in underserved areas and improve efficiency and consistency in specialized epilepsy centers.

Symptom Severity and Treatment Satisfaction in Patients with Idiopathic Hypersomnia: The Real World Idiopathic Hypersomnia Outcomes Study (ARISE).

Objective: Idiopathic hypersomnia is a debilitating sleep disorder characterized by excessive daytime sleepiness, sleep inertia, and prolonged sleep duration. The patient burden of idiopathic hypersomnia is poorly understood. The Real World Idiopathic Hypersomnia Outcomes Study (ARISE) evaluated symptoms and treatment effectiveness/satisfaction in participants with idiopathic hypersomnia. Methods: ARISE was a United States-based virtual cross-sectional survey. Participants were adults 21-65 years of age with idiopathic hypersomnia recruited from social media, the Hypersomnia Foundation website, and a patient panel. Self-assessments included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Treatment Satisfaction Questionnaire for Medication, version II (TSQM-vII), and additional treatment questions. Data were analyzed for all participants and for subgroups with/without long sleep time (LST; ≥11 hours in 24 hours). Results: Of 75 participants enrolled, most were female (81.3%). The mean (SD) age was 34.1 (10.7) years and 49% had LST. Most participants took off-label prescription medications (89.3%) and/or used other measures (93.3%) to manage their symptoms. The mean (SD) ESS score was 14.5 (3.5) and the mean IHSS score was 35.2 (7.6). Treatment satisfaction was low (mean [SD] TSQM-vII score: overall, 61.9 [21.2]; with LST, 57.9 [21.4]; without LST, 66.7 [20.3]), primarily driven by dissatisfaction with treatment effectiveness. The most common classes of prescription medications used were stimulants (61.3%), wake-promoting agents (28.0%), and antidepressants (18.7%); non-prescription measures used to manage symptoms included caffeine (73.3%), planned naps (34.7%), and individual accommodations (32.0%). Conclusion: Overall, participants with idiopathic hypersomnia, with or without LST, had substantial symptom burden despite most of the study population taking off-label medications and using nonprescription measures to manage symptoms.

Association Between Standardized Mortality Ratio and Utilization of Care in US Veterans With Drug-Resistant Epilepsy Compared With All US Veterans and the US General Population.

Importance: Drug-resistant epilepsy (DRE) is thought to be associated with increased mortality, but larger population-based studies are lacking. Additionally, the benefit of effective management in DRE lacks evidence. Objective: To examine the association of utilization of care with mortality in US veterans with DRE. Design, Setting, and Participants: Observational cohort study conducted between October 1, 2013, and March 31, 2020. Mortality statistics in US veterans with DRE were compared to the US general population and all veterans within the Veterans Health Administration. Epilepsy was defined as use of 1 or more antiseizure medications (ASMs) for 30 days or longer with a seizure diagnosis or 1 inpatient or 2 outpatient encounters with an epilepsy diagnosis. DRE was defined as the use of 2 or more ASMs. Among 9.6 million US veterans, 164 435 (1.7%) had epilepsy, of whom 55 571 (33.8%) had DRE. Epilepsy and DRE were administratively identified based on criteria noted in design. Identified participants were included for analysis. Exposures: Veterans with DRE. Main Outcomes and Measures: Standardized mortality ratio (SMR). Results: Among US veterans with DRE, the mean (SD) age was 58.3 (15.4) years, and 49 430 individuals (88.9%) were male. Of ethnicity data gathered, 3170 individuals (5.7%) were Hispanic or Latino, 50 599 (91.1%) were not Hispanic or Latino, 842 (1.5%) declined to answer, and 960 (1.7%) were recorded as unknown. Of race data gathered, 516 individuals (0.9%) were American Indian or Alaskan Native, 270 (0.5%) were Asian, 11 316 (20.4%) were Black or African American, 587 (1.1%) were of multiple races, 453 (0.8%) were Native Hawaiian or Pacific Islander, 39 543 (71.2%) were White, 1697 (3.1%) declined to answer, and 1189 (2.1%) were recorded as unknown. SMR was 1.50 (95% CI, 1.47-1.53) compared with the US general population and 1.56 (95% CI, 1.53-1.59) compared with all veterans. Utilization rates were 81.1% (n = 45 057) for neurology clinic evaluation, 66.4% (n = 36 905) for magnetic resonance imaging (MRI), and 49.6% (n = 27 546) for electroencephalography (EEG) testing. Only 8350 individuals (15.0%) had comprehensive epilepsy evaluations and 3357 (6.0%) had epilepsy monitoring. Multivariable analysis revealed an association between lower mortality and neurology clinic evaluation, EEG, MRI, epilepsy monitoring, and the use of more than 2 ASMs after adjusting for age and comorbidities. Conclusions and Relevance: Mortality rates were significantly higher in US veterans with DRE compared to the general population. Better utilization of comprehensive epilepsy care, diagnostic services, and medications were each associated with reduced mortality. These findings indicate that appropriate management of DRE is critical in this population.

Intraoperative Electromyography in Awake Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Case Study on Nerve Activation Under the Effects of Local Anesthesia.

SUMMARY: With the versatility of lumbar spine surgery continually expanding, intraoperative electromyography (EMG) has become a common adjunct used to reduce risk of nerve injury and postoperative neurologic deficit. EMG monitoring has been deemed particularly useful in the minimally invasive transforaminal lumbar interbody fusion. A more recent evolution of the minimally invasive transforaminal lumbar interbody fusion entails complete percutaneous access to the disc through Kambin's triangle, followed by a percutaneous lumbar interbody fusion. Given the lack of direct visualization of nervous structures with percutaneous entrance into the disc, there is risk of injury to surrounding nervous structures with this approach. In effort to reduce risk of nerve injury, application of triggered EMG to gauge proximity of nervous tissue has been evaluated. Recently, patients presenting with contraindications or concerns for general anesthesia have been offered the alternative to undergo their procedure with spinal anesthesia, allowing them to remain awake. Spinal anesthesia entails intrathecal administration of local anesthetic, which mechanistically acts to reduce overall excitability of surrounding neural structures. However, nerve activation under conditions of local anesthetic is relatively unknown, and the ability of triggered EMG monitoring to reliably detect nerve proximity becomes questionable. This case report demonstrates nerve activation at thresholds comparable with those seen under general anesthesia. Although this has sparked interest in the possibility that local anesthetic may not remarkably affect nerve excitability as measured by triggered EMG activation, further investigation is recommended to reliably apply triggered EMG monitoring in awake spine surgery.

Thermal Protection Strategies and Neuromonitoring during Ablation.

Advanced interventional pain management approaches seek to lesion neural targets to achieve desirable analgesia; however, equally important is preservation of motor and sensory function for regional bystander nerves. The topic of neuroprotection is also relevant for thermal ablation of metastatic bone tumors in the vicinity of neural structures. This report aims to provide an IR-directed framework of thermoprotective techniques available during thermal ablation.

Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial.

OBJECTIVE: Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and ≥1 second-line intravenous (IV) antiseizure medication (ASM). Guidelines recommend IV anesthesia when second-line ASMs have failed, but potential harms can outweigh the benefits. Novel treatments are needed to stop and durably control RSE without escalation to IV anesthetics. Ganaxolone is an investigational neuroactive steroid in development for RSE treatment. This study's objective was to determine the appropriate dosing for IV ganaxolone in RSE and obtain a preliminary assessment of efficacy and safety. METHODS: This was an open-label, phase 2 trial conducted from February 19, 2018 to September 18, 2019, at three sites in the United States. Patients were aged ≥12 years, had convulsive or nonconvulsive SE, and failed to respond to ≥1 second-line IV ASM. Twenty-one patients were screened; 17 were enrolled. Patients received IV ganaxolone added to standard-of-care ASMs. Ganaxolone infusion was initiated as an IV bolus (over 3 min) with continuous infusion of decreasing infusion rates for 48-96 h followed by an 18-h taper. There were three ganaxolone dosing cohorts: low, 500 mg/day; medium, 650 mg/day; and high, 713 mg/day. The primary end point was the number of patients not requiring escalation to IV anesthetic treatment within 24 h of ganaxolone initiation. RESULTS: Most of the 17 enrolled patients (65%) had nonconvulsive SE, and had failed a median of three prior ASMs, including first-line benzodiazepine and second-line IV ASM therapy. Median time to SE cessation following ganaxolone initiation was 5 min. No patient required escalation to third-line IV anesthetics during the 24-h period following ganaxolone initiation. Two treatment-related serious adverse events (sedation) were reported. Of the three deaths, none was considered related to ganaxolone; all occurred 9-22 days after completing ganaxolone. SIGNIFICANCE: IV ganaxolone achieved rapid and durable seizure control in patients with RSE, and showed acceptable safety and tolerability.

Dorsal root entry zone procedure and other surgeries for pain.

Pain is a very common symptom that often serves a protective function. It is typically treated medically. When pain becomes chronic and intractable, it no longer serves a protective function and often requires more aggressive forms of treatment. Many types of surgeries can be performed for the management of pain. These surgeries can involve ablation (destruction) or augmentation (stimulation or facilitation) of some part of the nervous system. In many of these surgeries, neurophysiologic intraoperative monitoring (NIOM) is not needed, however, in others neuromonitoring serves a mapping and monitoring purpose. The prototype of pain surgery for this chapter is the dorsal root entry zone (DREZ) procedure. Both mapping and monitoring can help improve lesioning precision and outcomes in this surgery. In this chapter, the DREZ procedures and other surgeries for primarily pain relief in which NIOM is used are discussed. Surgeries, such as spinal stenosis, in which pain relief is important but not the sole purpose, are not discussed here and are covered elsewhere.

Overview of intraoperative neuromonitoring.

Intraoperative neuromonitoring (IONM) is used widely to reduce neurologic adverse postoperative outcomes. A variety of techniques are used. Initial techniques were used as far back as the 1930s, and the variety of methods expanded greatly since the 1980s. Many methods monitor baseline findings over time. Other methods test for neurologic function to identify nerves or eloquent cortex. Physicians trained in neurophysiology are key for interpretation of findings, supervision of staff, and making medical recommendations to the surgeon or anesthesiologist. Some neurophysiologists provide the services personally, and in other circumstances well-trained technologist staff help with the techniques. Much IONM is provided by the neurophysiology physician in the operating room, whereas in other cases, the physician may be on-line in real time from a remote site. When monitoring identifies changes, the IONM team must give a clear, timely, and compelling message to the surgeon and anesthesiologist.

Motor Evoked Potentials Double Train Stimulation: Optimal Number of Pulses per Train.

PURPOSE: In neurophysiologic intraoperative monitoring, double train transcranial electrical stimulation (dt-TES) for motor evoked potentials (MEP) consists of an initial, facilitating train of stimuli followed by a second, testing, train. The optimal number of pulses per train has not been determined. The authors wanted to determine the optimal combination of pulses per train that produced the highest MEP amplitude. METHODS: Dt-TES of 4 + 4, 2 + 7, and 7 + 2 pulses were attempted in 20 patients and compared with single train TES of nine pulses. Latencies of the MEP responses were also compared. Additionally, statistical comparisons were made of the differences between the amplitude and latency measurements within the patients. RESULTS: The mean age of the patients was 44.3 years (range, 9-84 years). Dt-TES of 2 + 7 pulses resulted in significantly higher mean amplitudes than dt-TES of 4 + 4 and 7 + 2 pulses and single train TES of nine pulses ( p < 0.001). The MEP latency with dt-TES of 2 + 7 pulses was longer than the latencies of single train TES of nine pulses and dt-TES of 4 + 4 and 7 + 2 pulses. CONCLUSIONS: Asymmetric dt-TES with 2 + 7 pulses improved MEP amplitudes. This type of stimulation may be preferable to single train TES and dt-TES with symmetric pulse trains.