A novel effective paradigm of intraoperative electrical stimulation mapping in children

Alena Jahodová MD, PhD1, Barbora Beňová MD, PhD1, Martin Kudr MD, PhD1, Petr Ježdík MSc, PhD2, Radek Janča MSc, PhD4, Anežka Bělohlávková MD1, Petr Liby MD, PhD3, Róbert Leško MD3, Michal Tichý MD, PhD3, Pavel Čelakovský MSc, MD1, and Pavel Kršek MD, PhD1
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  • 1 Departments of Paediatric Neurology and
  • | 3 Neurosurgery, Second Faculty of Medicine and Motol University Hospital; and
  • | 2 Departments of Measurement and
  • | 4 Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Czech Republic
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OBJECTIVE

Resective epilepsy surgery is an established treatment method for children with focal intractable epilepsy, but the use of this method introduces the risk of postsurgical motor deficits. Electrical stimulation mapping (ESM), used to define motor areas and pathways, frequently fails in children. The authors developed and tested a novel ESM protocol in children of all age categories.

METHODS

The ESM protocol utilizes high-frequency electric cortical stimulation combined with continuous intraoperative motor-evoked potential (MEP) monitoring. The relationships between stimulation current intensity and selected presurgical and surgery-associated variables were analyzed in 66 children (aged 7 months to 18 years) undergoing 70 resective epilepsy surgeries in proximity to the motor cortex or corticospinal tracts.

RESULTS

ESM elicited MEP responses in all children. Stimulation current intensity was associated with patient age at surgery and date of surgery (F value = 6.81, p < 0.001). Increase in stimulation current intensity predicted postsurgical motor deficits (F value = 44.5, p < 0.001) without effects on patient postsurgical seizure freedom (p > 0.05).

CONCLUSIONS

The proposed ESM paradigm developed in our center represents a reliable method for preventing and predicting postsurgical motor deficits in all age groups of children. This novel ESM protocol may increase the safety and possibly also the completeness of epilepsy surgery. It could be adopted in pediatric epilepsy surgery centers.

ABBREVIATIONS

ESM = electrical stimulation mapping; fMRI = functional MRI; MEP = motor-evoked potential.

OBJECTIVE

Resective epilepsy surgery is an established treatment method for children with focal intractable epilepsy, but the use of this method introduces the risk of postsurgical motor deficits. Electrical stimulation mapping (ESM), used to define motor areas and pathways, frequently fails in children. The authors developed and tested a novel ESM protocol in children of all age categories.

METHODS

The ESM protocol utilizes high-frequency electric cortical stimulation combined with continuous intraoperative motor-evoked potential (MEP) monitoring. The relationships between stimulation current intensity and selected presurgical and surgery-associated variables were analyzed in 66 children (aged 7 months to 18 years) undergoing 70 resective epilepsy surgeries in proximity to the motor cortex or corticospinal tracts.

RESULTS

ESM elicited MEP responses in all children. Stimulation current intensity was associated with patient age at surgery and date of surgery (F value = 6.81, p < 0.001). Increase in stimulation current intensity predicted postsurgical motor deficits (F value = 44.5, p < 0.001) without effects on patient postsurgical seizure freedom (p > 0.05).

CONCLUSIONS

The proposed ESM paradigm developed in our center represents a reliable method for preventing and predicting postsurgical motor deficits in all age groups of children. This novel ESM protocol may increase the safety and possibly also the completeness of epilepsy surgery. It could be adopted in pediatric epilepsy surgery centers.

ABBREVIATIONS

ESM = electrical stimulation mapping; fMRI = functional MRI; MEP = motor-evoked potential.

In Brief

The authors developed and investigated a novel protocol for electrical stimulation mapping (ESM) for use in resective epilepsy surgery in children with focal intractable epilepsy. Although previous methods of ESM frequently fail in children, the authors found their method to be safe and reliable to use in children undergoing epilepsy surgery.

Resective epilepsy surgery is an established treatment for patients with intractable focal epilepsy.1,2 The most desirable outcome is to render patients seizure free without new neurological or cognitive deficits. Focal epilepsy in infants and young children has specific characteristics that must be considered in order to determine the optimal therapeutic approach. Epileptogenic cortical areas in children are almost exclusively neocortical, frequently more extensive than in adults, and often located in proximity to the eloquent cerebral cortex.3 These characteristics increase risks of postoperative deficits in this age group.

Moreover, a recent report from European centers for epilepsy surgery has shown the increasing complexity of both pediatric and adult epilepsy surgery patients during the past 2 decades.4 We see more patients who have extratemporal epilepsy and malformations of cortical development and those in whom the need for intracranial EEG studies is indicated, in part due to the proximity of presumed epileptogenic zones to eloquent cortical areas, most often the primary motor cortex and underlying motor pathways.5 In order to prevent postsurgical motor deficits in these children, it is critical to define the eloquent cortical and subcortical regions pre- and intraoperatively.

Cortical representation of primary motor areas varies considerably among patients,6–8 and therefore individualized functional information is required to guide definite resection planning. The authors of a recent study9 proposed resting state functional MRI (fMRI) as a promising method to identify the motor cortex; however, fMRI is difficult to interpret, particularly in small children and patients with intellectual disability who require general anesthesia for the procedure. In addition, fMRI does not routinely provide real-time information that could guide the decision-making process in the course of a surgical procedure. Overall, noninvasive neuroimaging methods often fail in precise delineation of the eloquent cortical areas and pyramidal tracts,6–8 and electrical stimulation mapping (ESM) of the brain remains a gold standard method to identify the motor cortex with certainty. In a recent pediatric epilepsy surgery survey, 90% of experts worldwide considered ESM a reliable tool in the identification of eloquent motor cortex.10

However, conventional paradigms of cortical stimulation that are effective in adults repeatedly fail in pediatric populations.7,11,12 No contralateral hand movement was elicited by electrical stimulation in 15 of 65 children of the average age of 3.4 years.11 The immaturity of the motor system in infants and children (less excitable motor cortex and neurophysiologically immature pathways) may be one of the reasons why it is sometimes impossible to evoke reliable motor activity in pediatric patients. Performing ESM is particularly complicated in children presenting with severe preexisting motor deficits.13 Cortical motor representation may be partially transferred to the opposite hemisphere after a perinatal cerebral insult.14 Mass lesions often increase stimulation thresholds, and lesion removal sometimes leads to decreases in thresholds.15 Moreover, developmental lesions, such as focal cortical dysplasia and benign tumors, often lead to atypical distribution of the eloquent cortex.6,11 These specific situations have not been systematically studied across age groups.

Use of an appropriate stimulation technique is crucial for ESM effectiveness.8 The classical Penfield’s ESM paradigm accounts for a sustained train of stimuli of 0.5-msec duration, delivered at a rate of 60 Hz with a maximum intensity of about 15–20 mA.16 This technique, however, is ineffective in about 20% of children, frequently induces seizures in the course of surgery, and cannot be employed for continuous monitoring.7 Thus, different stimulation paradigms have been proposed to overcome these limitations. Jayakar et al.7 developed a paradigm that relies on increments in both stimulus intensity and pulse duration, while ensuring responses at lower energy levels. The short-train technique performed using a monopolar stimulating probe has been proposed to allow both ESM and continuous monitoring.17 More recently, low-frequency (5 and 10 Hz) electrical stimulation has been shown to decrease the risk of afterdischarges.18

Available literature reveals a tremendous inconsistency in the ESM techniques used in children, and reports on results are scarce. Depending on the study and investigators, the stimulation pulse width varies between 0.14 and 200 msec, the frequency between 5 and 50 Hz, the current intensity between 0.5 and 20 mA, and the train duration between 3 and 25 seconds.19 Differences in responses to ESM between children and adults have only rarely been studied.15,20,21 In addition, there is an apparent lack of studies comprising large series of children undergoing resective epilepsy surgery in the proximity of the primary motor area and/or corticospinal tract, especially studies reporting results in the youngest age groups. Therefore, it is impossible to draw conclusions for clinical practice regarding the utility and effectiveness of ESM in children and infants undergoing epilepsy surgery.

Here, we present a novel electrical stimulation protocol that has proven effective over the entire age and etiological spectra of the pediatric population. In addition, we analyzed 1) patient-related variables that affect stimulation current intensities, 2) predictors of postsurgical motor deficits, and 3) the effects of ESM on epilepsy surgery outcomes.

Methods

Patient Selection

The study included 66 patients (age 7 months to 18 years, mean 9.3 years, median 8.75 years) who underwent 70 resective epilepsy surgeries at the Motol Epilepsy Center during the period of 2010–2017. All patients underwent standard presurgical evaluation as epilepsy surgery candidates. Based on findings from electrophysiological studies (videoEEG), anatomical and functional neuroimaging (MRI, fMRI, SPECT, PET, source imaging, etc.), and neuropsychological examinations, patients were indicated either for a single-step resective procedure or for a long-term invasive stereoEEG (SEEG) study with subsequent resection. SEEG study was indicated in patients in whom noninvasive methods provided inconclusive results regarding the extent and/or borders of the presumed epileptogenic zone. Intraoperative monitoring using the ESM method was indicated in children who underwent surgery in the proximity of the motor cortex and/or corticospinal tract. In children indicated for ESM, we invariably used propofol (8–12 mg/kg/hr) as the general anesthetic, as it has been demonstrated not to interfere with intraoperative electrocorticography or with cortical stimulation.22

In general, the dose range of propofol in all age groups of children ranges between 8 and 12 mg/kg/hr. Infants and toddlers younger than 3 years may require doses in the upper range of the spectrum due to their higher metabolic rate. The adequate dose of propofol is judged in real time in the surgical theater based on the actual patient’s physiological reactions (e.g., pulse rate, blood pressure) during the surgical procedure. When the child displays physiological signs of pain and distress (e.g., increase in pulse rate), the dose is increased until stable reactions to external stimuli are achieved. In addition, opioid analgesics (e.g., sufentanil) are used during the course of the surgical procedure.

Short-acting muscle relaxants, such as rocuronium and atracurium, are only used for temporary muscle relaxation of vocal cords to ensure smooth intubation. After intubation, the use of short-acting muscle relaxants is discontinued and no muscle relaxants are utilized during the entire course of the surgical procedure. Since volatile anesthetics are known to cause neuromuscular blockage and therefore interfere with the ESM, they were not used in the patients included in the study.

All patients or their legal representatives provided signed informed consent for study participation, and the study was approved by the ethics committee of Motol University Hospital.

Study Design

We adopted a previously published methodology23 and aimed to 1) validate the effectiveness of our ESM protocol over the entire age spectrum of children undergoing epilepsy surgery in our center; 2) stratify patients according to the feasibility of ESM, based on patient-related and surgery-related variables; and 3) assess the prognostic value of current intensity changes occurring during intraoperative ESM stimulation for the prediction of postsurgical motor deficits and seizure outcomes.

First, we assessed whether the ESM procedure described below elicited motor-evoked potential (MEP) responses in all patients included in the study. Second, we analyzed the association of selected patient- and surgery-related variables (see Table 1) and threshold stimulation current intensities. In addition, we analyzed the dynamics of changes in ESM stimulation current intensities before and after the resection procedure. Then, we studied whether the change in the threshold current intensities is related to the presence of postsurgical motor deficits, distinguishing between transient (duration < 2 weeks), long-term (duration ≥ 2 weeks), and permanent (duration > 6 months) motor deficits. Finally, we tried to ascertain whether the use of the presented ESM method in our center influenced the postsurgical seizure outcomes of our patients.

TABLE 1.

Characteristics of the data set: summary of the analyzed clinical data, neurological findings, and surgery-related data

Value
Total no. of patients66
 Male36
 Female30
Total no. of resections70
Total no. of previous brain ops9
 Malignant brain tumor2
 Epilepsy w/o ESM3
 Epilepsy w/ ESM4
Age at seizure onset, yrs3.73
Seizure frequency
 Monthly4
 Weekly11
 Daily51
Seizure type
 1 type
  Focal aware24
 Focal w/ impaired awareness12
  Unclassified7
 >1 type
  Combination of focal seizures5
  Focal + focal to bilateral tonic-clonic seizure12
  Focal + generalized2
  Focal + unclassified8
Etiology
 Focal cortical dysplasia32
 Tumors19
 Gliosis3
 Tuberous sclerosis complex12
Preop neurological findings
 Normal41
 Hemiparesis15
  Mild13
  Severe2
 Other deficits (aphasia, hypotonia)14
 Hemiparesis + other deficits3
Age at op, yrs9.3
Op localization
 Focal
  Frontal28
  Temporal7
  Parietal12
 Lobar
  Frontal5
  Parietal1
  Multilobar17
Benzodiazapenes, barbiturates at time of op14
Epileptogenic zone overlaps eloquent cortex18
Long-term invasive EEG23
Complication (motor deficit) duration
 <2 wks10
 ≥2 wks13
 Permanent5
Stimulation current change
 No change21
 Decrease29
 Increase16
 No response4
Seizure outcome (≥1 yr after final op)
 Engel I49
 Engel II6
 Engel III6
 Engel IV5

ESM and MEP Procedure

Safety Declaration

This novel ESM protocol is characterized by very short 28.4-msec trains composed of 15 anodal, monophasic, constant current electrical pulses, each of a 400-μsec pulse duration at a stimulation frequency of 500 Hz (Fig. 1). The induced temperature corresponds to the total delivered energy, which depends on electrode tissue resistance (typically < 2 kΩ), the effective value of the ESM current (different from maximal intensity), and the duration of its application. Therefore, in terms of ESM safety, the application of low-intensity current for a longer time is equal to high-intensity current for a shorter time.24,25 Significant reduction of the stimulation duration to only 0.03 seconds allows for increasing of ESM maximal intensity within the safety range of 1–100 mA. Under these conditions, the total delivered energy reaches 96 mJ (maximum 100 mA; effective 40 mA, 0.03 seconds), which is less than the 122 mJ delivered during a prolonged Penfield’s protocol (maximum 20 mA, effective 3.5 mA, 5 seconds). All ESM parameters are fully in accordance with the international safety limits. In addition, the safety of the proposed protocol was proven by 3 independent methods, as published previously: intraoperative thermography, histological tissue assessment, and numerical simulation;24,25 no signs of tissue damage were seen in any cases in which these methods were used.

FIG. 1.
FIG. 1.

Schematic comparison of the traditional stimulation paradigm utilizing biphasic pulses delivered at 50-Hz frequency (A) and our novel high-frequency stimulation protocol (B).

ESM Technique

After craniotomy, the brain surface was exposed, and the central sulcus and primary motor cortex were identified visually and with the aid of neuronavigation software (Medtronic). Afterward, the neurosurgeon placed a subdural strip electrode on the presumed motor cortical area.

Using subdural electrode strips and certified stimulation equipment (Endeavor IOM System, Natus Medical Incorporated), we applied electrical stimulation and elicited intraoperative MEPs. The aim of this setting is to reduce energy delivered to the brain and to facilitate motor responses. As mentioned above, the current intensity of the individual stimulation was adjusted within a safety range of 1–100 mA for stable MEP response.

The position of the stimulation electrode was always individually optimized before the resection in order to obtain the lowest possible threshold. The electrode was then fixated to prevent any movement during the surgery.

MEPs were recorded via subdermal needle electrodes from the muscle groups of contralateral limbs and face (orbicularis oculi, orbicularis oris, abductor pollicis brevis, abductor digiti minimi, tibialis anterior, and gastrocnemius muscles). The electrodes were inserted under general anesthesia to minimize patient discomfort. MEP stimulation was repeated with a minimum interval of 10–20 seconds between stimulation trains. Continuous intraoperative electrocorticography was recorded to monitor potential electrographical seizures induced by cortical stimulation.

The threshold current intensity was recorded, as well as the latency and amplitude of MEPs. This evaluation was done prior to the epileptogenic cortex resection, again during the whole course of the surgery, and finally, at the end of the resection. If the stimulation current intensity began to increase, the neurosurgeon was immediately notified and either the resection was paused until the current intensity returned to prior levels or the neurosurgeon discontinued the resection in the affected area.

In contrast to previously published warning criteria (50% amplitude attenuation and 10%–15% latency increase23), we analyzed only the effect of change in stimulation current intensity, based on our clinical experience and recommendations in the literature.8

Statistical Analysis

The stimulation current intensity was selected as a dependent variable. We performed univariate testing for observed (independent) variables and selected those with p values below 0.05 for multivariate analysis. We performed a Mann-Whitney test for variables and calculated the median difference and its 95% confidence interval using the Hodges-Lehmann estimator. For testing of the continuous variables we calculated Pearson’s correlation coefficient. In the multivariate analysis, we created a generalized linear regression model using a stepwise regression algorithm with the variables that reached statistical significance in univariate testing. The beta coefficients with p values of < 0.05 were considered statistically significant. Patients in whom we found it necessary to utilize significantly higher stimulation current intensities were excluded as this would skew the results of further statistical analyses (see Results section). For the outcome analysis, we excluded patients in whom the eloquent cortex and epileptogenic zone overlapped, because in these patients the surgery did not aim for complete removal of the epileptogenic zone. For the calculations, software MATLAB version 2017b and its statistical computing toolbox were used.

Results

ESM Reliably Elicits MEP Responses in the Entire Age Spectrum of Pediatric Patients

Using the methodology described above, we were able to elicit MEP responses in patients during all 70 of the surgeries performed in 66 patients. In 3 surgeries (3 patients), the stimulation was performed transdurally, as opposed to direct cortical stimulation in 67 surgeries (63 patients), due to the presence of tissue adhesions as a consequence of previous surgery (surgeries) that precluded placement of the stimulation electrode directly on cortical surface. We included patients with 1) obvious MRI lesions, 2) subtle MRI lesions, and 3) no visible MRI lesions, and some patients with negative MRI findings eventually had a histopathologically confirmed diagnosis of, e.g., focal cortical dysplasia or gliosis; the exact numbers of patients in respective subgroups are listed in Table 1. In all patients, including nonlesional cases, we utilized the same ESM methodology.

In all patients, including those stimulated transdurally, we were able to elicit motor responses by stimulation currents markedly below the upper limit of proven safe values9 (mean 21.5, range 2–90 mA in our cohort).

We recorded stimulation current intensities before, during, and after the resection of the presumed epileptogenic cortex. In 29 surgeries, the stimulation current intensity decreased postresection and in 21 the intensity did not change. In 16 surgeries the stimulation current intensity increased, and in 4 surgeries no MEP response was recorded postresection.

In 7 surgeries, the ESM induced perioperative electrographic seizures that were terminated with local cooling of the brain cortex. None of the seizures lasted longer than 30 seconds. No patient experienced status epilepticus as a consequence of ESM.

Patient-Related Factors Affect Stimulation Current Intensity in ESM

First, we univariately tested the effect of all patient-related variables (see Table 1) on stimulation current intensity. We observed that in patients with a history of brain surgery (n = 9), those in whom transdural stimulation was performed (n = 3), and those with a preexisting motor deficit (n = 15) significantly higher stimulation current intensities were reached (p < 0.01, p < 0.01, and p < 0.0001, respectively); data from patients with these features would disrupt the homogeneity of the data set and skew the results of further analyses, and therefore their data were excluded from further analysis.

Afterward, we selected variables that were significant in univariate testing and analyzed them using a generalized regression model in the reduced cohort (n = 49). We observed that the stimulation current intensity was significantly associated with patient age at surgery and the date of surgery (Fig. 2; F value = 6.81, p < 0.0003); the date of surgery and patient age did not correlate (rho = 0.0520, p = 0.7226). The association of the stimulation current intensity and the presence of postsurgical motor deficits was not rendered significant by the model.

FIG. 2.
FIG. 2.

Trend to higher stimulation current intensity in younger patients at surgery observed in our data set.

Intraoperative Increase in ESM Current Intensity Predicts Postsurgical Motor Deficit

Using the same methodology as described above, the multivariate model rendered increases in the threshold of stimulation current intensity during surgery, and no recorded responses in MEP at the end of resection were significant predictors of postsurgical motor deficit (F value = 44.5, p = 2.65e-06). In addition, when the threshold current intensity increased more than 10 mA, the motor deficit was most likely to be permanent, as opposed to increases below 10 mA, for which the deficit tended to be transient (p = 0.0064, Fig. 3).

FIG. 3.
FIG. 3.

Increase in the threshold of stimulation current intensity (I) of more than 10 mA during surgery predicts permanent motor deficits with high significance (p = 0.0064).

ESM Does Not Affect Epilepsy Surgery Outcomes

We found no significant association between stimulation parameters, including stimulation current intensities, and seizure outcomes of the epilepsy surgery.

Discussion

In the presented study, we investigated a cohort of 66 children who underwent intraoperative mapping with monitoring of MEPs. Our novel ESM technique reliably elicited motor responses in children of all age categories, including specific situations such as children with preexisting motor deficits, overlapping epileptogenic and eloquent motor areas, or those treated with benzodiazepines/barbiturates. Significantly higher threshold values were observed in children who underwent transdural stimulation, those with a history of previous brain surgery, and those with preexisting hemiparesis, irrespective of underlying brain pathology.

Previously, we published results of a complex safety control study designed to analyze the potential extent of brain damage caused by local tissue overheating. In vivo infrared thermography performed in 13 patients who underwent temporal lobe resections clearly showed that the increase in local temperature during ESM does not cause tissue damage, as evidenced by postsurgical histopathological examination.24 In another study, we set up a complex numerical model of brain electrical stimulation accounting for tissue perfusion, stimulation electrodes, and electrical fields during ESM that confirmed the results of the above-mentioned in vivo study.24,25

Next, we aimed to identify patient- and epilepsy-related variables that might influence ESM responses. In the first set of analyses, in accordance with our clinical experience, we observed that patients who had preexisting motor deficits, those who had undergone transdural stimulation, and those with a previous history of epilepsy surgery required exceedingly higher stimulation currents (although still within the safety limits of the technique). These patients represent obvious “outliers” in our series and in clinical practice and therefore, in the second step, we excluded them from further analysis in order to study potential predictors of ESM responses on a more homogenous and more clinically relevant population. This analysis showed that stimulation current intensity was associated with patient age at surgery and date of surgery; in older children, lower current intensities were utilized and epilepsy surgeries were performed later in the study period. The age of patients was distributed evenly over the study period. Therefore, we confirmed previous findings8 showing that younger patients require higher stimulation intensities. Independently of age, based on our observations, higher stimulation intensities were also required when the stimulation strip electrode was placed slightly askew from the primary motor cortex. Therefore, with greater experience of our surgical team and with progress in neuronavigation techniques, the neurosurgeons were able to properly place the stimulation strip directly over the motor cortex without unacceptable delays in the course of the surgery. This increasing experience was reflected in the finding that patients who underwent surgery later in the study period required lower stimulation current intensities.

Stimulation current intensities before the resection showed no relation to the presence of postsurgical motor deficits. On the other hand, the increase in stimulation current intensities during surgery and absence of recorded MEP response to stimulation at the end of resection reliably predicted the appearance of novel motor deficits. We identified the critical value of 10 mA as the threshold current intensity increase; exceeding this value predicted permanent postoperative motor deficits with high significance. We thus demonstrated practical usability of our ESM method in predicting postoperative motor outcomes in operated children. To our knowledge, this is the first study published so far that has identified the threshold value of increase in stimulation current intensity to predict the presence of postsurgical motor deficits.

Finally, we studied the potential effects of the proposed ESM protocol on epilepsy surgery outcomes. The obvious question is whether utilization of ESM leads to more limited, but potentially incomplete, resections or, conversely, allows for a more radical surgical approach that increases the proportion of complete resections even in close proximity to eloquent motor cortex. Naturally, to reliably answer this question, we would need to include a control group operated on without ESM—this, however, would be ethically unacceptable in light of a general consensus on ESM being a gold standard method in epilepsy surgery. However, observational data from another study by our center5 show that for the period during which the presented ESM protocol has been utilized, we saw no increase in complication rates and no significant changes in seizure outcomes. Conversely, we observed an increased proportion of complex epilepsy surgery cases, including those with epileptogenic zones adjacent to eloquent cortex.5

We found no association between the stimulation parameters themselves (both before and after the resection) and postsurgical seizure outcomes. Logically, we cannot predict the outcome of epilepsy surgery based on ESM parameters. It is, however, plausible that a more precise delineation of eloquent cortical and subcortical brain areas could prompt more aggressive (complete) resection of the epileptogenic zone, an approach that is undoubtedly associated with higher rates of postsurgical seizure freedom.10,26

Our study was limited by its retrospective nature, a rather heterogeneous patient population, and the absence of a control group, as discussed above. For one type of analysis, we had to exclude a subgroup of patients and this further reduced our sample size. Future studies on a larger and more homogenous patient population are needed to validate our findings.

To summarize, based on the results of our study, we suggest that introduction of the novel ESM method could help optimize epilepsy surgery procedures, improve patient counseling, decrease epilepsy surgery–related morbidity, and improve surgical outcomes and ultimately the quality of life in children with focal intractable epilepsy.

Conclusions

The presented novel ESM method can reliably elicit MEP responses in the entire age and etiological spectra of children undergoing epilepsy surgery. Younger children tend to require higher ESM stimulation current intensities to achieve reliable MEP responses. ESM stimulation current intensity can also be used as a predictor of postsurgical motor deficits. Based on this report and a previously published safety control study,24 the presented ESM method can be adopted in centers for pediatric epilepsy surgery.

Acknowledgments

This work was supported by the Ministry of Health of the Czech Republic, grant 15-30456A. The study sponsors had no role in the collection, analysis, and interpretation of data, and in the writing of the manuscript.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: all authors. Acquisition of data: Kršek, Jahodová, Beňová, Kudr, Janča, Bělohlávková, Liby, Leško, Tichý, Čelakovský. Analysis and interpretation of data: Kršek, Jahodová, Beňová, Kudr, Ježdík, Bělohlávková, Leško, Tichý, Čelakovský. Drafting the article: Kršek, Jahodová, Beňová, Kudr, Ježdík, Bělohlávková, Liby, Leško, Tichý, Čelakovský. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Kršek. Statistical analysis: Kršek, Jahodová, Ježdík, Janča. Administrative/technical/material support: Kršek, Jahodová, Kudr, Janča. Study supervision: Kršek, Jahodová.

Supplemental Information

Previous Presentations

Portions of this work were presented in poster and abstract forms at the American Epilepsy Society 2017 Annual Meeting in Chicago, IL.

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  • 23

    Neuloh G, Bien CG, Clusmann H, et al. Continuous motor monitoring enhances functional preservation and seizure-free outcome in surgery for intractable focal epilepsy. Acta Neurochir (Wien). 2010;152(8):13071314.

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  • 24

    Janca R, Jezdik P, Jahodova A, et al. Intraoperative thermography of the electrical stimulation mapping: a safety control study. IEEE Trans Neural Syst Rehabil Eng. 2018;26(11):21262133.

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  • 25

    Vrba J, Janca R, Blaha M, et al. Modeling of brain tissue heating caused by direct cortical stimulation for assessing the risk of thermal damage. IEEE Trans Neural Syst Rehabil Eng. 2019;27(3):440449.

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  • 26

    Krsek P, Maton B, Jayakar P, et al. Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome. Neurology. 2009;72(3):217223.

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Contributor Notes

Correspondence Pavel Kršek: Motol Epilepsy Center, Charles University, Motol University Hospital, Prague, Czech Republic. pavel.krsek@post.cz.

INCLUDE WHEN CITING Published online April 17, 2020; DOI: 10.3171/2020.2.PEDS19451.

A.J. and B.B. contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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    Schematic comparison of the traditional stimulation paradigm utilizing biphasic pulses delivered at 50-Hz frequency (A) and our novel high-frequency stimulation protocol (B).

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    Trend to higher stimulation current intensity in younger patients at surgery observed in our data set.

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    Increase in the threshold of stimulation current intensity (I) of more than 10 mA during surgery predicts permanent motor deficits with high significance (p = 0.0064).

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    Soriano SG, Eldredge EA, Wang FK, et al. The effect of propofol on intraoperative electrocorticography and cortical stimulation during awake craniotomies in children. Paediatr Anaesth. 2000;10(1):2934.

    • Search Google Scholar
    • Export Citation
  • 23

    Neuloh G, Bien CG, Clusmann H, et al. Continuous motor monitoring enhances functional preservation and seizure-free outcome in surgery for intractable focal epilepsy. Acta Neurochir (Wien). 2010;152(8):13071314.

    • Search Google Scholar
    • Export Citation
  • 24

    Janca R, Jezdik P, Jahodova A, et al. Intraoperative thermography of the electrical stimulation mapping: a safety control study. IEEE Trans Neural Syst Rehabil Eng. 2018;26(11):21262133.

    • Search Google Scholar
    • Export Citation
  • 25

    Vrba J, Janca R, Blaha M, et al. Modeling of brain tissue heating caused by direct cortical stimulation for assessing the risk of thermal damage. IEEE Trans Neural Syst Rehabil Eng. 2019;27(3):440449.

    • Search Google Scholar
    • Export Citation
  • 26

    Krsek P, Maton B, Jayakar P, et al. Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome. Neurology. 2009;72(3):217223.

    • Search Google Scholar
    • Export Citation

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