Pediatric Patients Undergoing Epilepsy Surgery Research Articles

The role of preoperative diffusion tensor imaging in predicting and improving functional outcome in pediatric patients undergoing epilepsy surgery: a systematic review.

Objective:Diffusion tensor imaging (DTI) is a useful neuroimaging technique for surgical planning in adult patients. However, no systematic review has been conducted to determine its utility for pre-operative analysis and planning of Pediatric Epilepsy surgery. We sought to determine the benefit of pre-operative DTI in predicting and improving neurological functional outcome after epilepsy surgery in children with intractable epilepsy.Methods:A systematic review of articles in English using PubMed, EMBASE and Scopus databases, from inception to January 10, 2020 was conducted. All studies that used DTI as either predictor or direct influencer of functional neurological outcome (motor, sensory, language and/or visual) in pediatric epilepsy surgical candidates were included. Data extraction was performed by two blinded reviewers. Risk of bias of each study was determined using the QUADAS 2 Scoring System.Results:13 studies were included (6 case reports/series, 5 retrospective cohorts, and 2 prospective cohorts) with a total of 229 patients. Seven studies reported motor outcome; three reported motor outcome prediction with a sensitivity and specificity ranging from 80 to 85.7 and 69.6 to 100%, respectively; four studies reported visual outcome. In general, the use of DTI was associated with a high degree of favorable neurological outcomes after epilepsy surgery.Conclusion:Multiple studies show that DTI helps to create a tailored plan that results in improved functional outcome. However, more studies are required in order to fully assess its utility in pediatric patients. This is a desirable field of study because DTI offers a non-invasive technique more suitable for children.Advances in knowledge:This systematic review analyses, exclusively, studies of pediatric patients with drug-resistant epilepsy and provides an update of the evidence regarding the role of DTI, as part of the pre-operative armamentarium, in improving post-surgical neurological sequels and its potential for outcome prediction.

The clinical utility of intraoperative electrocorticography in pediatric epilepsy surgical strategy and planning.

In this study, the authors aimed to determine 1) whether the use of intraoperative electrocorticography (ECoG) affects outcomes and complication rates of children undergoing resective epilepsy surgery; 2) which patient- and epilepsy-related variables might influence ECoG-based surgical strategy; and 3) what the predictors of epilepsy surgery outcomes are. Over a period of 12 years, data were collected on pediatric patients who underwent tailored brain resections in the Motol Epilepsy Center. In patients in whom an abnormal ECoG pattern (e.g., spiking, suppression burst, or recruiting rhythm) was not observed beyond presurgically planned resection margins, the authors did not modify the surgical plan (group A). In those with significant abnormal ECoG findings beyond resection margins, the authors either did (group B) or did not (group C) modify the surgical plan, depending on the proximity of the eloquent cortex or potential extent of resection. Using Fisher's exact test and the chi-square test, the 3 groups were compared in relation to epilepsy surgery outcomes and complication rate. Next, multivariate models were constructed to identify variables associated with each of the groups and with epilepsy surgery outcomes. Patients in group C achieved significantly lower rates of seizure freedom compared to groups A (OR 30.3, p < 0.001) and B (OR 35.2, p < 0.001); groups A and B did not significantly differ (p = 0.78). Patients in whom the surgical plan was modified suffered from more frequent complications (B vs A+C, OR 3.8, p = 0.01), but these were mostly minor (duration < 3 months; B vs A+C, p = 0.008). In all cases, tissue samples from extended resections were positive for the presence of the original pathology. Patients with intended modification of the surgical plan (groups B+C) suffered more often from daily seizures, had a higher age at first seizure, had intellectual disability, and were regarded as MR-negative (p < 0.001). Unfavorable surgical outcome (Engel class II-IV) was associated with focal cortical dysplasia, incomplete resection based on MRI and/or ECoG findings, negative MRI finding, and inability to modify the surgical plan when indicated. Intraoperative ECoG serves as a reliable tool to guide resection and may inform the prognosis for seizure freedom in pediatric patients undergoing epilepsy surgery. ECoG-based modification of the surgical plan is associated with a higher rate of minor complications. Children in whom ECoG-based modification of the surgical plan is indicated but not feasible achieve significantly worse surgical outcomes.

T161. Correlating magnetoencephalography (MEG) and high-density electroencephalography (EEG) with invasive recordings in pediatric patients undergoing epilepsy surgery

Introduction Epilepsy surgery is a potentially curative treatment for medically refractory epilepsy (MRE). The goal of epilepsy surgery is the resection of the epileptogenic zone. Before surgery, MEG and scalp EEG are used to estimate the epileptogenic zone noninvasively by localizing the irritative zone (IZ), which is the area where interictal epileptic discharges (IEDs) occur. Previous studies correlated MEG, scalp EEG and the gold standard intracranial EEG (iEEG), but no study compared their ability to localize IEDs in the same cohort solving the inverse problem. Our goal is to assess the ability of 306-sensors MEG and 70-channels EEG (HD-EEG) to localize the IZ in pediatric patients with MRE by comparing them with iEEG findings. Methods We analyzed interictal data from 25 children with MRE who underwent iEEG. We analyzed 12 min of simultaneous MEG and HD-EEG data, and 10–15 min of iEEG data recorded with subdural and/or depth electrodes. IEDs were detected on MEG, HD-EEG and iEEG data by two reviewers who were blinded to each other’s results. We determined the location of each iEEG contact on the patient’s cortex by co-registering presurgical MRI with post-implantation computerized tomography. All IEDs were localized using an Equivalent Current Dipole (ECD) method (forward model: Boundary Element Method). Only ECDs with goodness-of-fit >75% were considered. We measured the minimum distance of each MEG and HD-EEG ECD from iEEG ECDs. We classified each HD-EEG and MEG ECD as: (i) not-covered, if in a brain area not covered by iEEG (>30 mm far from iEEG); (ii) concordant, if within iEEG coverage and close to an iEEG ECD ( We also calculated, for each patient, precision and sensitivity of MEG and HD-EEG, as well as their localization error (i.e. the mean distance of their ECDs from iEEG ECDs). Results We included 13 patients in the analysis. HD-EEG showed a higher proportion of ECDs outside the iEEG coverage than MEG (26% vs 5%). MEG showed a higher proportion of ECDs concordant with iEEG compared to HD-EEG. MEG presented a higher precision to the iEEG ECDs than HD-EEG (50% vs. 31%, p = 0.04), with no difference in sensitivity. The localization error of MEG was lower than HD-EEG (p = 0.017). In 7 patients, MEG ECDs were closer to iEEG ECDs compared to HD-EEG (p Conclusion We compared for the first time the source localization of three non-invasive and invasive neuroimaging methods (HD-EEG, MEG, and iEEG) in the presurgical evaluation of children with MRE. Our findings showed that MEG can localize IEDs with lower localization error and higher precision compared to scalp EEG, even though EEG is more accurate than MEG in few cases. MEG and HD-EEG are complimentary valuable tools in the non-invasive mapping of IZ in epilepsy surgery.

Thirty-day outcomes in pediatric epilepsy surgery.

The aim of this study was to use the multicenter American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) to evaluate and identify risk factors for 30-day adverse events in children undergoing epilepsy surgery. Using the 2015 NSQIP-P database, we identified children (age 0-18years) undergoing pediatric epilepsy surgery and analyzed NSQIP-defined complications, unplanned reoperations, and unplanned readmissions. Multivariable logistic regression analysis was performed using perioperative data to identify risk factors for adverse events within 30days of the index procedure. Two hundred eight pediatric patients undergoing epilepsy surgery were identified for the year 2015 in the NSQIP-P database. The majority of patients were male (51.8%) and white (72.9%). The median age was 10years. Neurological and neuromuscular comorbidities were seen in 62.5% of patients. Surgical blood loss and transfusion was the most common overall NSQIP-defined event (15.7%) and was reported in 40% with hemispherectomy. Nineteen patients (6.8%) had an unplanned reoperation and 20 patients (7.1%) had an unplanned readmission. Multivariable logistic regression analysis showed that African American patients (OR 3.26, 95% CI 1.29-8.21, p=0.01) and hemispherectomy (OR 3.05, 95% CI 1.4-6.65, p=0.01) were independently associated with NSQIP-defined complications. Patients undergoing hemispherectomy (OR 4.11, 95% CI 1.48-11.42, p=0.01) were also at significantly higher risk of unplanned readmission after pediatric epilepsy surgery. Data from the 2015 NSQIP-P database showed that hemispherectomy was significantly associated with higher perioperative events in children undergoing epilepsy surgery. Quality improvement initiatives for hemispherectomy should target surgical blood loss and wound-related complications. Racial disparities in access to cranial pediatric epilepsy surgery and perioperative complications were also highlighted in the present study.

The effect of sevoflurane on electrocorticographic spike activity in pediatric patients with epilepsy.

Electrocorticogram (ECoG) spike activity is enhanced under general anesthesia with 1.5 minimum alveolar concentration (MAC) sevoflurane compared with lower concentrations in adult patients with epilepsy. However, the effect of concentration of sevoflurane on ECoG in children with epilepsy is less known. The primary endpoint was to investigate the effects of sevoflurane on ECoG spike activity in pediatric patients undergoing epilepsy surgery. The secondary endpoint was to examine its effects on baseline ECoG including burst suppression. Children of age 3-18 years with medically intractable epilepsy undergoing corpus callosotomy or resection of the epileptic foci (n = 11) were enrolled. Electrodes were placed on the brain surface and ECoG was recorded under anesthesia with endtidal carbon dioxide tension at 30 mmHg and sevoflurane at 2.5%, followed by age-adjusted 1.5 MAC (3.1-3.4%) for 10 min. The number of leads with spikes, the average number of spikes per lead per minute, median frequency of ECoG, and duration of suppression of ECoG ≥ 1 s were compared between 2.5% and 1.5 MAC sevoflurane. The number of leads with spikes increased [11 vs 14, P = 0.003, difference in mean (95% CI) is 3 (2-5)], and the average number of spikes increased [9 vs 14·lead-1 ·min-1 , P = 0.003, difference in mean (95% CI) is 5 (2-8) lead-1 ·min-1 ] under anesthesia with 1.5 MAC compared with 2.5% sevoflurane. Median frequency was decreased [2.8 Hz vs 2.0 Hz, P = 0.003, difference in mean (95% CI) is 0.8 (0.4-1.2) Hz], and the duration of suppression was increased [105 s vs 262 s, P < 0.001, difference in mean (95% CI) is 156 (90-223) s] with 1.5 MAC compared with 2.5% sevoflurane. Sevoflurane at 1.5 MAC significantly increased the extent and the number of spikes, prolonged the duration of suppression, and decreased median frequency of ECoG compared with those at 2.5% sevoflurane.

Pediatric epilepsy surgery: could age be a predictor of outcomes?

OBJECTIVE Like adults, many children suffering from intractable seizures benefit from surgical therapy. Although various reports indicate that early intervention may avoid severe developmental consequences often associated with intractable epilepsy, surgery is still considered a last option for many children. In this retrospective study, the authors aimed to determine whether pediatric epilepsy surgery, in particular during the first years of life, relates to measurable benefits. METHODS Data from 78 patients (age range 5 months to 17 years) who underwent epilepsy surgery at the Geneva and Lausanne University Hospitals between 1997 and 2012 were reviewed retrospectively. Patients were dichotomized into 2 groups: infants (≤ 3 years of age, n = 19), and children/adolescents (4-17 years of age, n = 59). Compared with children/adolescents, infants more often had a diagnosis of dysplasia (37% vs 10%, respectively; p < 0.05, chi-square test). RESULTS The overall seizure-free rate was 76.9%, with 89.5% in infants and 72.9% in the children/adolescents group. Infants were 2.76 times as likely to achieve seizure-free status as children/adolescents. Postoperative antiepileptic medication was reduced in 67.9% of patients. Only 11.4% of the patients were taking more than 2 antiepileptic drugs after surgery, compared with 43% before surgery (p < 0.0001). The overall complication rate was 15.1% (6.4% transient hemiparesis), and no major complications or deaths occurred. CONCLUSIONS The data show a high seizure-free rate in children ≤ 3 years of age, despite a higher occurrence of dysplastic, potentially ill-defined lesions. Pediatric patients undergoing epilepsy surgery can expect a significant reduction in their need for medication. Given the excellent results in the infant group, prospective studies are warranted to determine whether age ≤ 3 years is a predictor for excellent surgical outcome.

Intraoperative optical mapping of epileptogenic cortices during non-ictal periods in pediatric patients.

Complete removal of epileptogenic cortex while preserving eloquent areas is crucial in patients undergoing epilepsy surgery. In this manuscript, the feasibility was explored of developing a new methodology based on dynamic intrinsic optical signal imaging (DIOSI) to intraoperatively detect and differentiate epileptogenic from eloquent cortices in pediatric patients with focal epilepsy. From 11 pediatric patients undergoing epilepsy surgery, negatively-correlated hemodynamic low-frequency oscillations (LFOs, ~ 0.02–0.1 Hz) were observed from the exposed epileptogenic and eloquent cortical areas, as defined by electrocorticography (ECoG), using a DIOSI system. These LFOs were classified into multiple groups in accordance with their unique temporal profiles. Causal relationships within these groups were investigated using the Granger causality method, and 83% of the ECoG-defined epileptogenic cortical areas were found to have a directed influence on one or more cortical areas showing LFOs within the field of view of the imaging system. To understand the physiological origins of LFOs, blood vessel density was compared between epileptogenic and normal cortical areas and a statistically-significant difference (p < 0.05) was detected. The differences in blood-volume and blood-oxygenation dynamics between eloquent and epileptogenic cortices were also uncovered using a stochastic modeling approach. This, in turn, yielded a means by which to separate epileptogenic from eloquent cortex using hemodynamic LFOs. The proposed methodology detects epileptogenic cortices by exploiting the effective connectivity that exists within cortical regions displaying LFOs and the biophysical features contributed by the altered vessel networks within the epileptogenic cortex. It could be used in conjunction with existing technologies for epileptogenic/eloquent cortex localization and thereby facilitate clinical decision-making.

Cortical Mapping Of Language In The Basal Temporal Area In Pediatric Patients Undergoing Epilepsy Surgery Evaluation. (P3.287)

Cortical Mapping Of Language In The Basal Temporal Area In Pediatric Patients Undergoing Epilepsy Surgery Evaluation. (P3.287)

Evaluating and improving the quality of time-dependent, diffuse reflectance spectroscopic signals measured from in vivo brain during craniotomy

BackgroundOptical spectroscopy can be used to assess the pathophysiological characteristics of diseased and injured biological tissue in vivo in a non-destructive way. It is often used in conjunction with a contact optical probe for the purposes of operating and sensing in a sterile field. Since the probe is often held by the hand of an investigator during data acquisition, any hand instability can affect the quality of acquired data and, hence, degrade the accuracy of diagnosis. This study was designed to quantitatively characterize these artifacts, and then propose an effective engineering solution to remove them. MethodsTime-dependent diffuse reflectance spectra (Rd(λ,t)) were acquired from the normal cortex region of pediatric patients undergoing epilepsy surgery. They were acquired at a rate of 33Hz, and their range was 400 and 900nm. Two distinct ways of collecting data were tested: one with the fiber optical probe held by the surgeon's hand during data acquisition, and the other with the probe held by a specially designed probe holder. The probe holder was designed and constructed to minimize the variations in probe contact pressure and contact point for the full duration of any given investigation. Spectral data acquired using versus not using the probe holder were characterized and compared in the time, wavelength, and frequency domains, using both descriptive and inferential statistics. ResultsHand motion manifested as strong random variations in Rd(λ,t) which impacted temporal and frequency characteristics of Rd(λ,t). The percentage standard deviation %STD of Rd(λ,t) acquired without probe holder could be as high as 60%, and they are significantly higher than those with probe holder at all wavelengths. This difference is especially prominent between 400 and 600nm. Rd(λ,t) acquired without the probe holder also processed a higher spectral power energy in the frequency domain than those with the probe holder. The correlation analysis revealed that the hand motions induced synchronistic variations in Rd(λ,t) between 600 and 800nm, but this synchronicity is not obvious between 400 and 600nm. ConclusionThe results of this investigation demonstrate the nature and the magnitude of hand motion induced artifacts in in vivo diffuse reflectance spectra and propose one potential solution (i.e., a probe holder) to remove them. These findings allow us to improve the quality of time-dependent, diffuse reflectance signals acquired to study the dynamic characteristics of biological tissues, like brain, in vivo.

Time to Pediatric Epilepsy Surgery Is Longer and Developmental Outcomes Lower for Government Compared With Private Insurance

It is unclear if socioeconomic factors like type of insurance influence time to referral and developmental outcomes for pediatric patients undergoing epilepsy surgery. This study determined whether private compared with state government insurance was associated with shorter intervals of seizure onset to surgery and better developmental quotients for pediatric patients undergoing epilepsy surgery. A consecutive cohort (n = 420) of pediatric patients undergoing epilepsy surgery were retrospectively categorized into those with Medicaid (California Children's Services; n = 91) or private (Preferred Provider Organization, Health Maintenance Organization, Indemnity; n = 329) insurance. Intervals from seizure onset to referral and surgery and Vineland developmental assessments were compared by insurance type with the use of log-rank tests. Compared with private insurance, children with Medicaid had longer intervals from seizure onset to referral for evaluation (log-rank test, P = .034), and from seizure onset to surgery (P = .017). In a subset (25%) that had Vineland assessments, children with Medicaid compared with private insurance had lower Vineland scores presurgery (P = .042) and postsurgery (P = .003). Type of insurance was not associated with seizure severity, types of operations, etiology, postsurgical seizure-free outcomes, and complication rate. Compared with Medicaid, children with private insurance had shorter intervals from seizure onset to referral and to epilepsy surgery, and this was associated with lower Vineland scores before surgery. These findings may reflect delayed access for uninsured children who eventually obtained state insurance. Reasons for the delay and whether longer intervals before epilepsy surgery affect long-term cognitive and developmental outcomes warrant further prospective investigations.

Focal cortical dysplasia is more common in boys than in girls

Genetics and environment likely contribute to the development of medically intractable epilepsy; however, in most patients the specific combination of etiologies remains unknown. Here, we undertook a multicenter retrospective cohort study of sex distribution in pediatric patients undergoing epilepsy surgery and carried out a secondary analysis of the same population subdivided by histopathologic diagnosis. In the multicenter cohort of patients with intractable epilepsy undergoing surgery regardless of etiology (n=206), 63% were boys, which is significantly more boys than expected for the general population (Fisher exact two-tailed p=0.017). Subgroup analysis found that of the 90 patients with a histopathologic diagnosis of focal cortical dysplasia, 72% were boys, giving an odds ratio (OR) of 2.5 (95% CI, 1.34 to 4.62) for male sex. None of the other etiologies had a male sex predominance. Future studies could examine the biological relevance and potential genetic and pathophysiological mechanisms of this observation.

In vivodetection of epileptic brain tissue using static fluorescence and diffuse reflectance spectroscopy

Diffuse reflectance and fluorescence spectroscopy are used to detect histopathological abnormalities of an epileptic brain in a human subject study. Static diffuse reflectance and fluorescence spectra are acquired from normal and epileptic brain areas, defined by electrocorticography (ECoG), from pediatric patients undergoing epilepsy surgery. Biopsy specimens are taken from the investigated sites within an abnormal brain. Spectral analysis reveals significant differences in diffuse reflectance spectra and the ratio of fluorescence and diffuse reflectance spectra from normal and epileptic brain areas defined by ECoG and histology. Using these spectral differences, tissue classification models with accuracy above 80% are developed based on linear discriminant analysis. The differences between the diffuse reflectance spectra from the normal and epileptic brain areas observed in this study are attributed to alterations in the static hemodynamic characteristics of an epileptic brain, suggesting a unique association between the histopathological and the hemodynamic abnormalities in an epileptic brain.

Multimodality localization of the sensorimotor cortex in pediatric patients undergoing epilepsy surgery

The gold-standard method for determining cortical functional organization in the context of neurosurgical intervention is electrical cortical stimulation (ECS), which disrupts normal cortical function to evoke movement. This technique is imprecise, however, as motor responses are not limited to the precentral gyrus. Electrical cortical stimulation also can trigger seizures, is not always tolerated, and is often unsuccessful, especially in children. Alternatively, endogenous motor and sensory signals can be mapped by somatosensory evoked potentials (SSEPs), functional MRI (fMRI), and electrocorticography of high gamma (70-150 Hz) signal power, which reflect normal cortical function. The authors evaluated whether these 4 modalities of mapping sensorimotor function in children produce concurrent results. The authors retrospectively examined the charts of all patients who underwent epilepsy surgery at Seattle Children's Hospital between July 20, 1999, and July 1, 2011, and they included all patients in whom the primary motor or somatosensory cortex was localized via 2 or more of the following tests: ECS, SSEP, fMRI, or high gamma electrocorticography (hgECoG). Inclusion criteria were met by 50 patients, whose mean age at operation was 10.6 years. The youngest patient who underwent hgECoG mapping was 2 years and 10 months old, which is younger than any patient reported on in the literature. The authors localized the putative sensorimotor cortex most often with hgECoG, followed by SSEP and fMRI; ECS was most likely to fail to localize the sensorimotor cortex. Electrical cortical stimulation, SSEP, fMRI, and hgECoG generally produced concordant localization of motor and sensory function in children. When attempting to localize the sensorimotor cortex in children, hgECoG was more likely to produce results, was faster, safer, and did not require cooperation. The hgECoG maps in pediatric patients are similar to those in adult patients published in the literature. The sensorimotor cortex can be mapped by hgECoG and fMRI in children younger than 3 years old to localize cortical function.

Epilepsy Surgery Outcomes: Quality of Life and Seizure Control

A consecutive, retrospective analysis of seizure control and quality of life was performed among 83 pediatric patients undergoing epilepsy surgery at Children's Hospital of Wisconsin. Seizure outcomes were generally favorable, with 68.7% class I outcomes; class II, 12%; and class III, 19.3%. Seizure freedom was highest among temporal lobectomies (84.2%) and hemispherectomies (76.2%). Outcomes among hemispherectomies were substantially superior to those of multilobar resections. Cortical dysplasia was associated with lower seizure freedom, at 57.5%. Among age groups, seizure-free outcomes in infants were lowest, at 50%. The lower infant seizure-free rate was likely attributable to frequency of multilobar resections and type of pathology (cortical dysplasia). Quality-of-life measures generally paralleled seizure outcomes. These results indicate that epilepsy surgery in children with intractable epilepsy can result in significant improvements in seizure control, quality of life, and development. Anticipated type of surgery, presumed location of epileptogenic site, absence of a defined lesion on magnetic resonance imaging scan of the brain, and patient's age should not prevent surgical evaluations of children with intractable epilepsy.

Anesthesia for epilepsy surgery in children

The perioperative management of infants and children for epilepsy surgery should focus on the specific problems unique to the state of the disease, age of the child, and operative conditions. A basic understanding of age-dependent variables and the interaction of anesthetic and surgical procedures are essential in minimizing perioperative morbidity and mortality. Specific medical conditions that impact the conduct of anesthesia include congenital anomalies, chronic anticonvulsant therapies, and evolving coagulopathies. The neurosurgical procedure and neurophysiological monitoring will determine the type of anesthetic technique to be utilized during surgery. This review will provide a systematic approach to pediatric patients undergoing epilepsy surgery.