Seizures following surgery for supratentorial extratemporal low-grade tumors in children: a multicenter retrospective study

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  • 1 Department of Pediatric Neurosurgery, Dana Children’s Hospital, Tel Aviv Medical Center, Tel Aviv University;
  • | 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;
  • | 3 Division of Pediatric Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio;
  • | 4 Department of Neurosurgery, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas;
  • | 5 Pediatric Neurosurgery, Charité Universitätsmedizin, Berlin, Germany; and
  • | 6 Pediatric Neurology Unit, Dana Children’s Hospital, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel
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OBJECTIVE

Resection of brain tumors may lead to new-onset seizures but may also reduce seizure rates in patients presenting with seizures. Seizures are seen at presentation in about 24% of patients with brain tumors. For lesional epilepsy in general, early resection is associated with improved seizure control. However, the literature is limited regarding the occurrence of new-onset postoperative seizures, or rates of seizure control in those presenting with seizures, following resections of extratemporal low-grade gliomas (LGGs) in children.

METHODS

Data were collected retrospectively from 4 large tertiary centers for children (< 18 years of age) who underwent resection of a supratentorial extratemporal (STET) LGG. The patients were divided into 4 groups based on preoperative seizure history: no seizures, up to 2 seizures, more than 2 seizures, and uncontrolled or refractory epilepsy. The authors analyzed the postoperative occurrence of seizures and the need for antiepileptic drugs (AEDs) over time for the various subgroups.

RESULTS

The study included 98 children. Thirty patients had no preoperative seizures, 18 had up to 2, 16 had more than 2, and 34 had refractory or uncontrolled epilepsy. The risk for future seizures was higher if the patient had seizures within 1 month of surgery. The risk for new-onset seizures among patients with no seizures prior to surgery was low. The rate of seizures decreased over time for children with uncontrolled or refractory seizures. The need for AEDs was higher in the more active preoperative seizure groups; however, it decreased with time.

CONCLUSIONS

The resection of STET LGGs in children is associated with a low rate of postoperative new-onset epilepsy. For children with preoperative seizures, even with uncontrolled epilepsy, most have a significant improvement in the seizure activity, and many may be weaned off their AEDs.

ABBREVIATIONS

AED = antiepileptic drug; ECoG = electrocorticography; GTR = gross-total resection; LGG = low-grade glioma; STET = supratentorial extratemporal.

OBJECTIVE

Resection of brain tumors may lead to new-onset seizures but may also reduce seizure rates in patients presenting with seizures. Seizures are seen at presentation in about 24% of patients with brain tumors. For lesional epilepsy in general, early resection is associated with improved seizure control. However, the literature is limited regarding the occurrence of new-onset postoperative seizures, or rates of seizure control in those presenting with seizures, following resections of extratemporal low-grade gliomas (LGGs) in children.

METHODS

Data were collected retrospectively from 4 large tertiary centers for children (< 18 years of age) who underwent resection of a supratentorial extratemporal (STET) LGG. The patients were divided into 4 groups based on preoperative seizure history: no seizures, up to 2 seizures, more than 2 seizures, and uncontrolled or refractory epilepsy. The authors analyzed the postoperative occurrence of seizures and the need for antiepileptic drugs (AEDs) over time for the various subgroups.

RESULTS

The study included 98 children. Thirty patients had no preoperative seizures, 18 had up to 2, 16 had more than 2, and 34 had refractory or uncontrolled epilepsy. The risk for future seizures was higher if the patient had seizures within 1 month of surgery. The risk for new-onset seizures among patients with no seizures prior to surgery was low. The rate of seizures decreased over time for children with uncontrolled or refractory seizures. The need for AEDs was higher in the more active preoperative seizure groups; however, it decreased with time.

CONCLUSIONS

The resection of STET LGGs in children is associated with a low rate of postoperative new-onset epilepsy. For children with preoperative seizures, even with uncontrolled epilepsy, most have a significant improvement in the seizure activity, and many may be weaned off their AEDs.

ABBREVIATIONS

AED = antiepileptic drug; ECoG = electrocorticography; GTR = gross-total resection; LGG = low-grade glioma; STET = supratentorial extratemporal.

In Brief

The study focuses on seizure outcome in children with extratemporal low-grade tumors undergoing resection. This topic has not received much attention in the literature (as opposed to temporal tumors), and the authors try to answer a basic everyday clinical question regarding the risk of new-onset postoperative epilepsy in children with no prior history of seizure; they also look at the prognosis of epilepsy in children with preoperative seizures.

“What is the chance my child will have seizures following surgery?” is a common question parents ask, both for children with no history of seizures and for those presenting with seizures. Seizures are a frequent comorbidity in both low- and high-grade tumors, seen at presentation in up to 40% of children1–4 and with increased risk during long-term follow-up.2,3,5 As to low-grade gliomas (LGGs), seizures are the most frequent presenting symptom in children and result in a significant decrease in quality of life.1,6 About 50% of cases of LGG-related epilepsy in children involve temporal tumors, and most of the remaining are frontal tumors.1 In general, low-grade neoplasms have a higher propensity for causing epilepsy than high-grade tumors.7 For example, the most common causes of tumor-related epilepsy are glioneuronal tumors, accounting for approximately 40% of all tumors causing epileptic seizures.8,9

While in adults the most common form of epilepsy is temporal lobe epilepsy, in children the majority of cases are extratemporal epilepsy.10 Extratemporal epilepsy is characterized by a younger age at seizure onset than that of temporal epilepsy.11 Moreover, extratemporal epilepsy in children is often medically refractory and leads to a significant decrease in quality of life.10 Refractory epilepsy in general (temporal and extratemporal origin) is seen in about 25% of children with epilepsy.12

For lesional epilepsy (temporal and extratemporal), early intervention and gross-total resection (GTR) are associated with improved seizure control.3,10,13 Resection of these lesions reduces seizure activity in drug-resistant focal epilepsy, improving psychosocial and intellectual development as well as quality of life.14 Several publications have described the outcomes of epilepsy associated with temporal lobe LGG, leading to an 80%–100% seizure-free rate following tumor resection.8,15,16

Literature focusing on the occurrence of postoperative seizures following the resection of supratentorial extratemporal (STET) LGG in children (with or without a seizure history), and the impact of preoperative seizures or epilepsy on postoperative epilepsy risk is scarce.8,9 Several studies in children include temporal as well as STET lesions.8,9,17,18 Other studies in children include only patients with preoperative refractory epilepsy (including other pathologies besides LGGs).13,19 Many studies combine pediatric and adult patients with STET LGGs.6,20–24 However, pediatric and adult LGGs differ significantly. Children have mostly grade 1 tumors (glioneuronal and pilocytic) compared to adults, who mostly have grade 2 tumors (diffuse astrocytomas and oligodendrogliomas). Therefore, epilepsy outcomes in the pediatric population cannot be deduced from the adult population.

The objective of the current study was to examine the correlation between patient characteristics, history of seizures, preoperative antiepileptic drug (AED) treatment, and seizure outcome following STET LGG resection.

Methods

Following an institutional review board approval, we retrospectively reviewed the files of all children who underwent resection of STET LGGs at 4 large tertiary centers: Dana Children’s Hospital Tel Aviv Medical Center (51 cases, 1996–2017), Cincinnati Children’s Hospital Medical Center (9 cases, 2008–2016), Texas Children’s Hospital (23 cases, 1992–2016), and Charité Universitätsmedizin Berlin (15 cases, 2008–2016). Inclusion criteria were age at surgery < 18 years and patients who underwent resection for STET LGG (including any WHO grade I or II glial or glioneuronal tumors). Exclusion criteria were a history of intraventricular hemorrhage or shunting, patients with genetic syndromes leading to tumor development or associated with epilepsy (e.g., tuberous sclerosis or neurofibromatosis), insufficient available data, and any overt dual pathology (such as a vascular pathology in addition to the LGG). An occurrence of dysplastic tissue adjacent to a tumor was not an exclusion criterion. A second surgery, death, chemotherapy, or radiation therapy were all considered as endpoints of follow-up. Extent of resection was defined as subtotal resection (< 95% of tumor volume), gross-total resection (GTR; no tumor residual on postoperative MRI), near GTR (95%–99% of resection), and GTR plus resection of perilesional tissue (for instance, as guided by residual spikes on electrocorticography [ECoG]).

Collected data included demographics, seizure status before surgery, preoperative AED therapy, time from seizure onset to surgery, location and type of pathology, extent of resection, surgical approach, and new motor deficit following surgery. These variables were analyzed for any correlations indicating their suitability to predict postoperative seizure outcome and the need for AED. Postoperative seizures and AED therapy were evaluated at 4 different time intervals: 1) up to 6 months after surgery (excluding the 1st postoperative month); 2) 6–12 months after surgery; 3) 12–36 months after surgery; and 4) 36 months or more after surgery.

A patient was considered to have active epilepsy if he or she had a recent seizure (i.e., seizure within 1 month before the current follow-up evaluation). Uncontrolled epilepsy was defined as a continuation of seizures despite a trial of one AED. Refractory epilepsy was defined as continuation of seizures despite an appropriate trial of at least two AEDs. We classified uncontrolled and refractory seizures as one group and referred to them as uncontrolled.

Patients were evaluated according to their seizure history as follows: group I, patients without preoperative seizures; group II, patients with up to 2 seizures prior to surgery; group III, patients with more than 2 seizures prior to surgery, excluding uncontrolled epilepsy; and group IV, patients with uncontrolled epilepsy prior to surgery.

Statistical Analysis

Data were collected in FileMaker Pro 12 and extracted to a Microsoft Excel spreadsheet. SPSS software was used for all statistical analyses (version 25, IBM Corp.). Categorical variables are reported as numbers and percentages. Continuous variables were evaluated for normal distribution using histograms. Normally distributed variables are reported as the mean and standard deviation, while skewed variables are reported as median and interquartile range. Association between categorical variables was evaluated using chi-square test or Fisher’s exact test. Association between categorical and continuous variables was determined using ANOVA or independent-samples t-test. Generalized estimating equations model was used to evaluate differences in rate of use of AED and recent seizures between different time intervals. The generalized estimating equation model was performed separately for each patient subgroup. All statistical tests were two-tailed, and p < 0.05 was considered significant.

Results

Ninety-eight patients were included in this study: 56 males (57%) and 42 females (43%). Age at surgery ranged from 2 months to 17.4 years (mean 9.9 ± 4.5 years). Pathological diagnoses were pilocytic astrocytoma (n = 30), dysembryoplastic neuroepithelial tumor (n = 24), ganglioglioma (n = 13), oligodendroglioma (n = 8), ependymoma grade II (n = 6), angiocentric glioma (n = 4), diffuse astrocytoma (n = 2), pilomyxoid astrocytoma (n = 2), pleomorphic xanthoastrocytoma (n = 1), desmoplastic infantile ganglioglioma (n = 1), and other LGGs (n = 7). Frontal and parietal lobes were the two most frequent lesion locations, with 40 and 31 cases, respectively. Other locations included occipital in 14 cases, thalamus and basal ganglia in 14, lateral ventricles in 14, and the third ventricle in 4. Involvement of the primary motor cortex (M1) was seen in 9 patients. Nineteen patients underwent partial or subtotal resections, 66 underwent near GTR or GTR, and 11 underwent GTR plus resection of perilesional tissue. The reasons for not achieving GTR were not available for analysis. Twenty-one resections were guided by intraoperative ECoG, in which 2 patients had residual ECoG activity after the resection was completed. ECoG use was not associated with seizure freedom or use of AEDs at any of the follow-up time points. Preoperative uncontrolled seizures were significantly associated with the use of ECoG, as well as performance of GTR plus resections (p < 0.001 and p = 0.003, respectively).

Before surgery, 30 patients were seizure free, 18 patients had 2 seizures or fewer, 16 had more than 2 seizures, and 34 presented with uncontrolled or refractory epilepsy. Sixty patients were treated with AEDs preoperatively: 14 of 18 with 2 or fewer preoperative seizures, 12 of 16 with more than 2 preoperative seizures, and all 34 uncontrolled cases.

Following surgery, 8 patients (15.7%) had seizures during the 1st postoperative month (the data regarding the 1st postoperative month were based on 51 patients for whom this information was available). Eleven patients (11.2%) had seizures beyond the 1st month following surgery. Table 1 summarizes the seizure outcome and the need for AEDs at 4 different time intervals.

TABLE 1.

Postoperative seizure instances and AEDs at different time intervals

FUNo. of PatientsMedian FU (IQR), mosAED TherapyRecent SeizureNo AEDs & No Recent Seizures
1–6 mos493.5 (3–5)61.7%6.3%37%
6–12 mos3810.8 (7.7–12)41.2%7.9%52%
12–36 mos4424 (17.2–32.8)32.5%2.3%61%
>36 mos4766 (60–85)36.4%10.9%59%
Last FU9836 (12–63)40%8.2%57%

FU = follow-up.

Subgroup analysis of the 4 groups (no preoperative seizures, up to 2 preoperative seizures, more than 2 preoperative seizures, and uncontrolled seizures) showed significant differences among the groups in the need for AEDs at 3 time intervals: 1–6 months from surgery (p < 0.001), 6–12 months from surgery (p = 0.007), and 12–36 months from surgery (p < 0.001). At last follow-up there were significant differences among these groups as well (p < 0.001). There was no statistically significant difference in the need for AEDs among groups at 36 months or more from surgery (p = 0.08). Table 2 displays a summary of these findings. Despite the difference in AED use among groups, there were no significant differences in the rate of recent seizures at any of the time intervals and for any of the preoperative seizure groups (Table 3). For each patient subgroup, the change over time in the need for AEDs, or presence of recent seizures, was not significant (Tables 2 and 3).

TABLE 2.

Rate of postoperative use of AEDs, subgroup analysis

FUNo Preop Seizures (n = 30)Up to 2 Preop Seizures (n = 18)>2 Preop Seizures (n = 16)Refractory or Uncontrolled Epilepsy (n = 34)p1
1–6 mos14.3%57.1%80%93.8%<0.001
6–12 mos025%43%75%0.007
12–36 mos016.7%43%75%<0.001
>36 mos18.2%18.2%43%60%0.08
p2NA0.320.1350.151
Last FU11.1%22.2%35.7%72.7%<0.001

NA = not applicable; p1 = probability value comparing various subgroups for the same time period; p2 = probability value comparing different time periods for a certain subgroup.

Values represent the percentage of patients with AED therapy in each subgroup.

TABLE 3.

Rate of recent seizure, subgroup analysis

FUNo Preop Seizures (n = 30)Up to 2 Preop Seizures (n = 18)>2 Preop Seizures (n = 16)Refractory or Uncontrolled Epilepsy (n = 34)p1
1–6 mos012.5%10%6.7%0.6
6–12 mos0025%7.7%0.3
12–36 mos0012.5%00.3
>36 mos8.3%012.5%20%0.5
p2NANA0.5610.55
Last FU3.3%020%11.8%0.1

p1 = probability value comparing various subgroups for the same time period; p2 = probability value comparing different time periods for a certain subgroup.

Values represent the percentage of patients with recent seizures in each subgroup.

Similar results, showing a difference among preoperative groups in the use of AEDs, but no difference in the rate of recent seizures, were seen when analyzing the various subgroups in different combinations: seizure free before surgery, any controlled preoperative seizures, and uncontrolled epilepsy, and when patients were grouped into 2 groups (no seizures before surgery vs any preoperative seizures). For example, among the 30 patients who were seizure free before surgery, only 1 patient (3.3%) experienced postoperative seizures; whereas among the 68 patients who had preoperative seizures, 10 suffered from postoperative seizures (14.7%) (p = 0.16).

Patients who experienced seizures during the 1st postoperative month were at a greater risk of having seizures later in life (37% for those with vs 7% for those with no seizures during the 1st postoperative month; p = 0.004).

For the entire group, late (> 1 month) postoperative seizures were seen in 5 patients who underwent partial or subtotal resection (26.3%), 6 patients who underwent near GTR or GTR (9.1%), and none of the patients who underwent GTR plus perilesional tissue resection (0%) (p = 0.062). GTR plus resection of perilesional tissue was performed in 1 of 34 with controlled preoperative seizures and in 10 of 34 patients with preoperative uncontrolled seizures (p = 0.003). There was no significant added value for GTR plus perilesional tissue resection over GTR and near GTR for patients with preoperative controlled versus uncontrolled seizures.

ECoG was used in 3 of 34 patients with controlled preoperative seizures and in 18 of 34 patients with preoperative uncontrolled seizures (p < 0.001). The use of ECoG was not associated with improved seizure outcome for patients with preoperative controlled or refractory seizures.

The following factors were not associated significantly with postoperative seizure outcome: preoperative seizures, preoperative AED therapy, location of the tumor, involvement of the primary motor cortex, new motor deficit after surgery, age at surgery, sex, and time between first seizure and surgery.

Discussion

In this multicenter, multinational retrospective study, we present the seizure outcome of children undergoing resection of extratemporal low-grade glial tumors. Based on our results, several conclusions may be drawn:

  • • For children with no history of preoperative seizures, the incidence of postoperative seizures is very low; however, over time, seizures may occur.
  • • For children with refractory or uncontrolled epilepsy, tumor resection plays an important role, with a large reduction in seizure activity as well as a reduction in AEDs.
  • • Children with fewer preoperative seizures received less antiepileptic medication after surgery. This may reflect a lower seizure burden at the different follow-up points, despite no significant difference in the rate of “recent seizures.” Although not directly evaluated, this indirectly supports the notion that earlier surgery with respect to seizure onset may be advantageous—prior to the occurrence of multiple preoperative seizures.
  • • Immediate postoperative seizures (during the 1st postoperative month) correlate significantly with the risk of future seizures.

The pathophysiology of tumor-associated epilepsy is multifactorial and is associated with microenvironmental changes in the peritumoral tissue.25,26 Of all tumor histologies, LGGs in general, and glioneuronal tumors in particular, are often associated with epilepsy. A unique aspect of the current study is the relatively high proportion of gliomas that are not glioneuronal tumors (about 60%), as opposed to most series dealing with tumor-related epilepsy. This may reflect the population of the current series, which includes a significant number of patients with either no or a limited number of seizures prior to surgery (about 50% of patients) and thus did not present with tumor-related epilepsy, even if they had a presenting seizure.

All hemispheric lobe locations indicate a greater risk for seizures, although often, temporal locations are differentiated from extratemporal locations regarding seizure risk.6,9,21 However, despite the association between LGG and epilepsy, long-term outcome following resection of the LGG in children has focused mainly on temporal tumors, most often in the context of refractory epilepsy. Prior literature regarding LGG resection in pediatric temporal lobe epilepsy has stated seizure-free rates of above 80%.8,9,15,16 In a previous study by our group, there was an 87% good epilepsy outcome (Engel class I–III, the vast majority being Engel I) following tumor resection, most of which were LGGs located in the temporal or frontal regions.1 Our results regarding STET LGG suggest that after 3 years, 11% of all patients will have had recent seizures, and 36% will be on an AED.

Our results suggest that the extent of resection was associated with epilepsy outcome, with the best outcomes (0% seizures) for those undergoing GTR and resection of perilesional tissue. This too mirrors general experience with pediatric temporal lobe tumors, as well as with small series of pediatric extratemporal tumors.6,8,10,19,21 In adult LGG, the extent of resection has also been associated with improved epilepsy outcome.24,27,28

In a recent study relating to surgical treatment of pediatric frontal lobe epilepsy (including 12 patients with low-grade tumors), the factors associated with improved epilepsy control were as follows: no immediate postsurgical seizures, complete lesion resection, and epileptic zones not including primary motor cortex.13 Additionally, younger age at surgery and shorter epilepsy duration were both associated with better epilepsy outcomes. Our results generally concur with these results. However, in our series, involvement of the M1 region, age at surgery, and duration of epilepsy were not associated with epilepsy outcome.

According to our results, for refractory or uncontrolled preoperative epilepsy, at least 80% of patients did not have a recent seizure at any time point evaluated following surgery, with up to 40% of patients weaned off their AEDs. Note that AED use may reflect a more chronic epileptic disease that may well still be active, even if there were no seizures within the month of evaluation. This means that the “lack of a recent seizure” factor has a different implication for patients who are not taking any AEDs (representing true seizure freedom), compared to patients who are taking an AED (possibly representing only “lack of a recent seizure” but not a cure of the epilepsy). Particularly for patients with a more active “preoperative epilepsy history,” neurologists may be reluctant to stop AED therapy over a period of 36 months, even in the absence of active seizures; thus, the reduction of AEDs most probably reflects a true reduction in epilepsy over time.

The role of ECoG-tailored surgery for LGGs associated with epilepsy versus lesionectomy only is a matter of debate.8 Generally speaking, it is accepted that the extent of resection is a major contributing factor for seizure freedom and that ECoG-tailored surgery does not impact the epilepsy outcome.6,9,21 According to our results, ECoG was nearly exclusively used in children with preoperative uncontrolled seizures, and its use was associated with additional resection (GTR plus) as opposed to cases in which ECoG was not used; however, it did not affect the seizure outcome. Despite the lack of added value in our study, specifically in temporal glioneuronal tumors, some authors state that an ECoG-tailored resection increased seizure control compared to lesionectomy, possibly because of the association between glioneuronal tumors and cortical dysplasia.29,30

Among patients with no preoperative seizures, 14% were taking an AED at 6 months after surgery. Whether AEDs were administered for actual seizures or as a postoperative “prophylaxis” could not be determined from the collected data. Currently, the accumulating body of data for both adults and children supports avoiding prophylactic AED use for various craniotomy indications;31 however, the data include patients operated on several years ago, who potentially were treated with prophylactic AEDs. According to our results, in the absence of preoperative seizures, about 18% of the patients received AEDs after 36 months following surgery, and 8% of those with no preoperative seizures had recent seizures. This could reflect an accumulating risk of seizures over time. The literature regarding the development of new seizures after STET LGG in children is sparse and difficult to deduce from larger series. Following resection of LGGs (temporal and STET), the risk of new-onset seizures after surgery was 8%.18 Other series relating to the development of epilepsy following tumor resection in children include all tumor pathologies and locations, as well as additional treatments (chemotherapy and radiation therapy), and thus are not specific for STET LGGs.2,3,5

Limitations

This study has all the limitations related to its retrospective nature. Some of the data were missing or incomplete, including follow-up information. There may have been seizures or AED therapies that were not documented. Also, we could not confirm if patients were receiving adequate AED dosages. We did not collect data regarding EEG, nor did we obtain any seizure diaries. Furthermore, some patient files lacked information about AED treatment at certain time points. We assumed that if a patient received AEDs before that point and after that point, it is reasonable that the patient continued to receive AEDs at the point where the information about AED therapy was missing. Additionally, we could not confirm data accuracy regarding the actual rate of epilepsy. We presented information based on follow-up notes and neurological follow-up notes; however, not all patients had available neurological evaluations, nor were AED use or seizures sufficiently documented, and, thus, many patients could not be included. We also related to recent seizures, and not “any seizures”; thus, we could not deduce the Engel outcome scores, especially for patients with refractory seizures prior to surgery.

ECoG was used particularly in children with preoperative uncontrolled seizures, and its use was not associated with improved seizure outcomes. This may possibly be attributed to the low rate of postoperative seizures, even in the uncontrolled group. It is possible that to show an added value for ECoG, larger patient cohorts may be needed.

Moreover, the cohort in our study is composed of patients with various pathologies (such as glioneuronal and astrocytomas), location of pathology, semiology, and demographic criteria. Therefore, our ability to draw accurate conclusions about specific risk factors for postoperative seizures is limited. Dividing the cohort into groups according to semiology, pathology, or tumor location could not be done due to the relatively small number of patients in each group.

Children were operated on over a large time span (1992–2017), in 4 centers, by several surgeons in each center, and were seen by many neurologists over the years. Many routines have changed over the years, potentially affecting outcomes: use of prophylactic perioperative AEDs, use of intraoperative neuromonitoring affecting the ability to resect lesions in proximity to motor pathways, newer-generation AEDs, and so on. In this study, we did not collect data about these factors or for many other factors of potential importance.

Another limitation is that patients were included from different centers, treated by various neurosurgeons/neurologists, with different protocols regarding AED administration, even in the absence of seizures. We thus related to the use of AEDs in a binary fashion (yes/no), with no evaluation of number of AEDs or dosages, as it would be impossible to compare among the many treating teams (even in the same center).

Despite these limitations, this is the largest series to date focusing on STET LGGs in children, including data from several centers, giving an overview outcome analysis of the seizure outcome. We do, however, see the role of future studies focusing on patients with preoperative refractory seizures, evaluating preoperative workup, surgical nuances, and outcome. As the number of patients with STET LGGs and refractory seizures is small, there is a need for collaborative effort to gather a large enough patient cohort.

Conclusions

Resection of pediatric STET LGGs is associated with a low risk for new-onset seizures. For patients with preoperative refractory or uncontrolled seizures, surgery is associated with a meaningful seizure reduction and often a reduction of AEDs.

Acknowledgments

We thank Tomer Ziv-Baran, PhD, for assistance with statistical analysis, and Mrs. Adina Sherer for editorial assistance.

This work was performed in partial fulfillment of the M.D. thesis requirements of the Sackler Faculty of Medicine, Tel Aviv University, for the second author (O.B.).

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: Roth, Constantini. Acquisition of data: Roth, Bercovich, Roach, Mangano, Mohan, Aldave, Weiner, Thomale, Schaumann, Uliel-Sibony. Analysis and interpretation of data: Roth, Bercovich. Drafting the article: Roth, Bercovich. Critically revising the article: Roth, Bercovich, Weiner, Thomale, Uliel-Sibony, Constantini. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Roth. Statistical analysis: Roth, Bercovich. Administrative/technical/material support: Roth, Bercovich. Study supervision: Roth, Constantini.

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    Englot DJ, Berger MS, Barbaro NM, Chang EF. Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia. 2012;53(1):5157.

    • Search Google Scholar
    • Export Citation
  • 22

    Englot DJ, Han SJ, Berger MS, et al. Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery. 2012;70(4):921928.

    • Search Google Scholar
    • Export Citation
  • 23

    Harward SC, Chen WC, Rolston JD, et al. Seizure outcomes in occipital lobe and posterior quadrant epilepsy surgery: a systematic review and meta-analysis. Neurosurgery. 2018;82(3):350358.

    • Search Google Scholar
    • Export Citation
  • 24

    Rudà R, Bello L, Duffau H, Soffietti R. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro Oncol. 2012;14(suppl 4):iv55iv64.

    • Search Google Scholar
    • Export Citation
  • 25

    Shamji MF, Fric-Shamji EC, Benoit BG. Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev. 2009;32(3):275286.

    • Search Google Scholar
    • Export Citation
  • 26

    Van Breemen MS, Wilms EB, Vecht CJ. Seizure control in brain tumors. Handb Clin Neurol. 2012;104:381389.

  • 27

    Chang EF, Potts MB, Keles GE, et al. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg. 2008;108(2):227235.

    • Search Google Scholar
    • Export Citation
  • 28

    Xu DS, Awad AW, Mehalechko C, et al. An extent of resection threshold for seizure freedom in patients with low-grade gliomas. J Neurosurg. 2018;128(4):10841090.

    • Search Google Scholar
    • Export Citation
  • 29

    Babini M, Giulioni M, Galassi E, et al. Seizure outcome of surgical treatment of focal epilepsy associated with low-grade tumors in children. J Neurosurg Pediatr. 2013;11(2):214223.

    • Search Google Scholar
    • Export Citation
  • 30

    Giulioni M, Rubboli G, Marucci G, et al. Seizure outcome of epilepsy surgery in focal epilepsies associated with temporomesial glioneuronal tumors: lesionectomy compared with tailored resection. J Neurosurg. 2009;111(6):12751282.

    • Search Google Scholar
    • Export Citation
  • 31

    Kombogiorgas D, Jatavallabhula NS, Sgouros S, et al. Risk factors for developing epilepsy after craniotomy in children. Childs Nerv Syst. 2006;22(11):14411445.

    • Search Google Scholar
    • Export Citation

Contributor Notes

Correspondence Jonathan Roth: Dana Children’s Hospital, Tel Aviv Medical Center, Tel Aviv, Israel. jonaroth@gmail.com.

INCLUDE WHEN CITING Published online April 3, 2020; DOI: 10.3171/2020.2.PEDS19673.

J.R. and O.B. contributed equally to this study.

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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    Englot DJ, Berger MS, Barbaro NM, Chang EF. Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia. 2012;53(1):5157.

    • Search Google Scholar
    • Export Citation
  • 22

    Englot DJ, Han SJ, Berger MS, et al. Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery. 2012;70(4):921928.

    • Search Google Scholar
    • Export Citation
  • 23

    Harward SC, Chen WC, Rolston JD, et al. Seizure outcomes in occipital lobe and posterior quadrant epilepsy surgery: a systematic review and meta-analysis. Neurosurgery. 2018;82(3):350358.

    • Search Google Scholar
    • Export Citation
  • 24

    Rudà R, Bello L, Duffau H, Soffietti R. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro Oncol. 2012;14(suppl 4):iv55iv64.

    • Search Google Scholar
    • Export Citation
  • 25

    Shamji MF, Fric-Shamji EC, Benoit BG. Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev. 2009;32(3):275286.

    • Search Google Scholar
    • Export Citation
  • 26

    Van Breemen MS, Wilms EB, Vecht CJ. Seizure control in brain tumors. Handb Clin Neurol. 2012;104:381389.

  • 27

    Chang EF, Potts MB, Keles GE, et al. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg. 2008;108(2):227235.

    • Search Google Scholar
    • Export Citation
  • 28

    Xu DS, Awad AW, Mehalechko C, et al. An extent of resection threshold for seizure freedom in patients with low-grade gliomas. J Neurosurg. 2018;128(4):10841090.

    • Search Google Scholar
    • Export Citation
  • 29

    Babini M, Giulioni M, Galassi E, et al. Seizure outcome of surgical treatment of focal epilepsy associated with low-grade tumors in children. J Neurosurg Pediatr. 2013;11(2):214223.

    • Search Google Scholar
    • Export Citation
  • 30

    Giulioni M, Rubboli G, Marucci G, et al. Seizure outcome of epilepsy surgery in focal epilepsies associated with temporomesial glioneuronal tumors: lesionectomy compared with tailored resection. J Neurosurg. 2009;111(6):12751282.

    • Search Google Scholar
    • Export Citation
  • 31

    Kombogiorgas D, Jatavallabhula NS, Sgouros S, et al. Risk factors for developing epilepsy after craniotomy in children. Childs Nerv Syst. 2006;22(11):14411445.

    • Search Google Scholar
    • Export Citation

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