Preoperative Seizure Research Articles

SURG-33. RATES OF PRE-OPERATIVE SEIZURE IN PATIENTS WITH MENINGIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Recent literature has primarily focused on the factors influencing postoperative seizures following resection of meningioma, but many patients also suffer seizures preoperatively. This meta-analysis examined patient demographics, tumor characteristics, and preoperative symptoms to determine which factors are most associated with preoperative seizures. A literature search of Pubmed, Web of Science, and Scopus was conducted. All randomized controlled trials, case-control studies, and cohort studies reporting on preoperative seizure in patients with meningioma were included for analysis. The initial search yielded 4129 total studies, 33 of which were included for quantitative analysis. A total of 8221 patients were analyzed and the rate of preoperative seizure was 26%. Patients were classified as adult vs pediatric and male vs female for analysis. Meningiomas were classified as midline/bilateral vs left-sided vs right-sided, WHO grade 1 vs grade 2-3, greater than 4 cm3 vs less than 4 cm3, and skull base vs non-skull base location. The preoperative signs and symptoms analyzed included presence of headaches, tumor-related edematous change, and neurological deficits. Preoperative seizures were more common in pediatric patients (p< .02) and males (p< .0001). Patients with tumors classified as midline (p< .0001), WHO grade 2-3 (p< .0001), larger than 4 cm3 (p< .0001), and skull base location (p< .0001) were more likely to experience preoperative seizures. Preoperative headaches (p< .0001) were less common in patients with preoperative seizures. Edematous change (p< .0001) and neurological deficits (P< .0001) were more common in patients with pre-operative seizures. On assessment of risk for study bias, no publication bias was detected. This meta-analysis displayed that over 20% of meningioma patients suffer from preoperative seizures. Notably, pediatric patients, patients with midline and skull base meningiomas, and males of all ages were more likely to experience preoperative seizure. Interestingly, patients with preoperative seizures were less likely to experience headaches.

Effect of perioperative seizures on mortality and recurrence in patients with brain metastases.

To identify the independent risk factors for 30-day perioperative seizures, as well as to evaluate the effect of perioperative seizures on overall mortality and tumor recurrence among patients who underwent surgical resection of brain metastases. Patients who underwent surgical resection of brain metastases at our institution between 2011 and 2019 were included. 30-day perioperative seizures were defined as the presence of any preoperative or postoperative seizures diagnosed by a neurosurgeon or neurologist within 30 days of metastases resection. Independent risk factors for 30-day perioperative seizures were evaluated using multivariate logistic regression models. Kaplan-Meier plots and Cox regression models were constructed to evaluate the effects of 30-day perioperative seizures on overall mortality and tumor recurrence. Subgroup analyses were conducted for 30-day preoperative and 30-day postoperative seizures. A total of 158 patients were included in the analysis. The mean (SD) age was 59.3 (12.0) years, and 20 (12.7%) patients had 30-day perioperative seizures. The presence of 30-day preoperative seizures (OR=41.4; 95% CI=4.76, 924; p=0.002) was an independent risk factor for 30-day postoperative seizures. Multivariate Cox regression revealed that any 30-day perioperative seizure (HR=3.25; 95% CI=1.60, 6.62; p=0.001) was independently and significantly associated with overall mortality but not tumor recurrence (HR=1.95; 95% CI=0.78, 4.91; p=0.154). Among patients with resected brain metastases, the presence of any 30-day perioperative seizure was independently associated with overall mortality. This suggests that 30-day perioperative seizures may be a prognostic marker of poor outcome. Further research evaluating this association as well as the effect of perioperative antiepileptic drugs in patients with resected brain metastases may be warranted.

CNSC-24. THE EPILEPTIC LANDSCAPE OF IDH MUTANT GLIOMAS

Abstract Tumor-associated epilepsy (TAE) is a frequent complication of diffusely infiltrative gliomas, and impairs quality-of-life. We previously showed that isocitrate dehydrogenase 1 mutant (IDHmut) gliomas were associated with preoperative seizures, and that D2HG increased synchronized bursts in cultured neurons (PMID: 28404805). But the mechanism whereby this occurs, whether IDHmut inhibitors can block this, and whether seizure risk varies by IDHmut status post-operatively, are unknown. We discovered that exogenous 3 mM D2HG had a 150% greater effect on the firing rate of cultured mouse cortical neurons when nonneoplastic glia cells were present versus when they were absent (P=0.002). Coculture with patient-derived IDHmut glioma cells increased the firing rate of human cortical neuron/astrocyte spheroids by up to 272%, and the IDHmut inhibitor AG881 reduced the excitatory effect of IDHmut glioma cells on spheroids by 79% (P=0.0008). Using a novel in vivo model of TAE, wherein EEG recordings were taken of immunocompetent mice engrafted with isogenic mouse glioma lines (NRAS/ATRX/TP53mut ± IDHmut), we found that IDHmut gliomas produced 7.6-fold more epileptiform spikes than IDHwt gliomas (P=0.004). RNA-Seq analysis of the peritumoral mouse brain tissue showed that this increase in spikes was associated with significantly increased expression of key genes known to be upregulated in epilepsy, including SLC12A5, THSB1, VEGFA, FOSL2, and SYNPO. Treatment with 5 mg/kg AG881 by daily oral gavage reduced those spikes in IDHmut-engrafted mice by 51% within three days (P=0.027), whereas vehicle control had no effect (P=0.33). Among 247 patients with grade 2–4 adult-type diffuse gliomas, multivariable time-to-event analysis showed that post-operative seizure risk was positively associated with pre-operative seizures, subtotal resection, and IDHmut astrocytoma. Together, these data show that (i) the D2HG product of IDHmut gliomas increases neuronal excitation in a glial-dependent manner; (ii) IDHmut also affects post-operative seizure risk; (iii) IDHmut inhibitors may improve TAE control.

Effects of Botulinum Toxin Injection on Reducing Myogenic Artifacts during Video-EEG Monitoring: A Longitudinal Study

ABSTRACT Medically refractory seizures affect one-third of patients with epilepsy (PwE), for whom epilepsy surgery is considered. Video electroencephalography (vEEG) monitoring is a fundamental tool for pre-operative seizure localization. Facial and cranial myogenic artifacts can obscure vEEG findings, thus interfering with seizure localization. Studies have shown the beneficial effects of botulinum toxin type A (BTX-A) injection into cranial muscles for reducing myogenic artifacts. This longitudinal study aimed to assess the effects of BTX-A injection on these artifacts. Twenty-two patients with medically refractory hypermotor seizures with daily seizure frequency and undetermined epilepsy localization were included in this study and underwent Dysport® injection (200 units) into the frontotemporal region. vEEG recordings were performed at baseline (one week before the injection), and at three days and six days post-injection. Before and after the injection, the amplitudes of myogenic artifacts were compared during various states (ictal, blinking, chewing, bruxism, head lateralization, scowling, talking, and yawning). BTX-A injection significantly reduced the amplitudes of EEG myogenic artifacts, except during blinking (day three) and talking (days three and six). On day six, significant reduction in EEG myogenic artifacts were noted during blinking, chewing, and bruxism for the greatest number of patients (95.5%, 90.9%, 81.8%), while significant reductions in EEG myogenic artifacts during talking, head lateralization, and ictal phase were associated with the least number of patients (22.7%, 36.3%, and 40.9%). Therefore, BTX-A injection could be a convenient method for filtering myogenic contamination, improving EEG interpretation, and facilitating seizure localization in patients with medically refractory seizures.

Systemic Inflammation Is Implicated in De Novo Seizures Following Meningioma Resection

Abstract AIMS To investigate the association between perioperative peripheral blood inflammatory markers and seizures in patients who have undergone meningioma resection. METHOD A single neurosurgery tertiary centre blood bank database was screened to extract pre-operative and post-operative white cell count (WCC), neutrophils, lymphocytes, monocytes, platelets and neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR). All patients who underwent resection of meningioma from 2012 to 2020 were eligible. Patients were excluded if they had an inflammatory condition, peri-operative infection, medical illness or operative complication. RESULTS 30 patients suffered pre-operative seizures only, 16 experienced de novo post-operative seizures within 1 year and 42 patients did not experience seizures throughout their treatment timeline. In those who had never had a seizure, there was a significant increase in WCC post-operatively (15.2 vs. 10.6 × 109/L (95% CI 2.1-8.2), p=0.02). Patients who suffered de novo seizures had a significantly higher post-operative day 1 to 4 WCC than those with no seizures (21.1 vs. 14.8 × 109/L (2.1-12.6), p=0.48). However, this difference of WCC was poorly predictive of de novo seizures at one year (AUC 0.61). There was no difference in pre-operative inflammatory markers between pre-operative seizure patients, de novo seizure or never seizure patients. CONCLUSION There is a significantly higher post-operative systemic inflammatory response in patients who suffered de novoseizures after meningioma resection. Peripheral blood markers have the potential to predict seizures in patients with meningioma.

Correlation of Clinicopathological Factors with Brain Tumor-Related Epilepsy in Glioma.

Objectives Glioma patients with brain tumor-related epilepsy (BTRE) have a complex profile due to the simultaneous presence of two pathologies, glioma and epilepsy; however, they have not traditionally received as much attention as those with more malignant brain tumors. The underlying pathophysiology of brain tumor-related epilepsy remains poorly understood. The purpose of this study was to investigate the possible correlation between molecular neuropathology and glioma with BTRE and a wide range of BTRE-associated molecular markers of glioma patients. Methods A retrospective cohort study of 186 glioma patients was evaluated at our hospital, of which 64 had BTRE. The chi-square test, Spearman rank correlation, and multivariate logistic analyses were used to identify clinicopathological factors associated with BTRE in glioma patients. Results Of the 186 patients examined in this study, 64 (34.4%) had BTRE. Based on the analysis of the characteristics of these patients, the results showed that patient age (over 40 years; P = 0.007), low WHO grade (grade I, II; P = 0.001), IDH-1 positive mutation (P = 0.027), low ATR-X expression level (OR = 0.44; 95% CI: 0.21, 0.92), and low Ki-67 PI (OR = 0.25; 95% CI: 0.10, 0.68) were associated with the occurrence of BTRE. In our cohort, BTRE patients did not differ by sex, tumor location, or expression of olig-2 and CD34. The results of the matching study showed that low Ki-67 PI and negative ATR-X expression levels were independent factors for a higher incidence of preoperative seizures in glioma patients. Conclusion The current study updates existing information on genetic markers in gliomas with BTRE and explores the correlation of a wide range of clinicopathological factors and glioma patients with BTRE and suggests three putative biomarkers for BTRE: positive IDH1 mutation, low Ki-67 PI, and negative ATR-X expression. These factors may provide insights for developing a more thorough understanding of the pathogenesis of epilepsy and effective treatment strategies aimed at seizure control.

Postoperative Epileptic Seizures in Children.

Background: Postoperative seizures (PS) occur in 10–15% of patients. This study aims to provide an update on the role of surgery in PS. Methods: All children undergoing a craniotomy for supratentorial lesions in the last 10 years were considered except those with preoperative seizures, perioperative antiepileptic drugs prophylaxis, head-injury and infections, repeated surgery, or preoperative hyponatremia. Children undergoing surgery for intra-axial lesions (Group 1, 74 cases) were compared with those harboring extra-axial lesions (Group 2, 91 cases). Results: PS occurred in 9% of 165 cases and epilepsy in 3% of 165 cases (mean follow-up: 5.7 years). There was no difference between the two study groups with regard to demographic data or tumor size. Group 1 showed a higher rate of gross total tumor resection (p = 0.002), while Group 2 had a higher rate of postoperative hyponatremia (p < 0.0001). There were no differences between the two groups in the occurrence of seizures (6.7% vs. 11%) or epilepsy (2.7% vs. 3.2%). No correlations were found between seizures and age, tumor location, histotype, tumor size, or the extent of tumor resection. Hyponatremia affected the risk of PS in Group 2 (p = 0.02). Conclusions: This study shows a lower rate of PS and epilepsy than series including children with preoperative seizures. Hyponatremia has a significant role. Neurosurgery is safe but surgical complications may cause late epilepsy.

Symptom burden and surgical outcome in non-skull base meningiomas.

PurposeNon-skull base meningiomas (NSBM) are a distinct entity and frequently present with focal neurological deficits. This study was designed to analyze functional and oncological outcome following microsurgical tumor resection in patients with NSBM.Patients and methodsAn analysis of 300 patients that underwent NSBM resection between 2003 and 2013 was performed. Assessment measures for functional outcome were Karnofsky Performance Scale (KPS), Medical Research Council - Neurological Performance Scale (MRC-NPS), and improvement rates of focal deficits and seizures. The extent of resection; recurrence-free survival (RFS) and tumor-specific survival (TSS) were also determined.ResultsImpaired KPS and MRC-NPS were present in 73.3% and 45.7%, respectively. Focal neurological deficits were recorded in 123 patients (41.0%), with hemiparesis (21.7%) and aphasia (9.3%) the most prevalent form of impairment. Most meningiomas were localized at the convexity (64.0%), followed by falcine tumors (20.3%). Both KPI and MRC-NPS scores were significantly improved by surgical resection. Postoperative improvement rates of 96.6%, 89.3%, 72.3%, 57.9%, and 27.3% were observed for aphasia, epilepsy, hemiparesis, cranial nerve, and visual field deficits, respectively. Long-term improvement was achieved in 83.2%, 89.3%, 80.0%, 68.4% and 54.6% of patients, respectively. Gross total resection (GTR) over subtotal resection (STR) significantly improved preoperative seizures and visual field deficits and correlated with reduced risk of new postoperative hemiparesis. Poor Simpson grade was the only significant prognostic factor in multivariate analysis for long-term functional deficit, which occurred in 7.3%. Median RFS was 45.9 months (6.0 - 151.5 months), while median TSS was 53.7 months (3.1 – 153.2 months). Both WHO grade (p= 0.001) and Simpson classification (p= 0.014 and p= 0.031) were independent significant prognostic factors for decreased RFS and TSS by multivariate analysis, respectively. Furthermore, tumor diameter > 50 mm (p= 0.039) significantly correlated with decreased TSS in multivariate analysis.ConclusionSurgical resection significantly and stably improves neurological deficits in patients with NSBM.

P11.10.A An assessment of predictive factors for overall survival in glioblastoma - MGMT methylation is solely important for younger patients

Abstract Background Diverse groups of factors - neuropathological characters, tumor position and epidemiological data - have been proposed for outcome evaluation of glioblastoma (GBM). We compared clinical signs, neuropathological features and the locus of the tumor with the follow-up data. Material and Methods All adult patients with firstly diagnosed and histologically proven GBM (according to WHO 2016), which were operated in our center between January 2010 and June 2021 were retrospectively assessed. Epidemiological, clinical and neuro-pathological characteristics were acquired from our institutional neuro-oncological database. Results A total of 399 patients could be evaluated. The mean follow-up was 13.9 months (CI95 12.2-15.6), within 266 (67%) patients were deceased. Estimated mean OS for entire cohort was 24.2 months (CI95 19.8-28.7). Age, MGMT promoter methylation, brainstem localization or if a patient received biopsy only showed significant impact on OS. Each year of life accounted for 3.4% additional hazard to decease (HR=1.034, CI95 1.020-1.048, p&amp;lt;0.001). If patients were younger than 65 years, mean OS was 34 months (CI95 26.5-41.8) compared to older than 65 years patients with a mean OS of 14.3 months (CI95 10.5-18.1, p&amp;lt;0.001). Generally, an unmethylated MGMT promoter status was linked to 75% higher hazards to decease (HR 1.75, CI95 1.27-2.40, p=0.027). If MGMT promoter status was methylated, mean OS was 25.7 months (CI95 19.9-31.5) or more compared to unmethylated with 14.5 months (CI95 12.0-16.9, p=0.01). Presence of MGMT promoter methylation showed influence on OS only in the younger cohort (&amp;lt;65y, mean OS 38.7 months [CI95 28.9-48.6]; HR 2.60 [CI95 1.55-4.37], p&amp;lt;0.001) as opposed to unmethylated MGMT (mean OS 17.7 months [CI95 14.1-21.2], p&amp;lt;0.001). In the older cohort (&amp;gt;65y) presence of methylated MGMT promoter showed no significant difference (p=0.364). For patients who received only biopsy, 2.4 times more hazards for worse OS were revealed (HR 3.36, CI95% 2.30-4.90, p&amp;lt;0.001). In these cases, mean OS was 7.1 months (CI95 5.3-8.8). Other factors, including gender or preoperative seizures, as well as EGFR, p53, IDH1, ATRX and TERT status did not show impact on OS in our series. Conclusion In our cohort, MGMT promoter methylation showed an impact on OS only in younger patients &amp;lt;65 years of age. Biopsy of GBM should only be considered very selected patients when resection is not possible.

Postoperative progression of brain metastasis is associated with seizures.

Seizures in patients with brain metastases have an impact on morbidity and quality of life. The influence of tumor growth on the risk of seizures in these patients is not well defined. In this cohort study, we evaluated adult patients from the University Hospital of Zurich following resection of brain metastases from solid tumors, with or without preoperative seizures, at 3, 6, 9, and 12 months postoperatively. Brain magnetic resonance imaging was assessed for tumor progression using the Response Assessment in Neuro-Oncology criteria. The quarterly risk of unprovoked seizures was modeled with mixed effects logistic regression. We analyzed 444 time frames in 220 patients. Progression of brain metastases was independently associated with seizures during the respective quarterly follow-up period (odds ratio=3.9, 95% confidence interval=1.3-11.3, p= .014). Complete resection of brain metastases was associated with a lower risk of seizures (odds ratio= .2, 95% confidence interval= .04-.7, p= .015). Postoperative progression of brain metastases quadrupled the risk of seizures; therefore, vigorous follow-up may be useful to identify tumor progression and gauge the risk of seizures. The identification of patients at high seizure risk may have implications for treatment decisions and influence aspects of daily life. Breakthrough seizures may indicate brain metastases progression.

Predictors of postoperative seizure outcome in supratentorial meningioma.

Meningiomas are the most common primary intracranial tumor. Seizures are common sequelae of meningioma development. Meningioma patients with seizures can be effectively treated with resection, with reports of seizure freedom of 60%-90%. Still, many patients manifest persistent epilepsy. Determining factors associated with worsened seizure outcomes remains critical in improving the quality of life for these patients. The authors sought to identify clinical, radiological, and histological factors associated with worse seizure outcomes in patients with supratentorial meningioma and preoperative seizures. The authors retrospectively reviewed the charts of 384 patients who underwent meningioma resection from 2008 to 2020. The charts of patients with a documented history of preoperative seizures were further reviewed for clinical, radiological, operative, perioperative, histological, and postoperative factors associated with seizures. Engel class at last follow-up was retrospectively assigned by the authors and further grouped into favorable (class I) and worse (class II-IV) outcomes. Factors were subsequently compared by group using comparative statistics. Univariable and multivariable regression models were utilized to identify independent predictors of worse seizure outcome. Fifty-nine patients (15.4%) were found to have preoperative seizures, of whom 57 had sufficient postoperative data to determine Engel class outcome. Forty-two patients (74%) had Engel class I outcomes. The median follow-up was 17 months. Distinct margins on preoperative imaging (p = 0.012), Simpson grade I resection (p = 0.004), postresection ischemia (p = 0.019), WHO grade (p = 0.019), and recurrent disease (p = 0.015) were found to be the strongest predictors of Engel class outcome in univariable logistic regression. MIB-1 index (p = 0.001) and residual volume (p = 0.014) at last follow-up were found to be the strongest predictors of Engel class outcome in univariable generalized linear regression. Postresection ischemia (p = 0.012), WHO grade (p = 0.022), recurrent disease (p = 0.038), and MIB-1 index (p = 0.002) were found to be the strongest independent predictors of Engel class outcomes in multivariable analysis. Postresection ischemia, higher WHO grade, elevated MIB-1 index, and disease recurrence independently predict postresection seizure persistence in patients with supratentorial meningioma. Further understanding of the etiology of these markers may aid in elucidation of this complex disease process and guide management to prevent worse outcomes.

De novo epilepsy after microsurgical resection of brain arteriovenous malformations.

Seizures are the second most common presenting symptom of brain arteriovenous malformations (bAVMs) after hemorrhage. Risk factors for preoperative seizures and subsequent seizure control outcomes have been well studied. There is a paucity of literature on postoperative, de novo seizures in initially seizure-naïve patients who undergo resection. Whereas this entity has been documented after craniotomy for a wide variety of neurosurgically treated pathologies including tumors, trauma, and aneurysms, de novo seizures after bAVM resection are poorly studied. Given the debilitating nature of epilepsy, the purpose of this study was to elucidate the incidence and risk factors associated with de novo epilepsy after bAVM resection. A retrospective review of patients who underwent resection of a bAVM over a 15-year period was performed. Patients who did not present with seizure were included, and the primary outcome was de novo epilepsy (i.e., a seizure disorder that only manifested after surgery). Demographic, clinical, and radiographic characteristics were compared between patients with and without postoperative epilepsy. Subgroup analysis was conducted on the ruptured bAVMs. From a cohort of 198 patients who underwent resection of a bAVM during the study period, 111 supratentorial ruptured and unruptured bAVMs that did not present with seizure were included. Twenty-one patients (19%) developed de novo epilepsy. One-year cumulative rates of developing de novo epilepsy were 9% for the overall cohort and 8.5% for the cohort with ruptured bAVMs. There were no significant differences between the epilepsy and no-epilepsy groups overall; however, the de novo epilepsy group was younger in the cohort with ruptured bAVMs (28.7 ± 11.7 vs 35.1 ± 19.9 years; p = 0.04). The mean time between resection and first seizure was 26.0 ± 40.4 months, with the longest time being 14 years. Subgroup analysis of the ruptured and endovascular embolization cohorts did not reveal any significant differences. Of the patients who developed poorly controlled epilepsy (defined as Engel class III-IV), all had a history of hemorrhage and half had bAVMs located in the temporal lobe. De novo epilepsy after bAVM resection occurs at an annual cumulative risk of 9%, with potentially long-term onset. Younger age may be a risk factor in patients who present with rupture. The development of poorly controlled epilepsy may be associated with temporal lobe location and a delay between hemorrhage and resection.

Risk factors for preoperative seizures in meningiomas - base versus non-bases of supratentorial

Background: Meningiomas are the most frequent benign intracranial lesions. The literature review reported that 19-63% of the patients with meningioma suffer from preoperative seizures, and 35% experience epileptic seizures as the initial symptom. The present study attempted to establish the risk factors for seizures before surgery of supratentorial meningiomas. Objective: To compare predictive factors for preoperative seizures for skull base meningiomas (SBMs), with non-skull base meningiomas (NSBMs). Materials and methods: The clinical data of 244 patients with supratentorial meningiomas treated microsurgically between 2007 and 2018 were analyzed retrospectively. There were two groups; Group “A” with (NSBMs) and Group “B” with (SBMs). Demographic, clinical, imaging, histopathological, and electroencephalographic data were assessed. Univariate statistical analyses were performed among factors that might correlate with preoperative seizures. Results: A total of 244 patients with a diagnosis of intracranial meningioma were retrospectively evaluated. The mean age was 54.34 years (range 16- 84), females 165, meals 79. Of these 154 patients for the non-skull base, seizures in 65 (42.2%), whereas, 90 patients for skull base, with 32 (35.5%) patients with seizures. The groups had similar preoperative seizure occurrence in relation to age (p=0.154, p=0.819), gender (p=0.396, p=0.445) tumor size (p=0.318,p=0.244), tumor side(p0.836, p=0.702) for Group A and B respectively. The pre-op seizure was the third presentation in both groups after non-focal symptoms and (FND) respectively. For Group “A” seizure as the initial symptom was in 49.2% of patients versus 50.8% for others, while in Group “B” was in 37.5% vs 62.5%. The both groups had statistically significance between PTBE and pre op seizure, for Group “A”,PTBE was in 93(60.4%) patients,(seizure in 51patients 78.5%) vs (42 patients 47.2% for non-seizure), (?2=,15.356, p=0.000). For Group “B”, PTBE was in 43(47.8%) patients,(seizure in 25 patients 78.1%) vs(18 patients 31% for non-seizure),(?2=,18.328, p=0.000). The most frequently seizure for Group “B” was in OGM (seizure 25% vs 13.8 without seizure) and SWM (seizure 71.8% vs 65.5% non-seizure), while lesser overall in planum/tuberculum (seizure3.2% vs 20.7% non-seizure). There was a statistically significant relationship between tumour location and preoperative seizure for (SBM), (?2=5.985, p=0.050) while absent in Group “A”. (?2=1.373, p=0.503). There were no differences between the two groups with WHO grade and pre-op seizure. The unexpected finding in this study is that the presence of preoperative neurologic deficits has been less frequently associated with preoperative seizures in both groups. Careful analysis and further investigation are needed. Conclusion: We identified that the major risk factor for pre-op seizure in both group studies is PTBE, and location for skull base meningiomas, where the planum/tuberculum lesser overall risk for pre-op seizure. While other radiological and histopathological factors are statistically non-significant. Interestingly, the factors associated with preoperative seizures were the absence of preoperative neurologic deficits for both groups.

The epileptic landscape of IDH mutant gliomas.

2064 Background: Tumor-associated epilepsy (TAE) is a frequent complication of diffusely infiltrative gliomas. TAE not only impairs quality-of-life, but it can even be life-threatening. Furthermore, glioma cells have been shown to proliferate and migrate faster when exposed to firing neurons. We previously showed that isocitrate dehydrogenase 1 mutant (IDHmut) gliomas were more likely to cause preoperative seizures than IDH wildtype (IDHwt) gliomas, and that the chemical product of IDHmut, D2HG, increased synchronized network bursts in cultured neurons (PMID: 28404805). But the mechanism whereby this occurs, whether IDHmut inhibitors can block this, and whether seizure risk also varies by IDHmut status postoperatively, are unknown. Methods: Methods are embedded in Results. Results: We discovered that exogenous 3 mM D2HG had a 150% greater effect on the firing rate of cultured mouse cortical neurons when nonneoplastic glia cells were present versus when they were absent ( P=0.002). Although a recently published study suggested that D2HG causes seizures through mTOR activation (PMID: 34994387), we found that D2HG reduced neuronal mTOR activity in neuronal-glial cocultures by 54% ( P=0.0004). Patch clamp analyses showed that, while D2HG does not directly activate glutamate receptors, it does act as a glutamate transport substrate, thus potentially interfering with the ability of glial cells to take up glutamate released into the synaptic cleft. Coculture with patient-derived IDHmut glioma cells increased the firing rate of human cortical neuron/astrocyte spheroids by up to 272%, and an IDHmut inhibitor currently being tested in clinical trials, AG881, reduced the excitatory effect of IDHmut glioma cells on spheroids by 79% ( P=0.0008). Using a novel in vivo model of TAE, wherein EEG recordings were taken of immunocompetent mice engrafted with an isogenic pair of Sleeping Beauty transposase-engineered mouse glioma lines (NRAS/ATRX/TP53mut ± IDHmut), we found that IDHmut gliomas produced 7.6-fold more epileptiform spikes than IDHwt gliomas ( P=0.004). RNA-Seq analysis of the peritumoral mouse brain tissue showed that this increase in spikes was associated with significantly increased expression of key genes known to be upregulated in epilepsy, including SLC12A5, THSB1, VEGFA, FOSL2, and SYNPO. Treatment with 5 mg/kg AG881 by daily oral gavage reduced those spikes in IDHmut-engrafted mice by 51% within three days ( P=0.027), whereas vehicle control had no effect ( P=0.33). Among 247 patients with grade 2–4 adult-type diffuse gliomas, multivariable time-to-event analysis showed that postoperative seizure risk increased with preoperative seizures, subtotal resection, and IDHmut astrocytoma. Conclusions: Together, these data show that (i) the D2HG product of IDHmut gliomas increases neuronal excitation in a glial-dependent manner; (ii) IDHmut also affects postoperative seizure risk; (iii) IDHmut inhibitors may improve TAE control.

Indications, complications, and mortality rate following craniotomy or craniectomy in dogs and cats: 165 cases (1995-2016).

To determine the most common indications for cranial surgery and identify risk factors associated with the occurrence of complications and death in the perioperative period following cranial surgery. 150 dogs and 15 cats. For this multi-institutional retrospective case series, medical records of dogs and cats that underwent cranial surgery at any of the 4 participating institutions between 1995 and 2016 were reviewed. Variables were evaluated included species, sex, age, neurolocalization, history of preoperative seizures, surgical approach, histological results, perioperative complications, and outcome. Logistic regression analysis was performed to assess for risk factors for complications. The most common neurolocalization was the forebrain (110/165 [66.7%]), with 94 (57.0%) animals having had seizures preoperatively. The rostrotentorial (116/165 [70.3%]) and caudotentorial (32/165 [19.4%]) surgical approaches were most commonly reported. The most common indication was the treatment of meningioma (75/142 [52.8%]). Complications arose in 58 of the 165 (35.2%) cases within 24 hours and in 86 (52.1%) cases 1 to 10 days postoperatively. Perioperative complications included hypotension (38/165 [23.0%]) and anemia (27/165 [16.4%]). During the postoperative period, the most common complications were neurologic deficits, seizures, postoperative anemia, and aspiration pneumonia. The mortality rate with death or euthanasia perioperatively or ≤ 10 days postoperatively was 14.5% (24/165). Long-term complications occurred in 65 of the 165 (39.4%) animals, with seizures and neurologic deficits being the most common. Cranial surgery was performed most commonly for the removal of neoplastic lesions in dogs and cats, and most complications were not life-threatening.

Cerebral Edema Due to Chemotherapeutic Wafer Implantation for Malignant Glioma: Registry Study of Correlation with Perioperative Epileptic Seizures

Factors predicting adverse events following implantation with wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (carmustine, BCNU), which is used in local chemotherapy for malignant gliomas (MGs), are unknown. The association between cerebral edema (CE), which often occurs after implantation, and perioperative seizures, which are often observed in MG cases, is under debate. This study investigated risk factors for CE associated with BCNU wafer implantation and their relationship with perioperative seizures. A total of 31 surgical cases involving 28 adult patients who underwent BCNU wafer implantation for MGs were investigated and classified into those with and without postoperative transient CE. We assessed the correlations between CE caused by BCNU implantation and various factors, including postoperative epileptic seizures. World Health Organization (WHO) grade III MGs significantly affected postoperative CE (p = 0.003) and the occurrence of seizures (p = 0.0004). Factors predictive of postoperative seizures were WHO grade III MGs (p = 0.0026), increased postoperative CE (p = 0.0272), and history of preoperative seizures (p = 0.0316). Postoperative CE, WHO grade III MGs, and a history of preoperative seizures might predict the postoperative occurrence of seizures, necessitating stringent management of seizures and CE in the affected patients.

DNA methylation subclass receptor tyrosine kinase II (RTK II) is predictive for seizure development in glioblastoma patients.

Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25%-30% of glioblastoma (GBM) patients initially present with seizures, and an additional 30% develop seizures during the course of the disease. Early studies failed to show an effect of general administration of antiepileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups. 111 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n = 68). Receptor tyrosine Kinase (RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal (MES) GBM (P &lt; .01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (P = .02, OR 5.69) and RTK II (P = .03, OR 5.01) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (P &lt; .01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (P &lt; .01). Our study shows a strong correlation of RTK II glioblastomas with preoperative and long-term seizures. These results underline the benefit of molecular glioblastoma profiling with important implications for postoperative seizure control.

Feasibility of Tailored Unilateral Disconnection vs Callosotomy for Refractory Epilepsy in Patients with Bilateral Parieto-Occipital Gliosis Following Perinatal Insult.

Patients with perinatal hypoxia (PH) and drug-refractory epilepsy (DRE) often have bilateral parieto-occipital gliosis. Surgical management of such patients is a dilemma. To identify preoperative determinants for unilateral disconnection vs callosotomy, and analyze the surgical outcome in such patients. This was a retrospective analysis of patients with DRE and history of PH, with MRI abnormalities restricted to bilateral posterior quadrants. Preoperative semiology, epilepsy duration and seizure frequency were recorded. Based on the concordance between the results of non-invasive tests, patients underwent either posterior quadrant disconnection (PQD) or corpus callosotomy (CC). Preoperative variables were analyzed and corelated to the postoperative seizure freedom. Fourteen patients were identified, 6 underwent PQD and 8 underwent CC. At follow up of 39.17 ± 23.75 months, 66.66% of patients (4/6) in the PQD subgroup had an ILAE Class I outcome. While none in the CC group attained seizure freedom, 87.5% (7/8) had more than 50% reduction in seizure frequency (follow up: 42 ± 27.31 months). Patients with a poor outcome had significantly greater seizure frequency (P = 0.05) and history of drop attacks (P = 0.04) in both the groups. Magnetoencephalography (MEG) accurately localized the epileptogenic zone in all of the patients with good outcome (P = 0.015). Concordance with single photon emission tomography (SPECT) was also a predictor of favorable outcome (P = 0.041). A history of drop attacks with high seizure frequency is associated with poor postoperative seizure outcome. Unilateral PQD is feasible and leads to superior seizure-free outcomes, even in cases with widespread and bilateral imaging and electrical abnormalities, provided the other preoperative investigations are concordant in localizing the epileptogenic zone.

Preoperative antiepileptic drug prophylaxis for early postoperative seizures in supratentorial meningioma: a single-center experience.

Perioperative antiepileptic drug (AED) prophylaxis for early postoperative seizures (EPSs) in patients with supratentorial meningiomas without preoperative seizures is controversial. This paper discusses the incidence, risk factors, control rate and AED withdrawal indications of EPS in patients undergoing supratentorial convexity and parasagittal/falx meningioma resection without preoperative seizures. Patients treated for a histologically confirmed supratentorial convexity and parasagittal/falx meningioma at the authors' institution between 2015 and 2021 were retrospectively examined. Clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate regression analyses. A PubMed review of the literature published between 2011 and 2021 was performed. In total, 517 patients met the selection criteria. EPS (within the first postoperative week) was observed in 30/517 cases (5.8%). Multivariate analysis revealed that surgical/medical complications (OR 16.33, 95% CI 7.07-37.7, P < 0.001) were the only independent predictors of EPS. The dose of valproic was increased and levetiracetam was added based on the frequency of seizures (≤ 2, > 2 times and status epilepticus). EPS control rates were 94.1% (16/17) and 92.3% (12/13), respectively. AEDs were discontinued at 2weeks and 4-6weeks, respectively. The authors identified 10 relevant studies in the literature. Based on their review of the literature, the incidence of EPS was 3.7% (47/1282) with AED use and 6.2% (95/1525) without AED use patients in supratentorial meningiomas without preoperative seizures. The incidence of EPS was 9.0% (19/209) in patients without AED use with convexity and parasagittal/falx meningiomas without preoperative seizures. AED prophylaxis can reduce the incidence of EPS in patients with convexity and parasagittal/falx meningiomas without preoperative seizures. Avoiding postoperative complications is an important means to prevent EPS. Combined medication has a significant effect on controlling repeated EPS. The timing of AED withdrawal was evaluated according to the clinical symptoms and imaging findings.

Effect of Early Surgical Intervention for Brain Tumors Associated with Epilepsy on the Improvement in Memory Performance.

We evaluated the effect of early surgical intervention on the change in memory performance of patients with low-grade brain tumors associated with epilepsy. Twenty-three adult patients with low-grade brain tumors and epilepsy who underwent surgery at our institution between 2010 and 2019 were included. The Wechsler Memory Scale-Revised (WMS-R) was used to assess cognitive memory performance. Memory performance before and after surgery was retrospectively evaluated. In addition, the relationships among preoperative memory function, postoperative seizure outcome, preoperative seizure control, temporal lobe lesion, and change in memory function were examined. There were statistically significant improvements from median preoperative to postoperative WMS-R subscale scores for verbal memory, general memory, and delayed recall (p<0.001, p<0.001, and p=0.0055, respectively) regardless of preoperative sores and tumor location. Good postsurgical seizure control was associated with significant improvements in postoperative WMS-R performance. Our results indicated that early surgical intervention might improve postoperative memory function in patients with low-grade brain tumors and epilepsy.