Perioperative Antiepileptic Drugs Research Articles

P18.39.A SEIZURE PROPHYLAXIS IN GLIOMA SURGERY (SPRING): A MULTI-CENTRE, UNBLINDED, RANDOMISED TRIAL

Abstract BACKGROUND 50-80% of all glioma patients will suffer from seizures during their lifetime. Over half of these patients will have drug resistant seizures. Seizure risk is increased peri-operatively, at tumour progression, and shortly before death. Current guidelines do not support routine use of prophylactic peri-operative anti-epileptic drugs (AED) in seizure naïve patients; despite this, levetiracetam is frequently prescribed for this indication. The aim of this trial was to determine the clinical and cost effectiveness of prophylactic levetiracetam in seizure naïve patients undergoing surgery for a glioma at reducing the risk of seizures. MATERIAL AND METHODS Seizure naïve patients with newly diagnosed glioma undergoing surgery (biopsy or resection) were randomised (1:1) to receive 12 months prophylactic levetiracetam or no prophylaxis at 14 neurosurgery and neuro-oncology units in the UK. Participants received standard of care neurosurgery and neuro-oncology treatment and were followed until death or for a maximum of one year. The primary outcome was one year risk of first seizure analyzed using a logistic regression model and intention to treat analysis. Outcomes were analyzed by intention-to-treat. The target accrual was 804 participants. This trial was registered with ISRCTN 49474281. RESULTS Between Oct 10, 2019 and Aug 30, 2022, we randomised 96 patients, from 24 to 79 years of age, to levetiracetam (n=49) or no prophylaxis (n=47). Due to slow accrual during the Covid-19 pandemic the trial closed early. In the levetiracetam group there were 43 high grade glioma (HGG) and 6 low grade glioma (LGG), and in the no prophylaxis group there were 43 HGG and 4 LGG. Seventeen (35%) of 49 patients randomised to levetiracetam had a seizure, compared to 15 (32%) of 47 patients randomised to no prophylaxis (OR 1.25, 95%CI 0.49-3.21, p=0.64). Median time to first seizure was 4.8 months in the levetiracetam group and 3.0 months in the no prophylaxis group. In the levetiracetam group 20 (41%) of 49 patients died within 12 months (median overall survival 6.8 months; range 0.2-11.9), and in the no prophylaxis group 15 (32%) of 47 patients died within 12 months (median 4.7 months; range 0.1-12.0). There were no serious adverse events or suspected unexpected serious adverse events related to levetiracetam. CONCLUSION Due to poor accrual caused by the Covid-19 pandemic the SPRING trial closed early and is therefore underpowered. Based on the limited data there was no difference in the 12 month seizure risk in the prophylaxis and no prophylaxis patients undergoing surgery for newly diagnosed glioma. The role of prophylactic anti-epileptic drugs remains undefined.

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.

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.

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.

Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.

During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas. This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic-clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping. A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED). The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques.

Factors affecting incidence of epilepsy after cranioplasty

Objective To investigate the factors affecting the incidence of epilepsy after cranioplasty. Methods A retrospective case control study was conducted on the clinical data of 171 patients with skull defect who underwent cranioplasty between January 2012 and December 2015. There were 126 males and 45 females, with an average age of 50.9 years (range, 16-78 years). The patients were divided into epileptic seizure group (61 cases) and non epileptic seizure group (110 cases). The gender, age, defect cause, defect location, defect duration, perioperative antiepileptic drug use, skull defect regional depression volume (Vd), skull defect regional integrity volume (Vf), skull defect regional depression rate (Pd) of two groups were recorded. Univariate analysis and multivariate logistic regression analysis were used to identify the independent risk factor of epilepsy after cranioplasty. Results All patients were followed up for 54 months averagely (range, 18-90 months). Sixty-one patients (35.7%) had epilepsy after cranioplasty. Univariate analysis suggested that age, defect cause, defect location, defect duration, perioperative antiepileptic drug use, and Vf were not associated with epilepsy after cranioplasty (all P>0.05); while gender, Vd, and Pd was associated with epilepsy after cranioplasty (P<0.05). Multivariate logistic regression analysis demonstrated that Pd (OR=0.024, 95%CI 0.001-0.502, P<0.05) was independent predictor of epilepsy after cranioplasty. Conclusion Pd is an independent risk factor for epilepsy after cranioplasty and depression degree could significantly affect its incidence. Key words: Epilepsy; Craniocerebral trauma; Cranioplasty

Effectiveness of perioperative antiepileptic drug prophylaxis for early and late seizures following oncologic neurosurgery: a meta-analysis.

The purpose of this meta-analysis was to evaluate the impact of perioperative antiepileptic drug (AED) prophylaxis on short- and long-term seizure incidence among patients undergoing brain tumor surgery. It is the first meta-analysis to focus exclusively on perioperative AED prophylaxis among patients undergoing brain tumor surgery. The authors searched PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and the System for Information on Gray Literature in Europe for records related to perioperative AED prophylaxis for patients with brain tumors. Risk of bias in the included studies was assessed using the Cochrane risk of bias tool. Incidence rates for early seizures (within the first postoperative week) and total seizures were estimated based on data from randomized controlled trials. A Mantel-Haenszel random-effects model was used to analyze pooled relative risk (RR) of early seizures (within the first postoperative week) and total seizures associated with perioperative AED prophylaxis versus control. Four RCTs involving 352 patients met the criteria of inclusion. The results demonstrated that perioperative AED prophylaxis for patients undergoing brain tumor surgery provides a statistically significant reduction in risk of early postoperative seizures compared with control (RR = 0.352, 95% confidence interval 0.130-0.949, p = 0.039). AED prophylaxis had no statistically significant effect on the total (combined short- and long-term) incidence of seizures. This meta-analysis demonstrates for the first time that perioperative AED prophylaxis for brain tumor surgery provides a statistically significant reduction in early postoperative seizure risk.

Factors Associated With Pre- and Postoperative Seizures in 1033 Patients Undergoing Supratentorial Meningioma Resection.

Risk factors for pre- and postoperative seizures in supratentorial meningiomas are understudied compared to other brain tumors. To report seizure frequency and identify factors associated with pre- and postoperative seizures in a large single-center population study of patients undergoing resection of supratentorial meningioma. Retrospective chart review of 1033 subjects undergoing resection of supratentorial meningioma at the author's institution (1991-2014). Multivariate regression was used to identify variables significantly associated with pre- and postoperative seizures. Preoperative seizures occurred in 234 (22.7%) subjects. At 5 years postoperative, probability of seizure freedom was 89.9% among subjects without preoperative seizures and 62.2% with preoperative seizures. Multivariate analysis identified the following predictors of preoperative seizures: presence of ≥1 cm peritumoral edema (odds ratio [OR]: 4.45, 2.55-8.50), nonskull base tumor location (OR: 2.13, 1.26-3.67), greater age (OR per unit increase: 1.03, 1.01-1.05), while presenting symptom of headache (OR: 0.50, 0.29-0.84) or cranial nerve deficit (OR: 0.36, 0.17-0.71) decreased odds of preoperative seizures. Postoperative seizures after discharge were associated with preoperative seizures (OR: 5.70, 2.57-13.13), in-hospital seizure (OR: 4.31, 1.28-13.67), and among patients without preoperative seizure, occurrence of medical or surgical complications (OR 3.39, 1.09-9.48). Perioperative anti-epileptic drug use was not associated with decreased incidence of postoperative seizures. Nonskull base supratentorial meningiomas with surrounding edema have the highest risk for preoperative seizure. Long-term follow-up showing persistent seizures in meningioma patients with preoperative seizures raises the possibility that these patients may benefit from electrocorticographic mapping of adjacent cortex and resection of noneloquent, epileptically active cortex.

The Influence of Perioperative Seizure Prophylaxis on Seizure Rate and Hospital Quality Metrics Following Glioma Resection.

Antiepileptic drugs (AEDs) are frequently administered prophylactically to mitigate seizures following craniotomy for brain tumor resection. However, conflicting evidence exists regarding the efficacy of AEDs, and their influence on surgery-related outcomes is limited. To evaluate the influence of perioperative AEDs on postoperative seizure rate and hospital-reported quality metrics. A retrospective cohort study was conducted, incorporating all adult patients who underwent craniotomy for glioma resection at our institution between 1999 and 2014. Patients in 2 cohorts-those receiving and those not receiving prophylactic AEDs-were compared on the incidence of postoperative seizures and several hospital quality metrics including length of stay, discharge status, and use of hospital resources. Among 342 patients with glioma undergoing cytoreductive surgery, 301 (88%) received AED prophylaxis and 41 (12%) did not. Seventeen patients (5.6%) in the prophylaxis group developed a seizure within 14 days of surgery, compared with 1 (2.4%) in the standard group (OR = 2.2, 95% CI [0.3-17.4]). Median hospital and intensive care unit lengths of stay were similar between the cohorts. There was also no difference in the rate at which patients presented within 90 days postoperatively to the emergency department or required hospital readmission. In addition, the rate of hospital resource consumption, including electroencephalogram and computed tomography scan acquisition, and neurology consultation, was similar between both groups. The administration of prophylactic AEDs following glioma surgery did not influence the rate of perioperative seizures, nor did it reduce healthcare resource consumption. The role of perioperative seizure prophylaxis should be closely reexamined, and reconsideration given to this commonplace practice.

Risk Factors of Preoperative and Early Postoperative Seizures in Patients with Meningioma: A Retrospective Single-Center Cohort Study

Well-defined risk factors for the identification of patients with meningioma who might benefit from preoperative or early postoperative seizure prophylaxis are unknown. We investigated and quantified risk factors to determine individual risks of seizure occurrence in patients with meningioma. A total of 634 adult patients with meningioma were included in this retrospective cohort study. Patient gender and age, tumor location, grade and volume, usage of antiepileptic drugs (AEDs) and extent of resection were determined. Preoperative and early postoperative seizures occurred in 15% (n= 97) and 5% (n= 21) of the patients, respectively. Overall, 502 and 418 patients were eligible for multivariate logistic regression analyses of preoperative and early postoperative seizures, respectively. Male gender (odds ratio [OR], 2.06; P= 0.009), a non-skull base location (OR, 4.43; P < 0.001), and a tumor volume of >8 cm3 (OR, 3.05; P= 0.002) were associated with a higher risk of preoperative seizures and were used to stratify the patients into 3 prognostic groups. The high-risk subgroup of patients with meningioma showed a seizure rate of >40% (OR, 9.8; P< 0.001). Only a non-skull base tumor location (OR, 2.61; P= 0.046) was identified as a significant risk factor for early postoperative seizures. AEDs did not reduce early postoperative seizure occurrence. Seizure prophylaxis might be considered for patients at high risk of developing seizures who are for other reasons being considered for watchful waiting instead of resection. In contrast, our data do not provide any evidence of the efficacy of perioperative AEDs in patients with meningioma.

Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis.

Intraoperative mapping and monitoring techniques for eloquent area tumors are routinely used world wide. Very few data are available regarding mapping and monitoring methods and preferences, intraoperative seizures occurrence and perioperative antiepileptic drug management. A questionnaire was sent to 20 European centers with experience in intraoperative mapping or neurophysiological monitoring for the treatment of eloquent area tumors. Fifteen centers returned the completed questionnaires. Data was available on 2098 patients. 863 patients (41.1%) were operated on through awake surgery and intraoperative mapping, while 1235 patients (58.8%) received asleep surgery and intraoperative electrophysiological monitoring or mapping. There was great heterogeneity between centers with some totally AW oriented (up to 100%) and other almost totally ASL oriented (up to 92%) (31% SD). For awake surgery, 79.9% centers preferred an asleep-awake-asleep anesthesia protocol. Only 53.3% of the centers used ECoG or transcutaneous EEG. The incidence of intraoperative seizures varied significantly between centers, ranging from 2.5% to 54% (p < 0.001). It there appears to be a statistically significant link between the mastery of mapping technique and the risk of intraoperative seizures. Moreover, history of preoperative seizures can significantly increase the risk of intraoperative seizures (p < 0.001). Intraoperative seizures occurrence was similar in patients with or without perioperative drugs (12% vs. 12%, p = 0.2). This is the first European survey to assess intraoperative functional mapping and monitoring protocols and the management of peri- and intraoperative seizures. This data can help identify specific aspects that need to be investigated in prospective and controlled studies.

Perioperative seizure in patients with glioma is associated with longer hospitalization, higher readmission, and decreased overall survival.

OBJECTIVE Seizures are among the most common perioperative complications in patients undergoing craniotomy for brain tumor resection and have been associated with increased disease progression and decreased survival. Little evidence exists regarding the relationship between postoperative seizures and hospital quality measures, including length of stay (LOS), disposition, and readmission. The authors sought to address these questions by analyzing a glioma population over 15 years. METHODS A retrospective cohort study was used to evaluate the outcomes of patients who experienced a postoperative seizure. Patients with glioma who underwent craniotomy for resection between 1998 and 2013 were enrolled in the institutional tumor registry. Basic data, including demographics and comorbidities, were recorded in addition to hospitalization details and complications. Seizures were diagnosed by clinical examination, observation, and electroencephalography. The Student t-test and chi-square test were used to analyze differences in the means between continuous and categorical variables, respectively. Multivariate logistic and linear regression was used to compare multiple clinical variables against hospital quality metrics and survival figures, respectively. RESULTS In total, 342 patients with glioma underwent craniotomy for first-time resection. The mean age was 51.0 ± 17.3 years, 192 (56.1%) patients were male, and the median survival time for all grades was 15.4 months (range 6.2-24.0 months). High-grade glioma (Grade III or IV) was seen in 71.9% of patients. Perioperative antiepileptic drugs were administered to 88% of patients. Eighteen (5.3%) patients experienced a seizure within 14 days postoperatively, and 9 (50%) of these patients experienced first-time seizures. The mean time to the first postoperative seizure was 4.3 days (range 0-13 days). There was no significant association between tumor grade and the rate of perioperative seizure (Grade I, 0%; II, 7.0%; III, 6.1%; IV, 5.2%; p = 0.665). A single ictal episode occurred in 11 patients, while 3 patients experienced 2 seizures and 4 patients developed 3 or more seizures. Compared with their seizure-free counterparts, patients who experienced a perioperative seizure had an increased average hospital (6.8 vs 3.6 days, p = 0.032) and ICU LOS (5.4 vs 2.3 days; p < 0.041). Seventy-five percent of seizure-free patients were discharged home in comparison with 55.6% of seizure patients (p = 0.068). Patients with a postoperative seizure were significantly more likely to visit the emergency department within 90 days (44.4% vs 19.0%; OR 3.41 [95% CI 1.29-9.02], p = 0.009) and more likely to be readmitted within 90 days (50.0% vs 18.4%; OR 4.45 [95% CI 1.69-11.70], p = 0.001). In addition, seizure-free patients had a longer median overall survival (15.6 months [interquartile range 6.6-24.4 months] vs 3.0 months [interquartile range 1.0-25.0 months]; p = 0.013). CONCLUSIONS Patients with perioperative seizures following glioma resection required longer hospital and ICU LOS, were readmitted at higher rates than seizure-free patients, and experienced shorter overall survival. Biological and clinical factors that predispose to the development of seizures after glioma surgery portend a worse outcome. Efforts to identify these factors and reduce the risk of postoperative seizure should remain a priority among neurosurgical oncologists.

HCP-07THE INFLUENCE OF PERIOPERATIVE SEIZURE PROPHYLAXIS ON SEIZURE RATE AND HOSPITAL QUALITY METRICS AFTER GLIOMA SURGERY

BACKGROUND: Seizures represent one of the most common and feared perioperative complications following brain tumor surgery. Despite conflicting evidence regarding efficacy, prophylactic antiepileptic drugs (AED) are frequently administered in an effort to reduce seizure incidence and improve patient and hospital reported outcomes. The authors address this question by examining an institutional glioma population. METHODS: Patients with glioma undergoing craniotomy for resection between 1998 and 2014 were enrolled into our institutional tumor registry. Perioperative seizures were considered those occurring within 14 days of the index surgery. Student t-test and multivariate logistic regression were used to analyze differences in means between continuous and categorical variables, respectively. RESULTS: Among 347 patients undergoing craniotomy for glioma resection, 299 (86.2%) were administered prophylactic AED post-operatively. Levetiracetam was the preferred agent, utilized in 73.7% of subjects. Sixteen (5.3%) patients receiving prophylactic AED suffered a perioperative seizure, compared to 1 (2.1%) not on prophylaxis (p = 0.62). Among the 17 patients that suffered a perioperative seizure, only 6 (35%) had a prior history of seizure. Mean hospital length of stay (LOS) was similar between both groups: 3.29 (AED) vs. 3.54 (no AED) days, p = 0.626. Similarly, there was no difference in ICU LOS among patients receiving (2.25 days) and not receiving (2.64 days) seizure prophylaxis, p = 0.38. The prophylaxis group had a similar rate of 90-day ED visits as the non-prophylaxis group: 12.0 vs. 17.0%, p = 0.341. However, patients administered seizure prophylaxis were less likely to be readmitted within 90 days of the index surgery (21.9 vs. 35%, p = 0.041). CONCLUSIONS: To the authors' knowledge this is the first study specifically evaluating the influence of perioperative seizure prophylaxis on emerging hospital quality metrics including length of stay and readmission. Interestingly, while associated with lower rates of readmission, perioperative AED administration fails to reduce the risk of post-operative seizures or hospital and ICU LOS.

A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors

Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas. Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned. The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients. The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%-18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.

A retrospective two-center study of antiepileptic prophylaxis in patients with surgically treated high-grade gliomas

The effectiveness of antiepileptic prophylaxis in patients with newly diagnosed high-grade glioma is debated. Craniotomy, surgical manipulation and bleeding are believed to favor the onset of seizures and, therefore, perioperative antiepileptic drugs (AEDs) are generally used. Nevertheless, evidence to initiate preoperative AED prophylaxis are weak. Aim of this paper was to evaluate the need for AED prophylaxis in surgically-treated malignant glioma patients without history of seizures. We conducted a retrospective, two-center cohort study to assess the effectiveness of preoperative AED prophylaxis. Patients were divided in two groups: one with AED preoperative administration and the other without. Because of its non-hepatic metabolism, levetiracetam (LEV) was chosen. Logistic regression models were used to investigate the odds ratio for each group. The explanatory variables included the treatment received, sex, age, and site of lesion. The outcome measure of successful LEV prophylaxis was seizure vs. no seizure post-operatively, at three and six months after surgery. Our results showed that LEV prophylaxis was not a significant predictor of seizure occurrence, although the regression coefficient indicated a slight reduction in seizure risk following LEV administration. Patient's age was a significant predictor of seizure occurrence. Younger patients had a higher risk of seizure in the six months post-surgery. We conclude that AEDs prophylaxis does not provide a substantial benefit to surgically treated high-grade glioma patients and should not be administered routinely. Further investigations are required to detect subgroups of patients at higher risk of developing seizures in order to selectively administer AED.

Perioperative seizure incidence and risk factors in 223 pediatric brain tumor patients without prior seizures

The incidence of, and risk factors for, perioperative seizures and the need for perioperative antiepileptic drugs (AEDs) in previously seizure-free children with brain tumors remains unclear. The authors have undertaken a review of previously seizure-free pediatric patients with brain tumors undergoing resection to identify the incidence of seizures in the perioperative period, and to characterize risk factors for perioperative seizures in this population. A retrospective review was conducted of all patients between 0 and 19 years of age without prior seizures who underwent intracranial tumor resection at the authors' institution between January 2005 and December 2009. Of the 223 patients undergoing 229 operations, 7.4% experienced at least 1 clinical seizure during the surgical admission. Over half of all tumors were supratentorial. Only 4.4% of patients received prophylactic AEDs. Independent factors associated with perioperative seizures included supratentorial tumor, age < 2 years, and hyponatremia due to syndrome of inappropriate antidiuretic hormone or cerebral salt wasting. Tumor type, lobe affected, operative blood loss, and length of surgery were not independently associated with seizure incidence. Perioperative seizures in previously seizure-free children undergoing resection of brain tumors are associated with supratentorial tumor location, age < 2 years, and postoperative hyponatremia. Perioperative seizures are not associated with tumor pathology, tumor size, or frontotemporal location. Due to the low incidence of seizures in this series in patients more than 2 years old with normal serum sodium, the authors recommend that pediatric patients with brain tumors not routinely receive perioperative prophylactic AEDs. However, the role for prophylaxis in patients younger than 2 years of age deserves further study.

Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience

An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.