Perioperative Seizures Research Articles

Periodic focal epileptiform discharges

ObjectiveTo report intraoperative periodic focal epileptiform discharges (PFEDs) during awake craniotomy using high-density electrocorticography (HD-ECoG). MethodsWe retrospectively analyzed 81 patients undergoing awake craniotomy between 9/29/2016 and 7/5/2018. Intraoperative HD-ECoG was performed with direct electrocortical stimulation (DECS) for functional brain mapping. Real-time interpretation was performed and compared to scalp EEG when performed. Perioperative seizures, surgical complications, and characteristics of PFEDs were assessed. Results69/81 patients (mean age 48.5 years) underwent awake surgery; 55 operated for brain tumor, 11 for epilepsy and 3 for cavernomas. A focal abnormality on brain MRI was present in 63/69 (91.3%) patients. 43/69 (62.3%) patients had seizures preoperatively, 4/69 (5.7%) had seizures during DECS. PFEDs were identified in 11 patients (15.9%); 2 on depth recording and 9 during intraoperative HD-ECoG. 32 patients (46.3%) had preoperative EEG. HD-ECoG detected more epileptiform discharges (EDs) than standard EEG (32/43; 74.4% vs 9/32; 28.1%) (p = <0.001). Of 9/43 patients with PFEDs on HD-ECoG, 7 patients also had scalp EEG but only one case had EDs (p = 0.02), and 0/32 had periodic EDs. ConclusionsIntraoperative PFEDs are novel, highly focal EDs approximating a single gyrus. In patients with brain tumors, PFEDs did not demonstrate a relationship to pre-operative seizures though has similarities to other common waveforms in patients with epilepsy. SignificancePFEDs expand our understanding of the interictal-ictal continuum and highlight improved temporo-spatial information obtained from increasing sensor density during intracranial EEG recording.

Long-Versus Short-Term Seizure Prophylaxis After Craniotomy for Clipping in Aneurysmal Subarachnoid Hemorrhage; A Retrospective Cohort Study

Background: Seizures are quite common following subarachnoid hemorrhage (SAH) and due to increased mortality and morbidity in this setting, thus seizure prophylaxis is introduced as a common neurosurgical practice. Investigations are still ongoing to figure out the most efficient seizure prophylaxis guideline. Objectives: To compare the efficacy of two seizures prophylaxis protocols that have been practiced in a tertiary neurovascular center in Southern Iran through a retrospective cohort analysis Methods: A total of 426 patients who were operated due to aneurysmal SAH between September 2007 and March 2016 were included in this retrospective cohort study. From September 2007 to March 2011 the common practice was prophylaxis with phenytoin for 3 - 6 months, which was switched to a shorter 1-month course since March 2011. Seizure control was evaluated in telephoned patients and outpatient records. Results: Out of 426 subjects eligible for this study, 165 (38.7%) took the 1-month (short-term) regimen and 261 (61.3%) took the 3 - 6 months (long-term) regimen. Results revealed that achievement of seizure control was similar for both groups in those without perioperative seizures (P = 0.4); however, with perioperative seizures, the short-term protocol had inferior results for seizure control and higher odds (almost 109-fold) for developing post-operative seizures. Conclusions: Although short-term 1-month seizure prophylaxis with phenytoin provides adequate seizure control for most individuals after SAH, perioperative seizures necessitates a longer course of 3 - 6 month seizure prophylaxis.

Incidence and Risk Factors for Intraoperative Seizures During Elective Craniotomy.

Perioperative seizures may affect 1% to 50% of patients undergoing craniotomy and adversely impact outcomes. However, data on intraoperative seizures are limited. This retrospective case-control study investigated the incidence and risk factors for intraoperative seizures during elective supratentorial craniotomy involving evoked potential monitoring. Patients aged 18 years or above undergoing elective supratentorial craniotomy with evoked potential monitoring who experienced intraoperative seizures at our institution between December 2008 and March 2014 were compared with a control group generated using a random number generator. Six controls were used for each case from among the patients who underwent elective supratentorial craniotomy during the same calendar year. Multivariate analysis was conducted using logistic regression to identify the risk factors for intraoperative seizures. Among the 1916 patients who met the inclusion criteria, 45 (2.3%) had intraoperative seizures. The majority of seizures occurred during burr-hole placement or craniotomy, before lesion manipulation. Timing of seizures relative to motor evoked potential runs and stimulus intensity was variable. Significant risk factors for intraoperative seizures were seizure history (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07-4.46; P=0.03), diagnosis of brain tumor (OR, 2.41; 95% CI, 1.16-4.19; P=0.02), and temporal craniotomy (OR, 5.18; 95% CI, 2.03-13.25; P=0.001). Intraoperative prophylactic use of phenytoin/fosphenytoin and levetiracetam was protective against seizure (phenytoin/fosphenytoin: OR, 0.12; 95% CI, 0.04-0.35; P<0.001 and levetiracetam: OR, 0.40; 95% CI, 0.17-0.94; P=0.04). Phenytoin/fosphenytoin was more protective than levetiracetam (OR, 0.31; 95% CI, 0.10-0.99; P=0.048). The overall incidence of intraoperative seizures was 2.3%. Independent risk factors for intraoperative seizures were seizure history, diagnosis of intracranial tumor, and temporal craniotomy. Intraoperative prophylactic anticonvulsant use was protective.

Brain invasion and the risk of seizures in patients with meningioma.

Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma. Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses. Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81-162.22 cm3) and 1.38 cm3 (range 0.00-355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients' age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13-5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00-1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52-18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372). Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion.

Factors associated with early seizures after surgery of unruptured intracranial aneurysms

ObjectiveThe aim of the study was to better define the incidence of and risk factors for early seizures after repair of unruptured intracranial aneurysms in modern microsurgical techniques. Patients and methodsThe medical records of 414 consecutive patients who underwent neck clipping of unruptured intracranial aneurysms in our institution over a 5-year period were retrospectively reviewed. Clinical and neuroimaging variables were analyzed to investigate putative predictors of perioperative seizures using multivariate logistic regression analysis. ResultsOverall, 24 patients (5.8%) developed seizures within 14 days of surgery without routine prophylactic use of anticonvulsants. Eleven patients experienced partial seizures, while 13 experienced secondary generalized seizures. The interval between surgery and seizure onset was less than 6 h in 8 patients, 6–24 h in 3, and 1–14 days in 11. History of dialysis (odds ratio [OR] = 77.6, 95% confidence interval [CI] 7.5–1783.4, P < 0.001), and presence of cerebral contusion (OR = 5.1, 95% CI 1.3–16.9, P = 0.02) or infarction (OR = 13.9, 95% CI 3.9–48.5, P < 0.001) detected by postoperative computed tomography were independent and significant risk factors. No patients with early seizures went on to develop refractory epilepsy. ConclusionsDialysis and iatrogenic brain damage were associated with a higher risk of early seizures after aneurysm surgery. Our data support the selective use of anticonvulsants during the perioperative period of elective aneurysm surgery.

Epilepsy and seizures in children with congenital heart disease: A prospective study

PurposeChildren with complex congenital heart disease (CHD) experience high incidence of perioperative seizures. Population-based studies also report high epilepsy co-morbidity in CHD. Given the increasing survival of patients with CHD and the interference of seizures and epilepsy with the long-term outcomes, characterizing them in this population is of high relevance. This study investigated the incidence and risk factors of perioperative clinical seizures (CS) and epilepsy in a prospective cohort of children with complex CHD who underwent cardiac surgery. MethodsWe included 128 consecutive children with CHD, followed for at least two years at the neurocardiac clinic of Montreal’s Sainte-Justine University Hospital Center. We collected perinatal, surgical, critical care and clinical follow-up information and performed logistic regression to reveal risk factors of CS and epilepsy. ResultsTen patients (7.8%) experienced perioperative CS. Four of them (40%) developed epilepsy. The incidence of epilepsy was therefore 3.1%. Higher surgical complexity scores, delayed sternal closure, extracorporeal membrane oxygenation (ECMO) use, longer intensive care and hospital stay were associated with CS. ECMO use and hospital stay were also associated with epilepsy. Nine (90%) patients with CS had brain injuries: five strokes, one white matter and three hypoxic-ischemic injury (HII). All patients with HII developed epilepsy, which became intractable in one of them. ConclusionOur study reports high incidence, surgical risk factors and brain injury patterns underlying CS and epilepsy in CHD. Further studies are needed to investigate how epilepsy interferes with neurodevelopment and quality of life in CHD.

Laser interstitial thermal therapy (LITT): Seizure outcomes for refractory mesial temporal lobe epilepsy

BackgroundLaser interstitial thermal therapy (LITT) is a minimally invasive alternative with less cognitive risks compared with traditional surgery for focal drug-resistant epilepsy. ObjectiveWe describe seizure outcomes and complications after LITT in our cohort with intractable mesial temporal lobe epilepsy (MTLE). Material and methodsWe prospectively tracked Stanford's MTLE cases treated with LITT from October 2014 to October 2017. Primary endpoints were seizure outcomes by (1) Engel classification and (2) reduction in baseline seizure frequency. Secondary outcomes were postablation complications. ResultsA total of 30 patients underwent selective amygdalohippocampotomy via LITT. Mesial temporal sclerosis (MTS) was present in 23/30 (77%) patients. Median follow-up was 18 ± 12 months (range: 6–44 months). Almost all 28/29 (97%) patients had >50% reduction, and 22/29 (76%) patients had >90% reduction in seizure frequency. Engel Class I outcome was achieved in 18/29 (62%) patients; with complete seizure freedom in 9/29 (31%) patients (Engel Class IA). Three (10%) patients have had only focal aware seizures (Engel Class 1B). Seizures only occurred with medication withdrawal in 6/29 (21%) patients (Engel Class ID). Class II was achieved by 6/29 (21%) and Class III by 5/29 (17%) patients.Complications included perioperative seizures in 10/29 (34%) and nonseizure complaints in 6/29 (21%) patients. Three (10%) patients had neurological deficits including one permanent superior quadrantanopsia, one transient trochlear, and one transient oculomotor nerve palsy. ConclusionsOverall, Engel Class I outcome was achieved in 62% of patients with MTLE, and 97% of patients achieved >50% seizure frequency reduction. Complications were largely temporary, though there was one persistent visual field deficit. Laser ablation is well-tolerated and offers marked seizure reduction for the majority of patients.

Postoperative seizures in meningioma patients: improving patient selection for antiepileptic drug therapy

BackgroundEpilepsy is a major cause of morbidity and mortality in meningioma patients. The aims of this study were to determine which factors predispose meningioma patients to developing perioperative seizures and to understand the impact of antiepileptic drugs.MethodsPatients treated for a histologically-confirmed intracranial meningioma at the authors’ institution between 2010 and 2015 were retrospectively examined. Clinical and imaging data were assessed. Multivariate analysis was performed using binary logistic regression. The effect of antiepileptic treatment was assessed using survival analysis.ResultsTwo hundred and eighty-three patients met the selection criteria; seizures were present in 68 preoperatively (24%) and in 48 patients (17%) following surgery. Of the 68 with preoperative seizures, 19 continued to have them, whereas de-novo seizures arose postoperatively in 29 seizure-naïve patients. Risk factors of postoperative seizures were convexity location (OR 2.05 [95% CI 1.07–3.98], p = 0.030), fronto-parietal location (OR 4.42 [95% CI 1.49–13.16], p = 0.007) and preoperative seizures (OR 2.65 [95% CI 1.37–5.24], p = 0.005). The two locations, in addition to the presence of midline shift on preoperative imaging (OR 4.15 [95% CI 1.54–11.24], p = 0.005), were significantly correlated with postoperative seizures in seizure-naïve patients. Antiepileptic treatment in patients with those risk factors reduced the possibility of seizures at any time point within the 1st year postoperatively by approximately 40%, although this did not meet statistical significance.ConclusionProphylactic antiepileptic treatment might be warranted in seizure-naïve meningioma patients with ≥ 1 risk factor. High-quality randomised controlled trials are required to verify those factors and to define the role of antiepileptics in meningioma practice.

T57. Prediction of early tumor progression based on pre- and post-operative seizure frequency in low grade gliomas

Low-grade gliomas (LGG) are slow-growing tumors characterized by an infiltrative growth pattern and cortical predilection in the central nervous system (CNS). Up to 90% of LGG patients may have seizures as the initial presentation leading to tumor diagnosis, and up to 15% of them develop refractory epilepsy. Predicting which patient will evolve into refractory epilepsy versus have more benign disease course remains a challenge. Moreover, seizure recurrence following surgical resection may predict early tumor recurrence, especially in patients who have achieved long seizure-freedom period. This study analyzed 148 patients meeting inclusion criteria (age > 18 years, LGG diagnosis, at least one seizures event at some point of the disease process). All patients were treated by the Department of Neuro-Oncology and Neurosurgery at University of Texas MD Anderson Cancer Center (MDACC) from Jan/2000 and Dec/2015. Seizure frequency was divided in 4 categories: none, one, few (2–3 seizures) and several (>4 seizures). Perioperative seizures (up to 48 h from surgery) were excluded from this analysis. One hundred sixteen (78.4%) patients had seizures as the initial presentation. On average, the first seizure occurred 4.75 months prior to surgical resection (range 0.1–24.2). Pre-operatively, 54 (36.5%) patients had a single seizure, 23 (15.5%) patients had few seizures and 39 (26.4%) patients had several seizures. After initial event, most patients (74%) were started on antiepileptic drugs (AED). Ninety-two (63%) patients accomplished partial resection, whereas 54 (37%) patients accomplished gross total resection of the tumor. Univariate analysis of seizure frequency between the 6-month pre-op and post-op periods was significant in predicting recurrence-free survival in the following 2 (2-RFS) and 5 (5-RFS) years (p = 0.0379). Patients with no/one seizure pre-op who continued to have no/one seizure in the 6-month post-op period had the highest 2-RFS and 5-RFS (0.984 and 0.667 [CI 95%, 0.889–0.998 and 0.528–0.773], respectively); patients who had no/one seizure pre-op and developed few/several seizures in the 6-month post-op period had the lowest probability of being progression-free in the following 2 and 5 years (0.750 and 0.545 [CI95%, 0.463–0.898 and 0.274–0.753], respectively). Multicovariate cox-regression analysis on RFS based on the seizure frequency change between pre-op and post-op periods revealed that patients with no/one seizure pre-op who had increase in seizure frequency to few/several seizures on the 6-month post-op period had significantly more risk of progression compared to patients who initially had no/one seizure pre-op and continued to have no/one seizure in the 6-month post-op period (HR 2.431 [CI95% 1.318, 4.482], p = 0.0044). Seizure frequency following surgical resection of LGG and the seizure frequency change between the 6-month pre-op and post-op periods predict early tumor recurrence in LGG.

F19. Standardized perioperative care for epilepsy surgery patients

Approximately 45 patients a year undergo epilepsy surgery at Children’s National Medical Center. We initiated an individualized perioperative plan for epilepsy surgery patients 8 years ago in order to standardize management. Goals of the standardized perioperative care plan were to minimize medication errors, improve communication across teams and streamline care for efficiency and the patient experience. In 2009, we identified patients undergoing epilepsy surgery were at high risk for medication errors. We set out to devise a perioperative seizure plan that would improve safety for patients in this vulnerable time period. Opportunities for standardization included assignment of loading doses to specific teams (e.g. intraoperative Dilantin), documentation of current seizure medications, including dosing, formulation and schedule, documentation of historical intolerances of medication and a seizure rescue plan. The perioperative care plan has been in use for 8 years. All epilepsy surgery patients are cared for according to an individualized perioperative plan created by a multidisciplinary team prior to surgery. Implementation is shared by members of the care team including epilepsy, neurocritical care, anesthesia, neurosurgery and nursing. This plan is relied upon and recent modifications have broadened the scope to also include standardization of postoperative imaging. Perioperative seizure management can be standardized to minimize medication errors, improve communication and streamline care across multiple care teams and locations.

Intraoperative Seizures: Anesthetic and Antiepileptic Drugs.

Epilepsy is a common condition with up to 1% prevalence in the general population. In the perioperative course of neurologic surgery patients, the use of prophylactic and therapeutic antiepileptic drugs is a common practice. Nonetheless, there is limited evidence supporting the use of prophylactic antiepileptics to prevent perioperative seizures and there are no guidelines for which anesthetic technique is preferred. To discuss the seizurogenic potential of anesthetic drugs and to discuss intraoperative seizures in neurosurgical patients. We performed a search of the literature available in PubMed and Ovid MEDLINE. We also included articles identified in the review of the references of these articles. The incidence of seizures is heterogenic among neurosurgical patients. Seizure prophylaxis is widely administered despite limited available evidence of its effectiveness. In epileptic patients, the recommendation is to continue antiepileptic drugs in the perioperative setting. In these patients, anesthesiologists may also limit the use of medications that alter the seizure threshold and avoid medications that pose significant pharmacological interaction with antiepileptic drugs. In conclusion, a knowledgeable multidisciplinary perioperative team is essential to avoid, identify and treat intraoperative seizures competently. In patients with a history of epilepsy it is recommended to continue antiepileptic therapy. Therefore, clinical judgment should guide the decision of administering seizure prophylaxis in neurosurgery patients according to an individual assessment of potential risk for seizures. Furthermore, there is a need for randomized controlled trials that support new protocols and/or guidelines for anesthetic and perioperative regimens to prevent and treat intraoperative seizures.

Intraoperative Seizures in Awake Craniotomy for Perirolandic Glioma Resections That Undergo Cortical Mapping

Perirolandic motor area gliomas present invasive eloquent region tumors within the precentral gyrus that are difficult to resect without causing neurologic deficits. This study evaluates the role of awake craniotomy and motor mapping on neurologic outcome and extent of resection (EOR) of tumor in the perirolandic motor region. It also analyzes preoperative risk factors for intraoperative seizures. We evaluated 57 patients who underwent an awake craniotomy for a perirolandic motor area eloquent region glioma. Patients who had positive mapping (PM) or intraoperative identification of motor regions in the cortex using direct cortical stimulation were compared with patients with no positive motor mapping following direct cortical stimulation and negative mapping (NM). Preoperative risks, intraoperative seizures, perioperative outcomes, tumor characteristics, and EOR were also compared. A logistic regression model was used to evaluate the predictors for intraoperative seizures in this patient cohort. Overall, 33 patients were in the PM cohort; 24 were in the NM cohort. Our study showed an 8.8% incidence of intraoperative seizures during cortical and subcortical mapping for awake craniotomies in the perirolandic motor area, none of which aborted the case. PM patients had significantly more intraoperative and postoperative seizures (15.5% and 30.3%, respectively) compared with the NM patients (0% and 8.3%, respectively; p = 0.046 and 0.044). New transient postoperative motor deficits were found more often in the PM group (51.5%) versus the NM group (12.5%; p = 0.002). A univariate logistic regression showed that PM (odds ratio [OR]: 1.16; 95% confidence interval [CI], 1.01-1.34; p = 0.035) and preoperative tumor volume (OR: 0.998; 95% CI, 0.996-0.999; p = 0.049) were significant predictors for intraoperative seizures in patients with perirolandic gliomas. Awake craniotomies in the perirolandic motor region can be safely performed with a similar incidence of intraoperative seizures as reported for the language cortex. PM in this region may increase the likelihood of perioperative seizures or motor deficits compared with NM. Craniotomies that minimize cortical exposure for perirolandic gliomas that may not localize motor regions can still allow for extensive tumor resection with a good postoperative outcome.

Anesthetic challenges in a child with Lowe's and Fanconi syndrome.

Oculocerebrorenal syndrome of Lowe is a rare X-linked metabolic disorder complicated by Fanconi's syndrome. Anaesthetic management of Lowe syndrome with Fanconi's syndrome is challenging to the anaesthesiologists in view of difficult airway due to microcephaly, metabolic abnormalities, and risk of peri-operative seizures. We report a successful anaesthetic management of a case of 2-year-old child scheduled for evaluation under anaesthesia following bilateral lens aspiration surgery.

A systematic review of perioperative seizure prophylaxis during brain tumor resection: the case for a multicenter randomized clinical trial.

OBJECTIVE The majority of neurosurgeons administer antiepileptic drugs (AEDs) prophylactically for supratentorial tumor resection without clear evidence to support this practice. The putative benefit of perioperative seizure prophylaxis must be weighed against the risks of adverse effects and drug interactions in patients without a history of seizures. Consequently, the authors conducted a systematic review of prospective randomized controlled trials (RCTs) that have evaluated the efficacy of perioperative seizure prophylaxis among patients without a history of seizures. METHODS Five databases (PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL/Academic Search Complete, Web of Science, and ScienceDirect) were searched for RCTs published before May 2017 and investigating perioperative seizure prophylaxis in brain tumor resection. Of the 496 unique research articles identified, 4 were selected for inclusion in this review. RESULTS This systematic review revealed a weighted average seizure rate of 10.65% for the control groups. There was no significant difference in seizure rates among the groups that received seizure prophylaxis and those that did not. Further, this expected incidence of new-onset postoperative seizures would require a total of 1258 patients to enroll in a RCT, as determined by a Farrington-Manning noninferiority test performed at the 0.05 level using a noninferiority difference of 5%. CONCLUSIONS According to a systematic review of major RCTs, the administration of prophylactic AEDs after brain tumor resection shows no significant reduction in the incidence of seizures compared with that in controls. A large multicenter randomized clinical trial would be required to assess whether perioperative seizure prophylaxis provides benefit for patients undergoing brain tumor resection.

New-onset seizure during and after brain tumor excision: a risk assessment analysis.

OBJECTIVE Prophylactic use of antiepileptic drugs (AEDs) in seizure-naïve brain tumor patients remains a topic of debate. This study aimed to characterize a subset of patients at highest risk for new-onset perioperative seizures (i.e., intraoperative and postoperative seizures occurring within 30 days of surgery) who may benefit from prophylactic AEDs. METHODS The authors conducted a retrospective case-control study of all adults who had undergone tumor resection or biopsy at the authors' institution between January 1, 2004, and June 31, 2015. All patients with a history of preoperative seizures, posterior fossa tumors, pituitary tumors, and parasellar tumors were excluded. A control group was matched to the seizure patients according to age (± 0 years). Demographic data, clinical status, operative data, and postoperative course data were collected and analyzed. RESULTS Among 1693 patients who underwent tumor resection or biopsy, 549 (32.4%) had never had a preoperative seizure. Of these 549 patients, 25 (4.6%) suffered a perioperative seizure (Group 1). A total of 524 patients (95.4%) who remained seizure free were matched to Group 1 according to age (± 0 years), resulting in 132 control patients (Group 2), at an approximate ratio of 1:5. There were no differences between the patient groups in terms of age, sex, race, relationship status, and neurological deficits on presentation. Histological subtype (infiltrating glioma vs meningioma vs other, p = 0.041), intradural tumor location (p < 0.001), intraoperative cortical stimulation (p = 0.004), and extent of resection (less than gross total, p = 0.002) were associated with the occurrence of perioperative seizures. CONCLUSIONS While most seizure-naïve brain tumor patients do not benefit from perioperative seizure prophylaxis, such treatment should be considered in high-risk patients with supratentorial intradural tumors, in patients undergoing intraoperative cortical stimulation, and in patients in whom subtotal resection is likely.

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.

P01.19 Activation of the mTOR signaling pathway in peritumoral tissues can cause glioma-associated seizures

AbstractEpileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.

The risk of hypotension and seizures in patients receiving prophylactic anti-epileptic drugs for supratentorial craniotomy.

Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of levetiracetam (LEV) alone, LEV and lacosamid (LCM) as compared to phenytoin (PHT). After IRB approval, the charts of individuals who underwent craniotomy from April 2007 to September 2011 were reviewed. Those receiving PHT were compared to those receiving LEV alone and LEV/LCM. The patient data included demographic, indication and procedure related data. The cumulative dose of norepinephrine (NET), atropine (ATR) and the change in systolic blood pressure during and after the administration of the AED were analyzed. Five hundred thirty-eight patients were screened of which 122 were included for analysis. 40 patients with primary or secondary supratentorial brain tumors received LEV (19 female, 21 male; mean age 56 years), 41 patients received LEV/ LCM (16 female, 25 male; mean age 56 years) and 41 patients received PHT (15 female, 26 male; mean age 50 years). The commonest indications for craniotomy were glioblastoma (N.=14 vs. N.=12 vs. N.=15), meningiomas (N.=9 vs. N.=7 vs. N.=10), low-grade gliomas (N.=6 vs. N.=13 vs. N.=6) and brain metastases (N.=5 vs. N.=4 vs. N.=5). 1 LEV/LCM patient (2%) and 4 PHT patients (4.5%) had a seizure despite prophylaxis. Possible side effects were observed in 2 patients associated with PHT. During anesthesia there was a significant drop in systolic blood pressure in the PHT group after administration of the AED perioperatively when compared to LEV (P=0.001) and LEV/LCM (P≤0.0001) respectively. The mean cumulative doses of NET and ATR over the course of the operation did not differ significantly. LEV alone and in combination with LCM for patients without and with symptomatic epilepsy as seizure prophylaxis provides a safe and feasible alternative to PHT. PHT was associated with an unfavorable drop in blood pressure during anesthesia and more adverse reactions.

Activation of the mTOR signaling pathway in peritumoral tissues can cause glioma-associated seizures.

Epileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.

Considerations in the management of giant frontal mucoceles with significant intracranial extension: A systematic review.

Giant frontal mucoceles, characterized by significant intracranial and/or intraorbital extension, can present with significant neurologic symptoms. Although typical mucoceles are managed endoscopically, giant mucoceles are often treated with an open or combined approach due to various concerns, including frontal lobe displacement, size, and rapid decompression of the intracranial component. The impact of significant intracranial extension on outcomes is not well described. This review studied key neurologic considerations in the management of giant frontal sinus mucoceles and analyzed outcomes of different management strategies. Systematic literature review by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Thirty-two articles, which represented 85 cases, met inclusion criteria. Neurologic symptoms on presentation ranged from headache (24.7%) and vision loss (12.9%) to extremity weakness (1.2%), frontal lobe syndrome (2.4%), and seizures (4.7%). Twenty-eight patients were treated endoscopically (34.1%), and 54 (65.9%) were treated with an external approach. Twenty-five of the open procedures included a craniotomy. Indications for the open approach included subdural empyema, enucleation, or large anterior table defects. Perioperative antibiotics were not consistently used. No perioperative seizures were reported with any approach. There were six cerebrospinal fluid leaks, all in the patients who underwent open procedures. The overall recurrence rate was 3.5%, with no recurrences reported in patients treated with an open approach. Follow-up ranged from 1 week to 8 years. Giant frontal mucoceles often present with various neurologic symptoms. Both open and endoscopic techniques offer excellent results. Endoscopic management is effective and preferred, except in special circumstances. An interdisciplinary team approach should be used to optimize surgical planning.