Histopathology of new-onset refractory status epilepticus (NORSE) in adults.

OBJECTIVE: new-onset refractory status epilepticus (NORSE) is defined as de novo refractory seizures occurring in previously healthy adults, without a clear underlying etiology. Due to refractory seizures and insufficient understanding of pathophysiology, management of these patients remains challenging and often leads to poor clinical outcomes. Various infectious and autoimmune mechanisms have been proposed but have not been validated and a large number of patients are thus labeled 'cryptogenic'. Moreover, histopathological findings have rarely been described in NORSE and are usually autopsy evaluations. In this paper, we describe the clinical correlates and histopathological findings in patients presenting with NORSE. METHODS: A case series of five patients with NORSE who underwent neurosurgical intervention and had histopathological examination during their acute clinical course. RESULTS: In all patients,status epileptics was refractory to treatment with antiseizure drugs (ASDs) and anesthetic agents. Autoimmune work-up revealed elevated titer of anti-GAD antibody in one patient but was unremarkable in others. Empiric use of immunomodulation therapy in three patients did not lead to cessation of status epilepticus (SE). Due to failure of prolonged medical management, three patients underwent palliative surgery for resection of epileptogenic tissue whereas the other two had diagnostic brain biopsy. Histopathology obtained during biopsy revealed evidence of vasculitis in one and necrotizing vasculopathy in another. The patient with anti-GAD antibodies had evidence of lymphocytic infiltration in limbic structures. The remaining two had nonspecific histopathological findings. SIGNIFICANCE: Although our findings are limited by a small number of patients, it adds to the growing premise of NORSE being related to an underlying autoimmune process. Additional studies, especially with histopathological data are needed to better understand this devastating disorder.

Frontal lobe hypometabolism associated with Sudden Unexpected Death in Epilepsy (SUDEP) risk: An objective PET study.

OBJECTIVE: Abnormalities of brain structures and neuronal networks have been identified in MRI studies of patients with Sudden Unexpected Death in Epilepsy (SUDEP) as well as in those at elevated risk. The goal of this study was to identify common patterns of objectively detected brain glucose metabolic abnormalities associated with SUDEP patients and those at high SUDEP risk. METHODS: Patients with refractory epilepsy (n = 78, age: 16-61 years, 44 females), who underwent comprehensive presurgical evaluation, were assessed for their risk of SUDEP using the revised SUDEP-7 inventory. From the 57 patients with low SUDEP risk, 35 were selected to match their demographic and clinical characteristics to those with high SUDEP risk (n = 21). [18F]fluoro-deoxy-glucose positron emission tomography (FDG-PET) abnormalities were evaluated in the high- and low-SUDEP risk subgroups compared to FDG-PET scans of a healthy adult control group using statistical parametric mapping (SPM). Individual FDG-PET scans of 4 additional patients, who died from SUDEP, were also analyzed by SPM. RESULTS: Mean SUDEP-7 score was 6.1 in the high and 2.7 in the low SUDEP risk group. MRI showed no lesion in 36 patients (64%). Statistical parametric mapping analysis of the high SUDEP risk subgroup showed bilateral medial frontal and inferior frontal hypometabolism as a common pattern. The low-risk group showed no specific common metabolic abnormalities on SPM group analysis. Individual PET scans of all 4 patients who died from SUDEP also showed bilateral frontal lobe hypometabolism. CONCLUSIONS: These data show that bilateral frontal lobe involvement on FDG-PET, especially the medial and inferior frontal cortex, may be a common metabolic pattern associated with high SUDEP risk and SUDEP itself, in patients with refractory focal epilepsy.

Atypical representation of sensorimotor cortex in a patient with autism and epilepsy confirmed by direct electrocortical stimulation.

Prior studies have used functional neuroimaging to demonstrate that the organization of the autistic brain is different from that of the non-autistic brain. Similarly, patients with epilepsy have also shown cortical reorganization. We present a case study that provides direct confirmation of disorganized sensorimotor distribution in a patient with autism spectrum disorder and epilepsy. To our knowledge, this is the first time cortical mapping directly showing abnormal cortical organization in a patient with autism spectrum disorder and epilepsy has been reported in the literature.

Racial variations in lacosamide serum concentrations in adult patients with epilepsy.

Lacosamide (LCM) is a third-generation anti-epileptic drug (AED) for partial-onset epilepsy with minimal hepatic metabolism and drug-drug interactions. The impact of individual patient variables such as race on drug metabolism have been under-reported in AEDs and LCM has not been specifically investigated. Our aim was to assess the role race plays on serum LCM levels in the management of epilepsy. Thus, we retrospectively reviewed patients with focal seizures who received LCM and had LCM levels as part of their routine clinical care in our Level IV Epilepsy Center. Variables including age, race, gender, LCM serum levels, LCM daily dose, and concomitant AEDs were collected and analyzed. A total of 93 patients with 1-3 clinic visits yielded 122 LCM serum levels. African Americans (AA) comprised 62.3% of our serum samples. Daily LCM doses averaged 350 mg/day (range 50-1000 mg/day). Eighty-nine percent of patients took 1-2 other AEDs. Overall, AA patients had lower LCM levels (mean 6.8 µg/mL) compared to White patients (mean of 7.1 µg/mL) (p = .017) even when considering for the daily dose effect (p = .007). Analysis of co-variables did not have significant effect on LCM levels. Overall, AA patients had a weaker relationship between LCM daily dose (adjusted for weight) and serum levels as compared to White patients and require a higher LCM dose per weight to achieve similar levels. Differences in pharmacogenetics may play an important role in these findings and focus on how these variations impact seizure burden.

Seizure-related injury and postictal aggression in refractory epilepsy patients.

OBJECTIVE: In the general population, injury related to seizures often involves falls, head trauma, soft tissue injuries, burns and fractures. Additionally, postictal deleterious behavior changes can by experienced by patients. We seek to identify the risk for seizure-related injury (SRI) and postictal aggression (PIA) in patients with refractory epilepsy. METHODS: Self-reported SRI and PIA were gathered through a seizure questionnaire as part of the epilepsy center's seizure safety protocol. Retrospective review of questionnaire, clinical course, and demographic data was completed. Statistical analysis of variables of interest was done using nonparametric methods. RESULTS: 126 patient questionnaires were completed over a one-year duration. Most patients reported seizure related injury (56.3 %) and postictal aggression (52.4 %). Increased disease duration was associated with seizure related injury and its severity (Kwallis p = 0.025), with number of antiepileptic drugs (AEDs) as significant factors (p = 0.012). Postictal aggression was also associated with a longer duration of epilepsy (Ranksum p = 0.037, t-test p = 0.04) and higher seizure frequency (p = 0.017). Patients who reported seizure related injury and postictal aggression were on more AEDs (p = 0.0003, p = 0.01, respectively), with first-generation AEDs being most contributory. CONCLUSION: The majority of patients with seizures report seizure-related injuries and postictal aggression. Duration and AED regimen are significant risk factors and screening practices can potentially guide safety measures and recommendations.

Differential expression of senescence tumour markers and its implications on survival outcomes of breast cancer patients.

Breast cancer is a heterogeneous disease displaying different histopathological characteristics, molecular profiling and clinical behavior. This study describes the expression patterns of senescence markers P53, DEC1 and DCR2 and assesses their significance on patient survival as a single or combined marker with P16 or P14 using breast cancer progression series. One thousand and eighty (1080) patients with primary invasive ductal carcinoma, no special type, were recruited through an 11-year retrospective study period. We constructed tissue microarrays of normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient and performed immunohistochemical staining to study the protein expression. Statistical analysis includes Pearson chi-square, Kaplan-Meier log ran test and Cox proportional hazard regression were undertaken to determine the associations and predict the survival outcomes. P53, DEC1 and DCR2 expression correlated significantly with normal, benign, premalignant and malignant tissues with (p<0.05). The expression profile of these genes increases from normal to benign to premalignant and plateaued from premalignant to malignant phenotype. There is a significant association between P53 protein expression and age, grade, staging, lymphovascular invasion, estrogen receptor, progesterone receptor and HER2 whereas DCR2 protein expression significantly correlated with tumour grade, hormone receptors status and HER2 (p<0.05 respectively). P53 overexpression correlated with increased risk of relapse (p = 0.002) specifically in patients who did not receive hormone therapy (p = 0.005) or chemotherapy (p<0.0001). The combination of P53+/P16+ is significantly correlated with poor overall and disease-free survival, whereas a combination of P53+/P14+ is associated with worse outcome in disease-free survival (p<0.05 respectively). P53 overexpression appears to be a univariate predictor of poor disease-free survival. The expression profiles of DEC1 and DCR2 do not appear to correlate with patient survival outcomes. The combination of P53 with P16, rather P53 expression alone, appears to provide more useful clinical information on patient survival outcomes in breast cancer.

Long-term safety and efficacy following conversion to eslicarbazepine acetate monotherapy in adults with focal seizures.

OBJECTIVE: To assess the long-term safety and efficacy of eslicarbazepine acetate (ESL) monotherapy in adults with focal seizures (FS). METHODS: Study 050 was a long-term, multicenter, open-label (OL) safety extension of two conversion-to-ESL monotherapy studies in adults with refractory FS. After participating in Study 045 or 046, patients started on ESL 1600 mg once daily (QD) (or 1200 mg if they previously had a dose reduction), and could adjust the dose 400 mg/week to a dose between 800-2400 mg QD. Patients could add up to two additional antiepileptic drugs (AEDs). This post-hoc analysis focuses on the actual monotherapy subgroup, which included patients in Studies 045/046/050 who did not add additional AEDs. Study endpoints included treatment retention time, time on ESL monotherapy, change in standardized seizure frequency (SSF), change in quality of life (QoL) in epilepsy (QOLIE-31) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores, and incidence of treatment-emergent adverse events (TEAEs); serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs related to allergic reaction, hyponatremia and thyroid function were also evaluated. RESULTS: There were 274 patients in the Study 050 full intent-to-treat (ITT) population and 140 patients in the actual monotherapy subgroup. Median treatment retention time and time on ESL monotherapy were both >5 years. Median reduction in SSF from baseline was 66.4% in the full ITT population and 78.3% in the actual monotherapy subgroup; responder (≥50% reduction in SSF) rates were 62.4% and 74.3%, respectively. QOLIE-31 scores increased from baseline in the full ITT population and the actual monotherapy subgroup (4.1- and 7.5-point increases, respectively). MADRS scores decreased from baseline in both the full ITT population and the actual monotherapy subgroup (0.7- and 2.9-point decreases, respectively). TEAEs occurred in 85.4% of patients in the full ITT population and 81.4% of patients in the actual monotherapy subgroup. Incidences of SAEs and TEAEs leading to discontinuation, as well as dizziness, depression, fall, partial seizures with secondary generalization, and complex partial seizures, were higher in the full ITT population than in the actual monotherapy subgroup. Allergic reactions, hyponatremia, and hypothyroidism were infrequent, particularly in the actual monotherapy subgroup. CONCLUSIONS: The results of this post-hoc analysis suggest that long-term treatment with ESL was effective and well tolerated, both as a monotherapy and in combination with other AEDs for FS. QoL and tolerability appeared to be better, and incidence of depression lower, in the patient population taking ESL as a monotherapy, compared with the population that included patients taking ESL as an adjunctive therapy.

Tolerability of adjunctive eslicarbazepine acetate according to concomitant lamotrigine or carbamazepine use: A subgroup analysis of three phase III trials in adults with focal (partial-onset) seizures.

OBJECTIVE: To evaluate and compare the effects of concomitant lamotrigine (LTG) or carbamazepine (CBZ) on the incidence of treatment-emergent adverse events (TEAEs) in patients taking adjunctive eslicarbazepine acetate (ESL) for focal (partial-onset) seizures (FS). METHODS: These post-hoc analyses of data pooled from three randomized, double-blind, placebo-controlled studies of adjunctive ESL (BIA-2093-301, -302 and -304) included adults (≥16 years) with FS refractory to 1-3 antiepileptic drugs (AEDs). Patients were randomized equally to placebo, ESL 400 mg (Studies 301 and 302 only), 800 mg, or 1200 mg once daily (8-week baseline, 2-week titration, and 12-week maintenance periods). TEAEs, TEAEs leading to discontinuation, and serious AEs (SAEs) were evaluated in patients taking, or not taking, LTG (excluding those taking CBZ or phenytoin [PHT]; i.e., the +LTG and -LTG/-CBZ subgroups), or CBZ (excluding those taking LTG or PHT; i.e., the +CBZ and -LTG/-CBZ subgroups) at baseline. RESULTS: LTG was used concomitantly by 248 patients (+LTG; placebo, n = 81; ESL, n = 167) and CBZ by 613 patients (+CBZ; placebo, n = 172; ESL, n = 441); 361 patients were taking neither LTG nor CBZ (-LTG/-CBZ; placebo, n = 109; ESL, n = 252). The overall incidence of TEAEs with ESL (any dose) was numerically higher for +CBZ (77%) than for +LTG (73%) or -LTG/-CBZ (68%; statistical significance not tested). Among patients taking ESL, dizziness, diplopia, and vomiting were reported more frequently in the +CBZ subgroup (30%, 14%, and 10%, respectively) than in the +LTG (16%, 8%, 5%) or -LTG/-CBZ (11%, 3%, 5%) subgroups. The overall incidence of TEAEs leading to discontinuation with ESL was higher for +CBZ (21%) than for +LTG (13%) or -LTG/-CBZ (15%). Dizziness leading to discontinuation with ESL was reported more frequently in the +CBZ subgroup than in the +LTG or -LTG/-CBZ subgroups (9%, 3%, and 3%, respectively). The overall incidence of SAEs in patients taking ESL was comparable across subgroups (+LTG, 5%; +CBZ, 6%; -LTG/-CBZ, 5%). The results were similar when evaluating placebo-adjusted incidences. CONCLUSION: There was a potential pharmacodynamic interaction between AEDs with a putatively similar mechanism of action, with a seemingly lesser interaction between ESL and LTG versus ESL and CBZ. If combining ESL with LTG or CBZ, clinicians should be aware of the potential risk for an increased incidence of TEAEs typically associated with voltage-gated sodium channel inhibitors (e.g., dizziness, blurred vision, vertigo, diplopia, headache, or vomiting).

Inadequate benzodiazepine dosing may result in progression to refractory and non-convulsive status epilepticus.

Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first-line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university-based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non-convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator-dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Among 100 patients, the median dose of LE was 3 mg (IQR: 2-5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=-0.6; p=0.04) and NCSE with coma (correlation coefficient r=-0.7; p=0.003). Outcome measures were not influenced by BZD dosing. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital-wide protocol to guide first responders in the management of SE.

Updates in Refractory Status Epilepticus.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.

Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures.

OBJECTIVE: To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. METHODS: This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400mg (studies 301 and 302 only), 800mg, or 1200mg once daily (QD) for 14weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. RESULTS: The analysis population included 1447 patients (ESL, n=1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p=0.802). The incidence of depression and suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p=0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p=0.023); incidences of memory impairment, attention disturbance, apathy, and aphasia were higher for ESL 1200mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs (SAEs) were 0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL, and 0.7% and 0.5% taking placebo, respectively. CONCLUSIONS: In phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. The incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo.

Intraoperative hippocampal electrocorticography frequently captures electrographic seizures and correlates with hippocampal pathology.

OBJECTIVE: Relationship between electrographic seizures on hippocampal electrocorticography (IH-ECoG) and presence/type of hippocampal pathology remains unclear. METHODS: IH-ECoG was recorded for 10-20 min from the ventricular surface of the hippocampus following removal of the temporal neocortex in 40 consecutive patients. Correlation between intraoperative hippocampal seizures and preoperative MRI, hippocampal histopathology, and EEG from invasive monitoring was determined. RESULTS: IH-ECoG captured electrographic seizures in 15/40 patients (in 8/23 with abnormal hippocampal signal on MRI and 7/17 patients without MRI abnormality). Hippocampal neuronal loss was observed in 22/40 (Group 1), while 18/40 had no significant neuronal loss (Group 2). In Group 1, 4/22 had seizures on IH-ECoG, while 11/18 had electrographic seizures in Group 2. In 24/40 patients who underwent prolonged extraoperative intracranial EEG (IC-EEG) recording, hippocampal seizures were captured in 14. Of these, 7 also had seizures during IH-ECoG. In 10/24 IC-EEG patients without seizures, 3 had seizures on IH-ECoG. CONCLUSIONS: IH-ECoG frequently captures spontaneous electrographic seizures. These are more likely to occur in patients with pathologic processes that do not disrupt/infiltrate hippocampus compared to patients with intractable epilepsy associated with disrupted hippocampal architecture. SIGNIFICANCE: Intraoperative hippocampal seizures may result from deafferentation from the temporal neocortex and disinhibition of the perforant pathway.

Acute Resective Surgery for the Treatment of Refractory Status Epilepticus.

BACKGROUND: To identify the role of acute surgical intervention in the treatment of refractory status epilepticus (RSE). METHODS: Retrospective review of consecutive patients who underwent epilepsy surgery from 2006 to 2015 was done to identify cases where acute surgical intervention was employed for the treatment of RSE. In addition, the adult and pediatric RSE literature was reviewed for reports of surgical treatment of RSE. RESULTS: Nine patients, aged 20-68 years, with various etiologies were identified to have undergone acute surgical resection for the treatment of RSE, aided by electrocorticography. Patients required aggressive medical therapy with antiepileptic drugs and intravenous anesthetic drugs for 10-54 days and underwent extensive neurodiagnostic testing prior to resective surgery. Eight out of nine patients survived and five patients were seizure-free at the last follow-up. The literature revealed 13 adult and 48 pediatric cases where adequate historical detail was available for review and comparison. CONCLUSIONS: We present the largest cohort of consecutive adult patients who underwent resective surgery in the setting of RSE. We also reveal that surgery can be efficacious in aborting status and in some can lead to long-term seizure freedom. Acute surgical intervention is a viable option in prolonged RSE and proper evaluation for such intervention should be conducted, although the timing and type of surgical intervention remain poorly defined.

Three- and four-dimensional mapping of speech and language in patients with epilepsy.

We have provided 3-D and 4D mapping of speech and language function based upon the results of direct cortical stimulation and event-related modulation of electrocorticography signals. Patients estimated to have right-hemispheric language dominance were excluded. Thus, 100 patients who underwent two-stage epilepsy surgery with chronic electrocorticography recording were studied. An older group consisted of 84 patients at least 10 years of age (7367 artefact-free non-epileptic electrodes), whereas a younger group included 16 children younger than age 10 (1438 electrodes). The probability of symptoms transiently induced by electrical stimulation was delineated on a 3D average surface image. The electrocorticography amplitude changes of high-gamma (70-110 Hz) and beta (15-30 Hz) activities during an auditory-naming task were animated on the average surface image in a 4D manner. Thereby, high-gamma augmentation and beta attenuation were treated as summary measures of cortical activation. Stimulation data indicated the causal relationship between (i) superior-temporal gyrus of either hemisphere and auditory hallucination; (ii) left superior-/middle-temporal gyri and receptive aphasia; (iii) widespread temporal/frontal lobe regions of the left hemisphere and expressive aphasia; and (iv) bilateral precentral/left posterior superior-frontal regions and speech arrest. On electrocorticography analysis, high-gamma augmentation involved the bilateral superior-temporal and precentral gyri immediately following question onset; at the same time, high-gamma activity was attenuated in the left orbitofrontal gyrus. High-gamma activity was augmented in the left temporal/frontal lobe regions, as well as left inferior-parietal and cingulate regions, maximally around question offset, with high-gamma augmentation in the left pars orbitalis inferior-frontal, middle-frontal, and inferior-parietal regions preceded by high-gamma attenuation in the contralateral homotopic regions. Immediately before verbal response, high-gamma augmentation involved the posterior superior-frontal and pre/postcentral regions, bilaterally. Beta-attenuation was spatially and temporally correlated with high-gamma augmentation in general but with exceptions. The younger and older groups shared similar spatial-temporal profiles of high-gamma and beta modulation; except, the younger group failed to show left-dominant activation in the rostral middle-frontal and pars orbitalis inferior-frontal regions around stimulus offset. The human brain may rapidly and alternately activate and deactivate cortical areas advantageous or obtrusive to function directed toward speech and language at a given moment. Increased left-dominant activation in the anterior frontal structures in the older age group may reflect developmental consolidation of the language system. The results of our functional mapping may be useful in predicting, across not only space but also time and patient age, sites specific to language function for presurgical evaluation of focal epilepsy.

Management of brain tumor-related epilepsy.

Seizures are common in both primary and metastatic brain tumors, although the rate of seizures differ significantly between the different types of neoplasms. Patients with brain tumor-associated seizures need treatment with antiepileptic drugs (AEDs) to prevent recurrence, whereas strong clinical data exists to discourage routine prophylaxis in patients who have not had seizures. The newer AEDs, such as levetiracetam, lamotrigine, lacosamide, topiramate, or pregabalin, are preferable for various reasons, primarily related to the side-effect profile and limited interactions with other drugs. If seizures persist despite initiation of an appropriate monotherapy (in up to 30-40% of cases), additional anticonvulsants may be necessary. Early surgical intervention improves seizure outcomes in individuals with medically refractory epilepsy, especially in patients with a single lesion that is epileptogenic. Data for this review article were compiled by searching for scholarly articles using the following keywords: brain tumor, epilepsy, seizure, tumor-related epilepsy, central nervous system, epidemiology, review, clinical trial, and surgery. Articles were screened for relevance by title and abstract, and selected for review and inclusion based on significant contribution to the topics discussed.

Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials.

Patients with low-grade glioma frequently have brain tumor-related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed.