Surgical Treatments for Epilepsy.

PURPOSE OF REVIEW: More than 20 new antiseizure medications have been approved by the US Food and Drug Administration (FDA) in the past 3 decades; however, outcomes in newly diagnosed epilepsy have not improved, and epilepsy remains drug resistant in up to 40% of patients. Evidence supports improved seizure outcomes and quality of life in those who have undergone epilepsy surgery, but epilepsy surgery remains underutilized. This article outlines indications for epilepsy surgery, describes the presurgical workup, and summarizes current available surgical approaches. RECENT FINDINGS: Class I evidence has demonstrated the superiority of resective surgery compared to medical therapy for seizure control and quality of life in patients with drug-resistant epilepsy. The use of minimally invasive options, such as laser interstitial thermal therapy and stereotactic radiosurgery, are alternatives to resective surgery in well-selected patients. Neuromodulation techniques, such as responsive neurostimulation, deep brain stimulation, and vagus nerve stimulation, offer a suitable alternative, especially in those where resective surgery is contraindicated or where patients prefer nonresective surgery. Although neuromodulation approaches reduce seizure frequency, they are less likely to be associated with seizure freedom than resective surgery. SUMMARY: Appropriate patients with drug-resistant epilepsy benefit from epilepsy surgery. If two well-chosen and tolerated medication trials do not achieve seizure control, referral to a comprehensive epilepsy center for a thorough presurgical workup and discussion of surgical options is appropriate. Mounting Class I evidence supports a significantly higher chance of stopping disabling seizures with surgery than with further medication trials.

Intracranial EEG in the 21st Century.

Intracranial electroencephalography (iEEG) has been the mainstay of identifying the seizure onset zone (SOZ), a key diagnostic procedure in addition to neuroimaging when considering epilepsy surgery. In many patients, iEEG has been the basis for resective epilepsy surgery, to date still the most successful treatment for drug-resistant epilepsy. Intracranial EEG determines the location and resectability of the SOZ. Advances in recording and implantation of iEEG provide multiple options in the 21st century. This not only includes the choice between subdural electrodes (SDE) and stereoelectroencephalography (SEEG) but also includes the implantation and recordings from microelectrodes. Before iEEG implantation, especially in magnetic resonance imaging -negative epilepsy, a clear hypothesis for seizure generation and propagation should be based on noninvasive methods. Intracranial EEG implantation should be planned by a multidisciplinary team considering epileptic networks. Recordings from SDE and SEEG have both their advantages and disadvantages. Stereo-EEG seems to have a lower rate of complications that are clinically significant, but has limitations in spatial sampling of the cortical surface. Stereo-EEG can sample deeper areas of the brain including deep sulci and hard to reach areas such as the insula. To determine the epileptogenic zone, interictal and ictal information should be taken into consideration. Interictal spiking, low frequency slowing, as well as high frequency oscillations may inform about the epileptogenic zone. Ictally, high frequency onsets in the beta/gamma range are usually associated with the SOZ, but specialized recordings with combined macro and microelectrodes may in the future educate us about onset in higher frequency bands. Stimulation of intracranial electrodes triggering habitual seizures can assist in identifying the SOZ. Advanced computational methods such as determining the epileptogenicity index and similar measures may enhance standard clinical interpretation. Improved techniques to record and interpret iEEG may in the future lead to a greater proportion of patients being seizure free after epilepsy surgery.

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures.

OBJECTIVE: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System. METHODS: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up. RESULTS: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences. SIGNIFICANCE: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.

Antiepileptic drug effects on subjective and objective cognition.

RATIONALE: Cognitive impairment is one of the most common complaints for persons with epilepsy (PWE). These impairments are not only associated with seizures, but are also regularly reported as adverse effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the Centers for Disease Control and Prevention (CDC)-sponsored Managing Epilepsy Well (MEW) Network collaborative. We used three distinct archival datasets from the following: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multisite replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine. METHODS: This retrospective analysis combined baseline data from three datasets to determine how the number of AEDs and the type of AEDs were associated with subjective (patient-reported) and objective (examiner-assessed) cognition. Subjective cognition was captured using the cognitive subscale of the Quality of Life in Epilepsy Inventory (QOLIE-31) in all three datasets (n = 224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n = 65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n = 91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression, and history of prior epilepsy surgery. Nonparametric statistical tests were utilized to compare these matched subjects. RESULTS: Subjective cognitive impairment was significantly worse among individuals on polytherapy (2 + AEDs) compared with those on monotherapy (1 AED) (adjusted p  =  0.041). These findings were consistent with our propensity score matched comparison of monotherapy and polytherapy, which indicated that polytherapy was associated with worse overall subjective cognition (adjusted p = 0.01), in addition to impairments on the RBANS (Total score p = 0.05) and specific subdomains of the BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). Interestingly, older generation AEDs were associated with better language performance than newer generation and combined generation AED therapy (RBANS Language p = 0.03). These language-specific findings remained significant after controlling for the effects of topiramate and zonisamide (p = 0.04). CONCLUSIONS: A greater number of AEDs is significantly and negatively associated with subjective and objective cognition in PWE, and is in line with previous research. Antiepileptic drug type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs.

Cognitive tasks and human ambulatory electrocorticography using the RNS System.

BACKGROUND: Electrocorticography studies are typically conducted in patients undergoing video EEG monitoring, but these studies are subject to confounds such as the effects of pain, recent anesthesia, analgesics, drug changes, antibiotics, and implant effects. NEW METHOD: Techniques were developed to obtain electrocorticographic (ECoG) data from freely moving subjects performing navigational tasks using the RNS® System (NeuroPace, Inc., Mountain View, CA), a brain-responsive neurostimulation medical device used to treat focal onset epilepsy, and to align data from the RNS System with cognitive task events with high precision. These subjects had not had recent surgery, and were therefore not confounded by the perioperative variables that affect video EEG studies. RESULTS: Task synchronization using the synchronization marker technique provides a quantitative measure of clock uncertainty, and can align data to task events with less than 4 ms of uncertainty. Hippocampal ECoG activity was found to change immediately before an incorrect response to a math problem compared to hippocampal activity before a correct response. In addition, subjects were found to have variable but significant changes in theta band power in the hippocampus during navigation compared to when subjects were not navigating. We found that there is theta-gamma phase-amplitude coupling in the right hippocampus while subjects stand still during a navigation task. COMPARISON WITH EXISTING METHODS: An alignment technique described in this study improves the upper bound on task-ECoG alignment uncertainty from approximately 30 ms to under 4 ms. The RNS System is one of the first platforms capable of providing untethered ambulatory ECoG recording in humans, allowing for the study of real world instead of virtual navigation. Compared to intracranial video EEG studies, studies using the RNS System platform are not subject to confounds caused by the drugs and recent surgery inherent to the perioperative environment. Furthermore, these subjects provide the opportunity to record from the same electrodes over the course of many years. CONCLUSIONS: The RNS System enables us to study human navigation with unprecedented clarity. While RNS System patients have fewer electrodes implanted than video EEG patients, the lack of external artifact and confounds from recent surgery make this system a useful tool to further human electrophysiology research.

Depressive symptoms and suicidality among individuals with epilepsy enrolled in self-management studies: Results from the US Centers for Disease Control and Prevention Managing Epilepsy Well (MEW) Network.

Depression is a common comorbidity in people with epilepsy (PWE) that negatively affects self-management and a variety of health outcomes. Suicidal ideation is also more common among PWE than the general population. We examined correlates of depressive symptoms and suicidal ideation in adults using pooled data from epilepsy self-management studies conducted by sites in the Centers for Disease Control and Prevention (CDC) Research Center's Managing Epilepsy Well (MEW) Network that assessed depression severity with the 9-item Patient Health Questionnaire (PHQ-9). Of the 770 subjects in the analysis (mean age 42.4 ±â€¯13.0 years), the mean total PHQ-9 score was 9.4 ±â€¯6.6 and 334 subjects (43.4%) had moderate to severe depressive symptoms (PHQ-9 ≥ 10). Only ongoing seizures and low education were associated with moderate-severe depressive symptoms in multiple logistic regression analysis. Suicidality (PHQ-9, item 9 score ≥ 1) was endorsed by 155 subjects (20.1%). Only nonsuicidal depressive symptoms were associated with suicidality in multiple variable logistic regression analysis. We show in this large and regionally diverse dataset that both depression and suicidal ideation are common among PWE enrolled in self-management studies. Future studies are needed to examine whether suicidality exists independently of other depressive symptoms in some populations with epilepsy and investigate other correlates of suicidality that may inform screening practices.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Critical review of the responsive neurostimulator system for epilepsy.

Patients with medically refractory epilepsy have historically had few effective treatment options. Electrical brain stimulation for seizures has been studied for decades and ongoing technological refinements have made possible the development of an implantable electrical brain stimulator. The NeuroPace responsive neurostimulator was recently approved by the FDA for clinical use and the initial reports are encouraging. This device continually monitors brain activity and delivers an electric stimulus when abnormal activity is detected. Early reports of efficacy suggest that the device is well tolerated and offers a reduction in seizure frequency by approximately half at 2 years.

Resective epilepsy surgery for drug-resistant focal epilepsy: a review.

IMPORTANCE: Epilepsy surgery is indicated for patients with focal seizures who do not respond to appropriate antiepileptic drug therapy consisting of 2 or more medications. OBJECTIVES: To review resective surgery outcomes for focal epilepsy, to identify which patients benefit the most, and to discuss why epilepsy surgery may not be universally accepted. EVIDENCE REVIEW: Medline and Cochrane databases were searched between January 1993 and June 2014 for randomized clinical trials, meta-analyses, systematic reviews, and large retrospective case series (>300 patients) using Medical Subject Headings and indexed text terms. Fifty-five articles were included. Subpopulations and prognostic factors were identified. Systematic reviews for cognitive, psychiatric, quality-of-life, and psychosocial outcomes were included. FINDINGS: Two randomized clinical trials enrolling 118 patients with temporal lobe epilepsy found greater freedom from seizures with surgery when compared with continued medical treatment (58% vs 8% [n = 80] and 73% vs 0% [n = 38], P < .001). Nine systematic reviews and 2 large case series of medically refractory patients treated with surgery reported seizure-free outcomes in 34% to 74% of patients (median, 62.4%). The remainder of systematic reviews and meta-analyses examined subpopulations. Epilepsy surgery was less effective when there were extratemporal lesions, the epilepsy was not associated with a structural lesion, or both. Seizure-free outcomes were similar between children and adults. Hippocampal sclerosis and benign tumors were associated with better outcomes relative to other pathologies. Similar procedures such as selective amygdalohippocampectomy and temporal lobectomy for temporal lobe epilepsy were associated with subtle differences in seizure and neuropsychological outcome. There is low perioperative mortality (0.1%-0.5%) from epilepsy surgery. The most frequent neurologic complication is visual field defect occurring from temporal lobe resection. Quality of life improved after surgery but improved the most in patients who were seizure-free after surgery. CONCLUSIONS AND RELEVANCE: Epilepsy surgery reduced seizure activity in randomized clinical trials when compared with continued medical therapy. Long-term cognitive, psychiatric, psychosocial, and quality-of-life outcomes were less well defined. Despite good outcomes from high-quality clinical trials, referrals of patients with seizures refractory to medical treatment remain infrequent.

Long-term seizure, cognitive, and psychiatric outcome following trans-middle temporal gyrus amygdalohippocampectomy and standard temporal lobectomy.

OBJECT: Previous comparisons of standard temporal lobectomy (STL) and selective amygdalohippocampectomy (SelAH) have been limited by inadequate long-term follow-up, variable definitions of favorable outcome, and inadequate consideration of psychiatric comorbidities. METHODS: The authors performed a retrospective analysis of seizure, cognitive, and psychiatric outcomes in a noncontemporaneous cohort of 69 patients with unilateral refractory temporal lobe epilepsy and MRI evidence of mesial temporal sclerosis after either an STL or an SelAH and examined seizure, cognitive, and psychiatric outcomes. RESULTS: The mean duration of follow-up for STL was 9.7 years (range 1-18 years), and for trans-middle temporal gyrus SelAH (mtg-SelAH) it was 6.85 years (range 1-15 years). There was no significant difference in seizure outcome when "favorable" was defined as time to loss of Engel Class I or II status; better seizure outcome was seen in the STL group when "favorable" was defined as time to loss of Engel Class IA status (p=0.034). Further analysis revealed a higher occurrence of seizures solely during attempted medication withdrawal in the mtg-SelAH group than in the STL group (p=0.016). The authors found no significant difference in the effect of surgery type on any cognitive and most psychiatric variables. Standard temporal lobectomy was associated with significantly higher scores on assessment of postsurgical paranoia (p=0.048). CONCLUSIONS: Overall, few differences in seizure, cognitive, and psychiatric outcome were found between STL and mtg-SelAH on long-term follow-up. Longer exposure to medication side effects after mtg-SelAH may adversely affect quality of life but is unlikely to cause additional functional impairment. In patients with high levels of presurgical psychiatric disease, mtg-SelAH may be the preferred surgery type.

Occipitotemporal hippocampal depth electrodes in intracranial epilepsy monitoring: safety and utility.

OBJECT: Intracranial monitoring for epilepsy has been proven to enhance diagnostic accuracy and provide localizing information for surgical treatment of intractable seizures. The authors investigated the usefulness of hippocampal depth electrodes in the era of more advanced imaging techniques. METHODS: Between 1988 and 2010, 100 patients underwent occipitotemporal hippocampal depth electrode (OHDE) implantation as part of invasive seizure monitoring, and their charts were retrospectively reviewed. The authors' technique involved the stereotactically guided (using the Leksell model G frame) implantation of a 12-contact depth electrode directed along the long axis of the hippocampus, through an occipital twist drill hole. RESULTS: Of the 100 patients (mean age 35.0 years [range 13-58 years], 51% male) who underwent intracranial investigation, 84 underwent resection of the seizure focus. Magnetic resonance imaging revealed mesial temporal sclerosis (MTS) in 27% of patients, showed abnormal findings without MTS in 55% of patients, and showed normal findings in 18% of patients. One patient developed a small asymptomatic occipital hemorrhage around the electrode tract. The use of OHDEs enabled epilepsy resection in 45.7% of patients who eventually underwent standard or selective temporal lobe resection. The hippocampal formation was spared during surgery because data obtained from the depth electrodes showed no or only secondary involvement in 14% of patients with preoperative temporal localization. The use of OHDEs prevented resections in 12% of patients with radiographic evidence of MTS. Eighty-three percent of patients who underwent resection had Engel Class I (68%) or II (15%) outcome at 2 years of follow-up. CONCLUSIONS: The use of OHDEs for intracranial epilepsy monitoring has a favorable risk profile, and in the authors' experience it proved to be a valuable component of intracranial investigation. The use of OHDEs can provide the sole evidence for resection of some epileptogenic foci and can also result in hippocampal sparing or prevent likely unsuccessful resection in other patients.

Interictal PET and ictal subtraction SPECT: sensitivity in the detection of seizure foci in patients with medically intractable epilepsy.

PURPOSE: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. METHODS: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. KEY FINDINGS: Fifty-three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1-60 years). Twenty-seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty-three patients had surgical resection and >2 years of follow-up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. SIGNIFICANCE: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.

Subdural interhemispheric grid electrodes for intracranial epilepsy monitoring: feasibility, safety, and utility: clinical article.

OBJECT: Intracranial monitoring for epilepsy has been proven to enhance diagnostic accuracy and provide localizing information for surgical treatment of intractable seizures. The authors investigated their experience with interhemispheric grid electrodes (IHGEs) to assess the hypothesis that they are feasible, safe, and useful. METHODS: Between 1992 and 2010, 50 patients underwent IHGE implantation (curvilinear double-sided 2 × 8 or 3 × 8 grids) as part of arrays for invasive seizure monitoring, and their charts were retrospectively reviewed. RESULTS: Of the 50 patients who underwent intracranial investigation with IHGEs, 38 eventually underwent resection of the seizure focus. These 38 patients had a mean age of 30.7 years (range 11-58 years), and 63% were males. Complications as a result of IHGE implantation consisted of transient leg weakness in 1 patient. Of all the patients who underwent resective surgery, 21 (55.3%) had medial frontal resections, 9 of whom (43%) had normal MRI results. Localization in all of these cases was possible only because of data from IHGEs, and the extent of resection was tailored based on these data. Of the 17 patients (44.7%) who underwent other cortical resections, IHGEs were helpful in excluding medial seizure onset. Twelve patients did not undergo resection because of nonlocalizable or multifocal disease; in 2 patients localization to the motor cortex precluded resection. Seventy-one percent of patients who underwent resection had Engel Class I outcome at the 2-year follow-up. CONCLUSIONS: The use of IHGEs in intracranial epilepsy monitoring has a favorable risk profile and in the authors' experience proved to be a valuable component of intracranial investigation, providing the sole evidence for resection of some epileptogenic foci.

Outcome of frontal lobe epilepsy surgery.

PURPOSE: There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well-established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. METHODS: Fifty-eight patients underwent resective FLE surgery with a mean follow-up period of 79.3 months (range 12-208 months). Patient demographics, clinical seizure characteristics, seizure-onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow-up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. KEY FINDINGS: Thirty-three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0-208). Only 14 patients (24%) were completely seizure-free without auras (Engel IA) throughout the entire follow-up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. SIGNIFICANCE: Findings indicate that that long-term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI-negative patients.

Seizure prognosis of patients with low-grade tumors.

PURPOSE: Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. METHODS: Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. RESULTS: Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. DISCUSSION: Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and radiation therapy have a favorable impact on seizure outcome. Additional epilepsy surgery is effective.