Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy

Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long‐term outcomes of consecutive true MRI‐negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI‐negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high‐resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow‐up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure‐free (Engel class IA). Twenty‐one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12‐month follow‐up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR‐negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI‐negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long‐term also remain stable. Modern imaging techniques could further improve the postsurgical seizure‐free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.     

Factors associated with seizure freedom in the surgical resection of glioneuronal tumors

Purpose: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNETs) are low‐grade brain tumors of glioneuronal origin that commonly present with seizures. Achieving seizure control in patients with glioneuronal tumors remains underappreciated, as tumor‐related epilepsy significantly affects patients’ quality‐of‐life. Methods: We performed a quantitative and comprehensive systematic literature review of seizure outcomes after surgical resection of GGs and DNETs associated with seizures. We evaluated 910 patients from 39 studies, and stratified outcomes according to several potential prognostic variables. Key Findings: Overall, 80% of patients were seizure‐free after surgery (Engel class I), whereas 20% continued to have seizures (Engel class II–IV). We observed significantly higher rates of seizure‐freedom in patients with ≤1 year duration of epilepsy compared to those with >1 year of seizures [odds ratio (OR) 9.48; 95% confidence interval (CI) 2.26–39.66], and with gross‐total resection over subtotal lesionectomy (OR 5.34; 95% CI 3.61–7.89). In addition, the presence of secondarily generalized seizures preoperatively predicted a lower rate of seizure‐freedom after surgery (OR 0.40; 95% CI 0.24–0.66). Outcomes did not differ significantly between adults and children, patients with temporal lobe versus extratemporal tumors, pathologic diagnosis of GG versus DNET, medically controlled versus refractory seizures, or with the use of electrocorticography (ECoG). Extended resection of temporal lobe tumors, with hippocampectomy and/or corticectomy, conferred additional benefit. Significance: These results suggest that early operative intervention and gross‐total resection are critically important factors in achieving seizure‐freedom, and thus improving quality‐of‐life, in patients with glioneuronal tumors causing epilepsy.     

Epilepsy surgery in patients with bilateral temporal lobe seizures: A systematic review

We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow‐up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I–II (76%) and Engel III–IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.     

Levetiracetam may favorably affect seizure outcome after temporal lobectomy

Purpose: To study the prognostic implications of antiepileptic drug (AED) use on seizure freedom following temporal lobe resections for intractable epilepsy. Methods: Seizure outcome implications of epilepsy characteristics and AED use were studied in patients who underwent temporal lobectomy patients at the Cleveland Clinic between September 1995 and December 2006. Survival analysis and multivariate regression with Cox proportional hazard modeling were used. Complete seizure freedom was defined as a favorable outcome. Key Findings: Records of 312 patients were analyzed (mean ± standard deviation follow‐up 3.5 ± 1.7 years). The estimated probability of complete seizure freedom was 69% at 12 months (95% confidence interval [CI] 66–72%), and 48% at 36 months (95% CI 45–52%). The mean number of AEDs used per patient at the time of surgery was 1.78 (range 1–4), dropping to 1.02 at last follow‐up (range 0–4). Following multivariate analysis, a lower preoperative seizure frequency and perioperative use of levetiracetam predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43–0.89, and RR = 0.57, 95% CI 0.39–0.83, respectively), whereas nonspecific pathology (RR 1.71, 95% CI 1.15–2.47) and a higher number of AEDs used at the time of surgery correlated with higher rates of seizure recurrence (whole‐model log‐rank test p‐value < 0.0001). Better outcomes within the levetiracetam group were seen despite a higher proportion of several poor prognostic indicators within this patient group, and started as early as 4 months after surgery, gradually increasing to a 15–20% survival advantage by 5 years. No similar outcome correlations were identified with another AED. Significance: AED use may be a potential new modifiable seizure‐outcome predictor after temporal lobectomy. This possible prognostic indicator is discussed in light of proposed seizure recurrence mechanisms.     

Long-term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose: We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures. Methods: Eighty‐one patients underwent extratemporal resection at Austin Health, Melbourne, Australia (1991–2004). Seizure recurrence was any postoperative disabling seizure (complex partial seizure [CPS] ± secondary generalization). Multivariate Cox proportional hazards regression models examined potential preoperative and perioperative risk factors and the risk associated with early postoperative seizures (≤28 days postsurgery). The change between preoperative and postoperative seizure frequency was also measured. Key Findings: Median follow‐up was 10.3 years (range 1–17.7). The probabilities of freedom from disabling seizures (on or off antiepileptic medication) were 40.7% (95% confidence interval [CI] 30–51) at 1 month, 23.5% (95% CI 15–33) at 1 year, and 14.7% (95% CI 8–23) at 5 years postoperative. Reduction of disabling seizures to at least 20% of preoperative frequency was attained by 57% of patients at 5 postoperative years. Of the preoperative/perioperative factors, focal cortical dysplasia (FCD) type 1 (hazard ratio [HR] 1.90, 95% CI 1.08–3.34, p = 0.025) and incomplete resection (HR 1.71, 95% CI 1.06–2.76, p = 0.028) were independent recurrence risks. After surgery, an early postoperative seizure was the only factor associated with higher risk (HR 4.28 [2.42–7.57], p = 0.00). Significance: Distinction between subtypes of focal cortical dysplasia, which can be made using magnetic resonance imaging (MRI) criteria, may be useful for preoperative prognostication. Early seizures after surgery are not benign and may be markers of factors that contribute to seizure recurrence. Most patients achieve substantial reduction in seizure frequency. Further study of the significance of this reduction in terms of surgical “success” or otherwise is required.     

Epilepsy surgery in tuberous sclerosis: a systematic review

PURPOSE: Tuberous sclerosis complex (TSC) is often associated with intractable epilepsy. Although epilepsy surgery has gained interest in recent years uncertainties exist about which patients are good surgical candidates. A systematic review of the available literature has been undertaken to assess the overall outcome of epilepsy surgery and identify risk factors of seizure recurrence. METHODS: We searched MEDLINE, Embase, and bibliographies of reviews and book chapters to identify articles published in English since 1960. Twenty-five articles, describing postoperative seizure outcome and type of surgery in 177 TSC patients, were included in this study. Seizure outcome was analyzed both as seizure freedom and good outcome, including patients with >90% seizure reduction. RESULTS: Seizure freedom was achieved in 101 patients (57%). Seizure frequency was improved by > 90% in 32 patients (18%). Moderate or severe intellectual disability (IQ < 70) (RR 1.8; 95% CI 1.2-2.8) and the presence of tonic seizures (RR 1.7; 95 % CI 1.2-2.4) were related to seizure recurrence. CONCLUSIONS: A relation between multiple seizures types with early onset, multiple cortical tubers and multifocal epileptogenicity, and poor outcome is not supported by this systematic analysis. Although there is considerable variation among studies reviewed here, the literature suggests that resective surgery may offer benefit in a selected population of TSC patients with drug-resistant epilepsy.     

Seizure outcomes following multilobar epilepsy surgery

Purpose: Outcomes following unilobar surgeries for refractory epilepsy have been well described. However, little is known about long‐term seizure outcomes following multilobar resections. The aim of the current study was to identify long‐term seizure control and predictors of seizure recurrence in this patient population. Methods: Records of patients who underwent multilobar epilepsy surgery at the Cleveland Clinic between 1994 and 2010 were retrospectively reviewed. A postoperative follow‐up of at least 6 months was required. Patients were classified as seizure free if they achieved an Engel class I at last follow‐up. Long‐term chances of seizure freedom were illustrated using a survival analysis, and predictors of recurrence were identified using Cox proportional hazard modeling. Key Findings: Sixty‐three patients with medically intractable epilepsy underwent multilobar surgical resections during the study period (mean follow‐up of 4.6 years). Predominant resection types included extended occipital (temporoparietooccipital, parietooccipital, temporooccipital: 57%), frontotemporal (21%), and temporoparietal (17%). Mean age at surgery was 21.4 years and mean age at seizure onset was 10.1 years. Fifty‐six percent of the patients underwent extraoperative invasive electroencephalography (EEG) evaluations. At 6 postoperative months, 71% (95% confidence interval (CI) 65–77) were seizure‐free (SF), 64% (CI 58–70) were SF at 1 year, 52% (CI 46–59) were SF at 5 years, and 41% (CI 32–50) remained SF at 10 years. Forty‐one patients had at least one breakthrough seizure after surgery (median timing of recurrence 6.1 months), with an Engel class 1 achieved again by last follow‐up in 12 of these 41 cases. Nine patients required a reoperation. Patients who underwent extended occipital/posterior quadrant resections had more favorable outcomes as compared to the other groups. With multivariate analysis, the type of resection (p = 0.03), preoperative auras (p = 0.03), an incomplete resection (0.03), and the presence of postoperative spikes (p = 0.0003) correlated with seizure recurrence. The risk of seizure recurrence for an incomplete resection was 2.3 (CI 1.53–3.36), preoperative aura 2.3 (CI 1.34–3.87), and postoperative spikes on surface EEG 2.5 (CI 1.29–4.71). Significance: A favorable outcome can be achieved in 41% of patients undergoing multilobar resections for epilepsy surgery at 10 years of follow‐up. Close to one‐third of patients who have breakthrough seizures after surgery are able to regain seizure freedom by last follow‐up. Predictors of recurrence include resection type (frontotemporal and parietotemporal resections did worse), presence of preoperative aura, an incomplete surgical resection, and the presence of postoperative interictal discharges on EEG.     

Effects of temporal lobectomy on consciousness-impairing and consciousness-sparing seizures in children

Purpose

Most children with medically refractory temporal lobe epilepsy (TLE) become seizure free after temporal lobectomy, but some individuals continue to seize. As studies of temporal lobectomy typically focus on seizure freedom, the effect of surgery on seizure type and frequency among children with persistent seizures is poorly understood. Seizures which impair consciousness are associated with increased morbidity compared to consciousness-sparing seizures.

Methods

A retrospective cohort study was performed to evaluate the effects of temporal lobectomy on seizure type and frequency in children with intractable TLE.

Results

Among 58 pediatric TLE patients with a mean (±SEM) age of 14.0?±?0.7 years who received temporal lobectomy, 46 (79.3 %) individuals achieved an Engel class I seizure outcome, including 38 (65.5 %) children who became completely seizure free (Engel IA). Mean follow-up was 2.7?±?0.4 years. While the number of patients experiencing simple partial seizures (SPSs) (consciousness sparing) decreased by only 23 % after surgery, the number of children having complex partial seizures and generalized tonic–clonic seizures (consciousness impairing) diminished by 87 and 83 %, respectively (p?<?0.01). SPS was the predominant seizure type in only 11.3 % of patients before resection, but in 42.1 % of patients with postoperative seizures (p?<?0.01). Children with postoperative seizures experienced a 70 % reduction in overall seizure frequency compared to baseline (p?<?0.05), having consciousness-impairing seizures 94 % less frequently (p?<?0.05), but having consciousness-sparing seizures 35 % more frequently (p?=?0.73).

Conclusions

Seizure type and frequency are important considerations in the medical and surgical treatment of children with epilepsy, although complete seizure freedom remains the ultimate goal.     

Impact of epilepsy surgery on seizure control and quality of life: a 26-year follow-up study

Purpose: The short‐term efficacy and safety of epilepsy surgery relative to medical therapy has been established, but it remains underutilized. There is a lack of data regarding the long‐term seizure‐control rates and quality of life outcomes after epilepsy surgery. This study represents the longest follow‐up study to date, with a mean follow‐up duration of 26 years. Methods: We studied the seizure and health‐related quality of life outcomes of patients who underwent epilepsy surgery by Dr. Sidney Goldring from 1967 to 1990. Retrospective clinical chart reviews gathered perioperative data and surveys obtained follow‐up data. Seizure outcome was evaluated using the Engel classification system. Key Findings: Of 361 patients, 117 (32.4%) completed follow‐up interviews. Fifty‐six patients (48%) were Engel class I. Mean overall Quality of Life in Epilepsy (QOLIE‐31) questionnaire score for the cohort was 68.2 ± 16. Eighty percent of patients reported their overall quality of life now as being better than before surgery. Seizure freedom was associated with better quality of life. We did not observe a statistically significant association between postoperative complications and long‐term outcome. Patients who underwent temporal lobe resection achieved better seizure outcomes than those who underwent other types of procedures. Astatic seizures and bilateral surgery were associated with a worse Engel class outcome. Significance: Our study demonstrates that the beneficial effects of epilepsy surgery are sustained over decades, and that these beneficial effects are correlated with an improved quality of life. The confirmation of its durability makes us optimistic that the outcomes from modern epilepsy surgery will be even better and that our present enthusiasm for this treatment modality is not misplaced.     

Outcome of frontal lobe epilepsy surgery in adults

Our aim is to investigate seizure outcome and prognostic factors after pure frontal lobe epilepsy (FLE) surgery. We retrospectively studied the operative outcome in 97 consecutive adult patients who underwent resective surgery for intractable partial epilepsy between 1991 and 2005. Based on Kaplan-Meier, the probability of an Engel Class I outcome was found to be 54.6% (95% CI 44-64) at 6 months, 49.5% (95% CI 39.3-59.6) at 2 years, 47% (CI 34-59) at 5 years and 41.9% (CI 23.5-60.3) at 10 years. If the patient was seizure free at 2-year follow-up, the probability of remaining seizure free up to 10 years was 86% (95% CI 76-98). For 13.6% of the patients a running down of seizures could be shown. Factors predictive of poor long-term outcome were incomplete resection, using of subdural grids, IED in follow-up EEG, tonic seizures and an unspecific aura or a postoperative aura. Factors predictive of good long-term outcome were the presence of a well-circumscribed lesion in preoperative MRI, ipsilateral IED in preoperative EEG, surgery before age of 30 and short epilepsy duration prior to surgery. In the multivariate analysis, preoperative well-circumscribed lesion in MRI predicts seizure remission whereas persistent postoperative auras predict seizure relapse. FLE surgery should depend on restrictive patient selection to assure favorable outcome.     

Correlation of MRI and histopathology in epileptogenic parietal and occipital lobe lesions.

INTRODUCTION: To analyze the diagnostic accuracy of MRI in patients undergoing parietal and occipital lobe epilepsy surgery. METHODS: In a retrospective study, we analyzed MRI scans and neuropathology reports of 42 patients who had undergone resective epilepsy surgery in the parietal and occipital lobe between 1998 and 2003. We evaluated, whether lesions were precisely characterized by MRI and whether lesion characterization allowed to estimate postsurgical seizure outcome. RESULTS: Within the categories epilepsy associated tumors, focal cortical dysplasias, vascular malformations, scarring, and others, MRI was concordant with histopathology in 36 of 42 (86%) lesions. Among the discordant lesions, one lesion was re-classified following MRI-histopathology synopsis, another two lesions represented new tumor entities (angiocentric neuroepithelial tumor, isomorphic astrocytoma) which have been described recently. Seizure freedom (Engel class I) one year following surgery was achieved in 25 patients (60%). Seizure outcome was different for lesion categories (Engel class I: epilepsy associated tumors, 62%; focal cortical dysplasias, 71%; vascular malformations, 75%; scarring, 40%), and was unchanged if no lesion was found on preoperative MRI. CONCLUSION: If MRI and histopathology are discordant, not only the MRI findings may be debatable. MRI lesion detection is important, since chance of seizure freedom is low if no lesion is detected.     

Predictive value of electrically induced seizures for postsurgical seizure outcome

ObjectiveTo determine whether semiological similarity of electrically induced seizures (EIS) and spontaneously occurring habitual seizures (SHS) is associated with postsurgical seizure outcome in patients undergoing invasive video-EEG monitoring (VEM) before resective epilepsy surgery.MethodsData of patients undergoing invasive VEM were retrospectively reviewed and included if at least one EIS and SHS during VEM occurred and the brain region in which EIS were elicited was resected. Seizure outcome was evaluated at three follow-up (FU) visits after surgery (1, 2 years and last available FU) according to the classification by Engel and the International League Against Epilepsy (ILAE). The level of semiological similarity of EIS and SHS was rated blinded to the surgical outcome. Statistics were done using Fisher’s exact test and a mixed linear-logistic regression model.Results65 patients were included. Postsurgical seizure freedom was achieved in 51% (ILAE class 1) and 58% (Engel class I) at last FU (median 36 months). Patients with identical EIS and SHS displayed significantly better postsurgical seizure outcomes (ILAE class 1 at last FU: 76% vs. 31%, p < 0.001; Engel class I: 83% vs. 39%, p < 0.001).ConclusionEIS are useful to confirm the location of the epileptogenic zone. A high level of similarity between EIS and SHS is associated with a favorable postsurgical seizure outcome.SignificanceEIS may be used as an additional predictor of postsurgical outcome when counselling patients to proceed to resective epilepsy surgery.     

Predictors of psychiatric and seizure outcome following temporal lobe epilepsy surgery

Purpose: Neurosurgery is an effective therapy for selected individuals with medically refractory temporal lobe epilepsy (TLE). De novo psychopathology may complicate the postsurgical outcome. Our aims were to identify predictors of de novo psychiatric and seizure outcome following TLE surgery. Methods: Medical records of 280 patients who underwent TLE surgery were reviewed. Preoperative and postoperative psychiatric diagnoses were identified, in addition to information on seizure recurrence and neuropsychological status. Logistic regression analysis was used to identify predictors of having a de novo psychiatric diagnosis and remaining seizure‐free within 4 years following surgery. Key Findings: One hundred five patients (38%) had significant psychiatric problems within 4 years following TLE surgery. Fifty‐one patients (18%) developed de novo psychopathology; half of cases presented within 6 months and 90% of psychopathologies persisted 6 months or longer. A preoperative history of secondary generalized tonic–clonic seizure(s) (SGTCS) was an independent predictor of de novo psychopathology (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.14–6.59, p = 0.02). From patients with available seizure data, 49% (127 of 258) remained seizure‐free for 4 years after surgery. Patients with a history of SGTCS (OR 0.47, 95% CI 0.25–0.90, p = 0.02) and those with a preoperative psychiatric diagnosis (OR 0.53, 95% CI 0.28–0.98, p = 0.04) were significantly less likely to remain seizure‐free. Significance: De novo psychopathology is a significant complication of TLE surgery. Inclusion of neuropsychiatric assessments in the presurgical evaluation may lead to increase in the power of prognostic models used to predict the neurologic outcome of TLE surgery.     

Postoperative seizure and memory outcome of temporal lobe epilepsy with hippocampal sclerosis: A systematic review

We conducted a systematic review and meta-analysis to evaluate postoperative seizure and memory outcomes of temporal lobe epilepsy with different hippocampal sclerosis (HS) subtypes classified by International League Against Epilepsy (ILAE) Consensus Guidelines in 2013. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Library from January 1, 2013 to August 6, 2023. Observational studies reporting seizure and memory outcomes among different HS subtypes were included. We used the Newcastle–Ottawa scale to assess the risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the quality of evidence. Seizure freedom and improved outcome (Engel 1 or ILAE class 1–2) ≥1 year after surgery were defined as the primary and secondary seizure outcome. A random-effects meta-analysis by DerSimonian and Laird method was performed to obtain pooled risk ratio (RRs) with 95% confidence interval (CIs). The memory impairment was narratively reviewed because of various evaluation tools. Fifteen cohort studies with 2485 patients were eligible for the meta-analysis of seizure outcome. Six cohorts with detailed information on postoperative memory outcome were included. The pooled RRs of seizure freedom, with moderate to substantial heterogeneity, were .98 (95% CI = .84–1.15) between HS type 2 and type 1, 1.11 (95% CI = .82–1.52) between type 3 and type 1, and .80 (95% CI = .62–1.03) between the no-HS and HS groups. No significant difference of improved outcome was found between different subtypes (p > .05). The quality of evidence was deemed to be low to very low according to GRADE. The long-term seizure outcome (≥5 years after surgery) and memory impairment remained controversial.     

Intracranial EEG in predicting surgical outcome in frontal lobe epilepsy

Purpose: Surgery in frontal lobe epilepsy (FLE) has a worse prognosis regarding seizure freedom than anterior lobectomy in temporal lobe epilepsy. The current study aimed to assess whether intracranial interictal and ictal EEG findings in addition to clinical and scalp EEG data help to predict outcome in a series of patients who needed invasive recording for FLE surgery. Methods: Patients with FLE who had resective surgery after chronic intracranial EEG recording were included. Outcome predictors were compared in patients with seizure freedom (group 1) and those with recurrent seizures (group 2) at 19–24 months after surgery. Key Findings: Twenty‐five patients (16 female) were included in this study. Mean age of patients at epilepsy surgery was 32.3 ± 15.6 years (range 12–70); mean duration of epilepsy was 16.9 ± 13.4 years (range 1–48). In each outcome group, magnetic resonance imaging revealed frontal lobe lesions in three patients. Fifteen patients (60%) were seizure‐free (Engel class 1), 10 patients (40%) continued to have seizures (two were class II, three were class III, and five were class IV). Lack of seizure freedom was seen more often in patients with epilepsy surgery on the left frontal lobe (group 1, 13%; group 2, 70%; p = 0.009) and on the dominant (27%; 70%; p = 0.049) hemisphere as well as in patients without aura (29%; 80%; p = 0.036), whereas sex, age at surgery, duration of epilepsy, and presence of an MRI lesion in the frontal lobe or extrafrontal structures were not different between groups. Electroencephalographic characteristics associated with lack of seizure freedom included presence of interictal epileptiform discharges in scalp recordings (31%; 90%; p = 0.01). Detailed analysis of intracranial EEG revealed widespread (>2 cm) (13%; 70%; p = 0.01) in contrast to focal seizure onset as well as shorter latency to onset of seizure spread (5.8 ± 6.1 s; 1.5 ± 2.3 s; p = 0.016) and to ictal involvement of brain structures beyond the frontal lobe (23.5 ± 22.4 s; 5.8 ± 5.4 s; p = 0.025) in patients without seizure freedom. The distribution of ictal onset patterns was similar in both groups, and fast rhythmic activity in the beta to gamma range was found in 57% of seizure‐free patients compared to 70% of patients with recurrent seizures. Analysis of the temporal relation between first clinical alterations and EEG seizure onset did not reveal significant differences between both groups of patients. In multivariate analysis, resection in the left hemisphere (odds ratio [OR] 12.197 95% confidence interval [95% CI] 1.33–111.832; p = 0.027) and onset of seizure spread (odds ratio [OR] 0.733, 95% CI 0.549–0.978, p = 0.035) were independent predictors of ongoing seizures. Significance: Widespread epileptogenicity as indicated by rapid onset of spread of ictal activity likely explains lack of seizure freedom following frontal resective surgery. The negative prognostic effect of surgery on the left hemisphere is less clear. Future study is needed to determine if neuronal network properties in this hemisphere point to intrinsic interhemispheric differences or if neurosurgeons are restrained by proximity to eloquent cortex.     

Long‐term seizure outcome after resective surgery in patients evaluated with intracranial electrodes

Purpose: Despite advances in “noninvasive” localization techniques, many patients with medically intractable epilepsy require the placement of subdural (subdural grid electrode, SDE) and/or depth electrodes for the identification and definition of extent of the epileptic region. This study investigates the trends in longitudinal seizure outcome and its predictors in this group. Methods: We reviewed the medical records, and electroencephalography (EEG) data of 414 consecutive patients who underwent intracranial electrode placement (SDE and/or depth electrodes) at Cleveland Clinic Epilepsy Center between 1998 and 2008. A favorable outcome was defined as complete seizure freedom, discounting any auras or seizures that occurred within the first postoperative week. Survival curves were constructed, and Cox proportional hazard modeling was used to identify outcome predictors. Key Findings: The estimated probability of complete seizure freedom was 61% (95% confidence interval [CI] 58–64%) at one postoperative year, 47% (95% CI 44–50%) at 3 years, 42% (95% CI 39–45%) at 5 years, and 33% (95% CI 28–38%) at 10 years. Half of all seizure recurrences occurred within the first two postoperative months. Subsequently, the rate of seizure freedom declined by 4–5% every 2–3 years. After multivariate analysis, two independent predictors of seizure recurrence were identified: (1) prior resective surgery (p ≤ 0.002), mostly in patients with temporal lobe resections, and (2) sublobar or multilobar resection (p ≤ 0.02), mostly in patients following frontal lobe resections. Significance: Favorable seizure outcomes are possible in the complex epilepsy population requiring invasive EEG studies. We propose that mislocalization of the epileptogenic zone or its incomplete resection account for early postoperative recurrences, whereas epileptogenesis may lead to later relapses.     

The value of intraoperative electrocorticography in surgical decision making for temporal lobe epilepsy with normal MRI

Purpose: We hypothesized that acute intraoperative electrocorticography (ECoG) might identify a subset of patients with magnetic resonance imaging (MRI)–negative temporal lobe epilepsy (TLE) who could proceed directly to standard anteromesial resection (SAMR), obviating the need for chronic electrode implantation to guide resection. Methods: Patients with TLE and a normal MRI who underwent acute ECoG prior to chronic electrode recording of ictal onsets were evaluated. Intraoperative interictal spikes were classified as mesial (M), lateral (L), or mesial/lateral (ML). Results of the acute ECoG were correlated with the ictal‐onset zone following chronic ECoG. Onsets were also classified as “M,”“L,” or “ML.” Positron emission tomography (PET), scalp‐EEG (electroencephalography), and Wada were evaluated as adjuncts. Key Findings: Sixteen patients fit criteria for inclusion. Outcomes were Engel class I in nine patients, Engel II in two, Engel III in four, and Engel IV in one. Mean postoperative follow‐up was 45.2 months. Scalp EEG and PET correlated with ictal onsets in 69% and 64% of patients, respectively. Wada correlated with onsets in 47% of patients. Acute intraoperative ECoG correlated with seizure onsets on chronic ECoG in all 16 patients. All eight patients with “M” pattern ECoG underwent SAMR, and six (75%) experienced Engel class I outcomes. Three of eight patients with “L” or “ML” onsets (38%) had Engel class I outcomes. Significance: Intraoperative ECoG may be useful in identifying a subset of patients with MRI‐negative TLE who will benefit from SAMR without chronic implantation of electrodes. These patients have uniquely mesial interictal spikes and can go on to have improved postoperative seizure‐free outcomes.     

Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy

Purpose: Fluorodeoxyglucose positron emission computed tomography (FDG‐PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PET‐positive, MRI‐negative patients and compared them with those of patients with MTS. Methods: We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI?). We compared this group to the group of patients who underwent ATL and who had MTS on MRI. Patients with discordant ictal electroencephalography (EEG) were excluded. Surgical outcomes were compared using percentages of Engel class I outcomes at 2 and 5 years as well as Kaplan‐Meier survival statistic, with time to seizure recurrence as survival time. A subgroup of PET+/MRI? patients who underwent surgical implantation prior to resection was compared to PET+/MRI? patients who went directly to resection without implantation. Key Findings: There were 46 PET+/MRI? patients (of whom 36 had 2‐year surgical outcome available) and 147 MTS patients. There was no difference between the two groups with regard to history of febrile convulsions, generalized tonic–clonic seizures, interictal spikes, depression, or family history. Mean age at first seizure was higher in PET+/MRI? patients (19 ± 13 vs.14 ± 13 years, Mann‐Whitney test, p = 0.008) and disease duration was shorter (14 ± 10 vs. 22 ± 13 years, student’s t‐test, p = 0.0006). Class I surgical outcomes did not differ significantly between the PET+/MRI? patients and the MTS group (2 and 5 year outcomes were 76% and 75% for the PET+/MRI? group, and 71% and 78% for the MTS group); neither did outcomes of the PET+/MRI? patients who were implanted prior to resection versus those who went directly to surgery (implanted patients had 71% and 67% class I outcomes at 2 and 5 years, whereas. nonimplanted patients had 77% and 78% class I outcomes, p = 0.66 and 0.28). Kaplan‐Meier survival statistics for both comparisons were nonsignificant at 5 years. Dentate gyrus and hilar cell counts obtained from pathology for a sample of patients also did not differ between groups. Significance: PET‐positive, MRI‐negative TLE patients in our study had excellent surgical outcomes after ATL, very similar to those in patients with MTS, regardless of whether or not they undergo intracranial monitoring. These patients should be considered prime candidates for ATL, and intracranial monitoring is probably unnecessary in the absence of discordant data.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.