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      Predictors of Postoperative Seizure Recurrence: A Longitudinal Study of Temporal and Extratemporal Resections

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          Abstract

          Objective. We investigated the longitudinal outcome of resective epilepsy surgery to identify the predictors of seizure recurrence. Materials and Methods. We retrospectively analyzed patients who underwent resections for intractable epilepsy over a period of 7 years. Multiple variables were investigated as potential predictors of seizure recurrence. The time to first postoperative seizure was evaluated using survival analysis and univariate analysis at annual intervals. Results. Among 70 patients, 54 (77%) had temporal and 16 (23%) had extratemporal resections. At last follow-up (mean 48 months; range 24–87 months), the outcome was Engel class I in 84% ( n = 59) of patients. Seizure recurrence followed two patterns: recurrence was “early” (within 2 years) in 82% of patients, of whom 83% continued to have seizures despite optimum medical therapy; recurrence was “late” (after 2 years) in 18%, of whom 25% continued to have seizures subsequently. Among the variables of interest, only resection site and ictal EEG remained as independent predictors of seizure recurrence over the long term ( p < 0.05). Extratemporal resection and discordance between ictal EEG and resection area were associated with 4.2-fold and 5.6-fold higher risk of seizure recurrence, respectively. Conclusions. Extratemporal epilepsy and uncertainty in ictal EEG localization are independent predictors of unfavorable outcome. Seizure recurrence within two years of surgery indicates poor long-term outcome.

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          Most cited references27

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          Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.

          Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death. We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL). The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Receipt of continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation. Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio = ∞; 95% CI, 11.8 to ∞; P < .001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, -1.0 to 18.1; P = .08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect = 9.9; 95% CI, 2.2 to 17.7; P = .01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group. Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution. clinicaltrials.gov Identifier: NCT00040326.
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            Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis.

            Assessment of long-term outcomes is essential in brain surgery for epilepsy, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established, but less is known about long-term outcomes. We performed a systematic review and meta-analysis of the evidence on this topic. To provide evidence-based estimates of long-term results of various types of epilepsy surgery and to identify sources of variation in results of published studies, we searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles and book chapters to identify articles published since 1991 that contained > or =20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of > or =5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Seventy-six articles fulfilled our eligibility criteria, of which 71 reported on resective surgery (93%) and five (7%) on non-resective surgery. There were no randomized trials and only six studies had a control group. Some articles contributed more than one study, yielding 83 studies of which 78 dealt with resective surgery and five with non-resective surgery. Forty studies (51%) of resective surgery referred to temporal lobe surgery, 25 (32%) to grouped temporal and extratemporal surgery, seven (9%) to frontal surgery, two (3%) to grouped extratemporal surgery, two (3%) to hemispherectomy, and one (1%) each to parietal and occipital surgery. In the non-resective category, three studies reported outcomes after callosotomy and two after multiple subpial transections. The median proportion of long-term seizure-free patients was 66% with temporal lobe resections, 46% with occipital and parietal resections, and 27% with frontal lobe resections. In the long term, only 35% of patients with callosotomy were free of most disabling seizures, and 16% with multiple subpial transections remained free of all seizures. The year of operation, duration of follow-up and outcome classification system were most strongly associated with outcomes. Almost all long-term outcome studies describe patient cohorts without controls. Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity. The long-term (> or =5 years) seizure free rate following temporal lobe resective surgery was similar to that reported in short-term controlled studies. On the other hand, long-term seizure freedom was consistently lower after extratemporal surgery and palliative procedures.
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              Temporal patterns and mechanisms of epilepsy surgery failure.

              Epilepsy surgery is an accepted treatment option in patients with medically refractory focal epilepsy. Despite various advances in recording and localization noninvasive and invasive techniques (including electroencephalography (EEG), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetoencephalography (MEG), subdural grids, depth electrodes, and so on), the seizure outcome following surgical resection remains suboptimal in a significant number of patients. The availability of long-term outcome data on an increasing number of patients suggests two major temporal patterns of seizure recurrence (early vs. late) that implicate the following two different mechanisms for seizure recurrence: (1) a failure to either define/resect the epileptogenic zone, and (2) the nonstatic nature of epilepsy as a disease through the persistence of proepileptic cortical pathology. We describe the temporal patterns of epilepsy surgery failures and discuss their potential clinical, histopathologic, genetic, and molecular mechanisms. In addition, we review predictors of successful surgical interventions and analyze the natural history of epilepsy following surgical intervention. We hypothesize that the acute/early postoperative failures are due to errors in localizing and/or resecting the epileptic focus, whereas late recurrences are likely due to development/maturation of a new and active epileptic focus (de novo epileptogenesis). Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
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                Author and article information

                Journal
                Epilepsy Res Treat
                Epilepsy Res Treat
                ERT
                Epilepsy Research and Treatment
                Hindawi Publishing Corporation
                2090-1348
                2090-1356
                2016
                16 March 2016
                : 2016
                : 7982494
                Affiliations
                1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
                2Comprehensive Epilepsy Center, NYU Langone Medical Center, New York, NY 10016, USA
                3Seton Brain and Spine Institute, The University of Texas at Austin, Austin, TX 78701, USA
                4Department of Neurology, Baylor College of Medicine Medical Center, Houston, TX 77030, USA
                5Neurology Consultants of Dallas, PA, Dallas, TX 75231, USA
                6Department of Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
                Author notes
                *Pradeep N. Modur: pmodur@ 123456gmail.com

                Academic Editor: Morten I. Lossius

                Article
                10.1155/2016/7982494
                4812270
                27069682
                257498b2-fde8-4edf-ba45-81881f711faf
                Copyright © 2016 Hai Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 October 2015
                : 16 February 2016
                : 16 February 2016
                Categories
                Research Article

                Neurology
                Neurology

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