Confirmed! Durable Benefits of Epilepsy Surgery

Commentary

Long-Term Outcomes of Epilepsy Surgery in Sweden: A National Prospective and Longitudinal Study.

Edelvik A, Rydenhag B, Olsson I, Flink R, Kumlien E, Källén K, Malmgren K. Neurology 2013; 81:1–8

OBJECTIVE: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. METHODS: Ten- and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. RESULTS: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified =30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). CONCLUSIONS: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.

An 18-Year Follow-Up of Seizure Outcome After Surgery for Temporal Lobe Epilepsy and Hippocampal Sclerosis.

Hemb M, Palmini A, Paglioli E, Paglioli EB, Costa da Costa J, Azambuja N, Portuguez M, Viuniski V, Booij L, Nunes ML. J Neurol Neurosurg Psychiatry 2013;84:800–805

OBJECTIVES: To evaluate the very long-term clinical outcome of surgery for mesial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE/HS) without atypical features. The impact of surgical technique and postoperative reduction of medication on this outcome was investigated. DESIGN: Prospective longitudinal cohort follow-up study for up to18 years. SETTING: Epilepsy surgery centre in a university hospital. PATIENTS: 108 patients who underwent unilateral MTLE/HS. INTERVENTION: Surgery for MTLE/HS. MAIN OUTCOME MEASURE: Engel classification (I). Clinical evaluations were based on systematic interviews in person or by phone. Kaplan-Maier survival curves estimated the probability of remaining seizure free. The impact of medication management in the postoperative outcome was analysed using Cox regression. RESULTS: The probability of remaining completely seizure-free at 12 and 18 years after MTLE/HS surgery was 65% and 62%, respectively. The risk of having any recurrence was 22% during the first 24 months and increased 1.4% per year afterwards. Type of surgical technique (selective amygdalohippocampectomy vs anterior temporal lobectomy) did not impact on outcome. Remaining on antiepileptic drugs and history of generalised clonic seizure diminished the probability of remaining seizure free. CONCLUSIONS: MTLE/HS surgery is able to keep patients seizure free for almost up to two decades. Removal of the neocortex besides the mesial portion of the temporal lobe does not lead to better chances of seizure control. These findings are applicable to the typical unilateral MTLE/HS syndrome and cannot be generalised for all types of TLE. Future longitudinal randomised controlled studies are needed to replicate these findings.

When counseling patients about epilepsy surgery, its potential benefits—seizure freedom, reversal of disability, reduced burden of antiepileptic medication, and decreased long-term morbidity and mortality—are balanced against the immediate morbidity and the extremely small mortality risks of surgery. Implicit in this discussion is that the benefits of successful surgery are sustained over a lifetime. What is the evidence for this?

There are already considerable data that the benefits of epilepsy surgery on seizure control persist for many years (1–7). The largest study reported 615 adults from a single center in the UK receiving all types of epilepsy surgery over an 18-year period (497 anterior temporal lobectomies with a median of 8 years follow-up (1)). For the entire group, 47% were seizure-free at 10 years, but 78% of those seizure-free for the first 2 years after surgery were entirely free of seizures associated with loss of consciousness at 10 years. While most studies show a higher rate of long-term seizure freedom in those with hippocampal sclerosis or other lesions, this study also demonstrated that those with extra-temporal resections were somewhat more likely to have recurrence (1). Another study of 360 patients receiving a standard anterior temporal lobectomy at an Australian hospital with a mean follow-up of 9.6 years, revealed 55.3% to be seizure-free at 2 years, and 41% at 10 years (2). Complete discontinuation of antiepileptic drugs (AEDs) in selected seizure-free patients does not appear to increase the risk of seizure relapse (2, 8). The majority of patients that relapse have only a small number of seizures (3, 4), although early occurrence of any seizures after surgery is a negative prognostic factor. Epilepsy surgery can also produce a sustained improvement in health-related quality of life measures, with the greatest improvements in those free of seizures for at least 1 to 2 years (9).

Results of surgical series depend on many factors, especially case selection, approaches to the presurgical evaluation and surgical procedures, and the completeness and adequacy of follow-up. Therefore, the additional proof of long-term surgical efficacy provided by these two new studies is welcome. The report of Edelvik et al. is valuable because it is a survey of epilepsy surgery in an entire population, using a prospective national registry with a standard method of assessing seizure outcome. Patients received operations at 6 different Swedish hospitals with a variety of resection types—but not a standard presurgical evaluation or resection protocol. The majority had temporal resections: 81% of adults and 43% of children. An attempt was made to compare outcomes with a control group of patients assessed for surgery but not offered resection or declining surgery, though it may be assumed that this group must have had different characteristics than the surgery group; for example, a lower rate of discrete lesions on imaging. This implies different expected outcomes in these controls than those selected for surgery. Despite this, the study yielded useful findings, confirming that seizure freedom is sustained at 10 years for many patients, and that an abnormal MRI was a predictor of a favorable outcome for seizure control. It is notable that, in this series, increased epilepsy duration and a higher preoperative seizure frequency were negative seizure outcome predictors. Finally, the study had a high rate of eventual AED discontinuation in those that were seizure-free with all types of resections, especially in children, providing additional support for considering withdrawal of AEDs after surgery.

The Hemb et al. report is remarkable because it gives long-term follow-up on a very well-defined patient group at a single center receiving a standard presurgical workup followed by either a standardized anterior temporal lobectomy or a selective amygdalohippocampectomy by the same surgeon. The study cohort was carefully selected for “pure” hippocampal sclerosis, not only requiring typical MRI and ictal EEG findings without evidence of another lesion or focus but also excluding atypical semiologies such as atypical auras, early clonus or dystonia, or atypical locations of interictal epileptiform discharges (although bilateral independent anterior temporal spikes were allowed). Possibly because of these rigid selection criteria, these patients were more likely to have sustained seizure freedom than found in other series. About half received temporal lobectomy and half selective amygdalohippocampectomy, with equally favorable seizure outcomes, perhaps explained by the careful exclusion of patients with evidence of extrahippocampal involvement.

There is class I evidence of the short-term efficacy of temporal lobectomy for medically refractory epilepsy (10). While it is impractical to obtain that level of evidence for long-term surgical efficacy, the observational studies discussed above provide compelling evidence for durable control of seizures after resection. Nonetheless, important questions remain. There is emerging evidence that poorly controlled temporal lobe epilepsy is associated with progressive cortical atrophy, affecting regions near to and distant from the focus, and a degree of slow cognitive decline; there is a need to better document that these processes are arrested after successful epilepsy surgery. This is important to know, so that the risk of initial decline in cognitive abilities with some surgical resections can be balanced against the potential long-term benefits of seizure freedom on these functions. There is also the practical issue of when and if AED withdrawal should be attempted in seizure-free patients, along with the risk of seizure relapse if it is attempted. The problem of AED withdrawal should be addressed by defining a standard withdrawal protocol that could then be tested in a clinical trial.

In some patients, complete resection of the epileptic focus leads, in essence, to the end of epilepsy, with no seizures and freedom from AEDs. In others, continued AEDs may be needed, or infrequent, sporadic seizures may occur over the years. However, if the patient is seizure-free for the first two years after surgery, a return to frequent uncontrolled seizures is uncommon. We should advise our patients accordingly.