Letter: Risk Factors for Seizure Worsening After Epilepsy Surgery in Children and Adults: A Population-Based Register Study.

Abstract

To the Editor: We read with great interest the recently published article by Bjellvi et al,1 in which the authors analyzed a multicenter prospective database of patients with drug refractory epilepsy who had undergone surgery, in order to identify cases with seizure worsening postoperatively. A large number of patients were included with a uniform 2 yr of follow-up. Based on their analysis, the authors proposed certain risk factors for postoperative seizure worsening, which can be helpful to identify and thus prognosticate such patients preoperatively. WORSENING SEIZURES AFTER EPILEPSY SURGERY: A NEUROSURGEON’S TREPIDATION The goal of epilepsy surgery is to alleviate the patients’ ongoing seizures. The best possible outcome is complete seizure cessation, while even a worthwhile or small reduction in seizure frequency is acceptable. But despite best efforts, one of the worst possible outcomes of epilepsy surgery is postoperative seizure worsening. This phenomenon has been relatively less studied in literature and the mechanisms behind it are poorly understood. When considering overall surgical procedures, the incidence of postoperative seizure worsening varies between 3% and 4%,1,2 while it increases to as high as 11% when considering resection procedures alone.2,3 This is not an insignificant number, and as the authors rightly pointed out, the current epilepsy surgery outcome scales do not address this issue adequately. The Engel classification has just 1 subclass (IVC) in which this group of patients can be assigned.4 The International League Against Epilepsy (ILAE) classification5 divides this group into 2 classes—5 and 6, which still does not allow for a detailed description of seizure worsening. As reported by the authors, 4% of their patients had an increase in seizure frequency, while 2.8% had a >100 % increase in seizure frequency (ILAE class VI). This is a sizable number and should be properly accounted for. Future revisions of these outcome scales should keep this fallacy in mind. The risk factors identified by the authors are similar to the factors previously identified for predicting poor surgical outcome in large surgical series.6 A previous single-center retrospective study has been reported, which sought to identify risk factors for seizure worsening after surgery, albeit in a smaller cohort of patients who underwent unilobar epilepsy surgery. In the present study, the authors had access to a large multicenter database of patients who underwent all kinds of procedures, and thus a further subgroup analysis of variables such as completeness of resection or disconnection could have been done, especially since incomplete resection has been found to be a risk factor in the earlier study.2 Preoperative multiple seizure semiology was another significant risk factor identified in the previous study,2 which was not reported in the present study. The change in pattern of seizures and the incidence of postoperative status epilepticus could have been very informative. Given that these patients were enrolled in the database over a 25-yr period, a separate analysis of the long-term follow-up more than 2 yr and its effect on seizure frequency could also have been performed. Additionally, there are discrepancies with regard to the risk factors identified in previous studies, with Sarkis et al2 reporting seizure frequency < 30/mo and Ficker et al3 reporting older age at surgery in temporal lobectomy as a risk factor for seizure worsening, which is contradictory to the findings reported in the present study. Further research on this topic will be necessary to resolve this issue. The most important question to arise from this study is the reason as to why seizures should worsen after surgery. The frequency and semiology can be expected to stay the same in cases where the epileptogenic zone has not been identified correctly. However, the mechanisms of seizure worsening have not been elucidated and various unproven hypotheses have been proposed to explain the same. Sarkis et al2 proposed that surgery might somehow accelerate the process of seizure progression and that this phenomenon might just represent the natural history of disease evolution. Complex pathologies such as malformations of cortical development have been correlated with poor surgical outcome.7 Postoperative status epilepticus has been reported in cases with incomplete resection of focal cortical dysplasia and this could be another potential independent risk factor.8 The most recent hypothesis regarding facilitation of seizure propagation due to alteration of complex epileptogenic networks as a result of surgery seems promising.1 It is also the one that might be proved by the recent advances in connectomics, machine learning, and predictive modeling of data.9 The authors should be commended for addressing this unwelcome occurrence after epilepsy surgery. In order to prevent this complication, future research should be directed to understand the underlying etiopathogenesis of this phenomenon. Funding This study did not receive any funding or financial support. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.