A number of recent longitudinal long-term outcome studies report sustained seizure freedom after TLR. Most are retrospective single-center series, only a few are prospective. Sustained seizure freedom is reported as Engel I [4, 16, 17], Engel I A [18, 19], or Engel I A and B [20], and in a few studies as ILAE class 1 and 2 [14, 21]. The proportion of patients with sustained seizure freedom around 5 years postoperatively varies between 44 and 55 % [14, 15, 17, 18, 21] and 60–80 % [16, 19, 20, 22]. Among the studies with more moderate rates of sustained seizure freedom three of five are prospective [14, 15, 21]. All studies reporting higher rates of sustained seizure freedom were retrospective.

A few studies report longitudinal follow-up until 10 years. In one retrospective single-center study in 325 patients (adults and children), 48 % were continuously seizure-free (defined as Engel I A, B and D) after 5 years and 41 % after 10 years [17]. In the earlier mentioned study of 615 adults, 497 had TLR and 55 % of them were seizure-free (without or with auras) after 5 years and 49 % after 10 years [14].

TLR constitute the majority of resective epilepsy surgery procedures in adults. It is therefore not surprising that most of the long-term outcome studies and especially those presenting longitudinal outcome data using survival methods concern TLR. It is possible to study the long-term prognosis in this more homogenous group of patients. Many factors may influence seizure outcomes, for example, referral bias, epilepsy center experience and resources, time period, and histopathology. In Fig. 3.1, we present a Kaplan-Meier analysis of time to first seizure (defined as seizures with impairment of consciousness) in adult patients (18 and older) who have undergone any variety of TLR and in whom the main histopathology was mesial sclerosis. The analysis includes data from three large epilepsy centers from three continents and with data partly from different time periods. The patients from Austin Health, Melbourne, Australia were enrolled 1979–1998 (courtesy for sharing these data to Drs Anne McIntosh and Sam Berkovic), those from Jefferson Comprehensive Epilepsy Center, Philadelphia, USA, were included 1987–2014 (courtesy for sharing these data to Drs Ali Asadi-Pooya and Michael Sperling), and the patients from UCL, London, UK 1990–2008.

As seen in Fig. 3.1, the curves are remarkably similar, with most relapses in the first 5 years and then some flattening of the gradient. The similarity between the curves from three large single-center series from three continents indicates that although factors such as referral or selection bias and differences in presurgical evaluation or surgical procedures may influence outcomes, there are in these patient populations common underlying risks for relapse.

In a recent systematic review of long-term outcomes after FLR, the authors identified 21 articles from 1991 to 2010 containing data from 1,199 patients (adults and children) with a mean or median follow-up of at least 4 years [23]. All studies were retrospective or prospective single-center series and the seizure-free rates at long term varied from 20 to 78 % across individual studies with no significant trend towards better outcomes over time. The overall rate of postoperative seizure freedom reported as Engel I was 45 %. The seizure outcome at 5 years defined as Engel I in the two studies that provided longitudinal data were 47 % and 27 %, respectively [24, 25].

In a few of the studies published after 2010, the reports of long-term outcomes in patients after FLR or other extratemporal resections include information on sustained seizure freedom since surgery. Five years postoperatively these proportions range from 14.7 % (Engel I) [26], 27 % (Engel I) [25], 35 % after FLR, and 33 % in other extratemporal resections (Engel I A and B) [15] to 47 % (Engel I, 34.8 % Engel I A) [24]. In one cross-sectional FLR study with a mean of 6 years follow-up, 24 % were reported to have sustained seizure freedom (Engel I A) [27]. In another study focusing on patients who had undergone MEG as part of their workup, 48 % were reported to be seizure-free (Engel I A) after a mean of 5 years [28].

In long-term seizure outcome studies of extratemporal resections, seizure freedom rates vary from 14 % (mostly patients with focal cortical dysplasia) at 5 years (Engel I A and B) [26] to 52 % at 5 and also at 10 years (Engel I, mostly patients with lesional etiology) [29].

Corpus callosotomy (anterior or complete) is a palliative surgical procedure performed in both children and adults, most commonly because of traumatizing drop attacks (tonic or atonic). Most follow-up studies are single-center, retrospective, and report outcome cross-sectionally with different outcome measures making comparisons difficult. Series including both children and adults have outcomes comparable to the purely pediatric series [30]. In the only purely adult series comprising 15 adults with a mean follow-up of 2.6 years (range 0.6–10.2 years), 5 patients (33 %) reported >60 % reduction in all seizures while 7 (47 %) reported >60 % reduction in drop attacks [31]. One long-term outcome study of 95 patients, children and adults, with a minimum follow-up of 5 years reported improvement in GTCS in 77.3 % and in drop attacks in 77.2 % [32]. In another long-term study of 78 patients (27 adults) with a median follow-up of 8 years, 61/73 patients with drop attacks were reported free from these at follow-up (84 %) [33]. A recent long-term follow-up, which is population-based, multicenter, and prospective [34], also included both children and adults (N = 31). In this study, there was a sustained reduction in seizure frequency at long term, which even improved over time. At the long-term follow-up (5 or 10 years), 10 of the 18 patients with preoperative drop attacks were free of these attacks.

Surgical treatment of patients with hypothalamic hamartomas is another mainly palliative procedure that can be performed as open surgery, radiosurgery, or as a disconnective procedure. As for callosotomies, series are often single-center and retrospective with limited sample sizes. In a series of 24 children and adults who underwent interstitial radiosurgery 46% had an Engel I or II outcome after a mean follow-up of 2 years [35]. In a recent study of 40 adults who underwent gamma knife treatment, 29 % were reported to be seizure-free in the long term (mean 4.8 years) [36].

Predictors for seizure freedom (positive) or seizure recurrence (negative) at long term (at least 4 years) have been sought by several investigators. While some found no remaining predictors in multivariate analysis [18, 21, 27], others have identified a number of predictors. Commonly identified predictors for seizure freedom or “good outcome” are positive MRI and histopathology (varying depending on types of pathology included in analysis) [14–17, 25, 26, 37, 38]. Positive predictors in patients at least 4 years after FLR were lesional epilepsy, abnormal MRI, localized resection as opposed to more extensive frontal or multilobar resections [23]. In lesional cases, gross-total resection (as opposed to subtotal resection) led to better seizure outcome. In the study evaluating the predictive value of MEG, monofocal MEG and nondominant side resections were predictive of seizure freedom [28].

Several factors have been identified as predictors negatively related with long-term seizure freedom: SGTCS at baseline [17, 39, 40], long epilepsy duration [9, 15, 38, 41–43], higher age at surgery [14, 29, 40], high baseline seizure frequency [15, 44], postoperative interictal epileptiform discharges [37, 41, 45], and early postoperative seizures [25, 26, 46].

The one predictive factor that is tractable – epilepsy duration before undertaking presurgical investigation – has repeatedly been shown not to have shortened significantly over the years [7, 9, 47]. These results from long-term outcome studies underline the importance of earlier identification of good candidates for resective epilepsy surgery.

The duration of epilepsy in adults referred for presurgical evaluation is still 15–20 years [48], a time period that for many of the young adults referred is more than half of their lives. Earlier epilepsy surgery has the important potential to decrease or even prevent many of the disabling psychological and social consequences of epilepsy.

Although seizure outcome is often reported as a static measure (seizure-free or not at a certain time-point), seizure outcomes after epilepsy surgery are more complicated. Several studies have pointed out the changing pattern of seizure control over time that complicates the process of evaluating surgical outcomes. In a retrospective study of 175 patients who had been seizure-free for 1 year after resective epilepsy surgery, 63 % never relapsed during a mean follow-up of 8.3 years. The likelihood of remaining seizure-free declined to 56 % over 10 years, but half of the patients who relapsed had at most one seizure per year [49].

In a US multicenter follow-up of 223 patients who at some point during follow-up (2–7 years) had entered a 2-year remission, 25 % relapsed later. Patients who entered a 2-year remission immediately after surgery were less likely to relapse later than those who had a 2-year remission at a later time [39]. In another study of 285 patients who had 1 year of postoperative seizure freedom, 18 % had relapsed by 5 years and 33 % by 10 years, but at last follow-up (after a mean of 8 years), only 13 % were not seizure-free [40].

In the UCL long-term follow-up of 615 adults, 68–73 % of patients had been seizure-free (or had only aura) the previous year at any time during follow-up. Most patients were stable, but 3–15 % changed seizure status. Patients who were seizure-free 2 years after surgery, had an 80 % chance of still being seizure-free after another 5 years, and those who were continuously seizure-free 5 years postoperatively had an 89 % chance of still being seizure-free after another 5 years. So the longer the preceding seizure-free period was, the less likely it was that the patients would relapse, even if they would never be completely free of risk for recurrence [14]. Of those who were not seizure-free in the first 2 years after surgery, 24 % were seizure-free for the next 5 years. Of those who were not seizure-free in the first 5 years after surgery, 20 % were seizure-free for the next 5 years.

There are no systematic studies of the optimal timing of postoperative drug withdrawal in adults. The proportion of seizure-free adults (and children) in whom AEDs have been withdrawn after successful epilepsy surgery varies widely across studies. In a meta-analysis from 2007, nine studies were identified and a pooled analysis showed that 27 % of seizure-free children and 19 % of seizure-free adults had discontinued AEDs at a mean follow-up of 7 years [50]. However, in an Indian study, AED withdrawal was systematically planned for all seizure-free patients after TLR and was successful in 63 % of 258 patients who were followed for at least 5 years [37].

In a cross-sectional follow-up study after neocortical resections, 61/223 (27 %) had stopped AEDs after a mean of 7 years [51], which is the same proportion as in the UCL study where 104 of 365 (28 %) seizure-free individuals were off AEDs at the latest follow-up (median 8 years) [14].

In a study of outcomes in 106 patients after extratemporal (mainly lesional) resections in adults and children, 59 % were seizure-free without aura (ILAE 1) during the last year of follow-up. Twenty-five percent had stopped AEDs (and had been off AEDs for at least 1 year) after a mean of 4.6 years, and another 40 % had reduced the number of AEDs [41].

In the prospective-population-based Swedish long-term follow-up study, 43 % of the adults who were seizure-free 10 years postsurgery had stopped AED treatment [15].

Figure 3.2 illustrates the proportion of patients who are off AEDs 10 years after surgery but also the numbers of seizure-free patients who had reduced polytherapy 10 years after epilepsy surgery [52].

Epilepsy surgery is an efficacious treatment for selected persons with drug-resistant focal epilepsy, rendering many seizure-free and others significantly improved. For many years, follow-up data were limited to a few years after surgery. However, most adults who undergo epilepsy surgery are young and in order for them to make an informed decision about the treatment option of neurosurgery, they need not only short-term data but also data on the probability of long-term remission or improvement. In order to make their own risk-benefit assessment, they also need information on many other outcome aspects, many of which are discussed in other chapters of this volume.

Long-term longitudinal observational studies are necessary in order to obtain valid outcome data. From a number of such studies, the proportion of patients who have been continuously free from seizures with impairment of consciousness since resective epilepsy surgery seems to be 40–50 % after 10 years, while a higher proportion have been seizure-free at least a year at each time-point assessed. The best longitudinal data are in patients who have undergone TLR and in whom the histopathology was mesial sclerosis, and from these data (Fig. 3.1) it seems that the majority of relapses occur within 5 years, and after that there is a lesser relapse rate. Whether this course is applicable to other resection types and pathologies is not clear.

There is much less information on the longitudinal course in patients who have undergone other resection types and have other causes. For many resection types, the number of patients in single-center long-term follow-ups is limited and for almost all studies there is a lack of controls. Multicenter observational studies following both operated and nonoperated patients are needed in order to obtain more robust data.

In general, the visualization of structural lesions on MRI and certain specific histopathological findings predict good seizure outcomes, while negative predictors include biomarkers of more severe epilepsy such as SGTCS and higher seizure frequency at baseline. Shortening the duration of epilepsy at surgery by referring patients for presurgical investigation earlier is the single most important factor possible to influence that can improve the prognosis for good seizure outcome of epilepsy surgery. Even if earlier evaluation for epilepsy surgery does not per se carry a higher remission rate, earlier evaluation for surgery would also help preventing many of the psychosocial problems related to long-standing drug-resistant epilepsy.