Beyond seizure freedom: Dissecting long‐term seizure control after surgical resection for drug‐resistant epilepsy

Abstract

Objective

This study was undertaken to better understand the long‐term palliative and disease‐modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug‐resistant epilepsy.

Methods

This retrospective database‐driven cohort study included all patients with >9 years of follow‐up at a single high‐volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug‐resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow‐up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow‐up.

Results

We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure‐free at last follow‐up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure‐free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow‐up. Nearly half (47.1%) of those seizure‐free at last follow‐up were not seizure‐free immediately postoperatively.

Significance

Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

Key Points.

• Most patients who continue to have seizures after resection for drug‐resistant epilepsy experience substantial reductions in seizure frequency (mean = 76.2%)

• More than 70% of patients who underwent resection were seizure‐free at long‐term last follow‐up, with a median 11.9 years since their last seizure

• Almost half (47.1%) of patients seizure‐free at last follow‐up were not immediately seizure‐free postoperatively

• More than 90% of patients experienced seizure‐free periods of >1 year

• Surgical resection offers the greatest chance for seizure freedom and a high likelihood of substantial seizure frequency reduction over long‐term follow‐up

1. INTRODUCTION

For appropriate selected patients with drug‐resistant epilepsy (DRE), surgical resection provides the greatest opportunity for seizure freedom. ¹ , ² , ³ , ⁴ Reported rates of complete seizure freedom after resection for epilepsy usually range from 40% to 80%, depending on the study, location of surgery (i.e., temporal vs. extratemporal), positive magnetic resonance imaging findings, and length of follow‐up, but both clinical judgment and prognostic models have shown only a limited ability to predict which surgical patients are likely to achieve seizure freedom. ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ Most studies report outcomes after 1 or 2 years of follow‐up, but longer term studies have shown that seizure recurrence can occur in a delayed manner ¹¹ , ¹² , ¹³ and might follow a milder and more controllable course, ¹⁴ , ¹⁵ and those undergoing reoperation for recurrent seizures are often subsequently able to become seizure‐free. ¹⁶ , ¹⁷ However, the evidence supporting this view of recurrent postoperative seizures remains patchy, and detailed understanding of the long‐term behavior of recurrent seizures remains limited.

Neuromodulation for DRE has demonstrated safety and efficacy relative to medical treatment alone. ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , ²³ Recently, the long‐term outcomes of a prospective trial of brain‐responsive neurostimulation (RNS) reported an improving seizure frequency reduction from 58% to 75% over 9 years of follow‐up, and a subset of patients achieved at least 6 months or 1 year of seizure freedom (28.1% and 18.4%, respectively). ²⁴ Given these encouraging results, valid comparative effectiveness assessments of neuromodulation relative to resective surgery require a similar understanding of the benefits of resection. However, studies of resective or ablative epilepsy surgery have defined success through stricter standards, most commonly equating it to postoperative immediate, complete, and sustained resolution of all seizures. Less well understood is the impact of surgical resection on seizure frequency in patients not completely seizure‐free, and how many are able to achieve seizure freedom in a delayed fashion. Long‐term observation of surgical epilepsy patients has focused most often on the rates and predictors of late seizure recurrence, ¹² , ¹³ , ¹⁵ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ with only limited consideration of seizure frequency reduction, typically at a few fixed postoperative time points. ¹¹ , ³⁰ , ³¹

To address this knowledge gap, we report here a large and well‐followed heterogenous cohort of surgical epilepsy patients, with at least 9 years of postoperative follow‐up, to better understand the long‐term impact of epilepsy surgery on seizure frequency and seizure freedom.

2. MATERIALS AND METHODS

2.1. Patient selection

In this institutional review board‐approved study, we queried our prospectively maintained surgical epilepsy database for patients who underwent surgical resection for treatment of drug‐resistant epilepsy and had at least 9 years of postoperative follow‐up, from 1994 to 2012. Through the Epilepsy Center Outcomes Registry, we collect follow‐up information from clinic visits or follow‐up telephone calls carried by our surgery team and research coordinators to complete data collection in patients who miss their clinical follow‐up visits. Typically, patients are followed up at 3 months, 6 months, 1 year, and then yearly after surgery. Standardized clinic notes and outcome definitions ensure uniform data collection standards. Long‐term outcomes are available for >90% of our surgical epilepsy patients. We included here patients who underwent lobectomy, multilobar resections, and lesionectomies. We excluded patients who underwent hemispherectomies or had insufficient follow‐up. We used the patient's first resective epilepsy surgery as the index surgery for this study. If this surgery was outside our institution, or if preoperative records were not available, the patient was excluded from the study, as in these cases we were unable to reliably ascertain preoperative baseline variables or immediate postoperative outcomes.

2.2. Data collection and outcomes ascertainment

We collected baseline demographic, clinical, and treatment‐related variables. Baseline (preoperative) seizure frequency was defined as the monthly frequency of disabling seizures reported at the patient's presurgical multidisciplinary conference. When this information was not available, the frequency was estimated from inpatient and outpatient clinical records as close to the index surgery as possible. From the clinical record, we estimated the frequency of disabling seizures at 6 months postoperatively, annually up to 9 years, and at last follow‐up. We defined disabling seizures as those impairing awareness and according to Engel's classification ³² : auras, focal aware seizures, and convulsions or disabling seizures occurring during medication withdrawal were excluded from seizure frequency estimations and consideration of seizure freedom.

We determined the first date of 6 months or 1 year of seizure freedom, as well as the start and end dates of the longest period of seizure freedom, for each patient. We also collected the date of the last seizure experienced by each patient prior to last follow‐up. We considered patients who were free of disabling seizures for >1 year at the time of last follow‐up to be seizure‐free at last follow‐up. We collected procedural dates, details, and outcomes for patients who underwent subsequent surgeries for their epilepsy. These patients and their outcomes were included in the cohort for analysis through their last follow‐up.

We evaluated changes in antiseizure medication regimens at last follow‐up relative to the immediate preoperative baseline. An "increase" in antiseizure medication was defined as an increase in dose, the addition of a medication not taken at baseline, or both. A "decrease" was defined as a reduction in dose, the discontinuation of a medication, or both. Patients who had both a qualifying increase and a qualifying decrease were categorized as having a "mixed" change in medication.

2.3. Statistical methods

We calculated descriptive data using n (%) for nominal variables, mean ± SD for normally distributed continuous variables, and the median with interquartile range or range as appropriate. Seizure frequency outcomes at each postoperative time point were calculated as percentage reduction from preoperative baseline, and the number and fraction of patients achieving each seizure freedom outcome was quantified. We estimated lengths of seizure freedom for patients achieving at least 6 months of seizure freedom or who were seizure‐free at last follow‐up (with a period of at least 6 months since their last seizure). We performed time‐to‐event analyses to explore when patients experienced seizure recurrence or achieved seizure freedom after surgery.

3. RESULTS

3.1. Patient characteristics

Our initial query yielded 326 unique adult and pediatric epilepsy patients, and after applying exclusion criteria 251 patients remained (Figure 1). Patients were 30.6 years old on average, 59.4% were female, and 86.8% were right‐handed. A total of 198 (78.9%) were 18 years or older at the time of epilepsy surgery. Average duration of epilepsy was 14.6 years, and nearly three quarters of patients (71.8%) had more than weekly seizures immediately prior to surgery. More than half (56.2%) of resections were left‐sided, although more patients undergoing temporal lobectomy underwent right‐sided (55.8%) than left‐sided (44.2%) surgeries. A total of 104 (41.1%) patients underwent invasive evaluation with intracranial electrode grids and/or stereotactic depth electrodes prior to surgical resection. A summary of baseline patient and disease characteristics is found in Table 1.

FIGURE 1.

Patient flowchart. Of 251 patients included in this study, 96 never had another seizure after surgery. In the subgroup with recurrent seizures after surgery, 32 underwent repeat surgery for their epilepsy. Endpoints of >6 months, >1 year, and seizure freedom at last follow‐up (defined as >1 year since their last disabling seizure) are reported for this subgroup as well as the entire cohort. DBS, deep brain stimulation; f/u, follow‐up; RNS, responsive neurostimulation; SEEG, stereoelectroencephalography; VNS, vagal nerve stimulation

TABLE 1.

Basic demographic and baseline disease characteristics

Characteristic	n = 251
Age at surgery, years	30.6 ± 14.5 (range = .39–65.7)
≥18	198 (78.9%)
<18	53 (21.1%)
Sex
F	149 (59.4%)
M	102 (40.6%)
Handedness, n = 168
R	145 (86.8%)
L or ambidextrous	22 (13.2%)
Duration of epilepsy	14.6 [6.4–24.0] years
Baseline seizure frequency, n = 249	8 [4–20] seizures/month
≥Daily	42 (17.1%)
≥Weekly, <daily	134 (54.7%)
<Weekly	60 (24.5%)
Invasive monitoring	104 (41.1%)
Adverse events a	16 (6.4%)
Prior neuromodulation; i.e., VNS	2 (.8%)
Resection side
R	110 (43.8%)
L	141 (56.2%)
Resection type b	Total	Right	Left
Temporal lobectomy	163 (64.9%)	91 (55.8%)	72 (44.2%)
Mesial structures spared	33 (21% of 160)	11 (12.1% of 91)	23 (31.9% of 72)
Selective AH	7 (2.8%)	1 (14.3%)	6 (85.7%)
Frontal lobectomy	44 (17.5%)	22 (50.0%)	22 (50.0%)
Multilobar	22 (8.8%)	10 (45.5%)	12 (54.5%)
Lesionectomy	6 (2.4%)	1 (16.7%)	5 (83.3%)
Other	9 (3.6%)

Note: Values are presented as n (%), mean ± SD, or median [25%ile–75%ile] as appropriate.

Abbreviations: AH, amygdalohippocampectomy; F, female; L, left; M, male; R, right; VNS, vagal nerve stimulation.

^a Adverse events defined as death, reoperation (excluding subsequent surgeries for epilepsy), permanent disabling neurologic deficit, major cardiopulmonary or thromboembolic event within 30 days of surgery.

^b Thirty patients (12.0%) underwent resections in the parietal or occipital lobes. These patients fall within the "multilobar," "lesionectomy," or "other" categories, depending on the type of resection.

3.2. Seizure outcomes in overall cohort

Ninety‐six (38.2%) patients never had another seizure after surgery (i.e., they achieved Engel Class IA outcomes over >9 years of postoperative follow‐up). During a median 14.7 years of follow‐up, 232 (92.4%) achieved a period of at least 1 year of seizure freedom, and 234 (93.2%) patients achieved at least one period of 6 months of seizure freedom. Of these patients, the mean longest period of seizure freedom was >10 years. A total of 182 (72.5%) patients were seizure‐free at last follow‐up (defined as >1 year without seizures), with a median period of 11.9 years since their last seizure. To further explore the durability of seizure freedom at last follow‐up, we increased the threshold to be considered seizure‐free at last follow‐up to >2 years, and we found that 167 (66.5%) patients met this endpoint.

3.3. Seizure outcomes in the “not seizure‐free” group

For the 155 patients who had postoperative seizures, 59 (38.1%) had seizures within 6 months, and 71 (45.8%) had seizures within 1 year. A total of 136 (87.7%) and 138 (89.0%) of these patients experienced seizure‐free periods of 1 year and 6 months, respectively. Among this group of patients who were not completely seizure‐free, the median longest period of seizure freedom was 6.9 years, and 89 (55.5%) patients were seizure‐free at last follow‐up, with a median 7.4 years since their last seizure (Table 2).

TABLE 2.

Surgical outcomes

Outcome	All patients, n = 251
Length of f/u, years	14.7 [11.3–18.8]
No seizures since surgery	96 (38.2%)
Seizure freedom	All patients, n = 251	Not completely seizure‐free, n = 155
Seizure‐free 6 months	234 (93.2%)	138 (89.0%)
Seizure‐free 1 year	232 (92.4%)	136 (87.7%)
Seizure free at last f/u	182 (72.5%)	86 (55.5%)
For patients seizure‐free at last f/u, duration since last seizure, months	143 [127.3–209.3]	89 [36.8–143]
>2 years seizure‐free at last f/u	167 (66.5%)	71 (45.8%)
Longest period of seizure freedom, months	123 [62–169]	84 [25–141]
Underwent subsequent epilepsy surgery	32 (12.7%)
Seizure‐free at last f/u	12 (37.5% of 32)
Medication at last f/u vs. baseline a
Reduction	97 (39.3%)
Increase	19 (7.7%)
Mixed	131 (53.0%)
No change	0 (0%)
Change in # ASMs	−.58 ± 1.2 medications
No medications at last f/u	53 (21.2%)

Note: Values are presented as n (%), mean ± SD, or median [25%ile–75%ile] as appropriate.

Abbreviations: ASM, antiseizure medication; f/u, follow‐up.

^a Increase in medication defined as addition of new agent, increase in dose, or both. Decrease in medication defined as removal of a medication, reduction of dose, or both. Mixed defined as a qualifying increase and a decrease in medications.

Nearly all patients experienced substantial reduction in their frequency of disabling seizures. For all patients as well as those not completely seizure‐free, the median reduction in seizure frequency was 100% at all postoperative time points, and the 25th percentile was at or near 100%. Among all patients, the average 10th percentile seizure frequency reduction at each time point was 75.5%, and for those not completely seizure‐free, it was 47.0%. An average of 90.4% (range = 88.9%–92.8%) of these patients had ≥50% reduction in seizure frequency at each time point. Seven (2.8%) patients had an increase in their seizure frequency from baseline at last follow‐up. A summary of the average seizure frequency reduction is available in Figure 2 and Figure 3.

FIGURE 2.

Median, 25th percentile, mean, and 10th percentile seizure frequency reduction at each postoperative time point. (A) Among all patients, the median seizure frequency reduction is 100% (not pictured) and the 25th percentile is near 100%. The mean is skewed by a small minority who had significant increases in seizure frequency. (B) Among patients who were not completely seizure‐free, the median seizure frequency reduction is 100% and the 25th percentile ranges from 90.0% to 95.8%. The 10th percentile seizure frequency reduction ranges from 24.0% to 62.9%. F/U, follow‐up

FIGURE 3.

Seizure frequency reduction at last follow‐up per patient. Each bar represents the reduction in seizure frequency relative to baseline for a patient at last follow‐up. A bar at 100% indicates seizure freedom (no seizures within 1 year) at last follow‐up; 182 (72.5%) patients met this criterion. Negative bars indicate an increase in seizure frequency relative to baseline. Five patients had more than a doubling of their baseline seizure‐frequency, and their bars, which are truncated, are colored black. We were unable to estimate seizure frequency reduction for two patients at last follow‐up

3.4. Surgical complications

Sixteen (6.4%) patients experienced serious surgery‐related adverse events, which we defined as a permanent disabling neurologic deficit, an unplanned reoperation (excluding epilepsy surgery), or major thromboembolic or cardiopulmonary event within 30 days of surgery. Of these, the majority (56%) were reoperation for infection, which in some cases required multiple surgeries and/or bone flap removal and cranioplasty. Two patients required urgent surgery for intracranial hemorrhage, and three patients required surgery several years later for painful or loose hardware or bone flap issues. One patient required anticoagulation and a central venous filter for a deep vein thrombosis and pulmonary embolism, and the final patient required wound revision for cerebrospinal fluid leak.

The proportion of patients who experienced an adverse event was similar between those who did (6.7%) and those who did not (6.1%) undergo invasive evaluation prior to resection. Of patients who had adverse events, 56.2% (nine patients) were seizure‐free at last follow‐up.

3.5. Reoperation

Thirty‐two patients underwent subsequent surgery for epilepsy. This included 24 patients who underwent subsequent resection, seven who underwent neuromodulation, and two who had stereoelectroencephalography (SEEG) without further surgery. One patient underwent first vagal nerve stimulation (VNS), then resection after a lack of improvement. Of those who underwent repeat resection, 10 (41.7%) subsequently became seizure‐free. Of the six patients who received RNS or VNS (without repeat resection), one (16.7%) patient became seizure‐free. Although the remaining five patients had varied initial responses to neuromodulation (ranging from >100% increase to 99% decrease in seizures over the first several years), at last follow‐up, all experienced a reduction (mean = 54.7%, range = 12.5%–99%) in seizure frequency. Interestingly, one patient of the two who underwent SEEG alone without further surgery also became seizure‐free.

3.6. Medication reduction

At last follow‐up, 97 (39.3%) patients had a reduction in their antiseizure medication compared to their preoperative baseline. Nineteen (7.7%) had an increase, and 131 (53.0%) had a mixed change in their medications. Our definition of a "mixed" change in medications was quite inclusive, and many of these patients were on fewer overall medications or qualitatively lower regimens than at baseline. Patients had a mean reduction of .58 in the number of medications they were taking, and 53 (21.2%) were on no antiseizure medications at last follow‐up.

3.7. Time to recurrence or seizure freedom

Kaplan–Meier cumulative failure plots are presented in Figure 4. Although 45.8% of patients who had recurrence of seizures did so within the first year postoperatively, late recurrence occurred in a sizable proportion of patients, with another 41.2% of the recurrences occurring after at least 2 years seizure‐free. More than half (58.7%) of patients who recurred after 2 years of initial seizure freedom were seizure‐free at last follow‐up, whereas 50.7% of patients who recurred within 1 year were seizure‐free at last follow‐up.

FIGURE 4.

Kaplan–Meier cumulative event plots. (A) Time to first seizure postoperatively. (B) Time to the start of a 1‐year period of seizure freedom. Most patients achieving this endpoint do so immediately postoperatively, but some patients achieve this endpoint many years after surgery. (C) For patients who are seizure‐free at last follow‐up only, the time to onset of their last seizure. More than half of patients who achieve this endpoint are seizure‐free immediately postoperatively, but many more patients continue to achieve seizure freedom throughout the follow‐up period. Time to 6 months of seizure freedom, and time to last seizure for those seizure free for >2 years at last follow‐up are not pictured, as curves are very similar to those already presented

Whereas most (78.9%) patients who achieve 1 year of seizure freedom are able to do so immediately postoperatively, a minority initially have postoperative seizures but are able to achieve 1 year of seizure freedom later during follow‐up. More than half (52.7%) of patients who were seizure‐free at last follow‐up were seizure‐free immediately after surgery, but many patients achieved late remission; 119 (62.3%) patients achieved remission by 2 years, and an additional 41 (22.5%) patients achieved remission after >10 years of postoperative follow‐up.

4. DISCUSSION

We describe for the first time in a systematic fashion the meaningful reduction in seizure frequency experienced by a large cohort of patients undergoing surgical resection for DRE over the course of a long period of follow‐up. We defined disabling seizures as those that impaired awareness; this is the same definition used in the landmark randomized clinical trial demonstrating the efficacy of surgery over medical treatment alone for temporal lobe epilepsy. ¹ Although a few prior reports have described seizure frequency reduction in surgically treated epilepsy patients, this has largely been limited to secondary outcomes, during fewer postoperative time points, and over a shorter term follow‐up.

Routine assessment of seizure outcomes can be difficult; patient follow‐up is often not conducted exactly at the 3‐month, 6‐month, or 1‐year mark, or at regular intervals afterward. Through our Epilepsy Center Outcomes Registry, outcomes are obtained both through regular clinical care and telephone contact by our research team. As a result, our follow‐up intervals are likely more consistent than that found at most institutions. Furthermore, these practices minimize our loss to follow‐up. These factors combined minimize the impact of selection bias upon our findings. This further supports and expands upon prior reports that patients may experience meaningful seizure frequency reductions at 5 years postoperatively, ¹¹ or at a final follow‐up time point of 3–4 ³⁰ or 7.2 ³¹  years. We find that even patients in the 10th percentile, often considered to be "surgical failures," experience a reduction in their seizure frequency of approximately 75% relative to their preoperative baseline during most postoperative time points. This suggests that in addition to currently used standard outcome measures of seizure freedom, seizure frequency is an important outcome not only for the field of neuromodulation, but also for studies of surgical resection for DRE.

Importantly, we found that a small percentage of patients experienced a worsening of their seizure frequency after surgical resection, which in some cases was substantial. Prior research has identified patients with extratemporal resections, incomplete resections, and multiple ictal patterns to be more at risk for this outcome. ³³ Whether this phenomenon is due to incomplete resection or the misidentification of inhibitory components of the epileptogenic network as the seizure onset zone, investigating what clinical and electrophysiologic features may best identify patients at risk for worsening after resection is an important area for study.

We find that many patients experience late recurrence of their seizures (beyond 2–3 years of initial seizure freedom). This has been reported in a multitude of studies, and is reflected in most literature as a downward trend in the proportion of patients remaining completely seizure‐free as the length of follow‐up increases. However, late recurrence tends to follow a milder course than early recurrence, and patients are often subsequently able to reachieve remission with medical management. ¹⁴ , ¹⁵ Qualitatively, many patients in our cohort who experienced late recurrence of seizures often did so in a limited fashion. This is reflected in the significant proportion of patients who were seizure‐free at last follow‐up who were not completely seizure‐free throughout their postoperative course.

We also find that many patients are able to achieve remission in a delayed fashion. Although slightly more than half of patients who were seizure‐free at last follow‐up were seizure‐free immediately postoperatively, roughly 22% became seizure‐free after an initial period of >10 years. The so‐called "running‐down" phenomenon, described by Rasmussen in 1970, was postulated to be due to incompletely resected epileptogenic tissue that was potentially less autonomous and insufficient to perpetually continue the disease. Alternatively, although the epileptogenic network may continue to permit seizure activity, in some patients, disconnection of the presumed focus may, over time, permit adaptations resulting in delayed remission. Ultimately, 47.3% of patients in our cohort who were seizure‐free at last follow‐up were not initially seizure‐free.

A minority of patients with DRE are known to achieve intermittent periods of seizure freedom in the course of their disease. In one prospective study, 33.4% of patients with drug‐resistant disease experienced a period of 1 year of seizure freedom during 7 years of follow‐up without undergoing surgery. By 5 years, 71% of patients subsequently relapsed, emphasizing that brief periods of remission in this population do not substantially modify their long‐term outcomes. It should be noted that this 71% was reported from a combined cohort that included 10 patients who had surgery, and the proportion is likely higher for those managed with medication alone. ³⁴

Our database is prospectively maintained, but our study design is retrospective and is limited to the information available in the database and the clinical record. Our estimates of seizure frequency are, therefore, not of the granularity or consistency of those obtained in a prospective trial where patients and/or their seizure diaries are carefully monitored. Furthermore, our experience is limited to that of a single high‐volume epilepsy center, and surgical results obtained at our institution may not reflect those found elsewhere. Although we are a national and international referral center, our surgical population is 85.2% White, 7.2% Black or African American, and 7.2% patients of other races, and 3.5% are Latino. Black, Hispanic, and non‐English‐speaking patients have been found to undergo epilepsy surgery at lower rates than White patients, underscoring a racial health care disparity in an already underutilized treatment area. ³⁵ , ³⁶ , ³⁷ , ³⁸ Although this gap in access and treatment of DRE is an important area for investigation and improvement, we are not aware of any evidence that outcomes after surgical resection may be affected by patient race.

Nonetheless, our study is inclusive of many different forms of resection and follows a large patient cohort with a high degree of data integrity with a median of >14 years of follow‐up. We find that >90% of patients are able to achieve both 6 months and 1 year of seizure freedom during their postoperative course, and >70% are seizure‐free at last follow‐up. Furthermore, even patients who are not completely seizure‐free experience a substantial decrease in the frequency of their disabling seizures at every postoperative time point. For appropriately selected patients, surgical resection offers not only the greatest opportunity for seizure freedom, but also considerable seizure frequency reduction for patients who are not seizure‐free, and remains the standard of efficacy to which other treatment methods must be compared.

AUTHOR CONTRIBUTIONS

Jason K. Hsieh helped to conceive and design the study, acquired data, performed analysis, and drafted the manuscript. Francesco G. Pucci, Swetha J. Sundar, Efstathios Kondylis, Akshay Sharma, and Shehryar R. Sheikh helped to acquire data and revise the manuscript. Deborah Vegh helped to design the study and collected data. Ahsan N. Moosa, Ajay Gupta, Imad Najm, Richard Rammo, and William Bingaman helped to conceive the study and revised the manuscript. Lara Jehi conceived and designed the study, helped to collect data, and revised the manuscript.

CONFLICT OF INTEREST

None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Hsieh JK, Pucci FG, Sundar SJ, Kondylis E, Sharma A, Sheikh SR, et al. Beyond seizure freedom: Dissecting long‐term seizure control after surgical resection for drug‐resistant epilepsy. Epilepsia. 2023;64:103–113. 10.1111/epi.17445