We retrospectively reviewed the records of patients who underwent resective epilepsy surgery at the Seoul National University Children's Hospital (Seoul, Korea) between 2004 and 2015. The included patients underwent surgery at <18 years of age, were followed for at least 2 years after surgery, and were pathologically diagnosed with FCD type I, II, or IIIa based on the International League Against Epilepsy classification.15 To assemble a uniform cohort, patients with tumor-related epilepsy, vascular malformations, infections, and ischemic changes were excluded. Patients who underwent functional hemispherectomy or corpus callosotomy were also excluded. This study was approved by the local Institutional Review Board (IRB No. 1804-140-941). Given the retrospective nature of the study, the requirement to obtain informed consent was waived.

All patients underwent standard presurgical evaluations, including the detailed clinical history, a physical examination, scalp and video-EEG according to the 10–20 system, and high-resolution brain MRI with a 1.5- or 3-tesla epilepsy protocol. Intracranial EEG monitoring was performed when noninvasive investigations failed to localize the extent of the epileptogenic zone or suggested the wide involvement of extralesional areas, or the epileptogenic zone involved highly eloquent areas. Functional imaging such as ictal SPECT, interictal fluorodeoxyglucose PET, and magnetoencephalography was performed when clinically indicated. The type and extent of the resection were decided based on the presumed epileptogenic zone. Complete resection was defined if the region of the structural abnormality on MRI or the epileptogenic zone presumed from intracranial EEG was entirely removed.

Seizure recurrence was ascertained in a personal interview with each patient. Acute postoperative seizures within the first 2 weeks after surgery were not considered as part of the recurrence. When patients were seizure-free for at least 6 months after surgery, we discussed with them or their caregivers about the benefits of AED withdrawal and the likelihood of seizure recurrence. The decision to discontinue AEDs was always only made after discussion, and only with consent from the patients or their caregivers. The timing of AED withdrawal and AED reduction rates were decided on an individual medical basis. The dose was reduced in a stepwise manner every 2 to 3 months. Postoperative EEGs were obtained on individualized schedules. We selected data from a single EEG recording session that was performed closest to 3 months postoperatively.

Descriptive statistics were used for demographic data. Patients with and without seizure recurrence on AED tapering were compared using the Fisher's exact test and Mann-Whitney U test. The time to an event after surgery was plotted as a Kaplan-Meier survival curve to estimate the probability of seizure freedom after surgery. Also, logistic regression analysis with the forward stepwise (likelihood ratio) method was used to evaluate risk factors for seizure recurrence after a planned AED withdrawal. Odds ratio and 95% CIs were also calculated, with p<0.05 considered statistically significant. All analyses were performed using SPSS (version 22.0, IBM Corp., Armonk, NY, USA).

Seventy patients (37 males and 33 females) were eligible for the present analysis. The clinical characteristics and preoperative and operative variables for the entire cohort are summarized in Table 1. The age at seizure onset was 4.91±3.66 years (mean±SD), the duration of epilepsy was 5.27±3.82 years, and the follow-up duration after surgery was 5.45±2.77 years. The patients were taking a median of 2.5 AEDs. Of the 70 patients, 58 patients (82.9%) exhibited focal lesions including hippocampal sclerosis on MRI, and 45 patients (64.3%) received intracranial EEG monitoring. All except 6 patients underwent resection confined to a single lobe: temporal lobes in 36, frontal lobes in 19, parietal lobes in 5, and occipital lobes in 4. Forty-five patients (64.3%) underwent complete resection.

The longitudinal seizure and AED therapy outcomes in the overall cohort are illustrated in Fig. 1. AED withdrawal was attempted in 40 patients; the remaining 30 continued to receive medication throughout the follow-up period. One of these 30 patients was seizure-free for 4 years after surgery, but opted to remain on AED due to a fear of relapse. Over the follow-up period of 4.54±2.20 years (range, 2–12 years), 26 patients (37.1% of the entire cohort) achieved a seizure-free status without AEDs, and 8 patients (11.4% of the entire cohort) were seizure-free with AEDs. Twenty-six patients achieved a seizure-free and AED-free status at a mean follow-up period of 4.9 years after surgery, which was 4.1 years after starting AED withdrawal. One of the 26 patients experienced rare seizures after surgery and became seizure-free as a result of the runningdown phenomenon, and was able to discontinue AEDs.

Seizure recurred in 14 (35%) of the 40 patients who started AED withdrawal. The median time of starting AED tapering after surgery was 10.8 months (range, 6 months to 4.4 years). The clinical characteristics of patients who experienced seizure recurrence on AED withdrawal (n=14) were compared to those without recurrence (n=26) (Table 2). The rates of incomplete resection (p=0.001) and postoperative epileptic discharges (p=0.018) were significantly higher in patients who experienced seizure recurrence, while the timing of starting the AED taper did not differ between patients who did and did not experience recurrence (p=0.251). The timing of seizure recurrence in relation to AED withdrawal is depicted in Fig. 2. Seizures recurred while reducing the AED dose in 8 patients and after discontinuation in 6 patients. Seizures recurred at a mean of 9.6 months after AED withdrawal (range, 20 days to 2.3 years) in patients who recurred while the AED dose was being reduced, and at a mean of 4.2 years after the start of AED withdrawal (range, 1.2–8.5 years) in those who experienced relapse after AED discontinuation.

Half of the 14 patients who experienced postwithdrawal seizure recurrence regained seizure freedom after AED reintroduction. They achieved seizure freedom for a mean duration of 2 years (range, 3.6 months to 6.2 years) (Supplementary Table 1 in the online-only Data Supplement). Three of the 8 patients who experienced recurrence while reducing the AED dose became seizure-free after AED reintroduction. In addition, 4 of the 6 patients who experienced relapse after AED discontinuation were seizure-free after AED reintroduction. Six of the 14 patients received monotherapy and 8 patients received polytherapy. The AED dose or number was reduced in 8 patients (57.1%) and remained unchanged in two (14.3%) (Supplementary Table 1 in the online-only Data Supplement).

A comparison of possible predictors between patients with and without seizure recurrence on AED withdrawal, based on a logistic regression analysis, is presented in Table 3. Univariate and multivariate analyses found that incomplete resection (p=0.004) and epileptic discharges on postoperative EEG (p=0.025) were significantly associated with an increased risk of seizure recurrence following attempted AED withdrawal. Older age at surgery, longer duration of epilepsy, presence of a lesion on MRI, and intracranial electrode implantation were not significantly associated with seizure recurrence after AED withdrawal. In addition, the time after surgery to AED reduction was not associated with seizure recurrence.