Seizure outcome after temporal lobectomy for temporal lobe epilepsy

Methods.

Results.

A total of 57% of patients were men. Left temporal resections were performed in 57% of patients. The mean age (±SD) at the time of surgery was 23.9 ± 9 years. The mean duration of epilepsy was 12.9 ± 8.5 years. The average monthly frequency of CPS was 12.4 (range, 1 to 60 months), and was 10 or less CPSs in 53% of patients, 11 to 20 CPSs in 22% of patients, and more than 20 CPSs in 25% of patients. Thirty-eight patients (48%) were taking AEDs at the time of the last follow-up and 28 patients (35%) were not. Information on drug therapy was not available for the remaining patients.

Four patients died during the follow-up period. One patient who had been SF for 29.5 years developed breast carcinoma. Another patient died of a self-inflicted gunshot wound to the head 20 years postoperatively. This patient had experienced a marked improvement in seizure frequency. Another two patients, who experienced no change in seizure frequency, died of causes related to status epilepticus 4 and 12 years postoperatively.

The mean follow-up was 14.0 years (range, 2.1 to 33.6 years). A total of 75% of patients had a minimum follow-up duration of 8.5 years. Ten patients had less than 5 years of follow-up. At the time of last follow-up, seizure outcome using Engel’s classification was class I, 51 (65%); class II, 12 (15%), class III, 9 (11%); and class IV, 7 (9%). Twenty-eight patients (35%) were entirely SF and 8 (10%) had auras only. Forty-three additional patients (55%) experienced at least one recurrent seizure, and 30 of them (38%) experienced multiple seizures. Seizures recurred within 1 month in 19% of patients (8 of 43), by 6 months in 56% of patients (24 of 43), by 12 months in 67% of patients (29 of 43), and by 24 months in 86% of patients (37 of 43). The median time to first seizure was 5 months (mean, 24 months). Six patients experienced a recurrence after 24 months. The latest recurrence took place 300 months postoperatively after AED withdrawal. In two of these six patients, no additional seizures occurred. Another two patients had multiple recurrent seizures but achieved 2- and 5-year remissions, respectively, by the time of last follow-up. Yearly seizures occurred in the last two patients—one who relapsed after a closed head injury and another after a family death.

Kaplan-Meier survival analyses of time to first postoperative seizure were performed for the group overall and for early landmarks (figure 1). SF survival at 5, 7, and 10 years beyond the 12- and 24-month postoperative landmarks stratified by SF status at the landmark is shown in table 1. As an example, at 10 years past the landmark, an estimated 84% of subjects who were SF at 24 months remained so, versus 71% for subjects SF at the 12-month landmark. The likelihood of remaining SF 5 to 10 years beyond a given early landmark increased with each 6-month increment of seizure freedom from 6 to 24 months postoperatively (not shown).

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Figure 1. Kaplan-Meier estimates of postoperative seizure-free (SF) survival by early landmark. The median (50%) SF survival time was 8 years. The percentage of patients still SF at 5 and 10 years after surgery was 52% and 45%, respectively.

Kaplan-Meier survival estimates for time to first year with less than 75% improvement in seizures are summarized in table 2. By 10 years after surgery, 85% of patients had not experienced such a year. Only 12 patients experienced a year with less than 75% improvement during follow-up. In 10 of these patients, the first year with less than 75% improvement occurred within 4 years of surgery.

Age at surgery, duration of seizure disorder, gender, side of resection, recorded seizures during routine or prolonged EEG, and monthly CPS frequency were analyzed as predictors of seizure outcome. As shown in figure 2, preoperative monthly CPS frequency of less than 20 was associated with a higher likelihood of seizure freedom (p = 0.009, logrank test). SF estimates of 72%, 67%, 56%, and 50% at 6 months and 1, 5, and 10 years were observed in subjects with less than 20 seizures per month compared with 50%, 44%, 28%, and 17% for patients with more than 20 seizures per month. The other baseline variables were not predictive of time to relapse or time to a year with less than 75% improvement. Specifically, patients with recorded seizures during routine or prolonged EEG (n = 37) had similar seizure outcome to those who did not (n = 42, p = 0.73).

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Figure 2. Kaplan-Meier analysis of preoperative seizure frequency in quartiles of data. Seizure frequency was divided in 1 to 5, 6 to 10, 11 to 20, and more than 20 seizures per month. Patients with more than 20 seizures per month were significantly less likely to be seizure free (SF) than the rest of patients (p = 0.009).

Discussion.

This series demonstrates the sustained, long-term benefit of TL for the treatment of medically refractory TLE. Mean follow-up after TL is 14 years—to our knowledge the longest reported in the literature. An improvement in seizures of 75% or more was obtained in 91% of patients. At least one seizure recurred in 55% of patients. These data are comparable with a more recent series in which 55% of patients were SF or had only experienced auras after TL, 20% had rare seizures or more than an 80% seizure reduction, and 45% experienced at least one recurrent seizure during a 5-year follow-up period.3 An SF state was achieved in 80% of patients after TL for epilepsy due to temporal lobe tumors and vascular lesions with a median follow-up of 6 years.4 Similar to prior reports, we found that the percentage of patients SF at any given year remained relatively stable.3,5 In our series, patients with more than 20 seizures per month were significantly less likely to become SF than those with less frequent seizures. This finding has not been reported previously.

In an attempt to study outcome in patients with the longest possible follow-up, we chose to include patients who had surgery at least 10 years before data collection (1984), realizing that duration of follow-up would be shorter in some patients. During 1984, there was a change of staff in the epilepsy center that included the surgeon who performed the majority of procedures. Subsequently, fewer patients had long-term follow-up documented adequately. Also, at this time, the size of the TL evolved to a more limited lateral resection (3 cm) and a more aggressive resection of the hippocampus independent of electrocorticographic findings. For these reasons, we excluded patients operated after 1984. The decision to include patients with a minimum of 2 years follow-up was based on previous literature in which seizure outcome 2 years after surgery was found to be predictive of long-term outcome. Follow-up of less than 5 years was present in only 10 patients in the current series. We chose not to exclude these patients because the Kaplan–Meier analysis takes into account the variability in follow-up times. This method uses all available follow-up information for each patient and is geared particularly toward studies with differing lengths of follow-up.

Our data support the use of the 2-year landmark as the best predictor of subsequent seizure outcome after TL. Patients who were SF at 2 years had a 94% chance of still being SF at 5 years, 87% at 7 years, and 84% at 10 years. Others have also found the 2-year landmark to be a better predictor of outcome than 6 months or 1 year.3,6,7 Elwes et al.6 found that remission 1 year after TL was associated with a 90% chance of subsequent seizure freedom, a figure that rose to 94% after two consecutive SF years.6 In the same series, no patients who were SF after 2 years had a poor outcome at the time of last follow-up (median, 5 years). Sperling et al.3 reported the time to recurrence after TL in patients with a minimum follow-up of 5 years. In that series,3 seizures recurred within 6 months of surgery in 55% of patients, 1 year in 70% of patients, and 2 years in 93% of patients. By the fifth postoperative year, recurrent seizures were observed in 18% of patients who were SF during the first postoperative year and in only 6% of those who were SF for the first 2 years.

In the current series, the majority of recurrences (86%) took place within 2 years of surgery. Recurrences after 2 years occurred in six patients, only two of whom failed to achieve a 2-year remission subsequently during follow-up. Relapse rates within 10 years of TL were found to be higher for patients with developmental lesions and mesial temporal sclerosis (MTS; 25% and 14% respectively), compared with tumors and normal tissue (1%) and vascular lesions (10%).8 In another series, patients with MTS appeared to be at a slightly increased risk of recurrent seizures compared with those with foreign tissue lesions and normal pathology.9 In that series,9 all recurrences in patients with MTS occurred after 30 months. Explanations for these findings include the presence of dual pathology, bilateral TLE, and incomplete resection of the epileptogenic zone, which was the case in 10 of 11 patients who had recurrent seizures 10 years after TL.10 In a series of temporal and extratemporal resections,11 seizures recurred in the first postoperative year in 86% of patients. Multiple recurrences were observed in 80% of patients, and 40% became medically intractable.11 The interval to first recurrence was not predictive of subsequent course; however, no patients recurring more than 1 year from surgery became intractable. Our data support a previous finding that seizures recurring beyond the first few years after surgery tend to be controlled readily with medical therapy.10 The small number of late recurrences in our study precludes a comparison of outcome by etiology.

Our study has two major limitations. Before the mid 1980s at our institution, the mesial temporal structures were resected in a piecemeal fashion. This often rendered the pathologic specimen unsuitable for analysis. The absence of pathologic diagnoses in many of our patients precludes a direct comparison with contemporary series of patients with MTS—the most common pathologic substrate of patients with medically refractory TLE.12 Nevertheless, we suspect that majority of our patients had mesial temporal lobe epilepsy (MTLE) due to MTS based on the high incidence of febrile seizures, the types of auras and seizure symptomatology, and the distribution of interictal abnormalities.13

The other major limitation of this study is the lack of video-EEG monitoring, structural and functional neuroimaging, and neuropsychological assessments in all patients. Although all of our subjects had interictal EEG recordings, less than one-half had seizures recorded, and few had neuropsychological evaluations or intracarotid Amytal tests. The addition of MRI, PET, SPECT, and MRS to the presurgical evaluation came long after most of our patients were considered for surgery. It is now known that the likelihood of a favorable seizure outcome is increased in the presence of a lesion or unilateral hippocampal atrophy on MRI, concordance of EEG and MRI abnormalities, completeness of resection of the epileptogenic zone, and unilateral hypometabolism on [¹⁸F]fluorodeoxyglucose (FDG) PET.9,14-16 For these reasons, our data cannot be compared directly with contemporary series of patients with MTLE. Nevertheless, we believe this series is a valuable one, demonstrating the long-term benefit of TL in patients with refractory seizures arising from the temporal lobe.