Antiepileptic drug withdrawal after successful surgery for intractable temporal lobe epilepsy
Kim YD, Heo K, Park SC, Huh K, Chang JW, Choi JU, Chung SS, et al.;
Commented by , 22 Mar 2005
There is limited data on outcome after antiepileptic drug (AED) discontinuation following successful epilepsy surgery.
To assess prognosis associated with AED taper/discontinuation in patients achieving > 1 year seizure freedom after temporal lobe epilepsy (TLE) surgery.
Retrospective analysis of patients who had a follow-up of at least 3 years after TLE surgery. No fixed protocols were used for AED taper.
Of 88 eligible patients (age 11-41 years, mean follow-up 77 months), 66 became seizure-free for > 1 year. Of the latter, 60 attempted AED discontinuation.
One of 6 patients who did not taper AEDs had recurrence of auras.
Of 60 patients who underwent tapering, 20 relapsed (13 during tapering, 7 after discontinuation). Nine patients who remained seizure-free had their AEDs reduced but not discontinued. Of the 20 patients who relapsed and re-started AEDs, 9 regained full control and 5 more had only auras.
Seizures that recurred after complete AED taper had better prognosis than those that occurred while tapering AEDs (subsequent seizure freedom 86% vs. 23 % respectively).
Younger age and shorter disease duration at time of surgery were associated with a better outcome after AED discontinuation.
Professor Perucca's comments
The value of epilepsy surgery in treating refractory TLE is unquestionable, and supported by randomized clinical trial (RCT) evidence (ref. 1).
Seizure freedom rates after TLE surgery are reportedly in the range of 70 to 90%, (ref. 7), but these percentages are probably overestimates because relapses can occur late during follow-up (ref. 3). In a recent study, 44% of patients seizure-free at one year post-surgery relapsed during the next 10 years (ref. 4 ).
In some cases, relapse appears to be related to discontinuation of AEDs (ref. 5), but seizure recurrences can occur even when AEDs are continued (ref. 4; ref. 6; ref. 7; ref. 8).
There is hot debate on whether surgery is really curative, or whether in a sizeable group its value is limited to transforming epilepsy from drug refractory to drug responsive (ref. 7; ref. 2). The issue has major implications for long-term practical management.
One interesting aspect of Kim's study is the high percentage (91%) of seizure-free patients who attempted AED discontinuation. This is at variance with other studies (ref. 8; ref. 9) and may be explained by local factors, such as patients' desire to remove the stigma associated with AED therapy and lesser dependence of Korean lifestyles from holding a driving license.
About one third of seizure-free patients relapsed during/after AED discontinuation. This is in line with the results of a pooled analysis of previous studies in adults (ref. 2), whereas relapses may be fewer in children (ref. 2).
The fact that seizure relapses were less common in patients with a shorter duration of epilepsy at time of surgery is consistent with recent evidence suggesting that, even in patients continuing AEDs, long-term prognosis is better when hippocampal sclerosis patients are operated early (ref. 8).
A major interpretation difficulty with AED discontinuation studies to date is that they all used a retrospective design and none included adequate controls. Most notably, it is unclear how many comparable patients in each study would have relapsed without AED discontinuation.
A protective effect of AEDs is suggested by the consistent observation that reinstitution of AEDs results in regained seizure control in the vast majority of cases (in Kim's study, however, full control was regained in 45%).
A RCT is sorely needed to determine outcome after AED discontinuation compared with continuation of therapy. Until this information becomes available, there is suboptimal evidence to guide medical management after TLE surgery. The usually good prognosis after AED re-institution in relapsing patients, however, is relatively reassuring.
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