ANTIEPILEPTIC DRUG WITHDRAWAL AND LONG-TERM EPILEPSY RECURRENCE AFTER SURGERY.
Authors: R. YARDI, A. Irwin, D. Nair, A. Gupta, J. Gonzalez-Martinez, W. Bingaman, I. Najm, L. Jehi
Resective surgery in intractable temporal lobe epilepsy (TLE) is done with the dual aims of seizure-freedom and antiepileptic drug (AED) withdrawal. Most patients are rendered seizure-free with surgery, but there are no criteria for postoperative AED management,with limited prior retrospective series showing conflicting results. We investigate here the implications of AED withdrawal in a well-defined cohort that includes a “control group” where AEDs were unchanged.
We reviewed all patients with at least 6 months of postoperative follow-up who underwent temporal lobectomy for drug-resistant TLE from 1996-2011 in our center. The clinical, imaging, histopathological profiles, dates of initiation, reduction, and termination of AEDs were collected. Predictors of postoperative seizure outcome were defined using survival analyses and Cox-proportional hazard modeling and adjusted for while comparing longitudinal rates of seizure-freedom in patients for whom AEDs were unchanged after resection as opposed to reduced or stopped.
609 patients met study criteria and were analyzed. Most (86%) were adults. Follow up ranged from 0.5 to 16.7 postoperative years. Etiologically most common was mesial temporal sclerosis (389patients; 64%), followed by malformations of cortical development (17%); tumors (13%); vascular malformations (3%) and other pathologies (3%). The number of AEDs at the time of surgery ranged from 1 to 5; mean 1.95, median 2. The number of AEDs at last follow-up ranged from 0 to 5 (mean 1.42; median 1). By last follow-up, 229 patients (38%) had made no change in their baseline AEDs, while 380 patients (62%) had stopped (127; 21%) or reduced (253; 42%) their AEDs at some point. The AED management (continuing vs withdrawing AEDs) was independent of the side of resection, MRI findings, baseline seizure-frequency and presence or absence of convulsions. AEDs were more likely to be stopped in patients with tumors (p<0.0001). By the last follow-up, 338 (55%) patients had a seizure recurrence. Following multivariate modeling, only higher baseline seizure-frequency and history of generalization predicted seizure recurrence. In patients who did undergo AED withdrawal, the mean timing of earliest AED change was shorter in patients with recurrent seizures (1.04 yrs) compared to those who were seizure-free (1.44 yrs) (p=0.03) consistent prior literature suggesting higher rates of recurrence with earlier AED withdrawal. However, when analyzing patients who were seizure-free for at least 6 postoperative months, and comparing seizure outcomes in the group with AED withdrawal to the cohort where AEDs were unchanged, there was no difference in long-term rates of seizure-freedom, regardless of etiology (figure 1).
In patients who achieve a minimum of 6 months postoperative seizure-freedom, early AED withdrawal (reduction or discontinuation) correlates with earlier breakthrough seizures but may not necessarily alter long-term seizure outcomes. The results of this large retrospective controlled cohort study need to be further evaluated in a well-designed prospective randomized trial.
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