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Purpose: Up to one-half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy.
Methods: Analyzing 915 epilepsy surgery patients operated on between 1990 and 2007, we studied 276 who had ≥1 seizure beyond the immediate postoperative period. The probability of subsequent seizures was calculated using survival analysis. Patients were divided into seizure-free (no seizures for ≥1 year) and refractory (persistent seizures) and analyzed using multivariate regression analysis.
Results: After a first seizure, 50% had a recurrence within 1 month and 77% within a year before the risk slowed down to additional 2–3% increments every two subsequent years. After a second seizure, 50% had a recurrence within 2 weeks, 78% within 2 months, and 83% within 6 months. Having both the first and second seizures within six postoperative months [odds ratio (OR) 4.04; 95% confidence interval (CI) 2.05–8.40; p = 0.0001], an unprovoked initial recurrence (OR 3.92; 95% CI 2.13–7.30; p < 0.0001), and ipsilateral spikes on a 6-months postoperative electroencephalography (EEG) (OR 2.05; 95% CI 1.10–3.88; p = 0.025) predicted a poorer outcome, with 95% of patients who had all three risk factors becoming refractory. All patients with cryptogenic epilepsy and recurrent seizures developed refractoriness.
Discussion: Seizures will recur in most patients who present with their first postoperative event, with one-third eventually regaining seizure-freedom. Etiology and early and unprovoked postoperative seizures with epileptiform activity on EEG at six postoperative months may predict recurrent medical refractoriness.
Patients who undergo brain surgery for the treatment of medically intractable epilepsy anticipate a “cure.” However, up to one-half will have at least one seizure after surgery (McIntosh et al., 2004; Spencer et al., 2005; Jeha et al., 2006). Some undergo expensive reevaluations only to regain seizure-freedom without the need for further intervention(s), whereas others have recurrent seizures for years before the possibility of a reoperation is explored. No evidence-based guidelines exist for managing these patients.
Multiple factors may contribute to this uncertainty: first, the transition from recurrent but rather isolated breakthrough seizures to persistent intractable epilepsy after surgery is poorly defined. Several studies suggest that up to 30% of patients having seizures within the first 6–12 postoperative months eventually become seizure-free (Salanova et al., 1996; Ficker et al., 1999; Hennessy et al., 2000), but definite criteria allowing timely identification of the remaining 70% who will continue with persistent seizures remain elusive. Second, although multiple studies evaluated acute postoperative seizures occurring within 7–28 days of surgery (Garcia et al., 1991; Malla et al., 1998; Tigaran et al., 2003; Abou-Khalil, 2004; McIntosh et al., 2005), only few investigated later seizures (Ficker et al., 1999; Hennessy et al., 2000; Radhakrishnan et al., 2003). This resulted in the availability of rather limited information regarding patients who present with their first seizure beyond the immediate postoperative period. Third, surgical outcome series traditionally used either Engel class I (McIntosh et al., 2004; Sindou et al., 2006; Elsharkawy et al., 2008; Jehi et al., 2009), or seizure-freedom for 12–24 months (Hennessy et al., 2001; Janszky et al., 2003; Kelley & Theodore, 2005; Spencer et al., 2005) in the process of defining “seizure-freedom,” including patients who may have had “some disabling seizures after surgery, but [were] free of disabling seizures for at least 2 years” (Engel IC) or who had “convulsions with antiepileptic drug (AED) discontinuation” (Engel ID) in the same outcome group as patients who never had a seizure, on or off AEDs, after surgery. Conversely, series using the strict criterion of “complete seizure-freedom” since surgery (Yoon et al., 2003; Paglioli et al., 2004; Jeha et al., 2006) equate patients with a single postoperative seizure to those with long-term persistent epilepsy after surgery. This discrepancy in the definition of seizure-freedom or seizure recurrence resulted in the rather inadequate characterization of outcome in some patients after surgical resection, as the same group of patients achieving seizure-freedom after some postoperative seizures was either considered “seizure-free” or a “surgical failure” in various studies. Fourth, prior evaluations of this “running-down” phenomenon focused mainly on temporal lobe surgery (Bladin, 1987; Salanova et al., 1996, 1999b; Hennessy et al., 2000), therefore, limiting their applicability to an increasing number of extratemporal surgical resections.
This article aims to characterize the prognosis of patients presenting with their first seizure following epilepsy surgery, and provide some practical criteria allowing early identification of recurrent refractory epilepsy after surgery in a large cohort of patients operated on at a single comprehensive epilepsy surgery program. This may assist in avoiding unnecessary repeat presurgical evaluations, as well as in the timely performance of such evaluations in patients who truly need them.