BALTIMORE – Not all seizure recurrences following epilepsy surgery should be treated in the same way.

Rather, early seizure recurrences may indicate an incomplete resection or inaccurate localization of the epileptic focus, whereas late seizure recurrences are likely due to de novo epileptogenesis. Clinically, this suggests that "patients with early seizure recurrence should be monitored and evaluated for possible reoperation sooner rather than later, while more aggressive medical management may be enough to control seizures in those with late recurrences," Dr. Lara Jehi said at the annual meeting of the American Epilepsy Society.

At 12 years following resective epilepsy surgery of all types, just 45% of patients remain seizure free. For frontal lobectomy in particular, that rate is just 30% (Brain 2007;130:574-84), and for temporal lobectomy the outcome is a little better at 55% (Neurology 2006;66:1938-40). What’s more, that 55% rate has not changed in the past 60 years. "Whether we like it or not, epilepsy surgery is not a magic bullet. ... It doesn’t always work," said Dr. Jehi, a neurologist at the Cleveland Clinic Epilepsy Center, and the head of the Outcomes Research Group there.

But hidden within those statistics is a less-appreciated dichotomy: In the studies just mentioned, the median time of recurrence for all epilepsy surgeries was 4 months. For frontal lobectomy, it was 2 months, and for temporal lobectomy, it was 6.6 months. In all, about half of all failures occurred in the short term, and the rest were spread out over a decade or more, regardless of surgery type. "It’s a common, solid, reproducible observation that reflects two different mechanisms," said Dr. Jehi, who cited an as-yet unpublished study of 1,418 patients that she and her colleagues presented last year at the annual meeting of the American Academy of Neurology.

She noted that a range of factors have been associated with early recurrence in studies of the outcomes of epilepsy surgery. Among 371 patients who underwent anterior temporal lobectomy to treat pharmacoresistant epilepsy, predictors of early recurrence included preoperative seizure frequency, history of generalized tonic-clonic (GTC) seizures, bilateral abnormalities on MRI, use of subdural electrodes, and an epileptiform electroencephalogram at 6 months postoperatively. On the other hand, the only predictor of late recurrence was nonspecific pathology (Neurology 2006;66:1938-40).

In a study of outcomes following failed temporal lobectomy in 68 adult patients, Dr. Jehi and her associates found that there were no early seizure recurrences from foci that were contiguous to the area that had been initially resected, suggesting that early recurrences are likely the result of having "missed the spot," she said (J. Neurosurg. 2010;113:1186-94).

Two other studies by her group also documented a higher rate of early recurrences in "difficult to localize" epilepsies. One examined surgical outcome and prognostic factors of frontal lobe epilepsy surgery in 70 patients (Brain 2007;130:574-84), and the other is a longitudinal study of surgical outcome and its determinants following posterior cortex epilepsy surgery in 57 patients (Epilepsia 2009;50:2040-52).

But in a separate study of 285 patients who were initially seizure free following epilepsy surgery, the presence of preoperative GTC seizures predicted late seizure recurrence among 31 patients with neocortical epilepsy, whereas late age at surgery predicted late recurrence among the remaining 254 with medial temporal lobe epilepsy. Results of MRI and location of surgery were not predictive (Epilepsia 2006;47:567-73).

Dr. Jehi and her group found that there was less risk of intractability with breakthrough seizures that occurred beyond 6 months after temporal lobectomy surgery among 276 patients who had one or more seizures after the immediate postoperative period (Epilepsia 2010;51:994-1003). Her team also determined that late seizure recurrences after frontal lobectomy surgery tended to be milder and less frequent (Brain 2007;130:574-84). These findings suggest a pattern similar to new-onset epilepsy, or "epileptogenesis," she said.

In all, the data suggest that patients with early seizure recurrences need to be investigated as soon as possible for a reoperation via modalities such as video-EEG and repeat brain imaging, and require intense follow-up and management. "In other words, don’t waste much time on switching antiepileptic medications around," Dr. Jehi said in an interview.

On the other hand, patients with late recurrences need more aggressive antiepileptic medication management before another brain surgery is considered. If their seizures subsequently prove to be refractory, brain regions other than the focus of initial resection need to enter into the equation of possible areas in the brain that may be causing seizures, she said.

And, she added, this dichotomy hypothesis "opens the door to investigate antiepileptogenic measures as a tool to improve long-term seizure outcomes after surgery."

Dr. Jehi said that she had no relevant disclosures.

Different Mechanisms May Operate in Postoperative Seizure Recurrence