Almost half the patients who undergo surgery for epilepsy remain seizure free 10 years postop, but further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy are needed to improve success rates, according to findings from a prospective study.

Surgical treatment is increasingly used to treat focal epilepsy, most often if drugs have not been effective for controlling seizures for more than 2-3 years, yet few reports of long-term data exist.

Lead authors Jane de Tisi and Dr. Gail S. Bel of the National Hospital for Neurology and Neurosurgery, London, and their colleagues followed 649 consecutive patients who underwent epilepsy surgery between 1990 and 2008 and identified patterns of seizure remission and relapse up to Nov. 2009 (Lancet 2011;378:1388-95).

After eliminating 34 patients who died, were lost to follow-up, or underwent subsequent surgery within the same year, the researchers analyzed data on 615 patients (287 men and 328 women) aged 16-63 years. They had a median duration of epilepsy of 20.7 years prior to surgery. There were 497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and 7 palliative procedures (corpuscallosotomy or subpial transection).

The researchers obtained information annually from hospital notes, direct inquiry of individuals (who kept prospective seizure diaries) and their general practitioners, and, in some cases, the patient's next of kin. They asked about the occurrence of simple partial seizures (SPS), seizures with loss of awareness, and antiepileptic drugs taken. Median annual follow-up was 8 years. The researchers defined recurrence of seizures as outcome classification 3 on the outcome scale established by the International League Against Epilepsy.

Complete freedom from seizures or having only SPS was attained by an estimated 82% of patients at 1 year postop, 63% at 2 years, 52% at 5 years, and 47% at 10 years. Forty percent of patients had long-term complete seizure freedom after epilepsy surgery, and 11% had only SPS. No patient had substantial worsening of epilepsy.

Those who experienced SPS in the first 2 years after anterior temporal lobe surgery were 2.4 times more likely to experience subsequent seizures with impaired awareness than were those who experienced no SPS – a finding that has not been previously reported, the investigators said. This information “might affect the decision to taper or continue antiepileptic drugs,” the researchers wrote.

But overall, individuals who underwent anterior temporal resection were more likely to be seizure free than were those who underwent resections in other parts of the brain.

Relapse was less likely the longer a person was seizure free. Conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. Antiepileptic drugs were discontinued at the latest follow-up visit in 104 (28%) of 365 seizure-free individuals.

The researchers called for clinicians to refer appropriate patients sooner for possible surgery. But they also argued that the selection process and surgical methods need to improve because of “over-optimistic expectations” implied in some studies.

The study had several limitations to the assessment of outcomes in people with temporal lobe surgery, including “the small numbers [of patients], that the decision was not randomly assigned, and that patients with extensive disease and lesions close to the hippocampus were more likely to have anterior temporal resection than were other patients.”

All but three of the authors disclosed relevant financial conflicts of interest with manufacturers of antiepileptic drugs or devices.

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Epilepsy Surgery Validated, but New Questions Raised

This study looks at surgical outcome for 19 years postop, making it the largest and longest prospective study of surgical outcomes for epilepsy. It also is unlike other epilepsy surgery studies in that it prospectively analyzed seizure freedom at successive annual visits in individual patients instead of only at the last follow-up visit.

The investigators found that 70% of patients were seizure free for the last year at any time, but only 51% were completely seizure free throughout the follow-up because each year there was a 3%-15% change within the different groups of patients.

Also, simple partial seizures that occurred within 2 years of surgery were a significant risk factor for the long-term recurrence of seizures. This finding has implications for the decision to discontinue antiepileptic drugs in patients with only simple partial seizures.

This study validates the long-term effectiveness of epilepsy surgery, but it raises important questions and challenges. It makes us wonder if there are equal benefits of being seizure free among patients who have had continuous remission and those who had later remission, as well as if we can improve selection and resection strategies to optimize long-term seizure control.

Dr. Ahmed-Ramadan Sadek of Southampton (United Kingdom) University Hospitals NHS Trust and Professor William Peter Gray of University of Southampton wrote their comments in an editorial accompanying the epilepsy surgery study (Lancet 2011;378:1360-2). They reported having no conflicts of interest.

Nearly Half Have No Seizures at 10 Years Postop