LOS ANGELES—Surgical intervention for epilepsy is often seen as a last resort, even among patients with drug-resistant focal epilepsies, said Gregory D. Cascino, MD, a neurologist at Mayo Clinic in Rochester, Minnesota. One reason for this phenomenon may be concern about potential adverse effects. Research indicates, however, that clinical and functional outcomes of surgery significantly surpass those of treatment with antiepileptic drugs (AEDs) in selected patients with drug-resistant focal epilepsy.
Gregory D. Cascino, MD
“The three important goals of epilepsy treatment are no seizures, no adverse effects, and no lifestyle limitations. This is what patients want when they seek neurologic care,” said Dr. Cascino at the 70th Annual Meeting of the American Academy of Neurology. “Seizure freedom is important because of its beneficial effects on quality of life, which include the ability to drive, pursue an education, have a career, and live independently with no need for a caregiver. We need to consider the risk of any intervention, whether it is medical or surgical, against the natural history of the disease.” All patients with epilepsy, not just those with drug-resistant focal epilepsy, are at significant risk of mortality due to seizure complications, progressive cognitive disorder, mood disorders, and even sudden unexpected death in epilepsy, he noted.
Identifying Surgical Candidates
“As soon as a patient is diagnosed with drug-resistant focal epilepsy, the neurologist probably should begin to triage for alternative forms of treatment,” Dr. Cascino said. “That doesn’t mean that patients need surgery on the first visit. But perhaps physicians should consider them for inpatient epilepsy monitoring and carefully review a high-resolution MRI head seizure protocol.”
Research suggests that patients who tend to have the best outcomes are those who have neuroimaging abnormalities resulting from substrate-directed pathology (eg, tumor, vascular anomaly, malformation of cortical development, or mesial temporal sclerosis) and undergo a complete resection of the epileptogenic lesion and the site of seizure onset. “These patients have the highest likelihood of being seizure-free after surgery, although some will have to continue taking AEDs to remain seizure-free,” Dr. Cascino said. Approximately 75% of patients with a surgically remediable epileptic syndrome who undergo epilepsy surgery become seizure-free.Conversely, research also shows that patients with normal MRI studies, multifocal seizures, or incomplete resection of the region of seizure onset have a less favorable operative outcome. Age at time of surgery appears to be unrelated to seizure outcome. Thus, older people may be good surgical candidates, he added. But few data about cognitive, psychiatric, and psychosocial issues after surgery are available.
In one study from the University College London, 52% and 47% of 615 patients who underwent surgery for refractory focal epilepsy were seizure free at five and 10 years’ follow-up, respectively. Those with extratemporal resections were twice as likely to have seizure recurrence as those who had anterior temporal lobe resections.
Surgery Versus Medication
“When you compare best pharmaceutical treatment with best surgical practice, the numbers are strongly in favor of surgery, both in terms of efficacy and quality of life, for selected patients,” Dr. Cascino said. In one randomized controlled trial, 80 patients with temporal lobe epilepsy were randomly assigned 1:1 to surgery or optimal medical therapy with AEDs for one year. At one year, 58% of surgical patients were seizure-free versus 8% of the AED group. Quality of life was significantly higher among surgical patients. Four patients had adverse effects of surgery, and one patient in the AED group died.
Another randomized trial compared early referral to surgery of patients with drug-resistant mesial temporal lobe epilepsy with continued AED treatment for controlling seizures and improving quality of life. Although the study was halted prematurely due to slow accrual, none of the 23 patients in the AED group were seizure-free during year two of follow-up versus 11 of 15 surgery patients. Surgery had a significantly favorable treatment effect on quality of life. One person in the surgery group had a transient neurologic deficit attributed to postoperative stroke, and three participants in the medication group had status epilepticus.
Surgery in Patients With Normal MRI
One study followed 87 consecutive patients with normal MRI for one year after epilepsy surgery. “They all had temporal lobe epilepsy. Most of them had nonspecific gliosis, a few met the criteria for mesial temporal sclerosis, and none of them had tumors or lesions,” Dr. Cascino said. “About 55% were seizure-free, which compares quite favorably with neuromodulation and other treatments.” The best predictor of seizure freedom was unilateral interictal epileptiform discharge (IED) on scalp EEG and complete resection of brain regions generating IEDs on baseline intraoperative electrocorticography.
Another study demonstrated that the addition of PET to the diagnostic workup may improve outcomes. Among adults with PET-positive and MRI-negative temporal lobe epilepsy, three out of four were seizure-free postoperatively.
Trends in the Rate of Surgery
“Although there are high-quality clinical trials and major epilepsy surgical centers throughout the United States, the number of operative procedures for drug-resistant focal epilepsy has remained stable over the past 20 years,” Dr. Cascino said. “The patient population and surgical techniques have changed. The number of anterior temporal lobectomies may be decreasing, but more patients are being considered for surgery with MRI-negative extratemporal seizures or multifocal seizures.”
In one study, researchers examined epilepsy surgeries performed between 1991 and 2011 on 1,346 patients in nine major surgery centers in the US, Germany, and Australia. In eight centers, the highest number of surgeries for mesial temporal sclerosis occurred in 1991 or 2001, the researchers found. In 2011, the nine centers performed 48% fewer such surgeries, compared with 1991 or 2001, with a parallel increase in the performance of surgery for nonlesional epilepsy. In addition, the number of intracranial EEG implantations that did not lead to subsequent brain resections rose by 0.6% per year.
The study authors called for future research to improve the use of epilepsy surgery, to assess the effectiveness of various surgical procedures and presurgical evaluation tools, and to study extratemporal epilepsy, given its growing contribution to the surgical epilepsy burden.
—Adriene Marshall
Suggested Reading
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de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.
Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307(9):922-930.
Jehi L, Friedman D, Carlson C, et al. The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. Epilepsia. 2015;56(10):1526-1533.
Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015;313(3):285-293.
LoPinto-Khoury C, Sperling MR, Skidmore C, et al. Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy. Epilepsia. 2012;53(2):342-348.
Mohammed HS, Kaufman CB, Limbrick DD, et al. Impact of epilepsy surgery on seizure control and quality of life: a 26-year follow-up study. Epilepsia. 2012;53(4):712-720.
Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311-318.
Zhang J, Liu W, Chen H, et al. Identification of common predictors of surgical outcomes for epilepsy surgery. Neuropsychiatr Dis Treat. 2013;9:1673-1682.