Radiosurgery for Mesial Temporal Lobe Epilepsy – A Possible Alternative to Temporal Lobectomy
Abstract & commentary:
By Padmaja Kandula, MD, Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Medical College of Cornell University. Dr. Kandula reports no financial relationships relevant to this field of study.
Synopsis: This pilot study reports on the long-term efficacy, safety, and adverse events of focused radiosurgery as an alternative to temporal lobectomy for mesial temporal lobe epilepsy.
Source: Barbaro NM, Quigg M, Broshek DK, et al. A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: Seizure response, adverse events, and verbal memory. Ann Neurol 2009;69:167-175
Mesial temporal lobe epilepsy with mesial temporal sclerosis is the most surgically remediable epilepsy syndrome, with reported success rates of nearly 70%.1 However, in recent years, novel approaches to reduce the invasivenessand perhaps the cognitive deficitsof open surgery have become increasingly important. One prior study of 20 patients who were treated with radiosurgery reported no significant declines in memory or IQ during a two-year follow up period.2 This study by Barbaro and colleagues presents the second paper regarding long-term data on cognitive outcome, paving the road to a potential phase 3 trial comparing temporal lobectomy to focused radiosurgery.
Patients were included in this prospective study if they met criteria for unilateral mesial temporal lobe epilepsy as defined by ictal video EEG criteria, magnetic resonance imaging (MRI) (unilateral asymmetric increased hippocampal T2 signal or hippocampal atrophy), neuropsychological evaluations, and intracarotid sodium amytal (WADA) tests. All patients had an average of at least three complex partial seizures per month over a three-month baseline period. All participants were then randomized to treatment with either 20 Gy (low dose) or 24 Gy (high dose) of radiosurgery (50% isodose volume from 5.5-7.5 mL) targeted at the amygdala, anterior 2 cm of hippocampus, and parahippocampal gyrus.
After treatment, patients were examined every three months for 36 months with quantification and review of seizures by way of patient-documented seizure diaries. Seizure freedom was defined as no complex partial seizures with or without auras between months 24 and 36. MRIs were performed at 12 and 24 months, or more frequently if clinically warranted, along with visual field examinations at baseline and at 24 months. Neuropsychological testing was also performed at baseline and at 12 and 24 months. Patients were categorized as significant improvement, no change, or significant impairment based on indices of the California Verbal Learning Test and Wechsler Memory Scale–Revised.
Thirty patients met final inclusion criteria and were randomized to either high-dose (13 patients) or low-dose (17 patients) radiosurgery. Both groups showed significant reduction in complex partial seizures from baseline at approximately one year after treatment. Between months 24 and 36, the average seizure remission rate was 67% for both groups. Ten out of 13 patients in the high-dose group (76.9%) and 10 out of 17 patients (58.8%) in the low-dose group were seizure-free. However, the difference in remission rate between treatment groups was not statistically significant due to the small numbers in each group. Sixty-one percent of the high-dose group and 53% of the low-dose group required transient use of steroids for brain edema. One patient in the high-dose group eventually required temporal lobectomy for refractory edema.
Twenty-six out of 30 patients completed assessments of verbal memory. Verbal memory impairment was seen in 25% of patients with dominant hemisphere treatment and 7% of patients with non-dominant treatment. Significant improvement in at least one test was seen in 16% of dominant-treated and 7% of non-dominant-treated radiosurgery patients.
Commentary
Although temporal lobectomy is considered the "gold standard" for refractory mesial temporal lobe epilepsy, there is still room for improvement. Approximately one-third of patients relapse after anterior temporal lobectomy, with at least a third of those due to reduction in anti-epileptic medication. In this study, the remission rate of 67% at the three-year mark is similar to traditional open surgery. Unlike epilepsy surgery, seizure reduction is not immediate, but peaks at the one-year mark. Thus, larger numbers with longer follow-up are needed to assess the durability of radiosurgery.
An interesting finding in this study is the correlation of imaging with seizure reduction. Patients with transient increased T2 signal and contrast enhancement showed the best seizure reduction response. However, a single patient in the high-dose treatment group required temporal lobectomy for progressive clinical and radiographic cerebral edema, raising the question, "How safe is high dose radiosurgery?" Again, this study was not adequately powered to answer whether differences in radiation dosage correlated with increased edema. The improvement in verbal memory of 11% (3/26) of patients is suggestive that focused radiosurgery may play a role in limiting memory impairment and warrants further investigation.
There currently is not enough evidence to recommend gamma knife radiosurgery as an alternative to traditional anterior temporal lobectomy for mesial temporal lobe epilepsy. This largely is due to a delayed treatment response, possibly increased mortality from cerebral edema, and lack of well-defined dosing and target volume. Radiosurgery also may have a future role in epilepsy syndromes that are not easily surgically resectable, or alternatively in epilepsy surgery failures. The jury is still out on radiosurgery and a prospective, randomized trial comparing the two procedures is warranted before gamma knife can be enthusiastically offered as an alternative to the current gold standard of surgical excision.
References
1. Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal lobe epilepsy. N Engl J Med 2001;345:311-318.
2. Régis J, Rey M, Bartolomei F, et al. Gamma knife surgery in mesial temporal lobe epilepsy: A prospective multicenter study. Epilepsia 2004;45:504-515.
This pilot study reports on the long-term efficacy, safety, and adverse events of focused radiosurgery as an alternative to temporal lobectomy for mesial temporal lobe epilepsy.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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