An Interview with Mark Quigg MD, MSc and Nicholas Barbaro, MD

With the advent of new technologies, traditional surgery is being replaced when possible with minimally invasive to non-invasive techniques. Gamma Knife Radiosurgery (GKS) for mesial temporal lobe epilepsy (MTLE) is one such alternative to open brain surgery. However, Mark Quigg, MD, from the Department of Neurology at the University of Virginia told epilepsy.com that there are many unanswered questions regarding the safety and efficacy of the procedure. In order to further study GKS and determine the prognostic significance of spikes on postoperative EEGs after GKS for MTLE, Dr. Quigg with Nicholas Barbaro, MD, Neurosurgery, University of California at San Francisco, the study's primary investigator, and colleagues conducted a multicenter, prospective pilot study. They reported their results at the recent annual meeting of the American Epilepsy Society.

While they appeared to be optimistic about the findings, Dr. Barbaro emphasized to us: “It is important to note that the main reason for the Pilot Clinical Trial was to gain some preliminary information on safety and efficacy in order to proceed with a larger, definitive trial. We cannot reach conclusions regarding either safety or efficacy based on a 30 patient trial. What the Pilot Trial accomplished was to give a preliminary indication that Gamma Knife Radiosurgery is potentially safe and efficacious and to define the efficacy range from which to design a definitive trial.”

Methods

Dr. Quigg said, “We recruited 30 subjects and what we did was randomize them into one of two treatment dose groups according to the intensity of the radiation. We had a high-dose group and a low-dose group. All patients received an approved treatment protocol regarding where to direct the radiation.”

Specifically the study abstract noted: “GKS, randomized to 20 Gy or 24 Gy comprising 5.0-7.5 mL at the 50% isodose volume, was performed on mesial structures of patients with unilateral MTLE. Routine scalp EEGs were performed at presurgical baseline and at 24 months postoperatively and scored for the presence of clinically-significant interictal epileptiform discharges (IEDs) or focal slowing (FS) ipsilateral to GKS.”

Dr. Quigg said that “Treatment plans were approved at a central site to insure uniformity of GKS-induced lesions. Patients and treating physicians were blinded to the dose. This randomized group was treated with a protocol that we followed. We followed them every three months for up to a year and a half, then at the two year mark and finally at the three year postoperative mark.”

Results

Dr. Quigg said that the results can be broken into three parts; preliminary efficacy and safety, neuropsychological outcome, and EEG findings. The primary efficacy was seizure remission. “Among all the patients, 67% had remission of seizures in two years. Of the two treatment arms, the high-dose group did better than the low-dose group -- 85% remission vs. 56%, respectively,” he said.

Dr. Quigg noted that the difference in seizure remission between treatment groups was “not statistically significant.” He added, “There is an exacerbation in auras in the first 6 to 9 months that remits with time. And we had one definite adverse event – the patient developed edema and visual field abnormalities that became steroid-dependent and withdrew from the study.”

Overall, the study gave a preliminary indication that GKS is potentially safe and efficacious and defined the efficacy range from which to design a definitive trial.

Conclusions

With respect to neuropsychological outcome, Dr. Quigg said, “Verbal memory is largely preserved following GKS of the dominant temporal lobe. In general it was surprising given what we know about outcomes following standard open surgery of the temporal lobe. We also found things that one would expect in terms of the quality-of-life indices. For example, quality-of-life measures improved in patients who achieved remission, and there was no overall change in the incidence of depression.”

Dr. Quigg pointed out that “In open surgery studies, investigators have looked at post-operative EEG as a way to predict a seizure. But the scalp EEG becomes distorted after surgery, so EEG may have limited value as a prognostic indicator for open surgery.”

However, he noted, “With GKS, there is no skull defect, and we found that GKS caused remission of EEG abnormalities in the majority of patients, but that remission of EEG abnormalities was not significantly associated with seizure remission. This lack of correlation further supports the concept that different mesial networks are responsible for the generation of inter-ictal discharges versus seizures.”

Dr. Quigg emphasized that, “As a neurologist, I believe that epilepsy surgery may be underutilized. Gamma knife surgery, if it proves equally successful in treatment of this particular kind of epilepsy, can offer patients - who would otherwise avoid surgery - a noninvasive alternative. One disadvantage compared to open surgery, however, is that improvement in seizures is delayed from onset of treatment – it takes more than 6 months before the benefits begin to occur.”

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This interview with Dr. Quigg at the 2006 American Epilepsy Society meeting and follow-up with Dr. Barbaro was based on the research study, Two Year Outcomes of a Multicenter, Prospective Pilot Study of Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy: Neuropsychological Outcome. The authors are (1) Donna K. Broshek, (2) Mark Quigg, (3) Kenneth Laxer, (4) Nicholas M. Barbaro, and Epilepsy Radiosurgery Study Group from the following institutions. (1) Neurology, University of California San Francisco, San Francisco, CA, (2) Neurology, University of Virginia, Charlottesville, VA; and (3) and (4), Neurological Surgery, University of California San Francisco, San Francisco, CA.

Authored By: 
Rita Watson MPH
Mark Quigg MD MSc
Nicholas Barbaro MD
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Reviewed By: 
Steven C. Schachter MD
on: 
Sunday, December 31, 2006