ARTICLE IN BRIEF
One year after surgery, only four of 14 patients (28.6 percent) in the frequent-spike group remained completely seizure-free since surgery compared to 33 of 41 patients (80.5 percent) in the nonfrequent spike group.
The absolute frequency of interictal epileptiform discharges — “spikes” — seen on EEG is a strong predictor of surgical outcome in patients with medically refractory mesial temporal lobe epilepsy (MTLE) and MRI evidence of unilateral hippocampal atrophy (HA), according to a study published in the August 5 Neurology.
The authors, R. Krendl, MD, and colleagues of the Comprehensive Epilepsy Program at the University of Vienna, followed 55 patients with MTLE for a minimum of one year after first-time epilepsy surgery. Patients were classified as having frequent spikes if they had 60 or more spikes per hour from the affected temporal lobe, and infrequent spikes if they had 59 or fewer per hour. They were also classified into unitemporal (90 percent or more of spikes over the affected temporal lobe) and bitemporal groups (less than 90 percent of spikes over the affected lobe).
One year after surgery, only four of 14 patients (28.6 percent) in the frequent-spike group remained completely seizure-free since surgery compared to 33 of 41 patients (80.5 percent) in the nonfrequent spike group (p=0.001).
Could something as simple as absolute spike frequency accurately predict surgical outcome for patients with MTLE? And since the primary surgical approach used was the selective amygdalohippocampectomy (sAHE), could frequent-spike patients gain more effective relief from more comprehensive surgery? These are important questions because, as the authors note, about one-third of patients who have surgery for refractory epilepsy still have seizures.
‘THIS COULD CHANGE CLINICAL CARE’
“This could change clinical care. We're already talking about it here,” said Carl Bazil, MD, acting director of the Comprehensive Epilepsy Center at Columbia University Medical Center in New York. “We had thought that the more selective approach to surgery was the way to go, but this study suggests that might not be the best for patients with frequent spikes. The rationale is that we don't usually see activity coming from the interior of the temporal lobe, so frequent spikes may indicate that activity and may mean that the epilepsy is more widespread.”
Calling the study a “valuable and novel contribution to the literature,” New York University Epilepsy Center director Orrin Devinsky, MD, agreed with Dr. Bazil that the study suggests that patients with frequent spiking do not have seizures limited to the depths of the temporal lobe. “Although they may have started there years ago, over time they may have recruited a wider network of tissue into the seizure focus, which is reflected by the frequent spikes recorded on the scalp. If you only take out the deeper tissue, you will indeed fail in a majority of cases to control seizures.”
But as Dr. Bazil pointed out, “Nothing is ever as simple as it seems in epilepsy.” Leading epilepsy specialists acknowledge a number of limitations to the Vienna study. “Size is this study's key limitation,” he said. “And since there were three different subsets of the study group who had different types of surgery, that further limits the interpretation, although the differences seen are definitely significant.”
“The authors do recognize that these spikes don't actually come from the hippocampus or the mesial temporal lobe — they're projected, and come from the lateral temporal lobe,” said Susan Spencer, MD, director of the Yale Epilepsy Program. “So these spikes may be something other than mesial temporal lobe spikes, and might be a marker for some other kind of disease in the mesial temporal lobe. The editorial recognizes that more than the authors seem to.”
“I have no idea where that number came from; it's not in the literature,” Dr. Spencer said. “It's very arbitrary, and it's also very frequent.”
Drs. Spencer, Bazil, and Devinsky all suggested that a continuous variable analysis, rather than a single-number cutoff, might have been more illuminating. “It would have been nice, since they counted all these spikes, to see a table showing the overall distribution,” Dr. Devinsky said.
In addition, “the 90 percent figure for determining whether seizures are unitemporal or bitemporal also seems arbitrary,” Dr. Spencer said. “Their analysis on these two fronts depended on choosing cutoff points that the authors did not defend or even discuss significantly.”
“Spikes are much affected by seizures,” Dr. Spencer explained. “The authors excluded EEG samples for counting that were within 10 minutes of a seizure, but then everything was fair game. Ten minutes is not adequate, given that spikes increase for a variable amount of time — anywhere from five minutes to two hours — around a seizure.”
“These issues, and other issues of methodology, make me skeptical about drawing conclusions,” said Dr. Spencer. She suggests that even if those factors are disregarded, there are a variety of explanations for the study's results, such as additional disease beyond the temporal lobe.
“I would have liked to see them emphasize that more, and do more analysis of their patient population to clarify whether indeed there is evidence that there is additional disease or dysfunction in other parts of the temporal lobe — such as PET data and tests of memory, language, and neuropsychological function. They should have that data, and it would have been an interesting addition.”
Nonetheless, Dr. Spencer noted, the authors are absolutely right in the driving force behind their conclusions: that spikes and their frequency are much more important than they have been given credit for. “I agree that there is a tremendous amount to be learned from spikes,” she said. “Spikes possibly could add to our impressions of prognosis and brain function, especially in these kinds of refractory epilepsy. The influences that affect spikes could also clarify other aspects of epilepsy. But this may have been a little too easy, and it may be much more difficult to get the kind of information we need.”
In a move away from the more selective surgery, which was adopted on the “why take out more brain than you need to” theory, some centers are swinging back toward more comprehensive epilepsy surgery already.
“Here at NYU, less than 10 percent of our surgeries are selective amygdalohippocampectomies,” said Dr. Devinsky. “The fear is that such a limited removal has a high chance of not providing seizure freedom. This study would argue that yes, we're right in that approach, and the patients most likely to fail are the ones with frequent spiking.”
• Krendl R, Lurger S, Baumgartner C. Absolute spike frequency predicts surgical outcome in TLE with unilateral hippocampal atrophy. Neurology 2008;71: pages to come.
• Miller JW, Gotman J. Editorial: The meaning of interictal spikes in temporal lobe epilepsy — Should we count them? Neurology 2008;71: pages to come.