Transcript of Audio Interview with Dr. Jacqueline French
MD NetGuide: “I’m Bob Enteen reporting live for MD Netguide from the 58th annual meeting of the American Epilepsy Society, taking place this week, December 3-7, 2004 in New Orleans. Joining me now, December 4th, is Dr. Jacqueline French, who is Professor of Neurology at the University of Pennsylvania and Co-director of the Epilepsy Center. Our topic: Refractory epilepsy-epileptogenesis and the progressive nature of the disease.”
MD NetGuide: “Dr. French thank you very much for joining me and let me begin with this question: Your presentation addresses the issue of whether epilepsy is progressive. Could you characterize this presentation for us?”
Dr. Jacqueline French: “This was the topic of the symposium I chaired and spoke at and we heard some very eloquent presentations from both basic and clinical scientists addressing this topic. What I thought was very interesting is that... from a basic science perspective we heard from Doug Colter at the University of Pennsylvania who induces epilepsy through lesioning animals in various ways either by trauma, brain injury or status epilepticus, and then follows those animals until they develop epilepsy. There’s usually a latent period before the epilepsy occurs, and then once it does occur the seizures progress over time and he showed very clear examples of that…that seizures increase in frequency and sometimes in severity and pattern after the animals develop epilepsy. So, the question then becomes, is this the case in human beings or not? We really obviously do not have the opportunity to look at the untreated condition and nor would we want to because we certainly wouldn’t want to follow a patient whose not on medication just to see if the epilepsy becomes more severe over time. Therefore, we need to look at individuals who are on therapy and see what happens, and that is the only thing we can do in humans.”
“So, my presentation specifically addressed whether we can see changes depending on what antiepileptic drug is used and whether patients will follow a different course. In other words, if epilepsy is progressive one might imagine that certain medications may stop that progression, whereas others may not. And you might see a difference not in the number of seizures that are controlled today, but in the number of seizures that are controlled the next month, or in 6 months from now or 12 months from now. So I reviewed some long-term outcome data in individuals with refractory epilepsy who are in long-term studies of newer antiepileptic drugs and interestingly enough, in many cases, one sees quite the opposite. One sees a reduction in seizures over time. Most people continue on antiepileptic drugs, which raises another interesting question, which is, ‘Are the seizures quieting down or reducing in frequency over time specifically because that drug is having a certain effect on the brain such as neuroprotection or antiepileptogenesis, or is that in fact in human beings more of the natural history of refractory epilepsy?’ In fact, in contrast to the rats will a treated person with epilepsy eventually get better over time? I think that lots of physicians would sit up and say, ‘Well, that doesn’t seem to be the case in my clinic. I treat a lot of people whose seizures aren’t controlled and it seems to me that they either stay the same or they get worse. It doesn’t seem like they get better over time.’
“Thinking about these questions and reviewing this long-term data led Dr. Alan Hauser at Columbia and myself to start a study where we actually took 250 patients who were identified as refractory based on the fact that they had failed several antiepileptic drugs and were still having one seizure a month at the index date in 2000. We followed them from 2000-2003 to see, in fact, what happened to them over time and so far in the data we have looked at we were quite surprised to see that (although the outcome is not particularly cheery in this group) there was a remission rate of 5% per year. So each year of the study, 5% of the patients who had had refractory epilepsy and were seizing became seizure-free for at least 6 months. In fact, the ones who became seizure-free in the first six months remained seizure-free so many patients had a longer seizure-free interval. This was very encouraging to us. We would like to continue the work to see whether 5% per year remission rate continues over the lifetime of the patient. If that were the case then in fact, if one persisted in aggressive treatment of these patients over time, one might expect that many of them would go into remission because the 5% plus the 5% plus the 5% would finally add up. We don’t know whether that us the case. We do hope to be able to find this out in the future.”
“We also looked a little bit at what had been done to these patients to make them seizure-free. And many of then had had duration of epilepsy of 20 years and had failed 7-or-8 antiepileptic drugs. Many people would say there’s very little chance of that person now, of responding to drugs. So, what did you do? What was the miracle pill? So, we went back to try to look at whether there was a miracle pill and interestingly enough – there was not. In fact, there were a number of drugs that were started within three months prior to these individuals becoming seizure-free and surprisingly there was even a number of patients, not a very large number, but a very small number, who became seizure-free without any change in their medication. There were three who became seizure-free only with dose changes of their medication that they had been on chronically for a long period of time. And there was one patient who became seizure-free with no change in therapy either dose change or medication change in the three months prior to seizure freedom. So, all of these things are very interesting. They are quite preliminary, but we hope we can delve into this data even more so; to see what predicts refractory patients being able to become seizure-free and what may predict that they will not become seizure-free. So far in our data, we have discovered that patients with Lennox-Gastaut syndrome, which is a very severe form of epilepsy, never became seizure-free over the three years and that a history of status epilepticus in the past was also a very poor predictor of ever becoming seizure-free. So we’re looking for other characteristics that might give hope that aggressive therapy will or might work. On the other hand, say that we need to look at new therapy approaches for these individuals because aggressive therapy will never work. So we hope this research will continue and in fact expand in the future.”
MD NetGuide: “Are there any day-to-day clinical implications for practice or is it premature, and then where do you see the research going over the next five years in very concrete terms?”
Dr. Jacqueline French:: “As far as what the take-home message is for clinicians, I think the very strong take-home message is: ‘Don’t give-up.’ Just because somebody has failed a large number of antiepileptic drugs certainly is no indication that that person is now unable to ever respond to an antiepileptic drug. Again, we found many circumstances where people had been poorly responsive and for whatever reason responsive to a single drug when others had failed. So, I think the very strong take-home message I would give is don’t give up, continue to try new therapies in patients whose seizures are not controlled. As far as where the research will go in the future I certainly would like to involve other centers so that we can duplicate our findings among patients from other centers. We’re in fact intending to do that at Columbia and perhaps at other institutions. Again, I’d like very much to follow these patients not only over three years, but over a longer period of time so we could see whether they continue to increase numbers of remissions. The other side of the coin is, ‘Will those patients who became seizure-free remain seizure-free permanently or will they relapse at a later date?’ ‘How consistent will the data be?’ ‘Will there be the same number becoming seizure-free as the number that relapse back again?’ That would obviously not be a good outcome for these patients. So I think there’s a very rich vein of investigation in the future which we hope to follow.”
MD NetGuide: “Has there been any major critique or prevailing controversy in regards to what’s been found today?”
Dr. Jacqueline French: “As far as controversies I think the only controversy might be that there’s a difference of opinion as to whether, in fact, epilepsy is in fact progressive in a positive or negative way. There are some people who believe very strongly one way or the other. I think the other controversy is that these long-term databases for the new antiepileptic drugs have been used to say, ‘Look, our patients do better over time and it’s because of this treatment’, not only drugs, but devices and other thing. And again, I think that you have to compare those data with the population as a whole before you are going to make a definitive statement as to whether these patients vary from what you would expect from the population as a whole.”
MD NetGuide “Dr. Jacqueline French, I want to thank you for joining me.”
Adapted with permission from MD NetGuide. Interview conducted 12/04.