Further Establishing a Treatment Threshold in Epilepsy

Michael R. Sperling, MD: Is your threshold for recommending medicine different in young women or adolescents than it is in males of similar age?

Jesus E. Pina-Garza, MD: Not a lot, I have 2 comments in this scenario. In this particular situation, you may have someone on treatment who was never going to have a seizure without treatment. The last thing that you want … is adding adverse effects. So, whatever you select, if they decide to accept it—which is another challenge, because most people decide not to be on treatment than be on treatment—you have to select something that they completely tolerate and feel good. For males and females, it’s definitely an algorithm. So there are a few drugs that based on the pregnancy registry seem to have a better profile. So, definitely, if we offer it, you select it. But, in this case it’s not the situation of a pregnancy but a situation of driving. So it would be the same for a male or a female.

Michael R. Sperling, MD: And Trevor, suppose this young woman when you saw her revealed that perhaps 3 or 4 times in the past year or two she had this sudden feeling where she had done it before and it lasted for 20 or 30 seconds, this prolonged déjà vu, and perhaps was a little dizzy with it. So it was something that was reasonably convincing for a stereotyped aura, in fact. Would that alter your decision with regard to recommending therapy?

Trevor J. Resnick, MD: It may. I think under that scenario you have to dig a little bit deeper. You have to ask whether the episode that resulted in having a seizure was preceded by a similar aura.

Michael R. Sperling, MD: And then on second thought, perhaps it was.

Trevor J. Resnick, MD: And then under those circumstances—let’s say it wasn’t, to make it harder—she comes in, in terms of digging a little deeper, and just doing a routine EEG [electroencephalogram] may not be enough. That’s where you may want to do a long-term EEG to give you more information. And if under those circumstances you end up with recurrent episodes that are suspicious for seizures plus a defined clinical seizure and an abnormal EEG, then the risk changes. And, under those circumstances, I would recommend treatment.

Michael R. Sperling, MD: So the data that are very well established are interesting, and those show the first seizure happening while awake is much less likely to lead to a second seizure than a seizure that happens while asleep. Had she been asleep, the odds of relapse may have been 50% or 60%. It doubles the risk of relapse.

If she has an abnormality on her MRI [magnetic resonance imaging], this too increases her risk of relapse substantially. And should the EEG show an epileptic abnormality, a focal spike or generalized spike wave, the risk is substantially higher. And that might then lead to another discussion. Although being a young woman potentially of childbearing age, if the glass, rather than two-thirds full, is only 45% full, do you want to commit her to long-term therapy? Because the duration of therapy is another issue in this circumstance. So let’s say you decide to put her on therapy. Well, how long are you going to leave her on? Because that lesion is still going to be there on the MRI, right?

Trevor J. Resnick, MD: But now you’ve got a new patient. Now you have a patient with a lesion on their MRI.

Michael R. Sperling, MD: Yes, but if she has a lesion on her MRI and we decide to put her on therapy, the lesion will still be there in 2 years, it will be there in 5 years.

Trevor J. Resnick, MD: It’s a very tough question because just the mere presence of a lesion does not mean to say that the epilepsy is necessarily indefinite. And that’s a hard question because sometimes patients have lesions, cortical dysplasia, and they’ve never had a seizure before. And they have found out they have lesions independently. And you may have a patient who has a focal lesion with a variable incidence of association with seizure, and then that just ends up being 1 risk factor in terms of continuing or stopping medication. And you’re right, it ends up at a point after they’ve been seizure-free for X number of years, whether it’s 2 years, or 3 years, or 4 years. You end up sitting down and having a discussion of the relative risk of seizure recurrence. And, unfortunately....

Michael R. Sperling, MD: It’s still quite high.

Trevor J. Resnick, MD: Yes.

Michael R. Sperling, MD: It’s still quite high. Now, Eric, let’s suppose that the story was a little different. It was a child—but it could be an adult, Kate, for that matter—and the seizures are focal aware. So perhaps you have a little finger twitching for 20 or 30 seconds and it goes away, and the person has had several of these. Again, this could be a kid, this could be an older adult for that matter. Does the seizure type make a difference in your rush to treat or your reluctance to treat in that case? And perhaps you want to address it in the child first.

Jesus E. Pina-Garza, MD: So regarding seizure type, the more severe the seizure, clearly the lower threshold to treat. That’s very different, a twitching of your index versus a generalized convulsion. It’s just one of many factors. If you have a biomarker that tells you this kid has a tendency to have epilepsy until adolescence, like a rolandic type or benign epilepsy of childhood, or if you have a kid who has that and a comorbidity, it has been proved that in some of these kids, epilepsy is not just seizures. But sometimes you have an abnormal electrical activity that leads to all her symptoms, like less attention span, or learning, or other things.

So, if you have a kid who is completely healthy and cognitively functional and has just a little twitch, and you don’t have anything underlying like a structural abnormality, tumor, or other thing, we’re just thinking about the possibility of that giving you a crisis because that can generalize or not. So you have a little bit of a flexibility in that if it’s infrequent, you may not consider the treatment.

But, on the other hand, similar to the previous example, in the past it was always the case that you selected not to treat a very benign case because the options have all very bad adverse effects. I’m talking about what used to be called the gold standard treatment. All of them have long-term adverse effects, short-term adverse effects, higher risk of immunogenic reactions. So there was not a very safe option versus the illness. Fortunately, we have drugs that are better tolerated and have less risky adverse effects that can offer some potential benefit. I have a low threshold to treat even in these cases because I think there is always the possibility of having a bad outcome, and it would be hard if you could prevent it.