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What factors determine quality of life after pediatric epilepsy surgery, and how can clinicians set families up for success? Dr. Kette Valente talks with Dr. Mary Lou Smith, whose work has implications for treatment decisions and setting expectations about the impact of surgery.

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Podcast Transcript

[00:00:00] Dr. Kette Valente: Hi, my name is Kette Valente. I'm the chair of the Pediatric Commission of the International League Against Epilepsy and today I will be interviewing Mary Lou Smith that will introduce herself. Mary Lou, please.

[00:00:17] Dr. Mary Lou Smith: Thank you, Kette. My name is Mary Lou Smith, and I'm a neuropsychologist from Toronto, Canada.

I work at the University of Toronto and the Hospital for Sick Children, and I'm very pleased to be having this conversation with you today. Thank you.

[00:00:32] Dr. Kette Valente: It's a pleasure for us to have you here. And in this podcast, I'd like to address your work. There is an extensive work that I'd like to address everything that you published this year, and it was a lot.

So I will start with something that you published, an article in JAMA, a very elegant prospective study with 111 surgical and 154 medical cases, showing how health-related quality of life evolves after epilepsy surgery compared with medical therapy. Could you comment on this work and its main findings?

[00:01:17] Dr. Mary Lou Smith: Certainly. First of all, thank you very much for asking about this study. It was one that for many years I'd wanted to conduct. My colleagues and I strongly felt that it was important to have a longitudinal study. The evolution of health-related quality of life over time after epilepsy surgery is uncertain, as most studies that have previously addressed quality of life are cross sectional, and few studies measured health-related quality of life both before and after surgery across multiple time points.

So the longitudinal component really allows for understanding how change evolves over time, and that's such an important dimension when you work with children. We also wanted to include not only a surgical group, but also to compare such a group with children with drug-resistant epilepsy who receive treatment with anti-seizure medications alone.

The comparison group helps to understand whether and how the surgery itself influences outcomes. We know that cognitive, emotional, and behavioral characteristics of children can change over time, irrespective of treatment or of epilepsy.

So as you said, the study had a relatively large sample. It was a multicenter prospective cohort design and we recruited children from eight centers across Canada.

We recruited them at the time that they were being evaluated to determine whether or not they were candidates for epilepsy surgery. We conducted a baseline assessment at enrollment into the study and followed up six months, one year, and two years later. And I should say that during our discussion today, I may use the term “quality of life” as shorthand, but I always am referring specifically to the health-related aspects of quality of life.

We were fortunate to be able to recruit this relatively large sample of children and their parents, and that enabled us to do the needed statistical modeling of change and the influences on change. So I have to thank my many wonderful collaborators across Canada.

What we found was that health-related quality of life was similar among the surgical and the medical patients at baseline. We found that the surgical patients experience significantly greater health-related quality of life improvement over time, relative to the medically treated patients. In addition, we found that the largest improvement in quality of life occurred in the first six months after surgery. However, it continued to improve in the first year, and thereafter, it remained stable for about two years after surgery. And among the medically treated patients, the health-related quality of life remained relatively unchanged over this two-year period.

Now when we drill down into which aspects of health-related quality of life changed, we found that the improvement was mainly associated with an increase in social functioning, and again, the largest increase incurred in the first six months after surgery, but the increase continued over the first year, and then it was stable after surgery.

And we found that to be a relatively interesting finding because it was very consistent with the results of a qualitative study that we did a number of years ago. In this study, children who were seizure free after surgery reported increased satisfaction with their peer relationships, and they experienced increased greater social inclusion. The seizure freedom after the surgery improved their autonomy, it reduced their fear and anxiety related to the unpredictability of seizures. It improved their confidence and it enhanced their opportunities for social interactions. And it was very clear, the children and teens also told us loud and clear, that they felt such a great sense of relief that their parents reduced their amount of direct monitoring and supervision so that the kids felt freer to integrate into social activities.

In our recent study at the two-year follow up, about 72% of the surgical patients were seizure free, compared to 33% of the medical patients. And it was those patients who were seizure free that really reported a significantly higher quality of life. And this was true irrespective of treatment, so it didn't matter whether you became seizure free as a result of surgery or seizure free because of a change in the anti-seizure medications.

It’s an important finding because it reinforces that we should always be pushing towards better seizure control, even in children who are not surgical candidates. So that's basically a summary of the findings of that study.

But I also think that an important aspect of the study is that it informed us of the time course of the change. And that can be very important for parents and for the medical team from a number of perspectives. First of all, it reduces the uncertainty of what to expect and when to expect it. And it can help to frame realistic expectations.

I think also it's important because it helps us plan what supports children and families might need and when to implement these resources. So we know that if quality of life plateaus after two years, is that good enough? Or are there other issues that are still problematic? And if there are such issues, what resources or supports should we provide to families and their children to facilitate further improvements?

[00:06:51] Dr. Kette Valente: Okay, great. And then you have an amazing study and you mentioned some of these findings already, in Epilepsia this year, about the variables that influence health-related quality of life after epilepsy surgery. And the most important is seizure control. Again, can you comment on this, please?

[00:07:15] Dr. Mary Lou Smith: Sure, certainly. So, in that study, we looked more closely at what influences outcomes of health-related quality of life, not only seizure control, but other variables that could potentially have an impact. So we investigated depressive symptoms, both in children and in their parents, and also the availability of family resources: things like family income, social support, the family physical and emotional help, and mutual help that families receive from their relatives.

So we were trying to clarify further the trajectory of the health-related quality of life by asking whether the treatment type, whether it was surgery or medical management, and seizure control are related to these other variables. Another way of putting it is that we wanted to see whether the treatment or seizure outcome effects were mediated by child or parent depressive symptoms or family resources.

And our key findings were that the better health-related quality of life that we observed among the surgical patients was attributed principally to the effect of surgery on seizure control. And that the effect of seizure control was not mediated by these other variables, not by child or parent depressive symptoms or by family resources.

This finding was somewhat surprising to me, as we've done other studies showing the importance of the patient's psychological symptoms on mediating the effects of seizure control on health-related quality of life. But those studies were done with somewhat different patient populations, and I think that those differences are very important.

So our earlier studies included individuals who were older at the time of follow up. Many of them were older adolescents or young adults and they had much longer follow-up durations. So instead of just two years, we were looking at between four to 10 years. And these differences suggest to me that it's very important to continue to study the evolution of health-related quality of life, and that these predictors of mediators of change in health-related quality of life can change over the individual's lifespan or can change with whatever else is happening in the individual's life at that time.

It may, for example, be true that we didn't see this effect in our current study with the two-year follow-up because at this time, families are still engaging quite intensely with the medical system, and there may be many supports that are available to them, and after a certain period of time, they don't need as many follow-ups, or some of them transition to health care in the adult system, and they may not be getting as much support.

So it's possible at those later times that all of a sudden, the mood state, the depression, the anxiety and so on, come more to the forefront, and are then having more of an influence on the individual's quality of life. That's a speculation.

[00:10:28] Dr. Kette Valente: I have to confess that was a surprise to me as well, that depressive symptoms in children and family were not affecting [health-related quality of life]. But something that I would like you to explain is that I have this concern that people may misunderstand this finding, so could you explain the difference between your findings and the systematic screening of depression and anxiety, which is still very relevant?

[00:11:01] Dr. Mary Lou Smith: Yes, absolutely. I mean, we do know from many studies that depression and anxiety are in fact predictors of quality of life. What we didn't find here is that they mediated the change in quality of life. So that's an important thing to note. And we also found that the depressive symptoms were very similar in the surgical group and the medical treatment group at the time of follow up.

So I think that it’s quite right, the point that you're making is that we need to continue to monitor these kinds of symptoms. And that's what I was speculating is that maybe just because of this intense involvement with the health care system, patients are getting more support at that time. But over longer periods of time this may not be the case, but I think it's the difference between the impact on quality of life and the impact on change in quality of life. That's an important distinction. In this case, it appeared that the effect of the seizure control was great enough that it did not have to be mediated by the patient's depressive symptoms, but that that in fact could change over time.

[00:12:19] Dr. Kette Valente: And about your publication in Seizure. You have a manuscript in Seizure that was published also this year. It was about preoperative predictors. Can we predict a better quality of life after seizure? Could you talk about this?

[00:12:37] Dr. Mary Lou Smith: So let me start by telling you what doesn't seem to predict outcome, because in the study we looked at a whole range of variables, but we found that the child's age, the sex of the child, the laterality of seizure onset, the seizure frequency, and their parents’ depressive and anxiety symptoms did not predict who was going to have a good outcome or a poorer outcome in terms of health-related quality of life.

In our simple univariable regression analyses, predictive prediction analyses, we did, however, find a number of other variables that did predict health-related quality of life after surgery. And these were older age of seizure onset, children who were on fewer anti-seizure medications prior to surgery, and those children who had better quality of life before surgery were those who tended to have better outcomes after surgery.

And in terms of family functioning, we found another set of variables that were important. So those families that had more resources available to them, that had better family relationships, and had lower demands on the family tended to do better in terms of health-related quality of life outcomes. And that set of predictors together actually accounted for 53 percent of the variability that we saw in quality-of-life outcomes, which I think is quite impressive.

However, when we went to the next stage of the analyses where we tried to account for the very strong influence of the child's preoperative level of health-related quality of life, we found that the strongest drivers of the associations were older age at seizure onset and higher quality of life before surgery. Those seem to be the two variables that were the most predictive.

Now, we can't change the age of the child's seizure onset, but certainly, we can do whatever we can to maximize the child's health-related quality of life before surgery in order to improve long-term outcomes. And getting back to the point that you were talking about earlier with screening, you mentioned screening for comorbidities. We need to recognize these comorbidities early and implement strategies to mitigate their effects.

[00:15:05] Dr. Kette Valente: So it's reasonable to say that although surgery is extremely important, it will not solve everything. We have to work with these families prior to surgery and to prepare them.

[00:15:22] Dr. Mary Lou Smith: Right. Exactly. And if we don't work with them before surgery, it's likely that those problems are going to exist after surgery. I was struck by the comments that a father made to me with respect to his son when I saw him a few months ago. The son had a left temporal lobectomy and did very well with respect to seizures. And the dad said to me, “Okay, now the epilepsy is under control. It's time for us to unpack the other problems.” So they had always put them off to the side and focused on the seizures. And now, those other problems were still there.

[00:16:03] Dr. Kette Valente: Regarding parents, that's something that has been neglected, but we know that when the mother, the father is depressed, it is very hard to treat the child. So from the time of the child's evaluation for epilepsy surgery you try to establish different trajectories, and how is that…What trajectories did you determine? How important is the parents’ mental health, according to your work?

[00:16:32] Dr. Mary Lou Smith: Okay, so we did this work because we believe that you can't think of children with epilepsy without thinking of the family. They're embedded in the family and the epilepsy affects everyone. So we set out to try to identify these trajectories by jointly examining parents’ depressive and anxiety symptoms, and also family resources.

And what we found was that there were three distinct trajectories that were evident, and these three trajectories, or three groups, were defined by specific demographic and child characteristics.

Just before I start to describe the trajectories, I do want to say that we replicated previous studies showing very elevated rates of symptoms of anxiety and depression in parents. So, in our findings, at least once over the course of the two-year study, 36% of parents reported moderate to severe levels of depression and 32% reported moderate to severe levels of anxiety. And elevations in these symptoms are not surprising, given the severity of their children's epilepsy and the pathway through the surgical evaluation process and the decision making that's involved, which can be very stressful.

I just want to emphasize that to illustrate the importance of looking at these factors in parents.

So now about the reach, the trajectories. What we found was that about 25% of parents did very well throughout the time span of the study. They reported no or minimal depressive or anxiety symptoms. They had relatively high levels of family support. These ratings were stable across the two years of the study.

A second group of about 41% of our sample reported mild depressive and anxiety symptoms. And these decreased slightly over time over the first six months and then they plateaued. And again, these families had intermediate levels of family resources.

And lastly, there was a group that didn't do as well. It was about 34% of our sample. These parents reported moderate levels of depressive and anxiety symptoms. And they showed only a very small decrease over time. And they also had relatively low family resources.

So we then went on to try to identify the characteristics that were associated with these trajectories. Those who had the better trajectories of well-being were those parents of children who had higher health-related quality of life at baseline. They were fathers relative to mothers. And they were parents who were employed in a high, had a higher household income level at baseline.

We also found that the parents of children who were seizure free at the time of the last follow up were more likely to have better trajectories. But seizure freedom alone did not fully explain the trajectory of family well-being, because 47% of the parents in the good trajectory group had children who did not become seizure free.

And again, we found that over time, these trajectories were relatively stable. They were evident from the time of the initial evaluation, and that suggests to me that we should be focusing early on trying to identify those parents who are likely to have the less optimal trajectories of well-being and get back to the point that we were making before about trying to put into place support systems, not only for the children, but for the parents themselves before surgery.

And then continuing on after surgery, many of us work in systems where we claim family-centered care, that we have models of family-centered care. And if we're going to say we have models of family-centered care, we have to try to care for everyone in the family, not just the child.

[00:20:45] Dr. Kette Valente: Parents and siblings.

[00:20:47] Dr. Mary Lou Smith: We didn't look at siblings in our study, but I would bet that some siblings need help as well.

[00:20:54] Dr. Kette Valente: I think you have demonstrated over the years the importance of epilepsy surgery as early as possible. Do you think that pediatric epilepsy surgery remains neglected, is still considered the last resort? If you do, what is the impact?

[00:21:14] Dr. Mary Lou Smith: So I have been working many, many years now in the pediatric epilepsy surgery field. And my research and my clinical work with children and their families has firmly cemented in my mind the importance of epilepsy surgery. And I'm definitely in the “earlier is better” camp. I do think that surgery is still underutilized and we need to work constantly to make it more widely recognized and more available. It's really heartbreaking to think of the cumulative effects of ongoing seizures on so many aspects of the lives of these children and on their parents and the rest of their family.

Now, we know that some of the benefits of surgery on the comorbidities may take many years to emerge, but in the short term, there can be lessening of stress in the family, the reduction of the negative effects of stigma. We saw these social benefits as early as within the first six months after surgery.

And we know from our research that children and teens with epilepsy are yearning, they're crying out to be what they themselves called “normal.” In fact, my colleagues and I wrote a paper many years ago, which we titled I Just Want to be Normal, based on the themes that these kids gave us. So I believe strongly that a life without seizures is much superior to a life with seizures.

And the impact of the underutilization of surgery is heartbreaking. It's a waste of the resources in our healthcare system and in our society. There's just so much lost potential and so much wasted opportunity due to these delays.

[00:22:55] Dr. Kette Valente: Well, we have to remember that in the moment that we're discussing so much precision medicine, epilepsy surgery is precision medicine, we have precision medicine, we don't use it.

So, I think that the importance of your work is to demonstrate how important it is in all senses. So I'll leave you with the last words of this podcast, and first I'd like to thank you for your time and for your unbelievable and amazing work. I'm always reading everything you publish. So thank you very much.

[00:23:30] Dr. Mary Lou Smith: Thank you, Kette. It's been very rewarding to me over the years to work with so many wonderful medical personnel, neurologists and neurophysiologists and neurosurgeons who really care for these children, not just their seizures, but for the children themselves.

Thank you.