Doctor: Thank you for coming in today, Maria. I wanted to talk to you about the result of Ronald’s testing that we did after he had his first seizure.

Maria: Yes, I’m hoping we can get to the bottom of this. It was quite scary when he had the seizure, and I felt so helpless because there was nothing I could really do for him.

Doctor: I completely understand, and it can indeed be scary. Let’s go through the results, and please let me know if you have any questions at any time, ok?

Maria: All right.

Doctor: So we performed a physical exam and some imaging studies. From what we can see, it looks like Ronald has a condition called tuberous sclerosis complex (TSC). This is a rare, genetic disease that often affects the brain as well as possibly affecting other organ systems. Although we don’t understand what causes seizures in TSC, we think that the epilepsy is somehow related to the areas of their brain that develop unusually while in utero.

Maria: I was afraid of this. I was hoping his seizure might be a one-time thing, but this sounds like something more serious. But... I’ve never heard of that type of condition before. Is it the same as epilepsy? And does this mean that Ronald has cancer?

Doctor: No, the growths are not cancerous, so Ronald does not have cancer. Approximately 90% of individuals with tuberous sclerosis complex have epilepsy. Patients with TSC usually experience a type of seizure called a focal seizure, which starts in one area of the brain and may remain localized or spread to other areas on that side of the brain. Generalized seizures originate at one point and may spread rapidly to the whole brain. So the treatment approaches for these conditions may be quite different.

Maria: Does this mean there is a treatment available? My brother has epilepsy, but he takes his medication every day and hasn’t had a seizure in a long time.

Doctor: Well, at the moment there are several treatment options for treating focal epilepsy, including individuals who have epilepsy due to having TSC. In addition to all of our current antiseizure medications, 2 have been specifically approved for the treatment of seizures in the setting of TSC: cannabidiol and everolimus. However, there is no evidence that these are superior to our other antiseizure medications for focal seizures. I would like to try one of these for Ronald, to see if his condition improves.

Maria: All right. But... Would the treatment make him better right away?

Doctor: Well, our goal is to control the seizures, without any side effects from the medication. But sometimes the first medicine we try may not be effective, or Ronald may experience too many side effects. So we may have to try another treatment if the first one is not optimal. Some of the side effects associated with many of our antiseizure medications include somnolence, decreased appetite, diarrhea, fatigue or insomnia, rash, or infections. But hopefully Ronald won’t experience any of these. If he does and the side effects are significant, we will discuss other treatment options.

Maria: But aren’t there side effects with every medication? I thought that was just something that we would have to live with.

Doctor: Not necessarily. And hopefully we can find a treatment for Ronald that will be ideal for him. I would like to schedule some follow-up appointments with you, as we would like to see him about every 3 months to gauge his progress and see how he’s doing with the treatment.

Maria: All right, thank you doctor.

Arthur: So doctor, you said that Bella has something called tuberous sclerosis complex, and is experiencing focal seizures, together with infantile spasms. What are these, and what’s the difference between the 2? And is there any way to treat them?

Doctor: Well, Arthur, focal seizures are when one part of the brain sends out uncontrolled electrical signals. Usually, the signals remain in one part of the brain, which is why we call them “focal” seizures. These types of seizures can occur at any age. Infantile spasms are a type of seizure that can occur in babies; they usually start in infants between the ages of 3 and 8 months. Some babies may experience focal seizures prior to developing infantile spasms, and it seems Bella has now been experiencing both types.

Arthur: How can you tell what kind of seizures she’s been having?

Doctor: These are Bella’s electroencephalogram, or EEG, results. The patterns in her EEG, as well as your description of her episodes, help us identify what kind of seizures she’s been having.

Arthur: I understand. So she may grow out of the infantile spasms?

Doctor: Yes, she will hopefully stop having infantile spasms at some point, but may continue to have focal seizures, or even develop other seizure types. The seizures Bella is having are seizures we commonly see in TSC. Early onset of seizures, like we’re seeing with Bella, can also be associated with psychomotor developmental delays, cognitive impairment, and even autism. So it’s important that we identify Bella’s condition early, so we can start treatment as soon as possible.

Arthur: So there are treatments available that might help her?

Doctor: Yes, there are several options. However, it may take a little while before we find the optimal treatment for Bella, as we would have to see how effective the treatment is, and if she experiences any side effects.

Arthur: So how do we choose a treatment? Are there any that are more likely to cause side effects?

Doctor: We should consider what will help Bella right now based on her seizure types and EEG features, but also in the future. Ideally, we would like to find a treatment for her that will eliminate her spasms and improve her EEG features.

Arthur: I understand. Are there any specific treatments for children with Bella’s condition?

Doctor: The recommended therapy for children with infantile spasms due to tuberous sclerosis complex is a treatment called vigabatrin. Children can develop infantile spasms due to many causes. About one-third of children with TSC develop infantile spasms. Vigabatrin has been shown to be the most effective treatment for infantile spasms due to TSC in several studies.

Arthur: I see. And would she experience any side effects from this treatment? And what might they be?

Doctor: Vigabatrin is overall well tolerated, but can be associated with sleep difficulties, and there is also a possibility of toxicity to the retina of the eye, which could possibly affect her peripheral vision. This is pretty unusual, and we can discuss how we will follow her with regard to this possible side effect. We will follow her closely after starting treatment to gauge the impact on her seizure activity and also how well she tolerates the medication.

Arthur: I understand. But what if the treatment doesn’t seem to have any effect? What would happen then?

Doctor: We may want to consider a different treatment option then, Arthur. If we change treatments, we could add the second therapy and start slowly increasing the dose, while slowly decreasing the dose of the first therapy.

Arthur: Do you think that’s what we’ll have to do for Bella?

Doctor: It’s difficult to say right now, Arthur. We’ll have to see how she responds to the vigabatrin therapy first, and then make decisions from there. But we’ll have regular follow-up appointments to check in and see how Bella is doing.

Arthur: How often would you need to see her?

Doctor: I would prefer to keep a close eye on things, especially in the beginning. So I would like to see her at least once a month, ok, Arthur?

Arthur: Of course, that sounds like a good plan.

Doctor: Melody, I’m afraid we’re not seeing as much of a response to the vigabatrin and his other medications as we would like. Thomas is still having seizures, and he has been experiencing many side effects. It also sounds like his seizures look different to you, with episodes of him staring and not responding, as well as episodes during which his arms and legs stiffen.

Melody: Yes, I know. I’m just at a point now where I’m afraid nothing will work for him.

Doctor: I know it’s frustrating, Melody. It seems that Thomas’s condition has become refractory, meaning that the anti-seizure medications are not controlling his seizures. I also think that, with his seizure types changing, that he no longer has infantile spasms but may be becoming suggestive of Lennox Gastaut syndrome.

Melody: What is that? I thought Thomas had TSC?

Doctor: Lennox-Gastaut syndrome, or LGS, is an epilepsy syndrome due to many different etiologies associated with specific seizure types and a specific EEG pattern. Some children with TSC develop LGS. We’d have to do a little more testing, but that may explain why Thomas’s seizures are not responding to treatment.

Melody: So this might not ever improve?

Doctor: I understand your frustration, Melody. But there are still some options we can try.

Melody: Like what? I hope we can find something that will work soon. I keep telling him that we are still looking for the right medicine for him and hoping that we will find it, but it’s heartbreaking sometimes to see him go through this.

Doctor: I understand, Melody, and I know this can be a challenging journey for the patients and parents. But let’s keep going, and I’m hopeful we will find a strategy that will help Thomas, ok?

Melody: Yes, of course. So what might the next steps be?

Doctor: Well, for example, we have several alternatives that we can try. We could try combining 2 medications and see if he responds well to a combination treatment. We could also think about trying him with dietary therapy or think about possible surgical options if his seizures still occur with combined therapy. LGS can be very challenging to manage, but our goal for Thomas is still to optimize his seizure control, while improving quality of life.

Melody: Of course, but surgery sounds very serious. What kind of surgery are we talking about?

Doctor: Well, if we can pinpoint the exact area in his brain that is causing the seizures, usually associated with a tuber, the surgeon can remove that area, which can often significantly decrease the seizure frequency.

Melody: But... wouldn’t that be dangerous? And would Thomas still be the same? Would he still be able to function?

Doctor: It’s natural for you to have these questions, Melody, and of course I understand. If we get to the point where surgery might be indicated, we can go through the risks and benefits together. What I can tell you is that, in my experience, many people who have the surgery say that being almost free of seizures, or at least having less frequent and less intense seizures, makes them feel much better.

Melody: I see. And... the diet? How would that help Thomas?

Doctor: Well, we’re still not entirely sure why the diet works, but it does seem to be beneficial for many patients. Studies have shown that some children with epilepsy who stay on the diet have a better chance of reducing or even discontinuing their seizure medications. However, children treated with dietary therapy for epilepsy are followed very closely by specialized dietitians. The diet is a high-fat, low carbohydrates diet, and we would have to start it in a specific way and follow it strictly.

Melody: Hmmm. I’d like to think about it some more, but I think I’d like to explore other medication options first, to see if that works.

Doctor: Of course. We can start that right away once you decide for certain. I would also like to schedule follow-up appointments every 3 months, with telephone check-ins in between.

Melody: Yes, please. And can I call you if I have questions about anything?

Doctor: Of course, please do, Melody.

Melody: Thank you, doctor.