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Talking With Parents of Children With Tuberous Sclerosis Complex (TSC)–Related Seizures About Treatment Options

  • Authors: Elizabeth A. Thiele, MD, PhD
  • CME Released: 5/9/2023
  • Valid for credit through: 5/9/2024, 11:59 PM EST
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    Physicians - maximum of 0.50 AMA PRA Category 1 Credit(s)™

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Target Audience and Goal Statement

This activity is intended for neurologists, pediatricians, and primary care practitioners.

The goal of this activity is for learners to be better able to speak to caregivers/patients about antiseizure options for patients with TSC.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Goals of treatment for seizures associated with TSC
  • Have greater competence related to
    • Identification of appropriate antiseizure medicines for the management of TSC-related seizures that takes into account patient-related factors and preferences


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  • Elizabeth A. Thiele, MD, PhD

    Director, Pediatric Epilepsy Program
    Massachusetts General Hospital
    Herscot Center for Tuberous Sclerosis Complex
    Boston, Massachusetts


    Elizabeth A. Thiele, MD, PhD, has the following relevant financial relationships:
    Consultant or advisor for: Aditum; Azurity; BridgeBio; GW Pharmaceuticals/Jazz Pharmaceuticals, Inc.; LivaNova; Marinus Pharmaceuticals, Inc.; Nobelpharma; Radius Health, Inc.; Stoke Therapeutics; Zogenix, Inc.
    Research funding from: GW Pharmaceuticals/Jazz Pharmaceuticals, Inc.; Stoke Therapeutics; Zogenix, Inc.
    Contracted researcher for: GW Pharmacueticals/Jazz Pharmaceuticals, Inc.; Zogenix, Inc.


  • Frances McFarland, PhD, MA

    Medical Education Director, Medscape, LLC


    Frances McFarland, PhD, MA, has no relevant financial relationships.

  • Megan Breuer, PhD

    Medical Writer, Medscape, LLC


    Megan Breuer, PhD, has the following relevant financial relationships:
    Consultant or advisor for: Paratek Pharmaceuticals, Inc. (former)

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  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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Talking With Parents of Children With Tuberous Sclerosis Complex (TSC)–Related Seizures About Treatment Options

Authors: Elizabeth A. Thiele, MD, PhDFaculty and Disclosures

CME Released: 5/9/2023

Valid for credit through: 5/9/2024, 11:59 PM EST


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.

Elizabeth A. Thiele, MD, PhD: Hello, I'm Dr. Elizabeth Thiele, director of the Pediatric Epilepsy Program at the Massachusetts General Hospital, and also, Director of the Herscot Center for Tuberous Sclerosis Complex.

Tuberous sclerosis is a complicated multi-system disorder that can affect most organ systems, most often, the brain and the skin, each of which are affected in about 95% of individuals with TSC.

Epilepsy is the most common symptom associated with TSC, with about 85% of individuals with TSC developing epilepsy, 70% during the first year of life. Seizures in tuberous sclerosis are focal, and so many of our medications can be effective in treating the seizures.

As with other patients with epilepsy, the goal of treating epilepsy and TSC is seizure control, hopefully complete seizure control, with minimal treatment side effects. There are several treatments available, especially over the past 20 years, many new anti-seizure medications which could be used. And in tuberous sclerosis, in addition to all the medications, 2 medications, everolimus and cannabidiol, have specific approvals for the treatment of focal seizures associated with TSC. So our treatment armamentarium is really great.

Both CBD and everolimus, in the clinical trials, showed that they were superior over placebo in efficacy, with regard to treating seizures. Tolerability is also fairly good. As in CBD, the most common adverse events include diarrhea, decreased appetite, and somnolence. And with everolimus, the most common side effects are stomatitis, or mouth ulcers, and pneumonia.

To summarize, epilepsy is very common in tuberous sclerosis complex. And we, and others, have shown that the epilepsy is associated with cognitive impairment, autism, and also behavioral difficulties in TSC. Therefore, it's very important to control seizures in TSC. And it's also important to educate patients and their families, not only about epilepsy in tuberous sclerosis, but the other aspects of TSC, and that there's a spectrum of clinical severity. Some patients severely affected, both with regard to epilepsy and the other manifestations, and others, mildly affected. Tuberous sclerosis is a complicated disorder, but we're getting better at managing the symptoms of TSC, including the epilepsy.

Now let's take a look at our next case.

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.

Dr Thiele: About a third of children with tuberous sclerosis will develop infantile spasms. Therefore, it's very important to educate families, not only about the focal seizures in TSC, but the possibility of infantile spasms and what to look for.

If a baby is diagnosed with TSC, either with the family history, or from the identification of cardiac rhabdomyomas during pregnancy, or the skin lesions after birth, we spend a lot of time talking about seizures, focal seizures, what they can look like, and infantile spasms. And we actually sit and watch videos from YouTube, about various presentations of spasms, so that parents will recognize them when they see them.

The International TSC Clinical Consensus Group strongly recommends vigabatrin as first-line therapy for infantile spasms in TSC, as it's been shown in several studies to be superior over adrenocorticotropic hormone (ACTH) and steroids. Vigabatrin, as other medications in pediatric, is dosed based on body weight. And we recognize the potential side effects of vigabatrin, including constriction of peripheral fields, and possible white matter changes on magnetic resonance imaging (MRI). Therefore, we follow babies closely while they're on vigabatrin.

If vigabatrin is not effective, for it doesn't always work in every patient with TSC, then ACTH or oral steroids, prednisolone, can be added if no improvement is seen after 2 weeks. If the spasms continue, other options can be considered, including medications used to treat spasms such as valproate, zonisamide, topiramate. Also, consider cannabidiol and everolimus, although their efficacy in treating infantile spasms has not really been established. In addition, dietary therapy, the classic ketogenic diet, can be effective in treating spasms in TSC, as well as other etiologies. And since tuberous sclerosis is a focal epilepsy, if spasms are refractory, then patients should be evaluated to see if epilepsy surgery would be a possible option.

Children with behavioral, developmental, and cognitive challenges, may be more sensitive to side effects of medication, as with other children with epilepsy. So when talking to parents of a baby with TSC, it's very important not only to talk about the epilepsy, the focal seizures, but also, extremely important to make them aware of the possibility of infantile spasms. Although infantile spasms are common in TSC, interestingly, about a third of babies with TSC who develop infantile spasms will have a normal cognitive outcome. And it's been shown that the early identification and effective treatment of the spasms is a key variable in the prognosis for that child.

Now let's take a look at our next case.

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.

Dr Thiele: About 20% of children with tuberous sclerosis will go on to develop LGS. LGS is an epilepsy syndrome due to many, many etiologies. It's a syndrome we recognize as typically being highly refractory, and composed of mixed seizure types, including tonic seizures, which are really required for the diagnosis of Lennox-Gastaut, atypical absence, tonic-clonic seizures, and drop attacks. 

Lennox-Gastaut, typically, is highly refractory to medications. A first-line therapy, once LGS is recognized, is valproate, oftentimes in combination with lamotrigine or clobazam. Several medications have now been FDA approved for the treatment of seizures associated with LGS, including cannabidiol, rufinamide, fenfluramine, and topiramate. In addition to anti-seizure medications, non-pharmacologic therapies are often considered in the treatment of LGS, including the ketogenic diet, which can be very effective. Surgery, depending on the etiology of LGS in a patient. And surgery would be an option for patients with TSC, since as again, it is a focal epilepsy. And then also, the vagus nerve stimulation (VNS) is shown to be effective in treating seizures in the setting of LGS, in patients with TSC, as well as other etiologies. 

So it's important, if a baby or child with TSC starts to develop the various seizure types we see in Lennox-Gastaut syndrome, and their EEG shows the typical features we see in LGS. And again, kind of required for the diagnosis, and that's the slow spike and wave, 1 to 2 Hz slow spike and wave on EEG, as well as the paroxysmal fast activity during sleep. 

And it's important to discuss with the family that these seizures can often be difficult to control. These patients often end up on polytherapy, meaning more than one anti-seizure medication, often in combination with non-pharmacologic therapies. And it is also important to discuss that children who develop LGS are at risk for comorbid intellectual disabilities as other difficulties.  

Thank you very much for participating in this activity. Please continue on to answer questions that follow and complete the evaluation. 

This transcript has not been copyedited.

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