Epilepsy Essentials: Complex Epilepsy Syndromes in Adults

Most adults with complex epilepsy syndromes (eg, tuberous sclerosis complex [TSC] or Lennox-Gastaut syndrome) are diagnosed in childhood. Thus, diagnostic dilemmas in these patients are uncommonly encountered by the adult neurologist. The true complexities of these conditions during adulthood are twofold. First is that most individuals have already been treated with multiple antiseizure medications (ASMs), adding challenges to treatment planning. Second is that many of these individuals also live with some degree of intellectual disability, and so it’s not just their seizures that are a concern but rather their overall health and quality of life—the ability to have some degree of independence, to work, and to be able to do things for themselves. This second challenge requires actively engaging with family members or other caregivers in addition to the individual who is living with the condition.

Transitioning from Pediatric to Adult Neurology

Among the most important aspects of caring for adults with complex epilepsy syndromes is assisting them in making the transition from pediatric to adult care. Firstly, in terms of treatment, it is important to remember that some individuals in early adulthood may still grow, and dosages may thus continue to need adjusting. Secondly, as when any individual is entering adulthood, fostering independence is key goal to maintaining quality of life. In complex epilepsy, because the physician is working with people who often have intellectual disabilities, fostering as much independence as possible is the goal. Parents and other care partners can be engaged in this, encouraging the person with epilepsy to do as much as they can.

After the team approach with care partners, however, it is important to also interact with the patient without care partners in the room. The clinician should then ask what questions the patient has and what they would like to discuss or not discuss with their care partners present vs by themself. Useful dialog may include stating, “This is a private conversation between you and me,” and asking, “How do you feel? What are you worried about? What questions do you have” This is also an opportunity for the clinician to discuss their medicines and side effects from the patient’s unique perspective. Taking the time to ask these questions fosters independence, because simply creating the expectation that patients are responsible to answer questions can allow them to sense that they are in charge of themselves in relation to self-care.

Creating a Treatment Plan

When dealing with complex situations, try to differentiate between treating someone’s seizures and managing someone’s epilepsy and overall care. In a more global sense, my view for people with complex epilepsy syndromes is not to stay focused on their seizures alone, but to try and manage the epilepsy syndrome that has an impact on their overall health. This requires keeping in mind the complexity of their condition and other medications (nonASMs) they may be taking, as well as their intellectual needs and day-to-day needs for independence. The goal in epilepsy management is not just zero seizures, but also zero side effects, and because no medication yet achieves this, we have to balance between stopping seizures and maintaining function. This requires understanding what being “functional” means to the individual receiving treatment and designing a treatment plan for the specific individual and their needs and concerns.

As discussed, most adults with TSC, LGS, or other complex epilepsy syndromes have tried multiple ASMs. Discussing each ASM individually is essential to developing an individualized treatment plan. The clinician should seek to understand whether a medication was discontinued because it was ineffective at stopping seizures or because of side effects or other intolerance to the medication. It can be difficult for patients to remember the circumstances of discontinuation, and this is where relying on care partners and prior medical records becomes important.

I also try to tease out what other medications were being taken at the time another drug was discontinued to consider if an ASM was stopped because of drug-drug interactions. For example, if an individual was taking carbamazepine and then lacosamide was added, they may have felt intoxicated and lethargic or experienced ataxia because both block sodium channels and so have similar side effects. This may lead to discontinuation of the added ASM rather than the first that wasn’t providing adequate seizure control. When this is the case, it may be worth trying a particular ASM a second time while managing other medications with a goal of balancing seizure control with tolerable side effects.

Similarly, when the Food and Drug Administration (FDA)-approved prescription cannabidiol (pCBD; Epidiolex) is added to a treatment plan for LGS or TSC, it is important to consider whether a person is taking clobazam. Because pCBD increases clobazam levels, it can increase the side effects of clobazam. If this is not understood, pCBD might be considered the cause of intolerance, when instead decreasing the clobazam dose could afford the patient the benefit of both ASMs without the increased side effects.

Starting New Medications

It is important to understand that the package insert describes what worked for a population in clinical trials. Individuals in a real-world setting may require different dosages. I always start at a low dosage for people with complex epilepsy syndromes. Adults with TSC or LGS have typically been dealing with epilepsy for decades and adding a medication is not as urgent as if someone were having a seizure in the emergency department or intensive care unit. It often takes 2 to 3 months to safely add a medication and adjust not just other ASMs, but all concomitant medications.

During titration, it may be necessary to lower the dose of a new medication just a little, then adjust a concomitant medication, and then increase the new drug again. This balancing approach can allow the clinician to find the sweet spot that is best for the individual, which may not be zero seizures for every person. This is not because we don’t want to get everyone to zero seizures, but rather that we want to preserve their quality of life while getting as close to zero seizures as possible.

Setting realistic expectations means addressing that in order to have quality of life when not having seizures may mean accepting an occasional seizure. I also insist that patients contact me and my staff if they are considering adjustments to their medications, rather than making changes on their own. Sometimes a patient or care partner will consider changing a medication just to see what happens. I remind people that this is like changing the recipe for Coca-Cola, which was a huge flop in the 1980s or a Michelin star chef changing their award-winning dish. This is not to say that medications should never be changed; medicine should be changed in response to a clinical change or a new option becoming available.

Helping Patients Stick to Treatments

One of the most important elements of helping patients take their medications properly is making sure that they and their care partners have as much understanding as possible of the particular medications they are taking. It is important to combat the wealth of misinformation available on social media and elsewhere. For example, although vigabatrin and cannabidiol are considered higher potency medications with potentially higher risks, they are generally safe and effective. The risks vs benefits need to be considered within the context of the individual patient’s situation.

This becomes even more complex when discussing pCBD, a treatment for which I’ve never before seen such a clamoring for before it was even available. Because of the widespread availability of unregulated CBD, many people will say they have tried CBD and found it ineffective. What we then have to discuss is that the CBD that can be bought in drugstores, dispensaries, and over the internet is not necessarily a reliable trial of CBD.

The variability of dosage in what they are purchasing is high, resulting in fluctuations in seizure control and side effects, which are also sometimes increased because of impurities in these products. To use nonprescription CBD, patients need to understand that there should be an available analysis for every lot they purchase because they could be getting much higher doses with the same volume (eg, 50 mg/mL or 10 mg/mL) from different lots of the same product. This a particular concern for people who were using the Charlotte’s Web products, a higher potency and more consistent over-the-counter product, but switched to cheaper less controlled products, or for anyone who tries to substitute pCBD with unregulated CBD. This is why I strongly encourage my patients to use pCBD rather than unregulated CBD.

Finally, taking the time to lean into my role as a physician caring for a person, not just their disease, makes it easier to encourage patients not to change medications or add uncontrolled products to their regimen. Showing compassion and empathy for what the patient is living through, by simply asking, “How are you doing with all this,” can be extremely effective. This allows other reasons for nonadherence to arise naturally in conversation, including affordability, dislike of taking pills, or difficulty swallowing pills.

Referrals & Telemedicine

LGS, TSC, and other complex epilepsy syndromes are indeed complex and to achieve the best possible outcomes for patients, a general neurologist may need to refer people with these conditions to epilepsy specialists and comprehensive epilepsy centers. As soon as a clinician feels worried or uncomfortable about the treatment plan or outcomes, referrals should be made. There is also a great time investment needed for managing these conditions and if the setting of care prevents that, referral should also be made.

Many epileptologists will refer patients back to the general neurologist once a treatment plan is stabilized. Additionally, telemedicine has increased the opportunities for collaboration between general neurologists and epileptologists. There are many fine general neurologists in rural Georgia, 4 hours away from where I practice. They see all neurologic conditions and may have less time for each patient than I do. It is now possible to set up a consultation via telemedicine—among the few good things to come out of the COVID-19 pandemic—during which I simply need to talk to the patient about their seizures, their side effects, and their medicines. I can prescribe a medicine, send a lab slip, and use my more focused epilepsy-centric knowledge to help this person without them or the care partner(s)having to take days off work. With telemedicine we now have the capability of reaching patients who were unreachable.

Summary

Caring for the person with epilepsy as a whole person with the goal of maintaining quality of life and approaching zero seizures is essential for management of complex epilepsy syndromes. Expecting people to use medications just because you, the doctor, said so is unrealistic. Patients and care partners need to know that you care about their overall well-being and not just their seizures. It is important not to become complacent because there is no cookbook for managing epilepsy. What happens for a population in a clinical trial (the package insert) may differ from what occurs for an individual person you are treating. Often there is greater efficacy than in clinical trials but more issues of tolerability and adherence.