As children with pediatric epileptic encephalopathies grow into adults, they and their caregivers face unique challenges before, during, and after the transition from a pediatric neurologist's care to an adult neurologist's care. This transition is not to be mistaken as a single moment in time; it is a journey to be thoughtfully approached and planned.

The successful transition of care depends on close coordination among the key players involved: the pediatric neurologist, the person with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS), their family or caregiver, and the adult neurologist. Medscape recently sat with renowned advocates and thought leaders, Lawrence Brown, MD (child neurologist); Gregory Cascino, MD (adult neurologist); and Christina SanInocencio, MS (executive director, LGS Foundation) for a colorful discussion of their personal experiences as key players in care transition, as well as an exploration of the 8 common principles for transitioning that guide them today.^[1] (Figure 1.) Let's get started.

Figure 1. Eight Common Principles to Assist With the Transition of Care

Medscape: The first of the 8 common principles to assist with transition of care is the "Expectation of Transition (Figure 2)." What expectations are important to set with the patient/caregiver?

Figure 2. Expection of Transition

Lawrence W. Brown, MD: It is important to convey the reality that the child will grow into an adult and that, at some point, care will need to shift from a pediatric neurologist to an adult neurologist, even if the patient has significant intellectual disability. Also, we should set the expectation that transition of care is a long process that takes place over many years. Transition of care is not simply the transfer of care at a single moment in time. Transition is a process to help the patient and family prepare for adulthood and that moment in time, which we call transfer. I believe that my fellow panel member, Ms SanInocencio, who is both a caregiver for her adult brother with LGS and a leader in the field, has done some research in this area.

Christina SanInocencio, MS: Yes, thank you, Dr Brown. The research Dr Brown is referring to was an institutional review board-approved qualitative study conducted in 2018 to understand how caregivers view the transition process (unpublished). What we found was that, even in a level 4 academic center, many caregivers of youth with complex epilepsy, including intellectual disability, aren't being told about transition or being led through the transition process. Consequently, these children or adults fall through the cracks. There is a real disconnect between how well clinicians think that they are informing and guiding families and the experience of the family during the transition process.

Many of the caregivers interviewed who did have conversations about transitioning weren't doing so until almost the patient's 18th birthday. At this late stage, there isn't time to prepare for the medical transition process, or any of the other aspects of the transition. It's not to say that it's the clinician's responsibility to talk to the caregiver about things like day programs and what happens after they turn 21, or individualized education plans. Caregivers don't expect that from the neurologist but, rather, to broach the topic earlier and to think more holistically, beyond just the medical component, in terms of the different aspects of transitioning that the individual will go through and the time that it requires.

Medscape: When is the appropriate time and age to consider transition and transfer of care?

Dr Brown: One could say that the patient and caregiver should be made aware of the transition process as soon as the diagnosis is made, so that there's no confusion it will occur; realistically, however, we need to begin the work with adolescents. The first time that I see a patient in the office or hospital, whether they are an infant or age 16, I want the caregiver to understand that, all things considered, we are ultimately working toward self-management and taking on adult responsibilities.

Medscape: How do the seizure characteristics of LGS/DS typically change and evolve as a patient moves from childhood to adulthood?

Gregory D. Cascino, MD: There is a variable modification in seizure tendency and electroencephalographic (EEG) patterns as individuals with LGS mature into adulthood.^[2] Patients may experience a change in seizure characteristics with the appearance of atypical absence and focal impaired-awareness seizures. Tonic, atonic, and tonic-clonic seizures may persist. The patients are still at risk for injury with epileptic drop attacks. Nocturnal tonic seizures may be frequent in adults. The typical EEG-identified generalized slow spike-and-wave pattern of LGS may be less prominent. The electroencephalogram in adults may show multifocal spikes and generalized atypical spike-and-wave discharges. Patients with DS in adulthood may have brief nocturnal tonic-clonic seizures. They may be less likely to experience absence and myoclonic seizures or status epilepticus.

Dr Brown: Generally speaking, few of us have a lot of experience with DS in adulthood because the diagnosis doesn't go back more than a generation. It does appear, however, that the seizure types continue as both generalized and focal and that the sensitivity to heat-induced seizures seems to reduce over time. Although the rate of sudden unexpected death in epilepsy (SUDEP) is high in both children and adults with LGS or DS, many people believe that the risk of SUDEP actually goes up in adulthood. It's a very serious concern, especially in patients who have drug-resistant epilepsy.

Medscape: What healthcare issues commonly occur in adults with LGS or DS that are not seizure-related?

Dr Cascino: Most of the nonseizure issues seen with LGS or DS in adulthood are psychosocial.^[3-5] About half of patients with LGS develop behavioral problems over time, including hyperactivity, aggressiveness, and autistic features.^[5] Adolescents and adults may also develop other comorbid conditions, such as sleep disorders (sleep apnea), cardiac abnormalities, depression, and anxiety.^[3,5,6] These issues can undermine quality of life to the same degree as the seizure disorder.

Side effects from antiseizure medications are also a common healthcare issue, including risk for fracture, weight gain, sedation, and cognitive impairment.^[7] Commonly, patients will start an antiseizure medication and then continue to have a drug-resistant seizure disorder, but the healthcare provider does not discontinue the ineffective therapy. Patients can be unsteady or lethargic and have nystagmus, ataxia, and dysarthria; these findings may be related to the use of multiple antiseizure medications.

Medscape: "Yearly Self-Management Assessment (Figure 3)" and an "Annual Discussion of Medical Condition and Age-Appropriate Concerns (Figure 4)" are the second and third of the 8 guiding principles.^[1] How do you broach these discussions and assess a youth's self-management skills?

Figure 3. Yearly Self-Management Assessment

Figure 4. Annual Discussion of Medical Condition and Age-Appropriate Concerns

Dr Brown: The goal is to get the individual as independent as possible, regardless of cognitive level. Even if a child is slow in learning, they will learn. So we try to reassess self-management potential every year. Attention to the caregivers' ability to manage evolving care demands is also advisable. Topics for annual discussion with the patient and caregivers are listed in the Table; however, we must use both developmentally and age-appropriate parameters. For example, we wouldn't discuss driving or alcohol if a child has major intellectual disabilities. We'd discuss legal issues with their parents, such as guardianship or power of attorney. For every patient, we address education, sexuality, sleep, etc.

Medscape: From a healthcare provider perspective, what are typical patient/caregiver goals for adult services?

Dr Cascino: When I see a patient and their family or caregiver for the first time as the adult neurologist, I usually set the goal as no seizures, no side effects, and no lifestyle limitations. This is regardless of the patient's neurologic disorder and comorbidities. Now, obviously, you have to individualize your goals for individual patients, but reducing seizure frequency is an undeniable goal, especially if the patient is having physical trauma, atonic seizures, or tonic-clonic seizures or is at significant risk for SUDEP.

The concept of reducing seizure activity while eliminating the adverse effects of treatment is certainly attractive to patients and caregivers. Many patients arrive at the adult epilepsy clinic with significant neurocognitive adverse effects caused by their multiple antiseizure medications, yet they are still having intractable seizures. This is kind of the rock and a hard place -- the need to balance the medicine and the seizures. Again, our goal is to improve their seizure control, minimize their side effects, and improve their quality of life -- no seizures, no adverse effects, and no lifestyle limitations.

Dr Brown: From the point of view of a child neurologist, I would agree that no matter how complex the medical condition of a patient, the first goal is no seizures and no adverse effects. Aiming for a lesser goal would come as a compromise to the patient's quality of life. Providing the best seizure control is often the key to success in caring for these patients who also have academic challenges, social problems, and behavioral issues as a result of their disease. The chaos of frequent epileptic seizures can have an adverse impact on everything -- from learning, to sleep, to socialization. So we start with seizure control, but we also emphasize the other holistic qualities that make life worthwhile.

My goal for a youth with LGS or DS is to get them as independent as possible and equipped with self-management skills prior to the completion of transition and transfer to adult services. For example, I have kids with significant intellectual disability who learn how to remind their parents to give them their medicine if they forget.

Medscape: Let's hear from Ms SanInocencio, from a caregiver perspective, what are the patient's goals for adult services?

Ms SanInocencio: Yes, I agree, reducing seizures, minimizing adverse effects, and a focus on independence are important goals. But, when we talk about patients with catastrophic epilepsies, such as LGS or DS, our goal statements tend to appropriately end with the words "as much as possible." We're more focused on reducing the seizures "as much as possible" and allowing the individual to thrive in terms of quality of life.

Another goal for families is to minimize the disruption and unease that their loved one can feel when moving from a pediatric to an adult care setting. Most individuals with LGS and DS are cognitively still in either infancy or early childhood, but they have big, grown, adult bodies. It can be very scary for the individual to enter an adult care setting when they've grown accustomed to being catered to in the pediatric setting based on their cognitive age, rather than their actual age. This change can be very scary for the caregiver, too.

Medscape: What can clinicians do to create a better experience for the patient and the family?

Ms Sanlnocencio: I think the biggest things are to communicate and to empower the caregivers to start planning early. I'll just give you a quick anecdote with my brother, and it also aligns with the fourth principle for transition, "Evaluation of Legal Competency (Figure 5)."^[1] We were never told that we had to transition. We were never told that we needed to have legal guardianship, nor were we informed about any of the other aspects of transitioning, and my brother was being seen at a level 4 center. He was admitted into the psychiatric ward for behaviors, and we were not able to get him out because he was over the age of 18 (he was involuntarily committed). We didn't know that legal guardianship was necessary to have power over his medical decisions. Based on conversations with other LGS families, I found that this type of surprise is not uncommon.

Figure 5. Evaluation of Legal Competency

Clinicians can make the transition experience to adult services better by empowering families to start planning early, by communicating next steps, and by explaining what to expect in an adult setting. In general, better communication from the clinicians and between the clinicians will make the transition experience less scary for everyone.

Dr Brown: I think the other important thing is that we involve people beyond the neurologist. We need to think as a team. For example, at our center, we have nurses who do a phenomenal job readying the family and coordinating with our social workers regarding school and community services.

Medscape: What is the role of the primary care physician (PCP) in managing transition of care to an adult neurologist?

Dr Cascino: PCPs play a pivotal role throughout a patient's care, and I think we've probably underestimated their significance in the transfer and transition process. I find that the PCP's role has been undervalued, which is unfortunate. As Ms SanInocencio just mentioned, too often the patient feels like they're leaving one home where they felt very comfortable, which is child neurology, and then they're kind of abandoned. They arrive in adult neurology without any continuity of care, and that's a very difficult situation for the patient and their caregivers. In this sense, PCPs have an essential role to play and should participate in the entire transition process beginning with discussions at early ages.

Dr Brown: I agree. Many of the children that Dr Cascino will receive as patients at ages 18 to 21 years will identify the pediatric neurologist as their medical home. Whereas, in fact, all patients would be better served with the pediatrician or family physician as the central authority figure for their comprehensive care. This would be most important for patients who have complex medical conditions, such as LGS or DS, who require a higher degree of consistency in their comprehensive care and continual support. When we wrote the 8 common principles of good transition for neurology, we tried to emphasize the PCP as the medical home.^[1]

Figure 6. Annual Review of Transition Plan of Care

Dr Brown: The fifth transition principle (Figure 6), "Annual Review of the Transition Care Plan," focuses on developing and maintaining a comprehensive transition plan through the coordinated efforts of the child neurologist, school personnel, nurses, vocational specialists, social workers, caregivers, and the PCP who serves as the medical home.^[1] Ideally, the plan should address healthcare, financial and legal concerns, primary care, other specialty care, education to employment, housing, and community services. The child neurology team is responsible for the neurologic component of this plan, which is written into the sixth principle of transition, "Child Neurology Team Responsibilities" (Figure 7).

Figure 7. Child Neurology Team Responsibilities

Ms SanInocencio: I'll just add that many families rely on that medical home to help coordinate care, in general, and as they go through the transition process. From a caregiver perspective, there seems to be a fragmentation of care between PCPs and neurologists, and, for many, communication between the PCP and the neurologist is nonexistent. We have found that many families think of their neurologist as the center of their child's healthcare, and many are comfortable directing questions related to different specialties (eg, gastroenterology, psychiatry) to their neurologist.

Medscape: What information should the child neurologist be responsible for providing in the transition of care plan?

Dr Cascino: This information should include past and present issues related to the patient's seizure disorder, including frequency and seizure types, and the patient's antiseizure medication history -- not just that they've received 14 medications that have either been ineffective or poorly tolerated, but whether adherence was good and if they had a beneficial response. Let the adult neurologists know if you are in the middle of changing or tapering medications.

I also find it very helpful to know ahead of time the expectations, concerns, and treatment biases of the parents or the caregivers. That makes the initial contact a lot easier because you have a better understanding of where they're coming from.

Then, finally, describe the support system. Who is the legal guardian? It can be complicated. The patient may be living in a group home; the parents may be legal guardians but have little contact with a patient. I always ask my nurse, "Who is in the room?" The patient may be accompanied by an attendant who has very little knowledge of the patient's medical history. It's important to know who you're talking to, or rather who you need to talk to, particularly if there are major issues to be addressed.

Medscape: We know that seizures associated with LGS or DS are usually resistant to treatment; that said, what does the future of treatment look like?

Dr Brown: This is a changing landscape with new approaches that have recently been introduced and that are being rigorously evaluated as we speak. We have more treatment options for LGS than DS, but there is still an incredible unmet need. Stiripentol was approved by the FDA in August 2018 for the treatment of seizures associated with DS.^[8] A highly-purified, plant-derived cannabidiol oral solution was FDA approved in June 2018 for the treatment of seizures associated with DS or LGS.^[9] Compared with placebo, another agent, fenfluramine, significantly reduced convulsive seizure frequency in patients with DS and is actively being studied in LGS for the treatment of seizures.^[10-12]

Dr Cascino: Potential treatment options such as diet therapy (eg, ketogenic diet and low glycemic index diet) and neuromodulation (eg, vagus nerve stimulation and deep brain stimulation) may also warrant consideration.^[13-15] Neuromodulation therapy is presently approved for management of drug-resistant focal epilepsy.^[15-18]

Medscape: Aligned with the seventh principle supporting a good transition (Figure 8),^[1] what are best practices for identifying an adult provider?

Figure 8. Identification of Adult Provider

Dr Brown: This is a real challenge, and pediatric neurologists try hard to direct patients to appropriate providers. Gaining access to an adult epileptologist as a new patient can take several months, and it's not always intuitive who may be the best fit. The Epilepsy Foundation is fantastic about providing resources and connecting doctors in the community who are interested in this area. Most importantly, patients with LGS or DS require very complex care and preferably should be referred to clinicians who are part of a comprehensive epilepsy care team, including a neurologist who can provide up-to-date care and who is comfortable with the rapidly changing technology, pharmacology, and genetics of epilepsy.

Medscape: What are key considerations once the patient's "Transfer [is] Complete," the eighth and final principle (Figure 9)?

Figure 9. Transfer Complete

Dr Cascino: One is the education process. We should not presume the patient/caregiver received appropriate education in terms of management of seizures, what to do if they have a seizure, safety at home and in the workplace, etc. Unfortunately, caregivers can retain misconceptions and wrong information. We spend a fair amount of time making sure that the education issues have been resolved.

Dr Brown: From my point of view, I would like the adult neurologist to know that the child neurologist is there to help them to understand the patient's story and to answer any questions. I would like the family to know that, although we have passed the baton, we will always be there to share in life's ongoing journey.

Clinical pearls

• LGS and DS are 2 rare, severe, treatment-resistant epileptic encephalopathies with onset typically in childhood. Many patients with LGS or DS live into adulthood. Transition is the process of preparing families and children for the move from a pediatric to an adult healthcare system.
• Many patients with LGS and DS continue to receive insufficient transition planning. As clinicians, we can improve the transition process by starting transition planning earlier, engaging caregivers in discussions regarding transition earlier, and empowering the caregiver to plan ahead.
• Effective communication between caregivers and patients, as well as among the multidisciplinary team, is essential for preventing gaps in care transition. The transition process must be seen holistically, including medical, financial, and legal considerations.
• In addition to severe seizures, LGS and DS are associated with numerous psychosocial and comorbid features that complicate their management. A medical home must be established to meet these patients' complex physical and mental healthcare needs through a team-based approach to care.
• Although transitioning care can be a complicated process, there are steps to ensure appropriate communication and consistent care during the transition period. A consensus document developed by an independent panel of experts and published in the journal Neurology provides guiding principles to transitioning children to the adult healthcare system.^[1] Tools to help practices implement the 8 common principles are also available online.^[19]