Empowering epilepsy care: opportunities in managing rare epilepsy syndromes

Matsumoto JH, Wirrell EC. Empowering epilepsy care: opportunities for neurologists and pediatricians in managing rare epilepsy syndromes. Practical Neurology (US). 2024;23(9):43-46.

To help educate adult and pediatric neurologists on the management of epilepsy syndromes, Practical Neurology’s Publisher, Wendy Terry, spoke with two epileptologists, Joyce H. Matsumoto, MD, University of California, Los Angeles, David Geffen School of Medicine, and Elaine C. Wirrell, MD, Mayo Clinic Alix School of Medicine, about their experiences diagnosing and treating patients with rare forms of epilepsy.

This article emphasizes the critical role of general neurologists and pediatricians in recognizing and diagnosing rare epilepsy syndromes, highlighting the importance of thorough patient history, video documentation, genetic testing, and collaboration with epilepsy specialists to improve patient outcomes and management strategies.

Why Should General Neurologists and Pediatricians Take the Time to Diagnose Patients Living with Rare Forms of Epilepsy Syndromes?

Dr. Wirrell: For many neurologists, there’s a perception that persons diagnosed with early life epilepsies, particularly one of the developmental and epileptic encephalopathies (DEE) such as Lennox-Gastaut syndrome (LGS), have a drug-resistant epilepsy, and there’s not a lot of treatment options available. Clinicians may ask themselves, “So what am I really going to do to make a difference with this patient?” I would argue that we now have a number of new therapies that have been shown to be efficacious in clinical studies. I believe we can make a difference in reducing seizure burden in these patients, although the individual may not be seizure-free altogether.

Dr. Matsumoto: I would add that as we are gaining more knowledge of the different rare genetic conditions that can lead to epilepsy, clarifying the genetic diagnosis can, in unexpected ways, help identify other organ systems that may be involved. These details can help guide treatment and management options.

The more information we gather from these patients and their loved ones about their experience, the more we learn about these conditions. This understanding can lead to better treatments and outcomes for these patients. It’s also helpful for us to be better able to explain to family members what might happen during the course of their life with this illness. Of course, it’s always important to clarify to family members that not everything that they read about the condition is going to happen with their child. But it can be validating for them to be able to say, “Okay, other people have experienced this. And it’s not that we’re doing anything wrong.” So I think that it does help to have as much information as possible, including genetic test results. It can help even older patients who have been living with epilepsy for a long time. When we have been able to do genetic testing for people where it wasn’t available years ago when they were going through the initial diagnostic journey and we find a genetic diagnosis, it helps them.

Can We Walk Through the Overall Diagnosis Process for Patients and the Challenges Associated with that Process?

Dr. Wirrell: In terms of diagnosis, one of the challenges is that some of our DEEs, such as LGS, really take time to evolve. Research has shown that LGS, for example, often takes 2 to 3 years to evolve and for the patient to manifest all of the diagnostic criteria. This can be a tough time for families, as they see their child having a lot of seizures and not progressing developmentally. We know the seizure activity will likely be challenging, and we’re certainly concerned that they’re possibly moving towards a LGS diagnosis, but they’re very young, and they haven’t met the clinical criteria. So, it can be extraordinarily difficult sometimes to provide an accurate early diagnosis.

Additionally, some rare epilepsies will change as the child ages. For example, with Dravet syndrome, there is a dramatic difference in how this syndrome appears when you compare a 1-year-old child with this condition with a 20-year-old young adult. For a child with Dravet syndrome at 1 years old, they’re having prolonged convulsive seizures, often hemi-convulsive, switching sides from one seizure to the next. Although the seizures may not be that frequent, every time they have a seizure, it’s prolonged or it’s status epilepticus.

Then, as the patient moves forward into their teens or in their twenties, you don’t see those prolonged seizures very frequently, if at all. You often see more frequent, but briefer, tonic-clonic seizures or convulsive seizures that happen during sleep. So we do see that sort of evolution with time as well. That can be challenging for some of the general neurologists to appreciate certain characteristic features unless you have knowledge of that early patient history and familiarity with the varied presentations seen with genetic and rarer epilepsies.

Dr. Matsumoto: The diagnostic process can be challenging in situations involving the reevaluation of patient records to ensure diagnostic accuracy. For older patients, it is difficult to obtain electroencephalogram (EEG) test results from a long time ago when a lot of the findings might have been more obvious, especially if you’re dealing with an older child. There is also sometimes a challenge in cases in which the initial EEG tests or initial evaluations were performed by somebody who’s not familiar with LGS or familiar with children who have epilepsy that is difficult to control.

The reports alone may not describe the patient history, test results, and presentation in the way that we would expect them to. So sometimes it can be difficult to read between the lines and say, “Oh, this is what they were probably seeing,” because getting the raw data can be very difficult.

How Can the Diagnostic Process Be Improved for Patients Living with Rare Forms of Epilepsy?

Dr. Wirrell: What’s important to recognize is that for most patients, their first contact after they develop seizures is going to be with a general neurologist. So, it is essential that general neurologists are empowered to recognize relevant clues found in children with DEEs. They don’t necessarily need to recognize the features associated with every rare genetic epilepsy but they need to recognize what appears to be a DEE: children coming in with early life or early onset seizures, with seizures that are very frequent, seizures that appear drug resistant, and with certain types of seizures like spasms or tonic seizures or atonic seizures.

Additionally, children with DEEs often have very abnormal EEG test results, with marked slowing, high amplitude, and frequent discharges. Children have onset of developmental disabilities that may predate or certainly can worsen when seizures become more frequent. So, I think seeing children and looking for all of those clues and putting that together and saying, “Boy, this looks like a child with a DEE.”

Dr. Matsumoto: When we talk about trying to empower general neurologists, it’s also important to realize that a lot of these patients may not be seen by child neurologists for some of their initial evaluations. They may be seen by an adult epileptologist who is trying to do their best because of the shortage of pediatric specialists. What is important for all involved, whether general neurologists or pediatricians, is to understand some of the warning signs so that they can be empowered to say, “Okay, in this patient, there’s something very wrong, and they need to be seen more urgently.”

I believe that it’s important for us as epileptologists to be in contact with pediatricians and general neurologists and be able to say, “Hey, these are the things that you really need to tell us about,” because time is of the essence.

Helping our colleagues understand what we are looking for, and identifying concerns that we need to evaluate quickly are a couple of the biggest things that they can do to help the diagnostic process. This includes patients with developmental regression with a patient history that would predispose them to perhaps having a higher risk of seizures, a history of a challenging birth or hypoxic injury, and presentations that involve documented movements that happen very similarly in clusters around the same time of day or in certain situations that cannot be explained otherwise.

Dr. Wirrell: I think the other thing that can be helpful is to ask parents to record a video. Many times, we will get called by outside providers who will send a video, and they’ll say, “Geez, I’m a little worried about this kid.” And you look at the video, and say “Yes, that’s clearly spasms and we need to prioritize that child,” or “No, we don’t really need to worry about that, that looks more like shuddering or more like a tic.” Videos can be very helpful tools that can easily be sent around and reviewed.

What Recommendations Would You Share with General Neurologists or Pediatricians Who Are Unsure How to Best Manage a Patient’s Symptoms Once Confirming a Diagnosis?

Dr. Matsumoto: Initiate the referral process early and establish a collaborative relationship with an epilepsy center or a specialist who frequently manages complex cases. This partnership can enhance your ability to provide comprehensive care for patients with epilepsy. Although referral to a specialized center is crucial for certain cases, maintaining continuity of care at the local level is equally important. Many families prefer having a local physician they can consult regularly. As you follow these patients over time, you may not always feel comfortable making all treatment decisions, but you can monitor their progress, familiarize yourself with various medications, and understand the range of available interventions.

By combining local follow-up with specialized care, you can provide more comprehensive and coordinated management for your patients with epilepsy. This approach allows you to gain experience with complex cases while ensuring your patients receive optimal care.

Dr. Wirrell: Effective management of pediatric epilepsy often requires a collaborative approach involving a pediatric epileptologist and local neurologist. This multidisciplinary partnership is crucial for providing comprehensive care, especially for medically fragile children who may find long travel times for frequent visits challenging. Although telemedicine has alleviated some of these challenges, having a local neurologist familiar with the patient’s case remains critical for everything from managing potential seizure emergencies to providing timely interventions.

General neurologists should recognize that epilepsy management extends beyond seizure control. Yes, seizure reduction is a primary goal, but addressing comorbidities is equally important. When considering treatment modifications, clinicians should carefully weigh the potential benefits against possible risks and strive to achieve an optimal balance that considers the patient’s overall well-being. These should not only focus on seizure control but also prioritize the child’s cognitive function, learning potential, and overall quality of life for both the patient and their family. By considering these factors, clinicians can develop a more holistic treatment plan that addresses the complex needs of pediatric epilepsy patients.

What Diagnostic Tools or Tests Are Available for General Neurologists or Pediatricians to Identify Patients with Rare Forms of Seizure Disorders More Easily?

Dr. Matsumoto: I think that genetic testing is an important tool to know about and understand. It keeps evolving, and the availability keeps on improving. Exome sequencing, for example, is much more readily available than in the past. I think that genetic testing has really helped us in trying to better categorize people and to understand conditions, such as LGS, better.

Dr. Wirrell: With respect to EEG, I think one of the challenges is that the younger the child or infant, the tougher the EEG can be to interpret, because general neurologists may be more familiar with reading adult EEG tests in which there’s a lot less variability. It’s important to appreciate what is normal and what is abnormal and have the confidence if there is a pattern like hypsarrhythmia present to really recognize that and call it out. Identifying such patterns will then alert everyone to think about a potential diagnosis of infantile spasms. For infants who have potential for DEEs if they’re having frequent seizures or there’s developmental regression or presentations like that, it’s important to have the EEG test results reviewed by someone with expertise in pediatric epilepsy.

If We Improve the Diagnostic Process, What’s the Impact for the Patient and the Caregiver?

Dr. Wirrell: One of the impacts of genetic testing as a first-line test for those with unexplained epilepsy is that it can lead to an earlier diagnosis. With an earlier diagnosis, we can then select the most efficacious therapy for the specific condition, avoiding trial and error with medications that are contraindicated or that may potentially worsen seizures. Early intervention can mitigate the impact of frequent seizures on a child’s development. Although some developmental issues may be related to the underlying cause of epilepsy, others are related to the epileptic process itself, including frequent seizures and EEG discharges. Controlling seizures earlier can mean 6 months or even 1 year of less damage on the brain caused by seizures, potentially leading to better long-term developmental outcomes for the child.

With respect to genetic testing, having a definitive diagnosis provides parents with answers, alleviating guilt and reducing frustration. You can give the parents an answer and say, “Here is what caused this. It doesn’t relate to anything you did or didn’t do during the pregnancy.” It helps them understand their child’s condition and be able to connect with support networks for others with rare epilepsies.

By addressing these factors through early diagnosis and appropriate treatment, we can potentially improve both seizure control and overall developmental outcomes for children with epilepsy.

Dr. Matsumoto: I agree with Dr. Wirrell that improving the diagnostic process in epilepsy can have significant benefits, especially for parents. It can reduce parental frustration, for example. Validating parents’ concerns and instincts when they notice something is wrong with their child can be tremendously helpful. This is especially important if they were previously told not to worry about certain movements they have been observing. An earlier diagnosis also can help parents avoid feelings of guilt or regret for not bringing up concerns sooner. Lastly, an accurate and timely diagnosis helps set realistic expectations for both parents and healthcare providers regarding treatment efficacy and prognosis.

I want to underscore Dr. Wirrell’s comments about an early diagnosis leading to earlier treatment initiation, more targeted treatments, and better long-term outcomes. There is evidence supporting better outcomes when definitive treatment begins sooner. Although treatments may not work for everyone, having the opportunity to try appropriate interventions earlier is valuable.

Conclusion

In conclusion, the diagnosis and management of rare forms of epilepsy syndromes present significant challenges for healthcare providers. However, with advancements in genetic testing, improved diagnostic tools, and a growing understanding of these conditions, there is hope for better patient outcomes. For example, the Refractory Epilepsy Screening Tool for LGS (REST-LGS) is a validated screening tool that can help healthcare providers who don’t encounter many LGS patients identify and diagnose the condition.

General neurologists and pediatricians play a crucial role in recognizing early signs and symptoms, and collaboration with epilepsy specialists is essential. The importance of thorough patient history, video documentation of seizures, and appropriate EEG interpretation cannot be overstated. As research progresses and new therapies emerge, including potential disease-modifying treatments, the outlook for patients with rare epilepsies continues to improve. By staying informed about the latest developments and guidelines, healthcare providers can make a meaningful difference in the lives of these patients and their families.