The director of the pediatric epilepsy program at Boston Children’s Health Physicians shared his expertise with the challenges associated with diagnosing LGS, how the REST-LGS tool may help, and the need to collect more data.
Patients with rare epilepsies, such as Lennox-Gastaut syndrome (LGS), are often faced with challenges in their disease management, as these diseases are often difficult to treat and refractory by nature. Additionally, many individuals experience delays in diagnosis, often going some time without a clear understanding of the disease they are dealing with.
One novel attempt to address this challenge in LGS is the Refractory Epilepsy Screening Tool for LGS (REST-LGS), a diagnostic tool that can help healthcare providers accurately identify and help diagnose the rare disease. Developed based on years of patient experience and seizures, the tool helps in recognizing key consistencies across cases to distinguish between LGS and refractory epilepsy.
Steven Wolf, MD, pediatric neurologist, and director, pediatric epilepsy program, Boston Children’s Health Physicians, has been involved in the assessment and development of REST-LGS, and has plenty of clinical experience in treating the disease. To find out more about the state of care for patients with LGS, as well as the potential of improving the diagnostic process with REST-LGS, NeurologyLive® spoke with Wolf in depth.
Steven Wolf, MD: Well, I think LGS itself is such a mystery of a syndrome because there are so many different etiologies that cause Lennox-Gastaut syndrome, and the fact that many people miss the diagnosis. It's a rare epilepsy, and because it's got this very classic triad of multiple seizure types, developmental delay with the progression of cognitive delay as time goes on, and then this hallmark EEG signature—this slow spike and wave—that basically changes over time, the state of the art of Lennox-Gastaut has been sort of a moving target. As patients get older, they no longer look like the syndrome—the classic triad that I described. And as they get older, maybe they have fewer seizures—maybe only one type of seizure—but their developmental delay and their cognitive delay gets worse, so that becomes more of the main feature of the patient than just all the seizures. Then, the EEG findings sort of get muted and change, so the classic tried is gone.
The state of Lennox-Gastaut is really in flux because the patients change over time, and a lot of our neurologists don't realize that there is a change. I think, right now, where we're at is trying to reeducate all of ourselves on what LGS looks like over the lifespan, because our patients are getting excellent care and living longer and living better, so we now have older adults who were Lennox-Gastaut, who really still are Lennox-Gastaut. Things are changing because now there are more new medications for patients with Lennox-Gastaut than there were before, and if we aren't diagnosing them properly or keeping them in their syndrome properly, we might be missing opportunities.
So diagnosing Lennox-Gastaut hasn't changed too much because it's a clinical syndrome. But there are a few things that we've learned. One is in the genetics of patients with Lennox-Gastaut. We know about 15 to 20 different genetic mutations that are typically associated with patients who have Lennox-Gastaut, so it's really important that we do genetic testing early on to help the family with their diagnostic journey. But still, even if you have the genetics, you really want to look at what the clinical features are.
But what we saw when we were going around talking to adult neurologists and asking them about their Lennox-Gastaut patients, I had a roomful of adult neurologists saying, “Well, I don't have anybody with Lennox-Gastaut.” And I said, “Well, do you have anybody with developmental delay?” and they said, “Of course we do,” so we asked, “Do they have multiple seizure types?” They said that some do, and some don't. Those, probably, used to be what you would call classical Lennox-Gastaut, so we're trying to open up this idea of Lennox-Gastaut changing over time. That's why we developed this rating system, to help adult neurologists make the diagnosis when they are probably dealing with a patient with Lennox-Gastaut.
The screening tool has been tested. In 2019, we published an article in Epilepsy & Behavior with myself, the team at the University of Pennsylvania, as well as in Nashville, and us here at Boston Children's in New York City. Basically, we tested over 200 patients. We're looking at people who are epilepsy specialists, and then regular clinicians, and comparing the use of this tool and the reliability of the tool. We had a very good result, and this was the article in Epilepsy & Behavior back in 2019. What we did this year is we're testing it in people who are not neurologists. In residential homes and residential programs, trying to see the validity of using it in places where patients aren't classically diagnosed with Lennox-Gastaut syndrome, or they may be barely seeing neurologists. Essentially, testing in the real world. And that article is what is going to be coming out later this year.
As far as the screening tool, it's really a very simple questionnaire, where we recommend that you look just at the last 3 notes that are available in electronic medical records. The questions are pretty simple:
Each one of these gets a score of 1, and if you score over 8, then it's probable Lennox-Gastaut, and if you score over 11, then it's definitive Lennox-Gastaut. The first 4 questions are what we call the major criteria. The other ones are the minor criteria, but they seem to really add up to help the healthcare community to make a diagnosis. We also know that a lot of times, you don't have all the information because parents are passed away, or they're in a residential program, or we don't have the old paper chart because nobody converted it over. So this is a guestimation in the best way possible, with 8 of what we think are the most significant questions in these kinds of patients.
The words of wisdom are about how we do our documentation. What we really found is that we focus on what's going on at the moment. How are the seizures, how many seizures, and when was your last seizure? But what people frequently forget to do is have the old history in the notes. When did they first start having seizures? What medications have they been on in the past? What adverse effects were there from prior medications? We've been working with Zachary Greenspan, MD, MS, and the pediatric epilepsy learning healthcare systems out of Cornell—this is a nationwide program—trying to help standardize the questions that we ask epilepsy patients, but also trying to make sure that the old history travels with the patients from when they were young to when they're older. Especially in that transition from pediatrics to adult neurology, there is a need to know thatsome of the old details continue going forward. Some of that is on the onus of the child neurologist, in making sure that the adult neurologists get it, and, of course, then the adult neurologists, in making sure that the child neurologists are giving them this kind of information. Because of the electronic medical records, a lot of the old stuff gets lost. So, we make a really big point in our residential programs of trying to track down the old stuff and get the family to give us information, even though we're only seeing maybe a healthcare worker that's with these patients in the residential programs. That's the big pearl: How do we get the old stuff put into the new data so that goes with the patient forever?
I think I mentioned genetics in the past of this conversation, but I really think we need to change our mantra when we're working with patients with epilepsy. I think we need to be doing EEG, MRI, and genetics. As we collect more and more of these patients and collect more and more data, and sort of put these patients into little boxes, this DNA data is going to tell us a lot better of a story on how to predict patients over time with their seizures, and maybe give us clues on which medicines are better for which type of patients. I think that kind of information that we collect will really help. If you really look at what the cancer researchers and clinicians have done in collecting data, we need to do more with that kind of data, with genetics and with drug responsiveness. I think that certain genetic syndromes might show us that drug A is really the best drug for that genetic disorder. We're already seeing that, with these new indications with rare epilepsy, such as Lennox-Gastaut or Dravet syndrome. I think we have a lot more to learn, and we need to do a lot more, but I think we need to collect this information.
Transcript edited for clarity.