Reducing the Burden: Proactive Care Strategies for Lennox-Gastaut Syndrome

Babitha Haridas, MD, MBBS

Status epilepticus (SE) is a dangerous brain condition that happens when a person has seizures that last too long or happen too quickly in sequence. While its more likely to happen to people with epilepsy, many conditions can cause continuous or repeated seizures in people who don’t have epilepsy. Research on SE in patients with Lennox-Gastaut syndrome, a rare developmental and epileptic encephalopathy, has been limited, with little understood about how to manage this state of being.

A study presented at the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10, in Los Angeles, California, found that patients with LGS represent a sizable fraction of SE patients, and present frequently with intermittent seizures and delayed treatment, in the setting of seizure triggers. The research, led by Babitha Haridas, MD, MBBS, comprised of 845 patients from the pediatric Status Epilepticus Research Group, 51 of which had a diagnosis of LGS or a history of developmental delays with tonic seizures.

In the study, the duration of SE ranged from 1 hour to 8 days, with the most common etiologies being systemic infections (33%), changes in medication regimens (13%), and unknown causes (19%), while 76% of patients experienced intermittent seizures without returning to baseline between episodes, compared to 24% with continuous seizure activity. To better understand these findings, NeurologyLive® sat down with Haridas, who serves as a pediatric epileptologist at Johns Hopkins Medicine.

In the interview, Haridas highlighted the unpredictable nature of seizures in patients with LGS, emphasizing how triggers such as infections, changes in medication, and missed doses can precipitate SE. In addition, she spoke on the key takeaways from the study, including the importance of early identification of triggers and the need for clinicians to educate caregivers about emergency plans to reduce hospital visits and ICU admissions.

NeurologyLive: Provide an overview of the study and why this was a topic of interest for you?

Babitha Haridas, MD, MBBS: I'm very excited to be here and share the results of the study with all of you because I think the findings show there's so much we can do to improve care for these patients with refractory epilepsy. As we all know, epilepsy is a life-threatening condition affecting over 50 million people worldwide. This is why so many of us are passionate about improving epilepsy care.

Lennox-Gastaut Syndrome (LGS) is a severe developmental and epileptic encephalopathy affecting around one in 2,000 individuals globally. What we see is that children with LGS often experience refractory seizures, requiring numerous medications to manage them. These children face significant morbidity and mortality, frequently needing emergency room visits and ICU care.

Although LGS accounts for about 5% of childhood epilepsy cases, it contributes to nearly half of epilepsy-related healthcare costs in the United States. This is a substantial burden, and any improvements in care can help reduce morbidity, mortality, and improve these patients' overall well-being.

Regarding the findings, what stands out the most? What should clinicians/epileptologists focus on?

I think one of the most frustrating aspects of epilepsy is the unpredictable nature of seizures. If we could predict exactly when they might occur, it would transform the lives of patients and their families. I recall a session at last year's AES (American Epilepsy Society) meeting where a patient with epilepsy said something that stuck with me. She began her talk by saying, "While I’ve prepared for this talk for hours, I don’t know if I’ll finish it because I might have a seizure in the next 30 minutes."

With that in mind, let me share what we found in our study. We identified several potential triggers for status epilepticus in children with LGS. One of the most common triggers is infections, accounting for almost 40% of cases in our cohort. The next most common are changes in medication—whether switching from a brand-name drug to a generic, or missing one or two doses. Despite the best efforts of hardworking families, life happens, and this accounts for around 20% of cases.

It's important to note that causes are rarely black-and-white in epilepsy, especially in refractory epilepsy syndromes like LGS. For example, a child with viral gastroenteritis might vomit, miss their medication, and experience a drop in drug levels, leading to status epilepticus. This insight helps reduce some of the unpredictability surrounding seizures. By being aware of such triggers, clinicians can act more quickly. For instance, if a child prone to status epilepticus shows signs of an infection, short-term benzodiazepine therapy might help prevent an ER or ICU visit.

Is the clinical community fully aware of the downstream impacts of triggered infections in patients with LGS?

In the epilepsy field, we generally recognize that infections can lower the seizure threshold. However, there haven’t been studies specifically examining LGS and the likelihood of various triggers in this population. This is where our study contributes valuable new data.

Looking forward, can clinicians predict and act on triggers to reduce status epilepticus?

Absolutely. I think our study offers two key takeaways. First, when a child with LGS presents to the ER, it’s critical to carefully review their history. Look for any signs of infection or changes in medication, such as discontinuation of phenobarbital or a missed dose. The second takeaway is related to the variability in status epilepticus duration in patients with LGS.

We found that some children experience status lasting minutes to an hour, while others endure it for up to eight days. The median duration was around four hours, with an interquartile range of 18 hours. Interestingly, 75% of patients in our cohort had intermittent status epilepticus, while 25% had continuous seizure activity. This variability emphasizes the importance of early identification and intervention.

Understanding that intermittent seizures may indicate status epilepticus in LGS patients—rather than the textbook definition of continuous activity—can help clinicians reduce status duration and improve outcomes.

Are there conversations clinicians should have with families regarding the risk of status epilepticus?

Children with LGS can be considered fragile in some ways, but their caregivers are phenomenal. They go above and beyond to support their children, and they are often the best resources for identifying and managing status epilepticus.

I believe it’s essential to have conversations with families about the different forms of status epilepticus their child might experience and to develop a clear emergency plan. By equipping families with tools to take action at home, we can reduce the need for ER visits and ICU admissions, which are highly utilized by this patient group.

Transcript edited for clarity.