Raising Awareness and Advancing Management for Developmental Epileptic Encephalopathy With Spike Wave Activation

Lekha Rao, MD

Developmental/epileptic encephalopathy with spike wave activation in sleep (D/EE-SWAS) is a rare and complex neurological condition that predominantly affects children. It falls under the umbrella of epileptic encephalopathies, disorders in which epilepsy and associated abnormal brain activity significantly impair cognitive and neurological development. The hallmark of D/EE-SWAS is an abnormal pattern of electrical brain activity during slow-wave sleep, characterized by frequent spike-wave discharges that occupy a significant portion of sleep time.

At the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10 in Los Angeles, California, investigators presented a small-scale study that characterized this patient population and their response to certain therapies. Led by Lekha Rao, MD, the analysis included 30 children with D/EE-SWAS, with 5 excluded due to follow-up time of under 1 year. Of these patients, 80% had epilepsy, with an average age at seizure onset of 3.87 years. The features on the first EEG leading to the diagnosis of D/EE-SWAS was 60% focal spike waves, 24% multifocal, 12% generalized, and 4% combination of the above.

In the study, the most common medications were benzodiazepines, which were associated with the most favorable responses. In addition, the majority (64%) of patients fell in highest spike wave index of 75-100%, 20% at the 50-75% range, and 16% at 25-50% range.

Rao, an epileptologist at UCLA Health, sat down during the meeting to discuss the findings, and the interest behind studying patients with D/EE-SWAS. Rao, triple board certified in neurology/child neurology, clinical neurophysiology, and epilepsy, discussed the complexities with this patient population, the importance of accurate and early EEG assessment, and the challenges with diagnosis due to the variations in diagnostic criteria across institutions. In the discussion, she stressed the need for standardized definitions, increased awareness, and collaborative research to optimize diagnosis and treatment.

NeurologyLive: What was the interest in this type of study?

Lekha Rao, MD: Not many people know about this syndrome. Actually, it was recently renamed, so it's a little bit confusing because we use a lot of acronyms in neurology. D/EE-SWAS stands for "developmental epileptic encephalopathy with spike wave activation in sleep," which is quite a mouthful. So we simplify it by saying D/EE-SWAS. It’s an imperfect acronym because it doesn’t fully capture what the syndrome really is, and people still struggle to define it. There’s a lot of variation between institutions and practitioners regarding what this syndrome actually entails.

I’m part of the Pediatric Epilepsy Research Consortium and co-lead our special interest group on D/EE-SWAS. I thought it would be valuable to examine the patients at UCLA to understand our experience, especially because the way we treat this condition might differ significantly from how other centers approach it.

What were some of the major findings from the study?

This was a retrospective cohort study. We identified patients who came into the Epilepsy Monitoring Unit with a presumptive diagnosis of D/EE-SWAS or were being evaluated for something called ESES, which stands for "electrical status epilepticus in slow wave sleep." Depending on the journal, some call it "electrographic status epilepticus in slow wave sleep." Even the acronym varies!

We looked at patients who met the criteria for either ESES—where more than 85% of their slow-wave sleep was consumed by spikes—or had over 50% spike activity coupled with developmental changes indicative of epileptic encephalopathy. For example, they might have been developing normally but experienced regression or stagnation. Others might already have had developmental challenges that worsened or became static alongside their epilepsy onset.

What can the features of the first EEG tell us about a patient and their diagnosis?

The first step is raising awareness about this condition so practitioners know to look for it in the first place. It’s a unique disorder that can only be diagnosed using an overnight EEG that captures sleep. Specifically, these patients need to enter slow-wave sleep because that's when the characteristic activity becomes evident.

Abnormal electrical activity might already be present during wakefulness, but sleep tends to activate it further. Sleep, while generally a time for the brain to deactivate, causes highly synchronized discharges in these cases, making the abnormalities more prominent.

Different centers might calculate spike wave activation differently, but we look for significant differences, like a 50% increase in spike activity between wakefulness and sleep. When the EEG shows spikes occurring over 50% of the time during sleep, and there’s a clinical presentation consistent with D/EE-SWAS, we can diagnose the condition.

Do we know why diazepam and clobazam were considered the most favorable treatments in terms of response?

A large European trial compared high-dose clobazam to high-dose steroids, and steroids actually came out on top. However, in our study, we found that high-dose benzodiazepines like clobazam or diazepam were more effective.

This could be due to a selection bias at our institution. We tend to start with benzodiazepines as first-line treatments, so perhaps the initial treatment tends to be more effective. Alternatively, it could be something about how we identify or categorize patients. Our cohort is descriptive, so the findings might reflect institutional practices rather than universal trends.

Are there ways in which we can optimize treatment for patients with D/EE-SWAS?

Absolutely. We could improve treatments by refining how we define this disorder. Right now, there’s no consensus on what constitutes D/EE-SWAS. Standardizing diagnostic criteria—both clinical and EEG-related—would help eliminate variability between institutions.

We need clarity on what percentage of spike wave activation during slow-wave sleep qualifies, and greater awareness is essential. Pooling patient data and resources is another step forward. Because this is such a small and heterogeneous patient group, collaboration and increased research funding are critical. With more comprehensive studies, we can identify the best treatments for specific subsets of patients.

Do centers have the capability to properly diagnose D/EE-SWAS?

That’s a big challenge. Not all centers have overnight EEG capabilities. Many of these patients have comorbid neurodevelopmental disabilities, making it difficult for them to tolerate electrode placement without sedation. Specialized techniques or assistance may be necessary for these patients.

Resource disparities across the U.S. also play a role. Some hospitals can perform overnight EEGs, but others cannot. For example, I work part-time at a county safety-net hospital, where we don’t have overnight EEG capabilities. If I suspect D/EE-SWAS in one of those patients, I have to get creative—either by finding a way to refer them to UCLA or another center that can accommodate their diagnostic needs.

Transcript edited for clarity. Click here for more AES 2024 coverage.