Elizabeth Thiele, MD, PhD, describes what sunflower syndrome is and reacts to the significance of recent data presented on the use of fenfluramine as add-on treatment for children and young adults.
Elizabeth Thiele, MD, PhD
PUBLISHED June 04, 2020
Elizabeth Thiele, MD, PhD: An abstract that I was going to present at the AAN [American Academy of Neurology] Annual Meeting that I was really excited about was an open-label investigator-initiated trial of fenfluramine in Sunflower syndrome. Sunflower syndrome is a pretty rare epilepsy that, over the past 6 years, we’ve been spending a lot of time trying to better understand and characterize. Sunflower syndrome is kind of characterized by a child looking toward the sun, being drawn toward the sun, and then waving her hands in front of the sun, often several hundred times per day. Some of the children do this only when outdoors in sunlight, but many of them do it indoors as well. And it’s not only characterized by many seizures during the day, but it can really impact their safety, when walking in the street, and their ability to learn, since some of the children do this throughout the day in a classroom.
This is a very highly refractory epilepsy. We have seen over 50 kids with this. We also tried to characterize it through an online survey. Most of our anticonvulsant medications are not effective here. Drs Jean Aicardi and Henri Gastaut, in the early 1980s, had written a letter to the editor of New England Journal of Medicine describing 3 children with self-induced photo-stimulated epilepsy. The first was clearly a kid that would meet the definition of what we now call Sunflower syndrome, and all 3 benefited from fenfluramine. Zogenix gave us the ability to start 10 children with Sunflower syndrome on fenfluramine. At the meeting, I was going to get to give the results of the trial.
Of the 10, 1 did not complete the study. She developed a rash, which we do not think was drug-related since rash has really not been an adverse effect of fenfluramine. However, she decided not to continue. Of the other 9 who did complete the trial, 1 of them did not respond. The other 8 children did respond. These are children who had been on other prior anticonvulsant medications without efficacy. In these children, we saw a median of 84% reduction in their seizures. Pretty impressive.
The other thing we did as part of that trial was neuropsychological testing before and after. I was kind of surprised but excited to see that during that time, the children had a mean 18-point increase in their IQ [intelligence quotient], which is pretty impressive. We also looked at EEGs [electroencephalograms] before and after and saw that fenfluramine had a significant impact on EEGs. We saw a decrease in the frequency of epileptiform discharges. Often, these children also have a photoconvulsive or photoparoxysmal response with strobe during an EEG, and we saw a reduction in that. This suggests that, at least in these children, fenfluramine may be effective in this rare epilepsy where nothing else typically is. We were pretty wicked excited about that.
I’m very excited about the data we have in Sunflower syndrome. When we did this internet-based REDCap survey, we found that many of these children had been on all the broad-spectrum anticonvulsant drugs without benefit. Many had been on CBD [cannabidiol] without benefit. Diet can be effective for some. I’ve found that these children really suffer with this epilepsy. Even though most of them are cognitively fine, this is very impactful. Many are bullied, so some are home schooled. Most of them have poor self-concepts, self-esteem, because of the bullying, because of these episodes, and the parents are very concerned.
We’ve actually had families that have moved, literally, to places where they think there would be less sunlight, thinking that they could help reduce their children’s seizure frequency. The fact that fenfluramine helped 8 of 9 children who took the medication gives hope to this community that there will be an effective treatment.