Board President and founder, Anna Conkey, had the honor and privilege of interviewing Dr. Susan Swedo, Chief Pediatrics & Developmental Neuroscience Branch at the NIMH.
Can PANS ever persist into adulthood? Are there times when children under the age of three are impacted by PANS?
I believe it can definitely happen to children less than three. One of Judy Rapoport’s youngest patients was 18 months and he had to walk around man-hole covers. It came on very suddenly and he had older siblings who were in grade school and could have been bringing home strep. It is just a myth, a myth of medicine, that children less than two do not develop post-strep sequelae and therefore you don’t have to do a throat culture. I think there is absolutely nothing in the literature anywhere. It is just folklore.
Even for the child that you’re thinking about autism, it is my opinion, and as much as I beat on the table that if you’re going to give IVIG to a child with PANDAS, you better do the medical work up. The same is true for autism. Before pediatricians send them off to Infants and Toddlers, they better have done their homework and done the medical work up.
On the other end of it, it absolutely can persist into adulthood. It is an open question whether it can start for the first time in adulthood. The rheumatic fever data would suggest that it can because those studies were actually done with military recruits and the average age of onset was 21. So, 18 to 23 year olds and 21 year olds were getting rheumatic heart disease. They were getting Sydenham chorea, and they were having obsessive compulsive symptoms in association with that.
What percentage of the patient population do you think requires IVIG and is more than one necessary?
There is actually no way to guess. The two school studies we did, the one in Virginia and the one in Florida suggest that up to 10% of children have transient tics during strep season, so subclinical PANDAS is probably quite common. There are clinically significant cases that never come to a doctor’s attention but if you were doing a survey, they’d have all of the symptoms and those are also relatively common and may be as many as 1% of the children.
Of the number of children with PANS, the number requiring IVIG will be much less. There is really no way to guess and it may fluctuate. In terms of the numbers needing more than one course, again that is probably something we can’t estimate at this point in time. They tend to be the patients who have some type of immunodeficiency or are older patients. Tanya Murphy has anecdotal data, but collected in a systematic way, showing that three seems to be the magic number, especially for boys who are teenagers.
Do you see a difference in outcomes when children are treated promptly versus when they have been sick for years?
The short answer is yes. The longer answer is we don’t actually have that kind of data again because it is sort of extrapolation. We do know that within two weeks of onset and two years of onset, it doesn’t appear to have any difference in the effectiveness if you use IVIG or plasmapheresis. That was the range of duration of illness of the kids in our study. At least out to two, maybe three years, it doesn’t seem to impact it. Everybody’s fear and worry is that we will miss a child for years and years and then they are much more difficult to treat.
Is permanent brain damage a possibility?
[Yes] if the pathology is as comparable to Sydenham chorea as the presentation is. The old path[ology] reports from patients who died of rheumatic heart disease showed the brains of children with Sydenham chorea had evidence of destruction in the caudate and putamen.
Is there any research in the pipeline that you’re excited about or that you think will make a significant difference in the lives of children with PANS?
I think we are on the cusp of breaking this all loose. Dritan Agalliu’s work is sort of paradigm shifting and it really has the opportunity to teach us exactly what the disease mechanism is. Having that animal model means we can start investigating biomarkers. We can look for treatments and have an animal model to test. Kyle Williams has examined his patients looking for IgA deficiency and that paper will be coming out soon. That helps us reshape our thinking because that was a cohort of kids with PANS, not just PANDAS, and they had very low IgA levels. Probably the thing that I’m involved in that I’m most excited about is the nationwide characterization study where all the PANS/PANDAS centers as well as many practitioners have agreed to invite their children and families to participate in the NIMH trial. Our goal is to gather six hundred affected children per year and their family members and gather all of the clinical data and their biospecimen, hopefully eventually including throat cultures, stool samples, etc. Then we will have, almost immediately, a biobank that other researchers can come in and say “I want to look at this” or “I want to look at that” or “we heard that this drug works. Can you figure out if that makes any sense?” and we will have the samples to get it done.
Is there any translational research you’re excited about?
Typically it is bench to bedside and ours has always been bedside to bench. I’m very happy that Chris Pittenger at Yale, Dritan [Agalliu] at Columbia, and the group in Miami, and one in Texas, and many other places are all intrigued by this question and starting to look at it very systematically.
Do you have any advice for parents with children who have PANS?
I do, indeed. Remain hopeful. Stay good to each other as you’re trying to be good to your child. This is a curable disorder.