Board President and Founder Anna Conkey had the honor and privilege of interviewing Dr. Susan Swedo, Chief Pediatrics & Developmental Neuroscience Branch at the NIMH.
How did you first learn of PANS/PANDAS and what motivated your interest in it?
I first learned of the connection between strep and obsessive compulsive disorder when I got to the NIH in 1986. As a pediatrician I think I probably missed three or four cases of OCD, treating the rash on the kids’ hands when in fact, they probably had excessive hand-washing or anxiety. I was motivated to learn what OCD was and was really blessed that my partner Henrietta Leonard started the same day I did. She was a child psychiatrist and I was the pediatrician and we always joked that I was the hands and she was the head and between us we made a whole person.
Judy Rapoport gets all the credit for thinking about medical models for OCD and she was the one who had come across those old papers that children with Sydenham chorea, that we know is a post-strep illness, had obsessive compulsive symptoms start about two to four weeks before the movements did. At the time, it was punitive toilet training and a very psychological construct for OCD, so if the movements would have started before the OCD, we would have thought it was a coping mechanism and that the child was trying to regain control.
That led to the investigations of Sydenham chorea, one of which we actually did with Dr. [Ellen] Wald. That showed that children with rheumatic heart disease didn’t have any difficulties, but about two of three children with Sydenham chorea would have obsessions and compulsions and the behaviors could actually start before the movements began. They also had a lot of separation anxiety, ADHD, concentration difficulties, emotional lability—and emotional lability had been described as early as the 1800s. That is probably the most prominent symptom in OCD. They have terrible mood swings, irritability, aggression. We probably wouldn’t have made the connection except we were doing a treatment trial for Sydenham chorea and it was too hard as a pediatrician to have these children come in, do a work up on them, and send them home because they still had terrible symptoms. We had started a prednisone, IVIG, and plasmapheresis study and the first case of PANDAS was actually sent to us in that study. The doctor thought he had Sydenham chorea. He did have wild flailing movements with his arms but every time they were exactly the same. It turned out he was actually doing a flinging ritual in which he was trying to fling away the bad germs.
His mom gets the credit for the discovery of the strep connection to his tics and OCD. Her oldest son had Tourette’s and she was a medical technologist. Literally she or her husband would say “Oh his tics are getting bad, you better culture him” and sure enough, if his tics worsened the throat culture would be positive and he could be treated with antibiotics. So they were actually the ones that made this connection.
If we fast-forward a few months, we were looking at 125 children with OCD and discovered that one quarter had an abrupt onset. Unlike the other three quarters, the one quarter had the fine choreiform movements. By the time we got them, none of them were still relapsing and remitting, but that had been in their history so we set out and modified our protocol to look specifically for children with an abrupt onset of their OCD symptoms and from the next four years of recruiting kids, we got the next cohort of fifty kids that we described as PANDAS.
Are there children who did not have an abrupt or acute onset who have a PANS-like condition, and if so, do they respond to immunomodulatory treatments similarly to children who had an abrupt onset?
That is the million dollar question, so you get more than a million dollars for asking! That’s the question I’ve been trying to answer forever. We don’t know. I assume that there are because our model has moved from being a model of just Sydenham chorea to a model of autoimmune encephalitis. Autoimmune encephalitis has so many different presentations, many of which come on over the period of weeks to months rather than just a few days so what we call a sub-acute onset may certainly still have an immune basis to it.
The problem is we don’t know. OCD that clearly doesn’t have any immune dysfunction associated also comes on slowly so we’ve held on really tightly to our acute, abrupt onset until we can find a biomarker. As soon as we know, as soon as we find something like an NMDA receptor antibody or a thyroid antibody, or an equivalent lab test, some test we can do where we can say “yes, a child has it” or “no, a child doesn’t,” we have to use a strict clinical criteria.
Is it possible PANS isn’t actually all autoimmune and that there might be metabolic or other triggers?
Absolutely. The difference between PANDAS and PANS is PANDAS is actually a disease. It has a cause, a disease mechanism, and then a manifestation of clinical symptoms. We know exactly how to treat it to get rid of the problem. PANS is a syndrome and a syndrome is just a collection of clinical symptoms that hang together so consistently that if you see one you’re going to recognize the next one because one looks like another and another. PANS, almost by definition, has to be multi-factorial and have multiple causes. We know that there are infectious triggers and we know there are non-infectious triggers—anything from child abuse to environmental factors, genetics, metabolic disorders, brain trauma, concussion, and certainly brain injuries. There are multiple etiologies that are going to require multiple avenues towards treatment unless they all have the same common pathway of neuro-inflammation and I think that is the million dollar question you asked me before.
Are you aware of children who had been diagnosed with autism who ended up actually having PANS?
The reality is that a child with PANDAS can look incredibly autistic. They withdraw socially. They can lose their speech. They can become mute—completely mute. They are bothered by lights and sounds and the compulsive rituals of an autistic child really cannot be distinguished from those of a child with OCD. Again, that looks exactly the same.
The difference is the age of onset. If you present to me a two year old with a relatively abrupt onset—let’s say over the course of a week, lost skills and started to have sensory issues, I’m probably going to think autism first before PANS and PANDAS. If that child is four, there is no question you should think PANDAS first.
Are you aware of children who had been diagnosed with bipolar disorder, oppositional defiant disorder, mood disorder-NOS, Tourette's, etc. who actually had PANS and did their symptoms remit with treatment?
Yes—100% for Tourette’s. For children who have a primary tic disorder with a little bit of OCD, separation anxiety, as long as they have some other co-morbidities, we can bring them into remission with IVIG or plasma exchange.
In fact, half of the kids in the first study would have met criteria for Tourette’s if they’d had tics for another 2-3 months. Tourette’s is just motor and vocal tics for more than a year, so on day 364 you don’t get the diagnosis and on day 365 you do.
Bipolar and oppositional defiant disorder, even reactive attachment disorder, lots of the labels we throw onto children, and adults for that matter, match the symptoms of PANS/PANDAS, Sydenham chorea and very importantly, autoimmune encephalitis. I think my biggest fear is that a child would come in with a history on one or both sides of bipolar and nobody would even think that this is something other than genetic.