S3 E24: Dr. Sue Swedo Talks About the Past 40 Years of PANS/PANDAS

In this episode, we trace Dr. Swedo’s path from pediatrics to the National Institute of Mental Health and the early clinical observations that linked Sydenham chorea, rheumatic fever, and obsessive-compulsive disorder. Along the way, she explains why OCD is often hidden for years unless clinicians ask the right questions, and why structured checklists can change everything for families searching for answers. We also confront the reality of scientific pushback: how skepticism shaped stronger research, why medicine can take decades to accept an infectious or autoimmune mechanism, and what the autoimmune encephalitis era has taught the wider field of immunopsychiatry.

Then we look forward. Dr. Swedo lays out the research roadmap she wants to see now: multi-center collaboration across major PANDAS and PANS clinics, prospective studies that capture kids within days of symptom onset, better testing for rheumatogenic and potentially “pandasogenic” strep strains, and smarter use of models to evaluate immunomodulating treatments like IVIG and plasmapheresis. We also talk about safety and the urgent need to take self-harm intrusions seriously, especially when inflammation, impulse control changes, and demoralization collide.

If you care about PANDAS, PANS, pediatric OCD, tics, neuroinflammation, autoimmune brain disease, or the future of mental health diagnosis, this conversation will give you history, clarity, and practical next questions. Subscribe, share this with someone who needs it, and leave a review so more families and clinicians can find the science, faster.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

Follow us on:
Facebook
Instagram
LinkedIn

Transcript

What PANDAS And PANS Are

Susan Manfull, PhD 0:07

Untangling Pandas and Pans is a podcast about two little-known medical disorders characterized by the sudden and dramatic onset of symptoms such as obsessions and compulsions, vocal or motor ticks, and restricted eating behaviors, and a whole host of other symptoms following a strep or other bacterial or viral infection. I have the privilege of interviewing some of the top researchers and clinicians in this rapidly growing area, known by various names such as immune-mediated neuropsychiatric disorders, infection-associated neuroimmune disorders, and autoimmune encephalitis, or simply pandas and pans. My name is Dr. Susan Manfell. I am a social psychologist, the executive director of the Alex Manfell Fund, and the mother of Alex Manfell, who died at 26 years old due to pandas. A disorder my husband and I knew next to nothing about. Certainly not that our daughter could die from it.

William Manfull 1:18

This is episode 24 of Untangling Pandas and Pans, recorded July 31st, 2026.

Introducing Dr. Sue Swedo

Susan Manfull, PhD 1:28

Welcome to Untangling Pandas and Pans, a monthly podcast in which we talk about infection-associated immune-mediated neuropsychiatric disorders. I am thrilled to have with me today Dr. Sue Sweeto. Dr. Sweeto really needs no introduction to most listeners of untangling pandas and pans. But in case you stumbled onto this podcast, it's my pleasure to tell you that Dr. Suito is one of the most renowned researchers in the field of neuropsychiatry, or as it's often called in Europe, immunopsychiatry. But even that does not capture the immense importance of Dr. Sweeto, the gravitas of Dr. Sweeto in this field. Perhaps the founding mother of PANDAS would be a better way to express who she is. Pandas is the disease that she and her team recognized while studying patients with Sydenham's career, rheumatic fever, and OCD.

unknown 2:32

Okay.

Susan Manfull, PhD 2:32

And it set the stage for the later recognition of a syndrome that we now call PANS. And that subsumed PANDAS. Dr. Suito began this work 40 years ago this month, July 1986, when she began working with Dr. Judith Rappaport. She began as a senior staff fellow in the child psychiatry branch of the National Institute of Mental Health, NIMH. That was when she first learned about the connection between strep and obsessive compulsive disorder, a subject Dr. Rappaport was studying and one that Dr. Suito would continue to study until now and beyond. In 1998, after several earlier publications in this arena, she was the lead author of a seminal paper entitled Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections Clinical Description of the First 50 Cases. She has not stopped yet. She retired from NIH in 2019 and continues to work on her goal of thoroughly understanding the etiology of pandas and pans and most importantly finding a cure for these devastating conditions. Since the time that that she retired, she's done many things. I found one of the most interesting was that she was a member of the DSM V Task Force, which published the latest version of the DSM in 2013. I could list all of the other positions she's had and all of the other awards she has received. But you can Google those. I will tell you a little fact about Dr. Sweeto, now scientist emeritus at the National Institutes of Health that I imagine you don't know. Dr. Sweeto is the proud blue ribbon winner from the Iowa State Fair for her cornbread. It's all in how you stir it, she told me. The secret to making good cornbread is that you barely mix everything together. So she tells me that you must sift all the dry ingredients first, get your wet ones stirred nicely together, beat your egg before anything else, and then mix it as little as possible. That's her secret. I can't wait to try the recipe. Dr. Sweeto recently attended the Alex Manfell Fund dinner in Washington, D.C., where we had the honor of presenting a Lifetime Achievement Award for her 40 years in this field. She will talk with me today about those 40 years and what she'd like to see in the future for this field. So Dr. Sweeto, 40 years ago, this month, you began your research along with a team, as you always point out, but you began your research that eventually led to what we now know today as pandas and pants. And I'd I'd like to start right around there, but I'd like to back up a few years before that to hear what led you to apply for a position at NIH.

From Surgery Dreams To Pediatrics

Susan Manfull, PhD 6:17

What were you doing? What made you think you'd like to work at NIH?

SPEAKER_01 6:23

Oh, thank you for asking that question because it's the backstory that's always the most fun. I think I went to medical school thinking I was going to be a surgeon. And the first day of rotation, having to be there at 4:30 in the morning to do rounds and then stand on my feet all day at a time when medical schools were pretty chauvinistic, uh, convinced me that maybe surgery wasn't what I wanted to do. And so I started paying more attention to what I was interested in, and really was very torn between obigaine, psychiatry, and pediatrics, and had a great mentor who said, Do pediatrics, it allows you to sort of do a little bit of the rest. And so I did. My medical school was Southern Illinois, University, School of Medicine. It had been founded to produce more primary care physicians for downstate Illinois, outside of Chicago area. And when I graduated, my husband was in training in Chicago. So I was looking for a position in the Chicago area. And the one I wanted at Michael Reese Hospital, I didn't get, and I got an internship at Northwestern University. And there just had a wonderful opportunity to sort of learn a lot of pediatrics really fast. It was the battle days of medicine where it was every third night call. You were up for a day and a half, went home and crashed. Your day off, quote unquote, was about 12 hours on Sunday, if you were lucky, um, Saturday or Sunday when you were awake and able to get your laundry done and everything else. But but we learned a lot of pediatrics. And in that time, I kind of lost sight of that triple major, right? The psychiatry, the obigyney, and the peds, and really became very focused on pediatrics with an interest in psychiatry, but not enough to do a child psychiatry fellowship. I really became enamored of teenagers and discovered that apparently not a lot of people like them.

SPEAKER_03 8:31

They're somewhat misunderstood.

SPEAKER_01 8:33

They can be challenging. I think that's the right term for them. Whereas I find them fascinating. I just think that teens are so interesting as they think about life and and what it means, and there's that naivete, and so they're gonna solve all the world's problems. And I wanted to help them do that. So I was finishing my training, my husband was still heavily in the middle of his. He's a pathologist, so he had to train much longer than I did, and ended up uh needing to get a job and took a job at Evanston Hospital, one of the satellites for Northwestern, where my salary was paid by continuing to be the you know house staff member that was rescuing babies in the delivery room and taking them to the NICU, or my partner and I also ran the pediatric ICU. So doing a lot,

Teen Suicide Attempts And A Key Fix

SPEAKER_01 9:25

a lot of procedures, putting heart lines in, doing spinal taps, intubating kids, just using my hands all the time. But as part of that, I was the house physician. And so every child who was admitted to the pediatric ICU, I was their physician of record while they were in the hospital. And I started noticing this very troubling and awful phenomenon of seeing the same child come back into my ICU more than once with a suicide attempt. And the kids the first time would have taken 30 Tylenol, and they were in there to get their stomach pumped, and blah, blah, blah. And they would come back, they would have taken twice as much because what was going on? So it was awful. And how old were these teenagers, anywhere between 12 to 16 years of age, and a couple of boys who completed suicide, and it was horrible. And so, in exchange for saving the hospital a lot of money by covering probably three different people's positions, they were allowing me to go places. So I went out to Stanford University to Iris Litz Eating Disorders Unit, and I went to the University of Washington and spent a couple of weeks with their um sports medicine department and really focused in on this issue of why were these kids using a suicide attempt as their cry for help. And at the time there was a logo called A Cry for Help, which had been written about the kids on North Shore of Chicago, which Evanston served those children. So I met with my board at the hospital, and I sort of said, This is unacceptable. I need your permission to not discharge any child if they don't have an appointment with a psychiatrist or therapist before they leave. Because what the kids were telling me was that they would I would discharge them with the you know instructions you need to see a psychiatrist within the next week or two. Either they couldn't get an appointment or their parents would just sort of be like in denial, lots of reasons, right? And they and they would not get help, and nobody was hearing them. So we instituted mandatory discharge planning, and I had been keeping some just statistics in the little journal that I was keeping, and noticed that the recidivism rate really changed. And the very first paper I wrote was on how mandatory discharge planning took our recidivism rate from something in the 40s percent range down to zero.

Susan Manfull, PhD 11:57

Oh my.

SPEAKER_01 11:58

Yeah. And and then I wanted to, I was still very curious about why was this happening. And Susan Blumenthal was an NIH scientist at the time who was looking at doing psychological autopsies on patients with suicide, completed suicides, and had a lot of risk factors. And so I sort of modeled an interview study after hers and got a tiny grant from the hospital, which allowed me to hire a nurse part-time to help me do the interviews and start accruing the statistics. And in the middle of all this, my husband was finishing his training. And I, of course, had a plan. We were going to be in Chicago, my family was in the Illinois, my friends were all local. I was going to keep doing what I was doing. It probably would have killed me because, right? I told you my salary was paid by doing the PEEDS ICU and the NICU. And if my partner was out of town and we had a really sick kid come in the pediatric ICU, it would be me from like Sunday night rush to the hospital at 2 a.m. and I might get back home again Wednesday, Thursday, Friday. So fortunately, God intervened and Greg couldn't find a job in Chicago, but he found one in Virginia.

The Move To NIH And Reality Check

SPEAKER_01 13:14

Okay. And so that took you to the area. It got us to the area. Well, what really got us to the area was that the day Greg came out to interview, it was minus 10 in Chicago. We were expecting yet another blizzard. And Greg came out here, and it was one of those crazy days in February where you just get this amazing spring day. And he calls me, he goes, It's 65 degrees here, and I can see back. I said, We are there. And so I started applying for jobs in the DC area, wanting to try actually to stay in the area of adolescent medicine, but recognizing that if I was going to do any meaningful research, I really needed to know much more than I did about what research meant. And so I applied actually the Child Health Institute. They didn't have anything, and they sort of passed my application around, and Judy got hold of it. And Dr. Rappaport had just decided to let one of her fellows go. And so she promised me the world. She promised me I could work part-time, I could telecommute one day a week because we were living down south of the city, down in Alexandria, and the NIH is on the north side. So it was an hour and 15-minute commute on a good day each way. 30, 33 miles. Government job. I'll take it. My first day I showed up, and the secretary was the one that told me that no, no, this is a federal government job. It is full-time. Nine to five is your duty. You have to be here every day. And oh, by the way, you'll be taking in-house call for uh the National Institute of Mental Health, the National Institute of Aging, and the National Institute of Neurolog Neurologic Disorders and Stroke. So I was like, I know nothing about adults. You understand that? I said, that's okay. As the on-call physician, you have two, you have um one job to get the patient to somebody who can take care of them. Either their protocol doctor who does know them, or if it's a real emergency, call 911 and Suburban Hospital will come over and send an ambulance.

Susan Manfull, PhD 15:42

What an experience. You were pretty young.

SPEAKER_01 15:44

I was very young because I had gone through college and medical school in six years. So I was like at that point 27, 28.

Susan Manfull, PhD 15:51

Whoa. That's a full load for somebody who's not 30, even.

SPEAKER_01 15:57

Yeah.

Susan Manfull, PhD 15:58

You were young though.

SPEAKER_01 15:59

I was I was young, definitely younger than Henrietta, but that's the reason that it all worked was because uh Henrietta Leonard and I started the same day in a tiny little office in Dr. Rappaport's suite, and Henry had the desk by the door. She would have to get up out of her chair, push her chair into the desk to let me behind her to get over to my desk because it was like a little shotgun kind of office. But we had a window. It looked out on a brick wall, but we did have a window.

Susan Manfull, PhD 16:31

I've been in some of those offices and know how small they are and windowless as well.

SPEAKER_01 16:36

Off on windowless, which is what Marcus Cruzi had. And Henry and I looked at each other that first day and we're like, we're either gonna be best friends or not. Let's choose to be good friends.

Susan Manfull, PhD 16:47

Oh, that's that's a great beginning.

SPEAKER_01 16:50

It was a wonderful beginning. And it it worked because Henrietta was incredibly smart, an incredibly well-trained child psychiatrist, as with Judy Rappaport. I mean, Judy is one of the was one of the smartest women I smartest people I've ever met in my life. Just absolutely brilliant. And both of them were physician psychiatrists. They knew that mental illness could be called brain disease, and that it was coming out of a brain. It wasn't coming out of some psyche or some of the you know words that we use to pretend that it's not all neurologic. And so it was a great experience. I was the hands and Henrietta was the head, and and we were a great teen.

Susan Manfull, PhD 17:35

Wow. I just got out my book. Um, so I got that when it first came out. I was a big fan of that super book. Uh and for those who who are listening and not watching this, I just held up um Dr. Rappaport's book, The Boy Who Couldn't Stop Washington, about obsessive-compulsive disorder. Excellent book. So at that point, you were interested in and you were familiar, you knew that there was a relationship between strap and OCD. I I've read somewhere along the line.

SPEAKER_01 18:12

Judy actually had found that. Yep.

Susan Manfull, PhD 18:14

Okay. So did you go right into that research with Sydenham's career?

SPEAKER_01 18:20

Pretty soon Judy assigned Henrietta and I to the Obsessive Compulsive Disorder Project.

Building The OCD Research Pipeline

unknown 18:25

Okay.

SPEAKER_01 18:25

And so there was, we were our bread and butter of what we were doing was to enroll children and get them through a comparison of clomipamine and desiperamine. So clomipramine is a serotonin reuptake blocking form of imiprimine, and desiperamine is its first byproduct. So comparing desifermine and clomipramine, they had identical side effects. So you couldn't tell which one it was on, which drug the child was on. But the serotonin reuptake of the clamipermine actually treated their obsessive compulsive symptoms, and it was pretty remarkable. Judy had finished and was in the process of publishing the comparison of clamipermine versus placebo. And so we were following on that to show that clamipermine was even superior to dizipermine, and it was very superior. And unlike the fellow that I replaced, we were getting patients in at a rate of two or three new kids to come in a week. So we had a lot of children with obsessive compulsive disorder that we were evaluating, and they were hospitalized in our inpatient unit there for a week. We did extensive interviews with them, and that during that time, Dr. Rappelport and Henrietta taught me what OCD is, they taught me what depression was, they taught me a lot of things about um psychiatry and mental illness, but I can't still had my pediatric background of sort of, but these are kids, we should be able to make this better quickly, like given antibiotics for an ear infection or something. So it was a good combo. And Judy sent Henrietta to the library with a list of five basal ganglia disorders. And I had a different list of five, and my five included Sydenham, Korea, because she had, you know, been researching this literature forever and knew from the adult work that the basal ganglia were involved. And then her decades of research on attention deficit hyperactivity disorder, OCD conduct disorder, and all the rest. She had put together that picture of sort of the triad of symptoms of ticks, ADHD, and OCD seemed to be unique in children compared to adults or even teens who got obsessive compulsive disorder. Because adolescents tend to be girls and they tend to have comorbid depression and anxiety, not the ticks and the and the ADHD. So we we did some fun studies. We Henrietta and one of our nurse practitioners, Belinda Dupert, and I went out to rural Minnesota where there was a family that had a whole bunch of Sagawas dystonia, which is a particular kind of basoganglia disorder in which they actually have a muscle disease, but family members had ticks or obsessive compulsive disorder. We actually got a speeding ticket on a Sunday morning in rural Minnesota. It was the rental car, probably, but um that or the fact we were the only car on the road.

Susan Manfull, PhD 21:31

Probably something like that. Is it an autoimmune condition?

SPEAKER_01 21:36

No, it's an inherited form of uh dystonia.

Susan Manfull, PhD 21:40

Oh, okay.

SPEAKER_01 21:41

So yeah, it's just interesting. So Judy was putting together this beautiful kind of pieces in here, pieces in there. Huntington's Korea, right? We always think of Huntingtons as psychosis, but very sh for a very short period of time, early in the illness, patients with Huntington's have. Incredible obsessive thoughts and compulsive uh rituals, ritualized behaviors. And so all of these pieces were coming together. And because again, I was the pediatrician, Judy's like, Well, you should do the sit-and-ham career. Go, and she had already had the thought. The one piece I contributed was she wanted me to do uh throat cultures and ASO and uh titers on every kid when they were coming in for the drug treatment study. I'm like, Judy, the kids have been sick for four years, two years, you know, all kinds of different intervals. This is a time-limited test that's not going to help. So that was my one contribution to all of this was as a pediatrician to know it wasn't gonna help us to just do random titers on the children. And instead, we were able to just this is with Sydenham's career. No, these were children with obsessive compulsive disorders.

SPEAKER_03 22:51

Oh, okay.

SPEAKER_01 22:52

Judy was trying to look for strep connection related to etiology, but doing it sort of years after their illness had actually started and become entrenched, and that's why they were there for the drug treatment trial. So we decided that wasn't going to work unless you could get into a clinic where you could get fresh cases of obsessive compulsive disorder and get them as soon as their symptoms started and start cultureing them then. And that was actually a study did get done, not in a psych clinic, but in Picacchiero's pediatric clinic in that 2002 paper, excuse me, where Marie Murphy and Mike Picaciero in a pediatric practice looked at kids coming in with a new onset obsessive compulsive disorder. And many of them were coming in with urinary frequency. The urine culture would be negative, but the throat culture was positive. So years later, Judy was vindicated. It was the right idea, just the wrong execution. And instead of doing just sort of random throat cultures, we decided to compare children with Sydenham Korea against children who had equally severe rheumatic heart disease, but no Korea. So post-strep autoimmune response affecting the heart, the heart

Sydenham Chorea Links To Hidden OCD

SPEAKER_01 24:08

plus the brain, heart plus joints, brain alone. You know, Sydenham Korea is the brain manifestation, but acute rheumatic fever has five different manifestations, and they can all kind of come in different combinations. We took the group of kids who had absolutely no history of any kind of abnormal movements as part of the rheumatic fever, put those in the heart group, and those who presented actually with Sytenham Korea in the SC group, and then compared them against each other and found by interviewing the children that two-thirds of them had obsessive compulsive symptoms that actually began before the Korea started. And that that study was, to me, sort of the most definitive one that's ever been done because none of us expected to get the results that we did. And some of the stories that the kids told us were remarkable. It was the proof positive to me, again, the naive pediatrician, that what the psychiatrists were telling me was true, and that OCD is a disorder of sort of shame and hiding, and that the people think, you know, they're wary that they're crazy, and so they're not going to tell anybody about their symptoms unless very specifically asked. And it's still tragically true that patients are seen by therapists for a decade or more before the person ever knows that they have obsessive compulsive disorder, unless they've just done a very systematic assessment up front. So maybe a take-home message from this podcast would be for all of the therapists and counselors and anybody else taking care of a patient presenting with anxiety or depression or any of the internalizing disorders to also ask about obsessive compulsive symptoms and give them the checklist. The kids used to say seeing their symptoms on a checklist meant, oh, I can't be that crazy because they wouldn't have written it down if somebody else didn't have the same thing. It was very reassuring.

Susan Manfull, PhD 26:09

True. So with that study, you you had the patients who were identified as having rheumatic fever, uh, and the patients who were identified as having Sydenham's Korea. And you found the OCD in the Sydenham's Korea group. Yes.

SPEAKER_01 26:26

And none in the rheumatic in the heart disease group. Right, right. And it was at three different sites. Ellen Wald, who's since dropped out of any kind of relationship to pans, pandas, or OCD for decades after that study, but she was one of the sites in Pittsburgh, and then Don Hogar in Ohio, because it was the Ohio River Valley rheumatic fever belt. And there was another belt out in Salt Lake City with George VC. So those three sites were able to give us enough patients because Sydenham, Korea is very rare, and it takes the wrong bug in the wrong kid. Well, Ohio River Valley and Salt Lake City Basin were the only two places in the country at that time that had rheumatic fever cases. So it was pretty, pretty fun and exciting. And as I said, the kids were telling us stories that you know they hadn't shared with anybody.

Susan Manfull, PhD 27:28

So today as a lay person, I can pretty much draw the conclusion that that was a strap that was leading to the um to the OCD that you saw. Because of course, strap is what leads to rheumatic fever. And um and we now know, or we it's pretty conclusive, I think. Everybody, most everybody agrees that it leads to to Sydenham's Korea, correct? But I I was in one of your papers, I was surprised to read that it took a very long time for strep to be part of the diagnostic picture of rheumatic fever. I I'm gonna bring this to your attention here because I think it has relevance for pandas and pans, that you write here, you and your colleagues in the paper by Marjorie Garvey, Jay Gede, Gede, and you. You write that it was in 1880 that Fowler described 20 patients in whom the onset of rheumatic fever symptoms occurred two to three weeks after a Streptococcal infection. And then you go on to say, so that, you know, at the time you wrote this paper, it was about 100 years before. And then you go on to say that a few years later people concluded that an infectious agent of some sort was partly responsible for the disorder, although environmental and host factors also played a role. And then there was some discussion about how long the latency period was, which of course with Sydenham's Korea, it's um it's longer. And then in 1944, I pointed out just a few minutes ago that it was psychic trauma that was considered the most common cause of Sydenham's Korea. But in 1944, T. Duckett Jones, who came up with the Jones criteria for rheumatic fever, he acknowledged the association between streptococcal infections and rheumatic fever, but he didn't consider evidence of streptococcal infection to be an essential part. Same was true basically in 1965. And it wasn't until 1984, I mean a hundred years later, that that became part of the diagnostic criteria, which I just think it illustrates perfectly how slowly medicine moves.

SPEAKER_01 30:05

Yeah, and especially in pediatric medicine where it's so difficult to make these associations, right? Because the piece that P. Ducket Jones was in some ways correct, because strep throat is the occupational disease of the grade school child for Ed Kaplan and is incredibly common. If you don't have a strep throat, probably just missed it during the school year. And yet rheumatic fever being so incredibly rare, it wasn't crazy to think that there might not have been an association. But as I learned in my epidemiology course that we took as part of our research training at NIH, if everybody had smoked back when they were trying to make the connection between smoking and cancer, they would have never been able to make that association. And the same thing, obviously, with strip, because it takes that immune piece in the middle and sort of the genetic susceptibility. But yes, I think it's a beautiful example, Susan, of just how slowly things move. And I Henrietta and I used to say all the time that we were so jealous of the H. pylori folks because, right, the first time he presented at the conference and and showed his data suggesting that H. pylori was the cause of peptic ulcer disease and not, you know, stress or all the things that they had proposed up till that point. I mean, we were doing milk drips on patients when I was in medical school to just kind of coat the stomach and keep it cool so it could heal. In retrospect, it was probably the worst thing. We're probably making it worse for those people. But he was able to have his partner scope him, drink some H. pylori, get a riparing ulcer, take antibiotics and clear it. And he he documented every step of this way. And even with that, even with sort of this beautiful and unequivocal evidence that the the bacteria was causing the peptic ulcer disease, people still were unwilling to believe him.

Susan Manfull, PhD 32:11

It's that's fascinating. Of course, you know where I'm going with that. Uh, and I'm gonna jump ahead just a tiny bit because I want to make sure that I go back and and hear the story of your observations of um what became pandas in these children. But it does bring to mind the the slowness, the movement like molasses in medicine in accepting that strep, well, and I'll just stick with pandas, that strep could play a role in neuropsychiatric symptoms. It's it's shocking.

SPEAKER_01 32:47

And I think we

Why Medicine Accepts Ideas Slowly

SPEAKER_01 32:48

got a lot more pushback than ever should have been generated. And to this day, blame a handful of individuals for just being pig headed. And I just I to this day I don't have any notion what their motive was, their motivation. They ended up at one point publishing more than we did, negative opinion pieces. But Judy's philosophy was we're the NIH, we don't publish LPUs, least publishable units, right? You can increase your paper count if you report this test on that one and that test on another one, and just write a whole bunch of short papers. But she made us put it all together, and the most classic example of that was actually a spinal fluid study that I did that we had 20 different authors because they had all had to contribute the laboratory um assessments, and the discussion was it was a very, very difficult paper. But she didn't want us to say, okay, this is abnormal here and that's abnormal over there. She wanted the whole picture to be presented. And I think that bottom line of all it was that every time the critics came after us for something, if it was even remotely legitimate, we got right after it and said, Man, what if they're right? What if this is just a coincidence? What if this is just avoiding the real burning arrow in the room? Whatever. We and I think it made the research much stronger. When I look back at all of the decades of work that we did on pandas and then eventually were done on pans, I think it was really strong. It was hypothesis-based, it was driven by criticism, which is exactly what you need, right? If you don't have your own humility to say, oh, I could be wrong, I need to think about it this way. You're not going to do a good job. And Judy's philosophy, in addition to no LPUs, was that uh she wanted a paper to be publishable if it was negative as well as if it was positive. You need to be able to say something important. So having said that, I don't know why it took us 40 years and we're still actually fighting the battle, but it's coming around.

Susan Manfull, PhD 35:06

But it but it is the same pattern that you've seen when other uh research has surfaced, which uh suggested the opposite of what mainstream medicine was promoting with H. pylori, with uh what were rheumatic fever.

SPEAKER_01 35:23

Yeah, and I think our life would have been much easier if we were actually 20 years later. So we were 20 years ahead of our time. That was the problem. We were 20 years of our hot ahead of our time because it wasn't until 2008 that Joseph Daum published the first cases of anti-NMDA receptor autoimmune encephalitis. And that sort of Dr. Daumow is an incredibly impassioned and forceful personality and was quite capable of making everybody toe the line. And sort of like he did not brook any nonsense about whether or not this was true or real or whatever. Um, he actually published far fewer cases than we did, same mechanisms proposed, had some advantages in that he was dealing with adult patients, so he could do things that we couldn't do with the kids. Um but I I just always have wondered if we would have tried to describe post-reptococcal autoimmune encephalitis of the basal ganglia, which is what we would have called it if we had first described it in 2009, if it would have had a different history. I suspect we'd be at exactly the same point today, but we'd have a lot less evidence of support that we were right.

Susan Manfull, PhD 36:40

Mm-hmm. Well, he of course did find the NMDA receptor, the NMDA antibody. Right. Right? Right. Right. So he found that.

SPEAKER_01 36:53

And he did, but then he was very effective in squelching the subsequent reports that showed that that antibody is present in 5% of healthy people. So why don't they have anti-NMDA receptor and uh encephalitis? And that the rate is increased in patients with schizophrenia in chronic hospitals, uh, chronic psychiatric hospitals, and at least one study in Germany. I mean, NMDA is every bit as messy as pandas is. It's just you you had he did have the ability to have exactly the right antibody, but we did too. Our early studies, we had the D817 antibody, and it was able to separate our patients from patients with pandas from patients with Sydenham Correa from those with non-pandas, OCD, Tourette's ADHD, gorgeous, gorgeous separation. And so I think that, as I said, the criticism just made the research stronger.

Susan Manfull, PhD 37:53

I think maybe I'd be remiss if I didn't mention Semmelweiss and his hand washing. And uh unfortunately he died as a and never saw that that was finally accepted, but begrudgingly by by physicians, and now today,

Pushback Against PANDAS And The Data

Susan Manfull, PhD 38:10

of course, that's that's common practice. So let's go back to your work. You were working with OCD patients, and I think we left off where you brought some patients with Sidden Hems Korea in there. So can you pick up there a little bit? What made you think that that was the OCD and the ticks that you saw was a separate uh, as you eventually called it, disease?

SPEAKER_01 38:39

The study that separated Sydenham Korea from rheumatic heart disease was a retrospective study. And so we we couldn't get a lot of information about what was going on in the brain function or even what their neurologic exam looked like in those kids because some of them didn't have symptoms anymore. Um, Sydenham Korea is what's described as a semi-acute illness, and it lasts anywhere between a few weeks to as long as 18 months. But some of the children had recovered. So we wrote a study, and uh initially we're just going to bring them in and evaluate them in a typical NIH, get you in a room, ask you a bazillion questions, ask your parents even two bazillion questions, do spinal taps and head x-rays, everything we could think of, measure everything in the hopes of finding something, and decided that again, as as physicians first and researchers second, it didn't feel good to be bringing these kids in and just subjecting them to this horrific evaluation. We wanted to treat them. And so we again scouring the literature, we knew that prednisone had been used with some mixed results in Sytenham, Korea, and decided that if it's an antibody-mediated disease, which is what was proposed, that we could remove those antibodies and in theory remove the symptoms. So plasmapheresis is the way to do that effectively. So one of the arms of the study was plasmapheresis, and then the other arm was intravenous immunoglobulin or IVIG. And IVIG, nobody's actually still to this day, nobody knows how it works for sure. There's a lot of theories, but one of them is that it can inactivate circulating antibodies, and so it seemed like a reasonable thing. So we started a study uh to treat the children with Sydenham Coreia, and that allowed us then to get more cases from around the country. And we had them in the hospital as we had our drug drug trial children, and could observe them and compare them with the kids who were coming in to the drug treatment trial, who had obsessive compulsive disorder, who had tick disorders. The movements overlap, just like ticks and OCD overlap. There's sort of a middle zone where a compulsion begins to look like a tick because it's repeated. Maybe it's a simple thing that they have to do. The premonitory urge that's described for Tourette's syndrome sounds an awful lot to me like the obsessive thought that a person with a needing to do a ritual would have. And people now acknowledge that it's a continuum, it's not a dichotomy between ticks and obsessive compulsive disorder. Well, and Sydenham Korea is in there as well. And it's because the basal ganglia is the home or sort of the control for all three of those kinds of things: repeated thoughts, repeated behaviors, and uh repeated neuromotor disturbances. And what we started seeing was that just as had happened in the retrospective study, the children with Sydenham's Korea coming into that treatment trial would talk to us about how they had had bad thoughts, uh, separation, anxiety, fears, some of the light sensitivity. A lot of the symptoms that ended up being described later for as necessary for PAN's diagnosis were being taught to us by the kids with the Sydenham Korea, and that they all started before the movements did. But once the Korea comes and you're wheelchair bound or literally unable to get up out of bed because you're flailing so badly that you can't risk um trying to walk or throw in a cup of water across the room because you have a sudden choreathetoid movement, that kind of takes priority. And especially because the obsessional thoughts were not shared with people unless you specifically ask. Well, as I said, these studies were going on in parallel, the drug treatment trial, bringing in lots of kids with OCD and the Sydenham Korea treatment trial. And we saw a cohort of children in whom they were young boys who had a very abrupt onset of their symptoms, had family history that was not only enriched with obsessive compulsive disorder or Tourette's syndrome, but also with Sydenham Korea and rheumatic fever in the grandparents. And again, the entire reason to look at Sydenham Korea was that Judy had kind of read the old reports from the 1800s and early 1900s and said, there's something here. So we systematically recruited a group of children with very abrupt onset symptomatology. And that group then led to the publication of the paper describing the first 50 patients with pandas. And the reason that it was PANDAS by then, and not the first paper we published, which was antineuronal antibody mediated neuropsychiatric disorder of childhood, um, was A, it's hard to say that. B, there's not a good acronym, and the NIH loves their acronyms. And C, I had a bunch of uh research. Assistants who um I challenged to come up with a better name for this syndrome. And one of them had been down to the Washington Zoo and had spent the afternoon washing the two pandas and came up with pandas. So it it still makes me smile that that's how the disease got its name, but it kind of works.

Susan Manfull, PhD 44:20

I did not know that that was the origin of the of the name. Yeah.

SPEAKER_01 44:27

So I mean it it's Butan, if we had stuck with antineuronal antibody-mediated neuropsychiatric disorder of childhood, don't you think some of the controversy would have been avoided? People would have been too scared to criticize it. Exactly.

Susan Manfull, PhD 44:40

Certainly verbally and uh to trip over that word. So that's what that's with the first 50 cases. I mean, you published a lot that that year. This this article that I'm so taken with was published in the same year, but a few months afterwards. So how did it feel to identify something that was I mean, it's not a new concept. We've known for a long time that infections are associated with neuropsychiatric symptoms, but to um to identify a specific array of symptoms that all held together and you knew or you had at an idea at the time that strep was involved and the basal ganglia and antibodies and uh I I don't know if you were emphasizing inflammation at that time, but how does it feel to have identified something? And I realized it was also you're part of a team.

SPEAKER_01 45:47

We were a part of a team, and it it felt really good, and yet um almost immediately the critics came after us. And in fact, before that paper was published, and one of the reasons it took six years to get it out after we sort of had to cohort together, was Judy Judy just saw this as an extension of it, it was almost like common sense. It wasn't a new discovery, right? As you just said, it had been described before. If anything, maybe it was a rediscovery, but I think we all just thought of it as sort of a a re redisc, a new description or a pulling together of things that other people had already done, and that we were literally standing on the shoulders of giants. And and because of who who she is and who we are, there wasn't sort of a, oh, we discovered a new disease, let's name it after ourselves. It was more, this is a great way to think about this. And two things happened at the same time. So one of them was great. The American Academy of Child and Adolescent Psychiatry actually gave us a paradigm shift award for the Pitans paper, for the one where we just talked about acute onset after strep, but also after influenza and varicello. And that paper was published in '94. And in giving us the award, they literally said that this was going to change the face of child psychiatry. So that was the plus side. Wow. But two years before, Judy had sent me to the Tourette's meeting to present these data, and I gave my 15-minute talk and sat down. And one of the people that became a main critic for years afterwards stood up and said, This is ridiculous. This is just garbage. Another example of an NIH scientist inventing a disease for their own fame and fortune. And he was so vitriolic and it was so awful that they actually sent us off to this other little room. And I was kind of in shock and just sitting there like, I'm a girl from Iowa. We don't talk to people this way. So um, but Henry Tanya Murphy was in the back of the room looking at sort of this discussion, and he would fire off something, and I present our data, and he'd, you know, dismiss it. He literally accused us of of fabricating data and and lying, and it didn't get any better from that point forward. So it it never felt great for one thing, because the kids were coming in and I could make a lot of them better, but too many of them we couldn't begin to touch what was going on with their illness. And at the same time, as we we were still doing the drug treatment trials, and we would have children whose OCD was so severe that their repeating rituals had gotten to the point where they were they were catatonic, they could not move because they couldn't do it right. And there was one little boy I'll never forget, he couldn't answer any of our questions. So Judy uh Henrietta would have to pick him up out of the chair because, of course, he couldn't initiate the getting up out of the chair. He might have a bad thought, and so she would literally pull him up, and the two of us would get him into the exam room, let him stand, because we didn't want him have to get up again, asking the question. She was incredibly patient. She would wait a really, really long time. To me, it felt like hours, it probably was more like five minutes or so to see if he could maybe try and answer the question and then gently take him back out to his mom. And so that's how we knew he wasn't getting better. And by the end of the 12 weeks on the drug on the clamiprimine, he was able to answer three out of the 10 questions within you know the hour we had allotted. So that was a lot better. But you're experiencing that level of severity all the time, and it's hard to kind of step back from it and say, wow, this is exciting, this is a good day. But we still did once in a while.

Susan Manfull, PhD 49:52

Sorry. Because you needed well, as we still do, more research to try and understand the underlying pathophysiology.

How PANDAS Got Its Name

Susan Manfull, PhD 50:04

So after PANDAS, then it became uh apparent in the eyes of a number of other clinicians that it wasn't just strap that would lead to these symptoms. So then PANS was introduced, and I interviewed um Dr. Latimer uh some time ago, and she described uh one of those early meetings. Uh I won't read everything, but she said that there were probably 50 neuropathologists, ethicists, neurologists, psychiatrists, infectious disease people, child neurologists. She said I I can't even remember all the people, but there were a lot of people in the in the room. And uh she said there was a lot of tomato throwing, a lot of yelling, and it uh it could be from a contingent or a lot of it was from uh uh the Tourette's group who didn't want ticks to be involved, and somebody else who didn't want something else to be involved, and that it was just pandemonium, she said. Um It was crazy.

SPEAKER_01 51:17

They literally said you can't call this pans because pandas never existed. You have absolutely no evidence that it didn't exist, and it sounds too much like that. And literally there was an hour-long fight where they wanted to be called CANS Childhood Acute Onset Neuropsychiatric Syndrome. We wanted it to be pediatric, and actually pediatric was literally so that we could include youth up to 21, whereas childhood stops at 15. I mean, right, and we were it we were yeah, tomatoes were being thrown, but the two contingencies, it was like we weren't even discussing the same thing the whole time. So yeah, I I and then bless her heart, Beth was willing to come back another time when we had an equally. Contentious meaning you'd think we'd learn our lesson, but we didn't.

Susan Manfull, PhD 52:10

Well, you guys have waded through so much adversity and other types of challenges to to make your your case known. And I think that we're probably safe to say now that people are some people, uh, the Dartmouth clinic, for example, are looking at all of psychiatry as potentially related to infection and immune dysregulation and and inflammation. So I'm sure you never envisioned all the controversy around it, but you made it through and and there's real, I think we're in the midst of a of a paradigm shift. And I I should hope so.

SPEAKER_01 52:54

I agree. I think it'll be just wonderful. I was thinking about that a few weeks ago in the split between neurology and psychiatry, and that it's time that we think about the brain back together again. And that they take the same boards, but there's this animosity where if it's not motor, it's not sensory, then it can't possibly be real. And I think that that's beginning to ebb.

Susan Manfull, PhD 53:21

Um yeah, as a as a student of the history of psychology, that was one of my favorite periods, the end of the 19th century and the early 20th, when that split occurred. As you mentioned earlier, Charcot and his student Tourette viewed ticks unequivocally as a distinct hereditary and neurological disease. But Freud, also a student of Charcot, saw ticks as a psychological in origin, in neurosis. And it wasn't until the 1960s that medicine began to encourage people to see ticks as Charcot and Tourette had originally defined them neurological. I think that's incredibly interesting and very relevant to what's going on now.

SPEAKER_01 54:09

As you said, there is a paradigm shift underway, not just in the areas of coming from the mental health side, but all of the things we're seeing, you know, post-COVID uh symptomatology for patients, that ended up being huge for the autoimmune uh neuropsychiatry community because people were seeing it in huge numbers and recognizing that there's something here that the brain can get as sick as the body can, but it has a different way of expressing a symptomatology.

Susan Manfull, PhD 54:39

Right. So this is also have bearing on um on people with what's typically called uh refractory sort of disorder or treatment-resistant disorder. So they're getting some additional attention. So maybe they didn't have a straight uh clinical depression or schizophrenia or what have you. Maybe there are some other, we'd say, infection and uh inflammation and uh the immune system is playing a role. So I think that there's been tremendous benefits, those seeds that were set in place, you know, some 40 years ago. And I so I'm looking at that same paper that I I keep referring to, and it says here evidence for post-streptococcal etiology for pediatric autoimmune neuropsychiatric disorders associated with strep pandos is compelling, yet many questions are unanswered. Until the etiology of rheumatic fever is known and there is a specific diagnostic test, some confusion is inevitable. You go or your your team goes on to say that the pathogenesis of Sydenham's Korea, since the pathogenesis of Sydenham's Korea is by no means fully understood even today. The discussion over pandas is likely to continue well into the next century. And we're in the next century. So you were prophetic in that sense. And you write here, and so you wrote this, you and your team wrote this in 1998, and here we are in 2026. Studies of pandas will require careful preliminary planning, adequate funding, and multi-center collaboration.

The PANS Naming Fight

Susan Manfull, PhD 56:28

Yes, there'll be different camps, uh, enthusiasts and loyal opposition, and this should be encouraged, as you suggested earlier in our conversation, since it can lead to further research in time, a greater understanding of the disorders. Answers will come through basic research investigation that examine various features of the host and the microbe, studies that delineate the epidemiology and natural history of pandas and pans and trials of penicillin prophylaxis and immunomodulating treatments. It is possible that these studies will also provide insights into the etiology and pathophysiology of other neuropsychiatric disorders, as we just mentioned. So it seems that since I I as the executive director of the Alex Manfell Fund, and we have three primary goals: one being awareness, one being educating clinicians so that these disorders are and diseases are are recommended earlier, but the other is research. So we are very much aware of the lack of funding, particularly in recent years, for um for these disorders and diseases. But let's imagine for a moment that there was significant funding, there was sufficient time for careful planning and multi-center collaboration. What would you like to see? How would you like pandas and pans to be stud aid? I'm kind of dropping this big question on you.

SPEAKER_01 58:12

So you are as you read that those quotes from 1998. I was actually smiling because so much of it got done. I'm thinking of the work by Dritton Agayou and his colleagues with the strep mouse where they literally induced pandas. I'm thinking of some of the unpublished data that we had and that Madeline Cunningham had, and it couldn't be published because it was just too good to believe, and then couldn't be replicated. In our case, very early on, we had the opportunity to work with Pat Levitt and Peter Strick and take our kids' serum from children with pandas, children with sittenham career, and children with OCD or tick disorders that didn't have any evidence of an autoimmune component to it, and a group of controls. And they put those uh samples onto juvenile monkey brains. And we were sitting in a conference room in Building 10, and initially they would sort of ask us for the clinical description, and then they'd throw up the slide and be like, Well, that's the cutamin and that's the caudate. And you know, we started to see this, it was crazy. And if it was a control, there was nothing showing up on the slide at all. There was no staining. And about halfway through, we actually flipped it, and they put up the slide, and we're like, oh, and didn't know who it was going to be. They didn't tell us the number. We say, Oh, well, that child should have OCD because the caudates, there's antibody reactivity in the caudate and the putamin, and then we look at the look up the child, and that was exactly what they had. So it was just this moment of wow, this is not only it's individualized and yet common across the group. Well, we didn't have more serum, and we tried to use plasma, and we wasted a year, and then they both moved positions, and the opportunity was just lost to replicate that study, so it never was able to be published. But I've never forgotten that that this was always clear that it was antibody-mediated, clear that it was strep because they were then applying it against the strep bacteria, also getting reactivity, and others have done that as well. And Madeline Cunningham's study was equally just plain goofy because again, kind of didn't see the forest for the trees. They were in collaboration with the group in Israel giving the patient serum to these groups of mice, and they had to stop using the elevated maize because the mice would stop. They thought the mice would get anxious and they would stop eating. What they actually had was a model of anorexia using our kid serum. So it was like those kinds of discoveries along the way. And what I would love to see happen is as you have already read, I would love all of our sites who have large groups of patients, Dartmouth and Stanford and the Pace Clinics in Arizona, and some of the other places that have been established, and some that where the investigators are retired, like Florida and NMH, to be able to get back together again and do a large-scale study where not only are we evaluating the children who have the pandas, but let's do some prospective work of looking at their siblings and their classmates and trying to pull them in and get those kids within days of them having

Big Research Priorities For The Future

SPEAKER_01 1:01:52

their first episode, whether it be separation anxiety when they're kindergartners, but they've gone to kindergarten for the whole, you know, from September to February, and all of a sudden they have separation anxiety about going to school. That doesn't make any sense. That has to be a presentation of pandas. So I would love to see larger studies that way. I think we should be very bold and start looking at animal models of a lot of these interesting biologics, all the monoclonal blocking antibodies that are out there. Wouldn't it be amazing if we could find one of those that interacted with the antibodies that were described by Chris Pittinger or by uh Madeline Cunningham or some of the other ones, or even the ones from the 1970s that Husby had described, or Zabrisky's DH17. And let's just do the a big panel. And then for the strep, we need better tests of what the rheumatogenic, what the pandigenic strep is. And Pfizer had a panel, but because strep is not sexy, it's not getting a lot of money, right? You do the throat culture, you do PCR, and you treat it if the kid's got a strep throat, but the current guidelines are actually dangerous in that they're telling pediatricians not to even evaluate for strep if the child has a runny nose at the same time. Well, that doesn't make any sense. And it's certainly if you look at the old rheumatic fever literature, it's indefensible. So I would love to see a combination of good common sense among our clinicians and the policymakers, people at the American Academy of Pediatrics or at the NIH and in the federal government determining what's happening with our children. And in an ideal world, we would be spending money on epidemiologic studies again. There's no epidemiologic research on mental health, mental illness. There is none on bacterial infections. Rarely is there some on viruses, right? If you got COVID, suddenly you've got 400 papers a day being published on this virus. Um, but then once the lockdowns happened, you had 500 papers being published a day that were meta-analyses of people's work from before. So they weren't very helpful. Um, but it would be really nice if we could just have some field studies like we're done for rheumatic fever, and those were what actually made the definitive connection. Uh, the studies done in the 1940s among military recruits, where they were able to show the strep come into a training camp, rheumatic fever followed three weeks later. Then they started the prophylactic studies and showed that they didn't have those um recurrent, they didn't have the same risk coming through. And it has to be nationwide because just like with our very first study in the Sydenham, Korea versus rheumatic heart disease patients, it's it's not going to be common. It's going to be just little pockets here and there across the country, but we should be able to catch it. And I think as soon as we can get back to where we were, maybe in the 80s and 90s with 2026 technology, that to me it feels like the answer is right around the corner.

Susan Manfull, PhD 1:05:09

Well, let me follow up with a couple of questions about what you just said, just so I

Rheumatogenic Strep And Better Testing

Susan Manfull, PhD 1:05:14

understand. So is there a particular rheumatic strain of strep that causes rheumatic fever?

SPEAKER_01 1:05:20

They call it rheumatogenic.

Susan Manfull, PhD 1:05:22

Rheumatogenic, that's it. Uh strain that causes rheumatic fever.

SPEAKER_01 1:05:27

Yeah, there are in the historical literature, there were approximately a dozen described out of the 140 some Lancefield strains of strep. They've now with molecular techniques, we can go much finer than that. And there are people that are working, not many in the United States, but worldwide, there are people trying to identify what it is that makes it rheumatogenic. What is that cross reactivity? Because you might be able to prove produce vaccines that could protect against the cross reactivity and protect protect against the sequelae. And then it wouldn't be necessary to treat financially. The forces are not driving in favor of that because penicillin treatment of strep is so cheap. It it will always probably be cheaper to just treat the strep throat rather than try and only treat those who need to be prevent, you know, have their side effects prevented. But yes, there are rheumatogenic strep. And here in the Washington, D.C. area, it's now been probably 15, 20 years ago. But we had a mini outbreak of rheumatic fever and saw for the first time more than one child per year in our major hospital in the ANOVA hospital system with rheumatic heart disease with Sydenham Korea. And at that same time, the number of pandas cases just exploded, which makes me think that we were right early, early on in our observations of the kids with Sydenham Korea that whatever makes you, whatever it is about that strip to child interaction through the immune system that results in pandas or Sydenham Korea, the dose does not have to be as big to give you OCD as it does to give you abnormal movements. And so pandas is going to be a lot more common always than Sydenham Korea is. It's just that it doesn't come to people's attention. And that's probably also contributing to the controversy about is this a rare disease or is it a common disease? But the answer to your the simple answer to your question is yes. There are rheumatogenic strains, and I am very confident that there are pandesogenic strains as well.

Susan Manfull, PhD 1:07:45

Mm-hmm. Mm-hmm. So also looking at the future, as you know, we established a brain bank at Georgetown. And we feel strongly that more research on brains, where this begins, is really necessary. And in the case of Alex, in which an autopsy was done initially at NIH, and then there was one on which a paper was

Brain Circuitry And What Autopsies Teach

Susan Manfull, PhD 1:08:12

was was written. She did have, well, there are a number of things that were found, but she had parenchymal astrogliosis of the caudate nucleus, which you had mentioned, that part of the basal ganglia, and perivascular astrogliosis in the thalamus, which of course is right next to the basal ganglia. And there were a number of other things that that were found. And I like to think that understanding the pathophysiology of these diseases at a more molecular basis would be really helpful in terms of understanding and in terms of developing drugs. Do you have any thoughts on that?

SPEAKER_01 1:09:02

I agree completely. And I think that even what you just described from Alex's brain is exactly what we had predicted. Again, not that necessarily we came up with this, but in the late 80s, everyone was really focused on the five parallel circuits through the basoganglia. And the one that was most likely to be related to obsessive compulsive disorder was the corticostriatal thalamo loop, where it goes from the cortex through the basoganglia and the thalamus back up to the cortex. And people were actually trying to interrupt that with psychosurgery at different points in the circuitry to see if they could interrupt the obsessive compulsive thoughts. And some encouraging results were seen in patients who had had completely refractory symptomatology, otherwise. And frankly, that was what Judy's motivation was to get us started on all of these studies to begin with. Dr. Rappaport knew about that neuroanatomy, that neurophysiology, and she was trying to find diseases that sort of were a natural experiment of interruption or excitation of those, of that circuitry to see what the symptomatology would be. And that's where Sydenham Korea and this research all started. And literally, it would be fabulous if we could get that neurophysiologist and the neuroanatomist in the same room with some of the uh brain-based psychiatrists and neurologists to start thinking again about circuitry because now we do, as you pointed out, now we have molecular techniques. We don't have to just say, oh, well, somewhere in the thalamus, we can say it's this particular cell type or it's this synapse, it's this cluster of synapses that's actually aberrant. And once we know that, we'll be able to design better treatments for the general patient with obsessive compulsive disorder. And that was our goal all along. Judy didn't particularly care about basal ganglia-based OCD. She wanted to get obsessive compulsive disorder treated and thought that we needed a better drug than sort of a serotonin reuptake blocker because it just doesn't do the job for most patients.

Susan Manfull, PhD 1:11:18

Right. So this is too big a subject

Self Harm Intrusions And Keeping Kids Safe

Susan Manfull, PhD 1:11:21

to discuss now, but I'll uh maybe we can talk again. You mentioned at the beginning of our conversation that you became very interested in teenagers who made attempts to take their life, multiple attempts. And of course, I'm very familiar with that in cases of pandas and pans. And there are the widely known intrusive thoughts in very, very young people to harm themselves or to kill themselves. And at six years old, nine years old, most uh children have no idea what that what that means really. And I I'd like to see us do more research on why that is such a prevalent flavor of the intrusive thoughts and what happens when you act on them in the brain. I I think I'd really love to see some research in that area.

SPEAKER_01 1:12:21

I think that it would be incredibly important because just as we would learn, we had hoped that pandas and and post-strip OCD might be a model for the larger category of OCD. I think that we can learn more about the whole by studying these individual parts. And the the self-harm is kind of that combination of a very overwhelming depression, which is clearly cytokine driven, right? When you give uh certain cytokines and chemokines to cancer patients, for example, they go from having an incredibly euthymic, normal, happy mental state to being completely depressed and suicidally so within days. And I think so it's not surprising that you might see the same kind of picture in a post-strep patient. And similarly, you have at the same time a loss of impulse control. You get that ADHD kind of inability to hold two thoughts together in good sequence, make good decisions because you're acting impulsively. Or and then the final piece is just the demoralization. You go from being a child who's been the star student, everybody, the teacher's pet, everybody has loved them and they've worked very hard at that because our kids tend to be the superstars, and then suddenly their life is falling apart, and that comes with some demoralization, particularly if you're sorry, one of those that goes to doctor after doctor who's telling you that there's really nothing wrong with you.

SPEAKER_02 1:13:58

It destroys them.

SPEAKER_01 1:14:01

So, yes, I think you're right, Susan. We we need to be humble enough to kind of take people at their word and believe them when they're telling us these things and then meet them where they are and try to keep them safe. That's my goal for all my pandas kids for the first few weeks of their illness, keep them safe, then try to heal them.

Susan Manfull, PhD 1:14:24

And you you talked about the relay circuitry with the thalamus and the cerebral cortex and just what's going on there that you're if you're in the middle of a flare with multiple cytokines and what have you, what what's going on that would allow you to actually engage in that behavior. So on to our last subject.

Listening To Families And Closing

Susan Manfull, PhD 1:14:50

I had the pleasure of meeting your patient number one, she referred to herself. And I believe this is the patient that, oh, I I know because she told me this, uh, that kept track of the uh OCD symptoms and correlated that with uh strept titers. So she gave me her telephone number and I cannot find it. I've I've um I've got to look a a little harder so I can give her a call because I think that that's a great example of how you were doing your own research and you and Dr. Rappaport and your other colleague were making these observations, but you listened to the patient and to the patient's mother. Yes. And you credited her in one of the papers that I read. And I think there's a lot of conversation these days, and a lot that's written on how important it is to listen to our patients, and you were doing that. Yeah. That's to your credit.

SPEAKER_01 1:15:53

As I told you, my first job after pediatric residency was at the Evanston Hospital. And in addition to doing PICU and NICU duty and a little bit of adolescent medicine, I worked in the free clinic, and the two men that had been there for decades were both grandfathers and incredibly good pediatricians, and they're the ones that said the mother is always right, you will listen to her.

Susan Manfull, PhD 1:16:19

And clearly you have. Dr. Sweden, thank you so much. This has really been a pleasure. I I think I feel like we could have had tea together in this conversation. And I I wish we were actually sitting across from one another. But it's just been a delight to talk with you, and I'm honored to be able to have had this conversation with you. And I look forward to talking to you more about some of your ideas for continuing to move this field forward. And with any luck, we'll see you at our symposium and uh hear some of those ideas. That sounds fun.

SPEAKER_01 1:16:58

Thank you so much. This has been, yeah, I agree. We could have had tea. It's been very fun. Thank you.

Susan Manfull, PhD 1:17:04

All right, Sue, thank you.

William Manfull 1:17:06

This concludes episode 24 of Untangling Pandas and Pans. Thank you for listening. For more information about pandas and pans and the Alex Manful Fund, please visit the AlexManfulfund.org. The content in this podcast is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition.