S2 E19: Rheumatic Clues To Understanding the PANDAS/PANS Puzzle -- A Conversation with Dr. J. Patrick Whelan

A sore throat that ends in compulsions, tics, and a child who suddenly can’t sleep or attend school sounds improbable—until you hear a pediatric rheumatologist walk through the biology. Dr. J. Patrick Whelan of UCLA sits down with Dr. Susan Manfull, Executive Director of The Alex Manfull Fund, to unpack how infections and the immune system can collide with brain function, producing abrupt-onset OCD, motor and vocal tics, restricted eating, and anxiety that look psychiatric but respond to immunomodulatory treatments. Drawing from a variety of sources, including the history of rheumatic fever, the Lancefield classification of streptococci, and modern cases of Multisystem Inflammatory Syndrome in Children (MIS-C). Dr. Whelan explains why PANDAS and PANS challenge old categories and demand a broader clinical lens.

We dive into innate versus adaptive immunity, what “autoinflammatory” and “autoimmune” really mean, and why so many affected kids also show signs of immunodeficiency. If routine tests like ASO and anti–DNase B come back normal, does that rule out strep’s role? Not necessarily. Whelan shares how expanded antibody panels, trial responses to antibiotics or anti-inflammatories, and careful history-taking can reveal an immune trigger that standard workups miss. He also outlines the practical steps that matter right now: restore sleep, get moving, stabilize nutrition, and build companionship—simple interventions that reduce pain amplification and calm a dysregulated nervous system. Finally, we talk about why “listening to the patient” often illuminates key clues to understanding the case.  

If you care about pediatric mental health, infection-associated neuroimmune disorders, or how medicine evolves when data and curiosity meet, you’ll find both science and solace here.

If this resonates, follow the show, share with someone who needs it, and leave a review to help more families and clinicians find these insights.

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

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Transcript

Host Intro And Episode Framing

SPEAKER_01 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 Manfil 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.

SPEAKER_00 1:18

This is episode 19 of Untangling Pandas and Pans, recorded October 24th, 2025.

Guest Background And Training

What A Rheumatologist Really Does

SPEAKER_01 1:28

Welcome to Untangling Pandas and Pans, a monthly podcast in which we talk about infection-associated immune-mediated neuropsychiatric disorders. It's a real pleasure to have as my guest today Dr. Patrick Whelan, a pediatric rheumatologist and an associate clinical professor of pediatrics in rheumatology at UCLA. He completed his undergraduate work in biochemistry at Harvard University. Although, interestingly, he intended to major in economics until, fortunately for us, he was captivated by a lecture by Dr. David Dressler, a highly acclaimed professor who created Harvard's first course on biochemistry and molecular biology, which became one of the most popular courses at Harvard. Dr. Whalen continued his medical education with a PhD from Texas Children's Hospital in Houston and his MD from Baylor College of Medicine. He returned to Harvard for his rheumatology training and stayed for 20 more years as a pediatric rheumatist at Massachusetts General Hospital in Boston. Dr. Whalen began treating patients with pandas shortly after he gave a lecture as part of the annual Mass General Hospital Pediatrics Conference in 2009. Dr. Sue Suito had just published her seminal paper in 1998, and pandas was still a relatively unknown disorder. He spoke to a packed ballroom of pediatricians who wanted to learn more about this newly identified disorder. At that point, Dr. Whalen, to the best of his knowledge, had not yet seen a patient with pandas. But that quickly changed, and the rest is history. Beginning with what a rheumatologist brings to the understanding and treatment of pandas and pans, to the roles of immunodeficiency, autoimmunity, and auto inflammation, including some history, and ending with TILT, Stories on the Edge, Dr. Whalen and I talk. TILT, organized by the Alex Manfell Fund, is a brand new storytelling event and the brainchild of TAMF board member Sherry Strollson. This sold-out event premieres on Tuesday, October 28th in Hermosa Beach, California. And Dr. Whalen will be one of the storytellers. Listen to my interview with Dr. Whalen now on Untangling Pandas and Pans and meet him and the other storytellers on October 28th. That is, if you were lucky enough to have gotten a ticket. But if not, please know we hope to schedule more tilts. Okay, let's get started. Dr. Whalen, we are so very glad that you're here. I'm going to start off with a really basic question. Because I didn't know the answer. I didn't actually even think about asking the question until a few years ago when I began reading more about pandas and pants. I didn't know exactly what a rheumatologist was. What is a rheumatologist?

SPEAKER_03 5:03

So thank you so much, Susan, for inviting me onto your popular podcast. And I have been asked that question many times over the years, oftentimes by the patients that are sitting in front of me. Like, why am I here? You know, it's this curious befuddlement because the pediatrician has decided that this person should see a rheumatologist. And oftentimes, you know, they are unaware of what it is we do or why it would be helpful for uh them to see us. So the word rheumatologist is derived from a Greek word rumos that means to flow. And it was originally coined in the 17th centuries by a French doctor who was very famous, whose name was Baileu, B-A-I-L-L-O-U. And he appreciated that there was a form of arthritis, pain in the joints, that appeared to move from one joint to another. And so he had this idea that it was something flowing through the body, some kind of evil humor. And so he created this word rheumatism as sort of a reflection of that. And it turns out that the kind of arthritis that occurs in rheumatic fever is very unique to rheumatic fever in that it moves like that. It's very ephemeral. And we use a term now for historical reasons, palindromic rheumatism, which means inflammation that moves from one joint to another. And it was not appreciated by Bailu at the time, but he was describing rheumatic fever. And ultimately, it came to be appreciated that there were many different causes for arthritis. And the most common cause through the Industrial Revolution was the rich man's arthritis, gout, which overtook rheumatic fever as sort of the most common cause of inflammation in the joints. And later it was appreciated that you had these more corpulent men who developed gout and distinguished them from women who developed this chronic non-motal arthritis, particularly in their hands. So they started coining the term rheumatoid or like rheumatic fever. So that's the origin of rheumatoid arthritis. And it's really not until the middle of the 20th century before a field of uh rheumatology emerged as an independent specialty. And there was, I had the good fortune to do my training at Massachusetts General Hospital in Boston, which was one of the places where the field of rheumatology first came into existence. The other big ones were in Mayo Clinic, you know, in Rochester, Minnesota, and also Johns Hopkins. And there's there was a famous doctor at Johns Hopkins, who their first dean, who had a funny saying, he used to say, when a patient with arthritis comes in the front door, I go out the back door. And his name was Sir William Osler, O-S-L-E-R. So, and in some respects, it's funny that arthritis is such an intrusive disease process. It takes over people's lives, it disrupts their sleep, it interferes with their normal function. And remarkably, we still don't really understand very well why it takes place. But rheumatic fever is the one major exception. I think we understand rheumatic fever pretty well, and it's particularly germane to our conversation today because, in many respects, rheumatic fever is a model for the whole phenomenon of pants and cannabis.

Why Rheumatology Fits PANS And PANDAS

SPEAKER_01 9:00

Mm-hmm. Well, we'll definitely get back to that. That's that's really interesting. So, what drew you to rheumatology?

SPEAKER_03 9:09

Well, I was I was an economics major in college, and I always envisioned myself becoming an economist. And I, my junior year in college, I wrote a review of a course that was the introduction to biochemistry at Harvard. And there was a magnificent professor named David Dressler, who taught this course. And he basically taught a science course uh like it was a storytelling event. Every day he would get up there and he would just tell these wonderful stories about, you know, and then this scientist had this idea, but he tried it and he was completely wrong. And then he tried this idea. And the uh students loved this course so much. And as I was writing the review of it, I decided, uh gosh, I really should take this course, even though I was not in the sciences. And uh he really won me over. I really became more and more invested in it. And my mother, as fate would have it, had suffered from terrible rheumatoid arthritis, and she was a very accomplished pianist. She'd been a music teacher and she was a performance pianist. So she had this incredible gift to be able to sit down at the piano and play anything by ear or to read these complex scores. And when she was 33 years old, she came down with arthritis and it progressed rapidly, and she lost the use of her hands as a result. So I began thinking in terms of maybe I should invest myself in medicine in some way. And after I graduated from college, I ended up getting a job as a translator for a medical team that went down to the Dominican Republic. So I spent summer there as a Spanish translator for these doctors and dentists who were setting up clinics in little villages on the border with Haiti in the Dominican Republic. So that was really my first introduction to being in a clinical environment. And I ended up getting a job working in a rheumatology laboratory at Harvard Medical School.

SPEAKER_01 11:20

After this experience in the Dominican Republic?

SPEAKER_03 11:23

Yeah. So many of the doctors there were really frontline researchers. And I had an exposure to doing research in this field that was very exciting. And in fact, I was just together with many of them last Friday at the Cold Spring Harbor Laboratory in Long Island. We were having a symposium that was a tribute to one of the researchers there. So we had a chance to sit around and reminisce about what it was like in those days, you know, 40 years ago, trying to figure out all the nuts and bolts of how these rheumatic diseases came together. So I ended up applying to medical school, and I got a scholarship from the National Institutes of Health to support an MD PhD program. And I enrolled at Baylor College of Medicine in Houston. And my PhD advisor there was an amazing guy named Dr. Bill Shearer, who was an immunologist whose claim to fame was that he was the doctor for David Vetter, the boy in the plastic bubble. And so I did my PhD at Texas Children's Hospital in uh Houston, and I ended up working with a number of families that were beset by an inherited form of immune deficiency. So I've essentially built my career around studying the relationship that immunodeficiency has to the development of the rheumatic diseases. And I'll just share with you after I went to Boston and did a rheumatology fellowship at uh Brigham Women's Hospital and Boston Children's Hospital, which are Harvard-affiliated hospitals, I did a fellowship in AIDS oncology at Massachusetts General Hospital. So it brought together these three fields, which are the rheumatic diseases, uh, autoimmune and autoinflammatory disorders, the oncologic diseases, transformation, and cancer, and the susceptibility that immunodeficiency plays, and then clinical immunology, which is trying to understand how the immune system functions.

SPEAKER_01 13:28

You are a perfect candidate to work with pandas and pans patients, and I imagine started out uh ahead of many people in having so much knowledge about the immune system and how that works. So, in your mind, what does a rheumatologist bring to the understanding of pandas and pans? I think we can kind of deduce what your answer is, but what do you bring to the table? Which I should state right off, I think you bring a whole lot to the table, and it's probably underestimated by the average person. But what do you bring to the table in understanding and treatment?

SPEAKER_03 14:13

Maybe I could answer that by sharing with you a quick story that's related to a summer program that I helped to run for high school students that's been sponsored for 57 years now by the Los Angeles Pediatric Society. It's called the Eve and Gene Black Summer Career Program. And this past year we had more than 400 high school students from around the city who were involved in it. And I do my best every year to recruit people from many different walks of life and medicine to be presenters. And we have 48 presenters every year in the month of July who take turns making presentations to all these high school students and telling them about the excitement of a medical career, whether they're um as a physical therapist or a surgeon or emergency room doctor or a chaplain. And this one particular presenter who is a cardiologist was talking to the students, and one of the kids raised his hand and said, You know, why did you decide to become a cardiologist? And incidentally, within medicine, cardiologists are held in very, very high esteem because the heart is so important and it's kind of a stressful specialty, and it's very competitive to get into it. So, anyway, but this guy very humbly responded. He goes, Well, I wasn't smart enough to be a general pediatrician. That the heart he said is just about the right size for me. I can understand the heart.

SPEAKER_01 15:40

Oh, that's great. I love that.

Sleep, Pain, And Simple Interventions

SPEAKER_03 15:42

So I share that with you in part because being a rheumatologist is sort of all over the map that you have to know a little bit about everything, that it affects our brain and our nervous system, it affects the endocrine system and all the glands of the bodies. And obviously, the whole anatomy of the musculoskeletal system is something that's really part and parcel of what we do. So I think that rheumatologists bring a sensibility with regard to looking outside of just any one particular organ. So we don't think of pandas, for instance, as just a brain disorder. It's something that affects the body very broadly. And so I think that's sort of the unique sensibility. The one other thing I might share with you is that there's a condition that we take care of frequently in rheumatology called uh fibromyalgia. And it's something that has, it's a disease that shares a lot of commonalities with pandas, in that for many years people doubted that it existed. They questioned its existence. It uh was originally called neurasthenia or weakness of the nerves in the late 19th century. And because it particularly affected women, and because blood tests and other examination uh findings were not present in those individuals, a lot of older rheumatologists even discouraged the idea of making a diagnosis like that. Well, now we understand full well that fibromyalgia is a very real thing that impacts people's lives. And I mention it in part because fibromyalgia and the study of it have given me a model that I've used to try and develop a paradigm for understanding pans and pandas patients. And one of the things that has emphasized to me is that the simplest things make the most difference. So we know, for instance, that fibromyalgia is a pain amplification problem that results from poor sleep quality or inadequate sleep. And getting a good night's sleep is just absolutely critical to our well-being generally in life, but of particularly of importance to people with pans and pandas who virtually all have disrupted sleep. It's uh it's just a universal feature, and it's also part and parcel of the whole fibromyalgia phenomenon. But I think it's bigger than that because the other important simple things are things like exercising, things like our recently Finnish Surgeon General used to emphasize companionship and affection are essential human needs that are underappreciated. And I think when you look at the family stories that we see in Pans and Pandas, where these families are challenged like nobody's business with the child that can't get it together and oftentimes can't go to school and is screaming at their siblings. And I was always charmed by that wonderful expression that the children that require the most love will ask for it in the most unloving ways. And I think that that's an element to this that I hope I bring that to my work every day is trying to model how we can care for these children and make them feel valued and respected, all that. But nutrition is a big part of it, and exercise is critical. So it's the simplest things that make the most difference. And I think that rheumatology has really equipped me to think broadly about this in a way that maybe a neurologist or a psychiatrist isn't doing.

SPEAKER_01 20:33

So you've got that understanding that um some of the other people don't have, which is great.

SPEAKER_03 20:41

I imagine many of your uh listeners are probably familiar with an article that came out in the New Yorker in July, New Yorker magazine, who was by a woman named Rachel Aviv, and it was titled something like Mary Had Schizophrenia until she didn't.

SPEAKER_01 20:56

Yes, it was a great title.

SPEAKER_03 20:59

And uh it tells the story of this woman who was herself a physician who came down with you know these increasingly bizarre behaviors that really made being a parent and being a spouse impossible for her.

SPEAKER_01 21:14

And late in life.

SPEAKER_03 21:16

In her 40s, yeah. So it didn't fit the mold of somebody who comes up with schizophrenia in their 20s. That's more typical thing. And she um struggled for years, for like 15 years, until it turned out that she was diagnosed with lymphoma. And then she was treated for her lymphoma in a variety of ways, including with a drug called Rituximab that we frequently use in our pandas patients. And in a matter of a few weeks, all of her schizophreniform symptoms disappeared and she was like a new person. So I mention it in part because one of the people they quoted in that article is an MD PhD researcher at the National Institute of Mental Health. His name is Chris Bartley, D-A-R-T-L-E-Y. And he had a wonderful quote in the article, and he said, we have to accept that there are alternative models of disease. And I run into this frequently, that especially my child neurology colleagues are very skeptical of the panz and pantas field. And I think it's perfectly understandable that they have that skepticism because when you do the kind of advanced studies that they routinely do, lumbar puncture, MRI of the brain, electroencephalography, typically our patients don't show any abnormalities on those tests. And so their conclusion is well, this can't be an immunologically driven brain problem, because where's the evolution, where's the beef? You know. And I think part of the reason that I have been more attuned to seeing this as an immunologically driven disorder is because, first of all, immune-related interventions like IVIG can be very helpful. And um, I saw a patient yesterday, parents struggled for a year, and then they they put the child on motrin, and he was like dramatically different.

SPEAKER_01 23:21

Amazing.

Rare Disease Insights Informing COVID

SPEAKER_03 23:21

Motrin is a non-steroidal anti-inflammatory drug, and um, I don't use it very much myself because it's so short-acting. But, you know, this is sort of circumstantial evidence that there's a role for the immune system in impacting the parts of the brain that mediate involuntary movement, involuntary thoughts. And just the last thing I'll share with you is one of the other areas that I work on in my own research life is for the last 20 years, I've been studying a rare disorder called uh atrophic papillosis. It's a very unusual vascular disorder that used to be a fatal disease, and it still is pretty uh severe in young children when they get it. But about 15 years ago, we developed a set of treatments for it, and now we have quite a few patients who are long-term survivors from it. And one of the striking things about this disease that's so severe that it kills virtually all of the patients who are untreated is that their immune system looks like it's just flat on its back. They don't have elevations in the sedimentation rate or the C-reactive protein, and they don't have any blood test abnormalities, and yet the immune system is destroying their blood vessels. And uh, once we figured out what some of the elements were of how it was happening, we came to appreciate what you needed to do to save these people. And it's been very exciting. I just wrote two chapters for one of our medical texts called Up to Date on the Subject of this condition, Dagos disease or atrophic papillosis. So I mentioned it in part because this is a disease that defies all of the rules with regard to how the immune system damages parts of the body, which is what we see in all the different autoimmune and auto-inflammatory disorders. And it's turned out that the pathology of this rare disease that I study is very similar to what we see in people that have COVID vasculopathy, which of course is something that's affected tens of millions of people around the world. So this rare disease has given us a little window into understanding what's going on with something as profound as you know the whole COVID pandemic. And I'd like to believe, too, that if we have a better understanding of pans and pandas, it's going to open up a whole new window into understanding the broader issues of what is schizophrenia and what are schizophrenic form disorders, where do they come from? Why do they happen? Why this person and not that person? And uh the OCD world, for that matter, is still very poorly understood. But I think pandas may be a window into understanding it, benefit a much broader population by paying attention to these kids and learning from them, you know, which is what I try to do every day.

SPEAKER_01 26:17

Mm-hmm. So um I just want to respond in at least two ways to what you've just said. Uh, one, the case of Mary that was discussed in the New Yorker magazine. For me, I made copies of that article and took it to a conference where I was giving a talk to high school students to underscore the idea of curiosity and of being kind of like an investigator. Because with Mary, I mean, there were a lot of things that didn't quite fit with her. She wasn't responsive to the treatment, any of any of the many treatments that she had. And as you pointed out, she was in her 40s, which is absolutely not the typical age of onset for schizophrenia. So I'm hopeful that doctors will look at that and say, why? You know, what's going on here? What else do we need to look at? And nowadays, admittedly, quite different from when she was first diagnosed, we know that we should follow more avenues, like the immune system. So I I just found that article fascinating and and how the irony in developing cancer and the blessing that that was for her by getting the rituxamab.

SPEAKER_03 27:43

It's funny in that article they did not use the word perineoplastic, but that's a term we use in medicine for symptoms that accompany a cancer process that are not typically thought of as cancer type symptoms. And the one of the really interesting examples that I'm sure many of our PANDAS parents will be acquainted with is that uh they're they're all familiar with this term brain on fire disease, which is the anti-NMDA receptor antibody disease. And that can be associated with a form of ovarian cancer that's called uh teratoma. And so those are individuals who you know have a occult ovarian tumor, and then they develop these really unusual uh behavioral symptoms and sometimes seizures and that kind of thing. So it's the funny thing is, of course, in medicine, there are only so many hours in the day, and when you've got 15 minutes to see the patient, are you going to have the wherewithal and the energy and the resourcefulness to be able to pick out those cases? I think I think often about a woman I took care of one time. I was doing my psychiatry rotation in medical school, and I was on the locked ward, and there was I met this woman who was in her 40s, and she had tried to kill herself. And she was a very uh productive, accomplished person who never had depression problems, and just out of the blue, she developed depression and started having these terrible thoughts of self-harm. And and then she actually tried to kill herself. So she was came into the emergency, they brought her into the emergency room, she was admitted to a lock worn in the hospital. And I did a careful history and physical exam, like any medical student would. And it turned out that she had one thing that just did not fit with the rest of her condition. She had blood in her stools, and her bowel problems have been chalked up to IBS irritable bowel syndrome. But blood is not a feature of IBS. We did some additional tests and it Turned out she had colon cancer. So uh cancer frequently is accompanied by depression. It's just part of the biology of the endocrinology of cancer. And so there was just one of those things where there's a funny expression of medicine when you hear hoof beats, think horses, not zebras. Except that occasionally there's a zebra in there.

SPEAKER_01 30:25

That's great.

SPEAKER_03 30:26

You know, we really have to keep an open mind for that kind of thing because you can save the person's life.

SPEAKER_01 30:31

Absolutely.

SPEAKER_03 30:33

So with the second example, Dagos disease, D-E-G-O-S, yeah.

SPEAKER_01 30:39

And what was the full name again?

SPEAKER_03 30:41

So the the common name is atrophic papillosis.

SPEAKER_01 30:45

Okay.

SPEAKER_03 30:46

And the uh the eponymous name is Colmeyer Dagos disease.

SPEAKER_01 30:52

Okay. I read that that you do have an interest in that. Um, but uh so when it finally came to be understood what a prominent role the immune system was playing in that disorder, I'm curious, was that a team, a multidisciplinary team that tended to work in that area? I highly value the role of a multidisciplinary team, and with something as complicated as that disease sounds, I'm just wondering if if there were people from many different disciplines that worked to try and understand that.

Multidisciplinary Breakthroughs And Collaboration

SPEAKER_03 31:29

Yeah. Well, my my involvement with it was that I had a four-year-old boy who showed up in my office one day with severe abdominal pain. And I pulled up his shirt and he had the ugliest rash I had ever seen. And I thought, I have never seen a rash like this before. And we admitted him to the hospital and got a biopsy that showed that he had this rare condition. He died subsequently, but the drama of his condition sort of caught my attention. And mostly his parents stayed in touch with me and they, you know, we got to do something about this. And his parents lit a fire under me, and I ended up organizing an international symposium that brought together patients from around the world who had this rare disorder. And we had researchers that came all the way from Germany, and uh they spent a whole day giving talks about this in the famous Ether Dome at the Massachusetts General Hospital. And we had all of the residents come through, all the pediatrics residents came through and examined 19 patients that had this rare disorder. Chances are they never would have seen it otherwise. And so it's funny how just that one patient ended up being sort of an inspiration to me to work on this. And so once my name was out there, people started contacting me about this diagnosis. And the next sort of big moment, I wrote this case up, and it was in the New England Journal of Medicine as a clinical pathological correlation case. So it got a lot of attention. And I was contacted by some doctors in New York. We have a patient, he's severely ill, he's got this disease. What do we do? And so I offered them my best advice about how to proceed. And in the end, it was the pathologist at the hospital where he was hospitalized. She came up with the idea of using a drug for him that had never been used before in these patients. And uh, it took him a week to get authorization from the pharmacy review committee just to pull it off the shelf. And um, but the poor guy was on a ventilator in the intensive care unit, and they gave him the drug, and next day he came off the ventilator, and the day after that, he was up walking around. And he's still alive now. He's he's doing magnificently now, 16 years later. And it's been really exciting that he was sort of the first one for a parade now of families that have uh seen this sort of miraculous recovery. So, but to answer your question, we have a group of uh doctors from around the world now. We meet about every three months, we have a Zoom conference and we try and go into the details. And I've organized a whole series of study groups for the American College of Rheumatology annual meeting to discuss this. And so putting, you know, a bunch of smart people together in a room does have a synergy that brings out new ideas. And now we've got three different treatments for this disease, and our big focus now is trying to figure out how to treat the children because they don't respond as well to the therapies that we've previously described.

Rheumatic Fever As Historical Model

SPEAKER_01 34:50

Well, I love stories like that because they reinforce a phrase that we use in the Alex Manfo fund: uh, dialogue saves lives. And we make a great effort at our symposia and some research breakfast that we've held that I hope you'll come to next time. That if we bring a lot of people together, in the case of the research breakfast, it's 20 people or so that sit around the table. And in each symposium that we've had, we have provided the space for physicians and practitioners and researchers to get together and talk. Um people say some of the best conversations at a conference take place at a bar, and I think there's a lot of truth to that. So we provide many opportunities for them to just chat. And as a result of that, I probably have 10 different examples of researchers who didn't know one another beforehand but are now working together. I think that's how you you move forward. And then uh with regard to the pathologist that you mentioned, thinking out of the box is so important. But that's kind of hard to do if you've got a patient for 15 minutes and then another one immediately following, and another one and another one, that's kind of hard to have the opportunity to actually really think through cases as much as would be ideal. So let's go back to what you said at the beginning. And can you talk to me a little bit about the connection between rheumatic fever and oh, let's just go ahead and say rheumatic fever, syndrome's career, and pandas.

Strep Biology And Lancefield’s Legacy

SPEAKER_03 36:44

So the purists would be probably offended to say pandas and uh rheumatic fever in the same breath, because rheumatic fever has been known for a long time, you know, dating all the way back to the ancient Greeks. They were familiar with this phenomenon of heart failure associated with fever. But Sydenham was a British doctor, he was an old Oxford Don who uh came to appreciate that there was a neurologic dimension to rheumatic fever. And uh he uh coined the term um St. Vitus's dance, which was after a uh fourth-century saint. He connoted the term that there were these dance-like movements, involuntary uh movements that individuals with rheumatic fever had. And ultimately they ended up coining the term Korea as in the turn, the word choreography. So Korea is these writhing motions, and uh so Sydenham's name came to be associated with it's Sydenham's Korea, and it's one of the criteria that T. Ducket Jones incorporated into the Jones criteria for rheumatic fever, which were published only in the 1940s, subsequently. So when Sue Suito and her group at the National Institute of Mental Health first coined the term pandas in the late 1990s, they had very much in mind that this was like rheumatic fever, in that uh they were studying a group of 50 children who had had either strep throat or exposure to strep from siblings. And what they showed was that these kids all had the abrupt onset of OCD and TIC problems. And so they postulated that there was a role for strep in this, and they acknowledged that it was different from what strep does with rheumatic fever because none of those children went on to develop heart valve problems, which is one of the characteristic findings in rheumatic fever. And they didn't have arthritis, uh, or so they thought at the time. There have been some newer findings now in this past year from my colleagues at Stanford that there may be an association with certain kinds of arthritis, different from the kind of arthritis that we see in rheumatic fever. We could talk certainly more about that. But amazingly, a hundred years ago, rheumatic fever was the most common cause of childhood death in the United States, and just been a remarkable triumph of public health that we almost never see it anymore in the U.S., even though there are other parts of the world where, like in India and in parts of South America where it still occurs, and there are about 350,000 deaths a year in the world from rheumatic fever, but almost none of them are here in the United States. So it's interesting to think that something happened, and whether it's the use of antibiotics with the advent of penicillin and Alexander Fleming in the 1940s, or um, it seems like rheumatic fever's incidence was declining before Fleming's discovery became widely available. So antibiotics are clearly not the whole story for it. But anyway, there are many fascinating elements to the whole story. Um Sydenham was close friends at Oxford with a famous Enlightenment thinker named John Locke that will be well known to you know to most Americans. John Locke was a great inspiration to the founding fathers in the you know the nascent United States. But Locke was one of the first people to describe OCD, and he was a physician himself, in addition to being sort of an enlightenment thinker about freedom of thought and freedom of conscience. And so there's a really interesting tie-in to the involuntary elements of OCD, and Locke's he struggled with that whole idea of what what OCD was and what its relationship was to our primacy of conscience. So these larger issues. So anyway, he and he and the Syndam were were friends uh during that time. The biology of rheumatic fever is really interesting too, because like many things, there was just this very, very gradual peeling away the layers of the onion to try and figure out what was actually going on. And I might just share a quick story with you because it's relevant, I think, to many of the families that I see. That we know now that rheumatic fever is caused by group A strep. Strep is an enormous family of bacteria that have a particular appearance under the microscope. They're gram-positive cocci under the microscope, and they're big round, purpley things when you look at them once they're isolated on a swab of the throat. But there are many different kinds of strep. We have strep on our skin. Most of our stool is made out of what's called peptostreptococcus, and uh the children get vaccinated against a form of strep that's called strep pneumonia. And uh strep pneumonia is in a completely different category of strep. It's another branch of the family that's referred to as alpha hemolytic strep. And in that family is another bacteria called strep viridans that causes our, or the bacteria that causes cavities is also in the alpha hemolytic strep category. But it's beta hemolytic strep that are responsible for strep throat. And interestingly, if I could just share one quick story with you, because I think it's so fascinating, that at the beginning of the 20th century, there was a very famous microbiologist at Colombia whose name was Hans Zinzer. And Dr. Zinzer was a huge figure in American microbiology. He was the person who described, he isolated the bacterium that causes uh scrub typhus. And he had a laboratory at Columbia, and uh there was a young woman whose name was Rebecca Lansfield, who was a technician in the lab, and she decided that she wanted to get a PhD. And Dr. Zinzer was not too keen on mentoring a woman, that he didn't think that women had what it would take to be, you know, a microbiologist. So she ended up leaving his lab and going to work for another guy there in New York, whose name was Swift. And Dr. Swift in the Swift lab was uh one that focused on um strep, which is a much more common bacteria than the typhus that Zinzer was uh studying. And she decided that she was going to take a very meticulous approach to trying to understand strep. And so she started studying the individual characteristics of different kinds of strep. And later her name came to be attached with a classification that we still use in medicine today, the Lancefield classification. And when we speak about group A, group B, group C, and so on, it's Lansfield, group A strep. And so oddly enough, Rebecca Lansfield is much more famous now than Hans Zinzer, the guy that she was rejected by, even though Zinzer ended up leaving, going to Harvard, becoming this big name professor, and he was an inspiration to the doctors who won the Nobel Prize for ultimately developing the polio vaccine. So, but Rebecca Lansfield has her corner of history, and it's so highly relevant to what we're thinking about in the pants and pandas world, because now we understand that you know strep is part of the story. It's not the whole story, because the majority of the kids that we see who come in for a pants pandas evaluation don't fit the criteria exactly. They don't have an obvious history of strep throat that preceded the onset of uh their behavioral symptoms. But anyway, I think it's fascinating and inspiring that she played that role.

SPEAKER_01 45:24

And I love ironies like that. So I don't have these notes in front of me. Tell me, am I remembering that an article, I think it was a JAMA journal, you have a piece there, and 2024, so just recently. And did you mention a rheumat, like there was a different strain of strep that led to rheumatic fever?

SPEAKER_03 45:51

So the paper that you're referring to was authored by our colleagues at Stanford.

SPEAKER_01 45:56

No, it has your name on it.

SPEAKER_03 45:58

Well, there was a paper in the journal The American Medical Association that was a study of 193 children with PANS. And basically what they showed was that over a 10-year period, about 40% of the kids developed features suggestive of either psoriasis or psoriatic arthritis. So I wrote a commentary that accompanied that paper, and I started it out by just recounting some of this history about rheumatic fever and how profoundly it affected childhood 100 years ago. And I think what you're alluding to is that I mentioned in the in my commentary that people have just speculated why is it that rheumatic fever is so much less prevalent now than it was then, you know, in the 1920s, for instance. And people have speculated that maybe there were different kinds of strains of strep, and they referred to them as rheumatogenic strains that caused this cross-reactivity with the immune system, and that that cross-reactivity resulted in damage to the heart valves and also the creation of antibodies that bind to areas of the brain called the basal ganglia that participate in fine motor coordination and uh result in the development of ticks and also influence this whole intrusive thoughts issue that we see in pans and pandas with patients.

SPEAKER_01 47:22

So I ask you that um because another of your colleagues at one of our conferences pondered whether or not there was a panda specific strain or strains of um strep. Yeah.

Strains, Testing Limits, And Genetics

SPEAKER_03 47:43

So that's a very important question, and I think we're not smart enough to know the answer to that yet. We know that there are a lot of kids that come in with very typical uh symptoms, and uh they have had sore throats, but 95% of sore throats in kids are caused by viral infections, and uh they develop this abrupt onset of OCD kind of features, and then many of them you put them on antibiotics and they dramatically improved afterwards. So this fuels some of the skepticism because, well, hey, if they've got a viral infection, why would antibiotics have any benefit for them at all? But it's inescapable that they're uh, especially in the younger kids, you know, ages five, six, seven, you just see almost all of them respond to antibiotics in some way. So, what's going on there exactly? So it's it may be that there are certain strains that our our antibodies don't recognize. You know, there are only two tests that are routinely done by doctors. One is called the ASLO, antistreptolasin O. There's an old test, it's been around for almost 100 years. And then there's another one that we do called the anti-DNAs B test. But my colleague uh Mark Pasternak at Mass General Hospital has shown that if you do an expanded panel with another 12 antibodies that they've developed against strep, there are a lot of kids that are negative for the big two popular ones, ASLO and DNA's B, who have other antibodies that are uh reactive. So I'm sure that there's a lot more going on in the body than we're aware of by virtue of just the tests that we're sending off. And so it this this poses another really interesting question, Susan, which is why doesn't everybody get pandas? You know, strep is so widespread. And what is it that separates the child who has this kind of abnormal reaction from the vast majority who they get sick for a day and then they're better? And we don't know the answer to that question. There's probably a role that genetics plays in it because family history of anxiety uh andor OCD clearly is impactful. And there also is a higher incidence of pans and pandas in family members of affected individuals. So, like many things in medicine, there's probably multiple factors involved.

SPEAKER_01 50:14

So it was Mark Pasternak who posed that question at one of our symposia. Okay. And uh that's just stuck with me. I I would love to see some more research done on different strains of strep uh and relate them to some of the questions that you just posed.

SPEAKER_03 50:34

Yeah. Mark is like me, he's um he's a beleaguered uh pediatric specialist until recently. He was the chief of infectious diseases at Mass General Hospital. And when you walk into his office, the stack of charts on his desk is unbelievable. And, you know, it's uh we have this funny expression, it's like the gas law just expands to fill the available space.

SPEAKER_01 51:00

That's funny. Well, you both take your work very seriously and are interested in the details, and it is the details that are gonna help us move forward, I think. So, um, how did you get into pandas and pans? Was there a case? How did that happen?

SPEAKER_03 51:22

So uh the Dagos disease story started with one child that I took care of in the hospital, but my involvement with pandas was a result of my participation for years lecturing to the annual Massachusetts General Hospital Pediatrics course. So they have pediatricians that come from around the country. And in 2009, I was signed up to present at this conference, and I try not to be the kind of doctor who just recycles or rehashes the same thing they did the year before. You don't learn too much that way. Uh so that year, I just as luck would have it, I thought to myself, I wonder what this pandas thing is. I had heard of it, and I thought I should learn something about that. So I sent off an email to the course director and I said, I think I'll talk about pandas. And I showed up that day for my talk, and they had scheduled me in this ballroom that was filled from front to back with pediatricians, and I had never seen a patient as far as I know.

SPEAKER_01 52:30

Interesting.

SPEAKER_03 52:31

But I basically just shared what I was able to dig up from the literature. And of course, what happened next was people started getting referred to me. And in the intervening years, we've together with my colleagues at MGH like Mark and uh Kyle Williams, we've developed a really substantial effort at MGH looking at imaging studies and psychiatry and infectious disease to try and understand this better. And then I came to UCLA seven years ago, and they didn't really have any other doctors in Southern California who were doing this. So I brought my sensibilities that I developed during my years at MGH, and we really tried to create a whole new paradigm for studying this. And I think that there was some substantial skepticism, both within my institution and you know, at other places. But I think I can safely say now that we've become kind of a center in Southern California at UCLA. So that I get kids coming from all over the state, Children's Hospital, Los Angeles, and Ray Children's Hospital, Loma Linda. And also we get a lot of kids from San Francisco Bay Area that that come down to see me. In fact, really from all over the western United States, Washington, Oregon, Hawaii, Nevada, uh, and a lot of people from Minnesota have been coming to see us as well. So it's been interesting, you know, how a league of their own, you know, you build the ballpark and people will come to it. And that's essentially what's happened.

First Cases And Building A Center

SPEAKER_01 54:02

I think your ballpark is getting pretty full, though. I I would like to help you bring in some colleagues so that uh we wouldn't want to burn you out. You're too important. So let me just ask you a couple more questions based on what I've read about your interests. You have uh written or talked a lot about immunodeficiency. Can you talk a little bit about what role that plays in pandos and or pans?

SPEAKER_03 54:35

Yeah. So that's one of our biggest interests right now. Because when I first started working in this area, I came to appreciate that it just seemed like there was disproportionately uh children showing up in our clinic who had history of frequent infections. And in the in the time when I was going through my my training, there was a paradigm about immunity that it resided on a spectrum from too much to too little. And if you had too much immunity, you had autoimmunity with things like arthritis or thyroiditis or uh you know diabetes. And if you had too little immunity, then you got sick frequently, and that's immunodeficiency. And I think in retrospect, that was a very naive way for us to look at it because the immune system is a multi-layered, complex system that's evolved over millions of years. And it's fascinating that, for instance, humans have co-evolved with fungi, with molds, since, you know, since mammals first came on the scene. And many of the proteins in the human body that protect us against molds are actually inherited from as far back as flies. So Drosophila, fruit flies, have the same proteins that we have that protect us against fungal infections. So this is a very ancient evolutionary uh path for the development of these complex systems that protect us against things like mold. But more than that, around the time of the development of bony fishes and sharks, or sort of pre-just precede that, there was the advent of a whole new kind of immunity that developed in the complex organisms, and it came to be referred to as adaptive immunity. So, broadly speaking, the immune system is viewed as being divided into innate immunity and adaptive immunity. And the innate immune working parts are those that we share going all the way back into insects. And the adaptive immune system is a characteristic of more complex uh organisms, up to and including primates. And the amazing thing about the adaptive immune system is it's characterized by a new kind of cell called the lymphocyte. And lymphocytes are white blood cells that are action cells that make hormones and immune molecules like antibodies, which protect us against a whole variety of infections, including infections that no member of our species has ever been exposed to before. So it's just amazing that you can have a new virus like coronavirus of COVID fame, comes on the scene, and millions of people can make proteins that specifically immobilize and inactivate that virus, even though humans have never been exposed to this virus previously in the whole history of our species. So the reason I'm sharing with you this distinction between innate and adaptive immunity is because there are distinct diseases that are associated with the misfiring of the components of the innate immune system and the adaptive immune system. And broadly speaking, now we use the term auto-inflammatory diseases to describe those conditions that are associated with the misfunction or malfunction of the innate immune system. And we refer to the malfunction of the adaptive immune system as being autoimmunity. So that's the interesting distinction between the two. The innate immune system defects are typically single gene disorders, and the classic one is something called FMF or familial Mediterranean fever, which is a mutation in a gene called the pyrene gene. And pyrene is from the Greek term pyros, meaning for fire, as in fever. And uh when the pyrene gene misfires, the gas petal is put into the down position. And these are children who develop these frequent fevers associated with severe abdominal pain. It's very common in people from of Armenian descent, but also Sicilian and you know Sephardic Jewish descent and Turkish descent as well. We have a lot of Armenians here in Los Angeles, and especially the Glendale area of our city, people who immigrated from Armenia, a quarter of the people from Yerevan have one of these mutations. So there's a very, very high incidence of that disease in this population. And there are examples like this that are littered in different uh ethnic groups around the world. And so these are inflammatory conditions that have certain qualities to them, and they are broadly labeled as being autoinflammatory disorders. The autoimmune disorders are a little bit different because they are they represent developmental abnormalities that affect our B and T lymphocytes. And they are manifesting with diseases like arthritis, for instance. Probably diabetes and multiple sclerosis and other diseases like that.

Immunodeficiency, Autoimmunity, Autoinflammation

SPEAKER_01 1:00:05

So just to clarify, the FMF disease? That is an autoinflammatory disease. Okay. Very interesting. So whether it's an autoimmune or an inflammatory disease will to what extent does that dictate what the treatment will be?

SPEAKER_03 1:00:22

It very much influences how we respond to these things. So for instance, I'm sure everybody will recall that at the height of the pandemic, all of a sudden there were these cases of severely ill children popping up who had something called the multi-system inflammatory syndrome associated with COVID or MISC. These children were profoundly ill, and many of them ended up on ventilators in the ICU. And uh it turned out that what they had was an auto-inflammatory disorder that was a reaction to the COVID infection. And treating them with an anti-IL-1 drug called Anachinra turned out to profoundly turn around their condition. We didn't have even a single fatality at UCLA from that disorder, even though we took care of a lot of children that had it. So, yeah, so trying to make the right diagnosis clearly has an influence on what the appropriate response is.

SPEAKER_01 1:01:20

Very, very interesting. So in relating that to pandas and pants, we read about, well, of course, pandas is pediatric autoimmune neuropsychiatric disorder associated with DREP. Um, but there seems to be more and more written about it being an inflammatory, more of an inflammatory disorder. Can you help me understand the what's going on? Are are just views changing based on research, or are there different presentations of pandas and pans that suggest one might be more autoimmune and another more inflammatory, or is there a difference in terms of time that the individual has had it? What's going on?

SPEAKER_03 1:02:13

Yeah, good for you picking up on that distinction because the term pandas was coined at a time where we didn't really use the term auto-inflammatory disorders. That's a more recent uh use of the terminology. So the presumption, I think, uh when Sue Suito and her group were developing this literature was that because there were similarities with rheumatic fever, and because rheumatic fever is a lymphocyte-driven disease, it made sense to call it an autoimmune disorder. But I think now we're coming to appreciate that it's more complicated than that. And one of the interests that we have in our center is looking at the potential role of a variety of therapies like uh arthritis treatments, methotrexate, and uh the JAC inhibitors, like you know, aluminiant and um Zeljans to treat these disorders. We have some kids who've done remarkably well. So this happens in medicine a lot where you know you try different kinds of therapies or so-called empiric therapy, and you find something that works and then you run with it. And it's only in retrospect once you go back and figure out how the machine was actually put together that we can figure out exactly what it was that we were doing and why it was helping. So I think we're sort of at that stage of discovery, trying to figure out you know, where where is this going and where is it coming from?

SPEAKER_01 1:03:49

So given individual, is it possible that there are aspects of autoimmunity and uh inflammation, neuroinflammation?

Treatment Logic And MIS-C Lessons

SPEAKER_03 1:03:58

So I think that's a really good question. And what I tell our families is that I try and think outside the box when I do my evaluations to recognize other conditions that may be contributing to what they're experiencing. So, to go back to the question you asked before, one of the first observations we made uh as I started examining the data from all these kids that we were seeing was that about two-thirds of them have evidence for an immune deficiency. So I think that this is some good presumptive evidence that the immune system is clearly playing a role, even though you're not seeing typical abnormalities in the lumbar puncture for the kids who actually go that far in their evaluation. So trying to ferret out exactly what kind of immune deficiency is contributing and what the implications might be for treatment, that turns out to be an important thing. And I mentioned to you a moment ago that the paradigm used to be that, you know, we have uh, you know, the immune system resides on a spectrum from too much to too little. I think there's just an overwhelming amount of evidence now that suggests that most autoimmunity actually is itself a form of immune deficiency because there are uh what are called holes in the repertoire in a variety of immune diseases, and most particularly rheumatoid arthritis, which is one of the defining conditions in rheumatology, it's clear that people with rheumatoid arthritis have an immune system that's aging much faster than their peers. And so the paradigm is changing to suggest that when somebody ends up with hypothyroidism, Hashimoto's thyroiditis, what it represents is that the immune system would normally respond to particular viral infections in a particular precise way. But when we have a suboptimal immune response to those viruses, the immune system still has to come up with a plan B to deal with the infection, even though it can't respond the way that it might normally do so. And so what happens is you get a less discriminating immune response, and autoimmunity may turn out to be, broadly speaking, a form of collateral damage, where the immune system is damaging the tissues that it's trying to protect. And that's why these individuals develop these kinds of symptoms. And it also begins to explain why suppressing the immune system in somebody who's got an immune deficiency may not be a bad idea, because you can turn down the temperature with regard to the part of the immune system that's hurting the tissue. And that's what we see in people with rheumatoid arthritis, for instance, where the treatments now are dramatically better than they were 25 years ago. And um, so it's like so many things in medicine, too, that it's always a balancing act trying to minimize the side effects and maximize the benefits. And this is the kind of calculus that we're involved in day in and day out with each and every patient.

SPEAKER_01 1:07:07

So when the tissue is damaged, is that why some neuroinflammation and brain tissue is damaged? Is that why some neuroinflammation begins to occur?

SPEAKER_03 1:07:17

So that's a complex question. And parents frequently ask me, is this disease damaging my child's brain? We actually don't have any evidence that it damages the brain because uh many of the kids who are well treated have they sort of spring back, and it's amazing how resilient children's brains can be. And in children who are untreated, you don't see them go on to develop shrinkage of the brain or necrosis and areas of the brain that we think are affected by this disease. So the process is more complicated than sort of the classic encephalitis picture. And I'm never quite sure what to say when people say, Does my child have autoimmune encephalitis? Well, not in the classic sense, because we don't see the hallmarks of damage that you would see in children that have uh viral encephalitis, for instance. But I think there is a dysfunction that occurs in the brain, and it seems to me that there's strong evidence, circumstantial evidence at least, that the immune system is playing a role in that.

SPEAKER_01 1:08:28

Interesting. So a subject for another conversation, not now, but I don't know if you've had the chance to read the article that's written by uh Brent Harris, the neuropathologist at Georgetown, based on my daughter's brain, which did identify damage in the brain. But of course, that would be unclear if that was permanent or not. But an incredible amount of gliosis, among other things, in the pertinent areas of the brain. But I'd love to talk to you about that another time. So it's just so interesting. I think we probably should wrap up, but I do have a couple of questions. You mentioned the Los Angeles Pediatric Society summer program in which you work with high school students who might be interested in going into medicine. And that reminded me of a group that the Alex Mample Fund works with called the International Brain Bee. And it's an international program that's over 25 years old, and yet most people have never heard of it before. And what they do is to encourage high school students who are interested in neuroscience to become involved in various levels of competition, much like a spelling bee. And so our nonprofit has supported for two years now some of what they do. And we're interested because we want to get younger people interested in neuroscience. And if you can pique their interests at in high school, as I imagine you're thinking here with the summer program, if you can pique their interest in medicine, we may be able to increase the number of doctors or neuroscientists. So I just wondered is that why you're involved or why why are you involved?

SPEAKER_03 1:10:34

So the Los Angeles Pediatric Society, even though it's on the West Coast, is one of the oldest independent pediatric societies in the country. And in 1969, they had it in mind that they wanted to create opportunities to cultivate the interests of young people who wanted to take care of children. And it turns out to be not that easy to get experience, you know, finding out what a pediatrician does. And pediatrics is a little bit of a hard sell these days because pediatricians tend to be the among the lowest paid doctors and the hardest working. It's not unusual for a pediatrician to see 35 patients in a day. And uh obviously having a loving pediatrician is just invaluable in the life of a child and the life of a family. So um, and from the group of the broader group of pediatricians come all the pediatric specialists who tend to be a lot more poorly paid than their adult specialty confrares. So I think that the rationale initially was we want to create a new generation of enthusiastic pediatricians. And because this program's been going on now for 57 years, there are many pediatricians in Los Angeles who themselves participated in this program as high school students.

SPEAKER_01 1:11:57

Ah, that's great to hear.

SPEAKER_03 1:11:59

In the spring of 2020, uh, shortly after I had just finished my term as the president of the society, we were confronted with this real challenge that how do we take a program that had brought uh high school students physically into hospitals to meet patients and meet doctors? How do we keep it going in the middle of a pandemic? And so we came up with the idea, well, we're gonna try and take advantage of this Zoom revolution. And we created a template for it and started rushing around trying to persuade doctors. And as I mentioned before, you know, people from many different walks of hospital life with regard to child care, like child life specialists and occupational therapists and surgeons and so on. And boom, within a matter of about six-week period, we put together this program with 48 specialists who presented online. And so we had hundreds of kids that were tuning in every day during the month of July in 2020, right at the height of the pandemic. And I have to say it's been really a roaring success. And so I've had a chance to meet, you know, many of these kids myself who've actually come and seen patients with me at UCLA. And uh, one of the little things that I brought into the program, which I think has been really fun, is that every year, the end of the program, sort of the climax of the program, is I get to interview the pediatrics columnist for the New York Times, who's a wonderful pediatrician from Harvard named Perry Kloss, K-L-A-S-S. And she's written about 20 books. And so this past July, we had a whole hour and a half discussion about a book that she wrote with one of her pediatrics colleagues from Boston called Quirky Kids. And we really had a chance to focus not just on pans and pandas, but on you know, the broader population of children and what they wrestle with, you know, behaviorally uh through the complex developmental process of our childhood.

SPEAKER_01 1:14:10

Wow, that sounds really interesting.

SPEAKER_03 1:14:12

Yeah, so it was it was really fun. And I think I was telling you that I've been teaching a course through the Harvard Extension program the last four years called Music in the Mind. And it's about the evolutionary origins of our musicality. So I give a talk every year to all the high school students, and a lot of them write to me afterwards. They're just they're very animated by this because I think a lot of people that go into medicine have an interest in music. And so we have a lot of you know uh young growing violinists, for instance, who are also thinking about heading into the medical world.

SPEAKER_01 1:14:47

Well, that was on my list of questions, and I know we don't have enough time to explore that. So will you come back and talk to us about um music in the mind?

SPEAKER_03 1:14:58

With great pleasure.

SPEAKER_01 1:15:00

Good. I I'd love to sign up for your class. So I know you're taking a break maybe the the following year. And then just to go back to the the uh LA Pediatric uh society, how would students find out more about that or to well to register for it, to test for it, whatever is necessary?

SPEAKER_03 1:15:21

Yeah, thank you for asking. So we have a great website, it's called L A Ped Sock, L-A-P-E-D-S-O-C.org, short for Los Angeles Pediatric Society, lapeed sock.org, and uh there's an application on there. The deadline is the end of February, so it does involve trying to get a recommendation from a teacher and you have to send your grades in. But as I say, we had more than 400 students that participated this past year. So mostly they're juniors, they're between junior and senior year in uh high school.

Brain Dysfunction Without Classic Damage

SPEAKER_01 1:15:56

Okay, what an opportunity. With regard to the music in mind and thinking about questions, I just have one question for you. I'm not sure you can answer it. Maybe you'd just like to comment on it. But I am acquainted with a patient who is a viola player. She's been playing the viola since she was five, if I recall correctly. And she has also been diagnosed with panda's pants. And she and she's quite good. But what she does is to um wear an earbud in one of her ears that plays music at the same time that she's playing her viola. It's not classical music. She asked me. I mean, when I asked her, she laughed and said, no, it would never be classical music that she would be playing. I found that fascinating.

SPEAKER_03 1:16:57

Does that so she's listening to one kind of music while she's playing a different kind of music? That ties into some really interesting philosophical and neuroscientific issues because our brains are almost, without exception, not capable of carrying two melodies at the same time. So um you can't imagine in your mind two different songs simultaneously. And Bernstein touched on this using a phrase that had been popularized by his friend Aaron Copeland that music serves as the music of as the currency of the emotions or the language of the emotions in the brain. So it's interesting to ask the question how do we know how we feel at any given moment in time? And the brain uses melody and rhythm as sort of a currency of our current emotional state. And so this is part of the reason that listening to music has a transformative effect on us in terms of calming us down or getting us juiced or um uh creating a sense of a shared purpose in a religious setting, for instance, where music is widely used in liturgies, and so on. So one of the interesting ways to conceptualize OCD and pans and pandas is to think of it as a disharmony within the brain, that there's sort of an inner disharmony where the needs that we have to perceive what's going on in our environment, to balance our judgment about the danger or safety of different stimuli in our environment, and then to react appropriately with both some purpose, but also at the same time with a sense of inner peace. Those are those are things that I think are tied into the role that music plays in the normal human brain. So it's interesting to think that in a situation like hers, uh, it may be that because you know there's what's called a salience network in the brain, which is how we prioritize things that are going on around us. Uh, this is a problem for kids with ADHD, where they're everything is assaulting their senses at once and they have a hard time concentrating on one thing at a time. And for OCD patients, finding a distraction that pulls them away from the intrusive thoughts or the ticks that they're suffering from has a lot in common with the auditory processing networks that are involved in the way we listen to music and enjoy it and so on. So, anyway, that that may be a complicated way of saying, but I think music does intervene in our brains in some really interesting ways that plays into a whole variety of different larger neurologic functions that relate to who we are as human beings. And Noam Chomsky used to, he wrote a book one time that was entitled, What kind of creatures are we? And he dwells, he's was a you know a linguistics professor, and he dwelt on the role that language plays in defining us as a species. And Bernstein would say that uh music plays a similar role, that it's really just not not just defining, but maybe it helped to create our species. And I think that you know what what your friend is experiencing maybe uh gives us some hint at the role that that music plays in that regard.

Cultivating Future Clinicians

SPEAKER_01 1:20:34

Fascinating. Well, I do hope that that you'll come back to talk to us about that. Now, one last thing, I promise. I won't ask any more questions. But we will see each other next week. We're flying out from New Hampshire to see you in Hermosa Beach at the Tilt, right? So it's taking place on Tuesday, October 28th, very soon. I've already talked a little bit about Tilt, as you know. And um listening to you today, I I imagine I know the answer to my question. We are have decided to do this for many reasons. Awareness, bringing up awareness, and bringing up awareness to people who might not be familiar at all with pandas and pants. But we also, we, I I say myself and our board members, we like the idea of stories because we think by using stories we can pass on a lot of information and a lot of information that we stick with the person longer than if we recited facts to them. You're going to be one of the persons telling the story. But why did you agree to participate?

SPEAKER_03 1:21:53

Well, I have enormous respect for all the parents that I meet. They have gone through, you know, an enormous ordeal. Oftentimes, the children have taken over family life and they they didn't sign up to deal with the kind of conflict that they suddenly are witnessing. And I think that I really enjoy having a chance to meet these people in person in my office. And I told you at the beginning of our conversation about that funny quote from Sir William Mosler, the dean at Johns Hopkins, who said that uh when the arthritis patients come in the front door, he's he's on his way out. Uh, he has another famous quote, which I think about very frequently in my clinical practice, which is listen to the patient and they will tell you what's wrong. And the studies have shown that doctors, and especially male doctors, are notoriously terrible at listening to people. Uh, the average male doctor interrupts the patient in the first nine seconds. So I always try and make a point of just I start out my visits by saying, you know, tell me the story. Tell me what you've been through. And then I do my best to bite my tug and just listen. And I think in the spirit of Osler, most of the time they'll tell you exactly what's wrong if you if you have the ears to listen to what they have to say.

SPEAKER_01 1:23:23

Great. Well, those in the audience, which it it is sold out, I uh I think we'll learn a lot from listening to you. So uh we look forward to that. Well, that pretty much takes us to the the end of this podcast, and I want to thank you uh profusely for coming on uh this evening. And geez, we've talked about so many things, and it it's it's all been so interesting. I know that I'm going to close the lid to my computer and just be thinking about everything. Thank you, Dr. Whalen.

SPEAKER_03 1:24:03

Well, Susan, let me thank you and your husband for your incredible devotion to the well-being of all of our families. And that really is a gift to these people who are find themselves in such an extraordinarily trying circumstance in their lives.

SPEAKER_01 1:24:19

Thank you very much. I um I feel that every interaction that we have and every conversation, it's it's all very rewarding. And I'm glad that we can make this this contribution. I our daughter, when she was diagnosed, said that she wants to let everyone know about pandas and pans so that what happened in her life won't happen to them. She wanted to raise awareness, and uh she didn't get to do that, so we're doing it with the help of people like you. So thank you, Dr. Valen.

SPEAKER_03 1:24:58

So I'll see you on Tuesday.

SPEAKER_01 1:25:00

You'll see me on Tuesday. Thanks.

SPEAKER_00 1:25:02

This concludes episode 19 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.