Autoimmune and neurological conditions amongst children are on the rise.
Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) and Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) are two disorders affecting a growing number of families. They present as a deeply complex network of symptoms for the practitioner to unravel and this is what paediatrician and "Holistic Mama Doc" Dr Elisa Song specialises in.
This is a huge topic and will be covered in two-parts. Today, Dr Song will take us on a complex journey, to elucidate what PANDAS/PANS is, who is at risk and how to identify and test for them. As a paediatric physician in clinical practice, Dr Song has a wealth of information to share with her obvious passion for preventative healthcare using functional medicine.
Covered in this episode:
[00:47] Introducing Dr Elisa Song
[02:14] Dr Song's background
[06:01] The importance of paediatrics
[07:39] Today's topic: Autoimmunity and Kids
[08:06] Is autoimmunity on the rise?
[10:18] Allergy and atopic illness
[11:18] What are underlying the issues?
[14:40] Breaking out of reductionist views
[16:27] Working with immunisation(s)
[23:24] Calculating dosages for kids
[24:44] Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus
[26:22] Paediatric Acute-onset Neuropsychiatric Syndrome (PANS)
[27:57] The diagnostic criteria for PANS
[32:46] Identifying abuse
[35:29] Probiotic and pathogenic strains of GABHS
[38:16] Diagnosis: relevant lab tests
[43:41] Functional Medicine tests
[45:35] How common is PANS/ PANDAS
[47:08] Segmented filamentous bacteria
[48:43] Possibilities of genetics in medicine
[53:04] The relevance of Th17 in neonatal immune training
[54:36] Wrapping up and stay tuned for Part 2
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining me on the line today is “Holistic Mama Doc”, Dr. Elisa Song, MD. She is a holistic paediatrician, paediatric functional medicine expert and proud mum of two crazy fun kids and a great husband.
In her integrated paediatric practice, Whole Family Wellness and that's wholefamilywellness.org, she has helped thousands of kids to get to the root causes of their health concerns and helped their parents understand how to help their kids to thrive. That's body, mind and spirit by integrative conventional paediatrics with a functional approach including homeopathy, acupuncture, herbal medicine and even essential oils.
These health concerns have ranged from frequent colds, ear infections, through to asthma and eczema, even autism, ADHD, anxiety, depression and autoimmune illnesses. Dr. Song created Healthy Kids Happy Kids to share her advice and adventures as a holistic paediatrician and a mamma. You can follow her blog at healthykidshappykids.com and get daily tips and inspiration from her on her Facebook page. So you just go to Facebook, look it up: Dr. Elisa Song M.D. Now everyone can have their own virtual holistic paediatrician.
Welcome to FX Medicine, Dr Elisa Song, how are you?
Elisa: Good, thank you so much Andrew for having me. I was super excited to be on today.
Andrew: Well I’ve got to say, we’re super excited to have you and indeed you've got a very interesting background and history. Can you take our listeners through what sparked your interest, I mean you're a paediatrician, so what sparked your interest with functional medicine? Does this stem from your childhood? Or is it something that stemmed from, a health issue?
Elisa: Well, you know, it's interesting because it is actually neither!. You know my mother is a very conventionally trained OB/GYN. So we really didn't have any natural medicines in our household, I mean even growing up Korean, we didn't really have any traditional medicines. So I was only really ever exposed to conventional medicine.
Knock on wood, fortunately I have been healthy my whole life and so my children and so it wasn't really a chronic illness that brought me to this either, it actually was you know way back in my undergraduate years, long ago, when I was actually here in California at Stanford and I saw this flyer for this really interesting-sounding conference, and it was a conference of what was called back then the American Holistic Medical Association. With all this mind-body stuff that I'd never really heard of and so I went. I wasn't even a health major at that time, I was studying political science and I was going to be a lawyer.
Andrew: Oh really?
Elisa: Yeah, I was going to do health advocacy and children's advocacy and do a lot of good policy work. So I always wanted to work with kids but just in a different way, and that conference, that was back in 1990 and that was when, you know, people like two of the speakers were, Andrew Weil and Deepak Chopra, and back then, they were hardly known. And so I went to this conference and I was just hooked, I was fascinated, and so I actually decided to go to medical school at that point. And from there, I mean all of my med school fellow students and my dean, I mean, they just thought I was crazy for being interested in alternative medicine and so actually my dean would not even let me do an elective in complementary and alternative medicine back then, and there really was only one place to do that anyway.
So during my paediatric residency though here in San Francisco, there was a little more openness and so in my third year, I was able to create my own elective in the rheumatology division and I spent a whole month exploring alternative modalities and I wrote a primer for the fellows and the residents and my attendings on an integrative medicine approach to juvenile rheumatoid arthritis. And then it was after that, that I went to a Food as Medicine conference and for the first time, I heard Dr. Mark Hyman, and that was probably about '99 or so?
Elisa: And that totally hooked me, I mean I thought I have to know what this functional medicine thing is all about because there was nothing in residency that I saw that I wanted to do as a career. You know, I didn't want to do hospital work, I was tired of just putting out fires and putting Band-Aids on symptoms and it just felt like I had to do something more, so this was it, I mean this was the answer, right? To really healing kids and healing patients, and so from there, I believe I was the first paediatrician who actually took the Institute for Functional Medicine's course, the AFMCP course back in 2004, and back then you know, there were adult docs and practitioners practicing functional medicine but really not many paediatricians doing that or practicing functional medicine for kids.
Now I’ve kind of had to pave my own way, but this is why you know podcasts like yours are so important because I want to motivate and inspire functional medicine practitioners to treat children just as they treat adults. It's so doable and kids respond so beautifully and so thank you for doing this, because this is going to get the word out to get our generations healthier.
Andrew: Well, I totally agree with you like, there's a whole segment of the patient population, kids, who, there's not enough work being done, certainly, not enough research being done on how natural medicines work in them. Indeed, you know, you look at most supplements in Australia and it'll say from 12 onwards.
Elisa: That's right.
Andrew: And it's very hard to get something below 2 for instance, you know like even probiotics, which are deemed to be safe.
Elisa: Or they will say or it will say ask your practitioner, but your practitioner doesn't know!.
Andrew: Yeah, yeah that's exactly right. So, you know, there's a few people, a lot of commercial people doing some education on how to treat kids, obviously with a commercial interest behind it, and that's fine to a point. I don't mind commercial interest. I just can't stand commercial interest when it overrides patient health and this is why we need practitioners like you.
Elisa: Yes! and all over the world right? I mean you're in Australia, I'm here in the States and you know I consult with different practitioners in Europe to really help them integrate more of a functional medicine approach, so this has to be a worldwide movement.
More specifically though, about PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Strep) and PANS (Paediatric Acute-Onset Neuropsychiatric Syndrome), now I've got a say I went off on the wrong track when I first heard about PANDAS. I thought you were going to talk about a certain, brand if you like, of probiotics. So first of all though, in your practice, how common is autoimmunity in kids and indeed are you finding an increasing correlation with autoimmunity, just like we are seeing an increase in allergies?
Elisa: Yes, now I have to say unfortunately very sadly I see too many children with autoimmune illness. You know, when I first started the practice, this is now 12 years ago, I didn't see many children with autoimmune disease. I saw a ton of kids with autism and ADHD and behavioural issues, you know, asthma and eczema which is now considered an autoimmune illness. But over the years increasingly I'm seeing a larger and larger cohort of kids at younger and younger ages presenting with autoimmune disease. I have, you know, a ton of kids unfortunately with juvenile rheumatoid arthritis, a handful with multiple sclerosis, some with lupus and of course we'll talk today about PANDAS and PANS, which are autoimmune illnesses.
The ages are getting younger and younger. You know, a few years ago if you had asked me what my youngest child was with autoimmune disease, I would have said that it was an 18-month-old, who had been diagnosed with ulcerative colitis. While, you know just last year, I started seeing a kid, an infant, 6 months of age, diagnosed with Crohn's disease. I mean that to me is unacceptable. This should not be happening to our kids' period. But it should not be happening to our babies.
And so we need to figure out why on earth are kids suffering nowadays in this generation from these chronic illnesses that used to only be seen in older populations. This is where we have the opportunity in functional medicine to really have an impact if we can begin also with mamas, right? and papas before they start trying to conceive. Get them healthy and then my job will be so much easier.
Andrew: Yeah, that's right.
Elisa: But it doesn't just start when you're pregnant. It starts before, well before and it doesn't just start when the baby is born, I mean, we need to start taking care of everyone so that our future generations, you know, our kids' kids will be healthier, if we do this work now.
Andrew: What about these correlations though, I mean allergy, I remember that, you know, there was the ‘allergic salute’ and it was a thing that was noticed back when I was a child. It was “there’s the asthmatic kid” and yes there was a bit of a stigma back then and it was de-stigmatised very well in Australia, I have got to say. But not just because of the activity of normalising it, it was de-stigmatised because it became so common.
Elisa: I mean there's a huge rise in kids with allergies, environmental allergies as well as food allergies, you know, actual true anaphylactic IgE-mediated food allergies. Atopic illness is incredibly on the rise, asthma and eczema. I am seeing kids, you know, now I look at a baby and I'm surprised when they don't have a little eczema patch on them somewhere, and the norm is that the kids with these bright, red rosy excoriated, kind of scabbed cheeks with eczema.
So you know what is going on? Well, you know, there's a number of issues. We have all heard of the ‘hygiene hypothesis’ that we're too clean and it’s skewing our immune system. We’re not being trained early enough to have an immune-regulatory response. So then our, Th1 and Th2 arms of our immune system are going crazy. But it's not just that, though I do think plays a large role. You know, it's our birthing methods, the increasing C-sections, there's an awareness now of the immediate difference in the baby's gut microbiome when they are C-section born or vaginally birthed.
Feeding methods make a huge difference and I understand and this is not to make any mama feel guilty, but you know there are situations where breastfeeding is not going to be feasible or possible. But breastfeeding, has a huge role to play in establishing the healthy gut microbiome, from the prebiotics that are in breast milk to the probiotics that are transmitted.
Our babies are receiving antacids, you know, reflux medications almost from birth. Because they are "fussier" because they are “colicky". And we know that antacids are directly linked with a Th2 preponderance and increased likelihood of asthma and eczema and allergies later on in life.
The same thing with antibiotics, they have shown that the earlier they use antibiotics in infants, the higher the correlation with asthma. You know, we are not going to talk a whole lot today about vaccines. But you know, the number of vaccines our kids get at young-ages, younger and younger ages than what we received, you know, when we were infants, is incredible and the adjuvants that are in vaccines, are clearly linked with more and more autoimmune phenomena. There's a syndrome called ASIA (Autoimmune/Inflammatory Syndrome Induced by Adjuvants) that is in the literature and known to trigger autoimmune phenomenon in susceptible patients, I mean, this is not everyone but this is in susceptible patients.
I think our kids nowadays, you know, we talk about adrenal fatigue in adults, but I see kids, you know, school-age kids, 5-year olds, who already are showing signs of adrenal fatigue. You know, because our lives as adults are way too busy and that translates to our kids needing to be scheduled because we need to go to work, you know, and have our kids occupied and they're overscheduled. So we're not allowing their bodies to get into that parasympathetic rest and digest mode. Of course, digestion is the key right? in functional medicine to overall health and we're maintaining their daily lives in the ‘fight or flight mode’ and I think that has a huge amount to do with our immune system imbalance. Because I don't believe that there is more strep bacteria around or that there is actually more you know, Borrelia spirochete in the woods. But our kids are suffering a more from autoimmune reactions to strep and our kids and adults are suffering more from chronic Lyme disease. So our immune systems aren’t reacting the same way.
Andrew: So you've actually given me a big wake-up call right on my sort of first-second question into the podcast. But it’s seriously like you know, we tend to sort of focus on certain things that we learnt about were associated with a certain disorder in our textbooks. Dismissing these very relevant evidence-based, you know, true things like for instance, we're constantly on the ‘alert’ these days - even kids. The performance quite early-on academically is right there in school children. So of course, that's going to have an effect on immune surveillance. So you have given me a big wake-up call here about that not just thinking about the immune system, to think about what affects the immune system, so well done.
Elisa: Yeah absolutely. Because you know I think in functional medicine, we do a great job at uncovering, you know, biomedical imbalances, that's what we're trained to do. But sometimes connecting the pieces is more challenging. We often make the mistake of taking too reductionistic a view and think, "Oh, there's a chronic infection. Let's look just the immune system." But there is a cascade of events and triggers that may have happened years before that we often need to unearth.
Andrew: I’ve got to say, you know you're reminding me of the great heads up. It was basically like a smack in the head with a sledgehammer from Andrew Heyman. I've always been suspicious of this, you know, if you see low cortisol - give cortisol. ‘It's fine, don't worry’. ‘Just give it’. ‘Just normalise it’. ‘Band-Aid it’. And I've always been a very suspicious of that and I was so happy with the work of Andrew Hyman, having a no, no, no, “that could be an infection, you give cortisol, you are just covering up the infection letting it run free.”
So it's this real wake-up call about looking at what happened before? Why is something happening?
I have to ask, I know we're going to get off-topic. But I have to then ask about, because you brought it up with regards to immunisation; Now you know, I've previously said that given that I am pro-vaccination, as long as it's done responsibly. And I do believe that there's a little bit of a guinea-pig-thing happening. Where, as a society we're lumping so many vaccinations together with an immature immune system. I have rationalised that by saying well okay, as a functional medicine practitioner, that we have the best to offer these patients to actually provide that support, so that they don't necessarily wreck. There’s even work on probiotics helping the effectiveness of vaccines now. Traditionally, I've used things like herbs, you know like, Echinacea and some zinc along with some medications. But where do you think we sit with regards to what we're doing nowadays with vaccinations?
Elisa: Well, you know, it's such a challenging issue and I tell parents who come to see me, and you know about a third of the patients who come to see me are well children. So I have the joy of seeing healthy kids grow in my practice. And you know, I tell parents one of the most difficult decisions you'll ever make for your child is which or what or how many vaccines to give. I don't know what the laws are in Australia, but here in the United States, some states do allow parents, what's called a philosophical exemption, to be able to choose, that's the pace and the amount of vaccines that they would like to get. In California, we have that right but that was taken away last year. So now they are mandated if you would like to send your children to daycare or preschool or elementary school...
Andrew: That's in Australia.
Elisa: Yes, so what I tell parents is that you know, really, I am not anti-vaccine. But neither am I 100% pro-vaccine. I am ‘smart vaccine’.
Andrew: I am with you.
Elisa: We really need to look at, you know, how to, you know in this day and age, where some vaccines are going to be required and parents don't have the options to home-school, how can we then allow children to receive these vaccines safely? And is there a work around? We do you have in California the possibility for a medical exemption which is, at this moment defined fairly flexibly.
So I try to help parents identify which child might be more at risk for serious long-term adverse reactions. Not just a bump on the arm or a fever for a day, but you know longer term, you know, autoimmunity. So those are the kids who have a family history of autoimmunity for sure, any psychiatric illness, any neurodevelopmental disorder like autism or ADD, cancers in the family, infertility, blood clotting issues. Because those all point to methylation risks, right?
Elisa: And then also, you know, what we found here in the United States there’s something that's sort of colloquially called ‘vaccine courts’ and that's a court that awards patient's damages if they're found to be harmed by vaccines. You know, it's kind of under-the-radar and nobody talks about it. It’s not publicised, but millions have been awarded to patients. And some of these kids, who have been found to be harmed by vaccines, the most famous case is Hannah Poling, who was found to have developed autistic symptoms. They didn't say ‘autism’, but ‘autistic-symptoms’ because she had an underlying mitochondrial disorder. Now, mitochondrial disorders don't show up until your system is stressed like with a vaccine or with an illness.
Some signs to look out for your child that they might have some mitochondrial issues even in infancy, is if their tone is a little bit lower. If their suck isn't that strong. If they're, you know, still kind of slumped over, their back is still curved when you pick them up, not nice and straight when you hold them up, you know, under the arms, you know, they kind of slip through your arm. Older kids who sit in that W position, you know, what I mean when you're sitting on the ground with your bottom on the ground and the knees are kind of splayed out, right. If kids can't sit erect and upright on a swing or on their tricycle, you know, they're slouching. I mean kids have beautiful posture until they get to school!
So even when they’re toddlers, they're sitting slumped down or if they have a really weak pencil grasp. Those are all signs that; Wait a second, we might have to think about a mitochondrial issue and I'm more cautious with those kids.
So with those kids, and in general my guidelines for vaccines as I'd like to make sure that kids are entirely well. Not even a low grade fever. So that their immune system can A) respond appropriately to the vaccine and mount a good response like we want and be so that they don't actually get worse from their intercurrent illness. I also like to try to give in the beginning, one at a time, so that we know exactly which vaccines they might be reacting to as opposed to giving five at once and not knowing which caused the reaction.
Andrew: This is something we don't have in Australia, and I wish we did. Really wish we did.
Elisa: Oh are they all combination?
Andrew: Yep, they're all combination.
Elisa: Yeah. So then you know if we have the ability to wait, you know, if there's no other risk factors like, families who are traveling imminently at one month of age to India or to China or other developing countries. Then ideally waiting until the immune system is a little bit more mature and their liver detoxification capacities are a little bit more mature. Even at 6 months kids' immune systems respond differently. And when you wait they require even fewer boosters. When we check titers, antibody levels, on blood tests, we can see that they mount an appropriate response more effectively when they're older.
Andrew: And do the titers last longer?
Elisa: They do, they do and often, I mean, most of them are permanently. The measles mumps rubella titers and the varicella, they are lifelong. Tetanus of course wanes, so we know pertussis wanes, so we also know that the pertussis vaccine is hardly effective. Which is why we see whooping cough, you know, every year in the United States. And then I do like to support kids, especially who have these methylation of mitochondrial red flags, with CoQ10, with glutathione and with a little bit of methylated B12 or methylated folic acid.
So those are the different ways I work with families to try to come up with a schedule that feels good and safe and kids can tolerate. With that, I have had kids, even kids on the spectrum, who, have received vaccines and not had any further regressions or problems.
Elisa: Yeah, I mean it's so interesting because, you know, because dosage is always a huge question right. What dose I give to a child and that has so much to do with our detoxigenomics right, and how we process nutrients and medications. That really has almost nothing to do with weight. I mean there may be some children who require much more than, you know, a 40-pound child might require much more than 120-pound woman because of the way they're processing. But given that we don't have that capability just yet, hopefully, we'll get there. But typically, you know, for infants that might start at 2 to 400 mcg of 5-MTHF. You know, similar dosage with a methyl B12. Then you know for older kids, I might even do… I have a formula, its a chewable that has 1 mg of each, and that tastes delicious and kids like it. So that's a pretty easy way to give it.
Andrew: Excellent. So let's move away from that controversial subject of vaccinations. On to another in-depth, and I've got to say this one took me blind-side. I know nothing at all about this and that's the Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus: PANDAS. Can you explain to us and indeed me, what PANDAS involves and there's an associated thing called ‘PANS’, what are they?
Elisa: Well this is something that if you are going to start working with children, you will absolutely want to become familiar with. Because this is an increasing problem, I guess an increasingly recognised problem for kids, who have behavioural issues, autism, sensory issues. So paediatric acute neuropsychiatric disorders associated with strep or PANDAS, is really a phenomenon that was identified, you know back, probably I'm thinking that the National Institutes of Mental Health actually recognised it as a phenomena back in the ‘80s. And it was thought to be exceedingly rare but there were a subset of children, who after they were diagnosed with strep, typically a strep-throat, they would have a sudden-onset like - the light switched-off and overnight, have abrupt changes in their levels of anxiety, rages, tantrums, OCD behaviours and tics, you know, motor tics or verbal tics.
So then with further investigation, it was realised that it doesn't always follow strep. But then there were these kids, who are following a similar pattern with this abrupt onset of these neuropsychiatric symptoms. And so the term was changed to PANS. Which stands for Paediatric Acute-Onset Neuropsychiatric Syndrome. So PANs is much broader. PANS encompasses infectious triggers like strep, and also non-infectious triggers like environmental toxins, heavy metals and moulds. So when we look at the infectious triggers for PANS, we can further subdivide that into not just PANDAS, but we're recognising that there are more and more infections that can trigger these symptoms. Including very, very common childhood infections like coxsackievirus, which is the hand-foot and mouth virus. Like herpes-6, which is the roseola virus. Mycoplasma pneumonia which causes walking pneumonia, the Epstein Barr Virus or the Mono virus which of course is implicated in many autoimmune illnesses. Herpes 1 and 2, influenza virus and even Lyme and other tick-borne co-infections.
And so the criteria for PANS, and I will read the criteria to you just so you get an idea of what practitioners should be looking for. So the criteria is an abrupt, dramatic onset of OCD or severely restricted food intake. Symptoms are not better explained by known neurological or medical disorder and they have the addition of at least two of the following symptoms: Anxiety, emotional lability and/or depression, irritability, aggression and/or severely oppositional behaviours, behavioural or developmental regression, deterioration in school performance, sensory or motor abnormalities and somatic signs including sleep disturbances, enuresis or urinary frequency.
Now I will say as a caveat that the symptoms that are used for diagnostic criteria for PANS, those are the symptoms that the Stanford PANS Clinic uses as their admission criteria. Stanford PANS Clinic was actually opened back in 2013. They're my next door neighbours and I work closely with them. As soon as they opened their doors, they were flooded with patients, who came out of the woodwork because there was this article that was printed in one of the local newspapers about this child who has been hospitalised with major psychiatric disorders and was basically healed by recognising that he had underlying PANS. And so, but their criteria is very strict. They need a child who was totally neurotypical and then had a sudden onset after an infection of these neuropsychiatric symptoms.
Now the kids that I see in my clinic and I see a lot of overflow kids because they have a waitlist of maybe 18 months - 2 years and again a very strict criteria. But the more kids that I check the more I realise that many, many more kids don't have this ‘abrupt onset’. They often have this underlying sensory, maybe behavioural issues beforehand, but then they have a gradual worsening of these OCDs, anxiety, separation anxiety. That then all of a sudden parents are like, "Okay, this is not okay anymore, what's going on," and then we check and sure enough we realise either they have PANDAS or they have Lyme or they have Epstein-Barr.
So the more common presentation is a little bit more gradual. But if you do have parents, the tip off would be a parent say, you know, "Yeah, right around that time Johnny was 3, gosh, he was the easiest child, mellow, so easy, no problems going to daycare and then all of a sudden, he started clinging, having nightmares, having pee accidents when he was totally potty trained before.’ And so if I hear that if their parents notice that there was a change at some point, but they kind of chalked it up to something else, and I think well we should look at PANS. We should look to see if there is something more going on.
Andrew: That would be a really hard thing though to tease apart from emotional issues, wouldn't it?
Andrew: I mean as a practitioner, the first thing that would be going through my mind if a child had these sudden onset behavioural things. I mean, my first thing would be what's happening at home? What's happening even with regards to abuse? That would be my alarm bell, so how do you then tease that apart to then look at PANS?
Elisa: Yes, so that's a very, very good point because we also, you know, it's sort of like, you know, there's always I think in functional medicine a diagnosis du jour. It used to be Candida and then it was Lyme and there's always something that's the ‘big thing’. Right, so we never just want to say okay it's got to be PANS or PANDAS. In reality, PANDAS and PANS, they are what is called a diagnosis of exclusion, because there's no exact lab data to say this is 100% surely PANS. So you have to rule out emotional - behavioural stress, right like a child who started daycare. It could be the stress of starting daycare, right? Very often we might see it when the sibling is born that something changes.
So we want to see that, make sure that there's not other emotional stressors, make sure that there's not bullying going on in school, that there isn't abuse. We want to make absolutely sure that there's not another underlying medical illness. You know many kids with PANS actually also have concurrent autoimmune illness like juvenile rheumatoid arthritis, some have Crohn's disease. So we want to make sure that it's not a pain issue that's presenting as behavioural symptoms too. So we need to still do a very complete thorough history and a physical exam and do all our other lab works too, not just the PANS workup that we would do.
Andrew: Can I just ask, and I guess this is from a point of paranoia, I'm going to make the excuse that I want practitioners to be safe and aware. But how as a paediatrician, do you take out of the possible diagnoses, the risk of abuse? You know, like the things that I am aware of, are things like pretty obvious things, a rotational type fracture, a bruise in an unusual place, that sort of thing. What sort of clues do you need practitioners to be aware of to say you need to look at this first to exclude that, then you can go further? Are there any key things that you look at?
Elisa: Yeah, I mean of course you're going to get to know the family really well, right, and if you have concerns, you know, even getting permission to talk to the teachers, right, because that can give you a big clue. If the behaviours are only in one setting, that's a tip-off that something is going on in one of those settings. So really we want these, you know, for PANS and PANDAS, it doesn't just stop at home or it doesn't just stop at school. These kids are having trouble no matter where they are and who they're with.
You know you're going to be looking at fears around, let's say the genital exam, because for PANDAS, we do want to do rectal swabs to be able to check for perianal strep, and of course, many kids are going to be uncomfortable with that anyway. But, you know, we all have a sort of clinical spidey sense, so trust if you have that gut sense that something is not quite right, you know, with this family situation, then, you know, of course, you don't necessarily want to report them right away but you want to dig and you want to talk to all the family members. If only mom is there, you want to talk with the dad. You want to see how that child interacts with both parents and with the siblings. And of course you're doing a very thorough exam, you know, to make sure that there aren't bruises in odd places. Kids, their shins are often totally banged up, I mean, I look at my kids' shins and you know I mean they're just covered in bruises, so that does not mean anything to me, right?
Andrew: A mid-back, underneath an armpit or the bottom side of the head, you know that sort of things are unusual type of bruising.
Elisa: Yeah, exactly right, or on their buttock right, unless they just had a hard fall off their bicycle ride, but you know so, in unusual places that I'd really be kind of hard pressed to, just take that as, "Oh, Johnny fell on a chair." You know.
Andrew: Yeah, that’s right. Thank you for taking us through this. Like it’s settled my mind and given me some more confidence into how to tease apart to basically exclude those worrying reasons and then to be able to look further into an infectious-type cause.
So we'll talk more about PANDAS and PANS, and I guess we're going to lump them together a bit even though there's a lot more to PANS than what I thought. But with regards to PANDAS and you know it being due to a streptococcus, a group A, beta-haemolytic streptococcus. So we often talk about probiotics strains...no, first of all I'm going to ask this question. I've seen the term GABHS, that is Group A Beta-Haemolytic Streptococcus. I’ve also been aware of GAS, are they the same or are they different?
Elisa: Those are actually used interchangeably, so they would be considered the same.
Andrew: Yeah, cool, ok, that's the first thing out of my mind. The second one was, we commonly, you know, bang on about probiotic strains and you've got to have the right strain of probiotic to get a reasonable effect and that is given in certain studied situations, but we rarely think about strains of pathogens. Indeed, we know though that for instance, Helicobacter pylori is very largely innocuous and it's certain strains that tend to be the pathogenic ones. HPV, there are certain ones that are more likely to cause, you know, a cervical cancer than others. So what about the strains of GABHS?
Elisa: Well, you know, it's interesting because I don't even think that it really has to be just group-A strep. You know, it does seem and you know, in terms of probiotics too just as an aside, you know many kids will even be reactive to the streptococcus species that are in probiotics. So you know looking for a probiotic that does not have strep thermophilus in it, can be important. It just really depends on the sensitivity of that child. But I do see, you know, kids who have gamma strep in their comprehensive stool analyses and that seems like that can be a trigger for some kids.
I've had kids who grew up group-C strep which is not considered pathogenic, you know, but we culture their throats, they have group-C strep and as soon as we take care of that, their neuropsychiatric symptoms improve. So you know, I think that, yes we do want to know the strain, I think, mostly just to follow to make sure that the same strain isn't coming back, that they're not harbouring and being colonised with the infection, right. But I don't think necessarily the strain matters. That we may find in the future that yes it does matter, but for now what I'm seeing in the office is that it doesn't even necessarily matter that is group-A strep.
Elisa: Well so this is, you know, and I apologise, I don't know, I was actually going to try to find time to look to see what was available in Australia to test. But the two strep antibodies should be widely available, right, in Australia. The first thing that we want to know for PANDAS and PANS is; What exactly is the trigger? For PANS, it typically isn’t infection triggered. So even though I say that there can be a noninfectious trigger like heavy metals and moulds, for the vast majority of kids that used to be with these symptoms, they're going to have some sort of an infectious trigger.
So in terms of infection testing, that should be pretty widely available and can be, you know, fairly standard. So the strep antibodies that we're looking for are an anti-streptolysin O: an ASO titer; which goes up in an acute strep infection. Regardless of who has the infection, we're going to see that. So very often we'll see that very elevated and the other test is an all the tests that used to be used more commonly for post-streptococcal glomerulonephritis, which is the kidney disease that can occur after strep, which we hardly see anymore. That test, so in residency, this is something, that we check for in all kids who presented with glomerulonephritis, and that's called an anti-DNA B strep antibody. Now, you have to be careful when you order this because many labs, if they’re not familiar with these tests or they haven't seen it in a while, will order an anti-double stranded DNA antibody, right.
Elisa: That’s another autoimmune antibody. So they'll do an anti-dsDNA. Now what you want is an anti-DNAse B strep antibody, so an anti-DNAse B antibody. That should be easily available at any lab. And then the other infectious titers that I check; I check for IgG antibodies and IgM antibodies for herpes-6, herpes-1 and 2, mycoplasma pneumonia, a parvovirus B19, coxsackievirus A and B, CMV or cytomegalovirus, and an Epstein-Barr panel, and I do like to check a Lyme Western blot. An IgG, IgM Western blot, not just the Lyme antibody test, but the Lyme Western blot.
The reason why I check IgG and IgM antibodies is, while IgM antibodies are typically our acute infection antibodies and you would think well if you have PANDAS wouldn't your IgM antibodies be elevated? That's not typically the case, sometimes it is. But more often than not we see very elevated levels of IgG antibodies and while conventional docs would look at an IgG, an elevated IgG level, as meaning that you had a past infection, if it is very elevated and you have a persistent immune activation against that virus that can indicate a chronic latent infection. With chronic inflammatory triggers. So I will still treat for that as well. Because elevated Epstein-Barr and herpes-6 have been implicated, you know high IgG levels, in fibromyalgia and chronic fatigue, immunodeficiency syndrome, and I do find that for many of my PANS kids that some or many of these infectious titers are elevated.
So those are going to be the standard tests that are fairly easy to check in a conventional lab. To confuse the picture, we do know that there are patients who have sero-negative PANS. Now, these may be the kids who actually have the toxic exposures, so we don't know necessarily what those are, but here in the States, there's a panel called the Cunningham Panel, which was developed by Dr. Cunningham that's offered through a lab called Moleculera. And, you know, it was only fairly recently available in the States. At some point, hopefully, it will be available in Australia. But this panel checks for various autoantibodies in the brain including 2 dopamine receptors, anti-lysoganglioside antibodies and tubulin antibodies.
And also for activity of an enzyme called CaM kinase II which is found to cause neuronal excitation. So that can be helpful you know, if you're highly suspicious even after all these titers are negative, that this is a kiddo in front of you with PANS, then I would do the Cunningham Panel as a second line, it's certainly not a first line.
Andrew: Gotcha, so I've got to to ask so that would be a serology panel?
Elisa: Yeah, it is blood test.
Yep now as far as functional medicine testing goes, I always, always and I'm sure you know, that the most functional medicine practitioners would say this, but always check a comprehensive stool analysis. Because even if children have zero gut problems, there is very likely going to be an imbalance in the gut whether it's absorption issues or subtle inflammation or dysbiosis of any sort and of course many of these kids don't just have bacterial dysbiosis but they have yeast in their guts and many have parasites in their gut. So we have to regulate and balance the gut in order to have the optimal chance to have proper immune regulation.
And then the other test that I find very useful for kids is the urine organic acid test. Which you know, our conventional labs can do as well. But there are some markers that can be found only in the functional labs. And there's one marker called a quinolinic acid, which I never really paid that much attention to until I started treating kids with PANS. And quinolinic acid when it's elevated, that's another tip-off for me that I need to be looking at infections. You know, underlying neuroinflammation and its triggers.
Andrew: So, is that like an adduct byproduct or something? The quinolinic acid?
Elisa: Yes, it is a byproduct. And that's part, I mean, that's going to be if you order, you know, the organic acid testing through Genova, that should be, it's right there as one of the markers.
Is Genova available in Australia?
Andrew: Well, it's based in the U.S. but you can order it. I think you'd have to look at the stability of the actual samples during transit. But a lot of them, I know that you can still use them for certain tests. I don't know about the time stability of these tests, CDSA, I think you can.
Elisa: Yeah, yeah, great.
Andrew: So right back at the beginning you were mentioning something like even the rubeola virus being a potential cause and that's extremely common, but that PANS and PANDAS are not common, so how rare is it? What's the reason that some kids react and others don't, many of others don't?
Elisa: Yeah, you know it's probably had to do with an underlying susceptibility as in any chronic illness. Because very often when you look at family history, there is going to be, even if it's generations back, a family member who had Sydenham’s chorea, right, or who had rheumatic fever post-strep. So there's a susceptibility to this abnormal reaction to strep and very often, there is a family history of autoimmunity.
For the kids, who go on to develop PANDAS or PANS, we do find that there is, you know, we typically think of autoimmunity as sort of an up-regulation in the Th1 arm of the immune system and you know an improper up regulation of the T regulatory arm of the immune system in response to that inflammation. But in PANDAS, we are seeing that there is an up regulation in the Th17 response with interleukin-17 implicated, and so for whatever reason, you know these kids just have this inappropriate Th17 response and then they don't have that counter-regulatory mechanism responding to reduce the inflammation. The normal inflammation that we all have when we get infections but it's just not being brought down to appropriate levels.
Andrew: Have you ever met a guy called Dan Littman?
Elisa: I haven't, but I would love to, who is he?
Andrew: Segmented Filamentous Bacteria, SFB. They’re sort of cautiously classified, if you like, as Candidatus arthromitus, because they don't know where to put it. It's related to the clostridiae. It colonises the gut, the distal ileum, at around about 3 weeks of age. Its ‘job’, if you like, it was first thought for not to be in humans, only mammals and rodents, but now I think they have seen in humans and its job is basically to wake up the infant immune system to say “we've got a job to do, get moving, you need to be producing immune cells, you need to be on immune alert, from now on it's your job.” And then as long as we've got good guys to put the brake on, it just says, "Okay, my job is done, you've got an immune system and I'm not going to go any further." But if we take away that brake, then it primes interleukin-17 for Th17 and then you know what if you got, Th23? and for autoimmune disease. And this is brilliant work by Dan Littman, Ivaylo Ivanov. He is at New York State Uni. Ivaylo's at Columbus State Uni I think.
Elisa: Oh, I will definitely look that up, I mean because really, you know the problem is our infancy, you know, even from in utero, their immune systems are being trained properly. And so there's something going on with the way now that they're reacting to these common infections. So the more we know about that, the more we might have these areas for intervention very early on, even before they inhibit their first strep infection.
Andrew: Do you think, like that I was quite skeptical of genomic/genetic testing. The more I learn about it, the more I think this is where medicine can personalise itself. This is where you can uncover potential risks, preponderances to all sorts of diseases. I guess there's always that ethical risk, the dilemma of how is data held? You know, the old HeLa cancer cell argument, who owns what, but where do you think we are heading with regards to genetic testing looking at the risk of this?
Elisa: Oh gosh, that you know, that is such a good question. Because you know now the number of companies here in the States and I'm guessing probably in Australia and worldwide, who are really capitalising on the results of, you know, testing from you know from 23andMe, looking all those SNPs and then really taking those SNPs and suggesting various supplements or medications that might be able to bypass those SNPs.
I mean it's everyday or so, I got to looking there's another ad I see on my Facebook feed, you know, for another genomic company. For the most part, I tell parents, you know, we do know quite a bit about methylation, but the other SNPs we’re really in the infancy of understanding their clinical relevance and not just that, their interactions.
We don't know how all of these SNPs interact and I had patients who, they are homozygous C677T, for the MTHFR mutation and they’re the picture of health. And other kids, who have no MTHFR mutations and they are sick as can be. So it's not the only picture and so what I worry about, again I've mentioned earlier on that I do worry that we're becoming too reductionistic in all of this, and saying well this SNP causes that, it's not, you know, it's not one gene causes one disease, and we are moving back to that, that antiquated way of thinking if we're looking at SNPs in that way.
And so I don't think we're there yet, I do have high hopes that we will get there. And then that way then, we'll be able to know exactly, for instance, which kids are going to have what reactions to vaccines, the dose of vaccines...
Andrew: Oh goodness...
Elisa: You know, could we give maybe an eighth of the dosage, you know, to a child, as opposed to you know an infant receiving the same exact dose of hepatitis B at birth, when they are 7 pounds of weight as, you know, a 16-year old.
Andrew: Well, that's right. We have gotten there with other SNPs. You know, with regards to, you know, I talk about this because I've written about it and that is; Helicobacter pylori. You know, there are some SNPs that mean patients will require double the dose of the PPI segment of that triple treatment, triple therapy because of their genetics. And you know that is well documented. Not used, in Australia yet, but how far do we then have to wait to uncover the relevant SNPs that can help us treat, you know, this PANDAS and PANS, I think that's a long way off.
Elisa: Yeah, and you know what I'm seeing unfortunately in some of the practices here, I see some practitioners using, the 23andMe analysis and then from there, recommending 30 different supplements to try to bypass each SNP. So, I don't think that's the answer either. Because we don't know which is the most relevant, you know, for what's going on. What I tell parents, when it comes to kids and when I tell other practitioners, if you can find the one or two key imbalances, they're the core of the problem, and you really just address those. Many of the other imbalances fall into place, so you don't need to go chasing after those other imbalances with your nutraceuticals.
So you know, I don't think our body is that simplistic that we can really say well you need X, Y, and Z, and you know, that's going to take care of everything. I think we need to step back and say well what's the big picture, what are the maybe one or two or three things that I want to address now, and then let's reassess in a couple of months and see what are the other issues actually just fall away.
Andrew: Yep. Dr. Elisa Song, we are running out of time, but I could talk to you for hours. I think though that we need to round off a subject now. So would you be amenable if we invite you back on to FX Medicine for Part 2 of PANDAS and PANS and we'll delve into treatment regimes and what you can do to help these kids?
Elisa: Yes, that would be, Andrew, my honour and my pleasure, I would love that.
Andrew: Okay, so before I interrupted you, we were talking about Th17. How about we round off on that subject and then we'll get you back for part 2 later and we'll delve into treatment, how's that?
Elisa: Yes, that's perfect. Well you know, I just want to mention we've been talking about Th17 and really the implications for neonatal immune training. What I found fascinating was that this up-regulation of Th17 can actually cause disruptions in the gut mucosal barrier and also the blood brain barrier. That's fascinating because I think that could be one of the answers. I am so glad that you mentioned that research because I'm going to, as soon as I get off, look up Andrew Littman and his research. I think that could have a lot of potential answers for why our kids are getting so sick and their brains are on fire. You know, their brains are on fire like never before and so there's something happening to that blood brain barrier that they're more susceptible to infections and these auto-antibodies attacking.
Andrew: I got to say, I'm so impressed and I'm so enthralled that you put the very controversial hot topic of vaccinations in its place. That there is a responsible place. And I do find facility for these medicines, I actually do, I just totally agree with you that you need to do smart vaccinations. I just wish we had the facility to be able to do that in Australia. I think that's a bit of a shame, when you can. I'm so glad that you talk as a true expert in your field, obviously loving the kids that you look after as well as your own. I can just see you just being the favourite doctor that these kids want to go and see, because you are fun and you're also enlightened, but you're also passionate about treating them properly. So thank you so much for taking us through an introduction of a very heavy topic and that is PANDAS and PANS.
Elisa: Yes, well thank you so much for having me on the show today.