Today we are joined again by integrative paediatrician, Holistic Mama Doc, Dr Elisa Song to continue the discussion on PANDAS and PANS.
Today we dive a little deeper into how to identify patients who may have PANDAS or PANS. Dr Song takes us through the infectious triggers, her testing methods, identifying the pathogens and "putting out the fire" in these kids' brains. Dr Song expertly explains how she executes the integration of the best that medicine and functional medicine have to offer for this condition.
She is a truly dedicated practitioner with expansive knowledge on this subject which she delivers with heartfelt care for her patients.
Covered in this episode
[00:50] Welcoming back Dr Elisa Song
[02:23] Refresher: what is PANDAS/ PANS
[11:06] Identifying the PANS/PANDAS child
[13:36] Infectious triggers
[17:25] Selecting applicable testing
[27:43] Firstly, figure out the pathogen
[33:34] Stabilise and reduce the flares
[35:26] Controlling diet, histamine and inflammation
[42:02] Removing Vitamin A paranoia
[45:47] Naltrexone: shows some promise
[49:00] IV Immunogobulin (IVIG)
[53:02] Resources for further learning
[57:04] Look into underlying biofilms
[58:50] Final summary and thanks to Dr Song.
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. And joining me on the line again today is Dr. Elisa Song for part two of PANDAS.
Now Dr. Elisa Song is a holistic paediatrician, Paediatric Functional Medicine expert, and crazy mumma to two crazy fun kids.
In an integrative paediatric practice, Whole Family Wellness, she has helped thousands of kids get to the root cause of the health concerns and help their parents understand how to help their children to thrive. Mind, body, and spirit by integrating conventional paediatrics with Functional Medicine, homeopathy, acupuncture, herbal medicine, and essential oils.
These health concerns have ranged from frequent colds, ear infections, asthma and eczema, to 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 mumma. You can follow her blog at healthykidshappykids.com and get daily tips and inspiration from her on her Facebook page, that's Dr. Elisa Song, M.D. Now, everyone can have their own virtual holistic paediatrician.
Welcome back Elisa, to FX Medicine. How are you?
Elisa: Thank you, Andrew. I'm doing great. How are you?
Andrew: I'm excellent. We had such a fun time in our first podcast and, of course, you mentioned something and I ran with the tangent.
Andrew: So we're back for part two of PANDAS. And I think as a refresher, can you just remind our listeners; remind us what PANDAS and indeed PANS are?
Elisa: So, this is something that I believe any practitioner, whether you're a Functional Medicine practitioner, Family Practice doc, a paediatrician, anyone working with children, therapists, psychologists, should be really aware of because it's increasingly common. So, PANDAS, it looks like those two little panda bears, but it stands for...it's an acronym for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. This condition was recognised back in the late ‘80s, early '90s where kids were presenting with this abrupt onset of severe OCD behaviours and tics and behavioural regressions associated with a strep infection.
Now since then, our knowledge of what PANDAS has really broadened and then we recognised that there are many other infections that can trigger similar behavioural changes and physiologic changes. And so now we call it PANS. So PANS stands for paediatric acute onset neuropsychiatric syndrome. And it's kind of a catch-all phrase. So PANS can be infection triggered, so PANDAS is a type of infection-triggered PANS. But we know that other infections can definitely cause PANS as well. So these include viruses like the Epstein Barr virus, Herpes 1 and 2 virus, human herpesvirus-6, which is the roseola virus, the parvovirus B19, which is slapped cheek virus, Coxsackievirus, which causes hand, foot and mouth disease, Lyme disease, and other tick-borne infections can also trigger PANS. And then we also have non-infectious triggers like environmental toxins, moulds, heavy metals. But for the most part when people are discussing PANS and PANDAS, they’re really referring to infection-triggered PANS or PANDAS.
And the symptoms typically you will see.., now PANS is defined by an abrupt and dramatic onset of OCD or severely restricted food intake with symptoms that aren't better explained by another known neurologic disorder. So it's pretty sudden, and you have the two of the accompanying symptoms. So anxiety, emotional lability and/or depression, irritability and aggression, behavioural regression, deterioration of school performance, sensory or motor changes, and somatic signs that include sleep problems and urinary changes. Now, PANDAS is, of course, associated with strep so you have to have a diagnosed strep infection.
So, typically in the kids that I see, it's not a sudden onset. It can be, and it can be very dramatic, but sometimes it’s a little more subtle. And the symptoms that I see most often are definitely tics, you know, the eye-blinking tic or the throat-clearing tic, that you think is probably allergies at first but it doesn’t stop. OCD behaviours, definitely a lot of separation anxiety. So kids who all of a sudden become more infantile, inability to separate from parents, talking in a baby voice, wanting to watch really young cartoons that they hadn't watched in years in their middle school.
Handwriting, you know, watching handwriting, that significantly declines for most kids. Urinary problems, frequent urination, frequent daytime urination and even enuresis are very common. And then, of course, the more obvious ones where, you know, you’ll have these kids with, you know, sudden rages and tantrums and oppositional behaviours which can be so devastating. And less frequently I'll see kids who have misophonia or dysphonia. So misophonia is basically a hatred of sound. I have some kid with PANS who literally cannot stand to hear the sound of their mother swallowing.
Andrew: Oh, really?
Elisa: Oh my gosh, this is probably the hardest one. I've had moms come in where they cannot eat with their child, and usually misophonia is directed at one person, it's not a general hatred of sound, but if it's, for instance, you know, can't stand the sound of their mother swallowing, then they literally can't eat together. I've had kids for months not be able to eat in the same room as their mother.
And, you know, moms who have to wear a scarf around their neck so that their child can't see them about to swallow and even holding saliva in their mouth because the child will fly into a rage if they swallow. So, I mean it's, you know, it can be so extreme like that, and other times it can be more subtle. But, you know, these are definitely, kids who are sick and kids who need to be identified because we can treat them.
Andrew: Can I ask...we covered in our first podcast that something was triggering in my mind as a red flag and that was the, you know, sexual assault issues and things like that. That you've got to be able to tease apart. What about stressors other than that? You know, like the stressors of daily life just getting on top of a child and seeing regression.
This seems to be something that the practitioner must be aware of to be able to say, "Okay, well, is it PANDAS or indeed PANS, or is it another stressor in life? Like, how do you tease that apart? Indeed things like autism, like some of these behavioural threats, you’re reminding me of autism and ASD, so how do you tease it apart?
Elisa: Well, it's really interesting because, you know, my practice, I have a very large practice of kids on the autism spectrum and now, so they've become more and more aware of how common PANDAS and PANS can be. In testing many of my kids with autism, many actually do have underlying PANS that may have triggered their autistic symptoms in some cases.
Or, for some kids, because their sort of biochemical imbalances are so large and their immune systems are so dysregulated, it makes them more susceptible to developing PANS on top of their autism. You know, in terms of kids who are at baseline though neurotypical; and by that I mean kids who don't have diagnosed behavioural or sensory issues or, you know, psychiatric issues, which, in reality, I mean most of us have some sort of an under...you know, we all have some sensory issues, going on. And I guess I would be hard-pressed to find a kid if you look at them and really thoroughly examine them and question them was 100% "neurotypical," but you have a child who is developmentally doing well, you know, seems...
Andrew: Socially interactive.
Elisa: Yeah, interactive, doing well in school, very well adjusted, and then all of a sudden there’s a shift, of course, you know, we need to look for; well, what else could be going on? Is there bullying at school? Is there, you know, some sort of a molestation going on or an abuse? But as I mentioned really when we have that situation it's typically behavioural regressions all-around.
Oftentimes at PANDAS it's really...well, it's interesting because for the PANS, PANDAS kids sometimes they’re able to hold together school for a little bit but eventually not, right? And sorry I just misspoke, because really with the abuse oftentimes we'll see that it's more in one setting where there's lot of fear or lot of aggression. So PANDAS or PANS, because it's a neurologic inflammation and it's an autoimmune illness, they eventually can't hold it together anymore.
So the rages happen at school and they have to have school accommodations and even be home-schooled in some severe cases. But the interesting thing about stress, you know, you mentioned that, just really popped the thought in my mind that for some kids, when they have PANDAS or PANS flares, emotional stress can trigger those flares. Because we know that emotional stress triggers inflammatory responses in our body and it can cause an immune dysregulation. And so sometimes we do see, when there is a sudden, you know, break up with a friend or a sudden huge family stressor that the behaviour starts a flare and we see, when we check the antibody levels, that the numbers actually are going up, and it's the stress that triggers the flare.
Andrew: Okay. So, what tips and hints and tricks can you give our listeners as practitioners to be able to look for when considering working up a child for PANDAS or PANS?
Elisa: You know, it's interesting because when I speak with other practitioners here in the States, other paediatricians; there’s very little awareness of what PANS and PANDAS is and what to look for. There is a little bit more awareness, and it depends on where you practice and I think, you know, what you've been exposed to, of course.
But I would say if you're working with kids, if you have a child who has chronic anxiety, depression, fears, OCD behaviours, or any sort of cognitive processing difficulties, especially if parents say, "You know what? They were great in 1st grade but all of a sudden, you know, in 2nd grade, it seemed like they were in a fog," or, "2nd grade, they just got more fearful, and separating at the door was so much harder." And it doesn't necessarily have to be the severe rages and the misophonia and the tantrums that I was mentioning before. It can and usually is, when I see kids, more subtle.
The sudden changes are...I mean they're in a way, more easy to detect because those are the kids that might even be hospitalised. Because they are a harm to themselves, or a harm to others, and hopefully there's an astute psychiatrist or a physician involved who says, "Wait a second. This is too sudden. Let's look to see if this is a PANS or PANDAS." But for the kids who are a little bit more low grade and subtle I say just look, because the more you look the more you're going to find. Now, in fact, The PANDAS Network, which is here in the United States and is a resource for any parent anywhere in the world. They predict that at least in the U.S., maybe as many as 1 in 200 kids may have PANDAS or PANS.
It is remarkable, now, how often when I see a little red flag or for my kiddo who has anxiety and we’re trying all the right things like magnesium and maybe some 5-HTP and, you know, mindfulness and getting them into meditation, and it's just not working. And then I check for the PANS or PANDAS titers, then I realise, "Oh my gosh, it's because they have PANS." And unless we can get the neurologic inflammation down we're fighting an uphill battle. And we can throw all the supplements we want and we can try to get them into as much therapy as we want to, but they're not gonna get fully well.
Andrew: Right, right. So, I've gotta tease apart something here a little bit. A lot of the infectious agents you spoke about with PANS, you know, your Coxsackie, your Rubeola, things like that, Strep indeed. They tend to be more early-childhood. But then you've got EBV, which tends to be a teenager sort of thing, admittedly, what is it, 95% of people are infected with EBV. Causes no problems in most of us.
So, A) what age range do you see with presentation and B), how do you tease apart these as, let's say, risk factors that are definitely linked or just coincidental? You know, I mean each of these patients has two arms and two legs as well, so how do you tease that apart as a causation sort of thing?
Elisa: Yes, you're right. And, you know, I would say the age, gosh, I mean, of course, you know, with Coxsackie and with parvovirus B19, Herpes-6, I mean those are often toddlers, right, who are getting those infections. I do find Epstein-Barr in younger and younger kids.
Andrew: Do you? Oh, okay.
Elisa: You know, probably because Epstein-Barr for many kids just really looks like a sore throat and another upper respiratory infection. It's more obvious in the teens when they get the post-viral fatigue syndrome.
But what I think sometimes happens for these kids is a very common infection like Herpes-6 for Roseola, they get as a child and their immune system may be able to contain it for a time but then they get these repeated hits with an underlying susceptibility to autoimmune phenomena and immune dysregulation and then eventually their immune system can't contain the infections anymore.
So, what we'll find because, of course, if you check most kids for Coxsackie antibodies and Herpes-6 antibodies, they'll be elevated, they'll have evidence of past infection. And, of course, you know, when we check for antibodies, and this is how we know what to treat, right? We wanna know, when we have a child with PANDAS and PANS, first of all, what's the trigger? And for these children where they have Epstein-Barr antibodies or Coxsackie antibodies. What we're looking for is not necessarily IgM elevations. Because if it was a past infection it's possible that the IgM antibodies are still elevated which are, of course, antibodies for acute or ongoing infection. But very often those IgM antibodies have really, you know, resolved and now there are less of these IgG antibodies that are through the roof.
So, we know that if you have very, very elevated IgG antibodies, that represents a persistent immune activation against these infections. And there's no reason why your immune system years after having, you know, a Mycoplasma infection or a CMV infection, should still be churning out incredibly high levels of antibodies. So for those kids where they have very elevated antibodies, I'm highly suspicious that this represents continued immune activation, and that's their trigger.
So then we start really treating, right? We know that to be the case for chronic fatigue immunodeficiency syndrome where patients have very elevated Epstein-Barr or Herpes-6, you know, the two most common infections associated, that when they have very elevated IgG levels, if we can treat them with something like Famvir and bring their...or Valcyte...and bring their antibody levels down to more "normal range," that corresponds with clinical improvement.
Elisa: Right? So, yeah. So, we do want know though what is triggering the PANS or PANDAS. So that's the first step in really figuring out does a child have PANDAS and how do I start the treatment?
Andrew: Yeah. And I guess one of those is testing. So with regards to conventional versus functional testing. There's such an array of things that you could be looking here. How do you...what do you do, and how do you balance it with cost versus bang for buck?
Elisa: Yes. Well, this is where, you know, I don't know how the Australian insurance system works for laboratory testing. But most of the laboratory testing, the conventional testing for these infection panels should be covered by insurance plans, at least here in the States.
So with that, if we're looking specifically for PANDAS, the first thing we want to do is check to see is there an active strep infection? So, we're doing swabs, we're doing cultures. We're culturing not just the throat but we're doing a nasal culture and an anal swab. Because the number of kids who have PANDAS that I see with really...they're the only evidence of active strep being perianal or perivaginal strep, is really high. So, we do wanna check cultures.
Elisa: Yeah. I mean, strep can be on the skin and cause the same problems. Kids with recurrent impetigo, you know, that may be their source for PANDAS. So it doesn't always have to be a strep-throat.
So then in the blood what we're checking is, of course, an antistreptolysin O, and we're also checking for anti-DNAse B strep antibodies. Now this is an old-time antibody that is checked. You know, that...I mean I remember in residency in medical school we checked it for the poststreptococcal glomerulonephritis that we saw as an autoimmune complication. Well, we're not seeing that anymore but now we're seeing this shift into seeing PANDAS as the autoimmune reaction to strep.
So that is the anti-DNAse B strep antibodies, and the reason I spell it out is because unless your lab is familiar with all the tests that you run, which now my local labs are, but in the beginning they would run an anti-dsDNA antibody. So you don't want a double-stranded DNA antibody, that's not what you're looking for. You want the anti-DNAse B strep antibody, right? And then, of course, I'm checking quantitative IgG levels to Herpes-6, Herpes-1 and 2, Mycoplasma pneumonia, Epstein-Barr Virus, Parvovirus B19, Coxsackievirus A and B, CMV (Cytomegalovirus) and also measles, mumps, and rubella. Say if you've received the MMR or have had an actual infection.
You can look also to see this list, you don't have to memorise this, but in 2013 a PANS consensus statement was written and published in The Journal of Child and Adolescent Psychopharmacology where, you know, many of the experts in PANS and PANDAS treatments across the country developed the consensus statement for practitioners to know where should we start the testing and how do we go about thinking about the physical exam for these kids and eliciting a really great history including a family history.
So that's really the conventional testing. Now in terms of additional functional medicine testing, of course, the cost varies widely, and here in the States some of that is covered by insurance, some isn't. It can, yes, absolutely get quite costly. One of the tests that we have available in the States, relatively recently, in the last, you know, couple of years is something called the Cunningham Panel. I'm not sure if it's available in Australia, but if practitioners look up the Cunningham Panel and it is offered by a lab called Moleculera, M-O-L-E-C-U-L-E-R-A, Moleculera Labs. And these are a set of four auto-antibodies that were identified as being highly elevated in patients with PANDAS and PANS. So this is certainly not a first-line test. However, I do check the Cunningham Panel in patients who are “sero-negative," right, we don't find any elevated titers for any infections, but we're still highly suspicious for PANDAS or PANS. And oftentimes we will see elevated levels, and it's really interesting what they test for are two different types of dopamine receptors. The anti-dopamine receptors D1 and D2L, I think there are five markers so, that autoantibody, also lysoganglioside autoantibody. So lysoganglioside are molecules in the brain cell membranes and nerve membranes that aid in that sort of nerve to nerve communication. So you can imagine if your antibodies are attacking that, how erratic your brain wave and brain cell communication would be.
And then tubulin, right, antitubulin antibodies, which, of course, are the protein that really helps to maintain the neuron's cellular structure. So, those are the four autoantibodies. Then they also check something called CaM kinase II activity. So, CaM kinase II stands for calcium and calmodulin-dependent protein kinase II. And they’ve found that a high activity, of this enzyme can cause a tonne of over stimulation and over excitation in the brain. So, it's a useful test if your PANS and PANDAS titers are negative. I don't test it too often because it is quite expensive, although more and more insurance companies, I'm finding, are actually covering a portion of the test.
So, in terms of functional medicine testing. The two tests that I do do are, number one, of course, a comprehensive digestive stool analysis, and I'm sure that that's where most of our Functional Medicine practitioners start, because any immune dysregulation is going to start with the gut. But my interest too, is not just assessing gut regulation, is really looking specifically at their culture and see do they have strep species in their guts? Because we oftentimes gamma-strep and alpha-strep species that are not considered pathogenic.
However, if you have a child with PANDAS in particular where they are mounting an autoimmune response to strep anywhere their bodies and we need to clear that strep in their gut as well. So that's a very helpful test to do, especially if you're getting stuck where you're seeing some improvements, but you're not getting the improvements that you're hoping for.
And then the last test that I find very useful, and especially if I'm really trying to assess is this a child with PANDAS or PANS, is this something that I should pursue further? Is a urine organic acid test.
Elisa: And in that urine organic acid test, of course, there are so many valuable markers for our children with chronic illnesses and really anyone with chronic illness, including the mitochondrial markers and the methylation markers, but what I'm looking specifically for is their quinolinic acid. Because when quinolinic acid is very elevated, especially in relation to kynurenic acid. That can be an indication that there is neuroinflammation. And those patients I absolutely dig further in to the PANDAS and PANS testing.
Now, you can have PANDAS and PANS without an elevated quinolinic acid, but it's a tip off. If you're working with a child, let's say, with autism who comes to you for biomedical functional medicine approach to treat their autism and you get a urine organic acid test as part your initial battery tests and their quinolinic acid is very high. Then I know, okay, you know what, rather than the PANS and PANDAS testing being lower on my list and maybe several visits down. I'm going to start doing that right away. So that's just another little kind of red flag that one should be looking.
Andrew: Yeah. So do you look at high quinolinic acid on its own, or high quinolinic to kynurenic acid ratio?
Elisa: Both. I look at both. You know, the ratio is probably more important. But if the quinolinic acid is very high then I still want to know is there something going on there.
Andrew: And, of course, I'm picking up this sort of, kind of a crossover with maybe things like chronic inflammatory response syndrome. Like the CIRS of Ritchie Shoemaker? Do you see this sort of thing? Like when you're talking about a mould, as an antecedent to the triggering of the symptoms, do you find that the supportive measures can be as complex if you like, as something like people with CIRS?
Elisa: Yes, absolutely. And, in fact, you know moulds can be one of those PANS triggers. Remember, I mentioned that PANS can be infection-triggered or non-infectious-triggered. And so we do find for some kids where it's not any infection that we can find but, you know, they have huge amounts of moulds in their home. And, you know, many of the labs, if you run the Shoemaker Panel, are really abnormal. So, then we have to start working on really treating the mould toxicity and that's how you're gonna get rid of that neurologic inflammation and that autoimmune response that's going on.
Andrew: You know, podcasting with such experts in this area as Nicole Bijlsma, and she was talking about building biology. And her expertise has just blown the lid off of a massive problem that I see in Australia. I don't know about the U.S. I would say it's just as bad. But I was totally unprepared for the amount of buildings that have mould damage. And so, therefore, the amount of risk that we're placing these kids who have got a propensity for the PANS on that, you know, it's huge.
Elisa: Yeah, absolutely. And sometimes we find that kids do have infectious trigger PANS and they're getting better but something's holding them in place. So then we have to look at, well, what are the perpetuating factors, right? We talked about the triggers but then there can also be perpetuating factors, and that's anything that's going to be creating additional inflammation. And so that's absolutely an important piece in your treatment plan to figure out.
Andrew: So, key Functional Medicine and supportive interventions. I'm ready for about an hour long podcast right here. I'm suspecting that it's going to be way too much to cover in the short podcast.
But can you give us some hints and tips as to what are your favourites or most commonly used, you know, interventions and indeed which ones do you find more successful? Maybe even comparing with the things that you find useless?
Elisa: Yes. So, you know, now once you've figured out what you're treating, right, what bugs you're killing, and here I'm going to be mostly referring to infectious triggered PANS and PANDAS. Because that is much more common than non-infectious triggered PANS.
So once you know what the bug is, the basic principles are first, to kill the bug. The second is to put the fire out however you can. And the third one is where you're keeping that fire down, right? And finally we, of course, in any intervention that we do, we really need to know how to support the child and family through this process and through the flare.
So, the first step, you know, killing the bug. I would say that's the easiest thing, right, for the most part, right, because we know what herbal and pharmaceutical antimicrobials will probably work. So once, you know, is this a Mycoplasma, you know, bacteria, is it strep, is it Epstein-Barr, then you really use the appropriate antimicrobial. Whether or not you choose to use pharmaceuticals or herbal antimicrobials. Now, Azithromycin, when it comes to strep-induced PANS or PANDAS or Mycoplasma-induced PANS, is a great choice. Azithromycin by itself actually has its own anti-inflammatory properties. And a recent study, this is just last year in 2016, found Azithromycin to be very helpful for kids with sudden onset of OCD and tics. So, even without PANDAS, Azithromycin can be helpful.
You know, as far as herbal antimicrobials, I have some combinations that I use and really like. I don't know if they're available in Australia. But, of course, for viral infections, olive leaf extract works great. Typically with herbals, most herbal regimens do require more than one antimicrobial agent. So if I'm doing olive leaf extract I might also add some Lauricidin for its anti-viral properties and maybe some L-Lysine.
The benefit of an antimicrobial herbal regimen in my mind is because oftentimes for kids, they don't just have one bug. We often find that they have strep and they have really elevated Herpes-6 titers. And so now you have an antibiotic and, you know, like Azithromycin and maybe Acyclovir or, you know, Famvir that you have to add on board. So if you use an antimicrobial herbal cocktail, then you can actually have both antibacterial and antiviral properties. And then at the same time you have the antifungal properties to prevent the yeast overgrowth that we see if you just use antibiotics alone.
So, there is benefit to using antimicrobial herbs. I typically, though, you know, for a kid with PANDAS or with Mycoplasma pneumonia PANS, I will use the pharmaceutical. They do tend to work a little bit more quickly. And then, you know, follow up with antimicrobial herbs.
You know, in terms of length of time, that's a hard one. I mean most of these kids, we think probably until they hit puberty and beyond and when their immune system really starts to act more like a mature adult-like immune system we need to support them with some sort of an antimicrobial. And I really, you know, don't like the idea of keeping kids on antibiotic prescriptions for years and years and years. However, sometimes it is necessary. But if we can get them on antimicrobial herbs, because many of these there's also have good phytonutrient properties and antioxidant properties themselves.
But I do tell parents, expect to be on some sort of an antimicrobial cocktail for a prolonged period. I don't like to give specific dates, but its typically going to be, you know, a matter of years. And we can shorten that duration once you're in a good place. Sometimes, we'll go to a more prophylactic regimen of, you know, every other day and then every few days and once a week for the antibiotics and see how they do. Oftentimes, you do need to change the antibiotics.
Andrew: Yes. So this was where I was going head, is given that you're dealing with kids often, in this situation. You know, you're talking about a pneumonia Mycoplasma type issue. Doxycycline is used in adults, but there are certain issues with Doxy in kids with teeth development, right.
So is this where you probably prefer Azithromycin over Doxy?
Elisa: That's right, that's right, yeah. We don't use Doxy. You know, there are some indications where if that's your only choice you can use. And, for instance, with Lyme I might go to the Doxy a little bit faster, but otherwise going for Azithromycin and for other antibiotics, is preferred if you have young kids.
Andrew: Yeah. Okay, so the typical course for a child, are we talking, you know, you mentioned months, years here. That's gonna be frustrating as hell when you're looking at academic performance and how they're developing socially in school. Indeed setting up their friendships and how they're gonna be as a person later on in life. What's the typical course for a child with PANDAS and PANS? How does it change and what can they expect, what can parents sort of expect to come back to, if you like?
Elisa: Oh gosh. The typical course, you know, it does vary and, you know, it can be heartbreaking. But before we get into that, let me back up and just go to some of the other things that really help kids get more stable, right?
Because in the beginning when we're seeing a kid with PANS and PANDAS we really, you know, want to get them into a stable place so that we don't see a lot of flares. And if we can do that, then they have a much easier course. Because once you kill the bug PANDAS and PANS can flare and can stir quite often and can be really devastating.
And so when I mentioned putting out the fire, you know, lowering the inflammation, we need to do that as well. You can't just kill the infection, you know, fight the bugs and the microbes without getting the fire in their brain down. And, of course, you know, we all have our favourite anti-inflammatories, but, you know, essential are the Omega-3 essential fatty acids to really help with the inflammation. Curcumin is one of my favourite because curcumin can cross the blood brain barrier where we want the inflammation to go down. And then another favorite is quercetin. So quercetin has mast-cell stabilising properties to prevent histamine release, and we know from many kids and adults with chronic infections, histamine intolerance is a huge issue and histamine release is a huge problem.
And so we have histamine receptors on every single cell in our body. We have these relatively newly identified H4 receptors on our immune cells. Of course, we all know about our H1 receptors and our H2 receptors that are responsible for allergies and reflux. But we have H3 receptors in our brain and H4 receptors on our immune cells. So, if we can stabilise, you know, that histamine release and really modulate how our immune cells and our CNS (Central Nervous System) cells are working, that's gonna go a long way in lowering the inflammation.
Andrew: You've just given me a new subject to research tonight. I know nothing of H4.
Elisa: Yes, it's fascinating if you're looking into this, why are kids having these histamine problems? And it just makes so much sense to me. These histamine receptors are everywhere, and histamine is such an important modulator of virtually every action in our body including our immune cells. So, yes, that can be absolutely probably another topic for a huge podcast.
Andrew: Yeah, massive.
Elisa: Yeah. And then, you know, I never leave the discussion with parents without talking about their diet. They have to clean up their diet and remove anti-inflammatory triggers, and that almost always is gluten. And for our kids, you know, absolutely, if they get rid of all the artificial junk, the dyes, the artificial flavours, and the artificial preservatives. Because those are feeding the fire. So whatever fuel is feeding the fire we need to get rid of.
And for cases where they are having a lot of inflammation, what I typically start with is a week's worth of ibuprofen. You know, at anti-inflammatory doses so, you know, 10mg per kg per dose, three times a day for a week, and that can do wonders for calming that child and regulating their behaviours.
And this is a little test I might do. If I'm not quite sure, we're in the process of working up for PANS and we're willing to wait two weeks for the titers, after the blood is drawn, I'll tell parents, "You know what? Let's just try this. Get some ibuprofen for a week and you let me know what their behaviour is like." And if they say, "Oh my gosh, they're so much calmer, they stop wetting the bed, their handwriting is getting better," well, they have PANS. Now you just need to figure out what's causing it.
Andrew: Wow. I’ve got another issue here, is that given the new flavour of the month using NSAIDs (Non-steroidal anti-inflammatories) in kids for fevers, because, you know, paracetamol-overdose is the most common drug overdose of paediatrics seen in hospitals, and people can't read labels. And so now they turning to the next flavour of the month. I'm just waiting for two things, one, would they be covering up a PANDAS, PANS issue and, two, I'm just waiting for the day that we're gonna see a whole population basis of childhood ulceration, stomach ulceration. I'm just waiting.
Elisa: Yes. And, you know, that's a great point because really, you know, NSAIDs, you should not be prolonged if you can help it and, of course, it's going to disrupt gut microbiome and the pH of your gut and have tonnes of downstream effects. So, it's not something that I would like kids to be on long-term.
You know, the issue with fever, I mean I have long conversations about fever with families and with other practitioners. Because there's way too much "fever phobia", and I remind parents that fever is your body's natural response to fighting that infection. I say very simplistically, "What happens when you're hot? You slow down." So when your body heats up it's slowing down those bugs so your immune system can actually kill them.
And we know, there are studies showing that artificially, you know, using fevers with antipyretics, like acetaminophen and ibuprofen actually prolongs the duration of the illness. So you may temporarily be helping your child to feel better but you are prolonging their illness and you're not helping them fight their infection any better.
So, if we can just sit tight and preserve the NSAIDs for when their kids are not drinking very well or not sleeping well, because you need to drink and sleep to recover, but otherwise really, you know, letting that fever run its course. You know, if you are neurologically intact, I remind parents, your body has these thermoregulatory control mechanisms that your fever will not get "too high." And your child will not get brain damage, and children also often run, you know, to 39 degrees Celsius, 39.5, you know - 40, you know, very quickly, and they're running around and they're talking to you. You know, an adult at 38.5, you know, is acting like it's the end of the world.
Andrew: Particularly a male.
Elisa: Exactly. But kids are different.
Andrew: Just on that line, though. When do you worry about fitting with a fever?
Elisa: So, with the fever, you know, I tell parents look at your child. If they are more tired, but they're making good eye contact, they're answering your questions appropriately, they're staying hydrated; meaning they're having some urine output every six to eight hours even if it's a little darker or a little bit less in volume, then that's what I want to see. Many kids, you know, and there are going to be some kids who are, you know, 38.3 and they're laying on the couch listless, and again other kids are 39 and they're, you know, playing volleyball and running around like nothing's going on.
So, looking at your child is really important. So, no matter what temperature, if they're not making great eye contact, not answering your questions appropriately, they're dehydrated and you're really monitoring the urine output to see that. They really truly are "lethargic." Lethargic is a word I tell parents not to use unless they are truly lethargic, meaning they're on the couch and very difficult to arouse, right? Lethargic does not mean just wanting to be a couch potato.
Andrew: Not putting the bins out, yeah.
Elisa: Exactly, exactly. And so, and I tell parents I want your child to be a couch potato when they're sick. I do not want them acting "normal," because parents will worry, "Well, they're not acting their normal self." Well, when you're sick you should hunker down, you should cover yourself in a blanket, drink some warm soup and rest.
You should not be, you know, running around the backyard on the trampoline or riding bicycles with your friends.
So, just another step that I sometimes do take with bringing down the inflammation are steroid pulses. Now, you know, again, I do not use steroid prednisone lightly. However, just as you might with a child with a very severe asthma flare, you might consider a four or five-day course, a series, 2mg per kilogram per day, in which case you wouldn't have to do a taper. Now in some severe cases I have had kids on steroids with longer tapers, you know, some as a month long taper. Some kids who are very sick might even be on a longer taper. But that is something...if you're just having trouble getting the fire down, we want to get the fire down.
Whatever way we can to get kids feeling better, behaving better, functioning better, and then we keep the fire down.
This is where conventional medicine has very little to offer, unfortunately. We're gonna blast the immune systems, right? We're good at, you know, giving all sorts of immunosuppressants to bring the fire down, but we don't have a lot ways to keep the fire down, and this is where we have some fascinating interventions in the functional medicine world.
So think about, well, how can we apply what we know of pathophysiology and what's going on with this illness to think theoretically about what nutraceutical or pharmaceutical might be beneficial?
And in our first talk, we spoke about the Th17 imbalance, right? And so we know that with PANDAS now we're finding is a Th17 up-regulation with insufficient key regulatory support. So then I think, "Well, gosh, what can help increase the T-regulatory support?" Well, you know, things like vitamin D and butyrate, you know, that we find in ghee or pistachios, if you like pistachios? and exercise, and vitamin A can all enhance our T-regulatory function.
Andrew: Yes. Sorry, so do you find a resurgence in the use of vitamin A? We were so paranoid about it with for many decades and yet when you're looking at T-reg and, you know, it's use even in neurotransmitter production, Vitamin A, retinol has really a good purpose. A therapeutic action.
Elisa: Absolutely. You know, there is still a fear of vitamin A here, I wont lie. There's not a resurgence except, you know, in the autism world and the functional medicine world a bit more. I have had kids on fairly high dose vitamin A protocols for anti-viral support and, you know, I'm following levels and not a single one has become toxic. So, you know, yes, we do need to worry about Vitamin A toxicity but it takes a lot to get there.
Andrew: A lot, indeed. What is it? The World Health Organization International Vitamin A working group, I think it was, IVAG. You know, what is it? It is safe for a pregnant woman to take 10,000 IU, and this is retinol-equivalents, this is IU, international units, 10,000 IU, at any stage during pregnancy regardless of her existing status.
So, in other words, she could be already replete and she can take an extra 10,000 without causing birth defects. That’s; International Vitamin A Working Group. Now, you've got to think about paediatrics and then, you know, the doses used are massive. When I looked to toxicity, it was huge.
Elisa: Yeah, absolutely. Now, the other thing we've spoken about in terms of Th17 is really, you know, I started looking at, well, are there ways that we can actually lower Th17 responses? And there is an antioxidant called fisetin, "F," as in "FRANK," I, "S," as in "Sam," E, T," as in "TOM," I-N. And I've only begun to use this in a few patients and I've actually had some pretty good feedback on it.
So this is a naturally occurring antioxidant that's found in high levels in strawberries and, you know, other fruits and vegetables like apples and onions. Lotus root, of all things, if you eat Lotus root and persimmon. But fisetin, inhibits Th17. So that's another promising area for intervention.
Now, you know, the other two...actually other three interventions that if in Australia you have access to, to highly consider. The first one is low dose Naltrexone. So, I don't know if any of the practitioners are using low dose Naltrexone for autoimmune illnesses. But I am seeing great results with low dose Naltrexone in my kids with PANDAS and PANS and frankly any autoimmune condition.
Andrew: So where I'm going here with this, with low dose Naltrexone, this is a drug in Australia, so obviously prescribed by a GP. And I don't know about its appropriate use, it would be an off-label use for this sort of thing so I don't know where that sits with GPs, but where I'm thinking here is things like SIBO.
Elisa: So, you know, Naltrexone is really interesting because, of course, Naltrexone in "regular doses," the doses that physicians really know the use of Naltrexone for is as an opioid antagonist in cases of overdose, right? And so when parents look it up they'll say, "We'll my child doesn't take narcotics," right? But in low doses, and these are extremely low doses, and we do have to get it compounded here, so there are special compounding pharmacies that I will call in a prescription for. But there are opioid receptors on all of our immune cells, and so what we're finding is, if you give Naltrexone at the very low dosages at bedtime, there is a temporary blockade of something called opioid growth factor on some of these immune cells for a few hours overnight. And then in the morning you get this rebound sensitivity of the those immune cells with increased effect on immune modulation.
Because that's what we want with our kids with autoimmune illnesses and our adults with autoimmune illnesses. We want to modulate their immune response so that it’s a more normal immune response. It's not fire out of control. Jackie McCandless is a physician who in the early 2000's really pioneered worked with low dose Naltrexone with kids on the autism spectrum.
I remember back then, I tried low dose Naltrexone for several of my kids on the spectrum and I didn't see anything, I didn't see any lot wows. But now that I'm going back to it, and targeting the right kids and I realised I was not targeting the right child with autism because autism is so many different paths. And not all kids with autism have an infectious path. But the kids who do now and the kids with PANDAS and PANS, it is a game-changer for some of those kids. And, you know, the typical dosage for adults with autoimmune illness, we're getting them to about 4.5milligrams, so very low dosages and it has to be given at bedtime.
For children, you know, I'll start at a very low dose, 0.5mg and end up anywhere from 1.5mg to 3-3.5mg. And the interesting thing is, you know, it doesn't necessarily correspond with their body weight. Which we know, right, in the field of pharmacogenetics it doesn't make sense to just purely base your dosing on body weight, so you just have to titrate up slowly and see.
Andrew: Yeah. So start at 0.5mg and go up to around about the 3mg.
Elisa: Around about 3mg. And then if in Australia you have a severe kid with PANS or PANDAS, one of the interventions that has actually quite a bit of good literature support for is IV immunoglobulin (IVIG). So, you know, this is not to be taken lightly. IVIG can definitely have side effects. And yes, and absolutely it's invasive, requires IV treatments over several hours, however, for your severe kids with PANDAS and PANS, it can do an immune reset.
Andrew: How do you get that accepted? Like, you'd have to have a specialist, you're a paediatrician obviously, but how would a GP, they would need specialist intervention for that, wouldn't they?
Elisa: You know, it depends. Here, in the States you can, I as a physician can order IVIG on a patient. It does have to go to insurance approval and unfortunately most insurance companies, if you have any diagnosis of PANDAS or PANS in the chart, they will automatically deny IVIG. Even though, you know, there are several studies showing the benefits of IVIG, you know, as late as August of 2016 last year, Sue Swedo is a doctor at the National Institutes of Mental Health, she really pioneered this work, you know, way back in the '90s with PANDAS. But they found that those children who received IVIG had over 60% reduction in PANDAS symptoms. Oftentimes it's just a onetime IVIG dose. It's not, you know, monthly which we use to think is needed.
Now what I do is I do check kids for their total IgG levels and their subclasses, because very often kids will have low immunoglobulin type G levels. Is it a chicken or an egg thing? I don't know, because with chronic immune test over time you can expect your white blood cell count to drop and your neutrophils count to drop, and you can expect your IgG levels to drop.
However, there are some kids who actually have combined variable immunodeficiency and other primary immunodeficiencies that we know are more likely to develop PANS or PANDAS. So if I can find a low IgG number that's a little bit more of a push for insurance to approve it. Now, if it's going to be a one-time thing unfortunately I've had parents who just have to pay out of pocket, it's incredibly expensive, but it can be a very worth it, especially when you're getting stuck.
Now the dosage for IVIG for PANDAS and PANS treatment, and this may really cause some practitioners' jaws to drop. Because the replacement dose for immune IgG replacement is about 500mg per kilogram. Now, the treatment dose for PANS and PANDAS is 2g per kilogram given over two days. So, it's 1g per kilo daily for two days. You do not want to give a low dose replacement just because they found that that actually can worsen PANDAS.
Elisa: So that's a consideration.
Andrew: Yeah, I wonder if then you might have answered my question here, and that was, do you have a think about using...given that it’s not IV, it oral-dosing, but do you ever use things like colostrum with, you know, high IgA, IgG?
Elisa: Yeah. You know that's a great thought, and I do use colostrum and IgG proteins. Several supplement manufacturers now have IgG available as a supplement and that can be very helpful. That seems to have more benefit for the gut. So for kids who have the inflammatory and irritable bowel symptoms. I haven't found this to be helpful for the PANDAS and PANS symptoms but, of course, all of these kids have dysregulated guts. So that would be very helpful to support their gut, so that they don't get new infections in the first place.
So, you know, I do use that as supportive, and in fact there's one supplement called IgY Max. It's actually an egg-derived IgG. There are some good sites, looking at its effect on preventing recurrent strep infections. So that is one that I do use more frequently for kids with PANDAS.
Andrew: Gotcha. Obviously, we need to get you out of Australia to teach our practitioners. This is a specialist sort of area. I mean this is something where you can't just go, “Oh, I'm gonna treat it tomorrow." You really need to know what you're dealing with and how to treat and how to handle untoward effects.
What resources exist for practitioners to up-skill in this area though?
Elisa: So there are, you know, unfortunately I will say there aren't a tonne of resources for practitioners to get trained. This is, you know, you need to have that foundation of Functional Medicine and really have that foundation of working with kids on the autism spectrum through a biomedical approach, even if your kids aren't on the autism spectrum.
Because the foundation, the biochemical imbalances that we see are often very similar. So, if you’re a practitioner working with kids on the autism spectrum and you're comfortable with the biomedical approach, then absolutely, this is something you can start doing. Because you do need to have that foundation. But all those same Functional Medicine supports, at the very least, right, we need to address their leaky gut and their gut dysbiosis.
We need to support methylation and mitochondrial support is critical. Mostly if kids have nutrient deficiencies, and we were talking before, you know, we got onto the topic about adrenaline and thyroid dysfunction, but absolutely these kids need to be supported fully, otherwise they're not going to get better.
And so if you start from there and then you do the testing and see, well, what infections could be underlying, then what you can do is go to the PANDAS' physicians network. So, the PANDAS' physicians network is a U.S. based network. It's a website. It's www.pandasppn.org. And they have, you know, the latest research on their website. They have some work-up guidelines and some treatment guidelines on their website. It's not a training program, but they do also hold yearly conferences, so if anyone is interested in coming to meet them, happy to see them and say hi, but those are conferences where you can get more training from people who are specialising in PANDAS.
And then for parents, and even if you're not a parent, as a practitioner really, you know, new to this idea of PANDAS and PANS and really wanted to learn more about its impact on families and what other parents are trying and doing and have found successful. The PANDAS network, that's www.pandasnetwork.org, is a great resource.
And, of course, you know I learned the most from my families and from my parents. It is often the mummas and some papas, but it's usually the mummas, who are up all night doing research, Googling. On their Facebook groups, you know, on their list search, searching for answers. And they will come to me and say, "Have you heard of such and such? Someone on my board is getting good success with this, you know, this medication or that nutritional supplement." And then I do my research and look into it to see if this is a plausible, you know, therapeutic to try, right? Because our kids can't wait for all the evidence, but if there's a plausibility of evidence, that it may be helpful, and that it's not going to be harmful, then we work through it together, right, and that's how you learn.
Andrew: Well, we'll definitely be putting pandasppn.org and pandasnetwork.org up on the FX Medicine website for our listeners. So, if any of you listeners out there would like to access those resources, please do so. And indeed, I'll be putting up a whack of papers, my goodness.
Elisa: And I get you some resources, too.
I think, you know, the very final note, you know, for your Functional Medicine practitioners who have delved into PANDAS and PANS or chronic infections of any sort. If you know, you can get your kids better, it is amazing how well kids can get. It's a bumpy road because kids absolutely will flare at one point or two points or three points. So then you just go back to supporting their inflammation, bringing down the fire, supporting their gut and then, you know, there are times, though, where you might get stuck, right?
And some kids, you're doing all these treatments and you're not making any headway and you've done the IVIG. You've even done maybe something called plasmapheresis at a specialty hospital. And in those cases I just want to plant a little seed for those practitioners to really think about biofilm. And also about immune-activation of the hyper-coagulability cascade. So there can be the secondary hyper-coagulability that's also holding infections in place.
Andrew: Related to serotonin or...?
Elisa: No, it's actually related to chronic infection.
Elisa: These pathogens are really smart and they not just create biofilms around themselves to evade our immune system. But they also can literally activate our coagulation cascade and create these little fibrin clasts around themselves. And so you have a secondary hyper-coagulability. So, as soon as you can break through the biofilm or break through those clots, you have to be ready for a deluge of pathogens. So, you need to be ready to mop that up, but then you get the movement, if your child is stuck.
Dr. Elisa Song, I can't thank you enough for taking us through, me through. I mean, wow, obviously your expertise is evident, but I love the way that you care about your kids. You can see...I can, you know, just see you going back to little stories, little patients that you've had interactions with. And, you know, they're triggering how something worked or didn't work in them. And I can just see your mind flicking back to people.
You're obviously a lovely mumma, like I say, as I can't wait to learn more from you. I thank you so much for taking me through what PANDAS and PANS are, because I had no idea. I'm certainly going to be learning more tonight, that's for sure.
Elisa: You know, we always learn, right? I mean you never stop learning, which is why this field is so exciting.
Andrew: Very true. And I'll certainly be learning more about H4 receptors tonight.
Dr. Elisa Song, thank you so much for taking as through PANDAS and PANS on FX Medicine today.
Elisa: Oh, you're so welcome. It was a pleasure to be with you twice. I love talking to you, it's super fun.
And, you know, and I just wanted to give two more resources for practitioners and for parents. I think it can be really eye opening for practitioners who've never seen a patient, well, I will say the probably have seen patients with PANDAS or PANS and not realised it. But haven't really thought about what it could be and how it manifests.
There is a documentary film called "My Kid is Not Crazy." That is...it's heart-wrenching on some levels, but it just gives an insight into what these families are going through and how much they need help from you all listening as Functional Medicine practitioners to learn more about to how to help them.
And then there is a book that I have all my kids read. It's called "In A Pickle Over PANDAS." And it's amazing because kids will come in, I'll tell them that I think they might have an infection that's really causing their brain to hurt and causing them to do things that they really don't want to do, and then they'll read it and just you can see, and parents will call me and say they just start, you know, really crying and piercing, "This is me. You know, I'm so glad I'm not crazy, right? Now, I know there are something that's wrong and something that we can do." So, it's a great book for kids to read but, you know, any parent or practitioner who just wants to see, well, from a kid's perspective what does it feel like and what are they going through. It's a wonderful resource.
Andrew: Dr. Elisa Song, I can't thank you enough to your heart. This is FX Medicine. I'm Andrew Whitfield-Cook.
Research explored in this podcast
Chang K, Frankovich J, Cooperstock M, et al. Clinical Evaluation of Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference. 2015 Feb 1;25(1):3-13
Murphy T, Brennan E, Johnco C, et al. A Double-Blind Randomized Placebo-Controlled Pilot Study of Azithromycin in Youth with Acute-Onset Obsessive-Compulsive Disorder. J Child Adolesc Psychopharmacol. 2017 Mar 30. doi: 10.1089/cap.2016.0190. [Epub ahead of print]
Murphy M, Pichichero M. Prospective Identification and Treatment of Children With Pediatric Autoimmune Neuropsychiatric Disorder Associated With Group A Streptococcal Infection (PANDAS) Arch Pediatr Adolesc Med. 2002;156(4):356-361.