Renegade Research Clinician’s Roundtable
Dr Ilene Ruhoy & Dr. David Kaufman - March 15th 2024
Dr. Ilene Ruhoy and Dr. David Kaufman discussed the complexities of diagnosing and treating chronic infection-mediated illnesses, such as ME/CFS, Lyme disease, and fibromyalgia. They emphasized the need for a personalized approach to diagnosis and treatment, considering the interplay between infection, immune system dysfunction, and other factors impacting patient outcomes. They also highlighted the significance of connective tissue in chronic illnesses and the importance of thorough testing to identify pathologies. Dr. Ruhoy and Dr. Kaufman agreed that symptoms are crucial in diagnosis and treatment, but more objective data is needed to inform treatment plans. They also discussed the potential connections between autonomic disorders and mast cell activation, and the role of the glymphatic system in the brain.
Isabel Ramirez-Burnett 00:11
Welcome everyone. I am Isabel, Renegade CEO, and I have had ME for 43 years. I have dreamed of bringing clinicians together for a long time. This is the first step in a broader goal of networking clinicians globally in order to expand the pool of available clinicians treating infection-associated chronic illness. Long COVID has brought much needed attention to these conditions and this is perfect for today's COVID Awareness Day. But where we are now is definitely very necessary but not nearly sufficient,our organization as well as many talented researchers around the world are looking for patterns, biomarkers and mechanisms, but we need clinicians equipped to provide care and interventions that increase our function and thus our quality of life now. Most of the clinicians who are treating us have full panels or the wait is months or years. So we urge you today to join us in this effort by sharing your expertise if you have been in the trenches with us, or learning from them if you are just getting started. Now I'll pass it on to our visionary extraordinaire and founder Tess Falor
Tess Falor 01:30
Hi, everyone, I'm Tess and like Isabel said, I'm founder of renegade research and remission biome, and I have had MECFS for 19 years now. Renegade research is a community of patients, caregivers, clinicians, researchers, and other allies, all working together to push forward research and treatment of infection-associated chronic illness and we are patient-lead. We have a large team from all around the world. Some of them are here, but this is just a portion of our team. We are bringing together patients of varying levels of severity and trying to create this diverse team and just push, push everything together, forward that we can. As I mentioned originally, Remission biome is our largest project and we currently have 50 Self experimenters all working together as a community to try to understand remission events caused by antibiotics. You can learn more about remission bio at our new website, which I will show quickly here because it is beautiful. We just went live today. So if you go to our website remission biome.org You can sign up for our newsletter. You can learn more about our remission biome and all of our projects. So on the homepage, if you go to the bottom, click subscribe and you will get on our newsletter where we'll announce other events like we have some other ones coming up. And yeah, join our newsletter. I'm going to have some of the team very quickly just introduce themselves and say how long they have been sick if they don't mind sharing. So I'll start off with Richelle.
Richelle Sepulveda 03:24
Hi, I'm Michelle Sepulveda. I've been likely developing MECFS for the past 15 years, but in very was very mild and until four years ago this month, and I got COVID and that supercharged what I had to something that was a lot more obvious. So that really precipitated a significant decline. So yeah, I suppose anything else that I knew mentioned? We'll just we'll just keep it really short. So we can just quickly go around to Yeah, needs and how long so I'll go to Shelly.
Shelley Hayden 04:00
Hello, my name is Shelly Hayden. I'm so honored to have you guys join us today. I have had MECFS for 28 years. And I went 23 years without a diagnosis. And then 2020 hit and I got long COVID on top. So been in the trenches with us for a long time. We're so happy to have you here. Thank you.
Tess Falor 04:22
Alright, we'll go to Nick
Nick Melia 04:30
Nick Media, I'm a system scientist with the Remission Biome team. I got long COVID in March 2020.
Elly Brosius 04:43
Le Hi, I'm Ellie brushes. I was diagnosed with CFS 32 years ago, but I had lots of infection problems before that. I was diagnosed with ME and hypotension in pots after that and hypermobility, and then I joined a long club With Club in 2010. I'm in Northern Virginia, and I've had a support group here for for 31 years.
Tess Falor 05:09
Thank you and then Michael.
Michael 05:11
And Michael, I've had long COVID going on two years now.
Tess Falor 05:19
All right, I will pass it back to Isabel.
Isabel Ramirez-Burnett 05:22
Thank you, everyone. We are honored today to have doctors Ilene Ruhoy and David Kaufman from the Center for complex diseases. They are working members of the US political MECFS coalition and part of the guideline committee. Keep in mind this is a brief summary of their bios as they are very experienced and accomplished clinicians. Dr. Ilene Ruhoy is a board certified neurologist and environmental toxicologist who specializes in chronic and complex illnesses. She graduated from the University of Pittsburgh School of Medicine and completed her residency in neurology at the University of Washington, where she also did additional fellowship training in neuromuscular disorders. She earned a PhD in Environmental Toxicology at the University of Nevada, working directly with the EPA on her dissertation topic of pharmaceutical recipes in the water. Dr. Roho I also completed a fellowship in integrative medicine with Dr. Andrew whale at the University of Arizona. Dr. Rojas interests include connective tissue disorders such as EDS, autoimmune neurological disorders, neuromuscular disorders, inter cranial base, vascular and pressure disorders, infection associated neurological conditions such as lung COVID, MECFS, and pans and pandas, traumatic and inflammatory brain injury, mitochondrial disease, neurodegeneration and exposure illness. Dr. David Kaufman earned a BFA from New York University School of the Arts and filmmaking, an MA from Teachers College, Columbia University in education, and his MD from New York Medical College, Dr. Kaufman completed his internal medicine residency training in St. Vincent's Hospital and Medical Center in New York City. He began his internal medicine practice in Greenwich Village in New York City, just as the epidemic that came to be known as HIV AIDS exploded with St. Vincent at the epicenter of this outbreak, he became deeply involved in the care of HIV positive patients and in the research aimed at discovering ways to treat both the opportunistic infections they were dying from, and the virus that was causing the destruction of their immune systems. As HIV and AIDS became a treatable infection. The practice expanded to include more primary care and general internal medicine patients ranging from 80 to 105 years old. He also became involved in the diagnosis and treatment of a variety of chronic often difficult to diagnose and manage conditions, such as Lyme disease, fibromyalgia, chronic viral diseases, vitamin and nutrient deficiency, Dr. Roy and Kaufman also are hosting the unravelled podcast on Patreon, which I encourage all of you to go and listen. And without further ado, please welcome Dr. copelan. And, Dr. Robot.
Dr. Ilene Ruhoy 08:23
Thank you, that was some introduction. I always get emotional, David, every time I hear about your history starting out in the AIDS epidemic. And when we didn't know anything,
Dr. Patrick Hwu 08:36
I still do as well. Yeah.
Dr. Ilene Ruhoy 08:38
Good work. So we're very happy to be here. And I guess, Isabel, you can let us know how we can best get started.
Dr. David Kaufman 08:46
I'd like to say just two things before we hit the road here. First of all, thank you for doing this. I think it's incredible that you're able to bring all these clinicians to see this, right. I mean, that's been a goal for Dr. Robot and myself for several since we've known each other basically. And for me, it's something I'm very passionate about it because we just don't have enough physicians to take care of this population of patients, which as you all know, is exploding. The second thing I wanted to say is it's really interesting Isabel, a test as you were introducing everybody the in quotes the role that COVID and long COVID has played here and you know if ever there was a silver lining in something the silver lining and COVID is bringing attention finally to this, these chronic infection mediated illnesses so it's it's just great work you guys are doing Thank you. Thank you very much. And yes, if we can get started, just talk about what you do in your practice, how you approach patients, what test your order, you know, what's your rationale for going one way or the other and you know, how your patients are benefiting from this and what you've done along the years.
Dr. Patrick Hwu 10:03
Ilene, you want me to start? You can start, I'll start. Okay. So I think the most fundamental thing in my approach and and and I wouldn't approach as well, is taking a history. So that sounds pretty mundane. And for any physicians who are watching, you know, that is drilled into us endlessly in medical school. You know, we cite people like Dr. Osler ostler who talked about the history, it's so important, but sadly, it almost never really plays out in the real health care world, for a variety of reasons, including lack of time insurance systems, etc. What became clear to me is that taking a history, really in detail is the critical step in, in figuring out what's going on with our patients. And when I say detailed, I start with the patient's mother's pregnancy and delivery. And I go literally through the history from zero to two, two to five, five to 1212, to 18. And in sections like that, because I found it very revealing in terms of informing me or helping to suggest to me underlying conditions that might predispose to illness and a classic thing, for example, a patient comes to me and says, I got COVID in 2020. And I've never been the same since quote, therefore, I've long COVID. But I was totally healthy before that. And then when they take that history that I just described there, the history of chronic ear infections, and chronic sinus infections, and then they had exercise induced asthma. And they had rashes from certain foods. And then they developed some medication allergies, they had a couple of episodes of dizziness and college, and they played sports, and they kept twisting their ankle and spraining things. And all of those pieces of history are profoundly relevant to putting the long COVID in quotes, putting it into context and understanding it. So for me, that's the most critical piece. And, and I will spend, the initial patient visit is scheduled for at least 90 minutes. And I would say that 60 plus of those minutes, are simply taking the history back and forth talking. So, to me, that's the ballgame right there. If we as physicians, spend the time to tick that history, everything else kind of starts to make sense. Rather than say, Oh, you have long COVID, or you have MECFS, which really tells me nothing. Those are just two labels that are devastating labels, perhaps but their labels, they don't explain the underlying pathology.
Dr. Ilene Ruhoy 12:45
I'll stop there and you can only do more and I've often thought about this and I realized that when I trained in neurology I trained in both pediatric and adult neurology, so I have always sort of had this approach where I would ask about an ad for an adult patient where I would ask about the childhood and I would often find that there was evidence of what I would see when I worked at the Children's Hospital in the neurology department and so I started to put together how this had been somewhat of a lifelong struggle, or at least that it had its beginnings earlier in life and then the age at which they're sitting in front of me, or at least in their story, they might say, you know, two three years ago, sort of when it all really seemed to get worse, but actually, as you say, there's evidence that this would there was something brewing something simmering earlier in life. And so I think that's a real important part of the history because it does lend itself to this idea that this is a progressive disorder and we know that you know, not everything is an isn't a post, acutely post infectious. Some of these things sort of take a little bit of time to show itself at least clinically. We know that physiologically things are happening, but at least clinically, it's not apparent to patients or doctors even earlier on until you sort of take that history and collect the pieces of the puzzle. And so I completely agree with you, David, that I think it's an important part of the history taking that, you know, unfortunately, medicine has changed to such an extent where we don't we're not given a lot of time with patients, at least in the insurance model way. So a lot of doctors just don't have that luxury of being able to take this very long, extensive, comprehensive history, which is one of the reasons why David and I both went into private practice. I mean, separately, we didn't go into it to beginning but we both had those reasons for wanting to do this in a private practice environment, because we would be able to give the pupils at least a little bit more time to really ask those kinds of questions because it is very time consuming. So I agree that the history is a very critical component to understanding the patients in it. And the reason why it's important, in addition to all that we've already said is that I think the approach that which I know everyone likes to ask like what do I do for patients? What's my approach? It really, I mean, there's a lot of obviously general approaches and a lot of same things that I do for each patient, but a lot of it is tailored to the patient itself. And that's where the history plays such an important role and the symptoms that they've been struggling with and what has been importantly what symptoms have gotten worse, what symptoms are impacting the quality of their life. It really did does give us a flavor to that patient that can really tell her and helped me sort of tweak an approach differently for that patient versus the patient before them or the patient after them. So I always like to sort of start by saying that there really is no blueprint, there really is no template. Again, there's a lot of generalizations that can work and and and cannot work. But it really is very, it's very tailored, at least at this point in the game because we're still learning we're still I mean long COVID As David said, the silver lining is that we're learning a lot more about what what's happens to the body in these kinds of post infectious days and post exposure states I should say because it's not only infection, it's most commonly infection of course, but there are other exposures. So anyway, I think I'm rambling now.
Dr. David Kaufman 16:09
So let me let me before let me add a few specific thoughts on the history taking. And again, this is specially directed to clinicians that are that are listening. So we all know how to take a history we're all taught but one of the things that's become incredibly important and clear to me over these last 10 or 11 years is things that honestly before I wasn't necessarily as focused on so part of the history for me is where has the person lived throughout their life, where what countries what states what parts of the US because that alone begins to tell me something or at least suggest things that I need to look for. Did they live in an area with endemic tick borne infections and they live in an area where they might have had a Zika infection or whatever. So So that's number one. Number two, occupation alright. I have met so many patients where it turns out nobody asked the patient's occupation. And the patient is a veterinarian with amazing exposure risk for infections, or they're a field biologist, and that that changes that changes but it adds such a layer of important information. Another thing that I find useful is if a patient says you know, I was given antibiotics, I will often say, Well, when you took the antibiotic for your sore throat, did anything else get better and I can't tell you how often a patient will say Well, now you ask, everything got better. I completely felt better. All my symptoms disappeared during that short course of antibiotics. And again, that's a tip off, it's a it's a flag to tell me I better go down that road as well as all the other roads that are coming in. I mean, I could go on, there's lots of other examples, but I just want to emphasize again, the critical nature of that history taking. So for me after I've done this history, which has never really done that it's the first leap at it. I'll do an exam. Physical exam. For me the exam is not nearly as detailed I think is I leans exam I do sort of the usual stuff looking forward to orthostatic changes in blood pressure, signs of connective tissue disorder. Looking at the skin from walkers, that might be relevant to mast cell activation syndrome, and then the usual chest, heart, lungs, etc. listening for vascular abnormalities and what a cold brew is, and, you know, can I palpate things that I shouldn't be palpating stuff like that, and then come back and sit down and the next half hour or so is spent with pretty much me talking, trying to put in context what I think is going on, again, with the thinking that the MECFS is a label, it just means that checkboxes from the IOM criteria or consensus criteria have been checked. doesn't tell me anything. It tells me the person's fatigue a pm they have orthostatic excusable brain fog and they have aches and pains. But if I stop there, we both leave the room knowing nothing other than now we'll have a label, which most of the world doesn't recognize, anyhow. So to me, the goal is to dive under that label both for MECFS and long COVID, which to me are, are very similar, like overlapping and, and look for the key things that I think are drivers of the illness and usually, you know, I don't want to sound arrogant, but usually by that point, I have a pretty good idea of, of the various different pathologies that are occurring that has made make this person so ill, and we can go into that but I'll let you talk now.
Dr. Ilene Ruhoy 20:04
Well, I don't really have much to add to that part of I mean, I do the same, I guess I do do a more thorough exam, once a thorough is the wrong word, your exam is thorough enough. But I do do a neurological examination, which has a lot of pieces to it. So I do that full exam, because I want to be sure that I comprehensively examined them neurologically and make sure that I'm not missing anything. And they're, you know, I often will find some something on exam, something focal on exam. And I think that's always important piece of the puzzle. Although I don't always find something, sometimes it's a completely normal neurological examination. So it doesn't necessarily contribute. And but then I sit down and I, I talk more with him. And I've already know usually I've reviewed a lot of the records that they send with regards to previous labs and previous other workups and other testing that they've had. And I just put together a story about what I think is going on and what and what we could potentially do about it. But it usually requires sort of a next tier of diagnostic workup. So it depends sort of where the patient is in their journey. Oftentimes, I'm not seeing them until they've seen many different doctors already. So lots of work has been done. You know, sometimes I even asked why was this checked? What Why Why was this panel looked at like to see if they have any insight for me, because sometimes I don't know what that particular doctor was looking for. And, and so then I'll add my own diagnostic recommendations. And sometimes I can easily get it done. Sometimes I can't, because insurance can get in the way often. But I will recommend a set a second tier of diagnostic workup, and then have more discussion with them about what I'm looking for and why I'm looking for it. And then I you know, I and I also didn't you know, like to hold off on making any particular medication recommendations until I have my workup back, which is usually labs and some imaging. And some other panels that come in kits, I do a lot of genetics to sort of see what variants hold because I often wonder like, Well, why does one person get sick and the other person does, and yet they've had the same exposures. And that's, you know, something from my environmental toxicology training that we often think about the we did at the EPA. So I do that workup. And I and I often will say, No, I want I want to sort of understand more of your physiology before I make specific medication or treatment recommendations. But I also feel very strongly that they've been suffering from many, many years. So we'll recommend you know, sort of the low hanging fruit of things that we all regularly use because they regularly have benefit for patients. And I don't hold back on recommending things like mast cell stabilizers or anti histamines or some other you know, like low dose Naltrexone some things that can sort of take the edge off of the pain and the fatigue that many will will experience. And so I'll give those more generalized recommendations. And we'll get them started in the hopes that they can have some some clinical benefit while I'm doing my diagnostic workup. I will say many times the patients have already tried a lot of those low hanging fruit medications. And they'll tell me that they either didn't tolerate it or it didn't work, or they had an adverse effect. And so I note all that down so that I don't continuously recommended. What can happen if I don't remind myself that they did not tolerate a particular medication. But but so there's a lot of so that that whole first visit, there's a lot of sort of interaction that goes on with me and the patient to sort of decide how we're going to proceed and what we're going to do next and how we're going to do it.
Dr. Patrick Hwu 23:31
So, let me let me try to go to some details. Okay. During this conversation after the exam, and the history, I usually will try to break it down into what's some of you may have heard us now call a septet, which I've discovered is not actually the right word. I thought that meant seven but I'm totally wrong. I don't know what to do because we've used that term for years now. So the septet is referring to this kind of Eureka moment and recognition that many, most of the patients we see who come in with either an MECFS, long COVID, mast cell diagnosis, whatever they actually have in common five to seven different pathologies and it's it is it's astonishing how often that's correct. I mean, it's very rare for me not to find that to occur. So I'll walk through this with patients. So the first is autonomic nervous system dysfunction, which really is takes up two spaces in the septet in my mind and how which is POTS, which I use very loosely as a term. probably safer to call it orthostatic intolerance, which I think is an enormous driver of illness and in all of our patients, regardless of whether the patient says well I stand up and I don't get dizzy. That's not the only criteria so POTS. And then the other aspect for autonomic is gut motility disorder gi motility, which, inevitably, almost inevitably is associated with small intestine bacterial overgrowth, which is another completely treatable major driver of illness in our patients. So, so we're already talking about two big drivers which are diagnosable and treatable. If an exam or by history or both, it sounds like connective tissue disorder hypermobility, I'll discuss that. It is. It is truly amazing to me how often our patients have the connective tissue disorder. And I'll say, before I started doing this work, you know, the first 35 years of my career, I probably never thought about, I mean, it never occurred to me to look for EDS in a patient so it's there and then mast cell activation syndrome, which sometimes it's obvious patient says I can't eat. Like I have a very restricted diet because anything I eat makes me sick. It causes a rash. It makes my heart beat fast causes brain fog causes fatigue. But often it's much more subtle than that or it's suspicion based on history. The example the patients I said who had frequent infections and sinus stuff and exercise induced asthma, et cetera. And then, for me, a very big one is looking for infections. Does the patient have a risk for reactivation infection of vector borne illnesses are really have a Vizia Bartonella. We all have EBV is you know, we all get infected with EBV CMV HHV six, we all can have reactivation of those diseases. Many many MECFS patients have a history of mono could they be having ongoing reactivation especially with EBV so that becomes part of the discussion. And then as this discussion is laid out, it it becomes obvious to certain degree what the workup should be. So, you know, then we move on to testing related to these six or seven different pathologies that I'm describing, and the testing is arduous for the patient and can be expensive. I, I am I've learned that I'm relatively infamous and the LabCorp and quest draw stations because my patients have 35 to 40 tubes of blood based on the orders I write. I will readily admit I don't follow the teaching that physicians had which is you. You order a little bit and then based on that you order more. Basically my attitude is the patient's been sick for so long and not had a diagnosis. I'm not going to waste more time I order a lot of tests. Interestingly, all patients come in routinely saying, I've been to doctors and doctors and doctors and they say all my tests are normal. In fact, I always get abnormals back because I'm doing much more detailed testing. On immunology, immunocompetence infection, you know hormonal stuff and nutrients etc, etc. mess so of course, and then as Ilene said, I do these kids so I always look for small intestine bacterial overgrowth, positive and over 80% of patients, even if they don't complain about GI symptoms like bloating and gas. I almost always do saliva cortisol testing. Because most if not every patient has HPA Axis dysfunction. And I may do tick borne disease testing, although I usually wait until I see the other stuff unless the list the history is just glaring. think those are the basic tests right? I don't necessarily do imaging in the first visit. Although I may be suspicious of connective tissue disorder causing cranial cervical instability or similar type problems. And then as Ilene said, I will usually consider some initial medications but very limited so I often will if I'm, if I'm suspicious enough, excuse me. I will start histamine one receptor blockers, antihistamines, and histamine two receptor blocker which is formidable and or Pepcid. And I always discuss low dose Naltrexone It is a game changing remarkable drug which is just gonna be so effective. But I rarely will go beyond that even if I'm sure that pops. Because I want to get better testing first and I should have said, an another test I always do is the NASA lien tests, the 10 Minute leading test, which I find remarkably informative, and I use that all the time then to titrate and adjust medications. Your turn?
Dr. Ilene Ruhoy 29:39
Well, I agree with everything you said. Of course. And obviously, you know, at some point, I think the panel can interrupt us if there are questions that you know, that I think this was meant for us to help answer questions to those who have registered. So I don't want to take up all the time and us just sort of talking about what we do. But I do want to add that I do exactly the same and includes regards to the pots diagnosis. As you know, I feel like it's sort of the tip of the iceberg. There's a lot of dysautonomia, autonomic dysfunction that sort of underlies the POTS presentation. And I I do like the tilt table testing. I like the Vaseline. Obviously patients can do it at home and it's easy and it's free. The tilt table testing takes away the component of the skeletal skeletal muscle activation, so it's a little bit more reliable. And in fact, sometimes patients like let's barely meet the criteria on the gasoline test, but when you put them on a tilt table, they meet the criteria easily. So i i So but yes, it's very it's much easier for them to do the NASA lean test at home. And it's hard to find a tilt table as I've learned throughout the country, because I have patients, you know, through everywhere and it's hard for me to find where I can get them an autonomic. I actually prefer the entire autonomic testing as you know, but just just not the tilt table and there's also heart rate breathing is the Valsalva and QSART and so on but it's hard to find that so you know, we do the NASA lean test. But you're right i don't i unless the heart rate is like it's in front of me is sitting at 120. I will I will perhaps start a low dose beta blocker just because they're uncomfortable at that heart rate. They feel that they feel exercise intolerance, they feel short of breath, they feel like they're not getting enough blood supply to their brain. So I will try to lower the heart rate a little bit to sort of minimize those kinds of symptoms. But you're right i until I get more objective data with regards to their autonomic nervous system. I don't I don't go forward with any kind of real, more aggressive treatment plan than that.
Dr. Patrick Hwu 31:35
So I want to jump in and say something about the mescaline and the autonomic testing. This is this is a conversation Ilene and I have often okay I find the NASA lean just incredibly informative and revealing. And and so often I have patients come to me with their tilt table test and they were told it was completely normal. And then they do their NASA lean and and it is not normal. And and part of the issue is perhaps what we call normal and not normal. Okay. So there are very strict criteria for POTS. You know, it has to be greater than 30 beats and you can't drop your blood pressure and all that. And I think as often happens in medicine, we therefore miss a lot of diagnosis. It's like saying, there's a normal range from from 0 to 10 and lab tests. And if you're a number if you're one that's still normal, well, you know, one might not be normal. It may be abnormal, especially in the right setting and context. So, for me, I want to emphasize, at least in my opinion, when I have a patient to an NASA lean test, and they're lying down and their blood pressure is 120 over at the heart rate of 66 or 68. They stand up for 10 minutes, and their blood pressure. Let's say just doesn't change so I can get rid of that variable in this conversation doesn't change and their heart rate goes from that 68 up to 90 Or no, it goes to 60 it goes to 78 to 80 and stays there for 10 minutes. That's not normal in my mind. If any of the people listening who don't have an illness, stand up for 10 minutes. Your rate does not stay 20 beats above normal. That's not normal. Right? We have reflexes, thanks to a million years of evolution to deal with that. And then you revert back to your baseline give or take a few beats. But that patient would not qualify as POTS and they would be told their tilt table was normal. So I just think we need a little bit more liberal definition here.
Dr. Ilene Ruhoy 33:36
No, I agree. And I think the important point is about the symptoms, right? So if you are symptomatic from that sustained elevated heart rate that to me, that's that's a that's a deal breaker, right? That's an autonomic
Dr. Patrick Hwu 33:51
and symptomatic doesn't mean just dizziness. Or lightheaded. It means brain fog. It means fatigue. It means blue feet, you know, yellow hat, white hat, you know, purple colored hand, speckles, you know, it's, it's, it's it's very important to look at all the pieces together and and see what is normal versus not normal. If
Dr. Ilene Ruhoy 34:17
Do you want us to continue to talking about our approach? Yes,
Isabel Ramirez-Burnett 34:20
you can do that. We have questions whenever you're ready. Some people have asked if you would like to if you could share more detail about the most important tests that you do and what that list is.
Dr. Patrick Hwu 34:34
Sure. So so for me. I in terms of immunology, I'll do globulin, IgG subsets, not just a total. Most of the time patients come to me they may have had an IgG total without subsets. And very often the total is normal and there'll be subset deficiencies, which may be very relevant and Very important information. I look at the other immunoglobulins, you know, A and E and M. And I'll do lymphocyte subsets, which look at T cells and B cells. It is and continues to surprise me, excuse me how often a patient who has MECFS or long COVID, especially if it's a long history will have abnormally low B cells, B cells are the cells that make immunoglobulins or will have abnormal T cells, or will have very high IgG G subclass four, which may suggest chronic infection. So it's very useful information. I, I always do Serral antibody testing for the herpes family of viruses. Because, yes, we've all been exposed, but I want to see what the levels of those antibodies are. And that may be instructive. And I now routinely on the initial visit, initial labs will do EBV PCR testing because I've learned that just because the serology for EBV looks okay, I often am getting EBV positivity on the DNA PCR DNA test. So, to me, that's a crucial test. Now. I'll do the mast cell testing, which initially for me is a plasma histamine chromogranin a and prostaglandin D two, it was a very difficult test to get done properly. In fairness to the lab, it's they need to know and be able to immediately draw the blood immediately spin it immediately aliquot it immediately freeze it and make sure it's frozen until it gets to the lab. That's daunting and most of the time doesn't happen. So negative labs for Messel don't rule it out in my mind, I don't begin with the urine testing for mast cell because it's even more difficult for the patient. If the initial labs are negative, I might might then go to urine testing. If a patient has had endoscopy done in the past within, you know, recent enough that the samples are still in the pathology department, which is like five to seven years, I'll request some special staining called C D 117. To look for and get a quantitative count of mast cells per high power field which often gives you know, confirmatory histologic diagnosis for mast cell. I will do you know, some hormonal testing. As I mentioned, I do the four point saliva cortisol testing. I'll look at, you know, a vitamin panel of all the usual vitamins. What am I forgetting? I do an antibody panel auto antibody panel. Although I have to say that keeps changing. I can't decide what the best panel to do is. And sometimes I will order panels that are not available from LabCorp quest, particularly a lab in Germany called Celltrion, which has a panel now 16 I think it's 16 antibodies keeps growing with auto antibodies that have been associated or can be associated with orthostatic intolerance and pots. Now also with long COVID antibodies that we find in long COVID patients. I'm sure I'm missing some but that's the of the quick overview or lean stuff too.
Dr. Ilene Ruhoy 38:26
I do I do. Yes, I do. Some there are very few unfortunately there are very few biomarkers for Neuro inflammation but there are a couple like neuro filament light chain. I'll do the neuro filament light and then I'll also do the neuron specific interlace, which is a marker of inflammation, usually from hypoxia. And then I'll obviously do a lot of different auto antibodies with regard to certain immune mediated neurological diseases. Because it's a fatigue ability disease, and so I often will look for things like I like I'll do a myasthenia gravis panel just to make sure that there isn't a component of that. And sometimes I actually find it. I find, you know, I find one of the one of the acetylcholine receptor antibodies on the panel is something positive and I never really know what to make of it. I don't necessarily diagnose the myasthenia gravis, but I think that maybe this antibody is playing a role in at least their presentation of fatigue ability. I do do a lot of the immune studies that David had mentioned, I have found really, really use and doing the subclasses I mean, one three have been known to be associated with autoimmune diseases. So I find that to be supportive evidence and then two and four with infectious disease. So you know what, what we try to do is we try to find labs that help to support and end or explain the phenotype of the patient that the clinical presentation, and I do you know, I think a lot about the connective tissue as I'm sure everyone has done deliver, I feel like I ever talked about or at least I'm never asked to talk about but which is offered neurologists, right, because connective tissue is not our jam. But but I've really gotten into it because I over the years I have seen where connective tissue really plays a critical role in how our body responds to disease and exposure and, and how our body can heal and how our body can recover. And, you know, the mast cells, we always talk about the histamine, but it's got almost 1000 Different mediators, if not 1000 or more, but a lot of them I mean, most of them are inflammatory some of them are proteases. And they actually degrade collagen. But the chronic and systemic inflammation that happens results in a degradation of connective tissue really no matter what, and so, which is why oftentimes, you know, years into an illness, patients will will describe things like muscle pain and joint pain and just diffuse body pain. In fact, there's a lot of chronic pain syndromes in the fatigue elec world and in my long COVID patients and my MECFS patients. There's a lot of just sort of chronic pain, you know, the meninges our connective tissue and so a lot of my patients have, you know, changes of intracranial pressure which contribute to their symptoms. And the the vessels themselves are have a layer of connective tissue, so they're very compressible, and I always say with the slightest mechanical pressure, they can just press because the connective tissue is just, it's become a little bit friable and architecturally unsound, and that's just from the chronic inflammation. I think what happens in these diseases and again, a lot of what I say are just sort of my thoughts and theories. And my goal is to prove it one day, and I think a lot of the research that's coming out of the long COVID world is starting to sort of show what we see. And so this idea that you know, this chronic inflammation, you know, we all have endogenous stop gaps that we're born with, basically, that when there's an inflammatory response, and exposure, our body sort of, you know, fights that exposure and then sort of knows when to back off. I think with these chronic illnesses, especially when there's reactivation of these viruses that we're all exposed to. I think we lose that endogenous stopgap and so there's this perpetual inflammatory response. And so it just sort of chips away at the connective tissue, frankly, which holds our entire bodies together. I mean, our spine is just a series of joints, right. So I see a lot of spinal manifestations in patients that don't tell you have a history of hypermobility, but we know that hypermobility is a risk factor for a lot of these diseases. So there's just a lot of there's a lot of uncertainty, but yet a lot of certainty if that makes any sense, right? We don't have all the answers but we're seeing patterns. And I think these patterns are really important and we need to focus in on them. And that's obviously one of what David I always talk about with regards to our goal is for these patients to understand them more, and I'm real excited about all the research that's going on and you know, but you know, I always feel like my role isn't I'm a clinician, just like on the ground boots on the ground kind of thing where I'm just trying to help people. And while I'm involved in a lot of research projects, I really just sort of feel my primary role is just again trying to alleviate alleviate some of the suffering that's going on right now. So I don't know how I got off on that tension. But it was just talking about so yeah, so I do a lot of I do and then you know, there is like a you know, in the neurology world where like for neuropathy for this is an example like there's a neuropathy panel that we do that, you know, I will always do, which includes things like looking for blood, but dysplasia is like no multiple myeloma in our amyloid because that those two by the way, those diseases can have autonomic dysfunction as well and we obviously check the thyroid we look for via certain vitamin deficiency and we look at glucose metabolism, which we also know plays a role. I very commonly see hypoglycemia and these patients, I very commonly see cytopenias they have low white blood cell counts. And so we I do that. So I do a very, like classic neuropathy panel, which what while they are most of them have neuropathy, it's really because of the overall disease and I'm trying to find answers for so i Yes, yes, I do add a lot of neurological specific lab tests, but I do do imaging. I mean, I'm 90% of the time I'm ordering imaging and at the first visit if they haven't already hadn't had recent imaging of their brain and cervical spine. I'm usually ordering it just as I do think about obviously the brain. And I also want to look at the cranial cervical and then I'll follow up with even Vessel Imaging frankly because I'm always worried about compression because we know a lot more about compression syndromes and the diseases of which they're associated with specifically the symptoms that they're associated with. And most of the patients have these symptoms. So I just like to rule out at front because I always say that if there's an anatomical problem, like all of my medications aren't going to help they're not gonna fix it. They might in some ways tallied the symptoms a little bit, but they're not going to fix the problem. And so if there's an anatomical component, I'd like to know it for the patients sooner rather than later. And so I'll just do the imaging, usually at the first visit, if not the second
Dr. Patrick Hwu 44:59
so I just want to add something and emphasize something that Ilene said which I think is crucial. So in terms of emphasis. In terms of connective tissue, it is not only about hypermobility EDS, I cant say this stongly enough it is chronic inflammation, excuse me, which is injuring connective tissue, and the difference between an EDS patient and a non EDS patient, both of whom have MECFS, long COVID etc. Is that that class just overflows sooner for the EDS patient meaning that they start out half full and then well, maybe I should say half empty, and then they have chronic inflammation which just chews away just Nicks away death by 1000 cuts of that connective tissue, but they're already damaged their tissue and therefore they have a problem sooner. But you don't need EDS to ended up with the same connective tissue disorders that that we are seeing, such as CCI, cranial cervical instability, and it's all about inflammation. That's the name of the game. It's chronic inflammation and one of the areas are things I've been thinking about and talking about waking up at night thinking about it. In fact, what I think is the similarity between the diseases of aging and MECFS long COVID patients. So in the diseases of aging, it's got this fancy new name called inflammation, which is a fancy way of saying chronic inflammation. That's what our patients have. And if you start looking at it through that perspective, we'll put it in that context. How our patients have a kind of premature aging, secondary to chronic inflammation, which means that we need to go after every possible source of inflammation in order to reverse that tide and make them get better. I want to add something on testing, as I'm sure Eileen will agree. I have you know an order set like physicians with EMRs we have order set, you press a button and there's my 40 tests or 50 tests. But that is constantly a work in progress. I can't tell you how often that has changed over the years. As I learn more. I go to a meeting I get on to why my online 500 Plus Doctor group and we discuss something I say oh my god, I should be ordering that test. So as an example, a recent addition is this long test that I just name in my EMR is the clock test. Okay? Do what these are tests to look at the patient's propensity or vulnerability or risk for clotting and the reason I'm looking at all this data that many of you know that with the whole, quote, micro clot issue in long COVID And MECFS. It's very real. And the more I look, the more I find that patients have, you know, an undiagnosed factor five Leiden wishes a risk. Factor or a PA one genotype that puts them at risk, or a constantly positive d dimer showing they have small clots, and it now opens up another road that we can go down and manage and treat. So I just want to emphasize, it's always changing.
Dr. David Kaufman 48:13
And I
Dr. Ilene Ruhoy 48:14
I really that's an important point, actually. And I always say the long COVID research is telling us so much more about exactly if and I definitely adopt what we're learning about long COVID And what I even learned in in my long COVID patients and I apply it to the MECFS patients that that have been suffering for years and the endothelial dysfunction and the hypercoagulable states are really seem to be a real key player. And it's just because of the means of which of how they just damage the vessels, obviously, which is where it starts but then it's sort of it's stagnates blood flow. It's it you easily develop clots of differing sizes. In fact, as we know, and during the pandemic, we saw an increase in strokes. And heart attacks. So it's not just necessarily micro clots, so that seems to be behind the the long COVID The chronic fatigue, the chronic organ dysfunction, these endothelial dysfunction with with with the small clots that clog up those small vessels and we just did a podcast about that taping because it really does seem to be holding concern for a lot of the long COVID clinicians out there about what role this is playing in organ dysfunction and when I think about the brain and how it's fed, you know, with regards to large vessels, medium vessel small vessels in those tiny vessels and I think about how those small vessels feed all those crevices, and I realized and you know, we've long known that there's small vessel disease in the brain, and it's what we refer to when we see those hyperintensities and those flare signals on a brain MRI. And so, you know, when I did imaging on my MECFS and long COVID patients I see diffuse white matter disease, as it's called related to small vessel disease. And so then I start thinking about, well, how are we going to fix this? How are we going to reduce the risk of clot formation to reduce to repair the lining of the vessels so that there isn't as much platelet activation and platelet aggregation and platelet stickiness. And so there's, there's some ways that we do it. And you know, that's part of the treatment, let's talk of this, but it really is seems to be a very important component. And when there's constant reactivation of these viruses, hence constant chronic, chronic inflammation, this all of that gets worse, right? So we have to get ahead of the game. We have to rein it in and then get in front of it is how I see it. And that's that's what I started to try to do. And you know, I worry as you know, David because I'm always telling you my worries and fears, but I worry about you know, this epidemic of big cognitive impairment that's headed our way if it's not already here, because I noticed a lot of brain fog. When I do cognitive testing, thus far knock on wood, it's it seems fairly stable and normal, but I hear what patients are saying they are experiencing, I think something that we don't label yet in neurology, because the standard cognitive testing always appears okay, but they are experiencing a slowing of their ability to process information to do to react to recall words to remember what they were doing in the midst of a task to keep up with conversations. And so that's very scary to them and I get that frankly, I you know, but and so I worry about you know, now we have small vessel disease and chronic neuroinflammation and microglial activation and astrocytic dysregulation, and I really do worry about the brains of all these people.
Isabel Ramirez-Burnett 51:39
Yeah, we have a lot of questions. This has been absolutely amazing. So if you guys, are you guys ready to get started with some questions? Yeah,
Dr. Patrick Hwu 51:51
I actually would like to say one last thing first. was last word. I want it.
52:01
We had so much to say.
Dr. Patrick Hwu 52:02
I think one of the really important takeaways for the clinicians listening is that we were taught, again, I keep going back to how we were taught generally to think in single organ systems, in fact that most medical school curriculums least when I was there, you know, you have neurology and you have urology, and you have GI and you just go organ system by organ system. And the issue here is that these patients have multi system, multi organ chronic inflammatory disease everywhere. And we it almost requires a change in the brain. I think the reason it's interesting to me that the reason that the most heart, groups of doctors who are seeing these patients tend to be internal medicine, family medicine, amazingly, er medicine, because those groups tend to have been trained or think in terms of total body illness, not just one organ at a time. And and the second piece in particularly with this concept of the septet is that each of these pathologies interacts with the other so you have a mast cell degranulation moment that's going to knock normally, you're going to have trouble with your pots, you have a leaky gut from small intestine bacterial overgrowth, that's gonna cause a leaky blood brain barrier, and you're gonna have brain fog. It's all together, you know, interacting. And, and again, we're sort of most physicians are not trained to think that way, let alone of course, don't have the time to dive into it. So it's, it's the reason we spend so much time on the history, the explanation, and these huge, crazy workups which, you know, we could be criticized for, but it's, and we, yes, we are. But it's the nature of this illness. I just wanted to close out this little part with that.
Isabel Ramirez-Burnett 53:50
Absolutely. Thank you, Patrick.
Dr. Patrick Hwu 53:52
so much, you guys for putting this on. I'm a tumor immunologist. A medical oncologist. I have a daughter 23 years old with long COVID POTS very debilitated from this, but a lot of persons are from... So I study the immune system and I know there's some agents I totally agree with you about chronic inflammation because what to do with it. There's some really great papers but Akiko saqi and others looking at the immune response, really, we know a lot but the question is what to do about it? There's studies of F Kartika Mont Blanc, the antibodies which is really a great setting blank, we're getting some cutting edge agents. There's many other cutting edge agents that are available in the room and Elijah community. I don't see them being used for POTS or for long COVID that I think could be effective anti inflammatory signals, T cell subsets, soluble CTLA four there's even an Investigational Agent of a PD one agonist. I I learned of theirs type one interferon receptor blockers by AstraZeneca we get these really exciting agents into long COVID pots. I think they may be effective. Patients with wild COVID look like patients I gave interferon to the doctor, you know, and so I think if you block interference really could be helpful. How do we get these agents to patients? Well,
Dr. Ilene Ruhoy 55:19
I mean, I so I am I have been prescribing immunotherapies now for the past I would say four to six months. I really dived into that. I agree with everything that you just said. And I think a lot of the newer immunotherapies specifically the ones that are more targeted as some of them that you had mentioned haven't had been showing great promise and I've been used in fact like things like --- and things like Kinneret Copaxone even I've used in patients I've used there's various kinds that I well I even went to the old guard sometimes like the cyclosporine. Like I've used. I've used lots of immunotherapies. And, you know, to be honest with great response to a lot of them and not to all of them and not with every patient of course, and I'm trying to find that one that seems to be the answer and I haven't I haven't arrived at one yet but I agree with you right now there's a rapamycin trial going on to sort of look at rapamycin and its role and both David and I use rapamycin regularly and we we see patients respond to it. There's a particular immunotherapy called iboot Alas, that is not available in this country. But a couple of my patients were able to access it from other countries and are really doing well on it. And I don't know why it's a phosphodiesterase inhibitor and I don't know why it's not available in this country. To be honest, I'm sure there's a reason but it's not. But it seems to also show great efficacy for a lot of these patients and their symptoms. Specifically, by the way, their autonomic symptoms. I agree with everything you said. And I think we need more trials to really decide what it is we want to target in those immune pathways and we need an immunologist on board and we need a rheumatologist on board. So yeah, I completely agree with you and I'm finding great success with an immune therapy. approach. And I've done a lot of IVIG and rituximab, and now even plasmapheresis over the years and there's that's what led me to immuneotherapies right because they were effective, but they're expensive usually. But I'm not going to pursue this on this program. You want to hear me swear you can see that's on on Patreon. But, you know, so that's why I started to use some of the more oral immunotherapies that are so hard to get approved Sometimes though, the old guards are easy to get approved. So yes, I agree with that and I yeah, I'm excited about that area. I really am excited about that treatment plan.
Dr. David Kaufman 57:40
So I of course completely agree with you as well doc. What I would say is it's impossible nearly impossible to get those biologics those agents approved for our patients. So it's bad enough how much money our patients spend to see us and on the testing, but I can't get approval for $100,000 a year drug and, and honestly I don't want to get into politics too much here or at all but I can't help it, you know, a problem to me that the the NIH and sort of at the federal level, there's studies out there looking at studies for these biologics, you know, the PD one inhibitors and all these other agents which are really exciting, but virtually unattainable. For our patients, unless the FDA overnight makes any indication that you can give these drugs for long COVID And I guarantee that's not going to happen for years. So what do we do for our patients? So I think you're right, those drugs are great and you can do them that'd be wonderful, but and they do carry more risk. But realistically, I have patients that I'm going to see on Monday who need treatment right away. So I look at immune modulation with more easily available things. So Naltrexone is modulates that immune system. Talk about a cheap drug with virtually no side effects. That's there. It's just sitting there. I started using it back in HIV disease in the 80s. It's an amazing drug. rapamycin, I am like one of the recent obsessions. It can reduce inflammation, it can alter the whole immune system restore homeostasis, increase autophagy and take care of potentially a lot of the underlying pathology system would as Ilene mentioned, IVIG immune modulator we Ilene and I had become very interested in plasmapheresis as another way unfortunately very expensive but not nearly as expensive as the biologics. Another one, what to call it? I can't call it a drug. Another thing is exosomes. Unfortunately, not FDA approved. So we're extraordinarily limited in its use, but it is a remarkably effective molecule or not molecule, what do I call it? It's not a drug, right? And then what's the cause? So there's there's other stuff out there even some of the NSAIDs I find Celebrex reduces inflammation, more than say ibuprofen works in some different ways. You mentioned rapamycin keto, as you mentioned, there's a lot of stuff out there already on the shelf. Not necessarily so expensive. So, so yes, those biologics and those agents look great, and we should learn about them. But I'd rather see the research dollars directed at more readily available stuff that doesn't cost so much money and who has less side effects.
Dr. Patrick Hwu 1:00:32
And we could also get the biotech companies you realize it's such a great big market. research in this area, I don't think they realize that it's paid
Dr. David Kaufman 1:00:41
yeah, exactly
Dr. Ilene Ruhoy 1:00:44
fortune, if they let us study their drug in this patient population. I'll give
Dr. David Kaufman 1:00:50
I'm sorry to interrupt and I'm going to give you a perfect example of that. peptides. Okay, so something I lean in I love I've learned so much from Dr. Ruhoy. About peptides, and then the FDA in its infinite wisdom, banned peptides. They said no peptides. I mean, we felt like suddenly Trump just and it's been really, right there's a peptide called Phyliss. In alpha one, which has profound immunologic benefit increases NK cell function natural killer cell function is antiviral and is approved as a drug by the FDA in this country, but it's not available. And I've met with the company that makes it and say, look, we got to you got a drug that's approved, bring it back, let us test it in our MECFS patients before it was banned. I had great results, but it doesn't happen. It's it's it's a kind of bizarre. It's
Dr. Ilene Ruhoy 1:01:43
It's very bizarre. I mean, G Ray was another peptide that actually promotes the formation of collagen. And so for all of my connective tissue patients had such great response. I mean, I would say 80% of them reported improvement in their in decreased pain in their, their mobility, they were able to do more with a lot less pain and discomfort, and with a lot less fatigue. And it was banned. So I stopped, I couldn't get it for them any longer. So and
Dr. Patrick Hwu 1:02:10
these things were banned, not because something has to be clear. It's not like somebody had a dreadful infection B from a peptide, given sub q injection. So no, not
Dr. Ilene Ruhoy 1:02:18
at all, in fact, that it's actually still being used in burn centers, because it is so so great at promotion of healing. So it's still available, but only under very specific indications and in specific context. So yeah, so I we can go on about this topic.
Isabel Ramirez-Burnett 1:02:35
Yeah, a quick reminder, if you're a clinician, you can raise your hand and come on camera to ask you a question. And next, so
Dr. Maria Afzal 1:02:48
hello, hello, everyone. Can you hear me? Yes. I'm Dr. Mario Axel from Pakistan. And I'm really glad to have found you people, the panel and I was actually waiting for this kind of discussion. Because I'm interested in autonomic disorders. I aspired to be a neuro physician and I also happen to be a dysautonomia patient. So I have a lot of questions in my own experience to hear if you will. So basically, I have dysautonomia for the past nine years. And I also have stringer Mariette C six, seven level. So there has been a lot of controversy about it. Half of the new physicians and surgeons that I've seen believe that Trincomalee it has nothing to do with autonomic dysfunction if it is in this cervical spine, but half of them believe can actually cause and theoretically when we look at the cross section, it should be able to cause second, I do have symptoms that make me believe that I can also be having mast cell activation syndrome. So when we look at massive activation syndrome, single market doesn't fit in the picture. And when we look at single Maivia I feel that match activation doesn't fit into the picture. So firstly, I had to ask about it. Is there any connection between via Express, especially in the cervical spine, and mass admissions? Secondly, I had a question about the NASA Dean test. I wanted to use it for research purposes. But the literature that I saw it was hardly used anywhere, although I know that clinicians use it regularly even here in Pakistan. I have seen clinicians do that. And once during my house job that's like the foundation here. I have myself diagnosed one patient was being treated for dissociation in psychiatry, but I had this observation that turf symptoms used to get relieved when she lied down and they were always in the upright position. So what I did was that I performed that test over and And it turned out that her heart rate used to spike up to 150s without any decrease in blood pressure upon standing. And she was started on beta blockers still table this was advised but she unfortunately logged on. So these were the few things that I wanted to ask. And in addition to that, I wanted to ask the cutoff for the ganglionic acetylcholine receptor auto antibodies for autoimmune autonomic ganglia.
Dr. Ilene Ruhoy 1:05:26
Yeah, and I so I regularly test for those antibodies. And there's it's on a cell trend panel that Dr can refer to. But you could just get that one be alpha three, one alone on like LabCorp or quest they do have that option, but the soul panel of the different weather studies that are associated with dysautonomia goes on the cellphone panel, which right now is the only option to test for those antibodies, as far as I know, I don't think mail yet offers them. But and then with regards to so you're seeing on my Alia. So do you have a Chiari as well?
Dr. Maria Afzal 1:05:58
No, I don't have Carrie. And I don't have EDS, either. And I've got all the vascular imaging of the head and neck turn and there's no abnormality there.
Dr. Ilene Ruhoy 1:06:06
And do you have any evidence of intracranial pressure abnormalities? Oh,
Dr. Maria Afzal 1:06:14
no evidence of that. But a few times, I felt that I'm having throbbing headaches along with bradycardia and vomiting, a few episodes isolated?
Dr. Ilene Ruhoy 1:06:26
So I mean, it's hard to answer like, I'm trying, obviously not to give medical advice. And we should have sort of made that point earlier on in this. But just to answer your questions in a in a generalized format. So it's thought that sphingomyelin is sort of due to elevated intracranial sensing, sort of this pressure transduction, that sort of the fluid extrapolates in within to the court and creates this, this cystic space, basically. And then, but it's often associated, and I'm sure that you know, with the Chiari and that's thought to sort of what is impacting the the lack of appropriate CSF flow and changes of pressure and volume and which contributes to the syrinx. And then if you correct the PRA, we actually see the settings reabsorb and sort of resolve on its own, it says, question, and so if there isn't, sorry. I'm sorry. It hurts. Okay, so the question is, is it? Can it be related to autonomic disorders and or mast cell activation? Yes, I mean, I think, again, there's a lot of uncertainty and what I say are just sort of my thoughts and opinions. And I, you know, I can argue and disagree with me, but fine, many do. But, you know, I think that there's a loss of a component to this, because I think the mass while if you don't have evidence, although you did say you had some symptoms that could be related to intracranial pressures, specifically, high pressure. And so Miss vision, if it's chronic, it absolutely can increase the volume of fluid within the CSF spaces, it can also increase blood flow as well as does autonomic disorders, right, it changes blood flow. So what happens in the brain of is that there's there's there in amongst the fluid compartments, so the arterial and the venous system along with the CSF compartments, and that's actually how the glymphatic system works. In a very simplistic level, there's a lot more complexity to the glymphatic system that it relied upon the exchange that goes on between these these fluid spaces of the brain. And so anything that will increase volume can potentially increase intracranial pressure, and then, again, can potentially cause a Swingle myopia, but that's a Swingle myopia. But that has not been shown. And there's really two it's sort of support those connections. But, you know, those of us in the mast cell world and those of us in this in this septet world are always trying to sort of make the connection as to how one diagnosis can cause another diagnosis. And there's a lot of really strong and sound theories, frankly, and a lot of the research is that's that's being published is actually sort of proving some of these connections that we make. And that's just one of the connections that we've discussed. And so obviously, I can't say for sure, but And yes, it can contribute, like symptoms, just but by its basis of its its connection with the court, I mean, so the court has autonomic fibers, and so it can definitely have a connection with the autonomic nervous system just on that pure anatomical basis. So I think it is related to say more specifics of certainty, it would be hard to do at this time, but again, something that I'm so interested in, which is why I do the work that I do.
Dr. Patrick Hwu 1:09:39
So I would just add one, something in the mast cell here. Mast cells are right there most dense in our environmental interfaces like our skin and our gastrointestinal tract mucus. Everywhere there are wrapped around blood vessels and nerves. There's relatively recent research data from the neurosurgery people that are tethered cord the phylum is packed with mast cells. And I can tell you clinically when I have a patient who's had surgery on their neck and then they do great and all of a sudden they crash and their MKS goes out of control. They turned out to have their tethered cord, or occult. So it wouldn't surprise me at all that your spinal cord issue is causing mast cell activation, that mast cell activation degranulation could be causing your dysautonomia in parts and vice versa. So it's, it's an example of the multi connections that we talked about. And you know, I would, again, we can't make some medical suggestions but you might consider just some trials a mess. So medication just to see how you respond this really have side effects is
1:10:48
this seem to be helping? Good.
Isabel Ramirez-Burnett 1:10:52
We have Jennifer next.
Jennifer Bell 1:11:01
Hello, I'm Jennifer Bell. I'm a family nurse practitioner with the Bateman Horne Center. Dr. Kaufman, I was interested in hearing your experience about Rapamycin. We're on putting some patients on that and I'd like to get a better understanding of what you've seen what kind of side effects and whatever else you want to share.
Dr. Patrick Hwu 1:11:24
Thank you. Sure. Sure. So so for those of you who might not know rapamycin is a 50 year old drug, I think it just had literally its 50th anniversary. It transformed transplant medicine, it allowed people to get donated organs without rejecting them. So it's profoundly or family immune suppressive. However, like naltrexone in very, very low doses. It it works at the level of what's called mTOR it inhibits mTOR. And that promotes when mTOR is inhibited and promotes autophagy which is a evolved biologic housecleaning mechanism to get rid of zombie cells cells that should have died through apoptosis, both attended and they remain alive and they they are reducing inflammatory molecules. And again, this is all related to the work in the aging longevity world. So we started using it based on some of that rationale and the whole autophagy concept. And you know, what I've seen in low doses, roughly six milligrams a week, which is based on the clinical trials from done by Joe manic in people over 65. This is said no known side effects. The most common side effects in occur that can occur is mouth sores, canker assets, ulcers or canker sores. I've literally only seen it in two patients or three patients. It's, you know, it's you stopped the drug, it goes away, and you can restart, it doesn't necessarily come back. In terms of risk. I have not seen any of the issues related to blood counts dropping or increased infections. So I monitor that we do safety labs, but I haven't seen anything yet, anyhow. And I believe, probably close to two years. And then in terms of outcomes, I'm gonna just give you subjective reports, the patient's many, many patients, probably on the order of half to a little more, will say decreased fatigue, decreased pain, decreased brain fog. And they, that gets confirmed because you take a part of the protocols to take a treatment break after several months, and they will talk about how some symptoms may come back. Or they will forget to take their drug for a week, and then their symptoms come back. So you know, it clearly has efficacy, I had not seen any significant side effects. And I've certainly had patients who don't report benefit. But honestly, that doesn't mean there's no benefit. Sometimes you don't know you can't. There's no symptom of autophagy. So it may be doing something good. And it's just too soon to tell. The beauty of the study you're talking about that I'm seeing as well is that we're looking at a biomarker that we hope will predict or or relate to autophagy being up or down and how and how rapamycin impacts on that. And my hope is it will also help guide us to the right dose because I'm using the six milligram dose but we don't really know the right dose. And drug levels, I don't think give us enough information. So yeah, that's helpful
Dr. Ilene Ruhoy 1:14:41
is characterized as an effort. And it's a really effective drug and it's been used in certain growth diseases, you know, for decades. I mean, we used to use it in for tuberous sclerosis, for example. And I mean, we still do, but I use these all the time. So, I've had I have a very high count foot level with this particular drug. And I agree with what David said with regards to patients are seemingly receiving benefit without concerning side effects. And, you know, so I think it holds great promise. I really do. I think it holds great promise.
Isabel Ramirez-Burnett 1:15:13
Wonderful. Well enough tests come on and as some of the questions from the q&a.
Tess Falor 1:15:18
Yeah, we got a few in the q&a from clinicians. I'll start with Alba's LDLs question because you're headed to clinic. What is your experience with sex hormone testing and replacement, specifically females with low testosterone? David?
Dr. David Kaufman 1:15:38
Could you repeat it? I couldn't hear you.
Tess Falor 1:15:41
Yeah, what's your experience of hormone testing and replacement, specifically female.
Dr. Patrick Hwu 1:15:48
Yeah, I do routinely test male and female patients for testosterone levels. And very frequently find that their total or more important importantly, their free testosterone is either at the very low end of normal, inappropriately low but still, quote normal or below normal. And I will routinely give testosterone replacement as a usually as a Christian that a shoulder or the abdomen. In in men, I will sometimes use Clomid instead of the cream for reasons related to fertility and not wanting to suppress spermatogenesis. And, you know, for, for a subset of patients, just replacing their testosterone to a more appropriate level can significantly increase their energy, decrease their fatigue, and very importantly, but over the long term, if they're able to do some exercise, it helps with muscle mass muscle protein building, which is, you know, a critical problem in our patients that is very hard to address. So I always look for testosterone,
Dr. Ilene Ruhoy 1:16:56
I think it's important to have a comprehensive hormonal evaluation just to have to really be able to sort of somewhat guesstimate the right appropriate dosage of testosterone and too much testosterone will be converted to estrogen, sort of do want to be careful if you're just trying to replace good hormonal evaluation of what I fully admit, I'm not the expert at that. But I do think that it's important for appropriate dosing, because I have seen where it was inappropriately dosed, and there were some side effects that were not helpful to the patient. So yeah,
Dr. Patrick Hwu 1:17:28
I mean, let me emphasize the dosing is to get to a physiologic level. Right, right. I mean, I have patients who were on testosterone, their, their their levels are in the 1000s. It's like, it's crazy. Can't tell anything saying that
Dr. Ilene Ruhoy 1:17:38
you did the appropriate No, no,
Dr. Patrick Hwu 1:17:39
I know, I know. But I want to emphasize that, you know, intervention is okay, your your levels are low, take testosterone, come back and go to the lab in a month to get new levels. Right. This is one of those drugs where you don't just prescribe it and disappear. I never give more than one month, so that I make sure I get to levels.
Isabel Ramirez-Burnett 1:17:58
Thank you. Well, unfortunately, we are out of time, Dr. Ruhoy and Kaufman have other commitments that they need to get to. And we know that there are a lot of unanswered questions, you are going to get a recording of this presentation. And we're also going to send you a link to join us on slack for clinician so we can continue the conversation. And we have more roundtables planned for the future, as well. So please join us on the website, enter your email, so you can keep abreast of what we have going on.
Dr. Patrick Hwu 1:18:33
got so many great questions here.
Isabel Ramirez-Burnett 1:18:36
To answer back, yes, we can definitely have you back. Normally, we can answer another questions. It's totally up to you.
Dr. Ilene Ruhoy 1:18:47
Blimey, I'm sure you have other clinicians you wanted to invite like, not just so you want to take the place of other really fabulous clinicians that are doing the good work for these patients. But we would be happy to come back. And
Isabel Ramirez-Burnett 1:19:00
Yes, we'll have we'll have you back for sure. All right. Thank you, everybody. And we will continue the conversation. on Slack, we'll send you an email with the recording. Thank you so much. Thank you for your great questions. And thank you so much for being interested. And being part of the solutions and being part of the provider network that takes care of MECFS, low COVID and infection associated chronic illnesses. We need you so much. And we're thankful to have you today.
Dr. Ilene Ruhoy 1:19:30
And thank you as class and the rest of the panel for doing that for doing this. I think there's a remarkable project that you've been put on. So
Dr. Patrick Hwu 1:19:37
thank you very much. I can't emphasize how important this is.
Tess Falor 1:19:42
You want to add some weight before you
Shelley Hayden 1:19:45
really quick. We are doing this for you and we want to keep improving what we're doing with these roundtables. We've posted a link for you to give us a little feedback and a very short survey that is anonymous. If you Want because we want the real truth. We're on a mission. Thank you so much for being here.
Isabel Ramirez-Burnett 1:20:04
Thank you everybody. Bye