Podcasts about ivig

In his weekly clinical update, Dr. Griffin with Vincent Racaniello bewail the attack on science within the US and withdrawal from the global health communities, association between the shingles vaccine and reduced dementia occurrence, ending of Uganda's ebola outbreak, undermining effective responses to human bird flu infections, growing measles outbreak in the US and dire predictions of the return of vaccine preventable diseases including polio if vaccination rates continue to decline, before Dr. Griffin reviews recent statistics on RSV, influenza and SARS-CoV-2 infections the WasterwaterScan dashboard, how HHS is undermining the Novavax COVID-19 vaccine, if Paxlovid reduces stroke, where to find PEMGARDA, provides information for Columbia University Irving Medical Center's long COVID treatment center, where to go for answers to your long COVID questions and contacting your federal government representative to stop the assault on science and biomedical research. Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Lab animal RIFFing (NY Times) Herpes zoster vaccination and dementia occurrence(JAMA) The recombinant shingles vaccine is associated with lower risk of dementia (Nature Medicine) Uganda declares end to latest ebola outbreak (Reuters) Enhancing the response to avian influenza in the US and globally (LANCET: Regional Health-Americas) H5 Bird Flu: Current Situation (CDC: Avian Influenza Bird flu) Measles Update — United States, January 1–April 17, 2025 (CDC: MMWR) Measles in Europe……..but greater in the US (CIDRAP) Measles – Annual Epidemiological Report for 2024 (ECDC: European Center for Disease Prevention and Control) Measles (ECDC: European Center for Disease Prevention and Control) Measles cases and outbreaks (CDC Rubeola) Measles 800 in Texas…. (Texas Health and Human Services) 2025 Measles outbreak guidance (New Mexico Health) On the precipice of disaster': Measles may be endemic in 25 years if vaccine uptake stays low, model predicts (CIDRAP) Modeling Reemergence of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination in the US (JAMA) Measles vaccine recommendations from NYP (jpg)  Get the FACTS about measles (NY State Department of Health) Measles (CDC Measles (Rubeola)) Measles vaccine (CDC Measles (Rubeola)) Presumptive evidence of measles immunity (CDC) Contraindications and precautions to measles vaccination (CDC) Measles (CDC Measles (Rubeola)) Measles (CDC: Measles Rubeola) Adverse events associated with childhood vaccines: evidence bearing on causality (NLM) Measles Vaccination: Know the Facts(ISDA: Infectious Diseases Society of America) Deaths following vaccination: what does the evidence show (Vaccine) Influenza: Waste water scan for 11 pathogens (WastewaterSCan) US respiratory virus activity (CDC Respiratory Illnesses) Weekly surveillance report: clift notes (CDC FluView) Respiratory virus activity levels (CDC Respiratory Illnesses) 200 children die from flu (CIDRAP) Weekly surveillance report: clift notes (CDC FluView) FDA-CDC-DOD: 2025-2046 influenza vaccine composition (FDA) RSV: Waste water scan for 11 pathogens (WastewaterSCan) US respiratory virus activity (CDC Respiratory Illnesses) RSV-Network (CDC Respiratory Syncytial virus Infection) Waste water scan for 11 pathogens (WastewaterSCan) COVID-19 deaths (CDC) COVID-19 national and regional trends (CDC) COVID-19 variant tracker (CDC) SARS-CoV-2 genomes galore (Nextstrain) Health secretary RFK Jr. declares certain vaccines have ‘never worked,' flummoxing scientists…..what certain vaccines?(STAT News) More FDA uncertainty roils full approval for Novavax COVID vaccine (CIDRAP) FDA Punts on Major Covid-19 Vaccine Decision After Ouster of Top Official (WSJ) U.S. health officials inject new uncertainty into approval process for Covid boosters (STAT News) Interim Clinical Considerations for Use of COVID-19 Vaccines in the United States (CDC: COVID-19) Where to get pemgarda (Pemgarda) EUA for the pre-exposure prophylaxis of COVID-19 (INVIYD) Infusion center (Prime Fusions) CDC Quarantine guidelines (CDC) NIH COVID-19 treatment guidelines (NIH) Drug interaction checker (University of Liverpool) Infectious Disease Society guidelines for treatment and management (ID Society) Molnupiravir safety and efficacy (JMV) Convalescent plasma recommendation for immunocompromised (ID Society What to do when sick with a respiratory virus (CDC) When your healthcare provider is infected/exposed with SARS-CoV-2 (CDC) Managing healthcare staffing shortages (CDC) Steroids, dexamethasone at the right time (OFID) Anticoagulation guidelines (hematology.org) Into the Unknown: Practical Remdesivir Restriction in the Era of Widespread SARS-CoV-2 Seropositivity (CID) Tocilizumab and IVIG experience during the service follow-up in patients with severe COVID-19 pneumonia(Rev Insti MedTrop Sao Paulo) Daniel Griffin's evidence based medical practices for long COVID (OFID) Long COVID hotline (Columbia : Columbia University Irving Medical Center) The answers: Long COVID Risk of New-Onset Type 2 Diabetes Among Vaccinated Adults After Omicron or Delta Variant SARS-CoV-2 Infection(JAMA) Reaching out to US house representative Letters read on TWiV 1214 Dr. Griffin's COVID treatment summary (pdf) Timestamps by Jolene Ramsey. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv Content in this podcast should not be construed as medical advice.

This AANEM podcast features Dr. Joome Suh, a neurologist and neuromuscular specialist at Brigham and Women's Hospital, interviewed by neuromuscular fellow Dr. Nadia Khalil. They discuss HMG-CoA reductase immune-mediated necrotizing myopathy (HMGCR IMNM), a rare autoimmune muscle disease often associated with statin use. The discussion covers clinical presentation, epidemiologic considerations, histopathologic findings, and treatment approaches, with special focus on Dr. Suh's recent research published in Muscle and Nerve with co-author Dr. Anthony Amato. Their study found that patients receiving maintenance IVIG as part of their regimen were more likely to have a normal CK at 6 months and the daily prednisone-equivalent was lower. A sub-group analysis suggested IVIG as monotherapy is effective.

The inflammatory and infectious optic neuropathies are a broad, heterogeneous, and common group of diseases producing visual loss. Although many now-distinct syndromes have been previously combined as “typical or atypical optic neuritis,” recent developments highlight the importance of precision terminology as well as an individualized evaluation and treatment approach. In this episode, Gordon Smith, MD, FAAN speaks with Eric Eggenberger, DO, MS, FAAN, author of the article “Optic Neuritis” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Eggenberger is a professor of ophthalmology, neurology, and neurosurgery at the Mayo Clinic in Jacksonville, Florida. Additional Resources Read the article: Optic Neuritis Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing someone who really needs no introduction, Dr Eric Eggenberger, about his article on optic neuritis, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Eric, welcome to the podcast, and maybe you can introduce yourself to our audience. Dr Eggenberger: Thank you. Thanks for having me. So, my name is Eric Eggenberger. I work at Mayo Clinic Florida, and I am involved exclusively in neuro-ophthalmology. Dr Smith: I just had the pleasure, Eric, of talking yesterday with Lindsey De Lott about non-optic neuritis causes of optic neuropathy. And so, I'm going to kind of reference a little bit what I learned yesterday. She was great. I wonder if you might begin by talking a little bit about nomenclature. You talk about the need for use of precise terminology in your article. And yesterday she taught me a lot about the risk of misdiagnosis and other causes of optic neuropathy, and the two seem related. So, I wonder if you can maybe lay the foundation for our conversation by talking about terminology? Dr Eggenberger: I think that's a great point. So, we are in an era now where, instead of lumping all these different diagnoses together, we have learned to split apart some of these clinical entities. And so, I think it's really important that we focus on precise terminology and recognize that all optic neuritis is not the same. And we have very different, distinct clinical pathways for these imaging pathways, treatment pathways, for these different types of optic neuritis, whether that's MS related, whether it's MOG related or aquaporin-4 related. Dr Smith: So, I wonder maybe we can begin by just, you know, giving our listeners wisdom, pearls, and pitfalls about, how do you recognize when someone with a suspected optic neuropathy has optic neuritis versus a noninflammatory optic neuropathy? Dr Eggenberger: So, that's a really important issue because there's a lot of clinical overlap in terms of exam findings. So, for instance, in any optic neuropathy, let's say it's unilateral, you typically are going to see decreases in acuity and field and color, and you're going to see a relative afferent pupillary defect. And then it's really the context that that occurs in that helps us distinguish different disease entities. So, with optic neuritis, typically you're going to have pain. And that's oftentimes going to be in the younger populations compared to some of the other common optic neuropathies we see, like ischemic optic neuropathy, for instance. Dr Smith: Right. So maybe we can talk a little bit about, kind of, your overall diagnostic approach, right? A lot of this is, of course, based on age and context, but young people get ischemic lesions and older people can have inflammatory lesions. So, what's your overall approach to the patient you just described? Let's say it's a forty-eight-year-old woman who comes to the emergency department with subacute unilateral vision loss and there's dyschromatopsia, APD, reduced acuity. And, you know, let's just say a fairly, you know, benign-looking fundoscopic exam. What do you do to evaluate that patient? Dr Eggenberger: In that particular context, I think we're looking at other contextual clues. Is there other vascular risk factors or other things to point you in one direction or the other? One of the important parts you mentioned was the fundus exam. So, we know with ischemic optic neuropathy, 100% of the time with AIOM, you're going to see disc edema. And so, in the context of that story, we want to confirm on our exam an optic neuropathy, and then we can kind of focus on the retrobulbar courses or different types of optic neuropathies. From an exam perspective, in that particular patient we'd be looking to measure the acuity, quantify that. And in the ER, you're not going to be able to do a perfect field, but you'll get some sense of the field and how much field loss there is. And then as you mentioned, the afferent pupillary defect is critical. And we're going to get a little bit of the historical features in terms of pain. With typical retrobulbar optic neuritis, most of those patients are going to experience some pain, and usually it's pain on eye movements. And those would be the clinical things to focus on. Other exposures the patient may or may not have had, any other concomitant conditions, would all help point you in different directions, perhaps, and then we're probably on towards imaging. Dr Smith: Yeah, maybe you can talk a little bit about that? What's the appropriate use of imaging? I mean, presumably the patients, like the one I just threw out there, are pretty much all going to get neuroimaging. What's your approach to that? How do you protocol the study? What should we be looking for? Dr Eggenberger: In our clinic, we would typically be ordering an MRI orbit and brain, and each of those has a specific purpose. The orbit is going to show us the extent of the optic neuropathy. So, we're particularly looking for a longitudinally extensive optic nerve lesion or more than half of the optic nerve involved. And most patients acutely, if it isn't an “itis" situation, we'll see enhancement. And then the MR brain is going to be useful for looking for other evidence of demyelination within the central nervous system. We may at some point get down to doing an MR cord, but I think acutely it's going to be brain and orbit that most of our patients are getting. Dr Smith: Let's say that we did the scan and, sure enough, there's sort of a shorter segment, so less than half the length of the nerve region of enhancement. What's the rest of your diagnostic evaluation look like for that patient? Dr Eggenberger: So, in that particular case, we would look at the remainder of the brain. So, we're looking for other evidence of demyelination and any other contextual clues, systemically that would point you one direction or another. But with a shorter segment involved, one of the more common things we might encounter would be multiple sclerosis-related optic neuritis. Dr Smith: Would you look for aquaporin-4 and MOG in a patient with what appears to be an isolated, uncomplicated short segment optic neuritis? Dr Eggenberger: So, I think it really depends a bit on the context. I would never fault anybody for looking at MOG or an aquaporin-4 in that context because those are really treatment-altering diagnoses, but the yield in this particular case with a short segment involved and depending on the acuity and other features is probably going to be pretty low. Dr Smith: I really liked as an aside- I wasn't going to go there next, but you kind of got me thinking about it, you have a really nice section in your article. Which, all of it's great, but talking about how to manage low titer MOG antibodies. I wonder if you could talk about that because I think that's a lesson, maybe, that is transferable to a lot of other testing that we do. in terms of pre-prior probability and titer and so forth. Dr Eggenberger: Yeah, that's really an important point. So, we've seen this come up a number of times where the MOG antibody is a very good test, but in low titer it has a relatively low positive predictive value, perhaps 50%. In those cases, particularly without a classic clinical context, you have to be extremely alert for some other diagnosis that could mimic what you think is inflammatory demyelinating optic neuritis, but in fact is infectious or some other cause. Dr Smith: Yeah, super, super important and helpful. In terms of aquaporin-4, how does that compare in terms of predictive values, lower titer positive results? Dr Eggenberger: So aquaporin-4, the test has a very high specificity. So, it's quite useful if positive. You have to keep in mind there can be some false negatives, but the test otherwise is quite specific. And that is a diagnosis, you know, we never want to miss. It's a vicious disease. It tends to be a blinding disease, particularly without treatment. Bad things happen when we miss that, and we want to get on that diagnosis early and do pretty aggressive early and prophylactic treatment. Dr Smith: Your article covers not only the common causes of optic neuritis and, you know, MS, isolated optic neuritis, MOGAD NMO, you talk about a bunch of other things. I wonder, in this patient that we've been discussing, in the absence of any other historical information that seems relevant---or maybe you can define what would seem relevant---would you do other evaluation in that individual, other serologic evaluation and so forth, just in terms of diagnosis? Dr Eggenberger: In that particular case, without other red flags, I don't think I would initially. And follow-up is going to give you a lot of this context. So, you'd be on the lookout for other systemic conditions. So, if the patient had some arthropathy, if the patient had any pulmonary disease hints, if there was anything else that could lead you on a broader expedition. But I think in the context of this case, acutely in the ER, I probably wouldn't do a big lab plug for this. I probably would kind of go down the most likely road and start our treatments, and then follow that patient up. Dr Smith: Yeah, I know your article does a really great job, I think, of outlining when do you need to think about some of these less common causes. Well, can we talk about treatment, Eric? Because I want to move on to some other things. But- so, we've got a patient with isolated optic neuritis, nothing else, you know, in terms of the other antibodies we've talked about. What state-of-the-care- or, state-of-the-art treatment for that patient? Dr Eggenberger: So, the acute treatment for these inflammatory, optic neuritis-type cases is very similar Initially. High dose steroids remains kind of the standard. And then, in MS-related optic neuritis, we may or may not see a taper. So many times it's just an acute treatment of three to five days high dose. Whether that's oral or PO, we could institute either depending on the particular case. And then the taper would depend on the potential cause. So, for instance, with these antibody-driven diseases---so with MOG- or particularly with aquaporin-4---if it's a longitudinally extensive region of optic nerve involved, we tend to use a longitudinally extensive taper. And so, we use prednisone in those cases for several months while we're getting everything else set and deciding what the overall course is going to bring. Dr Smith: What about IV versus oral? There must be something about my practice. I was telling this to Lindsey. Every time on our hospital service, we seem to have at least two patients with optic neuropathies, which I always enjoy, but I find it's a little weird to admit someone who's doing just fine otherwise to the hospital with three days of IV SOLU-MEDROL. So, I'm always trying to figure out, like, how can I get this patient home? And your article had the best term I've heard in a long time, which is “SOLU smoothies.” I mean, are there other strategies that you sometimes use, other than just high-dose IV methylprednisolone? Dr Eggenberger: So, I agree with you. It's sometimes hard to admit somebody for just an IV therapy. And we'll do this as an outpatient, high-dose IV, but we'll also use high-dose orals. And in times in the past when there's been methylprednisolone shortage, we've used high-dose oral or IV dexamethasone as well. I think the IV form, although it's the gold standard, the high-dose oral forms have pretty equivalent bioavailability and are pretty tolerable in my experience. And certainly more convenient. Dr Smith: I wonder if we should switch and maybe talk a little bit about aquaporin-4, I mean, you emphasized that this is a vicious disease---I love the way you describe that---and often blinding. What updates do you have in terms of our therapeutic approach to NMO? That's been rapidly evolving of late. Dr Eggenberger: Right, so these are cases we're always going to share with neuroimmunology. And it requires kind of a multidisciplinary approach, in my opinion, for ideal or for best outcomes. And so, all of these patients are going to get put on prophylactic medications. So, this is a disease you just can't leave untreated. Bad stuff will happen for sure. And we now, fortunately, have some approved, FDA-approved medications that can positively impact the course of this disease. So, that's been a welcome addition. Dr Smith: What are the FDA-approved medications at this point for NMO? Dr Eggenberger: So, there are several at this point, and this is an area that's in growth, fortunately. And again, these are cases we're going to be sharing with our neuroimmunology colleagues. So, these are IV medications typically aimed at complement or CD19. And they all are relatively effective at quieting the course of the disease. Dr Smith: Maybe we can talk a little bit about MOG? I think that most of our listeners are probably pretty familiar with aquaporin-4 and NMO, what- maybe you could describe MOG a little bit and the therapeutic approach for patients with MOG-associated disease? Dr Eggenberger: So, MOG has been a real interesting kind of condition to learn more about. We certainly see a lot of MOG, and I'm sure we saw MOG before it was formally described, but I think we just thought it was kind of a benign, maybe monophasic MS type of presentation. But MOG tends to come in with a loss of acuity that kind of rivals aquaporin-4. So, the acuity tends to be pretty, pretty depressed, but it's very steroid-responsive. So, a lot of times these are the patients, you'll see that their vision will start to improve even when they're on the initial few days of the high-dose steroids. And many times we can get their vision back to 20/20 or very close to that. Dr Smith: And do these patients need chronic management? Dr Eggenberger: So, that's an area of controversy to some degree. About 50% of the optic neuritis MOG-related cases are going to have a relapsing course. And because the disease is steroid-responsive, many times we'll follow these patients after a first attack to see if this is the condition that's going to declare itself to be relapsing or if this is just going to be a monophasic kind of presentation of optic neuritis. We don't have great biomarkers to separate patients who are going to be in that 50% monophasic course versus the other half. It'll be relapsing. And so, it depends on the patient. If there's somebody that's, as many of these patients are, been very steroid responsive, they get back to 20/20, we can teach them about the disease so that if they do have a relapse, we can get them high-dose steroids in a relatively rapid fashion and they're otherwise healthy, we're probably going to watch that patient. And if it's somebody that doesn't recover 100%, there's other issues with treating them with high-dose steroids potentially in the future, then we may learn more towards an earlier prophylactic approach in that patient. Dr Smith: And what would that approach look like? Is it different from NMO or using more IVIG or B cell depletion as opposed to complement inhibition, for instance? Dr Eggenberger: In MOG, we know that the B cell depletion strategies don't work as well. And so most times we're turning to IVIG, and we found that pretty effective. That's kind of our go-to at this point. Dr Smith: Eric, it's a joy talking to you and I'd love to keep going about content, but I'll refer our listeners to your outstanding article. I mean, you're such a highly regarded neuro-ophthalmologist and educator. I wonder if you could talk to us about why you've done neuro-ophthalmology, and maybe this is an opportunity for you to convince all of our great residents that are listening or students what's great about being a neuro-ophthalmologist. Dr Eggenberger: I think neuro-ophthalmology is by far the most interesting part of neurology. So, it's an area that I think a lot of general neurologists, in my view, don't get enough of in their residency. But it's kind of the essence of neurology, where in neurology you're localizing down to the millimeter and in neuro-ophthalmology,  we're localizing down to the micron level. We have several new emerging diseases like these varieties of optic neuritis we're focused on. We're learning lots about those. You get to be involved in lots of different areas of neurology. So, we'll see not just demyelinating conditions, we'll see trauma as it relates to the visual system. And we'll see tumor, and we see all different flavors, stroke, and in any piece of neurology, commonly we'll have some vision aspect that we that we get involved in. So, we see a wide variety of conditions. So, I think it's been a really exciting place to be within neurology. And it's rapidly changing at this point. We're getting new therapeutics. So, it's, I think it's a great time to be a neuro-ophthalmologist. Dr Smith: Yeah, listening to you talk and just reflecting on it, it's really true. Neuro-ophthalmology does cover the entire span of neurology, right? I'm a neuromuscular guy and we see a lot of ocular myasthenia, which is another super exciting area. But we've been talking about optic neuritis, and your article talks about infectious causes and the paraneoplastic and a whole host of things. So, you're a great advocate and salesperson for your field. You convinced me. Dr Eggenberger: Efferent neuro-ophthalmology we love, we could talk about ocular myasthenia and other aspects for another hour. And we get involved in all kinds of cases: third nerve palsies, ocular myasthenia, trauma that involves the efferent system, all different aspects. It's really a great subspecialty, and you get to see a bit of all of neurology. Dr Smith: I'm trying to remember who it was, Eric. It was an attending of mine at medical school. I went to medical school at the Mayo Clinic in Rochester, and I want to say it was Manny Gomez, who was a very famous tuberous sclerosis person, who told me that neuro-ophthalmology was the most elegant specialty within neurology. That stuck with me. Thank you so much for joining me today. I really appreciate it. Dr Eggenberger: Thank you. I appreciate it as well. Dr Smith: So again, today I've been interviewing Dr Eric Eggenberger about his really wonderful article on optic neuritis, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum audio episodes from the neuro-ophthalmology and other issues. And listeners, thank you very much for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In this vital and technically complex presentation, Dr Scott Antoine explains why PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptoccocal Infection) are common and overlooked root cause of psychiatric symptoms in children (such as OCD, restrictive eating, anxiety, emotional distress, depression, dramatic mood swings, psychosis and suicidal ideation). In doing so, he encourages physicians to explore mental health in an entirely new way, especially in the treatment of children.    Dr Scott Antoine completed his undergraduate training at the University of Scranton, after which he completed his doctorate at the Philadelphia College of Osteopathic Medicine. He later served in active duty with the United States Army as an Emergency Physician and worked as an Emergency Physician at St. Francis Hospital until 2019. In addition to his board certification in Emergency Medicine, he achieved board certification in Integrative Medicine and holds certifications in Functional Medicine through the Institute for Functional Medicine (IFM) and A4M. His book The Comprehensive Physicians Guide to the Management of PANS and PANDAS was released in February 2024 to excellent reviews.    He discovered his calling when he and his wife Ellen, also a Functional and Integrative Medicine physician, battled to correctly diagnose the root-cause of their 12 year old daughter's sudden-onset OCD, insomnia, rage, as PANS. Since then, he has helped hundreds of children recover from PANS and PANDAS, and in 2019 helped to pass a law which prohibits insurance companies in Indiana from denying coverage for medical care (including IVIG) for children with PANS and PANDAS.   In this richly informative personable interview, he presents an evidence-based outline of the successful ways to both diagnose and treat PANS and PANDAS, and stresses that they are not nearly as rare as mainstream medicine seems to believe. He decodes complex medical expertise, referencing over 300 clinical studies and peer-reviewed medical literature, that identify biological mechanisms and the root causes that underlie PANS and PANDAS. In this episode, Dr Antoine unravels why PANS/PANDAS can have such a profound, often sudden impact on Children's psychiatric health, and demands that PANS and PANDAS be considered more broadly in psychiatric diagnoses. In this episode you will learn how infections, toxins and the immune system interplay in the expression of harmful psychiatric symptoms, why they cause PANS and PANDAS, and how they can be successfully treated.   In this episode learn about: Why PANS and PANDAS are hidden and common root cause of OCD, violent mood swings, depression, anxiety and suicidality, how they are diagnosed, and the role of testing. Why physicians routinely overlook and even deny PANS and PANDAS as a cause of mental health symptoms. Why toxins and infections can trigger PANS and PANDAS and their associated neuropsychiatric symptoms. How Strep is related to autoimmunity and why to treat it even if strep tests are negative.   Why a range of infections - not just strep or Lyme borrelia - can trigger neuropsychiatric symptoms (OCD, attention issues, hallucinations, psychosis, depression, suicidal ideation), including other tick-borne co-infections, influenza, Epstein Barr, chlamydia pneumonia and Covid. Ways environmental chemicals, heavy metals, pesticides and mycotoxins (mould) can lead to inflammation and autoimmunity. The concrete link between rheumatic fever and OCD, ADHD, mood issues and psychosis. Other causes of autoimmunity, including genetics, intestinal permeability, infection/T-cell activation and molecular mimicry  (the mechanism by which microbes can induce autoimmunity). The 4 vital components of treatment: 1) find and treat infections 2) find and remove toxins 3) re-regulate the immune system 4) break neurological loops (OCD, anxiety). How to treat infections using prolonged use of antibiotics, and which antibiotics to choose. Why herbs (isatis, baicalensis, cat's claw etc) can reduce the duration of antibiotic use, and the studies that prove it. The binders (activated charcoal, zeolites, humic acid) and bitters that help remove toxins. Ways medications (naltrexone and steroids) can help re-regulate the immune system. Why and when IVIG is used for the treatment, why it can relieve and cure symptoms (OCD, anxiety and tics) quickly. How Exposure Response Prevention (ERP) and hypnosis outperforms medications in breaking neurological loops (OCD, anxiety, intrusive thoughts) Other helpful interventions that assist healing; nutrients, diet changes and probiotics.

Renee improved CIDP, gastroparesis, anxiety, depression, migraines, eczema, and perimenopausal symptoms. Instagram: @eatingmeattowalk YouTube: @eatingmeattowalk  Timestamps: 00:00 Trailer 01:14 Introduction 05:34 Overcoming setbacks with IVIG treatment 09:53 Healing with carnivore diet 13:36 Medication weaning and lifestyle changes 15:12 Drug company influence and desperation 18:22 Normal EMG results discussion 21:38 Diet regret: harmed husband's health 26:09 Choosing health over heart risk 29:11 Reevaluating veganism and health 30:16 Veganism and misdiagnosed grip issues 34:16 Oncology: a revolving door experience 36:50 Struggles with suicide and anxiety 40:41 Vaccination experience and COVID challenges 44:54 Demyelination and nerve recovery process 48:31 Carnivore diet for chronic illness 51:57 Diagnostics beyond MRIs 52:51 Where to find Renee Join Revero now to regain your health: https://revero.com/YT Revero.com is an online medical clinic for treating chronic diseases with this root-cause approach of nutrition therapy. You can get access to medical providers, personalized nutrition therapy, biomarker tracking, lab testing, ongoing clinical care, and daily coaching. You will also learn everything you need with educational videos, hundreds of recipes, and articles to make this easy for you. Join the Revero team (medical providers, etc): https://revero.com/jobs ‪#Revero #ReveroHealth #shawnbaker  #Carnivorediet #MeatHeals #AnimalBased #ZeroCarb #DietCoach  #FatAdapted #Carnivore #sugarfree Disclaimer: The content on this channel is not medical advice. Please consult your healthcare provider.

John Navarro Jr. is the only person in Gibraltar to have Multifocal Motor Neuropathy (MMN), a rare, chronic neurological disorder that affects the peripheral nerves, leading to progressive muscle weakness and loss of function, usually in the hands and arms. Unlike other neuropathies, MMN is purely motor, meaning it does not cause sensory loss. It is often misdiagnosed as ALS due to its similar symptoms but is treatable with intravenous immunoglobulin (IVIG), which can help manage the condition and slow progression. Early diagnosis and treatment are crucial for maintaining mobility and quality of life. MMN is a very rare condition roughly affecting 1 in 200,000 people or 5 in every 1 million people.  Today he'll share his story.Learn more about MMN and John's work via the links below:GBS/CIDP Foundation:https://www.gbs-cidp.org/John also founded a MMN UK Facebook Group:https://www.facebook.com/share/g/18eLTDzYvi/?mibextid=wwXIfrMoorish Castle in Gibraltar was recently lit with an orange glow in celebration of MMN Awareness Month:https://www.gbc.gi/news/moorish-castle-lit-orange-gibraltars-only-multifocal-motor-neuropathy-patient-shares-his-storyIf you would like to reach out feel free to send an email to: atelierfuralle@gmail.com. You can also leave a review of the podcast and follow this show on:Instagram:https://instagram.com/atelierfuralle?igshid=OGQ5ZDc2ODk2ZA%3D%3D&utm_source=qr⁠⁠Facebook:⁠⁠https://www.facebook.com/profile.php?id=61551850785306⁠⁠Feel free to join the "JD Dragon Disability Rights Podcast" Facebook Group:https://www.facebook.com/share/g/12Eit9sBPuR/?mibextid=wwXIfrSnapchat:https://t.snapchat.com/FVWn1jmTDiscord ServerJD DragonX (formerly known as Twitter):@JDDragonPodcast

In this episode of the Bendy Bodies Podcast, Dr. Linda Bluestein welcomes Dr. Ilene Ruhoy, a board-certified neurologist and environmental toxicologist, for an in-depth discussion on brain fog, cognitive dysfunction, and chronic fatigue in conditions like Ehlers-Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), and dysautonomia. Dr. Ruhoy shares insights on the immune system's role in neurological symptoms, the impact of mast cell activation, and the role of treatments like peptides, IVIG (intravenous gammaglobulin), plasmapheresis, and immune modulators. They also discuss the hidden effects of histamine on the brain, how sensory sensitivity contributes to fatigue, and the role of regenerative medicine in connective tissue healing. This episode is packed with cutting-edge research and practical solutions for improving cognitive function and energy levels. Takeaways: Brain Fog & Fatigue Are Linked to Immune Dysfunction: Cognitive dysfunction in conditions like EDS, MCAS, and POTS is often tied to inflammatory responses and immune dysregulation rather than just histamine alone. Plasmapheresis & IVIG Can Help Some Patients: For severe cases, plasmapheresis removes inflammatory mediators from the blood, and IVIG helps regulate immune function, leading to cognitive and fatigue improvements. Histamine Plays a Complex Role in Brain Function: While histamine can trigger symptoms in MCAS patients, it also has neuroprotective effects, making antihistamine overuse a potential issue for some. Sensory Sensitivity Increases Cognitive Load: Many people with EDS and related conditions experience hypersensitivity to light, noise, and smells, which can overwhelm the nervous system and worsen fatigue. Regenerative Medicine May Support Connective Tissue Repair: Peptides, stem cell therapy, and targeted immune modulation are promising areas of research to help strengthen connective tissue and reduce systemic inflammation. Connect with YOUR Hypermobility Specialist, Dr. Linda Bluestein, MD at https://www.hypermobilitymd.com/. Thank YOU so much for tuning in. We hope you found this episode informative, inspiring, useful, validating, and enjoyable. Join us on the next episode for YOUR time to level up your knowledge about hypermobility disorders and the people who have them. Join YOUR Bendy Bodies community at https://www.bendybodiespodcast.com/. Learn more about Human Content at http://www.human-content.com Podcast Advertising/Business Inquiries: sales@human-content.com YOUR bendy body is our highest priority! Learn about Dr. Ilene Ruhoy Instagram: @IleneRuhoyMDPhD TikTok: @IleneRuhoyMDPhD Podcast (YT): @Unraveledpod Twitter: @RuhoyMD Bluesky: @ruhoy.bsky.social Keep up to date with the HypermobilityMD: YouTube: youtube.com/@bendybodiespodcast Twitter: twitter.com/BluesteinLinda LinkedIn: linkedin.com/in/hypermobilitymd Facebook: facebook.com/BendyBodiesPodcast Blog: hypermobilitymd.com/blog Part of the Human Content Podcast Network Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode of the Bendy Bodies Podcast, Dr. Linda Bluestein welcomes Dr. Ilene Ruhoy, a board-certified neurologist and environmental toxicologist, for an in-depth discussion on brain fog, cognitive dysfunction, and chronic fatigue in conditions like Ehlers-Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), and dysautonomia. Dr. Ruhoy shares insights on the immune system's role in neurological symptoms, the impact of mast cell activation, and the role of treatments like peptides, IVIG (intravenous gammaglobulin), plasmapheresis, and immune modulators. They also discuss the hidden effects of histamine on the brain, how sensory sensitivity contributes to fatigue, and the role of regenerative medicine in connective tissue healing. This episode is packed with cutting-edge research and practical solutions for improving cognitive function and energy levels. Takeaways: Brain Fog & Fatigue Are Linked to Immune Dysfunction: Cognitive dysfunction in conditions like EDS, MCAS, and POTS is often tied to inflammatory responses and immune dysregulation rather than just histamine alone. Plasmapheresis & IVIG Can Help Some Patients: For severe cases, plasmapheresis removes inflammatory mediators from the blood, and IVIG helps regulate immune function, leading to cognitive and fatigue improvements. Histamine Plays a Complex Role in Brain Function: While histamine can trigger symptoms in MCAS patients, it also has neuroprotective effects, making antihistamine overuse a potential issue for some. Sensory Sensitivity Increases Cognitive Load: Many people with EDS and related conditions experience hypersensitivity to light, noise, and smells, which can overwhelm the nervous system and worsen fatigue. Regenerative Medicine May Support Connective Tissue Repair: Peptides, stem cell therapy, and targeted immune modulation are promising areas of research to help strengthen connective tissue and reduce systemic inflammation. Connect with YOUR Hypermobility Specialist, Dr. Linda Bluestein, MD at https://www.hypermobilitymd.com/. Thank YOU so much for tuning in. We hope you found this episode informative, inspiring, useful, validating, and enjoyable. Join us on the next episode for YOUR time to level up your knowledge about hypermobility disorders and the people who have them. Join YOUR Bendy Bodies community at https://www.bendybodiespodcast.com/. Learn more about Human Content at http://www.human-content.com Podcast Advertising/Business Inquiries: sales@human-content.com YOUR bendy body is our highest priority! Learn about Dr. Ilene Ruhoy Instagram: @IleneRuhoyMDPhD TikTok: @IleneRuhoyMDPhD Podcast (YT): @Unraveledpod Twitter: @RuhoyMD Bluesky: @ruhoy.bsky.social Keep up to date with the HypermobilityMD: YouTube: youtube.com/@bendybodiespodcast Twitter: twitter.com/BluesteinLinda LinkedIn: linkedin.com/in/hypermobilitymd Facebook: facebook.com/BendyBodiesPodcast Blog: hypermobilitymd.com/blog Part of the Human Content Podcast Network Learn more about your ad choices. Visit megaphone.fm/adchoices

This podcast is sponsored by CSL Behring, manufacturer of Hizentra, subcutaneous immune globulin. In this episode, we will discuss Melaine's journey with PI, from her experience with IVIG, to her switch to subcutaneous IG, and what that meant in terms of self-administering her treatment at home. Melaine enjoys cycling, gardening, travel and she's also living with primary immunodeficiency or PI. Melaine will be sharing her story and also providing some information about Hizentra, for which she is a patient advocate. Patient advocates are not healthcare professionals or medical experts. For medical questions or advice, please contact your physician. Patient advocates are compensated by CSL Behring, LLC, for their time and/or expenses. Support the show

Episode summary and time stamps I. Introduction (0:00-1:31) Host Intro: Introduces Gillian Ehrlich, DNP, ARNP,(Neuroveda Health), highlighting expertise in complex chronic illness, blending #Ayurveda, conventional nursing, #functionalmedicine, and #integrativemedicine. Mentions therapies: #ketamine, #plasmapheresis, #IVtherapies, and conditions treated (e.g., #fibromyalgia, #chronicfatigue, #POTS, #longCOVID). II. Early Influences (1:31-10:38) Childhood: Grew up in polluted Cleveland, OH, noticing tired adults; standard American diet. Jane Esselstyn: Health teacher (daughter of Dr. Caldwell Esselstyn) inspired her with her focus on outdoor education and veganism. Hypermobility: Personal experience with #hypermobility, #EhlersDanlosSyndrome, #POTS, and #mastcellactivation led to finding exercise that worked (rowing). Exploration: Interested in health, but questioned the traditional medical model; explored outdoor leadership, farming, sailing. Ayurveda: Introduced to #Ayurveda by a friend, attended classes with Dr. Vasant Lad, then studied at the Ayurvedic Institute (2000-2001). III. Integrating Ayurveda with Western Medicine (10:38-13:48) Desire for Change: Aimed to bring #Ayurveda insights into conventional medicine; mentored by Keisha Ewers, Dr. Eileen Ruhoy, and Arti Chandra. Challenges: Faced limitations in using #Ayurveda in primary care systems (Swedish, Harborview), due to visit length restrictions. Neuroveda Health: Created own practice to practice freely, offering customized treatments and practical support. IV. Patient Experiences and Philosophy (13:48-18:11) Individuality: Believes people thrive when being themselves, not "average;" Sees beauty in human diversity. Teacher Role: Sees herself as a teacher, helping patients understand needs; emphasizes relaxation for healing (using humor for comfort). Patient Focus: Patients should leave feeling empowered and with the tools to improve their health. V. Neuroveda Health & Integrative Approach (18:11-32:04) Spectrum of Health: Sees complex disease and #longevity as a spectrum of #oxidativeStress, sharing similar approaches. Pancha Karma: Introduced #PanchaKarma (Ayurvedic detoxification), with key components: oilation, treatments, and elimination. Executive Longevity Program (ELP): Modeled on #PanchaKarma, offers 3-21 day programs. Includes #Ayurvedic bodywork, #plasmapheresis, #IVIG, #stemcells, #prolotherapy, ozone, #NAD, mitochondrial #IVs, #ketamine therapy. Designed for significant shifts and then a return to primary providers. Diagnostics/Therapies: Offers autonomic testing, EDS evaluation, skin biopsies, craniocervical instability testing, and other advanced therapies. Frustrations: Noted that patients find #Ayurveda after exhausting all other options. Emphasized the need for neuroplasticity. VI. Ayurvedic Principles in Practice (32:04-37:53) Core Philosophy: #Ayurvedic medicine is core, integrating therapies within this framework. Plasmapheresis/Raktamokshana: Links #plasmapheresis to #Ayurvedic practice of "Raktamokshana" (blood removal) part of #PanchaKarma. Personalization: Treatment is based on disease patterns and #doshas. Case Example: CRPS patient case of using gentle massage because of high #Vata; Digestion was a consideration in her case. Unique Approach: #Neuroveda has a unifying philosophy rooted in #Ayurveda, while other clinics may just combine modalities. VII. Closing Thoughts (37:53-39:35) Keywords: #Ayurveda, #IntegrativeMedicine, #FunctionalMedicine, #ChronicIllness, #PanchaKarma, #Plasmapheresis, #Ketamine, #IVTherapies, #Hypermobility, #EhlersDanlosSyndrome, #POTS, #MastCellActivationSyndrome, #NeurovedaHealth, #Doshas, #Vata, #OxidativeStress, #Raktamokshana, #Longevity, #MECFS, #longCOVID https://www.neurovedahealth.com/ https://www.neurovedahealth.com/executive

Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Robert Orlowski from MD Anderson Cancer Center to discuss groundbreaking studies presented at ASH 2024 focused on multiple myeloma. We dived into four key studies: 1.⁠ ⁠AQUILA: Explore the impact of early intervention using daratumumab for smoldering myeloma, which showed improved progression-free survival (PFS) and overall survival (OS). 2.⁠ ⁠Dara Based Quad Therapy: We discuss a meta-analysis reaffirming the use of quadruplet therapy with anti-CD38 for newly diagnosed multiple myeloma as the standard of care. 3.⁠ CARTITUDE-4: study highlights the benefits of CAR-T therapy in earlier lines of treatment for patients with lenalidomide-refractory disease. 4.⁠ ⁠Role of IVIG with BCMA Bispecific Antibodies: Discover how IVIG can reduce infection rates and improve overall survival when used alongside BCMA-targeted therapies. Tune in for an insightful discussion that will enhance your understanding of the latest advancements in multiple myeloma treatment. Don't forget to check out our other episodes on CLL, myeloma, and lymphoma from ASH 2024! Subscribe to the Oncology Brothers for more updates and expert insights in oncology! Website: http://www.oncbrothers.com/  X/Twitter: https://twitter.com/oncbrothers  Contact us at info@oncbrothers.com

In this powerful Tick Boot Camp Podcast episode, Lindsey Shaker shares her inspiring journey of overcoming Lyme disease and multiple co-infections. From battling years of misdiagnosis to navigating aggressive treatments, Lindsey's story highlights resilience, resourcefulness, and the importance of maintaining hope. She also emphasizes the role of movement, such as yoga and hiking, and the necessity of community and self-care in the healing process. Tune in for invaluable insights into managing chronic illness and learning how to advocate for yourself and others in the Lyme community. Introduction to Lindsey Shaker • Background: Director of Marketing for Shaker Auto Group and Lyme disease advocate. • Diagnosed with Lyme disease and multiple co-infections at age 31 after years of misdiagnosis. Lindsey's Early Life and Onset of Symptoms • Born with Lyme and Bartonella through maternal transmission. • Early symptoms: Full-body paralysis during high school track practices, emotional instability, memory loss, and balance issues in college. • Misdiagnosed with depression, ADHD, and Lyme carditis before her eventual diagnosis. The Turning Point • Mother's diagnosis prompted Lindsey to seek further testing. • Diagnosed with Lyme disease, Bartonella, Babesiosis, Typhus, Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis via blood tests conducted by Dr. Bouboulis. The Treatment Journey • Initial treatments: A combination of antibiotics, anti-parasitic medication (Mepron), and IVIG therapy. • Challenges: Managing severe Herxheimer reactions and navigating insurance for IVIG approval. • Milestones: Significant improvements in mobility and overall health over seven years of treatment. The Role of Mindset and Self-Care • Tools for resilience: Yoga, probiotics, CBD oil, and communication with Lyme-literate professionals. • Addressing environmental factors, such as mold exposure, through diet, sleep, and movement. Movement as Medicine • Physical activities: Hiking and yoga played crucial roles in her recovery journey. • Emotional benefits: Restored confidence and emotional well-being through consistent movement. Life After Lyme • Nearly 99% recovered but emphasizes the importance of continued vigilance. • Reflects on lost time but remains grateful for the progress made and the strength gained. Advice for Listeners • For Lyme patients: “Your outlook is everything. Fight for your recovery and never give up.” • For prevention: “Assign a tick-checking buddy and never skip tick checks after outdoor activities.” Lindsey's Call-to-Action • Follow Lindsey on Instagram: @LMshaker to learn more about her journey and advocacy work. • Explore Tick Boot Camp resources for tools and strategies to overcome Lyme disease and chronic illnesses. Conclusion: Lindsey Shaker's journey reminds us that recovery is possible with persistence, education, and support. Her story is a beacon of hope for others navigating the challenges of chronic Lyme and other tick-borne diseases Keywords: Lyme disease, Tick Boot Camp, Lindsey Shaker, Resilience, Misdiagnosis, Co-infections, Herxheimer reactions, IVIG, Movement, Mindset, Immune system, Chronic illness, Recovery, Advocacy, Tick-borne illnesses, Treatment journey

Description: Co-hosts Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist living with EoE who serves on APFED's Health Sciences Advisory Council, interview Jason Ingraham, an adult living with eosinophilic fasciitis (EF), and Dr. Catherine Sims, a rheumatologist at Duke University and a Health Services Research Fellow at the Durham Veterans' Affairs Hospital. They discuss Jason's experiences living with EF and Dr. Sims's experience treating EF. They share Jason's journey to diagnosis and the importance of working with a group of specialists. They share tips on medication and physical therapy, how to communicate with your medical team, and manage your activity and mindset. Disclaimer: The information provided in this podcast is designed to support, not replace the relationship that exists between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.   Key Takeaways: [:50] Ryan Piansky introduces the episode, brought to you thanks to the support of Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron, and co-host, Holly Knotowicz.   [1:14] Holly introduces today's topic, eosinophilic fasciitis, with guests, Jason Ingraham and Dr. Catherine Sims.   [1:25] Jason is an adult living with eosinophilic fasciitis (EF). Dr. Sims is a rheumatologist at Duke University and a Health Services Research Fellow at the Durham Veterans' Affairs Hospital.   [1:52] Dr. Sims explains what EF is. Patients may present with symptoms of large plaques on their skin, edema of arms and legs, Raynaud's Phenomenon, contractures of arms or legs, limited mobility, or loss of the ability to do tasks they used to do.   [2:42] EF, as with most eosinophilic disorders, doesn't follow the textbook. Some people will present with one symptom and some with multiple symptoms. There is a disconnect between how we diagnose conditions like EF and how patients present.   [3:01] There are major and minor criteria for the diagnosis. As in Jason's case, it takes time for the symptoms to present. Things develop over time. It took multiple specialists to diagnose Jason.   [3:38] Eosinophilic conditions are incredibly different from each other. When Dr. Sims sees a patient with high eosinophils, she thinks of three major buckets: infection, autoimmune diseases, and cancer.   [4:12] Patients will often see many different specialists. In Jason's case, they had done a skin biopsy that wasn't as helpful as they hoped. That led him to get a deep muscle biopsy to collect the lining of the muscle.   [4:47] Fasciitis is the inflammation of the muscle lining or fascia. A sample of the fascia can demonstrate under the microscope if there is a thickening, swelling, or inflammation of the lining of the muscle.   [5:24] Dr. Sims as a rheumatologist treats a number of rare diseases. Eosinophilic fasciitis is an ultra-rare disease.    [5:43] Jason had a local primary care doctor and a rheumatologist who both did a really good job and referred him to Dr. Sims. She had the benefit of their hard work to guide her next steps. Because EF is so rare, she has pitched Jason's case twice in rheumatology grand rounds sessions.   [6:18] During one of these sessions, Dr. Sims was advised to get the fascial biopsy that ultimately led to the diagnosis. She benefited from the intelligence and input of dozens of doctors.   [6:59] In the Fall of 2022, while hiking on vacation with his wife, Jason was extremely fatigued, and his forearms and lower legs swelled. His socks left deep impressions. It was difficult to reach his feet to put socks on. He spent a lot of time uncharacteristically resting.   [8:09] Jason's primary care doctor ran lots of blood tests. He thought it might be a tick bite. Jason started seeing specialists, having tests and hospital visits.   [8:57] Jason worked with a rheumatologist in Wilmington, an infectious disease doctor, and a hematologist/oncologist who reached out to a Duke expert. He also saw a pulmonologist and a dermatologist. He got the referral to Dr. Sims for March of 2023.   [9:57] The first diagnosis Jason received was after his first hospital stay in January of 2023, when he had bone marrow biopsies, CT scans, ultrasound, and other tests. He was deemed to have idiopathic hypereosinophilic syndrome (IHES).   [10:30] It was only a few weeks before his local rheumatologist said his panels were back and one tipped it from an IHES diagnosis to eosinophilic granulomatosis with polyangiitis (EGPA). He joined the Vasculitis Foundation and researched EGPA.   [11:03] Dr. Sims told Jason that EGPA was a working diagnosis but he didn't check all the boxes. There was the underlying thought that maybe it was something else. He had a second flare when he came off of prednisone in June of 2023.   [11:48] Dr. Sims scheduled Jason for a muscle biopsy while he was off steroids. That's how he got the diagnosis of eosinophilic fasciitis (EF). Jason says the disorder is hard for him to pronounce and he can barely spell the words.   [12:52] Jason's wife Michelle encouraged Jason to track his symptoms and medications and keep track of data. Going from specialist to specialist, the first thing he did was give the history.   [13:31] Jason found it helpful to create a spreadsheet of data with blood test results, meds, how he was feeling each day, his weight, and even notes about when he had difficulty putting his socks on. Jason is an advocate of owning your continuity of care as you see different doctors.   [14:42] Jason says the doctors at Duke talk very well between themselves.   [14:49] Jason likes to look back at that spreadsheet and see how far he's come, looking at the dosage he was on during and after flares and the dosage he's on now, or zero, on some of the medications. That's a little bit of a victory.   [15:16] Holly works at a private hospital without Epic or CareEverywhere so she gives physical notes to her patients to give to their doctors. She comments that a great PCP, like the one Jason had, can make all the difference in the world.   [16:18] Jason's PCP, Dr. Cosgrove, referred Jason to Duke for a second opinion. That was where he met Dr. Sims. He's glad to have both Dr. Sims and his PCP accessible.   [17:35] Jason says the number of questions you have with this type of thing is immense. When you look up EF, you find very little and the literature isn't easily digestible by patients. Being able to reach out to your doctors for a quick question is super helpful. [17:56] Jason has been able to do telehealth follow-ups and not always have to travel or take off work, which has been extremely helpful. He has been at Duke a good handful of times for various things but remote follow-ups are helpful.   [18:52] Dr. Sims says people just don't know about EF as it is an ultra-rare diagnosis. Even physicians don't understand what causes it. It's lumped in with all other eosinophilic conditions but these disorders don't all present the same way.   [19:19] EoE doesn't look like EF, even though they're both driven by the same immune cells. Dr. Sims says the first need is educating providers and patients on what the diagnosis is; awareness in general when a patient is having this swelling of extremities.   [19:44] Dr. Sims says at his baseline, Jason is very active with multi-mile hikes. When Dr. Sims met him, he was off from the baseline of what he was able to do. Being aware of your baseline and changes from that is very informative for doctors.   [20:07] Dr. Sims talks about the patient being a liaison between multiple specialists. Bringing data to your subspecialist always helps facilitate care and come up with a bigger picture of what's happening.   [20:23] Jason first went to Dr. Sims with the diagnosis of EGPA. She said, let's treat the EGPA and see what happens but they kept an open mind. With ultra-rare diseases, sometimes it's difficult for patients not to have a label for their condition.   [20:45] Dr. Sims explains to her patients that sometimes we live in the discomfort of not having a label. She keeps an open mind and doesn't limit herself to just one diagnosis. She seeks feedback from providers who have seen this before and know what works.   [21:07] Just as Jason described, you will go through multiple diagnoses. Is this cancer? Is it a parasitic infection? Where did you travel? You will see many subspecialists. It's extremely anxiety-provoking.   [21:31] When Dr. Sims did her grand rounds, she gave a third of the presentation, and the other two thirds were presented by an infectious disease doctor and a hematologist. In these cases, you need more than one subspecialist to complete the workup.   [22:10] Dr. Sims says there are a lot of misconceptions that the patient will get the diagnosis right away and the right therapy and get better. There are multiple therapies, not just medications. There are lifestyle and work modifications; it's a gradual process.   [22:22] One of Dr. Sims's goals for Jason and Michelle is to get back to doing the things that they enjoy, tennis and hiking. That's a measurement of the quality of life that a patient has.   [22:34] Talking to your doctors about how you're feeling and how you're functioning is huge. It may be that this is your new normal, but it may also be that we can make adjustments to maximize your quality of life.   [23:00] There are misconceptions about the journey of diagnosis and treatment. Have a close relationship with your subspecialist. PCPs have a high burden of expectations. As a rheumatologist who treats rare diseases, it's helpful to take on a part of that burden.   [22:31] If you don't have good communication with your providers and they aren't listening to you, you can always go get another opinion. The provider relationship is life-long.   [23:43] It's important for your provider to take what's important to you into consideration when they make treatment decisions.   [25:00] As a rheumatologist, steroids are a first-line therapy for Dr. Sims. Their role is the quick control of inflammation. The goal is always to get you off of the steroids as soon as possible, in the safest way possible.   [25:17] When Jason came to Dr. Sims, he was on mepolizumab for the working diagnosis of EGPA. Mepolizumab is one of the primary therapies for EGPA. They talked about not making treatment changes as they were navigating what was happening.   [25:40] They didn't want to make a change of medication and then have that be mistaken for disease activity. They didn't want too many variables moving at once.   [25:47] Typically, the first-line therapy is steroids, meant to help with the swelling, pain, and tightness that patients will get lining their muscles and give them a bit more functionality and decreased pain.   [26:00] Long-term, Dr. Sims gives immunosuppressant medication. She prescribed methotrexate for Jason. In EF, the immune system is overly activated, attacking the lining of the muscles and causing the symptoms.   [26:51] If you suppress the immune system activity, that leads to decreased inflammation and symptoms in the patient. Steroid use, over a few months, is detrimental, with low bone density, weight gain, high blood pressure, and diabetes.   [27:14] Dr. Sims starts with prednisone and folds in medications like mycophenolate or methotrexate.   [27:19] Mepolizumab is an interleukin 5 blocker. Interleukin 5 is part of the immune system and is necessary for eosinophils to grow, function, and multiply. The goal of using mepolizumab is to lower the eosinophils that are contributing to the disease symptoms.   [27:48] Methotrexate, prednisone, and mepolizumab can work synergistically or independently. Most rheumatologists start with methotrexate or mycophenolate which have fewer side effects and have been around longer. We know how to manage those.   [28:08] If there is no response, we may add something like mepolizumab. As Jason was already on mepolizumab, Dr. Sims added methotrexate.   [28:20] IVIG, an infusion of immunoglobulin, has also been used as a quick way to control inflammation. It is used in other autoimmune diseases like myositis, which is inflammation of the muscle itself.   [29:08] With untreated eosinophilic fasciitis, the lining of the muscle may continue to be inflamed and can lead to fibrosis, damage that cannot be reversed. The patient can become very disabled. Contracture is one result of this.   [30:16] Jason says when he tried a new medication, he monitored if it was a good fit and if the side effects were less impactful than the underlying disease. Dr. Sims adjusted his dosages or tried to get off certain medicines as needed.   [30:59] After his muscle biopsy from his left calf, it took about a month to get back to walking easily. He was already in physical therapy, going many times for a variety of things. He had back pain, potentially related to his EF. His physical therapist was great.   [31:56] The stretches alternated between upper and lower body. Jason bought tools to do the stretches at home. When he's not feeling as well, he goes back to some of those same stretches. When he was on steroids, he took long walks to strengthen his bones.   [32:39] Jason started making phone calls to supportive family and friends on his walks and started listening to podcasts related to his condition or medications. Getting back to tennis and hiking is important to Jason. He's happy to be out there.   [33:20] Jason was open with his employer about his condition. Some of the weekly meds can make him not feel well. His employer gives him some flexibility. He has good days that far outnumber the bad days. He doesn't have to think about EF too much now.   [34:33] It's nothing like when he was in a flare, especially when he was in a flare before being diagnosed. What gets him through a bad day is giving himself some grace and understanding while he waits for his meds to catch up. He rests more than he wants to.   [35:33] Low-impact exercises like walking help Jason. He's trying to find a support network that gets EF. That led him to APFED, to find anyone experiencing something like what he was. He saw a conference that included a session on EF.   [36:09] Jason signed up for the conference and there he met Ryan's mother who has EF. They were each the first person the other had met with EF. They decided to connect after the conference. They talked on the phone for about an hour.   [36:39] She told Jason how she got into APFED and talked a lot about her son who had eosinophilic diseases. Soon after, Jason talked to Ryan as a primer for this podcast.    [38:15] Having a community to relate to, even if it's one person, is massive. It can make you feel less isolated.   [38:42] Holly says it's hard having a chronic illness. She thanks both Jason and Dr. Sims for sharing so much information and their journey and she asks for last words.   [38:58] Dr. Sims believes finding a community is critical. She interviews a lot of patients for research and isolation is a frequent theme. Even the doctor doesn't know what it's like to live with the condition you live with daily. As Jason said, give yourself grace.   [39:33] Dr. Sims tells her patients that they're different from the general population because they have to spend so much time and energy managing their condition that they can't do x, y, or z today, and that is OK. She says to stay motivated and positive.   [40:12] Find what works for you. Walking is good for your physical and mental health. Have the goal of getting back to what makes you happy. Take initiative and find non-medication ways to recuperate. You have control over ways you can feel better.   [40:43] Connect with others and share your story, like Jason did today. It may make someone's journey a little easier and make them feel less alone. Utilize your condition for good, for a bigger purpose.   [41:04] Jason had wished he could meet someone who could tell him what EF would be like over the years. He says to stay positive and find out what you have control over. Jason believes the future is bright for being able to do many things for a long time.   [42:26] For our listeners who would like to learn more about eosinophilic fasciitis, please visit APFED.org and check out the links in the shownotes.   [42:33] If you're looking to find a specialist who treats eosinophilic disorders, like Dr. Sims, you can use APFED's Specialist Finder at APFED.org/specialist.   [42:43] If you'd like to connect with others impacted by eosinophilic diseases, please join APFED's online community on the Inspire Network at APFED.org/connections/.   [42:55] Ryan thanks Jason and Dr. Sims for joining us for this excellent conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron for supporting this episode.   Mentioned in This Episode: Dr. Catherine Sims, rheumatologist Duke University Hospital Durham VA Medical Center   APFED on YouTube, Twitter, Facebook, Pinterest, Instagram Real Talk: Eosinophilic Diseases Podcast apfed.org/specialist apfed.org/connections   Education Partners: This episode of APFED's podcast is brought to you thanks to the support of Bristol Myers Squibb, GSK, Sanofi, and Regeneron.   Tweetables:   “EF patients may present with large plaques on their skin, edema of arms and legs, Raynaud's Phenomenon, contractures of arms or legs, limited mobility, or loss of the ability to do tasks they used to do.” — Dr. Catherine Sims   “Steroids are … first-line therapy. Their role is the quick control of inflammation. The goal is always to get you off steroids as soon as possible, in the safest way possible.” — Dr. Catherine Sims   “Methotrexate, prednisone, and mepolizumab can work synergistically or independently. Most rheumatologists start with methotrexate or mycophenolate which have fewer side effects and have been around longer.” — Dr. Catherine Sims   “Stay positive and find out what you have control over. The future is bright for being able to do many things for a long time.” — Jason Ingraham

On today's episode of The Wholesome Fertility Podcast, Caryn Johnson of @_bondlife shares her personal journey through infertility, detailing her struggles with unexplained infertility and the eventual discovery of autoimmune issues affecting her reproductive health. She emphasizes the importance of understanding the immune system's role in fertility and the impact of lifestyle factors such as diet, stress, and environmental toxins. Caryn advocates for women to take charge of their health by educating themselves and seeking out supportive healthcare practitioners. She also discusses her supplement line, Bond, which aims to address these issues holistically.   Takeaways   Caryn's journey began with unexplained infertility. She experienced multiple failed IVF attempts. The immune system plays a crucial role in fertility. Many women with unexplained infertility have underlying immune issues. Stress and lifestyle factors significantly impact reproductive health. Gut health is linked to fertility and autoimmune conditions. Caryn's research led her to create a supplement line, Bond. Advocacy and education are essential for women facing infertility. Environmental toxins can affect fertility outcomes. Women should empower themselves with knowledge about their health.   Guest Bio:   Caryn Johnson is the Co-Founder and CEO of BOND, an innovative line of supplements reimagining hormone and reproductive health, inspired by her experience with infertility. The former Vital Proteins Chief Marketing Officer launched BOND in the Fall of 2023, fusing her professional expertise with her passion to help women take a more proactive and empowered approach to caring for their cycle and reproductive health.   In 2017, when trying to start a family, Caryn learned she was autoimmune infertile. What she discovered was a stark reality - the lack of open conversations and support for women facing similar struggles. The doctor's office often left much unsaid, and the information available was surprisingly scarce. Shocked by the limited support system in place, Caryn recognized the need for a change. She leaned on her industry knowledge and contacts to advocate for herself and uncover invaluable resources. Her personal journey became a catalyst for a larger mission to make her learnings accessible to women everywhere. It was this experience that led her to create BOND.    A natural born innovator, Caryn is disrupting the marketplace with this new line of products that offers women the opportunity to take control of their reproductive health before it's too late. BOND's proprietary formulations, designed to preserve fertility potential and lay the foundation for a healthier body, feature science-backed ingredients that work together to balance hormones, protect egg health, and provide cycle support. With BOND, Caryn aims to address women's health more holistically and encourage a more proactive conversation around reproductive wellness.    Caryn's career began in marketing and public relations where she worked with many notable beauty brands and PR firms before being recruited as the fifth employee at then startup, Vital Proteins. She was the first marketing hire at the organization and ultimately, became the company's Chief Marketing Officer leading the team through the brand's acquisition by Nestle Health Sciences. Following her tenure at Vital Proteins, Caryn took on the challenge of leading Owlet, a baby monitor company focused on preventing SIDS, where she served as Chief Marketing Officer and successfully guided the company through its initial public offering.   Caryn lives in Chicago with her husband and two children Elijah and Ruthie.    You can use coupon code THEWHOLESOME for 20% off all products. https://bond.life       For more information about Michelle, visit: www.michelleoravitz.com   The Wholesome FertilityFacebook group is where you can find free resources and support: https://www.facebook.com/groups/2149554308396504/   Check out Michelle's Latest Book: The Way of Fertility! https://www.michelleoravitz.com/thewayoffertility   Instagram: @thewholesomelotusfertility   Facebook: https://www.facebook.com/thewholesomelotus/     Transcript:   Michelle (00:00) Welcome to the podcast, Karin.   Caryn Johnson (00:02) Thank you. Thank you for having me.   Michelle (00:05) It's so nice to meet you. And I know that you do a lot of amazing work helping women I also know that you have your own story that you can share. And I would love to hear your story and really what got you inspired to do the work that you're doing.   Caryn Johnson (00:21) Yeah, absolutely. So I'm here to share really the start of how I got to where I am today. And that really is rooted in finding out that I couldn't get pregnant. So we can start there and then we can get into all of the details together. But my husband and I met when I was young, early 20s. And by the time we got married many years later, we were already   most right away to start having a family. There was a piece of me inside that knew that I was gonna have some sort of issue. I don't know, you already mentioned that you do visualizations to me before we started. So, you know, like I just had this feeling whether I manifested it for myself or not. I, you know, we did the full year of trying to get pregnant to no success and then went back to our doctor.   Michelle (01:03) Yeah, yeah.   Caryn Johnson (01:18) my typical OB-GYN and started the path of IUIs, did four IUIs, had beautiful eggs, each IUI, and reacted to the medicine quite well, but never got a positive from any of those. So we were recommended to move towards IVF. found a reproductive endocrinologist in Chicago, which is where I was located at the time.   started the path to IVF and went through the process of an egg retrieval. Ended up seeing similar to what we saw in the IUIs, which was that my reproductive system performed quite well. And I was able, they were able to retrieve just about 30 eggs from one retrieval, which is quite high, borderline too high, but.   just shows like the reaction to the medicine and the overall viability of my reproductive system. Of that, I had really normal odds and was able to bank close to 14, I believe, quality grade embryos. So I was really excited to move into implantation because at that point,   I just really thought like whatever was unexplained is just kind of, you know, over to the side now. you know, all these things are just working out in my favor. So this is gonna be, you know, it for me, which a lot of women I feel like go into IVF feeling like the IVF center is like the place where you get your baby, which isn't always true. So.   I started doing implantations and I started losing babies. Prior to that point, I had never even tested positive in any sort of like regard for a pregnancy test. And I wasn't one of those that, you know, jumped right off birth control, you know, to move into conception. I hadn't been on birth control for many, many, many, many years, you know, prior to this point. But the implantations started failing and   My doctor said, this embryo was only attached for two hours, maybe a couple of hours is what they said. I just thought, how on earth, like why on earth would something attach for just a couple of hours and then that be the situation where   It just doesn't work out from there. Like what is happening? And you know, got immediately, the immediate response was bad odds. You know, this happens, miscarriage happens. Just keep going. You know, one in four, in eight, you you get all the stats and there's definitely a piece of that when you're not working with really good quality embryos. But you know, I was, I knew that everything was genetically great. knew.   and had no reason to believe that my body wasn't in working order to, you know, produce a pregnancy. So I just started pushing harder and getting a little bit more more fearful of continuing down the path of losing babies because I just, it hit me so hard. Even the loss of two hours, I mean,   I just like, I've never felt sorrow like that. And I didn't, I just didn't feel like myself or really anyone should have to like continue down that path for like the sake of odds. So I started doing my own research and I was at the time experiencing some issues in my digestive system. I also now looking back had a definite cortisol issue.   which relates into the picture, but I was a CMO at Vital Proteins at the time, which is that blue tub collagen company. And so I had a high stress level and I knew that something was going on in my digestive system. This was, you know, 2016, 2015, 2016, 2017. So.   Michelle (05:39) yeah.   Caryn Johnson (05:58) almost prior to when we really started, you know, as a world, as a community talking about the microbiome and gut health. But I sought out a naturopath who ended up doing a blood panel on me and told me that I had, you know, hundreds of food sensitivities, which is a   a classic sign of gut dysbiosis, but at the time it wasn't translated back to like an issue in the microbiome. It was treated as like, yes, you have all of these, you have all of these issues with, you know, different foods, just avoid them. And that will be the solve versus, why do you have like, you know, why do you have a hundred things that you can't eat?   Michelle (06:42) Hmm.   Caryn Johnson (06:46) like watermelon seeds up to your typical gluten, et cetera. So I just started doing my own research online and I found a book called, Is My Body Baby Friendly? It's written by Dr. Alan Beer, who is now deceased, but it's over 700 pages of the science of how the immune system works with your reproductive system, your hormones, et cetera.   in order to effectively procreate or in order for conception and implantation to occur. And that's when I realized there was something greater going on in my body outside again of just my reproductive system that we just hadn't figured out yet. So I read the book Front to Back. It's a very science heavy book. So I had to do a lot of like   thinking about new terms and figuring and trying to remember what I was learning. At the end of the book, there was a recommendation at the time, there are more doctors now, but at the time for three doctors that practice this type of medicine, which is the field of reproductive immunology. And so,   Michelle (08:01) Mm-hmm.   Caryn Johnson (08:03) One of those doctors, Dr. Joanne Kwok-Kam of Rosalind Franklin ended up being in my backyard essentially 45 minutes away in the Chicago area. So I took that as a sign that I needed to call and get additional help above and beyond my RE who was doing the IVF. And I called over there and was immediately put on a six month wait list.   So proceeded with the next round of IVF because I was already on some hormones. So I was already going through the round. I had at that point only done my own research. So I wasn't really sure what was going on in my body or if I could believe what I had read because my doctors that were helping me with the IVF weren't really like saying that   They believed in the immunology side of things. They hadn't seen enough research, et cetera. So I wasn't really getting support on what I was researching. So it was around the holidays, October-ish, when I ended up calling into the clinic and I ended up getting a call right around   Thanksgiving that they had a cancellation and I got moved up on the wait list. So I ended up getting into the reproductive immunology clinic many months before they said I would two weeks before my next IVF transfer and that was just an awesome Hail Mary. They did a full ultrasound. So tip to toe thyroid, you know, your whole stomach area inside and outside.   And then they do the craziest blood panel that I've ever done. don't know how you can even draw that much blood, but vials and vials of blood to look at immune markers in addition to hormone markers, vitamin markers, and your typical blood panel. And they called me back 48 hours later and said, need to cancel this implantation. You have the highest level of antibodies that we've ever seen.   not that we've ever seen, but that we're able to track. So you're past like where the chart goes essentially. So if you proceed with your implantation, it's almost definitely gonna end in a miscarriage because your body is gonna fight it off. And at that point I was terrified because that was like the first real something's actually wrong with you that I had heard.   Michelle (10:21) wow.   Wow.   Caryn Johnson (10:50) Everything else was just unexplained, unexplained, unexplained. And I just went into shock. I didn't know what to do. I didn't know who to believe. You know, I had two sets of doctors saying different things. So I proceeded with the implantation and I ended up implanting both a boy and a girl embryo. And then   started treatment right away on my immune system through the reproductive immunologist. So what they did was they put me on a series of pretty intense medications to quiet my immune system. And then I did what is called IVIG, which are blood transfusions or infusions that essentially look   to wash your blood of the antibodies that are over protecting the immune system. So I went into this protocol and I ended up getting pregnant. It was positive right away. we saw, so the clinic ended up treating me one to three times a week with this IVIG infusion, which they're about two to three hours long based on, they're based on body weight.   Michelle (11:50) Mm-hmm.   Caryn Johnson (12:14) I was in their office, you know, at least one to two times a week, also for an ultrasound. So I knew by five weeks that both embryos had attached. you know, at that point, my immune markers were even more all over the place. We couldn't get my immune system to a stable level by any means. And I ended up losing the girl embryo at seven weeks.   her heartbeat slowed and then ultimately it stopped, which is one of the symptoms or issues when you have an autoimmune issue going into a pregnancy. So, you know, that was so sad and devastating and she was higher up in the womb than the boy embryo. So at that point,   It was pretty much 50-50 odds of if she was going to end up coming out and bringing him with her or if she was going to be what's called a vanishing twin, which is when your body reabsorbs the pregnancy for the sake of the other pregnancy, which is really the best case scenario because then you don't lose the other baby.   Michelle (13:18) my gosh.   Caryn Johnson (13:36) I was put on bed rest. This was the start of my bed rest between six and seven weeks, which continued until I gave birth, basically. I was able to go to work, but that was pretty much it. And I lived in fear that we were going to lose a little boy, but I ended up reabsorbing the girl embryo. So she never came out and we just really aggressively treated my immune system.   which held on until 34 weeks when I went into basically how the immune system works during the pregnancy is during the first trimester, there is more inflammation that can be in the body and then it has to subside for the second trimester to continue successfully and then your inflammation increases and that's   eventually causes or is part of why you go into labor. But my inflammation and my immune system increased really fast. my water broke early and I ended up having him, you know, early but he was healthy because some of the immune medications included steroids. So he was a little bit bigger than, you know, your typical   34, 35 weaker. But I was able to carry my son and that really started my story of what the heck happened and why is autoimmunity so under researched when it comes to your reproduction and your fertility chances and how can I actually do more now that I have my children here.   Michelle (15:06) Mm-hmm.   Mm-hmm.   Mm-hmm.   Caryn Johnson (15:33) to support other women so they don't have to go through this amount of trauma, right? But also this amount of like research and advocacy for themselves because at the end of the day, like we just can't expect that from everyone and we shouldn't. We should be able to support. Yeah, so I'll take a breath there.   Michelle (15:40) Mm-hmm.   Yeah.   Wow, that's incredible story. And I mean, it's it's mind boggling, you know, that, nobody really talks about something that is so prevalent. And I do see that a lot, actually. And it could be the reason why you have unexplained infertility or why transfers don't work. And I speak to Amy Ralph, Amy Ralph, she's a   Caryn Johnson (16:19) Yeah.   Michelle (16:20) she does the same thing, Chinese medicine. And she talks about this a lot. She says, if you miscarry or you have repeated transfer failures with a good embryo and your doctor doesn't look into like what your lining is doing and how your immune system is working, then go to a different doctor because it's so important to look into that because you could spend so much time.   and you can spend so much money and just so many precious years going through so much loss for something that could be treated but can also be prevented. So I'd love to actually get your input on what you've discovered and how the gut relates to it but maybe other things that you've noticed or learned for the listeners.   Caryn Johnson (16:59) Absolutely.   Yeah, absolutely. And I think what you're saying is just incredibly important. Like the immune system, I feel like is the secret starting point to a lot of issues. And what's happening in medicine right now is a lot of women are walking away with an unexplained infertility diagnosis, but they're accepting that as a diagnosis, right? When it's not, it's just, it's not an answer.   And if you look underneath kind of that answer, you see a lot of crazy statistics, such as over 65 % of women who have unexplained infertility actually have an issue in their immune system. And then similarly over 60 % have an issue in their metabolic system. So blood sugar, insulin, know, early signs of PCOS, et cetera. And then.   Michelle (18:05) You   Caryn Johnson (18:10) When you look, you see that there are deep, deep nutrient deficiencies happening in this group of women as well. So you're looking at vitamin D deficiencies, vitamin B deficiencies, magnesium, omegas. All of these start with modulations that occur in the immune system as well. So when you think about it on a deeper level and from the research that I've done,   Michelle (18:23) Mm-hmm.   Mm-hmm, yeah.   Caryn Johnson (18:39) you're looking at something that's happened to you before it's affecting your hormones and triggering one of these other issues in your reproductive system. So like for instance, not only do I have, you know, autoimmune infertility, I do carry PCOS and adenomyosis as well. And for me, and based on the research that I've done, those are secondary factors.   to my immune system modulating and creating an overly inflammatory environment in my body, which then produced those issues. So we're not going up far enough in the chain of our bodies as to understanding our full systems. And again, it kind of goes back to like what's happening in medicine, which is that our doctors are   Classically trained in our reproductive organs, right? So they know our uterus they know our ovaries they understand how those work, but we need to get into you know, a new phase where we have Practitioners that understand how all of the systems are working together in our body Including our immune system and our endocrine system because they do have such a big and almost starting impact   Michelle (19:57) Mm-hmm. Yeah.   Caryn Johnson (20:07) on what's happening with our fertility.   Michelle (20:10) yeah, I completely agree. And I also I'm wondering, like, what have you seen? Because I think that when you talked about the food sensitivities, you were saying that it's okay, I'm allergic to so many things, or I'm sensitive to so many things, but why? So like, what are the things that you've seen that cause it to begin with?   Caryn Johnson (20:28) Yeah.   Yeah. So there are a couple of things that I see as a starting factors. One is overall stress. So if you can't keep your stress in check, you can't keep your cortisol levels in check, then your adrenal function will not perform in the rest of your hormones will not function correctly, which then trickles into some of these other problems. and then you get into other factors like what you're putting in your body.   the nutrition that you have or you don't have. They're saying the American diet is still between 60 and 80 % processed food. So we're putting still mostly junk into our systems that's modulating and creating these environments that we don't want. Number three is dysbiosis of the gut, right? Which is a huge factor in   Michelle (21:13) Mm-hmm.   Yeah.   Caryn Johnson (21:31) overall well-being and then your chances at fertility because what happens is that if your gut is in dysbiosis, your mucosal lining is disrupted and all of the toxins that are supposed to be in this like, think of it like pipe in your body, piped to get to the outside are now permeating that pipe and moving into your system and causing again, these major inflammation issues.   these, this uproar of immune response that is hard to counteract. You know, once you have that level of bacteria and then toxins that are entering the bloodstream. And then the last kind of reason that you would be kind of in this situation is just based on what's going on in your environment. So are you living in a city, you know,   that a lot of people in Detroit, for instance, there's a bigger rate of infertility there versus, you know, your non-city residents. It's also based on the toxins that enter your home. So are you getting rid of your plastics? Are you looking at the cleaning supplies you're using, the makeup you're putting on your face? It seems simple, but this toxic overload, again,   Michelle (22:52) Mm-hmm.   Caryn Johnson (22:55) creates this inflammatory response, which modulates your immune system. So those are really the four categories that kind of put you in this place. And then it kind of gets into epigenetics, which is like, you know, you've created this new world for yourself that your body has become. And, you know, is it going to be like that or are you going to be able to get yourself out of it?   Michelle (23:23) Yeah. my God. It's so important and it's true. We hear all the different factors and actually those toxins and the endocrine disruptors can be found in food, I mean, through pesticides and that can also impact your gut dysbiosis. so it's just, it's like an entangled web and it really is like a reflection of how we're living today and what's allowed in this country, which   Caryn Johnson (23:38) Yeah.   Yeah.   Michelle (23:50) I'm starting to get more and more frustrated with, you know, the fact that other countries are protecting their citizens more from chemicals and pesticides and things that are harming not only our health and chronic disease, also future. it's, it's unbelievable. And for that reason, I often tell people just go gluten free. It's not that.   Caryn Johnson (23:58) Yeah.   Gosh, get me started on glyphosate. It's so sad.   Mm-hmm.   Michelle (24:16) It's not that wheat is bad. And actually, as a matter of fact, a lot of people don't have those same responses if they go to Spain or Italy, even though it's not considered GMO, they have genetically modified it over the years. So there's so many aspects. So sometimes I'm just like, just remove it, And I see people feeling a lot better.   Caryn Johnson (24:26) Right.   Yeah.   Michelle (24:41) just from that, and especially with autoimmune conditions, actually that like going gluten free can really help. That's what I've seen.   Caryn Johnson (24:50) Yeah, no, definitely. It's just our food source is really sad. And it's just, it's so hard to pinpoint at the end of the day because no one really has the exact answer. But I just like, you see the data, like women who are eating on a Mediterranean diet have a lower risk of endometriosis.   Michelle (24:55) Yeah.   Mm-hmm.   Caryn Johnson (25:15) women who have like vitamin sources through green leafy vegetables don't have as much PMS. So like the correlations are there. It's just like, how do we get people to make better decisions for their body and understand like, don't be me, don't make bad decisions and then get into a position where you can't have the life that you wanted or dreamed of, or you have to fight so hard for it because   Michelle (25:16) Right.   Yes.   Mm-hmm.   Caryn Johnson (25:43) of choices you made earlier in your life from lack of knowledge, you know?   Michelle (25:47) Right. Yeah, totally. And then I also look at the nervous system, which is what you're, I feel like it's really linked to the cortisol issue, like the high stress, because we're constantly being bombarded with too much information. Really, I think too much information that our nervous system is able to translate. And I think that takes a trickle down effect into our bodies. I'm very big on like mind body because of that, you know, like that, that's one aspect, but of course, I mean, there's so many   Caryn Johnson (26:02) Mm-hmm.   Yeah.   Michelle (26:16) Like I said, it's like a web and every single piece matters. And that's what you were talking about before with medicine, looking at the body as a whole, as a functioning system, rather than just one part.   Caryn Johnson (26:21) you   Right, right. And just going back to your comment on cortisol, you know, a lot of it does start with cortisol because if you put yourself into too high of a cortisol state, your body doesn't produce enough hormones. It basically triggers all of your other hormones to act inappropriately. It goes into your progesterone receptor.   Michelle (27:00) Mm-hmm. Yeah.   Caryn Johnson (27:00) pretends it's progesterone and then it goes on your thyroid and says slow down, slow down. Your body doesn't have enough energy for this and your thyroid slows. So it's really like easy to dismiss like, yeah, I'm so stressed but I don't have to be stressed today and to understanding like if your body is in a constant state of stress, like the impact it can truly have on your system and on your hormones because   Michelle (27:27) Mm-hmm.   Caryn Johnson (27:30) I guess also people think of like cortisol is like over here and then estrogen and progesterone as like over here because they work through different axes of the body, right? But it's all related because if you knock one off, you're messing with the others. So I just, I wish people ultimately would understand that cortisol is a huge starting factor to their fertility journey as well.   Michelle (27:38) Mm-hmm.   Right. Yes.   Caryn Johnson (27:57) and to a hormone journey if they're not on the road to fertility.   Michelle (28:02) Yes, because ultimately the body's always going to favor survival. And when you're in high cortisol, your body's basically or something is signaling your body to let it know it's not safe. So when you're constantly in this state of feeling unsafe, your body's going to worry about other things and put off other factors that it would normally pay attention to when you do feel safe.   Caryn Johnson (28:08) Yeah.   Right.   Michelle (28:32) And being in this chronically is just not conducive to high vitality period.   Caryn Johnson (28:32) Right.   Yeah, I feel like at least we're in a better state of mind, like as a world where, you know, 10 years ago it was chic and cool to be like chronically stressed and like drinking like three cups of coffee in the morning and like running yourself ragged. Like I feel like everyone understands a little bit more that they shouldn't. It's just about like knowing your body and actually being able to say to yourself like, no, this isn't how I should.   Michelle (28:52) It's true. Yeah, that's a good point. Yeah.   Caryn Johnson (29:09) be feeling. This isn't how I want to keep stress or maintain like my day-to-day life.   Michelle (29:17) No doubt that we are getting educated like never before. like, it's, it's one of those things that when like the information comes out and we start to open our eyes, it's painful because we're realizing things that are not working. However, even though it's painful, it's actually helping us in the long run. And it's kind of like the, blessing and the curse of social media and all of the technology, but the blessing is information.   Caryn Johnson (29:28) Right.   Yeah.   Michelle (29:45) that is very important for us to know it's important for us to receive. So that aspect of it is really important. And then talk to us about your supplement product bond. And I know that you created that based on really your own frustration and it's become your baby. And I want to know what specifically or how does that address autoimmunity conditions for people who are going through that or?   Caryn Johnson (30:03) Yeah.   Michelle (30:14) least thinking maybe to look into their immunity in regards to their fertility, listening to this.   Caryn Johnson (30:21) Yeah, absolutely. So I launched Bond just about a year ago. I concepted it. took a year prior to that from concept to launch.   So really it started in the world of advocacy for me. I was just really looking to help other women getting involved in some Facebook groups, some communities. you know, there's not a lot of knowledge, a lot of people talking about this yet. There certainly wasn't, you know, even just a few years ago. so I, I took a speaking opportunity in Detroit and   I went to Wayne State University, which is where they do a lot of the research for autoimmune infertility. the main head of that clinic asked me to come and speak to the researchers because they do all of this research and it's isolated into their facility. They don't actually see the impact of what's going on with women who are going through this.   Michelle (31:24) Mm-hmm.   Caryn Johnson (31:25) so I got to share my story and, you know, had a really nice day there learning and seeing their facility, their lab, what's going on. And on the drive home is really when it clicked for me that there's a lack of, or there's a gap in what's going on research wise and, know, what's being discussed and what's being carried out and brought to.   the consumer or the public's attention. And I just felt like if I didn't take a larger stand to do something bigger to help women, that we'd be many, many more years behind even. So I went back to my house in Chicago, sat in my basement and did just clinical research for months. And I logged over 300 clinical studies, all centered around   the immune system and how it relates to hormones to the reproductive system and built my thinking for original skews, which were, which are daily balance, which is our best seller conception boost, vitality, and cycle care on this thinking first. so it really started with research before it was brought forward to healthcare practitioners and then formulated out.   And a lot of the research that went into each of the products is above and beyond supporting the reproductive organs. So when you look at daily balance as a whole, it has 15 vitamins and nutrients in it. And a lot of those vitamins and nutrients were chosen to not only support hormone balance, but to take that up a level and to support the immune system as it relates to being a predecessor to hormone balance. So   adding a vitamin D, which is a huge hormone regulator, putting fiber, five grams of it into a supplement so that women are potentially protecting their gut lining better and producing those short chain fatty acids that are going to protect their gut in a way that just probiotics don't. Adding in a probiotic blend that   we studied as being healthy strains, or not healthy strains, but strains from healthy fertile women. So really focusing on these immune factors and how they pull into the world of fertility. But to the public now, you know, almost simplifying that message and making it more of like the underlying theme because we're still not necessarily totally there.   so the ingredients exists in these formulas with so much thinking and thought as it relates to the whole body. and then the formulas come out and, they're focused on hormone balance, right? As well as we have a conception product, and then we have our cycle care product, which is focused on, PMS support. So PMS, symptom alleviation, and then hormone detoxification.   Michelle (34:16) Mm-hmm.   Caryn Johnson (34:44) So they all have an immune angle, also address a hormonal need.  And the other great thing too is that you can shop at a discount as a special thanks for listening to us here. You can head over to the link. We'll link it here with this podcast episode and use the code, the wholesome to get 20 % off your order.     Michelle (34:54) Awesome. And do you have information on your site, just like support for people wanting to learn more?   Caryn Johnson (35:00) Yeah.   Yeah, absolutely. we're starting to add more and more to our site. I wrote a white paper on how the microbiome affects fertility that you can download off of our website as well to get more information. And yeah, we share a lot on social too with, you know, article connections there. So that's another great way to keep up with kind of like up and coming research that we're seeing.   Michelle (35:32) Mm-hmm.   Caryn Johnson (35:33) But yeah, I would say too, just going back to one other thing you mentioned earlier on the, on the doctor front, the best thing to do as a consumer, like when you're hitting these issues is to bring the articles in and show them to your doctor and choose advocacy for yourself. Because I found that the response from them is far greater when you have data in your hands as to why you want to.   Michelle (35:51) Mm-hmm.   Yeah.   Caryn Johnson (36:03) add a supplement, think about a different form of medication, think about a different program that might make sense for your system. So I would say, you know, that is as important as ever. And, you know, what we try to do more and more is link that PIMD article, like when we post something so that you can find the actual source and see for yourself, you know?   Michelle (36:24) Mm-hmm. Yeah.   Caryn Johnson (36:31) read the information and make smart decisions.   Michelle (36:31) Mm-hmm.   I love that. That's great. I'm all about empowerment. think that we need a lot of that now. So this is great information. I really appreciate you sharing your story for people listening. And for people who want to find you and learn more, how can they find you?   Caryn Johnson (36:41) Yeah.   Thank   Sure, so our website is bond.life. Our Instagram is underscore bond life and we're, you know, a newer company. I'm still really involved on our social. So we love to take DMs and interact with people one-on-one that way. If you have any questions or want to get into, you know, what you might be experiencing and what our different products are, like we're happy to get into it with you and.   I will say for anyone that wants to shop on bond on our website, absolutely love to support you. And again, really the place to start with, with us is our daily balance product. has the baseline of nutritionals you need to support your   nutrients stores, your hormonal balance, and of course, your immune system. that is our purple bag on the website there. But Michelle, thank you so much for having me. I really appreciate this opportunity.   Michelle (37:57) Yeah, it was great having you on and having this conversation, which I feel like is so important because it is kind of like the big question mark that a lot of people are facing when they're trying to conceive. So thank you so much for coming on.   Caryn Johnson (38:09) Yeah, you're welcome.        

In this episode I explore the autoimmune neurological disorder, myasthenia gravis. I review its classical manifestations as ocular and generalised myasthenia, and I highlight its complications such as refractory myasthenia and myasthenic crisis.The podcast also discusses the pathogenesis and triggers of the disease, its various mimics, and its indispensable investigations. I also review its treatments which include acetylcholine esterase inhibitors, steroids, immunosuppressants, IVIg and plasma exchange.I complement the podcast with historical anecdotes regarding the discoveries, frequently serendipitous, of the various treatments of myasthenia gravis. This narrative includes such stories as Mary Walker's miracle of Alfege's, the dream insight of Otto Loewi, the mystery of the headless torso in the Thames, and the role played by the Calabar bean in the history of myasthenia gravis. Other relevant historical themes were the role played by Alfred Blalock in introducing thymectomy for myasthenia gravis, and the first serendipitous self-treatment of myasthenia gravis by medical student Harriet Edgeworth.I rely on such illustrative patient memoirs as those of Kemi Olawaiye-Dampson titled Living with Myasthenia Gravis, of Howard Caras titled Permanent Detour, and of Ronald Henderson titled Attacking Myasthenia Gravis.I also cited such enlightening academic sources as Coping with Myasthenia Gravis, by Aziz Shaibani and colleagues, and The Spark of Life by Frances Ashcroft.

   Slam the Gavel welcomes Carrie Haight, a licensed therapist of 20 years to the podcast. Her story began in November of 2021 when her daughter's leg swelled out of no where. At the time it appeared like maybe she just got a small injury from new sports equipment, but that wasn't the case.     Her daughter began having more symptoms of swelling and severe pain in both legs, extreme migraines, constant vomiting, couldn't fight any virus or infection, fatigue and many more symptoms that made no sense at the time. Sadly, due to a false call to CPS, which led to nearly 2 years of knowingly false accusations and court orders that refused her to see a doctor.     In May of 2023, all was cleared, but her daughter was still not any better and she was getting worse. The legal fees alone were enough to break a two income household, but Carrie's daughter only has her mother. She is her MIRACLE child from an anonymous IVF donor.     In August of 2023 she saw her Rheumatologist who she hadn't seen in a very long time, due to court orders, who finally figured this out, but she also figured out there was more than just what she could diagnose and help treat. This was not Munchausen By Proxy as CPS was trying to label her with.    Carrie's daughter was diagnosed with AMPS (it is basically a wider spread version of Chronic Regional Pain Syndrome), but that wasn't explaining why she was constantly catching everything she came in contact with, but worse than an average healthy child. Her daughter has a permanent compromised immune system. She has a low Immunoglobulin M, which can't be treated any other way than monthly IVIG or a subcutaneous version of IVIG, given weekly. This is a treatment that she will need for the rest of her life.     Carrie thought she had great medical insurance, but she was wrong. Insurance will not cover the cost of an intensive outpatient that would be holistic approach as she's only 10 and the medications used are too dangerous, or the cost of a nurse to administer the IVIG.     Finally figuring this out, but not before they lost everything financially to fight the false allegation (and these treatments are ridiculously expensive).      Losing 2 years of being able to be a child, was just not right. Carrie is working 3 jobs, and it is still not helping to dent the bills so she can at least be around other children so she can socialize and play. Carrie having MS herself, was wearing herself so thin she feared that she won't be able to keep up with her daughter's needs if she doesn't slow down even a little.      Carrie will continue to advocate for others and in the future, run for Senate. To Reach Carrie Haight:  dismantlingfamilycourtcorruption.com******** Supportshow(https://www.buymeacoffee.com/maryannpetri)Maryann Petri: dismantlingfamilycourtcorruption.comhttps://www.tiktok.com/@maryannpetriFacebook:  https://www.youtube.com/@slamthegavelpodcasthostmar5536Instagram: Support the showSupportshow(https://www.buymeacoffee.com/maryannpetri)http://www.dismantlingfamilycourtcorruption.com/

In this comprehensive discussion, four prominent neuromuscular experts—Drs. Bhaskar Roy, Jeff Allen, Diana Castro, and Luis Querol—explore recent developments in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). The conversation centers on the new European Academy of Neurology and Peripheral Nerve Society guidelines, highlighting significant changes in diagnostic criteria and disease classification. The experts discuss the challenges of diagnosing CIDP, particularly in pediatric cases and variant forms, while emphasizing the importance of proper electrodiagnostic testing and the role of supportive criteria like CSF studies and MRI. They delve into the emerging field of autoimmune neuropathies and the significance of specific antibody testing. The podcast concludes with a discussion of treatment options, including traditional approaches (IVIG, corticosteroids, plasmapheresis) and newer therapies such as FcRn inhibitors and complement-targeting drugs, while also addressing the controversial role of rituximab in CIDP treatment. Throughout the discussion, the experts stress the importance of regular diagnostic reassessment and the need for more personalized treatment approaches based on patient profiles.

Lyme and PANS: A Critical Connection in TeenagersAt just 16, my patient found herself facing a complex and overwhelming set of symptoms. What began as ordinary teenage stress evolved into something far more debilitating—raging outbursts, severe compulsions, motor and vocal tics, and memory problems. Her academic performance plummeted, and her social life disintegrated. Diagnosed with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), she and her family embarked on a challenging journey for answers.PANS, a condition characterized by the sudden onset of severe neuropsychiatric symptoms, is often triggered by infections or autoimmune responses. These symptoms include obsessive-compulsive behaviors, severe anxiety, and a wide array of neurological issues. In my patient's case, the impact was profound, disrupting nearly every aspect of her life.A Frustrating Treatment JourneyHer school quickly implemented a 504 plan to accommodate her needs, but even with these supports, she struggled to attend classes regularly. The academic gaps widened, and the isolation grew. Initially, her treatment focused on intravenous immunoglobulin (IVIG) therapy, a standard approach for PANS aimed at modulating the immune system. Unfortunately, despite several courses of IVIG, her symptoms persisted, leading to a sense of despair for both her and her family.The Lyme Disease ConnectionIt wasn't until the family explored further that they discovered a potential link between Lyme disease and PANS. Lyme disease, transmitted by ticks and caused by the Borrelia burgdorferi bacterium, is notorious for its wide range of symptoms, many of which can overlap with neuropsychiatric disorders. When Lyme disease enters the picture, it can trigger or exacerbate PANS, leading to an even more complicated clinical scenario.Upon testing, my patient was diagnosed with Lyme disease and a co-infection, which had gone undetected. The realization that these infections were contributing to her PANS symptoms was a breakthrough. She began antibiotic therapy, which is often essential in treating Lyme disease, especially when co-infections are involved. Over time, this approach started to pay off—her symptoms gradually improved, the rage outbursts and compulsions became less frequent, and her cognitive function began to recover. 

On today's episode of The Wholesome Fertility Podcast, I speak to longevity expert Leslie Kenny. @lesliesnewprime   Leslie shares her personal journey of overcoming autoimmune diseases and infertility through patient empowerment and alternative therapies. She emphasizes the importance of partnering with doctors and exploring alternative treatments that resonate with individuals. Leslie's story highlights the power of lifestyle changes, such as an anti-inflammatory diet and the use of anti-aging molecules like spermidine in improving health and reversing the aging process.    Our conversation covers the topic of spermidine and its role in healthy aging. Spermidine is a compound found in our diet and produced by our gut biome. It is correlated with healthy lifespan and can be obtained from plants and fermented foods. Our conversation also touches on gluten-free options for spermidine, the importance of fiber in the diet, and the potential benefits of systemic enzymes.    Leslie also shared her personal experience with hypothyroidism and the importance of finding a doctor who will help you uncover solutions for your reproductive health.    Podcast Takeaways: Partnering with doctors and exploring alternative treatments can empower patients to take control of their health. Lifestyle changes, such as an anti-inflammatory diet, can have a significant impact on autoimmune diseases and overall health. Anti-aging molecules like spermidine and rapamycin have the potential to slow down the aging process and improve fertility. Maintaining a balanced hormonal system is crucial for reproductive health and overall well-being. Spermidine can promote cell renewal and recycling. Spermidine is correlated with healthy lifespan and can be obtained from plants and fermented foods. Fiber is important for the gut biome to produce spermidine. Finding a doctor who believes in you and is willing to explore your symptoms is crucial.   Guest Bio:   Leslie is a longevity expert, and co-founder of the prestigious Oxford Longevity Project, a non-profit that brings scientists together to discuss breakthroughs around the science of ageing and autophagy, which is our body's natural cell recycling system.   www.oxfordhealthspan.com - Use coupon code WHOLESOMELOTUS for 15% off all items!   https://www.instagram.com/lesliesnewprime/ https://oxfordlongevityproject.org       Learn more about my new book “The Way of Fertility” here: https://www.michelleoravitz.com/thewayoffertility   For more information about Michelle, visit: www.michelleoravitz.com   The Wholesome FertilityFacebook group is where you can find free resources and support:   https://www.facebook.com/groups/2149554308396504/   Instagram: @thewholesomelotusfertility   Facebook: https://www.facebook.com/thewholesomelotus/     Transcript:   Michelle (00:00) Welcome to the podcast Leslie.   Leslie Kenny Oxford Healthspan (00:02) Thanks so much for having me, Michelle. It's a pleasure.   Michelle (00:05) So I would love for you to share your story of how you got into the work that you do today. And I know that you're very passionate. We just had a little pre -talk and I'm very excited to get started.   Leslie Kenny Oxford Healthspan (00:14) You   Well, my story is one of patient empowerment, just like you. And it started, as it can with many women, with a fertility quest. So in my mid to late 30s, I really wanted to have a baby and found that I was having problems. So started with IUI, did three of those, didn't work, and then moved on to IVF.   And it was as I was doing my fifth IVF round with donor eggs, I might add, and being mixed race, I'll tell you, it's not easy to find a donor, you know? And it was a high stakes game, as it were. And right before embryo transfer, I began to notice pain in my hands. I was having trouble.   Michelle (00:54) Mm   Leslie Kenny Oxford Healthspan (01:08) using scissors, turning doorknobs, turning faucets. And I just thought, strange, I think this is probably what arthritis feels like. I better just have it checked out since obviously I want this IVF with donor eggs to go perfectly. And I went to the doctor, she ran some tests. I thought, you know, they'd say, you know, it's something, have steroids do something that I'd heard of before. And instead she called me and asked me to have a meeting with her in her office.   Michelle (01:17) Mm   Leslie Kenny Oxford Healthspan (01:38) and always a bad sign, right? If they can't explain it to you over the phone, and if it's not the nurse telling you, there's nothing to worry about. So I went and talked to her and she said, you do have arthritis, it's rheumatoid arthritis. This is where your body is attacking your joints. And here are some pre -filled syringes that you can inject into your belly, they're immune suppressants to basically   Michelle (01:40) Yeah.   Leslie Kenny Oxford Healthspan (02:08) halt your immune system from attacking your body. And, and I immediately said, Hmm, don't I want my immune system to be strong? Like, don't I need that? And she said, well, normally you would, but in this case, it looks like your body is fighting cancer, except you're trying to destroy your own tissues. So I thought, okay, well, fine. Got the drugs. these are tiny diabetic needles. It'll be okay.   And then she said, but you also have something else. You have lupus. And that I'd never heard of. It was almost as if she'd said, you you have funny tree disease or something. It just made no sense to me. I didn't know what it was, had never heard of it. And I said, what's that? And she said, another autoimmune disease. And I said, okay, so what's the prescription for that?   And she said, unfortunately, there isn't a prescription for that. There's really nothing that we have right now to treat it. And you will slowly and progressively get worse. And I said, this is really not a good time for me to have this happen because I'm doing my fifth IVF with donor eggs. I'm waiting for embryo transfer. This is a terrible time. Can't we do something?   something else, anything else? Is there anything I can do? No, there's nothing you can do. Like, could I do my diet, my sleep? No, there's nothing you can do. Well, but what about this round? You know, I've done a lot to tee this up and a lot of money has gone into this. As you probably know, I've put in over a hundred thousand US dollars at this point in time into all of these treatments. And she said, I wouldn't do it. Don't do it.   you have a good five years left. And I thought, okay, well, that's a big statement to make. And I was so gobsmacked by it.   Michelle (04:08) That's crazy.   Wait, wait, She was saying you have five years left to live? Is that what she was saying?   Leslie Kenny Oxford Healthspan (04:16) That's how I interpreted it. That's how I interpreted that if I, if this was successful, if this round was successful, I would only be able to parent this child for five years or four years, I guess, as it were. And I, it was a lot to process. you know, if you're a patient and you're told you have one thing that's a lot to take on, you know, and then you're thinking about.   the treatment protocol and the things you have to do. And I think already, if it's not a tablet to swallow, but you're injecting yourself, that's another big thing to take on board. Then an illness that you've never heard of before where they say there's no treatment, there's no cure, and then she says five years left. I'm thinking in the back of my mind, thinking, have this, I want to become a mother. I have this.   cycle I have to go through, we're going to embryo transfer. My uterus has to be in good shape. What are you doing? What are you saying? How does this impact that? Because I've got acupunctures lined up for embryo transfer, right, before and after. And so I did have at least the presence of mind to say to her, can I, well, could this be a false positive? She said, no, we've done multiple types of tests.   Michelle (05:11) Yeah.   Leslie Kenny Oxford Healthspan (05:35) and they all come back consistently indicating that you have these diseases. So then I said, can I test again? And she said, she shrugged her shoulders and said, sure, it's your insurance. So I vowed then and there that I would test again. And in the meantime, I would do everything possible. didn't matter what it was, whether it was my in uterine massage, which I did, or visualization, which I did.   Michelle (06:00) Mm -hmm.   Leslie Kenny Oxford Healthspan (06:05) or trauma work, which I did, or, you know, new therapy, intravenous immunoglobulin transfusions, which I did, an anti-inflammatory diet. I was gonna do it all. I was gonna throw the kitchen sink at it. And any woman who is trying to get pregnant knows exactly where I was and that feeling of, I've gotta make this happen. And I will just pull out all the stops. We're doing a full court press, right? And...   And so I did all those things and I came back within six months for a regular sort of review with your doctor. She opened the folder and she clearly not looked at the results ahead of time. And she said, well, look at that. You, don't have lupus and you don't have RA. And I said, would you like to know what I did? And she said, no, that's okay.   Michelle (06:54) What?   Leslie Kenny Oxford Healthspan (07:04) And I said, well, that is, you know, that's pretty, that's pretty groundbreaking, right?   Michelle (07:11) Yeah,   Leslie Kenny Oxford Healthspan (07:12) so in any event, I was so, I was so shocked by all of this and, really for me, the penny dropped that doctors don't know everything that we treat them as if they must, that they are the Oracle and that they are the, the guide to whom we can outsource our health problems.   Michelle (07:23) Mm   Leslie Kenny Oxford Healthspan (07:35) But in fact, we have to work in partnership with them. And sometimes they're not willing for insurance or liability reasons to talk about or consider alternative therapies that might work. But we patients have the opportunity to explore those things that resonate with us that might have a meaningful impact. so my journey has really begun   Michelle (07:38) Yes.   Mm   Leslie Kenny Oxford Healthspan (08:04) as a patient advocate, really telling other women, you have more power than you think to move the needle on your health. And as a matter of fact, the things that you do might even be more important than what happens when you go to your acute care doctor, right? When you go into the doctor's office or into a hospital. And it has then...   taken me on a journey all the way to Oxford, England, where I ended up meeting a wonderful group of scientists here, a number of whom I helped fundraise for their companies for, all in the regenerative medicine space, and some of whom I've worked on longevity, healthy longevity advocacy.   other scientists whom I've worked on to bring an interesting anti -aging molecule called spermidine to market. So those are the...   Michelle (09:04) Yes. Is that, that's, that comes from   Leslie Kenny Oxford Healthspan (09:10) We can get it from wheat germ. We can get it from mushrooms. can get it from a huge variety of foods that are all plants. Essentially, if you want spermidine, it's almost exclusively in plants. only animal source is chicken liver, which is ironic because, of course, I remember my mother saying, you have to eat chicken liver. So moms do know, right? They've got a wisdom.   Michelle (09:19) Mm   Mm -hmm.   Yes.   Leslie Kenny Oxford Healthspan (09:36) But it comes from plant sources. We also make it in our tissues. We moms make it in our breast milk. When we give it to our babies, it's there to help them grow. Men, of course, make it in their seminal fluid. is in there because DNA wraps itself around spermidine. And it's very tightly wound.   Michelle (10:00) Mm   Leslie Kenny Oxford Healthspan (10:04) Normally DNA is wrapped around something called histone bond. It's too big to really fit into semen. And it's also there in semen as an anti -inflammatory because it turns out that when men make sperm, it's a high reactive oxygen species event. Women and men can both make it in our gut biome as well. so those would be the main, the three sources would be from our tissue production.   Michelle (10:27) Mm   Leslie Kenny Oxford Healthspan (10:33) And that falls, that declines dramatically similar to the decline in production of estradiol, progesterone, testosterone, melatonin as we get older. And then the second area is the microbiome and then third is from our food.   Michelle (10:51) So interesting. So let's go back and talk about what, what do you think it was specifically that changed? Like, what do you think happened with your body? Because you came into the doctor and you had all the signs that showed that you had two different autoimmune diseases that she could pick up. And then you changed your diet, you changed your lifestyle. You really went through so much. and of course it's hard sometimes to figure out exactly what specifically, but now that you know what you know, and this is   Leslie Kenny Oxford Healthspan (11:03) Yeah.   Yum, yum.   Michelle (11:21) the work that you're doing. What are some of the things that come to mind?   Leslie Kenny Oxford Healthspan (11:22) Hmm.   I went on an anti -inflammatory diet. So one of the first things I did was I researched a lot about both of these illnesses and I could see that inflammation was part of the root cause. And I'd heard about a diet called the Zone Anti -inflammatory Diet. This was popular in the early 2000s. And so I did that and that had a high emphasis on omega -3fatty acids.   on extra virgin olive oil. These are anti -inflammatories. It had a high emphasis on plants. And so my diet changed dramatically from more meat and charcuterie, sort of salami, these types of things over to plants. I also eliminated things which were known to be inflammatory triggers for me. So I had an allergy test done.   I could see that dairy was a problem, gluten was a problem, eggs happened to be a problem, which was a shame because I loved eggs. But we can't eat them every day and think the body won't notice. We have to kind of mix it up and have a diverse diet. So I essentially removed the inflammatory triggers to the immune system. I added in things that were naturally anti -inflammatory, like the omega -3s. And at the same time, when I did the intravenous immunoglobulin,   Michelle (12:44) you   Leslie Kenny Oxford Healthspan (12:50) I reset my immune system and there were studies in, there were small groups of patients with both rheumatoid arthritis and lupus who had done IVIG already in 2004 when I was diagnosed and I could see it work for them and I sort of felt like I have nothing to lose. It's kind of this or I wait for the inevitable.   And I did have people tell me, don't do the IVIG, because this was the time of mad cow disease. And people were quite concerned about prions, these proteins in blood plasma. And they were worried that you might be able to get that or hepatitis C. These were things that had been transmitted through transfusion products previously. But I still felt that, what, five years?   Michelle (13:25) Mm   Leslie Kenny Oxford Healthspan (13:49) I have nothing to lose. So I'm so glad that I did do that. know that everyone has to weigh up the risk -benefit analysis of any new treatment and their own situation. But for me, that was a decision that I made, and I'm so glad I did, because I spent 20, my insurance company spent $24 ,000 US on two transfusions, eight hours in total. And I have   Michelle (13:52) Mm   Leslie Kenny Oxford Healthspan (14:19) Going into remission meant that I have foregone over a million US dollars worth of immune suppressing drugs or chemo drugs because often we autoimmune patients get moved on to methotrexate, which is a chemo drug. I've not had to do any of those over these 20 years. And of course, I also don't live in pain and I don't.   Michelle (14:29) Mm Right.   Leslie Kenny Oxford Healthspan (14:45) live in fear of because I'm suppressing my immune system, I have to avoid social situations where people might have a cold and give it to me and compromise my immune system. So it was a fantastic outcome for me. It's not one I think a lot of people hear about, but I think they should.   Michelle (15:06) for sure. I mean, it's good to hear everything. And I agree with you that everybody has to really assess their own personal situation. I think, I believe in the innate intuition that's kind of like our body's intelligence speaking to us, just like it does when we have an allergy or we feel some things off when we eat something. So I think that that is a really important component to that. And it's the thing that spoke to you when you were at your doctor's office, because it,   Leslie Kenny Oxford Healthspan (15:20) Yeah, agreed.   Yeah.   Michelle (15:36) You could have just said, okay, I'm going to completely bypass any questions that I have and fully just accept everything that I'm given. But something inside of you said, wait, hold up. Let me just do this again. Let me look at this. me think about this. So I really believe in that. think that is so important and important for people to hear because so often we do that. We bypass our own internal judgment and knowing.   You said something important is partnering up with your provider so that it's not an all or nothing. Of course you're going to utilize and you did, you got benefit from getting those tests because that woke you up to doing so many new and amazing things in your own life and implementing a better diet and so on. As far as Omega -3 goes, this is just something that I've been hearing of late.   that some of the supplements go rancid and that it makes it worse. it, have you heard about that?   Leslie Kenny Oxford Healthspan (16:36) Yeah, I've heard that. Yeah, and apparently what you need to do is take this supplement and put it into the freezer. And if it gets cloudy, that is what I've heard is that then that's not good. It's supposed to remain clear throughout. I'm not an omega -3 fatty acid expert. I have lived for a number of years, very nearby one here in Oxford, Professor John Stein.   Michelle (16:45) Mm   Leslie Kenny Oxford Healthspan (17:05) who's done a lot of the research on mental health issues and omega -3s and how important they are for brain health. But yeah, I think, you know, get it from your diet first and foremost. Fatty fish is a great source, right? Yeah. Salmon, if we, you haven't already eaten all of it. Yeah.   Michelle (17:18) Right. Good fish. Yeah.   Wild caught, yeah. Yeah, I know. It's so crazy. Well, also just the mercury in some of the salmon, you know, the chemicals, but wild caught, I always say just.   Leslie Kenny Oxford Healthspan (17:33) Yeah, wild caught. Yeah. And also anchovies, mackerel, sardines, right? The small fish are a really good source of omega -3 fatty acids. And those tend not to have the mercury. Obviously, if we're trying to get pregnant, mercury, definitely not your friend. So yeah.   Michelle (17:38) Sardines, yeah.   Yeah.   Yeah, for sure. I always say, you know, if you're not going to have it when you're pregnant and if you don't have it when you're trying to get pregnant because tuna, for example, they always caution not to have that because of the high mercury, but you don't want that in your system if you're trying to conceive. So for I was very intrigued by your story and I was also intrigued by what you do because when you think about egg quality, sperm quality and really reproduction,   Leslie Kenny Oxford Healthspan (18:02) Yum. Yum.   Hmm.   Michelle (18:18) you think anti -aging, that's like ultimately anti -aging in a nutshell. Like that's really what I do for people that I work with. And it benefits me because I'm like, okay, you know, I'm just going to apply a lot of these things as I learn. it definitely, but that's what it is. It's anti -aging. Like I'm big on meditation, which has also been shown take our clocks back, but food and diet and certain supplements,   Leslie Kenny Oxford Healthspan (18:20) Mm -hmm. 100%. Yeah.   Yeah. Yeah.   Michelle (18:46) can actually shift and slow down your aging or sometimes even like reverse your biological clock. And I know you're the expert in this specific topic. So I'd love for you to talk about that and what has been discovered and seen in this subject.   Leslie Kenny Oxford Healthspan (18:57) Sure.   So when we are at our peak health is when we are reproductively capable. And we visually know this when we go out and we see a woman with glossy long hair, with long eyelashes, with healthy radiant skin, of healthy body weight, we know that that is someone who is   who is really attractive and why are they attractive? Because they are at their reproductive height. And interestingly, all of the things I have described are also linked with your spermidine levels. And so that's quite interesting. But also, your hormones are in perfect balance when you can reproduce and that includes not just the usual female sex hormones,   Michelle (19:36) Mm   Mmm.   Leslie Kenny Oxford Healthspan (20:01) but also your thyroid hormones. So I'm also a Hashimoto's survivor as well. And so I'm a hypothyroid patient and that is also really important. So it's got to be in perfect balance then. And one of the things that happens with some of these anti -aging molecules is that they extend fertility.   Michelle (20:07) Mm   Mm   Leslie Kenny Oxford Healthspan (20:28) partly by reversing your age, but they will start the reproductive cycle back up for some people. And it kind of depends how far away from menopause you are. But we've certainly had clients who've said, what happened? I've been in menopause for two years and I've gotten my cycle back. And...   On the one hand, want to say, congratulations, that's great. But they're thinking, this means I can't wear white trousers now, right? And I thought I was done with the pads and the tampons. So I know it's a little bit of a double -edged sword. We women are often thinking about, how do we get rid of our cycles? But in fact, they are nature's way of saying that we are in peak health and are capable of bringing another life into this world.   Michelle (20:55) Hahaha   Yeah.   Leslie Kenny Oxford Healthspan (21:22) You know, we do have to bear that in mind. Of course, the same is true for men. And we know there's a problem with testosterone declining in young men, whether it's due to endocrine disruptors in our food and our water supply, toxins in the air. There is a challenge to men as well. And we do want to see them at their reproductive best in order to be at optimum health, too.   And that is also something that these geroprotectors, these senolytic drugs, these anti -aging molecules can do. They seem to restore fertility in men as well as women.   Michelle (22:03) Amazing. And so let's break it down for people who have never heard of these molecules and these supplements and spermidine. So take a step by step, like, so that people listening can understand what it is.   Leslie Kenny Oxford Healthspan (22:07) Yeah.   Sure. OK. Well, first, me just say that there are scientists believe that there are 12 reasons why we get older. And these are known as the hallmarks of aging. And they include things that you and your listeners will have heard of before, things like inflammation, leaky gut, stem cell exhaustion or dysfunction, mitochondrial dysfunction.   So, you know, where you have no energy. Telomere shortening. So telomeres are at our in caps and they limit the number of times that we can replicate ourselves. So all of these reasons why we get older, scientists have looked at different molecules that can inhibit those, you know, us going down those pathways. And they have a list of these molecules that   inhibit certain numbers of molecules. And the two that do the most are one called rapamycin, which is a bacteria, and the other one is spermidine, which we manufacture ourselves, like I said, in our gut, in our tissues, and also we get from food. But importantly, it is found in both breast milk and in sperm, and it's so necessary for the survival   the start and survival of the next generation, that it's also in the endosperm of all plants. So these two molecules, rapamycin and spermidine are kind of the darlings of the anti -aging set. And one of spermidine's superhero powers is that it activates cell renewal and recycling.   So if we think about staying in perfect health, one of the first things we want to do is make sure that we can do is every day oven cleaning, right? And the cells do have that function. Maintenance, exactly, exactly. Now, when we're young, it happens naturally and we don't think anything of it, but as we begin to age, that process falters and the cells, the dysfunctional cells,   Michelle (24:16) Mm -hmm. It's a maintenance.   Leslie Kenny Oxford Healthspan (24:32) which we call senescent cells, they begin to stack up. And the more of these senescent or zombie cells that we have, the less well the other cells function. And I sometimes say that these zombie cells are a bit like your uncle Ted who has too much to drink at a wedding, and he begins to say inappropriate things.   Michelle (24:45) Mm   you   Leslie Kenny Oxford Healthspan (24:56) and do really silly stunts and you just think, okay, we got to get Ted over with pot of coffee in the corner away from everybody else or he's going to ruin the party for everyone else. This is what senescent cells do to you. You have one senescent cell and it begins to leak inflammatory contents to the other cells nearby and zombie -izes them and does the same to the other cells. It's a cascade effect.   Michelle (25:09) Mm.   Leslie Kenny Oxford Healthspan (25:25) That is what spermidine can actually, one of the things it can help with in particular with immune cells, it can prevent those immune cells, well rather it can rejuvenate senescent immune cells and that is the work that was done at the University of Oxford.   Michelle (25:43) That's amazing. you moved there to work with them in the research?   Leslie Kenny Oxford Healthspan (25:48) Well, I came here anyway. I came here because my ex, now sadly my ex, but we have two wonderful children together. He was from Oxford and moved here to be closer to his family and still close to them and absolutely fell in love with the town and just the vibe. University towns are definitely my kind of place.   Michelle (26:09) Hmm. That's nice.   Mm   Leslie Kenny Oxford Healthspan (26:18) Just the scientific rigor here in the life sciences, it's phenomenal. It's really impressive.   Michelle (26:29) That's amazing. so the two things you're saying are spermidine and rapamycin. and so spermidine is something that you could take from supplements, but not so much rapamycin.   Leslie Kenny Oxford Healthspan (26:39) You can't, no, not rapamycin, no. It's not something you're going to find in food. So it was basically isolated on Rapa Nui, which is one of the Eastern islands. And one of the pharmaceutical company, a researcher basically took it back home to the United States and it was later researched and found to do.   some really amazing things, one of which is that it can suppress the immune system. And this is important for people who have organ transplants because the tissue match is not perfect and their bodies necessarily want to reject any foreign material in their bodies. So if you give these patients immune suppressants to stop the rejection of the organ, they can live quite nicely with   Michelle (27:16) Mm   Leslie Kenny Oxford Healthspan (27:33) with that organ and continue in reasonable health, understanding that their immune system has been suppressed. Spermidine, though, of course, it's in our diet. It's something that our gut biome, if it's not been compromised by too much exposure to broad spectrum antibiotics, it can make. And in all of the longevity hotspots of the world, these populations of healthy centenarians, their spermidine levels are   high, they're similar to those of people who are in their 50s. And it's correlated with healthy lifespan. So I always recommend that people try to get more plants in their diet because you will get spermidine in your plants. If you can have fermented foods,   Michelle (28:12) Mm   Mm   Leslie Kenny Oxford Healthspan (28:29) If you don't have a problem with histamine load, and some people do for allergy, you know, if they've got allergies, but if you don't have a problem with histamine, then, you know, kimchi, sauerkraut, even things that are long matured like cheese. And a lot of people can say, I'm not allowed cheese because it'll make me gain weight. Well, yes, but there is also some spermatine there. The longer the maturity of the, of the cheese, the more it's been aged, the higher the spermatine content.   Michelle (28:45) Mm   Leslie Kenny Oxford Healthspan (28:58) Usually these are harder cheeses like a Parmesan or a cheddar. These would be good sources. And then for individuals who need extra, then a supplement makes sense. But I always say, get it first from your food. Please do not rely on a supplement, right? That's not doing, it's a disservice to think that you can just have a bunch of little pills on your plate.   Well, at first you're not going to get any satisfaction from it. But the other thing is that we need the fiber in those plants because that fiber, although our bodies don't, don't digest it, the gut biome needs that. And so you, you want to also feed the colonies in your gut biome that can make more spermidine for you. You know, we have these little pharmaceutical factories that make   Michelle (29:46) Mm   Yeah.   Leslie Kenny Oxford Healthspan (29:54) everything from B vitamins and serotonin, one of the happiness hormones, and spermidine. So why waste it? actually in our supplement, the wheat germ derived one, we have a fructo -oleigosaccharide in there, an FOS, can selectively feed the bacteria that make spermidine. And the reason I want it there is because that's also what's in breast milk. In breast milk, you have   these fructo -aligosaccharides, you have spermidine, sperminine, another polyamine that actually helps turn good genes on, bad genes off, and then a precursor polyamine called putrescine. So you want some fiber, basically, that's the takeaway. Please, you want the fiber, yeah, exactly, because it's always better to, what do they say? Teach a man to fish, feed him for life, right?   Michelle (30:38) With the spermidine. Yeah.   Leslie Kenny Oxford Healthspan (30:49) rather than just give him the fish. And that's kind of what we want to do. We want to train your body to make more of it, especially as you get older, because you'll have to eat increasing amounts of plant material to make up the shortfall of your tissue production of spermidine going offline.   Michelle (30:57) Right.   It's fascinating. So wheat germ is not necessarily gluten -free. For people who are gluten -free, what do they do?   Leslie Kenny Oxford Healthspan (31:16) Well, OK, so yes, obviously, this is a problem in particular for autoimmune patients. And I went on the autoimmune paleo diet myself. I got rid of all gluten. I was off all lectins. Gluten is most famous lectin. So I had so many autoimmune patients getting in touch with me who'd heard my story that I actually looked for a plant source high in spermidine that was not a lectin. And I found it in an unusual strain of chlorella.   Michelle (31:28) Mm   Leslie Kenny Oxford Healthspan (31:45) So I went to Okinawa and had to test 120 different strains, substrains of chlorella to find the single one that had very high expression of spermidine. And we commissioned that to be grown in open -air freshwater ponds that are on land in Okinawa, but next to the ocean, but not in the ocean.   Michelle (31:46) Mm   wow.   It's wild.   huh.   Leslie Kenny Oxford Healthspan (32:11) And that's what we use in our gluten -free product, which also has Okinawan autumn turmeric and has Okinawan lime peel. So lime peel has another autophagy activator. That's that cell renewal process. This autophagy or cell renewal activator is called nobilitan. And it's also in bergamot, in bergamot, the citrus fruit.   Michelle (32:16) Mm -hmm.   Mm   Mm -hmm. Right.   Leslie Kenny Oxford Healthspan (32:38) And that actually, interestingly enough, is an Earl Grey tea. So if you're going to drink a tea, maybe some Earl Grey, you'll get some nobilitan in that. But that formulation was especially made for celiacs and for other autoimmune patients who really wanted the benefits of autophagy but couldn't use the defatted wheat germ version that we had brought to market first.   Michelle (32:42) wow. Interesting.   Mm   Mm   Amazing. Let me ask you a question. Have you looked into enzymes, pro proteleic? No, enzymes that are actually systemic enzymes that you have on an empty stomach. like things like wobe enzyme and yeah. And I think that there's another one, it's Nuzheim or there's another pretty well -known company. And I think it's from Europe.   Leslie Kenny Oxford Healthspan (33:11) You mean like digestive enzymes or?   I've taken wovenzyme.   So yeah, wabenzim is German. I took that, gosh, maybe it's been around for decades and it does work. I took that from my, interesting. I took it, I didn't know that. I took it for joint pain. And so this was something that I was taking as a way to try and treat myself for the rheumatoid arthritis. So it didn't, it wasn't enough for that. I think it can help.   Michelle (33:40) It was beneficial for thyroid. Yeah, yeah.   Yeah.   Yeah.   Leslie Kenny Oxford Healthspan (33:59) more mild things, but definitely these are of benefit. And having a coach like you, who, you know, a trained practitioner who knows about all of the menu items that could be selected, you have the different tools, right? It's overwhelming as a patient. I mean, even just having my doctor say, just inject this one drug, that was like, whoa, can I get my head around the idea of injecting myself, right?   Michelle (34:13) Yeah, like different tools.   yeah.   Yeah.   Leslie Kenny Oxford Healthspan (34:29) So you do need a guide and I think it's great that you've got that knowledge that you can share with your clients.   Michelle (34:37) Thank you. also, so for people who are interested, is it mostly the spermidine that you're focused on?   Leslie Kenny Oxford Healthspan (34:45) Yes, so basically we are a small all -women company and you know, women -led companies, we get around 2 % of all venture capital funding. We don't have venture capital funding like our competitors. We very much are growing organically and are looking at really focusing on something that we know very well and making the most excellent   Michelle (34:49) Mm -hmm.   Leslie Kenny Oxford Healthspan (35:13) product on the planet. And for me, with my group of advisors, this has been the right thing to do because we've had so many raw material manufacturers and suppliers come to us telling us, try this spermidine. And when we tested in the lab, we see that it's basically a tiny amount of wheat germ, and it's been cut like a street drug with synthetic spermidine.   Michelle (35:15) Awesome.   Leslie Kenny Oxford Healthspan (35:42) And the problem with synthetic spermidine is, firstly, OK, I am biased against the synthetic because I watch my mother take the synthetic HRT. I'm so glad I'm on bioidentical HRT. But the synthetic has never been tested for safety or efficacy in humans. So I'm reluctant to bring a product to market that has not been tested. And when it comes to fertility,   Michelle (35:43) wow.   Mm   Mm   Leslie Kenny Oxford Healthspan (36:11) We know that in mouse studies where they have used synthetic spermidine, small amounts seem to help. But then when you give just a little bit more, it actually impairs fertility. so with these...   Michelle (36:22) wow. That's important. That's really important, you guys, to listen to that because that's huge.   Leslie Kenny Oxford Healthspan (36:28) Yeah, that's huge. So the problem is finding the Goldilocks zone. Each of us is bio individual. We have different ethnic difference, genetic differences, age, body shape, height, and metabolism. All of these things mean you want the right amount for you, but we don't know what that right amount is when it comes to synthetic spermidine. With plants, however, it's not a problem.   because the body recognizes this, we have co -evolved with plant -derived spermidine for millennia. So when there's too much, the body says, right, we're going to turn this into spermine, which is going to help with turning good genes on, bad genes off with the DNA methylation. But this doesn't happen with the synthetic. I think that on the fertility front, as a woman, I would never make that.   Michelle (36:55) Yeah.   Leslie Kenny Oxford Healthspan (37:21) I would never go for something that might possibly hurt my fertility.   Michelle (37:25) absolutely. Absolutely. I mean, it's a complete waste of time because you're trying to do all these other things and then you're going to take something that's not, that's a risk. and then I was curious, it says you were talking about it you were saying that sometimes they'll find it in certain mushrooms, cordyceps by any chance.   Leslie Kenny Oxford Healthspan (37:30) Yeah. Yeah. Yeah.   Mmm.   it will be in cordyceps. It will be in all mushrooms and the ones that have the highest amount of swirmed in our shiitake, oyster and trumpet, but all mushrooms will have it. And, know, if you, if you don't have a problem with, mushrooms, know, this is fall, it's autumn. This is the right time to, you know, get some mushrooms into your stews and your soups and,   Michelle (37:43) Mm -hmm. Mm -hmm.   Awesome.   Mm -hmm.   Leslie Kenny Oxford Healthspan (38:06) It's really, it's so, so good also because it's got vitamin D and we're just coming off of this period where we've soaked up the vitamin D from the sun over the summer, but now we're going into winter and we're gonna get less. So there are so many reasons to get it also a wonderful source of fiber.   Michelle (38:16) Yeah.   Yeah, amazing. So if people are interested and want to learn more and then also want to look at your products, how can they find you?   Leslie Kenny Oxford Healthspan (38:32) They can go to Oxford HealthSpan, like the span of a bridge, it's all one word, .com. And if they're interested in learning more about healthy aging, we do bring breakthrough scientists who talk about things, not just about cell renewal or autophagy, but talk about other things as well. We also have them talk about, say, NAD, things like this. That's at the OxfordLongevityProject .org.   Michelle (38:56) Yeah.   Mm   Leslie Kenny Oxford Healthspan (39:01) And then I have kind of a side hustle helping my girlfriends with gray hair reversal. And that's on Leslie's new prime. Spermadine helps with that as well. It helps with hair health and eyelash and eyebrow health. That is on Leslie's new prime on YouTube. So L -E -S -L -I -E is how I spell my name.   Michelle (39:08) nice.   Fabulous. Leslie, this was fascinating. I really enjoyed talking to you. And also a key point, you got pregnant naturally at 40. Okay. important thing to mention. And I kept thinking about it as we're talking about, wait, wait, let's go. Let's go talk about that, even though it's kind of the end of the episode.   Leslie Kenny Oxford Healthspan (39:34) I did at Yeah. Yeah. Yeah. Well, it's a, it's a happy ending. So, so the fifth IVF with the donor eggs didn't work. As a matter of fact, the embryologist said on embryo transfer, said, I don't know why you didn't use your eggs. Your eggs are better than this younger donor. I was like,   You're kidding me because I can't tell you how much I just sacrificed to pay for that. And, but, know, basically fast forward, I adopted a little girl from China. So I became a mom. become parents, you know, mother is a verb. It's not a noun. So that was, that was great. And as I was taking care of her, I still felt very, very tired and I couldn't understand what was going on, why I saw these other moms.   Michelle (40:02) wow.   Leslie Kenny Oxford Healthspan (40:27) running around with scout troops, planting gardens, walking dogs, five children. You know, why? How do they do it? They're the same age and they have so much more energy. And I just, I did go to Dr. Google. I put in every symptom I had and it came up hypothyroid. So then,   The GP here in the UK said, no, you're in the normal range. No problem. I went to a private GP. No, you're normal. I went to a private endocrinologist. No, you're normal. And I just thought, I know I'm not. These doctors keep telling me I'm normal. I know. We patients always, if you do feel like that, follow your intuition, find a doctor who believes you, and we'll run the test. We'll work with you to uncover the mystery. It's like a murder mystery, right? So.   Michelle (41:09) Yes.   Yes.   Leslie Kenny Oxford Healthspan (41:14) So I went on patient forums. Patient forums have been great help. Went there and people said, there is one doctor who will help you and he won't just look at your blood test. A lot of doctors look at thyroid problems and they only look at your blood test, your TSH, your T3, your T4. I went to him and he looked at clinical symptoms and he also ran a cortisol test. And he said that my...   Michelle (41:33) Mm   Leslie Kenny Oxford Healthspan (41:43) Cortisol was the lowest he had ever seen. It was so bad, he didn't know how I was standing in front of him. And I had classic cold hands, cold feet. Yes, my hair was thinning. I was exhausted. I was breathless as I went upstairs. I was losing the outer third of my eyebrows. These are all clinical symptoms of hypothyroidism. He then said,   Michelle (41:50) Wow.   Mm   Leslie Kenny Oxford Healthspan (42:09) What you need to do is address your adrenals first because of the cortisol problem, and then two weeks after that, take some thyroid. And because I actually do not convert levothyroxine, which is a standard thyroid hormone that most people get, like 60 % of all Americans will get that, but I can't convert it into the bioavailable.   Michelle (42:22) Mm   Right. Yeah.   Leslie Kenny Oxford Healthspan (42:33) thyroid hormone known as T3. And your cell receptors only have receptors for T3, not for levothyroxine. So if you've been taking loads and loads of levothyroxine, you still feel wiped out. You probably are just like me and have a genetic, you're genetically challenged and you can take a test with Genova diagnostics. I think it's called the DIO2 genetic test, D -I -O -2. And   Michelle (42:35) Mm   Mm   Mm -hmm. Mm -hmm.   Leslie Kenny Oxford Healthspan (43:01) here in the UK cost about 75 pounds and you then can get T3 prescribed either synthetically or you can do what I do and Hillary Clinton also does. take something, we take a desiccated pig's thyroid. In America there's Armour, There's Armour, there's Urfa, there are a few brands and that within, you know, two to three weeks basically on that   Michelle (43:16) Is that armor? Yes, yeah.   Leslie Kenny Oxford Healthspan (43:29) Pregnant right away. No idea. Had not even, didn't check if I was ovulating. You remember the days when you're like, you've got a thermometer under your tongue and you're checking, am I ovulating? Could it be now? And all the calendar work that you've got to do when you're trying to get pregnant, none of that. It just happened. And I was so shocked. yeah. So my daughter, Marguerite, was born, you know,   Michelle (43:38) Yeah.   That is so crazy.   Leslie Kenny Oxford Healthspan (43:57) Eight months later, was just one day shy of being premature, so I got her over the premature line. And 10 out of 10 on the Apgar score delivered at age 43.   Michelle (44:08) Amazing. mean, that is just incredible. I'm sure, I mean, I'm so excited about this episode because I just feel like it's mind blowing, first of all, just all the different stories. And it also covers things that I feel are really important. advocating for yourself as a patient. I mean, that is huge. And I think a lot of us have been in those kinds of situations. You said something that I was like, wow.   That's a quote, find a doctor who believes you. You know, because also getting different opinions is super important and it's a game changer. It'll totally change your whole journey.   Leslie Kenny Oxford Healthspan (44:37) Yeah, yeah, yeah.   Yeah.   Yeah. Well, look what this doctor did for me. So what none of the doctors had realized with those other two autoimmune conditions was that I had my autoimmune, the system, the immune system had not only attacked my joints and my organs, but it had attacked my thyroid. And the way that he could see it was, you know, he could see with.   Michelle (45:07) Mm -hmm.   Leslie Kenny Oxford Healthspan (45:11) that I had all the clinical symptoms, but with an ultrasound, he could see that I had only one eighth of a thyroid left. I had so little viable thyroid left. There was just nothing of the organ left. yet, because he didn't want to fall in line here in Britain, he was actually hounded by the British Medical Council.   Michelle (45:23) Wow, that is so crazy.   Leslie Kenny Oxford Healthspan (45:35) Mary Schumann, the thyroid advocate in the United States, who's written a number of thyroid patient handbooks, actually got a campaign together to try to gather signatures. And he had tens of thousands of signatures from grateful patients. But the medical council actually wasn't listening. They wanted their protocol to be followed. And it had to be a blood protocol.   Michelle (45:55) It's so crazy to me.   Leslie Kenny Oxford Healthspan (46:02) And this is the problem is the blood does not show everything. But of course, we patients get these data points 24 -7.We know if our hair is falling out, if we can't shift the weight, if we can't walk upstairs without getting winded, if we've got cold hands and cold feet, our partners know because they tell us, God, you're freezing. What's going on? So we need.   Michelle (46:06) you   Yeah.   Mm   Yeah, yeah, totally, totally.   Leslie Kenny Oxford Healthspan (46:30) Our partners know it. If, if you happen to be sleeping with a doctor, maybe he can be a prescribed for you and he'll believe it because of the cold feet. but otherwise, you know, you have to rely on your powers of persuasion to find a doctor who's willing to go the extra mile with you and get curious. I only ask that I just find a doctor who's willing to get curious with you.   Michelle (46:35) Right? Yeah.   Yeah, I love that. I love that. Well, I mean, I could talk to you for longer than we have. But let's say this is amazing information, like really, really, truly amazing. And I love your story. And I love the way you truly believed in yourself. And that's something that I want to tell everybody who's listening, just believe in yourself because you know, and you know what? The body is so forgiving, way more forgiving than we give it credit for. It's just a matter of   Leslie Kenny Oxford Healthspan (47:21) 100%.   Michelle (47:22) figuring out like what is it exactly that it needs, like just figuring it out, its own way of communication. So thank you so much, Leslie, for coming on today.   Leslie Kenny Oxford Healthspan (47:28) Yeah.   absolutely. Thank you for having me on. really appreciate it. It was lovely chatting with you, really fun. And keep going with your amazing work. Women need guides they can trust like you, who are willing to take the extra time to get curious and share the knowledge that you've gained over the years and the hard work you put in to get pregnant yourself, right?   Michelle (47:57) Thank you so much.    

The DANGERS of IVIg. I'm Annette Leonard you can find me on Instagram https://www.instagram.com/theannetteleonard or my website https://www.annetteleonard.com Last week I talked about IVIg. This week I'm here to talk about the dangers of IVIg. Please note, the *vast* majority of people tolerate IVIg with minimal complications. However, for a small fraction of us there are few of us who will experience serious complications like these detailed in this episode. These reactions can sometimes be avoided or mitigated by receiving Ig subcutaneously rather than intravenously. Have you taken IVIg? Are you curious about IVIg? Have you had complications with IVIg? Leave a comment or ask a question. **I have a new mini-course I'm finishing about how to unlock the power of your next doctor appointment*** the first 50 people get FREE enrollment. Sign up here https://www.annetteleonard.com/waitlist Also, join me on Instagram for my Chronic Wellness Conversations. My next IG Live will be 9/26 at 1:00 pm PST. This is the Chronic Wellness Podcast. I'm Annette Leonard, speaker, coach, and sick person who believes that my illnesses do not define me. If health is the absence of disease and wellness is the presence of wholeness, then no matter what your disease status, we can work toward your wellness, your wholeness. Whether or not you are ever "healthy" on paper, you can be well. Join me and others on the path back to wholeness at AnnetteLeonard.com. Whether you are a person experiencing chronic illness or are someone who loves or serves people with chronic illness I have great resources here on this channel or on my website for you.

Over the past 20 years, more than 50 antibodies have been identified and associated with autoimmune neurologic disorders. Although advances in diagnostic testing have allowed for more rapid diagnosis, the therapeutic approach to these disorders has largely continued to rely on expert opinion, case series, and case reports. In this episode, Allison Weathers, MD, FAAN, speaks with Tammy L. Smith, MD, PhD, an author of the article “Therapeutic Approach to Autoimmune Neurologic Disorders,” in the Continuum® August 2024 Autoimmune Neurology issue. Dr. Weathers is a Continuum® Audio interviewer and associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Smith is a GRECC investigator and staff neurologist at George E. Wahlen Veteran Affairs Medical Center and an assistant professor of neurology, at the University of Utah in Salt Lake City, Utah. Additional Resources Read the article: Therapeutic Approach to Autoimmune Neurologic Disorders Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Transcript Full episode transcript available here   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology.  Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Weathers: This is Dr Allison Weathers. Today, I'm interviewing Dr Tammy Smith about her article on therapeutic approach to autoimmune neurologic disorders, which she wrote with Dr Stacey Clardy. This article is a part of the August 2024 Continuum issue on autoimmune neurology. Although, one of the things I love most about being an interviewer for Continuum is getting the opportunity to meet new neurologists and learn all about their areas of expertise, there's something really special when I get the chance to interview and catch up with old colleagues - and today, I'm fortunate to do just that. I had the privilege of working with Dr Smith when she was a resident at Rush, and I'm so excited to be able to speak to her today about her fantastic and really comprehensive article on this very timely topic. Welcome to the podcast, Dr Smith, and please introduce yourself to our audience.   Dr Smith: Hi. Yeah, thank you for inviting me to participate in the podcast and to write this article. So, I'm Tammy Smith. I am a neurologist who practices in Salt Lake City. I primarily work at the Salt Lake City VA Medical Center where I get to treat veterans with all sorts of neurologic diseases. I'm also an assistant professor of neurology at the University of Utah in the division of Neuroimmunology and Autoimmune Neurology, and I serve as a Clinical Consultant for ARUP Laboratories to help improve diagnostic testing for immune-mediated neurologic diseases.   Dr Weathers: Wow. That is a lot of different roles and things that you have on your plate. I want to start, actually, by talking about the article. Again, you cover so much ground (you and Dr Clardy) in this really comprehensive article, but if you had to choose the one most important message - if you wanted our listeners to walk away remembering one key point, what would it be?   Dr Smith: I think the key point I want our listeners to think about is just to use the resources that are available to you. Nobody can have all of these drugs (as we're talking about treatment of autoimmune neurologic diseases in this article) - no one can have all of those drugs memorized, all of the mechanisms of action, all of the approved treatments and off-label treatments, and all of the symptomatic therapies. But that's why resources like the Continuum exist - so that we can provide those resources to clinicians who are busy at that touch of, er, hopefully - or when they open their issue - to get the information they need to make decisions to take good care of their patients.   Dr Weathers: I think that is so reassuring. As I was reading this article, that was, like, one of the things that really struck me is that, you know, thinking about even being a resident and studying for something like the rate exam, you know, how much easier it used to be when there was such a limited number of drugs thinking about the autoimmune diseases or epilepsy, where just the number of drugs has just, kind of, multiplied so manyfold since I was in training, that it's really overwhelming. And I think you make a great (and as I said, a very reassuring) point that we don't have to memorize these, that there are these incredible resources (like Continuum) where it's not any longer about kind of memorization and keeping it in our heads, that it's more about knowing where to look and thinking about what's the right thing for the patient - knowing how to go and get the information is the more important knowledge there. And, actually, thinking about that and moving on, given your expertise, how do you personally approach the management of a patient with an autoimmune neurologic disorder? Again, in the article, you speak about all the different things to keep in mind, both from a therapeutic (really, treatment) standpoint, as well as a symptomatic standpoint - but what is your personal approach?   Dr Smith: My personal approach really involves considering whether the diagnosis of an autoimmune neurologic disorder is correct, first and foremost, and gathering the information to help support that diagnosis - and I think that's something that often gets overlooked in the excitement of a patient coming in with a rare-looking syndrome. Someone sends off diagnostic testing, rules out a few things, decides it's autoimmune, and starts down a pathway and keeps pushing forward. And I understand that inclination on a busy neurology service or in a busy clinic to just decide on one path and move forward, but I'm always questioning the diagnosis, even in the presence of positive antibody results sometimes. If my patient doesn't respond to the treatment that I'm giving them based on their presentation and the antibody results, I reassess and wonder if there's something else going on, are there two syndromes going on, or was that antibody result really not the right answer for some reason. So, I think my approach, really, is to always have a healthy amount of skepticism around the diagnosis, and even when I'm fairly confident in the diagnosis, to continually reassess that patient and their unique response to treatment. And then, also, their unique circumstances - so, everyone will need different symptomatic management, as well as different rehabilitation resources and other resources mobilized to help them maximize their recovery. And so, there's just not a “one size fits all” approach, but always keep talking to the patient, keep re-evaluating, stay curious, and don't be afraid to change paths when things aren't making sense.   Dr Weathers: I think that is incredibly sound, really thoughtful advice. So, I can imagine how incredibly challenging those cases must be when you think you have the right answer, it looks like it's lining up, the antibodies are pointing you in the right direction, and then, they're not responding. What else do you feel is the most challenging aspect of the management of these conditions? Is there some other kind of aspect that you also feel is really challenging in the treatment of these patients?   Dr Smith: Yeah, I think other challenges are really access to state-of-the-art therapies due to financial barriers - I think that's a pretty significant challenge for a lot of these patients, and I think we need to continue to work on advocacy efforts to make sure all patients have access to the medications they need to treat the disorders they are diagnosed with. And it's a real challenge, even when there's FDA-approved therapeutics - a lot of them are quite expensive, and then we end up playing the insurance game, and we learned that AI is automatically denying people's insurance claims, and so, we're battling computers as well as insurance companies. And I think that's a really significant challenge for a lot of these patients. And then, really, just the fact that a lot of immune-mediated neurologic disorders have a long tale. So, we don't treat a patient the same way we do for an infection and expect a dramatic and rapid recovery - a lot of the recovery for these patients happens over months to years. It's a process, and I think it's really important to be counseling patients and caregivers and other providers and educating them about this that we continue to mobilize resources to help our patients long past their inpatient hospitalization and the most dramatic part of their recovery.   Dr Weathers: Again, you raised some really insightful points there. No, I think they're really key. And I think, to your point, that even for some of these patients, that even if we can get over the economic barriers of the medications themselves and get them authorized, get them covered, you're left with, for a lot of patients, all of the other limitations of some of their social determinants of health challenges, right? So, the transportation challenges to even kind of get them to the appointments, and some of the other challenges they face, which makes some of these treatments very, very hard for them to be able to accomplish. So, it is very challenging - I think that's a very important call-out. What do you think is the easiest mistake to make when treating patients with autoimmune neurologic disorders, and how should our listeners avoid it?   Dr Smith: Yeah, that's an excellent question. One of the most common mistakes I see is either overvaluing diagnostic testing or not ordering the appropriate diagnostic testing for the clinical syndrome in any given patient. And where this comes into play, really, is the fact that when we order diagnostic testing in the United States for immune-mediated neurologic disorders, these autoantibody panels are available to us that test for a multitude of autoantibodies all at the same time, and if we don't choose the appropriate test for the clinical syndrome that the patient is there with, we run the risk of getting a positive result for an antibody that's unrelated to the syndrome we're seeing in the patient – and no test is 100% specific (or 100% sensitive, for that matter), but these low-specificity issues when you indiscriminately test really can cloud the clinical picture and delay getting the appropriate diagnosis. And so, I really think that one of the biggest mistakes is seeing maybe a low-positive result for an antibody that does not match the clinical syndrome if you go back to the books and use your resources to figure out if that result is meaningful - overvaluing that antibody result and maybe plowing forward with a treatment plan that involves a long course of immunomodulatory therapy is a pretty significant mistake. And then, on the flip side is that because these panel tests, you order them as a block, and you think that you ordered the right thing - or you think that whoever you asked to order the order for you ordered the right thing – and so often, people say the panel was negative, and they don't look at the individual results of the antibodies that were tested in the panel, and because different antibody panels are designed to test for different clinical phenotypes. I see the error where a clinician thinks that all of the antibodies necessary to test for were tested for and negative, and now they feel like their hands are tied. And so, it's both this overvaluing the diagnostic testing and forgetting to question the testing results if they're not what you expect once you get more clinical data - I think both of those are pretty big mistakes. And continuing, again, always be curious, always recheck results, and don't take laboratory values in an EMR that are in black and white as the stone-cold truth that tells you your answer - you have to stay curious about the patient, their history, their neurologic presentation, their response to treatment over time, and really keep assessing. My other soap box here about diagnostic testing is that, historically, a lot of the antibodies that we test for were called paraneoplastic (and that's because they were some of the first antibodies discovered, so, they were some of the earliest ones that we developed tests for), and clinical reference laboratories continue to offer paraneoplastic panels for historical reasons and because a lot of people think that that's what they want. But, paraneoplastic panels, in and of themselves, are not representative of a specific clinical phenotype - they just diagnose patients who have a high risk of malignancy associated with an antineural antibody. And so, most of the clinical reference labs I know of - certainly at ARUP, we have a notice on our testing page, I know Mayo Clinical Laboratories also has a notice that says, “Paraneoplastic panels are not generally the recommended panel to test for antineural antibodies. Consider ordering the phenotype-specific panel that fits the patient's clinical syndrome”. And I think that's super important – we still have paraneoplastic stuck in our head for historical reasons, and it is almost never the right answer.   Dr Weathers: It's really interesting. At my organization, you know, we actually have had some really thoughtful conversations about, do we really restrict it (you know, as part of lab stewardship efforts) - and, you know, these are expensive, and to your point, they can be frankly, really dangerous, you know, to really send somebody down this wrong path with a lot of surveillance, committing them to immunomodulatory therapies, and take you in completely the wrong direction when, actually, your low test probability was very low. So, I think that is an excellent one to really call out and for people to be very thoughtful of - and the way, again, to avoid it is to be very thoughtful about the panels. And for people, certainly, they are very convenient, but people need to be really aware of what's in them and what they are ordering and how to interpret them. And I love that advice about not just thinking about the wholesale as negative - really, you know, for many of us, they are still coming in as scan documents, you know, click into them, read every line, really understand what those results mean.   Dr Smith: And I would also say that I think people don't realize, but clinical reference laboratories would love for you to reach out when there are questions. So, if you don't understand the diagnostic testing that was performed or result, you pretty much all have hotlines. You can call and reach out to an expert in the testing and ask them some questions, and don't be afraid to reach out to your colleagues who might have more experience. We love hearing from people with questions and helping to direct them to the right testing and help them get the answers that they really want to for their patients.   Dr Weathers: I think that is a great plug. Before you order, preferably, before you send in.   Dr Smith: I do like when I hear from people before mistakes were made. Yes. That's nice.   Dr Weathers: It's a great point.   Dr Smith: When you order these panels, you do run the risk of having these low positive results that may or may not be clinically meaningful. And we do recommend that most of the diagnostic testing be ordered in both serum and CSF. And so, a good example of a mistake that can be made is a very low-positive NMDA-receptor antibody in serum - maybe it was ordered for a patient with cognitive decline or confusion (maybe not under the ideal clinical scenario for ordering), and then it's negative in the CSF. So, an NMDA-receptor positive, negative in the CSF, not the right clinical picture, people can get really jazzed and want to treat an NMDA-receptor encephalitis, that in that case, really isn't meeting diagnostic criteria, and there are excellent diagnostic criteria that have been developed and published for that disorder and for several other autoimmune neurologic disorders, and I think going back to those criteria and really questioning yourself before you start blindly down a path based on a lab result is really important.   Dr Weathers: I think that's excellent advice, too, always keeping that in mind that just because you have gone down this path and gotten that result doesn't mean that you are stuck and committed to it. Always keeping that criteria in mind, always going back, always checking it is really important as well. Moving on from mistakes to kind of an adjacent question, what do you think is the biggest controversy right now when it comes to the treatment of patients with autoimmune neurologic disorders?   Dr Smith: You know, one of the big controversies that I see and I'm concerned about is that we've gotten into a habit of treating the way we've always treated based on expert opinion, and while experts have their opinions based on a lot of experience, they don't take the place of well-designed randomized controlled clinical trials - and in rare diseases (like autoimmune neurologic diseases), it can be really challenging to conduct those trials, especially in the face of people who have a pathway that they always do with their patients. If they have a NMDA-receptor encephalitis patient, they feel very comfortable doing their standard of care with IV steroids and then either plasma exchange or IVIG, and then possibly (and very often), I see following with a B-cell inhibitor, like rituximab, as sort of just a “kitchen-sink” approach to treatment. And while I understand the passion and the desire to make a really sick patient sitting in front of us better as fast as possible, I don't think we have adequate evidence to support that being the “one-size-fits-all kitchen-sick” approach for treatment. And I really am passionate about all clinicians all over the world, supporting randomized controlled clinical trials that are well-designed with the backing of experts in the community, so that when we look at a patient and tell them that we recommend a course of treatment, we're recommending it based on the best quality evidence available, not just what everyone's always done before. I think we can do better than that. And I think there's some controversy in this. Some people think that it doesn't make sense, we already know the answer, but I would say we haven't asked the right question and thoroughly investigated enough. And this is especially important with children, right? We know pediatric patients often don't have well-designed clinical trials to guide their treatments - but in NMDA-receptor encephalitis, many of the patients are children, and I think that they deserve to be involved in well-designed clinical trials in order to support the recommendations that we make for treatment.   Dr Weathers: And in addition to children, think about all of the other patient populations that have traditionally not been well represented in trials, right - pregnant patients, patients of color (historically very underrepresented in trials) - many, many other patient populations that have not been adequately represented.   Dr Smith: Absolutely. Yeah. I think we need to really care about that and face that problem head on and speak to it. We can't just say this is the way we've always done things, so we're going to keep doing it that way. I think we owe it to our patients and ourselves, when we look our patients in the eye, to say that we have good evidence to support the recommendations we're making.   Dr Weathers: I think we have already answered this question in many ways with each of the questions we've already talked about, but is there any other strong arguments that you can make for why it's important for neurology clinicians to read your article?   Dr Smith: Dr Clardy and I spent a lot of time working on this article, trying to put together a piece that will be a resource that people could turn to again and again. I don't think that this article is something that you should read from top to bottom and think that you've absorbed and digested everything, right? So, what we work to do was to really provide a structure and a framework to think about the treatment of immune-mediated neurologic diseases. So, rather than memorizing specific drugs for specific conditions, we developed sort of a space where you could talk about B-cell targeting therapies and the different ways we can target B-cells, we talked about complement inhibitors, neonatal FC receptors, and, really, just at a high level, how these drugs work and how they're targeted, so that going forward in three, four, five years, what I believe we'll know more about each of the individual diseases mediated by antineural antibodies. When we understand what causes that disease, we'll be able to go to a resource like this and choose rationally based on mechanism of action, a drug to treat our patient - even if it's in a patient with such a rare disease that we don't have the luxury of a clinical trial to guide our choices.   Dr Weathers: That's a really excellent point - and I know I've said it a few times, but I think you guys did such a really excellent job at really laying it out in a way that makes it this really comprehensive, really easy-to-use resource at that point of care for providers to be able to do exactly that. Well, I always like to end on a hopeful note, so, this is always my favorite last question – but, what do you think is the next breakthrough coming in the treatment of patients with autoimmune neurologic diseases?   Dr Smith: Yeah, I think in the near future (I certainly hope, at least) that the next breakthrough is going to be in really being able to deliver personalized care based on what we understand about the mechanisms of a patient's rare disease. So, again, right now, I find we're kind of left with the “kitchen-sink” approach because we know so little about the mechanisms that drive each of these unique neurologic diseases and we don't have enough information from clinical trials to inform rational treatment decisions, so we go with these broad approaches - and I really think that in the near future, with work being done by a lot of people (dedicated people over the world) on biomarkers and things that predict either onset of disease or relapse or disease severity or really looking at basic fundamental mechanisms that drive disease, we're going to be able to make more rational choices in the treatment of these patients and mobilize the resources that are expensive, but valuable for the right patient at the right time.   Dr Weathers: That is a very exciting and hopeful future to look towards. Thank you, Dr Smith, for joining me on Continuum Audio. It was wonderful to get to spend this time with you again. Again, today, I've been interviewing Dr Tammy Smith, whose article on therapeutic approach to autoimmune neurologic disorders, written with Dr Stacey Clardy, appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Here are the truths about IVIG. I'm Annette Leonard of https://www.annetteleonard.com find me on Instagram https://www.instagram.com/theannetteleonard IVIG What is it? A blood product that's sold as a pharmaceutical product. IGg is a major component in our immune system. Intravenous immunoglobulin is used to treat a wide range of illnesses and conditions to bolster the immune system. Who is it for? For those of us with autoimmune diseases it is thought to overwhelm our immune systems and therefore, shut down our over-active immune systems. How is it administered? Are premeds required? How long does a dose last? How many donors are required for a dose of IVIG? What does IVIG therapy cost? Have you tried IVIG? For what condition? Has it worked? Did you have side effects? Leave a comment or ask a question. **I have a new mini-course I'm finishing about how to unlock the power of your next doctor appointment*** the first 50 people get FREE enrollment. Sign up here https://www.annetteleonard.com/waitlist This is the Chronic Wellness Podcast. I'm Annette Leonard, speaker, coach, and sick person who believes that my illnesses do not define me. If health is the absence of disease and wellness is the presence of wholeness, then no matter what your disease status, we can work toward your wellness, your wholeness. Whether or not you are ever "healthy" on paper, you can be well. Join me and others on the path back to wholeness at AnnetteLeonard.com. Whether you are a person experiencing chronic illness or are someone who loves or serves people with chronic illness I have great resources here on this channel or on my website for you.

Many autoimmune neuromuscular disorders are reversible with prompt diagnosis and early treatment. Understanding the potential utility and limitations of antibody testing in each clinical setting is critical for practicing neurologists. In this episode, Teshamae Monteith, MD, FAAN speaks with Divyanshu Dubey, MD, FAAN, author of the article “Autoimmune Neuromuscular Disorders Associated With Neural Antibodies,” in the Continuum® August 2024 Autoimmune Neurology issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Dubey is an associate professor in the departments of neurology and laboratory medicine and pathology at the Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Autoimmune Neuromuscular Disorders Associated With Neural Antibodies Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Guest: @Div_Dubey Transcript Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. Today, I'm interviewing Dr Divyanshu Dubey about his article on autoimmune neuromuscular disorders associated with neural autoantibodies, which is part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast. How are you?   Dr Dubey: Hi, Dr Monteith. Thank you for inviting me to be a part of this podcast. I'm doing well.   Dr Monteith: Well, why don't you introduce yourself to the audience? And, call me Tesha.   Dr Dubey: I'm Divyanshu Dubey (please, call me Div). I'm one of the autoimmune neurology consultants here at Mayo Clinic Rochester. I'm an Associate Professor of neurology, as well as lab medicine and pathology. My responsibilities here are split - partly seeing patients (primarily patients with autoimmune disorders, including neuromuscular disorders), and then 50% of my time (or, actually, more than 50%), I spend in the lab, either doing research on these autoimmune disorders or reporting antibodies in a clinical setting for various antibody panels which Mayo's neuroimmunology lab offers.   Dr Monteith: That's a nice overlap of subspecialty area. How did you get into this work?   Dr Dubey: I think a lot of it was, sort of, by chance. Meeting the right people at the right time was the main, sort of, motivation for me. Initially, I trained in India for my medical school and didn't really got much exposed to autoimmune neurology in India. I think our primary concern in my training was sort of treating TB meningitis and cerebral malaria - that was my exposure to neurology, including stroke and some epilepsy cases. As a part of application for USMLEs and coming here to residency, I did some externships, and one of the externships was at Memorial Sloan Kettering Cancer Center, and that's when I worked a few weeks with Dr Posner and got introduced to the idea of paraneoplastic neurological syndrome working with him. And that sort of started - I wouldn't call it vicious cycle - but my interest in the area of autoimmune neurology and paraneoplastic neurological disorders, which subsequently was refined further through residency and fellowships.   Dr Monteith: That's interesting. I actually rotated through - I did a externship also at Sloan Kettering, and I had a clinic with Dr Posner. And I thought, at the time, he was such a rock star, and, like, I took a picture with him, and I think he thought it was insane. And I didn't go into autoimmune neurology. So, you know, interesting pathways, right?   Dr Dubey: Yes. And I think he's inspired many, many people, and sort of trained a lot of them as well.   Dr Monteith: So, why don't you tell us what you set out to do when writing this article?   Dr Dubey: So, I think, given my background and training in various subspecialties in neurology, I was, sort of, formally did fellowships in autoimmune neurology, as well as neuromuscular medicine. One of the areas in these areas that I focus on is in my clinical practice, as well as in my sort of lab work, is autoimmune muscular disorders - and that to, specifically, autoantibodies and their clinical utility for autoimmune muscular disorders. So, that's what I wanted to focus on in an article. When I was invited to write an article on autoimmune muscular conditions in general, I thought it was very difficult to pack it all in one chapter or one article, so I narrowed my focus (or tilted my focus) towards antibody-positive disorders and trying to understand how we as neurologists can firstly sort of identify these conditions (which may end up being antibody-positive) – and then, on the other hand, once we get these antibody results, how we can find the utility in them or find them useful in taking care of our patients. At the same time, I also wanted to kind of highlight that these antibodies are not perfect, they do have certain limitations – so, that's another thing I sort of highlighted in the article.   Dr Monteith: So, why don't we just start with a very broad question - what do you believe the role of autoantibodies is in the workup of neuropathies and then neuromuscular disorders? Obviously, when we think of myasthenia gravis, but there are some presentations that you may not necessarily think to first order autoantibody tests. So, what is the role, and where does it fit in the paradigm?   Dr Dubey: I think it's extremely crucial, and it's evolving as time goes on, and it's becoming more and more clinically relevant. Let's say three, four decades ago, the number of biomarkers which were available were very limited and only a handful - and there has been a significant increase in these biomarkers with growing utilization of newer techniques for discovery of antibodies, and more and more people jumping into this field trying to not only discover, but try and understand and validate these biomarkers (what they truly, clinically mean). These antibodies, like you pointed out, ones for myasthenia (such as acetylcholine receptor-binding antibodies, or MuSK antibodies), they can be extremely helpful in clinical diagnosis of these patients. We all know the importance of EMG in managing our patients with neuromuscular disorders. But, oftentimes, EMG nerve conduction studies are often not available at every center. In those scenarios, if you have antibodies with very high clinical specificity, and you're seeing a patient on examination whom you're seeing ptosis (fatigable ptosis), double vision, you're suspecting myasthenia, you send antibodies, and they come back positive. It brings you closer to the answer that may, in turn, require you to refer to a patient to a place where you can get high-quality EMGs or high-quality care. In addition to getting to the diagnosis, it also, sometimes, leads you in directions to search for what is the trigger. A good example is all these paraneoplastic neurological syndromes (which we started our conversation with), where once you find a biomarker (such as anti-Hu antibodies or CRMP5 antibodies) in a patient with paraneoplastic neuropathies, it can direct the search for cancer. These are the patients where, specifically, these two antibodies, small-cell lung cancer is an important cancer to rule out - they require CT scans, and if those are negative, consider doing PET scan – so, we can remove the inciting factor in these cases. And then, lastly, it can guide treatment. Depending upon subtypes of antibodies or particular antibodies, it can give us some idea what is going to be the most effective treatment for these patients.   Dr Monteith: I think paraneoplastic syndromes are a very good example of how autoantibodies can help guide treatment. But, what other examples can you provide for us?   Dr Dubey: Yeah, so I think one of the relatively recent antibody tests which our lab started offering is biomarkers of autoimmune neuropathies - these are neurofascin and contactin, and those are great examples which can target or guide your treatment. I personally, in the past, have had many CIDP patients before we were offering these testings, where we used to kind of start these patients on IVIG. They had the typical electrodiagnostic features, which would qualify them for CIDP. They did not show any response. In many of these cases, we tried to do sort of clinical testing or sort of research-based testing for neurofascin and contactin back in the day, but we didn't have this resource where we can sort of send the blood, hopefully, and within a week, get an answer, whether these patients have autoimmune neuropathy or not. Having this resource now, in some of these cases, even before starting them on IVIG, knowing that test result can guide treatments, such as considering plasma exchange up front as a first-line therapy, followed by rituximab or B-cell depleting therapies, which have been shown to be extremely beneficial in these conditions. And it is not just limited to neurofascin or contactin (which are predominantly IgG4-mediated condition), but the same concept applies to other IgG4-mediated diseases, such as MuSK myasthenia, where having an antibody result can guide your treatment towards B-cell depleting therapies instead of sort of trying the typical regimen that you try for other myasthenia gravis patients.   Dr Monteith: And you mentioned where I was reading that, sometimes, nerve conduction studies and EMG can be useful to then narrow the autoantibody profiles. Oftentimes, in the inpatient service, we order the autoantibodies much faster, because it's sometimes harder to access EMG nerve conduction studies - but talk about that narrowing process.   Dr Dubey: Yeah. And it goes back to the point you just made where we end up sending, sort of, sometimes (and I'm guilty of this as well), where we just send antibodies incessantly, even knowing that this particular patient is not necessarily likely to be an autoimmune neurological disorder, and that can be a challenge, even if the false-positive rate for a particular test is, let's say 1% - if you send enough panels, you will get that false-positive result for a particular patient. And that can have significant effects on the patient - not only unnecessary testing or imaging (depending on what type of antibody it is), but also exposure to various immunotherapies or immunosuppressive therapies. It's important to recognize red flags – and that's one of the things I've focused on in this article, is talking about clinical, as well as electrodiagnostic, factors, which make us think that this might be an autoimmune condition, and then, subsequently, we should consider autoantibody testing. Otherwise, we can be in a situation - that 1% situation - where we may be sort of dealing with a false-positive result, rather than a true-positive result. In terms of EMGs, I think I find them extremely useful, specifically for neuropathies, distinguishing between demyelinating versus exonal, and then catering our antibody-ordering practices toward specific groups of antibodies which are associated with demyelinating neuropathies (if that's what the electrophysiology showed) versus if it's an exonal pathology (considering a different subset of antibodies) - and that's going to be extremely important.   Dr Monteith: You're already getting to my next question, which is what are some of the limitations of autoantibody testing? You mentioned the false-positivity rate - what other limitations are there?   Dr Dubey: So, I think the limitations are both for seropositive, as well as seronegative, patients. As a neurologist, when we see patients and send panels, we can be in a challenging situation in both of those scenarios. Firstly, thinking about seropositives - despite the growing literature about neurology and antibodies, we have to be aware, at least to some extent, about what methodologies are being utilized for these antibody tests. And what I mean by that is knowing when you're sending a sample to a particular lab, the methodology that they're utilizing - is that the most sensitive, specific way to test for certain antibodies? We've learned about this through some of the literature published regarding MOG and aquaporin-4, which has demonstrated that these antibodies, which we suspect are cell surface antibodies, not only generate false-positive, but also false-negative results if they are tested by Western blots or ELISAs. Similar can be applied to some of the cell surface antibodies we are investigating on the autoimmune neuromuscular side (we have some sort of unpublished data regarding that for neurofascin-155). Secondly, it's also kind of critical when you're getting these reports to kind of have a look at what type of secondary antibodies are being utilized, an example being we talked about neurofascin-155, and I mentioned these are IgG4-predominant diseases, so testing for neurofascin IgG4 and knowing that particular patient is positive IgG4 rather than neurofascin pan-IgG. That's an important discrimination, and important information for you to know, because we have seen, at least in my clinical practice, that patients who are positive for neurofascin IgG4 follow the typical story of autoimmune neuropathies - the ones who are not (who are just neurofascin-155 IgG-positive), oftentimes can have wide-ranging phenotypes. The same applies to neurofascin-155 IgMs. And then (not for all antibodies, but for some antibodies), titers are important. A good example of that is a3 ganglionic receptor antibodies, which we utilize for when we're taking care of patients who have autoimmune dysautonomia - and in these cases, if the titers of the antibodies are below .2 nmol/L, usually, those don't have a high specificity for AAG diagnosis. So, I get referred a lot of patients with very low titers of a3 ganglionic receptor antibodies, where the clinical picture does not at all look like autoimmune autonomic ganglionopathy. So, that's another thing to potentially keep in mind. And then, on the seronegative front, it's important to recognize that we are still sort of seeing the tip of the iceberg as far as these antibodies or biomarkers are concerned, specifically for certain phenotypes, such as CIDP. If you look at the literature, depending upon what demographics we're looking at or sort of racial profiles we're looking at, the frequency of these autoimmune neuropathy biomarkers range from 5% to 20%, with much higher frequency in Asian patients - so, a good chunk of these diseases are still seronegative. In the scenario where you have a very high suspicion for an autoimmune neuromuscular disorder (specifically, we'll talk about neuropathies, because that's why we utilize tissue immunofluorescence staining on neural tissues), I recommend people to potentially touch base with that tertiary care lab or that referral lab to see if they have come across some research-based antibodies which are not clinically validated, which can give you some idea, some additional supportive idea, that what you're dealing with is an autoimmune neuromuscular disorder. So, we have to keep the limitations of some of these antibody panels and antibody tests in mind for both positive, as well as negative, results.   Dr Monteith: So, you've already given us a lot of good stuff, um, about titer seronegativity and false-positive rates. And, you know, also looking at the clinical picture when ordering these tests, utilizing EMG nerve conduction studies, give us a major key point that we can't not get when reading your article.   Dr Dubey: I think the major key point is we are neurologists first and serologists later. Most of these patients, we have to kind of evaluate them clinically and convince ourselves at least partly that this might be an autoimmune neuromuscular disorder before sending off these panels. Also, I find it useful to narrow down the phenotype, let's say, in a particular neuropathy or a muscle disease or a hyperexcitability syndrome. So, I have a core group of antigens, autoantigens, or autoantibodies, which I'm expecting and making myself aware of - things beyond that will raise my antenna - potentially, is this truly relevant? Could this be potentially false-positive? So, clinical characterization up front, phenotypic characterization upfront, and then utilizing those antibody results to support our clinical decision-making and therapeutic decision-making is what I've tried to express in this article.   Dr Monteith: And what is something that you wish you knew much earlier in your career?   Dr Dubey: It's a very challenging field, and it's a rapidly evolving field where we learn many things nearly every year, and, sometimes, we learn things that were previously said were incorrect, and we need to kind of work on them. A good example of that is initial reports of voltage-gated potassium-channel antibodies. So, back in the day when I was actually in my medical school and (subsequently) in my residency, voltage-gated potassium-channel antibodies were closely associated with autoimmune neuromyotonia, or autoimmune peripheral hyperexcitability syndromes. Now, over time, we've recognized that only the patients who are positive for LGI1 or CASPR2 are the ones who truly have autoimmune neuromuscular disorders or even CNS disorders. The voltage-gated potassium-channel antibody by itself, without LGI1 or CASPR2, truly doesn't have a very high specificity for neurological autoimmunity. So, that's one example of how even things which were published were considered critical thinking or critical knowledge in our field of autoimmune neuromuscular disorders has evolved and has sort of changed over time. And, again, the new antibodies are another area where nearly every year, something new pops up - not everything truly stands a test of time, but this keeps us on our toes.   Dr Monteith: And what's something that a patient taught you?   Dr Dubey: I think one of the things with every patient interaction I recognize is being an autoimmune neurologist, we tend to focus a lot on firstly, diagnosis, and secondly, immunotherapy - but what I've realized is symptomatic and functional care beyond immunotherapy in these patients who have autoimmune neurological disorders is as important, if not more important. That includes care of patients, involving our colleagues from physical medicine and rehab in terms of exercise regimen for these patients as we do immunotherapies, potentially getting a plan for management of associated pain, and many other factors and many other symptoms that these patients have to deal with secondary to these autoimmune neurological conditions.   Dr Monteith: I think that's really well said, because we get excited about getting the diagnosis and then getting the treatment, but that long-term trajectory and quality of life is really what patients are seeking.   Dr Dubey: Yeah, and as you pointed out, most of the time, especially when we are in inpatient service, or even when we're seeing the patients upfront outpatient, we are seeing them, sometimes, in their acute phase or at their disease not there. What we also have to realize is, what are the implications of these autoimmune neurological conditions in the long term or five years down the line? And that's one of the questions patients often ask me and how this can impact them even when the active immune phase has subsided - and that's something we are actively trying to learn about.   Dr Monteith: So, tell me something you're really excited about in your field.   Dr Dubey: I think, firstly (which is pretty much the topic of my entire article), is novel antibodies and new biomarker discoveries. That's very exciting - we are actively, ourselves, involved in the space. The second thing is better mechanistic understanding of how these antibodies cause diseases, so we can not only understand diseases, we can also try and understand how to target and treat these diseases - this is being actively done for various disorders. One of the disorders which continue to remain a challenge are T-cell mediated diseases, where these antibodies are just red flags or biomarkers are not causing the disease, but it's potentially the T-cells possibly attacking the same antigen which are causing disease process, and those are often the more refractory and harder-to-treat conditions. I'm hoping that with some of the work done in other fields (such as rheumatology or endocrinology for type one diabetes), we're able to learn and apply the same in the field of autoimmune neurology and autoimmune neuromuscular medicine. And then, the final frontier is developing therapies which are antigen specific, where you have discovered that somebody has a particular antibody, and if that antibody is pathogenic, can I just deplete that antibody, not necessarily pan-depleting the immune system. And there is some translational data, there's some animal model data in that area, which I find very exciting, will be extremely helpful for many of my patients.   Dr Monteith: So, very personalized targeted therapies?   Dr Dubey: Correct. Without having all the side effects we all have to kind of take care of in our patients when we start them on, let's say, cyclophosphamide, or some of these really, really, significantly suppressive immunosuppressive medications.   Dr Monteith: Well, thank you so much. I learned a lot from reading your article to prepare for this interview, but also just from talking to you. And it's clear that you're very passionate about what you do and very knowledgeable as well, so, thank you so much.   Dr Dubey: Thank you so much. Thank you for inviting me to do this. And thank you for inviting me to contribute the article.   Dr Monteith: Today, I've been interviewing Dr Divyanshu Dubey, whose article on autoimmune neuromuscular disorders associated with neural autoantibodies appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information, important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Stiff Person Syndrome (SPS) is treatable if managed correctly from the outset. It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses. In this episode, Allison Weathers, MD, FAAN, speaks with Marinos C. Dalakas, MD, FAAN, author of the article “Stiff Person Syndrome and GAD Antibody–Spectrum Disorders,” in the Continuum® August 2024 Autoimmune Neurology issue. Dr. Weathers is a Continuum® Audio interviewer and associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Dalakas is a professor of neurology and director of the neuromuscular division at Thomas Jefferson University in Philadelphia, Pennsylvania; a professor of neurology and chief of the neuroimmunology unit and the National and Kapodistrian at the University of Athens in Athens, Greece. Additional Resources Read the article: Stiff Person Syndrome and GAD Antibody–Spectrum Disorders Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media @ContinuumAAN facebook.com/continuumcme Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology.  Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Weathers: This is Dr Allison Weathers. Today, I'm interviewing Dr Marinos Dalakas about his article on stiff-person syndrome and GAD antibody-spectrum disorders, which is part of the August 2024 Continuum issue on autoimmune neurology. Dr Dalakas is a world- renowned expert in neuromuscular diseases and, really, the first name any neurologist thinks of when they hear the diagnosis of stiff-person syndrome. Dr Dalakas, this is such an honor to be able to speak to you today. Welcome to the podcast, and would you please introduce yourself to our audience?   Dr Dalakas: Yes, thank you very much. I'm so happy to participate in this interview. I'm the Chief of the Neuromuscular Division at Thomas Jefferson University in Philadelphia, and I am interested in autoimmune neuromuscular diseases for many years and also on disease mechanisms and immunotherapy.   Dr Weathers: Thank you again for talking with me today. So, given how very rare stiff-person syndrome and the GAD antibody-spectrum disorders are, prior to December 2022, I would have started our time together by asking you to explain this collection of diagnoses to our listeners and by also talking about how often they occur. It feels like that's a bit unnecessary ever since Celine Dion went public with her diagnosis - that moment really changed the public awareness of what was previously outside of neurology and almost unheard-of disease. So, instead, I'll start with, what is the key message of your article? If our listeners are going to walk away remembering one thing from our discussion, what would you like it to be?   Dr Dalakas: Well, I think the publicity has been very good for the disease, this disease spectrum. On the other hand, there have been some misleading messages, like, it's extremely rare, it's untreatable, it's disabling – which, they are partially correct, so, my message is, first, to make sure the neurologists make the correct diagnosis, because there are a lot of diseases similar to stiff-person, but they are not stiff-person. So, to make sure the diagnosis is correct and to make the patients aware of what to expect when they have this disease and what therapies we have and what we may have in the future. So, the number one message is the correct diagnosis and then to avoid overdiagnosis or misdiagnosis, because now we see both - we see overdiagnosis and misdiagnosis.   Dr Weathers: I think that's such a critically important point, and one you really delve into really beautifully in the article, so I encourage our listeners who do have access to it to really read through it. As I said, you do a great job really explaining that - and, actually, to go into that further, could you explain how you approach the diagnosis of a patient with possible stiff-person syndrome or one of the other GAD antibody-spectrum disorders? And I know you probably get asked that on a daily basis. As I was telling you before we actually formally started recording, I remember back when I was a resident and saw my first case of a suspected patient with stiff-person syndrome, my mentor advised me to look up your case series, your articles at the time, and really use that to guide my diagnosis. What do you feel is the most challenging aspect of diagnosing a patient with one of these conditions?   Dr Dalakas: Well, the first is the clinical symptomatology. We say the patients present with spasms and stiffness, but also, there are phobias. They are very hyperexcitable to sudden stimulations, to sudden noises, to unexpected touches, and all of them can cause spasms, and then when you examine the patients, they have stiffness. Now, the stiffness (if there is a true stiffness) results in gait abnormalities (the patients are falling because they're so stiff), and also, the hyperexcitability causes a lot of anxiety and a lot of phobias (they're afraid to cross the street, they're afraid to make a destination promptly) – so, all these things are sort of suggestive of stiff-person. So, these are the symptoms that you hear, you listen, and you ask the patients, and then, when you examine the patient, you look for certain signs that there are, specifically, like stiffness of what we call agonist muscles and antagonist muscles, which means there is stiffness of the abdominal muscles and at the same time, stiffness of the back muscles - so, this concurrent stiffness of these opposing muscles is very specific, very characteristic of the stiff person, so if you see that, and then you listen to the history, you're very close to the diagnosis, and then you do the antibodies. And the antibodies (the specific antibodies, the GAD antibody), but it is specific as we say in the article, and we tried to make this very clear to the neurologists, that it's the high titers that matter, because low titers are not necessarily specific. So high titers of antibodies in the serum, above 10,000 by ELISA (or whatever method they use; but it has to be this many times above normal), and then if you have high serum titers and all the symptoms they mentioned, it is stiff-person. On the other hand, if the titers are low, then you may want to do a spinal tap to see if there is synthesis of antibodies in the spinal fluid. That helps you. Now if the GAD antibodies are negative, then you start wondering, is this seronegative SPS? And how do you confirm the seronegative SPS? You do electrophysiology, and the electrophysiology is, again, to see if there is activity (muscle activity) concurrently from the agonist and antagonist muscles - in other words, from the, let's say the tibialis anterior and the gastrocnemius (so, it's two opposing muscles, eg, biceps and triceps) - and if you see activity in both of these opposing muscle groups, and you see also hyperexcitability (you touch the patient, you stimulate just a little, and you see activity in other muscle groups). So, the electrophysiology is very important if the patient's antibody negative, but they have the other symptoms that I mentioned before.   Dr Weathers: I can imagine how challenging those must be (those seronegative cases) to try to really make sure you're identifying and carefully determining that you have the right disease as you alluded to at the beginning. I know how hard it must be for patients to want to at least have some answers to have a diagnosis.   Dr Dalakas: And this is the main thing today, because the publicity, as I mentioned, the beginning, increased the receipt of some information, so they overdiagnose it, like, “Oh, you have this and this and this, so it may be stiff-person”. And so, in fact, recently, we had a series of patients together with the Mayo Clinic Group of out of 173 patients referred to the Mayo Clinic for stiff-person – that's referred to them - only 28% had stiff-person. It's a low percentage, but it is an indication that the neurologists now refer patients to us for stiff-person, but we need to be very careful to correctly make a diagnosis.   Dr Weathers: On one hand, it's good that people are aware and considering the diagnosis, but it does highlight that risk of overdiagnosing.   Dr Dalakas: Yeah. It's the opposite of when I started this stiff-person syndrome (was close to 30 years ago at NIH) - at that time was underdiagnosed. This was the most rare disease, and I collected patients because at the NIH, I was also the Chief of the neuromuscular division there, and I was doing a study, so it was easy to collect patients (I collected more than 100 patients), but at that time, it was misdiagnosed. So, we had patients that I was seeing and they're really disabled, because they have been having the disease for many years, but they had been diagnosed either for Parkinson disease, for anxiety disorder, for psychiatric diseases, or for MS, or for myelopathies, or for myelitis - so many different things, and of course, they didn't have the correct diagnosis and they were disabled.   Dr Weathers: The side effect of having one of the most famous celebrities in the world having this rare disease - you know, the downside of the increased awareness, as we've said. So, moving on from the diagnosis to treatment - again, you do a, obviously, you know, an incredible job in the article, really going through the treatment options and your algorithms - what would you say is the most common misconception you've encountered in treating patients with this disease?   Dr Dalakas: The most common is now (with the publicity) is that it is a disabling disease. Well, it is disabling, but if you treat the disease correctly and early on, I'm not saying we're curing the disease - many diseases (autoimmune diseases), we help a lot, so there are some we make the patient feel normal, but the disease is there - so, if we start the correct therapy early, a good number of patients respond very well. But by the time the patients come to us, they are so stiff, they walk like a statue, or they come in a wheelchair - of course, it's difficult to reverse this, although we have been very happy to see patients with immunotherapies to get out of the wheelchair, to walk, to enjoy normal activities. So, we have made enough progress with the therapists to help a good number of patients. Now, what is the first therapy we do? Well, is what we call the antispasmodics - these are drugs that relax the stiffness that patients have, sort of a symptomatic therapy. It's not going to address the disease itself, but we address the symptoms. And of course, the symptomatic therapy in SPS is not just to relax the patients - it is related to the so-called GABAergic inhibition. So, the drugs that we use (like the benzodiazepines, or the baclofen, et cetera), these are the drugs that work on the GABAergic pathways. So, it is symptomatic therapy, but it works also on the mechanism, so it's not just a relaxing basis - but since the patients have a lot of phobias, the benzodiazepines also help the phobias. The anxiety and the phobias make the patients worse - they make them more stiff. And in the beginning, they go to psychiatrists because they are so phobic - they're phobic to walk. They hear something, they get so stiff. And I have patients coming at the National Airport in Washington to come to there needing aids in getting out of the plane - some of them get so stiff, they have to get an ambulance to come to the hospital because they're stiff everywhere. So, these phobias and anxiety have triggered a lot of my interest to the point of asking the investigators at the National Institute of Mental Health to see if there is any such thing like autoimmune phobias, because these patients have an autoimmune disease, so, well, maybe we can treat the phobias of immunology - well, we did not find anything, but I just sort of brought the idea maybe we have an autoimmune phobia. But on the other hand, when the patients get better, the phobias are reduced and they're more comfortable to walk. So, it's a very interesting complexity of the symptoms altogether.   Dr Weathers: That is – and, actually, that leads into my next question somewhat, that, as I mentioned in your introduction, you are the world expert in this rare disease. How did that happen? You talked about it a little bit just now. But how did you develop this particular interest and expertise? What drew you to this particular disease?   Dr Dalakas: Yes. It's interesting. I was interested in autoimmune neuromuscular diseases (many of them) and neuropathies and myopathies, and one day, I had a good friend of mine who was the clinical director of NINDS at that time, Dr Hallett. So, he saw patients in the movement disorder clinic and they had stiff-person (I don't know why they went to the movement disorder, but they went there), and Dr Hallett said, “Well, this is an autoimmune disease. You should work on this.” And then, I started seeing one or two patients, and I was very impressed. Really, the symptomatology is so interesting. The patients are suffering, and they sort of give the impression that they're neurotic. So, it's just a combination of when you listen to the symptoms, I was very impressed with the depth of the discomfort that they have and without seeing anything - but, when you examine the patient, you see the stiffness and nothing else. They're not weak, like, we see patients with MS, with myopathies, with neuropathies - they have weakness. They may use a cane, they may use two canes, they may use a walker, because they're stiff. So, it's a different disability than you see in patients who are weak. So, this really made me so interested to understand the mechanism - what's going on here - and that's the reason I started and I put the protocol. And then, we did a lot of immunological studies to understand the mechanism, electrophysiological studies to look at these agonist and antagonist muscles - and of course, we named it also. You know, in the beginning, the syndrome was described as stiff man (stiff-man syndrome), and they're all women. They are most of them, women. In fact, there is an article in a major journal, three women with stiff-man syndrome - and this was many years ago. So, stiff-person will be a more proper term. And then we're seeing a lot of patients or more women, but also we have enough men.   Dr Weathers: So, we've talked a lot about the change with this disease in public awareness. How has that changed your day-to-day life - has it (with the change in public awareness)? Are you bombarded with media requests?   Dr Dalakas: Well, it has stimulated me to write more about the disease and more articles, but also to highlight certain things that were not known before. For example, I had recently a paper on late-onset stiff-person. So, people, we see now patients who develop stiff-person at the age of seventy - they are above sixty or so, overall - and they have more severe disease. These patients also have not good tolerance to the medications we use - so, it's a more challenging group, so it is important to make the diagnosis even in patients with late-onset. These people do less well, because, first of all, they're all misdiagnosed, because if you're a little stiff at the age of sixty-five or seventy - well, you have a bad back, so you all have degenerative disc disease, so you don't think of stiff- person in that age. So, the stimulus was to identify some other issues with the stiff-person. The other is to think of new trials - and I have been working on two new trials. They're not out yet. I'm working to see how best to apply the new therapies. And also, it came up the idea of what are the best ways to assess, objectively, to assess the response, because this is an issue from the beginning. When I did controlled trials at the NIH, and we had established the so-called stiffness index to see how stiff they are measurably, but it is still subjective. It's not really objective, it's not (weakness to measure). So, we have gait analysis, we have the time to walk. So, I think establishing objective criterion to assess response to therapy, it's an important one - and so, I have been working on this how to make it more objective or as subjective as we can.   Dr Weathers: I think that's fantastic. And you actually, I think, have already answered my question - which is, what is the next breakthrough coming in the diagnosis and management of patients with stiff-person syndrome and the GAD antibody-spectrum disorders - and I think it's going to be the outcomes of these trials. Is there anything else that you're really excited about coming along in this field?   Dr Dalakas: Well, I think that the hope is, then, better immunotherapy, because the patients respond to IVIG based on the controlled study. We did one with anti-B-cell therapy - it was not statistically positive, but we had some placebo effects, because that second trial included some patients who did not have severe disease, so it was difficult to assess mild response. So, I'm interested in other similar immunotherapies, and we were approaching companies to see if they can sponsor such a trial. I think the publicity helps a lot, because if I was going to approach a company before the publicity, nobody would be interested in - there's no, you know - it's money-driven, so they will not do it. But at the NIH, I did it, because NIH had the grants there to sponsor the trials. So, I think the publicity will help us. And I know talking to companies, there are one or two companies that they have expressed a lot of interest, and, hopefully, we can do some new trials and go work on it, but I don't have any clear drug at the moment. I cannot discuss a real drug.   Dr Weathers: Of course, of course, more to come, but still very exciting. And so, still to learn more about you - again, you're so well known, obviously, for what you've done for the field of neurology. What do you like to do outside of seeing neuromuscular patients in your research career? What do you do for fun for your hobbies?   Dr Dalakas: Well, I have two hobbies. One is I'm an art collector of abstract expressionism. So, I go to a lot of auction houses, and I bid often for certain artists that I'm very interested, some French artists, some at the New York School of Modern Art. The eras of the forties and fifties of the abstract expressionism - so that's my collection and my interest in not missing auctions. And the other was I have a interest in wine collection – but, so, most of the time, I read art and I collect art.   Dr Weathers: That is a great answer. I appreciate art. I am not (fortunately) at the auction and collecting stage yet, but that I will have to learn from you. That's wonderful.   Dr Dalakas: Yeah. I'm originally from Greece, and I have also a professorship at the University of Athens, and also I go there. I also have some European artists in my collection.   Dr Weathers: That's wonderful. We have one more modern piece that we've been lucky enough to have.   Dr Dalakas: Yeah, I started with the impression impressionistic art, but I evolved into abstract.   Dr Weathers: Who is your favorite artist?   Dr Dalakas: Well, it's, you know, Rothko and Newman. So, these are very expensive artists, of course, so I can, but in that school, so these artists are not alive now, but people who are working with Rothko and Newman in the other group - so, there are four or five of them that I collect.   Dr Weathers: I feel like we need a whole separate interview just to talk about that.   Dr Dalakas: But, they are very stimulating, because the colors talk to you, and it's not like an impressionistic piece that, sort of, their flowers are nice, et cetera - so the colors talk to you differently.   Dr Weathers: They do. I love Rothko. Well, thank you, Dr Dalakas, for joining me on Continuum Audio. This has been a wonderful conversation. Again, today, I've been interviewing Dr Marinos Dalakas, whose article on stiff-person syndrome and GAD antibody-spectrum disorders appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. Growing availability of effective treatment options will lead to personalized therapies and improved outcomes. In this episode, Gordon Smith, MD, FAAN speaks with Elia Sechi, MD, author of the article “NMOSD and MOGAD,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Sechi is a neurology consultant in the neurology unit of the Department of Medical, Surgical and Experimental Sciences at the University Hospital of Sassari in Sassari, Italy. Additional Resources Read the article: NMOSD and MOGAD Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @EliaSechi Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Smith: Hello. This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Elia Sechi about his article on aquaporin-4 antibody-positive NMOSD and MOGAD, which appears in the August 2024 Continuum issue on autoimmune neurology. Dr Sechi, before we dig into this really exciting topic about NMOSD and MOGAD, perhaps you can tell our listeners a little bit about yourself, where you practice, how you got interested in this topic.   Dr Sechi: Hi, Dr Smith, and thank you for having me. So, my story begins here in Italy, actually - I did my med school and residency in neurology at the University Hospital of Sassari here in Sardinia. And after residency, I was lucky enough to be accepted at the Mayo Clinic in Rochester, Minnesota for a research fellowship - and that's where I spent the next three-and-a-half years, approximately. My fellowship was focused on autoimmune neurology, specifically demyelinating diseases of the CNS associated with antibodies – so, of course, NMOSD and MOGAD mostly, but also myelitis, MS, and autoimmune encephalitis – so, there's where I built most of my expertise in the field. And then, it was at the beginning of the pandemic (of the COVID pandemic) that I came back here to Italy to practice. And now, I work mostly as a neurohospitalist, and I also have my subspecialty outpatient service for patients with autoimmune neurological diseases.   Dr Smith: I wonder if you might just give us a minute or two about what it was like training in Mayo? I went to medical school there, and, you know, at the time, I thought that was just normal healthcare and normal training, and, you know, it was only later that I realized how amazing that was. I mean, this is where aquaporin-4 was discovered - I mean, what was that like? It must have been really cool training there with that team.   Dr Sechi: Yeah. You know, it's the temple of autoimmune neurology. It's fantastic. It's a great environment, very stimulating. You know, I think the great strength is that they see many patients with rare diseases, so, you get really confident with MRI features and clinical features with the history of the diseases, and this is important to recognize the typical features and differentiate from MS to do a good differential. And, of course, you know, the team is fantastic - superstars in the field. It's very, very stimulating. So, it's something that I definitely recommend. It was a fantastic experience.   Dr Smith: Well, you know what's great is, I don't know if you follow sports, but, you know, like, in the United States and college football, people refer to Gator Nation – right, these are all people who are fans of the Florida Gators. Or, maybe it's AC Milan nation in Italy. I don't want to get there (Roma, whatever), but there are all these people who've trained at Mayo, and, uh, what's great is it's a small world, right? So, I'm super excited to meet you and talk about this, because - I'm going to add you to my Rolodex, because when I see these patients (I'm a neuromuscular guy, but I do a fair bit of inpatient time), I'm always calling a small number of people, so I'm really pleased to meet you so I can put you on speed dial and ask you questions about these patients. I wonder if, maybe, we can begin? You know, in our preparatory discussions, I shared that I just came off our hospital service, and we had several of these patients, you know, where we were thinking about NMO or MOGAD as a cause for their problem - and I wonder if you just have any pearls or pitfalls in when we should suspect this, right? Most of us recognize bilateral optic neuritis, longitudinally extensive myelitis - we need to be thinking about these. Any pearls or pitfalls for when we should or should not be looking for these disorders?   Dr Sechi: Yeah, I think this is a great question. I think the first thing to pay attention is the phenotype. So, the clinical MRI phenotype that are typically associated with NMOSD and MOGAD, they are quite characteristic - and it's important to be aware of those phenotypes and how they differ from MS, because in my experience, one of the common misinterpretation (misconception) in clinical practice is just to test for AQP-4 and MOG antibodies in any patient with new-onset demyelinating disease of the CNS, even if it's typical MS. And, this is quite wrong, because MS is way more common in clinical practice - it's sixty, eighty times more common than NMO and MOGAD - and so, if you test all those patients without filter (indiscriminately) for antibodies, you increase the risk of false positivity exponentially, even if you have a highly specific test. So, first of all, I think it's good to select the right patients to test. As you said, patients with LTM, extensive involvement of the optic nerves on MRI, ADEM - there's also patients with cortical encephalitis phenotype (which is a rare phenotype of MOGAD), but not definitely good to test the typical MS patients. This is the first thing.   Dr Smith: Yeah, I mean, that's an issue in all of neurology, isn't it, right? I mean, it's an issue in sort of just sending, you know, the Mayo panel, the autoimmune encephalitis panels - you need to select patients carefully, but I think this attention to prior probability is something that we need to really focus on in multiple areas. So, I wonder if you might expand a little bit on assays. I do a lot of work in myasthenia and I know which labs do a really good job with, you know, acetylcholine receptor antibody testing and those that maybe do not, and there are different methodologies for testing - do you have any wisdom in terms of how to select a lab, what to look for, and how to interpret the results you see based on the particular assay that's being used?    Dr Sechi: Yeah, that's a critical point. I agree. And especially if you work in myasthenia, you're very well aware of the differences between different assays, and nowadays, most of the high-quality assays are cell-based assays (either fixed or live) - it's the same in myasthenia, and people need to pay attention to some of the less-specific assays. Let's say ELISA, for instance - testing AQP-4 and MOG antibodies with ELISA is quite dangerous, because the risk of false positivity is quite high. So, it's good to know what assays to trust most and also good to know what's the right specimen to send for antibody test. For instance, with AQP-4, we know that serum testing is recommended only, and the CSF doesn't add much, but with MOG, we know that approximately 10% of patients have an isolated positivity in the CSF, which is interesting, because it means that when you have a patient with a strong diagnostic suspicion as a phenotype that is highly suggestive for MOGAD and the serum testing is negative, you may consider testing the CSF to increase your sensitivity. So, this is very important.   Dr Smith: So, I have a question for you that may seem a little naïve, but I bet other people are thinking it - can you tell us why it is that these disorders affect optic nerve and spinal cord preferentially? And I think, for NMO, the whole area postrema thing seems awfully specific to me. What's the deal? Why are these areas preferentially affected by these antibody-mediated disorders?   Dr Sechi: This is a tough question. For NMO, we know, probably, there is higher expression of some of the isoforms. Let's say there is a higher density of AQP-4 molecules that target the most affected regions - so, of course, AQP-4 is preferentially expressed in the subependymal regions around the ventricles and in the spinal cord and optic nerves, but you may have, also, solutions along the cortical spinal tracts in case of the brain involvement. The area postrema is kind of a different explanation, because there is a sort of permeability - increased permeability - of the blood-brain barrier there. So, there are several factors in MOGAD - this is not very clear, so, this is a great topic to study in the future, I think.   Dr Smith: This is a really interesting area, and one that's really benefited by significant therapeutic development. I wonder if you might look a little bit in the future and tell us, maybe, the agent, or perhaps the target, that you're most excited about therapeutically that's coming down the road these days?   Dr Sechi: There are trials ongoing for MOGAD, which is the real need in terms of treatment, because for NMO, we already have three, four drugs that have been approved and which efficacy have been demonstrated by randomized clinical trials, and those are B-cell depleting agents, IL-6 inhibitors, and complement inhibitors. For MOGAD, this is still a gray zone, because the optimal treatment strategies remains to be defined. There are ongoing trials that are quite promising on IL-6 inhibitors and the inhibitors of the neonatal Fc receptor (which is also used in myasthenia gravis as you know). And something that seems to be quite effective - a good option for long-term treatment in these patients and relapse prevention - is also the periodic administration of IVIG (intravenous immunoglobulin), which is a nice option, for instance, in the children where you want to avoid immunosuppressants of other types. So, I think IL-6 is going to show to be very effective in the end. We'll see. We'll see.   Dr Smith: So, I wonder if I might just give you a vignette and get your thoughts about, kind of, acute management, right? I just took care of a patient who had a longitudinally extensive myelitis and she was essentially paraplegic and actually came in progressing fairly rapidly, and we, of course, started her on IV methylprednisolone, sent off the proper diagnostic testing - the question I have is, how quickly do you advance therapy and go to IVIG or plasma exchange when you're encountering these, right? It takes, you know, I think the turnaround time is, you know, often about a week to get these tests back (at least several days) - I mean, should we be going very quickly to plasma exchange in someone who has a severe phenotype? Is it okay to do three to five days of IV methylprednisolone and wait for the results to come back? What's the right approach?   Dr Sechi: I think this is a great question, actually. You know, management of the acute attacks probably is the most important thing, you know, to allow a good recovery, and I think timing of PLEX administration should be very short - so, the threshold for PLEX should be low, especially when the attack is severe, and this has to be done regardless of antibody testing results, which is typically not available before one or two weeks (at least a year in Italy), I think, in many hospitals. So, I think the risk-benefit ratio of administering PLEX is in favor of treatment in these patients, because the side effects (the potential side effects) are very rare and can be prevented. Some diseases, they can mimic NMO or MOGAD - they're very rare, and they can really worsen with PLEX. As an example, we can say spinal cord infarction can worsen, maybe, because of hypotension due to PLEX. Or some very rare infections, like one case, a bad case of intramedullary spinal cord abscess that looked really similar to an AQP-4 IgG-related LTM - and it was bad, because the patient had no fever, no signs of infection, the CSF culture was negative initially, so we ended up doing a biopsy after failure of PLEX and steroids. So, it is recommended to start within the first three to five days, preferentially, in severe cases, and this is great for the outcome of the patient, so, I do recommend PLEX as a second treatment option. And I'm not sure about IVIG acutely. There is some data on MOG, but it's still controversial - it works a lot when PLEX fails, but it can be considered after PLEX, of course. And there are some very rare patients that do not improve, even after IV methylprednisolone, PLEX, or IVIG, and so, you need to consider some rescue therapies. In those patients, it's kind of complicated, because there are some options, like IL-6 inhibitors seem to be quite effective and quite fast-acting for MOGAD attacks, and also eculizumab and complement inhibitors can be an option in patients with AQP-4 - but maybe less in patients with MOG. So, these are the possibilities (very quickly).   Dr Smith: So, you mentioned FcRn inhibitors a moment ago, and I wonder, do you see a future where - and I think you were mentioning them as maybe more chronic therapy? Correct me if I'm wrong.   Dr Sechi: Yeah, yeah.   Dr Smith: Do you foresee a role for these agents in acute management? I mean, there are some that, you know, very quickly lower immunoglobulin levels, though just looking out in the future, you think that these sort of infusion therapies that we think about chronic therapy (you mentioned, you know, complement inhibitors) are going to be useful in acute management?   Dr Sechi: Yeah, it depends. It's a good option to try. I'm not sure about the time to action. It's very dependent on that, because IL-6 inhibitors and complement inhibitors are very fast-acting (I think they can be effective already within twelve hours, 24 hours, which is good), but it's reasonable that, also, Fc inhibitors can be an alternative in the future. As far as I know, there is not much in the literature, but it's good to try in the future in case, acutely.   Dr Smith: Well, exciting times indeed. Elia, thank you so much for a great discussion. I thoroughly enjoyed this. I look forward to visiting you soon, and I want to congratulate you on a really great article that's very interesting and very clinically useful.   Dr Sechi: Well, thank you, Dr Smith. This is my pleasure, and thank you for great questions. I had a great time and hope the readers of Continuum will like the article and the nice figures we have put together. So, thank you, thank you very much.   Dr Smith: Well, again, congratulations. And for our listeners today, I've been interviewing Dr Elia Sechi, whose article on aquaporin-4 antibody-positive NMOSD and MOGAD appears in the most recent issue of Continuum, which is on autoimmune neurology. It's a very exciting issue. Please check out Continuum Audio episodes from this and other issues of Continuum. And thanks to you all for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Dr. Armando Hernandez-Rey is Conceptions Florida's medical director and triple-board certified in Reproductive Endocrinology and Infertility; Obstetrics and Gynecology; and Surgery. Dr. Armando Hernandez-Rey has over 24 years of experience in the medical field. He graduated from Universidad Autonoma de Ciencias Médicas de Centro America in 1998. He attended medical school at the University of Miami Miller School of Medicine for his specialization in Obstetrics and Gynecology. He specializes in treating patients with polycystic ovary syndrome (PCOS), recurrent pregnancy loss (miscarriage), and severe endometriosis. He is especially interested in fertility preservation (eggfreezing) for patients who must delay childbearing for personal or medical reasons, including cancer and systemic lupus erythematosus. Dr. Hernandez-Rey is an assistant clinical professor at the Herbert Wertheim College of Medicine at Florida International University and serves as an ad-hoc reviewer for the prestigious peer-reviewed journal, Fertility and Sterility. He has also published several articles and chapters in medical literature.   Website https://www.conceptionsflorida.com Instagram https://www.instagram.com/conceptionsflorida/ Facebook https://www.facebook.com/conceptionsfl Tiktok https://www.tiktok.com/@conceptionsflorida     For more information about Michelle, visit: www.michelleoravitz.com   The Wholesome FertilityFacebook group is where you can find free resources and support: https://www.facebook.com/groups/2149554308396504/   Instagram: @thewholesomelotusfertility   Facebook:https://www.facebook.com/thewholesomelotus/     Transcript:   Michelle (00:00) Welcome to the podcast, Dr. Hernandez -Ray.   Armando Hernandez-Rey MD (00:04) Thank you, Michelle. Thanks for the invitation. It's really an honor and a privilege to be on your show, on your podcast.   Michelle (00:09) Yes, well, I've heard a lot about you over the years because I've had a lot of patients go to you. And one of the things that I've heard is that you do really well with surgeries and fibroids and you're able to in and   but in a way that still preserves fertility. So that was one of the things that I've learned.   Armando Hernandez-Rey MD (00:32) Well, reproductive endocrinology and infertility as a subspecialty is a surgical subspecialty as is OB -GYN, which is a mandatory path to get to the infertility route. Unfortunately, a lot of the newer generation is not operating because they're not taught, not through no fault of their own, they're not taught. The reality is that it is...   Michelle (00:47) Mm -hmm.   Armando Hernandez-Rey MD (00:55) for a myriad of reasons this phenomenon has happened. Number one, the minimally invasive surgery tract has been developed where you have the person who's really just really perfected their obstetrical skills. And then you have the gynecologic oncology route and the pelvic urogynecology or pelvic reconstruction route and the minimally invasive surgical route. And a lot of the reproductive endocrinologists,   have said, you know what, I'm going to forego surgery and I'm going to refer it out. My personal philosophy, and this is in no way critical to absolutely anybody, it's just my own, is that I went into medicine to be a surgeon, I actually wanted to be an orthopedic surgeon. I ended up not liking it, I had a very bad fracture when I was in my teens playing competitive soccer, and I really had some PTSD from that fracture, so I just couldn't see myself doing   orthopedic surgery, but I somehow found my way towards OBGYN, absolutely loved it. And eventually towards the reproductive endocrinology route, which encompasses a lot of surgery, should you allow it. And so yes, like you said, fibroids are an important part of fertility. you, tubal reconstruction used to be much more important than it is now. People are more, are bypassing that route and going directly to in vitro fertilization.   Endometriosis, as I said, I was running a little bit late today. I was in a very, very complex endometriosis case with a patient with bilateral endometriomas and complete frozen pelvis and scar tissue. And, you know, just a little bit longer, I had to work with the colorectal surgeons to do some resection of the colon because it was, you know, endometriosis is such an awful, awful disease. So yes, to answer your question, I...   Michelle (02:41) Yeah.   Armando Hernandez-Rey MD (02:44) Absolutely love surgery. I think it's an integral part of the infertility journey to get a patient from being infertile to getting them to a high level of success with any sort of treatment. And hopefully it's more conservative than having to resort to artificial insemination or in vitro and with just surgery and corrective surgery, we can help the couple achieve a pregnancy.   Michelle (03:07) Yeah, and I think it's important because I think that a lot of people might not realize that there are certain people that specialize in this or have experience doing that, doing surgery and really getting in there because it is important to find somebody who's specialized if you have a complicated case.   Armando Hernandez-Rey MD (03:23) I think it's important. I think people feel well taken care of. Again, my perception, people feel well taken care of when everything is done in house. Meaning, you know, there's no messages that get lost as you refer a patient out who may have the minimally invasive surgery knowledge, but not necessarily the focus on infertility, reproductive endocrinology.   Michelle (03:33) Mm -hmm.   Armando Hernandez-Rey MD (03:50) specialist has and I think people feel comfortable with that.   Michelle (03:52) Yeah, absolutely. Because there's some people that will take out fibroids, but they're not doing it with fertility in mind. You know, for many women, it could just be just taking out fibroids, but you're doing these things with fertility in mind.   Armando Hernandez-Rey MD (04:07) There are many great surgeons out there that are not infertility specialists. You know, I want to make sure that I'm clear. I just think that I was, I always love surgery. I happen to do surgery and I feel my patients feel very comfortable with me doing the surgery and not being referred out. It's what I think. You know, the journey, the infertility journey is very complex. It requires a lot of a woman in particular more than the male and to be   Michelle (04:25) Yeah.   Armando Hernandez-Rey MD (04:36) you know, passed around, it gets complicated. And I think it's nice to be able to offer that service to patients.   Michelle (04:44) Yeah, for sure. And then you do specialize in miscarriages.   Armando Hernandez-Rey MD (04:49) Sure, I mean, I think we all really have a focus on on as you know, we're all specialized in miscarriages and and PCOS and all that there's some people that tend to see More miscarriage patients or they people will refer miscarriage patients to us We have a particular kind of focus on that, you know, I think a lot of it is   genetic, a lot of it is immunologic, a lot of it is just taking a holistic approach to things and not just focusing on one or the more common causes of infertility. And even now, I think that, you know, the use of supplements, which maybe 15 years ago was maybe considered some snake oil. Now, I think there's a lot of provocative data that has shown that supplements do work, in particular in   Michelle (05:18) Mm -hmm.   Armando Hernandez-Rey MD (05:44) cases with recurrent miscarriage. And now we have the ability to measure those levels and we are now ability to supplement those levels and they have tremendous impact positively on these patients.   Michelle (05:57) And what supplements have you seen help with miscarriages?   Armando Hernandez-Rey MD (06:02) Well, I think a lot of it has to do with what the cause of the miscarriages is. Oftentimes, believe it or not, miscarriages can alluded to fibroids, it could be anatomical, sub -mucosal myoma. Well, there's not gonna be any supplement that's gonna help with that. It's just purely the surgical route or the diminished ovarian reserve,   Michelle (06:07) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (06:29) cause for recurrent miscarriages, which is older women or ovaries that are behaving or eggs that are behaving older than what their chronological age would dictate, you have a higher chance for aneuploidy. And in those cases, there's a variable cocktail of supplements that we use, including ubiquinol, including N -acetylcysteine, including vitamin E, even melatonin has been shown to be very, very effective. And I can go on and on, even alpha lipoic acid.   Michelle (06:50) Mm -hmm.   Armando Hernandez-Rey MD (06:57) as well. There's some very nice studies coming out of Mayo Clinic that have shown that aflalipoic acid is very, very good for recurrent miscarriages. So again, things that we thought were, well, they can't hurt, now we know that they absolutely help.   Michelle (06:57) Yeah.   Right. Yeah. I mean, that's great because it just helps to know that there's something that people can do that really does make a difference. And it's not just like in theory with miscarriages when it comes to immunology. I'd love to talk about that because I know that that's a big one. Actually, I did see a study that showed that women who have are more sexually active, that their immune system calms down. It behaves differently in the luteal phase.   Armando Hernandez-Rey MD (07:31) Mm -hmm.   Michelle (07:44) so that it's able to receive life so that it's not seeing like the sperm as an invader the, yeah.   Armando Hernandez-Rey MD (07:50) So women that are more sexually active than others, it's probably a function of repeated antigen exposure, which is the more the woman is exposed to the antigens of the sperm, more there becomes an acquiescence by the immune system to be more receptive of that embryo. Because remember, the embryo is   Michelle (08:06) Mm -hmm.   Armando Hernandez-Rey MD (08:19) a haplotype, meaning it's half female, half the woman, half the mother, and half the male. And the only genes that the immune system of the mother has got to harbor the pregnancy are her own. And so oftentimes the immunologic processes are heightened because it does not recognize the male antigens that are formed part of the embryo in general. But as a whole, I mean, recurrent pregnancy loss,   Michelle (08:33) Mm -hmm. Right.   Armando Hernandez-Rey MD (08:47) is, is a small portion of the general population and, it's skewed towards advanced maternal age and advanced paternal age. so the immunologic component, while absolutely important, I think it's the one where we're still not a hundred percent sure how to absolutely treat it. Although supplementation and.   immune suppression definitely are known to work. It's the testing that I think we still need a lot more work in doing because you know people talk about NK cells and you know that was part of my thesis when I was a fellow. So we talk about NK cells and ANA and antiphospholipids and all of that and the reality is that these tests have very very   poor sensitivity in the realm of immunologic infertility or reproductive immunology. And so you may have COVID and then you can test positive or lightly positive for NK cells. And so I think that the overwhelming response by the treating physician is, well, they're positive, they must be immunologically incapable of handling a pregnancy. So therefore we should treat.   Michelle (09:40) Mm -hmm.   Armando Hernandez-Rey MD (10:04) with nowadays what we use as intralipids. Back in the day, we used to use IVIG that has kind of fallen by the wayside a little bit. I think it's better to treat empirically than to have someone treat or test for all of these different immune markers that really, really in the presence of immunology and reproductive immunology,   They have very low sensitivity. Now if you're treating or you're looking for lupus or rheumatoid arthritis or mixed collagen disorder or Sjogren's for sure, they are your go -tos every single time.   Michelle (10:44) And what about a PRP for ovaries? What has do you do offer that?   Armando Hernandez-Rey MD (10:50) ovaries. American study of reproductive medicine came out with a black box warning that they do not recommend PRP for ovaries. Now, PRP for recurrent implantation failure, poor lining development, there is some very robust data that there may be some room or benefit for this.   Michelle (10:57) okay.   Mm -hmm.   Armando Hernandez-Rey MD (11:14) And we do do offer that. We do not offer intra ovarian PRP because ASRM has a huge black box warning on this. It's a liability. The potential for infection is there. Tubo ovarian abscess have been reported, adhesions, periovarian adhesions, and with very little to no benefit whatsoever. I mean, the whole premise for it is that we are...   Michelle (11:16) Okay.   wow, okay, I didn't know that.   Mm -hmm.   Okay, got it.   Armando Hernandez-Rey MD (11:42) regenerating the follicle complex and therefore improving egg quality and that definitively has not been shown to be the case. Although anybody who suffers from that as I would be would be like, slide me up. But unfortunately, you know, it's very easy for us to fall prey to things that we desperately want without having the medical literature to corroborate it or back it up.   Michelle (11:49) Got it.   Right.   Got it. So that's actually showing to not necessarily be what a lot of people originally thought, but for the uterus, it has been shown to help.   Armando Hernandez-Rey MD (12:15) Yes, we are doing PRP installations and very select group of women with those diagnoses in particular. And.   Michelle (12:25) So who would be a good candidate? Somebody who's had failed transfers, inflammation.   Armando Hernandez-Rey MD (12:30) Yes, someone with very high quality embryos, high quality embryos that are not getting pregnant. Also patients, for example, patients who have adenomyosis that do not develop a nice lining, a thickened lining. Those have been shown. Our numbers are very small, you know, by no means.   Michelle (12:42) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (12:53) they are in the realm of what a randomized controlled trial should be. We're following the data from the randomized controlled trials and from the literature that's out there. So patients with adenomyosis who have poor lining development, recurrent implantation failure, so patients with euploid embryos, that means a normal embryo that's tested that looks to be high quality. Also, after a second implantation failure, we'll...   offer that to the patient as a possibility.   Michelle (13:19) Mm hmm. Got it. Awesome. And then also we were talking about Ozempic pre -talk. So I'd love to get your... Yes. Yeah. Ozempic babies.   Armando Hernandez-Rey MD (13:24) the topic du jour these days, right?   It's right. So as we were discussing, I mean, this, this phenomena is not really a phenomenon that's surprising at all. It is just a, a byproduct, a side effect of, of how the medication works and the effects that positive effects that I have on women with in particular, and ambulatory disorders, specifically polycystic ovarian syndrome, which is often tied to or associated with insulin resistance, obesity, sometimes even overt.   type 2 diabetes and the elevated levels of insulin, the elevated testosterone levels, they all work together to create this sort of environment within the ovary and the system of the female which creates an ovulatory disorder or dysfunction. And as a woman loses weight by virtue of the way that these GLP1s or glucocortes   Michelle (13:58) Mm -hmm.   Armando Hernandez-Rey MD (14:22) Glucagon like peptides work They're very successful. They're very good at number one slowing gastric emptying which in turn slows down the release of sugar into the blood system to the Number one number two it stops the the release of glucose produced by the liver and Number three increases insulin levels so increase insulin levels helps get the the   the sugar into the muscles out of the circulation and out of stimulating the ovaries and the theca cells to produce more androgens which then get produced produce more estrogen which then stops the hypothalamic pituitary ovarian axis from functioning correctly and as these levels drop patients automatically begin to have spontaneous ovulation if the system is working and the male has normal sperm and they're sexually active.   this is how the ozempic baby phenomena occurs. And what we discussed also is that the concern is of the downstream consequences of ozempic babies given that the current recommendations are to have at least a two month washout period before anybody starts to try to conceive.   Michelle (15:32) So two month washout means like really not trying anything. Yeah. And then also, I know like naturally, myonocytol is really helpful as well for insulin resistance. It might take a little longer. And then also metformin has been used as well.   Armando Hernandez-Rey MD (15:37) No exposure, right? No exposure.   Yeah. Yes. So, my own hospital is, is a, is a great product. my own hospital alone, although you will find oftentimes my, my own hospital with a D chimeric, hospital and really the literature shows that my own hospital by itself is the one that truly has the most benefit might be hard to find.   Michelle (16:06) Right, yeah.   Right because for a little while they said my own hospital and dechiro, but now they're going back to saying just my own ocital, correct?   Armando Hernandez-Rey MD (16:23) Yeah, well the way that it's normally found in the body is at a ratio of 20 to 1. And that's what those supplements show, 20 to 1. Although we know now that in the ovary it's almost 40 to 1 ratio of myoinocytol to D -chimeric, inocytol.   Michelle (16:30) Mm -hmm.   Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (16:49) Myo Inositol is actually not an essential vitamin, but it's considered like a vitamin, but it's in the category of B8 It's a glucose like peptide that basically helps to Help the system function by processing the circulating blood sugar in a way that's more physiologic and there by lowering insulin levels and thereby also helping tremendously with   Michelle (16:56) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (17:16) regularity of cycles and even spontaneous ovulation as well. And metformin obviously is medication that's been around for many, many years. It is somewhat of a controversial drug. It is an anti -aging drug even these days because we know that insulin levels are so profoundly toxic for aging for the muscle and for the system in general.   Michelle (17:29) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (17:45) And so we know it works, we know that it helps with the efficiency of insulin. And so it's certainly been used for many, many, many years in the presence of patients with polycystic ovarian syndrome. I would challenge people to be a little bit more meticulous about using it in patients who are the lean PCOS.   Michelle (18:11) Right.   Armando Hernandez-Rey MD (18:11) or the skinny PCOS or the ovulatory PCOS even though insulin levels have been shown to be higher, slightly higher in...   Michelle (18:19) So you're talking about being cautious with metformin, not necessarily myonositol. Yeah, yeah.   Armando Hernandez-Rey MD (18:22) Metformin, you also don't want very high levels of myelonostetal because they can be, you know, there is some quote unquote toxicity. I think the recommendations are up to four grams per day. I think all the recommendations are four grams per day in two divided doses, two grams in the morning and two grams at night. I've seen patients be on eight grams and 10 grams and toxicity really starts happening around the greater than 10 gram dose.   Michelle (18:29) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (18:52) I in our office we only use it, you know, what's recommended which is the four gram total per day two grams in the morning two grams at night and I don't think it's the end -all be -all I don't think it's you know treating anything in life is multi -pronged. It's not just one single thing perhaps but I definitely believe very wholeheartedly that it does assist in in adjunct treatment, although we certainly have patients put patients on on myocytil and combined with   Michelle (19:06) Yeah. Right.   Armando Hernandez-Rey MD (19:20) diet and exercise and have been able to achieve pregnancies on their own, which is obviously what we want instead of having to go through treatments.   Michelle (19:27) That's great. I mean, I will say that I was very surprised this past year. two different patients came from different, different places, not yours, it was other doctors, but I think the nutritionist there suggested metformin when they did not have insulin resistance or PCOS for egg quality.   Armando Hernandez-Rey MD (19:47) Yeah, I'm not familiar with any studies that have shown that have improved that. In fact, when I was a fellow, we were, just as I was coming into fellowship, where I trained, Rutgers was involved with a very well known and publicized study, it's called the PP COAS study, which looked at patients on placebo versus metformin alone versus metformin with Clomid, sorry.   placebo versus clomid versus clomid with metformin and there was no difference in pregnancy rates or anything else. I'll go one step further with them going back to the myonocytol. It has even been shown to decrease the rates of gestational diabetes and so in our patients with PCOS with who are you know   Michelle (20:18) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (20:39) Stage one, type one obesity, type two, we'll continue them on the myonostetal throughout the pregnancy and when they leave us and go to their OB -GYN, in our referral letter back, we'll say that we're recommending for her to continue on myonostetal because there have been improvements in sugar levels and glycemic control and reduction in gestational diabetes overall.   Michelle (20:54) Yeah, that's good to know.   another big one is vitamin D. A lot of people, even though we're in Florida here, we have a lot of sun. A lot of people are very deficient in vitamin D.   Armando Hernandez-Rey MD (21:11) Yeah, What it is is a combination of things. Number one, we're not as sun exposed as you think we are. You know, we're always in a car, we're always indoors, it's very hot. And yes, we go out to the beach and there is a lot of sun, but we become very, very sensitive to the sun and to the untoward effects of the sun.   Michelle (21:17) Mm -hmm.   Armando Hernandez-Rey MD (21:35) So we protect ourselves tremendously. That's number one. Number two is that I think the levels are set higher than what the average person can sustain with just diet and sun exposure. And actually the recommendations now in the infertility world that when you order a vitamin D from Quest, they'll tell you that the levels are, you want them at   Michelle (21:38) Mm -hmm.   Armando Hernandez-Rey MD (22:04) definitively above 20 Certainly above 30 and now recently now the recommendations are that for them to go above 40 and and and Yeah, I'm not yeah, so I heard I've read 40 I it was a Paper that came out of Either the Lancet or   Michelle (22:11) Yes, yep, I've been hearing that or even 50. Yeah.   Armando Hernandez-Rey MD (22:27) or fertility necessarily, anyone, one of, that they recommend now for vitamin D levels to be above 40. So that's really hard. I mean, I work really hard. I take a lot of vitamin D and I'm just barely scraping like 50. You know, I take about 5 ,000 units a day, which is what we're recommending nowadays, 5 ,000 units of vitamin D. And I take that every single day and I barely scratch,   Michelle (22:38) Mm -hmm.   Yeah.   Armando Hernandez-Rey MD (22:56) you know, 45, 50 every time I get an average check. So I'm not getting as much sun as I think I am, number one. I am out fairly often. I do play some golf, not enough. And yet it's not enough. So definitely supplementation's important.   Michelle (23:03) Mm -hmm.   Yeah, magnesium is also important. That's another thing. It's to not be deficient in magnesium because magnesium plays an important role of our absorption of D, which, you know, obviously doing this, I learned, I was like, that's might be deficient magnesium and be taking a lot of D and then their body's not processing, which is why it's important sometimes even in foods, foods have everything. So like,   even beef liver, you know, from Chinese medicine perspective is so beneficial because it has iron, but it has it in a combination of nutrients that helps the body absorb it.   Armando Hernandez-Rey MD (23:46) Yeah, B6, B12 are incredibly important for iron absorption as well. So all of these things are extremely important. Everything is all intertwined and we're just learning about this. And for us, I've really gotten grabbed hold of this whole longevity thing, hence my aura ring and all of this. And...   Michelle (23:57) It is.   Yeah.   Armando Hernandez-Rey MD (24:09) I'm just trying to apply a lot of the things that we know today work for longevity medicine and anti -aging principles to the infertility world because it's all intertwined. It's all intertwined.   Michelle (24:16) Yeah.   without a doubt. It's funny because that you say that because I always say it's pretty much anti aging. Yeah.   Armando Hernandez-Rey MD (24:26) Yeah, totally, totally. They're even coming up with a way to stop menopause.   Michelle (24:36) wow. How?   Armando Hernandez-Rey MD (24:37) which is extremely interesting. Believe it or not, recombinant antimullerian hormones.   Michelle (24:42) How is that? Explain that.   Armando Hernandez-Rey MD (24:46) So the way that antimullerine, the function of antimullerine hormone at the level of the ovary is that it stops follicular recruitment. That's why women with PCOS have higher AMHs and therefore they have higher egg counts and higher, they tend to go into menopause later on, et cetera. That's because they have high levels of antimullerine hormone. So by reproducing or creating it in the laboratory and then from an early stage,   This is in its infancy, by the way, okay? So this is, yeah, this company, I believe she's a Harvard scientist, biochemist or something, who's coming up. My point is that, listen, that it's all intertwined, aging and even in menopause, for God sakes. Now I've been doing this for so long that I now,   Michelle (25:18) It's new.   Mm -hmm.   Armando Hernandez-Rey MD (25:39) seeing menopausal patients who were like, you know, listen, you took care of my baby, you're a reproductive metachronologist, you understand the science, will you treat me? And, you know, like, and I realized, like, somewhere, some women got like, they got a some bad luck thrown their way because, you know, with the WHI results and the way they were interpreted, they made hormones bad. And somewhere along the way, someone said,   It's okay for women to suffer from menopause, just suck it up. Like it's not okay. That's not okay. That's not okay. And so if you start from very early on and, you know, and, and really practice what you preach, which is healthcare and not sick care, which is what we practice in the United States, you know, we're just very, we, we're not proactive. We're reactive to when a patient is sick instead of early intervention, early screening and all of that.   Michelle (26:25) Yeah, absolutely.   Armando Hernandez-Rey MD (26:30) And that goes for the infertility world and that goes for a woman's long reproductive life extending past menopause. I think we still have a lot of challenges to overcome, but I think that we're heading in the right direction. Sorry to digress a little bit. I went off on a tangent there for a second.   Michelle (26:43) Yeah, for sure. no, it's okay. But you know what? I love the passion and I love that, that, you know, ultimately is great. It's important, very important, because it's true. And I agree a lot with what you just said, that we should be proactive when it comes to healthcare. I mean, really when it comes to so many things and something else that I...   that I read, it was an animal study. It was a study on, I believe it was like, I don't remember which kind of animal it was. I think it was like either sheep or cows or some form of those where they actually gave them oxytocin right before IUI. And that improved the chances of the conception rates, which I thought was very interesting because I think that that's one of the things with IUI that's missing because obviously you're taking away the connection.   that is usually there when you're just under natural circumstance. And I thought it was interesting because I was looking into it for something else to understand from a Chinese medicine perspective, because they have this heart -uterusconnection, that connection, the bonding. And so what I found was interesting too is that oxytocin increases around ovulation and after intercourse. And usually what they look at it as its role is usually for labor.   not so much conception. So I was just going to kind of like pick your brain on that. Any thoughts on that?   Armando Hernandez-Rey MD (28:13) Well, I mean, oxytocin is secreted at the time of... I'm not sure of ovulation, I didn't know that. But definitely at the time of...   Michelle (28:21) or it increases around that time, like right before ovulation in the cycle, a woman cycle.   Armando Hernandez-Rey MD (28:27) What we know that it's involved is at the time of orgasm. And so this may promote uterine contractility, which is what is used for intrapartum, to promote contractility of the uterus, to promote descent and eventual delivery. And we know that it's intimately involved in orgasm, we're seeing.   Michelle (28:33) Mm -hmm.   Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (28:55) during intercourse and orgasm and so with you know the projection of with the secretion of oxytocin and it causing uterine contractility obviously not at the same level that it does during labor but at smaller amounts then I can see how there could be a role for oxytocin in artificial insemination.   Michelle (29:18) even in fertility in general and because it's got to be there for a reason why would the body produce it around that time?   Armando Hernandez-Rey MD (29:25) Well, yeah, I guess, but it's either IUI or IVF and we definitely don't want oxytocin during the IVF cycle.   Michelle (29:33) Right, because you don't want to contract, right?   Armando Hernandez-Rey MD (29:35) Right, because we're transferring an embryo where there should not be any oxytocin. And you can have the most beautiful embryo, but if you screw up the embryo transfer, through no fault, just because it's a difficult transfer for a myriad of reasons, and you cause uterine contractility, then there's a high likelihood of pregnancy not occurring during that time.   Michelle (29:57) Right. I think it would be an interesting thing to look into for IUI. There might be something to it, because if it works with animals, and the animals obviously have similar certain functions that we do, mammals, that seems like an interesting thing.   Armando Hernandez-Rey MD (30:10) Yeah.   I think there's not going to be a lot of resources put into improving IUI, to be honest with you. IUI, I think it is what it is. And I mean, I think the majority of research is going to go to improving even more IVF rates, because I think ultimately patients are going to want to go more.   Michelle (30:22) Mm -hmm. Yeah.   Armando Hernandez-Rey MD (30:40) towards IBF, no matter how hard we try to say, hey, listen, there's this option or this option or this option. It's more become a more of an instant gratification society. Number one, number two, people are waiting longer. So therefore they're more pressed for time, if you will. And I think there will be less of a motivation to go down a treatment option that frankly,   Michelle (30:48) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (31:07) You know, has a low pregnancy rate.   Michelle (31:09) Right. And then my other question is, what are your, thoughts about a lower intensity cycle?   like lower amounts of hormones for older women. In some cases I've heard it might be a little better. you do? Yeah, yeah.   Armando Hernandez-Rey MD (31:24) We use it all the time. Yeah, we use it all the time. I think it's...   a very successful option in cases with severely diminished ovarian reserve. I think that the senescent ovary does not do well with high impact medication or high doses of medication separately, but you know, jointly the medication costs are exorbitant and you end up having the same number of eggs that are mature, that get fertilized with a mini stent protocol as you do with   Michelle (31:38) Okay.   Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (31:59) a high dose regimen.   Michelle (32:02) Okay, so you've seen good success with that.   Armando Hernandez-Rey MD (32:06) Well, I mean, not good success because generally these cases are, we've seen success. Let's call it that. Because the patients that you're treating with these medics, with this protocol are patients who are POI, you know, premature ovarian insufficiency, diminished ovarian reserve, poor egg quality, high rate maniploidy. So these are your poor responders essentially. And they're very...   Michelle (32:12) Yeah, okay.   Mm -hmm. Mm -hmm.   Armando Hernandez-Rey MD (32:34) specific factors that propel a woman to have success with this protocol compared to her twin sister with almost the same testing who doesn't do as well.   Michelle (32:47) Got it. And then lastly, we talked about this in the pre -talk, let's talk about marijuana and sperm, data is showing. Yeah.   Armando Hernandez-Rey MD (32:55) I don't do it myself, but I have no problem with people that do. What the data has shown that we're just becoming more and more familiar because the overwhelming number of people who are using cannabis and open about it, which is the second part, which was very difficult to conduct studies because it was so people were ostracized. They were looked at.   not the wrong way and seen as in the fringe. And now it's, you know, it's so mainstream. but so now we're, we're keenly aware, of patients were able to analyze them and what we know without a shadow of a doubt that the potency of the cannabis that's being produced these days is anywhere between eight to 12 times more potent than I think I use the joke of the guys at Woodstock back in the sixties, right?   Michelle (33:21) Mm -hmm.   Mm -hmm.   Armando Hernandez-Rey MD (33:46) where everybody was getting pregnant and everybody was high on life, all of those things. And then what we've also known, which I did mention, is that using the vape pens, whatever types of inhalers as opposed to the traditional joint, if you will, increase the potency of that by a factor of two to three. The cannabis that was already potent to begin with.   Michelle (34:08) Yeah.   Right.   Armando Hernandez-Rey MD (34:14) So what you're seeing in males in particular, and I'm not sure that the literature is so complete on the female aspects, are that we're seeing a high levels of fragmentation. And what fragmentation is, is imagine that sperm is like an Amazon box. And inside that box, there's a porcelain doll that's wrapped in these packing cubes. They're held very, very tight. And under...   Michelle (34:26) Mm -hmm.   Armando Hernandez-Rey MD (34:40) The best of circumstances, those packing cubes are wound so tight, packed so tight that nothing, if I kick the box off the Amazon truck, nothing is gonna happen to the porcelain doll. Well, as fragmentation occurs and it happens under natural conditions and old guys like me, you know, patients who, occupational hazards, firefighters, exposed to toxins, a lot of people who use fertilizers, et cetera, et cetera.   you see high levels of fragmentation. I'm talking about DNA fragmentation. And so what we're seeing is high levels of fragmentation at the level of the DNA of the sperm, which has significant effects on embryo quality, embryo development, and pregnancy rates, and high levels of aneuploidy, which is abnormal embryos. So,   Michelle (35:10) So you're talking about DNA fragmentation. Yeah. Yeah.   Mm -hmm.   Armando Hernandez-Rey MD (35:33) You know, I'm not here to like, you know, slap you on the wrist and say don't smoke weed, but really that's what you're facing. And we know that this happens in women with cigarette smoking. Like this is a well -known cause of an accelerated transition to perimenopause. You know, 65 % of women who smoked a pack a day for greater than 15 years will go into menopause before the age of 40, assuming they started before their 20s. That's a pretty...   Michelle (35:40) Bye.   Mm -hmm.   Armando Hernandez-Rey MD (36:03) ominous number, actually. Thankfully, not many women smoke these days, cigarettes anyway. So I guess the results of cannabis on females is yet to be elucidated, but we definitely have some pretty compelling evidence in terms of the male data that show that it can have detrimental or deleterious effects on sperm quality and not necessarily on numbers.   Michelle (36:04) Yeah.   Mm -hmm.   right, which is what people look at usually when I mean, that's like the, the analysis is always on numbers shape and, numbers shape it. Yeah. And morphology and they won't necessarily look at the DNA fragmentation. That's actually not something that REIs usually initially look at.   Armando Hernandez-Rey MD (36:33) Exactly.   the thesis in morphology.   is done in a well not initially unless there's comorbid situations or things that raise your red flags. For example, advanced paternal age, we always do it. Particularly in egg donor cycles, right? Because patients will be like, well, I'm using an egg donor and why don't I have bad energy? Well, because your husband could be 70 or 60 and   Michelle (37:11) Yeah.   Armando Hernandez-Rey MD (37:14) And then their fragmentation is completely elevated and through the roof. So yeah. So, you know, firefighters, occupational hazards.   Michelle (37:18) Right. So, yeah, it's important. It's important for people to hear this because they can go in and say, the semen analysis was perfect. But that, like what you just said, is not really checked. So they may not, in a healthy, like, younger guy.   Armando Hernandez-Rey MD (37:35) It's not as nuanced as we once thought it was.   Michelle (37:38) Yeah. Yeah. Interesting. It's, it's fun. It's always fun for me to talk to our, our ease, you know, just to get, to pick your brain and get your thoughts. and you're my neighbors. So it's pretty cool.   Armando Hernandez-Rey MD (37:50) That's right. Thank you very much for the invitation. This was really fun. We spoke about a wide array of different topics here. So this was really nice to connect this way.   Michelle (37:53) Yeah.   Yeah.   Yeah, for sure. And I know that a lot of people are going to be like, this is interesting information. Cause I know that what you just mentioned, a lot of it is not common knowledge. people don't know automatically hear about this or really know to think about asking about it. So, so I appreciate all your information, all your good, good data. And, for people who would like to work with you or in town, how can they find more about you?   Armando Hernandez-Rey MD (38:27) Well, we are at Conceptions Florida. We have two offices in Merritt Park, Coral Gables and one in Miramar and hopefully soon also in Boca. And I'm there Armando Hernandez -Ray, MD I'm sure. Easy to find these days on Google, but I'm happy to help in any way that we can. We've been doing this for a long time, quite successfully, thankfully. And we take a lot of pride, humbly speaking, but probably also.   in having a good footprint in South Florida and the infertility world and trying to offer the best care possible.   Michelle (39:01) Awesome. Well, this was such a pleasure and thank you so much for coming on today.   Armando Hernandez-Rey MD (39:05) Thank you, Michelle.    

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Ariane Lewis, MD, who served as the guest editor of the Continuum® June 2024 Neurocritical Care issue. They provide a preview of the issue, which published on June 3, 2024. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Lewis is a professor of neurology and neurosurgery and director of the Division of Neurocritical Care at NYU Langone Medical Center in New York, New York. Additional Resources Continuum website: ContinuumJournal.com Subscribe to Continuum: shop.lww.com/Continuum More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Full episode transcript  Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Ariane Lewis, who recently served as Continuum's guest editor for our latest issue on neurocritical care. Dr Lewis is a Professor of Neurology and Neurosurgery at NYU, where she serves as the Director of the Division of Neurocritical Care. Dr Lewis, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Tell us a little bit about yourself. Dr Lewis: Thank you so much for having me, Dr Jones. It was a pleasure to be an editor of this issue, and I'm really excited for it to come out. As you mentioned, I'm a Professor of Neurology and Neurosurgery at NYU. I'm also a fellow of the American Academy of Neurology and a fellow of the Neurocritical Care Society. I serve on the Ethics Law and Humanities Committee for the AAN. I was a past chair of the Ethics Committee for the Neurocritical Care Society and also the past chair of the Ethics Committee at NYU. Dr Jones: So, pretty diverse professional interests. And I was going to ask you about the ethics - that feels like something that ties in pretty well to neurocritical care. I imagine that expertise comes in handy, right? Dr Lewis: Yes, absolutely. My area of expertise is related to brain death and ethical, social, and legal complications related to brain death determination. Dr Jones: Got it. And when we were talking before we started recording here, you're from the New York area and a lifelong Yankees fan, is that right? Dr Lewis: Yes, that's correct. Dr Jones: How are they going to do this year? Dr Lewis: We're hoping we're going all the way. Dr Jones: Okay. Dr Lewis: In a while. Dr Jones: Our listeners heard it here first. So, the issue – let's get into the neurocritical care topics – phenomenal issue, full of detailed diagnosis and management strategies for patients with, you know, all manners of severe neurologic disorders requiring critical level of care. With your perspective (which is a unique perspective) - you've just edited a full issue on neurocritical care, you got to delve into all the topics - what were you most surprised to learn, Dr Lewis? Dr Lewis: Well, you know, I think that one of the most exciting things about this issue is the fact that, in addition to dealing with the typical topics related to neurocritical care - like hypoxic ischemic brain injury and stroke and intracerebral hemorrhage and subarachnoid hemorrhage, of course - the issue delves into some very unique topics related to neurocritical care. There's an article written by Dr Barry Czeisler that focuses on emergent management of tumefactive and aggressive demyelinating disorders, Dr Casey Albin wrote about neuromuscular emergencies, and doctors Maciel and Busl wrote about neuroonc emergencies – and I think that these areas are really important areas for neurologists and trainees to know about, and they're not talked about all that often. And these topics are often focused on, of course, by other subspecialties, but the perspective of a neurointensivist related to these topics is infrequently addressed. So I think that these are really the most exciting aspects of this issue, because it's something so unique in terms of the spin on these topics. Dr Jones: Fantastic. And what else can we look for in this issue? What other topics can our listeners and readers expect to find there?  Dr Lewis: So, the issue starts off with the examination and workup of the neurocritical care patient. Dr Sarah Wahlster and Nick Johnson from the University of Washington did an awesome job really bringing the reader into the topic of neurocritical care as they address an overview of neuroemergencies, red flags related to life-threatening conditions, herniation syndromes, vascular territories, and mechanisms and management of acute neurodeterioration, and they summarize monitoring modalities in neurocritical care and clinical and radiographic scales and scores that are commonly used in neurocritical care – and that's a really nice overview to introduce the reader to this issue. The rest of the issue focuses on a wide range of topics pertaining to the emergent management of neurocritical care issues, including hypoxic ischemic brain injury (which was addressed by Dr Steinberg from the University of Pittsburgh),  management of stroke due to large vessel occlusion (which was addressed by Dr Leslie-Mazwi from the University of Washington), management of ICH (addressed by Dr Murthy from Weill Cornell), and then also management of spontaneous subarachnoid hemorrhage (addressed by Dr Soojin Park). Dr Clio Rubinos addressed emergent management of status epilepticus. Emergent management of TBI and spinal cord injury was addressed by Dr Podell and Dr Morris from the University of Maryland. And then neuroinfectious emergencies – which, again, is another unique topic in this issue – was  addressed by Dr Reynolds from Mount Sinai. And then the issue concludes with a paper that focuses on prognostication and neurocritical care by Dr Susanne Muehlschlegel from Johns Hopkins University.  Dr Jones: Yeah. And what a great list of authors and expertise. And really, you know,  having seen these articles, really just phenomenal guidance on a lot of different subtopics. And I imagine – you know, this is a dynamic area, there's a lot of evidence – but, you know, sometimes, there are controversies or debates or unresolved questions in the field. Having just reviewed and edited the issue, what do you think the biggest debate or controversy is in neurocritical care right now?  Dr Lewis: So there's definitely a lot of controversies that are addressed in each of these individual articles. For example, in the paper on subarachnoid hemorrhage, Dr Soojin Park provides a summary that compares the guidelines on management of subarachnoid hemorrhage that were written by the Neurocritical Care Society and the American Health Association / American Stroke Association in 2023 and really walks through what's similar and what's different between these guidelines. For the most part, they are very similar, but there are areas of differences. Additionally, in terms of management of acute neuroemergencies related to neuromuscular issues (in some cases, it's not clear whether to treat patients with IVIG or with plasmapheresis), Dr Casey Albin creates a nice summary addressing these issues in terms of what are the pluses and minuses associated with each of these medications. Additionally, there are a number of novel therapies that are not traditionally considered for various neuroemergencies that are walked through in each of the individual articles. For example, in the paper that focuses on management of status epilepticus, Dr Rubinos addresses alternative therapies, like immunomodulatory agents or neuromodulation, for management of super-refractory status epilepticus. So, I think, in addition to addressing the more traditional therapies for various neuroemergencies, the issue really goes above and beyond to address novel interventions.  Dr Jones: That's fantastic. And obviously, it continues to be a rapidly evolving area.  When you look out to the horizon – and the next generation of care for patients with critical neurologic illness – what do you see on the horizon? What should our listeners and readers be aware of to watch out for?  Dr Lewis: I think one thing that is really important to be aware of related to patients with neuroemergencies is the Curing Coma Campaign (which is organized by the Neurocritical Care Society), which focuses on research in terms of improving the clinical management, the prognostication, and the care of patients and addresses the goals for  improving recovery for patients who are comatose. And obviously, coma can be due to a wide range of different etiologies (many of which are described in this issue), and so I think that their work as we move ahead will be incredibly important and interesting to see how things evolve in that domain. Dr Jones: We will be on the lookout for the Curing Coma Campaign – sounds like a great initiative. And, I think, medicine is a team endeavor, right? We were talking about the Yankees earlier (baseball) as a team sport – so is medicine. When you think about the importance of teams, it's hard to imagine a setting where it's more critical to have, you know, well-functioning teams than in the neuro ICU. But there's also parts of the team (people on the team) who are outside the neuro ICU – and I'm thinking of other neurologists, our listeners and readers who might work in the inpatient setting, but not in this really specialized environment. When you think about those neurologists, is there a key message for those hospitalist neurologists or inpatient neurologists that you would want to share from your perspective as a neurocritical care specialist?  Dr Lewis: So, I think it's imperative for all neurologists to have an understanding of the existence of various neuroemergencies and the identification of when a patient is  having a neuroemergency so that they can escalate the management if it's something beyond their skills or expertise to somebody who is capable of appropriately managing the patient. Each of these articles walks through the differential diagnosis, the identification of the neuroemergency, the first steps in terms of management, the laboratory workup, and then the subsequent steps as well. And I think that, you know, for all neurologists, really, the key things to know about (even if you're not specializing in  neurocritical care) is how to identify a neuroemergency and what needs to be done as the first steps in terms of intervening and diagnosing these emergencies. Dr Jones: Great message, and that's one of the key things we learn in training, right,  is when to recognize that someone's sick and you need to escalate their level of care. What about – you know, I imagine the neurocritical care field is a relatively small community, and you know a lot of these folks – any key message that you would want to share with that audience? Dr Lewis: So, I think that this issue is still really important for all neurointensivists (in addition to for general neurologists and trainees), because of the fact that every article  really addresses in depth each of these aspects of neurocritical care and provides tidbits of information that not every neurointensivist would know. So, I think that the issue is beneficial both for trainees, general neurologists, and people who have expertise in the field of neurocritical care. Dr Jones: That's a great point. I think the fact that it is such a rapidly changing and broad field (you mentioned all the different article topics that are in the issue), it's a challenge to stay up to date on everything. And I think that's what this issue really brings  to the neurointensivist – is, you know, this is all (as of what's the latest in 2024) for the care of patients with critical illness. It's all there, right?  Dr Lewis: Absolutely. I think, you know, the issue is unique because neurocritical care is unique in that our role involves taking care of patients with a wide range of different neurologic disorders. So, the issue touches upon stroke (both ischemic and hemorrhagic). It touches upon seizure management. It touches upon management of traumatic brain injury. It addresses demyelination (so types of aggressive MS and other demyelinating disorders), neuromuscular issues, neuroonc issues – so I think that, really, there are so many subspecialties within neurology that it's important for them to have awareness of the emergencies that can emerge within their individual field. Dr Jones: So, we know that neurocritical care is pretty specialized work, and I imagine the expertise and the resources are not necessarily going to be available in every community. Are you aware, Dr Lewis, of any disparities in access or outcomes to neurointensivist expertise?  Dr Lewis: Yeah, absolutely. Unfortunately, as you look internationally, first, there are many places that don't have neurointensivists, so patients with neuroemergencies are being taken care of, in some cases, not even by general neurologists, but by specialists just in medicine. Additionally, the resources are often not available in terms of having an intensive care unit, having nurses with a good ratio to care for neurocritical care patients, having access to therapists who can participate in rehab and promote rehab, for patients having access to medications that are necessary, having access to various interventions (such as access to neurosurgeons who can do neurosurgical procedures or placement of an external ventricular drain), or other monitoring modalities are not available and accessible. So, all of these issues – in terms of resources, in terms of funding, in terms of other issues related to the existence of protocols as to how to  manage patients in the neuro ICU – all impact the outcome for patients in neurocritical care. Additionally, social issues and cultural issues can impact the outcome for patients in the neuro ICU. So, there's a lot of issues pertaining to equity in terms of the management of neurocritical care patients around the world.  Dr Jones: Those are great points. I know you and I both work with trainees in our field,  and when I talk to residents who are interested in neurocritical care, I think part of what draws them in is when they are exposed to it and they see how much, you know, the value of what their expertise brings to the outcome for that patient. I mean, it really does make a difference to understand the brain when you're caring for people with these critical neurologic disorders – and I think that's part of the appeal, right?  Dr Lewis: Yeah, absolutely. I think that people who are interested in going into the field of neurocritical care are interested in the more fast-paced aspect of neurology, rapid decision making, dealing with emergencies, also dealing with prognostication,  discussions (unfortunately, at end of life) – so that's really the kind of individual who turns to the field to specialize in. Dr Jones: And what about you, Dr Lewis? What drew you to this, you know, pretty high-pressure, intense, dynamic environment?  Dr Lewis: So I think, actually, you know, all the buzzwords you just used are really the things that made me want to go into neurocritical care. I am interested in much more  fast-paced management of patients, and, you know, unfortunately, obviously emergencies happen, and I find them to be exciting to be able to manage patients in that setting. And, you know, as you mentioned earlier, in the neuro ICU, it's a very multidisciplinary team, and I really enjoy being able to work with nursing, social work, care management, therapists, a variety of consultants – and addressing very acute issues with these individuals as a team in the ICU setting is really very rewarding.  Dr Jones: Yeah, and I hear that from others who are drawn to the field, and I think you really have to have kind of a broad skill set to manage actively, you know, critically ill patients, but also do the communication competencies and other things that are necessary. So, anecdotally, I would say I see more interest among trainees in this field. I don't know if you've seen the same thing in your world. Dr Lewis: Yeah. I think that, you know, as you mentioned, it's really important to emphasize that being a neurointensivist does not  just require expertise in the medical aspects of care for these patients, but really, also it's very important to ensure that we  promote education related to communication and neuroprognostication. So, our last article on this issue (by Dr Susanne Muehlschlegel) addresses prognostication and includes a variety of different details about how to address uncertainty, how to implement family and patient-centered prognostication and promote shared decision-making – and these topics are so important for everyone to know about when they're communicating with patients and families to address goals of care and to prognosticate. Dr Jones: Yeah. Thank you. And before we wrap up our discussion here, Dr Lewis, in addition to being a neurointensivist and being an expert on ethics and all of your clinical and research work, you do editorial work. You have editorial responsibilities not only for this issue of Continuum, but also at Seminars in Neurology and at “The Green Journal”.  For our listeners who might be interested in that career pathway, how did you get into that?  Dr Lewis: I very much enjoyed writing, and so I published a lot. And then I think that, you know, making connections is incredibly important and really looking out for those types of opportunities. Once you build a semblance of expertise in an area, then that often tends to lead to opportunities. So, I'm a Deputy Editor for the Disputes and Debate section of the Neurology journal. I'm also a Deputy Editor of Seminars in Neurology. I edited a book with Dr Jim Burnett on advances in neuroethics related to death determination by neurologic criteria, areas of controversy and consensus. And then I've also been a Guest Editor for a number of other journals, like the AMA Journal of Ethics that focused on socially situated brain death, a neurosurgical focus issue on primary and secondary infections of the brain, and a issue of Seminars in Neurology focused on ethics in neurology. Dr Jones: You must have like a twenty-eight or twenty-nine-hour day, Dr Lewis. I don't know how you do all that. I wasn't even aware of all those things that you do, but I can tell you, having looked at this issue, your editorial skills are off the charts. I really want to thank you not just for a wonderful issue, but for joining us today and for such a thoughtful, fascinating, and thorough discussion on the field of neurocritical care.   Dr Lewis: Thank you so much. I'm so excited for all the readers to look at our issue and learn about all of these different topics.  Dr Jones: Again, we've been speaking with Dr Ariane Lewis, Guest Editor for Continuum's most recent issue on neurocritical care. Please check it out. And thank you to our listeners for joining today.  Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice - and right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. Thank you for listening to Continuum Audio.

Dan and Janet are thrilled to welcome UBC's Dr. Fergus To to Around the Rheum for a fascinating conversation about Myositis.In this discussion, they delve into the general categories of Myositis that rheumatologists need to know about, important clinical features that help differentiate the subtype before you get the panel back, a broad approach to understanding serologies, establishing a firm diagnosis, most common mimics and how to differentiate them from Inflammatory Myositis, the decision making process when selecting first and second line treatments, when to use IVIG for both induction and maintenance, advances in the treatment of RPILD, as well as prognosis and cancer screening and what's in the pipeline.Dr To is a Clinical Assistant Professor at UBC and serves as a consultant rheumatologist at Vancouver General Hospital and Saint Paul's Hospital. He started the Vancouver Coastal Health Myositis Clinic for which he was awarded the BC Society of Rheumatology Award for Innovation. His research interests are in QI and novel therapies for myositis.If you have questions you would like answered by the experts, please get in touch through the CRA Twitter account (@crascrrheum) or by email (Info@rheum.ca). And for future Medical Mysteries episodes, please get in touch if you have challenging cases you want to present on the podcast! A special thank you to the podcast team, Dr. Dax G. Rumsey (CRA Communications Committee Chair), Dr. Daniel Ennis (Host), Dr. Janet Pope (host), David McGuffin (Producer, Explore Podcast Productions), and Erin Stewart (Marketing and Communications Director, CRA) for leading production. Our theme music was composed by Aaron Fontwell. For more on the work of the Canadian Rheumatology Association, visit www.rheum.ca (http://www.rheum.ca/) or check out our X (Twitter) account - @CRASCRRheum

Welcome back to our weekend Cabral HouseCall shows! This is where we answer our community's wellness, weight loss, and anti-aging questions to help people get back on track! Check out today's questions:    Vikki: My son had kawasaki disease at 5yo. In hospital for week, got 2 IVIG treatments & high doses aspirin. Heart always looked good. Hes 16 & has been dealing w mild hearing loss& tinnitus, what can he do to lessen ringing or reverse? Assuming it was caused by the disease. Covid made it worse (no shot). Dizzy when it's at its worst. Avoids loud places, like movie theatre/church. Tried hearing aids but says didn't help. Healthy otherwise. Also what do you know about Kawasaki& future complications? TY   Fiona: I have used your products to correct my autoimmune issues, thank you so much for helping me. My daughter is fighting a EBV infection and is so exhausted every day. She has just had an IV vitamin C treatment. She also has Enterococus Avium detected in stool. Bifidobacterium bifidium and breve, Lactobacillus plantarum, casei and acidophlis have low readings. What is the best protocol for her to follow please   Jay: Hi Dr. Cabral I want to thank you and your team for all the work you do - it has been life changing for both me and my clients. I ran the big 5 did FM 21 detox, HMD, Ultimate sleep, Estrogen detox, and in the CBO protocol. I am wondering if you could tell me when I could retest to see improvement (looking to concieve - want to make sure everything is optimized). For reference I had low DHEA, high cortisol, estrogen dominance, + mercury, + aluminum candida, and oxalic acid.   Patricia: Dear Dr. Cabral, thank you for all the information and knowledge you share, it has really made a difference in my life. This question is related to my father, he is 84 years old and recently diagnosed with skin cancer on different areas on his face,we believe it was caused to sun exposure and or chemicals due to his job when younger as a Petroleum Engineer working in the field. He has molds in his face and his back, some of those cancerous. One was recently removed from his tear duct cancerous. He is scheduled to have surgery soon for all the others found. Is there any recommendation you can give me on things that he can do before and after the procedure related to diet and supplements that can help him heal faster and prevent recurrencies? I value so much your opinion. Thank you so much   Fernanda: I bought an EquiLife heavy metal detox kit for me and my husband and I just did your regular detox course online. Now I am wondering how these 2 compare. We don't want to lose weight as we are overall healthy already. We have completed three 5-day fasts using another product (Prolon) recently. How does a 5-day fast compare to EquiLife 7 day detox as far as removing toxins go? Will the removal of toxins in a 5-day water only or Prolon fast be compromised because there may not be enough amino acids to aid the phase 2 detox pathways? Should I do the regular detox before the heavy metal one? Please feel free to email me directly if that is not a question that you would like to answer on the podcast. FYI: I am also currently an IHP1 student and I bought 8 of the books you recommended so far.   Thank you for tuning into today's Cabral HouseCall and be sure to check back tomorrow where we answer more of our community's questions!    - - - Show Notes and Resources: StephenCabral.com/3032 - - - Get a FREE Copy of Dr. Cabral's Book: The Rain Barrel Effect - - - Join the Community & Get Your Questions Answered: CabralSupportGroup.com - - - Dr. Cabral's Most Popular At-Home Lab Tests: > Complete Minerals & Metals Test (Test for mineral imbalances & heavy metal toxicity) - - - > Complete Candida, Metabolic & Vitamins Test (Test for 75 biomarkers including yeast & bacterial gut overgrowth, as well as vitamin levels) - - - > Complete Stress, Mood & Metabolism Test (Discover your complete thyroid, adrenal, hormone, vitamin D & insulin levels) - - - > Complete Food Sensitivity Test (Find out your hidden food sensitivities) - - - > Complete Omega-3 & Inflammation Test (Discover your levels of inflammation related to your omega-6 to omega-3 levels) - - - Get Your Question Answered On An Upcoming HouseCall: StephenCabral.com/askcabral - - - Would You Take 30 Seconds To Rate & Review The Cabral Concept? The best way to help me spread our mission of true natural health is to pass on the good word, and I read and appreciate every review!  

Welcome back Rounds Table Listeners!In this throwback episode, Drs. John and Mike Fralick discuss two papers – one, exploring IVIG in the treatment of dermatomyositis, and the second investigating the effect of tranexamic acid in patients with acute gastrointestinal bleeding.Trial of Intravenous Immune Globulin in Dermatomyositis (0:00 – 8:38).Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international, randomised, double-blind, placebo-controlled trial (8:38 – 18:04).And for the Good Stuff:Alberta using humour to attract workers (18:04 – 18:50).CBME in Residency Education (18:50 – 21:02).Questions? Comments? Feedback? We'd love to hear from you! @roundstable

After finishing her training in neurology at Mayo Clinic, Dr. Svetlana Blitshteyn started a Dysautonomia Clinic in 2009. Little did she know what was in store many years later when Covid hit!Ground Truths podcasts are on Apple and Spotify. The video interviews are on YouTubeTranscript with audio and external linksEric Topol (00:07):Well, hello, it's Eric Topol from Ground Truths, and I have with me a really great authority on dysautonomia and POTS. We will get into what that is for those who aren't following this closely. And it's Svetlana Blitshteyn who is a faculty member at University of Buffalo and a neurologist who long before there was such a thing as Covid was already onto one of the most important pathways of the body, the autonomic nervous system and how it can go off track. So welcome, Svetlana.Svetlana Blitshteyn (00:40):Thank you so much, Eric for having me. And I want to say it's a great honor for me to be here and just to be on the list with your other guests. It's remarkable and I'm very grateful and congratulations on being on the TIME100 Health list for influential people in 2024. And I am grateful for everything that you've done. As I mentioned earlier, I'm a big fan of your work before the pandemic and of course with Covid I followed your podcast and posts because you became the best science communicator and I'm very happy to see you being a strong advocate and thank you for everything you've done.Eric Topol (01:27):Well, that's so kind to you. And I think talking about getting things going before the pandemic, back in 2011, you published a book with Jodi Epstein Rhum called POTS - Together We Stand: Riding the Waves of Dysautonomia. And you probably didn't have an idea that there would be an epidemic of that more than a decade later, I guess, right?Svetlana Blitshteyn (01:54):Yeah, absolutely. Of course, SARS-CoV-2 is a new virus and we can technically say that Long Covid and post Covid complications could be viewed as a new entity. But practically speaking, we know that post-infectious syndromes have been happening for many decades. And so, the most common trigger for POTS happened to be infection, whether it was influenza or mononucleosis or Lyme or enterovirus. We knew this was happening. So I think it didn't take long for me and my colleagues to realize that we're going to be seeing a lot of patients with autonomic dysfunction after Covid.On the Front LineEric Topol (02:40):Well, one of the things that's important for having you on is you're in the front lines taking care of lots of patients with Long Covid and this postural orthostatic tachycardia syndrome (POTS). And I wonder if you could tell us what it's care for these patients because so many of them are incapacitated. As a cardiologist, I see of course some because of the cardiovascular aspects, but you are dealing with this on a day-to-day basis.Svetlana Blitshteyn (03:14):Yeah, absolutely. As early as April 2020 when everything was closed, I got a call from a young doctor in New York City saying that he had Covid and he couldn't recover, he couldn't return to the hospital. And his colleagues and cardiology attendants also had the same symptoms and the symptoms were palpitations, orthostatic intolerance, tachycardia, fatigue. Now, how he knew to contact me is that his sister was my patient with POTS before Covid pandemic. So he kind of figured this looked like my sister, let me check this out. And it didn't take long for me to have a lot of patience from the early wave. And then fairly soon, I think within months I was thinking, we have to write this up because this is important. And to some of us it was not news, but I was sure that to many physicians and public health officials, this would be something new.Svetlana Blitshteyn (04:18):So because I'm a busy clinician and don't have a lot of time for publications, I had to recruit a graduate student from McMasters and together we had this paper out, which was the first and largest case series on post Covid POTS and other autonomic disorders. And interestingly, even though it came out I think in 2021, by the time it was published, it became the most citable paper for me. And so I think from then on organizations and societies became interested in the work that I do because prior to that, I must say in the kind of a niche specialty was I don't think it was very popular or of interest to me.How Did You Get Interested in Dysautonomia?Eric Topol (05:06):Yeah, so that's why I wanted to just take a step back with you Svetlana, because you had the foresight to be the founder and director of the Dysautonomia Clinic when a lot of people weren't in touch with this as an important entity. What prompted you as a neurologist to really zoom in on dysautonomia when you started this clinic?Svetlana Blitshteyn (05:28):Sure. So the reasons are how I ended up in this field is kind of a convoluted road and the reasons are many, but one, I will say that I trained at Mayo Clinic where we received very good training on autonomic disorders and EMG and coming back to returning back to Buffalo, I began working at the large multiple sclerosis clinic because Western New York has a high incidence MS. And so, what they quickly realized in that clinic is that there was a subset of women who did not qualify for the diagnostic criteria of multiple sclerosis, yet they had a lot of the same symptoms and they were certainly very disabled. Now I recognize that these women had autonomic disorders of all sorts and small fiber neuropathy, and I think this population sort of grew and eventually I realized there is no one not only in Buffalo but the entire Western New York who is doing this work.Svetlana Blitshteyn (06:34):So I kind of fell into that. But another reason is actually more personal that I haven't talked about. So years ago I was traveling to Toronto, Canada for a neurology meeting to present my big study on meningioma and hormone replacement therapy using Mayo Clinic database. And so, in that year, the study received top 10 noteworthy studies of the year award from the Society of Neuro-Oncology, and it was profiled in Reuters Health. Now, on the way back from the conference, I had the flu, and when they returned I could no longer walk the same hallways of the hospital where I walked previously. And no matter how hard I try to push my body, we all do this in medicine, we push through, I just couldn't do it. No amount of wishing or positive thinking. And so, I think that's how I came to know personally the post-infectious syndromes. And I think it almost became a duality of experiencing this and also practicing it.Eric Topol (07:52):No, that's really striking and it wasn't so common to hear about this post flu, but certainly it changed in 2020. So how does a person with POTS typically present to you?Clinical PresentationSvetlana Blitshteyn (08:08):So these are very important questions because what I want to stress is though POTS is one of the most common autonomic disorders. Even if you don't have POTS by the diagnostic criteria, you may still have autonomic dysfunction and significant autonomic symptoms. How do they present? Well, they present like most Long Covid patients, the most common symptoms are orthostatic intolerance, fatigue, exercise intolerance, post exertional malaise, dizziness, tachycardia, brain fog. And these are common themes across the board in Long Covid patients, but also in pre-Covid post-acute infection syndrome patients. And you have to recognize because I think what I tell my colleagues is that oftentimes patients are not going to present to you saying, I have orthostatic intolerance. Many times they will say, I'm very tired. I can no longer go to the gym or when I go to the store, I have to be out of there in 15 minutes because the orthostatic intolerance symptoms come up.Svetlana Blitshteyn (09:22):So sometimes the patients themselves don't recognize that and it's up to us physicians to ask the right questions to get the information down. History is very important, knowing the pattern. And then of course, as I always say in all of my papers and lectures, you have to do a 10-minute stand test by measuring supine and standing blood pressure and heart rate on every Long Covid patients. And that's how you spot those that have excessive postural tachycardia or their blood pressure dropping or so forth. So we have the tools. We don't need fancy autonomic labs. We don't even need a tilt table test. The diagnostic criteria for POTS is that you need to have either a 10-minute stand test or a tilt table test to get the diagnosis for POTS, orthostatic hypotension or even neurocardiogenic syncope. Now I think it's important to stress that even if a patient doesn't qualify, and let's say many patients with Long Covid will not elevate their heart rate by at least 30 beats per minute, it could be 20, it could be 25. These criteria are of course essential when we do research studies. But I think practically speaking, in patient care where everything is gray and nothing is black or white, especially in autonomic disorders, you really have to make a diagnosis saying, this sounds like autonomic dysfunction. Let me treat the patient for this problem.Eric Topol (11:07):Well, you brought up something that's really important because doctors don't have much time and they're inpatient. They don't wait 10 minutes to do a test to check your blood pressure. They send the patients for a tilt table, which nobody likes to have that test done, and it's unnecessary added appointment and expense and whatnot. So that's a good tip right there that you can get the same information just by checking the blood pressure and heart rate on standing for an extended period of time, which 10 minutes is a long time in the clinic of course. Now, what is the mechanism, what do you think is going on with the SARS-CoV-2 virus and its predilection to affect the autonomic nervous system? As you know, so many studies have questioned whether you even actually infect neurons or alternatively, which is more likely this an inflammation of the neural tissue. But what do you think is going on here?UnderpinningsSvetlana Blitshteyn (12:10):Right, so I think it's important to say we don't have exact pathophysiology of what exactly is going on. I think we can only extrapolate that what's going on in Long Covid is possibly what's going on in any post infectious onset dysautonomia. And so there are many hypothesis and there are many suggestions, and we share this disorder with cardiologist and immunologist and rheumatologist. The way I view this is what I described in my paper from a few years ago is that this is likely a central nervous system disorder with multisystemic involvement and it involves the cardiovascular system, immunologic, metabolic, possibly prothrombotic. The pathophysiology of all POTS closely parallels to pathophysiology of Long Covid. Now we don't know if it's the same thing and certainly I see that there may be more complications in Long Covid patients in the realm of cardiovascular manifestations in the realm of blood clots and things like that.Svetlana Blitshteyn (13:21):So we can't say it's the same, but it very closely resembles and I think at the core is going to be inflammation, autoimmunity and immunologic dysfunction. Now there are also other things that are very important and that would be mitochondrial dysfunction, that would be hypercoagulable state, it would be endothelial dysfunction. And I think the silver lining of Long Covid and having so many people invested in research and so many funds is that by uncovering what Long Covid is, we're now going to be uncovering what POTS and other autonomic disorders are. And I think we also need to mention a couple of other things. One is small fiber neuropathy, small fiber neuropathy and POTS are very much comorbid conditions. And similarly, small fiber neuropathy frequently occurs in patients with Long Covid, so that's a substrate with the damaged small nerve fibers that they're everywhere in our bodies and also innervate the organs as well.Svetlana Blitshteyn (14:34):The second big thing is that needs to be mentioned is hyperactive mast cells. So mast cells, small nerve fibers and capillaries are very much located in proximity. And what I have usually is a slide from an old paper in oral biology that gives you a specimen where you see a capillary vessel, a stain small nerve fiber, and in between them there is a mass cell with tryptase in it stained in black. And so there is a close communication between small nerve fibers between endothelial wall and between mast cells, and that's what we commonly see as a triad. We see this as a triad in Long Covid patients. We see that as a triad in patients with joint hypermobility syndrome and hypermobile EDS, and you also see this in many of the autoimmune disorders where people develop new allergies and new sensitivities concurrent or preceding the onset of autoimmune disease.Small Fiber NeuropathyEric Topol (15:49):Yeah, no, it's fascinating. And I know you've worked with this in Ehlers-Danlos syndrome (EDS) as you mentioned, the hypermobility, but just to go back on this, when you want to entertain the involvement of small fiber neuropathy, is that diagnosable? I mean it's obvious that you can get the tachycardia, the change in position blood pressure, but do you have to do other tests to say there is indeed a small fiber neuropathy or is that a clinical diagnosis?Svetlana Blitshteyn (16:20):Absolutely. We have the testing and the testing is skin biopsy. That is simply a punch biopsy that you can do in your clinic and it takes about 15 minutes. You have the free kit that the company of, there are many companies, I don't want to name specific ones, but there are several companies that do this kind of work. You send the biopsy back to them, they look under the microscope, they stain it. You can also stain it with amyloid stain to rule out amyloidosis, which we do in neurology, and I think that's quite accessible to many clinicians everywhere. Now we also have another test called QSART (quantitative sudomotor axon reflex test), and that's a test part of autonomic lab. Mayo Clinic has it, Cleveland Clinic has it, other big labs have it, and it's hard to get there because the wait time is big.Svetlana Blitshteyn (17:15):Patients need to travel. Insurance doesn't always authorize, so access is a big problem, but more accessible is the skin biopsy. And so, by doing skin biopsy and then correlating with neurologic exam findings, which oftentimes involved reduce pain and temperature sensation in the feet, sometimes in the hands you can conclude that the patient has small fiber neuropathy and that's a very tangible and objective diagnosis. There again, with everything related to diagnostics, some neuropathy is very patchy and the patchy neuropathy is the one that may not be in your feet where you do the skin biopsy. It may be in the torso, it may be in the face, and we don't have biopsy there. So you can totally miss it. The results can come back as normal, but you can have patchy type of small fiber neuropathy and there are also diagnostic tests that might be not sensitive to pick up issues. So I think in everything Long Covid, it highlights the fact that many tests that we use in medicine are outdated perhaps and not targeted towards these patients with Long Covid. Therefore we say, well, we did the workup, everything looks good. MRI looks good, cardiac echo looks great, and yet the patient is very sick with all kinds of Long Covid complications.Pure Post-Viral POTS?Eric Topol (18:55):Right. Now, before we get into the treatments, I want to just segment this a bit. Can you get pure POTS that is no Long Covid just POTS, or as you implied that usually there's some coalescence of symptoms with the usual Long Covid symptoms and POTS added to that?Svetlana Blitshteyn (19:21):So the studies have shown for us that about 40% of patients with POTS have post-infectious onset, which means more than a half doesn't. And so of course you can have POTS from other causes and the most common is puberty, hormonal change, the most common age of onset is about 13, 14 years old and 80% of women of childbearing age and other triggers or pregnancy, hormonal change again, surgery, trauma like concussion, post-concussion, autonomic dysfunction is quite common.Eric Topol (20:05):So these are pure POTS without the other symptoms. Is that what you're saying in these examples?Svetlana Blitshteyn (20:12):Well, it's a very good question. It depends what you mean by pure POTS, and I have seen especially cardiologists cling to this notion that there is pure POTS and then there is POTS plus. Now I think majority of people don't have pure POTS and by pure POTS I think you mean those who have postural tachycardia and nothing else. And so most patients, I think 80% have a number of symptoms. So in my clinic I almost never see someone who is otherwise well and all they have is postural tachycardia and then they're having a great time. Some patients do exist like that, they tend to be athletic, they can still function in their life, but majority of patients come to us with symptoms like dizziness, like fatigue, like exercise intolerance, decline in functioning. So I think there is this notion that while there is pure POTS, let me just fix the postural tachycardia and the patient will be great and we all want that. Certainly sometimes I get lucky and when I give the patient a beta blocker or ivabradine or a calcium channel blocker, sometimes we use it, certainly they get better, but most patients don't have that because the disability that drives POTS isn't actually postural tachycardia, it's all that other stuff and a lot of it's neurologic, which is why I put this as a central nervous system disorder.TreatmentsEric Topol (21:58):Yeah, that's so important. Now you mentioned the treatments. These are drug treatments, largely beta blockers, and can you tell us what's the success rate with the various treatments that you use in your clinic?Svetlana Blitshteyn (22:13):So the first thing we'll have to mention is that there are no FDA approved therapies for POTS, just like there are no FDA approved therapies for Long Covid. And so, everything we use is off label. Now, oftentimes people think that because it wasn't evidence-based and there are no big trials. We do have trials, we do have trials for beta blockers and we know they work. We have trials for Midodrine and we know that's working. We also have fludrocortisone, which is a medication that improves sodium and water resorption. So we know that there are certain things we've used for decades that have been working, and I think that's what I was trying to convey in this paper of post Covid autonomic dysfunction assessment and treatment is that when you see these patients, and you can be of any specialty, you can be in primary care, you can be a physiatrist, a cardiologist, there are things to do, there are medications to use.Svetlana Blitshteyn (23:20):Oftentimes colleagues would say, well, you diagnose them and then what do you treat them with? And then I can refer them to table six in that paper and say, look at this list. You have a lot of options to try. We have the first line treatment options, which are your beta blockers and Midodrine and Florinef and Mestinon. And then we have the second line therapies you can choose from the stimulants are there Provigil, Nuvigil, Wellbutrin, Droxidopa is FDA approved for neurogenic orthostatic hypotension. Now we don't use it commonly, but it can still be tried in people whose blood pressures are falling on your exam. So we have a number of medications to choose from in addition to non-pharmacologic therapies.Eric Topol (24:14):Right now, I'm going to get to the non-pharmacologic in a moment, but the beta blocker, which is kind of the first one to give, it's a little bit paradoxical. It makes people tired, and these people already are, don't have much energy. Is the success rate of beta blocker good enough that that should be the first thing to try?Svetlana Blitshteyn (24:35):Absolutely. The first line medication treatment options are beta blockers. Why? Okay, why are they working? They're not only working to reduce heart rate, but they may also decrease sympathetic overactivity, which is the driving mechanism of autonomic dysfunction. And when you reduce that overactivity, even your energy level can improve. Now, the key here is to use a low dose. A lot of the time I see this mistake being done where the doctor is just prescribing 25 milligrams of metoprolol twice a day. Well, this is too high. And so, the key is to use very low doses and to use them and then increase them as needed. We have a bunch of beta blockers to choose from. We have the non-selective propranolol that you can use when someone maybe has a migraine headache or significant anxiety, they penetrate the brain, and we have non-selected beta blockers like atenolol, metoprolol and others that you can use at half a tablet. Sometimes I start my patients at quarter of tablet and then go from there. So low doses will block tachycardia, decrease sympathetic overactivity, and in many cases will allow the patient to remain upright for longer periods of time.Eric Topol (26:09):That's really helpful. Now, one of the other things, I believe it's approved in Canada, not in the US, is a vagal neuromodulation device. And I wonder, it seems like it would be nice to avoid drugs if there was a device that worked really well. Is there anything that is in the hopper for that?Svetlana Blitshteyn (26:32):Yeah, absolutely. Non-invasive vagus nerve stimulator is in clinical trials for POTS and other autonomic disorders, but we have it FDA for treatment of migraine and cluster headaches, so it's already approved here and it can also be helpful for chronic pain and gastroparesis. So there are studies on mice that show that with the application of noninvasive vagus nerve stimulator, there is reduction of pro-inflammatory cytokines. So here is this very important connection that comes from Kevin Tracey's work that showed inflammatory reflex, and that's a reflex between the vagus nerve and the immune system. So when we talk about sympathetic overactivity, we need to also think about that. That's a mechanism for pro-inflammatory state and possibly prothrombotic state. So anything that decreases sympathetic overactivity and enhancing parasympathetic tone is going to be good for you.Eric Topol (27:51):Now, let's go over to, I mean, I'm going to get into this body brain axis in a moment because there's another part of the story here that's becoming more interesting, fascinating, in fact every day. But before I do that, you mentioned the small fiber neuropathy. Is there a specific treatment for that or is that just something that is just an added dimension of the problem without a specific treatment available?Svetlana Blitshteyn (28:21):Yeah, we certainly have treatment for small fiber neuropathy. We have symptomatic treatment for neuropathic pain, and these medications are gabapentin, pregabalin, amitriptyline and low dose naltrexone that have been gaining popularity. We used that before the pandemic. We used low dose naltrexone for people with chronic pain related to joint hypermobility. And so, we have symptomatic, we also have patches and creams and all kinds of topical applications for people with neuropathic pain. Then we also have, we try to go for the root cause, right? So the number one cause of small fiber neuropathy in the United States is diabetes. And certainly, you need to control hyperglycemia and in some patients you only need a pre-diabetic state, not even full diabetes to already have peripheral neuropathy. So you want to control blood glucose level first and foremost. Now then we have a big category of autoimmune and immune mediated causes, and that's where it gets very interesting because practical experience from many institutions and many neurologists worldwide have shown that when you give a subset of patients with autoimmune small fiber neuropathy, immunotherapy like IVIG, a lot of patients feel significantly better. And so, I think paralleling our field in dysautonomia and POTS, we are looking forward to immunotherapy being more mainstream rather than exception from the rule because access and insurance coverage is a huge barrier for clinicians and patients, but that may be a very effective treatment options for treatment refractory patients whose symptoms do not improve with symptomatic treatment.Eric Topol (30:38):Now, with all these treatments that are on the potential menu to try, and of course sometimes it really is a trial and error to get one that hopefully works for Covid, Long Covid, what is the natural history? Does this persist over years, or can it be completely resolved?Svetlana Blitshteyn (31:00):That's a great question. Everyday Long Covid patients ask me, and I think what we are seeing is that there is a good subset of patients for whom Long Covid is going to be temporary and they will improve and even recover close to normal. Now remember that original case series of patients that I reported in early 2021 based on my 2020 experience in that 20 patient case series, very few recovered, three patients recovered back to normal. Most patients had lingering ongoing chronic symptoms. So of course mine is a kind of a referral bias where I get to see the sickest patients and it looks to be like it's a problem of chronic illness variety. But I also think there is going to be a subset of patients and then we have to study them. We need to study who got better and who didn't. And people improve significantly and some even recover close to normal. But I think certain symptoms like maybe fatigue and heat intolerance could persist because those are very heavily rooted in autonomic dysfunction.Vaccination and POTSEric Topol (32:26):Yeah, well, that's something that's sobering and why we need trials and to go after this in much more intensity and priority. Now the other issue here is while with Covid, this is almost always the virus infection, there have been reports of the vaccine inducing POTS and Long Covid, and so what does that tell us?Svetlana Blitshteyn (32:54):Well, that's a big, big topic. Years ago, I was the first one to report a patient with POTS that was developed after HPV vaccine Gardasil. Now, at that time I was a young neurologist. Then the patient came to me saying she was an athlete saying two weeks after Gardasil vaccine, she developed these very disabling symptoms. And I thought it was very interesting and unique and I thought, well, I'll just publish it. I never knew that this would be the start of a whole different discussion and debate on HPV vaccines. There were multiple reports from numerous countries, Denmark, Mexico, Japan. Japan actually suspended their mass HPV vaccination program. So somehow it became a big deal. Now many people, including my colleagues didn't agree that POTS can begin POTS, small fiber neuropathy, other adverse neurologic events can begin after vaccination in general. And so, this was a topic that was widely debated and the European medical agencies came back saying, we don't have enough evidence.Svetlana Blitshteyn (34:20):Of course, we all want to have a good cancer vaccine. And it was amazing to watch this Covid vaccine issue unfolding where more than one study now have shown that indeed you can develop POTS after Covid vaccines and that the rate of POTS after Covid vaccines is actually slightly higher than before vaccination. So I think it was kind of interesting to see this unfold where I was now invited by Nature Journal to write an editorial on this very topic. So I think it's important to mention that sometimes POTS can begin after vaccination and however, I've always advised my patients to be vaccinated even now. Even now, I have patients who are unvaccinated and I say, I'm worried about you getting a second Covid or third without these vaccines, so please get vaccinated. Vaccines are very important public health measure, but we also have to acknowledge that sometimes people develop POTS, small fiber neuropathy and other complications after Covid vaccines.Prominence of the Vagus Nerve Eric Topol (35:44):Yeah, I think this is important to emphasize here because of all vaccinations can lead to neurologic sequelae. I mean look at Guillain-Barre, which is even more worrisome and that brings in the autoimmune component I think. And of course, the Covid vaccines and boosters have a liability in a small, very small percentage of people to do this. And that can't be discounted because it's a small risk and it's always this kind of risk benefit story when you're getting vaccinated that you are again spotlighting. Now gets us to the biggest thing of all besides the practical pearls you've been coming up with to help everyone in patients and clinicians. In recent weeks, there's been explosion of these intra body circuits. There was a paper from Columbia last week that taught us about the body-brain circuits between the vagus nerve and the caudal Nucleus of the Solitary Tract (cNST) of the brain and how this is basically a master switch for the immune system. And so, the vagus nerve there and then you have this gut to brain story, which is the whole gut microbiome is talking to the brain through the vagus nerve. I mean, everything comes down to the vagus nerve. So you've been working all your career and now everything's coming into this vagus nerve kind of final common pathway that's connecting all sorts of parts of the body that we didn't truly understand before. So could you comment about this because it's pretty striking.Svetlana Blitshteyn (37:34):Absolutely. I think this pandemic is highlighting the pitfalls of everything we didn't know but should have in the past. And I think this is one of them. How important is the autonomic nervous system and how important is the vagus nerve that is the longest nerve in the body and carries the parasympathetic outflow. And I think this is a very important point that we have to move forward. We cannot stop at the autonomic knowledge that we've gained thus far. Autonomic neurology and autonomic medicine has always been the field with fellowship, and we have American Autonomic Society as well. But I think now is a great time to move forward and study how the autonomic nervous system communicates with the immunologic system. And again, Kevin Tracey's work was groundbreaking in the sense that he connected the dots and realized that if you stimulate the vagus nerve and the parasympathetic outflow, then you can reduce pro-inflammatory cytokines and that he has shown that you can also improve or significantly such disorders like rheumatoid arthritis and other autoimmune inflammatory conditions.Svetlana Blitshteyn (39:03):Now we have the invasive vagus nerve stimulation procedures, and quite honestly, we don't want that to be the mainstream because you don't want to have a neurosurgery as you go to treatment. Of course, you want the non-invasive vagus nerve stimulation being the mainstream therapy. But I think a lot of research needs to happen and it's going to be a very much a multidisciplinary field where we'll have immunology, translational sciences, we'll have neurosurgeons like Kevin Tracey, we'll have rheumatologists, neurologists, cardiologists. We'll have a multidisciplinary collaborative group to further understand what's going on in these autoimmune inflammatory disorders, including those of post-infectious origin.Eric Topol (40:02):I certainly agree with all of your points there. I mean, I'm really struck now because the immune system is front and center with so much of what we're seeing with of course Long Covid, but also things like Alzheimer's and Parkinson's and across the board with metabolic diseases. And here we have this connection with your sweet spot of the autonomic nervous system, and we have these pathways that had not been delineated before. I didn't know too much about the cNST of the brain to be such an important connect point for this. And I wonder, so here's another example. Concurrently the glucagon-like peptide 1 (GLP-1) drugs have this pronounced effect on reducing inflammation in the body before the weight loss and in the brain through the gut-brain axis, as we recently discussed with Dan Drucker, have you ever tried a GLP-1 drug or noticed that GLP-1 drugs help people with Long Covid or the POTS problem?Svetlana Blitshteyn (41:12):So I have heard anecdotally people with Long Covid using these drugs for other reasons, saying I feel much better. In fact, I recently had a woman who said, I have never been more productive than I am now on this medication. And she used the word productive, which is important because non-productive implies so many things. It's the brain fog, it's the physical fatigue, it's the mental fatigue. So I think we are, first of all, I want to say, I always said that the brain is not separate from the body. And neurologic manifestations of systemic disease is a very big untapped area. And I think it's not going to be surprising for me to see that these drugs can improve many brain parameters and possibly even neuroinflammation. We don't know, but we certainly need to study this.Eric Topol (42:15):Yeah, it's interesting because statins had been tried for multiple sclerosis, I think maybe not with very clear cut benefit effects, but here you have a new class of drugs which eventually are going to be in pills and not just one receptor but triple receptor, much more potent than what we're seeing in the clinic today. And you wonder if we're onto an anti-inflammatory for the brain and body that could help in this. I mean, we have a crisis here with Long Covid in POTS without a remedy, without adequate resources that are being dedicated to the clinical trials that are so vital to execute and find treatments. And that's just one candidate of many. I mean, obviously there's so many possible ones on the list. So if you could design studies now based on your extraordinary rich experience with Long Covid and POTS, what would you go after right now? What do you think is the thing that's, would it be to evaluate more of these noninvasive, non-pharmacologic treatments like the vagal nerve stimulation, or are there particular drugs that you find intriguing?Svetlana Blitshteyn (43:33):Well, a few years ago we published a case series of patients with severe POTS and nothing helped them, but they improved significantly and some even made close to recovery improvement and were able to return to their careers because they were treated with immunotherapy. So the paper is a subcutaneous immunoglobulin and plasmapheresis and the improvement was remarkable. I say there was one physician there who could not start her residency. She got sick in medical school and could not start her residency due to severe POTS and no amount of beta blockers, Midodrine or Florinef helped her get out the house and out of bed. And therefore, sheer luck, she was able to get subcutaneous immunoglobulin and she improved significantly, finished her residency and is now a practicing physician. So I think when we have these cases, it's important to bring them to scientific community. And I think I'm very excited that hopefully soon we're going to have trials of immunotherapy and immunomodulating treatment options for patients with Long Covid and hopefully POTS in general, I believe in novel, but also repurposed, repurposed treatment.Svetlana Blitshteyn (45:01):IVIG has been used for decades, so it's not a new medication. And contrary to popular belief, it's actually quite safe. It is expensive, it's a blood product, but we are very familiar with it in medicine and neurology. So I think we have to look forward to everything. And as I tell my patients, I'm always aggressive with medications when they come to me and their doctor said something like, well, let's see, it's going to go away on its own or keep doing your salt and fluids intake or wear compression sucks. Well, they're already doing it. It's not helping. And now it's a good time to try everything we have. And I would like to have more. I would like to have immunotherapy available. I would like to have immunosuppressants even tried potentially, and maybe we'll be able to try medication for possible viral persistence. Let's see how that works out. We have other inflammatory modalities out there that can potentially give us the tools. You see, I think being that it's a multifactorial disorder, that I don't think it's going to be one thing for everyone. We need to have a toolbox where we're going to choose what's best for your specific case because when we talk about Long Covid, we have to remember there are many different phenotypes under that umbrella.A Serious MatterEric Topol (46:40):Now, before we wrap up, I mean I guess I wanted to emphasize how there are clinicians out there who discount Long Covid in POTS. They think it's something that is a figment of imagination. Now, on the other hand, you and I especially, you know that people are totally disabled. Certain days they can't even get out of bed, they can't get back to their work, their life. And this can go on and on as we've been discussing. So can you set it straight about, I mean, you are seeing these people every day. What do you have to say to our fellow colleague physicians who tend to minimize and say, this is extremely rare, if it even exists, and that these people have some type of psychiatric problem. And it's really, it's distressing of course, but could you speak to that?Svetlana Blitshteyn (47:39):Absolutely. So as I always say, Long Covid is not a psychiatric or psychological disorder, and it's also not a functional neurologic disorder. Now, having said that, as I just mentioned, brain is not separate from the body. And neurologic manifestations of systemic disease are numerous. We just had a paper out on neurologic manifestations of mast cell activation syndrome. So certainly some patients will develop psychiatric manifestations and some patients will develop major depression, anxiety, OCD or functional neurologic disorder. But those are complications of systemic disease, meaning that you cannot diagnose a patient with anxiety and send them off to a psychologist or a psychiatrist without diagnosing POTS and treating it. And in many cases, when you approach an underlying systemic disorder with the right medications, like dysautonomia for example, all of the symptoms including psychological and psychiatric, tend to improve as well. And certainly, there is going to be a small subset of Long Covid patients whose primary problem is psychiatric.Svetlana Blitshteyn (49:01):And I think that's totally fine. That is not to say that all Long Covid is psychiatric. Some will have significant psychiatric manifestations. I mean, there are cases of post Covid psychosis and autoimmune encephalitis and all kinds of psychiatric problems that people may develop, but I think we can't really stratify well, this is physiologic and this word functional that I'm not a fan of. This is physiologic as we see it on MRI. But here, because we don't see anything on MRI, it means you are fine and can just exercise your way out of it. So I think with this Long Covid, hopefully we'll get answers as to the pathophysiology, but also most importantly, hopefully we'll get these therapies that millions of people before Covid pandemic were looking for.Eric Topol (50:02):Well, I just want to thank you because you were onto this well over 10, 15 years before there was such a thing as Covid, you've dedicated your career to this. These are some of the most challenging patients to try to help and has to be vexing, that you can't get their symptoms resolved no less the underlying problem. And we're indebted to you, Svetlana, because you've really been ahead of the curve here. You were writing a patient book before there were such things as patient activists in Long Covid, as we've seen, which have been so many of the heroes of this whole problem. But thank you for all the work you do. We'll continue to follow. We learned from you about POTS and Long Covid from your work and really appreciate everything you've done. Thank you.Svetlana Blitshteyn (50:58):Thank you so much, Eric, for having me. As I said, it's a great honor for me to be here. Remarkable, amazing. And thank you for all this work that you're doing and being an advocate for our field because we always need great champions to help us move forward in these complicated disorders.********************************The Ground Truths newsletters and podcasts are all free, open-access, without ads.Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff tor audio and video support at Scripps ResearchNote: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Join your host, Nicole Morris, LMFT and Mental Health Correspondent, as she joins her return panel of experts to dive into the complexities of PANS and PANDAS. We discuss symptoms like sudden onset of OCD and tics, emerging research from Columbia University, and effective treatments such as IVIG and steroids. Panelists share personal stories, emphasize the importance of finding knowledgeable doctors, and offer practical advice for managing flares. The conversation underscores the need for increased awareness and education, providing hope and resources for families navigating these challenging disorders.

New daily persistent headache is a syndrome characterized by the acute onset of a continuous headache in the absence of any alternative cause. Triggers are commonly reported by patients at headache onset and include an infection or stressful life event. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Matthew Robbins, MD, FAAN, FAHS, author of the article “New Daily Persistent Headache,” in the Continuum® April 2024 Headache issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Robbins is an associate professor of neurology and director of the Neurology Residency Program at New York-Presbyterian/Weill Cornell Medical Center in New York, New York. Additional Resources Read the article: New Daily Persistent Headache Subscribe to Continuum: continpub.com/Spring2024 Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @https://twitter.com/AaronLBerkowitz Guest: @ @mrobbinsmd Full Transcript Available: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: stay tuned after the episode to hear how you can get CME for listening.   Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Matthew Robbins about his article on new daily persistent headache, from the April 2024 Continuum issue on headache. Dr Robbins is an Associate Professor of Neurology and Director of the Neurology Residency Program at New York-Presbyterian/Weill Cornell Medical Center, in New York. Welcome to the podcast. Dr Robbins: It's great to be with you, Dr Berkowitz. Dr Berkowitz: Well, thanks so much for joining us this morning. To start, what is new daily persistent headache? I think it's an entity maybe that might be new to some of our listeners. Dr Robbins: Yeah - it's an entity that also struck me when I was in training. I didn't hear much of it as a neurology trainee until I did a fellowship in headache, where, all of a sudden, we were seeing patients with this syndrome (and labeled as such) all the time. And that actually inspired me to begin a research project to better characterize it - a clinical project that ended up helping to broaden the diagnostic criteria. New daily persistent headache really is just defined by what it says - it's new; it's every day; it persists; it's a headache. It can't be from some other identifiable cause, which includes both secondary disorders (you know, something that, where headache is a symptom of) or a primary headache disorder; distinguishes itself from, say, migraine or tension-type headache because there's no real headache history and there's an abrupt onset of a daily and continuous headache that has to last for at least three months since onset. And the onset is typically remembered - it's usually acute or abrupt; there may or may not be some circumstances that surrounded the onset that might have some diagnostic or causal or associated implications that we can explore. Dr Berkowitz: Okay. So, I always find it challenging in headache medicine and some other areas where we don't have a biomarker, per se - an imaging finding, a lab finding; we have an eloquent and detailed clinical description - to know how comfortable to be making a diagnosis like this. In this case, particularly, right - you said it has to be going on for three months. What if I see a patient one month into something I think could be this, but I can't technically say, per the criteria, right (it's three months)? When do you start thinking about this diagnosis in patients, and what are some of the main considerations in confirming the diagnosis, and what needs to be ruled out or excluded for making the diagnosis?   Dr Robbins: I think traditionally, in headache, the term “chronic” has that three-month time period. The reasons are twofold: one is that, typically, if there's some secondary disorder that might have some distinguishing feature (something that really evokes the headache or some other neurological accompaniment that develops in addition to headache), it would pretty much be likely to declare itself by the three-month mark. Or if it was something that was very self-limited, it would probably go away before three months have elapsed. Or if it resolved after some days or weeks but then declared itself as a more episodic disorder, then we might say someone who begins with continuous headache that might, for example, resemble migraine (maybe it presented a status migrainosis but then it devolved into a more episodic disorder that might just be migraine overall). So, I think that's pretty much why the three-month mark has been so prevalent in the International Classification of Headache Disorders, including how new daily persistent headache is diagnosed. But at the same time, there's lots of disorders that might mimic (or might be misdiagnosed as) new daily persistent headache, and they really are a secondary disorder. Probably the most common one that we think about is a disorder of intracranial pressure or volume, mainly because routine MRI features could be normal or could be easily missed if they had subtle abnormalities. The defining symptom of those disorders are also continuous headache, often from onset, with an abrupt and remembered nature. So, that's often the main category of secondary headache that might be misdiagnosed as primary headache. I think, probably, idiopathic intracranial hypertension as the prototypical disorder of high pressure often declares itself with visual symptoms, pulsatile tinnitus, and other abnormalities. And nowadays, there's much more increasing recognition for MRI abnormalities or even MRV abnormalities with such patients. But spontaneous intracranial hypotension (despite increasing recognition of CSF leaks in the spine that lead to intracranial hypotension or hypovolemia) really remains an underdiagnosed entity. I think that's one disorder where - for example, if I'm seeing a patient with new daily persistent headache and there's no orthostatic or positional nature to their headache - I will still do an MRI, with and without contrast, to be sure. But that the chances of them having a spontaneous CSF leak are low if that scan is unremarkable. Dr Berkowitz: That's very helpful. Yeah. It's interesting; when you talked about the criteria for this condition - that it has an acute onset, which is a red flag, right, and it is persistent for months, which for a new headache would also be a red flag. So, this is a condition - correct me if I'm wrong – that, if you're considering it, there's no way that you're going to make this diagnosis without neuroimaging because there are two red flags, in a way, embedded in the criteria before we get to the other diagnoses being excluded. Is that right? So, this would only be a diagnosis made clinically but after neuroimaging is obtained, given that two red flags are part of the criteria – isn't that right? Dr Robbins That's absolutely right. So, I can't imagine there's anyone who has new daily persistent headache who hasn't had appropriate neuroimaging, and that typically should include an MRI, with and without contrast, unless there's some compelling reason to avoid that. There's some other workup that could be done that's not universal but - for example, in clinic-based studies of patients who have new daily persistent headache versus those who may have, say, chronic migraine or chronic tension-type headache, you may find more abnormalities. The biggest and more compelling example of that is hypothyroidism, which presumably would be somewhat subclinical if it hadn't been brought to someone's medical attention earlier. It doesn't mean that hypothyroidism is the cause of new daily persistent headache, but it could be some type of triggering or priming factor that leads to headache perpetuation in some patients. Sometimes, if that hasn't been done already, that would be a blood test I might think about sending. And, of course, the context of onset; if someone lived in a place where tick-borne illnesses are endemic, if there are other neurological symptoms, that might prompt looking for serological evidence of Lyme disease, as one example. Dr Berkowitz: We see a lot of headache. I'm a general neurologist; I know you're a headache specialist; we all see a lot of patients with headache. You and I both work closely with residents. Often, residents will come to present a headache patient to me and they'll say, “The patient seems to have a new daily persistent headache. They haven't been imaged yet. They have a completely normal exam. The history fits.” And I always ask them, “Okay, we have to get neuroimaging, right? There's at least one red flag of the chronicity, maybe the red flag of something beginning relatively abruptly. Even though you're looking at the patients - I'm pretty sure that imaging is going to be normal, but we've got to do it.” But I always encourage residents, “Try to predict - do you think the imaging is going to be normal (this is a rule out) or do you think you're going to see something (this is a rule in)? - just to sort of work on calibrating your clinical judgment.” I'd love to ask you - as a headache specialist, when you're looking at the patient and say, “I know I need to get neuroimaging here to fully make this diagnosis of exclusion,” or you've heard something that sounds like a red flag; you know you're obligated to image, but your clinical suspicion of finding anything more than something incidental is pretty low. How often are you surprised in practice in a sort of enriched tertiary headache population? Dr Robbins: That's a great way to frame such a presentation on how a resident would present to you the case and whether it's a rule in or rule out. I totally agree with your approach. I think much of it depends on the clinical story. I think if it was just a spontaneous onset of headache that kind of resembles migraine that just continued, then likely the MRI is being done to just be sure we're not missing anything else. However, if the headache started – really, say someone coughed vigorously or bent over and the headache started, and there was some clear change that you could perceive in - that was, say, the Valsalva or a transiently raised intracranial pressure, or some other maneuver; then you might really say, “Well, this really could be a spontaneous CSF leak,” for example. Even if the MRI of the brain, with and without contrast, is totally normal, I'm not really sure I'm convinced - that you might even take it further. For example, you might do an MRI of the total spine, with a CSF-leak-type protocol, to see if there's some sign of a spontaneous CSF leak or an extradural collection. So, I think in the cases where the preclinical suspicion is higher for a secondary headache, it might not stop at an MRI of the brain (with and without contrast) that's normal. Patients with spontaneous CSF leaks - about eighty percent of them have abnormal brain MRIs, but twenty percent don't. We found, from some observational studies, that a newer cause of intracranial hypotension, such as a CSF venous fistula in the spine, is more likely to present than other causes of CSF leak - with say, Valsalva-associated headache or cough-associated headache. That might prompt us to really take a workup more deeply into that territory, rather than someone where it really just sounds like chronic migraine that switched on. And maybe in those patients, when you dig around, they were carsick as a kid, or they were colicky babies, or they used to get stomachaches and missed school as a teenager here and there, and you think migraine biology is at play. Dr Berkowitz: So, if you're thinking of this diagnosis before you can make it, these patients are going to get an MRI, with and without contrast. And it sounds like the main things you're looking to make sure you're not missing are idiopathic intracranial hypertension or intracranial hypotension from some type of leak. Any other secondary headaches you worry about potentially missing in these patients or want to rule out with any particular testing? Dr Robbins: Yeah - I think sometimes we think of other vascular disorders, especially - when these patients come to medical attention, it's often a total change from what they're used to experiencing. They may present to the emergency room. So, it depends on the circumstance. You might need to rule out cerebral venous thrombosis. Or if there was a very abrupt onset or a relapsing nature of abrupt-onset headaches with sort of interictal persistent headache, we might think of other arteriopathies, such as reversible cerebral vasoconstriction syndrome. There's the more common things to rule out - or commonly identified conditions to rule out - like neoplasm and maybe a Chiari malformation in certain circumstances; those usually would declare themselves pretty easily and obviously on scan or even on clinical exam. Dr Berkowitz: Another question I'd love to ask you as a headache specialist, in your population - sometimes we see this type of new daily persistent headache presentation in older patients, and the teaching is always to rule out giant cell arteritis with an ESR and CRP, in the sense that older patients can present with just headache. Again, my clinical experience as a general neurologist - I wanted to ask you as a headache specialist – is, for the countless times I've done this (older patient has gotten their neuroimaging; we've gotten ESR and CRP), I've never made a diagnosis of giant cell arteritis based on a headache alone, without jaw claudication, scalp tenderness, visual symptoms or signs. Have you picked this up just based on a new headache, older person, ESR, CRP? I'm going to keep doing it either way, but just curious - your experience. Dr. Robbins: Yeah. We're taught in the textbooks (I'm sure we're taught by past Continuum issues and maybe even in this very issue) about that dictum that's classically in neurology teaching. But I agree - I've never really seen pure daily headache from onset, without any other accompaniments, to end up being giant cell arteritis. Then again, someone like that might walk in tomorrow, and the epidemiology of giant cell arteritis supports doing that in people over the age of fifty. But almost always, it's not the answer; I totally agree with you. Dr Berkowitz: Good to compare notes on that one. Okay - so let's say you're considering this diagnosis. You've gotten your neuroimaging, you've gotten (if the patient is over fifty) your ESR and CRP, and you ruled out any dangerous secondary causes here. You have a nice discussion in your article about the primary headache differential diagnosis here. So, now we're sort of really getting into pure clinical reasoning, right, where we're looking at descriptions (colleagues like yourself and your colleagues have come up with these descriptions in the International Classification of Headache Disorders). Here again, we're in a “biomarker-free zone,” right? We're really going on the history alone. What are some of the other primary headache disorders that would be management changing here, were you to make a diagnosis of a separate primary headache disorder, as compared to new daily persistent headache? Dr Robbins: I think the two main disorders really are chronic migraine and chronic tension-type headache. Now, what we're taught about chronic migraine and chronic tension-type headache is that they are disorders that begin in their episodic counterparts (episodic migraine, episodic tension-type headache) and then they evolve, over time, to reach or culminate in this daily and continuous headache pattern, typically in the presence of risk factors for that epidemiologic shift we know to exist but that may happen on the individual level, which does include things that we can't modify, like increasing age, women more than men, some social determinants of health (like low socioeconomic status), a head injury (even if it didn't cause a concussion or clear TBI), a stressful life event, medication overuse, having comorbid psychiatric or pain disorders in addition to the headache problem, having sleep apnea that's untreated, and so on. New daily persistent headache - by definition, it should really be kind of “switched on.” Many years ago, Dr Bill Young and Dr. Jerry Swanson wrote an editorial where they labeled new daily persistent headache as the “switched-on headache.” Then, we're taught in headache pathophysiology that this chronification process happens over time because of, perhaps, markers of central sensitization that might clinically express itself as allodynia in trigeminal or extratrigeminal distributions. So, we're not comfortable with this new daily persistent headache, where we think the biology is like chronic migraine that gets switched on abruptly, but in so many patients, it seems to be so - it behaves like chronic migraine otherwise; the comorbidities might be the same; the treatments might still work similarly for both disorders in parallel. So, I think those are the two that we think about. Obviously, if there's unilateral headache, we might think of a trigeminal autonomic cephalalgia that's continuous, even if it doesn't have associated autonomic signs like ptosis or rhinorrhea (which is hemicrania continua) - and in those patients, we would think about a trial of indomethacin. But otherwise, I think chronic migraine and chronic tension-type headache are the two that phenotypically can look like new daily persistent headache. In patients with new daily persistent headache, about half have migraine-type features and about half have tension-type features. When I was a fellow, the International Headache Society and the classification only allowed for those who have more tension-type features to be diagnosed as new daily persistent headache. But we (and many other groups) have found that migraine-type features are very common in people who fulfill rigorously the criteria for new daily persistent headache otherwise. And then the latest iteration of the classification has allowed for us to apply that diagnosis to those with migraine features. Dr Berkowitz: That's very helpful. So, we've ruled out secondary causes and now you're really trying to get into the nuances of the history to determine, did this truly have its abrupt onset or did it evolve from an episodic migraine or tension-type headache? But it could be described by the patient as migrainous, be described by the patient as having tension features The key characteristics (as you mentioned a few times) should be abrupt onset and a continuous nature. Let's say, now you (by history) zeroed in on this diagnosis of new daily persistent headache. You've ruled out potential secondary causes. You're pretty convinced, based on the history, that this is the appropriate primary headache designation. How do you treat these patients? Dr Robbins: Well, that's a great question, Dr Berkowitz, because there's this notoriety to the syndrome that suggests that patients just don't respond to treatments at all. In clinical practice, I can't dispute that to a degree. I think, in general, people who have this syndrome seem to not respond as well, to those who have clear established primary headache disorders. Part of that might be the biology of the disorder; maybe the disorder is turned on by mechanisms that are different to migraine (even though it resembles chronic migraine) and therefore, the medications we know to work for migraine may not be as effective. In some, it could be other factors. There's just a resistance to appreciating that you have this headache disorder that - one day you were normal, the next day you're afflicted by headache that's continuous. And there's almost this nihilism that, “Nothing will work for me, because it's not fair - there's this injustice that I have this continuous headache problem.” And often people with new daily persistent headache may be resistant to, say, behavioral therapies that often are really helpful for migraine or tension-type headache because of this sort of difficult with adjustment to it. But at least there's observational studies that suggest that most of the treatments that work for migraine work for new daily persistent headache. There's been studies that show that people can respond to triptans. In my clinical experience, CGRP antagonists that work for the acute treatment of migraine may work. There is evidence that many of the traditional, older medicines (like tricyclic antidepressants, topiramate, valproate, beta-blockers, probably candesartan) and others that we use for migraine may work. There's observational studies specifically for new daily persistent headache that show that anti-CGRP therapies in the form of monoclonal antibodies and botulinum toxin can work for the disorder. Are there anything specific for some of the new daily persistent headache that might work? Not that we really know. There's been some attempts to say, “Well, if you get these people in the hospital early and try to reduce the risk of headache persistence by giving them DHE, or dexamethasone, or lidocaine, or ketamine, will you reduce the chances of headache persistence at that three-month mark or longer?” We don't really know (there's some people who believe that, though). Maybe there's good reason to do some type of elective hospitalization for aggressive treatment because we know that, notoriously, the treatment response is very mixed. There's been specific treatments that people have looked at. There's been some anecdotes about doxycycline as a broad anti-inflammatory type of treatment that might be used in a variety of neurological disorders, but there's really nothing in the peer-reviewed literature that suggests that is effective or safe, necessarily. And I think a lot of people in new daily persistent headache do develop a profile that resembles chronic migraine (they can develop medication overuse very easily). Often, goal setting is really important in the counseling of such patients. You really have to suggest that the goal for them might be difficult to have them pain-free at zero and cured, but we want this to be treated so the peaks of severity flatten out a bit, and then the baseline level of pain diminishes so that it devolves into a much more episodic disorder over time that looks like regular migraine or regular tension-type headache. Dr Berkowitz: I see. So, in addition to starting a migraine-type prophylactic agent based on the patient's comorbidities and potential benefits of the medication (the same way we would choose a migraine prophylactic), do you do anything, typically, to try to, quote, “break the cycle” - a quick pulse of steroids as an outpatient or a triptan in the office - and see how they do, or do you typically start a prophylactic agent and go from there? Dr Robbins: I think, like all things, it kind of depends on the distress of the patient and how they are functioning. If it's someone who's just out of work, cannot function - and someone like that might be very amenable to an elective hospitalization or some parenteral therapy, or maybe an earlier threshold to use a preventative treatment than we would be doing otherwise in someone with migraine overall - I think that it really depends on that type of a disability that's apparent early. I think it's compelling that, with new daily persistent headache, about a third of people report some antecedent infection that was around at the time. When new daily persistent headache was first described by this Canadian neurologist, Dr Vanast, in the 1980s, it was described in the context of Epstein-Barr virus infection, or at least a higher rate of serologies that are positive for, perhaps, recent Epstein-Barr exposure. And we know that Epstein-Barr is obviously implicated in lots of neurological diseases, like multiple sclerosis. And I mean, I think about these things all the time, and especially with COVID now. So, it's compelling - as a postinfectious disorder, do we, as neurologists (who are so comfortable with using pulse-dose steroids, IVIG) - do we use these things for a new daily persistent headache? But there's no great evidence that enduring inflammation in the dura that would spill into CSF analyses is really present in such patients. There was one study that looked at markers, such as TNF-alpha, in the CSF, but the rates of seeing that were the same in new daily persistent headache and chronic migraine, so there isn't really a specificity to that. Many people we see with new persistent headaches since 2020 may have it as part of a long COVID syndrome (or postacute COVID syndrome), and in those cases, often it's more like “new daily persistent headache-plus.” They might have something that resembles POTS (postural orthostatic tachycardia syndrome); they might have something that resembles fibromyalgia, chronic fatigue. Often in those patients, it takes management of the whole collection of neurological syndromes to get them better, not just the headache alone. Dr Berkowitz: Well, this sounds like such a challenging condition to treat. How do you counsel patients when you've made this diagnosis - what to expect, what the goals are, what this condition is, and how you developed your certainty? It's often challenging (isn't it?) sometimes with patients with headache disorders, when we're not relying on an MRI or lab test to say, “This is the diagnosis”; telling them, it's just our opinion, based on their collection of symptoms and signs. So, how do you give the diagnosis and how do you counsel patients on what it means to them? Dr Robbins: Yeah, it's a great question because it's high stakes, because people will read online, or on social media, or on support groups that this is a dreadful condition - that no one gets better, that they're going to be afflicted with this forever, and the doctors don't know what they're doing, and, “Just don't bother seeing them.” And the truth is not that; there's so many people who can get substantially better. I tell people that it's common; in some epidemiologic studies, one in one thousand people in any given year develop new daily persistent headache, and most of those people get better (they don't seek medical care eventually, or they do, just in the beginning, and then they don't have follow-up because they got all better) - and I think that really happens. I think the people who we see in, say, a headache clinic (or even in general neurology practice) are typically the ones who are the worst of the worst. But even amongst those, we see so many stories of people who get better. So, I really try to reset expectations - like we mentioned before about assessing for treatment response and understanding that improvement will not just mean one day it switches off like it switched on (which seems unfair), but that the spikes will flatten out of pain (first), that the baseline level of intensity will then improve (second); that we turn it into a more manageable day-to-day disorder that really will have less of an impact on someone's quality of life. Sometimes people embrace that and sometimes people have a hard time. But it does require, like many conditions in neurology, incremental care to get people better. Dr Berkowitz: Fantastic. Well, Dr Robbins, thanks so much for taking the time to speak with us today. I've learned so much from your expertise in talking to you and getting to pick your brain about this and some broader concepts and challenges in headache medicine. And I encourage all our listeners to seek out your article on this condition that has even more clinical pearls on how to diagnose and treat patients with this disorder. Dr Robbins: Thanks Dr. Berkowitz - great to be with you. Dr Berkowitz: Again, for our listeners today, I've been interviewing Dr Matthew Robbins, whose article on new daily persistent headache appears in the most recent issue of Continuum, on headache. Be sure to check out other Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

If there's one person you'd want to talk to about immunology, the immune system and Covid, holes in our knowledge base about the complex immune system, and where the field is headed, it would be Professor Iwasaki. And add to that the topic of Women in Science. Here's our wide-ranging conversation.A snippet of the video, Full length Ground Truths videos are posted here and you can subscribe. Ground Truths is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Transcript with many external link and links to the audio, recorded 30 April 2024 Eric Topol (00:06):Hello, it's Eric Topol and I'm really thrilled to have my friend Akiko Iwasaki from Yale, and before I start talking with Akiko, I just want to mention there aren't too many silver linings of the pandemic, but one for me was getting to know Professor Iwasaki. She is my go-to immunologist. I've learned so much from her over the last four years and she's amazing. She just, as you may know, she was just recently named one of the most influential people in the world by TIME100. [and also recognized this week in TIME 100 Health]. And besides that, she's been elected to the National Academy of Medicine, National Academy of Sciences. She's the president of the American Association of Immunologists and she's a Howard Hughes principal investigator. So Akiko, it's wonderful to have you to join into an extended discussion of things that we have of mutual interest.Akiko Iwasaki (01:04):Thank you so much, Eric, for having me. I equally appreciate all of what you do, and I follow your blog and tweets and everything. So thank you Eric.Eric Topol (01:14):Well, you are a phenom. I mean just, that's all I can say because I think it was so appropriate that TIME recognize your contributions, not just over the pandemic, but of course throughout your career, a brilliant career in immunology. I thought we'd start out with our topic of great interest on Long Covid. You've done seminal work here and this is an evolving topic obviously. I wonder what your latest thoughts are on the pathogenesis and where things are headed.Long CovidAkiko Iwasaki (01:55):Yeah, so as I have been saying throughout the pandemic, I think that Long Covid is not one disease. It's a collection of multiple diseases and that are sort of ending up in similar sets of symptoms. Obviously, there are over 200 symptoms and not everyone has the same set of symptoms, but what we are going for is trying to understand the disease drivers, so persistent viral infection is one of them. There are overwhelming evidence for that theory now, all the way from autopsy and biopsy studies to looking at peripheral blood RNA signatures as well as circulating spike protein and nucleocapsid proteins that are detected in people with Long Covid. Now whether that persistent virus or remnants of virus is driving the disease itself is unclear still. And that's why trials like the one that we are engaging with Harlan Krumholz on Paxlovid should tell us what percentage of the people are suffering from that type of driver and whether antivirals like Paxlovid might be able to mitigate those. If I may, I'd like to talk about three other hypotheses.Eric Topol (03:15):Yeah, I'd love for you to do that.Akiko Iwasaki (03:18):Okay, great. So the second hypothesis that we've been working on is autoimmune disease. And so, this is clearly happening in a subset of people, again, it's a heterogeneous disease, but we can actually not only look at reactogenicity of antibodies from people with Long Covid where we can transfer IgG from patients with Long Covid into an animal, a healthy animal, and really measure outcomes of a pathogenesis. So that's a functional evidence that antibodies in some people with Long Covid is really actually causing some of the damages that are occurring in vivo. And the third hypothesis is the reactivation of herpes viruses. So many of us adults have multiple latent herpes virus family members that are just dormant and are not really causing any pathologies. But in people with Long Covid, we're seeing elevated reactivation of viruses like Epstein-Barr virus (EBV) or Varicella-zoster virus (VZV) and that may again be just a signature of Long Covid, but it may also be driving some of the symptoms that people are suffering from.(04:32):So that's again, we see the signature over and over, not just our group, but multiple other groups, Michael Peluso's group, Jim Heath, and many others. So that's also an emerging evidence from multiple groups showing that. And finally, we think that inflammation that occurs during the acute phase can sort of chronically change some tissue tone. For instance, in the brain with Michelle Monje's team, we developed a sort of localized mild Covid model of infection and showed that changes in microglia can be seen seven weeks post infection even though the virus is completely gone. So that means that inflammation that's established as a result of this initial infection can have prolonged sequence and sequela within the person and that may also be driving disease. And Eric, the reason we need to understand these diseases separately is because not only for diagnostic purposes, but for therapeutic purposes because to target a persistent virus is very different approach from targeting autoantibodies, for example.Eric Topol (05:49):Well, that's great. There's a lot to unpack there as you laid out four distinct paths that could result in the clinical syndrome and sequelae. I think you know I had the chance to have a really fun conversation with Michelle about their joint work that you've done, and she reminded me how she made a cold call to you to start as a collaboration, which I thought was fantastic. Look what that yielded. But yeah, this is fascinating because as I think you're getting at is that it may not be the same pathogenesis in any given individual so that all these, and even others might be operative. I guess maybe I first delve into the antibody story as you're well aware, we see after people get Covid a higher rate of autoimmune diseases crop up, which is really interesting because it seems to rev up self-directed immune response. And this I think many people haven't really noted yet, although obviously you're well aware of this, it's across all the different autoimmune diseases, connective tissue disease, not just one in particular. And it's, as you say, the idea that you could take the blood from a person suffering from Long Covid and give it to an experimental animal model and be able to recapitulate some of the abnormalities, it's really pretty striking. So the question I guess is if you were to do plasmapheresis and try to basically expunge these autoantibodies, wouldn't you expect people to have some symptomatic benefit pretty rapidly or is it just that the process is already far from the initiating step?Akiko Iwasaki (07:54):That's a great question. Plasmapheresis may be able to transiently improve the person if they're suffering from these autoantibody mediated diseases. People have reported, for example, IVIG treatment has dramatically improved their symptoms, but not in everybody. So it's really critical to understand who's suffering from this particular driver and appropriately treat those people. And there are many other very effective therapies in autoimmune disease field that can be repurposed for treating these patients as well.Eric Topol (08:34):The only clinical trial that has clicked so far, interestingly, came out of Hong Kong with different types of ways to manipulate the gut microbiome, which again, you know better than me is a major modulator of our immune system response. What are your thoughts about taking advantage of that way to somehow modulate this untoward immune response in people with this condition?Akiko Iwasaki (09:07):Yeah, so that is an exciting sort of development, and I don't mean to discount the importance of microbiome at all. It's just the drivers that are mentioning are something that can be directly linked to disease, but certainly dysbiosis and translocation of metabolites and microbiome itself could trigger Long Covid as well. So it's something that we're definitely keeping our eyes on. And as you say, Eric, the immune system is in intimate contact with the gut microbiome and also the gut is intimate contact with the brain. So there's a lot of connections that we really need to be paying attention to. So yeah, absolutely. This is a very exciting development.Eric Topol (09:57):And it is intriguing of course, the reactivation of viruses. I mean, we've learned in recent years how important EBV is in multiple sclerosis (MS). The question I have for you on that pathway, is this just an epiphenomena or do you actually think that could be a driving force in some people?Akiko Iwasaki (10:19):Yeah, so that's really hard to untangle in people. I mean, David Putrino and my team we're planning a clinical trial using Truvada. Truvada obviously is an HIV drug, but it has reported antiviral activity to Epstein-Barr virus (EBV) and others. So potentially we can try to interrogate that in people, but we're also developing mouse models that can sort of recapitulate EBV like viral reactivation and to see whether there's any sort of causal link between the reactivation and disease process.Eric Topol (10:57):Right now, recently there's been a bunch of anecdotes of people who get the glucagon-like peptide one (GLP-1) drugs which have a potent anti-inflammatory, both systemic and in the brain. I'd love to test these drugs, but of course these companies that make them or have other interests outside of Long Covid, do you think there's potential for a drug like that?Akiko Iwasaki (11:23):Yeah, so those drugs seem to have a lot of miraculous effects on every disease. So obviously it has to be used carefully because many people with Long Covid have issues with liver functions and other existing conditions that may or may not be conducive to taking those types of GLP-1 agonists. But in subset of people, maybe this can be tried, especially due to the anti-inflammatory properties, it may benefit again, a subset of people. I don't expect a single drug to cure everyone. That would be pretty amazing, but unlikely.Eric Topol (12:09):Absolutely. And it's unfortunate we are not further along in this whole story of clinical trials, testing treatments and applauding your efforts with my friend Harlan there to get into the testing which we had hoped RECOVER was going to do with their more than billion dollars or allocation, which didn't get us too far in that. Now before we leave Long Covid, which we could speak about for hours, I mean it's so darn important because so many people are really out there disabled or suffering on a daily basis or periodically they get better and then get worse again. There's been this whole idea that, oh, it's going away and that reinfections don't pose a threat. Maybe you could straighten that story out because I think there seems to be some miscues about the risk of Long Covid even as we go along with the continued circulating virus.Akiko Iwasaki (13:11):Right, so when you look at the epidemiological evidence of Long Covid, clearly in the beginning when we had no vaccines, no antivirals, no real good measure against Covid, the incident of developing Long Covid per infection was higher than a current date where we do have vaccines and Omicron may have changed its property significantly. So if you compare, let's say the Delta period versus Omicron period, there seems to be a reduced risk per infection of Long Covid. However, Omicron is super infectious. It's infected millions of people, and if you look at the total number of people suffering from Long Covid, we're not seeing a huge decline there at all because of the transmissibility of Omicron. So I think it's too early for us to say, okay, the rates are declining, we don't need to worry about it. Not at all, I think we still have to be vigilant.(14:14):We need to be up to date on vaccines and boosters because those seem to reduce the risk for Long Covid and whether Paxlovid can reduce the rate of Long Covid at the acute phase for the high risk individual, it seems to be yes, but for people who are not at high risk may or may not be very effective. So again, we just need to be very cautious. It's difficult obviously, to be completely avoiding virus at this time point, but I think masking and anything you can do, vaccination boosters is going to be helpful. And a reinfection does carry risk for developing Long Covid. So that prior infection is not going to prevent Long Covid altogether, even though the risk may be slightly reduced in the first infection. So when you think about these risks, again we need to be cognizant that reinfection and some people have multiple infections and then eventually get Long Covid, so we're just not safe from Long Covid yet.Nasal Vaccines and Mucosal ImmunityEric Topol (15:24):Right. No, I think that's the problem is that people have not acknowledged that there's an ongoing risk and that we should continue to keep our guard up. I want to applaud you and your colleagues. You recently put out [Yale School of Public Health] this multi-panel about Covid, which we'll post with this podcast that gave a lot of the facts straight and simple diagrams, and I think this is what you need is this is kind of like all your threads on Twitter. . They're always such great educational ways to get across important information. So now let's go onto a second topic of great mutual interest where you've also been a leader and that's in the mucosal nasal vaccine story. I had the privilege of writing with you a nice article in Science Immunology back in 2022 about Operation Nasal Vaccine, and unfortunately we don't have a nasal vaccine. We need a nasal vaccine against Covid. Where do we stand with this now?Akiko Iwasaki (16:31):Yeah, so you're right. I mean nasal vaccines, I don't really know what the barrier is because I think the preclinical models all support the effectiveness against transmission and infection and obviously disease. And there is a White House initiative to support rapid development of next generation vaccine, which includes mucosal vaccine, so perhaps that's sort of pushing some of these vaccine candidates forward. You're probably more familiar than me about those kinds of events that are happening. But yeah, it's unfortunate that we don't have an approved mucosal booster vaccine yet, and our research has shown that as simple as a spray of recombinant spike protein without any adjuvants are able to restimulate immune response and then establish mucosal immunity in the nasal cavity, which goes a long way in preventing infection as well as transmission. So yeah, I mean I'm equally frustrated that things like that don't exist yet.The Neomycin and Neosporin SurpriseEric Topol (17:52):Well, I mean the work that you and many other groups around the world have published on this is so compelling and this is the main thing that we don't have now, which is a way to prevent infection. And I think most of us would be very happy to have a spray that every three or four months and gave us much higher levels of protection than we're ever going to get from shots. And your whole concept of prime and spike, I mean this is something that we could have had years ago if there was a priority, and unfortunately there never has been. Now, the other day you came with a surprise in a paper on Neomycin as an alternate or Neosporin ointment. Can you tell us about that? Because that one wasn't expected. This was to use an antibiotic in a way to reduce Covid and other respiratory virus.Akiko Iwasaki (18:50):Right. So yeah, that's a little known fact. I mean, of course widespread use of antibiotics has caused some significant issues with resistance and so on. However, when you look at the literature of different types of antibiotics, we have reported in 2018 that certain types of antibiotics known as aminoglycoside, which includes Neosporin or neomycin, has this sort of unintended antiviral property by triggering Toll-like receptor 3 in specialized cell types known as conventional dendritic cell type 1. And we published that for a genital herpes model that we were working on at the time. But because it's acting on the host, the Toll-like receptor 3 on the host cell to induce interferon and interferon stimulated genes to prevent the replication of the virus, we knew that it could be pan-viral. It doesn't really matter what the virus is. So we basically leverage that discovery that was made by a postdoc Smita Gopinath when she was in the lab to see if we can use that in the nasal cavity.(20:07):And that's what Tianyang Mao, a former graduate student did, in fact. And yeah, little spray of neomycin in the nose of the mice reduce this infection as well as disease and can even be used to treat shortly after the infection disease progress and using hamster models we also showed that hamsters that are pretreated with neomycin when they were caged with infected hamsters, the transmission rate was much reduced. And we also did with Dr. Charles Dela Cruz, a small clinical trial, randomized though into placebo and Neosporin arms of healthy volunteers. We asked them to put in a pea size amount of Neosporin on a cotton swab into the nose, and they were doing that twice a day for seven days. We measured the RNA from the nose of these people and indeed see that more than half the participants in the Neosporin group had elevated interferon stimulated genes, whereas the control group, which were given Vaseline had no response. So this sort of shows the promise of using something as generic and cheap as Neosporin to trigger antiviral state in the nose. Now it does require a much larger trial making sure that the safety profiles there and effectiveness against viral infection, but it's just a beginning of a story that could develop into something useful.New Frontiers in Immunology and Tx CellsEric Topol (21:51):Yeah, I thought it was fascinating, and it does bring up, which I think has also been underdeveloped, is our approaches for interferon a frontline defense where augmenting that, just getting that exploiting the nasal mucosa, the entry site, whether it be through that means or of course through even more potent a nasal vaccine, it's like a missing, it's a hole in our whole defense of against this virus that's led to millions of people not just dying, but of course also sick and also with Long Covid around the world. So I hope that we'll see some progress, but I thought that was a really fascinating hint of something to come that could be very helpful in the meantime while we're waiting for specific nasal vaccines. Now added to all these things recently, like last week you published a paper in Cell with your husband who's in the same department, I think at Yale. Is that right? Can you tell us about that and this paper about the whole new perspectives in immunology?Akiko Iwasaki (23:05):Yeah, so my husband Ruslan Medzhitov is a very famous immunologist who's in the same department, and we've written four or five review and opinion pieces together over the years. This new one is in Cell and it's really exploring new perspectives in immunology. We were asked by the editors to celebrate the 50th anniversary of the Cell journal with a perspective on the immune system. And the immune response is just a beautiful system that is triggered in response to specific pathogens and can really provide long-term or even sometimes lifelong immunity and resistance against pathogens and it really saves our lives. Much has been learned throughout the last 20, 30 years about the innate and adaptive immune system and how they're linked. In this new perspective, we are trying to raise some issues that the current paradigm cannot explain properly, some of the mysteries that are still remaining in the immune system.(24:22):And we try to come up with new concepts about even the role of the immune system in general. For instance, is the immune system only good for fighting pathogens or can it be repurposed for conducting normal physiology in the host? And we came up with a new subset of T-cells known as, or we call it Tx cells, which basically is an interoceptive type of T-cells that monitor homeostasis in different tissues and are helping with the normal process of biology as opposed to fighting viruses or bacteria or fungi. But these cells, when they are not appropriately regulated, they are also the source of autoimmune diseases because they are by design reactive against auto antigens. And so, this is a whole new framework to think about, a different arm of the immune function, which is really looking inside of our body and not really fighting against pathogens, but we believe these cells exist, and we know that the counterpart of Tx cells, which is the T regulatory cells, are indeed well known for its physiological functions. So we're hoping that this new perspective will trigger a new set of approaches in the field to try to understand this interceptive property of T-cells.Eric Topol (25:59):Yeah, well, I thought it was fascinating, of course, and I wanted to get into that more because I think what we're learning is this immune system not only obviously is for cancer whole. We're only starting to get warmed up with immunotherapy where checkpoint inhibitors were just the beginning and now obviously with vaccines and all these different ways that we can take the CAR-T cells, engineered T-cells, take the immune system to fight cancer and potentially to even use it as a way to prevent cancer. If you have these, whether it's Tx or Tregs or whatever T-cells can do this. But even bigger than that is the idea that it's tied in with the aging process. So as you know, again, much more than I do, our senescent immune cells are not good for us. And the whole idea is that we could build immune resilience if we could somehow figure out these mysteries that you're getting at, whereby we get vulnerable just as we were with Covid. And as we get older, we get vulnerable to not just infections, but everything going wrong, whether it's the walls of our arteries or whether it's the cancer or the immunity that's going on in our brain for Alzheimer's and neurodegenerative diseases. How can we fix the immune system so that we age more healthilyThe Immune System and Healthy Aging Akiko Iwasaki (27:37):Oh yeah. A lot of billionaires are also interested in that question and are pouring money into this question. It's interesting, but when you think about the sort of evolutionary perspective, we humans are only living so long. In the very recent decades, our life expectancy used to be much shorter and all we had to survive was to reproduce and generate the next progeny. But nowadays, because of this amazing wealth and health interventions and food and everything else, we're just living so much longer than even our grandparents. The immune system didn't evolve to deal with such one to begin with. So we were doing fine living up to 30 years of age or whatever. But now that we're living up to a hundred years, the immune system isn't really designed to keep up with this kind of stressors. But I think you're getting at a very important kind of more engineering questions of how do we manipulate the immune system or rejuvenate it so that we can remain healthy into the later decades? And it is well known that the immune system itself ages and that our ability to produce new lymphocytes, for example, decline over time and thymus that is important for T-cell development shrinks over time. And so anatomically it's impossible to help stop that process. However, is there a way of, for example, transferring some factors or engineering the immune cells to remain healthy and even like hematopoiesis itself can be manipulated to perhaps rejuvenate the whole immune system in their recent papers showing that. So this is a new frontier.Eric Topol (29:50):Do you think that some point in the future, we'll ex vivo inject Yamanaka factors into these cell lines and instead of this idea that you know get young plasma to old folks, and I mean since we don't know what's in there and it doesn't specifically have an effect on immune cells, who knows how it's working, but do you foresee that that might be a potential avenue going forward or even an in vivo delivery of this?Akiko Iwasaki (30:22):Yeah, it's not impossible, right? There are really rapidly evolving technologies and gene therapies that are becoming online. So it's not impossible to think about engineering in situ as you're suggesting, but we also have to be certain that we are living longer, but also healthy. So we do have to not only just deal with the aging immune system, but preventing neurodegenerative diseases and so on. And the immune system may have a role to play there as well. So there's a lot of, I mean, I can't think of a non-genetically mediated disease that doesn't involve the immune system.Eric Topol (31:03):Sure. No, I mean, it's just, when I think about this, people keep talking about the digital era of digital biology, but I actually think of it more as digital immunobiology, which is driving this because it's center stage and in more and more over time. And the idea that I'm concerned about is that we could rejuvenate the relevant immune cells or the whole immune response, but then it's such a delicate balance that we could actually wind up with untoward, whether it's autoimmune or overly stimulated immune system. It's not such a simple matter, as I'm sure you would agree. Now, this gets me to a broader thing which you've done, which is a profound contribution in life science and medicine, which is being an advocate for women in science. And I wonder if you could speak to that because you have been such a phenomenal force propelling the importance of women in science and not just doing that passively, but also standing up for women, which is being an activist is how you get things to change. So can you tell us about your thoughts there?An Activist for Women in ScienceAkiko Iwasaki (32:22):Yeah, so I grew up in Japan, and part of the reason I left Japan at the age of 16 was that I felt very stifled because of the societal norm and expectation of what a woman should be. And I felt like I didn't have the opportunity to develop my skills as a scientist remaining in Japan. And maybe things have changed over the years, but at the time when I was growing up, that's how I felt. And so, I was very cognizant of biases in society. And so, in the US and in Canada where I also trained, there's a lot less barrier to success, and we are able to do pretty much anything we want, which is wonderful, and that's why I think I'm here. But at the same time, the inequity still exists, even in pay gaps and things like that that are easy to fix but are still kind of insidious and it's there.(33:32):And Yale School of Medicine has done a great job partly because of the efforts of women who spoke up and who actually started to collect evidence for pay gap. And now there's very little pay gap because there's active sort of involvement of the dean and everyone else to ensure equity in the medical school. But it's just a small segment of the society. We really need to expand this to other schools and making sure that women are getting paid equally as men in the same ranks. And also, I see still some sexual harassment or more just toxic environment for people in general in academia. Some PIs get away with a lot of behavior that's not conducive to a healthy environment, so I have written about that as well and how we can have antidotes for such toxic environments. And it really does require the whole village to act on it. It's not just one person speaking up. And there should be measures placed to make sure that those people who does have this tendency of abusive behavior that they can get training and just being aware of these situations and corrective behavior. So I think there's still a lot of work left in academia, but things have obviously improved dramatically over the last few decades, and we are in a very, very good place, but we just have to keep working to achieve true equity.Why Don't We Have Immunome Check-Ups?Eric Topol (35:25):Well applauding your efforts for that, and I'm still in touch with that. We got a ways to go, and I hope that we'll see steady and even more accelerated and improvement to get to parity, which is what it should be. And I really think you've been a model for doing this. It isn't like you aren't busy with everything else, so to fit that in is wonderful. In closing up, one of the things that I wonder about is our ability to assess back to the immune system for a moment isn't what it should be. That is we do a CBC and we have how many lymphocytes, how many this, why don't we have an immunome, why doesn't everybody serially have an immune system checkup? Because that would tell us if we're starting to go haywire and then maybe hunt for reactivated viruses or what's going on. Do you foresee that we could ever get to a practical immunome as we go forward? Because it seems like it's a big missing link right now.Akiko Iwasaki (36:33):Yeah, I think that's a great idea. I mean, I'll be the first one to sign up for the immunome.Eric Topol (36:40):But I'm depending on you to make it happen.Akiko Iwasaki (36:44):Well, interestingly, Eric, there are lots of amazing technologies that are developed even during the pandemic, which is monitoring everything from antibody reactivity to reactivated viruses to the cytokines to every cell marker you can imagine. So the technologies out there, it's just I think a matter of having the right set of panels that are relatively affordable because some of these things are thousands of dollars per sample to analyze, and then of course clinical validation, something that's CLIA approved, and then we can start to, I guess the insurance company needs to also cover this, right? So we need to demonstrate the benefit to health in the long run to be able to afford this kind of immunome analysis. But I think that very wealthy people can already get this done.Eric Topol (37:43):Yeah, well, we want to make it so it's a health equity story, not of course, only for the crazy ones that are out there that are taking 112 supplements a day and whatnot. But it's intriguing because I think we might be able to get ahead of things if we had such an easy means. And as you said during the pandemic, for example, my friends here in La Jolla at La Jolla Immunology did all kinds of T-cell studies that were really insightful and of course done with you and others around the country and elsewhere to give us insights that you didn't get just from neutralizing antibodies. But it isn't something that you can get done easily. Now, I think this immunome hopefully will get us to another level in the future. One of the most striking things I've seen in our space clinically before wrapping up is to take the CD19 CAR T therapies to deplete the B cells of people with lupus, systemic sclerosis and other conditions, and completely stop their autoimmune condition. And when the B cells come back, they're not fighting themselves. They're not self-directed anymore. Would you have predicted this? This seems really striking and it may be a clue to the kind of mastering approaches to autoimmune diseases in the future.Akiko Iwasaki (39:19):Yeah, absolutely. So for multiple sclerosis, for example, where B cells weren't thought to be a key player by doing anti-CD20 depletion, there's this remarkable clinical effects. So I think we can only find the answer experimentally in people when they do these clinical trials and show this remarkable effects. That's when we say, aha, we don't really understand immunology. You know what I mean? That's when we have to be humble about what we think we understand. We really don't know until we try it. So that's a really good lesson learned. And these may be also applicable to people with autoimmune phenotype in Long Covid, right? We may be able to benefit from similar kinds of depletion therapy. So I think we have a lot to learn still.Eric Topol (40:14):Yeah, that's why, again, going back to the paper you just had in Cell about the mysteries and about some new ideas and challenging the dogma is so important. I still consider the immune system most complex one in the body by far, and I'm depending on you Akiko to unravel it, not to put any weight on your shoulders. Anyway, this has been so much fun. You are such a gem and always learning from you, and I can't thank you enough for all the work. And the fact is that you've got decades ahead of you to keep building on this. You've already done enough for many people, many scientists in your career, and I know you'll keep going. So we're all going to be following you with great interest in learning from you on a frequent basis. And I hope we'll build on some of the things we've talked about like a Long Covid treatment, treatments that are effective nasal vaccines, maybe even some dab of Neosporin, and keep on the momentum we've had with the understanding of the immune system, and finally, someday achieving the true parity of gender and science. And so, thank you for all that you do.Akiko Iwasaki (41:35):Thank you so much, Eric.************************CreditsHeadshot photo credits by Robert Lisak, Yale School of MedicineMy producer for Ground Truths is Jessica Nguyen, Scripps Research and our technical support for audio/video is by SInjun Balabanoff at Scripps Research.I hope you found the spot informative. Please share itThe Ground Truths newsletters and podcasts are all free, open-access, without ads.Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in.Comments are welcome from all subscribers. Get full access to Ground Truths at erictopol.substack.com/subscribe

Welcome to another episode of The Remedy Revolution podcast with your host, Erin Paige, a seasoned homeopath. In this episode titled "The Dangers of SSRI and IVIG Treatment in PANS/PANDAS, Depression, and Other Disorders," Erin delves into critical issues surrounding conventional treatments for various conditions. She highlights a groundbreaking meta-data analysis in Molecular Psychology titled "The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence," which challenges the widely accepted serotonin theory of depression, revealing a lack of substantial evidence to support it.Moreover, Erin discusses the alarming Factor 8 scandal in the UK, where thousands of patients were infected with HIV and Hepatitis C due to tainted blood products. She sheds light on mounting evidence suggesting that some doctors involved in administering Factor 8 were aware of the risks of infection, emphasizing the need for caution when dealing with blood products. To learn more about this scandal, listeners are directed to visit factor8scandal.uk.Despite these grim realities, Erin offers hope through alternative solutions such as supplementation and homeopathy. These approaches not only present fewer potential side effects but also aim for comprehensive healing. By exploring alternatives to conventional treatments, Erin encourages listeners to consider holistic approaches that prioritize well-being. To access the serotonin study discussed in this episode, visit: [The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence](https://www.nature.com/articles/s41380-022-01661-0). Join Erin as she navigates the landscape of healthcare, advocating for safer and more effective remedies.Additionally, some of these topics were covered in a recent episode of The Highwire, which can be found here: https://thehighwire.com/ark-videos/ground-rules/Connect with Erin at: https://heartwinghealing.com

In this Nutritional Therapy and Wellness Podcast episode, host Jamie Belz interviews Rachel Ballard, an RN who wasn't willing to accept the prognosis of a slow, painful, premature death. Rachel is a Registered Nurse, farmer, and Food As Medicine teacher who is currently completing her Nutritional Therapy Practitioner (NTP) certification. After battling back from a rare, paralyzing autoimmune disease, she's helping individuals use food as a tool so they can fight back against chronic conditions and defy the odds. A lover of British television dramas, raising medicinal plants, and scratch cooking, Rachel lives on her Kentucky cattle farm with her husband of twenty-three years and two teenage children. In talking with Jamie, Rachel walks us through her declining health, eventual diagnosis of CIPD (Chronic Inflammatory Demyelinating Polyneuropathy), and her long road to recovery. 04:50 – Symptoms and red flags leading up to diagnosis: Hashimoto's, muscles in eye, limp leg, loss of strength, paralysis, felt like she was “on fire” 07:10 – CIPD Diagnosis with Central Nervous Symptom Overlap causing issues with vision, hearing, digestion, bowel and bladder control, and promoting cardiac arrhythmia 9:00 - IVIG (Intravenous Immunoglobulin) Treatment, Plasmapheresis, Stem Cell Transplant, slow decline 10:10 – Five years to live 11:02 – Subcutaneous IVIG Therapy Failed 13:02 – Hitting the point of desperation, looking at natural medicine for the first time, found the wrong natural medicine professionals for her preference and bio-individuality at the time 19:34 – Buying-in on the alternative approach 21:30 – Corruption in science, “follow the money” 22:30 – Working with an NTP, starting with digestion, making slow progress 27:53 – New hope, new career 30:31 – Bioindividuality 31:57 – TALKING ABOUT FOOD! Simple swaps, things to buy 40:17 - Mindset 42:04 – Car analogy 43:15 – Rachel's list of reversed symptoms/conditions 44:21 – Last question As you'll hear, taking the first steps into a more natural approach to wellness can be challenging, frustrating, expensive, and a little “weird.” Rachel shares how she didn't find any luck or answers with the alternative medicine practitioners she initially saw.* Her story is fun, relatable, and inspirational for those suffering from illness, as well as those looking to peek over the fence from the world of conventional medicine. You can find Rachel's food blog at www.feastandfarm.com. Please SUBSCRIBE and visit www.nutritionaltherapy.com/podcast to record a question for the show. *Not all practitioners of each title are created equally. Remember to give multiple practitioners under one umbrella a chance. This is true for both allopathic and alternative care. :)

The spinal cord is a fragile network containing hundreds of millions of neurons, all passing through a conduit about the size of a dime. A consistent, organized approach to the diagnosis of spinal cord disease is necessary to give patients the best possible care. In this episode, Teshamae Monteith, MD, FAAN, speaks with Carlos Pardo, MD, author of the article “Clinical Approach to Myelopathy Diagnosis,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Pardo is a professor of neurology and pathology at Johns Hopkins University School of Medicine and director of the Johns Hopkins Myelitis and Myelopathy Center in Baltimore, Maryland. Additional Resources Read the article: Clinical Approach to Myelopathy Diagnosis Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud American Academy of Neurology website: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Transcript Full Transcript Available Here Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal, from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast of the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. Today, I'm interviewing Dr Carlos Pardo about his article on an Integrative Clinical Approach to Myelopathy Diagnosis, which is found in the February 2024 Continuum issue on spinal cord disorders. Dr Pardo is a professor of neurology and pathology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Welcome to the podcast. Carlos, thank you so much for this wonderful article. I think it was great! Dr Pardo: Thank you very much for the invitation and, particularly, to continue to write about myelitis and myelopathy - that is one of my passions in my activities as a clinical neurologist. And I think that this is basically one of the areas in which I thought, after finishing my residency training here, to focus, because there was absolutely no good understanding of the biology, clinical profile – particularly, understanding of the pathophysiology of myelitis and myelopathies, and what was called (at that time) transverse myelitis. So, that is what I have spent the past 25 years is try to understand that concept and apply what I was trained, as a neurologist and neuropathologist, to be translated in the clinical practice. Dr Monteith: Great. Well, I definitely want to know - how did you get into this area? Dr Pardo: That's a very nice question. Dr Monteith: I'm going to give you an easy one. Dr Pardo: I was trained as a clinical neurologist, but at the same time was trained as a clinical and experimental neuropathologist. When I finished my residency training, along with some of my co-residents and colleagues in my residency training, we took the challenge to take a neurological disorder that was called at that time transverse myelitis, to investigate diagnosis, clinical neurology of those patients, and investigate the etiological factors contributing to that. Very soon, we discovered that that group of patients that we call transverse myelitis was a very heterogeneous group of patients. And that basically put us in the situation to expand our approach to investigate what were those etiological factors contributing to those pathologies that we call, at that time, transverse myelitis. Since then, we have been focused on that. We have been focusing on characterizing patients with inflammatory myelopathies, with vascular myelopathies, with patients with infection disorders associated myelopathies. That is one of the main messages of the paper, and is - we need to think in a very etiological approach, because the variety of etiological factors that may contribute to spinal cord disorders is quite broad - it's very extensive. We need to be extremely careful when we approach those patients. There are very common myelopathies, there are very rare myelopathies. So, obviously, we always look for the commonalities and common pathologies, but we shouldn't basically forget about those myelopathies that may be rare but are present. I will say, frequently, we ignore the possibility of metabolic-associated myelopathies because we don't see those too much. But after we do an analysis of that equation - the clinical profile, temporal evolution, lesion topography, and biomarkers in imaging, blood, spinal fluid - and we don't find a clear explanation, we need to stop a little bit and think more about other things that we are missing. And frequently, metabolical disorders of the spinal cord are missed, or other type of pathology. That the reason the clinician need to have open mind and, occasionally, need to think out of the box, particularly when there is no clear answer to the search for etiological factors. Dr Monteith: I mean, when we think about spinal cord lesions, they can obviously be devastating because they affect patient's ability to ambulate. Why don't you tell us the most important takeaways from your article? Dr Pardo: Yeah, so this is a very important aspect of the article. The first thing is, if we are going to treat the patient, if we are going to focus in the management of a clinical problem, we need to understand first, what is the clinical diagnosis? What is the cause of the problem? Importantly, what is the etiology or the etiological factors contributing to that problem? The first thing that I always emphasize is, we are not able to treat a patient with a neurological condition if we don't have a very precise diagnosis, regardless what we are investigating in that patient. Specifically, for spinal cord disorders, there is a multitude of etiologies and pathogenic factors and other causes of the disease that may be involved. For that reason, the clinician, the health care provider, need to be aware about how to approach that question; is, we need to answer first the cause and the profile of the spinal cord disorder. And when we need to answer the cause, we need to focus first in evaluating clearly what has been the evolution of the symptoms, how is the neurological exam, how the evolution of the symptoms are going to help us to identify those etiological factors that we are looking for. For that reason, in the approach that I am suggesting to take in patient with the spinal cord disorder, the first critical element of that approach is to sit down and talk very well with the patient about what is going on - what are the main symptoms that are present, what has been the temporal evolution of those symptoms, and what has been basically the pattern of progression of those symptoms - because those are the clinical elements that will facilitate the clinician a much better understanding for the clinical diagnosis. Evaluating the clinical profile of symptoms and evaluating the temporal profile of symptoms is probably the first step for solving that critical equation about the diagnosis of spinal cord disorders. The main target is to establish a diagnosis. Dr Monteith: And that's really the bread and butter of neurology, because we have a global audience and we have some neurologists that practice in areas with very limited resources. But you do speak of some very cool things that I want to also touch on, such as precision medicine, the advances in biomarker development and neuroimaging, as well as investigating different viral etiologies in the pathology of spinal cord disease. So, can you just speak to some of that? You've been in this field now - you said, 25 years - how that evolution has helped you better treat patients. Dr Pardo: That's a very important question, because in 25 years we have learned tons about myelopathies, myelitis, and noninflammatory myelopathies - and it's quite amazing. I think that one of the most important aspects of spinal cord disorders is that, in the past 25 years, we have learned about mechanism of the disease in spinal cord disorders. Back in the 20th century we used the term transverse myelitis, and one of the main messages that I have for the clinicians who are reading the article is, please stop using that terminology. We have now capability to establish a more precise diagnosis, a more etiologically oriented diagnosis. If you can take a look at what happened in the past 25 years, understanding spinal cord disorders is quite amazing. We have a better understanding of the immunological factors that contribute to myelopathies. We are able to diagnose myelopathies associated with aquaporin 4 disorders, or MOG-associated disorders, or demyelinating diseases, or infectious disorders. So, in the past 25 years, with a combination of different tools in laboratory studies, studies of spinal fluid analysis, studies of the blood, we have basically able to identify biological markers that may guide us to treat more precisely those patients that are suffering from immune-related disorders. In the same way, imaging has contributed dramatically to improve our understanding of myelopathy. We are able to use neuroimaging studies to differentiate in better way, what are the myelopathies that are associated with vascular etiology, versus myelopathies that are associated with inflammatory etiology. In other words, the 25 years have provided all set of tools (assays, imaging techniques) that allow us to establish a better and precise diagnosis that facilitate etiological diagnosis. And in that way, we avoid the use of the term, transverse myelitis, that I frequently say is a basket diagnosis that is not taking us anywhere, because we are not using properly the etiological diagnostic approach. Dr Monteith: In the setting of all of this evolution, what do you still find challenging, and as well, rewarding in treating these types of patients? Dr Pardo: The best reward that we obtain when we establish this type of diagnosis is that we are able to facilitate better recovery, we are able to identify the factors associated with the problem, and eventually, to target, in a better way, those factors that are contributing to the problem and identify potential avenues for full recovery of the spinal cord. If we are dealing, for example, with patients with suspected inflammatory myelopathies, and we are able to identify an antibody that is contributing to that inflammatory myelopathy - like in the case of neuromyelitis optica - I think that the reward is that we are going to avoid a very long process that is going to decrease our ability to rescue that spinal cord and facilitate improvement of that patient. If we identify a vascular myelopathy and we are able to establish promptly a precise diagnosis of a stroke of the spinal cord, that will avoid that the patient goes in a very long road of treatments that even may be more harmful for that patient. And in that way, we are able to contribute the recovery and facilitate improvement of those patients with vascular spinal cord disorders. This is the reward: the reward is that we are able to facilitate a much better recovery of those patients and, in that way, to improve outcomes in those patients that are suffering myelopathies. Dr Monteith: What's been some of the more surprising cases in your practice, in terms of patient presentations, surprise recoveries, or whatever? Dr Pardo: One of the best rewards that we have seen in our research (clinical research) in the past several years is to be able to provide a much better framework for evaluating patients. The other aspect is to be able to identify patients that have very specific pathologies, like strokes of the spinal cord - ischemic pathology of the spinal cord that may be acute ischemic pathology or even chronic evolving pathology. In that way, actually, we have been able to establish much better protocol for assessment of those patients. That is actually one of the major aspects of our progression in terms of understanding the spinal cord disorders. And that is the reason - once again, I emphasize that when we use the term transverse myelitis and we erroneously diagnose patients with transverse myelitis when they are experiencing vascular pathologies of the spinal cord, we are basically not serving well those patients. That is one of the emphasis that I always include in the manuscript is, it is much better to spend time establishing a diagnosis (etiological diagnosis) rather than treating empirically diagnosis that probably are not going to be very well served by using treatments that probably are not going to benefit the patient. For example, when we deal with patients that have vascular myelopathies associated with chronic venous abnormalities, like happen in dural arteriovenous fistula, we are deserting those patients by treating them with IV methylprednisolone or treating them with IVIG, or treating them with immunosuppressive treatments. This is a critical element of the precision approach to establish a better diagnosis in patients with myelopathy. Dr Monteith: And then, your article spoke a little bit about recent outbreaks of infectious etiologies - viral etiologies. Can you talk a little bit about that? Because sometimes we send off these tests and they come back nonspecific or negative, and we have a sense that this was an infectious process. Maybe there was a prodromal phase, or something like that. Can you speak about your excitement in the area of advances in these methodologies? Dr Pardo: Yeah - this is an important aspect of the clinical conversation. Our patients may provide initial clues for identification of potential risk factors, such as infections, as etiological factors contributing to spinal cord disorder. When you are discussing with patients about specific symptoms that emerge after they have experienced either illnesses or systemic symptoms (like fever, chills, rash, or anything that look like an infection disorder) it's extremely important for the clinician to try to characterize that in much better way so we can use those elements of the investigation to determine if infection disorders may be involved as etiological factors in those myelopathies. We were trained to think about transverse myelitis as either an immunological-mediated disorder or an infection-mediated disorder. That's the reason I think that the clinician need to be open-minded when he's interviewing the patients to acquire, as much as possible, elements of the clinical history that may focus  or avoid that the clinician pay too much attention to things that are not involved as etiological factor. Infection disorders frequently may produce neurological problems, and, obviously, spinal cord inflammation is one of those neurological problems. However, it's very important that the clinician be critical in the assessment of those potential risk factors. I frequently discuss with the students and residents in our ward that it's okay to think about West Nile myelitis when we are in the summer, but we are not able to discuss specifically about West Nile myelitis in middle of the winter, and particularly because those are etiological factors that are associated with seasonality and those are etiological factors that are associated with some risk factors that include, for example, mosquito transmission of a virus. When we talk about acute flaccid myelitis with our pediatric patient population, we need to think about circulation of viruses, and we need to think about if that is the right period of circulation of the virus that we are suspicious that is producing that spinal cord disorder. Again, the clinician need to be aware about the particularities of some infection disorder - seasonality, modes of transmission - to think about what is going on in terms of etiological factors, particularly infections, as part of causes of spinal cord inflammation. Dr Monteith: Let's talk a little bit about some controversies - things that maybe lead to overdiagnosis or underdiagnosis. Dr Pardo: It's a very good question, and I appreciate the controversy, always. One thing that is going back to the basis of the article is the precise diagnosis is strictly dependent of equation that involves different factors. We are not able to diagnose spinal cord disorders just using one factor of that equation. This is something that is extremely important for the clinician and health care provider. We are not able to establish a precise diagnosis just when we use only neuroimaging studies. We need to bring the clinical profile of that patient, the neurological examination, the neuroimaging studies, the spinal fluid analysis to the same equation. That is one of the controversies, because in the past, we relied heavily on neuroimaging studies for establishing a diagnosis of myelopathies. But I believe that has been a little bit of a mistake because we have been ignoring major elements of the clinical history and neurological examination. And probably the best example of that is the example of spinal cord strokes. When patients show up in the emergency department with acute onset of weakness and sensory problems, and an MRI show a lesion in the spinal cord, that is not automatically a myelitis. That is an acute spinal cord disorder in which the clinician has the responsibility to establish the precise diagnosis. This is one of the major messages that I want to give to our colleagues in the clinical setting is, we need to interview the patient; we need to characterize the clinical profile and make sure that what we see in the spinal cord MRI fits the clinical profile, the neurological examination, and even the spinal fluid analysis of that patient. One of the controversies that we have frequently is to diagnose patients with spinal cord strokes, because there is no gold standard for those diagnosis, unfortunately. It's a diagnosis that is comprised by several layers of assessment. In that way, we need to reach, basically, a consensus how to deal with those patients and how to manage those patients correctly. Dr Monteith: So, of course, we have a broad, I guess, “background” of listeners - from residents, medical students, even lay audience, as well as, of course, from neurologists. But why should a resident go into spinal cord disease as a subspecialty? Dr Pardo: It's a very important aspect of the central nervous system function. I always equate the spinal cord as the major avenue for the neurological function in the human body. If there is a very good connectivity in our brain and brain hemispheres, that connectivity is not going to be effective if there is not a healthy and very good function in the spinal cord. The spinal cord is the best avenue for execution of many of the function of the central nervous system. And in that way, a clinician who is working in neurology need to be aware about the spinal cord - need to be aware about the pathophysiology of the spinal cord. Because even if there is not any element of cognitive function in the spinal cord, we have all of the major avenues that facilitate the human function in the spinal cord - motor function, autonomical function, sensory function – so, most of the central nervous system function needs to go through the spinal cord. And the clinician (neurologists and residents) need to be aware - fully aware - about how to approach disorders of the spinal cord, how to identify correctly disorders of the spinal cord, and how to evaluate and treat those disorders. Dr Monteith: Well, thank you - I really appreciate this talk. I really appreciate your article. It was very thorough, including “the bread and the butter,” the approach to a patient clinically, but also all the new innovation in your field and all of the excitement. And of course, your story, too. So, thank you so much. Dr Pardo: Thank you, Tesha, for inviting me to this interview, and I hope that at least the main message is very well taken. Remember, the main goal of my proposal in this article: number one, is to get rid of the diagnosis of transverse myelitis; number two, that the clinician and health care providers establish a better etiological diagnosis that facilitate better recovery of patients, better management, and better outcomes in patients with spinal cord disorders. Dr Monteith: Thank you, Dr Pardo for joining me on Continuum Audio. Again, today we've been interviewing Dr Carlos Pardo, whose article on an integrative clinical approach to myelopathy diagnosis appears in the most recent issue of Continuum on Spinal Cord Disorders. Thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members,go to the link the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio. 

In this episode I discuss my second round of IVIG treatment for neuropathy and my follow-up visit with my neurologist.

In this episode I discuss the aftermath of my IVIG treatment for neuropathy.

In this episode I talk about my hospital stay in early August of 2023 for IVIG treatment.

In this episode, Raymund Razonable, MD, discusses cytomegalovirus (CMV) management strategies beyond primary prophylaxis in solid organ transplantation recipients including:CMV treatment goals CMV treatment and monitoring recommendationsRole of secondary prophylaxisUse of CMV cell–mediated immunity (CMI) monitoring for CMV relapse riskUse of CMV CMI for secondary prophylaxis Proposed use of CMV CMI monitoring for secondary prophylaxisIncidence and outcomes with antiviral resistance Risk factors for CMV resistanceWhen to suspect antiviral resistance Testing for antiviral resistance using genotypic assaysOutcomes in patients with ganciclovir-resistant vs ganciclovir-susceptible virusTreatment recommendations for resistant/refractory CMVEfficacy and safety of maribavir vs investigator-assigned therapy for resistant/refractory CMV infections from the phase III SOLTICE studyTreatment algorithm for resistant/refractory CMV Adjunctive, investigational, and off-label treatment options for resistant/refractory CMV Faculty:Raymund Razonable, MDProfessor of MedicineProgram Director, Infectious Diseases FellowshipVice Chair, Division of Infectious DiseasesMayo ClinicRochester, Minnesota Content based on a CME program supported by an educational grant from Merck & Co., Inc., Rahway, NJ, USA.Follow along with a downloadable slideset at: https://bit.ly/476v2wILink to full program: https://bit.ly/47lNK2K

To know Jenny Tooley is to love her! Jenny is one of the funniest, most genuine people you will ever meet. She is full of laughter and always up for a good dress-up theme day. She is the ultimate youth worker! Jenny and John have three children: Cody, Kyle, and Lindsey. When Lindsey was in high school, she had a strange thing happen physically. She started limping and having pains that did not have an explanation. After several doctor and specialist visits, they finally realized she had CIDP, an autoimmune disease. Lindsey went through a lot of turmoil throughout the rest of her high school years often having to get IVIG blood treatments. However, they had many "God-experiences" in this journey, including a visit from possible angels! The story you'll hear in this episode reminds us that our help comes from the Lord, especially in seasons of trouble and trial. God is good, all the time. Deuteronomy 31:8 Proverbs 3:27 Exodus 14:14 Psalm 46:10 Psalm 121 Isaiah 41:10 Mercy Me- "Even If" #afrayedknotpodcast #CIPD #TribeofFriends #EvenIf

Neurology Today Editor-in-chief Joseph E. Safdieh, MD, FAAN, discusses research that assesses the safety of endovascular treatment post-stroke for people with intracranial tumors, the AANEM guideline on IVIG use for neuromuscular disorders, and the latest data on donanemab.

The healthcare system is designed to make money rather than promote health, and Emma Fox and David Contorno discuss how to be a more informed and empowered consumer of healthcare. They provide advice on how to access financial assistance programs and discuss the high salaries of hospital executives, who are not necessarily making decisions based on clinical outcomes. Emma and David share their story of how they were quoted $6,500 for a medical bill, but received a bill for $22,000, and how they were able to get the bill adjusted to $6,900 by exercising a legal term called accord and satisfaction. They also discuss the importance of understanding the financial assistance programs available, even for those who make into the six figures as a household, and how the top executives of Novant were paid $458.7 million from 2010 to 2021.Episode Outline:(00:04:10) IV Infusion Treatment(00:00:00) IVIG Infusion Cost(00:12:53) Financial Assistance Programs(00:08:28) Financial Assistance Programs(00:17:10) Health Care SystemQuotes:(00:17:33) I can't wait to get into more of these. I feel like we could chat forever, but let's give someone a little break from the mind blown that is finding this stuff out because it's heavy and I hope people get as angry as we got, which kind of led us to this path.(00:03:00) Where else in the world does both the customer and the provider of services not know the cost or the price until after services are rendered, except in the US. Healthcare system?(00:07:23) Why do we not start with that? But we took the oral steroids and they actually had a longer lasting and more positive effect.(00:11:33) I almost think the first thing is the clinical. I don't think anyone should be afraid anymore to ask questions and I didn't ask enough questions. What other treatment options are available? Why did you choose this one? Maybe get a second opinion even.(00:15:49) There's absolutely no reason to feel bad. The whole reason that they get the tax breaks that they get for being nonprofit is because they're required to give away what's called charitable care. They're required to do it.Blog Post:It's no secret that the healthcare system is designed to make money rather than promote health. Emma Fox and David Contorno recently discussed how to be a more informed and empowered consumer of healthcare. They shared their story of how they were quoted $6,500 for a medical bill, but received a bill for $22,000. Through exercising a legal term called accord and satisfaction, they were able to get the bill adjusted to $6,900. Emma and David's story is a powerful reminder of the importance of understanding the financial assistance programs available for medical care. Even those who make into the six figures as a household can benefit from these programs. It is also important to remember that the top executives of Novant were paid $458.7 million from 2010 to 2021. Most of these executives have business degrees and make decisions based on financial outcomes, not necessarily clinical outcomes.It is also important to note that drug companies make less money when people are healthy, and insurance companies make more money when people are healthy. This means that there are little things done to ensure people don't get healthy. Emma and David got angry and this led them to this path of exploring how to be an informed and empowered consumer of healthcare. To be a more informed and empowered consumer of healthcare, there are a few tips and tricks to keep in mind. Firstly, healthcare estimates are now legally required to be a good faith estimate and cannot vary by more than $400 from what was quoted pre-service. Patients should not be afraid to ask questions and seek a second opinion when receiving medical treatment.Nonprofit hospitals are required to offer financial assistance programs based on income alone, which can reduce or eliminate a patient's bill. Patients can present themselves as cash pay to get more effective assistance. Financial assistance counselors are often bonded money by the hospital if they get a patient to agree to any payment plan. The true 501 R required financial assistance policy is often hidden on the hospital's website.Finally, people should not feel bad about using hacks and tricks to get financial assistance. Tax breaks are given to nonprofit hospitals, and the taxes they don't pay are made up for by the local community. Nonprofit hospitals are also required to give away what's called charitable care. It's important to be an informed and empowered consumer of healthcare. With the right knowledge and understanding of the system, you can save yourself a lot of money and heartache.Episode LinksConnect with Emma FoxWebsiteEmma's WebsiteConnect with David ContornoLinkedInWebsiteOther MaterialsThese materials help you promote your podcast. Quotes can be used for audio & video grams or quote cards. Blog and social posts will help your website and social media presence.

Dr. Wallskog obtained his medical degree at the University of Wisconsin and completed his orthopedic surgery residency at the Medical College of Wisconsin. He completed fellowship training specializing in joint replacement at Case Western Reserve University in Cleveland, Ohio, then entered private practice in 2002.After being exposed to COVID-19 in August/September of 2020, Dr. Wallskog followed CDC recommendations to wait three months before getting his first COVID vaccine. He subsequently developed numbness, weakness, and balance difficulties and, in the following months, experienced periods of severe lower thoracic back pain. He was subsequently diagnosed with transverse myelitis with a demyelinated lesion at the T8-T9 level. Although he has been treated with high-dose steroids and IVIG and has participated in physical therapy, his symptoms are essentially unchanged since his diagnosis in January 2021. His acquired disability has affected his career and he can no longer physically practice medicine as an orthopedic surgeon. Refusing to allow this to stop him, Dr. Wallskog has made his mission to change his negative reaction into  POSITIVE ACTION. He helped found REACT19, a non-profit that offers financial, physical, and emotional support to tens of thousands of people injured by the COVID shots in the United States.Join the Ken & Eric of the GCP as Dr. Wallskog tells his story of injury and efforts to protect childrenand adults from further injury at the FLCCC educational conference 2023.REACT19 https://react19.org/FLCCC 2023 Educational Series & Lectureshttps://covid19criticalcare.com/courses/conference-2023-spring-basic/Please LIKE & SHARE and use code “HERO” for a free month of GCP RAW!If you ever want to ask a question for upcoming guests, just click here and give GCP RAW a try on us:https://gutcheckproject.locals.com/support/promo/HERO

Ashley mapped out each step in her infertility journey based on what would get her nearest the finish line. Yet she still found herself detoured into brutal choices along the way. This is her story. ANNOUNCEMENTS: The Hope Narrative Infertility & Loss Conference in Atlanta, Georgia is September 22–23, 2023. Register now at hopenarrative.org! Sarah's Laughter is turning 20 in 2024. We're celebrating with a Caribbean Cruise! Dates are April 25–29, 2024. Details & signup at sarahs-laughter.com/cruise24. Want Beth to speak at your event? Contact us here. For more about Sarah's Laughter, please visit our website at sarahs-laughter.com. You can follow us on social media linked here: Sarah's Laughter on Facebook & Instagram, and @sarahs_laughter on Twitter. Sarah's Laughter is a 501(c)(3) non-profit public charity. If you'd like to help support what we do, including this podcast, please visit sarahs-laughter.com/give. Thank you. Want to share your infertility story on this podcast? Email us at podcast@sarahs-laughter.com

4.02 Medium Vessel Vasculitis Rheumatology review for the USMLE Step 1 exam. Vasculitis: inflammation of blood vessels, classified by the size of the blood vessels affected Medium vessel vasculitis affects the main visceral arteries and veins, and their initial branches Three types of medium vessel vasculitis are discussed: polyarteritis nodosa, Kawasaki disease (mucocutaneous lymph node syndrome), and Buerger disease (thromboangiitis obliterans) Polyarteritis nodosa affects middle-aged to older men and is idiopathic, but can be secondary to other diseases, including hepatitis B Histology findings show transmural inflammation with fibrinoid necrosis in early lesions, and string-of-beads sign in angiogram Symptoms include constitutional symptoms, abdominal pain and melena, and hypertension caused by damage to the renal arteries Kawasaki disease most commonly affects young Asian children, and is triggered by upper airway infections Symptoms include conjunctival injection, desquamating rash, cervical lymphadenopathy, strawberry tongue, and prolonged fever Kawasaki disease has a predilection for the coronary vessels, which can lead to aneurysm rupture and thrombi development Treatment for Kawasaki disease includes IVIG and aspirin to prevent complications

In this special episode, Liza shares details of her daughter's story and how she healed herdaughter (Ava) from Lyme, Tick-Borne Diseases and PANS (Pediatric Acute-onsetNeuropsychiatric Syndrome) over the course of three years. Through this unique interview, Lizachronicles the many different phases of the journey, which first started with psychiatricpresentations including anxiety, OCD and an eating disorder. Together, mother and daughterdiscuss the many different treatments Ava used to battle her every-changing conditionsincluding chronic fatigue, psychosis, joint pain, and even seizure-like episodes. Some of thetreatments they shed light on include partial hospitalization programs, family therapy,antibiotics, whole body hyperthermia, IVIG and herbalprotocols.Listen to this story from the lens of the child too, as Ava shares the emotional strain of specificprograms and the healing tools that worked best for her–the patient. Together, they share thegood, the bad and the ugly.Ultimately,they share their Gratitude and their family's very happy story.Vital Plan Herbs :In this episode, we testify to our personal benefits of being on Vital Plan Herbs. If you would like to try Vital Plan please use our discount code for 15% savings. Our code is VERYHAPPY15. Click here to access the Vital Plan Shop by Dr. Bill Rawls. The products we are currently on include Immune Boost Bundle Herbs and Mitochondrial Support.Connect with Liza Online :Liza's Personal and Group Coaching https://www.veryhappystories.com/workLiza on Instagram https://www.instagram.com/lizasveryhappystories/Liza on Facebook https://www.facebook.com/veryhappystorieswithLizaBlas/Subscribe to Liza's Newsletter www.veryhappystories.comGrateful for our sponsor : Green Valley NutritionHave you heard of all natural CBD products by Green Valley Nutrition? This company was founded by an entrepreneur who overcame PANDAS. Get 20% off. Click the link below and use the code VERYHAPPY.https://greenvalleynutrition.com/Very Happy Stories is Partners with the LymeLight FoundationThe LymeLight Foundation is a charitable partner in the Lyme community that provides grants to enable eligible children and young adults with Lyme disease to receive proper treatment and medication as well as raising awareness about Lyme disease. LymeLight has awarded grants totaling over $7.7M to more than 1,000 individuals in 49 states. To donate directly toward LymeLight grants which help those struggling to receive treatment > click here to DONATE. To learn more about treatment grants > click here for GRANTSSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Jonathan shares his experience as a nurse who has been doing home infusions for patients needing IVIG. He talks about the highs and lows of his job with humor. You can read the transcript for this episode here: https://tinyurl.com/potscast126 Please click the "subscribe" button so that you don't miss an episode of The POTScast. Subscribing also helps us reach other people just like you! If you liked this episode, we hope you will help to support our production costs by donating to Standing Up to POTS at https://www.standinguptopots.org/donate Tell us what you think of The POTScast or send us your idea at info@standinguptopots.org! Find out more about Standing Up to POTS! Check us out on our Website: www.standinguptopots.org Facebook: https://www.facebook.com/standinguptopots/ Instagram: https://www.instagram.com/standinguptopots/ Twitter: https://twitter.com/POTSActivist Pintrest: https://www.pinterest.com/TheStandingUpToPOTS/ Medical Disclaimer: The information provided here is not intended to serve as professional medical advice, diagnosis, or treatment. If you have health related issues, please contact a qualified health professional to get the personalized assessment, advice, and treatment that you need. Standing Up to POTS will not be liable for any direct, indirect, or other damages arising from the use of this podcast.