Podcasts about nmda

Aujourd'hui, je vous emmène dans un voyage fascinant à l'intérieur du cerveau...Un moment mystérieux que beaucoup ont vécu, mais que peu comprennent vraiment : l'anesthésie générale.Remontons un instant dans le passé.Le 16 octobre 1846, à Boston, au Massachusetts General Hospital, un dentiste du nom de William Morton réalise la première démonstration publique réussie d'une anesthésie générale à l'éther.Ce jour-là, un patient subit l'ablation d'une tumeur au cou... sans douleur, ni cri.Une révolution est née.Avant cela, la chirurgie relevait de l'épreuve de force : on opérait à vif, rapidement, et dans la souffrance.Depuis cette date, l'anesthésie générale a sauvé des millions de vies en rendant possibles des interventions longues, complexes… et indolores.Lorsque vous êtes allongé sur la table, une équipe vous entoure. Une seringue est connectée à votre bras, une substance s'écoule. Et, très vite... plus rien.Pas de rêve, pas de sensation, pas de douleur. Comme si l'on avait appuyé sur un bouton "off".Mais ce n'est pas un simple sommeil.Des études en imagerie cérébrale montrent que l'anesthésie ne mime pas le sommeil, mais provoque une déconnexion brutale entre les différentes zones du cerveau, notamment entre le thalamus – une sorte de centre de tri sensoriel – et le cortex, responsable de la conscience.Les signaux sensoriels n'arrivent plus à destination. Résultat : le cerveau ne perçoit plus le monde extérieur.Ce phénomène est orchestré par des molécules puissantes : propofol, kétamine, halogénés comme le sévoflurane… Ces agents anesthésiques modifient en profondeur la chimie cérébrale.Leur cible principale ? Les neurotransmetteurs, ces messagers chimiques entre les neurones.Parmi eux, le plus important ici s'appelle GABA, le grand régulateur de l'activité neuronale.Les molécules anesthésiques agissent comme des "amplificateurs" de ce neurotransmetteur.En se liant à ses récepteurs, elles renforcent son effet inhibiteur, ralentissant ou stoppant carrément la transmission des signaux nerveux.Résultat ?Le cerveau devient moins excitable, les réseaux de neurones cessent de communiquer efficacement entre eux, et l'activité cérébrale s'effondre progressivement, un peu comme si on plongeait un ordinateur en mode veille.Mais ce n'est pas tout.D'autres molécules anesthésiques comme la kétamine bloquent un autre récepteur fondamental : le NMDA, impliqué dans la transmission de la douleur et de la conscience.D'autres encore agissent sur des canaux ioniques, modifiant la façon dont les neurones échangent les signaux électriques.En clair : c'est tout un orchestre neurochimique qui est désorganisé volontairement, pour plonger le cerveau dans un état de silence contrôlé.Et pourtant, le cerveau n'est pas mort. Il continue de réguler la respiration, le rythme cardiaque, la température... comme s'il restait en mode automatique.Puis vient le réveil. Là encore, c'est mystérieux : certains patients mettent quelques secondes, d'autres plusieurs minutes.Le cerveau se reconnecte progressivement. Il n'est pas rare de se sentir confus, désorienté, voire agité dans les premières minutes.Et dans de très rares cas – un pour 15 000 environ – une conscience résiduelle peut persister pendant l'opération : on parle alors de conscience peropératoire.Le patient est paralysé, incapable de parler, mais entend ou ressent partiellement. Cela reste rare, mais suffisamment sérieux pour que les anesthésistes utilisent aujourd'hui des moniteurs de profondeur d'anesthésie. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

In this episode, we dive deep into the basics of anesthesia pharmacology—perfect for ICU nurses starting CRNA school or senior residents needing a solid refresher. We break down foundational topics like pharmacodynamics, pharmacokinetics, and pharmacogenomics, and explain why understanding physiology is key to mastering pharmacology. You'll learn about drug targets like GABA and NMDA receptors, and the real mechanisms behind anesthetics, opioids, local anesthetics, and muscle relaxants. We also walk through “top drawer drugs” in the OR, including quick quizzes to reinforce your understanding of real-time drug decisions—like when to choose ephedrine over phenylephrine. This is a science-heavy episode, but one that sets the groundwork for more advanced content.

Nerinetide is a neuroprotective eicosapeptide designed to reduce ischemic brain injury by disrupting the interaction between N-methyl-D-aspartate (NMDA) receptors and downstream excitotoxic signaling. It was tested in two major clinical trials for acute ischemic stroke: • ESCAPE-NEXT Trial: Assessed Nerinetide in patients undergoing endovascular thrombectomy (EVT) without prior thrombolysis, finding no significant improvement in functional independence at 90 days. • FRONTIER Trial: Evaluated prehospital Nerinetide administration within 3 hours of stroke onset, showing no overall benefit but potential efficacy in ischemic stroke patients receiving reperfusion therapy.   Although Nerinetide was safe, its clinical benefit remains uncertain, with timing and patient selection emerging as key factors for its potential role in stroke treatment. Further studies are needed to refine its use in combination with reperfusion therapies.

کیس تغییر سطح هوشیاری: آنسفالیت خودایمنی ضد گیرنده‌های NMDA Anti NMDA receptor encephalitis

In this episode of the Addict to Athlete podcast, Coach Blu Robinson welcomes Dr. Faried Banimahd to discuss the complexities of ketamine therapy in the context of mental health and addiction recovery. They explore the history of ketamine, its medical uses, particularly in pain management and mental health treatment, and the implications of its recent popularity as a therapeutic option. Dr. B provides insights into the mechanisms of ketamine, its FDA approval for treatment-resistant depression, and the importance of caution in its use, especially for individuals with a history of substance abuse. The conversation emphasizes the need for a comprehensive approach to mental health treatment, integrating therapy with any pharmacological interventions. In this conversation, Blu Robinson and Dr. Faried Banimahd delve into the complexities of psychedelics, particularly ketamine, and their potential therapeutic benefits for mental health. They discuss the risks associated with psychedelics, personal experiences, and the importance of controlled environments for treatment. The conversation also highlights the stigma surrounding these substances, the necessity of ongoing treatment, and the role of medical professionals in guiding patients through their mental health journeys. Ultimately, they emphasize the need for a multidimensional approach to treatment and the importance of understanding individual experiences within the broader healthcare system. Takeaways Ketamine is chemically related to PCP and has a history of abuse. It is used as a disassociative anesthetic in medical settings. Ketamine's role in pain management is significant, especially for chronic pain patients. The FDA has approved ketamine for treatment-resistant depression under specific protocols. Ketamine works by blocking NMDA receptors, affecting pain perception and mood. Long-term efficacy of ketamine therapy is still under research and not well established. Caution is advised for individuals with a history of substance abuse when considering ketamine therapy. Matthew Perry's case highlights the risks associated with unsupervised ketamine use. Therapy should be the first line of treatment for depression, even when using ketamine. Meaningful existence and self-development take time and should not be rushed. People with a history of severe bipolar and schizophrenia should be cautious with psychedelics. Psychedelics can awaken dormant psychological issues. Personal experiences with psychedelics can lead to significant insights and awareness. The perception of psychedelics as dangerous hinders their therapeutic potential. Therapeutic environments are crucial for the safe use of psychedelics.   Dr. B YouTube · Dr.B36087.1K+ followersDr.B360 insta Instagram · getdrb2.4K+ followersAddiction Medicine (@getdrb) • Instagram photos and videos     Please join Addict to Athlete's Patreon support page and help us turn the mess of addiction into the message of sobriety! https://www.patreon.com/addicttoathlete Please visit our website for more information on Team Addict to Athlete and Addiction Recovery Podcasts. https://www.AddictToAthlete.org Join the Team! Circle, our new social support event, along with the team and athlete communication platform, is designed to help us break free from doom scrolling and shadow banning and foster stronger connections among us. Follow the link, download the app, and start this new chapter of Team AIIA! Join Circle https://a2a.circle.so/join?invitation_token=16daaa0d9ecd7421d384dd05a461464ce149cc9e-63d4aa30-1a67-4120-ae12-124791dfb519

OCD, or Obsessive Compulsive Disorder, is a debilitating condition that involves intrusive thoughts and time-consuming, repetitive behaviors. It impacts 80 million worldwide, 2-4% of the US population or 1 in 100 people here in the US.It can be difficult to overstate the suffering caused by OCD, not only for those with this condition but also for their family members. In addition to the distress caused by the obsessional thoughts and compulsions, there can be shame and loss - loss of more meaningful, purposeful, or pleasant thoughts and behaviors. and loss of time connecting with others or engaging in purposeful or enjoyable activities.Other conditions associated with obsessive-compulsive disorder include:* Body dysmorphic disorder* Skin picking* Trichotillomania (hair pulling)* Hoarding* Hypochondria* Olfactory reference syndrome (an irrational feeling or belief that one emits a foul smell and often attempts to remove the odor).It´s not unusual for someone with OCD to have other conditions, such as:* Other forms of anxiety* Depression* ADHD* Autism spectrum disorder* Eating disorders* TourettesResearch suggests that having OCD raises one´s vulnerability to developing dementia. Many other brain conditions, however, also appear to increase this vulnerability similarly.Treatment ChallengesOCD is particularly challenging to treat. Of those with OCD, 60% do not respond to typical therapies (often medication in combination with psychotherapy involving gradual exposure to that which is being avoided). Typical medications include:* SSRI´s (Selective Serotonin Reuptake Inhibitors) -e.g., sertraline, fluoxetine, fluvoxamine, citalopram, paroxetine* Tricyclic antidepressant - clomipramine* SNRI - (Serotonin and Norepinephrine Reuptake Inhibitor) - venlafaxine* Atypical antipsychotic medications are sometimes addedMedication is combined with CBT (Cognitive Behavioral Therapy), which involves exposure and response prevention, or CBT is used alone.As you can see, most medication approaches aim to increase serotonin activity. Serotonin, however, is just one of the neurotransmitters involved. What has become increasingly clear from the research is that OCD involves abnormal activity at the NMDA receptor - a glutamate receptor.NMDA & GlutamateThe NMDA receptor is found throughout the brain. Glutamate, the primary excitatory neurotransmitter in the central nervous system, binds to the NMDA receptor. NMDA and glutamate are involved in synaptic plasticity (creating neuronal connections), learning, memory, and motor function.The synapse is the space between communicating neurons. Presynaptic neurons release glutamate, which binds to the NMDA receptor on postsynaptic neurons. This results in a cascade of signaling events that lead to “neuronal excitation.” The problem arises when this receptor has too much (or too little) activity. In the case of OCD, there is too much activity.Implications* Dysregulation at the NMDA receptor appears to play a role in OCD, depression, PTSD, schizophrenia, bipolar disorder, and substance use disorders.* Weak memory extinction can result from high activity at the NMDA receptor. While memory is a good thing, we can have problems with too much memory - or rather, problems putting our memories aside. This can look like thoughts getting stuck, for example:* Intrusive thoughts in OCD* Flashbacks in PTSD* Delusions in psychotic disorders* Cravings in addiction.* Neurodegenerative disorders, such as Alzheimer's, Parkinson's, and ALS, have also been linked to NMDA receptor malfunction.Methylation & NMDAThose who are undermethylated, especially those with OCD or addictions, have high activity at the NMDA receptor. To remind you, undermethylation is a biochemical process with many functions, including the breakdown of histamine, support of detoxification, and support of serotonin activity. When someone is undermethylated, they can tend to have allergies (from high histamine), be perfectionistic, competitive, strong-willed, have obsessive-compulsive tendencies, be ritualistic, have dietary inflexibility, and have high accomplishment or have family members with high accomplishment. Undermethylation can contribute to the low serotonin activity seen in OCD. Simply addressing undermethylation, like merely addressing serotonin, will only bring partial benefit. To address undermethylation, those of us trained by the Walsh Research Institute, use SAMe and/or methionine, B12, B6, magnesium, and antioxidants. We address this before starting methylation treatment for those with high homocysteine. But how can we also decrease activity at the NMDA receptor?Blocking NMDA & Normalizing Glutamate ActivityEsketamine or Ketamine, which has been getting much attention in recent years, can impact the brain in various ways; however, its primary mechanism is as an NMDA blocker or antagonist. For some, it can serve as a rapid-acting and highly effective antidepressant. It can also decrease OCD symptoms. Other NMDA-blocking drugs include memantine and dextromethorphan (combined with bupropion). Lamotrigine can decrease glutamate release and has been used as an adjunct medication for OCD.Nutrients, however, play an important role in the NMDA receptor. NAC or N-acetyl cysteine is a precursor to glutathione and, thus, an antioxidant. It is also anti-inflammatory and a binder for a particular toxin made by candida and mold. But, it is also a potent NMDA antagonist (decreases activity at NMDA) and has been shown to reduce obsessions and compulsions of OCD. It has also been studied in alcoholism, opiate addiction, cocaine abuse, gambling disorder, shopping disorder, cigarette addiction, and trichotillomania. It has been used by itself and as an adjunct to medication therapy. NAC has become part of the Walsh undermethylation nutrient protocols for those with OCD and/or addiction.Zinc also plays an important role in regulating functioning at the NMDA receptor. The Walsh Research Institute found that 90% of those with brain symptoms had relatively low zinc. Dosing of zinc is determined after testing plasma zinc levels using a narrow range (the Walsh/Pheiffer range differs from typical lab ranges). Zinc is checked in conjunction with copper. Zinc has been found to improve treatment response in those with OCD treated with SSRIs. Zinc can be depleted because of very high oxidative stress and/or high pyrroles, which also cause low B6. Because B6 is needed to make serotonin, pyrroles are also important to address if elevated.Inositol is a nutrient involved in the serotonin and glutamate signaling systems. It, too, is beneficial for OCD symptoms; however, it can require very high doses.The challenge of research, as you can see, is that these approaches are all looked at in isolation, as opposed to, for example, addressing undermethylation, optimizing zinc, decreasing activity at the NMDA and addressing sources of oxidative stress.Candida & MoldAside from undermethylation, low serotonin activity, and high activity at the NMDA receptor, those with OCD appear to have high oxidative stress, as is the case with most brain-related conditions. One of the more common sources of oxidative stress I see in my practice is candida overgrowth in the GI tract, which often follows antibiotic exposure and /or mold toxicity due to water damage causing seen or unseen toxic mold. Because mold and candida (yeast) thrive on sugar and a high-carb diet, symptoms can fluctuate with sugar or carb intake. How might candida and mold intersect with the NMDA receptor? Mold and yeast can contribute to high histamine states. Histamine can increase activity at the NMDA receptor. EstrogenFor women and teen girls that I see with OCD, there is often a fluctuation in their OCD symptoms with their cycle. Typically, their symptoms worsen during the times of the month when estrogen is the highest. This may be because estrogen can increase activity at the NMDA receptor.PANDAS & PANSWhen a child has an abrupt onset of OCD symptoms, PANDAS and PANS should be considered.* PANDAS = Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections* PANS = Pediatric Acute-Onset Neuropsychiatric SyndromePANDAS and PANS are autoimmune conditions, meaning the immune system is acting on the body, in this case, a part of the brain called the basal ganglia, that involves an acute onset of OCD symptoms. Other symptoms can include restricted eating, mood symptoms, regression in academic or social skills, and motor tics. While triggers are often viral, bacterial (strep in the case of PANDAS), candida,or other microbial source, what is underlying the dysregulated immune response to such microbes, in my experience, is mold toxicity. SummaryBecause OCD can be difficult to treat, my hope in sharing this information is to raise awareness that effective OCD treatments can require a multifaceted approach that includes:* addressing methylation (and high pyrroles if present) to improve serotonin activity* decreasing activity at the NMDA receptor* by optimizing zinc* using supplements or medication* addressing sources of inflammation and high histamine* address sources of oxidative stress - trauma, stress, toxins, inflammation If you find this information helpful and would like to help me get this out into the world, please consider sharing:As always, I welcome your comments, questions, and experience.Until next time,CourtneyP.S. To learn more about non-patient consultations, treatment, and monthly mentorship groups, please visit my website at:CourtneySnyderMD.comMedical Disclaimer:This newsletter and podcast episode is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for yourself or others, including but not limited to patients you are treating (if you are a practitioner). Consult your physician for any medical issues that you may be having. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com/subscribe

Welcome to the SHE MD podcast! Today hosts Dr. Thais Aliabadi and Mary Alice Haney dive into a groundbreaking topic with Dr. Peyman Tashkandi and Anabel González: the transformative potential of ketamine therapy for mental health. From treatment-resistant depression and severe anxiety to postpartum depression, this episode explores how ketamine is reshaping the landscape of mental health treatment.Dr. Tashkandi breaks down the science behind ketamine's unique mechanism, which boosts neuroplasticity, reduces inflammation, and balances neurotransmitters to offer life-changing relief for those who haven't found success with traditional treatments. Anabel shares her deeply personal story of overcoming postpartum depression and lifelong mental health struggles through a structured ketamine infusion program paired with therapy.You'll also hear about the importance of integration therapy, how to identify who is—and isn't—a good candidate for ketamine, and the need to advocate for innovative mental health solutions. Whether you're a medical professional, a patient seeking new options, or simply curious about cutting-edge treatments, this episode is packed with insights to transform how we approach mental health. Let's get started!Access more information about the podcast and additional expert health tips by visiting our website at shemdpodcast.com and Ovii.com/shemd. Sponsors: Cymbiotika: Go to Cymbiotikia.com/SHEMD for 20% off your order + free shipping today.Lume: Control Body Order ANYWHERE with @lumedeodorant and get 15% off with promo code SHEMD at Lumepodcast.com/SHEMD! #lumepodDR. PEYMAN TASHKANDI & ANABEL GONZALEZ TAKEAWAYS:Explore Ketamine as a Transformative Option: Ketamine therapy offers rapid relief for individuals suffering from treatment-resistant depression, severe anxiety, and postpartum depression. Its unique mechanism of action—boosting neuroplasticity, reducing inflammation, and balancing neurotransmitters like glutamate—makes it life-changing for patients where traditional medications have failed.Understand the Science Behind Ketamine's Impact: Ketamine works differently from standard antidepressants by targeting NMDA receptors, increasing glutamate activity and enhancing neuroplasticity. This helps patients break free from patterns of chronic depression or anxiety, offering not just temporary relief but lasting mental health improvements with proper infusion protocols.Recognize the Spectrum of Mental Health Needs: Ketamine therapy is not a one-size-fits-all solution. It is most effective for those with clinical depression, severe anxiety, or debilitating conditions like postpartum depression. Understanding the distinction between everyday stress and clinical symptoms is essential for determining who can benefit from this cutting-edge treatment.Pair treatment with integration therapy for maximum impact: Therapy within 72 hours of ketamine infusions enhances the benefits by helping process and integrate experiences. While infusions alone can be effective, combining them with tools like EMDR can lead to profound and lasting emotional breakthroughs. Advocate for awareness and education: Despite its potential, ketamine therapy remains underutilized due to slow guideline changes and resistance from some mental health professionals. Push for greater understanding and open discussions with providers about innovative treatments, especially when conventional methods aren't meeting your needs.THIS EPISODE: [4:27] Ketamine for depression and how it works scientifically[13:53] Clinical depression and anxiety and Anabel shares her story of depression and her first ketamine infusion[22:31] Therapy, the infusion experience and who is not a good candidate[31:24] Long-term effects of ketamine treatments and finding the right clinic[38:45] Treating a child or adolescent with ketamine and the difference between women's and men's symptomsRESOURCES:Dr. Tashkandi's InstagramKetamine Clinics of Los Angeles WebsiteDr. Tashkandi's Private Psychiatry Practice WebsiteAnabel's Company, Good BacteriaGood Bacteria's Instagram GUEST BIOGRAPHY:Dr Peyman TashkandiDr. Tashkandi is a Double Board Certified Psychiatrist in Child and Adolescent and General Adult psychiatry. He is a former Associate professor of psychiatry at University of Southern California School of Medicine and is currently in Private practice in Beverly Hills, California. For the past two years he was the Director of psychiatry at Ketamine Clinics Los Angeles. Dr. Tashkandi has spent his career exploring the inner workings of the mind and is especially interested in the relationship between psychiatry, medicine, and the human experience.Anabel GonzálezAnabel's postpartum journey led her to seek transformative healing through ketamine therapy and a focus on gut health. The profound impact of these approaches not only helped her recover from severe postpartum challenges but also ended a lifelong battle with depression. This personal transformation inspired her to start developing Good Bacteria, now in its pre-launch phase, dedicated to creating science-backed solutions that bridge the gap between real food and microbiome support. As a mom on a mission, Anabel is committed to helping other women heal and thrive, sharing her story to remind us all that our bodies, minds, and spirits are powerful and capable of profound recovery.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Anti-amyloid therapies provide the first FDA-approved option to alter AD pathology, but an understanding of overall utility and value to patients remains in its infancy. In this episode, Teshamae Monteith, MD, FAAN, speaks with David S. Geldmacher, MD, FACP, FANA, author of the article “Treatment of Alzheimer Disease” in the Continuum® December 2024 Dementia 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. Geldmacher is a professor and Warren Family Endowed Chair in Neurology and the director of the Division of Cognitive and Behavioral Neurology, Department of Neurology, Marnix E. Heersink School of Medicine at the University of Alabama at Birmingham in Birmingham, Alabama. Additional Resources Read the article: Treatment of Alzheimer Disease 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 Transcript Full interview 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. Today, I'm interviewing Dr David Geldmacher about his article on treatment of Alzheimer's disease, which appears in the December 2024 Continuum issue on dementia. Welcome to our podcast, Dr Geldmacher. How are you?  Dr Geldmacher: I'm very well, thank you. It's a pleasure to be here.  Dr Monteith: Yeah. So, why don't you introduce yourself to our audience? Dr Geldmacher: Sure. I'm David Geldmacher. I'm a professor of neurology at the University of Alabama in Birmingham and I lead the division of Cognitive and Behavioral Neurology.  Dr Monteith: So, I'm really excited about this, to personally learn, and I know that or neurology community is also really excited about this interview. So, why don't we start off with your main objective.  Dr Geldmacher: So, my main goal in the article was to review the FDA-approved pharmacologic treatments for dementia. There's lots of ways of thinking about treatment of dementia; psychosocial, caregiver support, and so forth. But I really wanted to focus on the issues of drug treatment because that's what has been our backbone for a long time and now has recently expanded.  Dr Monteith: Why don't we talk a little bit about, first of all, the boom in the field? What's that been like?  Dr Geldmacher: So, the big change in the field is over the last several years, we've had treatments become available that actually attack the underlying Alzheimer pathology, and that's new and different. For decades, we've been able to treat the symptoms of the disease, but this is the first time we've really been able to get to the root of the pathology and look toward removing amyloid plaques from the brain.  Dr Monteith: Let's step back a little bit and talk about the framework of diagnosis and how that leads into the therapeutic potential. I know you're going to dive into some of the biologics, but we should probably talk about the kind of holistic approach to considering the diagnosis. Dr Geldmacher: Sure. So, you know, when someone comes to the clinic with memory complaints, our question we have to ask is, is this neurologic origin, a structural origin like Alzheimer's disease or vascular dementia? Are there complicating factors, the software issues of mood disorders and sleep disorders and pain that can all magnify those symptoms? The clinical reasoning is a critical part of that, but in Alzheimer's disease, typically the problems revolve around difficulty forming new memories of events and activities, the episodic memory. And then it's often accompanied by changes in word finding and semantic knowledge. And those are the things that we look for in the clinic to really point toward an AD diagnosis. And then we support it with exclusion of other causes through blood work and identification of patterns of brain atrophy on MRI. And then most recently in the last couple of years, we've been able to add to that molecular imaging for amyloid with PET scans as well as, most recently, blood-based biomarkers for Alzheimer's pathology. So, it's really been a revolution in the diagnosis over these last several years.  Dr Monteith: And when approaching patients or populations of individuals, there seems to be a real full spectrum with looking at the societal burden, the biological impact, of course, risk factors of primary prevention, and now this whole area of brain health and secondary prevention. How do you kind of tie all of this together when talking to patients and family members?  Dr Geldmacher: Sure. So, the approaches for brain health apply to everyone. In basically every clinic visited, our brain aging and memory clinic, we reviewed lifestyle approaches to brain health like regular physical exercise, healthy diet, cognitive and social stimulation. And those are fundamental to the approach to everyone, whether they have cognitive impairments that are measurable or not. These are all things that are good for our brain health. And then, you know, focusing on the vascular risk factors in particular and working with the patient and their primary care team to ensure that lipids and blood sugar and blood pressure are all in good healthy ranges and being appropriately treated.  Dr Monteith: You know, there's this kind of whole considerations of clinically meaningful endpoints and clinical trials, and even when we're talking to our patients. What would you say the field has kind of identified has the best endpoints in helping patients? Would you call it impaired daily function? Is that like the best hard endpoint? Obviously, there are other things such as caregiver burden, but you know, how do you approach assessing patients? Dr Geldmacher: Defining the endpoints is very difficult. Typically, if we talk to patients and their families, they would like to have better memory or improve memory. How that applies in everyday life actually is daily function. And so, we focus very much on daily function. And when I talk about our therapies, whether they're symptomatic therapies or the new disease-modifying therapies, I really talk about maintenance of function and delays and decline or slowing of decline, helping to foster the person's independence in the activities that they have and be able to sustain that over the longer term.  Dr Monteith: And when thinking about diagnosis- and we're going to get into treatments, but when thinking about the diagnosis, and of course, it's full-spectrum from mild cognitive impairment to moderate and severe forms of dementia, but who should have CSF testing and PET imaging? Obviously, these are invasive, somewhat invasive and expensive tests. Should all people that walk in the door that have memory complaints? How do you stratify who should have tests? Dr Geldmacher: I think about this in a big funnel, basically, and the starting point of the funnel, of course, is the person with memory complaints. Then there's that neurologic reasoning. Are these memory complaints consistent with what we expect from the anatomy of Alzheimer's disease, with atrophy in in the hippocampus and temporal lobe? Do they have episodic memory loss or not? That first step is really trying to characterize, do the clinical patterns act like those of Alzheimer's disease or not? And then we follow the Academy of Neurology guidelines, looking for reversible sources of cognitive decline, things like B12 deficiency and depression, sleep disorders and the like, and try to exclude those. We start with structural imaging with everyone, and MRI, typically, that will help us understand vascular burden and patterns of atrophy, looking for things like mesial temporal atrophy or precuneus atrophy that are characteristic of Alzheimer's disease. If those things are all pointing in the direction of AD as opposed to something else, then typically before moving on to CSF or PET scan, we will use blood-based biomarkers, which are one of the big changes in the field in the last year or so, and there are now multiple panels of these available. The downside is they are typically not covered by insurance. On the other hand, they can really help us identify who is likely to have a positive PET scan or positive findings on CSF. We start to provide that counseling and information to the patient before they get to those more definitive tests. We can push people in the other direction. We can say, your blood-based biomarkers are negative or do not indicate AD as the most likely source of your condition now, so let's treat other things. Let's see what else we can focus on. The blood-based biomarkers are now, in our clinic at least, the critical choke point between the routine workout that we've always done on everyone and then the more advanced workup of proving amyloid pathology with CSF or a PET scan. Dr Monteith: How sensitive are those blood biomarkers and how early are they positive?  Dr Geldmacher: The sensitivity is generally pretty good, in the ninety plus percent range on average and it depends on which panel. And as you point out, when in the course of symptoms that they're done, we know that they become positive and presymptomatic or asymptomatic people. We're using these kinds of markers to screen people for prevention trials. So, I think when someone is symptomatic, they're a good indicator of the presence or absence of AD pathology. Now that doesn't mean the AD pathology is the sole cause of their symptoms. And so, we still need to think about those other things like sleep and mood and so forth. But they do point us in the in the direction of Alzheimer's change.  Dr Monteith: So why don't we talk about some of the more standard older treatments, and it's also important to leave with kind of some rational approach to when we start and what should we be counseling our patients on. So why don't we start with the older, you know, choline esterase inhibitors and then some of the MDA- I guess there's only one modulator, SEPTA modulator. Dr Geldmacher: So, I've been really fortunate in my career span, the time from the first of those symptomatic agents reaching the market in 1993 to seeing the disease modifying drugs enter the market now. I think most neurologists actually have entered practice after those clinical trials of the colon esterase inhibitors were published. So, one of my goals in this article was to review that primary data and what can we expect from those symptomatic drugs. We know that they are inconsistently effective in mild cognitive impairment, and the Academy of Neurology guidelines says there is not strong evidence to use them in mild cognitive impairment. But in mild AD and beyond, the cholinesterase inhibitors provide meaningful benefits. They delay decline, they can delay nursing home placement. They reduce overall costs of care. So, I think they provide real value. So, in the article I have reviewed what the data looked like on those. My approach is to start with oral Donepezil at five milligrams and increase it to ten in everyone who tolerates the five. If for whatever reason the oral Donepezil is not well tolerated, I'll switch to transdermal rivastigmine to help improve tolerability. There are very few head to head comparisons, but nothing suggests that one of the cholinesterase inhibitors is superior to the other for clinical outcomes, and there's no evidence to support conjoint use of more than one at a time. Should someone be showing decline then on typical cholinesterase inhibitor therapy - and people will, it's often delayed, but the decline will reemerge - then I will add the NMDA receptor, a modulator memantine and titrate that up to full dosing, either 10 mg twice a day for the conventional release or 22 mg extended release. And at that point we're sort of on maximal pharmacologic therapy for Alzheimer's disease. These agents can provide some benefit in other conditions, they're off-label except for Lewy body disease where rivastigmine is labeled. But they can provide benefit across different conditions. And there's some preliminary data, for instance, of acetylcholinesterase inhibitors being helpful in vascular cognitive impairment. So, I will use them, but I expect the greatest response when someone really does follow the patterns of Alzheimer's disease.  Dr Monteith: And you have a great chart, by the way, and nice figures looking at some of the meta-analyses on cognitive outcomes as well as functional outcomes. So, thank you for that.  Dr Geldmacher: In general, all of those tables favor treatment over placebo in the domains of cognition, daily function, neuropsychiatric symptoms. And it's that consistency of result that lets me know that we really are seeing a drug effect, that it's not a class effect with those, that we really are helping our patients. It's not like some studies are positive and some are negative. They are very consistently positive. Small magnitude, but consistently positive.  Dr Monteith: And I know we have a lot of patients coming in where, at least, their caregivers are complaining about agitation, and sleep is also a problem for others. And so how do you help that patient? I know you have a good algorithm that also you included in your article, but why don't you summarize how we should approach these symptoms? Dr Geldmacher: Sure. So, for nonpsychotic agitation, you know, just restlessness, wandering, pacing and so forth, my first choice is an off-label use of citalopram. And there is good clinical trials evidence to support that. if someone has psychotic agitation that is with delusions or hallucinations and so forth, I think we do need to move to the antipsychotic drugs. And the one drug that is now approved for treatment of agitation and Alzheimer's disease does fall into that antipsychotic category, along with its various black box warnings - and that's brexpiprazole. For many of our patients, getting coverage for that agent is difficult. It's not on many formularies. So, it is something I progress toward rather than start with. Similarly, for sleep, there is one approved agent for sleep, that's a dual orexin agonist. And it shows effectiveness, but can have some negative cognitive effects, and so I tend not to start with that either. My first choice when sleep is the primary issue for our patients with dementia is trazodone, and there are some small, limited studies for it's off-label used to enhance sleep. It's safe, inexpensive, often effective, and therefore it's my first choice. Dr Monteith: So, now let's get into the big conversations that everyone is having. Let's talk about the newer disease modifying anti amyloid therapies. Give us a summary dating back 2021 probably, although we can hold the preclinical work, but let's talk about what is available to our patients. Dr Geldmacher: Sure. And the development of anti-amyloid therapies goes all the way back to 1999. So, it's a pretty long course to get us to where we are today.  Dr Monteith: Yeah, that's why we limited that.  Dr Geldmacher: With that first approved agent with aducanumab in 2021, it received a limited or accelerated approval in FDA parlance. These agents, the aducanumab, lecanemab and donanemab, all approved, are known to remove amyloid pathology from the brain as measured by CSF and/or BIPET. They are amyloid lowering therapies, often called disease-modifying therapies. And across the agents there's some variable results. But if we look at the two with full approval, lecanemab and donanemab, they slow clinical progression by 25% to 35% on average. And that's measured by either cognitive measures or global measures or composite measures, but it's pretty consistent in that range of about one-third slowing. That makes it really difficult to discern in an individual patient, though, because there's so much variability in the progression of the disease already that it can be difficult to tell in one person that these drugs are working. They're also complex to use, so there's a qualification process that involves MRI to exclude things like a high tendency toward hemorrhage. It includes genetic testing for papal E4 status to help us understand the risk for complication, and then once-monthly or twice-monthly infusions with standardized schedule for MRI scanning. So, there's a lot that goes into managing these agents. And they are expensive, and we don't yet know their cost effectiveness. The cost effectiveness of the cholinesterase inhibitors was questioned when they first came out back in the 1990s, and it took five or ten years to really understand that they provided benefit to society and to individuals in those domains of quality of life and return on investment. And we're still learning about that with the disease modifying therapies.  Dr Monteith: So, two questions. One, the case that you presented was an individual having symptoms and kind of voiced their desire to be on these therapies. So, people are going to be asking, coming to clinic asking and then of course, they're going to be people that you select out. So, how do you make that decision to recommend this treatment for patients given the potential risk? Dr Geldmacher: We've got some really good guidance from appropriate use recommendation papers for aducanumab and lecanemab, and I'm expecting one from donanemab fairly soon. But the key is to identify individualized risks, and that involves knowing their APOE4 status, knowing their- whether they've had microhemorrhages in the brain previously, and then documenting that they really do have amyloid pathology with something like PET scan to establish those baselines. I talk to people about the burden of twice-monthly infusions or, now with donanemab, once-monthly infusions. And for instance, for someone who's got a working caregiver, getting to an infusion center twice a month can be a significant burden. And then if there are complications, frequent MRI scans and so forth. So, we talk about the burden of entering into this therapeutic pathway. The reality is that people who are qualified generally want it. I have relatively few folks who have said, no, these risks are more than I'm willing to accept. For decades my patients have said, anything you can do to slow this down, I'm willing to try. And now we're seeing that translated to reality with people willing to accept high-risk, high-cost treatments with the chance of slowing their individual progression.  Dr Monteith: And how do you select between the two treatments? Dr Geldmacher: So far that's been easy because donanemab's not readily available.  Dr Monteith: Outside of clinical trials, right?  Dr Geldmacher: Exactly. For prescription use, it's coming in - the first cases have now been infused - but it's not generally available. Nonetheless, what I will do for patients in this is look at the risk tables. So donanemab appears to have in general some higher rates of the Aria complications, amyloid-related imaging anomalies, and some people are going to be more risk tolerant of that for the payoff of potentially faster response. The donanemab trials restructured that. They did their first assessment of effectiveness. I had amyloid removal at six months and a significant proportion of people were eligible to discontinue treatment at six months because their amyloid was below treatable thresholds. So higher risk, perhaps faster action and fewer infusions for donanemab. Lecanemab we have more direct experience with, and between the two of them, the eighteen month outcomes are pretty much the same and indistinguishable. So are we in it for a quick hit, or are we in it for the long race? And different patients and different families will have differing opinions on where they want to accept that risk and burden and so forth. But so far, the data don't indicate a lot of difference in their longer-term outcomes. We still have plenty to learn.  Dr Monteith: And so, it sounds like, as you mentioned, we're looking at eighteen months out for kind of a hard outcome, and that there is a lot of variability in response rate. How are you tracking patients- you know about the imaging, so just in terms of clinical outcomes and efficacy?  Dr Geldmacher: Sure. So, for Medicare to reimburse on these treatments, people need to be enrolled in a registry program - and there are several of these, CMS runs one of their own. But the requirement for that is, every six months, to do cognitive and functional outcomes through the first two years. Cognitive outcomes are up to the clinician, but things like the mini mental state exam, the MoCA, are appropriate. In our own program, we use something we developed locally called the Alabama Brief Cognitive Screener. As for the cognitive outcomes and then for functional, we use an instrument called the General Activities of Daily Living Scale, but there are many other ADL scales that could be used as well. CMS does not mandate specific tests. Since the progression of the disease is variable to begin with, we don't really know how to interpret these results in reference to whether the drug is working, but I can tell a patient or a family member, your scores are stable, or, you have a decline of three points in this test. That's typical for this duration of illness. But there isn't a good way to know whether the drug is working in this person at this time, at least with our current levels of data.  Dr Monteith: So, I think we have to talk about health equity, and it sounds like Medicare is reimbursing for some of us. We look at different socioeconomic backgrounds, educational backgrounds, race, ethnicity. Not everyone is aware of these treatments. So, how do we get more patients to become aware of these treatments? And how do we get them to more people to help people? Dr Geldmacher: Yeah, I mean, that's- it's a major, major issue of inequity in our population. We've done some work at UAB looking at the flow of members of minority communities into memory clinics. So, we know that the overall population of, and I'll choose, for an example, blacks and African Americans, that they are represented a much higher rate in our overall UAB treatment population than they are in our memory clinic population. So, they're not even getting to us in the specialty clinic at the same rates as other segments of our population. We also know that blacks and African Americans in our population are not receiving PET scans as often as the overall treatment population. So yes, there are real, real problems with access. There are cultural issues behind this as well. And in many communities, a change in cognition, a loss of memory is an expected part of the aging process rather than recognized as a disease. So, people who come to us from minority communities are often further along in the course of cognitive and functional decline and beyond the point where they might qualify for the disease-modifying therapies, where early AD is the sort of defining boundary. So, I think more awareness and more screening in primary care settings, perhaps more community outreach to let people know that changes in memory that affect daily function are not normal as part of the aging process and should be evaluated for intervention. So, there's lots of places in our healthcare community where we could foster better outreach, better knowledge to get more folks access to the medicines. And this is before we even get to cost. Dr Monteith: Yeah, yeah. And obviously, there's some stigma as well.  Dr Geldmacher: That's right.  Dr Monteith: Really recognizing what the issues are and diving and asking those questions and funding research that asks those questions, as you mentioned, is really important. And then you have also a nice area where, you know, looking on the impact of treatments on caregiver-related outcomes, and of course ultimately want to keep patients out of nursing homes and prevent death. And so, can you talk a little bit about that? And, you know, mainly the caregiver burden.  Dr Geldmacher: So, my research in that area goes back a long way now. But I learned early in the course of therapy that many times the outcome that the family is noticing for symptomatic therapies is not a change in the patient's memory per se, but that there is less work involved in the caregiving. Less time is spent in direct caregiving roles. The patient may shadow less and because they have better independent cognition. I remember one family member once told me, the medicine you started is a godsend because now I can go to the bathroom by myself and he's not pounding on the door saying where are you, where are you. He's able to recall long enough that I'm in the bathroom that I have that moment of privacy. That was very meaningful to me to hear that. So. Dr Monteith: Cool. So why don't you just help us wrap this up and just give us, like, three main takeaway points that we should be getting out of your article? Dr Geldmacher: The three points that I would emphasize from my article is that the symptomatic therapies provide meaningful benefits and measurable, consistent, meaningful benefits. The second is that those benefits extend beyond things like cognitive test scores and into things like caregiver well-being and maintenance of independence in the home environment. And the third is that the disease-modifying therapies are an exciting opportunity to modify the pathology, but we still are learning about their cost effectiveness and their long-term benefit both to individuals and to society. But the only way we're going to learn that is by using them. And that was the experience that we gained from the symptomatic therapies that took use in the community for years before we really began to understand their true value. Dr Monteith: Thank you. That was excellent. And I put you on the spot, too.  Dr Geldmacher: No problem.  Dr Monteith: Again, today I've been interviewing Dr David Geldmacher, whose article on treatment of Alzheimer's disease appears in the most recent issue of Continuum on Dementia. 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 contentpub.com/AudioCME. Thank you for listening to Continuum Audio.

Recently, an interview by Christiane Amanpour caught my attention. It was with Coralie Fargiat, the director of “The Substance.” Though I haven't seen this 2024 body horror movie (nor do I intend to), the story brings up several teaching points about the left brain, undermethylation, neuroplasticity, and our collective obsession with beauty.The movie is about an actress, Elizabeth, who loses her job hosting a fitness television show when she turns fifty. She has “aged out.” While in the hospital after a car accident, someone directs her to a product - the substance - a neon green liquid that will allow her to bud off a younger version of herself - Sue. The rule is that Sue can only go out into the world for one week at a time, alternating each week with Elizabeth while the other lies dormant. Not surprisingly, Sue has more advantages in the world (that Elizabeth inhabits), including replacing Elizabeth on her former TV show. Increasingly, when it's time to switch, Sue breaks the one-week rule. This results in part of Elizabeth's body becoming increasingly deformed. The culmination is a grotesque battle of gore between the two, who initially were instructed to remember, “You are one.”In the interview, the director, Coralie Fargeat, discusses her personal experience:“I turned 40 and was more impacted than ever about what it's like to be a woman, the feeling that if I wasn't young and pretty and sexy, I would be totally erased from the surface of the earth. So there was this kind of emergency, this vitality to the things I speak about in my film.”Research supports this thinking that beautiful people are treated better and thus have more advantages. With the use of photoshopping, social media filters, and even plastic surgery, many teens and young adults are experiencing neuroplastic changes that are making real people, including themselves, appear increasingly off or even grotesque. Left Brain“The Substance” is a left-brain nightmare. It shows us the self-destructive path the left brain can take us on, especially in a world that tells it exactly how things should look. Elizabeth, the main character in the movie, is rigid in her thinking, addicted to an image of herself, perfectionistic, and highly competitive. In some ways, these left-brain attributes have served her, but unchecked, they destroy her. If the left brain were a person, it would have the following traits and perspective on appearance: (These traits are oversimplified and pulled from Dr. Iain McGilchrist's work) - * Detail-oriented, narrow focus of attention - “That doesn't look right.”* Prefers what it knows and prioritizes what it expects - “I should look this way.”* Has difficulties disengaging - “I can't stop thinking about this and how to fix it.”* Sees parts (as opposed to the whole) * Sees the body as a sum of parts * Doesn't have a whole image of the body (as found in those who have damage to the right hemisphere)* Is competitive - “I need to look better than they do”* Fears of uncertainty and lack of control (As you can imagine, this is a problem for anyone human and thus who will age)The left brain will set its sights on beauty, success, titles, money, objects, or anything else that feeds the “I.” Because the left brain can't see the “big picture,” it has a hard time pulling back far enough to see how its way of thinking may be getting in the way. The Right BrainOur ability to feel embodied is a job for our brain's right hemisphere. When the voice in the movie reminds Elizabeth, “You are one,” it may as well be speaking on behalf of the right hemisphere.Our right brain allows us to have compassion, including self-compassion. It honors diversity and differences. It can see the bigger picture of our lives that involve multiple developmental stages. It can sit with uncertainty. It knows that our imperfections and differences promote connection with actual humans.UndermethylationLeft brain tendencies strongly overlap with undermethylation traits. Methylation is a biochemical and cellular phenomenon that serves many important functions. If we “undermethylate,” we can have more difficulties breaking down histamine, more difficulties detoxifying, and lower serotonin activity. Methylation is impacted by a number of genes, the most well-known being MTHFR.Undermethylated traits include perfectionism, obsessive-compulsive tendencies, being highly competitive, having ruminations, and addictive tendencies. The NDMA ReceptorThose of us who are undermethylated can have high activity at the NMDA receptor, resulting in a problem with “memory extinction” or letting go of a thought. This could look like obsessive-compulsive tendencies (including those seen in body dysmorphia) and addictive tendencies. High histamine (again due to undermethylation) can increase activity at this receptor. Low zinc, high estrogen, and low magnesium can also be at play.I suspect Elizabeth is undermethylated and has high activity at the NMDA receptor. Both could be assessed for and treated (in part) using targeted nutrients. I say, in part, because the brain training / neural training that occurs through social media is difficult to override if someone is still “using.” Interestingly, EMF exposure (from phones and wireless technology) can increase histamine, further driving these issues.Neuroplasticity and Images of PerfectionThe more images of beautiful images of people we see, the more those images become the norm in our mind, and the more any deviation from that norm will stand out as problematic. This was already a problem with the photoshopping of celebrities and models. But now, with social media filters, teens and young women aren't just comparing themselves to celebrities and models; they're comparing themselves to a filtered image of themself.Filters can create larger eyes, bigger lips, more angular jawlines, whiter teeth, slimmer faces, and smooth and even skin tones. Research into the use of filters:* Millennials are predicted to take 25,000 selfies on average over their lifetimes* About 90% of women aged 18-30 report using beauty filters before posting selfies on social media. * Repeated interactions with filtered images and associated beliefs and worries are increasing the risk of mental health issues such as:* depression* social anxiety* reduced self-esteem* appearance anxiety* body dysmorphia* increase of plastic surgery* 62% of plastic surgeons report that their patients wanted cosmetic procedures because of dissatisfaction with their social media profiles* Snapchat dysmorphia” is what plastic surgeons are calling the act of taking a picture of one's self and using a filter.* Selfies are the leading cause of plastic surgery among young people* Girls who routinely shared self-images on social media had considerably higher body dissatisfaction relative to those who share selfies less frequently. * Body Dysmorphic Disorder among young women has been linked to social media use.In short, the research shows that investing in one's self-presentation on social media is often a harmful practice. The more one does it, the more damaging it tends to be. It encourages hyperattention to unrealistic beauty standards and a desire to change one's physical appearance. This problem of hyperattention to unrealistic beauty standards isn't just a phenomenon of teenage girls and younger women. I´m 57 and understand these things, and still, I´ve had to be intentional about how much attention and neuronal wiring I put into what increasingly feels like defying the very full and lovely reality of my current age. A SequelIf I could write a sequel to “The Substance,” it would be about how Elizabeth (the main character) gets off screens and finds a group of real women (her age and older) that she comes to trust, finds refuge, and who she is inspired by. Instead of looking through a lens of culturally defined beauty, she is struck by the strength, courage, and peace they never could have embodied at a younger age. These women who inspire and shape her would like Helen Mirin (79), who corrected a podcast interviewer after they said to her, “But you are young at heart.” She tells him that no, she is not….”My spirit is the age that I am. When you say 'youthful', I'm not full of youth. I'm full of the life that I've lived up to this point.As girls and women, we need these women in our lives. We can do our part to become these women - the desperately needed embodiments of the right brain. Wishing you peace and wholeness,CourtneyCourtneySnyderMD.comP.S. This Saturday begins the mentoring group for MDś, NDś, DOś, NP and PAś. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com

In this episode of The Vet Dental Show, Dr. Brett Beckman, a board-certified veterinary dentist, shares valuable insights into pain management, anesthesia protocols, and best practices in veterinary dentistry. The episode discusses the cautious use of lidocaine in cats, the role of bupivacaine for effective local blocks, and the potential applications of Renia for managing chronic pain in refractory stomatitis cases. Packed with actionable advice, this episode is a must-listen for veterinarians and technicians looking to elevate patient care in their practice.     Podcast Details Host: Dr. Brett Beckman, DVM, FAVD, DAVDC, DAAPM     Key Highlights Topic 1: Lidocaine Use in Cats Question: Should lidocaine be used with caution in cats? Answer: Yes, lidocaine can potentially cause seizures in cats, especially when used as a continuous rate infusion (CRI). Recommendation: Replace lidocaine with bupivacaine for local nerve blocks to ensure longer-lasting analgesia (6-10 hours). Use lidocaine sparingly and with proper discretion. Topic 2: Lidocaine for Intubation Discussion: Historically, lidocaine was applied to the larynx for intubation in cats. Dr. Beckman and his team now prefer using a blunt cannula for safer intubation without the risks associated with lidocaine.     Topic 3: Pain Management for Chronic Cases Case Example: Use of Renia (NK1 antagonist) in refractory stomatitis Mechanism: Blocks Substance P at the postsynaptic membrane to prevent ascending pain signals. Clinical Context: Effective for managing chronic pain when combined with ketamine (NMDA receptor antagonist). Outcome: While Dr. Beckman's team hasn't used it extensively, anecdotal feedback from the veterinary community is positive.     Topic 4: Local Blocks with Bupivacaine Best Practice: Use 0.5% bupivacaine for local nerve blocks in cats and small animals. Dosage: 0.2 mL per foramen ensures safety and efficacy. Rationale: Provides prolonged analgesia compared to lidocaine, minimizing the risk of complications.     Actionable Takeaways Transition to bupivacaine for local nerve blocks to enhance patient comfort and safety. Consider using Renia for managing chronic pain in severe stomatitis cases. Adopt safer intubation techniques, such as using blunt cannulas, to mitigate risks in feline patients. Leverage evidence-based pain management protocols to improve patient outcomes.     Sponsor Mention: This episode is brought to you by the Veterinary Dental Practitioners Program. Learn more and request an invitation at ivdi.org/inv. Closing Note: "I hope you enjoyed this episode filled with actionable items to elevate your dentistry practice. Implement these tips today and see the long-term benefits for your patients and practice!"     If you're ready to take your dentistry skills to the next level, visit ivdi.org/inv to join the Veterinary Dental Practitioners Program!  

In this episode of the In Vivo podcast, Peter Flynn, CEO of Arialys Therapeutics, discusses the exciting field of autoimmune neuropsychiatry and the company's monoclonal antibody, which it is investigating for the treatment of a rare condition called anti-NMDA receptor encephalitis and potentially other indications.

On this episode of the Real Life Pharmacology Podcast, I cover 5 more medications of the top 200. Fenofibrate is a medication used primarily to reduce triglycerides. This medication differs from statins which tend to focus on LDL management. Doxazosin is an alpha-blocker. The primary indications of doxazosin are hypertension and BPH. Naproxen is an NSAID. Of all the NSAIDs, naproxen is one of the lower-risk agents with regard to cardiovascular risk. Spironolactone is an aldosterone antagonist and also classified as a potassium sparing diuretic. Memantine is an NMDA antagonist that is indicated for the management of Alzheimer's dementia. If you are looking for study materials and our list of popular Amazon books, check out meded101.com/store!

FREE! CRNA School Interview Prep Guide: https://www.cspaedu.com/uc9a5ih4Ketamine: A Unique Anesthetic with Diverse ApplicationsDive deep into the world of ketamine, exploring its history, pharmacology, mechanism of action, clinical uses, and side effects. Dr. Kelly Elmore, Assistant Program Director at Mary Baldwin University's Nurse Anesthesiology Program, guides listeners through this fascinating drug, highlighting its potential for anesthesia, pain management, and even mental health treatment.Targeting NMDA Receptors for Dissociative AnesthesiaKetamine is classified as a dissociative anesthetic, distinct from depressant anesthetics like propofol. It primarily works by blocking NMDA receptors in the central nervous system, thereby reducing excitatory signals and producing profound analgesia and amnesia. This mechanism also contributes to the characteristic dissociative state, where patients may appear detached from their environment and experience hallucinations.Beyond Anesthesia: Exploring Ketamine's Diverse UsesBeyond its role in anesthesia, ketamine offers a range of benefits in various clinical settings:Pain Management: Ketamine's analgesic properties make it valuable for treating acute and chronic pain conditions, including neuropathic pain, complex regional pain syndrome, and post-surgical pain.Mental Health: Emerging research suggests ketamine's potential in treating treatment-resistant depression, PTSD, and suicidal ideation. Low-dose ketamine infusions combined with psychotherapy have shown promise in these areas in the form of ketamine-assisted therapy.Emergency Medicine: Due to its bronchodilatory effects and ability to maintain airway patency, ketamine is a valuable tool in emergency departments for managing patients with respiratory distress.Important Considerations for Ketamine UseWhile ketamine offers numerous advantages, it's crucial to be aware of its potential drawbacks:Side Effects: Nausea, vomiting, and hallucinations are common side effects, particularly at higher doses.Abuse Potential: Ketamine's popularity as a street drug necessitates caution, especially in outpatient mental health settings.Cardiac Effects: In critically ill patients with depleted catecholamines, ketamine can worsen cardiovascular depression.Mental Health Risks: Ketamine may exacerbate symptoms in some mental health disorders.S-Ketamine: A Promising Option for Treatment-Resistant DepressionThe FDA-approved S-ketamine nasal spray offers a new avenue for treating treatment-resistant depression. This medication is typically used alongside other oral antidepressants.Conclusion: A Multifaceted Drug with Ongoing ResearchKetamine's unique properties make it a valuable tool for CRNAs across various healthcare settings. Ongoing research continues to explore its potential benefits and refine its use for optimal patient care.Join the Free CSPA Community! Connect with a network of Aspiring CRNAs, Nurse Anesthesia Residents, practicing CRNAs and CRNA Program Faculty Mentors here: https://www.cspaedu.com/communityNeed Interview Prep Help In A Hurry?Fast-Track Your CRNA School Interview Prep with our CRNA Interview Crash Course! https://www.cspaedu.com/4wotmldsGet access to application & interview preparation resources plus ICU Educational Workshops that have helped 1,000s of nurses accelerate their CRNA success.Become a member of CRNA School Prep Academy:https://cspaedu.com/joinGet CRNA School insights sent straight to your inbox! Sign up for the CSPA email newsletter: https://www.cspaedu.com/podcast-emailBook a mock interview, resume or personal statement critique, transcript review and more: www.teachrn.comAttend an upcoming Virtual Information Session with Mary Baldwin University Nurse Anethesiology Program: https://marybaldwin.edu/programs/nurse-anesthesiology-dnp/Special Note- Application Deadline for their next cohort is 12/15/2024!

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.

“Addicted” - “exhibiting a compulsive, chronic, physiological or psychological need for a habit-forming substance, behavior, or activity.” Like other health conditions, addiction is multifactorial. It is the result of an alignment of root causes. In this newsletter, I'll discuss:* Substance addiction and behavioral addictions* Why addiction is not simply about dopamine and why there are multiple addictive personalities* How & why we differ in our physiologic response to substances* Our culture's shaming and punishment of addiction while fueling addiction* The role of attachment disruption, trauma, emotional dysregulation, and social isolationSubstance AddictionWhen it comes to addiction, you might expect me to talk a lot about dopamine.  Not all substance addictions are the same, however. Opioids act very differently on the body than alcohol, which acts differently than cocaine.  Some substances are more addictive than others, and even more so in certain people.  For most people, marijuana is less addictive, while alcohol, cocaine, and opioids are more addictive. Addictive Substances:* Alcohol* Caffeine* Cannabis* Hallucinogens* Sedatives and Hypnotics/Anxiolytics* Inhalants* Opioids* Stimulants* TobaccoSeemingly, 10-20 % of people who try substances will have problems with addiction. Our genetic makeup and the expression of our genes will impact how we react to substances, just as they will affect how we metabolize specific medications or environmental toxins.  We could, for example, have a weak enzyme that slows our metabolism of alcohol and results in our becoming more intoxicated more quickly.  We may have high neurotransmitter activity that we're trying to calm down with substances, or we may have low neurotransmitter activity and are taking substances or even carrying out certain behaviors that increase our neurotransmitter activity.   Behavioral AddictionWhile we can become severely addicted to substances, we can also become addicted to behaviors or the feelings brought on by the behavior or anticipation of the behavior. Examples of Behavioral Addiction:* Food addiction* Sex addiction* Love and relationship addiction* Codependence is considered a relationship addiction in that relationships are often one-sided, emotionally destructive, or even abusive.* Exercise addiction* Body dysmorphic disorder* Health addiction* Shopping addiction* Gambling addiction* Work addiction* Video game addiction* Internet addiction* Smartphone addiction* Social media addiction* Porn addiction* News addiction* Information addiction* Self-harm addiction* Extremism is also felt to overlap with addictionWe can become addicted to anything that spikes the reward chemicals in our brains.  If we're not sure if we're addicted, we can ask ourselves, “Is the compulsive behavior having negative consequences?”The severity of our addictions falls on a spectrum.  I may not have a gambling addiction where I am putting myself at financial risk; however, I could be addicted to sugar, which I know negatively impacts my health, gives me brain fog and fatigue, and causes me to check out of my relationships, including my relationship with myself. Culture: Shame & Punishment The last thing that we need if we are addicted to a substance or behavior is shame and punishment. Our culture still tends to see addiction as a moral failing or even a sin that can be removed with punishment.  This thinking leads to simplistic consequences such as rejection by family and friends and even imprisonment.  The same happens with other forms of mental illness, but in this case, there is even less understanding, less compassion, more anger, and more disdain.Culture: Fueling AddictionMeanwhile, most of us are becoming more addicted - addicted to our cell phones, social media, divisive stimulating news and information.  We have more information coming at us than we can process.  Our brains are flooded with catecholamines as we stay in highly stimulated states. One of those catecholamines is dopamine, which will drive motivation and have us in pursuit of “more.”  While there may be a type of pleasure in that pursuit, it's not a joyful or even content type of pleasure. When we are in pursuit, we are not present in our lives.   Many of us can barely process our moments, days, and lives in these modern times. For many, what was a life of memorable moments (positive and painful) has become a blur of days quickly passing by. Before we've had time to process what has happened, what we've experienced, or what we've felt, our minds are in pursuit of the next thing we need to know or have.With addictive technology comes the marketing and its messages - “more food, more sex, more youth and beauty, more health, more money, more success, and even more love - the elusive movie kind.  We are forgetting how to be satisfied and tolerate uncomfortable feelings.Attachment & TraumaWe haven't all had the same early attachment experiences. Some of us have experienced childhood trauma. We don't know what safety feels like. Two-thirds of those with opioid addiction have childhood trauma. This doesn't account for the trauma that can occur before verbal memory, which is usually not reported.Childhood trauma impacts our autonomic nervous system, our limbic system, and our hormonal stress response. Before we even experience a stressor, our baseline neurotransmitters may already be too high. Our trauma, in combination with our genetic variants, may result in high neurotransmitters that we may try to calm down with our addiction, or our trauma, in combination with our genetic variants, may have us seeking out stimulation so we can feel more alive and connected.Social IsolationPart of our understanding of addiction comes from the work of American psychologist Dr. Bruce Alexander, who did the “Rat Park” study.  Previous research had already shown that when rats were put in solitary confinement and given a choice between water and heroin or cocaine, the rats repetitively consumed the drug-laced water until they overdosed and died.Alexander realized that the problem may not be the rats but the environment.  Rats are social animals, just as we are.  So, he created “rat parks,” where the rats could roam, play, socialize, and have sex.  Despite being given the same access to the two types of drug-laced water, these rats preferred the plain water.  Even if they did drink the drug-laced water occasionally, they never did obsessively, nor did they overdose.  The social environment was protective against addiction. If we want to help those with addiction, we need to think about connection. If we want to help ourselves with an addiction, we need to think about connection.Emotional RegulationOur ability to regulate our emotions (increase calm and decrease fear and anger) comes through interactions with other humans - safe humans. Ideally, we learn to regulate our emotions during our first three years. When we were distressed as infants and toddlers, we communicated that distress through our cries and facial expressions, our caregivers responded, and our physiology returned to a sense of calm and safety. This repeated process - not necessarily perfect, but “good enough” - resulted in our internalizing that early relationship and, with that, an ability to recognize our feelings, trust others, feel worthy, respond to uncomfortable feelings with coping skills, and return to our baseline emotional state.  Without this skill we acquire through attachment, we can become overwhelmed by our feelings or detached from our feelings. Our experiences, genetics, and temperament will impact which direction we go.There is not one “addictive personality” but many addictive personalities. Some of us will be highly sensitive, and others will have a low level of sensitivity. Some of us will become overwhelmed by stress or stimulation and use addictions as a way to try to calm our emotional and high neurotransmitter states.  Others will seek sensory stimulation or risk-taking to bump those neurotransmitters and increase the feeling state. Of course, our biochemical differences impact this as well:* For those of us who are undermethylated, we may find that we are sensory seeking, have high activity at the NMDA receptor, and find ourselves craving whatever has come to have meaning or has left a mark on our neurophysiology.  * For those of us who are overmethylated, we may have the desire to calm things down, slow our racing thoughts, and lower our high neurotransmitter activity.* For those of us with high pyrroles (and or CAPs profile), we may feel socially anxious or overstimulated and desire to feel calm and comfortable, but at other times, we may feel brave and invincible.“Being bold and adventurous and being sad and cautious seem like opposite personality types. However, these two paths to addiction are actually not mutually exclusive. The third way involves having both kinds of traits, where people alternatively fear and desire novelty and behavior swings from being impulsive and rash to being compulsive, fear driven, and stuck in rigid patterns. ……My own story spirals around this paradoxical situation: I was driven enough to excel academically and fundamentally scared of change and of other people—yet I was also reckless enough to sell cocaine and shoot heroin.” - Maia Szalavitz We need to think more broadly about addiction, just as we would any other health condition.  We need to address the underlying physiological root causes, meet our human need for connection, and learn ways to experience, tolerate, and cope with our very human and necessary feeling states.  In this week's paid newsletter, I look forward to discussing cases to illustrate how various neurotransmitters can be at play with different substance addictions and how targeted nutrients can be used in the treatment of addictions - both substance and behavioral. Until next time,CourtneyIf you'd like to dive deeper into the root causes of brain symptoms, consider becoming a paid subscriber. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com/subscribe

Nous parlons de la progestérone et de ses effets multiples chez les femmes et pourquoi on l'appelle l'hormone de la zénitude et du sommeil profond. On vous parle aussi des symptômes de déficit et de surcharge, des indications et contre-indications ainsi que des options thérapeutiques de remplacement hormonal. Abonnez-vous à notre infolettre pour ne pas rater nos prochaines annonces de lancement de nouveaux programmes et autres offres exceptionnelles. Rendez-vous sur solutions-sante.ca et descendez en bas de la page pour vous inscrire. Les symptômes de déficit en progestérone les plus fréquentsUne mise en garde : il est important de se rappeler que chacun des symptômes énumérés pourrait aussi avoir d'autres causes que le déficit en progestérone, donc il vaut mieux toujours en parler avec son médecin et ne pas simplement présumer que ça doit être les hormones. Sites de production des hormones dans le corps de la femme La progestérone et les œstrogènes travaillent en complémentarité, comme le ying et le yang. Les surrénales et le cerveauLes 4 stéroïdes neuroactifs (neurostéroïdes) : L'allo-pregnanolone L'iso-pregnanolone La pregnanoloneet l'épipregnanoloneIl y a des récepteurs à progestérone ou aux neurostéroïdes qu'on vient de mentionner dans plusieurs endroits du cerveau, dont : hypothalamusamygdaleshippocampethalamus cortex frontalLa progestérone peut aussi aller directement sur les récepteurs GABA et les récepteurs NMDA. En plus de cela, la progestérone et les stéroïdes neuroactifs peuvent moduler les systèmes de neurotransmetteurs suivants : sérotoninergiquescholinergiquesdopaminergiquesLes bienfaits de la progestérone et des neurostéroïdes au niveau du cerveauLes fonctions de la progestérone dans le corps. Les causes possibles d'un déficit en progestéroneLes signes et symptômes fréquent d'une surcharge en progestéroneLes options thérapeutiquesLes indications Les contre-indications Qu'est-ce qui distingue le plus les progestines de la progestérone? Conclusion sur le sujet C'est maintenant l'heure de l'astuce de la semaine : Il faut écouter l'épisode pour la connaître!Les messages clés de l'épisode sont : La progestérone a de multiples fonctions dans le corpsIl faut arrêter de croire, en 2024, que si une femme n'a plus d'utérus, cela signifie qu'elle n'a pas besoin de prendre de la progestérone dans un contexte d'hormonothérapie de remplacementOn peut avoir un déficit en progestérone n'importe quand à partir de la puberté Si on a un SPM très intense, il ne faut pas hésiter à consulter. Il y a des options thérapeutiques. Il y a peu de contre-indications à la prise de progestérone bio-identique et celle-ci n'augmente pas les risques de cancer du sein ou de thrombo-embolie. À ne pas confondre avec les progestines qui sont de la progestérone synthétique, qui, elles, peuvent augmenter ces risques. Hébergé par Ausha. Visitez ausha.co/politique-de-confidentialite pour plus d'informations.

We are BACK for SEASON FIVE of the pod! In this episode, Dr. Jessica Steier and Dr. Sarah Scheinman discuss Alzheimer's disease and cognitive decline. They cover essential topics including the definition and symptoms of Alzheimer's, the genetic and epigenetic basis of the disease, brain changes associated with Alzheimer's, risk factors such as age, genetics, and lifestyle, modifiable risk factors and prevention strategies, and current treatments and their controversies. The scientists emphasize that maintaining overall health is crucial for brain health. They recommend a combination of lifestyle choices that promote general well-being, which in turn support cognitive health. They explore various treatment options, including cholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies targeting amyloid beta. The conversation highlights the ongoing debates about treatment efficacy and the need for further research. The episode aims to provide valuable insights and alleviate fears surrounding Alzheimer's disease. It concludes with a rapid-fire Q&A segment addressing listeners' questions. All our sources from this episode are available at: https://www.unbiasedscipod.com/episodes/dont-you-forget-about-me-unraveling-alzheimers (00:01) Music and Season Five Welcome (04:30) Introducing Dr. Sarah Scheinman and the Topic of Alzheimer's (07:49) Understanding Alzheimer's Disease and Its Symptoms (10:50) The Genetic and Epigenetic Basis of Alzheimer's (18:23) Risk Factors for Alzheimer's: Age, Genetics, and Lifestyle (26:02) The Role of Amyloid Plaques and Tau Tangles in Alzheimer's (30:37) Promoting Early Diagnosis and Intervention for Alzheimer's (35:21) Breaking Down the Stigma and Building Scientific Literacy (41:51) Treatments for Alzheimer's Disease (46:27) Monoclonal Antibodies and Controversy (53:50) Diagnosing Alzheimer's Disease (55:32) Final Thoughts: Q&A: Common Questions About Alzheimer's Disease Interested in advertising with us? Please reach out to advertising@airwavemedia.com, with “Unbiased Science” in the subject line. PLEASE NOTE: The discussion and information provided in this podcast are for general educational, scientific, and informational purposes only and are not intended as, and should not be treated as, medical or other professional advice for any particular individual or individuals. Every person and medical issue is different, and diagnosis and treatment requires consideration of specific facts often unique to the individual. As such, the information contained in this podcast should not be used as a substitute for consultation with and/or treatment by a doctor or other medical professional. If you are experiencing any medical issue or have any medical concern, you should consult with a doctor or other medical professional. Further, due to the inherent limitations of a podcast such as this as well as ongoing scientific developments, we do not guarantee the completeness or accuracy of the information or analysis provided in this podcast, although, of course we always endeavor to provide comprehensive information and analysis. In no event may Unbiased Science or any of the participants in this podcast be held liable to the listener or anyone else for any decision allegedly made or action allegedly taken or not taken allegedly in reliance on the discussion or information in this podcast or for any damages allegedly resulting from such reliance. The information provided herein do not represent the views of our employers. Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Will Van Derveer, joins Dr. Jill Carnahan to discuss the promising advancements and therapeutic benefits of psychedelic substances in treating mental health conditions like **PTSD**. Dr. Van Derveer is a renowned expert in integrative psychiatry and brings invaluable insights into how these unconventional therapies are reshaping the future of mental health care. Key Points ✅ Could psychedelics may become legal and appropriate treatment for depression and PTSD this year? ✅ What are the different potential indications of NMDA, psilocybin (magic mushrooms) or ketamine therapy in the treatment of psychiatric disorders and PTSD ✅ Why is it important to have trained medical staff and therapists for these types of therapies  and their success in treating patients with depression, anxiety or PTSD Will Van Derveer, MD Will Van Derveer, MD is co-founder of Integrative Psychiatry Institute, which offers comprehensive training for mental health professionals in psychedelic-assisted psychotherapy and other continuing education programs.   He is medical director of Integrative Psychiatry Center of Boulder, CO, providing integrative psychiatry for a broad range of conditions and ketamine-assisted psychotherapy for treatment-resistant depression and PTSD.   In addition to his clinical practice and teaching, he has been involved with several studies sponsored by MAPS, investigating MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, a breakthrough treatment which could be approved in late 2024 by FDA.

Paraneoplastic neurologic syndromes can present with manifestations at any level of the neuraxis. In patients with high clinical suspicion of a paraneoplastic neurologic syndrome, cancer screening and treatment should be undertaken, regardless of the presence of a neural antibody. In this episode, Katie Grouse, MD, FAAN, speaks with Anastasia Zekeridou, MD, PhD, author of the article “Paraneoplastic Neurologic Disorders,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Zekeridou a senior associate consultant in the departments of neurology, laboratory medicine, and pathology, and for the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Paraneoplastic 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 Guest: @ANASTASIA_ZEK 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, 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 Grouse: This is Dr Katie Grouse. Today, I'm interviewing Dr Anastasia Zekeridou about her article on classical paraneoplastic neurologic disorders, which is part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast, and please introduce yourself to our audience.   Dr Zekeridou: Hi. Thank you, Dr Grouse. I'm always excited to talk about paraneoplastic neurological diseases. So, I'm an autoimmune neurologist at Mayo Clinic in Rochester, and I spend my time between the lab and seeing patients in the autoimmune neurology clinic.   Dr Grouse: Thank you so much for joining us, and we're really excited to talk about this really important topic. So, to start, I'd like to ask what, in your opinion, is the key message from this article.   Dr Zekeridou: That's a good question - there are a lot of messages, but maybe if I can distill it down. For me, one of the first things is that paraneoplastic neurological diseases can actually affect any level of the neuraxis. It can manifest with different types of presentations. If we do suspect a paraneoplastic neurological syndrome, then we need to look for the cancer, and then if we're not certain, even do an immunotherapy trial. A negative antibody does not make for an absence of a paraneoplastic neurological disease (because, often, we depend a lot on them), but you can see patients with paraneoplastic disease that do not have neural antibodies. And then, we always need to be thinking that if we have a paraneoplastic neurological disease, we actually need to be thinking of both the cancer and the immune response together - so, we need to be treating the cancer, we need to be treating the immune response – because, essentially, paraneoplastic neurological syndrome is evidence of this antitumor immune response. So, the main (if I can distill this down in one) is probably that we need to be discussing all of these patients with the treating oncologist, because they have complicated care.   Dr Grouse: Great. Thank you so much for that summary. It's very helpful. While many of our listeners are likely familiar with paraneoplastic disorders in their workup (which you've mentioned just now), the concept of neurologic autoimmunity in the context of immune checkpoint inhibitor therapy has more recently become widely recognized. Can you summarize this briefly for our listeners who may be less familiar with this?   Dr Zekeridou: I think that we learn more and more about this and we see more and more patients with immune checkpoint inhibitor-related neurological immunity, so, I always think about it in a very straightforward way. So, I think the way we think about immune responses is a balance between tolerance and regulation and immune activations. And then, immune checkpoints are the molecules that help us maintain self-tolerance. So, our immune system - it's probably the best tool that we have to fight against cancer. So, essentially, when we inhibit the immune checkpoints, we actually use our own immune system to fight cancer, but taking the breaks of the immune system essentially can lead to a lot of complications that are immune-mediated. Some of them are neurological - the neurological complications are rare, especially the ones that we need to do something about (so, it's 1% to 4%, in some cases up to 14%), and they do increase when you use multiple immune checkpoint inhibitors together. The main thing for me with the neurological complications is that, sometimes, they are difficult to recognize, they can (again) affect every level of the neuraxis - like, it can be the neuromuscular or the central nervous system (even though neuromuscular complications are much more common than central nervous system complications) - and then a lot of them (the vast majority) will happen within the first three months, but they can also happen even after you stop the immune checkpoint inhibitor. But this three-month interval, it's sometimes useful when you're in a diagnostic silence - it kind of helps you make the decision more towards an immune-related adverse event affecting the nervous system. And then, I think that, practically, once we have diagnosed this patients, we still are not very certain how to treat. All of them will get steroids upfront, but some of them will be difficult to treat, so then, we have to decide on the next treatment depending on evolution. And then, I will just say that (I mentioned it previously, but) these are the patients that the coordination with other subspecialties is one of the main things that we need to do (eg, oncologists) - they often have immune-related adverse events from other systems, so, there is a lot of coordination of care. And, always, the question at the end comes up, Should we be putting these patients back to their immune checkpoint inhibitor cancer immunotherapy that might help them with the cancer? And I think that this is difficult sometimes, and it needs to be decided - most cases - in a case-by-case basis, even though there are some recommendations that I've been discussing in the Continuum article.   Dr Grose: That's great, and I encourage everyone to read more about this, because it is a very complex and fascinating topic. On the note of the immune checkpoint inhibitor neurologic dysfunction - I would imagine these are pretty rare - how common are these? And I would suspect they're getting missed a lot - is that correct?   Dr Zekeridou: I think it's a very good question. Essentially, what we say for the neurological immune-related adverse events (the ones that we need intervention) - so, they are at least of grade two. (I think that there are less than 4%, mostly, probably close to 1.5%.) There was a study where they used double immune checkpoint inhibitors (so CTLA-4 and PD-1, PD-L1) - they were up to 14%, but this was any grade (so, a little bit of tingling, a little bit of headache), while the ones that we actually need to act upon and we need to actually do something about, they are probably closer to 1.5%. So, are they being missed? I am certain that some of them never make it to the neurologist. So, the ones that we know that we are underestimating is definitely the meningitis - because I think it's more common – but, often, when the patients present, they have something else as well. So, the oncologists will put them on steroids and then they will get better - so, we don't really see them in the neurology clinic (the ones with the very mild side effects). And then, also, these patients are often very sick, and they have a lot of things going for them, so they sometimes do not make it to the diagnosis.   Dr Grouse: So then, I want to just take a step back and ask you, what's the most challenging aspect of paraneoplastic neurologic disorders in your opinion?   Dr Zekeridou: I think, for me, one of the main things, the classic paraneoplastic disorders - and when I say “classic paraneoplastic disorders”, they are the ones that we think more of with antibodies that are mostly biomarkers of the immune response, and they suggest a cytotoxic T-cell mediated disorder (so, like PCA1 [or anti-Yo] or ANNA-1 [or anti-Hu]) - these patients are very sick often, and we don't have a lot of good treatments for them. And then, even if we treat them, we actually sometimes do not manage to reverse their course - the best that we can do is stabilize. So, I think that this is part of the discussion that we have upfront with these patients - but it is quite challenging, because most of them, we will be giving them a cancer diagnosis ourselves, because we recognize the paraneoplastic neurological syndrome, and we look for the cancer, and then we'll be giving them a cancer diagnosis. And even if we treat their cancer and we treat the immune system, sometimes, then, we don't make a real improvement – like, we stabilize their disease and we sometimes get improvement, but there are cases that we do not and they continue to progress – so, that has been the most challenging aspect of this, and I think that's kind of where we really need more things coming – like, we need more treatments, we need to better understand these diseases and get more straightforward.   Dr Grouse: I agree. I think that's absolutely, uh, what we all hope for these types of disorders, and I can imagine we all can remember at least one case just like this where someone had this type of problem and just didn't respond to treatment. So, strong hopes that there will be improvement with this in the years coming. Another question I have for you is, what in your article do you think would come as the biggest surprise to our listeners?   Dr Zekeridou: I think that, because we discussed that immune checkpoint inhibitors (maybe we don't know as well), so one of the main things for me is when we first started thinking of neurological complications of immune checkpoint inhibitors, there was a lot of myasthenia gravis mentioned (patients presenting with myasthenia gravis), and then some of them antibody-positive, some of them antibody-negative. Now, with the time that has passed by, we recognize that myasthenia gravis is very rare. Like, I've seen tons of patients (probably more than that, actually) – and then, maybe I've seen one patient with de novo myasthenia gravis. We realize that the immune checkpoint inhibitor myasthenia gravis that we were thinking of are – they're mostly the immune checkpoint inhibitor myocytes cases - so, then, this is one of these myopathies that looks like no other. So, it really has a very predominant oculobulbar involvement (that's why everybody was thinking that this is myasthenia gravis), but, practically, the EMGs are negative, the patients do not respond to pyridostigmine - so, practically, these are really myopathy cases. And why is that important? Because 30% to 40% of these cases might also have a cardiomyopathy, for example, and then we're putting all these patients on pyridostigmine and medications that they do not necessarily need. So, I think one of the chains in concepts that we have in the later years is that, really (and this is one of the most common immune-related adverse events that we see in our clinic), that these patients with ICI myositis really present with the oculobulbar involvement and proximal involvement that we can see in myasthenia, but they do not have a neuromuscular junction problem.   Dr Grouse: Now, we've all struggled with identifying a primary malignancy in patients where a paraneoplastic syndrome was strongly suspected. Do you have any tips on how to make this workup as high yield as possible?   Dr Zekeridou: Yeah, I think that's a difficult question. I think it depends a little bit on your patient as well. So, if you have an antibody that makes things easier (and we can discuss about that, but), practically, for me, a patient that I have a high suspicion, that we get a CT chest, abdomen, and pelvis upfront - and often, we don't get PET scans, right, directly, because we have insurance companies maybe playing a role in what we would do. So, I would get this for a woman - she has to have a mammogram. For a man, they have to have a testicular ultrasound. That's the basics for me. And then, when we see more younger women or when we suspect an MDA, then they will need to have the ultrasound to look for the ovarian teratomas or an MRI of the abdomen - so, the PET scan for me, if I have a high suspicion, it will always be the next step. Like, we have increased diagnostic yield with PET scans, but we also need to remember, what are the tumors that you will not find on a PET scan? Teratomas are not PET-avid, and, often we say, “Oh, we found the lesion in the ovary and the PET scan was negative.” That doesn't matter. In an NMDA-receptor antibody patient, if you find the lesion in the ovary, you need to make certain it's not a teratoma, because PET scans will not necessarily pick up a teratoma - it's not an avid malignancy. So, if the patient is a smoker and I suspect small-cell lung cancer, so I would always get the PET scan. If I have a patient with a high-risk antibody like PCA1 (or anti-Yo) and I didn't really find the tumor with the CT chest, abdomen, and pelvis and the mammogram, I will always get the PET scan. Same for the patients with the smoking history. I will also say that, sometimes, we forget other malignancies. So, for example, we have neuronal intermediate filament antibodies (so, ANNA-3 antibodies), and some of them will have Merkel cell. So, depending on the patient, on the antibody, and if we didn't find anything else, I would do a skin check. If they have GI symptoms, I would look for the GI tumor as well. So, even though the basics are what I mentioned, I will adapt depending on the patient symptoms. And all of these patients should have age-appropriate cancer screening, so if they didn't have a colonoscopy, they will have to have a colonoscopy. So, this is part of the main things. And then, the question for me that always comes up is, “Who is the person that you're going to keep on repeating the screen?” And then, practically, if you have a low-risk paraneoplastic antibody that comes (let's say LGI1), we know it's a low risk, so I would actually do the cancer screening - I will look for the thymoma once, and then that would be it. But if you have a patient with a high-risk paraneoplastic antibody (let's say ANNA-1 [or anti-Hu] or anti-Yo [anti-PCA1]), these are the patients that I will keep on screening - and then I will do every four to six months for two years (that's the current recommendation), but I will probably continue yearly after. And then, we need to also remember that whenever you have a neurological relapse, that's exactly when you need to be looking for the cancer as well - so, you must be thinking that the idea is that maybe you have the immunological relapse because there is cancer somewhere. So, these are the types of things that I kind of adapt to specific patients. But I think when we're not certain, broad screening is what we need. And then, again, the PET scan - for me, it's a great test, but we need to know its limitations. So, that's the other thing that comes up a lot in the phone calls or in the patients that I see that we do a PET scan - but practically, it's not good for some of the malignancies that we're looking for.   Dr Grouse: That's really great to point out, and I'm glad you brought up the risk level of the particular syndrome. You have a great table in your article that summarizes the risk level of some of the various syndromes - so, you know, just a reminder for everyone to check that out if you want to have more information about this and how this applies to the screening - so very helpful. What is the easiest mistake to make, and also maybe to avoid, when treating patients with paraneoplastic neurologic disorders?   Dr Zekeridou: That's a great question, actually. So, there are two things here. One is that we need to be thinking about paraneoplastic neurological syndromes, because if you don't think about them, then you don't look for them. So that's the one thing. So, patients that come with a subacute onset of neurological dysfunction - they have systemic features, or they are smokers, they have autoimmunity in the family (all those things) – like, we need to be thinking about paraneoplastic neurological syndromes. On the other side, we also see a little bit more of overdiagnosis that's coming in the later years. So, one of the things that we see a lot is that we kind of have difficulties with the interpretation of the neural antibodies - so, sometimes, we will get a neural antibody, and then it will not fit, but we will base our diagnosis on the neural antibody presence. And then, some neural antibodies are great - we don't really see false-positives - but some of them are not great and we do see false-positives. So, for me, the main thing that I would say is that we need to have a clinical suspicion - we're treating the patient and the clinical syndrome if it is compatible with a paraneoplastic neurological disorder, and then the neural antibodies are the ones that are going to help us, like, diagnose or point to a cancer - but we are really treating the patient. And then, if we give a treatment and it doesn't make sense how the patient evolves, we actually need to reassess the diagnosis, because we do have both overdiagnosis, but also we have underdiagnosed in patients that it's not suspected - so I think it's kind of the increased awareness that helps, but we also need to be going back always to the clinical manifestations of the patient.   Dr Grouse: Really great points to make, and thank you so much for that. What is the most common misconception you've encountered in treating patients with paraneoplastic disorders?   Dr Zekeridou: So, one of the things that we see a lot is that patients wait to be treated - even with high suspicion of paraneoplastic neurological syndromes - until we have the neural antibodies, and sometimes, if the neural antibodies are negative, we have patients that are not given a paraneoplastic neurological syndrome or autoimmune neurological syndrome diagnosis because of the negativity of the antibodies. So, for me, one of the main things is that the patients actually fit clinically with a paraneoplastic neurological syndrome - and there are scores that can help us, clinical manifestations that can actually help us make this diagnosis. We need to be looking for the cancer and treating them, regardless of the presence of the antibody. Some patients will not have the antibodies for weeks. The second aspect to this is that, often, we want to say, “Oh, it's a paraneoplastic neurological syndrome. They will treat the cancer and, like, that's the oncologist's job.” But, practically, I think that the neurologist will really need to be involved with this. I think the patients need treatment of the immune response and treatment of the tumor. So, I think we are part of the treatment team for these patients and it's not only the oncologists that are treating the tumor.   Dr Grouse: Where do you think the next big breakthrough in this area will be?   Dr Zekeridou: Where I hope it would be - and I'm hoping that it's actually what it is going to be – is, really, better understanding and treating the classic paraneoplastic neurological diseases, that they are T-cell mediated disorders that lead to neural cell distraction, and we don't have good treatments for these patients and we cannot get any improvement. So, there is a lot of research going on there. How can we prevent? How can we treat? But, I think that would be the next big milestone for us, because the antibody-mediated diseases - so we now have a lot of good treatments. Like NMDA-receptor encephalitis, AMPAR encephalitides - these antibody-mediated disorders, we have good treatments. The disorders that the antibodies are biomarkers  - and they are the cytotoxic diseases, the effectors of the autoimmunity - we don't. So, that's where I hope and think our breakthrough will be.   Dr Grouse: Definitely hoping to see more advancements in this area and already, I think, very quickly developing field. So, I wanted to talk a little bit more about you and what brought you to this area of neurology I think which most of us find to be a very fascinating field  that would love to hear more about what brought you to it. How did you become interested in this area of neurology?   Dr Zekeridou: I did my medical school in Greece. So, in Greece, towards the end of the sixth year, you need to decide what your specialty would be, and for the life of me, I could not decide between oncology and neurology - I was changing my mind all the time. And then, I decided that the diagnosis is more important to me in terms of a physician - that's why I went more with neurology and I was clear on my choice. So, practically, then, I went and did my residence in Switzerland, and something happened and I found myself in the outpatient autoimmune neurology multiple sclerosis clinic for a year, and it was evident to me that this is my passion. Like, the multiple sclerosis, I thought was a great disease, but it was the cases that they were not multiple sclerosis, that they were the ones that they were the most fascinating for me. So, then, I did my peripheral nerve year - so even more, it was clear for me that this is the immune system interactions, the cancer, and the neurological symptoms - that's what I wanted to do. And practically, I pursued a fellowship in Lyon in the French Reference Center for Paraneoplastic Diseases, and I was sold. There was nothing else for me. So, eventually I came here at Mayo (and then I stayed) - but it was very clear, even since the beginning - and I really found something that combined both of my passions even from medical school.   Dr Grouse: What are you most excited about in this field? And, specifically, you know, what might you impart to other trainees who are thinking about choosing this field for themselves?   Dr Zekeridou: So, I think that there are many things. So, autoimmune neurology or paraneoplastic neurological syndromes, they can affect every level of the neuraxis, so, practically, your clinician, that we see everything - we'll see central nervous system, peripheral nervous system, neuromuscular junction – so, that's actually very fascinating for me. The second part of it is that we have diseases that we can actually treat. We see differences in patients that we will intervene and we will really change their disease course. And the other thing for me is all the research that is ongoing. So, practically, the research in paraneoplastic syndromes or neurological immunity is directly translational to the patient - like, we have kind of a bed-to-bedside type of research that is going on. And basic research is important and there is a lot of advances, but you can see them directly, like, being translated in patients - so, essentially, the research is directly translational to clinic, and that makes it very exciting.   Dr Grouse: I think that your excitement about this field is very inspirational and will hopefully inspire many future trainees who are interested in this field. So, when you're not learning more about paraneoplastic syndromes and their treatment and diagnosis, what else do you like to do? Tell us something about your outside interests.   Dr Zekeridou: So, again, I come from a very diverse background and the way that I arrived in the states, but, I really like traveling. So, we would travel a lot lately. We travel more in Greece, because when you're coming from Greece and you're not living there, your summers are always there - but we try to explore different places there. And one of my main things and passions that I like is, essentially, cooking. So that relaxes me, that helps me - cooking and having friends over – so, that's my favorite thing of doing outside of work.   Dr Grouse: Well, I have to say it's hard right now to imagine anything more fun than traveling and enjoying good food and Greece. So, I think your hobby seems like one we can all get behind.   Dr Zekeridou: It's relaxing the mind.   Dr Grouse: Yes, yes. This has been a really great discussion on what I think is a very interesting area of neurology, and we really appreciate you taking the time to talk with us today.   Dr Zekeridou: Thank you so much for having me. It was great talking to you.   Dr Grouse: Again, today, I've been interviewing Dr Anastasia Zekeridou, whose article on classical paraneoplastic neurologic disorders appears in our 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 so 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 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. Full transcript available at URL to come

Autoimmune neurology is a rapidly evolving subspecialty that focuses on neurologic disorders with atypical immune responses. In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sean J. Pittock, MD, an author of the article “Overview and Diagnostic Approach in Autoimmune Neurology,” in the Continuum August 2024 Autoimmune Neurology 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. Pittock is the director for the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Overview and Diagnostic Approach in Autoimmune Neurology 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: @AaronLBerkowitz 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, 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 Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr Sean Pittock about his article, “Introduction to Autoimmune Neurology and Diagnostic Approach”, which he wrote with his colleague, Dr Andrew McKeon. This article is a part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast, Dr Pittock. Could you introduce yourself to our audience?    Dr Pittock: Well, thank you very much, Dr Berkowitz. So, yeah, I'm a neurologist at the Mayo Clinic. I direct the neuroimmunology laboratory with Dr McKeon and Dr Mills here, and I have also been very much involved in the autoimmune neurology section at the American Academy of Neurology.    Dr Berkowitz: So, many of you probably know Dr Pittock - or if you don't know, you've certainly diagnosed diseases that he has described and written about, and so it's a real honor to get to talk to you today and pick your brain a little bit about some of these complex diseases. So, autoimmune neurology is certainly one of the most exciting subspecialties of our field. I feel like when I talk to students and they ask me to make a case for why they should consider neurology as a career, I tell them, “Of course, I have many reasons I love neurology”, but one thing I mention is that, although many other fields of medicine may have made incredible advances as far as treatments, I can't think of too many other fields outside neurology where entirely new diseases have been described since I've been in training and come out of training - and many of those have been in your field of autoimmune neurology. I can think of cases where I've heard you or one of your colleagues on a neurology podcast describing a new antibody, new disease, and a few weeks later, we see that disease and give a patient a diagnosis that had been elusive from other physicians and hospitals. It's a very exciting, gratifying area. It's also daunting, like, every time I go to the AAN and hear one of your colleagues, there's a new disease, and we realize, “Oops! Was I missing that?” or, “Am I going to see this?” And so, hoping to pick your brain a bit today about some of the key concepts and how to keep them in mind so our listeners can recognize, diagnose, and treat these conditions, even if they can't remember every single antibody in your article and all the new ones you and your colleagues will probably discover between now and when this, um, podcast is released. So, before we get into some of the important clinical aspects of these conditions, could you just lay out sort of the broad breaststrokes, the lay of the land of cell-mediated versus antibody-mediated paraneoplastic versus nonparaneoplastic cell surface versus intracellular - how can we sort of organize this area in our minds?    Dr Pittock: Yeah. It's complex, and it's really an evolving story. But the importance, really, from the perspective of the reader and the perspective of the clinician is that we're talking about disorders where we can actually do something - we can actually impact patients.  And we think about the concept of stopping and restoring in neurology now. We're talking about disorders where we have the potential to stop these inflammatory immune-mediated disorders and, potentially, by stopping early, we may be able to restore function - so, a really important new and evolving field in neurology, because you don't want to miss these conditions. Trying to get your head around the complexity of these entities is difficult, but what we've done in this chapter is, really, to try and lay the groundwork for the following chapters, but provide somewhat of a simplistic approach, but a practical approach that really, I think, can help clinicians. So, the way I think of it, a lot of autoimmune neurology really has stemmed from the discovery of antibodies that cause neurological disease, and the examples of those would be going back to myasthenia gravis (with antibodies to the acetylcholine receptor), going back to Lambert-Eaton syndrome. And then, you know, even if you go back to the older traditional paraneoplastic disorders (the Hu, the Ri, the Yo), at the end of the day, you really have two essential entities, if you want to be very simple. The first is disorders that are caused by an antibody, and the second are disorders where the antibodies you detect are not causing the disorder, but they're telling you that there's predominantly a cellular or T-cell mediated attack of the nervous system. And I think thinking about the diseases in those kind of simple terms helps us when we think about what would be the best treatment to use in these types of cases.   Dr Berkowitz: Fantastic. I think that's very helpful. And just to make sure it's clear in the minds of our listeners when we're dividing into these sort of causative antibodies versus antibodies that might be, uh (I don't know if I'm using the word properly), but, sort of epiphenomena (or they're present, but they're not causative) as you said, can you just give some examples of the ones on either side and how making this distinction helps us in practice?    Dr Pittock: Yes. So, antibodies that are causative of disease - I think, you know, the one that I've done a lot of work on is in neuromyelitis optica, where you have antibodies that are targeting a water channel that sits on an astrocyte, and so it causes NMOSD, or what we consider an autoimmune astrocytopathy. And we know that when the antibody binds to the target, many things can happen. So, when aquaporin-4 antibodies bind to aquaporin-4, they can do a lot of things. They can cause internalization, they can activate complement that results in the killing of the cell - but there can be other situations. For example, when NMDA-receptor antibodies bind to the NMDA receptor, then a variety of different things can occur different to water channel autoimmunity - where, for example, the receptor (the NMDA receptor) is downregulated off the cell surface, and that results, to some extent, in the neuropsychiatric phenomenon that we see in NMDA-receptor autoimmunity. And, obviously, when you have a situation where the antibodies are causing the disease, removal of those antibodies, or the reduction in the production of those antibodies, is going to help patients. Now, on the other side, we have antibodies that we detect in the blood or in the spinal fluid, and those antibodies are targeting proteins that are inside the cell - so those antibodies we don't consider as being pathogenic. Now, remember, there are sometimes situations where proteins that are inside the cell occasionally can be available for antibodies to bind at certain situations. So, for example, in the synapse, amphiphysin or the septins, may at times become available. And so, sometimes, there are targets or antibodies that are somewhat in between those two simplistic concepts. But when we're talking about antibodies that are targeting proteins on the inside of the cell, remember that antibodies don't just suddenly occur. There's a whole process of presentation of target antigen at the lymph node, and then both a T- and a B-cell response. The B-cell response potentially produces the antibodies but also triggers and stimulates T-cells, and those T-cells then go on to cause the disease. And those T-cells are very problematic, because those classical paraneoplastic and the newer ones we've described (and many have described) - these are associated with quite severe neurological disability, and they're very, very difficult to treat. And if you ask me, “Where is the holy grail of autoimmune neurology therapeutic research?” It's in trying to actually figure out ways of treating the predominantly T-cell mediated paraneoplastic and autoimmune neurological disorders. We're making great headway in terms of the treatments of the antibody-mediated neurological disorders.   Dr Berkowitz: That's a helpful overview. So, sticking with this framework, you mentioned as sort of the “causative antibody” category and the antibodies that are predominantly for intracellular antigens, but not believed to be causative - I want to make sure I'm understanding this correctly and we can convey it to our listeners - I believe you said in your paper, then, that the antibodies that are predominantly causative are more likely to be associated with conditions that are very treatable, as compared to the intracellular antibodies that are not thought to be causative, as you just said the disability can be irrecoverable or very hard to treat. And I believe another theme in your paper that you brought out is the antibodies that tend to be causative tend to be cell surface and tend to be less likely to be associated with underlying cancer (although not a perfect rule), and the intracellular antigens more commonly associated with cancer in those cases to look very hard for a cancer before giving up. Are those themes that I understand them from your paper properly, or anything else to add there?    Dr Pittock: Yes, I think that that's exactly the message that we were trying to get across, so that's good news that you've picked up on the themes. I think, yeah, in simple terms, remember that when a cytotoxic T-cell identifies the peptide that its T-cell receptor will target, the ultimate outcome is poor, all right? T-cells are like the marines - they don't mess around. Once they find their target, they eliminate that target, and so, it's really difficult to treat those types of diseases if you get them late. And most patients with cytotoxic T-cell mediated paraneoplastic neurological disorders, oftentimes, by the time they get to a center of excellence, the boat has left the dock in many respects - in other words, it's too late. So, you know, I will often see patients, for example, with progressive cerebellar degeneration (say, in the context of Purkinje cell autoantibody type 1 antibodies and a breast cancer), and if those patients are in a wheelchair at the time that I see them, there's very, very little that we can do. So, you really want to try and get that patient into the office, you know, when they're using a cane (or not), and then, potentially, you have the opportunity - using very aggressive immunosuppressive medications - to make a difference. And that is quite different to other scenarios, where, for example, if you have NMDA-receptor encephalitis - as many of the readers will know, this is a condition that is very treatable, and most patients do very well, because the antibodies, they're disrupting function, but they're not killing the neuron, as we see in those more aggressive, paraneoplastic cytotoxic T-cell mediated diseases.   Dr Berkowitz: Also, in terms of searching for an underlying cancer, another theme in your paper as I understood (but want to make sure I'm understanding and conveying to our listeners and hear your thoughts), that the cell surface and treatable antibody-mediated syndromes, as you mentioned (NMO, NMDA) tend to be less associated with underlying cancers (although can be), whereas the intracellular antigens, um, a much higher percentage of those patients are going to end up having underlying cancers. Is that correct, or any notable exceptions to be aware of in that framework?    Dr Pittock: Yeah, I think the major exception to the rule for the antibodies that are targeting intracellular antigens is the GAD65 antibody story. We generally don't consider the stiff person syndrome, cerebellar ataxia, or other autoimmune neurological disorders associated with very high levels of GAD65 antibodies - those are generally not paraneoplastic. And then there are always exceptions on both sides. You know, one of the benefits of understanding the implications of certain antibodies is trying to understand, you know, what is the likelihood of identifying a malignancy, which antibodies are high-risk antibodies (in other words, high-risk paraneoplastological disorders), and which are low risk in terms of cancer? And, you know, age and the demographic of the individual is often important, because we know, for example, with NMDA-receptor antibodies, the frequency of ovarian teratoma varies with the age of the patient.   Dr Berkowitz: Fantastic. And we encourage our listeners to read your articles – certainly, some very helpful tables and figures that help to elucidate some of these broad distinctions Dr Pittock is making - but just to summarize for the antibody-related part of autoimmune neurology, we have one category of cell-surface antibodies and another of intracellular antibodies. Both can cause very severe and varied neurologic presentations, but the cell surface tend to be more treatable, less likely to be associated with the underlying cancer, and the intracellular less treatable, more likely to be associated with the underlying cancer - but, as with everything in neurology and medicine, exceptions on both sides. Is that a fair aerial view of some of the details we've discussed so far, Dr Pittock?    Dr Pittock: Yeah, I think so. I mean, I also think that, you know, not only, at least, for the antibody-mediated disorders (you know, as we discussed) we have drugs that will reduce the production of those antibodies, but we're also learning a lot more about the cytokine and chemokine signatures of these disorders. For example, NMO, water-channel antibody-mediated diseases are associated with elevated levels of IL-6. We know, for example, in LGI1 encephalitis and other encephalitides, that IL-6 also is elevated at the time of that encephalitic process. And so, the potential to target IL-6 with, you know, drugs that inhibit IL-6 and the IL-6 receptor, these potentially have, you know, a role to play in the management of these types of patients - whereas in the T-cell mediated disorders, you know, no advance has been made in the treatment of those conditions, I would say, in over 50 years. So, for example, the standard of treatment is steroids and then drugs that impact the bone marrow, and so we really haven't moved forward in that respect. And that, I think, is an area that really needs drive and enthusiastic out-of-the-box thinking so that we can try to get better treatments for those patients.   Dr Berkowitz: This has been a helpful overview. I look to dive into some of the scenarios that frontline practitioners will be facing thinking about these diseases. An important point you make in your article is that autoimmune and antibody-mediated neurologic syndromes can affect any level of the neuraxis. Even just our discussion so far, you've talked about anti-NMDA receptor encephalitis, you've talked about myasthenia gravis (that's at the neuromuscular junction), you've talked about paraneoplastic cerebellar degeneration - there can be an “itis” of any of our neurologic structures and that “itis” can be antibody-mediated. So, one of the key messages you give us is, one, that these are sort of in the differential diagnosis for any presenting neurologic syndrome, and, two, sort of one of the key features of the history, really, to keep in mind (since we could be anywhere along the neuraxis) is the subacute presentation when this should really sort of be top of mind in our differential diagnosis - so, many of these patients are going to be mystery cases at the outset. And one striking element you bring out in the paper is that, sometimes, the MRI, CSF, electrophysiology studies may be normal or nonspecifically abnormal, and although it's very helpful when we can send these antibody panels out, in some cases, resources are limited or institutions have certain thresholds before you can send these out (because neurologists love to send them in). Sometimes, they are not necessarily appropriate. So, love to hear your thoughts on when we should be sending these panels. What are some clues? Um we have a subacute neurologic presentation at any level of the neuraxis, and when it's not anti-NMDA receptor encephalitis, that is sort of a clear phenotype in many cases. How you would approach a patient, maybe, where the MRI is either normal or borderline abnormal (or people are squinting at the medial temporal lobe and saying, “Maybe they're a little brighter than normal”), CSF is maybe normal or nonspecifically, um, and the protein is a little high, but no cells? What clues do you use to say, you know, “These are the patients where we should be digging deep into antibody panels and making sure these are sent and not miss this diagnosis?”    Dr Pittock: Well, thank you. That's a good question. So, I think, you know, first of all, these are complex cases. So, the patient is sitting in front of you and you're trying to figure out, first of all, Is this a hardware or a software problem? Are we definitively dealing with an encephalitis or an organic neurological entity that's immune-mediated? And, you know, the way I think of it is, for me, you see a patient, it's a twenty-five-piece jigsaw puzzle and you've got two pieces, and you're trying to say, “Well, if I step back and look at those two pieces, do I have any sense of where we're going with this patient?” So, the first thing you need to do is to collect data, both the clinical story that the patient tells you (and I think you make the good point that that subacute onset is really a big clue), but subacute onset, also fluctuating course, sometimes, can be important. The history of the patient - you know, Is the patient somebody who has a known history of autoimmune disease? Because we know that patients that have thyroid autoimmunity are more likely to have diabetes, they're more likely to have gastrointestinal motility or dysmotility, they're more likely to have a variety of different immune-mediated conditions. So, is there a family history or a personal history of autoimmunity? Is the patient at high risk for malignancy? Are there clues that this potentially could be a tumor-initiated immune process affecting the nervous system? The neurological exam also is extremely important because, again, that helps you, first of all, kind of define and get some objectivity around what you're dealing with. So, does the patient have hyperreflexia? Are there signs that there is neurological involvement? And then, really, what I think we need to do is to try and frame the predominant neurological presentation. So, what is the major issue? Because a lot of these patients will have multiple complaints, multiple symptoms, and it's very important to try and identify the major presentation. And that's important, because the neural autoantibody tests are now presentation-defined - in other words, they're built around the neurological presentation, because the old approach of just doing, apparently, a plastic evaluation is gone, because we've got to a stage where we have now so many neural antibodies, you can't test every single neural antibody. So, if you're suspecting that there may be an autoimmune neurological component, then you really need to think about what would be the most appropriate comprehensive evaluation I need to do for this patient. So, for example, if a patient comes in with a subacute-onset encephalopathy, you're probably going to want the autoimmune encephalitis evaluation, and then you have to pick whether it's going to be serum or spinal fluid - and as we outlined in the paper, there are certain antibodies that are better detected in serum versus spinal fluid. So, for example, in adults over the age of 50, LGI1 is much more accurately detected in serum than spinal fluid, and the absolute opposite is true for NMDA-receptor antibody detection. One of the most important components of the neurological evaluation is the spinal fluid, but actually looking at the white cell count - and in fact, sometimes, it's quite interesting to me that I'll often see patients referred with a diagnosis of encephalitis and autoimmune encephalitis, and yet they haven't had a spinal fluid examination. So, the presence of a white cell count, you know, greater than five is hugely helpful - it's like two pieces of that twenty-five-piece jigsaw, because that really tells you that there is something inflammatory going on. And now, in terms of imaging, you're right - some patients will have normal MRI. And if you really do think that there's evidence of - you know, for example, you do an MRI, but you're getting a good sense that there's a temporal lobe seizure occurring, MRI looks normal, the EEG shows some abnormalities in the mesial temporal area - you know, considering additional imaging modalities (like PET scan of the brain), I think, is reasonable. We know that in NMDA-receptor encephalitis cases, 30% of patients will have normal MRI but they'll often have abnormalities on the PET scans. So, I think, what we do is we try to gather data and gather information that allows us to add in pieces of that jigsaw so that, eventually, after we've done this evaluation, we can see now we have ten pieces. If we step back, we say, “Yes, now we know what this condition is”, and then we essentially plan out the therapeutic approach dependent on what we've found. In terms of identification of underlying malignancy, you know, different people have different approaches. Our approach generally has been to try to get a PET-CT scan of the body as our first go-to test, because, actually, we found that CT chest abdomen and pelvis really actually delivers the same amount of radiation - and from a cost perspective, it's about the same - and we have found that PET-CTs really do provide a higher sensitivity for cancer detection.   Dr Berkowitz: Perfect. A lot of very helpful clinical pearls there. So, in closing, Dr Pittock, I've learned a lot from you today. I'm sure our listeners will as well. What does the future hold in this field? What's coming down the pipeline? What are we going to be learning from you and your colleagues that are going to help us take care of patients with these diseases going forward?    Dr Pittock: Well, thank you, Dr Berkowitz, for that question. I think the future is very bright and very exciting, and, hopefully, some of the more junior members will be enthused by this Continuum series, and, hopefully, we'll go into this area. So, let's talk about the future. The future, I think, is going to be of great interest. Firstly, there's going to be continued discovery of novel biomarkers, and the reasons for that is because of the technical and technological advances we've seen. So, for example, there have been many, many antibodies discovered by us and others that have been discovered on the basis of, for example, phage technology. In fact, the Kelch 11 biomarker discovery in collaboration with UCSF and our group was done on the basis of Joe DeRisi and Michael Wilson's phage approach. And we're actually using that now at Mayo Clinic, and we've discovered about three or four new antibodies just in the last couple of years using this technology (and that here is led by John Mills and Div Dubey). And then, we're also going to see, I think, the evolution of protoarrays much more in biomarker discovery, so, we'll have more antibodies, and again, I think, generally, those antibodies will fall into the two categories we kind of described - so, you know, in terms of the approach to those conditions, maybe not so much change. I do think, though, that the introduction and the utility of comprehensive cytokine and chemokine analysis in the future will assist us in making diagnoses of seronegative encephalitis, but also potentially will direct therapy. So, for example, cytokine A is elevated - maybe that would be a potential target for therapy that's available for these patients with rare and potentially very disabling disorders. Then, when we look at the cytotoxic T-cell mediated disorders, I think the major areas of advance are going to be in better understanding the immunophenotype of cytotoxic T-cell mediated diseases, and then the potential development of tolerization strategies using the specific targets, those specific epitope targets that are involved in paraneoplastic and nonparaneoplastic diseases, and seeing if we can vaccinate patients, but move that immune response into more of a tolerogenic immune response rather than a cytotoxic killing response. And then I think, lastly, we're going to see a dramatic revolution in CAR-T therapeutic approaches to these types of disorders moving forward - and not just, you know, CAR-T therapies that are targeting, you know, CD19 or CD20, but CAR-Ts that are actually personalized and developed so that they can target the specific B- and T-cells in an individual patient and actually do a very fine removal of that autoimmune pathologic process that I think would have significant benefit for patients not only in stopping progression, but also in significantly reducing the potential of side effects - so, a much more targeted approach. So, that's where I think the next ten years is going to be. I think it's very exciting. It's going to require the collaboration of neurologists with, you know, immunologists, hematologists, you know, across the board. So, a very exciting future, I think, for this field.    Dr Berkowitz: Exciting, indeed. And we have learned so much from you and your colleagues at the Mayo Clinic about these conditions, and I definitely encourage our listeners to read your article on this phenomenal issue that really gives us a modern, up-to-date overview of this field and what's coming down the pipeline. So, a real honor to get to speak with you, pick your brain about some of the clinical elements, pitfalls and challenges, and also hear about some of the exciting signs. Thank you so much, Dr Pittock, for joining me today on Continuum Audio.   Dr Pittock: Thank you very much.    Dr Berkowitz: Again, today, I've been interviewing Dr Sean Pittock, whose article with Dr Andrew McKeon on an introduction to autoimmune neurology and diagnostic approach 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 so much 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.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Eoin P. Flanagan, MBBCh, FAAN who served as the guest editor of the Continuum® August 2024 Autoimmune Neurology issue. They provide a preview of the issue, which publishes on August 1, 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. Flanagan is a professor of neurology at Mayo Clinic in Rochester, Minnesota. 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 Guest: @EoinFlanagan14 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, 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 have access to exclusive audio content not featured on the podcast. If you're not already a subscriber, we encourage you to become one. For more information, 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 Eoin Flanagan, who recently served as Continuum's guest editor for our latest issue on autoimmune neurology. Dr Flanagan is a neurologist at Mayo Clinic in Rochester, Minnesota, where he's a professor of neurology. Eoin, why don't you introduce yourself to our listeners?   Dr Flanagan: Yeah, it's a great pleasure to be here today. I'm a neurologist. I'm originally from Ireland – I did my medical school training over there, and then came over to the Mayo Clinic to train in neurology and in neuroimmunology. And delighted to be able to edit this exciting issue of autoimmune neurology of Continuum. I think, um, it's a really fascinating area that's moving very quickly, and I'm hoping that we can educate listeners to be able to feel comfortable when they come to see these patients and to realize how much of a growing specialty it is and how we're getting treatments, and we can really help these patients.     Dr Jones: Yeah, it's a pretty exciting area. And, so, not only are you the Guest Editor for our latest issue of Continuum, this is the first-ever Continuum issue dedicated to autoimmune neurology, so I want to thank you for taking it on. This is something that our readers have been asking for for many years. I hope the topic wasn't too daunting.   Dr Flanagan: No, absolutely, it's a pleasure to be able to do it, and it's just great when you read all the articles to kind of feel where the field is going and how much of  a benefit we can now make for our patients. So, that's been a real joy to do.   Dr Jones: Well, congratulations, and it's a magnificent issue. You have a lot to be proud of putting this group of authors together. So, for a few of our issues now, we've had the opportunity on the Continuum Audio podcast to interview the Guest Editor, which is really fun for me. I have to confess it's really a joy to talk to someone who is up to the minute not only in their narrow area of expertise at the article level, but, really, across the entire breadth of the subspecialty. And so, you've had an opportunity to delve into all relevant topics in autoimmune neurology. When you look at the issue as a whole, or the field as a whole, what do you think the biggest debate or controversy in the world of autoimmune neurology is right now?     Dr Flanagan: Yeah, I think there's some changes happening. You know, initially, people used to recognize a disease called Hashimoto's encephalitis, where patients would have a presentation of encephalitis in the setting of thyroid antibodies. And what we're now realizing is that many of these patients actually have antibodies to neural-specific targets, because we know that the antibodies that target the thyroid don't really impact the brain. And what we're now realizing is that there's many antibodies out there that bind to different receptors in the brain (the NMDA receptor, for example, AMPA receptor), so we're really trying to refine the field towards these different antibody-associated disorders - and each different disorder may behave very differently. A patient with NMDA receptor encephalitis, for example, may be in the ICU, in hospital, may take them six, nine months to recover. On the other hand, a patient with LGI1-antibody encephalitis may get five days of steroids and be almost back to normal within a few weeks. So, it's a really broad spectrum. And, I think, what we're now learning is that each antibody has a role in helping define the disease, guide your treatment, guide your search for cancer - but, also, they behave differently - so these neural-specific antibodies are really important, while the older antibodies (like the thyroid antibodies) may just be a bystander and something that's happening in the background in a patient who's more prone to autoimmune disease.   Dr Jones: Very helpful, and I think that resonates with our listeners who have taken care of patients with autoimmune neurologic disorders, and it really is, I think, a great prototype in our specialty, maybe (for lack of a better word) of how observations start at the bedside, and then discoveries are made at the bench, and those benefits are brought back to patients. You know, there's been a recognition of autoimmunity in neurology for a long time, right - responsiveness to immunosuppression, even before the biomarkers were discovered - tell us a little story about how that works for our listeners.    Dr Flanagan: Yeah, so, I think one of the first steps is defining a clinical syndrome. So what you'll find is that some of these syndromes (for example, neuromyelitis optica spectrum disorder, where they have longitudinally extensive lesions within a spinal cord) provoked people to be interested that these looked different to MS, and then that went to the lab, and the aquaporin-4 antibodies were discovered - or, more recently, MOG antibodies were discovered. The aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder is a good prototype, because that went to the laboratory. Initially, they saw complement deposition on the pathology of these patients, they saw antibody deposition - the antibody was then discovered to aquaporin-4. And then, many labs around the world went to their own labs and they tried to delve in to determine what the pathogenesis was, and they found that complement was important in cell killing, that interleukin-6 elevation was important, and that complement appeared to be important. So, then, what they did was they tried to find treatments that would target those pathways. So, and now, we have treatments that are successful for this disease that can target complement, target interleukin-6, and target B cells (be it CD19 or CD20). So, we now have many different treatments, and this disease used to be very severe (so, had a 33% mortality at five years), and now these patients can live a long life with these treatments. So, I think that gives you an example of how you can follow the immunology of the disease and use targeted treatments to help our patients, and I think we can use that as a good prototype for many of   the other antibodies, because every year we discover two to three new antibodies, and each disease is a bit different in its mechanism. So, there are now clinical trials in NMDA receptor encephalitis starting up. There's clinical trials in MOG antibody-associated disease. And I think we're going to see that as we move forward, that these treatment trials will come and we'll be able to help our patients better with proven treatments that we know work, rather than a history of we would just use five days of steroids and then we didn't know exactly what to do in the long term - and we could manage some of the relapse as well, but we couldn't really take care of the disease in the background - so, I think the NMO is a good model for moving forward, and the pharmaceutical companies are supporting moving forward with different trials for the disease.   Dr Jones: So, a key message there is understanding the biology so we can be a little more targeted and less indiscriminate in the immunomodulation we're going to use. And we have parallels to that in the neuromuscular world, right, like using B-cell depletion for MuSK-associated neuromuscular junction disorders, as opposed to the trial-and-error approach, right? That's got to be a little more patient-centric and you get to a therapeutic response faster, right?   Dr Flanagan: I think so. Yeah, and I think, in the future, that might be something where, you know, a different patient, if they had elevated cytokines that pointed more to an IL-6 elevation, then maybe, in that patient, you would target IL-6, while the next patient with the same disease has more prominent complement activation, maybe you would target complement, or another patient has more prominent B-cell markers elevated, that you would target B cells. So, I think, we're really moving towards a more individualized treatment in some of these disorders. So, it's a very exciting time, but we've only really made that breakthrough in one of the antibodies, and we have probably sixty, seventy antibody-mediated disorders now. So, it's going to get complicated, but it's also going to be, really, an exciting time for our patients, and I think an exciting time for neurology trainees and people who see patients in practice that we can now make diagnoses and guide their treatment that, previously, you know, these patients were told they might have presumed infectious encephalitis or we didn't know the exact cause.   Dr Jones: So targeted not only to the diagnosis, but to the individual.   Dr Flanagan: Yeah.   Dr Jones: So, that's a level of complexity that I think is going to blow a lot of our minds, right? And it's exciting, but I think it also is a little daunting, right?   Dr Flanagan: Absolutely. Yeah. Yeah, it's going to be complicated, and these are rare diseases, so they're difficult to do clinical trials in. But I think we can be guided, and our experience tells us that if you follow the mechanisms, that you can find targeted treatments. Now, you can also find targeted treatments in MS - you know, it took us a longer time to find successful high-efficacy treatments, but now we're doing much better with many high-efficacy treatments available. But, I think in these autoantibody-mediated diseases, really looking at the mechanisms and trying to figure out that and then targeting the treatment in that direction makes the most sense and is the most likely to be successful.   Dr Jones: So, one of the purposes of Continuum is to educate our readers and our listeners, and because neurology is so broad, because it is evolving so quickly,   it's really hard to stay current. And so, again, that's part of the purpose of the journal. I think one of the challenging areas is autoimmune neurology, because it changes fast, and it's complicated, and the treatments are high stakes and complicated to administer - so, I think this is an important topic. I know from my own experience in clinical practice, one of the challenging scenarios is you see   a patient who may have an autoimmune neurological disorder, you obtain some serum or CSF markers of neurologic autoimmunity, right? And of the ten antibodies you check, one of them comes back, and it's a low titer-positive antibody. I know that's something that you get a lot of questions about. How do you approach that?     Dr Flanagan: Yeah, I think, you know, we're all neurologists, and, you know, it's immediately back to the history, the examination, and the investigations, and what do they support - so, are you really dealing with an antibody-mediated disorder? And I think, from a neuroimmunology laboratory standpoint, we're always trying to get better tests, remove those less-specific tests (so, move away from the thyroid peroxidase antibodies) and really hone in on the exact targets and their mechanisms. So, I suppose, when you find a low-positive result, it's really important to go back to that clinical. And, I think, you know, that is job security for neurologists, right? Because you really have to interpret these in context. And, I think when you're seeing autoimmune cases, you need to have a good, broad understanding of differential diagnosis, because there are many different disorders that can present in a similar way, and you don't want to get distracted by that low-positive antibody and then put a patient on long-term immunosuppression that has many different risks. So, there is a potential for misdiagnosis, and I think that's an emerging area that we're recognizing that we always have to put the antibodies into clinical context. And, you know, there are more and more studies coming out that will help guide you, and I think the issue in Continuum will help guide you in terms of your understanding of, you know, what does a positive antibody mean? And it'll give a little bit on the methodology of how the antibodies are tested and how that can help you – or, sometimes, be it the titer may be very high that can help you. So, different aspects of the antibody test results can also help guide you in the likelihood of that being kind of a true positive versus a false positive. But I think always back to the history, exam, and the investigations, too.   Dr Jones: You're being very gracious there, and I'm glad you bring it up that it's really not just about the laboratory performance of the test, right? It's about the pretest probability of the clinical syndrome if it doesn't clinically resemble an autoimmune neurological disorder. So, I'm not going to pretend to be an expert in Bayesian statistics, but I think we should recognize that if we obtain any test when there's a low likelihood of the syndrome or the diagnosis being present, we're more likely to have false positives than in other scenarios or other settings. So, I think that is a charge to the clinician, where if we are obtaining these tests, we do really need to think about the likelihood of there being a clinical autoimmune neurology syndrome, right?   Dr Flanagan: That's exactly right. You know, one of the teachings that I sometimes give to the trainees is that, you know, if you have a ninety-year-old patient with mild cognitive impairment who comes into the emergency department with some worsened altered mental status, you know, you want to check for a urinary tract infection, you want to check a chest x-ray - you don't want to test neural antibodies upfront. So, you always have to consider the setting and avoid overtesting, because like any test, they're not perfect, and you can run into trouble if you order it too frequently - so, that's another thing that we try to educate people. And then if you do order the test, we like to educate people on, you know, what the positive test results mean, and is there any potential for false positives like we talked about?   Dr Jones: And I think, keeping in mind - obviously, there are exceptions - but the subacute onset of multifocal neurological disorder is really suggestive of autoimmunity. It doesn't mean that it can't happen in other contexts. And it has been exciting not only on the diagnostic side, but on the therapeutic side. There are so many exciting new treatments. What do you think is on the horizon beyond what we've seen in the last few years with small- and large-molecule therapies for these disorders?     Dr Flanagan: Yeah, I think there's new things. You know, people are always looking at different approaches. So, for example, there's a lot of interest in tolerance, and is there a way you could tolerize yourself out of some of these autoimmune conditions? There's a lot of work on CAR-T treatments, looking particularly in the field of lupus and other systemic autoimmune diseases, and I suspect that they will also be applied to autoimmune neurologic conditions. And then the other thing to mention is that we're seeing the more frequent use of immune checkpoint inhibitors in patients with lots of different types of cancers, including neuroendocrine tumor. So I think, in the future, everybody's going to have to learn about autoimmune neurology, because we're going to be seeing these patients more often, because there's going to be more neurologic immune-related adverse effects related to those immune checkpoint inhibitor treatments – so, I think we're going to continue to see autoimmune neurologic disorders pop up. And, you know, the immune checkpoint inhibitors are almost real-world laboratory experiments, because you're ramping up the immune system, and you can trigger many different types of autoimmune conditions. We're actually learning a lot from these patients that can help us in the way we diagnose and the way we treat these patients in the future, but I will say that, sometimes, they can cause a challenge, because some of these patients have difficult-to-control cancer - you need to up their immune system, but then they get autoimmune complications. We try and dampen down the immune system, and then we need to kind of ramp it back up to treat the cancer. And we've had some challenges where managing such cases can be difficult with that balance of cancer-directed immunotherapy versus immune-related adverse events, and, sometimes, that can pose a challenge for autoimmune neurologists when we see these patients.   Dr Jones: So, those are challenges, and I imagine it's a challenging and often rewarding field. What is the most rewarding thing about caring for patients with autoimmune neurological disorders?     Dr Flanagan: I think it's a few things. You know, one is that it's a multidisciplinary area,   so many of these patients will have different subspecialties of neurology involved. So, we'll get to work with our colleagues, and we may work with our oncology colleagues, we work with our ophthalmologist, and we work with our physical medicine and rehab team – so, it's a real team approach to help the patient. So, that's one aspect that's very enjoyable, because everybody needs to work together. And then, you know, these are treatable conditions. So we can have patients who are in the intensive care unit - you know, quadriplegic, in a coma - and then we treat them, we see them back, and they can be back close to normal. So, particularly, with some of these antibodies that target the cell-surface receptors (like NMDA receptor encephalitis, MOG antibodies), these patients can really go from being really, really sick in the ICU to coming back to normal – so, that's very satisfying, and much of that is related to the improvements we have in treatments, and then we can manage them in the long term with some of these newer treatments that are coming along for these diseases. So, I think it's a very exciting area and exciting time for our patients with these disorders, and we're getting more and more clinical trials, so we're hoping that we'll have more and more treatments available into the future.   Dr Jones: I think that has to be part of why the interest in autoimmune neurology has grown so much. I know as an educator - I hear this a lot from trainees - you know, the level of interest in MS and autoimmune neurology has really only grown over time. It must be because of better understanding of the pathobiology of disease, better treatment options, and something that our listeners may not know. Not only is Dr Flanagan an expert in autoimmune neurology - he's very well trained, he did fellowship in MS and autoimmune neurology, and behavioral neurology, right?   Dr Flanagan: That's correct. Yeah. Yeah.   Dr Jones: And, you know, it's going to sound like I'm trying to flatter Eoin here, but I'm really not (this is going to lead to a question). Eoin is, you know, very well recognized for his work in autoimmune neurology and discovery in this area. Uh, he happens to be one of the best doctors I know. And Eoin, you've won the Teacher of the Year Award several times. So, for our listeners who are looking into their careers and trying to manage multiple areas of interest, how do you do it? You do so many different things so well.   Dr Flanagan: Well, you know, I'm lucky to have had the opportunity to work here at the Mayo Clinic and in the neuroimmunology lab. So, we have a lot of resources, and it's an exciting area, you know? We need to bring up the next generation of leaders, so we need to be enthusiastic about these conditions, and we really can do a lot for these patients. So I think when I cover on the hospital service - you work with the residents or work with the fellows and clinic - you know, these cases (when they come around) are really enjoyable to see you can get an answer, we can figure out what type of treatment to do, and we can really help these patients. So, I think that makes it a very exciting area and an easy area to teach residents and to convey some of the excitement that's happening in the field. So, it's just a great honor to be able to work with trainees to kind of let them know the field. And, you know, there's more and more fellowship opportunities in different centers in neuroimmunology, and I think more residents are becoming interested in the field of autoimmune neurology because of so much happening. But, in saying that, with these challenges, it's very hard to keep up with all these antibodies - I find it hard. There's 70 different antibodies - it's hard to know every single thing about every single one. So, we need to continue to educate, to try and simplify, to try and help our younger people be able to manage these patients, because no matter who it is in neurology, you're going to encounter these patients - if you cover the hospital, if you see regular patients in clinic, if you do consult service, you'll come across these patients - and we're going to see them more and more with immune checkpoint inhibitors and other treatments coming along. So, I think it's an exciting area, and it's an important area for everyone to be aware of. So, it's just a great pleasure to be able to be involved in the field and see such enthusiasm in junior people.   Dr Jones: So, in addition to doing all those things well, you're also very humble. So, that's a great answer, and I think it is important - even though these are collectively rare - the opportunity to treat these patients and have wonderful outcomes is great, and I think the ability to recognize and feel comfortable. And, hopefully, Continuum has a place in that. I think your issue, Dr Flanagan, is a stellar issue and, uh, will be a benchmark for a generation of neurologists and how to approach these disorders. So, I want to thank you for being our Guest Editor for that topic and joining us today for such a thorough and fascinating discussion on autoimmune neurology.   Dr Flanagan: Thanks so much. And thank you to the Continuum team for highlighting autoimmune neurology. It's an exciting field, and I think, really, there is a great group of authors that cover neuroimmunology comprehensively, and I think, hopefully, people will enjoy the edition.   Dr Jones: Again, we've been speaking with Dr Eoin Flanagan, Guest Editor for Continuum's most recent issue on autoimmune neurology. Please check it out. And thank you to our listeners for joining today.     Dr Monteith: This is doctor 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. Thank you for listening to Continuum Audio.

Use AI to Speed up Your Work Flow Ethically and Securely. There are lots of courses on AI out there, but this one is specific only to medical writing and editing.  Access the AIMWE course waitlist. https://www.learnamastyle.com/waitlist/ Leqselvi for Alopecia Areata: The FDA has approved deuruxolitinib (Leqselvi) as a first-line treatment for adults with moderate to severe alopecia areata (AA). Developed by Sun Pharma, this oral selective inhibitor of Janus kinases JAK1 and JAK2 is typically dosed at 8 mg twice daily. The approval, based on the THRIVE-AA1 and THRIVE-AA2 trials, marks an important addition to limited treatment options for AA, which has significant psychological impacts. Femlyv Dissolvable Birth Control: The FDA has approved norethindrone acetate and ethinyl estradiol (Femlyv) as an oral dissolvable birth control pill, expanding access for those who have difficulty swallowing. This form of hormonal birth control, in use since 1968 as a swallowable tablet, also helps manage conditions like endometriosis and PMDD. The approval, based on a study of 743 women, offers a new option with common side effects like headache and nausea. Brineura for Batten Disease: The FDA has expanded the indication for cerliponase alfa (Brineura) to treat neuronal ceroid lipofuscinosis type 2 (CLN2 disease) in children under 3 years of age. Developed by BioMarin Pharmaceutical, this enzyme replacement therapy, initially approved in 2017, is administered by infusion into the brain. The expanded approval was based on a phase 2 trial showing reduced motor function decline and delayed disease onset. Erzofri for Schizophrenia: The FDA has approved paliperidone palmitate (Erzofri) extended-release injectable suspension for treating schizophrenia and schizoaffective disorder in adults. This long-acting injectable (LAI) antipsychotic, administered once a month, improves patient adherence by reducing dosing frequency. Developed by Luye Pharma Group, it was granted a U.S. patent in 2023 and approved under the 505(b)(2) pathway. Eque-cel for MS: The FDA has approved the IND application for equecabtagene autoleucel (Eque-cel) for treating multiple sclerosis (MS). Developed by IASO Biotechnology, this chimeric antigen receptor autologous T cell injection showed promising efficacy in six autoimmune diseases in a Chinese trial. MS, affecting 3.07 million people worldwide, is characterized by CNS demyelination and neuronal injury, with Eque-cel offering a new treatment option. Spravato for TRD: Johnson & Johnson has submitted an sNDA for esketamine (Spravato) as a monotherapy for adults with treatment-resistant depression (TRD). Already approved in combination with an oral antidepressant, esketamine is an NMDA receptor antagonist that rapidly alleviates depressive symptoms. The submission is based on Phase 4 TRD4005 study results, showing rapid improvement in depression scores with a consistent safety profile. ZW191 Anti-Tumor Agent: The FDA has cleared the IND application for ZW191, a novel antibody-drug conjugate (ADC) targeting folate receptor alpha (FR⍺) in cancers like gynecologic and NSCLC. Developed by Zymeworks, this TOPO1i ADC uses a novel payload, ZD06519, showing robust antitumor activity and a tolerable safety profile in preclinical models. Clinical development of ZW191 is planned to begin in the second half of 2024.

Neste episódio falaremos do aminoácido Glicina. Este audio é uma aula rápida e prática do nosso curso BrainBoost, mais de 50 suplementos para seu cérebro. ENTRAR LOGO NESTA BAGAÇA: https://drdupr.at/bb O que esperar deste episódio? O que é a glicina? Onde encontramos ? Pq suplementar? Como pode impactar nosso sono ? Artigos Dicas práticas referências: (Kawai N, 2015)     Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi: 10.1155/2017/1716701. Epub 2017 Mar 1. Erratum in: Oxid Med Cell Longev. 2022 Feb 23;2022:9857645. doi: 10.1155/2022/9857645. PMID: 28337245; PMCID: PMC5350494.   McCarty MF, O'Keefe JH, DiNicolantonio JJ. Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. Ochsner J. 2018 Spring;18(1):81-87. PMID: 29559876; PMCID: PMC5855430.   Zafra F, Aragón C, Olivares L, Danbolt NC, Giménez C, Storm-Mathisen J. Glycine transporters are differentially expressed among CNS cells. J Neurosci. 1995 May;15(5 Pt 2):3952-69. doi: 10.1523/JNEUROSCI.15-05-03952.1995. PMID: 7751957; PMCID: PMC6578198.   Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, Takeda T, Bannai M, Nishino S. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015 May;40(6):1405-16. doi: 10.1038/npp.2014.326. Epub 2014 Dec 23. PMID: 25533534; PMCID: PMC4397399.   Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 2007;5:126–131.   Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahashi M. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 2006;4:75–77.    Cruz M, Maldonado-Bernal C, Mondragón-Gonzalez R, Sanchez-Barrera R, Wacher NH, Carvajal-Sandoval G, Kumate J. Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes. J Endocrinol Invest. 2008 Aug;31(8):694-9. doi: 10.1007/BF03346417. PMID: 18852529.     Müller P, Dammann HG, Bergdolt H, Simon B. Einfluss von Glycin auf die gastroduodenale Verträglichkeit von Acetylsalicylsäure. Eine endoskopisch kontrollierte Doppelblindstudie an gesunden Probanden [The effect of glycine on the gastroduodenal tolerability of acetylsalicylic acid. An endoscopic, controlled double-blind study in healthy subjects]. Arzneimittelforschung. 1991 Aug;41(8):812-4. German. PMID: 1781803.   Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, Cárdenas ML. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. J Biosci. 2009 Dec;34(6):853-72. doi: 10.1007/s12038-009-0100-9. PMID: 20093739.

About the guest: Christoffer Clemmensen, PhD is scientist running the Metabolism & Molecular Pharmacology group at the University of Copenhagen in Denmark. His lab studies the biological basis of obesity & other metabolic disorders.Episode summary: Nick and Dr. Clemmensen discuss: GLP-1 & gut hormones; obesity & metabolic disease; GLP-1 agonists and weight loss drugs (e.g. Ozempic); novel, dual-action weight loss drugs his lab has created; and more.Previous discussion: Metabolism, Obesity & Psychedelics for Metabolic Disease | Christoffer Clemmensen | #105*This content is never meant to serve as medical advice.Support the Show.All episodes (audio & video), show notes, transcripts, and more at the M&M Substack Try Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase.Try SiPhox Health—Affordable, at-home bloodwork w/ a comprehensive set of key health marker. Use code TRIKOMES for a 10% discount.Try the Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for $50 off.Learn all the ways you can support my efforts

BUFFALO, NY- June 5, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 10, entitled, “Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats.” Aging is associated with a decrease in N-methyl-D-aspartate (NMDA) receptor function, which is critical for maintaining synaptic plasticity, learning, and memory. Activation of the NMDA receptor requires binding of the neurotransmitter glutamate and also the presence of co-agonist D-serine at the glycine site. The enzymatic conversion of L-serine to D-serine is facilitated by the enzyme serine racemase (SR). Subsequently, SR plays a pivotal role in regulating NMDA receptor activity, thereby impacting synaptic plasticity and memory processes in the central nervous system. As such, age-related changes in the expression of SR could contribute to decreased NMDA receptor function. However, age-associated changes in SR expression levels in the medial and lateral prefrontal cortex (mPFC, lPFC), and in the dorsal hippocampal subfields, CA1, CA3, and dentate gyrus (DG), have not been thoroughly elucidated. In this new study, researchers Linda Bean, Prodip K. Bose, Asha Rani, and Ashok Kumar from Indiana University School of Medicine, North Florida/South Georgia Veterans Health System, and the University of Florida aimed to determine the SR expression profile, including protein levels and mRNA, for these regions in aged and young male and female Fischer-344 rats. Their results demonstrate a significant reduction in SR expression levels in the mPFC and all hippocampal subfields of aged rats compared to young rats. No sex differences were observed in the expression of SR. “These findings suggest that the decrease in SR levels may play a role in the age-associated reduction of NMDA receptor function in brain regions crucial for cognitive function and synaptic plasticity.” DOI - https://doi.org/10.18632/aging.205841 Corresponding author - Ashok Kumar - kash@ufl.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205841 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, serine racemase, hippocampus, medial prefrontal cortex (mPFC), NMDA receptor About Aging-US Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer's disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Wondering what the ADA is doing for you lately?  Well let's go straight to the source to find out.  We were very appreciative that Dr. David Manzanares was willing to sit down with us to discuss all things organized dentistry.Dr. David J. Manzanares, a general dentist in Albuquerque, New Mexico, is the First Vice President of the American Dental Association. Dr. Manzanares has been a member of the ADA since 2009.Dr. Manzanares served as member to the ADA Council on Communications, where he was also Chair of the Volunteer Engagement Program and the Council Self-Assessment Committee, as well as part of the Spokesperson Review Committee and the Integrated Marketing Workgroup. He is also a graduate of the ADA Institute for Diversity in Leadership.Dr. Manzanares is involved with numerous other dental organizations, including the New Mexico Dental Association (NMDA), Albuquerque District Dental Society (ADDS) and Academy of General Dentistry. An engaged member of the NMDA, Dr. Manzanares previously served as Secretary-Treasurer from 2015 to 2022, chaired several committees and was the Albuquerque Representative of the NMDA Board of Trustees from 2013 to 2015. He was also a member of the Board of Directors for the NMDA Foundation. Starting in 2020, he became part of the New Mexico Dental COVID- 19 Advisory Team. From 2009 to 2015, he was a delegate of the NMDA House of Delegates and continues to be on the NMDA Council on Government Affairs. His other duties include serving as Secretary-Treasurer of the Southwest District Dental Society from 2010 to 2011, and he has served as Advisor to the Leadership Board with the ADDS since 2015.Dr. Manzanares is a Fellow in both the International College of Dentists and the American College of Dentists and was awarded with both a Fellowship in 2015 and a Mastership in 2018 from the AGD. He is a graduate of both the Dawson Academy and the Piper Education and Research Center.Originally from Espanola, NM, Dr. Manzanares attended the University of New Mexico as a Regent's Scholar, graduating in 2005. He graduated from the University of Missouri-Kansas City School of Dentistry in 2009. He has also served as the pre-dental advisor at New Mexico State University and was a faculty member at Dona Ana Community College, teaching radiology to dental hygiene students. Dr. Manzanares comes from a dental family; his father, Dr. Robert Manzanares, was president of the NMDA from 2010 to 2011 and his younger brother, Dr. Michael Manzanares, is also a dentist.

Contributor: Travis Barlock MD Educational Pearls: Ketamine is an NMDA receptor antagonist with a wide variety of uses in the emergency department. To dose ketamine remember the numbers 0.3, 1, and 3. Pain dose For acute pain relief administer 0.3 mg/kg of ketamine IV over 10-20 minutes (max of 30 mg). Note: There is evidence that a lower dose of 0.1-0.15 mg/kg can be just as effective. Dissociative dose To use ketamine as an induction agent for intubation or for procedural sedation administer 1 mg/kg IV over 1-2 minutes. IM for acute agitation If a patient is out of control and a danger to themselves or others, administer 3 mg/kg intramuscularly (max 500 mg). If you are giving IM ketamine it has to be in the concentrated 100 mg/ml vial. Additional pearls Pushing ketamine too quickly can cause laryngospasm. Between .3 and 1 mg/kg is known as the recreational dose. You want to avoid this range because this is where ketamine starts to pick up its dissociative effects and can cause unpleasant and intense hallucinations. This is colloquially known as being in the “k-hole”. References Gao, M., Rejaei, D., & Liu, H. (2016). Ketamine use in current clinical practice. Acta pharmacologica Sinica, 37(7), 865–872. https://doi.org/10.1038/aps.2016.5 Lin, J., Figuerado, Y., Montgomery, A., Lee, J., Cannis, M., Norton, V. C., Calvo, R., & Sikand, H. (2021). Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study. The American journal of emergency medicine, 44, 306–311. https://doi.org/10.1016/j.ajem.2020.04.013 Stirling, J., & McCoy, L. (2010). Quantifying the psychological effects of ketamine: from euphoria to the k-Hole. Substance use & misuse, 45(14), 2428–2443. https://doi.org/10.3109/10826081003793912 Summarized by Jeffrey Olson MS2 | Edited by Jorge Chalit, OMS II

In Part 2 of the Excitation and Inhibition phenomena, we discuss Metabolic "bank" account and demands of navigating the social world. We discuss if we have enough resources or if we will run a metabolic deficits (think burnout and avoidance, and social isolation). We cover NMDA and AMPA and different Autistic Phenotypes. In addition, we review Neuromodulators, which are vast in our biology and determine how and where to direct our attention and energy. Lastly, we discuss the medial Prefrontal Cortex and how it integrates the "self" with the outside world.Don't try to change an Autistic person because they are different than you or different than others. Don't let that offend your beliefs and capacity to apply critical thinking in life.https://www.nature.com/articles/s41398-023-02317-5https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723386/https://www.nature.com/articles/s41398-018-0155-1https://www.nature.com/articles/nature10360https://onlinelibrary.wiley.com/doi/full/10.1034/j.1601-183X.2003.00037.x?sid=nlm%3Apubmedhttps://www.nature.com/articles/s41380-022-01506-w(0:00) Introduction; Know Autism and Make Informed Decisions; Biological Aspects influencing Excitation / Inhibition Phenomena(4:30) Metabolic "Bank" Account and Resources; E/I creates criteria A and B; NMDA and AMPA, and more on the Striatum(10:02) Neuromodulators- Serotonin, Dopamine, Epinephrine and Norepinephrine, Acetylcholine; Active versus Passive Coping; Activating Systems and Cells and influencing Learning and Memory (Neuroplasticity); Nicotinic Receptors and Rapid-Excitation(15:20) medial Prefrontal Cortex (mPFC)- Metabolic demands and planning while considering Feelings, Integrating the Self and the Outside World; How E/I interacts; a brief explanation on Default Mode Network; Quieting the Body, or not; Information-Processing; Thalamocortical(20:19) Pursuits and Preference- Wanting and Having and being Autistic is fine, and others need to accept our phenotypes; sensory-input causes Faster Firing Rates in normal E/I- Image an imbalanced E/I(22:25) Wrap-up and understanding Autism, and Contact Info

Historically a range of psychiatric and medical conditions have been erroneously attributed to 2 gynecological organs/function. During the time of Hippocrates, the “wandering womb” theory blamed emotional disturbances in women on this condition. Not only was that erroneous, it was nonsensical. However, certain gynecological conditions can indeed manifest with neuro-behavioral disturbances. One of these syndromes can be triggered by the presence of an ovarian dermoid. Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a paraneoplastic limbic syndrome which may be caused by ovarian teratomas containing neural components. Neural tissue in a teratoma can trigger the production of anti-NMDA-R antibodies, which causes neuronal dysfunction and loss by altering the neuronal cell-surface NMDA receptors in the limbic system. This syndrome presents with a range of psychiatric, neurological and autonomic features and if not promptly recognized and treated may be associated with long-term morbidity and mortality. Rare…yes. But it is out there in the community and patients are at HIGH risk of misdiagnosis. In this episode we will discuss this “Brain on Fire” syndrome and highlight a real case contributed by one of our podcast family members (HIPPA protected).  

Ketamine, once known as an anesthetic and recreational drug, has evolved into a revolutionary mental health treatment. With a complex mechanism of action on the brain's NMDA receptors, ketamine shows promise in addressing conditions like Treatment-Resistant Depression (TRD), PTSD, and chronic pain. Administered in clinical settings, its rapid efficacy contrasts with the gradual effects of SSRIs. The unique "psychedelic" experience it induces sets it apart, making it a beacon of hope for those seeking alternatives beyond conventional treatments. https://ketamineclinics.com/ https://www.instagram.com/thesammandel/ Instagram: https://www.instagram.com/cupofnurses/ Website: https://fanlink.to/CONsite Shop: https://fanlink.to/CONshop Free Travel Nursing Guide: https://fanlink.to/Travelnursingchecklist Nclex Guide: https://fanlink.to/NCLEXguide Interested in Travel Nursing? https://fanlink.to/TravelNurseNow Cup of Nurses FB Group: https://www.facebook.com/groups/cupofnurses YT: https://www.youtube.com/@CUPOFNURSES

Lake Conferenceレポート、DJ Clubなどについて雑談。論文紹介は、intrabodyベースの順行性モノシナプティックトレーサ、CSとUSが離れた味覚嫌悪条件づけの神経基盤、授乳期の骨形成を担うホルモンの発見、ライティング時の注意に関するエッセイ (10/14収録) Show Notes (番組HP): Lake Conferences トゥーンでの開催 ASCONA Pico Caroni Silvia Arber Rainer Friedrich 元ボス ゲオルグ Rui Costa DeepLabCutのMathis Brain Behavior Observatory (BBO) IBL Enhancer-AAV その１ その２ その３ 千歳さん 第一回論文紹介 SfNでの発表 トーラスの発達含め他のポスター群も面白そう 脇 エントライナルを潰しても場所細胞は残る by ロイトゲブ・ロイトゲブ  ムシモルじゃなくてNMDA lesionでした 萩 エントライナルのグリッドの形成が場所細胞の形成より遅い Leutgebのレビュー NR(Nucleus Reuniens)からの場所情報コード acuteでのdisruptionはリマッピングにしか影響なさそう 脇 Ilana Witten AndreasラボのCTA論文 Zimmermanさん Scott Sternson Yuki Oka Zachary Knight 一番搾りの写真 五十嵐さん 吉良さん Hide Inagaki氏 Rajesh Raoさん Predictive Codingの伝説的なNN論文 古館さん回 1 2 Arisの論文　2012 Neuronはゲオルグ筆頭のやつでした… 脇 DJ Club 新築の建物 Dissect Podcast In Rainbows High and Dry 実際の歌詞は don't leave me high/dry なのですが、なんか通じましたね笑　-確かに！ Don't let me downのルーフトップコンサート　Let it beセッションの収録だがGet backのB面 SpotifyでPodcastの中に音楽埋め込みができる Spotifyのドキュメンタリードラマ 戦場ポスドク氏回 Ofer Yizher のTwitterで外人ポスドクがEvacuateしている様子 Harvardが声明文出すの遅くて抗議されていた 論文紹介パート 論文１：ATLAS: A rationally designed anterograde transsynaptic tracer Don Arnoldラボ AAV1 YFV-17D NeuroRadioで扱った回 Intrabodyとは 10th Fibronection Type 3 mRNAディスプレイ(in vitro virus)の根本先生による日本語解説 FingR論文 使われているAnti-Creの抗体 AAV2-rgのトロピズム、これのTable S2 論文２：A neural mechanism for learning from delayed postingestive feedback Richard Palmiter Parabrachial CGRP がCTAに効いてるというNeuronの仕事 慈恵の渡部さん の仕事 Hailan Huの2報 1 2 (と言ってたら10/18に続報がまたNに) リチウムはこれとHailan Huが混乱してた感じが 萩 ジョセリンのexcitability-based allocation selection 同じ路線の質問応答をマークのポスドクとイラーナがtw上でやってた。cAMPはありそう。萩 Mark Andermann MarkAndermannの興味が(Sリバレスとのコラボで)そちらに向いてた 遅れて反応するVTA細胞もいるというZachKnightの仕事 論文３：Brain-Derived CCN3 Is An Osteoanabolic Hormone That Sustains Bone in Lactating Females Ingrahamラボ Amrosiラボ Ingrahamラボの前報 冬眠っぽい表現型が出るセルタイプ 宮道先生 のグループによるARC Kiss1の閉経後ダイナミクス 苅郷さん 論文４：Point of View: Beware ‘persuasive communication devices' when writing and reading scientific articles 日本の時にやってた仕事 Orchestrateしてるかは怪しい仕事 RabiesのSci Adv論文、supplementary notes Natureのアブストの書き方指南 この前の北沢さん回 Editorial Notes: 風邪治りたてで喉がダメでした…すみません。15 Stepって一発録りだったんですね（脇） 爆発音ビビりました。銃声より全然デカかった。記念に残してます。(萩)

Contrary to the common notion that focus issues are exclusively tied to ADHD, emerging research underscores the critical role of magnesium in cognitive function. Low levels of magnesium have been shown to profoundly affect focus, learning abilities, and impulse control in both children and adults. Magnesium, an essential mineral, plays a vital role in numerous physiological and neurological processes, making it a compelling avenue for addressing attention and focus challenges beyond the scope of ADHD. Studies have begun to shed light on how magnesium deficiency may manifest as attention difficulties and cognitive impairments, paving the way for a deeper exploration of this mineral's potential in enhancing mental wellness and focus.And as we aim to explore safe and scientifically-backed natural solutions for enhancing focus and mental well-being, we will focus on magnesium's benefits for individuals with ADHD.Magnesium supplementation for ADHD symptoms, treatment and management.Scientific evidence strongly suggests that low serum levels of magnesium are linked to ADHD. This crucial information warrants widespread sharing and dissemination, especially among those caring for individuals with ADHD. Understanding the association between magnesium levels and ADHD prompts the important question of why magnesium levels aren't routinely checked in individuals with ADHD. Magnesium plays a key role in this by aiding neurotransmitter regulation, dispelling the misconception that only pharmaceutical interventions can positively impact brain function. Natural strategies such as proper nutrition, physical exercise, PEMF, and neurofeedback also contribute to neurotransmitter regulation, emphasizing the importance of exploring safe and natural options. The recommended intake is up to bowel tolerance, but consulting a healthcare provider and choosing the right kind of magnesium supplement is essential. Fortunately, Multi-Mag brain formula is a reliable source of magnesium, containing magnesium threonate and glycinate, a form rarely found in other supplements due to cost and dosage challenges. You can read more about magnesium threonate and glycinate here: https://drroseann.com/magnesium-threonate-vs-glycinate/The benefits of magnesium for ADHD are backed by clinical evidence, demonstrating its effectiveness in reducing hyperactivity, inattention, impulsivity, and impulsive behaviors. It has also been shown to help reduce restlessness and aggression resulting in improved sleep quality as it provides a calming effect on the body, aiding in emotional regulation and mood support which then leads to reduced sleep disturbances. Magnesium's role in brain function and learning.Magnesium supplementation is advocated for people of all ages, including children, due to its essential role in brain function. That is why it is essential to have magnesium readily available and accessible in every household, as it is a vital nutrient for overall well-being, particularly brain health. Magnesium also contributes positively in brain functioning and learning by regulating essential brain chemicals and communication systems, facilitating focus and enhancing the learning process in children. It positively impacts NMDA receptor modulation, crucial for proper cognitive functioning, attention, and learning abilities and supports synaptic plasticity, ensuring optimal flexibility and balance in brain activity, ultimately aiding in attention and learning. Furthermore, magnesium exhibits a notable crossover into the realm of neurofeedback by influencing brainwave regulation. While neurotransmitters often take center stage in discussions about brain health, understanding and addressing brainwave communication are equally significant. Research...

Magnesium, my all-time favorite brain nutrient, not only helps boost the immune system but even our mental health. Its significance is amplified in today's stress-filled environment, making it a valuable component for overall well-being.The good news is that there are many safe and natural ways to calm the brain and support and today, we're here to empower parents by exploring more about magnesium and how it plays a crucial role in enhancing mental well-being. Magnesium's role in brain health and inflammation reduction.Magnesium significantly supports brain health through several key mechanisms. Firstly, it helps regulate calcium levels within neurons, preventing neurotoxicity associated with excessive calcium influx. This is vital in managing conditions linked to overstimulation, including anxiety and depression. Magnesium also modulates the NMDA receptor, contributing to a balanced nervous system.Moreover, magnesium plays a critical role in stress hormone regulation, particularly cortisol. Chronic stress can lead to persistently elevated cortisol levels, impacting overall well-being. To battle this, magnesium helps regulate cortisol activation, promoting a healthier stress response.In terms of neurotransmitter function, magnesium aids in serotonin production and function, influencing calcium pathways. Often overlooked, magnesium's impact on gut health is essential for serotonin production, challenging the common notion that only psychiatric medications affect serotonin levels.Additionally, magnesium's anti-inflammatory properties are crucial in reducing neural inflammation. Inflammation is linked to various mental health conditions, and magnesium helps mitigate brain inflammation, a vital aspect of maintaining optimal brain health.Incorporating magnesium into daily supplementation can provide these benefits and address the common prevalence of neural inflammation. Monitoring its effects through pre and post brain mapping can offer valuable insights into its effectiveness in managing brain health. Understanding these aspects of magnesium underscores its significance in promoting a balanced and healthy brain.Neuroplasticity, magnesium, and GABA for cognitive function and mental health.Magnesium positively impacts synaptic neuroplasticity, a key element essential for memory, learning, and overall cognitive performance. At the core of memory consolidation, learning mechanisms, and broader cognitive performance lies this vital component. Its significance in neuroplasticity, the brain's remarkable adaptive capacity, cannot be emphasized enough. Magnesium emerges as a potential stimulant in influencing cognitive function, offering exciting possibilities to enhance the complex operations of the brain. By boosting neuroplasticity, magnesium demonstrates its potential as a major contributor to improving cognitive abilities. This points to a hopeful pathway for individuals aiming to enhance mental sharpness and intellectual potential.Additionally, magnesium enhances GABA functioning, an inhibitory neurotransmitter that promotes relaxation and inhibits excitatory neurotransmitters. This calming effect can be particularly beneficial for individuals, especially children, dealing with anxiety and depression. Magnesium's role in mental health and wellness.Magnesium offers significant brain protection by preventing various forms of brain damage. Chronic stress, known to cause brain damage, triggers an excessive release of cortisol, disrupting the brain's equilibrium. To maintain optimal brain health, it's crucial to nourish the brain with the right nutrients, manage stress, and adopt a healthy diet. Magnesium supplementation becomes essential, especially for individuals with genetic mutations impacting nutrient utilization. This vital mineral plays a role in balancing blood sugar...

Magnesium, often described as a powerful mineral, has a lot of benefits. Its impact extends far and wide, influencing everything from energy production to nerve function, muscle regulation, heart health, and even mood regulation. In today's episode, I'm excited to delve into the fascinating role that magnesium plays in optimizing communication within our brain, consequently enhancing our overall mental well-being. It's truly remarkable how this mineral, often underestimated, holds a pivotal position in ensuring that our cognitive functions operate at their best. Magnesium's benefits for a holistic approach to brain health and mental wellness.I have long been an advocate for magnesium and its varied health benefits. However, we have to emphasize that not all magnesium supplements are the same. That is why my focus is on L3 and L8 glycinate, backed by research for a holistic approach to brain health and mental wellness. Magnesium plays a crucial role in energizing our cells and facilitating the conversion of food into energy, primarily by aiding ATP production. This function is paramount in promoting and maintaining cellular health, ensuring that our body's fundamental units are supplied with the necessary energy to carry out various biological processes. Research strongly suggests that magnesium is excellent for long-term cardiac health, underscoring its pivotal role in supporting the heart muscle. The heart, being a vital organ responsible for pumping blood and supplying nutrients throughout the body, requires optimal functioning to maintain overall health. Magnesium steps in as a key player in this process, aiding in muscle relaxation and contraction, maintaining a steady heartbeat, and ensuring the heart's efficient performance. Moreover, it modulates NMDA receptors, crucial for memory and learning, emphasizing its significance in brain function. It also quickly calms neurotransmitter communication, offering noticeable effects, making it easier to incorporate into daily routines. As for the improvement of brain flexibility, magnesium enhances neuroplasticity. This also helps develop stress resilience and overall cognitive function. In fact, it's been shown to guard against neurodegenerative conditions like Alzheimer's, offering a simple preventive measure.Magnesium supports neurotransmitters, aiding in mood stability and providing much-needed emotional support. And in our stressful world, magnesium offers a science-backed solution to combat stress and its adverse effects on mental health. Low magnesium levels are associated with migraines, and magnesium supplementation can play a role in their prevention.Magnesium stands out as a personal favorite when it comes to enhancing the quality of sleep and facilitating the onset of a peaceful night's rest. Its effectiveness in promoting relaxation and soothing the nervous system has positioned it as a pivotal supplement for those seeking restorative sleep. By aiding in calming the mind and body, magnesium sets the stage for a restful night by easing any tension or anxiety that may interfere with the ability to fall asleep. Additionally, this essential mineral plays a significant role in neurotransmitter regulation, a critical factor for maintaining a well-functioning sleep cycle. Magnesium's capacity to diminish overstimulation within the brain represents a transformative element, supporting the health of brain cells and cultivating a sense of mental calmness conducive to achieving ideal sleep. Magnesium's role in blood sugar control and mood regulation.I believe we often overlook the crucial connection between blood sugar regulation and mood. Those infamous 'hangry' commercials hit close to home because my own children experience mood swings when they're hungry, struggling to maintain consistent energy levels. Magnesium, an often underestimated mineral, plays...

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities, and episodes originally aired from 2016 to 2021. Originally released: July 12, 2018 It seems like a new antibody in autoimmune central nervous system disorders is being discovered every day. Well, maybe not that frequently. But autoimmune encephalitis may now be as common as infectious encephalitis. In this week's program, we revisit an episode from 2016 where Dr. Ramani Balu (neurocritical care) shares his experience in evaluating and managing patients with these conditions. Produced by James E Siegler. Music by Three Chain Links, Lee Rosevere, and Kevin McLeod. Sound effects by Mike Koenig. Voiceover by Erika Mejia. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision-making. REFERENCES Anderson NE, Barber PA. Limbic encephalitis - a review. J Clin Neurosci 2008;15(9):961-71. PMID 18411052Dubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018;83(1):166-177. PMID 29293273Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69(5):892-900. PMID 21416487Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77(2):179-89. PMID 21747075Rosenfeld MR, Dalmau JO. Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis. Continuum (Minneap Minn) 2012;18(2):366-83. PMID 22810133Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012;79(11):1094-100. PMID 22933737Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157-65. PMID 23290630 We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

Episode 152: ALS FundamentalsFuture Dr. Rodriguez explains the symptoms of ALS, including UMN and LMN symptoms. Dr. Arreaza discusses the principles of symptomatic treatment by primary care. This is a brief introduction to ALS.  Written by Adraina Rodriguez, MSIV, Ross University School of Medicine.  You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Arreaza: It is rare but you may encounter it and you should be able to identify the most common symptoms. ALS Challenge in 2014: Ice bucket challenge. Adriana: Patrick Quinn was an ALS patient and activist who created the ICE Bicket Challenge and helped raise US$220 million for medical research.Arreaza: What is ALS?Adriana: ALS stands for Amyotrophic Lateral Sclerosis, formerly known as Lou Gehrig's Disease. It is the most common form of acquired motor neuron disease. ALS is a progressive, incurable neurodegenerative motor neuron disorder with Upper motor neuron (UMN) and/or Lower motor neuron symptoms that cause muscle weakness, disability, and eventually death. There is no single diagnostic test that can confirm or entirely exclude the diagnosis of motor neuron disease. Arreaza: When should you suspect ALS in a patient?Adriana: The classic patient presentation is insidious, slowly progressive, and unremitting UMN and/or LMN symptoms present in one of four body segments - cranial/bulbar, cervical, thoracic, and lumbosacral - followed by spread to other segments over a period of months to years. Arreaza: What would you see on the physical exam when the Patient is in the clinic? There is a system to send signals from your brain to your muscles. It involves basically two neurons: Upper and lower motor neurons. The UMN goes from your cerebral cortex to your spinal cord and there it connects to a lower motor neuron through synapsis. The LMN then sends the signal to your muscles, causing contraction or relaxation. Tell us about the UMN and LMN symptoms.Adriana:LMN Symptoms: Weakness, Fasciculations, Muscular atrophy, Decreased muscle tone (flaccidity) and reduced or absent reflexes. UMN Symptoms: Increased tone and increased extremity deep-tendon reflexes, presence of any reflexes in muscles that are profoundly weak and wasted, pathological reflexes (crossed adductors, jaw jerk, Hoffman sign, Babinski sign 50%), syndrome of pseudobulbar affect (inappropriate laughing, crying, forced yawning).Arreaza: What are important factors to help narrow your differential to ALS?Multifocal motor neuropathy, cervical radiculomyelopathy, benign fasciculations, inflammatory myopathies, post-polio syndrome, monomelic amyotrophy, hereditary spastic paraplegia, spinobulbar muscular atrophy, myasthenia gravis, hyperthyroidism, and many others.There are pertinent negatives to look out for: Usually negative neuropathic or radiculopathic pain, sensory loss, sphincter dysfunction, ptosis, or extraocular muscle dysfunction (20-30% positive sensory symptoms or “pins and needles” and “electricity” in the affected limbs).Note: Cognitive dysfunction does not exclude ALSArreaza: What are the diagnostic criteria for ALSAdriana: Gold Coast Criteria 2019 proposed over El Escorial criteria:Progressive upper and lower motor neuron symptoms and signs in one limb or body segment, ORProgressive lower motor neuron symptoms and signs in at least two body segments, ANDAbsence of electrophysiologic, neuroimaging, and pathologic evidence of other disease processes that might explain the signs of lower and/or upper motor neuron degeneration.Arreaza: What diagnostic tests should be ordered for further evaluation?Adriana: Electrodiagnostic studies: Electromyogram and nerve conduction studies (EMG and NCS)Laboratory testing: creatine phosphokinase up to 1000u/LNeuroimaging: to exclude other causes mainly. Brain MRI whenever bulbar disease is present. Cervical and lumbosacral spine MRI for LMN findings in the arms and legs.Genetic testing: FALS 10% of ALS defect in C9ORF72 gene that makes motor neuron and brain nerve cell protein, the exact cause is unknown. Arreaza: Finally, how do you treat ALS?Adriana: Disease-modifying treatment: Riluzole is recommended for all patients with ALS. Shown to prolong survival and slow functional deterioration. The mechanisms of action that reduce glutamate-induced excitotoxicity: 1) inhibit glutamic acid release, 2) non-competitive block of N-methyl-D-aspartate (NMDA) receptor-mediated responses, 3) direct action on the voltage-dependent sodium channel. Arreaza: Riluzole is given 50 mg by mouth twice a day. It may cause drowsiness or somnolence, hepatic injury: Not recommended for patients with elevation of transaminases >5 times the upper limit of normal. It is recommended to monitor for hepatic injury and discontinue if there is evidence of liver dysfunction, such as hyperbilirubinemia.Adriana: Symptom-based management is the mainstay of treatment. You may involve a multidisciplinary team to treat the symptoms. For example: palliative, hospice, respiratory function management (Noninvasive Positive Pressure Ventilation vs mechanical ventilation.Arreaza: PCPs may be in charge of managing symptoms because you are the closest provider to the patient. Wherever available, it is recommended to refer your ALS patients to a specialized center. Many patients do not have availability to an ALS center or a neurologist, but they have you to manage their symptoms or complications.Adriana: Dysphagia: It is a common and distressing symptom. It is suggested PEG tube placement for patients with ALS with normal or moderate respiratory function who have dysphagia. It is controversial, some studies found no benefit on survival or quality of life and other studies suggest that it is safe to give a high-carb, hypercaloric diet to ALS patients. Arreaza: Spasticity: Use medications such as baclofen and tizanidine may be helpful, and botulinum injections are an option for those who are not responding to oral muscle relaxants. Adriana: Sialorrhea: Use medications such as atropine, hyoscyamine, amitriptyline, and scopolamine. If these medications are not effective or tolerated, used botox injections into the salivary glands. It is considered safe and useful for treating sialorrhea in patients with ALS. Botox is not only for wrinkles!Arreaza: There are many other symptoms that will require management, but you are invited to review your preferred source of information such as Up to Date, AAFP, or the ALS Association website. ______________________________Conclusion: Now we conclude episode number 152, “ALS Fundamentals.” You heard from future Dr. Rodriguez that ALS can present with upper motor neuron symptoms, such as spastic muscles and hyperreflexia; or lower motor neuron symptoms, such as flaccid and weak muscles. Some other symptoms include dysphagia, shortness of breath, difficulty talking, fatigue, thick mucus, and pseudobulbar affect. Dr. Arreaza explained that primary care physicians are in a special situation to help diagnose and treat the symptoms of ALS, especially in communities with limited access to an ALS center. You may need to involve a multidisciplinary team to improve the quality of life and possibly the survival of ALS patients. This week we thank Hector Arreaza and Adriana Rodiguez. Audio editing by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Galvez-Jimenez, Nestor and Colin Quinn, Symptom-based management of amyotrophic lateral sclerosis, Up To Date, updated on July 31, 2023. https://www.uptodate.com/contents/symptom-based-management-of-amyotrophic-lateral-sclerosis. Royalty-free music used for this episode: Good Vibes: Sky's The limit, downloaded on July 20, 2023 from https://www.videvo.net/ 

This is an episode of the Frontier Psychiatrists Podcast. It's a conversation between my Fermata team member, Chelsey, and Myself. This conversation is about us, at work, trying to understand neuroscience together. We recorded this one! An edited version of the transcript follows.Owen Muir, M.D.: So we were chatting about the amygdala, and if you want to ask me any questions about it, I can answer them and edit it together. And that's a podcast. Chelsey Fasano, BA: There's a lot of discussion in the field right now about location neuroanatomy or chemistry neurobiology. And I'm always thinking about how the two crossover, so we're talking about the up-regulation or down-regulation of the amygdala.What are the neurochemical aspects of how the amygdala would be up- or down-regulated?Owen Muir, M.D.: Neurochemistry is a great way of selling drugs and selling explanations that are easy to understand.When we talk about neurochemistry, we're talking about a synapse between two nerves that are trying to communicate. There's a tiny little gap, and the way a nerve communicates with another nerve cell is a neurotransmitter is released from one and floats its way across a tiny little gap, and then hits a receptor on the other side, and that creates a change in that subsequent cell, which makes it either more likely or less likely to fire.What's happening next is within that cell. There are intracellular changes that lead to an increasing likelihood of reaching an action potential and itself firing and effectuating the next change in its neighbor cells. We focus narrowly on neurochemistry, because we can look at and modify it.We're getting obsessed with answerable questions— not with important questions. For example, we don't give people “hyper-glutamate,” the excitatory neurotransmitter in the brain. They'll have a seizure. Those excitatory impulses open ion channels that cause immediate depolarization and firing of neurons. Uncontrolled depolarization leads to seizure and death. GABAergic drugs do the opposite thing. So, anything binding to the GABA receptor opens a chloride channel. Chloride's negatively charged.And that changes the inside of the cell's voltage to negative, which means it's less likely to fire because you need more glycine and glutamate to increase the voltage. GABA is safe to agonize, because you're not going to get a seizure—but withdrawal is dangerous because now you're more likely to fire in the absence of the GABA drug.We're focusing on other compounds like serotonin, norepinephrine, and dopamine, which functionally regulate the internal cellular environment, making firing more or less likely. And we focused on it because it's safer. We got obsessed with what we knew we could do and not immediately kill somebody— as opposed to what might actually be effective or is happening naturally because, on their own, our cells are firing and releasing neurotransmitters and pulling them back up and regulating their voltage without us messing with it at all.For example, the chemistry argument at the amygdala level is part of the story. But when we're talking about what information the amygdala is kicking out, it's really how fast it is firing. That's my kind of argument. It's a rhythm answer. If we looked at the stage plot for AC/DC and saw they had a lot of cables and started worrying about which cable plugged into the guitar as opposed to they are going to play in time --and you can replace the strings, the guitar, the cables. You do not have a good AC/DC show if they play at a time, and if they're playing in time, even if the guitar cuts out like bass drums, Angus is still locked in, and it rocks.We've focused on what's focused-on-able, not what matters.Chelsey Fasano, BA: The primary neurotransmitters of the amygdala are precisely the ones you were talking about!Owen Muir, M.D.: The n methyl D aspartate receptor is a binding site that modulates glutamine.Chelsey Fasano, BA: So that makes sense as to why ketamine would strongly affect PTSD since it works primarily on NMDA and GABA. That would downregulate the amygdala, which would help to buffer against the overactivity associated with PTSD and subcortical areas.Owen Muir, M.D.: The firing rate functionally comes down because each nerve in the amygdala firing becomes less likely by some amount. Chelsey Fasano, BA: Is the feeling something to this whole hippie thing of vibration and vibe?Owen Muir, M.D.: It's true at the level of the neurons in the brain. Yes. I think wavelength is an accidental term. I don't know. But it's the literal truth.Chelsey Fasano, BA: We know that neural firing from some research that I've read affects motor movements and speech patterns, and so there probably is some truth to the fact that upregulation of specific circuits is going to cause speech pattern and motor movement differences that are going to be the bodily rhythmic reflection of the brain activity. We would pick up a vibe because we all sense those things about each other through our brains.Owen Muir, M.D.: We're building a model of the vibe. I propose that a firing pattern represents everything in the brain. It's click click of one nerve group, right? And in the other person's brain, it's click click.But in our brains, we build a model of our click. And then, we make a model with clicks in our neurons of the other person. We're constantly building models of other people's minds in our minds with our pattern of firing. Then, we pick up signals from their motor movements and behavior. We're resynchronizing our model. with their model, and we're constantly just getting it a little bit wrong and getting back into sync, and what humans love is feeling in sync.When we dance, we're dancing in time. Like the guy who dances badly, we find displeasure. When we dance together, we find it joyous. When we're dancing to the beat, we enjoy that because our brains all represent the beat simultaneously. We can look and see and feel with high bandwidth sensory cortex and high bandwidth motor cortex that we are together, and that lets us not bump into each other when we're dancing and emotionally not bump into each other's feelings when we're communicating.The dopamine system, for example, which profoundly regulates ventral striatal activity around motor gating, is also implicated in not just motor gating but also the gating of behavior. Some of that behavior is our feelings, how we react to the feelings, and how we talk, think, or sing.This is how we can do things like lie to each other politely and not get enraged. Because there are times when someone lies to you, and it's bad, and how dare you lie to me. There are times when someone says, thank you so much for calling. And we recognize that their thanks may not be sincere.And both of us are definitely on the same page about that, but the underlying intent we have modeled for the statement is beneficent.We're both on the same page about that metadata, which is, oh, the person's lying to me, but it's because they care and want me to feel good. And so I'm going to think this lie is kind in this context, and in other contexts, my internal model was that they shouldn't have lied as opposed to should have lied.So it's not the lie; it's the intent that we model and can reconnect to that allows human behavior and motion. To go well. If someone's a lousy dancer because they have Parkinson's, you're not going to love it, even if you don't know they have Parkinson's, and you may feel more positively inclined to them if you understand they have a reason for it.But it doesn't feel good. We feel good when we move together.Chelsey Fasano, BA: We've had some discussions about this previously about you not valuing agreeableness or not liking that quality of when people pretend to be polite, and I tend to be more like that.And I think when I do that. Often, when I attempt politeness or I attempt positivity, even in a situation where things feel pretty dire, and I don't think that way, what I'm doing, my intention, is I'm trying to slow down the dance. I'm trying to introduce something to the dyad that I'm a part of that is not necessarily totally authentic in that I'm not feeling it at that moment, but I want both me and the other person to handle it.I desire. So, I create the desired state in affect, hoping the dance will move in that direction. It often works. If you fake it till you make it, and you choose grace, and you choose to give someone calmer and more positivity than you might feel like they deserve, they often follow suit by giving it back to you.Owen Muir, M.D.: What mentalizing and Peter Fonagy would say about this is like the way to do that most successfully because some people will interpret it because their experience and trauma, for example, as a lie—an aversive lie— and that'll create mistrust, and they'll get agitated, right?Like, how dare you be polite to me, right? For those individuals and people who like politeness, you can do the same thing: mark your intentions. I'm going to be polite now. It's just that much—set it up. “I am behaving in a way because I hope it will be helpful.”You can tell me if that's different from how it comes across. You can do whatever you want, and you have the spoonful of acknowledging the rationale for your behavior that gives them the additional information that you're doing it within the intent of XYZ, as opposed to just being polite. They can assume you're scamming them with your politeness.Because they're people who've been harmed, scammed, and traumatized by polite people who wanted to abuse them. Thus, politeness for them may be a signal of risk. And so it's the ability to mark that I wonder if politeness is the right way to go, but I will try it out. That is the kind of permission slip to behave; however, you need to behave and also eat if it goes poorly… in a tolerable way.“Wow, my politeness came across badly there. I can see by the look on your face that politeness was the wrong approach,” Then suddenly, they feel understood and don't want to argue with you anymore.Chelsey Fasano, BA: We've talked before about having a mini version of the other person in your head, which, according to this conversation, the mini representation of the person that we have would be not only our conceptions of them and abstract representations but be a literal rhythmic firing of neurons, which explains sort of emotional contagion and how you can feel someone else's feelings.Owen Muir, M.D.: Mirror neurons are a metaphor for mirror patterns of circuits firingChelsey Fasano, BA: When we're looking at different schools of therapy, and some people are saying all of the feelings that you're feeling are definitely counter-transference are all coming from your past. It sounds like what you're saying is that's not accurate. What is happening is that we're getting rhythmic representations of the person that are combining with the conceptions that we previously had of what those rhythmic representations mean to create a sort of mini person inside of us that then informs both Our immediate affect as well as our ability to predict another person's behavior across time.Owen Muir, M.D.: a million percent correct. So it's yes. Therapy is neuromodulation using the sensory experience of another plus the representation they have of us and the representations we have of them, and the desync/resync on repeat —is what therapy is. If you've seen projective identification when you come across that term, the ability to invoke in another person Psychodynamically a behavior that's true because of my ability as a human to create a model of you and perturb that model and react to the perturbances. I see it in a way that's in keeping with my internal representation.It's a fish swim in schools. They're not sending a letter to all the other fish in advance, being like, okay, so in second 17 — turn left. They're modeling all of the other fish and then swimming in context with the model and then adjusting the model in each fish, so there's the constant adjustment of how much the school is moving because we're all building models of the school and checking them with each of the nodes in the network.In therapy, you have a dyad that's doing the same thing. I move left, and I expect you to move right, and you move right as far as you move right. And then that hits or doesn't hit the model I have, and then we move back to the center and do it repeatedly. That's the misunderstanding that is the neuromodulatory agent in psychotherapy. Still, it's brain rhythms in both people's brains firing and then checking, and error checking against the visual sensory interpretation as presented to consciousness and heavily edited by subcortical structures that make that dance happen. It's the getting it wrong, just like in meditation, -- we're attending, losing the attention, bringing it back to the flame. And bringing it back to the flame is why we meditate, not simply “staying on the flame.” It's supposed to be challenging.It's better if it's hard because it's a workout. -- Therapy is better if it's hard because it's a workout. But it's not just for attention regulation; it's a process of re-syncing to better inter-human and intra-personal things because when you do it in therapy, you get to do it out in the world when the therapist isn't there to help. So, being a therapist who's a little bit wrong all the time and then gets back to it is the honest answer. Ta-da! How's that?Chelsey Fasano, BA: Good.Owen Muir, M.D.: Let's see if it turns into anything. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit thefrontierpsychiatrists.substack.com/subscribe

How to Get Superior Health with Dr. Matt Chalmers   In today's episode, our guest is Dr. Matt Chalmers. He is a health and wellness expert, author, and speaker who specializes in the areas of long-term wellness, nutrition, women's health, weight loss, athlete wellness, and holistic healing. He is also the author of the bestselling book “Pillars of Wellness,” which helps readers cut through the information overload about wellness, exercise, and diet to figure out the actions they can take that will have the greatest impact.  [2:30] Why should I listen to you?  Typically, the conversations I have with people revolve around important health issues. I specialize in various areas that conventional medicine may not address effectively, such as hormone therapy and cardiac prevention. Currently, my primary goal is to combat the opioid epidemic by leveraging the benefits of cannabis and ketamine. Many people either have misconceptions or limited knowledge about the tools we have to combat this crisis. [3:40] How did you arrive at this point? Can you share the journey that led you to confidently discuss this topic on a podcast?  It's actually quite amusing. I play the medical role in what's essentially a venture capital (VC) company. Our primary task involves evaluating various deals. We work extensively with NFL athletes because they often come across questionable deals and require someone to tell them when something isn't right. So, when someone brought us a cannabis-related opportunity, it piqued our interest. At first, we didn't pay much heed, assuming it was just another offering. However, it turned out that cannabis has incredible medical potential. In fact, it can alleviate pain in 64% of cases, which rivals opioids. This completely changed my perspective on cannabis. We realized that many people were missing out on its remarkable health benefits, primarily due to misconceptions or concerns about smoking or vaping. To address this, we employ a unique technology that allows users to benefit from cannabis without smoking, vaping, or ingesting it. This method provides pain relief without the psychoactive effects. For instance, I discussed in my TED Talk how I used these cannabis strips to help my 10-year-old son recover from surgery without experiencing a high. We've found great success in using this approach to manage pain for various medical conditions. This journey started as a response to the opioid epidemic, and we believe more people should be aware of these alternatives. [5:58] In your journey of doing this work, what sparked your passionate connection to it? Was it driven by personal experiences, childhood influences, or a desire to help a specific demographic in need? Interestingly, I have a personal connection to this endeavor, although it's not the primary reason for my involvement. I'll share that connection with you. Back in 2007, I was in a car accident that left me with a broken left foot, a fractured left femur, and my face meeting the car's dashboard, resulting in a severe concussion. To address the pain, I was prescribed opioids. Now, here's where it gets interesting: Due to the concussion, I completely forgot that I had already taken two of those pills, and I ended up taking two more. If I hadn't woken up and realized what happened, I could have been in a dire situation. So that incident is certainly part of my connection to this cause. But the primary reason I'm deeply committed to this mission is my network of connections and driven individuals who share this vision. I firmly believe that if you have the means to make a significant positive impact on people's lives and you choose not to act, it's a tragedy. I have the resources and the drive to make a difference, and I can't let that opportunity slip by. I understand firsthand the challenges faced by individuals in similar situations, and it's a matter of doing our absolute best because there aren't many people with the kind of access we have to make a meaningful change in this field. [7:56] So, considering that this concept has existed for a while, why do you think it's relatively unknown, and why aren't more people aware of these potentially life-changing treatments? First of all, cannabis has been unfairly demonized for a long time, which has created a lot of skepticism and hesitation around it. People tend to view it in a negative light. As for ketamine, it's a relatively recent discovery that it can effectively break addictions about 85% of the time. This breakthrough has only come to light in the last decade or so. Despite ketamine's extensive use in pediatric surgery for its safety, its potential for addiction treatment remained largely unknown. We're working to change that by bringing this knowledge to the forefront. While there are ketamine clinics here and there, not many people are aware of its potential in addiction treatment. What sets us apart is that we've developed a technology using sublingual strips that can deliver ketamine safely and effectively. This means we can reach more people and help them overcome addiction. As we continue to share this information through platforms like podcasts, we hope to create greater awareness and meet the growing demand for this groundbreaking approach, ultimately helping more individuals break free from addiction. [9:25] Could you explain what ketamine is? I've heard of it, but I'm not entirely sure what it is and how it works. Can you break it down for us? Ketamine serves a dual purpose – it's used for pain management and as an anesthetic to induce unconsciousness. The crucial difference is how opioids and ketamine affect the brain. Opioids impact various brain regions, including the one responsible for autonomic respiration, which controls breathing during sleep. The danger with opioids is that they can suppress this part of the brain, causing respiratory failure and, ultimately, death. That's the primary reason opioids are so deadly. On the other hand, ketamine doesn't interfere with the part of the brain that controls respiration. This is why it's considered a safer option. Ketamine has been a staple in the medical world for some time due to its safety profile, particularly in surgeries where it's used as an anesthetic. Ketamine works by targeting NMDA receptors in the brain. Think of your brain as a tangled string, and NMDA helps straighten it out. When used in a specific regimen, known as a ketamine cycle over several days, it can effectively flush out addictive behaviors. Some individuals have reported that after a five-day session, they experienced a significant reduction in their cravings and addiction, such as in the case of cocaine. In essence, ketamine offers a safer alternative for addiction treatment without the life-threatening respiratory risks associated with opioids. [15:56] How can we reconsider the demonization of substances like marijuana and psychedelics for potential benefits? It's fascinating how politics often shifts with public opinion and perception. When it comes to topics like medical cannabis, it's reassuring to see that the vast majority of individuals support expanding doctors' choices for patient care, especially when these alternatives are safer. Public sentiment can have a significant impact on motivating policymakers to contemplate changes in laws. Engaging in nationwide discussions and open dialogues on these topics can help dismantle any existing barriers and clarify misunderstandings. Individuals need to express their backing for policies that resonate with their principles and the welfare of the community. In doing so, we can offer guidance to our representatives and ensure they remain attentive to our shared aspirations and necessities. [21:10] What does life look like for you?  You know, it's one of those things when you're able to help somebody with something they've never had anyone else help them with. We do this with lives, and we do this with conditions like ulcerative colitis, and more. When you finally fix an issue that someone has been desperately struggling with, it's the most rewarding feeling you can experience. Helping someone in need is incredibly fulfilling, and I aspire to make a positive impact on as many lives as possible. I envision our work expanding beyond Dallas, reaching other areas such as California. We're also planning to offer online services. My goal for the next five years, looking ahead to 2027 or 2028, is to significantly reduce the number of deaths related to addiction. I believe we might see an increase in the next two or three years, possibly reaching around 150,000, but after that, we can make substantial progress.   [26:56] How do you envision your role in the future of this mission? Do you aspire to be the enduring face of this initiative, or are you open to passing the torch to someone else if it serves the cause better? This is just one facet of what I do. I'm passionate about many things, and I often speak about various topics in the medical field. For example, I frequently discuss hormones, which can be a hot topic. But the truth is, I've witnessed incredible transformations in people's lives by addressing hormone imbalances. It's remarkable how it can help with brain function and other health issues. As for being the face of this movement, I'll gladly do it as long as it benefits the cause. If someone else, maybe younger or more attractive, comes along and can take the reins, that's fantastic. I'm not possessive about it. My goal is to see this initiative reach its full potential. If I don't contribute to that, it would feel like a failure because, right now, this is my purpose to make a difference. [30:28] What promise did God make to the world when he created you?  I believe my gifts are strongly connected to an understanding of physiological function and a deep passion for improving health. My purpose seems to revolve around being a doctor for as many people as I can, dedicated to enhancing their overall health and wellness. In the grand scheme of all the things I've done, this aspect might be the most significant. How to connect with Dr. Chalmers Instagram: https://www.instagram.com/chalmerswellness Facebook: https://www.facebook.com/DrChalmers LinkedIn: https://www.linkedin.com/in/matt-chalmers  

Contributor: Travis Barlock MD Educational Pearls: Alcohol binds the GABA receptor, which produces an inhibitory response, hence the “depressive” effects of ethanol beverages. Over time, alcohol downregulates the GABA receptors, leading to unopposed glutamate activity. Given that glutamate is excitatory, this can lead to seizures. Alcohol also suppresses REM sleep; in patients with chronically suppressed REM sleep, the brain starves for dream sleep and it spills over into the wakeful state, inducing a dream-like state when someone is awake. The awake dream-like state of delirium tremens (DT) differs from alcohol hallucinosis Alcohol hallucinosis presents with visual hallucinations in a wakeful state DT presents with a generalized clouding of the sensorium and a dream-like state Treatment for DT is better achieved with phenobarbital due to predictable pharmacology Phenobarbital acts on GABA and NMDA receptors References 1. Davies M. The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci. 2003;28(4):263-274. 2. Fujimoto J, Lou JJ, Pessegueiro AM. Use of Phenobarbital in Delirium Tremens. J Investig Med High Impact Case Reports. 2017;5(4):4-6. doi:10.1177/2324709617742166 3. Walker, M. Chapter 13: iPads, Factory Whistles, and Nightcaps In: Walker, M, Why We Sleep. Scribner; 2017, pg. 272.  4. Zarcone V. Alcoholism and sleep. Adv Biosci. 1978;21:29-38. Summarized & Edited by Jorge Chalit, OMSII  

5.05 Hallucinogens (Types, Intoxication, and Withdrawal) Psychiatry review for the USME STEP 1 Exam. Hallucinogens are a diverse class of drugs that cause hallucinations and other symptoms. Common hallucinogens discussed in the podcast are LSD, marijuana, PCP, and ketamine. LSD activates serotonin receptors, causing visual and auditory hallucinations, time and reality distortions, mood elevation, and dilation of the pupils. No notable withdrawal symptoms. Marijuana acts as a depressant, stimulant, and hallucinogen. THC binds to cannabinoid receptors, increasing neurotransmitters like dopamine and serotonin. Intoxication symptoms include red eyes, anxiety, euphoria, increased appetite, dry mouth, paranoid delusions, and perceived slowed time. Mild withdrawal symptoms include irritability, depression, sleep problems, and decreased appetite. Heavy cannabis use in adolescence is linked to an increased risk of schizophrenia. PCP antagonizes NMDA glutamate receptors and activates dopaminergic neurons. Intoxication symptoms include increased pain threshold, agitation, hallucinations, nystagmus, ataxia, and tachycardia. No notable withdrawal symptoms. Ketamine is structurally similar to PCP and acts as a milder version. It causes hallucinations and dissociation and is used medically for analgesia.  

Over the past ten years, essential oils have gained tremendous popularity, partly because of their ability to make almost any environment smell better and do so without the harmful chemicals and compounds found in most air fresheners and candles. Yet, they do much more than make a room smell better. They have significant physiological effects depending on whether you inhale them, use them topically, or take them internally, including effects on your nervous system. A fascinating paper just published in the journal Molecules, titled The Effects of Essential Oils on the Nervous System: A Scoping Review, sheds light on the powerful effects of essential oils on our nervous system, with implications for both physical and mental well-being.Sattayakhom A, Wichit S, Koomhin P. The Effects of Essential Oils on the Nervous System: A Scoping Review. Molecules. 2023;28(9):3771. Published 2023 Apr 27. doi:10.3390/molecules28093771 The Impactful Essence of Essential Oils Essential oils are concentrated extracts derived from plants. They capture the plant's scent and flavor, or its "essence," which is packed with beneficial compounds. The aromatic compounds in these oils interact with your body's olfactory system and impact the limbic system, the part of your brain that plays a role in emotions, behaviors, and long-term memory. But it doesn't just stop there. Essential oils also directly impact your central nervous system, affecting your physiology and pathophysiology, impacting everything from stress response to cognition. An In-depth Look at the Research The study set out to provide a comprehensive view of the effects of essential oils on the nervous system, conducting a broad search across multiple databases and including both human and animal research in their analysis. They found that essential oils affect your: hypothalamus: The hypothalamus is responsible for maintaining homeostasis by regulating physiological functions such as body temperature, hunger, thirst, sleep, mood, and sexual behavior. It also directs the endocrine system through its control of the pituitary gland, thus influencing hormone secretion and playing a crucial role in maintaining circadian rhythmsGuyton, A. C., & Hall, J. E. (2011). Textbook of medical physiology. Elsevier Health Sciences. limbic system: The limbic system is a complex set of brain structures that is primarily involved in regulating emotion, behavior, motivation, long-term memory, and olfaction, with key components including the hippocampus, amygdala, thalamus, and parts of the hypothalamus. It also influences with the prefrontal cortex, contributing to decision-making and emotional processing, thus playing a crucial role in human behavior and psychological functionBear, M., Connors, B., & Paradiso, M. (2016). Neuroscience: Exploring the Brain. Wolters Kluwer. prefrontal cortex: The prefrontal cortex is essential for higher-order functions such as planning, decision-making, social behavior, personality expression, and moderating correct social behavior, often referred to as executive functions. It also plays a significant role in working memory and attention, enabling you to think, plan, and behave in socially acceptable waysMiller, E. K., & Cohen, J. D. (2001). An integrative theory of prefrontal cortex function. Annual review of neuroscience, 24(1), 167-202. For instance, essential oils can reduce the release of stress hormones like cortisol, decrease sympathetic (fight-or-flight) activity, and increase parasympathetic (rest-and-digest) activity. They can even distract patients from feelings of anxiety, stress, and pain, providing a natural alternative to pharmaceutical interventions. Moreover, essential oils interact with various neurotransmitter receptors, including gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), and serotonin receptors, which can lead to a range of effects, from sedation to stimulation and have implications for conditions s...

Major Depressive Disorder (MDD) is common psychiatric condition that causes significant disability and disease burden.  Treatment for this condition may require multiple medication trials.  Up to thirty percent of individuals with MDD do not receive adequate benefit from several antidepressant drug trials and are considered treatment resistant.  The management of treatment resistant depression (TRD) often requires novel approaches.  One such approach is to use N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine or esketamine.  This session will review the use of ketamine and esketamine for TRD. The information presented during the podcast reflects solely the opinions of the presenter. The information and materials are not, and are not intended as, a comprehensive source of drug information on this topic. The contents of the podcast have not been reviewed by ASHP, and should neither be interpreted as the official policies of ASHP, nor an endorsement of any product(s), nor should they be considered as a substitute for the professional judgment of the pharmacist or physician.

You're invited to the first AJP-RJ journal club! The media editors get together to discuss highlights of the December 2022 issue of the American Journal of Psychiatry Residents' Journal. We discuss various topics ranging from diabulimia, peducular hallucinosis, and anti-NMDA receptor encephalitis. 

In this episode, we discuss the evidence, safety, and place in therapy of Auvelity® (dextromethorphan-bupropion), a newly approved antidepressant with a unique mechanism of action and interesting pharmacokinetic considerations. Key Concepts Auvelity® (bupropion-dextromethorphan) was FDA approved in 2022 for major depressive disorder (MDD). The bupropion component inhibits CYP2D6 metabolism and increases serum concentrations of dextromethorphan. The proposed mechanism of benefit in MDD is via dextromethorphan (as an NMDA antagonist) and possibly with bupropion (as a dopamine/norepinephrine reuptake inhibitor). Although the bupropion component in Auvelity® is being used for its drug interaction, the dose is a therapeutic dose and carries several warnings and precautions, including the risk of seizure and hypertension. In short (6-week) clinical trials, Auvelity® improved depression symptoms quickly (within 1-2 weeks), which is faster than many other antidepressants. Auvelity® is associated with dizziness, anxiety, hyperhidrosis, nausea, headache, diarrhea, and dry mouth. As a CYP2D6 inhibitor, the bupropion component of Auvelity® will cause drug interactions with many other medications, including some antidepressants, antipsychotics, and opioid analgesics (among others). References Iosifescu DV, Jones A, O'Gorman C, et al. Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). J Clin Psychiatry. 2022;83(4):21m14345. Published 2022 May 30. doi:10.4088/JCP.21m14345 Tabuteau H, Jones A, Anderson A, Jacobson M, Iosifescu DV. Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Am J Psychiatry. 2022;179(7):490-499. doi:10.1176/appi.ajp.21080800 Kotlyar M, Brauer LH, Tracy TS, et al. Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol. 2005;25(3):226-229. doi:10.1097/01.jcp.0000162805.46453.e3

Join Dr. Jeffrey Gladden, Steve, Dr. Brent, and Andrea Turnipseed in this episode of the Gladden Longevity Podcast.  Dr. Brent Turnipseed, M.D., is the Co-Founder of Roots Behavioral Health and serves as their Medical Director. A board-certified psychiatrist with a deep interest in innovative approaches to providing behavioral healthcare, Brent sits on the Scientific Advisory Board for Ninnion Therapeutics, and he is the creator of all treatment protocols at Roots Behavioral Health. Andrea Turnipseed, LCSW, is Roots Behavioral Health's co-founder and serves as their Executive Director. Andrea has training and a background in adult mental health and has worked with clients in acute inpatient and outpatient psychiatric settings, facilitating both group and individual therapy. She is trained in providing Ketamine-Assisted Psychotherapy. In this episode, they talk about all things psychological health, the use of Ketamine-Assisted Psychotherapy to treat depression, lifestyle habits that will improve brain health and boost well-being, and how our digital habits affect our brain health.  Listen to this episode to learn about making a 100 the new 30 and living beyond 120!    Dr. Gladden introduces Dr. Brent and Andrea Turnipseed as they talk about all things about psychological health. (0:35)  Andrea explains how they started as a traditional practice and how they found out that traditional medicine is not always working for their clients. (1:30)  Brent notes that over one-third of clients were not seeing improvements with traditional medicine. (3:00)  Brent shares that we are currently in a time when the paradigm is being questioned. (5:43)  Brent reveals that staying on antidepressants and other similar medications changes the physiology of how brain chemistry works. (7:15)  Brent points out that there are some genes that indicate whether a person will metabolize a medicine quickly or slowly. (9:20)  Andrea discloses that they ask about patients' history and lifestyle when trying to help patients. (11:00)  Dr. Gladden recalls having read that neuroinflammation is associated with depression. (14:00)  Dr. Gladden says that neuroinflammation is interesting because aging comprises increasing mechanisms of inflammation. (16:10)  Dr. Gladden refers to what he is currently doing at Gladden Longevity called Brain Frequency, which is a modified form of transcranial magnetic stimulation. (18:34)  Brent brings up the observation that no one has really done a clinical trial in the last 20 years testing the effects of NAD. (20:32)  Dr. Gladden advocates that if you are interested in improving the energetics of the neuron, then getting intracellular NAD is what you are going to be after. (21:59)  Andrea talks about the effectiveness of ketamine and how about sixty percent of the time it works for people with treatment-resistant depression. (25:55)  Andrea points out that people seem to open up a little bit more after taking ketamine, and it helps them open up better than traditional therapy. (29:00)  Brent throws light on ketamine, its use, and its FDA approval status. (31:00)  Brent says ketamine is an NMDA receptor antagonist. (33:00)  Brent states that glutamate can be toxic if much of it floats around the body. (35:55)  Andrea says ketamine can be psychedelic. (37:40)  Brent clarifies that when some people are disassociating from their physical bodies, they feel like they are dying, but the presence of a therapist can be reassuring. (40:02)  Andrea presents how ketamine helps patients make sense of everything they have been told or be more receptive to the advice given. (45:55)  Brent cites studies that show ketamine, for many people, rapidly reduces suicidal thoughts, feelings and behavior. (47:30)  Brent really looks forward to the future with enthusiasm to make the treatment available to more people. (51:46)  Dr. Gladden reveals that there are many things you can start doing while waiting to get into the ketamine clinic that can serve you afterward. (53:39)  Steve wants to know how people outside Texas can access a ketamine clinic or a center. (56:40)  Dr. Gladden shares that if you are in Texas, Roots Behavioral Health does take insurance, and they provide ketamine. (58:45)  Dr. Gladden thanks Brent and Andrea for joining them. (59:10)         Visit our website, www.gladdenlongevitypodcast.com, for more information on this episode and other episodes as well. Click on the link to let us know what you'd like us to talk about on the podcast too!               Follow us on social media!              Instagram: @gladdenlongevity              Twitter: @gladdenlongevit              Facebook: @GladdenLongevity       LinkedIn: @GladdenLongevity     For more information on our practice or how to become a client, visit: www.gladdenlongevity.com    Call us: 972-310-8916    Or email us: info@gladdenlongevity.com    To learn more about Dr. Brent and Andrea, check out the following:   Website: https://rootsbehavioralhealth.com/  Email: frontdesk@rootsbehavioralhealth.com  Phone: +1 512-707-1629  Facebook:  @Roots Behavioral Health Instagram: @rootsbehavioralhealth To get a complimentary consultation, call Roots Behavioral Health or email their front desk and let them know you heard from them on our podcast.  

Natalie T. Hagy, PharmD describes the monoamine and glutaminergic pathway for the treatment of major depressive disorder, recognizes response and remission rates of first line treatment for major depressive disorder and describes the clinical trials for dextromethorphan-bupropion and its impact on the landscape of major depressive disorder. For more pharmacy content, follow Mayo Clinic Pharmacy Residency Programs @MayoPharmRes or the host, Garrett E. Schramm, Pharm.D., @garrett_schramm on Twitter! You can also connect with the Mayo Clinic's School of Continuous Professional Development online at https://ce.mayo.edu/ or on Twitter @MayoMedEd. 

Natalie T. Hagy, PharmD describes the monoamine and glutaminergic pathway for the treatment of major depressive disorder, recognizes response and remission rates of first line treatment for major depressive disorder and describes the clinical trials for dextromethorphan-bupropion and its impact on the landscape of major depressive disorder. For more pharmacy content, follow Mayo Clinic Pharmacy Residency Programs @MayoPharmRes or the host, Garrett E. Schramm, Pharm.D., @garrett_schramm on Twitter! You can also connect with the Mayo Clinic's School of Continuous Professional Development online at https://ce.mayo.edu/ or on Twitter @MayoMedEd. 

How to evaluate the patient with unexplained encephalopathy, and a practical approach to diagnosing autoimmune encephalitis with an emphasis on anti-NMDA receptor encephalitis—with Dr. Casey Albin (@CaseyAlbin), neurologist and neurointensivist, assistant professor of Neurology and Neurosurgery at Emory, and part of the NeuroEmcrit team. Claim your CME credit here! Find us on Patreon here! Buy … Continue reading "Episode 55: Undifferentiated encephalopathy and autoimmune encephalitis, with Casey Albin"

In this episode of the Psychedelic Medicine Podcast, Dr. Steven Mandel returns to discuss ketamine treatments for alcohol use disorder. Dr. Mandel is an internationally recognized expert and pioneer in the use of ketamine-infusion therapy to treat mental health disorders and chronic pain. He is a board-certified anesthesiologist with a masters in psychology and over 40 years of experience working with ketamine. He is the founder and president of Ketamine Clinics Los Angeles and also the Founder and first president of American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP3). In this conversation, Dr. Mandel explores the topic of using ketamine to address alcohol use disorder, discussing findings from research and sharing his professional experience with this treatment protocol. He begins by unpacking the specifics of alcohol use disorder before relaying an incredible success story from a client who was able to conquer a very significant alcohol addiction due to ketamine therapy treatment.  However, Dr. Mandel notes that actual scientific research for this particular therapeutic use of ketamine is still in the early days, though he notes that the first non-anesthetic use of ketamine was for treating alcoholism in Moscow, and this intervention appeared to be quite effective. He also shares results from animal studies, noting that one study found outcomes of ketamine treatment for alcohol dependent mice was significantly mediated by sex, with the female mice being less responsive to the treatment. However, Dr. Mandel notes that it is too early to know if these same patterns appear in humans.  In terms of the theoretical basis for this treatment protocol, Dr. Mandel discusses glutamatergic transmission and the nucleus accumbens as being important in both alcohol use disorder and ketamine treatment. He also mentions that ketamine potentiates the NMDA receptors which are desensitized in the case of chronic alcohol use.  But Dr. Mandel insists that these pharmacological mechanisms are not the whole story when it comes to the efficacy of ketamine therapy for alcohol use disorder. At his clinics, treatment consists of a five point model which also addresses things like sleep hygiene and diet to provide a more holistic approach to wellness. He also stresses the importance of including talk therapy in the treatment protocol, as patients are primed for effective therapy following infusions. This is due to the improved neuroplasticity resulting from the neurological effects of ketamine, but since this does not last forever Dr. Mandel maintains there is a sweet spot where therapy will be most effective, which is between a few hours after the ketamine treatment and a few days later.  In combination with therapy and other interventions to promote patient wellness, Dr. Mandel is confident ketamine therapy presents a promising treatment option for those struggling with alcohol use disorder, and he thinks it may even be a helpful support for those who've shaken their addictions but still struggle with cravings in abstinence.  Ketamine Clinics Los Angeles phone number: (310) 270-0625   In this episode: What is alcohol use disorder? Patient success stories from Dr. Mandel's ketamine treatments The research on ketamine for alcohol use disorder How set and setting differentiates alcohol and ketamine use in important ways The importance of the experiential aspect of ketamine for its clinical efficacy Why Dr. Mandel's clinic focuses on sleep hygiene and diet alongside ketamine therapy to help achieve the best patient outcomes Dr. Mandel's protocol for ketamine infusions The history of AA and psychedelic therapies   Quotes: “[Ketamine's] first major use… outside of the operating room for anesthesia was by Krupitsky in Moscow in a government program treating chronic alcoholism. That was the first behavioral use of ketamine! And it was profoundly effective.”  [9:25] “We're really at a frontier here. Just getting ketamine in people and seeing the transformation is amazing. And trying to sort out how to optimize it—we're not there yet.” [20:41] “There's a whole other population of people who are successfully abstinent, but are beginning to have cravings. And those people are so helped by a little experience with ketamine. Ketamine is amazing at helping people to resist cravings.” [24:08]   Links: Ketamine Clinics Los Angeles American Society of Ketamine Physicians, Psychotherapists & Practitioner Previous Episode: Ketamine Practitioner Methods with Dr. Steven Mandel Psychedelic Medicine Association Porangui