A sore throat that ends in compulsions, tics, and a child who suddenly can’t sleep or attend school sounds improbable—until you hear a pediatric rheumatologist walk through the biology. Dr. J. Patrick Whelan of UCLA sits down with Dr. Susan Manfull, Executive Director of The Alex Manfull Fund, to unpack how infections and the immune system can collide with brain function, producing abrupt-onset OCD, motor and vocal tics, restricted eating, and anxiety that look psychiatric but respond to immunomodulatory treatments. Drawing from a variety of sources, including the history of rheumatic fever, the Lancefield classification of streptococci, and modern cases of Multisystem Inflammatory Syndrome in Children (MIS-C). Dr. Whelan explains why PANDAS and PANS challenge old categories and demand a broader clinical lens.

We dive into innate versus adaptive immunity, what “autoinflammatory” and “autoimmune” really mean, and why so many affected kids also show signs of immunodeficiency. If routine tests like ASO and anti–DNase B come back normal, does that rule out strep’s role? Not necessarily. Whelan shares how expanded antibody panels, trial responses to antibiotics or anti-inflammatories, and careful history-taking can reveal an immune trigger that standard workups miss. He also outlines the practical steps that matter right now: restore sleep, get moving, stabilize nutrition, and build companionship—simple interventions that reduce pain amplification and calm a dysregulated nervous system. Finally, we talk about why “listening to the patient” often illuminates key clues to understanding the case.  

If you care about pediatric mental health, infection-associated neuroimmune disorders, or how medicine evolves when data and curiosity meet, you’ll find both science and solace here.

If this resonates, follow the show, share with someone who needs it, and leave a review to help more families and clinicians find these insights.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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What makes some people vulnerable to devastating chronic illness after infections that most recover from easily? Dr. Michal "Mikki" Tal, pioneering immunoengineer at MIT, is tackling this question through her groundbreaking Maestro study - the largest clinical research project currently underway at the prestigious institution.

Personal tragedy fuels Dr. Tal's scientific mission. After losing both an uncle to HIV/AIDS and a cousin to meningococcal meningitis, she developed a profound respect for infectious diseases and determination to understand immune system dysfunction. Now, her research examines why infection-associated chronic illnesses like Long COVID and chronic Lyme disease disproportionately affect women, what biological mechanisms prevent recovery, and how we might predict who's at risk.

The conversation explores fascinating biological concepts, including how our immune cells recognize "eat me" versus "don't eat me" signals, and how some pathogens have evolved to manipulate these systems. Dr. Tal introduces her powerful metaphor: "If you took a bacterial road to Rome or a viral road to Rome, once you're in Rome, does it matter anymore how you got there?" This question frames her approach to understanding whether treatment should focus on the triggering infection or the resulting immune dysfunction.

Dr. Tal advocates for a revolutionary "systems medicine" approach that bridges traditional medical specialties to address complex conditions. Her research employs cutting-edge techniques to objectively measure everything from blood vessel appearance to cognitive function, seeking patterns that might predict or explain chronic illness development. Most exciting are the preliminary findings showing significant cognitive impacts, particularly in reaction time, that could immediately inform clinical care.

The Maestro study continues seeking participants, particularly those newly diagnosed with Lyme disease. By examining genetics, microbiome, immune responses, and countless other variables simultaneously, Dr. Tal hopes to finally unlock the mystery of why some people can't bounce back from infections - and how we might help them recover. If you've recently been diagnosed with Lyme disease, consider participating in this groundbreaking research that could change medicine's understanding of chronic illness forever.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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Transitioning to college marks a significant milestone for any young adult, but for those with PANS/PANDAS, this journey demands unique preparation and understanding. In this illuminating conversation, Dr. Susan Manfull welcomes Sheila Gauch, Principal and Clinical Director of Dearborn Academy, who brings both professional expertise and profound personal experience to the table.

Gauch, whose own college experience as an all-American swimmer was derailed by what she believes now was undiagnosed PANS symptoms, shares eight critical strategies each—for parents and for students—that transform the college transition from daunting to doable. Her guidance stems from both professional wisdom and her journey supporting two college-age children with PANS.

For parents, the process begins with helping their children truly understand their condition's immune-mediated nature, recognizing how different it is from primary psychiatric disorders. This knowledge becomes crucial when students need to advocate for themselves in college health centers where PANS/PANDAS awareness may be limited. Equally important is parents understanding their own stress responses, often shaped by years of hypervigilance and advocacy.

"I think caregiver stress and trauma, particularly with PANS families, is so ingrained," Gauch explains, comparing it to "a frog in a pot of boiling water—you don't realize you're boiling alive." Learning to manage this response becomes essential when letting children navigate college independently.

For students, success hinges on understanding how stress triggers inflammation, potentially causing symptom flares. They must become attuned to their bodies, practice effective coping strategies, and embrace self-advocacy—particularly when accessing disability support services. Perhaps most challenging is learning to accept imperfection and mistakes, especially difficult for those with perfectionistic OCD tendencies.

Gauch also introduces the Everest Program, a comprehensive coaching service helping students bridge the gap between high school structure and collegiate independence through academic, clinical, and transition support.

Whether you're a parent preparing to launch your child or a student planning your college journey, this episode offers practical wisdom for navigating this significant transition while managing PANS/PANDAS. Ready to build that bridge to college success? Listen now and discover how to transform challenges into stepping stones toward independence.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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Dr. Andrew Baumel's story reveals how curiosity, compassion, and clinical observation can lead to breakthrough care for children suffering from immune-mediated neuropsychiatric disorders.

After 18 years as a traditional pediatrician, Dr. Baumel's professional trajectory changed dramatically when a parent asked if he knew anything about PANDAS. Though initially somewhat skeptical, attending an educational lecture with the parent in 2014 convinced him this was a genuine medical condition affecting children's brains following infections. Fast forward, he has now treated over 300 patients with mild to moderate cases of PANDAS and PANS using straightforward medical approaches in his regular pediatric practice.

Dr. Baumel shares fascinating clinical insights, including his identification of "protopans" – early, limited symptoms following infections that, when treated promptly, appears to prevent progression to full-blown disorders. 

"I have a regular practice of 1500 kids, ages 0 to 23 years. I just incorporate these [mild cases of] PANS/PANDAS into my regular practice as my regular patients. This is doable," Dr Baumel said.

Dr. Baumel offers thoughtful perspective on why acceptance of PANDAS/PANS has been slow, drawing parallels to historical medical discoveries that initially faced skepticism before becoming standard practice.

Link to video of 2014 PANDAS Doctor's Breakfast that Dr. Baumel mentioned in this podcast: https://aspire.care/videos/qa-breakfast-for-doctors-featuring-national-pans-pandas-expert-panel-nepans-2014/  (Aspire website)

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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How does a common strep infection become a brain disorder? Dr. Uğur Akcan's journey from Istanbul to the cutting edge of PANDAS research with Dr. Dritan Agalliu reveals the fascinating intersection of immune system and brain function that could transform how we understand and treat neuropsychiatric disorders.

In this captivating conversation, Dr. Akcan shares his research path from studying complement levels in patients with bipolar disorder to pioneering work on the blood-brain barrier, ultimately contributing to groundbreaking discoveries about PANDAS and PANS in the Agalliu Lab at Columbia University. With remarkable clarity, he explains how mutations in the RxRA gene may explain why only some children develop these disorders after streptococcal infections, and how microglia—the brain's immune cells—fail to properly regulate neuroinflammation when this gene is compromised.

The discussion takes an unexpected turn as we learn how Dr. Akcan's vital research was nearly derailed in March 2025 by sudden NIH funding cuts directed by the Trump administration at Columbia. In a dramatic development, the PANDAS/PANS community rallied to save his position through a GoFundMe campaign, demonstrating the powerful connection between affected families and researchers working to solve this medical mystery.

Beyond the scientific discoveries, Dr. Akcan's personal story reflects the qualities that drive medical breakthroughs: curiosity about why peripheral infections trigger brain symptoms, perseverance through research challenges, and passion for helping those affected by these devastating disorders. His development of a 3D blood-brain barrier model and investigations into Th17 cells represent frontier science with real-world implications for treatment.

When Dr. Akcan is not in the lab, you may find him watching football, rooting for his favorite team, Galatasaray, or spending time with his wife and young child.

Dr. Agalliu also joins me to discuss how the NIH funding cuts have affected his lab.

Support Dr. Akcan's  crucial PANDAS/PANS research by visiting this  GoFundMe page and join the community working to unravel PANDAS and PANS. Your contribution could help transform our understanding of how infections trigger neuropsychiatric symptoms and lead to better treatments for children, adolescents, and young adults suffering from these disorders. Both researchers express deep gratitude to supporters of this work. 

The goal is to raise $100,000 to cover Dr Akcan's annual salary and benefits --  only $15, 602 left!

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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In this powerful episode of Untangling PANDAS and PANS, host Susan Manfull, PhD sits down with Jen, a resilient young woman whose health took a devastating and mysterious turn in her early twenties. From being taken out of work on a stretcher—twice—to struggling for answers amidst an array of debilitating physical and psychiatric symptoms, Jen shares a deeply personal account of navigating a fragmented medical system while battling PANS/PANDAS and related autoimmune conditions.

Jen recounts her long history of strep infections, early signs of neurological distress, misdiagnoses, and the profound impact of being dismissed by the medical community. She opens up about the moment she was finally heard, the diagnosis that changed everything, and her journey toward recovery with IVIG treatment. Now in graduate school and reclaiming her life, Jen offers hope, insight, and advice to others walking a similar path.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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In this illuminating conversation, Dr. Sarah O'Dor—Harvard instructor and Director of Research at Massachusetts General Hospital's PANDAS Clinic—reveals how strep infections and other triggers can cause sudden, dramatic psychiatric symptoms in children and young adults.

Dr. O'Dor paints a vivid picture of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome), conditions where infections trigger obsessive-compulsive behaviors, tics, restricted eating, and a host of other psychiatric, cognitive, emotional, somatic, and medical symptoms. Through the compelling case of "Ms. K," a six-year-old who developed severe handwashing compulsions following a strep infection, Dr. O'Dor demonstrates how these conditions often go misdiagnosed as traditional psychiatric disorders.

The conversation explores the critical role psychologists can play in recognizing these disorders and providing effective treatment. Dr. O'Dor describes how cognitive-behavioral therapy can be adapted for these patients, how families are affected by sudden behavioral changes in their children, and how psychologists can support not just the child but the entire family system. Also very importantly, she emphasizes the need for collaboration between mental health professionals and medical specialists—a multidisciplinary approach reflecting the complex nature of these disorders. 

For parents, clinicians, and anyone interested in the fascinating intersection between immunology and mental health, this episode offers a roadmap to better understanding, earlier diagnosis, and more effective treatment. The discussion culminates with reflections on a growing paradigm shift in psychiatry—one that increasingly recognizes the role immune function plays in mental health.

Whether you're a healthcare provider, a parent concerned about your child's sudden behavioral changes, or simply curious about emerging understandings of brain-immune connections, this episode will transform how you think about certain psychiatric symptoms. 

To read the article reference in the podcast, click here.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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This podcast episode features an interview with Dr. Brent Harris, the Director of Neuropathology at Georgetown University where he wears many hats, including overseeing the Georgetown Brain Bank. In 2020, he accepted the brain of Alex Manfull who had died from complications due to PANDAS and, eventually, with the help of The Alex Manfull Fund, established the POND Brain Bank for brains and brain tissue from individuals who had been diagnosed with "PANDAS/PANS and Other Neuroimmune Disorders."  Dr. Harris talks about neuropathology, the role of brain banks in facilitating research on brain disorders, and findings from the first published clinicopathologic case report of a young adult diagnosed with PANDAS. He explains how gliosis, a marker of brain injury found in that case, can occur after a neurological insult and how it might be reversible in some cases; it is not a condition expected to be observed in healthy 26-year-old individuals.  Additionally, he emphasizes the importance of more research and better recognition of conditions like PANDAS/PANS in the medical community to improve diagnosis and treatment. The episode touches on the evolving understanding of these diseases and the critical role of clinical research and education.

The POND Brain Bank at Georgetown University

https://neurology.georgetown.edu/patientcare/pond-brain-bank/

Clinicopathologic Characteristics of PANDAS in a Young Adult: A Case Report

https://karger.com/dne/article/45/6/335/862829/Clinicopathologic-Characteristics-of-PANDAS-in-a

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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Dr Herb Lachman is a physician, behavioral geneticist, and professor at the Albert Einstein College of Medicine in New York City.  In his 44 years on the faculty, he has studied the molecular basis of schizophrenia, autism, and the broad category of neurodevelopmental disorders. More recently, a serendipitous inquiry about a major DNA Damage Response Gene, PPMD1, prompted Dr. Lachman to shift his focus to PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome).

In the 11th episode of “Untangling PANDAS and PANS,” we discuss some basic information about genetics so that laypersons with an interest in this subject are able to assimilate his findings about DNA damage repair genes and their potentially significant role in neuropsychiatric conditions. These genes not only underscore the complexity of PANS and PANDAS but also point to the multifaceted interplay between genetics and the immune system at the intersection of the brain.

Genes are surely Dr. Lachman’s muse. He is quick to acknowledge that his sample sizes are small and biased, but they are nonetheless generating hypotheses to study more fully with larger data sets.

The simple question of why, given the ubiquity of Group A Strep, does only a small subset of patients develop PANDAS? Genetic mutations will very likely help to provide answers in the future.

To learn more about Dr. Herb Lachman's recent genetics findings on PANS, please refer to these two articles: 

https://karger.com/dne/article/doi/10.1159/000541908/914745/Ultrarare-Variants-in-DNA-Damage-Repair-Genes-in

https://pubmed.ncbi.nlm.nih.gov/35773312/

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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Juliette C. Madan, MD, MS wears many hats. Dr. Madan is an Associate Professor of Pediatrics, Psychiatry, Epidemiology, and Quantitative Biomedical Data Science at Geisel School of Medicine at Dartmouth. She is the Clinical Director of the Children’s Environmental Health and Disease Prevention Research Center within Geisel and Dartmouth Hitchcock Medical Center. She is widely recognized for her research in understanding the intestinal microbiome’s role in health and disease and in interventions such as nutritional, probiotic regimens, and fecal matter transplant. 

My relationship with Dr. Madan grew out of her role as co-founder of the Psychiatry Immunology and Neurology Group (known as PING) which is now named the Neuroimmune Psychiatric Disorders (NIPD) Clinic, one of only a handful of clinics in the nation devoted to treating PANDAS and PANS in children and adults. That was founded in 2019.  Today, she and Dr. Richard Morse, a neurologist with whom she founded PING, are the co-chairs of The Alex Manfull Fund Scientific and Medical Advisory Board

I could have talked to Dr Madan about a multitude of subjects but, for this interview I asked her to wear her Epidemiology hat.  (She promised to return to discuss other areas).

Current estimates of the incidence of PANDAS/PANS varies widely from 1 in 46,000 to as high as 1 in 200.  The latter figure is bandied around but it is not based on research, epidemiological or otherwise.  Dr Madan discusses her own recent (2023) research with Dr. Ellen Wald, a highly respected pediatric infectious disease physician, and others on the prevalence of PANDAS and PANS.  Because there were many limitations in that study, she and Dr. Wald are about to conduct an (NIH-supported) epidemiological study to answer the prevalence question using a different methodology,  

Dr Madan is a graduate of Brown University School of Medicine, after which she completed a fellowship program in neonatal-perinatal medicine at Tufts University and while at Tufts, completed a master's degree in clinical and translational research.

When Dr. Madan is not in her clinic or her lab, look for her on the Connecticut River as she is a passionate rower. She also manages to find time with her ducks and chickens!

NOTE: My conversation with Dr. Madan was recorded prior to the December 16, 2024 release of the preliminary clinical report on PANS by The American Academy of Pediatrics (AAP).

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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