Neurology® Podcast

Dr. Zohaib Siddiqi talks with Dr. Michel Toledano about the diagnosis and management of infectious rhombencephalitis in patients receiving immunomodulatory therapy. Read the related Resident & Fellow Section article in Neurology®. Disclosures can be found at Neurology.org.

Dr. Katie Krulisky talks with Dr. Kelsey Smith about the impact of menopause on women with epilepsy, including therapeutics and clinical management during midlife. Read the related article in Neurology®Clinical Practice. Disclosures can be found at Neurology.org. Podcast Transcript: Dr. Jose Merino: This is Jose Merino, Editor-in-Chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week. Dr. Katie Krulisky: Hello, and welcome to this episode of the Neurology Podcast. This is Katie Kruliski from the VA and University of Utah in Salt Lake City, Utah. Today, I have the pleasure of talking with Kelsey Smith. She's a neurologist and epileptologist at Mayo Clinic in Rochester, Minnesota. We will be discussing her recent paper published in the Neurology Clinical Practice Journal titled The Menopause Transition and Epilepsy: A Focus on Therapeutics. Welcome, Kelsey, and thank you for joining us. Dr. Kelsey Smith: Thank you so much for having me. I'm really excited to be here today to talk about this paper and this really important topic. Dr. Katie Krulisky: Yes. Your paper highlighted a staggering statistic, that women spend approximately 40% of their lives post-menopause. That shook me when I was reading this for a presentation on management of women in epilepsy. Being a woman, I felt totally blindsided by the statistic. I've never thought about it this way. I feel like so much of the emphasis of our clinical practice in epilepsy is choosing the right medications for pregnancy. And there is a lack of information and focus on women in perimenopause and post-menopause, even though a much larger percentage of the lifespan is spent in this phase. Let's go ahead and start with the clinical scenario. A 45-year-old woman with focal epilepsy is having some symptoms attributed to perimenopause and is interested in pursuing hormonal treatments. As her epileptologist, what is your approach to counseling her based on the current available data? Dr. Kelsey Smith: And when it comes to patients like this, it's a very important topic. And the first thing is that it really requires both an individualized and multidisciplinary approach. So I think first as an epileptologist, I want to understand all I can about her epilepsy, what the current seizure control is, what the current therapy is, what the epilepsy's been like over other life stages if she's had epilepsy no earlier, to understand how seizures may have been during menstrual cycles to know if there's kind of a hormonal driver of seizures that's been noticed through the lifespan. And then also I really want to understand about her menopause symptoms. What are the symptoms that are really bothering her that she's hoping to start the hormonal therapy for? And are those symptoms things like vasomotor symptoms or sleep disturbances? And are those actually also influencing her current seizure control? If the vasomotor symptoms are waking her up at night and she's not getting good rest, is this lowering the seizure threshold and actually driving worse seizure control? Understanding all of this background's really important. And then to discuss with her what the data is about menopausal hormonal therapy and how it's related to epilepsy, how that data is really limited. And so we don't have a lot of data to go off of to provide counseling in this scenario. And all the studies that have really looked at this topic are really quite old, over 20 years old and have not used the same formulations of menopause hormonal therapy we use nowadays. And a lot of these studies didn't even use the anti-seizure medicines that we use nowadays. It's important to work with a patient like this and really let her know that despite the limited data, that epilepsy itself should not be a strict contraindication to considering menopausal hormonal therapy, but there are special considerations that we would need to think about, especially interactions between the hormones and anti-seizure medications and that she would probably require close following throughout using menopause hormonal therapy. I would also collaborate closely with a women's health expert so they can help us decide what the best hormonal therapy may be if it's indicated to treat her symptoms. Dr. Katie Krulisky: So a lot of these patients will ask, "When looking at hormones, I want to know where my hormonal levels are at now." Are you ordering their hormone levels? Dr. Kelsey Smith: Yeah, this is a common question that patients ask and I've also been working some with the women's health experts here at Mayo. And as we've worked on papers and things, it's not standard of care to draw these levels even throughout perimenopause and into menopause because of the fact that menopause is a clinical diagnosis. And also during perimenopause, there can be such wide fluctuations in hormonal levels. And so it's difficult to know what to make of different values and how that would influence clinical care. So overall, I'm typically not ordering hormonal levels, but would work with a women's health expert and if they though it would be helpful in a specific scenario, then definitely would consider it. Dr. Katie Krulisky: So on a very basic level, I've come to understand that in general, estrogen can make you more likely to have a seizure. Progesterone is protective. With that in mind, it sounds like you're not saying completely no to addition of estrogen in the hormone replacement therapy. Is that accurate? Dr. Kelsey Smith: Yeah, that is accurate. One of the things I learned by putting this paper together is that although some direct comparison of estrogen levels is difficult, but overall, usually actually estrogen that's used in menopausal hormonal therapy, the estrogen is less than the estrogen in oral contraceptive pills. And we don't see epilepsy as a contraindication to considering oral contraceptive pills, although obviously we need to take into consideration interactions with anti-seizure medications and things like that. But I don't think overall it should be a broad contraindication to considering the hormonal therapy. During perimenopause, the endogenous hormonal levels can fluctuate very significantly and there could potentially be an influence of seizure control based on those fluctuations. At least in theory, even menopausal hormonal therapy could potentially help with some of those fluctuations and could potentially be helpful, especially if some of the symptoms associated with menopause, like the sleep disturbances, like the vasomotor symptoms are actually making seizure control worse by reducing the seizure threshold. Dr. Katie Krulisky: That's a really good thing to keep in mind because there's a lot of fear-based decision-making surrounding women's health and seizure medications because a lot of that, we see a lot of that in pregnancy, right? We also see a lot of that in perimenopause and menopause. I think historically we've though, oh, estrogen is dangerous. You shouldn't have any exogenous estrogen. And then it seems like women are suffering the consequences from exactly like you've pointed out, very limited actual data. So just for review, what is the actual data that we're extrapolating this from? Dr. Kelsey Smith: Yeah. So there's a few older studies from the late 1990s and then early 2000s that are mostly observational studies asking women with epilepsy how did their seizures change with menopause hormonal therapy and things like that. And then there's one randomized controlled trial. It was published I believe around 2006, but it had very limited numbers, less than 25 patients. And that study said that with menopausal hormonal therapy, with the higher doses, there was a dose dependent relationship where seizures worsened with that therapy, the menopausal hormonal therapy. However, this study was using formulations that aren't typically in clinical practice anymore for menopausal symptoms as they're using more like estrogen patches and things like that. And so we really don't have data that looks at our currently used treatments in women's health and how it influences seizure control. Dr. Katie Krulisky: So I'll just say that the available data is extremely outdated and not even necessarily applicable to our current treatment standards in that area. Dr. Kelsey Smith: I would agree with that statement. I think we need more research, more data. And that was one of the motivations of putting this paper together, is just highlighting some of the gaps, but also using some of what we know from other life stages to highlight some of those interactions with anti-seizure meds, some of those things that we can at least talk to our patients about and we can try and improve clinical care. Dr. Katie Krulisky: And when you're selecting an anti-seizure medication for women, how heavily are you considering its association with osteoporosis? Dr. Kelsey Smith: Yeah, this was another very important topic when we're thinking about epilepsy and the menopause transition is osteoporosis. It's never too early to consider this and what anti-seizure medications are better for bone health because we know that there's many anti-seizure medications like enzyme inducing anti-seizure medications that can negatively impact bone health. And then there's even data that epilepsy itself can negatively impact bone health. So I don't think there's ever a time where it's too early to consider it and we should probably be considering it over the lifespan because if you get someone on an anti-seizure medicine that's really controlling their seizures, it's more difficult to switch them off to something else. But I do think that as people are reaching perimenopause age 40 or so, really reconsidering looking at that anti-seizure medication and how it could impact bone health. And also just considering bone health in general is important for us epilepsy doctors. And so thinking about both recommending lifestyle modifications that are good for bones, but then also thinking about things like vitamin D calcium or when they should have screening. And really as they reach menopause and estrogen levels drop significantly, that's when we know that bone mineral density is really impacted and this is a time where we really need to be thinking about this and considering it. Dr. Katie Krulisky: The medication that always sneaks up on me is clobazam because I always think of it as a newer medication, but it can make you more likely to have osteoporosis, right? Dr. Kelsey Smith: Yeah. Some of the newer medicines, there's still less data out there, but most of the anti-seizure medicines or even some of the newer medicines suggest some newer data that they can negatively impact bone health. And then also interestingly, some newer studies that suggest even epilepsy itself, taking populations of patients with epilepsy that for different reasons may not be on anti-seizure medicines may have impacted bone health. And all these things are so important to consider when we have patients who are having seizures, who are at higher likelihood of having falls related to seizures, or as they're aging and they're on anti-seizure medicines that can make them dizzy and predisposed to falls as well. Dr. Katie Krulisky: That's so true. It's in addition to the epilepsy that can make you more likely to fall, all these other factors, the seizure medication, the sodium channel side effects, we have to keep in mind. When it comes to the screening tests, are you yourself ordering the DEXA scans or are you partnering with primary care? I've done it a little bit of both ways depending on the patient situation. Dr. Kelsey Smith: I've done it a few different ways. Sometimes it's easier if they have that close primary care and I'm going to rely on primary care to help me out if the DEXA is really abnormal anyway. So if I can, I'd probably collaborate with their primary care provider, but in some scenarios I have ordered the DEXA scans. Dr. Katie Krulisky: Because I know we both had these patients where it's like, if you don't order it, you know it's not going to happen. Dr. Kelsey Smith: Yeah. Yeah. And then, yeah, if I get the result and it's very abnormal, then I can work with other folks or even refer to endocrinology to consider treatment. Dr. Katie Krulisky: And we've touched on this a tiny bit, but overall, how do sex hormones impact seizure control? Dr. Kelsey Smith: Really simplifying a very complicated relationship we don't completely understand. So overall, it's felt that estrogen is to be pro-convulsive, can reduce the seizure threshold and make seizures more likely to occur. While progesterone, especially through its metabolite allopregnanolone, is more kind of anti-convulsant in nature. But like I said, it's simplifying something that we don't completely understand, but there's some basic science data that supports some of that. Dr. Katie Krulisky: When I do my presentation on this topic, I say exactly that, is that this is a gross oversimplification of the available information, but something that I always find interesting is that those GnRH cell populations themselves are vulnerable to injury from seizures themselves. So I wonder if that ties into the whole... Anyways, there's a lot more to learn. We can- Dr. Kelsey Smith: Yes, I totally agree with that statement. I think there's a lot more to learn. Dr. Katie Krulisky: So what's a practical approach to balancing the lamotrigine and estrogen interaction in midlife women? Dr. Kelsey Smith: It's just really something we need to anticipate the interaction as opposed to saying, "Oh, you're on lamotrigine, you can't be on anything with estrogen in it." And we need to be prepared for it. And so if menopause hormonal therapy is indicated and is being started, we need to know that baseline serum concentration of lamotrigine and need to recheck levels within two to four weeks of starting something with estrogen in it and adjust the dose as needed based on those serum concentration levels. So also if they've had epilepsy throughout their lifespan and have had changes in estrogen earlier in life, like during pregnancy, for example, or with oral contraceptives, we may have some idea by their history if they're more likely to have that drop in the lamotrigine level. Dr. Katie Krulisky: And when you're ordering lamotrigine levels, are you really going for a trough or are you more trying to get a consistent time of day? What's your approach with that? Dr. Kelsey Smith: Yeah, as much as possible, a trough. You need at least a consistent time of the day, but I do prefer trough levels, just because that's what a lot of the reference range is based on. And then if it's a true trough level, it will be a consistent time of the day. Dr. Katie Krulisky: What inspired you to put this review together? Dr. Kelsey Smith: This review was a lot of fun to put together and I really learned a lot about menopause and menopausal hormonal therapy. This was an effort though that was actually initiated through the Epilepsy from Childbearing Age to Menopause Consortium. This was from the menopause committee of this consortium, and so got to work with a lot of great co-authors on this paper to put it together, really learned a lot and really excited to see what this consortium can do over time to really advance care for women with epilepsy. Dr. Katie Krulisky: That is so cool. Can you say the name of this consortium again? Dr. Kelsey Smith: Yeah. So it's ECAM for short, and it's Epilepsy from Childbearing Age to Menopause Consortium. And it's only been around for a few years. I joined it a couple years ago, but it's really got a lot of wonderful people involved and different committees looking at care for women with epilepsy really across the lifespan. Dr. Katie Krulisky: I want to be a part of this group. That's so exciting. Dr. Kelsey Smith: Yeah, you should be. There's a website and everything. So yeah, if you Google it, you'll find it. Dr. Katie Krulisky: I feel like I have been somewhat radicalized by the process of having a child because all of just the things that women go through with the hormone fluctuation and truly the lack of available information on the impact of those hormone fluctuations is crazy. It is such a wild experience and to be in such a modern society and have so many blind spots within women's health is incredible in not a good way. Dr. Kelsey Smith: I totally agree with that statement and some of that sentiment as well, is that once I had children myself, then you really start looking at some of these things in different ways. And it's not something that us as epileptologists need to overlook or shy away from in clinic. Our patients a lot of times want to talk to us about these things, especially if they think it's influencing seizure control. And now trying to work on some research studies in the area and stuff, menopause is so hard to find in the chart. We're not always bringing it up. We're not addressing it. It's a topic that we really need to be thinking about because it definitely can impact our patients. And we do know some about the best ways to manage things over this life stage, especially based on some of the data we have from other life stages. Dr. Katie Krulisky: In general, what age range is menopause usually happening? Dr. Kelsey Smith: Yeah. So the average age of menopause in the United States is around 51 to 52. There's some earlier data from those other studies I already mentioned about menopause and epilepsy that suggests the age may even be younger for women with epilepsy, especially with uncontrolled seizures. We need to be thinking about this really between the ages of 40 to 55 or so. Dr. Katie Krulisky: So maybe even, considering I'm always asking women about childbearing potential, but maybe even including it in that discussion of are you still having a menstrual cycle? Dr. Kelsey Smith: Yeah, I think so. Are you still having a menstrual cycle? Is there association with your seizures? And if we get more comfortable with this topic, even understanding eventually menopause symptoms and how they could influence seizures. The other thing that's a little interesting in terms of epilepsy and menopause is vasomotor symptoms. People get these hot flashes. They just last a few minutes. They can happen any time of the day. And so I could even see how clinically it could be somewhat difficult for some patients to maybe differentiate from focal seizures and things. So it's just interesting in that scenario. They could not be clear, are those seizures, what are these new symptoms? So important for us as epileptologists to recognize. Dr. Katie Krulisky: It's important in epilepsy and I also think it's important, because I do some general neurology. I do general neurology and epilepsy as my practice, and I see it actually pervasively in neurology. I've had people come to me with symptoms of difficulty swallowing and just really broad symptoms. And then I remember one case specifically that they came back to me and said, "Oh, I was just going through menopause. I feel much better now." Dr. Kelsey Smith: Yeah. And the brain fog and other things that can come with menopause obviously can span different potential neurologic diagnoses. Dr. Katie Krulisky: Totally. And I have to say somewhat embarrassingly that I feel like I myself am not the most comfortable with discussing vasomotor symptoms associated with menopause. What topics are you screening for or what symptoms are you screening for? Dr. Kelsey Smith: When you see someone in this midlife stage just asking, "Are you still having menstrual cycles? Do you feel like you've gone through menopause?" Because it's difficult to get that information or impossible to get that information without just asking about it. And then just asking if they're having symptoms they think that have changed with fluctuations in menstrual cycles as well to suggest they're in perimenopause and if they're having vasomotor symptoms or new sleep disturbances, what those could be like. Dr. Katie Krulisky: I know the sleep thing comes up a lot with our patients. Do you have a first step of approaching that with the sleep issues or are you referring, trying to manage it yourself? Dr. Kelsey Smith: I try and understand what the sleep disturbance is. Is it falling asleep? Is it frequently waking up? If there's any chance there could be potential sleep apnea playing a role, then I usually do an overnight oximetry and consider referral to look for that because sleep disturbance from sleep apnea, which can obviously start at any age, but mostly in older adults, if they're having problems with sleep apnea, then that needs to be managed first. Dr. Katie Krulisky: Thank you so much, Kelsey, for taking the time to discuss your review on management of epilepsy in midlife women. The paper is titled The Menopause Transition in Epilepsy: A Focus on Therapeutics, and you can read all the details in the Neurology Clinical Practice Journal. Dr. Stacey Clardy: This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword in your podcast app for any neurology specific topics.

Dr. Jason Crowell talks with Dr. John McDonough about the historical and economic factors shaping the US healthcare system and why understanding these systemic forces matters for neurologists and patient care. Read the related article in The Harvard Gazette. Disclosures can be found at Neurology.org. Podcast Transcript: Dr. Jose Merino: This is Jose Merino, Editor-in-Chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week. Dr. Jason Crowell: Hey, this is Jason Crowell from Norton Neuroscience Institute in Louisville, Kentucky. Thanks for listening to today's Neurology Podcast. Most of our audience members are practicing neurologists, you're in training or you're in an academic setting or in private practice. And for those of us who are in practice, we are well aware of the challenges of helping our patients access drugs, getting prior authorizations approved, the other areas of friction that exist in our healthcare system. And I would say that whether we realize it or not, these areas of friction are symptoms of larger choices about how our hospitals and clinics operate. And so to help us think about these things, today we've invited John McDonough to join us. John is a professor of public health practice at the Harvard T.H. Chan School of Public Health. We recently read an article about John's work published August 18th, 2026 in the Harvard Gazette and wanted to invite him to join us today. So John, thank you so much for your time. Dr. John McDonough: Pleasure to be here with you, Jason. Thanks for inviting me. Dr. Jason Crowell: So John, in this piece that I read in the Harvard Gazette that was describing some of the work you've done, you point to a specific historical pivot around 1980 when US healthcare spending grew at a pace that's disconnected from the rest of the industrialized world. And that was 40 to 50 years ago, so most of our audience does not have experience with the practice of medicine prior to that time. The title of your upcoming book is America's Wrong Turn: US Healthcare in the Neoliberal Era. Can you help summarize what you mean by this wrong turn that happened? And also, can you just give us some background about what you mean by this neoliberal era? Dr. John McDonough: So I've been influenced by a Yale political scientist, Stephen Skowronek, who suggests that there's a helpful way to look at American political economic history, not through the lens of individual presidential terms like say the Nixon era or the Reagan era or the Obama era, but to look at larger multi-decade politico economic eras where there are dominant political strains. And Skowronek says we've had five of these eras over the 250 years. But just to talk about the two most modern ones that are most relevant to our discussion here. The first one started in 1933 with Franklin Delano Roosevelt's inauguration as president in the midst of the Great Depression. And inaugurating an era that became known as the New Deal era, which was an era of muscular federal and state governmental leadership and guidance in terms of steering the economy toward greater productivity, toward higher wages, toward all different kinds of innovations like social security and Medicare and Medicaid. That era didn't end when FDR died. It went on until 1980 when it collapsed in the end of the Jimmy Carter presidency with upset and anger over what was then called stagflation, the Iran hostage crisis, the gas crisis from the Middle East with OPEC. So it was succeeded in 1980 with the inauguration of Ronald Reagan. And Ronald Reagan came in openly talking about let's move away from the New Deal era. It's not working anymore. We have to go forward. And that era was in some ways, people call it the neoliberal era because it was an era defined by a set of economists like Milton Friedman, Friedrich Hayek, other folks, Robert Bork, James Buchanan and others. And it represented a move toward let's have a much more muscular free market defining all manner of sectors of American economy and American society. Let's de-emphasize government to the maximum extent possible and just allow the free market to run. We have a professor at Harvard in the college, Naomi Oreskes, who refers to the era as the free market fundamentalist era. That's her label. I prefer neoliberal just because neoliberalism was actually a global movement in the '70s, '80s and beyond. It still lives on today in many places and in many ways. And it was not aimed at trying to transform American medical care or our healthcare system, but healthcare and medical care in the US is so huge and so important that it's really impossible to imagine that we would go through this societal revolution and medical care would go untouched. So my premise is that it did get touched quite a bit in a series of ways that I look at and say it created a lot more harm than benefit. And so inviting people to look at the neoliberal phenomenon in terms of its impact on health and medicine in the United States. Dr. Jason Crowell: One of the key shifts that you highlight is the massive market consolidation that has occurred here in the healthcare system. And we've seen this in our own neurology practices. Small independent subspecialty practices are very rare these days. Many of them have been bought up by health systems or private equity firms. And we understand that when healthcare merges occur, the claimed value is in regards to more efficiency, less overhead, but you cite research that shows prices actually increase following hospital mergers. So has this consolidation in healthcare, how has it affected the delivery of healthcare? Dr. John McDonough: So antitrust, anti-monopoly, anti-oligopoly began in earnest in the United States in the 1890s after the passage of the Sherman Antitrust Act. And over the succeeding 90 years, we had a belief that big corporate concentration in any sector, whether it's a humongous sector like steel or railroads or even relatively minor sectors that mattered in the economy, had to be confronted and addressed when you had companies that were growing by consolidating, swallowing up hostile takeovers that created then market dominance for one or several firms. And in the 1970s, and this came straight out of the neoliberal era, it was led by a man by the name of Robert Bork, who many people have probably heard of, former Solicitor General under President Richard Nixon, failed candidate for the Supreme Court in the mid-1980s. But in the 1970s, he took on the antitrust consensus that had governed the nation for 80 to 90 years. And he said, "We've got it all wrong. Big is not bad. If companies get big, it's because they deserve to be big and we should just let that happen. And if they get beaten up by the market, that'll take care of it, the discipline of the market." And he put these ideas together into a book and the book was called in 1978, The Antitrust Paradox. And he proposed what he called the consumer welfare theory of antitrust, which says that if two companies want to come together and they can demonstrate that consumers will benefit from lower prices, then it should be a green light. Do what you want, go ahead. And in the early 1980s, they rewrote fundamentally the federal antitrust guidelines, which provide the consensus to federal judges, federal prosecutors, states, everybody. Here's how we see it. And they rewrote them in 1981 and '82 to bring the consumer welfare hypothesis of Robert Bork into the mainstream in terms of this is how we look at antitrust. And so we had about 40 years of diminished antitrust enforcement kind of going into hibernation that affected the medical and healthcare community. So by the year 2020, in US counties, about 95% of US counties had what's called highest levels of corporate concentration. And with medical specialization at that point, it was about 65%. It's more now. For insurance companies, it was 75% highly concentrated markets all over the country. And there's a lot of newer economic research over the past several years that says that if we really want to understand why medical care, healthcare prices, insurance premiums, everything else is going up so much, they're looking at it. They're saying the extraordinary degree of corporate concentration over these decades has to be considered one of the prime, if not the most important culprit in terms of explaining what went on and how we got so consolidated relative to today versus where we were in the late 1970s. Dr. Jason Crowell: Let's turn to drug costs for a second. We have talked about drug costs on this podcast for several years. We have closely followed the work of ICER, the Institute for Clinical and Economic Review, and the work that they've done in helping us understand the value of drugs. Our multiple sclerosis colleagues are very familiar with the high cost of drugs. We now have these anti-amyloid therapies available for patients with certain neurodegenerative disorders that our cognitive neurologists are using. And of course we celebrate these new drugs for our patients with neurological diseases, but the price tags that come with some of these drugs can be staggering and are often associated with significant friction in terms of accessing them. So whether it's step therapy or prior authorizations or large out-of-pocket copays. Would you say that these administrative frictions are a deficiency of our current system, or a necessary feature to contain the cost? Dr. John McDonough: They are to some extent signs of dysfunction in the system in the sense that they've led to outcomes that have significantly diminished the level of competition and competitiveness. Just one data point for you, between 1985 and 2002, the market share of the top 10 firms in the pharmaceutical industry more than doubled from 20% in 1985 to 48% in 2002 in global sales, and it's gone up even more today. So we've seen the same story of heavy corporate consolidation. We see that far more than the money that pharmaceutical companies spend on research and development, which is the claim of what they need all this money, is substantially greater amounts of money sent out to their shareholders in terms of dividends and financing stock buybacks to an extraordinary extent that we've never seen before. Stock buybacks are when a company basically just buys back shares from stock owners just to shrink the share so that everybody's price then rises. Prior to the 1980s, since the 1930s, the New Deal era, buybacks were illegal. They were outlawed. They were considered to be corporate exploitation and manipulation that should not be permitted. And now it is just a regular feature that is part of another related growing phenomenon that we've seen over these past 40 to 50 years, which is the term financialization. That across the medical care sector, more and more of what is done is not being done with the prime purpose of creating products, improving care, improving people's health. It's being done to increase the financial wealth of the holders of capital to an extent that we have never really seen since way early in the 20th century, a long time ago. And so we see it in pharmaceuticals, we see it in medical devices, we see it across the board, we see it in hospitals. We even see it to a significant extent in the nonprofit hospital sector where we have had the creation of what we call mega providers who are now no longer just care delivery organizations, but they are major research institutes. And that has advantages and that has a role, but it is like everything else there's sometimes something called too much of a good thing. Or too much of the magic of the market in a way that then has harmful side effects and harmful results in terms of what people most want. We've had 40 years of tremendous growth in the size of our healthcare system in the United States as we have seen life expectancy still continue to grow, but grow way, way behind all of the other leading advanced industrial nations. And if we're not here about improving life expectancy, what are we here for? Dr. Jason Crowell: To quote you, you said it's going to take radical action, quote, "Radical action to make changes that fix the system." So I would ask if you were advising healthcare policymakers today, what's the top two or three things, the top interventions that you would provide to improve the lives of our patients? Or by proxy to help us as neurologists and physicians who are trying to help these patients? Dr. John McDonough: I would say right now that we are in an incredibly vital and dynamic period right now in 2026. In some ways it reminds me of 2005 and '06 when people were thinking about the next wave of health reform in the United States, which ended up resulting in the Affordable Care Act. But the people were looking three and four and five years ahead and starting to ask the questions, what's most important? What would have the greatest impact? I see us in a similar phase right now, and so there are loads of individual ideas. I put them into categories. We really need to re-empower patients and consumers in this system who have been turned into widgets for the financialization of the whole sector. We need a brand new patient bill of rights in the United States that gives patients protections around prior approvals, around excessive cost sharing, around various forms of manipulation by the market. Signing non-disclosure agreements and mandatory arbitration, rather than being able to take grievances to court, for example, that is now almost universal. We need a new set of protections for physicians, nurses, and other parts of the healthcare workforce to be able to exercise their rights and protect their professional values and identities in the face of a corporate takeover of so many parts of American medicine. We're dealing so much with moral injury to providers who find themselves at the wrong end of the stick of private equity, for example, and other kinds of corporate irresponsibility. We need a new code of conduct for corporations. We need a much more aggressive attitude toward market consolidation, whether it's monopoly or oligopoly or whatever. And we saw that, we started to see that in the first four years of this decade when President Biden put in a woman named Lina Khan in charge of the Federal Trade Commission and Jonathan Cantor in charge of the Justice Department's anti-monopoly division. We saw over those four years, and it was too brief a time to take full hold, but an extraordinary turning of the tide in terms of the ability of the large companies to take over at will anything that they wanted and to be able to merge and consolidate in ways that has been harmful, particularly looking at the vertical integration of major companies such as, for example, United Health Group or CVS. We've seen no longer just growing in their own spaces, but so United Health taking over providers, taking over pharmacy benefit management, taking over health data in ways that are just, it's too much power in one entity. And it has the tail wagging the dog and probably at this point, the tail is larger than the dog itself in many ways. Lots of categories also. We need to really rethink access to care in the United States, how people obtain it. And so a lot of not just individual interventions, we're going to need whole categories. We didn't get to this place through one or two or three or four policy changes. We saw 40 years of policy changes inside and adjacent to the medical care sector, and that needs to be addressed, but it's not going to happen overnight. It's a long-term project. And it's not about moving backwards to where we used to be 50 years ago. It's about a new vision of where we have to move forward in this age, in this era right now. Dr. Jason Crowell: And John, as we wrap up here, I started by saying most of our audience members are busy in clinical care, maybe some do research, but we see a lot of patients, inpatient hospital duties. It can be easy to hear about these massive, very large scale policy issues and feel ill-equipped to make any difference. And so for the neurologist who's listening to this podcast on her commute home, who wants to provide great care, but she feels overwhelmed by the surrounding systems of care, do you have any recommendations about what she and all of us can be doing to meaningfully engage with or push back against some of these issues we face? Dr. John McDonough: I know people in your specialization, Jason, are incredibly challenged keeping up with the fast pace of innovation in terms of research and innovation and discovery, and find it hard to keep up with that in many ways because of how fast things are moving in this new environment. I would suggest that it's also important to pay attention to the political and economic factors that surround your specialization. To understand and think about how changes going on in these areas that are adjacent to medical care practice and to surgical practice today are having real impacts in terms of how people are able to deliver care in ways that they think is most effective and efficient for their patients. And so I'd say that paying attention to some of these economic and political factors, weighing in with members of Congress who are considering perhaps changes to the rules around monopoly and consolidation or private equity, or other manifestations of the financialization and corporatization of American medical care, it's very important to do some education. For example, if you want to understand where we are or where we've come from in terms of market concentration and monopoly, I just recommend a single book called Goliath by a guy named Matt Stoller, S-T-O-L-L-E-R. Which is a 140 year history of monopoly and antitrust in American society. A different explanation, one that I find quite compelling and quite important. Dr. Jason Crowell: Terrific. We really appreciate you joining us today, John. Again, I've been speaking with John McDonough. He's a professor of public health practice at the Harvard T.H. Chan School of Public Health. We came across his work that was described in the Harvard Gazette published back on August the 18th. John, thank you again for your time and your expertise. We really appreciate it. Dr. Stacey Clardy: This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword on your podcast app for any neurology specific topics you want to learn about.

Dr. Kait Nevel talks with Dr. Katharina Schmidbauer about primary CNS T-cell lymphoma, highlighting diagnostic challenges, imaging characteristics, and treatment approaches for this rare disease. Read the related article in Neurology®. Disclosures can be found at Neurology.org. Podcast Transcript: Dr. José Merino: This is José Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week. Dr. Kait Nevel: Hello, my name is Kait Nevel. Today, I am interviewing Katharina Schmidbauer on her article, "Clinical Manifestations of Primary CNS T-Cell Lymphoma." Welcome to the Neurology Podcast. And Katharina, I would love to hear a little bit about you. Dr. Katharina Schmidbauer: Thank you, Kait. Thank you for having me. It's a pleasure. I am a neurologist with a great research interest in neuro-oncology, working at the University Hospital of Munich. Dr. Kait Nevel: Wonderful. Thank you for that. What do you think the most important takeaway is from your article for the practicing neurologist? Dr. Katharina Schmidbauer: Primary CNS T-cell lymphoma is very rare and the diagnosis is often really difficult to establish. In this study, we present hallmarks of the disease that could help with the diagnosis in the future. And our case series really illustrates many diagnostic challenges. The first important message would be how to deal with diagnostic uncertainty. If you have a progressive tumefactive CNS lesion and the clinical course, the imaging, and pathology don't quite fit together, CNS lymphoma and also T-cell CNS lymphoma need to remain on the differential, even if the first biopsy is inconclusive. And in this context, it's also important to avoid, of course, steroids before biopsy because they could cause regression of the lesion and therefore make the biopsy non-diagnostic, which is not the same as a negative biopsy. Dr. Kait Nevel: Thank you for that. And before we get into some more of the details of the findings of your study, could you give us a brief overview of the background and methods of your study? Dr. Katharina Schmidbauer: Sure. Primary CNS T-cell lymphoma is very rare and an aggressive subtype of CNS lymphoma. Most primary CNS lymphomas are B-cell lymphomas, but for T-cell lymphoma, we have very little systematic data. In fact, there are only three case series so far, and therefore we performed a multicenter retrospective study across three centers in Munich, Heidelberg, and Boston. And there we identified 16 adult patients with histologically confirmed primary CNS T-cell lymphoma without systemic disease treated between 2008 and '24. We looked at several levels of the disease, the clinical presentation, of course, histopathology, immunophenotype, T-cell receptor gene rearrangement testing, and if available, next-generation sequencing. And we also gathered MRI and PET imaging, treatment regimes, and of course outcome data. We also centrally reviewed the imaging and histopathology results in a multidisciplinary setting. And the study is mainly of course descriptive. However, we also tried to find associations that are relevant for outcome. Dr. Kait Nevel: Getting into some of the things that you found or discovered through this study, what's one thing that surprised you? Dr. Katharina Schmidbauer: One surprising finding of the study was the heterogeneous presentation on MRI and the high number of misdiagnosis on MRI in more than half of the patients. If you look into the imaging figures in the paper, these tumors can present as like any other disease. They can mimic neuroinflammatory disease, high-grade glioma, small vessel disease, and even meningioma or leptomeningeal disease. So the most common misdiagnosis was high-grade glioma, and indeed these lesions often showed very infiltrative growth patterns and almost streaky or perivascular patterns of contrast enhancement. And another interesting finding was the PET imaging. You might expect an aggressive tumor to show very high metabolic activity on FET PET, such as in high-grade glioma. But in our small subgroup of patients who underwent FET PET imaging, uptake was often relatively low to moderate or also completely photopenic, especially on FDG PET. Dr. Kait Nevel: Yeah. I found that part of your findings fascinating that the imaging is so unlike what we see in the much more common diffuse large B-cell lymphoma that we see in the CNS. It's much more common than T-cell lymphoma. Was there any understanding of why the imaging looks so different, particularly on the PET and FET imaging, as you mentioned? Dr. Katharina Schmidbauer: CNS lymphoma is a very heterogeneous entity itself. And we also know that from other PET imaging studies and CNS lymphoma that it can present heterogeneously with low or moderate, but also high uptake. And on MRI, we also know that in the CNS lymphoma, it's not always the common picture and the involvement of subcortical or deep brain structures. So it's a mimicking disease also in other studies, but in this rare subtype of T-cell lymphoma, this was pretty striking. Yeah. Dr. Kait Nevel: One thing that you've already mentioned that stood out to me was the number of initial misdiagnoses before reaching a diagnosis of primary CNS T-cell lymphoma. How do we work as a team, do you think, when we're evaluating these patients to reach the correct diagnosis more quickly? Is there anything that we should be doing differently? Dr. Katharina Schmidbauer: I feel the solution is early multidisciplinary discussion. We need to involve all disciplines pretty early, neuroradiology, neuropathology, and neurosurgery of course, and plan the diagnostic steps together, especially the biopsy. In some cases, we also used FET PET imaging to look for potential hotspots within the lesion that might provide a more representative biopsy target. Interestingly, of course, the uptake was only moderate in our cases, but I would potentially give it a try to have additional information when to plan and where to plan the biopsy. Of course, also histopathology needs to be regarded when we talk about misdiagnosis. I don't have a good explanation for why even when we obtain enough tissue, some characteristic findings we would expect such as T-cell receptor clonality were simply not detected. Yeah, this is not solved so far. Dr. Kait Nevel: Has anything you discovered in your results changed the way that you evaluate patients with brain lesions that have yet to be diagnosed or maybe the patient who has an unusual imaging or unusual clinical history coupled with imaging that maybe isn't totally typical for anything? Dr. Katharina Schmidbauer: Yeah, there are several things. I would be cautious about the diagnostic approach and sometimes especially the imaging or also the histopathology creates some uncertainty. If CNS T-cell lymphoma or CNS lymphoma in general is suspected, I would try very hard to obtain tissue before the application of steroids. This is maybe the first point. And next is how I deal with an apparently negative biopsy. I would distinguish between a truly negative biopsy and a non-diagnostic biopsy. So the histopathology findings show non-specific inflammation. For example, I would ask, was the patient exposed to steroids? Was enough viable tissue obtained? Was the right part of the lesion sampled? Was there necrosis? And also what you mentioned, how is the imaging pattern and does it fit also the clinical course? Is it relevant like the lesion behaves? Is it like an inflammatory disease? Does it regress and recur or progressively enlarge? If these questions leave you uncertain, then I would plan to reperform another biopsy. But what sometimes happens in the retrospective of the study, in some cases you jump to the next plausible diagnosis and of course, such as an inflammatory tumefactive CNS lesion that may also have responded to steroid treatment in the beginning, you could also go with another plausible diagnosis. So we need to be careful to reassure is it really a negative biopsy or is it a non-diagnostic one and how to proceed? Dr. Kait Nevel: What did you learn about outcomes in your patient cohort and do you think that we can use your results to guide treatment decisions for patients with primary CNS T-cell lymphoma? Dr. Katharina Schmidbauer: Yeah, of course we looked also at associations with outcome based on the treatment regimens that we found in our study. However, in my view, our results provide somehow supportive evidence, but I would be careful about using the small retrospective series to recommend specific treatment regimes. In our cohort, MTX-based treatment was commonly used and patients who received high-dose MTX-based treatment with autologous stem cell transplantation had longer overall survival, which is of course consistent with general treatment principles we know from primary CNS B-cell lymphoma. But of course we have only 16 patients and there is obviously substantial selection bias. Younger and fitter patients are more likely to receive intensive treatment and transplantation. So overall, I would say that our results support MTX-based treatment, including stem cell transplantation in selected patients as an important therapeutic strategy. Dr. Kait Nevel: Do you think that it is important or helpful to get next-generation sequencing on the samples of patients who have established primary CNS T-cell lymphoma? Dr. Katharina Schmidbauer: I would say molecular characterization is really important, but I would not say that every patient needs broad NGS. In my view, it's extremely valuable when you have an unusual histological phenotype, diagnostically difficult case, disease relapse, or when the result could potentially change treatment. And of course our ALK1-positive case is a good example. She had a fast progressive subtype and of course knowing about the mutation that changed the treatment algorithm, but in other cases we look at our small NGS subgroup. We also found variants of uncertain significance and we cannot term them as pathogenic mutations. So I would go for it if you have the facility to do it, but maybe not in every case. Dr. Kait Nevel: That makes sense. And it sounds like important to consider because as you highlight in our conversation and in your paper, you can uncover something that could be potentially pretty impactful to treatment for some patients. What do you think that we could do to learn more about this very rare oncologic condition? I mean, in your study, this was a multicenter. There were three different centers involved over a decade, almost 14-year timeframe, I think it was, or 16 years. Dr. Katharina Schmidbauer: Yeah, exactly. Dr. Kait Nevel: And you identified 16 patients, so about one patient per year over three academic centers, so pretty rare. What can we do or what do you think we should do as a neuro-oncologic community maybe to understand this group of heterogeneous, somewhat heterogeneous diseases better? Dr. Katharina Schmidbauer: The biggest challenge is of course the rarity of the disease and to gain any evidence that is useful. So as a single center, we would have never had enough patients and international collaboration of course is key for gaining any evidence. Yeah, I'm also really thankful for the great work and collaboration with the centers in Heidelberg and Boston. But yeah, we need larger registries for rare CNS tumors and ideally prospective standardized data sets to gather all the relevant information. And of course, I believe there are many distinct molecular subgroups of primary CNS lymphoma. They may behave differently or respond differently to treatment. And the next step in my view would be to really focus on the molecular subtypes and also aim for biology-driven treatment. But still the first steps, the number of misdiagnosed cases is maybe also not that low and should in the first place aim for not to miss any diagnosis of primary CNS T-cell lymphoma and to remember to keep it on the differential. Dr. Kait Nevel: Yeah, that sounds like a good goal. And your article and this podcast hopefully is a call out to people to remember this in the differential diagnosis for patients who have brain lesions, that it's not really clear what they are and diagnosis has been elusive to keep this in the list of possibilities. Dr. Katharina Schmidbauer: That would be great. Yeah. Dr. Kait Nevel: Great. Thank you so much for talking with me today, Katharina, and thank you for sharing more information about your study with us and educating all of us about primary CNS T-cell lymphoma. Dr. Katharina Schmidbauer: Thank you so much for having me. Dr. Kait Nevel: So again, I've been talking with Katharina Schmidbauer about her article, "Clinical Manifestations of Primary CNS T-Cell Lymphoma." Dr. Stacey Clardy: This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword on your podcast app for any neurology-specific topics you want to learn about.

Dr. Dara Albert talks with Dr. Bruce Cohen about the future of child neurology residency training, exploring current models, consensus areas, and challenges in evolving the curriculum to meet future healthcare needs. Read the related article in Neurology® Education. Disclosures can be found at Neurology.org. Podcast Transcript: Dr. Jose Merino: This is Jose Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week. Dr. Dara Albert talks with Dr. Bruce Cohen: Hi, this is Dara Albert from Nationwide Children's Hospital and Ohio State University. I am delighted to be joined today by fellow Ohioan, Bruce Cohen, a child neurologist at Akron Children's Hospital and an expert in the care of children and adults with mitochondrial disorders. Bruce is the lead author of a paper published in June 2026 called Education Research: The Future of Child Neurology Residency Training: The Perspective of a Child Neurology Society Task Force. Child neurology occupies this unique space at the intersection between pediatrics and adult neurology and pediatric neurology. And really there are a few topics in our field that generate as much discussion amongst child neurologists as how we should train the next generation. You get 10 child neurologists in the room, maybe there's 15 different opinions on how we should do this. Recognizing that there's a lot of evolution in our field, the Child Neurology Society, or CNS as I'm going to refer to it, assembled a task force to explore whether the current training models continue to meet the needs of our trainees, practicing physicians, and the patients that they serve. And we're going to talk about the results of that task force and what was published in the paper. Before we dive into that though, I do want to note that Bruce is joining us today as a representative of the task force and its findings. And while he contributed to this work, the perspectives and recommendations outlined in the paper are going to reflect the collective views of the task force and may not always fully align with his individual opinions. So Bruce, welcome to the podcast. Dr. Bruce Cohen: Thanks. It's great to be here. Dr. Dara Albert talks with Dr. Bruce Cohen: Absolutely. Let's start with a little history. Many may not be as familiar with how child neurology training developed in the United States. Can you tell us a little bit more about the current training model, how it came to be, and how it has evolved over the decades? Dr. Bruce Cohen: The current training model is about 50 years old. 50 years ago, there was no CAT scans or MRI scans or genetic testing. We had pneumoencephalograms. So there really have been major changes in the last 50 years in how we take care of children with neurological problems and how we treat them. And one would expect that the training needs would change as well over that timeframe. So here we are today to discuss the differences of opinions among my colleagues. Dr. Dara Albert talks with Dr. Bruce Cohen: It's hard to imagine doing an encephalogram these days. We've come a long way from that. Dr. Bruce Cohen: Well, it just shows my age. I remember taking tours of medical school, seeing the pneumoencephalogram suite. It was still up and running when I was in training. It doesn't seem that long ago. It was in the 1980s, but they still had the chair. Dr. Dara Albert talks with Dr. Bruce Cohen: Wow. Why did the Child Neurology Society or CNS feel that this task force was needed at this particular moment? What questions or challenges were you hoping to address? Dr. Bruce Cohen: So we know the ACGME is going to go on their 10-year cycle and look into the training requirements of child neurology in 2027. They're getting set up to do that. And it was just seemingly an appropriate time at the end of my term as president of the Child Neurology Society, which ended in 2023 to set up this task force just to see what we could contribute to the body of knowledge and the differences of opinions. I didn't really expect us to reach a consensus when we set up this task force, but I just wanted to lay out the differences of opinions that are out there. Dr. Dara Albert talks with Dr. Bruce Cohen: Yes. And we will definitely get into the opinions that came up as part of this task force. But before we talk about that, one of the strengths of this effort was the attempt to bring together a variety of perspectives. Can you walk us through how the task force was assembled, how you approached building consensus around these complex issues during discussions? Dr. Bruce Cohen: So the task force was assembled over a period of a month or so. I don't think I lost any friends by not asking them to join the task force, but I certainly got a lot of calls asking me why I didn't appoint them to the task force. But we started out with nine task force members that were mainly people that have dedicated their lives to education of child neurologists or have been some authoritative positions in the field of child neurology. But we needed to balance those appointed members of the task force with younger and more diverse group of individuals, some right out of training. We also tried to get people who practice mainly in a private practice environment. We didn't really succeed on that in terms of balancing that aspect of the membership, but we basically asked for volunteers and we got 65 applications or four additional members of the task force. We did have some diversity. Nine were female, 10 were white, 12 had US board certifications through the American Board of Psychiatry and Neurology. And initial certification ranging from 1988 to 2022, one was certified through the Royal College of Physicians and Surgeons of Canada. In the meantime, since the initial certification was 14 years with a range of two to 36 years, 12 members were currently clinically active in academic or hospital-based practices. So we did have a bit of diversity. We didn't get the private practice applicants that we hoped to have gotten. And so we may have missed a bit in terms of what those opinions may have been. We also had some diversity among the sub-subspecialty education of the members. We had one person trained in developmental disabilities, three trained in epilepsy neurophysiology, one in neuromuscular neurology. And again, the majority having held positions of authority within the child neurology, either child neurology training or child neurology national administration as officers in the CNS or AAN child neurology section. Eight of the members either currently or formally were residency program directors. Dr. Dara Albert talks with Dr. Bruce Cohen: Seems like a nice slice through a lot of different aspects of our field, although as you mentioned, not as much in private practice, but otherwise a good diversity of experience and time out from training and all of that. That's awesome. So it seems from reading the paper that the task force met and had discussions around these topics and tried to form consensus, identify lack of consensus around a lot of topics related to child neurology training. So I'm curious, where did the task force find the strongest consensus or areas of agreement and where were the opinions most divided? Dr. Bruce Cohen: Going back a little bit to maybe your first question is how are child neurologists trained in the first place? The majority of child neurologists enter a two and sometimes three year pediatric training program, but currently the majority have two years of general pediatrics followed by a three-year neurology residency. We sometimes refer to this as our neurology fellowship, but it's really a residency. That neurology residency is classically one year of adult neurology and two years of child neurology with the electives divvied up between both specialties. And at the end of this five-year training track, which majority of people go through, we call it the two plus three program, allows one to sit for the general pediatric boards as well as their neurology boards. And the certificate awarded to a child neurologist trained in this fashion is neurology with special qualifications in child neurology. And that ostensibly allows us to take care of patients of any age with neurologic problems. Of course, one shouldn't venture into taking care of patients that one doesn't have experience taking care of. And certainly child neurology has changed over the course of the years. 50 years ago, neonatal neurology was pretty much non-existent and probably consisted of children born 26 to 28 weeks gestation and older. And of course now neonatal neurology is blended into topics that are covered in fetal neurology, something that I have no training in doing. I didn't do it when I trained 40 some odd years ago and I certainly haven't picked that up any time along the way. I would also say that I would never take on patients with adult onset multiple sclerosis. The training I had back when I was in residency was intrathecal steroids and we've come a long way since then. So there's a constant learning curve on what we should be doing and what we're boarded to do. There's two issues of non-consensus. One is how long the training program should be in the first place. And the second is do we really need that whole year of adult neurology? So the strongest consensus has to do with the definition of what a neurologist is. We're on solid footing in that regard. We need structured programs both in terms of didactic activities and the residents must be provided protected time to participate in these core didactic activities. So issues like that we all agreed upon with almost unanimity as we discuss these areas. We also agree that residents must attend a longitudinal continuity clinic at least one half day a week throughout the duration of the program. Something that really didn't exist 50 years ago was a topic of neurogenetics and that we needed to have a ramped up education in neurogenetics and it be mandatory part of our training. And although not available at all training sites, new therapies including molecular therapies that would include but not limited to gene therapy should be at least part of the didactic training, if not part of the actual hands-on training. So we really had a lot of areas of consensus. Dr. Dara Albert talks with Dr. Bruce Cohen: So one of the biggest takeaways for me in reading the paper is that the task force could not really reach consensus on what to do with the adult neurology and the general pediatrics components of training. Why do you think these questions remain so difficult for our field to answer? Dr. Bruce Cohen: When I look back at my old textbooks of pediatrics and my old textbooks of neurology, they were thin. There wasn't a whole lot in them and now they're thick and two volumes, some of them. The last edition of Swaiman's weighs about as much as a bowling ball. I'm referring to Swaiman's Textbook of Pediatric Neurology. There's a lot more to learn in these two plus three years or one plus three years or however we're going to do it. And one of the questions being raised, is it time to give up that full year of adult neurology so we can squeeze more into our 36-month training program of neurology? And again, that's been an area of non-consensus ever since I started having this discussion back probably about 15 years ago. Dr. Dara Albert talks with Dr. Bruce Cohen: Yes. I likewise have had many conversations with colleagues over the few years I've been a child neurologist and that seems to be an area of a lot of disagreement. So a challenging question to answer, but it is quite remarkable how much we have grown and expanded and learned as a field such that like you gave the example of the textbook being really small when you were in training and now we're in these big giant multi-volume textbooks. That's so true. I'm curious, was there a perspective or argument raised during the discussion that changed your thinking or at least maybe challenged some of your assumptions about this topic? Dr. Bruce Cohen: It certainly opened up my mind. Again, some of the people I chose to be on this task force I knew would disagree with my own personal opinions about this. And I chose them because the purpose of the task force is to lay all the issues out on the table so that the RRC can deliberate and come up with what's going to be best for the field. 50 years ago, we really didn't think about how much debt a resident would land themselves into after four years of college and four years of medical school and being paid a salary that would likely be considered a poverty salary if that resident had a small family. And one of the questions is that if you can train an adult neurologist in four years, one year of adult general medicine, three years of neurology, can you train a pediatric neurologist in four years, one year of pediatrics, three years of pediatric neurology? So that was one issue that came up. And just the finances of that is daunting. The other question is would we improve our labor force of child neurologists if we cut a year of training out? And then of course, no one's really done that and the question that arises, is it safe to do this? And we talked about that as well. Dr. Dara Albert talks with Dr. Bruce Cohen: Like safe for our patients. Dr. Bruce Cohen: Safe for our patients. Safe for us too. There were some members of the task force thought that it really took five years of post-graduate maturity and training to become a fully trained child neurologist, the two plus three model, but you could also tiptoe into what about a one plus four model if you're going to do that? And of course, I don't think once we create a one plus three model, my own personal opinion is that there's no stepping back on going back to a two plus three model if we chose to go to the one plus four. Dr. Dara Albert talks with Dr. Bruce Cohen: Yeah, sure. If we shorten training, it's going to be hard to lengthen it again after that change has been made for sure. Yeah, lots to consider. And yeah, the student debt is not an insignificant factor at this point in time, unfortunately. What do you see as the most important next step for our field? Who else needs to be involved in this conversation and what other perspectives might we be missing? Dr. Bruce Cohen: We need the perspective of the American Board of Pediatrics and the RRC of general pediatrics because we've been part of their first two years of training for a half a century and to pull back unilaterally saying we're changing our training to a one plus three model or a one plus four model or whatever without consulting the pediatricians would be not taken well. About half of us work in departments of neurology and half of us work in departments of pediatrics. And it varies between hospital and university, the university as to where pediatric neurology lands. And it's not an insignificant portion of the patients either that are being cared for. And so if you're in the department of pediatrics and all of a sudden you're changing the training of the labor force that will be taking care of these children, we may have something to say about it. Dr. Dara Albert talks with Dr. Bruce Cohen: Yeah. Gosh, there are just so many perspectives to think about. This is such a complex issue and lots of potential downstream consequences to any decision that might come out of this review, even if that decision is to keep things the way they are. Throughout this process, the task force spent considerable amount of time thinking about the future of our specialty. So looking ahead 10 years, what do you think the task force would consider an ideal outcome for child neurology training and how would we know if we've achieved it? Dr. Bruce Cohen: The most important thing is that we have a labor force that can take care of the children, the newborns, the pre-borns, and be able to do so not only in big cities like Northeast Ohio or Columbus, Ohio, but in the tiny towns. Ohio's an interesting state because it's really got a lot of pediatric neurology going on in it, but there are lots of states without pediatric neurologists. There are certainly not enough pediatric neurologists to take care of the kids. So how do we make sure that those children get taken care of? So anything that we do, we really need to think about putting boots on the ground so that we can deliver the care that we need to be able to deliver. So that would be one measure of success for sure. Being able to build our numbers up, I think would be another measure of success. Child neurology has done a great job, especially compared with what's going on in some of the subspecialty fields of pediatrics that are really having difficulty with creating a stable labor force. So we've done a really nice job, but we certainly could do better. And being able to attract more students into the residency programs I think would be another measure of success. Dr. Dara Albert talks with Dr. Bruce Cohen: Another thing that I've heard in talking with colleagues about this topic, about what the future of residency could look like is maybe allowing some flexibility for individual programs to tailor training to what makes the most sense at their institution or for their trainees. Did the task force address this question? And if not, do you have an opinion on this question? Dr. Bruce Cohen: In some respects, programs are already doing this. At our hospital, for example, we're now defining pediatrics up to the age of 26. Where pediatrics ends and adults begin is now becoming more of an economic and political debate more than we think about adulthood beginning at 16 or at 18. To some extent, training programs are already taking some leeway, the program requirements. I don't think the programs are overstepping their bounds. For a program to differ or make themselves different, there would have to be agreement amongst the child neurology core of trainers and the adult neurology core of trainers. You'd have to get the programs to agree internally to make any changes. There are some members of the task force that are pushing for this within their own programs. And so that's one possible solution is to let the programs have a little more flexibility on how much adult training would be required. The bigger issue about how many years does it take to train a child neurologist, that's going to have to be something decided on a national level. Dr. Dara Albert talks with Dr. Bruce Cohen: To some extent, the flexibility also needs to be decided on a national level, just in the sense that we don't want to give programs the opportunity to change their training such that their graduates would not be board eligible, for example. So we need the boards and the governing body, the ACGME, to allow for that flexibility with retained board eligibility at the end of it. Dr. Bruce Cohen: I personally think the most important or if not one of the most important aspects is the training certificate that says I'm boarded in neurology with special qualifications in child neurology. I really personally would not want to see that certificate type disappear. Dr. Dara Albert talks with Dr. Bruce Cohen: Yeah. So if program A decided they wanted to do less than 12 months of adult neurology, but the ABPN, the American Board of Psychiatry and Neurology said, "Nope, you wouldn't get that certificate at the end of it," then that flexibility isn't really supported. So there needs to be that conversation with the governing bodies as well. Dr. Bruce Cohen: Yeah. And I guess one of the questions would be, could we define how you spend your month? If you're going to do, let's say a two-month stroke rotation, can you get both adult and pediatric credit if the ratio of patients, adults and kids fits the bill? Dr. Dara Albert talks with Dr. Bruce Cohen: Sure. Yeah. Dr. Bruce Cohen: Same thing with neurophysiology. How many adult EEGs versus child EEGs do you interpret over the course of that one to three month training period? Dr. Dara Albert talks with Dr. Bruce Cohen: Yes. There are so many facets. It's so complicated to think about all of the things that go into training and where are the areas where we can be flexible and where are the areas where we can't? It's just interesting to think about, but I am optimistic for the future that we're having this conversation, that the CNS is behind that you assembled this task force to have these discussions, and hopefully we can move forward as a field together with something that makes sense. Dr. Bruce Cohen: I think what we both would agree upon is that this is the best time to be a child neurologist. Dr. Dara Albert talks with Dr. Bruce Cohen: Absolutely. It's a great field. Thank you so much, Bruce. I've been speaking with Bruce Cohen from Akron Children's Hospital and lead author on a paper published in June 2026 in neurology education titled Education Research: The Future of Child Neurology Residency Training: The Perspectives of a Child Neurology Society Task Force. Thank you, Bruce, so much for your time and your insights into this important topic. Dr. Bruce Cohen: Thank you. Dr. Stacey Clardy: This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword on the podcast app for any neurology-specific topics you want to learn about.

Dr. Justin Abbatemarco talks with Dr. Irene Cortese about recent advances in the treatment of progressive multifocal leukoencephalopathy (PML), focusing on immune-based therapies like virus-specific T cells and immune checkpoint inhibitors. Read the related article in The New England Journal of Medicine. Disclosures can be found at Neurology.org. Show transcript: Dr. José Merino: This is José Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening, and have a great week. Dr. Justin Abbatemarco: Hello and welcome. This is Justin Abbatemarco with the Cleveland Clinic here with Irene Cortese to discuss an update on progressive multifocal leukoencephalopathy treatment in light of a New England Journal of Medicine correspondence, Resolution of PML After Treatment with Virus-Specific T Cells and HCT. Irene directs the Experimental Immunotherapeutics Unit at NINDS. Hello and welcome. Dr. Irene Cortese: Hi, thank you for the invitation to join you today. Dr. Justin Abbatemarco: It's a pleasure to have you on and to talk about this expanding space in rare disease. And maybe if we could start off, can we just take an overview on how PML usually presents and why does it remain so difficult to treat? Dr. Irene Cortese: PML, or progressive multifocal leukoencephalopathy, is an opportunistic infection of the brain that is caused by the JC virus. And most of us carry this virus lifelong and without any symptoms, and it really only causes disease when the immune system is significantly compromised and loses the ability to keep it in check. And so when that happens, the virus can gain the ability to infect oligodendrocytes, and this can lead to the rapidly progressive demyelinating infection called PML. These lesions that develop in PML are typically located in the white matter, and they are most often multifocal. And this leads to the clinical manifestation of a combination of cortical and subcortical symptoms that evolve over weeks to months. And, unfortunately, if immune competence can't be restored quickly, then the disease is fatal within just a few months. And so that's really the core of the problem here, is that there is no effective direct antiviral treatment. And the only thing that works is restoring the immune system ability to control it, but that's often very difficult to do. When it's even possible, it's frequently just not even fast enough. And so you can see this even in situations where you'd think that we'd have an advantage, for example, in HIV-associated PML, where we do have effective antiretroviral therapy. Even there, restoring immune competence can sometimes just take too long relative to how quickly PML progresses. And so on top of all that, PML is really quite rare and is also remarkably heterogeneous because it can occur in very different patient populations from HIV to hematological malignancy to genetic immune deficiencies. And this rarity and heterogeneity really make both the diagnosis difficult and also treatment development quite difficult. Dr. Justin Abbatemarco: It's such a interesting story, and these different backgrounds really present different challenges. But at these last few years, this has been a success story in some way because we've seen so much effort and research into this rare disease space, which is encouraging. We mentioned this at the top, but there are immune checkpoint inhibitors that have at least been trialed for this T cell exhaustion to see if we can boost the immune system, and then more recently with your work around allogeneic-specific T cells to help clear the infection. What have you taken away from those updates? Dr. Irene Cortese: The biggest takeaway is that these two approaches, checkpoint inhibitors and Virus-Specific T Cells, have really transformed the way that we think about PML. So for decades, our only option was really to try to reverse the underlying immune suppressive condition and just hope that the immune system caught up in time. And now we have these two active strategies to try to speed this process up. Importantly, both these strategies have validated the same core hypothesis that even without a direct antiviral agent, we can improve PML outcomes by restoring effective antiviral immunity. And that said, each of these approaches has real limitations. So first of all, they don't work in all patients. And we have best estimates of success rates somewhere in the 50 to 60% range overall. With checkpoint inhibitors, the fundamental issue is that you're trying to unleash an immune response that has to already be there in some latent or exhausted form. For example, in patients with very advanced immune compromise where the T-cell compartment is essentially absent, there's just nothing left to invigorate, and so checkpoint blockade is really unlikely to help. And even when they do work, there is a real risk of exacerbating underlying autoimmune disease as well as the risk of leading to immune reconstitution inflammatory syndrome, or IRIS, where inflammation in the central nervous system of this immune system waking up and attacking the infection can actually lead to severe morbidity and even death in some patients. Virus-Specific T Cells have a whole different set of limitations. These are mostly practical and logistical at this point. Access is really the big one because there are only a handful of centers worldwide that can manufacture Virus-Specific T Cells. And so this just isn't something you can easily do everywhere or quickly. And also, biologically, every virus-specific T-cell product which is made from a different donor is essentially a different drug. And so it's really hard to predict how any given cell product will actually behave in a given patient. I should also mention that for both these approaches, they truly are still experimental. We don't have any controlled studies, and so most of what we're working from is really retrospective series and case reports. And we definitely have no head-to-head data. And so while we apply general principles estimating residual immune capacity or weighing the risk of exacerbating immune-mediated adverse events, we're really making individualized judgment calls rather than following an evidence-based algorithm. Dr. Justin Abbatemarco: And could you talk about those Virus-Specific T Cells? It's not something we use commonly in neurology. How do those work? And have they been used in other spaces successfully that we've been able to maybe apply some of those principles here? Dr. Irene Cortese: Yeah. So Virus-Specific T Cells were really first developed in the transplant setting, and they were essentially a way to bridge patients immediately following myeloablation. And in the period of time it took them to fully immune reconstitute a brand new immune system, it was a way to protect them from the common viral infections mostly that can develop in this time period and that led to such high morbidity and even mortality. And so the way this is done is that you basically take healthy lymphocytes from a healthy donor, and you can train them in vitro by ex vivo expansion and stimulation to basically become professional killers of the particular virus of interest so that, at the end of this expansion period, you basically have a enriched antiviral product that can be adoptively transferred to the patient recipient. And they may not last for a very long time, however, they can, especially with repeated infusions, provide the necessary immunity to bridge until definitive immune reconstitution is achieved. And so the initial experience with Virus-Specific T Cells was really against the various viruses that are so common in the post-transplant setting, like CMV, EBV, adenovirus, and also BK virus, which is a cousin, let's say, of the JC virus. And over time, the process for manufacturing Virus-Specific T Cells has become more and more streamlined. And so back as in 2015, 2017, we started to realize that perhaps these types of cell products might even be used to treat an acute infection and not just to administer in the setting of a planned transplant. And so essentially we've done exactly this, basically copied these manufacturing methods from the transplant world to make Virus-Specific T Cells against the JC virus and can then use them to treat PML. I should mention that BK virus is very similar in structure to the JC virus. And for that reason, what we learned early on when we started to apply Virus-Specific T Cells to the treatment of PML was that we could actually use Virus-Specific T Cells that were made against BK virus and successfully treat PML. More recent years, groups have been manufacturing JC virus-specific BST, but those BK Virus-Specific T Cells can still be used to treat PML. Dr. Justin Abbatemarco: That's really incredible. And it's so cool when we borrow things from these other fields to help inform rare diseases within neurology space. Maybe it's a perfect segue into the cases report in New England Journal of Medicine where you had two cases with inborn errors of immunity. You've utilized the strategy and then stem cell transplant. Walk us through those cases. What did you see? What did we learn from these that we can apply more broadly? Dr. Irene Cortese: Our paper really told the story of our experience of treating these two young men. Both of them had developed PML in the setting of an inborn error of immunity. One of them had DOCK8 deficiency, and he also had Sézary syndrome as a comorbid condition. And the second patient had a CD40 ligand deficiency. And for both these patients, we basically adopted the same strategy, which was to first try to gain control of the JC viral infection. And once that infection was actually under control, then we went ahead and proceeded to definitive treatment of their underlying genetic immune deficiency, which was transplant in their setting to correct the real root problem that they had. And what I think was perhaps most instructive in this experience is what happened after transplant in both cases. So transplant obviously involves a period of renewed immune vulnerability, and that's exactly when we feared that the PML might come back, even though we had been able to gain control, at least temporarily, using this adoptive transfer Virus-Specific T Cells. Fortunately, in these two cases, that didn't happen. And in fact, patient one actually developed IRIS shortly after engrafting with worsening neurological symptoms and also imaging that showed active inflammation, which responded well to steroids. And he's now years out with no evidence of PML or his prior malignancy, which was also treated by the transplant. The second patient's course was complicated by cryptogenic organizing pneumonia, or COP, which can happen in the post-transplant setting, and did require steroids. And this did cause a transient uptick in the JC viral copy number in the spinal fluid, but this resolved once the steroids were tapered. And this patient also is now several years out with only mild residual neurological deficits. So it's important that for both these patients, the transplant donors, in addition to undergoing collection for the transplant itself, they also underwent a collection to make extra rescue Virus-Specific T-Cell products that we had on hand just in case the PML relapsed post-transplant, which of course was not, in the end, needed. And so basically, the overall strategy for both these patients was sequential and deliberate. First to establish virus-specific immune control, and only then proceeding to the definitive but higher risk step of transplant with the safety net available in case virus reactivated during that post-transplant period. Dr. Justin Abbatemarco: The complexity of these cases, though, and the successful outcome is just incredible. And again, we don't always treat these level of patients, but most neurologists will see PML during their career. How do you think this helps inform this broader field of PML treatment in your mind? Dr. Irene Cortese: For me, these two cases really crystallized the idea of immune facilitation as a bridge rather than as a standalone endpoint. For example, in these two patients, Virus-Specific T Cells could not have led to a definitive cure because the underlying immune defect was still there, but they could buy time and control the virus long enough to get to something that could actually fix the underlying problem, which in this case was the transplant. And I'll be honest, proceeding to transplant in a patient with active or recent PML was really frightening. And clearly that is not an option or appropriate at all for the majority of patients with PML. So I guess that the broader lesson here is that Virus-Specific T Cells or potentially other immune-facilitating strategies might serve as a bridge to get us to the point where we either have a way to address that root cause of immune suppression or just buy us the time needed to recover from immune suppressive exposures and perhaps opens up the question of how we might use sequential strategies and combinations of strategies to optimize the care of these patients. Dr. Justin Abbatemarco: Really appreciate your paradigm of how you think about these cases in treatment, and yet you can have these short-term strategies to bridge patients to have an improved immune response to get this under control. Could we talk about other common examples? So we have natalizumab-induced PML cases, HIV-associated PML cases. How would you think about managing those, so outside of these inborn errors of immunity? Dr. Irene Cortese: Each PML patient is somewhat unique, and definitely the underlying condition that is driving the immune suppressed state is really critical in mapping out what we need to do. I think of HIV-associated PML or even natalizumab-related PML as being somewhat unique. Because unlike most other causes of PML, we actually do have clear and reliable ways to restore immune competence, so basically antiretroviral therapy in HIV infection or simply discontinuing the non-immune-depleting drug natalizumab in the case of natalizumab-related PML. And so this is obviously a real advantage compared to many of the other underlying conditions where there really is no good way to reverse that immune suppression at all. That said, in some patients, for example, with advanced AIDS and very low CD4 counts, immune reconstitution can still be very slow even when the HIV replication itself is well controlled. And so in a subset of patients, the PML can still really pace the recovery. And so we do sometimes need strategies to bridge that gap. And basically. we would consider the same immune restoration approaches that we've been talking about right now. There is an added layer of complexity here that's a bit more, let's say, unique to HIV-related PML or to the setting of natalizumab-related PML, which is that in both these cases, immune reconstitution is going to happen eventually. And when it does, then many of those patients do experience PML IRIS where the constituting immune response paradoxically worsens the neurological injury by attacking the infected tissue. And so this really needs to be watched for and managed typically with steroids. And certainly this risk of developing PML IRIS needs to be really considered if we are going to use strategies to boost or facilitate immune reconstitution in the setting of HIV infection or natalizumab-related PML. And we just have to be particularly mindful because there's already a very high likelihood of developing PML IRIS independently of getting that extra boost. Comparatively, in the setting of non-HIV-related PML or not in the setting of natilizumab treatment, I think that strategies like checkpoint inhibition and Virus-Specific T Cells have really been game-changing because, historically, these patients had no equivalent to antiretroviral therapy with no reliable path to reconstituting immunity. And we're really hoping that these approaches will start to bring the outcomes that we've seen, for example, among HIV-related PML and in the setting of natalizumab and PML to these other underlying conditions and achieve the same immune control and survival rates that are achieved in at least a substantial portion of these patients. Dr. Justin Abbatemarco: It's been so exciting. Again, the updates in this field when we really did... We had nothing to offer patients for so long and now to have conversations that are a little bit different. Can I ask you to peer around the corner? What does the future look like in your mind? Do you see other therapies that are potentially at play and maybe right now are there clinical trials that we could enroll patients so that we can help inform the field more broadly? Dr. Irene Cortese: Yeah. So I think that ways to facilitate and accelerate immune reconstitution have clearly been shown to be a valid strategy. And so what I expect and hope is that in the years to come, we'll learn to harness that better and learn to identify which patients are most likely to respond to particular types of strategies to facilitate immune reconstitution. It's really important, I would say, that patients participate in trials because the field really does lack controlled data and it lacks head-to-head comparisons. And so every patient enrolled in a trial or a well-structured registry is really contributing to how the next patient gets treated. And given just how rare and heterogeneous PML is, we're just not going to advance this field through isolated case reports alone. And so we really do need patients and their physicians to be willing to participate in structured and collaborative research. The Holy Grail is, of course, a direct antiviral agent that would really broaden our ability to treat patients and potentially also continue to treat whatever that underlying condition was that led them to the risk of PML in the first place, so, for example, patients receiving treatment for cancer or patients having an autoimmune disease that requires immune suppression. And so I am hopeful that eventually the direct antiviral will be identified. And along that line, what I can mention is there are certainly clinical trials that are ongoing. At NIH, we have an active natural history study from where we can funnel patients into various experimental treatment strategies, including Virus-Specific T Cells or checkpoint inhibitors. Or right now, we actually do have an ongoing trial of intravenous brincidofovir as a possible direct antiviral strategy. What I hope for the future is that we will find ways to really collaborate and to form national as well as international consortia so that we can accelerate the development of these treatments. Dr. Justin Abbatemarco: We have things we can do now, and then we can help inform care for our future patients as well. So these are great messages, and I can't thank you enough for coming on. Again, most of these developments have been under your guidance, and we appreciate your leadership in this space and helping to give us this insight into this really rare disease. For folks, they can check out the article. It's in the New England Journal of Medicine, Resolution of TML After Treatment with Virus-Specific T Cells and HCT. Irene, thank you for coming on. Dr. Irene Cortese: Thank you so much. Dr. Stacey Clardy: This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org\podcast for our full list of past episodes, or you can also search by keyword on your podcast app for any neurology-specific topics.

Dr. John Ney talks with Dr. Daniele Piomelli about the evolving role of cannabis in neurology, exploring its history, current research, and potential future applications. Read the related article in The New England Journal of Medicine. Disclosures can be found at Neurology.org.

In part one of this two-part series, recorded at this year's AAN Annual Meeting, Dr. Gregg Day talks with Drs. Joel Salinas and Sarah Song about the evolving landscape of brain health, practical approaches to incorporating brain health assessments into routine care, and the importance of collaboration across specialties. Visit the newly launched BrainHealth.com to access trusted brain health information and stay informed. Disclosures can be found at Neurology.org. Show transcript: Dr. Jose Merino: This is Jose Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week. Dr. Gregg Day: Hello, this is Gregg Day from Mayo Clinic, and welcome to this special conversation. Today's episode was recorded live at the Brain Health Hub during this year's AAN Annual Meeting in Chicago. Because it was recorded on site, the audio may sound a little different from our usual episodes, but bear with us because it's absolutely worth it. In this conversation, our panel explores the evolving landscape of brain health, including growing use of wearables, digital tools, direct to consumer tests, and artificial intelligence. We discuss how neurologists can help patients to navigate brain age scores, consumer health data, and emerging technologies while integrating brain health into everyday clinical care. This panel discussion is totally aligned with AAN's mission of bringing brain health to all, and on point with the release of brainhealth.com, AAN's new website, bringing together our resources for clinical practice and for research in this space. We hope you enjoy this panel discussion as much as we enjoyed recording it. We appreciate people joining this special session on integrating, educating, and implementing systems of care around brain health for the practicing neurologist. I've got a great team of practicing neurologists here as well. We're looking forward to sharing some of this discussion with lots of opportunities for questions as well. And we're going to kick into the contact right away. I'm Gregg Day. I'm a behavioral neurologist at Mayo Clinic in Florida. I'm joined by Joel Salinas and Sarah Song. I'm going to let them introduce themselves and then I'll provide a bit of scope for our discussion. Dr. Joel Salinas: Great. Thank you, Gregg. So I'm Joel Salinas. I'm a behavioral neurologist, and then I'm also a clinical associate professor of neurology at NYU Langone Health. Dr. Sarah Song: My name is Sarah Song. I'm a stroke neurologist here at Rush University in Chicago, and my favorite job is at the editor-in-chief of Brain and Life, soon to be brainhealth.com. Dr. Gregg Day: Over the past few years, the AAN has definitely taken a clear and very intentional position. Brain health is part of the central nervous system of our academy. It is not meant to be on the periphery, and it's going to become increasingly central to what we do in our practice. And so along with that call, we're really seeing this shift in our field being called to move beyond simply episodic disease management towards a launch of a comprehensive brain health platform and a development of a shared definition of brain health, which we want to conceptualize as this continuous state of attaining and maintaining optimal neurological function to meet the needs of our patients. So this vision raises some real questions in clinical practice. What does preventive neurology look like when we integrate it into our clinic visit? How do we integrate health screening into the clinic visit? We all have time constraints and we're going to be honest and open about that. And what's the future? How do we start educating people on how to actually do this in practice? And maybe even a little bit more challenging, how do we address some of those social structural problems that are often a bit beyond our immediate control, but we all know are critically important here? So today we're going to talk about some of these questions head on. We do want this to be a bit of a dialogue. We want to invite perspectives. We want to hear other perspectives from the audience as well. And we're not here to debate whether brain health is important. I'm going to argue if you're sitting here joining us, you already know why it's important. And if you don't think it's important, you're in the wrong place, but that's okay. Instead, we're going to focus on some of the realistic challenges and maybe strategies to address this. And this key question, what's the AAN going to look like if we're successful in this mission moving forward? So I've asked Joel and Sarah not just to share successes here, but we're going to be candid about the challenges. And so some of these things we just don't know yet about, but we do recognize what we need to be doing to move things forward. And we're going to begin by reframing the neurologist's role in brain health and what that shift means for the people that we care for. So as we've said, the AAN has a definition of brain health. It's changing our view on clinical practice on research and education. So love to hear from Sarah first on your perspective on how this definition has changed or maybe challenged your role as a neurologist in day-to-day practice. Dr. Sarah Song: So I think as a stroke neurologist, my biggest challenge was moving from a reactive to a proactive preventive situation. So I see people on their worst day when they're having a stroke in the hospital, in the ER. I show up and the effects of whatever they've been doing to their brain has ultimately reached some sort of conflict. I think in that sense I was always, okay, how do we prevent a recurrent stroke? But less so thinking on the front end, less so thinking about the lifespan. When we talk about brain health, it starts from prenatal all the way to senescent. It doesn't start when you're 75 and you show up in the ER and I meet you. It should really be starting before you have disease. What can we do upfront? What can we tell your mother before you're even born? So that was the biggest takeaway for me was thinking not just reactive, but proactive, preventive. Dr. Gregg Day: Expanding the scope for sure. Joel, what would you like to add to that? Dr. Joel Salinas: Yeah, with this definition of brain health, which bears repeating again, and it's like over here on one of the posters over here, it's a continuous state of attaining and maintaining the optimal neurologic function that best supports one's physical, mental, and social wellbeing through every stage of life. And as a neurologist, I'm coming from the lens of a behavioral neurologist, it can seem a little overwhelming to feel like you have to now tackle all these different elements of a person's care, but it's really just more than anything reframing something that we've already been doing in practice, which is really claiming responsibility over helping to prevent disease, prevent risks, managing those risks, really being much more proactive. And it's a little bit more of a public health framing, but it's helpful to really claim that responsibility of things that happen before the patient presents in the hospital in the acute state. And there's so much that we can do, which I know we'll get to, but it's an important framing for neurologists in particular to own. Dr. Gregg Day: And this emphasis on prevention, obviously very important. That's the best way to manage disease is going to be to prevent it, certainly best for our patients. But Sarah, as you pointed out, the lifespan perspective isn't within any one of our reaches. So of course the importance of working as a team. Thankfully, we have amazing representation of neurologists here at the AAN, and we all have our own contacts, people that we work with, and so can broaden this mission. Thinking about preventive neurology though, this implies this earlier, broader, sometimes non-traditional interventions to improve our patient's ability to maintain and attain the function that they need. So Sarah, what aspects of brain health promotion feel most natural for you in your clinical environment? Maybe which are some of the areas where you think as a field or as a neurologist, we're going to have more struggles or we're going to hesitate? Dr. Sarah Song: So think as a stroke neurologist, the first thing that really comes up is risk factor management. You both were essential in creating the safest brains, and I'll just refer to some of it. I'll let you guys talk more about that. But for me, it's blood pressure. Above and beyond anything, blood pressure causes strokes of hemorrhagic and ischemic strokes. So talking about risk factor control, especially blood pressure. And then the other one that among risk factor control, just there are so many other risk factors that contribute to stroke. More interesting to me though is the other end, the things that I don't think neurologists are comfortable with. So the addressing mental health, for example. Mental health is something that we learn about, of course, in neurology. We do psychiatry rotations, but we're not necessarily equipped with all of the medication wherewithal or the social strategies that we can use to help so with mental health. And I also think in that same sense, we're not necessarily given the tools to deal with the disparities in health, so socioeconomic disparities that really do affect brain health outcomes as we've learned. So approaching those sorts of situations that we're not comfortable and finding a solution upfront, whether in training or whether in CME or something like that, that we can become more proficient in will actually help us to become more of a well-rounded brain health practitioner. Dr. Gregg Day: And you referenced the safest brains. And Joel, thank you for joining the team in writing that article. Of course, we should credit our lead author, Dr. Selwa, who really coined that term. It's a little hard to remember all of the elements, but when you actually read them or think about them, they really do frame that comprehensive approach to prevention in our patient population. And so we're talking about here screening at every neurological visit, or at least thinking about it in your patients, the importance of sleep, affect, food, exercise, supportive, social interactions, trauma avoidance, blood pressure control. It gets its own statement there. And then other risks attributed to metabolic and genetic factors and affordability and adherence to medication recommendations, infection prevention, negative exposures, that's where drugs and alcohol, tobacco come into place. And last, definitely not least, those structural and social determinants of health. And so it's a long list. It's a daunting list for any of us to tackle on our own, but an important list to think about. What's one brain health domain that you believe neurologists could realistically and meaningfully integrate into a routine visit back in their offices? Dr. Joel Salinas: When you look at all of the different factors, it can, again, feel very overwhelming as a neurologist. How am I going to tackle all these things? It's helpful to frame it as the responsibility of the field or the whole care team, and everybody has their own favored factor that they go on the hill and preach about. Whatever your subspecialty, whatever condition, whatever specific area that you feel most confident to really speak to, whatever is most relevant to that patient in that moment, that's the one to really bring up. So when you are in that patient visit and your patient is mentioning how, "I don't do anything all day." That's an opportunity to maybe ask some more questions about physical activity or try to identify what limitations might be. If your patient mentions to you, "There's nobody for me at home." maybe talking about supportive social interactions and loneliness or social isolation is really relevant there. If you frame that also with identifying those which are most modifiable, that also becomes not just a moment of gathering data, but an empowering moment to really make an impact. Dr. Sarah Song: And I love that. So framing it in that individual moment to pivot to say, "For you, but let's focus on this right now or this today." That's just listening to the patient and having all those factors in the back of your mind, hitting upon them, but you don't feel like you need to hit each one with the same hammer stroke or whatever, reflex hammer. But I love that because then it's individualized for that person, for that patient, and it's more meaningful that way. Dr. Gregg Day: And it's a natural continuation of what we're all doing anyway, trying to optimize the care for our patients, but recognizing in ourselves that we're actually taking time for brain health promotion, for preventive health promotion, and sometimes tying that back to the patient as well. I tell all of my patients frequently that your work you're doing with your cardiologist to manage your heart disease, good news, you're also improving your brain health over time. We think that's important. And my favorite one to choose is sleep. Sleep is one of those ones that there's no area of neurology where it's not relevant. It's a common complaint and it affects more than just our patient as well. It affects everyone tied to them too, as we usually find out through that discussion. Dr. Sarah Song: I was just going to add, sleep is also a favorite of mine because it's very actionable. You can screen for it easily. You can just say, "How are you sleeping? How long are you sleeping?" Ask them about apnea stuff. And I know you guys address this in your paper, but what I love about it is you can actually do something by it. You can talk to them about sleep hygiene, you can refer them for a sleep study. So yeah, sleep's a good one. Dr. Gregg Day: It's a favorite for me. The AAN vision talks about some other actionable achievements, and what we'd really like to see, we want to see a brain health visit becoming a part of routine care at each of our life stages. And so Sarah, from your perspective, what structural or cultural changes within neurology practices would we actually need to see happen to make that feasible rather than aspirational? Dr. Sarah Song: Yeah, it's tough because our visits are all becoming shorter and we have less time to spend with patients. We're getting that squeeze. So one of the thoughts I had was whatever work that patients can do before they even show up in your office might be really beneficial. So a lot of times before you go to a doctor's office, they'll send you a list and they'll say, it's like a review of systems, but if you're able to do that before you even show up in your doctor's office, that takes the burden of collecting that information. And it can be simple questions like a PHQ-2 or four, a GAD score, something like GAD score, GAD. Yeah. So basically taking care of some of that upfront. And then another idea would be having an MA collected as part of the check-in process, so going through some of those screens, creating a real brain health screen that you might be able to do in just under five minutes. And nothing like that has really been validated yet. Obviously, that we have a good handle on what the components are. Would it increase administrative burden? Possibly, but I do think that the more that we normalize collecting that information, the better off we're going to be to provide a longitudinal assessment of where somebody is going in terms of their brain health. Dr. Gregg Day: And that can provide that next steps to the discussion in the office of the framing of that as well. Yeah, really important suggestion. You will find the brain health article that we've referred to, it's included in the online content for this session if you're accessing it on your app. It does have some tools in there, basically beginning thoughts of how we might start to achieve some of this. The questions that you can ask, the surveys that could be filled out and other validated tools can all be a part of that as well. Most neurologists though, and you said it, we operate under pretty tight timelines, and that's partly by design. We want to see and provide care to the greatest number of patients. It's partly out of constraints of funding and return on investment and all the other things that hold our feet to the fire. Joel, how do you make time for brain health conversations in that busy clinic practice while still remembering that our patients are usually coming to see us for a very important chief complaint that requires extensive time and commitment to solve? Dr. Joel Salinas: Even the question of how do you find time comes with its own assumptions is how do you add it in there into the visit? I think you're already coming from a place of adding the burden on it if you approach it that way. It's almost like thinking that brain health is something that comes after the real visit has happened rather than thinking about it as something that you add onto as an additional responsibility, really think about it how you integrate it within your practice because these questions about sleep and mood and diet, think about it, they're already in our visit, you're already asking these questions, especially based off of the chief complaint that's coming. If you're not asking them, you probably should be wondering why you aren't asking for risk factor related questions. And at the end of the visit, when you're really wrapping things up and talking recommendations is where you have an opportunity to really reflect back as a part of your overarching care plan. If the patient told you that they're having a hard time with medications, that's an important point that you want to bring up at the end where you can say, "I heard that you had a hard time managing the dosing of the medication. Let's figure out how we can prescribe a more simpler dosing or make it extended release." Or if they brought up the point about mood, thinking about how you can prescribe a medication that might actually have a positive additional benefit on their mood as well. So I don't see it as one more thing to do. I see it as something that gets woven throughout your care and it's more about how you really think about the whole patient. Dr. Gregg Day: That's a perfect perspective. And we could of course think about stroke. Most people aren't there to find out, "What can I do about the stroke that I had?" They're in your office to make sure I don't want to have another stroke. We want to prevent that. And so this is really all consistent with that. And in our practice, we've got the patient there, but almost always somebody else providing that collateral history. And inevitably I'm going to be asked that question of what do I need to do to decrease my dementia risk? So you're right, this is an opportunity for us to build this into the assessment to provide better care with that more forward-thinking perspective. Sarah, I want to shift gears a little bit here. So we've all highlighted some of the ways we can already do it with the skills that we have now, but what are the other competencies related to brain health that might be a little bit lacking in neurologists that we want to be encouraging and that as the AAN, we want to be continuing to develop as we move forward? Dr. Sarah Song: That nutrition has become really important in brain health and certainly has received a lot of attention that we need to feel comfortable with that. And that means maybe bringing in some partners to help us with education if that's the case. I mentioned a little bit about mental health, so understanding what the issues are, taking in perspectives of family members and caretakers is really important. Part of what I was thinking about was when I was reading the article again, which is fabulous and I encourage all of you to read it, it'll be attached, but a lot of what has to do with brain health requires behavior change, that we are not necessarily equipped with those tools for motivational interviewing or how do you change someone's behavior? How do you track that over time? What do we say to elicit a behavior response from our patients or their families? So receiving education in that makes sense and is certainly something that we don't necessarily focus on so much. We're more focused on diagnosing and treating, but not necessarily how do we think about holistically, how do we change this patient's behavior for the better? Dr. Joel Salinas: I totally agree. I think the competencies of things like lifestyle medicine are really important, motivational interviewing. These are really concrete skills that we can teach, but I would suggest one more competency that is a little less obvious, which is systems thinking. Just thinking about what you recommend and how that person will interact with the rest of the healthcare ecosystem that they're in, because that really boils down to the reality of the patient. We do a really great job of training really excellent neurologists, but we could continue to do a better job to train neurologists who can change neurology. Dr. Gregg Day: That's two really important perspectives. And it may be that some of us develop skills in one area, some in another, some in all of the competencies. When do we begin training and teaching on this? Maybe we should all say as soon as possible, but at what level of our traditional training, how do we start to fill some of those gaps so that we are bringing up leaders in this area and continuing to train and develop our own competencies here? Dr. Joel Salinas: Some of it does begin at medical school where people do start to get an understanding of different systems and they learn about preventative care, highlighting where brain health fits into that because so much of what a lot of people get that education is coming from usually internists and people who have a lot of expertise within cardiometabolic risk factors. It'd be helpful whenever they get their neurology lectures or their brain and behavior lectures that there's a mention about risk factors and linking ideas together, making sure that people know that regardless of what specialty they go into, the central nervous system supports who we are. And so everybody should really care about that. Within neurology residency specifically, it's helpful within all the different clerkships or rotations. Because again, it's like adding the specific module, adding a specific curriculum becomes a little bit more challenging, but it's something that we should be integrating throughout. So when you have a patient where they came in with a hemoglobin A1C of 10, that's a great moment for teaching about how important to bring in prevention early. And then what are the factors that came into play beyond just saying that it's the "patient's fault" for not following along with recommendations. Think about the system that they're in and how you can prevent in the future that they won't come in with another stroke. Dr. Gregg Day: The AAN obviously envisions brain health as fundamental to what we are doing, but we are going to need partners. We're going to need partners well outside of our specialty to engage the entire house of medicine. And we've got a lot of amazing staff and other advocates that are already involved in this important work. But we also want, as neurologists, we want to remain the vanguards of brain health. We are best positioned to lead in this area and to continue what the initiatives that's been started here. Sarah, when you're thinking about top priority partners though, who should we be looking to in our own practices, our own health systems as an AN organization? Who do we need to engage to really move this forward effectively? Dr. Sarah Song: The first partner that comes to mind is primary care physicians. So from every point of the life stage, whether it's OBs, pediatricians, all the way up to gerontologists, because they are for people at the touchpoint, we are the neurologists, so we're the caretakers of the brain itself, but they certainly see components of brain health in their practice. So making sure that we're connecting with them to help them in any way we can or to use our resources, pool our resources together to take care of that patient's brain health. Number two, psychiatrists, mental health professionals, so understanding psychiatric context of brain health and being able to work with them. And the third are therapists. So rehab physicians, people who can help support brain recovery is going to be really essential. Dr. Gregg Day: Joel, any other priority partners? Dr. Joel Salinas: I'll echo the importance of building that bridge with primary care, but I'll suggest one that's slightly controversial, which is to build better partnerships with health system administrators and payers. This kind of care is just not possible if you don't have the systems of care that are well aligned with being able to provide it and then you don't have the incentives, the financial incentives within that care to be able to promote the systems that'll then deliver that care. There's a lot of room for alternative payment models. I don't think we can solely rely on alternative payment models if that comes in partnership with health plans themselves. As a practicing neurologist, it seems like how am I ever going to reach that payer? But if you start to build that alliance with your health system administrator, the person that runs your clinic, the admins of your department, and let them know this is important, at least they can begin to connect you with the right resources or they can connect you with the right advocacy to build that or figure out how can you be creative about our current codes and billing structures that are available so that way you can not only do that kind of care, but actually get credit for doing that care. Dr. Gregg Day: And of course we'd have to add our political partners as well and the important work that happens through Neurology on the Hill, our lobbyists in DC and at our state government levels. All of this really matters in gaining the recognition that we need. And importantly, helping our politicians to develop that longer term perspective, thinking about the lifespan, not the two, four, six-year reelection span. Obviously there's a lot of focus on. Joel, this is one that I know is close to your heart and the AAN recognizes the importance of social and structural determinants of health and certainly has big determinants in brain health. How do we, and again, in that clinic visit setting, how do we begin to responsibly address some of these factors without getting beyond our expertise or creating unrealistic expectations with our patients about what we can control and manage? Dr. Joel Salinas: When it comes to the structural and social determinants of health, and I'm always really keen on making sure that distinction is clear where social has more to do with the elements of the person's interactions with the world around them, their environment, structural has more to do with the factors and the built environment around them. And it can also be not necessarily built, but also the political structures, the economic structures that they're influenced by. Again, as a neurologist in the clinic, it can feel pretty disappointing when you realize that's an issue and it is more helpful to realize that you don't have to be that person who fixes that issue so much as you are the person who can identify that it exists and be honest about it and then help to pass that on to the next person in the situation that can help to make that better. When you are chatting with your patient and they're bringing up issues related to lack of access to care or lack of finances or issues with insurance or difficulty with secure housing, again, you're not going to be that person who's going to bring the secure housing to them, but you need to be able to be honest that it's there, that it doesn't have an impact, that you document it in your note as a factor. And then think about what you have access to. Maybe in your department or in your clinic, you have access to social work. Maybe you have access to a local advocacy group specific to that person's condition that does have access to somebody who can then provide ways to connect them with local community-based resources. We have care navigators who they do a lot of work. I almost think of them as the heartbeat of a person's care because they're helping to identify what the person has access to within their own communities and helping to understand what benefits they have access to so that way we can begin to address that. But from the clinician standpoint, we're not the ones who are making the phone calls to make sure that they get that kind of grant for respite care. We just have to say, "This is an issue and I'm going to help you with this issue by connecting to someone who can then help to point you in the right direction." Dr. Gregg Day: And how powerful sometimes to just giving voice to those realities in that patient experience, building that relationship, acknowledging how some of the things that we feel are beyond our immediate control totally impact our health, our access to resources, our affordability and adherence with medications, nutrition, exercise and sleep and all of these other factors that are so important. Thank you for bringing more of a voice to that as well. Sarah, are there other partners in your mind that we should be trying to engage who can help to mediate this? We've talked about social work, some other people that can be the in betweens here, but in your experience, other thoughts to add to that? Dr. Sarah Song: The one important group to include obviously are the patients in the communities. Our patients don't live in silos, they live in communities. We need to build those bridges to them, let them know how can we help you? Here's what we have available. What are the resources that you need or the problems that you see in attaining ideal brain health in your community? And patients have that lived experience. They know what works for them or what hasn't worked for them. And it can be very powerful to reach out to patients, whether it's patient advocacy groups or nonprofits or the patients themselves in the community, like in the churches, in the apartment buildings, wherever people congregate within a community and ask them, "How can we help? How can we help you? These are what we see. What do you think about that? What is something that might work for you that might not work down the street two miles down?" So we're in Chicago. Chicago is incredibly divided. There is a huge disparity of life expectancy within 10 miles. If we go north, you're going to hit the Gold Coast. People live to be quite old. And then you head southwest and the life expectancy drops by 15 years. Understanding what works in what community and making sure that we're sensitive to those needs is really the only way that doctors can bridge that gap toward ideal health to practical real health. Dr. Joel Salinas: I would just build on that. When it comes to partners, yeah, absolutely. The patient themselves, their care partner, they are key partners and it doesn't always come up as clearly within the clinic. There's more and more conversation around thinking about what is the unit of care and going beyond the patient, thinking about the family unit as that unit of care and really getting that alliance built across that family unit. I come from a Hispanic community and whenever I have patients that are also from the Hispanic community, I know how important it is to really get everybody who's in the home on board with the plan because everybody is a part of that person's care. There's been work also coming out of the Institute for Healthcare Improvement, which is really interesting, looking at how do you build systems that are better for older adults. And one of the things they promote is a thing called the 4M model, and that stands for what matters, mentation, mobility, and medication. Mentation, for us as behavioral neurologists, that's a key part of what we do, but mobility is something that applies to everybody and same thing with medication. But what matters most, it gets missed a lot. And unless you've had very specific training or mentorship within your training, we often miss it. Rochelle Walensky, she's a former CDC director, she mentions when she was doing a lot of HIV counseling, whenever a patient would have a positive test result, she was trained to be quiet after you tell the result and just wait to see what the patient says. But whatever is the first thing that comes out of their mouth is their signal to that is what matters to them the most. There's something really valuable because as you're doing your counseling with your patients, listen to what they're saying. If what matters to them is not being a burden for their family, bring things back to that. If what matters to them is being independent, bring things back to them. If feeling more cheerful or being more engaged matters to them, find ways to connect your recommendations and your lens of care back to what really matters to them. Dr. Gregg Day: And of course by involving the family, involving the broader community, we're touching on the lifespan here. So dementia specialists affecting the youngest people in the room and the neonates that yet to become a part of the discussion. So great things to think about. Dr. Stacey Clardy: That wraps up part one of this fantastic discussion from the AAN Annual Meeting on Brain Health. We will pick up with part two in the next episode, focusing on practical suggestions on how to easily implement preventative brain health interventions in your clinic, and then wrap up with the comments and questions from the audience who were present at the Brain Health Talk at the annual meeting. This is Stacey Clardy, your podcast editor. If you've enjoyed the podcast, please take a few moments to subscribe, rate, and review the Neurology Podcast through Apple Podcasts, Google Podcasts, Spotify, or wherever you listen. And remember, you can always head to neurology.org/podcast for our full list of past episodes, or you can also search by keyword in your podcast app for any neurology specific topics you want to learn about.

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