Continuum Audio

Many serious medical illnesses are associated with some degree of serum electrolyte abnormality, renal impairment, or both. The neurologist must determine if the patient's neurologic symptoms are related to the renal and electrolyte disturbances or whether a concurrent primary neurologic process is at play.
In this episode, Casey Albin, MD, speaks with Eelco F. M. Wijdicks, MD, PhD, FAAN, FACP, FNCS, author of the article "Neurologic Manifestations of Renal and Electrolyte Disorders" in the Continuum® February 2026 Neurology of Systemic Disease issue.
Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia.
Dr. Wijdicks is a professor of neurology and attending neurointensivist for the Neurosciences Intensive Care Unit at Mayo Clinic in Rochester, Minnesota.
Additional Resources
Read the article: Neurologic Manifestations of Renal and Electrolyte Disorders
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More about the American Academy of Neurology: aan.com
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Host: @caseyalbin
Guest: @EWijdicks
Full episode transcript available here

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Aaron L. Berkowitz, MD, PhD, FAAN, who served as the guest editor of the February 2026 Neurology of Systemic Disease issue. They provide a preview of the issue, which publishes on February 2, 2026.
Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.
Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California.
Additional Resources
Read the issue: continuum.aan.com
Subscribe to Continuum®: shop.lww.com/Continuum
Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud
More about the American Academy of Neurology: aan.com
Social Media
facebook.com/continuumcme
@ContinuumAAN
Host: @LyellJ
Guest: @AaronLBerkowitz
Full episode transcript available here
Dr Jones: The human nervous system is so complex. You can spend your whole career studying it and still have plenty to learn. But the human brain does not exist in isolation. It's intricately connected with and reliant on other bodily systems. When those systems go awry, sometimes the first sign is in the nervous system. Today we will speak with Dr Aaron Berkowitz, an expert on the neurology of systemic disease, and learn a little about how these disorders can present and what we can do about it.
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast.
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Aaron Berkowitz, who is Continuum's guest editor for our latest issue of Continuum on the neurology of systemic disease. Dr Berkowitz is a professor of clinical neurology at the University of California, San Francisco, and he has an active practice as a neurohospitalist and in outpatient general neurology---and, importantly, as a clinician educator. In addition to numerous teaching awards, Dr Berkowitz has published several books and also serves on our editorial board for Continuum. Dr Berkowitz, welcome. Thank you for joining us. Why don't you introduce yourself to our listeners? 
Dr Berkowitz: Thanks, Lyell. As you mentioned, I'm a general neurologist and neurohospitalist here in San Francisco, California at UCSF and very involved in resident education as well. And I was honored, flattered and a little bit frightened when I received the invitation to guest edit this massive issue on the neurology of systemic disease. But I've learned a ton, and it's been great to work with you and the incredible authors we recruited to write for us. And I'm excited to have the issue out in the world. 
Dr Jones: Yeah, me too. And you and I have talked about it before: you're one of a very small group of people who have guest edited multiple issues on different topics, right? 
Dr Berkowitz: That's right. I did the neuroinfectious disease issue in… was it 2020? 2021? Something like that. 
Dr Jones: Yeah. So, congratulations, more people have walked on the moon than done what you've done. And I'm looking forward to chatting, Aaron, and really grateful for your work putting together a fantastic issue. I think our listeners will appreciate that the nervous system does not function in isolation. It's important to understand the neurologic manifestations of diseases that originate within the brain, spinal cord, nerves, muscles, etc., but also the manifestations of diseases that begin in other systems and, you know, may masquerade as a primary neurologic disorder. So, it's obviously an important topic for neurologists, since many of these patients are receiving care in another setting, perhaps from another specialist. I almost think of this issue of Continuum as a handbook for the consultant neurologist, inpatient or outpatient. I don't know. Do you think that's a fair characterization of the topic?
Dr Berkowitz: Absolutely. I completely agree with you. I think, yeah, many of us go into neurology interested in our primary diseases, whether it's stroke or Parkinson's or neuropathy or particular interest in neurologic symptoms, whether they're cognitive, motor, sensory, visual. And we quickly learn in residency, right? As you said, a lot of what we see is neurologic manifestations of primary diseases. So, I don't know how similar this is to other training programs. But it seemed like, if I'm remembering correctly, my first year of residency was mostly on primary neurology services, general stroke, ICU. And we moved into the consultant role more in the PGY-3 year the next year. And I remember explaining to students rotating with us on the consult services, this is actually much more complex in a way, because the patient has some type of symptom in a much broader and much more complicated context of multiple things going on. And I call it "neurology in the wild." There's, like, neurology of, this patient's had a stroke and we know they have a stroke and we're trying to figure out why and treat it. That's all interesting. But our question here, is there a stroke needle buried in this haystack of all of these medical or surgical complications? And learning what I call neurology of X, which is really what this issue is; as you said, that there's a neurology of everything. There's a neurology of cardiac disease. There's a neurology of the peripartum. There's a neurology of rheumatologic disease. There's every new treatment that comes out in oncology has a neurology we learn, right? There's a neurology of everything. 
Dr Jones: There's a lot of axes, right? There's the heart-brain axis and the kidney-brain axis. And… I think we cover everything except the spleen-brain axis, which maybe that's a thing, maybe not. I'll probably hear from all the spleen fans out there. So, I want to do a little bit of an experiment. We're going to do something new today on the podcast. Before we get into the questions, we're going to start with a Continuum Audio trivia question. So, this will be a first time ever. Dr Berkowitz, we all know that chronic hyperglycemia, or diabetes, can lead to many neurologic and systemic complications and that optimal glucose control is our goal. For our listeners, here's the question: what neurologic complication can occur from correcting hyperglycemia too quickly? What neurologic complication can occur from correcting hyperglycemia too quickly? Stick around to the end of our interview for the answer. So, Aaron, let's get right to it. You had a chance to review all the articles in this issue on the neurology of systemic disease. What do you think in all of those is the most exciting recent development for patients who fit into this category?
Dr Berkowitz: Yeah, that's a great question. I think we talked about when we were putting this issue together, right, a lot of the Continuum subspecialty topics; there should have been updates on particular disease diagnostics, treatments, new phenotypes. Whereas here probably a lot less has changed in primary heart disease, primary cancer. As I'd like to say to our students trying to excite them about neurology, most specialties have new treatments, but I can name a large number of new diseases, right, that have been discovered since we've been out of training. So, a lot of the primary medicine stays the same, and the neurologic complications stay the same. But probably the thing that many readers will want to keep handy and will probably be much in need of update again in three years are the neurologic complications of all the new cancer treatments. So, if we think back to I finished training just over ten years ago when a lot of the fill-in-the-blank-umabs were coming out, CAR T therapy, and we were starting to see a lot of neurology, I remember, related to these and telling the oncologists and they said, oh, you just wait. We are seeing at the conferences that there's a lot of neurology to these. And I feel like that is always a moving target. And I think we are seeing a lot of those and it's hard to keep up with which treatments can cause which complications, which syndromes and which severities require holding the treatment when you can rechallenge longer-term complications of CAR T cell therapies now that we've learned more about the acute complications. So, Amy Pruitt from Penn has written us a fantastic article for this issue that covers a lot of the updates there. And I learned a lot from that. I feel like that's the one that just like every time the carnioplastic diseases are reviewed in Continuum, it seems like the table is another page longer from your colleagues there in Rochester teaching us about new antibodies. And I feel like, for this issue, that's one of the areas that felt like there was a lot of very new content to keep up with since last time. 
Dr Jones: That's good news, right? It's good that we have new immunotherapies for cancer, but it does lead to neurologic catastrophes sometimes, and it is a moving target, really rapid. So, you mentioned that just over ten years ago you finished your training and now we see a lot more of these complex immunotherapy-related neurologic complications. What about in the other direction? Are there any things that you see less commonly now in your practice than you might have seen ten years ago right when you were finishing training? 
Dr Berkowitz: I would say no, I think. I think we're seeing a lot of new stuff, and we're still seeing a high volume of the classic consults we tend to get, whether that's altered mental status in a patient who's systemically ill; weakness or difficulty reading from the ventilator in a patient who's critically ill; patient has endocarditis and has a stroke hemorrhage or mycotic aneurysm, what do we do? Yeah, one of the parts that was really fun and educational editing this issue is, I really wanted to ask the experts the questions I find that are really troubling and challenging and make sure we could understand their perspective on things like the endocarditis consult, which I always feel like each time there's some twist that even though the question is what do we do about this stroke and/or hemorrhage and/or aneurysm and is surgery safe? It seems like each time I always feel like I'm reinventing the wheel, trying to really sort out how to think about this. And we have a great article from Alvin Doss at Beth Israel and Steve Feskey from Boston Medical Center. It covers a lot of cardiology, as you know, in that article about a great section on endocarditis where every time it came back for review, I would say, but what about this? This comes up. What about this? Can you explain how you think about this for our readers? I don't know. I'd be curious to hear your perspective. It sounds like we agree on what has become more common. I don't think anything in neurology seems to become less…
Dr Jones: Well, no, I guess we haven't really solved anything, I guess we haven't cured any problem. But that's okay, right? I mean, it's building on an established foundation of experience and history in our field. And you know, we mentioned earlier that in many ways this issue is kind of like a neurology consultant's handbook. We did something a little different with it in that sense. In addition to you serving as the guest editor, you have authored an article in the issue. It touches on something that we've talked about a couple of times, and I'd be interested to hear you talk through it with our listeners a little bit on how to approach the neurologic consultation. Tell us a little more about that and your article and how you approached it. 
Dr Berkowitz: Oh, yeah, thanks. Well, thanks first of all for inviting me to think about a sort of introductory article to this issue. And I was trying to think about what to write about because, as you've said and we've been talking about, no one could know every neurologic complication of every medical disease, treatment, surgery, hospital context. Probably many of us don't even know all the muscle diseases, right, within neurology. So how could we know all this stuff? And we need some type of manual from our colleagues that can explain, okay, I know this patient has inflammatory bowel disease and they've had a stroke. Is that- are these related? Are these unrelated? And I thought the articles kind of answer all of these questions. What would I say beyond this patient has disease X and is on drug Y? Well, look up in this issue disease X and see what the neurology can be, common and rare and how often it's associated, how often it's the presenting feature, how often it means the treatment is failing, etc. I thought, I'm not sure there's much to say there. That's about a paragraph. And I thought, well, let's think even more broadly about neurologic consultation. And as you know, I like to think about diagnostic reasoning and clinical reasoning. And we talk a lot about framing bias right? And I think that is very common in consultative neurology because we'll be told in the consult or in the page or E-consult or whatever it is, this is a blank-year-old blank with a history of blank on treatment blank. And right away your mind is starting to say, oh, well, the patient just had heart disease, or, the patient is nine months pregnant, or, the patient is on an immune checkpoint inhibitor. And whether you want to do it or not, your mind is associating the patient's neurology with that. And it's- even if we know we're framing or anchoring, it's hard to kind of pull away from that. And most of the time, common things being common, a patient with cancer develops new neurology, It's probably the cancer, the treatment, or sometimes a paraneoplastic syndrome. But I've definitely found if you do a lot of inpatient neurology and a lot of consults that you're seeing so much and you have no choice but to apply these heuristics, because you're seeing a lot of volume quickly and the patients are in the hospital or they're being closely followed and outpatient setting by another specialist. You presume if you didn't get it quite right the first time, it's going to come back to you. And there's a little bit of difficulty figuring out, this is a case, actually, of all the altered mental status in acutely ill patients I got today, this is the one I should dig deeper in that I think this could turn out to be a stroke or encephalitis as opposed to delirium. I felt like that I really haven't approached that except knowing that it's easy to fall into traps. And so, I started to think about framing bias. You know, we talked about if we become aware of our biases, right, we're better at not falling prey to them. But it's subconscious. So, we might be applying it without even realizing, or even saying, I might be framing this case the wrong way, you can go right on framing it the wrong way. So, I want to kind of get a little more granular on what types of framing biases actually are relevant, specifically, to the console setting. And so, I tried to come up with a few more specific examples and try to think about ways that we could at least have a quick, if our knee-jerk is to associate primary disease X that the patient has or primary treatment X with neurologic symptom Y, what's at least a quick counter-knee jerk to say, what if it could be something else? So, for example, one of them I call "low signal-to-noise ratio bias." Altered mental status in the acutely ill hospitalized patient. What would you say, Lyell? 99 out of 100- 99.9 out of 100, it's not a primary neurologic disease. Is that fair to say?
Dr Jones: Very high, yep. I agree.
Dr Berkowitz: Yeah. But could it be a stroke? Could it be non-convulsive status epilepticus, meningitis encephalitis? So, how do we sort of counteract low signal-to-noise ratio bias, acknowledging it exists, acknowledging most of the time there is a low signal-to-noise, that it's not going to be neurology---to just for example, use the time course. This is pretty acute. Have I convinced myself this is not a stroke or a seizure or an acute neurologic infection? And if I'm not sure at the bedside, should I err on the side of more testing? Or the "curbside bias," as I call when your colleague just sends you a text message on your phone, No need to even open the chart, Dr Jones. Patient had a cerebellar stroke. Incidental. They're here for something else. Aspirin, right? Just like a super tentorial stroke. And you might reply thumbs up. And then imagine you open the CT scan and it's a huge cerebellar stroke with fourth ventricular compression- and patient can hide a lot of stroke back there, might just have a little ataxia. You were curbsided and that framed you to think, oh, they asked me, is aspirin okay for a cerebellar stroke and I said yes, without realizing actually the question should have been posed is, how do you manage a huge stroke with mass effect in the posterior fossa? So, these types of biases, I come up with five of them, I won't go through all of them. I'm in the article to sort of acknowledge for the reader, most of the time it's going to be what you look up in this issue, but how to think about the times where it might not be and how to be more precise about what framing is and different types of framing that occur specifically in the consultant arena.
Dr Jones: And I think the longer we practice, the more of those low-frequency exceptions that you see. And, you know, and then it sticks in our mind and sometimes the bias swings the other way; people, you know, think primarily about the low frequency. And so, it's tricky. And what I really enjoyed about that article, we started talking about this probably more than a year ago, and more than a year ago, I would say relatively few clinicians were using a now widely popular large language model for clinical decision-making; we won't name the model. And now I think most clinicians are using it almost every day, right? And I think it puts a premium on how to think and how to engage with the patient, and less about the facts and the lists that a lot of conventional medical education really is derived from. So, I really appreciate that article. We can pat ourselves in the back. We had some foresight to put it in the issue, and I think it's a great addition to it.
Dr Berkowitz: Thank you.
Dr Jones: So, the list of potential topics when we think about the neurologic manifestations of systemic disease, we tend to break it down by organ systems, right? But the amount of things that could end up in the issue is almost infinite. Is there anything that, when you were putting this issue together---either in terms of the topics or editing the articles---is there anything that you wanted to include, but we just didn't have room?
Dr Berkowitz: I certainly won't say we covered everything, but I will say we were able to recruit a fantastic team of authors. And as you and I also talked about at the beginning, although you could say, we're doing the movement disorders issue, let's find all the top movement disorders folks who are expert specialists in this field, there's not really a neurohematologist or a neurogastroenterologist out here. So, you and I put our heads together to think of phenomenal general neurologists in most cases, some subspecialists who know a lot about this but were also excited to read a lot more about it and assemble the existing knowledge by the practicing neurologist for the practicing neurologist. And I think with that approach and letting folks have kind of, you know, I asked some specific questions. These are topics I hope you'll cover. These are vexing questions in this area. I hope you'll find some answers to how often can this neurology be the primary feature of this rheumatologic disease with no systemic manifestations and when should we look or as we mentioned, the complicated endocarditis consult. I won't say we covered everything. This could be, and is, textbook-sized, and there are textbooks on this topic. But I think on the contrary, authors came back and had sections on things that I might not have thought to ask- to cover. Dr Sarah LaHue, my colleague here at UCSF, I asked for an article, as traditionally in this issue, on the neurology of pregnancy in the postpartum state and included, I think probably for the first time in Continuum, a fantastic review of neurologic considerations in patients in menopause, which I'm not sure has been covered before. So, things that I wouldn't have even thought to ask for. Our authors came back with some fantastic stuff. And the ICU article by Dr Shivani Ghoshal, instead of focusing just on altered mental status in the ICU, weakness in the ICU---those are all in there---I also asked her to discuss complications of procedures in the ICU. How often do procedures in the ICU cause local neuropathies or vascular injury, these types of things.
Dr Jones: Yeah, me too. And I guess that's a great advertisement, that there probably are things that we didn't cover, but if there are, we can't think of them. We've done as best as we can. So now let's come back to our Continuum Audio trivia question for our listeners. And I'll repeat the question: what neurologic complication can occur from correcting hyperglycemia too quickly? And I actually think there might be two correct answers to this one. Dr Berkowitz, what do you think?
Dr Berkowitz: Yeah, I was thinking of two things. I hope these are the things you're thinking of as well. One is what I think used to be referred to as insulin neuritis, sort of an acute painful small fiber neuropathy from after the initiation of insulin, I think also called treatment-induced diabetic neuropathy or something of that nature. And then the other one described, defined and classified by your colleagues there in Rochester, the diabetic lumbosacral radiculoplexis neuropathy or Bruns-Garland syndrome or a diabetic amyotropy, I think, can also---if I'm not mistaken---also occur in this context; you should have weight loss in association with diet treatment of diabetes. But how did I do?
Dr Jones: Yeah, you win the prize, the first-ever prize. There's no monetary value to the prize, but pride, I think, is a good one. Yeah, those were the two I was thinking of. The treatment-induced neuropathy of diabetes is really nicely covered in Dr Rafid Mustafa's article on the neurologic complications of endocrine disorders. It's a rare condition characterized by the acute/subacute onset of diffuse neuropathic pain and some usually some autonomic dysfunction. And it occurs when you have rapid and substantial reductions in blood glucose levels. And you can almost map it out. There was a study from 2015 which is referenced in the article, which found that a drop in hemoglobin A1c of 2 to 3% over three months confers about a 20% absolute risk of developing this treatment-induced neuropathy of diabetes, and a drop of more than 4%, more than 80% risk. So, very substantial. And then in the other---we see this commonly in patients with diabetic lumbosacral radiculoplexis neuropathy---they have the subacute onset of usually asymmetric pain and weakness in the lower limbs that tends to occur more frequently in patients who have had recent better control of their sugar. We can also see it in the upper limbs too. So, you get a perfect score. Dr Berkowitz, well done. Again, I want to thank you. I want to thank you for such a great issue, a great article to kick off the issue, and a great discussion of the neurology of systemic disease. Today I learned a lot talking today, I learned a lot reading the issue. Really grateful for your leadership of putting it together, pulling together a really great author panel, and I think it will come in handy not just for our junior readers and listeners, but also our more experienced subscribers as well.
Dr Berkowitz: Thank you so much. Like I said, it was a big honor to be invited to guest edit this issue. I've read it every three years since I started residency. It's always one of my favorite issues. As you said, a manual for consultative neurology, and I learned a ton from our authors and really appreciate the opportunity to work with you and the amazing Continuum team to bring this from an idea, as you said, probably over a year ago to a printed issue. So, thanks again, Lyell.
Dr Jones: Thank you. And again, we've been speaking with Dr Aaron Berkowitz, guest editor of Continuum's most recent issue on the neurology of systemic disease. Please check it out, and thank you to our listeners for joining today.
Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio.

Clinicians and patients are in a state of prognostic uncertainty when they are unsure about the future course of an illness. By embracing uncertainty while cultivating prognostic awareness, neurologists can serve the critical role of supporting patients and families through the living and dying process.
In this episode, Casey Albin, MD, speaks with Robert G. Holloway, MD, MPH, FAAN, author of the article "Managing Prognostic Uncertainty in Neurologic Disease" in the Continuum® December 2025 Neuropalliative Care issue.
Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia.
Dr. Holloway is the Edward and Alma Vollertsen Rykenboer Chair and a professor of neurology in the department of neurology at the University of Rochester School of Medicine and Dentistry in Rochester, New York.
Additional Resources
Read the article: Managing Prognostic Uncertainty in Neurologic Disease
Subscribe to Continuum®: shop.lww.com/Continuum
Earn CME (available only to AAN members): continpub.com/AudioCME
Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud
More about the American Academy of Neurology: aan.com
Social Media
facebook.com/continuumcme
@ContinuumAAN
Host: @caseyalbin
Full episode transcript available here
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Albin: Hello, this is Dr Casey Albin. Today I'm interviewing Dr Bob Holloway about his article on managing prognostic uncertainty in neurologic disease, which appears in the December 2025 Continuum issue on neuropalliative care. Welcome to the podcast, and please introduce yourself to our audience.
Dr Holloway: Hi, Casey, and thank you. Again, my name is Bob Holloway. I'm a clinician and neurologist up in Rochester, New York, and I've been doing both neurology and palliative care for many years.
Dr Albin: Well, that's fantastic. And I really wanted to emphasize how much I really enjoyed reading this article. I know that we're going to get into some of the pearls that you offer, but I really want to tell the listeners, like, this is a great one to read because not only does it have sort of a philosophical take, but you also really provide some pragmatic tips of how we can help our patients manage this prognostic uncertainty. But maybe just tell us a little bit, what is prognostic uncertainty?
Dr Holloway: Yes, thank you. Well, I think everyone has a sense of what prognostic uncertainty is. And it's just the uncertain futures that we as clinicians and our patients face. And I would just say that a way to summarize it is just, how do we manage the "not yet" of neurologic illness?
Dr Albin: I love that. In neurologic illness, there is so much "not yet" and there are so many unknowns. And what I thought was really helpful about your article is you kind of give us three buckets in which we can think about the different types of uncertainty our patients are facing. What are those?
Dr Holloway: This is, I think, an area that really is of interest to me, thinking about how to organize the prognostic "not yet" or that landscape. And one way I've tried to simplify it is to think about it as data-centered. And that's the world that we mostly live in as neurologists. That's the probability distributions. We also have kind of system-level uncertainties, and that's the uncertainties that our health system affords for our patients. And then we have, also, the patient-centered uncertainties and the uncertainties that those two prior categories cause for our patients. And that's a big uncertainty that we often don't address.
Dr Albin: In reading the article, I was really struck by, we spend a lot of time thinking about data uncertainty. Can we get population-based research? Can we sort of look at prognostication scoring? I live in the ICU, and so we think a lot about these, like, scoring metrics and putting patients into buckets and helping us derive their care based on where their severity index is. And I'm sure that is true in many of the divisions of neurology. But what I did not really appreciate---and I thought you did a really fantastic job of kind of drawing our attention to---is there's a lot of system-centered uncertainty. Can you give us a little bit of examples, like, what is system-based uncertainty?
Dr Holloway: I think system-level uncertainties just encompass the practical information gaps that may arise during our healthcare encounter. And a lot of, I think, the uncertainty that our patients face and families, they actually describe it as they feel captive by the uncertainty. And it's just the unknowns, not just what affords from the actual information about the disease and its prognosis in the future, but actually the level of the system, like, who's going to take care of them? How do you manage arranging for nurses to come into the home or all those practical-level uncertainties that the system provides that sometimes we don't do a good job of road-mapping for patients.
Dr Albin: Absolutely. Because I feel like we have a little bit of a gap in that often as physicians. Like, the family asks, what will hospice at home look like? Well, you know, that's a question for case management. I think they'll come in and they'll tell you. But it strikes me that that's a real gap of my being able to walk patients through. Will they get home health care? Will they have transportation set up? Will there be a nurse who comes in to check? How often are they available? What's the cost going to be? All of these practical aspects of dealing with an illness that are beyond sort of our scope of knowledge, but probably have a huge practical impact to the patient.
Dr Holloway: Without question, every encounter patients wonder about, that kind of future wish landscape that we- all our future-oriented desires and hopes. And so much of that is the practical aspects of our health system, which is often fragmented, kind of unknown, uncertain. And that's a huge source of uncertainty for our patients and families. And then that leads to many other uncertainties that we need to address.
Dr Albin: Absolutely. I think another one that we, again, maybe don't spend quite as much time thinking about is this patient-level uncertainty. What's going on there?
Dr Holloway: Yeah. So, I think patient-level uncertainty is that uncertainty that they experience when confronted with the two other types of uncertainty: the actual data-centered uncertainty and the system-level uncertainty. And that's that, kind of, very huge kind of uncertainty about what it means for them and their family and their future futures. And that's a source of huge stress and anxiety, and often frankly bordering on dread and fear for our patients and families. That actually gets into very levels of uncertainty that I would call maybe over even in the existential realm. Patient-level uncertainty in the actual existential questions or the fear and the dread or the kind of just unnerving aspect of it is actually even more important to patients than the scientific or data-centered uncertainty that we focus most of our attention on.
Dr Albin: Yeah, I think this is, to me, was getting towards that, like, what does the patient care about and how are they coping with what is in many times a really dramatic shift in their life expectancy or morbidity expectations and this sort of radical renegotiation about what it means to have a neurologic illness? And how does that shift their thinking about who they are and their priorities in the world? Is that right?
Dr Holloway: One thousand percent, and in fact, I will say---and I think is one of the main take home messages is that, you know, managing prognostic certainty is not an end in itself. It really is to help patients and families adaptively cope to their new and often harsh new reality, that we could help them adapt to their new normal. I think that is one of our main tasks as neurologists in our care teams is to help patients find and ultimately maybe achieve existential or spiritual or well-being even in their new health states. You know, that you certainly often see in the intensive care unit, but we often always see in the outpatient realm as well, and all our other diseases.
Dr Albin: I think that's really hard to do. I think those conversations are incredibly difficult and trying to navigate where patients want to be, what would bring meaning, what would bring value. I think many of us struggle to have these pretty real and intense conversations with families about what really is important. And one of the things I really liked about this article is you kind of walk us through some steps that we as clinicians can take to get a little bit more comfortable. Maybe just walk us through, what are some of the things that you have found most helpful in trying to get families and patients to open up about what brings them meaning? How are they navigating this new, really uncertain time in their life?
Dr Holloway: Yeah, so I do kind of have a ten-point recommendations of how to help cultivate a more integrated awareness of an uncertain future. I mean, I think the most important thing is actually just recognizing that embracing uncertainty as an amazingly remarkable cognitive tool. I mean, let's face it, uncertainty, when it happens with neurologic illness and disease, is often fearful. It's scary. It kind of changes our world. But on the flip side of it, it's a remarkable cognitive tool that actually can help us find new ways and new paths and new creativity. And I think we can use that kind of opposites to help our patients find new meaning in very difficult situations. So, thinking about uncertainty, kind of being courageous, leaning into it and recognizing that it does create anxieties and fear, but it also can kind of help create new solutions and new ideas to help people navigate.
Dr Albin: I was hoping that maybe you could give us an example of, like, how would you do that? If a patient comes in and they're dealing with, you know, a new diagnosis and they're navigating this new uncertainty, what are some of the things that you ask to help them reframe that, to kind of take some of the good about that uncertainty? How do you navigate that?
Dr Holloway: One of the other recommendations is actually just resetting the timeline and expectations for these conversations. That it shouldn't be expected that patients should accept their harsh new reality immediately, that it takes time in a trusted environment. And that there's this, like, oscillating nature of hopes and fears and dread, and you've just got to work with them over time. And with time, and once you understand who the patient and family are and understand where they find meaning and where they find, actually, joy in their life, or what actually brings them meaning, you can start recasting their futures into credible narratives in their kind of future landscape in ways that I think can help them enter into their new realities within the, you know, framework of disease management that you can offer them within your healthcare team or your healthcare system or wherever you are in the world and the available resources that you have to offer patients and families.
Dr Albin: So, this sounds like a lot to me like active listening and really trying to get to know what is important to the family, what is important to the patient. And I guess probably just creating that space even in that busy clinical environment. Do I have that right?
Dr Holloway: You can absolutely do that, right. You know, and honestly, active listening, we are challenged in our busy healthcare system to do this, but I think with the right listening skills and the appropriate ways of paying attention, you can definitely illuminate these possible, kind of future-oriented worlds for patients and help them navigate those new terrains with them. Frankly, I think that's a real new space for us in neurology. We don't think about and train how to create credible narratives for patients and families. We do it on the fly, but I think there's so much more work to do. How do you actually keep, you know, that best-case, worst-case, most likely credible narratives for patients that can help them adapt to their new realities and support them on their new journeys?
Dr Albin: I love that best-case, worst-case, most likely case. I find that framework really helpful. But you talk in your article, it's not just about using that best case or worst case or most likely, but it's actually building some forecasting into that and having some real data to kind of support what you're saying. And there's a lot of growth towards actually becoming good as a medical forecaster. Can you describe a little bit, what did you mean by that?
Dr Holloway: You're absolutely right. I think, actually, one of the skillsets of becoming and managing prognostic uncertainty is actually becoming a skilled medical forecaster. And it's a really tall order. So, we've got to be both good medical forecasters as well as helping patients adaptively cope to their new reality. But the good medical forecasting is actually now going more quantitative in thinking about the data that's available to help think about the important outcomes for patients and families and then predicting what their probabilities are so you can shape those futures around. So, yes, we do have to have an open mindset. We do have to actually look at the data that's available and actually think about, what are those long-term probabilities and outcomes? And we can be honest about those and even communicate them with families. But it's a really good skill set to have.
Dr Albin: Yeah. This to me was a little bit about, how do you bring in the data knowledge that we try to get over time as we develop our expertise? You're developing not just a reliance on population-based data, but in my experience, I have seen this. And that sort of ability to kind of look at the patient in front of you, think about the big picture, but also a little bit about their unique medical comorbidities or prior life experiences. So, some of that database knowledge, and then bringing in and getting to know what is important to the patient. And so, sort of marrying that data-centric/patient-centric mindset.
Dr Holloway: I love it. I guess the other way of saying that, too, is we need to think with precision, but communicate in narratives. And it's okay to gently put more precise estimates on our probability predictions with patients and families, what we think is the most likely case, best and worst case. Because patients and families want us to be more precise. We often shy away from it, but- so, it's okay to think in precisions, but we've got to put those in narratives in the most likely, best-, and worst-case scenarios. And don't be afraid if you think in terms of ninety percents, ten percents, fifty percents; most patients and families don't mind that. And what they're telling us is they actually want to hear that, if you are comfortable talking in those terms.
Dr Albin: Yeah, absolutely. And giving a sense of the humility to say, like, this is my best guess based on medical data and my experience, I would say, but again, none of us have a crystal ball. And I do think families, as long as you're sort of couching your expectations into the sort of imperfect, but I'm doing my best, really appreciate that.
Dr Holloway: They totally do all the time. Just say, I simply don't know for certain, but these are my best estimates. That's a good way of just phrasing that.
Dr Albin: Yeah. So powerful. I don't know for certain. And then I wanted to just kind of close out, because there's this one term that you use that I thought was so interesting. And I wanted you to kind of tell our listeners a little bit about what you mean here, which is that, when you're actively open-minded, you're using this, quote, "dragonfly eyes." What do you mean by that?
Dr Holloway: So, the dragonfly eyes, as you know, they can look at three sixty around them and they just, they move in all directions. Being actively open minded, I guess the biggest example I would say is, I don't like the term prognostic discordance, which means that there's a difference of subjective estimates of prognosis between patients and families. Being openly minded is actually embracing the potential information that the family has about prognosis and incorporating that into your estimates. So, I wouldn't say it's discordances, per se; I think being really actively open-minded is taking that all in and utilizing that as, you know what, they know more than you do about the patient and their loved ones, and they may have insights that can inform your best estimates of prognosis. So, the true dragonfly prognosticator actually is one who embraces and doesn't consider it discord, but considers it kind of new, useful information that I just need to weigh in so I can help the family in my best professional way in terms of developing a prognosis, whatever the condition may be.
Dr Albin: I can imagine this is just so challenging and something that takes a long time to sort of perfect all of this. I think you say right below that, you need a growth mindset to do this because it is hard, and it's going to take an active participation and an active desire to get better at these conversations with our families.
Dr Holloway: One thousand percent. You are so right that it takes time, effort, and not feeling like you're being challenged, but that actually you are including them in your entire body of knowledge, that you're just- it's part of all you're collecting. And even, I was on service last week, and I talked to residents and students about that very issue. It's like take their prognosis. And someone who came in, we thought CJB, very sad, tragic case, but we were thinking about what the future may look like and how do we actually work with the family who had very what we thought was unrealistic expectations. I said, well, no, this is not discordance. This is just useful information that we can take understand where they're coming from and incorporate that into the ways we want to build relationships, build trust, and over time we'll get to a point where we hopefully can work with them and have them have that fully integrated awareness of their future.
Dr Albin: Yeah, that's beautiful. It really is this ongoing negotiation that really requires so much listening, understanding, and then obviously information and expertise about the data that we're presenting and the likelihood outcome, recognizing that there's a lot of uncertainty in all of this. Which, you know, again, this is kind of a 360 talk. At every level there is uncertainty, and that's what makes it so hard.
Dr Holloway: Yeah, you're absolutely right. And actually, even in the article I kind of used the term radical uncertainty as that, no matter how resolvable all this uncertainty is, there will always still remain that radical element of our existence which we have to actually incorporate and be prepared for. And actually, not only of ourselves, but actually for patients and families and helping manage that. Using narratives and credible narratives and kind of ranges of possibilities is the best way to do that in a personalized way.
Dr Albin: Well, this has been a fantastic conversation, and I know that we are running a bit short on time. So, as we wrap up and you think about this topic, are there any key take-home messages that you hope our listeners will walk away with?
Dr Holloway: I think one main emphasis is that despite all the successes we feel we have in neurology, is that we all have to recognize that prognostic uncertainty is just going to increase in the future. But this is going to be for several reasons. One is that, just, the illness uncertainty of all of our great therapies are just going to be creating more uncertainty for the future. And precision medicine is paradoxical, and that actually it creates more uncertainty. So, I think we need to be prepared that we have to manage prognostic uncertainty better, because it's definitely going to increase. And two, it's what I said earlier, is that actually managing prognostic uncertainty is not an end to itself. It's actually helping patients and families adapt to their new and sometimes harsh new reality and actually help them to ultimately get to a place where maybe either their condition is neither dreaded, but actually they can accept it as their new reality and actually achieve some sort of existential well-being and existential health. I think that we have a lot more to emphasize in this area. And for far too long, we've focused on the certainty aspect of our field and not enough on the uncertainty in the world of medicine to help our patients and families.
Dr Albin: And gosh, isn't there just so much uncertainty? And I think this has been beautiful. So, thank you again for coming and sharing your expertise.
Dr Holloway: Thank you very much. It's been a pleasure.
Dr Albin: For all of our listeners out there, this is a truly fantastic article, and I would just like to direct you to going to read the cases because not only do the cases offer a little bit of practical advice, but there's one that's actually sort of a philosophical discussion about, what does it mean to be alive and confront death? There's some beautiful artwork that's featured as well. So this is just a really unique article, and I'm excited for our listeners to have a chance to check it out. So again, today I've been interviewing Dr Bob Holloway about his article on managing prognostic uncertainty in neurologic disease, which appears in the December 2025 Continuum issue on neuropalliative care. Be sure to check out Continuum Audio episodes from this and other issues.
Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.