Good morning. Thanks so much for being here on this sunny, sunny morning. I know there are other places some of you might be thinking about going to soon. So we really appreciate you being here this morning, especially on this wonderful day. So my name is Lisa Pascual, I am the chief of PM&R in the Department of Orthopedic Surgery at the University of California in San Francisco. It's my pleasure to moderate this session about neuroprognostication and the elusive crystal ball. Our first speaker will be Dr. Angela Carboni. She is a clinical assistant professor at the Indiana University School of Medicine. Her special interests include neurologic and neuromuscular rehabilitation, as well as cancer and palliative care rehabilitation. She has expertise in both the rehabilitation of stroke and spinal cord injury, as well as traumatic brain injury and the non-surgical treatment of low back and neck pain. She is currently the medical director and director of stroke rehabilitation at the Rehabilitation Hospital of Indiana. Dr. Carboni will be speaking on neuroprognostication in the area of stroke. Dr. Carboni. I'll try this. I know. Me too. This is high technology. Good morning, everyone. Thank you for coming here so early and listening to me. I've been practicing exclusively stroke rehabilitation for the past 20 years. This topic, I'm going to start off telling you that I am not going to make this crystal ball any clearer than you already know. We will talk about some interesting things, I promise. Which one's forward? The one here on the white? No, not the top one? Yes. Okay. I have a couple of financial disclosures to give you. I just thought we would start with some fun stroke facts. It is now the fifth leading cause of death in the United States. When I started out in my residency and finished in 1997, it was the third leading cause. I would like us to pause before we celebrate that this is a woo-woo moment. What's taken over number four is COVID-19. Two years ago, it was number three, so naturally, that would move stroke down. Number three now is accidental deaths. There's some preventable things. COVID-19, I think, is going to continue to drop. It's the fourth leading cause of death today. We still have a lot of work to do in preventing death after stroke. Because of that, because we have made some major improvements in acute stroke management, thrombolytics, mechanical thrombosis, we have really impacted survival, which also makes stroke the number one leading cause of disability in the United States. I want to go back. I wanted to say one thing. This number, 3.15, is pi, so this is an easy way for you to remember it. It's a very sad statistic. Every three minutes and 14 seconds, someone dies of a stroke. Every 40 seconds in the United States, someone is having a stroke. It's about 40 patients per hour that are having a stroke. The other... Oh, we'll just move on. Some other fun facts. I'd like to focus on the fatality of stroke survivors. In the first month, it's anywhere between 22 and 37. At 10 years, only 25% survive. There are cancers that have better prognosis than stroke. The leading cause of death after stroke is heart disease, long term. How do we define recovery? The majority of my conversation with you today is about there are different ways. The literature has different ways of measuring it. I'll give you an example, a famous example, the FLAME trial. Has everybody here heard the FLAME trial? Then there were trials that came out after. The FLAME trial said, hey, using fluoxetine actually helps motor recovery. They used a Fugge-Meier score, which is an impairment score. Further studies on drug trials show that there was no benefit in disability with SSRIs. They used a modified Rankin score. How do we reconcile these two very different things to our patients and to ourselves, and how do we practice medicine? You have impairment, you have disability, and then you have handicaps. These are the outcomes that people look at. Here is one of ... I took this from Dr. Quinn in 2011. He was looking at drug trials and what measures are being used. The most common one is the modified Rankin score. That's a disability score. That's actually measuring what someone can and cannot do after their stroke. A Barthel index is also a disability score. It's using ADLs and mobility. Then the Fugge-Meier and the NIH Stroke Scale are really impairment scores, actually measuring what someone's strength, range of motion, sensation, coordination, and how that's impacting their function. I love this slide. This is from Saver in 2021. Again, at the end of these slides, there are all sorts of references that you can look at later. What I really like about this slide is it gives you a visual of what a modified Rankin score actually means at the different levels. Zero means you have zero impairments, zero disabilities. You are 100% independent in all areas of your life. You've gone back to work. You don't need anybody to help you. Six is death. Laugh, right. Where in the modified Rankins would you consider a good outcome? That's the question. Some studies say one or zero is a good outcome. Other studies say no, two, one, and zero are good outcomes. That's why we have this ... I changed it a little bit. This actually came out of the same article, but I've changed it a little bit because I defined it can and but differently than the article did. If you want to look at the original, there is a reference to that. I think that's a really good visual for you to see. What does good look like for a patient, for a family, and for a physician? We all know that's varied and different for all three groups. Defining outcome is good. Back to that again. The Barthel index, 95 or greater, is considered a good outcome. In the NIH stroke scale, anything less than six is considered a good outcome. Here's the timeline. I think this is where most of the meat is when you're meeting with your patients. The families and the patient want to know, how long am I going to be like this? This is the elusive crystal ball. When I first finished my residency, the common talk track that I would give was something like this. Well, your first three to six months, you're going to find you have the most dramatic recovery. You'll make some fine tumors by one year, and then usually right after around that, that's as good as you're going to get. There's been a lot of changes in rehab medicine since 1997. We have task-specific therapies. We have high-intensity gait training that have impacted that and have actually shown that that is not true. Three to six months, yes, neurological recovery probably maxes out somewhere about there, but we as therapists, we as physiatrists, we as a community have resources to help people get better beyond the year mark, and we'll talk about that. This is your classic chart, if you will, of something that you could use to say, well, this is what's going on. By the way, a lot of recovery, as you know, depends on cognitive ability, age, and we'll talk also about that a little bit, but those are things that really impact somebody's recovery. If I looked, and if anybody can help me out here, and if you know of another study, this is from 1995. This is the Copenhagen study, and so this was where a lot of this verbiage and a lot of my conversations with my patients came from, so I put that up there as a historical. I tried to find an equivalent study today because, like I said, there's so much that has changed in rehab medicine that would respond to what are really the trends population-wise. Individuals are individuals, but population and trends, how does that help? This is one of those slides where that's how I spoke to my patients. This is what I used to use to say, but I haven't really found anything that is of equivalent to that. Time of recovery. Let's talk about this. I love this thing, and I wish I can ... Can I step down, but I can't talk without that, right? Okay. There's a pointer. Okay. Pointer. That thing? Okay. Pointer. This dotted green line where it says normal, that's normal aging process. We all know that as we get older, we lose muscle mass, therefore we lose strength. There are things that we can do. Lifestyle medicine has proven that there are things that we can do. We have proven that before it became lifestyle medicine, that there are things you can do to prevent or to flatten the slope of decline. Here is you have your stroke. There is a drop in your functional and your motor recovery, and then there's a slow increase, and then over time, you start to vary off. What they found is that at five years, you're about where you were at six months. What's going on here? This right here, this dotted line, is the challenge. How do we help our patients after their strokes to maintain what they have hard-fought gain in their recovery in the first year after their stroke? How do we as physiatrists help them maintain that? Lifestyle medicine is one, constant boost therapies is another, but some way of educating on why exercise. Exercise for a hemiplegic is very different than exercise for an able-bodied, but they can exercise nonetheless. How do we help them maintain and have a parallel slope as the normal? That is the question for us, and it takes resources, family, social, medical, health resources to make this happen. This is another slide that I put together, and this came out of an article in 2018. I'm not really going to go through all of this, but I already alluded to some of the things that affect someone's recovery. The older you are, the more time you need to recover. The older you are, the less likely you're going to have a good outcome. That doesn't mean you're not going to, it just means it's less likely to happen. That's another one to study over time. I only have 15 minutes, so I can't go through all of this stuff. Then there are some new ways to prognosticate, I guess is how you say that word. Here they are. There are biomarkers that are coming out. They're not universally used. They are great at university centers, but how do you do it in rural Indiana? That's where I'm from. I live in Indiana. How do you do that in a rural setting to get some of these biomarkers to help you? It's a tool. It's not the absolute. These are tools that you can use to talk to your patients about what it can be expected over the next year or two with your loved one and to the patient themselves. Then there's a model called the proportional recovery model. Basically what that says is you get an NIH stroke scale or you get a Fugamaro score within the first week of their stroke and times that by 0.7 and that's what you should expect to see as their recovery number. There are non-fitters in that as well. I don't know. It does most of the time kind of predict what you should expect or how to expect, but there are also other factors that I don't think we can measure. We can't measure someone's motivation. We can't measure how a family member can impact someone's recovery. I tell my residents, and there are a few of them that are here in the audience, it takes a village to recover from a catastrophic event. I don't care if it's traumatic brain injury. I don't care if it's spinal cord. I don't care what it is. It could be a heart attack with a gentleman on the first day of our plenary session where his wife had to give him CPR for 10 minutes. It takes a village to have that man recover back to what he was formerly was, and that's a miracle in and of itself, and the miracle there is that he had a family that cared, and I can tell you it's amazing to me that people have some mild strokes and if their family only comes once during their rehab visit, I see a decline, and so one of the first things that I do when a family member comes is tell them how important it is that they come, visit, watch, encourage during their therapy sessions. Don't just come on the weekends. Try to take a couple of hours off from work to come and see your family member. It makes all the difference in the world. Connection makes all the difference in the world, and how do we measure that? I don't know. So predictive values, again, are challenging. They're not available across every place that you treat. So those are just some interesting things. How does then cognition play a role in rehab recovery? All the other things I showed you before were around motor recovery. How does somebody's cognitive function really actually help, and how do we, and we're grappling with this now in the stroke rehab world, is what is the dose we need to be giving? How intense should be our PT, OT, and speech? That's a dose. How frequent should we be giving it? Once a day, three times a day, five hours a day, five days a week, seven days a week? These are things that we're trying to figure out. Medicine is easy, right? You have lisinopril. You give somebody 10 milligrams. You can measure the effect of that, and you know that you do it once a day because there's a lot of great research around that. But how do we look at therapy as a medicine, and how are we doing that? And so that's all playing a role, and I think there's a lot of great research that's happening now that will really, really help us to decide and figure out what is best, and then how to implement that across the entire country, right? Cities, research centers have that ability, but then how do we take it immediately to those in the outreaches? And if you look at the stroke map of the stroke belt, let's talk about that. That's really where it needs to happen as well. Language, we don't really have a lot of literature out there regarding that. It seems to fit the same pattern with the other neurological recovery patterns for motor strength. Three to six months seems to improve. I can tell you there's literature out there that also says you can improve up to two years, and again, I think it's the same thing. Brain can be viewed as a muscle. Let's keep using it, or we lose it, right? And what are the right activities to do in order to keep the brain function moving in the proper direction? So long-term impact of strokes in caregivers. Several years ago, I tried to use the caregiver burden scale in my clinic, and it's an easy scale to use. The issue I had is I had no resources for them, which was very devastating to have no resources for your caregiver who is struggling with this new norm that they have to manage and feeling isolated. So we truly, truly, truly try to identify those caregivers that are feeling isolated. In the beginning, they said, oh, people were coming all the time, bringing meals, catching up, and over time, they went back to their life, and now I don't have any visitors. And once I was done with therapy, which became our social outlet, we were just home together alone, and how do I manage that? So when I looked at the literature on this, I was really astonished to see that caregiver depression actually diminished over time. I have to be honest with you, that's not what I saw in my practice. So I don't know. I felt like it accelerated, but it diminished, but not to a point where I would say that we should all give ourselves a high five that the caregiver wasn't experiencing depression. I think in the beginning, there's a lot of grief, and that's what we were measuring. And then there's a plateau, and that plateau is still not, in my opinion, adequate. I wouldn't say that we've made any gains there. And so I think we also need to focus, just like what was a great reminder, and I think physiatrists are great at this, it was really sad for that gentleman who's, no one asked his wife how she was doing. We naturally do that. We have our patients with us for three months. We're interact, I mean three weeks, love it, I would love it if it had been three months. Interacting for three weeks or 17 days or 14 days with a family member, with the caregiver. And we get to know them, intimately more so than they do in the acute care hospital with only there for four days in their home. And so I think we are really, really in tune with the needs of our caregivers as well. And I think we can have a massive impact on that. So the take home message is, and I think I talked over 15 minutes, so I apologize for that. But the take home message is I want you to ask yourself, it's a rhetorical question, it's for you to answer. What are acceptable outcomes? And in that question, what does good look like is really what I'm asking. But I also want you to go a little deeper on that question. That's an external answer. How do we help people with their internal struggles? Because you have, and I know you know this, you've seen people go through some major suffering and still experience joy. How do we, what's the secret sauce there to help those that are suffering and no longer feel joy? So what does good look like? And can that be part of our question? Stroke recovery timelines are not measured in months, they're measured in years. And spontaneous recovery does happen in the first several months. That's been well established. And then staying active as long as possible, I think that just needs to be our talk track. We just need to figure out ways to give them resources to do that. One of my favorite things I like to do is patients come, and this is gonna be more difficult as the next generation comes through because they like to stream all their shows so they don't see commercials. But in traditional TV, in a one hour commercial, I mean one hour program, there is 20 minutes of commercials. So I always ask, hey, do you watch TV? Yeah. Do you watch TV with commercials? Yes. Because you gotta ask that now because streaming is gonna take this away so I gotta figure out a new talk track for this. So during your favorite TV show that you see every night, every time there's a commercial, which is usually asked anywhere between two and a half and three minutes, I want you to exercise, exercise. Stand up with your rolling walker, walk in place for two and a half minutes. You're not gonna do it the first time, but your goal is to stand up and walk for two and a half minutes in that position while you're watching the commercial that you don't really care about. So then watch your show, and the next time, figure out what you wanna do with your arms. And go make it a game. And then I look at the loved one, I said, and you can do it too. Right? So how simple is that? You don't even feel like you've exercised, but guess what, you got 20 minutes of movement while you're sitting there in sedentary work. So we do need to have more resources for that year out and beyond. And then also developing some sort of resources and interventions for our caregivers. So that's what I'm leaving with you. And like I said, I didn't make this crystal ball any clearer, but I hope I provided some passion for you as you move forward to try to help your patients. Thank you so much. Thank you very much, Dr. Carboni. I think I saw Dr. Ivanhoe. There she is. Dr. Ivanhoe is fellowship trained in brain injury and stroke rehabilitation at what was then the Baylor College of Medicine and now is Tier Memorial Hermann. She's the director of the Asbestos and Associated Syndrome Movement Program, or SPASM, at TIER. She is a clinical professor of PM&R in the McGovern School of Medicine and the University of Texas Health Science Center. She has won multiple awards, including the Sheldon Beryl Clinical Service Award from the Brain Injury Association of America and the Humanitarian Award from the Brain Injury Alliance of Texas. Dr. Ivanhoe will be speaking to us on the topic of neuroprognostication and TBI. Dr. Ivanhoe. Something that was said by the last speaker that I'm going to start with is because there was a lot of overlap and a lot of very similar considerations in what we're going to be talking about. But when I do a lot of talks on spasticity and movement disorders, I always usually end my talks with, would good enough be good enough for you? And so having listened to the first speaker, I would like to sort of frame this as we're going to go through some of the data and some of the issues fairly quickly, but try to keep that in mind because while I've done this obviously for a long time and we're still asking many of the same questions, I still hear patients with brain injury as with stroke who are told the families have this incredible added pressure that you only have six months to get better and the extra pressure doesn't add to anything. Maybe that's where the flame trial comes in, make everybody a little less anxious about the process. For this, there are no disclosures. If you come to the spasticity lecture later, there'll be a few. But traumatic brain injury, I can barely see this, is a public health issue. It's a socioeconomic issue. There are acute and chronic considerations. The patient that we see in those first three to six months, one of the benefits of the model systems is patients are followed longitudinally for many, many years, but also think about how has the care changed over all of these years. There's a person in this room, Dr. Mann, who was involved with the original model systems. I was the second vintage model systems and I'm back there again, but we don't collect the same data and we don't necessarily collect the data the same way. Severe and moderate traumatic brain injuries are associated with long-term disability obviously and that's what we're going to focus on today. Factors that affect triage are polypharmacy. You don't really know who's getting what drugs out there and when they stop and why they stopped. I'm never going to be a proponent of PRN medication. It was nice to hear that in one of the other brain injury talks this week because you don't know why a patient got it or what the side effects might have been. The frailty of the patient and our biases that are very often influenced by the frailty of that patient, by their age for example. Anticoagulant, anti-platelet medications, comorbidities in general if they're diabetic or have renal failure or what have you. Psychoactive medications, one of Ivanhoe's pet peeves and then toxic metabolic disturbances. It still shocks me sometimes when I have to remind people to look at a sodium level or to consider that there might be pituitary dysfunction after traumatic brain injury and then whether or not there's hypothermia or hypothermia. In terms of brain death, it's important to keep in mind that there are variable definitions based on state, based on your hospital policy. Patients are supposed to be off sedating medication before this diagnosis is made and they should be off ventilators but that's not always the case. But essentially no response to central pain, etc. You can see brain stem reflexes are often a measure we'll be talking about. In terms of disorders of consciousness, which is where our more severe, back in the day we didn't call them that. We called them minimally conscious patients. We still use that in variable ways. We call them low level brain injury patients and very often even, at TIER we find you take patients off the medications they get sent to rehab on and they are following commands. Maybe inconsistently but they're more in there than we think and we'll get to that. Is that hard for you to say? There's one more. I think you're behind one. I'm behind one? So where am I? Yeah. Okay. Sorry about that. Brain death. Mine apparently. So now I'll go to disorders of consciousness. How's that? Maybe I can see it better now. Vegetative state, term that we have shied away from, though you'll hear it. Minimally conscious state, continuing vegetative when it's longer than four weeks in traumatic brain injury by definition, though there could be some argument there. And then permanent when it's more than 12 months. Minimally conscious, substratified into plus and minus whether or not there's some evidence of appreciation of language and cognition. And then you always have to rule out that your patient has locked in syndrome. I recently have to write this up somewhere. I have a patient who has a diagnosis of locked in syndrome that happened from a stroke eight years ago and he can move his entire left side and he can speak badly and I can't get him rehab because his insurance company, which you can't avoid in an Ivanhoe talk, had said if I'd had his diagnosis, I wish they would have pulled my plug and denied him. So we're fighting that battle right now. So speaking of biases, correct? Coma recovery scale is what is used for the disorders of conscious population. It's a standardized neurobehavioral assessment. The scale is intended to be used to help establish a diagnosis, monitor behavioral recovery, predict outcomes, assess treatment effectiveness, et cetera. It takes a long time to do, depending on who's doing it, can be 30 minutes to an hour. So think about institutions you might work in if they're going to give up a therapist to do that and who gets training in how to do it. Early detection of consciousness does however have prognostic relevance and is a primary determinant of the goals of care decisions for our patients and their families. In terms of the coma recovery scale, these are the levels of consciousness that are assessed, auditory function, visual function, motor, oral motor, communication, and arousal. There is the four, which we don't do it here. It's the full outline of unresponsiveness and you can see how that's broken down. It'll be in your handout. In terms of making the diagnosis of disorders of consciousness and then moving on to prognosticate, these are the things that you would look at. You would look at their Glasgow coma scale. You'd look at their imaging, CTs, MRIs, biomarkers. Has anybody had patients show up on their doorstep with biomarkers having been tested? Because I know we talk about them, but I don't see them yet. I think it will be a very exciting area, particularly for those of you who are newer in this field because there will be a lot of information that can be gleaned by it, but it'll also be a while until we know what to do with that information potentially. Intracranial pressure, EEG monitoring, and then other things that are not regularly done are somatosensory evoked potentials, functional MRI. The only patients I've had who've had functional MRIs have attorneys, TMS, it's true, PET scans and SPECT scans. So a poor outcome. What defines it and who defines it? We can define it based on scales. I have families who are satisfied with the fact that their loved one is still alive no matter what their situation is, and that is their life to live. And then I have patients where it may be 10, 20 years since the injury, and I'm finally having, they're ready, they're asking me about hospice conversations. And I find that I do have those conversations. I know that a lot of docs are very uncomfortable having those conversations, but sometimes there's realism in the world. Death, just like in the stroke literature, is a poor outcome in the brain injury literature, traumatic brain injury. Permanent unconsciousness, permanent loss of independence. I would drive my family crazy if that happened to me, but who knows, because you never know until you're in that position, and we try to make a lot of decisions for people, with people, based, again, on our biases of our perspectives of life. Uncomfortable outcomes occur in up to 20% of patients, or their families, in people who were still unconscious at four weeks after their traumatic brain injury, and that is important. And there are other socioeconomic factors that I'll also touch on, practically over time. In terms of the model system data, I'm going to kind of give you the highlights. Over 18,000 participants in the data have to be 16 years of age. You can have complicated, mild, or severe traumatic brain injuries. We're talking about moderate to severe. And then there's the definition of how it is defined in the model systems database. The thing that I think is a strength of it is that you have follow-ups of one, two, five, 10, 15, 20, 25, and 30 years. But again, how we treat brain injury now is not how we treated brain injury 30 years ago. The definition of DOC, for purposes of the model systems database, if you have two of those variables, data participation, exhibited command following on two consecutive days, which is very much like the GOAT was, two consecutive days, when we did the Galveston orientation amnesia test. Within a 24-hour period, acute medical records have been reviewed in detail. And then the GCS motor score is most predictive. In terms of the nine emergence from the disorders of consciousness state, which just means consciousness. It doesn't mean you got up and you went holiday shopping at the mall. It's you were able to follow a couple of commands. Of 9,000-plus patients, 396 were not following commands on admission to rehab, evaluated at rehab after discharge at one, two, five years, 66% recovered consciousness, following commands across two consecutive days. This is during rehab. So late emergence based on the disability rating scale, 132% basically were not following commands at rehab discharge, but at five years, 74% are. Now it doesn't really give you information about what the quality of their life is or is it enough if you can blink on command. But it's significant that over time, not six months to a year, we see that people are emerging. And is it to a degree that they're emerging in ways that we can see? Or were they always listening? You know, some of you may be aware of those fMRI studies where people, where there was a patient who could in her mind demonstrate that she was playing tennis, even though she couldn't. We can talk about that later. For emergence of those comatose at rehab on admission, I can't see this, my goodness, I have to get my eyes checked, 1,682% basically recovered consciousness during inpatient rehab. Okay, now we could have a whole nother conversation that I talk about every day, which is how long do we get to keep people in inpatient rehab? We were commiserating. There was a time where it was three months inpatient rehab after a traumatic brain injury. I just dated myself, but so moving on. Rehospitalization versus mortality, it's not going to be a surprise, I believe, that patients who are at a lower level of functioning are more likely to get readmitted, especially within that first year. Those unable to follow commands on admission to rehabilitation, 50%, oh no, boy, 13% died. And then there's a two-fold higher rehospitalization in the first year post-injury. And anybody want to throw out what the usual causes are? Lung, thank you, lung. And then there's bladder, skin can sometimes become an issue. I have many patients who developed osteo because they couldn't get services early on. So how much are we, or our system, contributing to the problems our patients are having? Functional status 10 years post-injury, basically this is interesting, this is my friend Flora. Substantial proportion of patients unable to follow commands when they admitted to the inpatient rehab achieved independence in cognitive, mobility, and self-care functioning, with improvements up to 10 years post-injury. So late functional decline is actually considered to be infrequent in this population if they survive those 10 years. So in terms of prognosis, the reason we're here, there is no early indicator that really helps us predict what's a poor outcome. Bottom line, no matter what your peer-to-peer may tell you when you make that phone call, 20% of those who do not regain consciousness in the first four weeks will go on to outcomes that are acceptable to the patient and the family. What their quality of life looks like after that, that's actually being looked at now in the database. A Glasgow Coma Scale of 5 or less on mechanical ventilation, those patients have been referred to organ procurement. I have a whole group of patients I follow who were supposed to be organ donors at some point, and they're satisfied with their lives. So I know how we call it, so biases. There is really limited long-term data on their quality of life and on their life satisfaction. There is a very pessimistic view of a severe TBI, what a severe traumatic brain injury looks like. I have patients at that full spectrum. I have patients who have gone back to work in some form or fashion. I have patients who volunteer at animal rescues and have personal trainers, and I'm working my butt off, but nonetheless, and they're happy with their lives. And then I have the opposite, where the family is a 24-7 caregiver and the patients are immobile and they are getting readmitted, even if they're making it past that 10-year period, because they're having all the medical complications that come with it. There is still considerable variability in clinical management. Even if you get a bunch of brain injury docs in the same room, you may see that there's considerable variability. I see it. What meds you're going to use for which indication, and it's going to be really hard to get really good data. So sometimes all you've got is your clinical acumen and the patient in front of you and trying to make your best call. But I wonder sometimes, we did a talk years ago at a different meeting, if we aren't sometimes overly optimistic as well and we need to watch that bias. So there's a fine line between how we speak with our patients and their families about what's coming, what we think we can predict, and I'm always very clear, I think I am anyway, about what I don't know, what their particular circumstances are. I told somebody the other night about a patient of mine where we withdrew support in the rehab setting. That's not the first time and it probably won't be the last, but it was the reality is he had a spinal cord and a severe TBI and the family couldn't do it. They just couldn't do it. And I think they struggle, particularly from their religious perspective on the decisions they made, but nonetheless we do all live in our real world. So considerations, you cannot be in this field, I don't think, without considering social determinants of health, particularly when you're doing neurorehab. There are differences in how their insurance will change if they're under 21 and then they turn 21 and they can't get services that they've gotten before. There are differences in who's gonna be taking care of them. There are gonna be differences in your state. I live in a state with no Medicaid expansion. That's not had a positive effect for patients. Communication, not just the patients or the families, but ours. What options are we giving them? We try to be as objective, but at the same time we also have to be human and talk about how things might change or might not change. And it's true, whatever the diagnosis, those family friends disappear. They may be there acutely, but it's a lot to ask and their lives get complicated and it's draining. And it's particularly draining for the family members and caregivers. External pressures on the families, caregivers, hospital systems. We are living in a time where it's changing radically. I told you we had patients who used to stay three months, sometimes they stayed longer. And I think I spend more time trying to figure out what their insurance is, when it's changing, what it'll cover, than I sometimes get to spend with the patient, much less doing a peer-to-peer. Access to care, I call it the F word, funding and finances. And what kind of care are they gonna get? Where are they going? It's one thing to say you can put these splints and casts on this posturing patient and then you send them to a Medicaid bed in a nursing home. What do you think is gonna happen there? We do have to be realistic and it's hard and it's painful for everybody. What constitutes care? And what can the families pull off? I've been a caregiver, not for a DOC patient, but for other family members. And I had little kids and they were both being potty trained and I had a father who kept falling on the floor and I was working my, there it is again, I was working full-time. You know, what would be realistic in those situations? And I have resources that other people don't have. So things to consider. And then there have been some really good presentations about traumatic brain injury as a chronic disease and there has been a movement for probably over 20 years to get people to realize that this is a brain injury, that a brain injury is chronic. And it's not, like cerebral palsy doesn't go away when you turn 21 and this traumatic brain injury has longer term complications and sometimes if people in this field are going to go into this field, you should be aware of what those longer term complications are, whether they're endocrine or all the risks that we all have from immobility, but on steroids, so to speak. So based on standardized mortality ratios, individuals with traumatic brain injury are over twice as likely to die when compared to their age, gender, race, and matched U.S. general population. So I'm gonna catch up. Withdrawal or withholding of life-sustaining, why aren't people getting rehab if we know that a lot of them are gonna go on to have quality lives? Well, there's withdrawal of care. There's that pessimistic view in acute care. There's the availability of DOC programs or brain injury specialists and people who are gonna take you off those bad drugs. There are insurance denials and who isn't, who isn't getting burned out from doing peer-to-peers every week? No discharge plan will keep people out of a lot of rehab facilities, because they don't want to get burned either, and not being referred because somebody who isn't the person to make that decision made the decision for you, and that's true at all levels of care in traumatic brain injury. There is impatience for placement, lengths of stay. We measure lengths of stay a little bit more than we measure some other things that might be significant in people's lives. There's the path of least resistance to discharge someone to an LTAC or a skilled nursing facility, and then you lose time. You lose patience to bad drugs or skin breakdown or more pneumonias. There's bias, and how many times have I heard they have no rehab potential over my career? Or unable to participate. Well, it depends how you define participate, and then again, depending who the funding source is, will be how they define participation, so take-home points. Considerable recovery potential in the disorders of consciousness population. Patients with persisting disorders of consciousness can benefit from inpatient rehab. Sometimes I would get people admitted to inpatient rehab if it was for nothing more than to get them the appropriate wheelchair, the appropriate initial training for a family member, get them on the appropriate social services lists, just to get them into a system that will help perpetuate a better quality of their lives. A lot will achieve independence and lower the risk, hopefully, of mortality. Caution is warranted in the consideration of withdrawing support, and now you're supposed to wait 28 days or four weeks. We need to enhance advocacy, and we've been saying that all, you know, this whole meeting, and we all know it, but advocacy, education, prognostic data, which will take a lot longer to get, and then communication of the data, and then highlight the need for longitudinal management of these patients. It's not, you had your brain injury, and we're gonna put you in the corner. So these are the guidelines that have come out from AAN and ACRM. These are available, and then this has just come out in American College of Surgeons, and that's it. Thank you very much. Thank you. Thank you, Dr. Ivanhoe. Next, we have Dr. Greg Carter. Dr. Carter is a professor in the Elson S. Floyd College of Medicine and a research fellow at the Gleason Institute for Neuroscience at Washington State University. He, too, is the recipient of multiple awards, including the Distinguished Researcher and Ernest Johnson Outstanding Educator Awards from the ANEM. He's co-authored over 250 peer-reviewed papers focusing on the characterization of neuromuscular disorder, focusing on ALS and hereditary neuropathies. He's currently the Chief Medical Officer and Residency Program Director at Providence, the St. Luke's Rehabilitation Center. And on a personal note, he was my attending during residency and a longtime career mentor. Thank you, Dr. Carter. Thank you. Which one advances? This one. And then that's backwards. And then that's to highlight. Hopefully I won't screw this up. ALS is a very challenging disease. You don't need me to tell you that. And often within the first few visits, people with ALS want to know, well, how long am I going to live? It's a very challenging question. And I always advise people to be cautious in how you answer. Because really, in the course of the disease, you don't really know if it's going to be atypical or not. There are a lot of theories out there. But we still do not have a singular unifying hypothesis about the underlying cause of ALS. It's hard to believe, but we don't. And there are no universally accepted prognostic models for ALS either. So I generally tell people right up front that for the most part, the prognosis is not good. I think it's important to say that so they don't have false hope. You can bad that however you want. But you've got to get that bad news across. Because they need to get prepared for their passing in maybe two years, five years, 20 years. But you don't know. But they need to be prepared. So I think it's a disservice if you don't discuss that early on. However, most people, by five years, the majority of people have passed away. Maybe about 20% will survive longer than that. Of course, those people don't have typical ALS. So what are some fairly well-defined prognostic factors? Age. So people that are older than 50, late 50s, they generally do not live as long. Site of onset, I think this is the most reliable. People that come in and already have bulbar problems, that's not good. They're going to end up on a peg and probably need ventilatory assistance early on. So that early onset of bulbar palsy is not good. And it's actually particularly bad in women, unfortunately. And the bulbar palsy is often associated with nutritional and respiratory issues. So if you can't swallow, you're going to get on a peg. And oftentimes, the bulbar dysfunction parallels the decline in respiratory function. The other thing that people don't often think about, but if you can make the diagnosis of ALS like that, that's not a good sign. So it's those people that come back and, well, you've got a denervation in two limbs, doesn't quite meet the criteria. That's actually a good prognostic sign. And I'm sure you've all seen that. But if somebody comes in, they've got a lot of axonal loss, they're super weak, that's not good. So some of this is common sense. About 30% of people with ALS will get frontotemporal dementia. That's not a good prognostic sign. And generally, those people are very hard to care for. So I found, in my experience, not much literature on this, although we started to look at it ourselves. The ALS patients with frontotemporal dementia really burn their caregivers out because they have a lot of physical demands. But they're also confused, maybe irrational. So those are the super challenging ones. People that present with a predominance of lower motor neuron dysfunction, so a lot of rest activity on your EMG, that's not a good sign. And think about the predominantly upper motor neuron presentation. That's actually a better prognostic sign. Now, biomarkers are the wave of the future, and I'm doing some research myself on that. Neurofilament light chain is basically a cytostructural protein that's found in axons. And it's a good prognostic indicator in a lot of diseases, including MS, ALS, and Guillain-Barre. So elevated levels of neurofilament light chain indicate active and ongoing axonal deterioration. And it's a reasonably good prognostic indicator, ALS. There's also a heavy chain neurofilament, but that's way less studied. Moving on to Guillain-Barre, I think this is much more challenging. Some people with Guillain-Barre do really well, and they will also ask you up front, am I going to be permanently disabled or whatnot? Sort of parallels ALS in some ways. Older at the time of diagnosis is generally a not good prognostic indicator. And then, and I found this to be very true, medical comorbidities. So if somebody's a brittle diabetic, that's not good. Hypertension. And then their presentation, if they lose strength and have a lot of axonal loss on EMT, that generally portends a worse prognosis. Not always. You can go back and look at some of Peter Dix's work in Mayo. It holds up pretty well. So if there's a lot of axonal loss, generally going to be a rougher ride. There are some scales, certainly in ALS and also in Guillain-Barre. I don't know of anybody that uses them. The Erasmus, the Guillain-Barre scales, it's a typical scale strength, independence in function, ability to self-feed. It's a very standard scale. It does hold up. I don't use it. If they had a clearly defined preceding infection, that actually is associated with a poorer outcome. I'm not sure why. I don't know if anybody knows that. Same is true with kidney function. People that have deteriorated kidney function also have a poorer prognosis. And then the neurofilament light chain is actually pretty good in Guillain-Barre. There's just one study that just came out, I didn't even have it in my references, that is showing a pretty good correlation with elevated neurofilament light chain and a poorer prognosis. That's it. Thank you very much. Thank you. Thank you, Dr. Carter. Here we go with, we've heard about stroke, we've heard about traumatic brain injury, ALS, Guillain-Barre. Now it's time to talk a little bit about spinal cord injury. We're going to wait for those to come up. We're going to be going through this. There's a bunch of slides that I'm going to go really quickly through. This is part of a bigger talk that I give about neuroprognostication, so I'm just going to give you the highlights. Let's see, get this going. I have no relevant disclosure. We're going to look quickly about the AS, the ASIA classification over time, conversion and recovery, and the prediction rules. When I went down this rabbit hole to look at neuroprognostication and spinal cord injury, it all brought me back to the Frankel score, the Frankel grade. Actually, that should read circa 1969, because that's when we start to see it. It has morphed since then to the ASIA classification or the AIS or the ASIA impairment scale. Where I come from, we call it affectionately the INSCE. The Frankel scale in 1969 was kind of very interesting. They looked at completeness as no sensory and or motor function below the zone of injury. It was interesting. They called an incomplete level motor useless and motor useful, so we're not really quite sure what that meant, and it's unclear how the zone of injury was determined, so certainly there was room for improvement there. It was not until about 1991, and my eyes are going out as well, that Waters basically said, and we changed how we looked at completeness and incompleteness and determined probably the best way to look at completeness and incompleteness would be defined by the absence or presence of sacral sparing. Since then, we've had multiple iterations of the INSCE, ASIA impairment scale, and the latest one is circa 2019, which I'm sure many of you are familiar with. One of the common questions that we get is, when should we actually obtain, when's a good time to get an INSCE if you're going to be looking at neuroprognostication? Back in the 1990s, it was like, okay, one month post-injury was a common baseline, or maybe now, should we get a little bit earlier? Should it be between after 72 hours? Should it be within a week? And if you get it ultra early, in which they're doing in some centers, are your results skewed by the facts that they're intubated, they're fatigued, they have a cognitive deficit, and they also have a traumatic brain injury, or are they sedated? So you can get them earlier, but you have to just be careful of the confounders that might be in place by the time you get them. So the advantages of once you get a really reliable or a good INSKEY is it precisely defines the level and degree of the patient's deficit, which can then be used widely in research and measuring outcomes. And it also allows for better patient counseling regarding the expectations of recovery. Just so in general, Kirschblum did a really nice review of the natural history of spinal cord injury, and it looks like there can be some consensus that getting the INSKEY within 24 hours up to one week is probably a good time, but of course, as we always say, further study is warranted. But the questions we get from families and the patients tend to be, am I gonna get better? And for us, a good way to look at this is conversion from being complete to incomplete. And in general, for all spinal cord injury, ASIA-As, if they are ASIA-A within 30 days of their injury, about 20 to 30% move on to being incomplete at approximately one year. In terms of late conversion, that is if you're still ASIA-A at one year, you're of course, intuitively this makes sense, but your chances of moving on to an incomplete status, ASIA-B, C, or D, significantly decreases. For those who do get to D, is that an under-representation because maybe they're not presenting to your clinic anymore? Now, if we just look at complete tetraplegia for ASIA-As, the conversion is about 30% to ASIA-B, C, or D, but interestingly, if you look at complete paraplegia, for ASIA-A, it's about 15 to 20% moving on to incompleteness. Now, why is that? So we'll look at that in just a second. If we look at late conversion in tetraplegia, that is if you're in ASIA-A at one year, what will you be looking like in about five years? Again, the conversion rate is low. However, if you look at complete paraplegia, you'll see that it's even lower. So what's going on there? So in some studies, one of the things that you see is the problem when we're looking at paraplegia is the presence of high thoracic injuries. And what does that mean? So as we know, in the upper thoracic region or the watershed zones, in terms of vasculature, that's where we get a lot of difficulty if you have injuries that are that bad in thoracic spine. The thoracic spine, which is thick, and you have internal organs potentially protecting your thoracic spine and your rib cage. If you ended up with a spinal cord injury, after getting through all of those structures, you know it was a really bad injury. And for these patients... Oh, wow, somebody's moving things around here. Okay, for these patients, patients with thoracic injuries have the lowest rate of improvement. And I think that skews that whole conversion in the paraplegic population. So what happens if you start out as incomplete and you're not start out as an Asia A? If you're an Asia B, you actually have a pretty good chance of moving on to a C or a D. Here we have 50 to 65%. If you're a paraplegic and you start out as an Asia B, you also have a pretty good chance of moving on to a C or a D at 60%. Now, what if you were really incomplete, which we love to see if we can. And those are patients with Asia C and Asia Ds. They have an excellent chance of moving on up to Asia D or E. And in general, and this is kind of the mantra we heard from, I think, Dr. Carboni. It kind of looks just like this. What do we tell patients in terms of rate of recovery? And this is kind of what you still see in the literature, although I'm sure there are people out there who are skewing beyond these statistics. And it'd be great if we could look even further out in terms of recovery, that your fastest rate of recoveries was in the first three months. Your majority of recoveries when the first six to nine months, and you can continue to have ongoing recovery for up to one and a half years. And for many of you who are in practice, we know that we still see ongoing recovery beyond that. So how do we capture those statistics in the future? There was a meta-analysis and systematic review by, and I never get this name right, Corazan-Zadeh, sorry if I messed that up, who took a look at what population would really improve in terms of moving up an Asia level, like going from a B to a C or a D or an E. And the Cs do really well. They have a lot of room for improvement when they are incomplete, followed by the Bs, and then the Ds. And the Ds is because they're almost at the top of the Asia scale, so you have that ceiling effect. And then there's the As, of course. Okay, so a lot of patients, you could talk to them about recovery, you could talk to them about the Asia or the AIS classification being complete and incomplete, but those are somewhat abstract, I think, for a lot of patients and their families. Some of the concrete endpoints or outcomes tend to be questions about, will I be able to walk again? So from about 2011, I found about three different prediction rules, people trying to predict what, if somebody looks like A when they first present in a year, what will they be looking like? Will they be able to walk? Can I predict who will be able to walk? So the first one came from Van Middendorf, who I think there was an N of almost 500. And they did a prediction rule and it was based on age. It was the age, L3 motor score, S1 motor score, light touch sensation at L3 and S1, and they gave them a numerical weight. And as you can see, you got negative 10 if you were over 65. So that was not good. And then what they did is they took this population and they looked at what they looked like in a year and they looked at it based on their SCIM score, so the Spinal Cord Independence Measure for household ambulation with or without assisted devices. And they came up with this, let's just go to the graph. So here's the graph. So basically, you would tally your scores based on the weighted numbers that they give you, and that would be on the X axis. And then, let me see if this works, there we go, the X axis, and here's your probability of ambulation. So if you scored perfectly at 40, yes, you would be, your probability of ambulation would be about 100, but you can already see for individuals less than 65 years, they're already getting kind of the bum rush of starting at negative 10 right off the bat. So here is one prediction rule that did come up, and I don't know, does anybody use it? Nobody really uses it, and actually, that's what happened. Somebody else said, nobody uses this, maybe we need a better one, so somebody came up with another one. We'll go and look at that really quickly. And that was in 2021 by Jean et al. They said, can we look at it a different way? They said, household level ambulation, maybe not the best outcome, because people really want to know about community level ambulation. So they looked at the highest motor strength for L3 and L5, and preserved light touch sensation at S1, they said, what would that look like in terms of prognosticating community level ambulation, which is a different SCIM score in the SCIM testing range. And they found that, they came up with, when they threw all this data together and figured out how do we figure it out, what's the metric for that, they came up with this equation, which is a complicated formula, although if you plug in everything, it's fairly straightforward, provided you like doing algebra. So the overall accuracy, however, was about 85%. And they looked at the motor score, sensory score, and this was 85% potentially predictive. Again, does anybody use this? So again, not being necessarily used. So finally we come up to, what is this, 2024, I found this one. This one said, hey, we don't need to do all these calculations. This was actually developed by a PT. What if, and they looked at the same thing, they looked at about 3,600 people, and they said, what do they look like at the beginning, after they had their spinal cord injury, a year out, we're gonna be looking at community level ambulation with the roughhousing assistive device. And they came up with pinprick sensation at the lateral heels, accurately identified future walkers one year after spinal cord injury. And they found that using this, instead of calculating something, there is nine over 10 people with normal pinprick sensation bilaterally endorsed independent walking, and eight of 10 people who did not have this did not endorse independent walking. So really, really interesting. So that was really fast. I threw out a lot of information in a short period of time, but here are some takeaways. Timing of exam, 24 hours to one week, maybe, for prognostication. If you have an Asia A, intuitively it makes sense, about 20 to 30% convert to incomplete. If you have an Asia A at one year, your prognosis for moving on to ongoing incompleteness is not great. Thoracic injuries don't do as well as lumbar injuries. And of course, as we all know, the more incomplete the injury, the better in terms of recovery. And as I said from these last three presentations, then there are novel instruments being developed seeking to predict outcome for ambulation based on early physical examination. And that's all I have for you. I think we have some questions as well, maybe? Thank you. Dr. Russell, and this is to all the speakers. So I don't know if all the speakers want to come up in case there's a lot of questions for the speakers. And I've got somebody's phone here too. Okay, I was gonna say, don't walk out without it. Okay, for all the speakers, do you typically have spiels that you give to patients when you are getting asked questions on prognosis? Anybody can start. Yeah, my spiel hasn't really changed very much since I started after my residency. But I do have a little asterisk for them. And that is that, and it's all around moving, continue to move. But my spiel is what I told you in my talk. Three to six months to see the neurological recovery and then I go on to explain what that means. And then I say functional recovery is unknown at this point and I do tell them that in the past I used to say one year to two years. And it could be that, but it's all really a matter of how much they participate in their own mobility and care. With an elderly patient who has cognitive impairments, the conversation's a little bit different because that is a big hurdle in the elderly. And they might have underlying dementia to start with. So it becomes a little bit more nuanced. But the spiel starts out with three to six months, one to two years type of thing. Doctor, I don't know. If they ask me about prognosis, I try to clarify what they're thinking of as prognosis. And I still spend a fair amount of time telling them that we're not great at it, especially with traumatic brain injuries. And that they have to do the work as well. And it'll be also in sort of fits and starts. You know, they may have time periods where things are going better and then they do, I don't use the plateau word, but they kind of stay at a particular level for a while. And then they may regroup because we're gonna have to work the system and I do tell them that. Thank you. Doctor Carter. I think there's, here it is. I'm not clear. Okay, do you have typical spiels that you may give to patients when you're asked questions regarding prognosis? Not really. That's fair. Fair. Yeah, it's different for everybody. This is Doctor Carter's spiel. But has anybody ever heard of the movie No Ordinary Campaign? It's from the ReelAbilities vault. ReelAbilities is a film festival. We do a big one in Houston, but it's in other cities. And it's to raise people's awareness about life with different disabilities. No Ordinary Campaign's about ALS. It's an excellent movie. It'll either, it'll fill you with hope and despair all at the same time. But it's worth watching. I think it's on Netflix. No, it's on Amazon Prime. It's on Amazon Prime. There we go. You can support Jeff Bezos. That's why I'm here. Do we have any questions from the audience and we don't have a speaker set up. So if you want to come forward, I'm gonna repeat it so that the people back home. My question is about the ALS that football players and rugby players get. Hang on a second. Okay. The question is about ALS that football players and rugby players get. And is that different than the ALS that we see in the general population? And is that different from the ALS that we see in the general population for those of you at home? Are you referring to Steve Gleason? That's a very challenging question, actually. So our Neuroscience Institute is sponsored by the Steve Gleason Foundation. Steve was, there have been so many athletes, that's how, you know, we could really get in the weeds here, but heavy physical labor, air trauma, athleticism, high physical performance is actually a risk factor for ALS. There have been many high-profile athletes that have come down with ALS. Everybody knows about Lou Gehrig, Catfish Hunter, I mean, it goes on and on. I'll talk about Steve Gleason, because I know Steve, he has tremendous support. So he's got the best equipment, round-the-clock caregivers, but he is almost locked in. You know, he cannot move anything, he's on a full-time ventilator. So is his prognosis really any better than someone with typical ALS? I don't know. I mean, a big part of why he's alive is he chose full-time mechanical ventilation, and he has outstanding caregivers. So I don't know that I can answer that question for you, because that's part of the equation. Your average person certainly would not have access to that level of care, and they may not choose that either. You know, I mean, that's a little harder to talk about, but, you know, if you've got a diagnosis of ALS, I've had many, many patients over the years just say, we'll be right into palliative care or osmosis, I don't want any of this. You know, they make peace with it, and they're done, and they generally do expire faster. Now is that a physiological thing? I think it's more of a psychological brain influencing how you proceed, because they're, I wouldn't say thrown in the towel, but they accept it, and they just live what time they have left to the best of their ability, as opposed to someone like Steve Gleason, who, you know, he got a big tube ventilator, round-the-clock care. He has some really sophisticated equipment, too. He uses eye gaze to type letters on his computer, and that then comes out in an approximation of his voice, because we use voice banking on him. So he can actually talk like his own voice. So I don't know if I answered your question or not, but... »» That's good. The answer is we don't know. »» Right. Right. Yeah, I should have just said that and been done with it. »» I think that wraps it up time-wise. If you have other questions, I think maybe people can take them up here, but I'm getting the high sign that we need to move on. So I appreciate all of you being here this morning.

neuroprognostication

stroke recovery

traumatic brain injury

ALS

Guillain-Barre

spinal cord injury

acute stroke management

recovery prediction

ASIA impairment scale

prognostic models

patient care