All right, I got AO2 on my clock, so let's go ahead and get started. So thanks everyone for coming. Welcome to the AAP Medical Student Journal Club. We have a great host of presenters and clinician experts that were very thankful to come and help us out and present on some great material related to spinal cord injury. So let me give the intro to our clinician expert here first. We have Natasha Bhatia, MD at a spinal, she's out of Shirley Ryan Ability Lab, and she's the current spinal cord injury fellow there. So we're very happy to have Dr. Natasha here to lend her brain to us and help us kind of add some clinical flavor to a lot of these really great articles our presenters are presenting today. Just want to kind of give a shout out to John Lasko, who'll be taking over for facilitating the Journal Club moving forward as a part of the new AAP Medical Student Council. So I want to thank all the new AAP Medical Student Council members and council members who are online today. So welcome and congratulations again. Congratulations to all the fourth years out there. Hopefully Monday went well and now you're just waiting on Friday and excited for all y'all. And then let's go ahead and get rocking. So first off, we have Samuel Cicconetti. He's our third year medical student out of the Ohio University Heritage College of Osteopathic Medicine. Going to talk to us today about the early clinical prediction of independent prediction of independent outdoor functional walking capacity in a prospective cohort of traumatic spinal cord injury patients. Thank you. Yeah, it's, it's quite the title. It's a long one, but I'll go ahead and take over. Congrats John on taking over for Nathan next year. Is this like the unofficial official passing of the torch? Yeah, pretty much. I was going to maybe try to do it, but I'm presenting today right after you know, so we didn't want to put too much on play day one. That's understandable, but all right, let's begin anyway. So yeah, I'm Sam Cicconetti. I'm a third year from OUHCOM in Athens, Ohio, and today I'm presenting an early clinical prediction of independent outdoor functional walking capacity in a prospective cohort of spinal cord injury patients. I know typically we present on, you know, like randomized control trial studies and whatnot, but I saw this in the American Journal of PM&R from this past November and just thought it would be really interesting to present on. So it is a prospective cohort, a little change of pace. All right. So the background, what we know right now is that spinal cord injury, it has a devastating effect on ambulation and that long-term ambulation after spinal cord injury is a crucial prognostication conversation between us as clinicians and our patients very early on. I'm sure many of you are familiar with the AGIS scale and that's used to classify spinal cord injuries depending on severity, A being the most severe, classified as complete injury, and then D being the least severe, but obviously still severe, and E being normal. The study that I'm going to talk about today uses this classification system. Here we have kind of the universal grading scale that we use to assess the level of injury, severity, whether it's incomplete or complete, and what we have, what the patient has preserved following the injury. So I'm sure many of us have probably used that, and if not, we'll probably be using it in the next couple of years. So what we know, a man named Middendorp in 2011 created a prediction for following spinal cord injuries for injuries that typically result in, I would say, like, you have to hang on. Can you excuse me for a second? All good, Sam. Take your time. It happened to me while I was practicing. I, like, was mid-sentence and then had a drink and, like, take it 30 seconds, so I feel that, brother. All good. You got to have water handy, but it's roughly Don's wash line, but he's all good. All right. We're good. Sorry. All good, man. So anyways, that prediction, it really only was used to predict a shorter distance for indoor walking on even surfaces, and typically those involve, like, higher energy gait patterns and extensive assistive devices. We also know that increased community and social participation is one of the main goals that patients want that they desire following an injury, and those typically are associated with longer walking distances, walking independently with or without assistive devices, and can typically require less higher energy gait patterns. So just as a question, I don't really expect anyone to know this because I didn't know it, but if you had to say what percentage of people return to work one year after a spinal cord injury, you can just throw your best guess into A, B, C, or D, and I won't hold it up for long, maybe, like, five seconds or so. We got quite a combo of A's, B's, and C's, Sam. A, B, A, B. The last one is actually C. It's about 13%. This was from the NSC ISC 2020 status report, so about 12.7% return back to work, and about 53 to 53 and a half remain unemployed, and this isn't, like, a direct correlation with involvement back in the community or community participation, but it kind of just gives a broad estimate of what we see following patients with spinal cord injury. So this is a study. As I said before, it was published in the PM&R Journal this past November. So the main significance and importance of this study was to demonstrate quality of life following a spinal cord injury, and that is the top patient priority, as it should be as a clinician when trying to get our patients through rehab and back into the communities. The ability to control gait patterns of at least 100 meters with one or no assistive devices is known to be associated with functional community ambulation. So there's two main objectives from this, identify a method for early prediction of walking one year following an injury, and then also develop a clinically relevant rule or kind of formula that we as clinicians would be able to use for our patients early on that would be accurate. So there are single patients admitted to a single level 1 trauma center between April 2010 and August 2017. There's three inclusion criteria, that being that they had to have a spinal cord injury graded between A and D, as we kind of talked about before. And that they had to consist of an injury within the cervical spine down to L2, and that they also had to complete a spinal cord independence measure at 6 or 12 months following the injury. Exclusion criteria, there were four, pregnancy, history of ankylosing spondylitis, a previous neurological condition, and then a previous spinal surgery or with neurological deficits that could have impacted the results during the post-op period. So the myelotome and dermatome were the independent variables, and these were measured at two time points, one at admission, and this was done by a qualified orthopedic surgery team within about three days from the trauma, and the second was following a spinal surgery, and this was done by a single physiatrist who specialized in spinal cord injury. So the myelotome levels, they were categorized, well, there's three methods in order to measure the myelotome levels. The first method recorded the highest motor strength between the left and right side for a given myelotome, that score could be between 0 and 5. The second method was the sum of the left and right scores, and that could range between 0 and 10, and then the third method was whether the sum of the scores was 5 or above. As for the dermatomes, these were assessed based on light touch and pinprick sensation. The first method was either altered or intact versus absence of sensory, and then the second method was fully intact versus absent or partially intact for a given myelotome. Some of the confounding variables, age, sex, burden of injuries, and comorbidities were collected. None of these really were showed to have a significant impact on the results. The most caudal level of the neurological level of injury was the one that was used, and it was grouped into four categories, either high tetraplegia, low tetraplegia, high paraplegia, and low paraplegia. As for the outcome variables, the independent and functional outdoor walking capacity was defined by a score of 6 and above, and that had to consist of more than 100 meters of walking outdoor. The non-functional was defined as a score between 0 and 5, and typically these were included with patients who were walking with a walking frame or more assistive devices. So, the statistical analyses, a little drier, but descriptive analyses were used to describe the cohort, and then direct comparison analyses was used to compare baseline characteristics of patients both at 12 and 6 months, and we can see that 117 of the patients were assessed at the 12-month post-op period versus 42 at the 6-month. In order to develop the prediction rule, where you determine the assessment of motor strength and sensory function for the specific levels of dermatome and myelotomes, and then a clinical prediction rule was used using a multivariable linear regression model, and then the resultant prediction rule was simplified using discrete rather than continuous variables just to facilitate its clinical use by us as clinicians. So, this shows the baseline characteristics of the study sample. As I said, it consisted of 159 patients, average age of about 48. 117 were followed up at 12 months, while 42 were at 6 months. Those followed up versus 12 versus 6 were pretty similar in terms of socio-demographic characteristics, and then the mean delay between trauma and the post-op period was a little bit over 10 days. As for the results, so for the motor scores and the myelotomes, we can see over here on table 2, method 1 showed the highest correlation coefficient with the outcome variables, and then myelotomes L3 and L5 showed the highest correlation, and these were the ones that were included as the variables within the linear regression model calculation. As for the sensory and the dermatomes, method 1 as well was used, and this was the method that assessed light touch. L4, L5, and S1 also showed a higher correlation coefficient with the outcome, but ultimately S1 was the variable that was used for the calculation, and you can see these down here. I kind of just noted on the slide, myelotomes L3 and L5 and myelotomes S1 were used to calculate the prediction rule, and this is pretty much the final and simplified prediction rule that the study came up with. So you can see that they use the motor score L3, coefficient of 5, motor score L5, coefficient of 7, and then sensory sensation with a coefficient of 29. So as for the results, the overall accuracy was about 85%, sensitivity was 84%, and specificity was 85%. With that, the model was able to correctly predict the walking capacity of 66 of the 76 walkers and 67 of the 83 non-walkers, so I'd say that's pretty good. So looking at the specific levels for the myelotomes, so L3 innervates the hip flexors adductors, and both of these were the ones with the highest correlations. Part of the reason we think that is, the study claims that is, because L3, it also innervates the hip flexors adductors, which are of huge importance for ambulation, and L5 is associated with the ankle dorsiflexors, stabilizers, and hip extensors. S1 is essentially functional right below the foot, and it may explain a significant correlation based on the fact that with S1, you're most able to feel the ground below you and help keep your balance. One of the main takeaways, so this proposed a simple clinical prediction rule to predict the ability to walk, but this one was more aimed at outdoor independent walking for longer distances, greater than 100 meters, mostly associated with increased community and social participation. Motor and sensory function during acute care can be affected. Motor and sensory function during acute care can be used to predict level mobility one year after with excellent accuracy, and it's really important to us as clinicians because it'll allow us to determine the long-term walking prognosis, and also when planning rehab resources for our patients. Some of the limitations is, was a smaller cohort size, and there was only a single institution using the study. The neurological assessment in the post-op period was a little bit over 10 days after the injury, when the current guidelines do recommend between three and seven days. The timing of outcome assessment, where it was a little bit split, about three quarters were assessed at 12 months, and the other quarter was at six months. Also, any non-neurological medical conditions that could have influenced the functional status were not considered or assessed. So to conclude, this study is the first to identify clinical factors associated with the ability to walk outdoors independently for a long distance at levels associated with increased community and social participation. Malatones L5 and L3, as well as dermatomes S1, hold the strongest association with independent outdoor walking capacity when you're out. And then also this proposed rule that can be easily used in a clinical setting, again, clinical staff for acute support injury, and I included it again at the bottom. So this study, it aimed to enhance the previous work of the kind of simplified prediction rule, and work to identify individuals with spinal cord injury will reach mobility level fostering, social participation, but most importantly, quality of life. Thank you, and a few of my sources, and questions or comments. Thank you, Sam. Grab a drink of water, man. You earned it. Great work. I know. I'm like choking over here. All right. Let's take it over to Dr. Natasha for her thoughts. Yeah. So great presentation, Sam. And I think this is a really important article to talk about. So, you know, when you're translating this to the bedside, talking about prognosis for walking is a really important conversation that you'll have with your patients after spinal cord injury. And, you know, based on some of these historical studies, including some of the ones that were mentioned, there's quite a few things that we know about prognosis for ambulation. But first, just kind of taking a step back. So what is actually needed for ambulation? Many patients think that you need to regain full motor function of both legs in order to walk. Right? So in their mind, they need to be back at full strength in order to meet that goal of walking. But really, the studies have found that what you really need to ambulate is bilateral hip flexion with strength 3 out of 5 and then unilateral knee extension of 3 out of 5. The rest of the weakness can be managed with AFOs, crutches, other assistive devices. So that's an important thing, you know, when you're counseling patients, especially if they have an incomplete injury, they're, you know, they may be quite weak at the beginning. They don't need to get everything back in order to ambulate. So then again, you know, when we're talking about these prognostic factors, there was the, you know, the Van Mittendorp study from 2011. They had talked about age less than 65 is a positive prognostic factor, having motor strength in L3 and S1 and a light touch in L3 and S1 dermatomes as, you know, positive prognostic factors for walking. And then there was a Hicks study in 2017 that basically simplified that down, but similar kind of prognostic factors. You know, other things that are important for talking about ambulation is the kind of what your level and completeness of injury is. So, you know, it's kind of intuitive, but incomplete paraplegia is kind of the group of injuries that have the best prognosis for walking, you know, which makes sense. When we talk about incomplete spinal cord injury syndromes, so things like brown saccades, central cord, anterior cord, posterior cord. So brown saccade or hemisection of the cord is, has the best prognosis for ambulation. It kind of makes sense. You know, if you think about people with hemiplegia, they're pretty functional with walking, you know, or they can be. And then central cord is kind of second best prognosis after that. You know, and you may remember that central cord has more upper extremity involvement compared to the lowers. So, you know, these are all things that you can kind of look at within your patients to help figure out, you know, what their overall prognosis is. As far as imaging, having hemorrhage within the spinal cord is actually a negative prognostic factor. So hemorrhage within the cord, as opposed to just edema, is a predictor for poor functional outcomes. Okay. so those are just some things that we know from prior studies that can have an impact on, you know, patients' ability to ambulate. You know, I think there was a really important point made in the limitations that were discussed for this article, so just kind of for the sake of discussion, you know, what would be some non-neurologic factors that would affect likelihood of walking? And feel free, anybody, to chime in or type it into the chat. Other factors not related to motor strength or sensation that might impact someone's ability to walk after a spinal cord injury? Maybe the resources they have, like their healthcare access and their family support? Yeah, absolutely. So, family support, we've got motivation, mood, BMI, confidence, how long insurance will pay for rehab, orthostatic hypotension. Yeah, absolutely. So, you guys are all kind of thinking about these factors. So, yeah, BMI, absolutely. You know, the kind of more weight that people have, the more difficult it is, not just for walking, but even things like transfers to things like pain, premorbid history of arthritis. You know, a person may have minimal weakness or minimal weakness in their legs, but if their knee arthritis is so severe that they can't put any weight on it, that's, you know, it doesn't matter how strong or how much, you know, neuro-recovery they have, that's going to impact them for sure. Things like cardiopulmonary fitness as well, kind of aerobic capacity, deconditioning, and then things like contractors and spasticity can also have a big impact. So, I think that's another important point when we talk about these factors or prognostic factors, we're sort of thinking of it like in an ideal situation with an ideal body habitus and no pain and no comorbid conditions. But in reality, there's very few patients that are kind of in that situation. So, it's important to use these really well-researched and these well-studied tools, but put that in the context of the patient that's sitting in front of you. Um, and then, you know, the question kind of comes up, how would you use this information at the bedside or, you know, how would you apply it in, if you're the head of your rehab department, what would you take from this? Well, you know, looking at patients' prognosis to ambulate really helps you focus their therapy time and the therapy resources. So, you know, if there's someone who you feel like they are really good prognosis to ambulate, I think we're going to get them there. Your focus with rehab is a little bit different than someone who maybe has a complete injury, you know, maybe has a complete tetraplegic injury where you really want to be focusing on other things that are going to impact their functional status and getting them home, you know, with maybe with family or caregivers, that's really going to make more of an impact than, you know, focusing on trying to walk. So, just kind of very helpful when you're talking about goals with family, expectations, and, you know, setting goals together. Perfect. Thank you, Dr. Natasha. Thank you for that. I was going to say, for the sake of time, let's keep on rocking through because we got a lot of other great articles and kind of in the same realm of things. We have John Lasko coming up, our third-year student out of Lake Erie College of Osteopathic Medicine. He'll be kind of taking over facilitating moving forward, like I mentioned. He's taking his first crack at presenting today, though, so good luck to him. We'll be talking about the early term effects of robotic-assisted gait training on ambulation and functional capacity in patients with spinal cord injury. So, take it away, John. Thanks, Nathan. Yeah, everyone here, you'll be seeing a little bit more of me, whether you like it or not, if you come to these sessions. So, I'm going to just share my screen quick. Oh, one second. All right. There we go. Sorry about that. All right. So, I'm not going to repeat the title again, but it's a study from the Turkish Journal of Medical Sciences from 2019. So, introduction, what is robot-assisted gait therapy? So, I started with what is a robot, and it's defined by the Robot Institute of America as a programmable, multifunctional manipulator designed to move materials, parts, or specialized devices through variable program motions for the performance of a variety of tasks. All right. That was a mouthful. So, robot-assisted gait therapy is something that utilizes orthoses with computer controlled motors that support joint movement with various levels of autonomy to simulate the gait cycle. It's something that's used in post-stroke patients, TBI patients, and spinal cord injury patients, which is the focus of this study. So, there's different versions of robot-assisted gait therapy. The first one are exoskeletons, which is an example is the local mat machine, which you see on the top right. And this is a machine where the axes of the robot align with the patient's anatomical joint axes and provide direct control of the joints to reduce abnormal posture and movement. There's another type called end effector or known as end effector robots. An example is the GEO system in the bottom right. You can see these move only the feet and the patient is placed on foot plates, which impose specific trajectories and simulating the stance and swing phase. And you can have single jointed or multi-jointed systems. You can have static versus dynamic. So, static would be walking on a treadmill in a fixed place. In dynamic, you can be walking around the room with the robot on. So, this is a quick video I got from Einstein Rehab. A local mat is primarily used with Moss Rehab patients who have experienced a stroke, spinal cord, or brain injury. The local mat takes a long-standing form of physical rehabilitation, treadmill therapy, several steps further than ever before with game-like exercises to increase patients' motivation and effort. The local mat pro automates gait therapy on a treadmill and improves gait training efficiency. Because of this technology, Moss Rehab therapists can provide longer and more intensive treatment sessions. Therapy with local mat pro has established itself as an effective intervention for improving overground walking function. It's a little longer, but I think you get the point. There we go. So, what are the possible benefits of robot-assisted gait therapy? It can improve gait speed and stability, decrease pain, decrease spasticity, improve endurance, and it provides less physical burden on the actual therapist because less manpower is needed to assist with therapy. So, what are the physiological kind of theories for these benefits? The keyword is neuronal plasticity. So, for gait and spasticity, the theory is that sending afferent inputs from the simulation of gait causes the reorganization of neurons in the brain as well as the spinal cord. Improvements in pain are related to decrease in spasticity. Muscle strength, because you're allowing the patient to bear some weight, it enhances muscle activation, and it may improve endurance because the activation of muscles challenge the cardiopulmonary system in an increased way. So, as good as it sounds, what are the issues with robot-assisted gait therapy? It's very expensive. Per my brief research, a local mat device costs around $300,000, so not cheap. It's a pretty complex system as well. You need someone that's a trained provider that knows how to use it. You can't just all of a sudden pick someone off the street that knows how to use it. There's currently really no standardized treatment protocol pertaining to the best use of these robots, and there remains a question of does it really work or is it really more effective than conventional therapy? So, there haven't been that many RCTs completed, and the results of the studies really haven't shown a consistent improvement over conventional therapy. So, the methods for this study, it's a single blind and randomized control trial to evaluate the effects of robotic-assisted gait training on ambulation and functional capacity in patients with spinal cord injury. There was inclusion criteria. You needed to be Asian impairment scale, A, B, C, or D, 18 to 65 years old, injury within the last six months, and patient was able to walk independently before injury. And some exclusion criteria were previous robotic therapy, severe spasticity and rigidity, severe osteoporosis, pressure ulcers, other neuro disorders affecting gait, and uncontrolled heart disease, pregnancy, severe cognitive disorders. So, what was the protocol? They evaluated 121 total patients, and they were just a side note, patients with the neurological level greater than or equal to T6 had to be Asian impairment scale, C or D. They said they excluded A or B due to the risk of autonomic problems at that level. So, overall, they had 88 total patients in the study, 44 allocated to experimental, and 44 were in the control. So, the control group was basically conventional therapy for rehab with joint range of motion, stretching, strengthening, and gait training with the therapist, which was done five days a week, twice a day for eight weeks. And the experimental group was the conventional therapy, plus they added the robot-assisted gait training twice weekly for eight weeks for 30 minutes. So, it was 16 total sessions that were 30 minutes long. And they measured progress using two scales. One is the walking index for spinal cord injury two, and the other one was the functional independence measure, which I'll go over briefly. Oh, well, first, this is the machine they used. I did a video, or I showed you the video on it, the local mat performed with a trained physiotherapist. The machine has the ability to adjust the patient body height and weight, as well as to change the amount of body weight that's supported. The experimental group that used the robot had one half their body weight supported to start, and the support was gradually reduced over the course of the study as able. So, this is the walking index for spinal cord injury two scale. It's a zero to 20 scale, zero being unable to stand or participate in any walking, with 20 being ambulating with no devices, braces, or physical assistance for 10 meters. The patients were evaluated by a blinded researcher who assigned the scores. And then this study will, once we get into the results, you'll see they used the healing rate percentage, which was basically a determination of the percentage of points the patient's score changed. So, if the patient ended at a 12 after the eight weeks, but prior on admission was a 10, this would be a two point improvement. So, since there's 20 points on the scale, this would be a 10% improvement. The functional independent measure is a different scale, once again, evaluated by a blind researcher. These are 13 motor and five social cognitive measures, scored one to seven for a total of 126 points. They also use this healing rate percentage to report results. And it's similar to previously, if the patient ended at 50, but had started at 38, this would be a 12 point improvement on the scale, which over 126 is a roughly 10% improvement. So, for the results, this table is basically just showing the groups were not determined to be significantly different in age, sex, spinal cord injury, etiology, percentage of traumatic, non-traumatic injury level, injury level of injury, and Asian impairment scale. You can see all those numbers on the right were not significant. So, the group should be somewhat similar. This table is a little bit hard to read. I did want to mention that they did report the results, or they did do a test for distribution. I don't know if I missed that slide. Oh, yeah, I guess I did. So, they did do a normal distribution test with this Kolmogorov-Smirnov test, and the participants were found not to be normal. So, they did do a normal distribution test, were found not to be normally distributed. So, the control and experimental groups had to be compared using Mann-Whitney U test, and the pre- and post-hab within the same group were compared using Wilcoxon test. So, just a quick biostats review. The numbers you see are medians, and the parentheses are interquartile ranges instead of the normal mean value with standard deviation. So, this table is a little confusing to read at first, but group one is the experimental group, and group two is the control group. And on admission, if you could go left to right, you could see there was no significant difference between the FIM score and the WSCCI score on admission between the two groups. And then after treatment, the FIM score improved from 69 to 85. The median FIM score improved from 69 to 85, I should say, in the in the experimental group, and it improved from 67 to 77 in the control group. And then the WSCCI score actually improved with it from a median of five to a median of nine, which was a significant improvement. And the control group also had a significant improvement from a median of five to 6.5. Now, getting to the healing rate percentage, which is kind of the scale they kind of made up a little bit, but so the median healing rate for the experimental group was four percent with a pretty large interquartile range, and then the median for the control was two percent. So, this was actually reported, this was a significant difference in the percentage they improved on the scale. And the same thing down here for the healing rate percentage going left to right, it was a median of five percent improvement on the WSCCI scale for the robotic group and a median of zero percent for the conventional therapy group. I hope that made sense. So, the discussion in this, in this study, both conventional therapy alone, which was the control and the conventional therapy plus the robotic group, they both significantly, those groups both significantly improved and had improved ambulation and functional status as measured on the WSCCI-2 and FIM scales. However, the healing rate percentage for the WSCCI scale and the FIM scale was found to be significantly higher in the experimental group. So, the authors concluded that they believed based on their results, robot-assisted gait therapy is not an alternative therapy, but a worthwhile adjunctive option to conventional therapy. The authors did acknowledge that due to limited randomized control trials evaluating the effects of REGT on functional status, the effects remain unclear. And they suggested more RCTs need to be confirmed using larger sample sizes to evaluate additional performance measures, as well as establish a more standardized protocol for how to use it. So, what were some of the limitations with the study? There was quite a few. It's obviously a pretty small sample size, only 88 total patients. It was non-normally distributed sample and the results had large interquartile ranges, which goes along with having a small sample size. There was the presence of both paraplegic and tetraplegic patients. They evaluated only those two parameters and they didn't, maybe they could have used a few more. It was also a pretty intense exercise program. And I mean, I know a lot, obviously a lot of patients are in the inpatient acute rehab setting after an injury like this, but you would definitely have to be in one to complete the program they were completing. And this only looked at early period results because the injury was, all the injuries were within the last six months and they only did therapy for eight weeks. They did not really follow the patients over a more extended time period. So in conclusion, based on the healing rate percentage, the study did show a benefit to using robot assisted gait therapy as an, as an adjunctive treatment to conventional therapy. However, it is notable that the control group, which used just the conventional therapy alone also had significant improvement in regards to both the walking index for spinal cord injury scale and the functional independence measure. So that kind of leaves us with the, you know, the question is, is, is robot assisted gait training worth the price training and extra therapy time required? I mean, obviously you're not going to get that conclusion off one study, but it does, it does raise that question in my eyes and that's it. Those are my sources. Thank you, John. All right, let's send it over to Dr. Natasha for her thoughts. Yeah, thanks, John. That was great. So just a couple of thoughts here, you know, when we're comparing the use of Locomat and some of these robot assisted gait training devices, we're sort of comparing it to traditional gait training, and that's often with a body weight support system or support device. The patient is kind of in a harness that's connected and you can sort of adjust how much of the patient's body weight they are actually supporting with with the gait training. And that can either be attached to a treadmill or over ground, you know, attached to the ceiling. And you know, the, the reason that we kind of use this as part of therapy is that we know there's a lot of physiologic benefits to ambulating, even if it's just for exercise or just during therapy, it helps with orthostasis, it helps prevent osteoporosis with the weight bearing, you're strengthening the muscles, you know, you can prevent spasticity and provide a really good stretch. And then psychologically, it means a lot for patients as well. But the traditional gait training with, you know, some of those body weight support systems usually required one therapist for, you know, to advance each leg for the patient as they're walking, as well as another therapist to run the machine, and then maybe one more to kind of assist with safety and positioning. So the traditional devices can be very labor intensive, and require, you know, up to three or four therapists at a time to make it a worthwhile session for the patient. So a big benefit of the robotic assisted devices is that you don't need that intensive number of people, you know, it's usually one therapist that can sort of assist with this. So that's huge, especially, you know, when resources are spread thin, you know, short staff, short staffing is an issue. So that's definitely one benefit that we see with some of these devices. And then I think it's also just, you know, just another quick aside, I want to be kind of, you know, figuring out the time here. But for, you know, there's a big range of kind of ambulating functionality, I should say. So it goes all the way from ambulating independently in the community using walking as your primary means of mobility, you know, all the way to walking just with therapy as a therapeutic or as an exercise, and then using another kind of device like a wheelchair in the community. And I think the walking index for spinal cord injury scale, it goes from the zero to 20. And even kind of going all the way to 20 is ambulating with no assistive devices or physical assistance for a distance of 10 meters. So, you know, 10 meters is, it's a good, it's an important kind of outcome. But that doesn't necessarily translate to independent walking as your full means of mobility. So just something to think about kind of comparing some of these outcomes as well. I think I'll stop there. All good. Questions from our audience for Dr. Natasha, Sam, I know we didn't get to ask questions for you, and then John as well. So questions from our audience? Y'all are just that comprehensive, no questions. Well, that's okay. So we got another great presenter coming up here. do want to do a quick plug, if you're excited about the process of possibly presenting at a journal club in the future, I want to put that link in the chat here. We got a lot of great topics coming up, so I just want to kind of give everyone a little plug in case they want to sign up for future presentations. Next up, I'll give Greg his intro. We got Gregory Gregoropoulos, third-year med student at Loyola Stritch School of Medicine. He'll be talking about the emergence of epidural electrical stimulation to facilitate sensory motor network functionality after SCI. So take it away, Greg, when you're ready. All right, sweet. Let me share my screen. All right, y'all see that? Indeed. Sweet. All right, let me just move some stuff around here. Okay. All right, folks. So yeah, I'm not going to repeat the title again, but this was a study that came out of a journal called Neuromodulation in 2019. So a quick little introduction on this. Spinal cord injury, as we know, is a disconnection or a disruption of the pathway between the brain and the spinal cord. Loss of sensory motor, autonomic function, drastic changes in quality of life, metabolic fitness, ability to perform ADLs and function in our community. So we have about three quarters of a million new traumatic SCI injuries per year worldwide. And can anyone tell me what the most common cause is below 30 years old? You can like type it in or say it out loud. Car accident. Yeah, there we go. There we go. Thanks, guys. And then how about above 30 years old? Yup. Dude, Ahad's got it. He's on fire. So yeah. So that's like some board style information that you might want to know. So the standard of care for spinal cord injury right now is really all about like medical management, compensation strategies, and lifestyle modifications like modifications like using a chair, creating a bladder or bowel regimen and physical therapy to really maximize whatever residual function does exist. And new technologies aren't really standard of care yet. But maybe after this talk, you might think they definitely have potential. And especially with John's talk with the robotic assisted gait therapy may have an avenue there, just need more studies, obviously. So we've been delivering stimulation to the spinal cord for the past 50 years. But this is mostly for pain. So it's things like chronic pain, failed back surgery, diabetic neuropathy. And while we were studying it for pain, we actually saw that we had some evidence to show that it reactivated or activated some sensory and motor circuitry. So at this point, we have about 30 years of preclinical data to show us that this may be the case and that it may restore some function in spinal cord injury patients. So this device is called epidural electrical stimulation, I'll be referring to it as EES. And at the top right of the screen, it's like these paddles, it's an invasive procedure. So you do need to have a laminectomy to get this in your spine, it's kind of placed flush with the dura mater on the dorsal aspect of the spinal cord. And the whole idea is that it's activating some sort of sensory motor circuitry to produce a tonic or rhythmic motor activation and those with spinal cord injury. So again, this paper is a historical account over 20 years between 98 and 2018 of 22 studies, mostly in AIS grade A and B. So a little bit of background on all this. So initial investigations of EES was on spinal central pattern generators or CPGs, and it was an animal. So this is like a neurocircuitry that's capable of rhythmic output that's with or without brain activity. So it's things like walking, swimming, breathing, and chewing. And it was first kind of studied in transected cats. So that's my little, my little Sue on the bottom left, her disgusted transected look. So they obliterated sensory motor function in cats, and then they installed this ISMS, which is like an intraspinal micro stimulator. And then they put their hind legs like on a little treadmill. And so without the stimulation, they're completely paralyzed. But with the stimulation and with a little bit of sensory with the treadmill, they were able to actually get some locomotion like movement. And this was kind of given to the CPGs that do exist. So a way that I like to describe CPG using this picture on the right is that it's like a triad of signaling coming from the spine proprioceptive receptors in the brain that allows for like functional locomotive movement. And the whole idea of EES is that without the brain, it kind of attenuates the residual aspects that exist within the CPG and within like the proprioceptive feedbacks intraspinally to create some sort of locomotive movement. So the first reported study of CPGs was in 98 with Dimitrijevic. He took six AISA, basically put them in a supine position, installed the EES, and he saw that there was involuntary rhythmic lower extremity movement. Even though there were supine, it was like, I guess they reported like a locomotion like movement. And again, with like no brain input. And it was hypothesized that whatever movement that was coming out was intraspinally. Okay. And then Manassian 2004 just kind of played around with the location. He reproduced some of the data that Dimitrijevic did, but also just moved the panel around and saw that if you place it in different places, you get different effects. Hofstadter in 2015 played with like the parameters. So a continuous low frequency kind of produced like a monosynaptic projection. So what that looked like, it was dorsal stimulation and that created like a really short latency muscle twitch activity. But then at continuous like intermediate or high frequencies, we saw more of like a polysynaptic projection on EMG. And what that looked like was actually like alternating large and small movements. And that was kind of interpreted as the spinal cord, like reorganizing continuous stimulus to produce like a motor output that is more complex than just like a basic reflex arc. So Danner in 2015, then took 10 AS, A and Bs, put them in a supine versus like a passive treadmill suspended position, installed the EES, and then saw different EMG responses. So this kind of tells us that CPG activation may come through like multiple mechanisms if you have this kind of like sensory input. So all this can be interpreted as evidence of the spinal cord achieving like pretty complex motor output with little to no super spinal input. And that demonstrates like the possibility of like intraspinal modulation that may be used for patients with spinal cord injury. So the first time that restoration of function happened in humans using EES was a study from Herman and Carhartt, and that was 2002. But this was in a one patient of AISC, so not A or B, so a little less severe. It was a single subject study, and they were able to have him ambulate on a treadmill and then eventually above ground with actually like without extensive physical therapy. With a little bit more extensive physical therapy, they got them up to a twofold increase. And this was actually also the first study to show that neuromodulation with the stimulation and physical therapy actually has like a pretty synergistic effect. Then a couple of landmark studies came out in 2011, and then updated some evidence in 2015 by Hart-Framer and Resch, and these were four AIS A and Bs. So it was two complete, so two A and then two B. And this was the first study to really put PT versus EES hand in hand in the same study. So they did 37 weeks of PT only, and they showed no functional, and what they defined as functional was able to stand and sustain full weight bearing. So they were not able to see that, and they weren't really able to see like significant activation on EMG. When they did a 79-week period of physical therapy plus EES, they were able to see that functional improvement, so able to stand and sustain, and then they saw like significant activations on EMG. But the curious, oh yeah, so all four subjects were able to execute voluntary movement. The curious thing about this study was that although like the supraspinal input was not needed for movement, like weight bearing and sensory input from like receptors, like skin receptors or cutaneous receptors, joint receptors, was deemed critical, and EES was only successful in generating significant standing-related muscle activation while the subjects were standing upright, but not when they were seated, which is like interesting. So then the Mayo Clinic kind of goes out to replicate these results a couple years later, and they did, but they found some different stuff too. So they reported that they saw EES-enabled independent standing, voluntary ambulation, and task-specific muscle activity all within two weeks, but they also saw some activity while the patient was sidelined, so not standing and not getting that like constant proprioceptive feedback. So this might suggest that there might be like multiple mechanisms at play here. And then these studies also kind of showed that physical therapy plus optimizing the parameters of the stimulation shows like a synergistic effect to getting folks to walk. And then lastly, Liu in 2018 took two AIS tetraplegics and really saw how high we could take this technology up the spinal cord. So he placed the panel at C4-T1. Both subjects in the study gained intentional control of their hand, and then with physical therapy and electrical stimulation, they saw a three-time increase in hand strength. So this all basically tells us that the spinal cord holds capacity to reorganize when given appropriate inputs like physical therapy or the stimulation. Consequently, we could achieve like functional outputs even years after chronic severe spinal cord injury in humans. So underlying mechanism to this, first we have to really consider like what is the role of like super spinal or brain input, and does complete really mean complete? So there was a study that looked at 85 percent, a study that reported 85 percent of individuals that were graded ASIA-A could be rediagnosed as sensory discomplete. So they redid an exam. I'm not exactly sure how they did that exam, but they saw that there was sensory at that exam in 85 percent of those people. And then another study that I saw reported that 89 percent of below the knee muscles in 12-AISA actually showed voluntary and recordable EMG. So we know that the corticospinal, appropriate spinal, all these kind of tracks are important in spinal cord injury, but we have now pre-clinical and clinical data in this kind of like discomplete individual that shows evidence of some sort of like unidentified descending signal that has some sort of like super spinal influence over the spinal circuitry below the level of the lesion, which is like regulated or being like amplified by this like stimulation to enable motor activity. So the primary hypothesis of how EES works is it's basically stimulating the dorsal root afferent nerves that synapse with motor neurons. And further, like there's enough data to show that like the sensory aspect of this whole thing, it plays a critical role to enable EES. So it's not just direct activation of muscles. It's something in between. A cool study that was also mentioned in the paper was that they did a rhizotomy on rats. And they saw that when they had the EES in place, the contralateral side to the rhizotomy was the only one that had locomotive movement, which kind of tells us when we sever the dorsal root ganglion and these dorsal kind of aspect of the spinal cord and we're cutting off our sensory aspect, we're really not getting the benefit from EES or that locomotive activity. So all this again tells us dorsal root fibers are going to be stimulated in like a trans-synaptic kind of way to activate motor circuitry. And it's this combination with some sort of like unidentified, maybe like super spinal signaling that allows for motor function to come back. So quick schematics. So we have brain activity coming down. We have a lesion, that brain activity is not coming down below the lesion, but regardless there's intact afferent and efferent sensors below the level of the lesion. So when we slap on that EES, we basically think of it as helping in two ways. So we see, we say that EES is like stimulating dorsal aspect to the spinal cord, and that's just stimulating the sensory, that's upregulating sensory signaling, but it also may be amplifying this residual descending brain signals, which may currently be unidentified. And this all kind of influences like an intra spinal circuitry that helps achieve super threshold activation of like proprioceptive neurons and intraneurons that are happening like within the spinal cord to indirectly activate motor neurons and promote function. So the paper also kind of commented on some extra therapeutic things on other areas and domains of health that are relevant for spinal cord injury patients. So I started the ones that were mentioned in the paper. So postural hypotension is an issue in spinal cord injury patients. There were two studies. One of them was saying that how EES has potential for improving cardiovascular function. And it showed that across sessions and subjects within the physical therapy sessions while using EES, they showed like an elevated and maintained mean arterial pressure at normative ranges, which is great. There was another study by DeMarco in 2019 that showed like EES had increased cough and inspiratory function. So that may decrease things like aspiration or atelectasis. And then there's been some work on increasing like voiding function because like bladder and bowel issues are huge in spinal cord injury. So EES is hypothesized to like target parasympathetic outflow and has been shown to actually have a more complete void by increased like detrusor contraction and then more synchronized urethral sphincter relaxation. So limitations of EES. It's a surgical procedure. You need a laminectomy. It's risky. The configurations are hard, different electrode sizes, voltages, frequency, software, so many variables. It's very time-consuming, laborious, expensive, and pretty much left to clinical research right now. We also have to consider that we have been doing a lot of this research with repurposed old technology that was initially used for pain. So conventional EES is like a continuous signal. It's non-pattern, it's open loop, right? And there's actually been some evidence to show that like a continuous stimulation kind of messes with some of the proprioceptive kind of circuits. And that actually might be counterproductive for making EES work. And then kind of figuring out what the role of rehab is kind of hard, like picking up those two pieces. And then there's obviously accessibility issues. It's expensive, limited to clinical research, not even FDA approved. And lastly, like all the physical therapy that was happening in these studies, like all the patients, all the subjects were getting like extensive physical therapy that far exceeds the physical therapy that an average spinal cord injury patient is also going to get out in the real world. So I couldn't help but mention this study. There's really no better way to like talk about the future of this by not talking about this study, but this was released last month. And it was in a single day, the use of EES returned in three AISA individuals, the ability to stand, walk, cycle, swim. And then after six months, they were able to sufficiently restore functional ambulation, like within their community. So the way they did this was they had a hypothesis that if they took a more biologically aware approach and they kind of targeted not only the dorsal aspect of the spinal cord, but more so like the dorsal root and specific ensembles that that might be a little bit more superior. So they kind of created something that was non-continuous, something biomedic and something that was more of like a closed loop system. So we're looking here at the bottom left. This is so cool. So they basically took data from like able-bodied individuals to create like a timing and location heat map of motor activation. And then from that, they made like a library of anode cathode configurations to like stimulate certain sequences of like muscle activity that aims to reproduce activation patterns. And then from there, they like created a software enabling live adjustments of stimulation patterns and parameters based on like real-time feedback from muscle activity that are like synchronized to stimulation sequences. So super cool. They created something that was like a non-continuous, spatio-temporally aware, targeting dorsal root ensemble, specifically something closed loop. It's lively, adaptive, and it creates a program that mimics human physiology. So B here basically shows them on day one, they were able to support themselves and ambulate even without physical therapy within the study with some body support. And by six months, all three subjects were able to ambulate without any body support. And then C just tells us that before epidural stimulation, they basically had no distance covered and no walking speed. And then afterwards, but they obviously, they got some function back there. Show them at the gym, drinking a beer, walk-in, so really cool. So conclusion, spinal cord stimulation has been studied for the past 50 years, originally for pain, but it's been repurposed to study returning function back in spinal cord injury. It has shown efficacy in restoring voluntary movement and function, but this is all, every single person had some sort of physical therapy that did regain some function. It targets large diameter, afferent sensory fibers, and there's evidence to show that there's going to be improvements in cardiopulmonary, bladder, hemodynamic issues, amongst some other stuff. It's a new study that, or the new study that I kind of talked about shows evidence that a spatio-temporal biomedic approach is kind of superior. And there's really urgency now in the spinal cord community to really translate into a therapeutic tool to get into the clinic. And I think this last study kind of gives us a realistic pathway to do that. It's not FDA approved. So that needs to happen too. And lastly, we just got to figure out what like the underlying mechanism of this is so we could implement it a little bit more readily and manipulate it. And that's all, that's all I got. That's also my cat, that's Sue. Please take your medicine. Very nice, Greg, great work. Summing up so much literature all in a good 15 minute portion. Great work. Let's go over to Dr. Natasha. Great. Yeah. Thanks, Greg. I mean, you did a great job distilling down a very complex topic. And I'm so glad that you brought up the recent article that was published last month. You know, you sort of pointed out some key features that make the new study really unique. So in the past, the EES, it was used that implanted array of electrodes, and it was really targeting the dorsal columns like was described, you know, in the articles, in the first article that you presented. But that new study really created a new target electrode array that was focusing on the dorsal roots, especially those involved in leg and trunk movement, rather than just the general dorsal columns. And they also created an activity specific simulation programs, which is kind of, you know, sort of way above the level that we talk about some of these things, but they basically use very personalized and very targeted approaches that built on the technology that was used and studied, you know, through the last however many 50 years or so. And I think that's the reason that they had such great results with, you know, the participants being able to stand, walk and cycle. And again, important to remember, they had very extensive neuro rehab that was coupled with the EES therapy as well. So it's definitely an exciting area with a lot of potential for future applications. Definitely still has limitations to widespread adoption. You know, it is a big surgery, it requires a laminectomy to place the electrodes. You know, that's expensive. It's very time and resource intensive to make this happen. And, you know, it requires a lot of intensive therapy as well. It's not something that you just implant, turn on and set people loose. They're kind of very closely monitored and followed with, you know, therapy and assistance afterwards. So yeah, I mean, I think this will continue to be a huge area of study and progress. And so it's really important to know kind of the steps along the way that make this kind of technology possible. Are you super excited as like a spinal cord injury fellow that this is like the future of spinal cord injury, like when you're like 50, 60, whatever? Yeah, it's super exciting. I mean, to be honest, when the first when that new study came out last month, I first saw it in, you know, like CNN science articles or something. And a lot of times they're so over, over hyped, you know, there's, it's a very kind of measured study, and then the headline kind of goes crazy with it. So I was kind of expecting that when I actually went and read the article, but the I mean, their results were pretty dramatic, which is cool. Again, lots of limitations. This is not something that's just going out there and everyone's going to get and be cured, but definitely lots of potential for future applications. Yeah, I know. I hadn't mentioned it when my mom actually brought up this study, not knowing I was going to do this, but she brought it up like outside of this and was like, Oh, I was like reading people magazine. And I saw this crazy. I was like, that's how you know. Cool. Awesome. Any last minute questions from our audience? That's okay. We hit on a lot of different components of spinal cord. It's a really great session from prognostication to robots to now these brand new kind of interventions out there. So thanks to our presenters for coming in. Thanks for Dr. Natasha for lending her expertise to us. And thank you all for coming. Next Journal Club coming up is on April 19th. It's always the third Tuesday of the month. So feel free to join us for that and sign up for future Journal Clubs in the future. And I want to thank you all for your time and have a great night. Thank you so much for having me. Great job to all three presenters. Thank you, Dr. Bhatia. I appreciate it. That was awesome. I learned a lot. Great. Awesome. Glad to hear it.

robot-assisted gait therapy

spinal cord injury patients

conventional therapy

walking ability

functional independence

epidural electrical stimulation

sensory motor network functionality

motor function

cervical spinal cord injuries

hand strength