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    #16
    Originally posted by Sparky831 View Post
    "They won’t be available outside trials for several years, says Bloch." That sounds familiar
    HOC NON PEREO HABEBO FORTIOR ME

    Comment


      #17
      FYI Onward CEO - recent interview
      https://www.youtube.com/watch?v=LM72CfUR4CM

      It's a sales pitch but ... still interesting to hear an update....

      Comment


        #18
        Scott Chesney Discussion with ONWARD CEO Dave Marver

        https://youtu.be/noUxz5Ivi_M
        "Some people say that, the longer you go the better it gets the more you get used to it, I'm actually finding the opposite is true."

        -Christopher Reeve on his Paralysis

        Comment


          #19
          The abstract of the Nature article sounds very wham, bam, this thing actually works. Am I missing something? Maybe we need input from ActionXPotential?

          Comment


            #20
            Any info on whether any of the subjects had horrific spasticity and/or baclofen pumps and/or found their spasticity treated by the stim device? I thought I saw somewhere that participants with high spasticity and/or pumps were excluded.

            Comment


              #21
              Originally posted by Sheri View Post
              The abstract of the Nature article sounds very wham, bam, this thing actually works. Am I missing something? Maybe we need input from ActionXPotential?
              https://www.nature.com/articles/s41591-021-01663-5


              Im assuming you are referencing the Courtine paper that was just released using eStim? This stuff is indeed incredibly exciting. In short, people who have been Asia A for years are regaining some motor and sensory functions immediately after a stimulator is turned on. This appears to be true and reproducible across time and labs now for several years. The extent of return is minimal, with most people being able to have some faint recognition of some kinds of sensation and some very mild movement of the legs. To the best of my knowledge this stuff has been focused primarily on lower limb movement, i do not know where we stand with upper limb stuff.

              What has been the case with electrical stimulation is that upon turning on the machine, movement is minimal, but this seems to be sufficient for an extensive rehabilitation period to be able to build up the muscles and neural circuits enough to make some very significant progress. The paper that Courtine just published attempted to improve the efficiency of this entire process by targeting a more appropriate region of the cord, in a more appropriate way. The specifics of this stuff is very, very complicated and way over my head, it would take an electrophysiologist to break down the technical details. I dont think that is necessary for the conversation though. In short, the modest adaptations made was efficient enough to allow consciously driven stepping behaviors on day 1 of turning on the stimulators, which is a benchmark only achieved after extensive rehabilitation from prior stimulation paradigms. The types of stepping on day 1 were body weight supported, with upwards of 80% of the body weight being suspended by a harness. They put individuals through 5-months of extensive rehab while using the stimulators to enhance function and each participant was able to take steps with walkers, regain trunk support, walk up stairs etc.. now we are not talking walking like normal, but going from Asia A for years to this is about as close to a miracle as it comes. One other caveat that is not meant to take away from the findings but provide realistic expectations is that the stimulation paradigms were unique for each modality of function. i.e. walking was a different form of stimulation than standing, which was different from walking up stairs. Participants switched back and forth from different pre-programmed modalities depending on the task at hand using a custom interface designed for ease of use, but was as quick as pushing a button.

              There are alot of implications for these findings that should get us excited beyond the idea of making people walk with greater efficacy. We have known the sitmulation paradigms work for a few years now but have required extensive rehabilitation before and after the implant to make significant progress. This rehabilitation period is likely going to be essential to some degree regardless, but anything we can do to minimize the amount of time needed will make these types of procedures cheaper and more realistic to scale up to the larger population. Further, again, finding that these stimulators can restore voluntary movement and sensation immediately after turning them on tells us that most individuals deemed motor and sensory complete actually have some fiber tracks in tact but those tracts are just insufficient to bring movement and sensory function to and from the brain. This is really exciting stuff and has critical implications for alot about how we move forward with SCI research as a whole. The finally piece of data ascertained from these participants that is the most exciting to me, is that two of the three participants were able to generate modest movements of the legs without the stimulator on at the end of the rehabilitation period. This is likely because those spared fibers I just mentioned get re-enforced and strong enough from the rehab process to be able to work without the stimulation.

              Finally, i do not know about the inclusion/exclusion criterion. It would be my assumption that both Baclofen and spasticity could be exclusion criterion for the sake of the experiment. these stimulation paradigms work by providing something like 80-90% of the amount of electricity needed to make a neuron fire so that the 10% remainder is sufficient to be generated by the user. This makes it possible for people who can only put 10% into the system to actually generate motion and feeling, when that same 10% was insufficient without stimulation. Spasticity puts a bit of a complication to this because the circuitry below the cord will generate 100% of the threshold at random. Applying an extra 80-90% would likely make spasticity much worse and could be unsafe if a spastic attack were to occur when someone is trying to weight support. Now, that doesnt mean that spasticity will ALWAYS be an exclusion criterion. We dont know a lot about what causes spasticity but it might actually be caused, in part, from a lack of descending input from the brain, therefore generating more input from stimulation paradigms could, potentially, improve spasticity as well, but i dont know where we stand on that at the current moment. Baclofen on the other hand is a drug that does the opposite of what this stimulation is doing. Baclofen adds a negative amount of bioelectricity to neurons. So, if the stimulation paradigm was providing 80-90%, the baclofen could, in theory, take away 20%, making your body need to make up for 30% which might be the difference from these paradigms working and not working. Again, thats something that could likely be overcome on a person by person basis by providing more electrical activity, but for experimental purposes its best to have individuals who fit a pretty tight mold just to show proof of concept. Because people with bad spasticity also tend to take Baclofen, i imagine that researchers want to avoid both of those confounds at the current moment. I wouldnt see it as a death sentence for it to be used in people with spasticity, but for experimental purposes it is probably the right call.

              Comment


                #22
                Re what they’re doing vs what spasticity is doing…are they amplifying bi-directional signal? I guess I was hoping that spasticity is a misperceived incoming signal. In other words, it’s normal to recoil if we step on a nail but with spasticity we recoil in response to everything. So, absent actually treating spasticity and not just inducing weakness, it does seem that stim would augment it but if it can actually be treated, then maybe we could stim outgoing effectively?
                Last edited by Sheri; 13 Feb 2022, 1:34 PM. Reason: Original post was a circular mess! My edit is barely any better

                Comment


                  #23
                  Originally posted by Sheri View Post
                  Re what they’re doing vs what spasticity is doing…are they amplifying bi-directional signal? I guess I was hoping that spasticity is a misperceived incoming signal. In other words, it’s normal to recoil if we step on a nail but with spasticity we recoil in response to everything. So, absent actually treating spasticity and not just inducing weakness, it does seem that stim would augment it but if it can actually be treated, then maybe we could stim outgoing effectively?
                  there are likely a couple of mechanisms underlying spasticity. One train of thought is that after the injury unspecific aberrant plasticity causes reflexes to be hyperactive. That would mean the wiring below the lesion is causing hyperactivity of the neurons controlling the muscles. The other train of thought is a bit more complicated to understand. Essentially much of the input coming from the brain that makes connection to the lower parts of the spinal cord actually confers inhibition over neuron activity. The descending input tends to quiet down neuron firing. Obviously not all descending input does this, but a bunch of it does. Some descending input activates muscles, others stop activity. The neurons that stop activity have been associated with regulating pain and reflexes, of which spasticity "could be" inappropriate reflex. take for example the classic return of the Babinski reflex after complete SCI, where stimulation on the bottom of the foot causes a withdrawal like reflex instead of a flexion response. The descending input from the brain stops this reflex from occurring, so after an SCI it returns. Its, therefore, potentially likely that increasing descending input from the brain "could" quiet down spasticity... maybe. However, if those particular connections are not maintained and all that is happening is inappropriate reflex, than stimulation could likely make spasticity worse. It would be very nice to have the knowledge from one of the experts in this field to help really break down where spasticity falls on the epidural stimulation stuff.

                  So in short you are pretty much correct, but missing the element for the inhibitory involvement of the brain in regulating these reflex responses. If the inhibitory signals from the brain are lost from the SCI, my predictions are that stimulation could make a spastic event more exaggerated. If the inhibitory signals are in tact, perhaps stimulation would make spasticity less likely to occur. Its a very interesting question that I do not see as particularly damning for this epidural stimulation stuff from a clinical perspective, but from a research perspective and trying to get clean data i can see why it could be a complication. Perhaps this would be its own question worth investigating. I will probe around my research center to see if anyone has any further insight into this question.

                  Comment


                    #24
                    I would love to know how much something like this can help a person like me who has the ability to ambulate but not community walk?

                    I would like to think just that extra little zap, get 20% or 30% stronger and be so much closer to normal. But I have no idea how the mechanics work...

                    Comment


                      #25
                      The Christopher & Dana Reeve Foundation is sponsoring a round-table on-line with with Clinical Trial Investigators Drs. Grégoire Courtine and Jocelyne Bloch, and ONWARD CEO David Marver explaining STIMO on Feb 17, 2022 11:00 AM (EST). It's free. Register here:

                      https://us02web.zoom.us/webinar/regi...=Christopher+% 26+Dana+Reeve+Foundation&utm_campaign=d51b3cf309-STIMO_webinar_2022_02_14&utm_medium=email&utm_term =0_8d9a09467d-d51b3cf309-120681989

                      (KLD)
                      The SCI-Nurses are advanced practice nurses specializing in SCI/D care. They are available to answer questions, provide education, and make suggestions which you should always discuss with your physician/primary health care provider before implementing. Medical diagnosis is not provided, nor do the SCI-Nurses provide nursing or medical care through their responses on the CareCure forums.

                      Comment


                        #26
                        For anyone unable to attend the live webinar from the Christopher & Dana Reeve Foundation, here is the video:

                        To view the webinar recording, please visit: https://youtu.be/ziDM-SkRycI

                        (KLD)
                        The SCI-Nurses are advanced practice nurses specializing in SCI/D care. They are available to answer questions, provide education, and make suggestions which you should always discuss with your physician/primary health care provider before implementing. Medical diagnosis is not provided, nor do the SCI-Nurses provide nursing or medical care through their responses on the CareCure forums.

                        Comment


                          #27
                          http://mus.acrofan.com/article_sub3....r=660185&lang=

                          Comment


                            #28
                            Originally posted by ActionXPotential View Post

                            https://www.nature.com/articles/s41591-021-01663-5


                            Im assuming you are referencing the Courtine paper that was just released using eStim? This stuff is indeed incredibly exciting. In short, people who have been Asia A for years are regaining some motor and sensory functions immediately after a stimulator is turned on. This appears to be true and reproducible across time and labs now for several years. The extent of return is minimal, with most people being able to have some faint recognition of some kinds of sensation and some very mild movement of the legs. To the best of my knowledge this stuff has been focused primarily on lower limb movement, i do not know where we stand with upper limb stuff.

                            What has been the case with electrical stimulation is that upon turning on the machine, movement is minimal, but this seems to be sufficient for an extensive rehabilitation period to be able to build up the muscles and neural circuits enough to make some very significant progress. The paper that Courtine just published attempted to improve the efficiency of this entire process by targeting a more appropriate region of the cord, in a more appropriate way. The specifics of this stuff is very, very complicated and way over my head, it would take an electrophysiologist to break down the technical details. I dont think that is necessary for the conversation though. In short, the modest adaptations made was efficient enough to allow consciously driven stepping behaviors on day 1 of turning on the stimulators, which is a benchmark only achieved after extensive rehabilitation from prior stimulation paradigms. The types of stepping on day 1 were body weight supported, with upwards of 80% of the body weight being suspended by a harness. They put individuals through 5-months of extensive rehab while using the stimulators to enhance function and each participant was able to take steps with walkers, regain trunk support, walk up stairs etc.. now we are not talking walking like normal, but going from Asia A for years to this is about as close to a miracle as it comes. One other caveat that is not meant to take away from the findings but provide realistic expectations is that the stimulation paradigms were unique for each modality of function. i.e. walking was a different form of stimulation than standing, which was different from walking up stairs. Participants switched back and forth from different pre-programmed modalities depending on the task at hand using a custom interface designed for ease of use, but was as quick as pushing a button.

                            There are alot of implications for these findings that should get us excited beyond the idea of making people walk with greater efficacy. We have known the sitmulation paradigms work for a few years now but have required extensive rehabilitation before and after the implant to make significant progress. This rehabilitation period is likely going to be essential to some degree regardless, but anything we can do to minimize the amount of time needed will make these types of procedures cheaper and more realistic to scale up to the larger population. Further, again, finding that these stimulators can restore voluntary movement and sensation immediately after turning them on tells us that most individuals deemed motor and sensory complete actually have some fiber tracks in tact but those tracts are just insufficient to bring movement and sensory function to and from the brain. This is really exciting stuff and has critical implications for alot about how we move forward with SCI research as a whole. The finally piece of data ascertained from these participants that is the most exciting to me, is that two of the three participants were able to generate modest movements of the legs without the stimulator on at the end of the rehabilitation period. This is likely because those spared fibers I just mentioned get re-enforced and strong enough from the rehab process to be able to work without the stimulation.

                            Finally, i do not know about the inclusion/exclusion criterion. It would be my assumption that both Baclofen and spasticity could be exclusion criterion for the sake of the experiment. these stimulation paradigms work by providing something like 80-90% of the amount of electricity needed to make a neuron fire so that the 10% remainder is sufficient to be generated by the user. This makes it possible for people who can only put 10% into the system to actually generate motion and feeling, when that same 10% was insufficient without stimulation. Spasticity puts a bit of a complication to this because the circuitry below the cord will generate 100% of the threshold at random. Applying an extra 80-90% would likely make spasticity much worse and could be unsafe if a spastic attack were to occur when someone is trying to weight support. Now, that doesnt mean that spasticity will ALWAYS be an exclusion criterion. We dont know a lot about what causes spasticity but it might actually be caused, in part, from a lack of descending input from the brain, therefore generating more input from stimulation paradigms could, potentially, improve spasticity as well, but i dont know where we stand on that at the current moment. Baclofen on the other hand is a drug that does the opposite of what this stimulation is doing. Baclofen adds a negative amount of bioelectricity to neurons. So, if the stimulation paradigm was providing 80-90%, the baclofen could, in theory, take away 20%, making your body need to make up for 30% which might be the difference from these paradigms working and not working. Again, thats something that could likely be overcome on a person by person basis by providing more electrical activity, but for experimental purposes its best to have individuals who fit a pretty tight mold just to show proof of concept. Because people with bad spasticity also tend to take Baclofen, i imagine that researchers want to avoid both of those confounds at the current moment. I wouldnt see it as a death sentence for it to be used in people with spasticity, but for experimental purposes it is probably the right call.
                            This is very interesting. It does lead to a question that I've had for a very long time. Outside of the stimulation, stem cells, any type of science...

                            If someone can move a bit. Perhaps even walk small distances... It sounds like what you are saying is "extensive rehabilitation", whatever that really means should be enough to bring somebody to a very significant amount of recovery?

                            If the stimulation is meant to get them to that point, and they are already at that point, perhaps the stimulation is not needed? Maybe just hours and hours and hours a day of walking...

                            Comment


                            • ActionXPotential
                              ActionXPotential commented
                              Editing a comment
                              This is a fantastic question that I bet others in the community could answer first hand. From my understanding as a scientist working on gene therapies and biological interventions (which is quite removed from rehab science), there is a window of opportunity within a few months post SCI where rehab efforts go much further and are much more effective than in chronic SCI conditions. I would wager, that extensive rehab could potentially still benefit some in the chronic condition but it might be a system of depreciating gains (more work for less gains). I have certainly heard empirical stories of people making progress in chronic SCI, and I have also heard stories of people who simply cannot seem to improve no matter their efforts. It could likely be a person-by-person basis. I am not going to speculate too much on this because it is outside my area of expertise but I would actually like to know the answer to this question as well. You should throw the question out to the greater SCI community or physical therapists or PMR docs. Alternatively there might be some good research discussing this in a more scientific manner on PubMed, unfortunately it is just outside of my scope. If you find out the answer to this question please fill me in!

                              Edit: A quick pubmed search revealed more literature than I can handle. Here is a place to start. It looks like the answer to your question seems to be "yes" (im sure its more complicated than that), but the extent to which the improvements are meaningful to day-to-day life I can not speculate.

                              https://pubmed.ncbi.nlm.nih.gov/29081250/

                            #29
                            Any news on the ARCEX? At this point we should have more info, taking into account they want to commercialize it in 2023.
                            HOC NON PEREO HABEBO FORTIOR ME

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