Thread: ChinaSCINet Update

  1. #1671
    I moved several posts about the pattern of recovery to http://sci.rutgers.edu/forum/showthread.php?t=216632 Wise.

  2. #1672
    Senior Member Wills77's Avatar
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    I've been following the best that I can and sorry if this was already posted but if phase III trials will be in the united states in 2013. When will they be available for incomplete injuries? Do you have to start over at phase 1 for incomplete trials or can they receive the same injections/therapies as completes
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  3. #1673
    There has been some recent controversy regarding whether regeneration has been observed. I have also seen some questioning by the same person regarding glial scarring, which WY does not consider a major barrier. I don't wish to reignite any of that (I feel there are better places for that sort of professional disagreement/discussion). But it does raise an interesting question, and I would like to know whether there are ways of generating and detecting electrical pulses along the spinal cord, both across the glial scar and along the white matter below it (which I understand WY can see in MRIs (?) of some of the patients). I think that would go some way towards settling those questions. It is an obvious point so I assume there is no way. I guess that generating the impulse would be the tricky part as detecting it should be easy with a sensitive inductive device. Anyone know about this?

  4. #1674
    Quote Originally Posted by dukevanwillem View Post
    There has been some recent controversy regarding whether regeneration has been observed. I have also seen some questioning by the same person regarding glial scarring, which WY does not consider a major barrier. I don't wish to reignite any of that (I feel there are better places for that sort of professional disagreement/discussion). But it does raise an interesting question, and I would like to know whether there are ways of generating and detecting electrical pulses along the spinal cord, both across the glial scar and along the white matter below it (which I understand WY can see in MRIs (?) of some of the patients).
    You could private message WY.

  5. #1675
    Quote Originally Posted by dukevanwillem View Post
    There has been some recent controversy regarding whether regeneration has been observed. I have also seen some questioning by the same person regarding glial scarring, which WY does not consider a major barrier. I don't wish to reignite any of that (I feel there are better places for that sort of professional disagreement/discussion). But it does raise an interesting question, and I would like to know whether there are ways of generating and detecting electrical pulses along the spinal cord, both across the glial scar and along the white matter below it (which I understand WY can see in MRIs (?) of some of the patients). I think that would go some way towards settling those questions. It is an obvious point so I assume there is no way. I guess that generating the impulse would be the tricky part as detecting it should be easy with a sensitive inductive device. Anyone know about this?
    Sure, there are ways of doing this.

    for instance:

    A novel command signal for motor neuroprosthetic control.
    Christa W Moss, Kevin L Kilgore, P Hunter Peckham
    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA. caw30@case.edu
    BACKGROUND Neuroprostheses can restore functions such as hand grasp or standing to individuals with spinal cord injury (SCI) using electrical stimulation to elicit movements in paralyzed muscles. Implanted neuroprostheses currently use electromyographic (EMG) activity from muscles above the lesion that remain under volitional control as a command input. Systems in development use a networked approach and will allow for restoration of multiple functions but will require additional command signals to control the system, especially in individuals with high-level tetraplegia. OBJECTIVE The objective of this study was to investigate the feasibility of using muscles innervated below the injury level as command sources for a neuroprosthesis. Recent anatomical and physiological studies have demonstrated the presence of intact axons across the lesion, even in those diagnosed with a clinically complete SCI; hence, EMG activity may be present in muscles with no sign of movement. METHODS Twelve participants with motor complete SCI were enrolled and EMG was recorded with surface electrodes from 8 muscles below the knee in each leg. RESULTS Significant activity was evident in 89% of the 192 muscles studied during attempted movements of the foot and lower limb. At least 2 muscles from each participant were identified as potential command signals for a neuroprosthesis based on 2-state, threshold classification. CONCLUSIONS Results suggest that voluntary activity is present and recordable in below lesion muscles even after clinically complete SCI.

    Here is another:

    World Neurosurg. 2013 Jan 12. pii: S1878-8750(13)00104-6. doi: 10.1016/j.wneu.2013.01.043. [Epub ahead of print]
    Transcranial Magnetic Stimulation Following Spinal Cord Injury.
    Awad BI, Carmody MA, Zhang X, Lin VW, Steinmetz MP.
    Source
    Department of Neurosurgery, Mansoura University School of Medicine, Mansoura, Egypt; Department of Neurosciences, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH.
    Abstract
    OBJECTIVE:
    to review the basic principles and techniques of transcranial magnetic stimulation and provide information and evidence regarding its applications in spinal cord injury clinical rehabilitation.
    METHODS:
    A review of the available current and historical literature regarding transcranial magnetic stimulation and a discussion of its potential use in spinal cord injury rehab was conducted.
    RESULTS:
    TMS provides reliable information about the functional integrity and conduction properties of the corticospinal tracts and motor control in the diagnostic and prognostic assessment of various neurological disorders. It allows one to follow the evolution of motor control and to evaluate the effects of different therapeutic procedures. MEPs can be useful in follow-up evaluation of motor function during treatment and rehabilitation, specifically in spinal cord injury and stroke patients. While studies regarding somatomotor functional recovery after spinal cord injury have shown promise, it will require further trials to provide strong and substantial evidence.
    CONCLUSIONS:
    TMS is a promising non-invasive tool for the treatment of spasticity, neuropathic pain and somatomotor deficit following SCI. Further investigation is needed to demonstrate whether different protocols and applications of stimulation, as well as alternative cortical sites of stimulation may induce more pronounced and beneficial clinical effects.
    Copyright © 2013 Elsevier Inc. All rights reserved.
    PMID: 23321378 [PubMed - as supplied by publisher]
    Last edited by jsilver; 02-24-2013 at 11:15 AM.

  6. #1676
    Quote Originally Posted by Wills77 View Post
    I've been following the best that I can and sorry if this was already posted but if phase III trials will be in the united states in 2013. When will they be available for incomplete injuries? Do you have to start over at phase 1 for incomplete trials or can they receive the same injections/therapies as completes
    We are planning to do phase III trials in the U.S. The upcoming phase III trial will very likely to limited to ASIA A. If the phase III suggest that the treatment is beneficial for ASIA A chronic injury, we are planning phase II for patients that are older than 64 and younger than 18, and possibly ASIA B and C.

    Wise.

  7. #1677
    Quote Originally Posted by dukevanwillem View Post
    There has been some recent controversy regarding whether regeneration has been observed. I have also seen some questioning by the same person regarding glial scarring, which WY does not consider a major barrier. I don't wish to reignite any of that (I feel there are better places for that sort of professional disagreement/discussion). But it does raise an interesting question, and I would like to know whether there are ways of generating and detecting electrical pulses along the spinal cord, both across the glial scar and along the white matter below it (which I understand WY can see in MRIs (?) of some of the patients). I think that would go some way towards settling those questions. It is an obvious point so I assume there is no way. I guess that generating the impulse would be the tricky part as detecting it should be easy with a sensitive inductive device. Anyone know about this?
    dukevanwillem,

    I am putting together a team of experienced clinical neurophysiologists to travel to the centers to test patients, specifically to look for the following, using electrophysiological tests:

    1. Cranial Magnetic Motor Evoked Potentials. This is a standard test where the motor cortex is activated by an electromagnetic pulse. When the electromagnetic coil is placed on the apex of the motor cortex, it can activate motor responses that would be recorded from muscles as electromyograms (EMG). Usually, this test is relatively insensitive to motor function in patients with spinal cord injury. On the other hand, I think that in the situation where we are seeing patients who can activate stepping activity but who cannot voluntarily move individual muscles, it would be very interesting to see if the motor cortical stimulation can indirectly activate the muscle. Note that such activation should be delayed.
    2. Central pattern generator (CPG) stimulation. Dimitrijevic and his colleages in Vienna have shown that the CPG can be electrically activated transcutaneously, i.e. from the skin surface around L2. We are interested to know if stimulation of the CPG with subthreshold currents, i.e. currents that do not produce overt walking motions, will allow the subjects to walk better or to move individual muscles of the legs better.
    3. Conditioning stimuli. We want to try interacting cranial magnetic motor cortex stimulation with H-reflexes. It is possible that the descending pulses cannot produce activation but it may do so if spinal cord is facilitated with a peripheral nerve activation that causes an H-reflex (a monosynaptic reflex). It would be of interest to know whether this would facilitate a voluntary motor cortex activation or a magnetic motor cortex stimulation.


    We have been discussing placing epidural electrodes to both record and activate ascending and descending action potential volleys. We have not decided how invasive we are willing to go for the testing.

    Wise.

  8. #1678
    Thanks to Dr Silver and Dr Young for informative replies, also thanks to Grammy. I should have thought of TMS (which I was aware of) as a way of generating an impulse. If it generates hand movement then obviously it is crossing the gliar "scar" and perhaps also can be used to test transmission along the white matter below the scar. Cranial Magnetic Motor Evoked Potentials sounds like a similar technique, but is more of a mouthful. They need to think of a snappier title. I'm glad to know that WY is already putting together a team to run these tests, and I am sure that I am not alone in looking forward to the results.

    Dr Silver mentioned a paper on TMS by Awad et al. I missed that one. Another paper which I did see was one by Monica Perez and co-authors from the University of Pittsburgh published a very nice paper late last year that found the optimal stimulation frequency for TMS (if I understood correctly), which led to SCI patients having increased grip for the duration of treatment (plus a little while longer, I think). The nice thing about TMS is that it is non-invasive. Apparently there are multiple groups working on this technique.

    Of course we'd all like to see a cure-all but it is becoming pretty clear that the cure-all will involve a combination of approaches, and perhaps something like TMS or its mouthful cousin will be part of that. Also hoping that the non-motor functions manage to hop a ride on some of these axons and come alive again too. (I make that point to save Paolocelli the bother!) (-:

  9. #1679
    Quote Originally Posted by Wise Young View Post
    dukevanwillem,

    I am putting together a team of experienced clinical neurophysiologists to travel to the centers to test patients, specifically to look for the following, using electrophysiological tests:

    1. Central pattern generator (CPG) stimulation. Dimitrijevic and his colleages in Vienna have shown that the CPG can be electrically activated transcutaneously, i.e. from the skin surface around L2. We are interested to know if stimulation of the CPG with subthreshold currents, i.e. currents that do not produce overt walking motions, will allow the subjects to walk better or to move individual muscles of the legs better.


    We have been discussing placing epidural electrodes to both record and activate ascending and descending action potential volleys. We have not decided how invasive we are willing to go for the testing.

    Wise.
    http://www.ncbi.nlm.nih.gov/pubmed/17343947

    http://www.ncbi.nlm.nih.gov/pubmed/9928325

    http://www.ncbi.nlm.nih.gov/pubmed/6975070

  10. #1680
    Dr. Young,
    Whenever you have some time, was there anything of note that came from the investigators meeting in Xian? In particular, anything about the manuscript for the paper on the Phase I/II trial? Trial design/regulatory approval/funding/timeline for starting the Phase III in China? Future trials and therapies?) I think everyone here is interested in whether or not the animal studies using Cethrin have gotten going.) Thanks as always.

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