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Thread: Lima's published follow up of first 7 patients

  1. #1
    Junior Member kamazots's Avatar
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    Lima's published follow up of first 7 patients

    This was publisheb at the American paraplegia society journal.
    http://www.apssci.org/pages.php?catid=1&pageid=1
    I found it interesting.

  2. #2
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    Thumbs up

    Thanks for posting this. I have been waiting to read this one

    klj

  3. #3
    kamazots,

    Thank you very much for posting this. I have had an opportunity to read the article and have a few comments.

    The article included only the first 7 patients that received the procedure, whereas we know from reports from the media, presentations by Dr. Lima at public meetings from over a year ago, and patient reports on this site that as many as 60 patients have received the procedure to date. Nevertheless, it is a very useful report because it provided detailed descriptions of the methodology, the rationale, and the results in these 7 patients.

    Surgical Procedure. As the article detailed, the patients received a three part procedure. First, a laminectomy was performed to expose the spinal cord and "scar" tissues from the lesion were removed. Second, olfactory mucosa was removed endoscopically through a submucoperiosteal tunnel from the posterior-superior aspect of the medial side of the olfactory groove. Third, the graft was minced, soaked in saline or cerebrospinal fluid for 2 hours, and inserted into the cavity in the spinal cord.

    Histology. The authors claimed that the "scar tissue" was removed "(within limits as to not harm normal cord tissue) to expose the gross viable nervous tissue in both stumps". This description does not clearly indicate how the limits were determined and how the authors avoided removing viable tissue. They used the Masson trichrome stain and GFAP immunohistology to examine the removed tissue. Sections of the removed tissue in one case revealed extensive collagen present with bundles of "Schwann cell ensheathed nerve fibers". A picture (figure 4a) indeed suggested dense (blue-green) collagenous material with cross-sections of what may be axons. It is unclear how the authors determined that these were "Schwann cell ensheathed nerve fibers" or "peripheral type axons", as opposed to oligodendroglial ensheathed axons. The results section described the "scar" from two patients but the discussion (on page 199) suggested that the tissues from all 7 patients were examined and compared, and "will be the object of further studies." The authors further stated that the "most common observation in all the cases done to date, including those in this study, was a scar of mixed composition containing both astrocytic processes, collagen, and laminin with axons interspersed". Unfortunately, the causes of injury were not described, i.e. whether contusions or penetrating injuries had occurred. The authors indicated that there was "variability in the amount of hemorrhagic tissue present in the scar"; it is surprising that there would be any hemorrhagic tissue in the spinal cord at 0.5-6.5 years after injury. The authors stated that "despite the presence of some peripheral-type axons, it is believed that the chronic scar is an important obstacle to regeneration of the spinal cord." In my opinion, the histological appearance of the tissue removed are important observations because the presence of collagenous scar is rarely seen in animal contusion models.

    Magnetic resonance images (MRI) . At 6 months after the operation, MRI studies revealed "complete filling of the cystic cavities". This is not surprising since the authors had removed tissue and then packed autologuous nasal mucosal tissue into the cavity of the removed tissue. They described a "salt and pepper" appearance but this was not apparent in the images shown in Figure 1c or 1f. Some possible adhesions were still present in 1c but 1f appeared to be surrounded by cerebrospinal fluid. It was unclear from the description of patient 5, who had 2 cystic cavities at T4 to T6, what was removed and where the nasal mucosa was transplanted. Figure 1d-f was from patient 3 who was a high tetraplegic with C3 through C4 lesion. It is quite worrisome that the surgeon had removed spinal cord tissue so close to the phrenic nucleus which is responsible for controlling breathing and is located at C3. However, this patient had a C4 motor and sensory level before surgery and recovered motor function to C7 on the right and C5 to the left, and sensory function to T2 on the right and left. Patient 4 is notable because they had difficulty "finding the lesion site at surgery" and this was also the patient who had some loss of sensation after the surgery with slight return of motor function in the legs.

    Neurological scores. The authors had carried out ASIA classification scoring of motor and sensory function, reporting examinations done before, at 6, 12, and 18 months after surgery. All but one patient recovered sensory function, with scores ranging from -13 to +36 points for light touch and -11 to +34 points for pinprick sensation. Patient 4 was the one who had lost sensation and did not change motor function in the arms but gained 3 points motor function in the legs. The reporting of the scores was quite complete, including even the examiners. Dr. Lima had examined all the patients preoperatively with Dr. Eugenia Veiga in patients 3-7. Apparently, 2 of the patients converted from ASIA A to C, with one of the patients recovering anal sphincter motor function and the other presumably anal sensation. Several of the paraplegic patients recovered hip flexors while one of 3 tetraplegic patients recovered hip flexors. None of the patients had systematic rehabilitation. The degree of motor improvement appears to be significant but modest.

    Adverse events. One patient had loss of sensation (patient 4). Two patients had transient (2-3 month) increase in neuropathic pain treated with gabapentin and some patients had dysesthesia (tingling sensation) in the areas that eventually recovered some sensation. None of the patients had any problems with olfaction by 6 months after the surgery. Most significantly, one of the patients developed an infection. Incidentally, this was one part of the paper that actually referred to 41 patients that the authors had operated at the time of the last manuscript revision (p. 201). they claimed that all 41 patients had received the transplants with "no indications of infection". All the patient apparently received "prophylactic antibiotics" shortly before surgery.

    Mechanisms. The mechanism of recovery is unclear. In a study of this type, this is not surprising. While the transplants appeared to fill the cavity, without actual histological analysis, it would be difficult to state with certainty which cell type survived. While the authors suggested that there are pluripotent "stem-like" progenitor cells in nasal mucosa, it is equally likely that the cavity was filled by fibroblasts or other cells that are prresent in nasal mucosa. As the author pointed out, the limited motor recovery observed below the injury site may be due to myelination or sprouting as well.

    In summary, I think that this is a credible report of the first seven patients that received olfactory mucosa transplants to the spinal cord. Adverse events were minimal, suggesting that the procedure is safe. A majority of the patients showed significant sensory improvement and modest motor gains. The authors indicated that they had detethered the spinal cords and the extent to which this was responsible for some of the functional recovery is not clear. To me, the most interesting part of the study was the histological examination of the "scar" tissue. They report that most of the tissues that they removed from the patients had collagen in them. If so, this is substantially different from the experience that we have in animal studies where collagen is seldom present in contused spinal cords. The fact that there are axons in the material is worrisome and I am not sure that I am ready to believe that these are only "peripheral axons". Nevertheless, this is a very useful and important paper. I am glad to Dr. Lima finally published their first paper of this procedure. I am looking forward to the report of the rest of their results.

    Wise.
    Last edited by Wise Young; 06-29-2006 at 09:25 AM.

  4. #4
    I would really like to see "intensive rehabilitation" defined and factored into the equation. I think it would be of enormous benefit to have a trial (for any procedure) in which a predetermined period of pre and post rehabilitation is implemented.
    Wildwilly

  5. #5
    wildwilly, I agree.

    For others who may be interested, Laurance Johnston has a two part article concerning Dr. Carlos Lima. The second one recounts what the patients thought of the procedure:

    http://www.healingtherapies.info/OlfactoryTissue2.htm

    Wise.

  6. #6

    Lima

    Wise’s comments on the scar tissue are intriguing.

    There is some interesting research being published concerning the transplantation of glial-restricted precursor cells (GRP’s, a type of stem cell) into animal models of acute SCI. Basically, adult neural stem cells can differentiate into neuron- or glial-restricted precursor cells, the former evolving into neurons and the latter into oligodendrocytes and astrocytes. Apparently, GRP transplantation alters scarring by imposing a linear orientation on host glial cells, which is more permissive to regenerating axons. Speculatively, perhaps some components of Lima’s transplanted olfactory nasal tissue, such as stem cells or olfactory ensheathing cells, can do the same thing.

  7. #7

    Laurance

    Quote Originally Posted by Laurance
    Wise’s comments on the scar tissue are intriguing.

    There is some interesting research being published concerning the transplantation of glial-restricted precursor cells (GRP’s, a type of stem cell) into animal models of acute SCI. Basically, adult neural stem cells can differentiate into neuron- or glial-restricted precursor cells, the former evolving into neurons and the latter into oligodendrocytes and astrocytes. Apparently, GRP transplantation alters scarring by imposing a linear orientation on host glial cells, which is more permissive to regenerating axons. Speculatively, perhaps some components of Lima’s transplanted olfactory nasal tissue, such as stem cells or olfactory ensheathing cells, can do the same thing.

    I just finished reading your book, it is very good reading material and very informative, great job. Please see my new topic on Alternating pulsed electronic accupuncture treatment here in the Cure forum. I would like to get your opinion of what I am thinking of trying on myself.
    Last edited by Curt Leatherbee; 07-02-2006 at 08:57 PM.

  8. #8
    This was in 2006 and seemed like there was something to be gained. It's now 2009 almost 2010 and what have we learned? These procedures don't ever or most of the time restore function/sensation? If I knew I could at least get sensation, that might be a plus.. Or maybe not if it was associated with pain. I want to feel again and take a nice bubble bath!
    Donnie: Dr. Xiao, What are your thoughts on a cure/combination therapy for SCI's??
    CG Xiao: Donnie, I don't want to disappoint you, but I think it is impossible to restore the continuity of the cord or "bridge the gap" in the near future, let's say: 50 years. Dr Wise Young has been my most respected scientist in SCI. He has dedicated and contributed to SCI no other can match.

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