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Dr. W. Young - Cord Tethering, again and again....

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  • #31
    Thank you very much Dr. Young, Seneca, Jan, and Arnie for contributing your knowlege and ideas to this thread. I'll definitely see to it that Will knows of all your excellent advice! (I just wrote to him, urging him to visit the site.)

    Teamwork works!

    James Kelly
    James Kelly


    • #32
      Dr. Young, with what knowledge you have of Adcon Gel, can you for foresee any challenges/problems getting OEG, Shwan or Stem cells to grow after Adcon Gel is used?


      • #33
        carthief, I have never worked with adcon gel and do not know what effect the gel has when applied directly to the spinal cord. It has been used to prevent peri-dural (epidural) adhesions after surgery. There is not much information on the effects of the gel when applied to the exposed spinal cord. When I find the time, I will try to review the literature. Here are some recent abstracts on the subject.

        • BenDebba M, Augustus van Alphen H and Long DM (1999). Association between peridural scar and activity-related pain after lumbar discectomy. Neurol Res. 21 Suppl 1: S37-42. Summary: The purpose of this study was to investigate the correlation between activity-related pain six months after first surgery for herniated lumbar disc, and the extent of lumbar epidural fibrosis present at the surgical site, assessed by magnetic resonance imaging. The 298 patients who underwent surgery for lumbar disc herniation were studied in a randomized, controlled, double-blind multicenter clinical trial to test the effectiveness of the scar-inhibiting device ADCON-L. Clinical assessments were conducted pre-operatively and at 1, 3, and 6 month intervals post-operatively, and included wound examination, magnetic resonance imaging scar assessment, and the Johns Hopkins activity-related pain questionnaire. In addition, a longer-term follow-up assessment was conducted at 12 months post-operatively. The association between the presence of epidural scar and activity-related pain was analyzed at the 6-month interval, when successful surgical excision of protruding disc material should have eliminated chronic pain. Logistic regression analysis demonstrated a significant association (p = 0.02, odds ratio = 0.7) whereby the odds of extensive scar decreased by 30% for every 31% decrease in activity-related pain score. In addition, those patients receiving ADCON-L at surgery developed significantly less scar in the months following operation (p = 0.01, 6 and 12 months post-operatively). Repeated measures analysis demonstrated that patients who received treatment with ADCON-L at the time of surgery experienced less activity-related pain through the 12-month assessment (p = 0.05). A significant association between extensive epidural scar and activity-related pain is demonstrated. Patients with less scar had less activity related pain, confirming the finding that the use of the scar inhibitor ADCON-L has a positive effect on surgical outcome. Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
        • Boyce DE, Bantick G and Murison MS (2000). The use of ADCON-T/N glycosaminoglycan gel in the revision of tethered scars. Br J Plast Surg. 53 (5): 403-5. Summary: Recurrent subdermal scar tethering is a difficult management problem in areas of high tissue mobility. We describe a novel solution to this clinical problem, which involves instilling the anti-fibrotic gel ADCON-T/N in the plane between the skin and the underlying structures. We present our results in three difficult clinical situations where excellent results have been achieved using this method. West Midlands Regional Plastic and Jaw Surgery Unit, Wordsley Hospital, Stourbridge, West Midlands, UK.
        • de Tribolet N, Porchet F, Lutz TW, Gratzl O, Brotchi J, van Alphen HA, van Acker RE, Benini A, Strommer KN, Bernays RL, Goffin J, Beuls EA and Ross JS (1998). Clinical assessment of a novel antiadhesion barrier gel: prospective, randomized, multicenter, clinical trial of ADCON-L to inhibit postoperative peridural fibrosis and related symptoms after lumbar discectomy. Am J Orthop. 27 (2): 111-20. Summary: A prospective, multicenter, randomized, double-blind, controlled study of ADCON-L Anti-Adhesion Barrier Gel (a medical device by Gliatech Inc, Cleveland, OH) was conducted in 298 patients undergoing first-time lumbar discectomy to evaluate the safety and effectiveness of ADCON-L in preventing postoperative peridural fibrosis and in improving patient clinical outcome. After lumbar discectomy, patients were randomized to receive either ADCON-L gel or nothing (control group) at the conclusion of the surgical procedure. Six months after surgery, peridural scar was evaluated by magnetic resonance imaging, and postoperative pain and straight-leg-raise angle were assessed. No statistically significant differences between the ADCON-L and control groups were observed in terms of adverse events or wound healing characteristics. ADCON-L gel was shown to be safe and to significantly inhibit peridural scar compared with the control group (P = 0.002). That peridural scarring was reduced with ADCON-L gel was further supported by direct visualization of scar tissue at reoperation in both groups. ADCON-L-treated patients had better clinical outcomes than did control patients. The incidence of activity-related pain was significantly reduced (P = 0.013), straight-leg-raise examination scores were significantly improved (P = 0.024 on the operative side and P = 0.015 on the nonoperative side), and ADCON-L reduced low back pain when it was most severe (P = 0.047) and at the end of the day (P = 0.044). Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
        • Fischgrund JS (2000). Perspectives on modern orthopaedics: use of Adcon-L for epidural scar prevention. J Am Acad Orthop Surg. 8 (6): 339-43. Summary: Adcon-L is a biodegradable gel matrix that was recently approved by the Food and Drug Administration for use during single-level posterior lumbar laminectomy or laminotomy procedures. Experimental and clinical studies have suggested that the use of this product will decrease postoperative epidural scarring. However, the relationship between epidural fibrosis and patient outcome remains unclear. If the treating surgeon is of the opinion that there is a need to reduce epidural scar, the use of this product appears worthwhile. However, further studies are needed to evaluate clinical outcome and justify the use of this product on a routine basis. William Beaumont Hospital, Royal Oak, Mich., USA.
        • Geisler FH (1999). Prevention of peridural fibrosis: current methodologies. Neurol Res. 21 Suppl 1: S9-22. Summary: Lumbar discectomy is a common surgical procedure with a physician-reported 'good' outcome of 85%-95% for successfully relieving pre-operative sciatic pain. Up to 40% of patients post-operatively, however, have persistent limitations in activity. Peridural fibrosis is a natural consequence of the normal post-operative healing that can cause symptoms by tethering the nerve roots. ADCON-L was developed to decrease the peridural fibrosis reaction. Cell culture analysis demonstrated that ADCON-L blocked the ingrowth of fibroblasts, and animal laminectomy models demonstrated a major decrease in the amount of peridural fibrosis. ADCON-L has been studied in two prospective randomized multicenter trials, one in Europe with 298 patients and the other in the United States with 223 patients at the interim analysis. Noting the differences in the quantity of peridural scar on post-operative MRI and in clinical outcome between the two groups assessed the effect of the addition of ADCON-L to the surgical procedure. Both studies had statistically significant positive beneficial effects in both the radiologic index and the clinical outcome scores. These two studies provide the evidence for the clinical use of ADCON-L to improve outcomes after lumbar discectomy. Chicago Institute of Neurosurgery and Neuroresearch, IL, USA.
        • Isla A and Alvarez F (2001). [Spinal epidural fibrosis following lumbar diskectomy and antiadhesion barrier]. Neurocirugia (Astur). 12 (5): 439-46. Summary: Although diskectomy after hemilaminectomy always produces some fibrosis, only few patients develop clinical symptoms. Fibrosis is one of the causes for failed lumbar disc surgery. Identification of fibrosis as the cause of recurring lumbar or sciatic pain requires the existence of a good clinical history and selective physical examination of the patient. MR is the imaging technique of choice although CT and myelography can be useful in some cases. Surgery can correct recurrent hernias, segmentary instability or spinal stenosis, but good results are less likely in patients with epidural fibrosis. When this exists, surgery should be directed to performing an arthrodesis of the vertebral space since the operation itself can destabilize the segment resulting in instability of the affected segment. Application of ADCON-L did not worse and in some cases improved the clinical condition of patients in double blind studies. Our multicentric double blind study showed no clinical differences among 253 patients at six months after surgery. Additionally, since this gel seems to avoid the development of fibrosis, it may prevent one of the main causes of failed disc surgery and, if reoperation is necessary due to disc remains or a lateral stenosis, the absence of fibrosis would facilitate surgery. Servicio de Neurocirugia, Hospital La Paz, Madrid.
        • Kalogrianitis S, Barrett P and Shackleford I (2001). ADCON-L and hypotension during lumbar microdiscectomy. Br J Anaesth. 87 (5): 770-1. Summary: ADCON-L anti-adhesion gel is used as an antifibrotic agent in surgery for herniated lumbar disc. We report seven patients undergoing lumbar microdiscectomy, in whom ADCON-L gel was applied to the nerve root before closure of the surgical site. After the administration of ADCON-L, tachycardia and hypotension were noted, and were quickly and effectively reversed by i.v. fluids and ephedrine. Since its routine introduction into our practice, we have given ADCON-L on 212 occasions, with an incidence of adverse haemodynamic reactions of 3.3%. Adverse cardiovascular reactions do not appear to have been reported before. Department of Musculoskeletal Science, Royal Liverpool University Hospital, UK.
        • Kramer KM (2001). RE: Unrecognized durotomy after lumbar discetomy: a report of four cases associated with the use of ADCON-L. Spine 2001; 26: 115-8. Spine. 26 (21): 2405. Summary:
        • Lo H and Frederickson RC (1999). Use of ADCON in neurosurgery: preclinical review. Neurol Res. 21 Suppl 1: S27-32. Summary: ADCON-L and ADCON-T/N are two bioabsorbable adhesion barrier gels designed to inhibit post-operative fibrosis around the dura and nerve structure. Two ADCON products were evaluated in animal models emulating their use in neurosurgery. In all studies ADCON-L and ADCON-T/N were safe and effective barriers to post-operative peridural and perineural fibrosis. Gliatech Inc., Cleveland, Ohio 44122, USA.
        • Maroon JC, Abla A and Bost J (1999). Association between peridural scar and persistent low back pain after lumbar discectomy. Neurol Res. 21 Suppl 1: S43-6. Summary: The purpose of this study was to investigate the correlation between low back pain persisting six months after first surgery for herniated lumbar intervertebral disc and the extent of peridural fibrosis present at the surgical site, as defined by magnetic resonance imaging (MRI). The 298 patients who underwent first-time, single-level unilateral discectomy for lumbar disc herniation were evaluated in a controlled, randomized, double-blind multicenter clinical trial to test the effectiveness of the scar-inhibiting device ADCON-L. Clinical assessments were conducted pre-operatively and at 1, 3, and 6-month intervals post-operatively, and included MRI scar assessment and the assessment of low back pain by visual analog scales. There were 267 patients available for low back pain assessments. The data obtained at the 6-month follow-up visit were statistically analyzed for the association between the presence of peridural scar and the persistence of low back pain. Those patients treated with ADCON-L at surgery had significantly less scar than did control patients (p = 0.007), and had less low back pain than did control patients when the pain was most severe (p = 0.047) and when the pain was assessed at the end of the day (p = 0.044). Patients with extensive scar reported continuing and debilitating low back pain more frequently than those with no or minimal scar. These findings demonstrate a direct correlation between persistent low back pain and extensive scar, since patients with increased amounts of scar had increased low back pain, regardless of their treatment group (p = 0.0003). Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA 15212, USA.
        • Mastronardi L, Pappagallo M, Puzzilli F and Tatta C (2002). Efficacy of the morphine-Adcon-L compound in the management of postoperative pain after lumbar microdiscectomy. Neurosurgery. 50 (3): 518-24; discussion 524-5. Summary: OBJECTIVE: Epidural analgesia is a pharmacological technique for operative and postoperative pain control. It has been used with lumbar microdiscectomy to facilitate management of surgical pain, shorten patient recovery time, and increase patient satisfaction with the procedure and the hospital stay. Adcon-L (Gliatech, Inc., Cleveland, OH) (adhesion control in a barrier gel) has been demonstrated to act as a barrier to the development of epidural fibrosis after lumbar procedures, minimizing the formation of fibrotic scar and improving the long-term outcome. In this study, we used Adcon-L as a vehicle to administer 1 mg of morphine epidurally to patients who underwent lumbar microdiscectomy. Our objective was to evaluate the safety and analgesic efficacy of this compound. METHODS: A randomized, controlled, double-blind study was conducted in 100 patients. Patients were randomized to two groups: the morphine-Adcon-L (M-ADL) group (n = 51 patients) or the Adcon-L control group (n = 49 patients). Outcome measures included: 1) a visual analog scale to assess the intensity of spontaneous low back and radicular pain, 2) a straight leg-raising maneuver to assess the degree of leg elevation in relation to evoked sciatic pain, 3) postoperative time to comfortable walking, 4) duration of postoperative hospitalization, 5) required amount of postoperative analgesics, and 6) postoperative work time loss. RESULTS: No intraoperative or postoperative complications were observed. No clinically relevant adverse events, such as urinary retention, respiratory disturbances, or wound infections were reported in the M-ADL group. At the time of hospital discharge, results were as follows: 1) the M-ADL group had significantly lower pain intensity scores (mean value of postoperative visual analog scale, 12.3 mm +/- 0.9 in the M-ADL group versus 24.7 mm +/- 11.5 in the control group[P < 0.0001]); 2) the M-ADL group consumed significantly less analgesics: 57.4% of M-ADL patients versus 95.9% of controls received analgesics in the hospital, and 23.5% of M-ADL patients versus 55.1% of controls used analgesics at home [P < 0.0001); 3) the M-ADL group had significantly shorter hospital stays [1.37 +/- 0.07 d versus 2.53 +/- 0.12 d in the control group[P < 0.0001]); 4) the M-ADL group had a significantly higher degree of symptomatic leg elevation in the straight leg raising [mean postoperative straight leg-raising test, 64.41 degrees +/- 1.59 versus 57.77 degrees +/- 1.85 in the controls[P = 0.02]); and 5) the M-ADL group lost significantly less postoperative work time [21.67 +/- 0.92 d versus 29.47 +/- 1.18 d in the control group). In addition, at 1 year of follow-up, there was no clinical evidence of late-onset neurological complications. CONCLUSION: The epidural application of the compound M-ADL after lumbar microdiscectomy was found to be safe and effective, and it significantly improved postoperative pain control and return to function. Division of Neurosurgery, Sandro Pertini Hospital, Rome, Italy.
        • McCall TD, Grant GA, Britz GW, Goodkin R and Kliot M (2001). Treatment of recurrent peripheral nerve entrapment problems: role of scar formation and its possible treatment. Neurosurg Clin N Am. 12 (2): 329-39. Summary: Surgical management of peripheral nerve entrapment syndromes is usually successful, but the recurrence of symptoms after initial improvement can and does occur. Extraneural fibrosis is one possible cause of recurrent peripheral nerve problems as a result of nerve compression or tethering. Several approaches to prevent extraneural scarring after surgery have been studied, including wrapping the involved nerve with a graft, the application of various chemical compounds, and radiation. ADCON-T/N, an antiscar bioabsorbable gel device was evaluated in a retrospective clinical review. Sixty-seven percent of patients treated with ADCON-T/N after reoperation of a peripheral nerve experienced prolonged clinical improvement compared with 50% of patients who did not receive ADCON-T/N. These preliminary results suggest that ADCON-T/N may prove to be clinically useful in the surgical treatment of peripheral nerve problems. Additional more rigorous clinical studies are necessary, however. Department of Neurological Surgery, University of Washington School of Medicine, Seattle, USA.
        • McKinley DS and Shaffer LM (1999). Cost effectiveness evaluation of ADCON-L adhesion control gel in lumbar surgery. Neurol Res. 21 Suppl 1: S67-71. Summary: Patients, physicians and third-party payers are becoming increasingly concerned with the economic burden resulting from advances in health care. Many economic health studies have focused on patients with sciatica and low back pain. An Economic Survey was conducted on lumbar discectomy patients who had been enrolled at least 12 months prior in a prospective randomized controlled clinical study of the adhesion control device ADCON-L. The survey measured patient satisfaction, return to work, additional medical treatment and medications after surgery. In addition, the duration of any re-operations from patients in the clinical study was analyzed. The results of the Economic Survey and re-operation time analysis show significant advantages for lumbar discectomy patients who received ADCON-L compared to control patients who did not. Patients who received ADCON-L not only had less scarring and less back pain than control patients but also were more satisfied with their surgeries and were able to return to work more often, as originally planned (p = 0.02). In addition, ADCON-L patients returned to their original jobs an average of 3.6 days sooner, changed jobs 50% less often, did not seek additional medical treatment as often, and took 20% less pain medication than did control patients (p = 0.01). In addition, patients receiving ADCON-L who required subsequent re-operation at the same lumbar space (e.g., reherniation) had a significantly shorter duration of secondary surgery (56.6 min vs. 130 min, p = 0.001) compared to patients who did not receive ADCON-L at the first surgery. Overall, ADCON-L patients demonstrated significant clinical and economic advantages over control patients. If all lumbar surgical patients in the US were to receive ADCON-L, annual savings to the health care system would exceed one half billion dollars. Gliatech Inc., Cleveland, OH 44122, USA.
        • Mentzel M, Hoss H, Keppler P, Ebinger T, Kinzl L and Wachter NJ (2000). The effectiveness of ADCON-T/N, a new anti-adhesion barrier gel, in fresh divisions of the flexor tendons in Zone II. J Hand Surg [Br]. 25 (6): 590-2. Summary: In a prospective randomized clinical trial, ADCON-T/N was investigated with regard to its effectiveness in fresh traumatic injuries of the flexor tendons in Zone II of the hand. Thirty patients participated in the trial. Following a standardized technique of tendon repair, the total active motion (TAM) and total extension lag (TEL) were determined after 12 weeks and evaluated according to the Buck-Gramcko score. Excellent results were achieved in 15 out of 16 patients in the ADCON-T/N group and 12 out of 14 in the control group. However, no statistically significant difference was found between the mean TAM and TEL in the two groups. Department of Traumatology, Hand- and Reconstructive Surgery, University of Ulm, Germany.
        • Porchet F, Lombardi D, de Preux J and Pople IK (1999). Inhibition of epidural fibrosis with ADCON-L: effect on clinical outcome one year following re-operation for recurrent lumbar radiculopathy. Neurol Res. 21 Suppl 1: S51-60. Summary: In a prospective multicenter study, 20 patients underwent re-operation for recurrent radiculopathy after lumbo-sacral discectomy, and were treated with ADCON-L (Adhesion Control in a Barrier Gel) to inhibit epidural fibrosis following secondary surgery. Outcomes after re-operation were assessed at six and 12 months using: Visual Analog Scales to measure radicular and back pain, straight leg raising exams, and self-assessment of activity-related radicular pain. Each parameter was compared to baseline values, obtained immediately prior to the re-operation. The long term clinical results at 12 months after re-operation (summarized below) demonstrate a significant improvement of all clinical parameters, and correlated with the results seen at six months. Radicular pain, measured when most severe, was reduced from an average pre-operative score of 8.1-3.7 (p < 0.005). The straight leg raising angle increased from an average pre-operative value of 41 degrees-67 degrees [p < 0.005). Activity-related pain mean score was 4.6, vs. 17.0 pre-operatively [p < 0.005). Low back pain, measured when most severe, was reduced from an average pre-operative score of 6.1 to 3.1 [p < 0.012). These clinical findings compare very favorably with data reported in the literature. There were no adverse events or complications related to the use of ADCON-L. Service de Neurochirurgie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
        • Richter HP, Kast E, Tomczak R, Besenfelder W and Gaus W (2001). Results of applying ADCON-L gel after lumbar discectomy: the German ADCON-L study. J Neurosurg. 95 (2 Suppl): 179-89. Summary: OBJECT: Failed-back syndrome is still an unsolved problem. Use of ADCON-L gel, already commercially available, has been proven to reduce postoperative scarring in animal experiments. The authors of two controlled clinical studies have also shown positive results when applying the gel. They did not, however, establish patient-oriented endpoints. The authors report a study of ADCON-L in which they focus on patient-oriented endpoints. METHODS: Patients with lumbar disc herniation were randomized to an ADCON-L-treated or control group. Therapeutic success was evaluated using the validated Hannover Questionnaire on Activities of Daily Living (FFbH) 6 months after surgery. The study took place between November 14. 1996, and April 20, 1998, in eight neurosurgical centers in Germany. A total of 398 patients was recruited; 41 patients dropped out during follow up. The mean functional FFbH score (100 points = all activities are possible without problem; 0 points = no activity is possible) was 78.5 points in the ADCON-L-treated group compared with 80 points in the control group. Furthermore, in terms of secondary outcome variables, the ADCON-L group did not have an advantage over the control group. Only the mean magnetic resonance imaging score showed a slight advantage of ADCON-L over the control group. CONCLUSIONS: The authors found no positive effect of treatment with ADCON-L gel in patients in whom one-level lumbar microdiscectomy was performed. Because of its rather large sample size and its homogeneity, the study had sufficient power to detect even small differences between the two groups. Department of Neurosurgery, University of Ulm, Germany.
        • Robertson JT, Maier K, Anderson RW, Mule JL and Palatinsky EA (1999). Prevention of epidural fibrosis with ADCON-L in presence of a durotomy during lumbar disc surgery: experiences with a pre-clinical model. Neurol Res. 21 Suppl 1: S61-6. Summary: A potential complication of lumbo-sacral surgery is the inadvertent tear of the dura mater, which sometimes eludes intra-operative detection. ADCON-L, a bioabsorbable gel used in lumbosacral laminectomies or laminotomies, is a physical barrier to post-operative epidural fibrosis. Three experimental lumbar laminectomy studies were designed to assess in vivo the effects of ADCON-L when applied in presence of dural punctures in a rat model. In the first study, the durotomy was repaired with fibrin sealant, in the second experiment the dural defect was microsurgically sutured, while in a third protocol the durotomy was left unrepaired. In each study, dural healing was assessed respectively at 4, 8, or 12 weeks post-operatively. Blinded anatomical dissection and histopathology were used to compare results between treatments (sham operated control vs. ADCON-L). In the fibrin sealant experiment, an additional treatment group (fibrin sealant used together with ADCON-L) was included. The results of these studies consistently demonstrate that ADCON-L is an effective anti-fibrotic agent, and does not interfere with the normal dural healing processes following a meningeal puncture. The application of the gel may therefore be safe in presence of dural incisions, even when they are not identified during surgery, as demonstrated in these in vivo studies. Department of Neurosurgery, University of Tennessee, Memphis, USA.
        • Ross JS, Obuchowski N and Modic MT (1999). MR evaluation of epidural fibrosis: proposed grading system with intra- and inter-observer variability. Neurol Res. 21 Suppl 1: S23-6. Summary: The purpose of this study is to present a grading system for the Magnetic Resonance (MR) appearance of epidural fibrosis, and to present the inter- and intra-observer variability of the system. The study population was from a randomized, double blind, controlled multicenter clinical trial evaluating the safety and effectiveness of ADCON-L anti-adhesion barrier gel, in preventing epidural fibrosis and dural adhesions following single-level unilateral laminectomy/discectomy for lumbar disc herniations. MRI of the lumbar spine was obtained, without and with gadolinium enhancement, pre-operatively and at six months post-operatively. Patients having extensive epidural scar have been shown to be 3.2 times more likely to experience recurrent radicular pain than those patients with less extensive epidural scarring. New agents have appeared in the marketplace and in clinical trials that may be used intra-operatively to modulate the presence or absence of epidural scar tissue. Given these factors, the need to accurately describe the location and amount of epidural scar tissue has assumed more pressing importance. Two readers, blinded to clinical findings and to the other reader, independently evaluated the MR examinations in 50 post-operative lumbar spine surgery patients using the previously defined categorization of epidural scar for five levels in each patient, four quadrants per level. In addition, 114 examinations were separately evaluated by the same reader for evaluation of intra-observer variability. For the purposes of epidural fibrosis identification, only the axial T1-weighted images with and without contrast were utilized. The amount of epidural fibrosis was graded on a scale of 0-4 for each quadrant at each imaging slice encompassing the operative level: 0 = no/trace scar; 1 = > 0% and < or = 25% of quadrant filled with scar; 2 = > 25% and < or = 50% of quadrant filled with scar; 3 = > 50% and < or = 75% of quadrant filled with scar; 4 = > 75% and < or = 100% of quadrant filled with scar. Each reader evaluated a total of 1000 epidural quadrants for the inter-observer assessment. The estimated kw index is 0.68 with 95% confidence interval [CI) of [0.64, 0.71]; this is substantial agreement. There were a total of 2,280 quadrants evaluated overall for the intra-observer assessment. The estimated kw index is 0.94 with 95% CI of [0.93, 0.95]; this is almost perfect agreement. Substantial intra-observer and near perfect inter-observer agreement was achieved for evaluation of epidural scar using a relatively simple, semi-quantitative approach to the T1-weighted axial MR images. A standard grading system for epidural scar is proposed. Division of Radiology, Cleveland Clinic Foundation, OH 44195, USA.


        • #34
          Dear Dr. Young,

          I wanted to thank you for this extensive collection of information on the status of ADCON-L gel and other anti-adhesive agents. I've been looking for this for months. Other than the research abstracts on anti-adhesive gels for epidural/peridural fibrosis, I haven't been able to find any common-sense, basic information on the real challenges of using anti-adhesive agents within the dura.

          I was especially interested in what you said about some of the agents interfering with dural healing. I always wondered if this would be a potential complication, but couldn't find an answer one way or another. My tethering (after surgery to remove a cauda equina tumor) is felt to be in large part a result of a prolonged, unfixed CSF leak and pseudomeningocele, which allowed several nerve rooots to herniate out of the dura and scar shut there. I have a real respect for the kinds of complications a long-term CSF leak can cause.

          Again, thanks so much for the insights into what's happening in the labs. I can't tell you how much it helps to finally find an up-to-date discussion of the current science.



          • #35

            You are of course very welcome. Adcon gel is controversial... Here is a very recent web site article on the legal status of the drug:




            • #36
              Dear Dr. Young,

              Thanks so much for the link. I've definitely been wondering about the reasons for the Adcon recall, and this clarifies it.

              It has been tremendously encouraging for me simply to find out that you're putting a concentrated research effort into the whole tethering problem. I know there are real obstacles here, because anything that gets inside the dura seems to trigger inflammation, and any surface that gets inflamed tends to stick. You start treating those problems, only to find that the stickiness was essential in keeping the dura together so the incision could seal. It's easy to convince yourself that preventing spinal adhesions is an impossible goal.

              As a patient, I know it's important to be realistic, and understand how stubborn the problem of intradural adhesions can be. But at the same time, I am so grateful that someone has the persistence to keep testing new substances. I don't mind the slowness of progress as long as I know that someone is out there, running the experiments I would want to do if I could. That, in and of itself, is extremely reassuring.

              One of my other thoughts has been to try to develop better imaging techniques, so tethering can be spotted more easily and precisely. It can be suprisingly hard to say with certainty that the cord is tethered, and where it's tethered. I've had some interesting talks with neuroradiologist friends about this. I'd love to get your input at some later time, if I put together a few of the ideas we've been kicking around.

              In any case, this note was primarily to say thanks.



              • #37
                Kirsten, as you may have already found out from your conversations with radiologists, some places are now offering to scan patients while they are moving, to see where the spinal cord may be tethered. Here are some references that you might be interested in. Wise.

                • Witkamp TD, Vandertop WP, Beek FJ, Notermans NC, Gooskens RH and van Waes PF (2001). Medullary cone movement in subjects with a normal spinal cord and in patients with a tethered spinal cord. Radiology 220:208-12. Summary: PURPOSE: To compare movement of the normal medullary cone when the patient has changed from a supine to prone position with that in patients with known or suspected tethered spinal cord syndrome. MATERIALS AND METHODS: Fifty-six individuals divided into three groups were examined with lumbar spine magnetic resonance (MR) imaging performed with the patient in the prone and supine positions. Group 1 consisted of 15 healthy volunteers and six patients with a herniated disk; group 2, 25 patients clinically suspected of having a tethered cord; and group 3, 10 patients who previously had undergone tethered cord surgery. RESULTS: All group 1 subjects showed distinct and statistically significant medullary cone movement (range, 21%--41%); no patient in group 3 showed movement (Wilcoxon rank sum test, P <.001). In group 2, the 20 patients in whom a definite diagnosis of tethered cord syndrome was made on the basis of initial supine MR image findings showed no movement, whereas two of five patients with normal supine MR images had abnormal and decreased cone movement at prone imaging. CONCLUSION: Prone MR imaging has no additional value when the supine MR image has clearly shown the cause of tethering or in patients who have undergone tethered cord surgery, but it can provide additional information in patients clinically suspected of having a tethered cord and in whom supine MR imaging depicted no abnormalities. Department of Radiology, University Hospital Utrecht, HPnr: E.01.132, Heidelberglaan 100, NL-3584 CX Utrecht, the Netherlands.

                • Levy LM (1999). MR imaging of cerebrospinal fluid flow and spinal cord motion in neurologic disorders of the spine. Magn Reson Imaging Clin N Am 7:573-87. Summary: In summary, MR imaging of CSF and cord motion helps to evaluate diseases affecting cord and CSF motion and to identify the specific pathophysiology involved. A number of significant points have been made. First, MR imaging flow studies can be useful in evaluating CSF spaces and cystic diseases. Second, longitudinal and transverse motions occur in the spinal cord and CSF. Traveling wave motion occurs along the length of the spinal cord. Third, spinal cord tethering is associated with decreased cord velocity and loss of cord displacement at tethering site. Decreased transverse velocities occur with lateral cord tethering to the spinal canal. Fourth, in spinal dysraphism, longitudinal cord velocity is decreased by tethering, and is normal in asymptomatic patients with low conus. Normal cord motion helps to rule out possible tethering in symptomatic dysraphism with hydromyelia. Fifth, in acquired and nonmyelodysplastic symptomatic tethering, spinal cord motion is decreased. Sixth, in symptomatic cord compression, CSF flow and cord motion decrease, but recover after surgical decompression and after compensatory atrophy. Seventh, in asymptomatic spinal stenosis, cord motion is normal or increased. Diffuse spinal stenosis with cord atrophy leads to diffuse cord acceleration and prolonged cord caudal velocity, possibly related to the loss of the transverse mobility of the cord. Finally, focal spinal stenosis leads to focal dynamic cord deformation and can be associated with prominent intramedullary deformations. When compression is severe or symptomatic, cord motion is significantly decreased. Postoperative cases demonstrate good recovery of cord and CSF motion, unless compression or obstruction is still present. Neuroimaging Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

                • Johnson DL and Levy LM (1995). Predicting outcome in the tethered cord syndrome: a study of cord motion. Pediatr Neurosurg 22:115-9. Summary: Thirty-two children with spinal dysraphism have been studied with phase MRI to assess longitudinal cord motion. Seventeen children who were asymptomatic and who had normal or slightly decreased motion were not operated. Fifteen had signs and symptoms of spinal cord tethering as well as decreased cord motion and underwent surgery. None of the nonsurgical patients have become symptomatic. The children with markedly decreased cord motion did not improve after surgery. A trend was seen toward a better outcome in younger patients with slight or moderate decrease in cord motion. All children with worse outcome were previously operated meningomyeloceles who had markedly decreased cord motion and who were greater than 10 years old. Division of Neurosurgery, Children's Hospital, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pa 17033, USA.

                • Vernet O, O'Gorman AM, Farmer JP, McPhillips M and Montes JL (1996). Use of the prone position in the MRI evaluation of spinal cord retethering. Pediatr Neurosurg 25:286-94. Summary: In order to determine the impact of magnetic resonance imaging (MRI) in the management of spinal cord retethering, we retrospectively reviewed case and imaging records of 51 patients who underwent MRI examination in supine and prone positions. Group 1 included 8 control patients without cord tethering. They exhibited a normal level of the conus medullaris with normal surrounding subarachnoid space, and consistent anterior migration of the conus within the dural sac on MRI in prone position. Group 2 included 17 patients with tethered cord secondary to occult spinal dysraphism (spinal cord lipoma in 6 patients, thick filum terminale in 4, diastematomyelia in 4, myelomeningocele manque in 2, and dermoid tumour in 1). Supine and prone MRI performed at a median period of time of 6 months after untethering showed resolution of posterior tethering in 5 out of the 7 patients who exhibited pre-operatively dorsal attachment of the spinal cord to the dura. Anterior migration of the conus or of the cord/filum complex in prone position was observed in only 24% of the cases. Group 3 included 26 patients with secondary tethered cord following prior myelomeningocele closure. Their MRI performed at a median interval of time of 11 months following untethering demonstrated resolution of the posterior cord tethering in only 8 out of the 24 patients who exhibited this feature pre-operatively. Anterior migration within the expanded dural sac was never noted in this group. We conclude that spine MRI is of limited value and that prone-positioned MRI is of no additional use in the evaluation of spinal cord retethering. Department of Medical Imaging, The Montreal Children's Hospital, Que., Canada.

                • Wang D, Bodley R, Sett P, Gardner B and Frankel H (1996). A clinical magnetic resonance imaging study of the traumatised spinal cord more than 20 years following injury. Paraplegia 34:65-81. Summary: One hundred and fifty three patients who had sustained a spinal cord injury more than 20 years previously were assessed neurologically and by MRI scanning of their spinal cords. The spinal cord pathologies shown were, in order of prevalence, extended atrophy, malacia, syrinx, cyst, disruption and tethering. There was no relationship between the prevalence of any type of pathology and the degree of spinal canal compromise or angulation of the spine adjacent to the level of injury. Neurological changes after initial neurological stabilisation were seen only in patients with extended atrophy, malacia or a syrinx, not in those with only a cyst or cord disruption. Tethering is always associated with other lesion(s). Longer syrinxes were more likely to have associated neurological changes than shorter ones. The most common neurological change was pain. National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, UK.

                • Johnson DL and Levy LM (1995). Predicting outcome in the tethered cord syndrome: a study of cord motion. Pediatr Neurosurg 22:115-9. Summary: Thirty-two children with spinal dysraphism have been studied with phase MRI to assess longitudinal cord motion. Seventeen children who were asymptomatic and who had normal or slightly decreased motion were not operated. Fifteen had signs and symptoms of spinal cord tethering as well as decreased cord motion and underwent surgery. None of the nonsurgical patients have become symptomatic. The children with markedly decreased cord motion did not improve after surgery. A trend was seen toward a better outcome in younger patients with slight or moderate decrease in cord motion. All children with worse outcome were previously operated meningomyeloceles who had markedly decreased cord motion and who were greater than 10 years old. Division of Neurosurgery, Children's Hospital, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pa 17033, USA.

                • Brown E, Matthes JC, Bazan C, 3rd and Jinkins JR (1994). Prevalence of incidental intraspinal lipoma of the lumbosacral spine as determined by MRI. Spine 19:833-6. Summary: STUDY DESIGN. The prevalence and appearance on MRI of lipomas of the filum terminale was studied in a random population referred to MRI for evaluation of the lumbosacral spine. The MRI scans of 100 patients selected at random were retrospectively reviewed. OBJECTIVES. The study sought to determine the frequency and MRI appearance of incidental filum lipomas in a random population. SUMMARY OF BACKGROUND DATA. Postmortem studies have reported a 4%-6% incidence of occult fibrolipomas of the filum terminale in what were thought to be otherwise normal spinal cords. The improved resolution of MRI imaging allows the detection of small amounts of fat associated with the filum terminale that heretofore had not been demonstrated on radiologic imaging examinations. METHODS. The lumbosacral spine unenhanced MRI scans of 100 patients not previously operated upon were selected at random and were retrospectively reviewed by two of the authors (EB and JCM). RESULTS. Of the 100 MRI examinations reviewed, four patients were found to have small lipomas of the filum terminale. No spinal dysraphism or cord tethering were present in these four patients. Their clinical symptoms were related to disc herniation in two patients, spinal stenosis in one, and discitis in one. The lipomatous tissue was hyperintense to cerebrospinal fluid (CSF) on T1-weighted images and hypointense to CSF on T2-weighted images. CONCLUSIONS. Incidental lipomas of the filum terminale were present in 4% of 100 lumbosacral spine MRI examinations in a random population. Neuroradiology Section, University of Texas Health Science Center at San Antonio.

                • Gundry CR and Heithoff KB (1994). Imaging evaluation of patients with spinal deformity. Orthop Clin North Am 25:247-64. Summary: CT myelography and MRI provide the best means of preoperatively assessing patients with spinal deformities. Owing to its noninvasive nature and its superior soft-tissue contrast, MRI represents the single best modality in the evaluation of a patient with any deformity. MRI allows complete preoperative surgical planning and obviates the need for any additional studies. Screening of the entire cord in a patient with a deformity is best accomplished with sagittal and coronal (as needed) T1W images. These images allow assessment of the cord for compression, tethering, syrinx, enlargement, and Arnold-Chiari malformation. Evaluation of cord compression at the apex of a curve is the single most important consideration other than the diagnosis of intrinsic cord abnormality. Subsequent sagittal or axial T2W images may be helpful if specific abnormalities are noted on T1W screening images. Coronal images are particularly helpful in patients with prominent curves or in those with vertebral anomalies. Additionally, coronal images may be useful in assessing patients with suspected diastematomyelia. Advances in hardware and software design have resulted in marked improvements in the ability to satisfactorily image all aspects of patients with spinal deformities. New phased array coils allow rapid imaging of larger portions of the spine. For instance, a complete MRI of the spine can be performed in a child in the same length of time that would have been necessary for a single lumbar examination when MRI was in it's infancy. The use of fast spin-echo imaging also permits more rapid acquisition times. CT myelography remains useful for those patients who cannot undergo MRI or for those with specific abnormalities such as multilevel central spinal stenosis when dynamic information obtained during the myelogram might be helpful. CT myelography represents the only means of assessing the central spinal canal of patients with metallic instrumentation in place. With the exception of these limited applications, MRI has replaced CT myelography as the imaging study of choice in the evaluation and examination of patients with spinal deformities. Center for Diagnostic Imaging, St. Louis Park, Minnesota.

                • Falcone S, Quencer RM, Green BA, Patchen SJ and Post MJ (1994). Progressive posttraumatic myelomalacic myelopathy: imaging and clinical features. AJNR Am J Neuroradiol 15:747-54. Summary: PURPOSE: To describe the imaging features, surgical management, and clinical outcome of progressive posttraumatic myelomalacic myelopathy (PPMM), a relatively unrecognized but important cause of progressive myelopathy in patients with previous spinal cord injuries. METHODS: The clinical records, imaging studies, and postoperative outcome of 10 patients with PPMM were reviewed. Fifteen preoperative and five postoperative MRs were analyzed for intramedullary signal abnormalities, the nature of these signal abnormalities, and cord tethering. All patients had intraoperative sonography. RESULTS: Neurologic signs and symptoms found in our patients included 1) progressive loss of motor function (6/10), 2) sensory level changes (4/10), 3) increased spasticity (4/10), 4) autonomic dysreflexia (4/10), 5) loss of bowel or bladder control (4/10), and 6) local and/or radicular pain (4/10). Preoperative MR in nine patients revealed intramedullary T1/T2 lengthening (9/9), extramedullary tethering/adhesions (9/9), ill-defined lesional borders (6/9), cord expansion (5/9), and increased signal intensity of the lesion on T1-weighted images compared with CSF (7/9). Proton density images in five patients demonstrated a relative increase in signal intensity over CSF. In all five postoperative MRs, there was evidence of untethering of the spinal cord and a decrease in cord size in two patients. Intraoperative sonography revealed cord tethering and abnormal cord echotexture in all cases. Postoperative clinical evaluation revealed neurologic improvement in nine patients. CONCLUSIONS: PPMM may clinically and radiographically mimic progressive posttraumatic cystic myelopathy (PPCM). MR provides clues to the diagnosis of myelomalacia preoperatively. Intraoperative sonography confirms the absence of a confluent cyst. These points are crucial in the surgical procedures in PPMM vs PPCM. In PPMM, lysis of intradural adhesions results in an improvement in symptoms in a manner similar to the shunting of PPCM. Department of Radiology, University of Miami/Jackson Memorial Medical Center.

                • Inoue HK, Kobayashi S, Ohbayashi K, Kohga H and Nakamura M (1994). Treatment and prevention of tethered and retethered spinal cord using a Gore-Tex surgical membrane. J Neurosurg 80:689-93. Summary: The incidence of the tethered cord syndrome after repair of spinal dysraphism is not insignificant. A retethered spinal cord may also develop after an untethering operation. In order to treat and/or prevent the tethered and retethered spinal cord, the authors developed and successfully used a new method in 12 cases. After complete release and reconstruction of the spinal cord, a Gore-Tex surgical membrane was placed over the cord and fixed to the lateral dural surface with stay sutures. During a postoperative follow-up period ranging from 23 months to 7 years, no further neurological deterioration was observed in the 12 patients and magnetic resonance imaging studies showed no adhesion of the spinal cord to the operative site. It is concluded that this simple new method is effective for the treatment and prevention of tethering and/or retethering of the spinal cord, although a longer follow-up study is required. Department of Neurosurgery, Gunma University School of Medicine, Maebashi, Japan.


                • #38
                  Wow! This is terrific. Thanks so much. Some of these references I have, but others are new to me.

                  The tricky part of my situation is to find out if I have cervical/thoracic tethering in addition to whatever is stuck in the lumbosacral area, where my tumor was removed. My problems started two years ago (14 months after my initial L1-L2 tumor removal in 2000), with lower body symptoms. New injuries were always triggered by body positions that put tension on the cord (prolonged sitting, driving, certain physical therapy exercises). I slowly accumulated overlapping patches of perineal sensory loss, some muscle weakness/wasting in the legs, buttocks and feet, and significant bowel retention. And, of course, pain.

                  A clear site of tethering was eventually found at L3, where several nerve roots had herniated out of an unfixed gap in the dura. However, the surgery to free this up (September 2001) did not seem to make any difference. I still get nerve injuries from normal, everyday things, like sitting upright (which I no longer do). Basically, I still feel very much tethered.

                  For a year and a half, I've had upper body symptoms very typical of those seen with higher-level tethering, but always assumed this must be from transmitted tension through the cord, since patients with lumbosacral tethering do sometimes develop CSF flow problems and syringomyelia at higher levels of the cord.

                  However, a few weeks I ran across a story that made me think twice. A friend with a similar level tumor (around L1), had a successful reoperation a few years after her original tumor removal, to untether her cord not only at the original lumar operative site, but also at T2. I checked with her again to make sure: that's T2, not T12. Perhaps the post-surgical inflammmation, and possibly free blood in the CSF, caused her cord to stick at a site so far removed from the original surgery.

                  Her symptoms were very similar to mine: mainly upper body tightness/tugging when bending the head forward. I have this all the time, but also have some permanent muscle wasting in my hands, in my neck and between the shoulder blades, positional burning pain/numbness going down my arms into the 4th and 5th fingers, and some intermittent cranial nerve/brainstem-ish symptoms brought on by the same positions (blurred vision, tinnitus, voice changes, breathlessness, a sensation of choking in the throat, gagging, pressure behind the ears, and intense downward pressure at the base of the skull). Basically, Chiari-type symptoms (at least that last group), which were puzzling for a long time, but I've found described by other patients with tethering, even non-congenital tethering.

                  I would never have considered the possibility of higher-level tethering after lumbar surgery, if not for my friend's documented tethering at T2. I just can't see how they'd be able to see this definitively on MRI. I recently had a cervical and thoracic MRI to rule out a syrinx (there was none, and no Chiari either). But my cervical cord certainly was plastered against the cervical curvature.

                  It's hard to see how they'd be able to tell for sure if anything was actually stuck, and not just pulled in that position temporarily. I guess it's worth asking my doctors if a prone cervical MRI might do any good. It's hard to justify more of these tests, though, when the likelihood of anyone actually operating on whatever they find it very low, for good reason. I think it would help me to find out either way, though, so I can keep this in mind during daily life and physical therapy.

                  All my doctors, except one, have been totally stumped by the upper body symptoms. That "one" was Dr. Donlin Long, at Johns Hopkins, who felt that whatever the explanation was, I had some sort of positional Chiari-like situation going on. I have no way of knowing what the real answer is, but as a patient it feels like something mechanical is causing this, since all the step-wise, permanent injuries are brought on by the same positions of spinal flexion. It actually does feel as if the cord is stuck. As I move around, I can feel a simultaneous tugging at the base of my skull, between my shoulder blades, and somewhere down in the sacrum.

                  I've been checked out for tumor recurrence, MS, and a long list of other things. There's not an inch of my nervous system that has not been scanned. I do have a few very minimal disk protrusions in the cervical spine, but these seem to have come up after I began to have muscle wasting in the neck, not before (as you can imagine, I have whole books of old MRI's).

                  Okay - I did not actually mean to burden you with my whole tumor and tethering story. Thanks again for all the helpful information. I think there is a great deal more buried in this website, since you have written so extensively on this subject, and I will slowly make my way through those previous notes. If it sounds like I'm trying to be my own doctor, I don't mean to be, and I wish things were different. It's just that everyone involved keeps telling me they've never seen this before, and don't know what to do about it. We seem to have hit a dead end. I'm grateful to have as much function as I do (which is quite a lot). It's just not stable, and keeps getting whittled away by nerve injuries from ordinary activities.

                  You've helped me a lot with your references, and I'll let you know how things pan out.


                  [This message was edited by Kirsten on 01-18-03 at 19:34.]

                  [This message was edited by Kirsten on 01-18-03 at 19:36.]