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ABSTRACT: We have studied the application of voltage gradients to injured spinal cord which enhanced regeneration of axons and reduced their retrograde degeneration after injury. This led to an implanted electronic device producing electrical fields sufficient to induce regeneration in both ascending and descending tracts of white matter (called oscillating field stimulation [OFS]), which has been associated with behavioral recovery in animal models of spinal cord injury (SCI). OFS has also proven to benefit neurologically complete spinal cord injured dogs and humans in clinical trials. These studies, however, have failed to confirm benefit if applied after the sub-acute period of SCI. Here we report on combining OFS with the application of a non-toxic neurotrophic factor, inosine, using a behavioral model for "chronic" SCI, the cutaneous trunci muscle (CTM) reflex in adult guinea pigs. Inosine was delivered subcutaneously in guinea pigs for 28 days using implantable "osmotic pumps"--alone or in combination with OFS. In all animals, experimental and control treatments were withheld for three months after a right lateral hemisection of the thoracic spinal cord. Both inosine and the combination therapy produced a statistically significant recovery of CTM receptive fields silenced permanently by spinal cord hemisection in controls--though the combination therapy enhanced the time of the appearance of recovered regions of skin. Retransection of the cord in three recovered animals eliminated the CTM recovery confirming changes in neural connections were restricted to the cord and not due to changes in cutaneous peripheral innervation. Morphometry of anterogradely labeled white matter revealed a statistically enhanced regeneration of ascending and descending projections in animals treated with the combination "therapy" compared to inosine alone. These data suggest that combining neurotrophic factors of differing modes of action likely enhance the outcome from "chronic" SCI.
Journal of Neurotrauma 06/2007; 24(5):846-63. · 3.65 Impact Factor
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ABSTRACT: An electrical field cathode (negative pole) has trophic and tropic effects on injured spinal cord axons in in vitro and in vivo models of sea lamprey, rodent, and canine spinal cord injury (SCI) and it improves functional outcome. A human oscillating field stimulator (OFS) was built, a Food and Drug Administration (FDA) exemption number was obtained, and institutional review board approval was given for a Phase 1 trial to study 10 humans with complete motor and sensory SCI.
Entry criteria were complete SCI between C-5 and T-10 in patients 18 to 65 years of age and no transection demonstrated on magnetic resonance imaging. All participants received the National Acute Spinal Cord Injury Study (NASCIS) III methylprednisilone protocol. Cord compression and/or vertebral instability was treated before study entry. After treatment complete SCI (according to the American Spinal Injury Association [ASIA] score) remained in all patients with no somatosensory evoked potentials (SSEPs) below the injury level after surgery or for 48 hours. All patients underwent implantation of the OFS within 18 days. Patients underwent evaluation every 2 weeks postimplantation; the OFS was explanted at 15 weeks. Independent neurological status was assessed based on the ASIA score, visual analog scale (VAS) pain score, and SSEPs at 6 weeks, 6 months, and 1 year. Statistical analyses were performed using the two-tailed Wilcoxon test and analysis of variance (ANOVA). There were no complications at insertion of the OFS; there was one case of wound infection after explantation (5% infection rate). One patient was lost to follow up after 6 months. In all 10 patients the mean VAS pain score was 8 at implantation, 2 at 6 months, and in the nine attending follow up for 1 year it remained 2. At 1 year, the mean improvement in light touch was 25.5 points (ANOVA p < 0.001, Wilcoxon test p = 0.02), the mean improvement in pinprick sensation was 20.4 points (ANOVA p < 0.001, Wilcoxon test p = 0.02), and the mean improvement in motor status was 6.3 points (ANOVA p < 0.01, Wilcoxon test p = 0.02). Of five cases involving cervical cord injuries, bilateral upper-extremity SSEPs were normal in one, unilateral upper-extremity SSEPs were recovered in four, bilateral upper-extremity SSEPs were recovered in one, and abnormal lower-extremity SSEPs resolved in one case. In one of the five cases involving thoracic injuries an abnormal lower-extremity SSEP resolved.
The use of OFS treatment in patients with SCI is safe, reliable, and easy. Compared with the outcomes obtained in compliant NASCIS III plegic patients, the results of the present study indicate efficacy, and the FDA has given permission for enrollment of 10 additional patients.
Journal of Neurosurgery Spine 02/2005; 2(1):3-10. · 1.53 Impact Factor
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ABSTRACT: The authors report the case of patient with a lumbar vertebral body osteoporotic compression fracture who underwent percutaneous transpedicular polymethylmethacrylate (PMMA)-assisted vertebroplasty in whom extravasation of the cement into the spinal canal caused immediate neurological deterioration. Lateral lumbar radiography and computerized tomography scanning demonstrated the presence of intraspinal PMMA. The patient suffered severe low-back pain, left-sided sciatica, and profound left L2-4 distribution weakness and numbness. She underwent immediate L-2 laminectomy, the extra- and intradural PMMA was removed, and instrumentation-assisted lateral mass fusion was performed. The patient recovered without incident and her neurological deficit improved. Extravasation of cement into the spinal canal, neural foramen, paraspinal veins, or disc space has been reported in 11 to 73% of percutaneous transpedicular PMMA-assisted vertebroplasty procedures. It is disturbing that more than one group of authors has documented symptomatic spinal canal PMMA extravasation and that the patients were left severely handicapped because of a stated fear that surgery to remove the cement would be difficult and make them worse. The results achieved in this case refute that published notion. It is important to document that decompressive surgery and PMMA removal from the spinal canal are easy and can lead to immediate neurological improvement. With the increasing popularity of percutaneous transpedicular PMMA-assisted vertebroplasty, the authors suspect that more of these cases will be seen.
Journal of Neurosurgery 02/2003; 98(1 Suppl):90-2. · 2.96 Impact Factor
