Oscillating field stimulation for complete spinal cord injury in humans: a Phase 1 trial

2005 ◽  
Vol 2 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Scott Shapiro ◽  
Richard Borgens ◽  
Robert Pascuzzi ◽  
Karen Roos ◽  
Michael Groff ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Upper Extremity ◽  
Phase 1 ◽  
Wilcoxon Test ◽  
Content Type ◽  
Cord Injury ◽  
Asia Score ◽  
The Mean ◽  
Fine Print

Object. 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. Methods. 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. Conclusions. 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.

The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats

1994 ◽  
Vol 80 (1) ◽  
pp. 97-111 ◽  
Author(s):  
Shlomo Constantini ◽  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Weight Loss ◽  
Ganglioside Gm1 ◽  
Rat Spinal Cord ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Fine Print

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

Therapeutic trial of hypercarbia and hypocarbia in acute experimental spinal cord injury

1984 ◽  
Vol 61 (5) ◽  
pp. 925-930 ◽  
Author(s):  
Ronald W. J. Ford ◽  
David N. Malm
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Mortality Rates ◽  
Therapeutic Trial ◽  
Tissue Preservation ◽  
Content Type ◽  
Experimental Spinal Cord Injury ◽  
Cord Injury ◽  
Fine Print

✓ Hypocarbia, normocarbia, or hypercarbia was maintained for an 8-hour period beginning 30 minutes after acute threshold spinal cord injuries in cats. No statistically significant differences in neurological recovery or histologically assessed tissue preservation were found among the three groups of animals 6 weeks after injury. No animal recovered the ability to walk. It is concluded that maintenance of hypercarbia or hypocarbia during the early postinjury period is no more therapeutic than maintenance of normocarbia. Mortality rates and tissue preservation data suggest, however, that postinjury hypocarbia may be less damaging than hypercarbia.

Ultrastructural scoring of graded acute spinal cord injury in the rat

2002 ◽  
Vol 97 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Selcuk Palaoglu ◽  
H. Selcuk Surucu ◽  
Mutlu Hayran ◽  
Etem Beskonakli
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Behavioral Assessment ◽  
Traumatic Injury ◽  
Significant Negative Correlation ◽  
Content Type ◽  
Cord Injury ◽  
Contusion Injury ◽  
Weight Drop ◽  
Fine Print

Object. There is a need for an accurate quantitative histological technique that also provides information on neurons, axons, vascular endothelium, and subcellular organelles after spinal cord injury (SCI). In this paper the authors describe an objective, quantifiable technique for determining the severity of SCI. The usefulness of ultrastructural scoring of acute SCI was assessed in a rat model of contusion injury. Methods. Spinal cords underwent acute contusion injury by using varying weights to produce graded SCI. Adult Wistar rats were divided into five groups. In the first group control animals underwent laminectomy only, after which nontraumatized spinal cord samples were obtained 8 hours postsurgery. The weight-drop technique was used to produce 10-, 25-, 50-, and 100-g/cm injuries. Spinal cord samples were also obtained in the different trauma groups 8 hours after injury. Behavioral assessment and ultrastructural evaluation were performed in all groups. When the intensity of the traumatic injury was increased, behavioral responses showed a decreasing trend. A similar significant negative correlation was observed between trauma-related intensity and ultrastructural scores. Conclusions. In the present study the authors characterize quantitative ultrastructural scoring of SCI in the acute, early postinjury period. Analysis of these results suggests that this method is useful in evaluating the degree of trauma and the effectiveness of pharmacotherapy in neuroprotection studies.

The therapeutic window for spinal cord decompression in a rat spinal cord injury model

2005 ◽  
Vol 3 (4) ◽  
pp. 302-307 ◽  
Author(s):  
Christopher B. Shields ◽  
Y. Ping Zhang ◽  
Lisa B. E. Shields ◽  
Yingchun Han ◽  
Darlene A. Burke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Stenosis ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Therapeutic Window ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Fine Print

Object. There are no clinically based guidelines to direct the spine surgeon as to the proper timing to undertake decompression after spinal cord injury (SCI) in patients with concomitant stenosis-induced cord compression. The following three factors affect the prognosis: 1) severity of SCI; 2) degree of extrinsic spinal cord compression; and 3) duration of spinal cord compression. Methods. To elucidate further the relationship between varying degrees of spinal stenosis and a mild contusion-induced SCI (6.25 g-cm), a rat SCI/stenosis model was developed in which 1.13- and 1.24-mm-thick spacers were placed at T-10 to create 38 and 43% spinal stenosis, respectively. Spinal cord damage was observed after the stenosis—SCI that was directly proportional to the duration of spinal cord compression. The therapeutic window prior to decompression was 6 and 12 hours in the 43 and 38% stenosis—SCI lesions, respectively, to maintain locomotor activity. A significant difference in total lesion volume was observed between the 2-hour and the delayed time(s) to decompression (38% stenosis—SCI, 12 and 24 hours, p < 0.05; 43% stenosis—SCI, 24 hours, p < 0.05) indicating a more favorable neurological outcome when earlier decompression is undertaken. This finding was further supported by the animal's ability to support weight when decompression was performed by 6 or 12 hours compared with 24 hours after SCI. Conclusions. Analysis of the findings in this study suggests that early decompression in the rat improves locomotor function. Prolongation of the time to decompression may result in irreversible damage that prevents locomotor recovery.

Cruciate paralysis

1986 ◽  
Vol 65 (1) ◽  
pp. 108-110 ◽  
Author(s):  
Daniel Dumitru ◽  
James E. Lang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rare Case ◽  
Motor Vehicle ◽  
Motor Vehicle Accident ◽  
Cervical Spinal Cord ◽  
Content Type ◽  
Vehicle Accident ◽  
Cord Injury ◽  
Fine Print

✓ A rare case of cruciate paralysis is reported in a 39-year-old man following a motor-vehicle accident. The differentiation of this syndrome from a central cervical spinal cord injury is delineated.

Bladder function after incomplete spinal cord injury in mice: quantifiable outcomes associated with bladder function and efficiency of dehydroepiandrosterone as a therapeutic adjunct

2004 ◽  
Vol 100 (1) ◽  
pp. 56-61
Author(s):  
Pierre-Yves Mure ◽  
Mark Galdo ◽  
Nathalie Compagnone
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mouse Model ◽  
Collagen Type ◽  
Neurological Recovery ◽  
Bladder Function ◽  
Type I ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

Object. The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. Methods. A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. Conclusions. The authors found that early recovery of controlled voiding is predictive of motor recovery.

Immediate effects of spinal cord stimulation in spinal spasticity

1985 ◽  
Vol 62 (4) ◽  
pp. 558-562 ◽  
Author(s):  
Giancarlo Barolat-Romana ◽  
Joel B. Myklebust ◽  
David C. Hemmy ◽  
Barbara Myklebust ◽  
William Wenninger
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Stimulation ◽  
Content Type ◽  
Clinical Observations ◽  
Cord Injury ◽  
Epidural Spinal Cord Stimulation ◽  
Stimulation System ◽  
Fine Print

✓ Six patients with intractable spasms after spinal cord injury underwent implantation of an epidural spinal cord stimulation system. All the patients experienced good relief postoperatively. In three patients spinal cord stimulation consistently produced immediate inhibition of the spasms. This was evident within less than 1 minute of stimulation. Conversely, the spasms reappeared within less than 1 minute after cessation of the stimulation. The clinical observations were confirmed by polygraphic electromyographic recordings.

Intrathecal phenol and glycerin in metrizamide for treatment of intractable spasms in paraplegia

1985 ◽  
Vol 63 (1) ◽  
pp. 125-127 ◽  
Author(s):  
Brett A. Scott ◽  
Zelig Weinstein ◽  
Robert Chiteman ◽  
Morris W. Pulliam
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Intrathecal Injection ◽  
Fluoroscopic Guidance ◽  
Content Type ◽  
Therapeutic Modalities ◽  
Comparative Review ◽  
Cord Injury ◽  
Fine Print

✓ Intractable lower extremity spasms after spinal cord injury is a significant source of morbidity. A case of refractory spasticity in paraplegia was successfully converted to flaccid paraplegia by intrathecal injection of phenol and glycerin in metrizamide. This chemical rhizolysis is simple and effective, and the presence of metrizamide allows both fluoroscopic guidance for accurate intrathecal phenol placement and good miscibility with cerebrospinal fluid. A brief comparative review of alternative therapeutic modalities is presented.

Effect of anti—rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes

2001 ◽  
Vol 95 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Metin Tuna ◽  
Sait Polat ◽  
Tahsin Erman ◽  
Faruk Ildan ◽  
A. Iskender Göçer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Tissue ◽  
Inos Activity ◽  
Content Type ◽  
Cord Injury ◽  
Oxide Synthase ◽  
Fine Print ◽  
Inducible Nitric Oxide

Object. The inflammatory cells that accumulate at the damaged site after spinal cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce the expression of inducible nitric oxide synthase (iNOS). Any increased production of NO by iNOS activity would aggravate the primary neurological damage in SCI. If this mechanism does occur, the direct or indirect effects of IL-6 antagonists on iNOS activity should modulate this secondary injury. In this study, the authors produced spinal cord damage in rats and applied anti—rat IL-6 antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the spinal cord tissue activities of Na+-K+/Mg++ adenosine-5′-triphosphatase (ATPase) and superoxide dismutase, evaluated iNOS immunoreactivity, and examined ultrastructural findings to assess the results of this treatment. Methods. Seventy rats were randomly allocated to four groups. Group I (10 rats) were killed to provide normal spinal cord tissue for testing. In Group II 20 rats underwent six-level laminectomy for the effects of total laminectomy alone to be determined. In Group III 20 rats underwent six-level T2–7 laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in the 20 Group IV rats, but these rats also received one (2 µg) intraperitoneal injection of anti—rat IL-6 antibody immediately after the injury and a second dose 24 hours posttrauma. Half of the rats from each of Groups II through IV were killed at 2 hours and the other half at 48 hours posttrauma. The exposed cord segments were immediately removed and processed for analysis. Conclusions. The results showed that neutralizing IL-6 bioactivity with anti—rat IL-6 antibody significantly attenuates iNOS activity and reduces secondary structural changes in damaged rat spinal cord tissue.

Peripheral nerve grafts promoting central nervous system regeneration after spinal cord injury in the primate

2002 ◽  
Vol 96 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Allan D. O. Levi ◽  
Hector Dancausse ◽  
Xiuming Li ◽  
Suzanne Duncan ◽  
Laura Horkey ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Peripheral Nerve ◽  
Content Type ◽  
Nerve Grafts ◽  
Cord Injury ◽  
Peripheral Nerve Grafts ◽  
Fine Print

Object. Partial restoration of hindlimb function in adult rats following spinal cord injury (SCI) has been demonstrated using a variety of transplantation techniques. The purpose of the present study was twofold: 1) to determine whether strategies designed to promote regeneration in the rat can yield similar results in the primate; and 2) to establish whether central nervous system (CNS) regeneration will influence voluntary grasping and locomotor function in the nonhuman primate. Methods. Ten cynomologus monkeys underwent T-11 laminectomy and resection of a 1-cm length of hemispinal cord. Five monkeys received six intercostal nerve autografts and fibrin glue containing acidic fibroblast growth factor (2.1 µg/ml) whereas controls underwent the identical laminectomy procedure but did not receive the nerve grafts. At 4 months postgrafting, the spinal cord—graft site was sectioned and immunostained for peripheral myelin proteins, biotinylated dextran amine, and tyrosine hydroxylase, whereas the midpoint of the graft was analyzed histologically for the total number of myelinated axons within and around the grafts. The animals underwent pre- and postoperative testing for changes in voluntary hindlimb grasping and gait. Conclusions. 1) A reproducible model of SCI in the primate was developed. 2) Spontaneous recovery of the ipsilateral hindlimb function occurred in both graft- and nongraft—treated monkeys over time without evidence of recovering the ability for voluntary tasks. 3) Regeneration of the CNS from proximal spinal axons into the peripheral nerve grafts was observed; however, the grafts did not promote regeneration beyond the lesion site. 4) The grafts significantly enhanced (p < 0.0001) the regeneration of myelinated axons into the region of the hemisected spinal cord compared with the nongrafted animals.

Sign in / Sign up

Export Citation Format

Share Document