Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: Phase I study results

2005 ◽  
Vol 3 (3) ◽  
pp. 173-181 ◽  
Author(s):  
Nachshon Knoller ◽  
Gustavo Auerbach ◽  
Valentin Fulga ◽  
Gabriel Zelig ◽  
Josef Attias ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adverse Events ◽  
Phase I ◽  
Sensory Function ◽  
Content Type ◽  
Study Results ◽  
Cord Injury ◽  
Complete Spinal Cord Injury ◽  
Fine Print

Object. A Phase I, open-label nonrandomized study was conducted to assess the safety and tolerability of incubated autologous macrophages administered to patients with acute complete spinal cord injury (SCI). Methods. This therapy was first tested in rat models of spinal cord transection and contusion, in which it was shown to promote motor recovery. The procedure developed for clinical use consists of isolating monocytes from patient blood and incubating them ex vivo with autologous dermis. The resulting incubated autologous macrophages were injected into the patient's spinal cord immediately caudal to the lesion within 14 days of injury. Patients underwent preoperative and follow-up neurological assessment (American Spinal Injury Association [ASIA] standards), electrophysiological monitoring (motor evoked and/or somatosensory evoked potentials), magnetic resonance imaging, and safety monitoring. Before macrophage administration, complete neurological functional loss (ASIA Grade A) was confirmed in all patients. Of the eight patients in the study, three recovered clinically significant neurological motor and sensory function (ASIA Grade C status). During the study period, some adverse events were encountered, the most serious of which involved two cases of pulmonary embolism and one case of osteomyelitis that were treated and resolved without further complication. These and other adverse events appear to be similar to those encountered in other spinal cord—injured patients and are not considered a consequence of the experimental therapy. Conclusions. It is concluded that incubated autologous macrophage cell therapy is well tolerated in patients with acute SCI. Further clinical evaluation is warranted.

A Phase I trial of naloxone treatment in acute spinal cord injury

1985 ◽  
Vol 63 (3) ◽  
pp. 390-397 ◽  
Author(s):  
Eugene S. Flamm ◽  
Wise Young ◽  
William F. Collins ◽  
Joseph Piepmeier ◽  
Guy L. Clifton ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Phase I ◽  
Phase I Trial ◽  
Loading Dose ◽  
Content Type ◽  
Cord Injury ◽  
Group 2 ◽  
Time Of Admission ◽  
Fine Print

✓ Results of a Phase I trial of the opiate antagonist naloxone for treatment of patients with acute spinal cord injury are reported. Naloxone was administered in doses ranging from 5 to 200 mg/sq m (0.14 to 5.4 mg/kg) for up to 48 hours. The patients ranged in age from 16 to 79 years (mean 37 years). Twenty patients received naloxone as a loading dose of 5 to 50 mg/sq m (0.14 to 1.43 mg/kg), followed by a maintenance dose of 20% of the loading dose given as a continuous infusion hourly for 47 hours (Group 1). Nine patients received a loading dose of 100 to 200 mg/sq m (2.7 to 5.4 mg/kg) and a maintenance dose of 75% of the initial dose hourly for 23 hours (Group 2). These higher doses (2.7 to 5.4 mg/kg) have been found to be effective in experimental spinal cord injury. Neurological examinations were performed and somatosensory evoked potentials (SEP's) were obtained as soon after admission as possible and again 1, 2, 3, and 7 days, 3 weeks, and 6 weeks to 6 months after admission. The 20 Group 1 patients who received 1.43 mg/kg or less of naloxone showed no improvement in neurological status or SEP's. All but three (15%) of these patients had a complete neurological deficit at the time of admission. Treatment was begun an average of 12.9 hours after injury. Among the nine Group 2 patients treated with 2.7 mg/kg or more, there were five patients (56%) with incomplete deficits. This group received naloxone an average of 6.6 hours after admission. Two of the five Group 2 patients with incomplete lesions showed improvement in their neurological condition and/or SEP's within 36 hours of receiving the drug. One of the four Group 2 patients with a complete lesion at the time of admission was able to localize pressure sensation in his legs 36 hours after completion of the drug infusion. Four Group 2 patients (two with complete and two with incomplete lesions) have shown improvement in their SEP's, suggesting recovery of SEP's in a dose-related fashion. Four patients experienced increased pain after administration of the loading dose and during the maintenance infusion; in only one patient was this severe enough to require discontinuation of the drug. Of the 29 patients treated with naloxone, four died within 6 weeks of admission, for a mortality rate of 13.8%. This study demonstrates that, in spinal cord-injured patients, naloxone given as an intravenous loading dose of 200 mg/sq m, followed by a continuous infusion of up to 150 mg/sq m/hr for 23 hours, has minimal side effects. The observed improvement in the clinical examination and SEP's at the higher doses, while not statistically verified in this Phase I trial, is encouraging.

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.

EFFECT OF LOWER EXTREMITY EXOSKELETON ROBOT IMPROVING WALKING FUNCTION AND ACTIVITY IN PATIENTS WITH COMPLETE SPINAL CORD INJURY

2019 ◽  
Vol 19 (08) ◽  
pp. 1940060
Author(s):  
XINGANG BAI ◽  
XIANG GOU ◽  
WENCHUN WANG ◽  
CHAO DONG ◽  
FANGXU QUE ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adverse Events ◽  
Lower Extremity ◽  
Controlled Trial ◽  
Walking Ability ◽  
Walk Test ◽  
Exoskeleton Robot ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

The objective of this research was to evaluate the effectiveness and safety of Lower Extremity Exoskeleton Robot improving walking function and activity in patients with complete spinal cord injury. A prospective, open and self-controlled trial was conducted which include eight patients with complete spinal cord injury accepted Lower Extremity Exoskeleton Robot training with Aider 1.0 and Aider 1.1 for 2 weeks. The 6[Formula: see text]min Walk Test (6MWT), 10[Formula: see text]m Walk Test (10 MWT), Hoffer walking ability rating, Lower Extremity Motor Score (LEMS), Spinal Cord Independence Motor (SCIM), Walking Index for Spinal Cord Injury Version II (WISCI II) were recorded before, 1 week and 2 weeks after training. During the training, the incidence of adverse events (AE), the incidence of serious adverse events (SAE), the incidence of device defects and other safety indicators were observed. Compared with the pre-training, indicators (6MWT, 10MWT, Hoffer walking ability rating, WISCI II) were significantly different after 1 week of training and after 2 weeks of training. Four adverse events occurred during the training period and the incidence of adverse events was 50%. And there was no SAE or device defects. Therefore, it is safe and effective to use the lower extremity exoskeleton robot to complete the walking ability of patients with complete spinal cord injury.

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.

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