Neurological and functional status 1 year after acute spinal cord injury: estimates of functional recovery in National Acute Spinal Cord Injury Study II from results modeled in National Acute Spinal Cord Injury Study III

2002 ◽  
Vol 96 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Michael B. Bracken ◽  
Theodore R. Holford
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Acute Spinal Cord Injury ◽  
Neurological Injury ◽  
High Dose ◽  
Content Type ◽  
Function Recovery ◽  
Cord Injury ◽  
Fine Print

Object. In the second National Acute Spinal Cord Injury Study (NASCIS II) investigators evaluated several standard neurological parameters but not functional activity. This has led to questions concerning the clinical importance of the increase in neurological recovery observed following administration of methylprednisolone (MP) within 8 hours of acute spinal cord injury (SCI). The safety of the therapy has also been questioned. Methods. Both neurological and functional recovery were assessed in NASCIS III, a trial that followed an almost identical protocol to NASCIS II. In the current analysis locally weighted scatterplot smoothing (LOESS) nonparametric regression is used to model the extent of recovery in the Functional Independence Measure (FIM) that is predicted by improvement in the NASCIS/American Spinal Cord Injury Association motor scores that were documented in NASCIS III 1 year after SCI, and the models are applied to the extent of motor recovery demonstrated in NASCIS II. The models predict improvement in FIM that would be expected from the motor function recovery observed in NASCIS II. Estimates are provided overall and for patients with complete and incomplete neurological loss at time of injury. The authors review recent evidence obtained from randomized studies documenting adverse effects that may result from high-dose MP therapy. The relationship between motor function and FIM is strongly nonlinear and dependent on initial level of injury and degree of injury severity. In the best statistical model, the expanded motor score could be used to explain 77.2% of the variability in the FIM. Based on the mean MP-related 3.6-unit improvement in the motor score for patients with complete injuries and 7.3 for those with incomplete injuries owed to MP in NASCIS II, 18.6% of patients would improve six or more FIM points and 9% nine or more points, respectively. In those with complete neurological injury, the mean motor improvement of 3.6 predicted that 63.9% of the patients would improve three or more FIM points and 12.1% six or more points to a maximum of eight points. Of those with incomplete neurological injury, a 7.3 mean improvement in motor function predicted that 27.4% would gain six or more FIM points and that 21% would gain nine or more points to a maximum of 15 points. Analysis of the current best evidence from SCI and other randomized surgical trials in which high-dose MP has been administered provides no grounds for concern about commonly studied adverse effects. Conclusions. The extent of MP therapy—related motor function recovery observed in NASCIS II predicted clinically important recovery in the FIM. Reasons to be cautious with regard to this prediction include the lack of robustness in statistical modeling, some loss of validity in the FIM, and considerable heterogeneity in the SCI population. Whatever functional activity is ascribed to high-dose MP therapy, it is does not appear to be associated with risk of adverse outcomes.

Spinal blood flow in 24-hour megadose glucocorticoid treatment in awake pigs

2003 ◽  
Vol 99 (3) ◽  
pp. 286-290
Author(s):  
Wolf R. Drescher ◽  
Karen P. Weigert ◽  
Mathias H. Bünger ◽  
Ebbe S. Hansen ◽  
Cody E. Bünger
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Body Weight ◽  
High Dose ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Methylprednisolone Treatment ◽  
Fine Print

Object. Because of the controversy regarding the benefits of 24-hour administration of methylprednisolone in patients with spinal cord injury (SCI), it is important to investigate its mechanism of action and side effects. This study was conducted to determine if high-dose methylprednisolone modulates neural and vertebral blood flow in an awake large-sized animal model without SCI. Methods. From a group of 18 immature female domestic pigs born to nine different litters, nine animals were randomly allocated to receive methylprednisolone treatment, whereas their nine female siblings served as controls. Drug or placebo was applied in a blinded fashion by a third person not involved in the study. The following treatment for SCI, as suggested by the North American Spinal Cord Injury Study, was administered to the awake pig: methylprednisolone (30 mg/kg of body weight) was infused into the jugular vein during a 15-minute period, followed by a 45-minute pause, and the infusion was maintained over a 23-hour period at a dose of 5.4 mg/kg body weight/hour. By means of the radioactive tracer microsphere technique, spinal cord blood flow (SCBF) was measured in the awake standing pig in the cerebrum, and in spinal gray and white matter, nerve roots, endplates, cancellous bone, cortical shell, and T12—L2 discs. Blood flow was measured before, 1 hour after initiation of infusion, and 24 hours postinfusion. Examination of blood flow in the neural and vertebral tissue samples, as well as of central hemodynamics, revealed no significant difference between the experimental and control groups, and this parity was maintained throughout the experimental phases. Conclusions. In the awake pig model, 24-hour methylprednisolone treatment does not modulate cerebral or SCBF, nor does it increase the risk for vertebral osteonecrosis by producing vertebral ischemia.

Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data

1992 ◽  
Vol 76 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Michael B. Bracken ◽  
Mary Jo Shepard ◽  
William F. Collins ◽  
Theodore R. Holford ◽  
David S. Baskin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Controlled Trial ◽  
Acute Spinal Cord Injury ◽  
Sensory Function ◽  
Content Type ◽  
Cord Injury ◽  
Multicenter Randomized Controlled Trial

✓ The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.

Early Administration of l-Arginine in Experimental Acute Spinal Cord Injury Impairs Long-Term Motor Function Recovery

2011 ◽  
Vol 70 (5) ◽  
pp. 1198-1202 ◽  
Author(s):  
Abdieel Esquivel-Aguilar ◽  
Gilberto Castañeda-Hernández ◽  
Angelina Martínez-Cruz ◽  
Rebecca E. Franco-Bourland ◽  
Ignacio Madrazo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Acute Spinal Cord Injury ◽  
Early Administration ◽  
Function Recovery ◽  
Cord Injury

Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up

1998 ◽  
Vol 89 (5) ◽  
pp. 699-706 ◽  
Author(s):  
Michael B. Bracken ◽  
Mary Jo Shepard ◽  
Theodore R. Holford ◽  
Linda Leo-Summers ◽  
E. Francois Aldrich ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Acute Spinal Cord Injury ◽  
Double Blind ◽  
Content Type ◽  
Mortality And Morbidity ◽  
Cord Injury ◽  
Tirilazad Mesylate ◽  
Fine Print

Object. A randomized double-blind clinical trial was conducted to compare neurological and functional recovery and morbidity and mortality rates 1 year after acute spinal cord injury in patients who had received a standard 24-hour methylprednisolone regimen (24MP) with those in whom an identical MP regimen had been delivered for 48 hours (48MP) or those who had received a 48-hour tirilazad mesylate (48TM) regimen. Methods. Patients for whom treatment was initiated within 3 hours of injury showed equal neurological and functional recovery in all three treatment groups. Patients for whom treatment was delayed more than 3 hours experienced diminished motor function recovery in the 24MP group, but those in the 48MP group showed greater 1-year motor recovery (recovery scores of 13.7 and 19, respectively, p = 0.053). A greater percentage of patients improving three or more neurological grades was also observed in the 48MP group (p = 0.073). In general, patients treated with 48TM recovered equally when compared with those who received 24MP treatments. A corresponding recovery in self care and sphincter control was seen but was not statistically significant. Mortality and morbidity rates at 1 year were similar in all groups. Conclusions. For patients in whom MP therapy is initiated within 3 hours of injury, 24-hour maintenance is appropriate. Patients starting therapy 3 to 8 hours after injury should be maintained on the regimen for 48 hours unless there are complicating medical factors.

Evaluation of time-dependent spread of tissue damage in experimental spinal cord injury by killed-end evoked potential: effect of high-dose methylprednisolone

2003 ◽  
Vol 98 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chikashi Fukaya ◽  
Yoichi Katayama ◽  
Masahiko Kasai ◽  
Jun Kurihara ◽  
Sadahiro Maejima ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Conduction Block ◽  
Time Dependent ◽  
High Dose ◽  
Injury Site ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

Object. Histopathological studies on spinal cord injury (SCI) have demonstrated time-dependent spread of tissue damage during the initial several hours postinjury. When the long tract within the spinal cord is stimulated, a large monophasic positivity occurs at the injury site. This type of potential, termed the killed-end evoked potential (KEEP), indicates that a nerve impulse approaches but does not pass beyond the injury site. The authors tested the hypothesis that the damage spread can be evaluated as a progressive shift of the KEEP on a real-time basis. The effect of high-dose methylprednisolone sodium succinate (MPSS) on the spread of tissue damage was also examined by this methodology. Methods. The KEEP was recorded using an electrode array placed on the spinal cord at the T-10 level in cats. This electrode array consisted of multiple 0.2-mm-diameter electrodes, each separated by 0.5 mm. Spinal cord injury was induced using a vascular clip (65 g pinching pressure for 30 seconds). The midline posterior surface of the spinal cord was stimulated bipolarly at the C-7 level by applying a single pulse at supramaximal intensity. During the initial period of 6 hours postinjury, the localization of the largest KEEP shifted progressively up to 2.5 mm rostral from the injury site. The amplitude of the KEEP recorded at the injury site decreased to 55 to 70% and became slightly shortened in latency as the localization of the largest KEEP shifted rostrally. These findings imply that the injury site KEEP represents the volume-conducted potential of the largest KEEP at the site of the conduction block. It moved away from the injury site in association with the damage spread, and this was confirmed histopathologically. A decrease in amplitude of KEEP at the injury site appeared to be the most sensitive measure of the damage spread, because the amplitude of the volume-conducted KEEP is inversely proportional to the square of the distance between the recording site and site of conduction block. Administered immediately after SCI, MPSS clearly inhibited these events, especially within 30 minutes postinjury. Conclusions. The KEEP enables sequential evaluation to be made of the time-dependent spread of tissue damage in SCI in the same animal. It is, therefore, useful for detecting the effect of therapeutic interventions and for determining the therapeutic time window. The efficiency of MPSS to inhibit the spread of damaged tissue appeared to be maximized when it was administered within the initial 30-minute period postinjury.

Methylprednisolone for acute spinal cord injury: an inappropriate standard of care

2000 ◽  
Vol 93 (1) ◽  
pp. 1-7 ◽  
Author(s):  
R. John Hurlbert
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Injured Patient ◽  
Standard Of Care ◽  
Acute Spinal Cord Injury ◽  
Content Type ◽  
Recommended Treatment ◽  
Cord Injury ◽  
Post Hoc ◽  
Fine Print

Object. Since publication in 1990, results from the National Acute Spinal Cord Injury Study II (NASCIS II) trial have changed the way patients suffering an acute spinal cord injury (SCI) are treated. More recently, recommendations from NASCIS III are being adopted by institutions around the world. The purpose of this paper is to reevaluate carefully the results and conclusions of these studies to determine the role they should play in influencing decisions about care of the acutely spinal cord—injured patient. Methods. Published results from NASCIS II and III were reviewed in the context of the original study design, including primary outcomes compared with post-hoc comparisons. Data were retroconverted from tabular form back to raw form to allow direct inspection of changes in treatment groups. These findings were further analyzed with respect to justification of practice standards. Although well-designed and well-executed, both NASCIS II and III failed to demonstrate improvement in primary outcome measures as a result of the administration of methylprednisolone. Post-hoc comparisons, although interesting, did not provide compelling data to establish a new standard of care in the treatment of patients with acute SCI. Conclusions. The use of methylprednisolone administration in the treatment of acute SCI is not proven as a standard of care, nor can it be considered a recommended treatment. Evidence of the drug's efficacy and impact is weak and may only represent random events. In the strictest sense, 24-hour administration of methylprednisolone must still be considered experimental for use in clinical SCI. Forty-eight-hour therapy is not recommended. These conclusions are important to consider in the design of future trials and in the medicolegal arena.

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.

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