Acute Spinal Cord Injury Study Research Articles

Methylprednisolone in acute spinal cord injuries.

Methylprednisolone is the only neuroprotective therapy advocated in acute non-penetrating spinal cord injury. Trials indicate improved neurological outcome following early administration of a high dose regime. The National Spinal Injuries Unit (NSIU) has promoted this regime by a simple laminated poster sent to all Irish A&E departments. To assess the use of methylprednisolone in patients with spinal cord injuries. A retrospective audit of patient data for all patients admitted with traumatic neurological impairment over a 12-month period. One hundred ninety-six patients were admitted during the study period, 28 (14%) received intravenous methylprednisolone of which six had clear records documenting compliance. One patient received both dexamethasone and methylprednisolone in high doses and three had incorrect bolus dosages administered. Six patients received methylprednisolone infusion longer than the protocol, while five patients were given infusions shorter than recommended. Three patients were admitted to the unit that could have received the steroid regime at the point of transfer. There was poor documentation of prescription orders and timing of administration. Only six patients had clear documentation allowing confirmation of adherence to the protocol of the National Acute Spinal Cord Injury Study (NASCIS) III trial.

Failure to administer methylprednisolone for acute traumatic spinal cord injury—a prospective audit of 100 patients from a regional spinal injuries unit

Overview: The National Acute Spinal Cord Injury Studies (NASCIS II and III) and the Cochrane review advocate the administration of high dose methylprednisolone following acute traumatic spinal cord injury. Objective: To determine the actual use and correct implementation of the NASCIS protocols in patients referred to a regional spinal injuries unit. Design: Observational study on the timing and correct dosage of methylprednisolone. The admission Frankel grade, American Spinal Injury Association (ASIA) neurological classification were recorded prospectively. Subjects: The 100 consecutive patients with complete or incomplete spinal cord injuries (Frankel grade A–D) were studied over a 2 years period. Main outcome measure: Correct administration of methylprednisolone according to the NASCIS protocols. Results: During the study period only 25% of the patients admitted to our spinal injuries unit received methylprednisolone at the referring hospital according to the NASCIS protocols. An additional 10 patients were given methylprednisolone incorrectly. Conclusion: Evidence based medicine is not being practiced in the management of patients with acute spinal cord injury.

Steroids for acute spinal cord injury.

Acute spinal cord injury is a devastating condition typically affecting young people with a preponderance being male. Steroid treatment in the early hours of the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. To review randomized trials of steroids for acute spinal cord injury. The review draws on the search strategy developed by the Cochrane Injuries Group. In addition, files of the National Acute Spinal Cord Injury Study have been reviewed and a Medline search conducted. All published or unpublished randomized controlled trials of steroid treatment for acute spinal cord injury in any language. Data have been abstracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. There are few trials in this area of medical care. Only one steroid has been extensively studied, methylprednisolone sodium succinate, which has been shown to improve neurologic outcome up to one year post injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg administered over 15 minutes with a maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial was replicated in a Japanese trial but not in the one from France. Data has been obtained from the latter studies to permit appropriate meta-analysis of all three trials. This analysis indicates significant recovery in motor function after methylprednisolone therapy when administration commences within eight hours of injury. A more recent trial indicates that if methylprednisolone therapy is given for an additional 24 hours (for a total of 48 hours), additional improvement in motor neurologic function and functional status is observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries and a modified regimen found to improve recovery after surgery for lumbar disc disease. High dose methylprednisolone steroid therapy is the only pharmacological therapy shown to have efficacy in a Phase Three randomized trial when it can be administered within eight hours of injury. A recent trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacological therapy for acute spinal cord injury.

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.

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. 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. 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.

Is the role of steroids in acute spinal cord injury now resolved?

Steroids have long been used in the context of acute spinal cord injury but the evidence for doing so is limited. The second National Acute Spinal Cord Injury Study trial had the potential to provide such evidence for the first time, as this was a placebo controlled, prospective, randomized trial. From the outset, however, some clinicians found the methodology and consequently the results unsatisfactory. This concern has been revisited within the evidence-based framework of critical appraisal of the accumulation of clinical studies. High-dose methylprednisolone cannot be justified as a standard treatment in acute spinal cord injury within current medical practice.

Predictive value of the initial quantified relative afferent pupillary defect in 19 consecutive patients with traumatic optic neuropathy.

To study the predictive value of the initial quantified relative afferent pupillary defect (RAPD) in patients with indirect traumatic neuropathy as it relates to final visual outcome. The RAPD was measured and quantified by neutral density filters in patients with unilateral indirect traumatic neuropathy. All patients were treated with megadose methylprednisolone by of the protocol established by the Second National Acute Spinal Cord Injury Study. Patients were followed twice daily during treatment and then at 3-month intervals. Nineteen patients were enrolled over a 23-month period. Patients ranged in age from 12 to 78 years old; 18 of the 19 patients were male. No patient with an RAPD of 2.1 log units or greater had visual recovery to better than hand motion vision. The 7 patients with an initial RAPD of less than 2.1 log units showed improvement in their RAPD and were found to have vision of 20/30 or better during the follow-up period. In patients treated with megadose methylprednisolone with an initial RAPD of less than 2.1 log units, visual acuity improved to 20/30 or better; however, patients with an initial RAPD of 2.1 or greater showed little visual improvement. The initial quantified RAPD appears to have a predictive value related to final visual outcome.

Acute spinal cord injury, part II: contemporary pharmacotherapy.

Spinal cord injury (SCI) remains a common and devastating problem of modern society. Through an understanding of underlying pathophysiologic mechanisms involved in the evolution of SCI, treatments aimed at ameliorating neural damage may be developed. The possible pharmacologic treatments for acute spinal cord injury are herein reviewed. Myriad treatment modalities, including corticosteroids, 21-aminosteroids, opioid receptor antagonists, gangliosides, thyrotropin-releasing hormone (TRH) and TRH analogs, antioxidants and free radical scavengers, calcium channel blockers, magnesium replacement therapy, sodium channel blockers, N -methyl-D-aspartate receptor antagonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-kainate receptor antagonists, modulators of arachadonic acid metabolism, neurotrophic growth factors, serotonin antagonists, antibodies against inhibitors of axonal regeneration, potassium channel blockers (4-aminopyridine), paclitaxel, clenbuterol, progesterone, gabexate mesylate, activated protein C, caspase inhibitors, tacrolimus, antibodies against adhesion molecules, and other immunomodulatory therapy have been studied to date. Although most of these agents have shown promise, only one agent, methylprednisolone, has been shown to provide benefit in large clinical trials. Given these data, many individuals consider methylprednisolone to be the standard of care for the treatment of acute SCI. However, this has not been established definitively, and questions pertaining to methodology have emerged regarding the National Acute Spinal Cord Injury Study trials that provided these conclusions. Additionally, the clinical significance (in contrast to statistical significance) of recovery after methylprednisolone treatment is unclear and must be considered in light of the potential adverse effects of such treatment. This first decade of the new millennium, now touted as the Decade of the Spine, will hopefully witness the emergence of universal and efficacious pharmacologic therapy and ultimately a cure for SCI.

High-dose methylprednisolone may do more harm for spinal cord injury

Because of the National Acute Spinal Cord Injury Studies (NASCIS), high-dose methylprednisolone became the standard of care for the acute spinal cord injury. In the NASCIS, there was no mention regarding the possibility of acute corticosteroid myopathy that high-dose methylprednisolone may cause. The dosage of methylprednisolone recommended by the NASCIS 3 is the highest dose of steroids ever being used during a 2-day period for any clinical condition. We hypothesize that it may cause some damage to the muscle of spinal cord injury patients. Further, steroid myopathy recovers naturally and the neurological improvement shown in the NASCIS may be just a recording of this natural motor recovery from the steroid myopathy, instead of any protection that methylprednisolone offers to the spinal cord injury. To our knowledge, this is the first discussion considering the possibility that the methylprednisolone recommended by NASCIS may cause acute corticosteroid myopathy.

Surgical treatment of spinal hemangioblastomas.

The routine use of magnetic resonance imaging (MRI) in recent years for the diagnostic assessment of the spinal column and especially for screening patients with von Hippel-Lindau (vHL) disease has shown that spinal hemangioblastomas (sHBs) are more common than assumed so far. Since most sHBs are thus discovered while they are still asymptomatic, especially in vHL disease, the question arises whether and when these tumors should be treated. The present article reports the results of the surgical treatment of sHBs using the protocol described below and compares them to the course in a control group of patients with conservatively treated sHBs. A total of 30 sHBs were treated microsurgically in 15 patients. Hemangioblastoma-associated cysts were merely opened in 14 cases, drained with the help of Teflon cotton in 2 of these cases, and not opened in 4 instances. Laminoplasties were performed with insertion of absorbable, MRI-compatible microosteosynthesis plates. Perioperatively, all patients were administered methylprednisolone according to the NASCIS (National Acute Spinal Cord Injury Study) scheme, and sensory evoked potentials were monitored intra-operatively in all cases. Nine patients in whom the course of primarily conservative treatment of a total of 17 asymptomatic sHBs was documented served as controls. The follow-up time was 7 to 51 months (mean 20) after surgery and 10 to 51 months (mean 21) in the control group. Preoperative HB-associated pareses showed transient postoperative deterioration (n = 5). The other accompanying neurological deficits improved in 6 HBs and remained unchanged in all other HBs (n = 19), of which 16 had been asymptomatic before surgery. In the control group, 6 HBs (in 6 different patients) became permanently symptomatic despite subsequent surgical treatment according to the study protocol. With the new diagnostic tools now available, microsurgical removal of spinal hemangioblastomas has a low morbidity rate, suggesting that surgical treatment should be considered even for asymptomatic sHBs in certain circumstances.

Are steroids really ineffective for severely head injured patients?

The "Guidelines for the Management of Severe Head Injury" states that the use of glucocorticoids is not recommended for improving morbidity outcome. Conversely, the "National Acute Spinal Cord Injury Study" (NASCIS) in the United States concluded that treatment with very high doses of methylprednisolone (30 mg/kg) is indicated for acute spinal cord trauma. In this paper the author will discuss the reasons for this great discrepancy between head injuries and spinal cord traumas. A 30-mg dose of methylprednisolone was used as a bolus dose in the spinal cord study to inhibit oxygen free radical-induced lipid peroxidation. In most of the papers cited containing Class I data on severe head injury studies the investigators used smaller doses of glucocorticoids as compared with those in the spinal cord study. Moreover, some of the papers included cases in which the time from insult to the initiation of treatment had been poorly controlled. Therefore, based on previous papers, it is appropriate to relinquish megadose steroid therapy for head injury patients. A good prospective multicenter trial of high-dose methylprednisolone for traumatic brain injury should be considered in which dosage and timing parameters similar to those enacted for the NASCIS studies are used.

GM1 Ganglioside Acute Spinal Cord Injury Study II: Efficacy and Safety

Geisler, Fred; Grieco, Giacinto; Dorsey, Frank C.; Patarnell, Francesca; Poonian, Devinder; Fiorentini, Roberto

Traumatic optic neuropathy: a case report

Traumatic optic neuropathy (TON) is considered to be a true ophthalmic emergency. The National Acute Spinal Cord Injury Study 2 (NASCIS 2) established the current treatment protocol for the management of TON, which indicates that treatment should start within 8 h of injury. Therefore, diagnosis should be made as soon as possible. Traumatic optic neuropathy is a rare but potentially devastating complication of closed head injury. Knowledge concerning the pathophysiologic mechanisms of TON is limited. The optic nerve is a tract of the brain, therefore the cellular and biochemical pathophysiology of brain and spinal cord trauma and ischemia provide insight into the mechanisms that may operate in TON. The management of TON rests on an accurate diagnosis, which begins with a comprehensive clinical assessment and appropriate neuroimaging.

Acute management of spinal cord injury.

Demographic trends in the occurrence of injury and improvements in the early management of spinal trauma are changing the long-term profile of patients with spinal cord injuries. More patients are surviving the initial injury, and proportionately fewer patients are sustaining complete injuries. While preventive efforts to reduce the overall incidence of spinal cord injury are important, a number of steps can be taken to minimize secondary injury once the initial trauma has occurred. Recent efforts have focused on understanding the biochemical basis of secondary injury and developing pharmacologic agents to intervene in the progression of neurologic deterioration. The Third National Acute Spinal Cord Injury Study investigators concluded that methylprednisolone improves neurologic recovery after acute spinal cord injury and recommended that patients who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone therapy is initiated 3 to 8 hours after injury, it should continue for 48 hours. In addition to the adoption of the guidelines of that study, rapid reduction and stabilization of injuries causing spinal cord compression are critical steps in optimizing patients' long-term neurologic and functional outcomes.

Corticosteroids in head injury--the CRASH trial.

The CRASH trial (Corticosteroid Randomisation After Significant Head injury) is a large simple placebo controlled trial, among adults with head injury and impaired consciousness, of the effects of a short...

Surgical treatment for acute spinal cord injury study pilot study #2: evaluation of protocol for decompressive surgery within 8 hours of injury

Acute spinal cord injury (SCI) is a major public health problem for which there is still only limited treatment available. The National Acute Spinal Cord Injury Study-2 (NASCIS-2) and -3 clinical trials demonstrated that the use of acute pharmacotherapy with methylprednisolone can attenuate the secondary injury cascade if administered within 8 hours of acute SCI. However, no trial has been performed to examine whether acute surgical decompressive procedures within this critical 8-hour time window can improve patients' neurological outcome. The purpose of the current prospective Surgical Treatment for Acute Spinal Cord Injury Study (STASCIS) pilot study was to determine the feasibility of obtaining a radiological diagnosis of spinal canal compromise of 25% or more and to perform spinal cord (C3-T1) decompressive procedures by 8 hours postinjury. One of the following three decompressive methods was used: 1) traction alone; 2) traction and surgery; or 3) surgery alone. Twenty-six patients from eight North American centers were entered into the study between 1996 and 1997. Significant difficulties were encountered in many centers in performing immediate magnetic resonance imaging examination in patients with acute SCI. Fewer than 10% of acute cervical SCI patients could be enrolled into this protocol mainly because the combination of the required time for rescue, resuscitation, transport, imaging study, and surgical preparation exceeded the 8-hour injury-to-decompressive surgery window. Eleven patients underwent decompressive procedures initially by being placed in traction at a mean time of 10.9 hours postinjury. Those patients not undergoing this procedure underwent decompressive surgery at a mean time of 40.1 hours. However, the surgical decompressive procedure was completed within 12 hours in seven patients. As a result of these findings, several major changes have been made to the STASCIS protocol for early decompressive therapy.

Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials.

The National Acute Spinal Cord Injury Study (NASCIS) 2 and 3 trials are often cited as evidence that high-dose methylprednisolone is an efficacious intervention in the management of acute spinal cord injury. Neither of these studies convincingly demonstrate the benefit of steroids. There are concerns about the statistical analysis, randomization, and clinical end points. Even if the putative gains are statistically valid, the clinical benefits are questionable. Furthermore, the benefits of this intervention may not warrant the possible risks. This paper comments on these two clinical trials.

SYGEN Acute Spinal Cord Injury Study

SYGEN Acute Spinal Cord Injury Study

Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord Injury

Objective. —To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. Design. —Double-blind, randomized clinical trial. Setting. —Sixteen acute spinal cord injury centers in North America. Patients. —A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. Intervention. —All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. Main Outcome Measures. —Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. Results. —Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. Conclusions. —Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.

Steroids and gunshot wounds to the spine.

The second National Acute Spinal Cord Injury Study demonstrated that there were neurological benefits from "spinal cord injury" doses of methylprednisolone for blunt spinal cord injuries. In this review, we examined the relative risk/benefit ratio of intravenously treating spinal gunshot wound victims with steroids. A retrospective review was conducted of 254 consecutive patients who were treated between 1979 and 1994 for gunshot wounds to the spine (C1-L1) and a spinal cord injury. Three subgroups were established based on the administration of the steroids methylprednisolone (National Acute Spinal Cord Injury Study 2 protocol), dexamethasone (initial dose, 10-100 mg), and no steroids. All patients who received steroids were initially treated at another hospital and then transferred. No patients received steroids at our institution. The data analyzed included neurological outcome and infectious and noninfectious complications. No statistically significant neurological benefits were demonstrable from the use of steroids (methylprednisolone, dexamethasone). Infectious complications were increased in both groups receiving steroids (not statistically significant). Gastrointestinal complications were significantly increased in the dexamethasone group (P = 0.021), and pancreatitis was significantly increased in the methylprednisolone group (P = 0.040). The mean duration of follow-up was 56.3 months. In this retrospective, nonrandomized review, no neurological benefits were detectable from intravenously administered steroids after a gunshot wound to the spine. Both infectious and noninfectious complication rates were higher in the groups receiving steroids. Patients who sustain a spinal cord injury secondary to a gunshot wound to the spine should not be treated with steroids until the efficacy of such treatment is proven in a controlled study.

Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study

Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study