EBQ:High Dose Steroids in Cord Injury
Does high-dose methylprednisolone treatment of acute cervical spinal cord injury within 8 hours of injury improve neurologic motor function outcomes?
High dose methylprednisolone sodium succinate (MPSS) was associated with greater improvement in motor score than those in the non methylprednisone group. However after multiple negative studies, methylprednisolone should not be administered for acute spinal injuries.
Overview of Controversy
Steroid use in acute spinal cord was a controversal treatment between the early 1990s and early 2000s. The original studies: National Acute Spinal Cord Injury Study I (NASCIS I) (1984) and NASCIS II were negative studies with regard to primary outcome. The benefits of the NASCIS II and III trials stemmed from subgroup analysis of patients who received steroids between 3-8 hours. At 1-year follow up no significant difference was found in motor scores among the three groups of patients treated within 12 hours of injury. The NIH faxed letters to every emergency department providing the instructions for correct steroid dosing for spinal cord injuries
Multiple cochrane reviews performed by the author of the NASCIS trials concluded neurological improvement after injuryA review of all individual studies demonstrate negative outcomes for both the retrospective and the prospective trials
Study Specific Highlights
- In patients with incomplete paralysis at admission, American Spinal Injury Association motor scores in the MPSS group were significantly improved compare to the non-MPSS group at 6 weeks and 6 months post-injury.
- In patients with complete paralysis at admission, there was no significant difference in improvement between the two groups.
- No significant difference was noted in improvement of myotomal level, or in early complications in the two groups.
- Retrospective single-center study conducted at the Spinal Injuries Center in Fukuoka, Japan
- Patients in the MPSS group were treated with MPSS within 8 hours of their injury according to the Second National Acute Spinal Cord Injury Study protocol 
- Bolus of 30mg/kg of actual body weight, followed by infusion of 5.4mg/kg for 23 hours
- Patients assessed at 6 weeks and 6 months post-injury with ASIA impairment scale and ASIA motor scale (0-100)
- Improvements in the American Spinal Injury Association motor score compared
- In patients with complete motor loss, improvements of myotomal levels (most caudal level of intact motor function) compared
- Sensory function not evaluated
MPSS group vs. non-MPSS group
- Men: 86% vs. 91%
- Mean age: 50.2 years vs. 51.6 years
- ASIA A: 49% vs. 76%
- ASIA B: 8% vs. 6%
- ASIA C: 24% vs. 3%
- ASIA D: 19% vs. 15%
- There were significant differences in ASIA impairments between groups, P=0.02
- Patient with acute mid-to-lower cervical spinal cord injury admitted to center between 1998 to 2002
- Admitted to center within 7 days of injury and were followed for 6 months.
- Patients with partially flawed medical records
- Follow-up less than 6 months
- Admission to study center later than 7 days after injury
- Administration of MPSS non-conforming to NASCIS-2 protocol
- Bone fracture of extremities
- Death with complications
- Brain injury
- Multiple spinal cord injury
- Mental disturbance
- Peripheral nerve injury
- Spine injury without paralysis
N=70 patients Patients with complete motor loss in MPSS group (n=15) and non-MPSS group (n=21)
- The patients in the MPSS group had significantly more improvement in motor score than those in the non-MPSS group at 6 weeks and 6 months after injury
- No significant differences in improvement in myotomal level
- The non-MPSS group had more early complications than the MPSS group, although the difference was not significant
Criticisms & Further Discussion
- Low powered study, retrospective study with no blinding or randomization.
- Unclear methods or reviews leading to possible bias with regard to chart review and due to retrospective study, a causal relationship between steroids and outcomes cannot be determined
- Updated guidelines from the Congress of Neurological Surgeons (CNS) discourage against the use of steroids in spinal cord injury, citing harmful side effects including death. 
- Hurlbert RJ et al. Pharmacological therapy for acute spinal cord injury. Neurosurgery. 2013 Mar;72 Suppl 2:93-105.
- Hurlbert RJ. Methylprednisolone for acute spinal cord injury: an inappropriate standard of care. J Neurosurg. 2000;93(1 Suppl):1-7.
- Bracken MB et al. Methylpredni- solone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow-up. Results of the third National Acute Spinal Cord Injury Randomized Controlled Trial. J Neurosurg 89:699–706, 1998
- New Republic Study Break
- Bracken MB. Steroids for acute spinal cord injury. Cochrane Database Syst Rev. 2012 Jan 18;1:CD001046
- Steroids for Spinal Cord Injury http://www.trauma.org/archive/spine/steroids.html#NASCIS_1.2C_USA_1984
- Bracken MB et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury:Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990;322:1405-11.
- Anderson P. New CNS/AANS Guidelines Discourage Steroids in Spinal Injury. Medscape Medical News. Mar 28 2013.