Methylprednisolone is a prednisolone derivative that belongs to the glucocorticoid group of corticosteroids. Methylprednisolone has potent anti-inflammatory properties and has been used for the treatment of acute spinal cord injury (SCI). Some sensory and motor improvements have been reported when methylprednisolone is administered within 8 hours after spinal cord injury.
The National Spinal Cord Injury Study (NASCIS) has conducted three trials I, II and III on early steroids after spinal cord injury. Acute steroid therapy is believed to reduce the cellular damage resulting from secondary injury processes such as lipid peroxidation. The conclusions from these trials have been questioned in recent years for reasons including relatively modest neurologic improvements compared to risks of high-dose steroids. Based on these studies, the early use of high-dose steroids has practically become the standard of care in acute traumatic spinal cord injury.
NASCIS II studies intravenous methylprednisolone at 30 mg/kg bolus followed by twenty three hours of infusion at 5.4 mg/kg per hour, compared to naloxone bolus of 5.4 mg/kg with 4.0 mg/kg per hour for 23 hours, and placebo bolus with infusion. After six months, those treated with methylprednisolone within eight hours of SCI had significant improvement in motor and sensory function compared to placebo. After the eight-hour window, no difference has been demonstrated in neurologic outcome in those given naloxone* or methylprednisolone, as compared to placebo. The three groups had similar mortality and major morbidity (delayed healing, gastrointestinal bleed, and wound infection) rates.
In NASCIS III, all patients received intravenous methylprednisolone bolus of 30 mg/kg. The treated patients were subsequently divided into three groups. Group 1 received methylprednisolone infusion at 5.4 mg/kg per hour for twenty four hours, Group 2 the same for forty eight hours, and Group 3 received tirilazad mesylate** 2.5 mg/kg bolus infusion every six hours for forty eight hours. The methylprednisolone-treated patients for forty eight hours showed improved motor recovery over those treated with methylprednisolone for twenty four hours. The improvement was significant for those started on methylprednisolone between three and eight hours after spinal cord injury, but they also had more severe infections (sepsis and pneumonia) than the group treated for twenty four hours. Those treated with tirilazard for forty eight hours showed motor recovery equivalent to the patients treated with methylprednisolone for twenty four hours.
The use of methylprednisolone has been challenged in recent years. Despite its administration to patients with spinal cord injury at many institutions, evidence of deleterious effects continues to accumulate that include immunosuppression with increased susceptibility to infections (pneumonia, sepsis, etc.) in addition to increased risk of gastrointestinal disturbances (ulcers, bleeding, and ileus), adult respiratory distress syndrome, hyperglycemia, deep venous thrombosis (DVT), and pulmonary embolism.
Current standard management includes support of arterial oxygenation and spinal cord perfusion pressure.
*An alkaloid antagonist of morphine and of the opiate peptides ** A 21-aminosteroid lacking glucocorticoid receptor-mediated activity
- Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J (1990): 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. 322: 1405-11.- Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M (1997): 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. JAMA 277: 1597-604
- Greenberg MS (2001): Handbook of Neurosurgery. Thieme, Fifth edition.- Hurlbert RJ(2006): Strategies of medical intervention in the management of acute spinal cord injury. Spine. 15; 31(11 Suppl): S16-21; discussion S36.
- Lim PA, Tow AM: Recovery and Regeneration after Spinal Cord Injury (2007): A Review and Summary of Recent Literature. Ann Acad Med Singapore. 36: 49-57
- Short DJ, El Masry WS, Jones PW (2000): High dose methylprednisolone in the management of acute spinal cord injury - a systematic review from a clinical perspective. Spinal Cord. 38: 273-86.
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