Prolonged Treatment With Methylprednisolone Improves Recovery In Spinal Cord Injured Patients

May 28, 1997

Since 1990, thousands of spinal cord injured patients have received the first effective treatment for acute injury. Now, a new study shows that giving the drug for a longer period of time can significantly improve recovery over the standard treatment.

Scientists and physicians from a 16-center National Acute Spinal Cord Injury Study (NASCIS III), led by Michael B. Bracken, Ph.D., of Yale University School of Medicine in New Haven, Connecticut, report that giving the steroid methylprednisolone over a 48-hour period results in improved function in patients with spinal cord injury if treatment begins within three to eight hours following injury. The standard treatment is 24 hours of the drug. The study, funded primarily by the National Institute of Neurological Disorders and Stroke (NINDS), is published in the May 28 issue of the Journal of the American Medical Association.

The announcement comes exactly two years after the spinal cord injury that paralyzed actor Christopher Reeve on May 27, 1995. Reeve, who received methylprednisolone shortly after he was injured, is one of the approximately 250,000 Americans living with the devastating effects of a spinal cord injury. Some 10,000 people, the majority of whom are young males, suffer spinal cord injuries in the United States each year.

"These investigators have provided us once again with clear, compelling evidence that methylprednisolone makes a difference in the lives of spinal cord injured persons, reducing the extent of their disabilities and providing a chance of better recovery, " said Michael D. Walker, M.D., director of the Division of Stroke, Trauma, and Neurodegenerative Disorders at the NINDS.

NASCIS III compared three treatments: methylprednisolone given over a 48-hour period; an antioxidant drug, tirilazad mesylate, administered over a 48-hour period; and, as a control, 24-hour treatment with methylprednisolone. Nearly 500 patients were evaluated in the emergency room and again 6 weeks and 6 months later as part of the randomized, controlled trial. Patients who began treatment three to eight hours after injury showed significantly better long-term recovery if they received methylprednisolone for 48 hours than if they received it for 24 hours, or if they received tirilazad. Patients who were treated within the first three hours after injury, however, showed about the same degree of recovery regardless of which drug they received or how long they received it. Investigators found that patients who received tirilazad three to eight hours after injury developed slightly fewer complications than patients in either methylprednisolone group, but did not regain as much of their physical ability.

"Based on these results, we recommend that patients receive 24 hours of methylprednisolone if treatment is begun within three hours after injury. If patients cannot be treated within the first three hours, however, they should receive methylprednisolone for 48 hours," says Dr. Bracken, lead author of the report.

The investigators measured improvements in patients' ability to move, perceive sensation, and take care of themselves without assistance. About 60 percent of patients treated with 48-hour methylprednisolone starting at three to eight hours recovered a substantial degree of independence, compared to about 40 percent of those given the standard treatment or tirilazad. Ultimately, recovery also depended upon the extent of initial injury.

Scientists believe both methylprednisolone and tirilazad work by interfering with a kind of secondary damage called lipid peroxidation that eats away at highly vulnerable cell membranes. They think this secondary damage becomes more difficult to interrupt the longer initial treatment is delayed, which may explain why extending methylprednisolone treatment is useful in patients treated three hours or more after injury. While tirilazad and methylprednisolone are both powerful inhibitors of lipid peroxidation, methylprednisolone may inhibit other kinds of secondary damage, such as the release of chemicals that cause inflammation, the researchers say. "Researchers still need to discover if tirilazad given in different doses, and perhaps for a longer period, could be more effective," says Dr. Bracken.

The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system and a lead agency in the Congressionally designated Decade of the Brain.
* The 16 regional centers participating in NASCIS III were: Yale University School of Medicine, New Haven, Connecticut; New York University-Bellevue Medical Center, New York; Medical University of South Carolina, Charleston; University of California, San Diego; University of California, Davis; University of California, San Francisco; Barrow Neurological Institute, Phoenix, Arizona; the University of Iowa hospitals and clinics, Iowa City; University of Washington - Harborview Medical Center, Seattle; Allegheny General Hospital, Pittsburgh; Toronto Western Hospital, Ontario; Sunnybrook Medical Centre, Toronto; University of Maryland, Baltimore; Henry Ford Hospital, Detroit; Washington Hospital Center, Washington, D.C.; and the University of Texas Medical Branch, Galveston.

**This trial was funded in part by Pharmacia and Upjohn, Inc.

Reference: Bracken, M.B.; Shepard, M.J., et al. "Methylprednisolone administered for 24 or 48 hours, or 48 hour tirilazad mesylate, in the treatment of acute spinal cord injury; results of the third National Acute Spinal Cord Injury randomized controlled trial." Journal of the American Medical Association, Vol. 277, No. 20, May 28, 1997; pp. 1597-1604.

NIH/National Institute of Neurological Disorders and Stroke

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