Pathophysiology and pharmacologic treatment of acute spinal cord injury

Abstract

Background context

The past three decades have witnessed increasing interest in strategies to improve neurologic function after spinal cord injury. As progress is made in our understanding of the pathophysiologic events that occur after acute spinal cord injury, neuroprotective agents are being developed.

Purpose

Clinicians who treat acute spinal cord injuries should have a basic understanding of the pathophysiologic processes that are initiated after the spinal cord has been injured. A familiarity with the literature on which the current use of methylprednisolone is based is also essential.

Study design/setting

Literature review.

Methods

Literature review of animal data on pathophysiologic mechanisms, and of both animal and human trials of neuroprotective agents.

Results

The mechanical forces imparted to the spinal cord cause primary damage to the neural tissue, but a complex cascade of pathophysiologic processes that imperil adjacent, initially spared tissue to secondary damage rapidly follows this. Attenuating this secondary damage with neuroprotective strategies requires an understanding of these pathophysiologic processes. Many researchers are investigating the role of such processes as ischemia, inflammation, ionic homeostasis and apoptotic cell death in the secondary injury cascade, with hopes of developing specific therapies to diminish their injurious effects. Beyond methylprednisolone, a number of other pharmacologic treatments have been investigated for the acute treatment of spinal cord injury, and even more are on the horizon as potential therapies.

Conclusions

This review summarizes some of the important pathophysiologic processes involved in secondary damage after spinal cord injury and discusses a number of pharmacologic therapies that have either been studied or have future potential for this devastating injury.

Introduction

Individuals paralyzed by trauma to the spinal cord are left with one of the most physically disabling and psychologically devastating conditions known to humans. Over 10,000 North Americans, most of them under the age of 30 years, experience such an injury each year [1]. A decade ago, the cost for the medical, surgical and rehabilitative care for spinal cord–injured patients was estimated at over $4 billion annually [2], a societal expense that has undoubtedly increased substantially in the new millennium. Although undeniably enormous, this economic impact fails to recognize the incalculable loss experienced by these patients, who are often young, otherwise healthy and in the most productive years of their lives. This has prompted much investigation from the clinical and scientific communities to develop therapeutic strategies for spinal cord–injured patients, in order to enhance neurologic function in what was historically deemed an untreatable condition [3], [4]. Substantial insight has subsequently been generated about the pathophysiology of acute spinal cord trauma, giving rise to a number of clinically applicable neuroprotective treatments to maximize the functional integrity of the remaining spinal cord. In this review we summarize these pathophysiologic mechanisms that contribute to the “secondary injury” that follows the initial mechanical trauma to the spinal cord, and discusses current and experimental pharmacologic treatments. As evidenced by the poor neurologic recovery after most spinal cord injuries and the paucity of pharmacologic treatments currently available, it should be obvious to even the most casual observer that our present understanding of these pathophysiologic processes and how to manipulate them is fairly rudimentary.