Spinal cord injury and repair

Many victims of spinal cord injury are young and will live a near-normal lifespan (Fig. 47.1). Therefore, the toll to individuals and society is high. The average lifetime cost of treating a person with traumatic spinal cord injury in the United States runs between $500000 and $2 million, depending on factors such as the extent of injury and where the cord is injured (higher levels correspond to greater disability and greater costs). Total direct costs of caring for Americans with spinal cord injury exceed $8 billion per year (DeVivo, 1997). Current state of acute pharmacological treatment This enormous human and economic toll calls for effective therapies. It was not until the 1990s, however, that the first proven therapy for spinal cord injury was introduced. A multicentre clinical study (National Acute Spinal Cord Injury Study, NASCIS 2) revealed that a high dose of the steroid methylprednisolone reduced disability when administered within 8 hours of the trauma (Bracken et al., 1990). Although the effectiveness of this drug was modest, the availability of any treatment for spinal cord injury was heartening. Subsequently, the multicentre NASCIS 3 trial compared treatment with methylprednisolone for 24 h (same treatment as in NASCIS 2) vs. treatment for 48 h. All patients treated with methylprednisolone within 3 hours of injury showed essentially identical rates of motor recovery. When treatment was initiated between 3 h and 8 h of injury, patients receiving the 48-hour protocol showed significantly more improvement in motor function. Therefore, the US standard of care is administration of methylprednisolone (bolus 30 mg/kg) within the first 8 h after injury. Treatment initiated within the first 3 h is continued (5.4 mg/kg/h) for 24 h, whereas treatment initiated between 3 h and 8 h is continued for 48 h. Despite these studies, methylprednisolone remains controversial in other countries (Short et al., 2000). Additional experimental drugs, including SYGEN (GM-1 ganglioside), naloxone, and trilizad, have been tested in multicentre clinical trials, but primary endpoints were never achieved. More recently, cellular and molecular advances in neurobiology have provided powerful insights into the nature of spinal cord injury and opened up new horizons for neural repair and restoration of function. In this chapter we describe how this rapidly burgeoning knowledge might be harnessed to help individuals with spinal cord unjury regain lost functions.