Repairing the Damaged Spinal Cord:

Activity-Based Restoration Therapies

 

John W. McDonald, M.D., Ph.D.

 

Once thought impossible, repairing the damaged nervous system is now entering the realm of feasibility. Two important concepts are shortening the path to successful restoration: 1) It is not necessary to cure a nervous system injury, and 2) a disproportionate return of function can result from a small degree of regeneration. Substantial loss of spinal cord tissue, particularly gray matter, does not preclude near-normal long-tract function.

 

It is important for clinicians and scientists to learn from variability and outliers, which offer key insights into mechanisms of disease and repair. Thus, it is instructive to identify the features shared by the 3 percent of individuals with severe ASIA A SCIs who recover

sufficiently to walk.

 

This article summarizes the importance of continuous cross-talk between the laboratory and clinic for reaching readily achievable goals that improve quality of life. The spectrum of regenerative strategies that scientists are studying, when ranked by feasibility, range from the impossible, such as long-tract reconnection, to the more feasible, such as optimizing spontaneous regeneration by modulating patterned neural activity. We contrast two similar regenerative approaches that appear very divergent: stem cell transplantation for repairing the spinal cord and optimization of spontaneous regeneration for recovery of function. We note that strategies that once held great excitement now seem limited and complex, whereas others that once were considered unimportant may be more practical. We also advocate attention to the logistics of potential therapies because no one will benefit from treatments that medical insurers and consumers reject due to fiscal or time constraints. Neurosurgery is at the front line of care and treatment of catastrophic neurologic injuries, including spinal cord trauma. Advances in acute trauma care, interventional surgery, instrumentation for advanced spine stabilization, and rehabilitation have vastly reduced morbidity and mortality following spinal trauma. Neurosurgical care is also entering into the realm of restoration of neural function through optimization of regeneration. Although neural regeneration is an active research field today, there are no current treatments to aid regeneration following spinal cord trauma. This article will review the feasibility of spinal cord repair and provide an overview of the range of strategies scientists are taking toward regeneration. Its major focus will be the future role of stem cell transplantation versus simpler rehabilitative approaches designed to optimize spontaneous regeneration by mobilizing endogenous stem cells.

 

THE PROBLEM

After spinal cord trauma, secondary injury progresses rapidly, leaving only a donut-like rim of mostly white matter at the trauma level. Thus, the outcome for spinal cord injury is quite poor. More than 60 percent of traumatic injuries in the United States are graded as ASIA A or “complete.” Fewer than 3 percent of these individuals ever recover the miracle of walking. In fact, fewer than 10 percent regain enough sensory function to be reclassified as ASIA B, C, or D. Despite these statistics, 60 percent to 90 percent regain at least one motor level, a gain typically attributed to recovery of segmental nerve roots injured by traction injury. The old adage is that most recovery occurs in the first six months and that; if recovery has not been observed in the first year to two, it will not occur thereafter. In fact, there has not been a single clinical report of substantial return of function (e.g., 1–2 ASIA grades) more than one year from injury in patients who showed no initial recovery. It is important to keep in mind, however, that most outcome data were gathered more than a decade ago. In the intervening years, there have been dramatic improvements in quality of care, particularly in the neurosurgery field. Two of the greatest advances have been early surgical decompression and internal stabilization of the cervical spine, which avoids the need for external halo stabilization. Internal stabilization allows a more rapid transition to rehabilitation and early mobilization, reducing complications associated with immobilization.

 

GOALS OF RESTORATION

Despite the poor outcomes for most patients with spinal cord injury, occasional individuals have regained near-normal function. Figure 30.1 shows the spinal cord of a man who was injured at C4–5 more than 20 years ago. He lost more than two thirds of the central spinal cord including substantial damage of ascending and descending axons. Despite these deficits, he can now compete in Iron Man Triathlons. This case demonstrates an important concept for neurosurgical residents: It is not necessary to cure spinal cord injury to restore function; partial repair can suffice. Thus, small anatomical gains can translate into disproportionate gains in function. Animal studies suggest that restoring only 10 percent to 15 percent of connections is sufficient to allow walking.

 

Extract from Chapter 30, Repairing the Damaged Spinal Cord:  From Stem Cells to Activity-Based Restoration Therapies   John W. McDonald, M.D., Ph.D.

 

Copyright © 2004 by Lippincott Williams & Wilkins

0148-703/04/5101-0001

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Clinical Neurosurgery • Volume 51, 2004 1