SCI Forum Reports
Current and Future Management of SCI
April 4, 2000
"How your injury was managed is probably somewhat of a blur to you now," said Christopher Shaffrey, who recently came to the UW as associate professor in the Department of Neurosurgery and consultant to the Northwest Regional SCI System.
Of the approximately one million spinal injuries requiring medical attention each year in the U.S., most are minor and treated only with anti-inflammatory medications and heat. But 50,000 are spinal fractures, and 10,000 of these are injuries to the spinal cord with associated neurological deficits such as weakness, numbness, or paralysis.
"Up until the last few years, the vast majority of SCIs were due to motor vehicle accidents," Shaffrey said. But more recently, with the advent of air bags and increased use of seatbelts, car accidents are responsible for a diminishing proportion of injuries. Other major causes are falls, diving accidents, and gunshot wounds."
The thoracolumbar (junction of thoracic and lumbar spine) and cervical areas of the spine are the most commonly injured areas, and most fractures occur in the C5-6-7 and T11-L3 vertebrae. Fractures to more than one area of the spine occur in 5-20% of cases, and 5-15% of people with spinal cord injuries also have major injuries to organs or other parts of the body.
Since early management of patients with multiple trauma can have a profound effect on the long-term outcome of a spinal injury, "we as physicians always assume a person with multiple injuries does have an injury of the cervical spine until we can prove otherwise," Shaffrey said.
There is a high risk of SCI associated with all head injuries, especially those with frontal or facial trauma; penetrating wounds near the spine; falls from a height greater than the patient's own height; and situations involving major accelerating and decelerating forces, such as motor vehicle accidents.
After medically stabilizing a trauma patient, a thorough neurological evaluation is conducted to determine the extent of sensation, strength, and reflexes. "It is critical to make an accurate assessment," Shaffrey said. "Root specific muscle strength testing of the upper and lower extremities and rectal examination for tone and sensation should be performed." Accurate evaluation and careful grading and documenting of functional level helps determine the course of action and allows the physician to see if there is improvement over time.
While regular lateral x-rays of the neck detect 85% of significant cervical injuries, they are not a definitive diagnostic tool, Shaffrey said. "CT (computed tomography) remains the standard for demonstrating fractures and canal compromise of the spine."
MRI (magnetic resonance imaging) can show bruising and other soft tissue damage that might not show up in other studies but nonetheless can cause SCI. "Not all injuries that result in SCI necessarily have a fracture associated with them," he said.
In the absence of abnormal initial x-rays, neck pain, and neurological deficit, injury can sometimes be detected using flexion and extension x-rays of the neck. These studies are conducted on patients who are awake and "can tell you if there may be a subtle injury present, especially to the ligaments of the neck," Shaffrey said.
Although damage caused by the initial injury to the spine cannot be reversed, secondary injury can be reduced if the patient's condition is diagnosed and treated promptly. Since continued pressure on the cord caused by misalignment of the spine can increase injury, "the best thing we can do is restore normal alignment as quickly as we can," Shaffrey said.
It is also critical to identify as soon as possible those patients who can benefit from decompression either by realignment by skeletal traction or surgery to remove bone that may be pressing on the spinal cord, Shaffrey said. "Studies have shown that neurological recovery is improved by early decompression in acute SCI." After surgery or realignment, traction using a halo, orthosis, or tongs stabilizes the spine as it heals.
Low blood pressure is another symptom that could cause further damage to the spinal cord by reducing blood flow to the nerve cells. Often low blood pressure is a signal that there is another injury present, such as a penetrating wound that is causing significant blood loss.
Patients with acute SCI are at risk of getting blood clots in their legs, called deep venous thrombosis. "We do a variety of things to try to prevent that, including using sequential compression devices of the legs, and giving blood thinning medications," Shaffrey said.
Studies in animal models repeatedly show that the majority of damage to the spinal cord occurs at the moment of injury. "We as researchers try to find ways to limit any additional damage and to provide the best environment for the body to repair itself as much as possible," Shaffrey said. "Several animal studies have shown that if you can maintain 10-15% of spinal cord function through the area of injury, there is the potential for very substantial recovery. You don't need to save every cell to make it work."
Secondary injury to nerve cells is caused by ischemia (lack of blood flow); tissue hypoxia (insufficiency of oxygen getting to the tissue); and delayed cell death, which can continue for days after injury and is one of the major areas of SCI research today, according to Shaffrey.
Researchers have found that at the moment of injury, a cascade of complex chemical events is set in motion, in which partially injured cells further injure themselves. "Lots of different chemical pathways in the body are involved," Shaffrey said. "Chemicals are released that injure marginally injured cells or even healthy cells. This is called lipid peroxidation."
Methylprednisilone, which is the "gold standard" of SCI treatment and is given within the first eight hours after injury, reduces secondary injury by stabilizing cell membranes, inhibiting lipid peroxidation, reducing transcellular sodium and potassium imbalance that damage cells, and reducing the breakdown of neurofilaments that support and provide nutrition to nerve cells.
A promising drug that has enhanced recovery in animal studies is monosialotetrahexosyl-ganglioside (GM1), a glycoprotein normally present in central nervous system cells. Studies suggest that GM1 may "induce regeneration and the sprouting of neurons, and may be effective even if administration is delayed up to 48 hours," Shaffrey said.
Progesterone, an aminosteroid, has been shown to limit secondary injury in stroke patients. Preliminary animal studies have shown a sparing of white matter, and the effect seems to be about as strong as methylprednisilone but with fewer side effects. "What we're currently testing is whether progesterone is effective when given to people who come to the ER more than eight hours after injury," Shaffrey said.
Shaffrey and other SCI researchers also are investigating the role of apoptosis (programmed cell death) in secondary injury. "In different areas of the body, if there is an appropriate stimulus, the cells die in a controlled manner," he said. This contrasts with necrosis, in which cells die in an uncontrolled manner and produce noxious chemicals.
While it's not completely clear what initiates apoptosis in SCI, researchers know that it occurs as a normal part of central nervous system development during embryogenesis (the growth of the embryo). "It is a natural process in each of us, but the way to control it is the important thing," Shaffrey said.
His research has focused both on using nerve growth factors to enhance the sprouting of new axons after injury, and on harnessing apoptosis to improve nerve growth. After SCI, damaged nerve cells are prevented from growing because the supporting structures, called glia, form scars, which nerves cannot grow through. In one study he found that low dose radiation inhibited the growth of scars by causing apoptosis of the glia, which allowed better growth of the neurons.
"We and others have shown that in the supporting cells, if you can enhance apoptosis, you get better recovery," Shaffrey said. "So you've got two things going here. Probably, if we can cause programmed cell death of supporting structures, but enhance the growth of neurons themselves, this would be the best way" to prevent secondary injury.
According to Shaffrey, about 70% of SCI research today is focused on the acute phase of SCI, which is the period when destructive processes can be stopped or avoided. Reducing secondary injury can have a profound effect on a patient's eventual level of functioning and quality of life.
Because people with incomplete injuries have at least some intact neurons, most research in chronic SCI today is focused on ways of enhancing those remaining cells to produce the most recovery possible. Although "a miraculous cure for complete injuries is still pretty far down the road," Shaffrey said, "the day is coming closer when we will be able to make substantial progress to improve function in patients with incomplete injuries."
In the long run, Shaffrey believes that "the real advances (in SCi treatment) are going to come as the human genome project grows to completion, and we have ways to turn on cells and reproduce the things that go on with embryogenesis."