Possible treatment window for spasticity in spinal cord injury

Nov. 27, 2002
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GAINESVILLE, Fla. — It’s a cruel irony that strikes many victims of spinal cord injury: In those who suffer only partial paralysis, limbs that should remain healthy become stiff and useless because of chronic spasticity, a painful condition that causes muscles to contract involuntarily.

But University of Florida medical experts charting the development of spasticity in rats with spinal cord injuries were surprised to find the process briefly reverses itself. This discovery raises the possibility that physicians could someday find a way to spare patients its debilitating effects by intervening at a critical time, said Dr. Prodip Bose, a research assistant professor of neuroscience and a faculty member with the Evelyn F. and William L. McKnight Brain Institute of UF.

UF researchers reported the novel findings in the October issue of The Journal of Neurotrauma.

“In rats, spasticity begins to set in during the first week after a spinal injury, and we expected to see the condition worsen at a consistent pace from that point,” Bose said. “However, during the second and third weeks it improved somewhat before becoming fully established in the fourth week. Previously, no one knew this happened.”

Spasticity causes muscle stiffness and periodic spasms, he said. It occurs when a muscle exhibits abnormal resistance to movements, and is associated not only with brain and spinal injury but also with stroke, multiple sclerosis and cerebral palsy.

“Spasticity is considered a secondary consequence of spinal injury, but it can be one of the most difficult aspects for the patient,” Bose said.

About 10,000 people in the United States each year sustain spinal cord injuries from car and sporting accidents, falls and other mishaps, and as many as two-thirds of them develop spasticity, he said.

In people with spinal injuries, spasticity develops over four weeks, beginning with about three weeks of “spinal shock,” in which little nerve activity can be detected in muscles that should remain healthy, said Floyd Thompson, a UF neuroscience associate professor who co-authored the study with Bose and UF senior biological scientist Ronald Parmer. In the fourth week nerve activity resumes and with it comes an abrupt onset of spasticity.

“Once spasticity is established, it appears to be permanent,” he said. “Presently, the after-the-fact treatment options focus on reducing the level of spasticity. We’re researching possibilities for treatment and early intervention at UF’s Neurophysiology of Spinal Cord Injury and Repair Laboratory.”

Thompson directs the laboratory and collaborates on studies of ways to decrease spasticity using small implanted pumps to continuously deliver medications directly to the spinal cord.

The UF study indicates that rat models are more helpful to researchers investigating spasticity than was previously believed, said Dr. Jay Meythaler, a professor of medicine at the University of Alabama at Birmingham and a noted spasticity expert. The delay in spasticity development in rats has parallels to the “spinal shock” that occurs in human patients and indicates that new treatments should be used in rats before studies in people are attempted.

“The mechanisms that cause spasticity aren’t completely clear, but the first step is to understand which nerve pathways are involved,” Thompson said. “We’re determining that now. The next step is to understand how those pathways are altered by the injury.”

Spasticity causes hyperactivation of reflexes that normally regulate a muscle’s resistance to being stretched, he said. When the reflexes are activated too easily and too often, unwanted muscle contractions occur, interfering with smooth, accurate movement. Stiffness and painful muscle spasms also result.

Meythaler said the UF study supports the hypothesis that spasticity is caused by complementary nerve pathways being thrown out of balance as some neurotransmitters are able to transmit messages but others are not.

“If we could moderate the changes in the neural pathways, we might be able to stop the development of spasticity,” he said. “That’s why this is an important study-it shows that we can try therapies in rats and then try the successful methods in clinical trials.”

In UF’s four-month study, researchers compared 10 rats with identical spinal injuries with four healthy rats. They examined specific hind leg muscles for reflexes and electrical activity.

After one week, the injured rats’ leg muscles began to exhibit increased muscle tension and hyperactive reflex excitability, a condition that contributes to spasticity by reducing the amount of stimulus needed to make the muscle fibers contract.

Muscle tension and hyperactive reflex excitability decreased during the second and third weeks after the injury, Thompson said. In the fourth week, tension and excitability substantially increased and then remained constant until the study ended.

“Rat models help us gather data faster because these animals have a life expectancy of about two years,” he said. “We were able to see how the condition affects them at various stages of their lives without waiting years for results as we would if we followed human patients.”

The National Institutes of Health, Paralyzed Veterans of America, and the Brain and Spinal Cord Injury Rehabilitation Trust Fund of Florida funded the study.