SCI Forum Reports
Spasticity and Spinal Cord Injury
January 14, 2003
"It's said that the brain is the most complex structure in the universe," said James Little, MD, PhD, associate professor in the UW Department of Rehabilitation Medicine. "If that's true, then the spinal cord is the second most complex structure."
"The brain is made up of millions of neurons-nerve cells-and trillions of synaptic connections," he continued. "It's an incredibly compact structure. The spinal cord itself has millions of neurons and billions of synaptic connections."
Spasticity is a common problem after SCI and results from increased reflex activity that develops following damage to the spinal cord. In order to understand how this happens, Little described some of the basic workings of the spinal cord.
The brain and spinal cord are made up of complex circuits of neurons. Information is carried from one neuron down its axon, or nerve fiber, to the next neuron by an electrical signal. This signal stimulates a chemical signal, called a neurotransmitter, which communicates across to the next cell, excites that cell, and so on down the pathway. This area of chemical transmission between one nerve cell and the next is called the synapse.
Neurons that carry messages from the brain down to the spinal cord are called upper motor neurons (UMNs). Lower motor neurons (LMNs) are the neurons that branch out from the spinal cord to the muscles and tissues of the body. The synapses allow the UMNs to communicate with the LMNs, carrying sensory information from the body up to the brain and motor information from the brain to the muscles.
Communication from the body to the brain begins with sensory fibers that send messages about what the tissues are doing. There are many different kinds of specialized sensory fibers. One type carries information about velocity of stretch in the muscle, sending a signal to the brain that tells how quickly your muscle is being stretched at any given moment.
When a spinal cord is injured, LMNs also are damaged at the level of injury but are normal above and below. "We still have a reflex connection from the sensory fiber to the LMN, making a synaptic connection," Little said. "One of the things we think happens to explain spasticity is that the reflex inputs from the sensory fibers to the LMNs grow new synapses. Where before a fiber made only a few synaptic contacts with the LMN, now it's making many; it has grown more synapses and now has a stronger reflex connection. So now, if someone stretches your muscle, it fires the reflex connection much stronger than before."
Reflex axons grow new synaptic connections over a period of months after injury. This is thought to occur because there are vacant synaptic sites on the neurons left by the degenerating fibers from above. "We think (the vacant sites) elicit some release of neurotrophins and other growth factors that stimulate synapse growth by whatever inputs are still out," Little said.
Spasticity appears in many varieties. With extensor spasms the legs straighten and become rigid; this can be so severe as to throw people out of their wheelchairs. Flexor spasms are the opposite: the legs pull up toward the chest. Clonus is the repetitive jumping of the muscle, most often the ankle, causing the foot to bounce repeatedly on the foot rest.
Little noted that spasticity can be beneficial or detrimental. It can interfere with function and quality of life in several ways: by impairing balance, endurance or transfers; by hindering the patient's or the partner's sleep, or both; by causing pressure sores; or by contributing to pain.
On the other hand, some people learn to use their spasms to assist with transfers or standing. Spasticity can help maintain muscle bulk, stimulate blood flow and increase bone strength. "When it comes to deciding how aggressive to be about treating spasticity, you have to look at the good aspects of it," he said. It is also important for the physician to sort out spasticity from other, possibly coexisting conditions that cause similar symptoms, such as contractures or weakness.
"Like any medical condition, treatment for spasticity usually starts with a noninvasive procedure or treatment and then moves on to the more invasive methods, if necessary," explained Fahrad Sepahpanah, MD, the UW SCI Medicine Fellow at the Veterans Affairs Medical Center.
Sometimes reducing pain will decrease spasticity, he said. "Even if the patient doesn't feel pain, giving pain medications can reduce spasticity and make a big difference."
Sepahpanah noted that "Stretching can be a very effective treatment for spasticity, but we need to pay attention to two things." First, the stretch must be held for 45 to 90 seconds; less than that is unlikely to be effective. Second, it should be done five-to-seven times a day and become a routine part of the patient's daily life. Stretching only reduces spasticity for a few hours, so "if you stop stretching," Sepahpanah warned, "spasticity will return."
Sometimes special equipment can be helpful. For example, spasticity that is triggered when doing pressure releases can be avoided by using a reclining system that tilts the patient in space.
Medications that act like naturally occurring inhibitory neurotransmitters to screen out unnecessary sensory messages coming from the environment can be effective against spasticity. Such medications include diazepam, baclofen, clonidine and tizanidine. Baclofen can also be delivered directly to the target nerve cells in the spine using an intrathecal catheter and a pump device implanted under the skin. This method reduces side effects, and only very tiny doses are needed. The downside is that surgery is required to implant the system, and the pump needs to be refilled every two-to-three months. The entire pump needs to be replaced every four-to-five years.
Chemical nerve blocks are used to suppress either the muscle or the nerve involved in the spasticity, either locally or generally. Botox injections reduce spasticity by paralyzing the muscle. Botox is very safe and effective, but it is expensive and it wears off after four-to-six months, so it requires repeated injections.
Alcohol and phenol injections are used to block nerves locally, reducing spasticity in the muscle stimulated by those specific nerves. Nerve blocks are inexpensive, effective, and relatively long-lasting (about six months).
The most invasive spasticity treatment option is a myelotomy, a surgical procedure in which the reflexive nerves are cut. This method effectively eliminates spasticity, Sepahpanah explained, but is always a last resort because it permanently and irreversibly changes the anatomy of the spinal cord. Also, it eliminates all reflexes, including the helpful reflexes used for bladder emptying, erection and bowel movements.
Avenues of Research
A major focus of spasticity research today is in the area of weight-supported ambulation, Little said. In this method, patients are supported in a harness and assisted to make stepping motions on a treadmill (see the Spring 2003 issue of our newsletter, SCI Update, at http://depts.washington.edu/rehab/sci/updates/03_spring.html for more information on body-weight-supported ambulation). "There is some evidence to indicate that this can result in enhanced recovery and may improve spasticity," Little said.
"One area of interest is the idea that spasticity may be interfering with recovery in someone with incomplete injury by blocking some synaptic growth that might allow recovery," Little said. UMNs that are spared might be able to grow new synaptic connections and mediate some recovery, but they may be competing for vacant synaptic sites with the reflex inputs, which are growing new synapses as well. Little and others wonder, therefore, whether spasticity-resulting from the growth of too many reflex inputs-may interfere with the potential for recovery of voluntary movement.
Little has seen this process at work in some of his patients. For example, a patient with C4 incomplete tetraplegia started getting some recovery back in his left elbow extensor muscle. But 90 days post injury this progress stopped, at the same time that spasticity started to develop. "We decided to try a low concentration alcohol block in the triceps muscle. It has the ability to reduce spasticity and spare most voluntary movement," Little said. "And the patient did improve his voluntary movement. It supported the idea that spasticity that develops in someone with an incomplete injury might possibly be interfering with the potential for voluntary recovery." Little has received a grant from the Paralyzed Veterans of America to investigate whether early spasticity treatment may yield some additional recovery.
There is some evidence, Little added, that spasticity treatment may play an important role in spinal cord regeneration modalities. Recent breakthroughs in axonal regeneration research have determined that neurons do not regrow across the damaged area of the spinal cord because the myelin (the insulation surrounding the axon of the nerve cell) in the central nervous system has proteins that inhibit long-distance growth. By contrast, the myelin in the peripheral nerves does support long-distance growth. Speculating that a grid of peripheral nerve cell myelin might be able to guide spinal axons across the area of injury, researchers grafted peripheral nerve sections to the damaged spinal cords of rats, adding growth factors to encourage axonal regrowth. As a result, these rats were able to voluntarily move their legs. "It wasn't functional walking," Little noted, "but it's huge progress from what was possible 10 to 20 years ago."
Once these axons have grown across the area of injury, the next problem is getting them to make new synaptic connections with the normal neurons on the other side. Growth factors can assist with this, but Little and others conjecture that by the time the axons grow across the gap, all the vacant synaptic sites may be taken up by the excess reflex connections that cause spasticity. Some researchers theorize that destabilizing the reflex synapses will make more synaptic sites available for axons to make functional connections. "If we get to the point that we could regenerate axons," Little said, "one aspect of recovery might be to reduce spasticity at the critical time, to destabilize some of those reflex synapses causing spasticity, and try to open up vacant synaptic sites."