Discoveries in clinical research
Advances in basic research are also being matched by progress in clinical research, especially in understanding the kinds of physical rehabilitation that work best to restore function. Some of the more promising rehabilitation techniques are helping spinal cord injury patients become more mobile.
Restoring function through neural prostheses and computer interfaces
While basic scientists strive to develop strategies to restore neurological connections between the brain and body of spinal cord injured persons, bioengineers are working to restore functional connections via advanced computer modeling systems and neural prostheses. Discovering ways to integrate devices that could mobilize paralyzed limbs requires a unique interface between electronics technology and neurobiology. A functional electrical stimulation (FES) system is one example of this kind of innovative research.
FES systems use electrical stimulators to control muscles of the legs and arms to encourage functional walking and to stimulate reaching and gripping. Electrodes are taped to the skin over nerves or surgically implanted and then controlled by a computer system under the command of the user. For example, to assist reaching, electrodes can be placed in the shoulder and upper arm and controlled by movements of the opposite shoulder. Through a computer interface, the spinal cord injured person can then trigger hand and arm movements in one arm by shrugging the opposite shoulder.
These systems are useful not just for restoring functional movements. They also help people exercise paralyzed muscle systems, which can provide significant cardiovascular benefits. So far, relatively few people utilize them because the movements are so robotic, they require extensive surgery and electrode placement, and the computer interface systems are still limited. Bioengineers are working to develop more natural interfaces.
Because the brain plans voluntary movements several seconds before the command is sent out to the muscles, people whose spinal cords no longer carry signals to their limbs might still be able to complete the planning phase in their brains but use a robotic device to carry out the command. A recent experiment used microwires implanted in the motor cortex area of the brain (in this case a monkey's brain) to record brain-wave activity, which was then relayed to a computer that analyzed the data, predicted the movement, and sent the command to a robotic arm. A device such as this could be used to control a wheelchair, a prosthetic limb, or even a patient's own arms and legs.
In the future, researchers expect that these kinds of brain-machine interfaces could be planted directly into the brain using microchips that would do the processing and transmit the results without wires. Work is already being done with hybrid neural interfaces, implantable electronic devices with a biological component that encourages cells to integrate into the host nervous system.
Retraining central pattern generators
Scientists have known for years that animals' spinal cords contain networks of neurons called central pattern generators (CPG) that produce rhythmic flexing and extension of the muscles used in walking. They assumed, however, that the bipedal walking of humans was more dependent on voluntary control than on CPG activation. Therefore, scientists thought that without control from the brain, movements produced by a spinal CPG weren't likely to be useful in restoring successful walking without regulation from the brain. Current research is showing, however, that these networks can be retrained after spinal cord injury to restore limited mobility to the legs.
Using a technique called sensory patterned feedback, researchers are attempting to retrain CPG networks in spinal cord injured patients with special programs that break down walking movements into their component patterns and force paralyzed limbs to repeat them over and over again. In one of these programs, the patient is partially supported by a harness above a moving treadmill while a therapist moves the patient's legs in a stepping motion. Other researchers are experimenting with combining body weight support and electrical stimulation with actual walking rather than treadmill training.
Another technique uses an FES bicycle in which electrodes are attached to hamstrings, quadriceps, and gluteal muscles to stimulate the pedaling motion. Several studies have shown that these exercises can improve gait and balance, and increase walking speed. NINDS is currently funding a clinical trial with paraplegic and quadriplegic subjects to test the benefits of partial weight-supported walking.
Delieving pressure through surgery
The timing of surgical decompression (alleviating pressure on the spinal cord from fractured or dislocated vertebrae or disks) is a controversial topic. Animal studies have shown that early decompression can reduce secondary damage, but similar results haven't been reliably reproduced in human trials. Other studies have shown neurological improvement without decompression surgery, which has led some to believe that either avoiding or delaying surgery, and using pharmacologic interventions instead, is a reasonable (and non-invasive) treatment for spinal cord injuries. Additional research is needed to determine if early surgical intervention is sufficiently beneficial to offset the risk of major surgery in acute trauma.
Treating pain
Two thirds of people with spinal cord injury report pain and a third of those rate their pain as severe. Nonetheless, both diagnosis and treatment of post-injury pain still remain a clinical challenge. There is no universally recognized scheme for classifying pain from spinal cord injury, nor is there a uniformly successful medical or surgical treatment to prevent or reduce it. The mainstays of neuropathic pain treatment are antidepressants and anticonvulsants, even though they are not uniformly effective.
Research suggests that spinal cord pain syndromes stem from the spread of secondary damage to spinal cord segments above and below the injury site. Pain can be at the level of the injury or below the level of the injury, even in areas where sensation is limited or absent. Findings indicate that at-level (junctional) pain probably results from damage to grey and white matter one or more segments above the injury site, whereas pain below the injury results from the interruption of axon pathways and the formation of abnormal connections within the spinal cord near the site of injury.
Studies suggest that functional changes in neurons, which make them hyperexcitable, could be a cause of chronic pain syndromes. Consequently, giving more aggressive treatment for spinal cord injury in the first few hours after injury could limit secondary damage and prevent or reduce the development of chronic pain afterwards.
Investigators are currently testing neuroprotective and anti-inflammatory strategies to calm overexcited neurons. Other studies are also looking at pharmacological options, including sodium channel blockers (such as lidocaine and mexiletine), opioids (such as alfentanil and ketamine), and a combination of morphine and clonidine. Drugs that interfere with neurotransmitters involved in pain syndromes, such as glutamate, are also being investigated. Other researchers are exploring the use of genetically engineered cells to deliver pain-relieving neurotransmitters. These treatments appear to alleviate pain in animal models and in preliminary clinical studies with terminally ill cancer patients.
Controlling spasticity
The mechanisms of muscle spasticity after spinal cord injury are not well understood. Recent studies indicate that the loss of particular descending axonal pathways most likely results in the decreased activity of inhibitory interneurons, which causes the overreaction of motor neurons to excitatory stimuli.
Unlike treatments for post-injury pain, medical and surgical treatments for spasticity are established and highly successful. These include oral medications that act within the central nervous system (baclofen and diazepam) and one that acts directly on skeletal muscle (dantrolene). For spasticity that is resistant to drug interventions, surgical rhizotomy or myelotomy is sometimes performed to sever reflex pathways.
Investigators are currently exploring neuromodulation procedures based on preliminary results showing that electrical spinal cord stimulation below the injury can modulate spasms. Other techniques used clinically and experimentally involve implanting pump systems that continuously supply antispasmodic drugs such as baclofen.
Improving bladder control
A promising area of research on treatments for bladder dysfunction involves using electrical stimulation and neuromodulation to achieve bladder control. The current treatment for reflex incontinence includes a surgical procedure that cuts the sacral sensory nerve roots from S2 to S4. With the hope that a cure for spinal cord injury could be imminent, and the reluctance among men to lose any of their already compromised sexual function, few patients are willing to have these nerves cut.
Development of a sacral posterior and anterior root stimulator implant is being explored to better coordinate bladder and sphincter contractions. In preliminary studies people were able to achieve suppression of reflex incontinence and clinically useful increases in bladder volume with the use of the implanted stimulator.
Researchers hope that by combining neuromodulation for reflex incontinence with neurostimulation for bladder emptying, the bladder could be completely controlled without having to cut any sacral sensory nerves.
Understanding changes in sexual and reproductive function
Sperm count in men may or may not change due to spinal cord injury, but sperm motility often does. Researchers are investigating whether or not spinal cord injury causes changes in the chemical composition of semen that make it hostile to sperm viability. Preliminary studies show that the semen of men with spinal cord injury contains abnormally high levels of immunologically active leukocytes, which appear to have a negative impact on sperm motility.
Recent animal studies have revealed what appears to be a neural circuit within the spinal cord that is critical for triggering ejaculation in animal models and may play the same role in humans. Triggering ejaculation by stimulating these cells might be a better option than some of the current, more invasive methods, such as electroejaculation.