To understand how treatment for spinal cord injury can be improved, it is important to understand the normal spinal cord and its functions, how these functions change after injury, and the status of current treatment.
The Normal Spinal Cord
The spinal cord and the brain together make up the CNS. The spinal cord coordinates the body’s movement and sensation. Unlike nerve cells, or neurons, of the Peripheral nervous system (PNS), which carry signals to the limbs, torso, and other parts of the body, neurons of the CNS do not regenerate after injury.
The spinal cord includes nerve cells, or neurons, and long nerve fibers called axons. Axons in the spinal cord carry signals downward from the brain (along descending pathways) and upward toward the brain (along ascending pathways). Many axons in these pathways are covered by sheaths of an insulating substance called Myelin, which gives them a whitish appearance; therefore, the region in which they lie is called “white matter.” The nerve cells themselves, with their tree-like branches called dendrites that receive signals from other nerve cells, make up “gray matter.” This gray matter lies in a butterfly-shaped region in the center of the spinal cord. Like the brain, the spinal cord is enclosed in three membranes (meninges): the pia mater, the innermost layer; the arachnoid, a delicate middle layer; and the Dura Mater, which is a tougher outer layer.
The spinal cord is organized into segments along its length. Nerves from each segment connect to specific regions of the body. The segments in the neck, or Cervical region, referred to as C1 through C8, control signals to the neck, arms, and hands. Those in the Thoracic or upper back region (T1 through T12) relay signals to the torso and some parts of the arms. Those in the upper Lumbar or mid-back region just below the ribs (L1 through L5) control signals to the hips and legs. Finally, the Sacral segments (S1 through S5) lie just below the lumbar segments in the mid-back and control signals to the groin, toes, and some parts of the legs. The effects of spinal cord injury at different segments reflect this organization.
Several types of cells carry out spinal cord functions. Large Motor neurons have long axons that control skeletal muscles in the neck, torso, and limbs. Sensory neurons called Dorsal Root ganglion cells, whose axons form the nerves that carry information from the body into the spinal cord, are found immediately outside the spinal cord. Spinal interneurons, which lie completely within the spinal cord, help integrate sensory information and generate coordinated signals that control muscles. Glia, or supporting cells, far outnumber neurons in the brain and spinal cord and perform many essential functions. One type of glial cell, the Oligodendrocyte, creates the myelin sheaths that insulate axons and improve the speed and reliability of nerve signal transmission. Other glia enclose the spinal cord like the rim and spokes of a wheel, providing compartments for the ascending and descending nerve fiber tracts. Astrocytes, large star-shaped Glial Cells, regulate the composition of the fluids that surround nerve cells. Some of these cells also form scar tissue after injury. Smaller cells called microglia also become activated in response to injury and help clean up waste products. All of these glial cells produce substances that support Neuron survival and influence Axon growth. However, these cells may also impede recovery following injury.
Nerve cells of the brain and spinal cord respond to insults differently from most other cells of the body, including those in the PNS. The brain and spinal cord (i.e., the CNS) are confined within bony cavities that protect them, but also render them vulnerable to compression damage caused by swelling or forceful injury. Cells of the CNS have a very high rate of metabolism and rely upon blood glucose for energy. The “safety factor,” that is the extent to which normal blood flow exceeds the minimum required for healthy functioning, is much smaller in the CNS than in other tissues. For these reasons, CNS cells are particularly vulnerable to reductions in blood flow (Ischemia). Other unique features of the CNS are the “blood-brain-barrier” and the “blood-spinal-cord barrier.” These barriers, formed by cells lining blood vessels in the CNS, protect nerve cells by restricting entry of potentially harmful substances and cells of the immune system. Trauma may compromise these barriers, perhaps contributing to further damage in the brain and spinal cord. The blood-spinal-cord barrier also prevents entry of some potentially therapeutic drugs. Finally, in the brain and spinal cord, the glia and the extracellular matrix (the material that surrounds cells) differ from those in peripheral nerves. Each of these differences between the PNS and CNS contributes to their different responses to injury.
Anatomical and Functional Changes After Injury
The types of Disability associated with spinal cord injury vary greatly depending on the severity of the injury, the segment of the spinal cord at which the injury occurs, and which nerve fibers are damaged. In spinal cord injury, the destruction of nerve fibers that carry motor signals from the brain to the torso and limbs leads to muscle paralysis. Destruction of sensory nerve fibers can lead to loss of sensations such as touch, pressure, and temperature; it sometimes also causes pain. Other serious consequences can include exaggerated reflexes; loss of bladder and bowel control; sexual dysfunction; lost or decreased breathing capacity; impaired cough reflexes; and Spasticity (abnormally strong muscle contractions). Most people with spinal cord injury regain some functions between a week and six months after injury, but the likelihood of spontaneous recovery diminishes after six months. Rehabilitation strategies can minimize the long-term disability.
Spinal cord injuries can lead to many secondary complications, including pressure sores, increased susceptibility to respiratory diseases, and Autonomic Dysreflexia. Autonomic dysreflexia is a potentially life-threatening increase in blood pressure, sweating, and other autonomic reflexes in reaction to bowel impaction or some other stimulus. Careful medical management and skilled supportive care is necessary to prevent these complications.
Researchers studying spinal cords obtained from autopsy have identified several different types of spinal cord injuries. The most common types of spinal cord injuries found in one large study were contusions (bruising of the spinal cord) and compression injuries (caused by pressure on the spinal cord). Other types of injury included lacerations, caused by a bullet or other object, and Central Cord Syndrome.
In contusion injuries, a cavity, or hole, often forms in the center of the spinal cord. Myelinated axons typically survive in a ring along the inside edge of the cord. Some axons may survive in the center cavity, but they usually lose their myelin covering. This Demyelination greatly slows the speed of nerve transmission. Slowing of nerve impulses can be measured by a diagnostic technique called transcranial magnetic stimulation (TMS).
Another example of a spinal cord injury is central cord syndrome, which affects the cervical (neck) region of the cord and results from focused damage to a group of nerve fibers called the corticospinal tract. The corticospinal tract controls movement by carrying signals between the brain and the spinal cord. Patients with central cord syndrome typically have relatively mild Impairment, and they often spontaneously recover many of their abilities. Patients usually recover substantially by 6 weeks after injury, despite continued loss of axons and myelin. Delays in motor responses persist, but permanent impairment is usually confined to the hands.
Complete severing of the spinal cord is rare in humans, but even axons that survive the initial injury often lose their ability to function. Secondary damage, which continues for hours, can cause loss of myelin, degeneration of axons, and nerve cell death. Patients with their spinal cords completely severed often show abnormal reflexes that emerge more than 8 months after injury. These reflexes, such as twitching of muscles in the arm and hand in response to sensory stimulation of the legs and feet, may result from “sprouting” of new branches from sensory fibers just below the Lesion. They may also result from activation of nerve pathways that are normally suppressed. Other abnormal responses, such as sweating in response to movement of a hair, may be due to sprouting of nerves in the Autonomic Nervous System. The autonomic nervous system is the part of the PNS that controls involuntary body functions such as sweating and heart rate.
Since even a small number of nerve fibers can support significant nervous system function, measures that reduce damage could allow much greater function than would otherwise be expected. Devising interventions that will achieve this goal is one of the major challenges in spinal cord injury research today.
Medical care of spinal cord injury has advanced greatly in the last 50 years. During World War II, injury to the spinal cord was usually fatal. While postwar advances in emergency care and rehabilitation allowed many patients to survive, methods for reducing the extent of injury were virtually unknown. Although techniques to reduce secondary damage, such as cord irrigation and cooling, were first tried 20 to 30 years ago, the principles underlying effective use of these strategies were not well understood. Significant advances in recent years, including an effective drug therapy for acute spinal cord injury (methylprednisolone) and better imaging techniques for diagnosing spinal damage, have improved the recovery of patients with spinal cord injuries.
Current care of acute spinal cord injury involves three primary considerations. First, physicians must diagnose and relieve cord compression, gross misalignments of the spine, and other structural problems. Second, they must minimize cellular-level damage if at all possible. Finally, they must stabilize the Vertebrae to prevent further injury.
The care and treatment of persons with a suspected spinal cord injury begins with emergency medical services personnel, who must evaluate and immobilize the patient. Any movement of the person, or even resuscitation efforts, could cause further injury. Even with much-improved emergency medical care, many people with spinal cord injury still die before reaching the hospital.
Methylprednisolone, a steroid, has become standard treatment for acute spinal cord injury since 1990, when a large-scale clinical trial showed significantly better recovery in patients who began treatment with this drug within 8 hours of their injury. Methylprednisolone reduces the damage to cellular membranes that contributes to neuronal death after injury. It also reduces inflammation near the injury and suppresses the activation of immune cells that appear to contribute to neuronal damage. Preventing this damage helps spare some nerve fibers that would otherwise be lost, improving the patient’s recovery.
A controversial topic in the acute care of spinal cord injury is whether surgery to reduce pressure on the spinal cord and stabilize it is better than traction alone. A study in the 1970s showed that, in some cases, surgical intervention actually worsened the patient’s condition. This finding prompted many physicians to become more conservative about using these techniques, although advances in care since that time have reduced the risk of complications due to surgery. While there is no proof that surgeons must operate to decompress the spinal cord within the 8-hour time window established for methylprednisolone, many believe it may help and try to do it then. Early surgery also allows earlier movement and earlier Physical Therapy, which are important for preventing complications and regaining as much function as possible. Use of imaging methods such as computed tomography (CT) scans to visualize fractures and magnetic resonance imaging (MRI) to image contusions, disc herniation, and other damage can help define the appropriate treatment for a particular patient. Several types of metal plates, screws, and other devices also are now available for surgically stabilizing the spine.
Once a patient’s condition is stabilized, care and treatment focus on supportive care and rehabilitation strategies. Attention to supportive care can prevent many complications. For example, periodically changing the patient’s position can prevent pressure sores and respiratory complications. Rehabilitation, which focuses on the patient’s physical and emotional recovery, is also very important. Almost all patients with spinal cord injuries can now achieve a partial return of function with proper physical therapy that maintains flexibility and function of the muscles and joints. Physical therapy can also help reduce the risk of blood clots and boost the patient’s morale, while counseling can help a person adjust emotionally to the injury and its consequences.
Recent years have seen many advances in understanding and treating spinal cord injury. These include the development of CT and MRI scans to visualize injuries and the use of methylprednisolone to reduce damage. However, many facets of what happens when the spinal cord is injured are still unknown. An exact description of the structural and tissue changes that occur in spinal cord injury is necessary for planning effective interventions. Studies aimed at better describing what happens following spinal cord injury may lead to improved treatments.