Causes and Symptoms
Most people take certain basic tasks for granted, such as walking up a flight of stairs, brushing their teeth, or using a personal computer. Motor neurons in the
spinal cord control the hundreds of muscle fibers that are involved in each of these activities. At the same time, other neurons of the spinal cord serve as part of the sensory pathways that provide information regarding body position and motion, which contributes to the coordination of these activities. In amyotrophic lateral sclerosis (ALS)
, also known as Lou Gehrig’s disease, the motor neurons in the spinal cord die, leaving patients without control of their muscles. This example of a spinal disorder serves to emphasize the important role that the spinal cord plays as it serves as an interface (input-output system) between the brain and the body.
Similarly, most people have experienced pain in the hand, which is followed by an instantaneous, automatic movement of the hand away from the object causing that pain. Such reflexes represent the simplest of movements, yet they still require the integrative and relay action of neurons of the spinal cord to cause immediate hand withdrawal without requiring the individual to think about the act consciously. Only after the reflex has occurred does the spinal cord activity “inform” the brain that something happened. Therefore, in addition to sensory and motor interface functions for the brain, the spinal cord performs basic integration tasks as it controls reflexes, contributes to the coordination of movement between the left and right sides of the body, and prevents opposing muscle groups from trying to move a joint in opposite directions at the same time. As with any other vital organ of the body, spinal cord damage or defects have serious consequences for the health and well-being of humans.
In the medical research laboratory,
paralysis results from complete or partial transection of the spinal cord. In the real world, a fracture or dislocation of vertebrae or damage done by a bullet can cause paralysis in the same fashion. Acute transection of the spinal cord can also result from an inflammatory condition or from any situation in which the spinal cord is compressed, such as by a tumor. The spinal cord is contained within the vertebral column, which is divided into the cervical, thoracic, lumbar, and sacral regions, each of which is associated with a specific set of functions. Transection typically results in the loss of sensory and motor functions below the level of the lesion.
Spinal cord injuries and defects are the result of three basic types of pathological conditions. The first of these conditions is traumatic physical injury to spinal cord tissue, such as the severing of the spinal cord during a car accident. The second condition is a congenital or inherited genetic problem with spinal cord development and function, as illustrated by spina bifida. The third is an acquired condition, such as damage caused by a viral or bacterial infection. In each case, the severity of the pathological condition is dependent upon the location and extent of the resultant spinal cord lesion. In the clinical setting, physicians utilize information regarding all aspects of spinal cord function, such as sensory, motor, reflex, and coordination functions, as well as information from a variety of imaging techniques to diagnose pathological conditions and select appropriate treatments.
Trauma. The neurons of the spinal cord carry out their functions by way of their long nerve processes (axons), which extend to form synapses with, and control, target cells (muscles and other neurons). Some of these nerve processes extend out of the spinal cord to the body, others extend either up to or down from higher-brain regions, and yet others extend from one side of the spinal cord to another. Trauma mainly damages the nerve process of cells and in this fashion disrupts their function in controlling target neurons and muscles. Often, after nerve processes have been damaged, the neuron itself will die because of loss of neurotrophic influences from their target cells. It has been estimated that every year, between ten thousand and twelve thousand people in the United States are disabled by some degree of paralysis resulting from traumatic injury to the spinal cord. The spinal cord can be also damaged by blocked blood flow to the cord, blood accumulation (hematoma) in or near the cord, or the presence of a ruptured or herniated disk, all of which can be caused by trauma.
Congenital defects. Spinal cord defects are not the result of trauma but rather are generally attributed to abnormal events during
embryonic development. In particular, most major spinal cord defects arise around the third week of development. During this time, the flattened neural plate is beginning to fold upward as its lateral edges come together and fuse to form the top margin (dorsal aspect) of the neural tube. If this process is incomplete, then the spinal cord remains open and exposed along the embryo’s back, as the vertebral bones fail to surround the spinal cord tissue completely. This condition is referred to as spina bifida. Often, rather than simply being exposed, some normal contents of the vertebral canal, including spinal cord tissue, protrude out of the back as a bulge. Spina bifida is most common in the lower lumbar and upper sacral regions of the spine, but more severe cases may involve the cervical and thoracic regions.
Depending on the level and extent of the defect, the clinical symptoms of spinal abnormalities range from mild impairment to fatality. The type of neural tube defect seen in spina bifida often causes some degree of motor and sensory handicap. The cerebrospinal fluid is continuous from the ventricles of the brain to the central canal of the spinal cord. If the spinal defect impairs the normal flow of cerebrospinal fluid, other problems may occur, such as retardation resulting from
hydrocephalus (fluid on the brain). Although there is still much to learn about the causes of spinal cord defects, in many cases scientific evidence points the finger at genetic problems (mutations) and the disruptive action of teratogens such as environmental pollutants and drugs.
Infections. Acquired spinal cord lesions are related to such conditions as tumor development and viral or bacterial infections. In general, invasion of the spinal cord by viruses or bacteria can produce inflammation known as myelitis.
Multiple sclerosis (MS) and ALS are the two most common nontraumatic disorders of the spinal cord. Many of the nerve fibers of the central nervous system are covered by a myelin sheath produced by neuroglia cells, known as oligodendrocytes. This sheath contributes to the speed and efficiency of the nerve cells as they carry electrical information. MS involves the destruction of this important myelin sheath, which leads to the disruption of motor and sensory nerve pathway functions, manifested by such symptoms as abnormal sensations, paralysis, and exaggerated reflexes. Although its cause is not clearly understood, researchers believe that viral infections are involved in some cases, while in others the individual’s own immune system might be mistakenly destroying normal myelin tissue (an autoimmune disorder). ALS is a fatal condition that is restricted to the loss of motor neurons. As with MS, there is much speculation regarding the causes of ALS. Acquired immunodeficiency syndrome (AIDS) is a viral infection that can involve the disruption of spinal cord neuron function.
Other infections that can cause spinal cord lesions include tabes dorsalis,
poliomyelitis, meningitis, and syringomyelia. Tabes dorsalis involves the degeneration of sensory neurons from the dorsal region of the spinal cord as a result of the invasion of the syphilis spirochete bacterium. The polio virus infects and kills spinal motor neurons in a disease called poliomyelitis; if the disease destroys the brain-stem neurons that control respiration and heart rate, then this condition is fatal. Meningitis is a bacterial inflammation of the layers of cells that cover the spinal cord (collectively referred to as meninges), producing high fever and sometimes inducing a comatose state that can lead to death.
Tumors and cysts
. Growths within the spinal cord can also disrupt normal spinal cord function. Syringomyelia is such a condition, in which fluid-filled cysts develop among the neurons of the spinal cord. Cancerous tumors are often the result of uncontrolled growth of the neuroglia cells, which can damage neurons and nerve fiber pathways.
Treatment and Therapy
Spinal cord defects, either congenital or hereditary, pose serious challenges for the medical community. Surgical intervention is the only option in mild cases of spina bifida; in severe cases, there is no effective treatment. The advent of intrauterine surgery prior to the birth of the baby for the correction of minor cases of spina bifida is a major step toward alleviating serious problems. It is believed that better prenatal care may reduce the risk of spinal cord defects. For example, consumption of the vitamin folic acid in pregnancy greatly reduces the incidence of spina bifida. Numerous other causative factors have been implicated in spinal cord defects, including alcoholism, drug use, and even environmental pollution. In some cases, genetic screening may provide a method to reduce certain types of defects, while in other cases reduced exposure to risk elements is the most effective preventive action.
Treatments for acquired spinal cord injury involve antiviral and antibacterial drugs that combat infection and, in so doing, reduce inflammation and cell damage. It is clear that early detection and intervention is an important factor in being able to save as many neurons as possible and limit the extent of the lesion. Neurotrophic factors are likely to be important therapeutic agents as doctors try to stimulate the maximum recovery of neuronal function. In cases in which the immune system itself may be damaging healthy neurons, as is suspected in some cases of MS, drugs are used to suppress immune function.
Perspective and Prospects
Medical researchers are taking numerous approaches to understanding spinal cord development and function in the hope of utilizing that information to develop new therapies to prevent or treat these clinical conditions. One interesting aspect of the problem is that, unlike most other organ systems, the adult
nervous system appears to retain only a few selected stem cell populations after embryonic development. Stem cell populations are groups of cells that divide to produce cells for the growth and regeneration of tissues and organs.
It was previously believed that human babies were born with all the neurons in their central nervous system that they would ever have, meaning that no new neurons would be produced. Recent work in rodents and nonhuman primates, however, has unequivocally demonstrated that neural stem cells exist in the adult mammalian brain and give rise to millions of new neurons during an individual’s life span. This process generates new neurons predominantly in two areas of the brain—the olfactory bulb, which controls the sense of smell, and the hippocampus, a memory center—but not to any appreciable extent in other brain areas. Scientists are beginning to identify stem cells in other brain regions, but there appear to be only a few, and those lack the ability to repair spinal cord injuries. Many laboratories are working on harnessing the potential of stem cells for cell replacement therapies, which hold significant promise for brain repair. As an individual ages, the nervous system becomes more efficient in processing information as neural networks are modified. This modification involves changes in nerve cell connections (plasticity) and new neuron generation (neurogenesis), but only in a few areas of the adult brain. Researchers hope to utilize information about the biological basis of normal plasticity to help repair damaged or impaired nervous systems.
Modern neuroscience research quickly vanquished the long-held belief that it is impossible to repair neurons damaged by trauma or disease. Experiments with animals and in tissue culture have demonstrated that damaged neurons can survive, regrow nerve processes, and once again carry electrical impulses. In fact, neurons from human spinal cords have been grown in tissue culture under conditions that stimulated them to regrow their axonal process. One of the most important aspects of understanding nervous system development is the fact that the cells communicate with one another not only with neurotransmitters but also with neurotrophic factors. Basic research and clinical trials are being done on neurotrophic factors with the expectation that they will become important parts of therapeutic treatments to stimulate the repair and regeneration of damaged neurons. These neurotrophic factors hold such promise because they are important in stimulating normal cell differentiation during embryonic development and for the subsequent survival of neurons after birth into adulthood. Therefore, clinical treatments are being designed to recreate the embryonic conditions that contributed to normal development. In addition, it is believed that one of the major factors in the lack of a regeneration response in damaged spinal cords is that the neuroglia cells, known as astrocytes, form scar tissue that is not conducive to nerve fiber regeneration. Therefore, medical researchers are looking at treatments that, in addition to prolonging the life of neurons, reduce the formation of scar tissue.
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