Transverse Myelitis (TM)
Transverse myelitis is a localized inflammatory disorder of the spinal cord that results in weakness, numbness and bowel, bladder and sexual dysfunction. It is a rare disorder with an incidence of between one and eight new case per million people a year. TM is one of a group of disorders in which the immune system becomes abnormally activated and “attacks” and injures the nervous system. The inflammation is confined to the spinal cord and usually occurs only once.
At Johns Hopkins, we have established the only transverse myelitis clinical and research center in the United States. We have dramatically improved the treatments and care of TM patients. As part of that effort, in 2001 we formed an international group of academic centers dedicated to defining the critical clinical features and natural history of TM. One of the immediate benefits of this group has been the publication of a critical paper in the medical literature which defined diagnostic criteria of TM and proposed a strategy for diagnosing and treating patients. This paper has been of great service to treating physicians throughout the world who have utilized it to rapidly diagnose and treat patients. We are aware of many examples where this approach has resulted in paralyzed patients returning to normal or near normal function.
Much work still remains to understand the natural history and the pathogenesis of transverse myelitis. There are three areas that require advanced understanding and research:
- A common underlying theme of ALL autoimmune diseases is that the central function of the normal immune system is to attack foreign substances and to ignore self tissue. The central derangement of the abnormal immune system is to attack self tissue. It is critical to understand the events that trigger the immune system to become abnormally activated. What are the “triggers” and what is the genetic susceptibility that renders some patients susceptible to that “trigger” while others are relatively resistant?
- Once the immune system is “tricked” into thinking that the nervous system is a “target,” how does it injure the brain and spinal cord? What are the cell injury pathways? How can we block them to render the nervous system resistant to injury during this attack from the immune system? We have begun to identify novel strategies that allow the nervous system to withstand the immunologic attack. These strategies will ultimately be applicable to a wide array of neurologic disorders, including Alzheimer’s disease, Parkinson’s disease, traumatic spinal cord injury and stroke.
- How do we restore function to patients with neurologic injury and paralysis as a result of transverse myelitis? Following the inflammatory injury, many patients are left with a spinal cord injury in which nerve cells in the spinal cord have died, leading to permanent weakness, loss of sensation and bowel and bladder dysfunction. Recently, we have learned how to direct stem cells to become motor neurons AND how to begin to direct them to reconnect with muscle. This represents the only hope for restoration of function in patients with long-standing paralysis. Recently, we and others have proved that this is a realistic goal and we believe it WILL be achieved in the future.
Multiple Sclerosis (MS)
Multiple sclerosis is a chronic disease affecting the central nervous system (the brain and spinal cord). It occurs when the immune system attacks nerve fibers and myelin sheathing in the brain and spinal cord, resulting in abnormal nervous system function. Myelin is a fatty substance that surrounds healthy nerve fibers, insulating the fibers to help transmission of electrical messages along the nerves to various parts of the body. Nerve cell processes and myelin sheathing are destroyed by the inflammation that occurs with this abnormal immune attack, causing an interruption or distortion of the message.
There are several types of MS that reflect different courses of illness:
Relapsing-Remitting MS:
At the time of diagnosis, 90 percent of patients will have relapsing-remitting pattern of disease. This form of multiple sclerosis is characterized by the onset of the following symptoms over a period of hours to days:
- Numbness
- Tingling
- Blurred vision
- Unsteady gait
These symptoms tend to persist for days or weeks, and then disappear partially or completely on their own or with treatment. Patients may then remain symptom-free for weeks, months or even years. The periods of disease activity are called exacerbations or relapses. The periods without symptoms are called remissions. Without treatment, most people with MS will develop disease symptoms that will gradually worsen over time. In most cases, this will be without discernable relapses and remissions.
Secondary Progressive MS:
If the condition progresses to a point where there are no discernable relapses and remissions, the diagnosis is secondary progressive MS.
Primary Progressive MS:
About 10-15 percent of patients will have gradual worsening from the start of their MS disease. This is referred to as primary progressive MS.
Benign MS:
Benign MS is a mild course where an individual will have mild disease after having MS for about 15 years. This occurs in about 5-10 percent of patients. There is no good way of predicting which patients will follow this course.
Multiple Sclerosis typically affects those with the following characteristics:
- MS usually affects young adults, typically between the ages of fifteen and fifty.
- MS affects women more often than men.
- MS affects people of European descent more often than individuals of African or Asian ancestry.
- MS occurs more frequently in temperate zones than states near the equator.
- People with family members diagnosed with MS are at a slightly higher risk for developing the disease.
The exact cause of MS is unknown. It appears to be an autoimmune disease in which the immune system is stimulated to attack myelin in the central nervous system. The source of the initial stimulus has not been clearly identified. In certain people who inherit a predisposition to MS, the trigger may be infections (such as viruses) or other factors in the environment. Individuals may also have a genetic predisposition for developing the disease as people with family members diagnosed with MS are at a slightly higher risk.
Symptoms vary greatly from person to person, over time and in intensity. They may include sensory symptoms, such as paresthesia (numbness and tingling) and pain, visual symptoms such as double vision, motor symptoms such as weakness, tremor, dizziness, spasticity, autonomic symptoms such as frequent urination, urgency and other symptoms, such as fatigue.
The Relationship Between Transverse Myelitis and Multiple Sclerosis
TM and MS are both inflammatory disorders of the central nervous system where the immune system becomes abnormal and attacks the nervous system. TM is largely a “one-time” disease (monophasic) that involves only the spinal cord. MS is always a “many-time” disease (multiphasic) that involves the brain, optic nerves and spinal cord. Regardless of the regional specificity and temporality, the underlying mechanisms of these two diseases are largely similar. What makes this collaboration interesting and productive is that depending on the series, 15-to-43 percent of TM patients may ultimately be diagnosed with MS.
Further, TM is a unique model system to study novel neuroprotective and neurorestorative therapies. This is because of the monofocal and monophasic nature of the disease. Where all injury and subsequent disability in TM can be attributed to one lesion in the spinal cord, in MS it is a cumulative burden of disease based on number and location of lesions. The use of TM as a model system to study novel therapies is largely due to the fact that one can measure outcomes quickly and understand mechanisms better, thereby enabling the development of clinical trials soon in diseases such as MS.
