Transverse Myelitis: Symptoms, Causes and Diagnosis

Joanne Lynn, M.D.

Transverse myelitis (TM) is a neurologic syndrome caused by inflammation of the spinal cord. TM is uncommon but not rare. Conservative estimates of incidence per year vary from 1 to 5 per million population (Jeffery, et.al., 1993). The term myelitis is a nonspecific term for inflammation of the spinal cord; transverse refers to involvement across one level of the spinal cord. It occurs in both adults and children. You may also hear the term myelopathy, which is a more general term for any disorder of the spinal cord.

Clinical Symptoms

TM symptoms develop rapidly over several hours to several weeks. Approximately 45% of patients worsen maximally within 24 hours (Ibid.). The spinal cord carries motor nerve fibers to the limbs and trunk and sensory fibers from the body back to the brain. Inflammation within the spinal cord interrupts these pathways and causes the common presenting symptoms of TM which include limb weakness, sensory disturbance, bowel and bladder dysfunction, back pain and radicular pain (pain in the distribution of a single spinal nerve).

Almost all patients will develop leg weakness of varying degrees of severity. The arms are involved in a minority of cases and this is dependent upon the level of spinal cord involvement. Sensation is diminished below the level of spinal cord involvement in the majority of patients. Some experience tingling or numbness in the legs. Pain (ascertained as appreciation of pinprick by the neurologist) and temperature sensation are diminished in the majority of patients. Appreciation of vibration (as caused by a tuning fork) and joint position sense may also be decreased or spared. Bladder and bowel sphincter control are disturbed in the majority of patients. Many patients with TM report a tight banding or girdle-like sensation around the trunk and that area may be very sensitive to touch.

Recovery may be absent, partial or complete and generally begins within 1 to 3 months. Significant recovery is unlikely, if no improvement occurs by 3 months (Feldman, et. al., 1981). Most patients with TM show good to fair recovery. TM is generally a monophasic illness (one-time occurrence); however, a small percentage of patients may suffer a recurrence, especially if there is a predisposing underlying illness.

Causes of Transverse Myelopathy and Myelitis

Transverse myelitis may occur in isolation or in the setting of another illness. When it occurs without apparent underlying cause, it is referred to as idiopathic. Idiopathic transverse myelitis is assumed to be a result of abnormal activation of the immune system against the spinal cord. A list of illnesses associated with TM includes:

Table: Diseases Associated with Transverse Myelitis

Parainfectious (occurring at the time of and in association with an acute infection or an episode of infection).

Viral: herpes simplex, herpes zoster, cytomegalovirus, Epstein-Barr virus, enteroviruses (poliomyelitis, Coxsackie virus, echovirus), human T-cell, leukemia virus, human immunodeficiency virus, influenza, rabies

Bacterial: Mycoplasma pneumoniae, Lyme borreliosis, syphilis, tuberculosis

Postvaccinal (rabies, cowpox)

Systemic autoimmune disease

Systemic lupus erythematosis

Sjogren's syndrome

Sarcoidosis

Multiple Sclerosis

Paraneoplastic syndrome

Vascular

Thrombosis of spinal arteries

Vasculitis secondary to heroin abuse

Spinal arterio-venous malformation

The cause of idiopathic transverse myelitis is unknown, but most evidence supports an autoimmune process. This means that the patient's own immune system is abnormally stimulated to attack the spinal cord and cause inflammation and tissue damage. Examples of autoimmune diseases which are more common include rheumatoid arthritis, in which the immune system attacks the joints, and multiple sclerosis, in which myelin, the insulating material for nerve cells in the brain, is the target of autoimmune attack.

TM often develops in the setting of viral and bacterial infections, especially those which may be associated with a rash (e.g., rubeola, varicella, variola, rubella, influenza, and mumps). Approximately one third of patients with TM report a febrile illness (flu-like illness with fever) in close temporal relationship to the onset of neurologic symptoms. In some cases, there is evidence that there is a direct invasion and injury to the cord by the infectious agent itself (especially poliomyelitis, herpes zoster, and AIDS). A bacterial abscess can also develop around the spinal cord and injure the cord through compression, bacterial invasion and inflammation.

However, experts believe that in many cases infection causes a derangement of the immune system which leads to an indirect autoimmune attack on the spinal cord, rather than a direct attack by the organism. One theory to explain this abnormal activation of the immune system toward human tissue is termed "molecular mimicry." This theory postulates that an infectious agent may share a molecule which resembles or "mimics" a molecule in the spinal cord. When the body mounts an immune response to the invading virus or bacterium, it also responds to the spinal cord molecule with which it shares structural characteristics. This leads to inflammation and injury within the spinal cord.

Vaccination is well known to carry a risk of the development of acute disseminated encephalomyelitis (ADEM) which is an acute inflammation of the brain and spinal cord. This was particularly common with the older antirabies vaccine which was grown in animal spinal cord cultures; the use of the newer antirabies vaccine grown in human tissue culture has almost eradicated this complication. This is also thought to occur as an immune system response.

Transverse myelitis may be a relatively uncommon manifestation of several autoimmune diseases including systemic lupus erythematosis (SLE), Sjogren's syndrome, and sarcoidosis. SLE is an autoimmune disease of unknown cause which affects multiple organs and tissues in the body. Features of this illness include arthralgias (joint pain) and arthritis (joint inflammation), rashes, kidney inflammation, low blood counts (including white and red blood cells, platelets), oral ulcers and the presence of abnormal autoantibodies (antibodies which are directed against the person's own tissues) in the blood. The fully developed syndrome of SLE is easy to recognize; however, this illness may begin with just one or two signs and is then more difficult to diagnose.

Sjogren's disease is another autoimmune disease characterized by invasion and infiltration of the tear and salivary glands by (lymphocytes) white blood cells with resultant decreased production of these fluids. Patients complain of dry mouth and dry eyes. Several tests can support this diagnosis: the presence of a SS-A antibody in the blood, ophthalmologic tests that confirm decreased tear production and the demonstration of lymphocytic infiltration in biopsy specimens of the small salivary glands (a minimally invasive procedure). Neurologic manifestations are unusual in Sjogren's syndrome, but TM can occur.

Sarcoidosis is a multisystem inflammatory disorder of unknown cause manifested by enlarged lymph nodes, lung inflammation, various skin lesions, liver and other organ involvement. In the nervous system, various nerves, as well as the spinal cord, may be involved. Diagnosis is generally confirmed by biopsy demonstrating features of inflammation typical of sarcoidosis.

Multiple sclerosis is an inflammatory autoimmune disease of the central nervous system (brain and spinal cord) which results in demyelination or loss of myelin (the insulating material on nerve fibers) with resultant neurologic dysfunction. A definite diagnosis of MS is not given until a patient has had at least two attacks of demyelination (hence, multiple) at two different sites in the central nervous system. The spinal cord is frequently affected in multiple sclerosis and may be the site of involvement of the first attack of MS. This presents the possibility that patients with acute transverse myelitis could later go on to have a second episode of demyelination and receive a diagnosis of MS.

Just what percentage of patients with a first attack of acute transverse myelitis will go on to develop MS is unclear in the medical literature, ranging from 15 to 80%; however, the majority of studies show a low risk. We do know that patients who have abnormal MRI scans of the brain with lesions like those seen in MS are much more likely to go on to develop MS than those who have normal brain MRIs at the time of their myelitis (between 60 and 90% for those with abnormal brain scans, less than 20% for those with normal scans in one study). It is also suggested in the medical literature that patients with "complete" transverse myelitis (which means severe leg paralysis and sensory loss) are less likely to develop MS than those who had a partial or less severe case. The literature also suggests that patients who have abnormal antibodies in their spinal fluid, called oligoclonal bands, are at higher risk to develop MS subsequently.

Myelitis related to cancer (called a paraneoplastic syndrome) is uncommon. There are several reports in the medical literature of a severe myelitis occurring in association with a malignancy. In addition, there are a growing number of reports of cases of myelopathy associated with cancer in which the immune system produces an antibody to fight off the cancer and this cross-reacts with the molecules in the spinal cord neurons. It should be emphasized that this is an unusual cause of myelitis.

Vascular causes are listed because they present with the same problems as transverse myelitis; however this is really a distinct problem primarily due to inadequate blood flow to the spinal cord instead of actual inflammation. The blood vessels to the spinal cord can close up with blood clots or atherosclerosis or burst and bleed; this is essentially a "stroke" of the spinal cord.

Diagnosis

The general history and physical examination are first performed, but often do not give clues about the cause of spinal cord injury. The first concern of the physician who evaluates a patient with complaints and examination suggestive of a spinal cord disorder is to rule out a mass-occupying lesion which might be compressing the spinal cord. Potential lesions which might compress the cord include tumor, herniated disc, stenosis (a narrowed canal for the cord), and abscess. This is important because early surgery to remove the compression may sometimes reverse neurologic injury to the spinal cord. The easiest test to rule out such a compressive lesion is magnetic resonance imaging of the appropriate levels of the cord. However, if MRI is not available or the images are equivocal, myelography must be performed. A myelogram is a set of X-rays taken after a lumbar puncture has been performed either in the neck or in the low back and a contrast agent (dye) is injected into the sac that surrounds the spinal cord. The patient is then tilted up and down to let the dye flow and outline the spinal cord while the X-rays are taken.

If the MRI or myelogram shows no mass lesion outside or within the spinal cord, then the patient with spinal cord dysfunction is thought to have transverse myelitis or vascular problems. The MRI can sometimes show an inflammatory lesion within the cord. It is difficult to get to the cause of the inflammation, because biopsy is rarely done on the spinal cord because of the damage this would cause. The physician would next send blood for general bloodwork and studies for SLE and Sjogren's syndrome, HIV infection, vitamin B12 level to rule out deficiency and a test for syphilis. The next test which is commonly performed is a lumbar puncture to obtain fluid for studies, including white cell count and protein to look for inflammation, cultures to look for infections of various types, and tests to examine for abnormal activation of the immune system (immunoglobulin level and protein electrophoresis). A MRI of the brain is often performed to screen for lesions suggestive of MS. If none of these tests are suggestive of a specific cause, the patient is presumed to have idiopathic transverse myelitis or parainfectious transverse myelitis, if there are other symptoms to suggest an infection.

References

1. Jeffery DR, Mandler RN, Davis LE. "Transverse myelitis: retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events." Arch Neurol, 1993; 50:532.

2. Berman M, Feldman S, Alter M, et. al. "Acute transverse myelitis: incidence and etiological considerations." Neurology, 1981; 31:966.

3. Stone LA. "Transverse Myelitis" in Rolak LA and Harati Y (eds.) Neuroimmunology for the Clinician. Boston, MA: Butterworth-Heinemann, 1997; 155-165.


Dr. Lynn is an Assistant Professor of Neurology at The Ohio State University. She received her medical degree from The Ohio State College of Medicine and then served residencies in internal medicine and neurology at Stong Memorial Hospital, University of Rochester. She then returned to The Ohio State University for fellowship training in neuromuscular disease. She is currently on the staff of The Ohio State University Multiple Sclerosis Center and has special interests in clinical research on the treatment of MS.

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