Diagnosis of TM is based on clinical and radiological findings. Clinical characteristics of myelopathy are bilateral signs and/or symptoms of sensory, motor or autonomic dysfunction attributable to the spinal cord or a clearly defined sensory level. Evidence of inflammation either on MRI as gadolinium enhancement or on lumbar puncture as elevated white blood cells or IgG index is frequently observed.
If a myelopathy is suspected based on history and physical examination, a gadolinium-enhanced magnetic resonance imaging (MRI) of the spinal cord is first obtained to assess if there is a compressive or inflammatory (gadolinium enhancing) lesion as signs and symptoms may be alike. It is essential to rule out compressive myelopathy (compression of the spinal cord), which can be caused by a tumor, herniated disc, stenosis (a narrowed canal for the cord), hematoma or abscess. Identifying these disorders is critical since immobilization to prevent further injury and early surgery to remove the compression may sometimes reverse neurologic injury to the spinal cord.
Lumbar puncture is used to look for surrogate markers for inflammation in the cerebrospinal fluid (CSF). These include elevated white cell counts, elevated protein and an elevated IgG index. It should be noted, however, that a significant percentage of individuals with a clinical pattern that otherwise resembles TM do not meet these inflammatory features and, therefore, the absence of inflammatory markers does not rule out TM.
To identify the underlying cause of the inflammatory process, further tests are recommended to assess for the presence of a systemic inflammatory disease – such as Sjögren’s syndrome, Lupus (SLE) and neurosarcoidosis. It is important to test for HIV infection, syphilis, vitamin B12 and copper levels to rule out possible causes of myelopathy.
A MRI of the brain is performed to screen for lesions suggestive of MS. If none of these tests are suggestive of a specific cause, the diagnosis is idiopathic transverse myelitis or parainfectious transverse myelitis (if there are other symptoms to suggest an infection).
In the absence of a systemic inflammatory disease, the regional distribution of demyelination within the CNS should be defined since several disorders (i.e. MS, NMOSD, or ADEM) may present with TM as the initial manifestation of a multiphasic disease. NMOSD involves primarily, but not exclusively, the optic nerve and the spinal cord. A gadolinium-enhanced brain MRI and visual evoked potential should be obtained to look for these entities. The absence of multifocal areas of demyelination would suggest a diagnosis of isolated TM and lead to appropriate treatment measures.
Non-inflammatory myelopathies include those caused by arterial or venous ischemia (blockage), vascular malformations, radiation, fibrocartilaginous embolism or nutritional/metabolic causes and appropriate work ups under these situations might include aortic ultrasound, spinal angiogram or evaluation of pro-thrombotic risk factors.
Sub-Types of Myelitis (Longitudinally Extensive and Partial Myelitis)
Within the category of idiopathic TM, it may be of further value to distinguish between acute partial TM, acute complete TM and longitudinally extensive TM (LETM), since these syndromes present distinct differential diagnoses and prognoses.
Acute partial transverse myelitis refers to mild or grossly asymmetrical spinal cord dysfunction with an MRI lesion of less than 3 vertebral segments. Acute complete TM refers to complete or near complete clinical deficits below the lesion and an MRI lesion of less than 3 vertebral segments. LETM has a complete or incomplete clinical picture but an MRI lesion that is longer than or equal to 3 vertebral segments. By definition, a brain MRI is considered to be negative in this population. There is a lesser likelihood of presenting with oligoclonal bands (abnormal antibodies), or relapse with a second bout of myelitis, and a very low transition rate to MS (likely < 5 percent).
The possible causes of transverse myelitis can be quite varied. Transverse myelitis may occur in isolation or in the setting of another illness. Idiopathic transverse myelitis is assumed to be a result of abnormal and excessive activation of an immune response against the spinal cord that results in inflammation and tissue damage.
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). The term parainfectious suggests that the neurologic injury associated with TM may be related to direct microbial infection and injury as a result of the infection, direct microbial infection with immune-mediated damage against the agent, or remote infection followed by a systemic response that induces neural injury. Approximately one third of individuals 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, AIDS and Lyme neuroborreliosis). However, causality has not been established. A bacterial abscess can also develop around the spinal cord and injure the cord through compression, bacterial invasion and inflammation.
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 that 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.
Although a causal relationship has not been established, TM has been anecdotally reported following influenza and booster Hepatitis B vaccinations. One theory suggests that it is possible that the vaccination may have excited an autoimmune process. It is critically important to bear in mind that extensive research has demonstrated that vaccinations are safe, and the potential link to TM may only be coincidental or at worst an exceptionally rare complication.
As mentioned above, TM may be a relatively uncommon manifestation of several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren’s syndrome, and sarcoidosis. SLE is an autoimmune disease of unknown cause that affects multiple organs and tissues in the body. Sjogren’s disease is another autoimmune disease characterized by invasion and infiltration of the tear and salivary glands by white blood cells with resultant decreased production of these fluids leading to 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 spinal cord inflammation (transverse myelitis) can occur. Sarcoidosis is a multisystem inflammatory disorder of unknown cause and 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.
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 noted 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.