Diagnosis of TM is based on clinical features, imaging, and laboratory findings. Clinical characteristics of spinal cord injury are bilateral signs and/or symptoms of sensory, motor or autonomic dysfunction attributable to the spinal cord or a clearly defined sensory level. Evaluation for signs of inflammation to distinguish TM from other spinal cord disorders typically involves a magnetic resonance imaging (MRI) of the spine with contrast and spinal fluid analysis (which requires a lumbar puncture).¹⁹

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 can overlap. 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.¹⁹

Lumbar puncture is used to look for surrogate markers of inflammation in the cerebrospinal fluid (CSF). These include elevated white cell counts, elevated protein or other markers such as oligoclonal bands. While these markers are supportive of TM, it should be noted that they are not present in all individuals.¹⁹

A series of blood tests are often recommended for patients with spinal cord disorder suspicious for TM. This commonly includes testing for aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) antibodies, in addition to tests associated with systemic autoimmune disorders such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome. If sarcoidosis is suspected based upon history and imaging characteristics, a CT of the chest may be considered to look for lung findings. Other common ordered tests include HIV, syphilis, vitamin B12 and copper levels.¹⁹

An MRI of the brain is often performed to screen for lesions suggestive of a demyelinating disorder such as MS, NMOSD, or MOG antibody disease. In patients with imaging features of TM that are consistent with MS, brain imaging may be repeated over time to see if characteristic MS lesions develop.¹⁹

If none of the tests are suggestive of a specific cause, a diagnosis of idiopathic transverse myelitis can be made.

Non-inflammatory myelopathies include those caused by arterial or venous ischemia (blockage), vascular malformations, radiation, fibrocartilaginous embolism or nutritional/metabolic causes. The work-up for suspected vascular spinal cord disorder may include angiograms of the spinal cord vessels and blood testing for a predisposition to developing blood clots.¹⁹

Potential Causes

There are many disorders that can cause spinal cord inflammation, so TM should be thought of as a group of disorders, and not a single condition. “Disease-associated transverse myelitis” refers to TM that occurs in a patient with an identified autoimmune disorder. Disorders such as neuromyelitis optica spectrum disorder and multiple sclerosis are common causes of TM and may also cause inflammation in other parts of the nervous system. Autoimmune disorders targeting other organs, such as Systemic Lupus Erythematosus,^20-22 Sjögren’s syndrome,^20,23,24 and sarcoidosis,^25,26 are also known to cause TM.

Even after comprehensive medical evaluation, there remains a significant proportion of individuals with spinal cord inflammation that is without a clear identifiable cause. This is a condition called “idiopathic transverse myelitis”.¹⁹ When a healthcare provider diagnoses someone with “transverse myelitis,” they are typically referring to idiopathic TM. Even among those labeled as having idiopathic TM, it is likely that there are multiple yet-to-be-identified causes for this inflammation.

TM may develop in the setting of a viral or bacterial infection, even if the symptoms from the infection are mild. Approximately 30-60% of individuals with TM report a febrile illness (flu-like illness with fever) around the time of neurologic symptoms.^4-6,14,27-29 Certain infections, such as polio, enteroviruses, and herpes zoster, can directly infect the cells of the spinal cord and cause injury.¹⁹ In other cases, damage may be mostly due to the immune system’s response to the infection.¹⁹

Experts believe that in many cases, an infection triggers a misdirected immune response without directly infecting the spinal cord. This is supported by evidence that infections are an important factor in the development of autoimmune disorders of different types. Infections may trigger autoimmunity through a variety of ways, but one mechanism that has significant evidence is called molecular mimicry.¹³ 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, resulting in TM.¹³

Although a causal relationship has not been established, TM has been rarely reported following influenza and Hepatitis B vaccinations.^13,30-32 One theory suggests that it is possible that the vaccination may have excited the immune system, similar to an infection. 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.

Myelitis related to cancer (called a paraneoplastic syndrome) is quite rare.^19,33 When this occurs, the symptoms usually accrue over a much longer timeline (usually several months) than is typical of other causes of myelitis. This is thought to occur due to an immune response to proteins in the cancer cells that are also present on spinal cord cells, resulting in a misdirected immune response.

Vascular causes are noted because they present with the same problems as transverse myelitis.³⁴ 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.