There are several pieces of evidence suggesting that infectious agents may be important in the cause of TM. In general, it is believed that 40% of TM cases are preceded by an upper respiratory infection, though some special groups may have as many as 81% preceded by a febrile illness. There is clear evidence that inflammation is present in TM, including elevation of CSF lymphocytes and neutrophils, and often the presence of elevated IgG levels or oligoclonal bands. The fact that the immune system is activated during TM suggests that TM is caused by either an infection or an autoimmune process. However, TM involves a rather limited area of the nervous system. Only the spinal cord is involved, so there must be some local factors provoking the inflammation at that site. One local factor that may be responsible is an infectious agent. Though the evidence described thus far is indirect, there are many cases where direct evidence of an infectious agent is available and infectious agents have been identified. These are described in more detail below.

Diagnosing infectious causes of TM can be very difficult. There are a large number of infectious agents that can cause TM, and they generally do not have differentiating characteristics. This means that when a person develops TM, it is usually not possible to determine from the history or examination whether an infection is responsible or which infectious agent should be searched for. It is often necessary to look for many different infectious agents in each patient. This is difficult because there are few tests that can screen for several agents at once, e.g. cultures for herpes viruses. In particular, serology tests and PCR testing search for only a single agent. Each patient must have many different laboratory tests as a result. Many of the suspect viruses are common, with most people being infected with them. In these cases, it is not enough to show that a person has been infected with a particular virus at some time; rather it must be proven that the virus is infecting the patient at the time the TM strikes. This is not always possible.

When patients present with an acute spinal cord syndrome, the initial diagnostic emphasis is on anatomical/surgical lesions. This leads to extensive clinical evaluations and imaging before blood work and lumbar punctures are performed. The search for infections can be delayed as a result. By the time an infection is sought, the infectious agent may be eliminated by the patient's immune system. Complicating the search further, when the patient presents it may already be too late to identify an infection. In some cases, it is likely that the symptoms of TM result from collateral damage from the immune attack rather than from the infection itself. Thus, when the patient develops symptoms, the infectious agent is already being removed by the host's inflammatory response. Finally, many viruses remain latent in our bodies. This means that once we acquire them, we never totally eliminate them. They can then reactivate from time to time. An example of this is chicken pox, which most people get in childhood, yet continues to live in a latent state in our sensory nerves, and then episodically reactivates in the form of shingles. The reactivation may be due to changes in the immune system, such as inflammation. Thus, it is often impossible to tell whether a virus is causing the TM or whether the inflammation of the TM is causing the virus to reactivate.

Infectious causes of TM can result from viral, bacterial, fungal, parasitic, or postvaccinal inflammation. A number of viruses can cause TM. The herpes family includes: Epstein-Barr virus (EBV, which causes mononucleosis), Varicella zoster virus (VZV, which causes chicken pox), Cytomegalovirus (CMV), Herpes Simplex Virus (HSV, which causes fever blisters and genital herpes), Human Herpes Virus 6 (HHV6, which causes a childhood rash), and Herpes B (which infects monkeys, but can be transmitted to humans who work closely with monkeys). The enterovirus family commonly causes gastrointestinal illnesses including diarrhea. Several members of this family may cause TM, including Coxsackieviruses, Echoviruses, hepatitis (A,B and C), rubella, measles, mumps, and Poliomyelitis. Retroviruses tend to cause TM that develops over months or years. Retroviruses include HTLV-I and II, and HIV (AIDS). Rarely, other viruses are reported to cause TM, including Influenza (flu), Lymphocytic Choriomeningitis (LCM, a childhood disease), rabies, and West Nile Virus.

There are several bacterial infections that can cause TM. Lyme Disease (neuroborreliosis) is the most commonly recognized. It occurs in the spring and summer when ticks are most active, and typically has a myelopathy accompanied by pain radiating down the limbs, cranial nerve abnormalities, or encephalitis. It is often preceded by a rash. Mycoplasma pneumoniae usually occurs in children where it causes upper respiratory infections and ear infections. Cases have been reported of TM due to Yersinia enterocolitica (which causes abdominal pain), Chlamydia psittaci (Psittacosis, which is caught from certain birds), Rochalimaea henselae (cat scratch fever), syphilis, and tuberculosis.

The only fungal organism that causes TM with much frequency is cryptocossus. Aspergillus may also cause TM. Both are usually seen in patients with suppressed immune systems.

A number of parasitic diseases can cause TM. In general, these may be identified in patients that have appropriate exposure histories. Eosinophils may be seen in the CSF. These include schistosomiasis, toxoplasmosis, cysticercosis, toxocaraisis, gnathostoma, and angiostrongyllus.

The bacteria, funguses and many of the viruses can be cultured from either the blood or spinal fluid during the acute phases of the TM. However, some of the viruses, bacteria and parasitic diseases require serology to make the diagnosis. Serology tests measure the antibodies that a person makes against a particular infection. For the most part, each organism is tested separately. Serology tests are usually optimal when a blood sample at the time of the acute TM is compared to a second sample 6 weeks later. Finally, several of the infections can now be diagnosed using PCR. Several PCR tests can be obtained on a single spinal fluid sample. The PCR test looks for DNA from a particular virus, with each virus requiring a separate test. It can measure extremely small quantities of a virus with results available in a few hours.

With continued advances in our understanding of and ability to diagnose infectious diseases, we should continue to expand the list of infections that can cause TM. As we learn more about what organisms are found in TM patients, we should be able to explain more of the idiopathic cases. It is also hoped that we will be able to better understand the causes of TM and perhaps minimize the disability or prevent cases due to infectious causes.