By Benjamin Greenberg, MD, MHS and Allen DeSena, MD – University of Texas Southwestern, Dallas.
News reports from California have recently come out identifying a series of patients, mostly children, affected by a polio-like illness with symptoms that can mimic transverse myelitis (TM). Naturally, these reports have raised questions within our community so we thought it would be important to address some of the concerns. First, it’s important to have some background.
The spinal cord is comprised of several different pathways and cell types. Connections from the brain descend in the spinal cord and ‘attach’ to neurons in the spinal cord that then project out to muscle groups. When a person wants to move their hand, their brain sends a signal down a pathway to a set of cells within their cervical spinal cord and form a connection (a synapse). The signal from the brain activates the neurons in the spinal cord, which in turn, propagates the signal to the muscles of the hands, leading to the intended movement. This pathway can be interrupted in many ways.
Polio is caused by a virus that specifically infects the cells within the spinal cord responsible for projecting out to muscle groups (the so called lower motor neurons). When these cells die the muscles they connect to cannot be activated. Classically, transverse myelitis causes damage to the wires that are responsible for connecting the brain to these lower motor neurons, leaving the connection from spinal cord to muscle intact, but interrupting the signal that was originally meant to activate the pathway. In clinic, we tend to describe this as “wire number 1 and wire number 2”. Wire number one goes from brain to spinal cord and wire number two goes from cord to muscle. Polio damages wire number 2 and traditionally, TM damages wire number 1.
The second issue that must be addressed is the mechanism of injury. In traditional transverse myelitis a “confused” immune system inappropriately causes damage to the spinal cord. When the immune system invades the cord there is no virus there to be fought off. In the cases of patients reported from California, a virus directly infects and kills the cells. Any inflammation in the spinal cord is responding to the virus. TM is often a missed diagnosis. Sometimes this occurs because of a lack of vigilance from medical personnel, but sometimes it is because the diagnosis is unclear. In addition, the problem with diagnosing TM is that there is no single blood or spinal fluid test that definitively identifies TM. In addition, the spinal fluid markers of inflammatory responses cannot differentiate between an autoimmune response and a response to an infection.
Sometimes people will read that a virus has been associated with TM, but these reports are difficult to interpret. The infection could have been the inciting event but the spinal cord injury was caused by a secondary autoimmune process after the infection, or the association could have been incidental in that the patient had previously had the infection but now has an unrelated process. Also there could actually be two processes causing the spinal cord injury – both an infection-related component and a separate inflammatory component. Finally, the patient could have tested positive for the infection even though they did not have the infection at all (a false positive). Keeping these in mind, it makes it difficult to interpret many of the case reports regarding infection and TM. In addition, we must always keep in mind that the viruses and pathogens we do actually know about (and can test for) are a fraction of those that exist in nature, there are likely hundreds and hundreds of viruses or virus subtypes (meaning we know several but not all in a certain virus “family”) that we are not aware of.
Although we do not know the intricate details of the cases in California, the clustering of extremely similar cases in a short time frame is more suggestive of a common infectious cause, likely a virus, that has a tendency to target the same and/or closely similar areas in the spinal cord and, thus, causing similar symptoms.
In a series of upcoming papers, our team at UT Southwestern and Children’s Medical Center has described differences among patients classically diagnosed as having TM. Some of these patients have evidence of damage to BOTH wire number 1 and wire number 2. We are using these features and others to differentiate patients relative to treatment options and outcomes. In California, the public health system has identified a series of polio-like illnesses, where only wire number 2 has been affected. Some of these patients may have originally been diagnosed with TM, but in retrospect this may have been an inaccurate diagnosis. While we do not have specific case details, this is not an unexpected event given the rate of misdiagnosis of TM.
There is a virus that has been identified in some patients – a previously recognized cousin of the poliovirus – that may be the causative agent. It is also worth noting that this syndrome (viral damage to wire number 2) has been described with multiple viruses, including west nile virus. In the end, this is a reminder of the importance for improved diagnostic algorithms for patients and increased research into the world of acute paralyzing illnesses. The TMA and the UT Southwestern/Children’s Medical Center TM program will continue to monitor events and update our community.
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