Originally Published in The Siegel Rare Neuroimmune Association Journal
Volume II
April 2007

Chitra Krishnan, MHS, Adam I. Kaplin, MD, PhD, Carlos A. Pardo, MD, Douglas A. Kerr, MD, PhD, and Sanjay C. Keswani, MBBS, MRCP

Original Publication: Current Neurology and Neuroscience Reports 2006, 6:236–243

This article is an update on Transverse Myelitis (TM) based on our experience at the Johns Hopkins Transverse Myelitis Center (JHTMC).  TM is a monophasic monofocal demyelinating disorder of the central nervous system and can be classified as idiopathic or disease associated.  We diagnose disease-associated TM when there is direct evidence of illness, such as lupus, sarcoidosis or infection, such as herpes myelitis, varicella zoster myelitis.  Idiopathic TM, on the other hand, is when there is no known underlying cause of the acute myelitis onset.  Of the 356 cases reported in the 36 months prior to publication of the paper, 64% were idiopathic.  TM can be a presenting feature of MS in patients who have an abnormal brain MRI at acute onset or other features, such as oligoclonal bands in the cerebrospinal fluid.

Though largely monophasic in 75-90% of patients, several factors can increase the chances of a TM reoccurrence.  Having multiple lesions in the spinal cord or in the brain, a mixed connective tissue disorder, oligoclonal bands and serum auto-antibodies in the cerebrospinal fluid can all be factors that put the patient at risk for another attack or conversion to MS.

Most patients with TM experience spontaneous recovery within 6 months and recovery may continue for up to 2 years after symptom onset.  It has been reported in the literature that 1/3^rd of the patients with TM have good outcomes and 1/3^rd worse outcomes.  In the patient cohort followed at JHTMC, there is likely a referral bias for severe cases with only 20% of patients who had a good outcome.  Recent studies at the JHTMC suggest that abnormally high levels of cytokines, especially IL-6, may suggest poor prognosis and recurrence.

TM affects all ages with bimodal peaks at 10-19 and 30-39 years, and there is no gender or familial predisposition.  Clinical characteristics at onset include weakness that occasionally progresses to the upper extremities followed by spasticity.  Pain, paresthesias, urinary urgency, bowel or bladder or sexual dysfunction are other features of TM at acute onset.  Dr. Kaplin and his colleagues have found a high prevalence of depression in patients with TM.  However, it is shown that the severity of disability does not correlate with depression.  It is currently hypothesized that cytokines, or immune messengers, in the brain play a role in depressed mood.  In our case series, depression resulting in suicide is the leading cause of mortality in TM, accounting for 60% of the deaths that we have seen in our clinic (Kaplin, Unpublished observations).  Regardless of the correlation, it is very important to detect and treat depression.

Histopathologic studies of spinal cord tissue obtained from biopsies and autopsies of TM patients reveal evidence of focal spinal cord inflammatory changes – perivascular infiltration by monocytes and lymphocytes in addition to astroglial and microglial activation.  Demyelination in spinal cord white matter tracts and axonal injury and loss is also revealed, with the latter known to correlate with disability.

IV steroids are a common treatment that is shown to increase ambulation as well as motor recovery.  Plasma exchange (PLEX) is used in more severe cases that may not respond to steroids.  Predictors of good response to PLEX include early treatment (< 20 days from symptom onset) and a clinically incomplete lesion.  Cyclophosphamide is a chemotherapeutic drug that helps to kill the multiplying immune cells that cause cord destruction and is also used in aggressive and fulminant cases of TM.  All of these treatments are given right after an attack for a brief period.  If the patient is at risk for recurrence, chronic immunomodulatory therapies are recommended. There are several novel therapies that are currently under investigation.  One involves filtration of the CSF which removes all of the attacking immune cells from the fluid surrounding the spinal cord and has been used in Europe in a clinical trial in acute inflammatory demyelinating polyneuropathy compared to PLEX and was found to be at least as effective and better tolerated.  A neuroprotective approach to treating TM is also being studied as axonal injury and loss in TM likely correlates with permanent neurologic disability.  Clinical trials to study the combined approach of anti-inflammatory and neuroprotective therapies using erythropoietin will commence this summer at the JHTMC.  

Acknowledgment

We acknowledge the support and efforts of The Siegel Rare Neuroimmune Association (SRNA) and its president Sanford Siegel. SRNA serves a critical role to the TM community and to researchers striving to understand and treat this disorder.