Douglas Kerr, MD, PhD
Dr. Kerr is an Assistant Professor in the Departments of Neurology and Molecular Microbiology and Immunology, Johns Hopkins Hospital. He is also the Co-director of the Johns Hopkins Transverse Myelopathy Center. Dr. Kerr serves on The Transverse Myelitis Association Medical Advisory Board.
How long has TM been around? Reports in the medical literature of “acute myelitis” date back to 1882 and are credited to Dr. H.C. Bastain, an English neurologist (Bastain, Quain’s Dictionary of Medicine, 1st Edition, 1882). He described several cases of acute myelitis resulting in “softening of the spinal cord.” He presented the pathologic findings of several autopsies from patients who died of the myelitis and divided the cases into those that he thought were due to “thrombotic events to blood vessels supplying the spinal cord” and those that were due to acute inflammation. A thrombotic event means a “stroke” of the spinal cord in which a clot forms in one of the spinal arteries, thus depriving the spinal cord of oxygen and causing death of nerve cells in that area. Most of these cases were due to syphilis (syphilitic endarteritis – meaning that the syphilis causes an inflammation of small arteries as they enter the spinal cord). The ‘inflammatory’ cases were postulated to be due to an infectious or an allergic mechanism. (Unfortunately, 118 years later we don’t have a markedly improved concept of inflammatory transverse myelitis).
Dr. William Spiller at the University of Pennsylvania published a report in 1909 detailing thrombosis of the cervical anterior spinal artery and proposed strongly that virtually all cases of acute myelitis are due to blood clots, not inflammation (we now know that either blood clots or inflammation may cause TM). His patient in that report (named John W.) was an employee of the Philadelphia General Hospital who was required one morning to lift 100-pound blocks of ice with assistance of another man. (These blocks were then transported to each patient’s room as “air conditioning” and to provide cool washcloths). Shortly after lifting the fourth ice block, John W. “began to have a sensation of coldness and pain between the shoulders.” He then noted “stiffness, then lower limb numbness and weakness.” He became paralyzed by the next day, and despite utilization of an iron lung ventilator, John W. died shortly thereafter. Autopsy of his spinal cord showed a blood clot in the cervical anterior spinal artery, and it was proposed that the lifting had caused the clot to form.
In 1922 and 1923, physicians in England and Holland became aware of a rare complication of smallpox vaccination: inflammation of the spinal cord and brain (reviewed by Dr. T. M. Rivers, JAMA, 1929). Given the term post-vaccinal encephalomyelitis, over 200 cases were reported in those two years alone. Pathologic analyses of fatal cases revealed inflammatory cells and demyelinization rather than the vascular pathology noted above. It was interesting to note that the ratio of cases to vaccination was 1:50,000 in England and 1:5,000 in Holland. England carried out all its smallpox inoculations in children less than one year of age, giving rise to the notion that “infants are relatively insusceptible to post-vaccinal encephalomyelitis.” What was perplexing then (and continues to be perplexing today) is that family members got the identical vaccine (or in many cases today got the same “cold”), but only one member of the family developed acute myelitis.
Dr. Frank Ford reported in 1928 (Ford, F.R.: Bulletin of Johns Hopkins Hospital, 1928) his hypothesis that many cases of acute myelitis are post-infectious rather than infectious in cause. His reasoning was that in many cases of acute myelitis associated with mumps, the patients’ “fever had fallen and the rash had begun to fade” when the myelitis symptoms began. He proposed the idea, therefore, that it was an “allergic” response to the virus rather than the virus itself that caused the spinal cord damage. Dr. Ford also noted that “neuroparalytic” accidents had been noted even dating back to 1887. Specifically, many patients had become paralyzed following rabies virus vaccination. The paralysis was not found to be due to the rabies virus itself, but rather to the repeated inoculation of patients with brain tissue carrying the virus. Dr. Ford was not aware of the functions of the immune system, but we would conclude today that the immune response generated against the brain tissue then attacked the spinal cord and caused the paralysis.
Several cases were then reported over the next two decades showing that though Dr. Ford may be right in some instances, several infectious agents can directly cause acute myelitis, notably measles and rubella viruses (Morris and Robbins, Journal of Pediatrics, 1943; Senseman, Archives of Neurology and Psychiatry, 1945). It was in 1948 that Dr. Suchett-Kaye, an English neurologist at St. Charles Hospital in London, utilized the term “acute transverse myelitis” (Suchett-Kaye, The Lancet, 1948) in reporting a case of acute TM complicating pneumonia. Though not indicated in the initial report, the addition of ‘transverse’ reflected the common clinical finding that patients reported a ‘band like’ horizontal area of altered sensation on the neck or torso. Below this area, sensation was absent or at least altered and was associated with bowel and bladder dysfunction and weakness. Above this area, patients were normal. We now know by looking at MRIs of the spinal cord that this reflects inflammation or injury in a particular area of the spinal cord, with uninjured nerve cells above this area.
Since that time, the syndrome of progressive paralysis due to spinal cord inflammation has been known as transverse myelopathy or transverse myelitis. What is the difference between ‘myelopathy’ and ‘myelitis?’ Technically, any ‘.itis’ means ‘inflammation’: ‘Arthritis’ means inflammation of the arthus (joint); ‘sinusitis’ means inflammation of the sinuses, for example. Inflammation means that the immune system is activated and recruited to the area, potentially causing damage. But several of the cases we see today may be due to vascular events like thrombosis, hemorrhage or dural AV fistulas (abnormal collection of blood vessels on the surface of the spinal cord). These are not truly inflammatory conditions since the clinical events are due to blockage of blood flow. Therefore, we utilize the term first introduced by Paine and Byers (American Journal of Diseases in Children, 1953) of ‘transverse myelopathy.’ This is an all inclusive term which indicates any focal injury to the spinal cord, whether it be infectious, post-infectious, vascular, traumatic or the dreaded idiopathic (which is a fancy term to mean that we do not know what caused the myelopathy).