Assistant Professor of Neurology, Multiple Sclerosis Center, The Ohio State University; TMA Medical Advisory Board
The following information is offered as a general response to questions related to Transverse Myelitis and is not to be construed as a specific medical recommendation for any individual. This information is based on the information provided in a brief question and is without the benefit of a complete history or an examination. Any decisions regarding diagnosis or treatment should be made in consultation with your personal physician who is best suited to make appropriate medical recommendations for you.
1. What is the purpose of steroid treatment at the onset of TM? Is there a point after onset when the steroid treatment is no longer useful? Is there a difference in how steroids are used between patients who have an acute onset and those who have a slowly progressing form of the condition?
Corticosteroids may be administered in acute TM in an attempt to cut down inflammation of the spinal cord. There are no controlled studies of the treatment of TM with corticosteroids, but they are given in the hope that they may decrease tissue damage and hasten neurologic recovery. Corticosteroids have multiple actions including: 1) redistributing lymphocytes or white blood cells that may be involved in the autoimmune attack on the spinal cord into other tissues of the body, 2) inhibiting the functions of macrophages, a type of white blood cell that may be involved in the production of spinal cord inflammation, 3) reducing the abnormal activation of lymphocytes, and 4) reducing the production by white blood cells of chemicals that participate in tissue damage.
We have the most information about the use of pulses of high dose steroids during acute inflammation of the central nervous system from studies of the use of high dose intravenous methylprednisolone (IVMP) in acute attacks of multiple sclerosis. Several studies in MS have shown that IVMP shortens the duration of a MS attack. The standard treatment of an acute severe MS attack is 1 gram of methylprednisolone every day for 3 to 5 days. This is a regimen that is often given to people with acute TM. There are no studies available to give information about when steroid treatment is no longer useful in acute TM. In general, it is assumed that typical acute TM is a transient process with acute inflammation and tissue damage occurring over a period of three weeks or less. It is reasonable to consider a course of IVMP after initial diagnostic studies if there is no evidence of an infection of the spinal cord that might be made worse by steroid treatment that suppresses the immune system.
We have few controlled scientific studies of the window of opportunity for treatment of an acute attack of MS, and some worsenings of neurologic function in MS develop more gradually than TM. However, there is some evidence that suggests that IVMP is most likely to be beneficial in the treatment of optic neuritis (demyelination/inflammation of the optic nerve – one type of MS relapse) if it is started within 10 days of the onset of neurologic symptoms.
The above discussion referred to patients with typical acute TM that does not progress after 3 weeks and either stabilizes or improves. Many of these patients have a post-infectious etiology for their TM. The small subset of patients who have a more subacute course with worsening that continues on for longer than one month are already different than the average TM patient. There is a higher likelihood that there is some sort of underlying systemic autoimmune disease, such as Multiple Sclerosis, Systemic Lupus erythematosis or something else. These patients need careful evaluation for such underlying diseases. When one of these underlying diseases is diagnosed, progressive inflammation of the spinal cord may be treated with more chronic use of steroids. Unlike acute TM where it is assumed that the duration of inflammation is relatively limited, in subacute TM that continues to worsen past one month, it would be logical to assume that the underlying inflammatory process in the spinal cord is chronic. That is the reason that steroids are used differently in the situation of subacute TM – it might respond to longer term suppression of the immune system/anti-inflammatory agents. In that case, there is again very little medical literature to guide treatment. Neurologists may start with a pulse of IVMP and then follow with oral steroids at a gradually tapering dose or just skip the IVMP and start with the oral steroids (usually prednisone, sometimes Decadron). The problem with this is that there are many side effects to the use of long term oral steroids that are not a problem with a short burst of high dose IV steroids. The physician will watch carefully for improvement and attempt, gradually, reduction of steroids often to avoid these side effects. In some cases such as a definite diagnosis of SLE-related myelitis, it is frequent that long term steroids are required. In that case, the neurologist may decide that additional immunosuppressive agents should be added to the treatment regimen to reduce the need for steroids.
Milligan NM, Newcombe R, Compston DA. A double-blind controlled trial of high-dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects. J Neurol Neurosurg Psychiatry 1987;50:511.
Durelli L, Cocito D, Riccio A et al. High dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical immunologic correlations. Neurology 1986;36:238.
Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The optic neuritis study group. N Engl J Med 1992:326:634.
2. What is the purpose of IV Immunoglobulin therapy for TM? (What is it and how does it work)?
Intravenous immunoglobulin (IVIg) refers to the infusion of human immunoglobulins or antibodies in an attempt to modulate the immune system. Blood is obtained from pools of 3,000 to 10,000 donors and the immunoglobulins are extracted from the plasma fraction of that blood. The immunoglobulin preparation is then treated in several ways to kill or inactivate viruses, including human immunodeficiency virus (HIV) and the various hepatitis viral agents. HIV has never been transmitted through IVIg. There are cases of hepatitis transmission via IVIg in the past, but newer methods of treatment of the IVIg have proven safe in prevention of the transmission of hepatitis virus.
IVIg is currently used to treat many autoimmune diseases. The exact manner in which it works is unclear. However, each batch is a mixture of human antibodies directed against a wide spectrum of human and foreign proteins. Many of these antibodies actually bind to the antibodies in the patient who receives them as a treatment and may inactivate antibodies that cause autoimmune diseases. IVIg has also been shown to interfere with the function of macrophages and other white blood cells which are involved in autoimmune and inflammatory attacks on many tissues. IVIg readily crosses the blood-brain-barrier and enters into the central nervous system gaining access to the brain and spinal cord.
IVIg treatment has been tried in many autoimmune neurologic diseases. The best scientific evidence for beneficial effect exists for the following diseases: Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy – two autoimmune diseases affecting the peripheral nerves – and dermatomyositis – an inflammatory autoimmune disease of the muscles. There have been small trials of IVIg treatment in myelopathy (spinal cord disease) related to infection with human T-cell lymphotropic virus-1 infection (a relatively rare viral infection in this country), paraneoplastic diseases of the central nervous system and multiple sclerosis.
Various regimens are given. The typical dose is 2 grams/kilogram of the patient’s body weight. This may be divided into 1 gm/kg each day for 2 days or into 5 daily doses of 400 mg/kg each. Maintenance therapy is often given as a single dose every few weeks as needed for control of the autoimmune disease. IVIg has been tried in most autoimmune diseases of the immune system. This treatment has been shown to be especially useful for management of chronic inflammatory demyelinating polyneuropathy (CIDP) which is a chronic autoimmune attack on the peripheral nerves. Some small studies have suggested benefit for relapsing MS. There are no significant studies of its treatment in transverse myelitis. Intravenous steroids would be the usual first choice treatment for typical acute monophasic transverse myelitis. However, IVIg might be tried in more atypical subacute, progressing cases. Potential complications are relatively uncommon, but can include severe allergic reactions, kidney failure, infections, triggering of migraine headaches, rashes, aseptic meningitis, and rarely stroke.
Dalakas MC. Intravenous Immune Globulin Therapy for Neurologic Diseases. Annals of Internal Medicine. 1997:126:721-730.
Kazatchkine MD, Kaveri SV. Immunomodulation of Autoimmune and Inflammatory Diseases with Intravenous Immune Globulin. N. Engl J Med 2001;747-755.
3. What is the purpose of Plasmapheresis for TM? (What is it and how does it work)?
Plasmapheresis or “therapeutic apheresis” is a procedure in which blood is removed from the body and “cleansed” of circulating antibodies, complement, cytokines and other plasma proteins that may participate in an inflammatory attack. Apheresis is derived from a Greek term that means “to remove” or “to take away by force.” One session usually removes 3-5 Liters of plasma and fluids are then replaced with albumin. Therapeutic apheresis is very costly and there are very few well-controlled, rigorous studies to assess its benefits in autoimmune neurologic disease. Plasmapheresis is a standard treatment with proven benefit for several autoimmune diseases affecting the nervous system including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. Plasmapheresis may be done through a regular intravenous catheter in a peripheral vein at the elbow in people with “good veins.” However, for many people, a larger catheter may need to be placed in the central veins in the chest (a “central line”). Complications of pheresis range from mild to potentially fatal: muscle cramps, electrolyte imbalances, hypotension (low blood pressure), nausea and vomiting, and bleeding due to depletion of clotting factors. Complications related to catheter placement may include infection, pneumothorax (collapse of the lung), and bleeding.
Weinshenker’s group performed a randomized controlled trial of plasma exchange in 22 patients with acute severe inflammatory demyelinating disease of the central nervous system. This was a mixed group of patients (12 had MS, five with TM, and five with acute disseminated encephalomyelitis ADEM or variants). All patients were first treated with at least five days of IV corticosteroids but had failed to respond. Patients were not immediately treated with PE or sham (pretend) PE, but were observed 14 days from the onset of IV steroids or 12 days from the onset of the neurologic deficit, if the patient continued to worsen despite the IV steroid treatment. The patients were then treated with either active PE (7 exchanges over 14 days, 54 milliLiters/kg body weight, 1.1 plasma vol/exchange) or sham PE. If a person did not improve with 14 days of sham PE, they were crossed over into 14 days of active PE. Moderate or greater improvement of neurologic disability occurred with 8 of 19 (42.1%) of patients after active PE and only 1 of 17 (5.9%) after sham treatment. This suggests that there is a subset of patients with acute demyelinating events who may respond to PE. Obviously, this study involved only a small number of patients, but it has generated new enthusiasm for PE as a treatment for severe acute TM and for the need for additional larger studies. However, this is an invasive and expensive (up to $18,000) form of treatment and the current recommendation would be that PE should be considered in catastrophic episodes of acute demyelination with significant neurologic disability that has been refractory to treatment with conventional high-dose corticosteroids.
Weinshenker BG et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Annals of Neurology 1999;46:878-886.
Weiner HL et al. Double-blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis. Neurology 1989;39:1143-1149. (an interesting related article regarding the use of PE in combination with other immunosuppressive therapy in acute attacks of MS – some immediate benefits but no clear long-term benefits).
Clark WF et al. Therapeutic plasma exchange: An update for the Canadian apheresis group. Annals of Internal Medicine 1999;131:453-462. (PE does not help progressive MS much. Good review of literature on PE in neurologic disease).