Member Questions and Answers from Dr. Lynn

Joanne Lynn, MD is an Assistant Professor of Neurology at The Ohio State University. She is currently on the staff of The Ohio State University Multiple Sclerosis Center and has special interests in clinical research on the treatment of MS. Dr. Lynn serves on the Medical Advisory Board of The Transverse Myelitis Association.

The following information is offered as a general response to questions related to 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 detailed 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 the appropriate decision for you.

1. How do people cope with leg and foot spasms, especially at night? The neurologist told me to stretch well before I go to bed and try to keep legs from touching each other in bed. I've also learned to keep them as warm as possible. These things don't work well. Any suggestions.

Normally there is a balance between relaxation and excitation of muscles and this is controlled by the nervous system. When there is injury to the spinal cord from myelitis, there is often a loss of this balance, with an increase in muscle tone known as spasticity. This may cause cramps and spasms or, when very severe, a lasting stiffness causing inability to put a joint through a normal range of motion. Passive stretching is an effective way to decrease spasticity for many people and also helps to maintain normal range of motion for joints despite weakness. A person can learn a regimen of passive stretching from a physical therapist or can consult books. People with multiple sclerosis also have problems with spasticity and one helpful description of stretching is offered in Shapiro R. Syptom, Management in Multiple Sclerosis, 2nd ed., 1994, New York: Demos Publications.

However, sometimes stretching just doesn't do the trick by itself. There are several medications to try. Lioresal (baclofen) is a very common antispasticity drug which can help with cramps and spasms. Lioresal works on nerves in the spinal cord that control muscle tone. The amount needed or tolerated differs from individual to individual. Some people develop sedation, nausea, or worsening of weakness from this medication. It is common to start with a low dose such as a half or whole 10 mg tablet at night and then gradually increase the dose. There are other medications which can also help with spasms and cramps and these include: flexeril, tizanidine, clonazepam and valium. Use of any of these medications should be supervised by a physician. Often neurologists and physiatrists who see many patients with spinal cord injury are more comfortable prescribing these medications than other types of physicians.

2. What is cyclosporine? Why is it used? What are the benefits and risks?

Cyclosporine is an immunosuppressive chemical produced by the fungus Tolypocladium inflatum. It suppresses the immune system by blocking the ability of T helper cells to

produce molecules important to the production of inflammation and tissue damage. T helper cells are one type of white blood cells that may abnormally attack human tissues in autoimmune disease.

Cyclosporine has been used to suppress the immune system in organ transplantation to prevent or lessen rejection. It has also been used to treat several autoimmune diseases that attack the human nervous system and there is significant experience in myasthenia gravis and inflammatory muscle diseases (dermatomyositis and polymyositis). Cyclosporine has shown some benefit in animal models of multiple sclerosis but results have been discouraging in clinical trials in multiple sclerosis.

There are many potential complications from treatment with cyclosporine as there are with any agent that is used to suppress the immune system on a chronic basis. This is not meant to be an exhaustive list but gives the most common complications. Chronic

suppression of the immune system carries an increased risk for common infections and for opportunistic infections, which are infections that generally do not occur in healthy

people but may occur in people whose immune systems are not functioning normally. Hypertension (high blood pressure) is the most common side effect and is usually reversible when the drug is discontinued. Cyclosporine may also cause dysfunction of the kidneys by causing constriction of the arterioles (small arteries) in the kidneys. There is less risk of this when a dose of less than 5 mg/kg/day is used. There is also a risk of cancers with use of cyclosporine. This risk is 3.0 to 4.9 times higher than the risk of the general population. Most often these are lymphoproliferative cancers (e.g., lymphoma, leukemia) or skin cancer. Cyclosporine can also have toxic effects on the brain, especially the cerebellum. Other side effects include liver inflammation/injury, gallstones, decreased appetite, imbalances of body potassium and magnesium, and abnormal sensations (e.g., burning or tingling) in various parts of the body.

When a person is being treated with cyclosporine, he or she should be followed closely by the physician, with frequent checks of blood pressure, blood tests to check blood counts, renal function, and routine chemistries, as well as screening examinations to check for skin and lymph node cancer.

3. Have you heard of intravenous cytoxan treatment for Transverse Myelitis associated with lupus?

Systemic lupus erythematosis (SLE) is a chronic autoimmune disease that affects many organs and may vary greatly in severity and which organs are affected from person to person. Some people with SLE have rashes, arthritis, mouth ulcers, or problems with kidneys, lungs, or blood cells. Involvement of the central nervous system (brain and spinal cord) is also common in SLE. Transverse Myelitis may occur in SLE and often this may be severe, recurrent or progressive. Because of this, aggressive immunosuppression is recommended by some researchers.

Prednisone is the traditional treatment for the various problems associated with SLE. However, chronic prednisone use is often associated with significant side effects, such as osteoporosis and catarracts. In addition, at times the myelitis associated with SLE may be so aggressive that it does not respond to prednisone alone. One regimen that has been recommended is the use of corticosteroids in combination with cyclophosphamide. One approach is to give monthly intravenous doses of cyclophosphamide along with corticosteroids for some period of time (six to twelve months) followed by oral prednisone with or without oral cyclophosphamide.

Cyclophosphamide is a form of nitrogen mustard and damages the DNA in rapidly dividing cells which include white blood cells. Moderate doses are used for immunosuppression in autoimmune diseases. Toxicities include, but are not limited to, bleeding from the bladder wall, bladder cancer (risk dependent on cumulative dose), low blood counts, nausea, vomiting, hair loss, infertility.

Several references regarding the use of cyclophosphamide for treatment of myelopathy associated with SLE:

1. McCune WJ, et. al. "Clinical and Immunologic Effects of Monthly Administration of intravenous cyclophosphamide in severe systemic lupus erythematosis," New England Journal Medicine. 1988, 318:1423-31.
2. Barile L and Lavalle. "Transverse Myelitis in systemic lupus erythematosis: the effect of IV pulse methylprednisolone and cyclophosphamide," Journal of Rheumatology. 1992, 19:370-2.
3. Bevra Hannahs Hahn. "Management of Systemic Lupus Erythematosis," in Kelley WN, Harris Jr ED, Ruddy S, and Sledge CB. Textbook of Rheumatology, Volume 2, Fifth Edition. W.B. Saunders Co., Philadelphia 1997 (a major comprehensive rheumatology text)

Deanne Gilmur Honored at FOP/TMA Conference

Deanne Gilmur was recognized during the awards banquet of the FOP/TMA Conference on May 9, 1998. The award was presented by Paula Lazzeri, representing the TMA Board of Directors, and on behalf of the membership of the TMA. The certificate of appreciation recognizes Deanne: