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. If you have questions for Dr. Lynn regarding the Transverse Myelitis condition, please send those to Sandy Siegel; we will attempt to have your questions addressed in the next newsletter.

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.

What is a lesion? What are doctors describing when they explain that they have identified a lesion or lesions at particular levels of the spinal cord in regard to TM? Why are people effected in one place on the spinal cord and others over larger areas of their spinal cord, and still yet others in non-contiguous areas - is that possible? Why do some people with TM have lesions and others do not?

The dictionary definition of the word lesion is an abnormal change in the structure of an organ or tissue due to injury or disease. Most patients with TM undergo examination of the spinal cord by MRI (magnetic resonance imaging). Often this type of imaging will display an area of abnormal signal within the cord, which is circumscribed and well defined; this is a detectable lesion. Lesion is a very nonspecific word meaning any abnormality of structure. In TM, the abnormality may be the result of inflammation, swelling or destruction of cord tissue.

Sometimes there is tissue damage that does not show up on a MRI of the cord. In this case, a microscopic lesion or area of inflammation or tissue injury is presumed to have occurred at a certain level of the cord based on findings on neurologic examination, but the MRI was not able to pick it up. One would assume that if a biopsy was done of the injured area of the cord, abnormalities such as inflammation would show up on microscopic examination of the tissue.

It is true that the lesion may be small, limited to one level of the cord, and well localized. Other people with TM have a lesion that spans many inches of the spinal cord. And yet others can have multiple lesions at different levels of the cord. We do not know the reasons for this variation at this time. However, if one assumes that TM is caused by inflammation of the cord caused by the immune system reaction to various infections, etc., then it is understandable that the white cells of the immune system can come to any level of the cord through the bloodstream.

People are told they can resume all of their physical activities, but sometimes when they have completed these activities (running, walking, weight lifting, swimming, aerobic exercise, golf), their symptoms are intensified for a while afterward. Are these people hurting themselves from a healing standpoint? Are they causing any damage to the nerves that have been injured? How should a person evaluate the type and amount of exercise they are doing? What factors need to be considered?

There is more information about exercise in multiple sclerosis than in transverse myelitis. However, the basic principles regarding exercise in MS also apply to TM and other spinal cord injuries. An interesting phenomenon can occur when a person with MS experiences an increase in body temperature either by exercise, hot external temperatures or fever. Weakness or other neurologic symptoms may worsen. This is attributed to the fact that electrical nerve signals do not travel through demyelinated nerve tracts as well as through normal nerves at hot temperatures. (Myelin is the insulation around nerve fibers; it is destroyed in MS). Some people with TM also have demyelination of parts of their spinal cord and may also experience worsening of neurologic symptoms such as weakness, numbness, tingling or other abnormal sensations when they exercise and raise their core body temperature. This transient worsening does not mean that another attack of multiple sclerosis or transverse myelitis will occur with exercise.

Because of this worsening of function with elevated temperature, neurologists used to warn against exercise in MS. However, there is more understanding now of this phenomenon and most neurologists would recommend exercise for people with MS and TM if certain principles are observed. A proper exercise program designed for a particular individual should include type of exercise, duration, frequency, and intensity of exercise.

Stretching is an important part of any exercise workout but is especially important for people with spinal cord injury who may have abnormally increased muscle tone (called spasticity). Muscles and tendons should be stretched gently before starting on an exercise routine. It takes more energy to exercise when there is significant spasticity.

For those who have significant weakness in the legs, it is best to start with gentle aerobic exercises such as walking if possible, propelling a wheelchair, swimming, water aerobics, bicycling. The goal should be to gradually increase endurance and stamina. As Randall Schapiro, MD has written, the "no pain, no gain" approach to exercise is exactly wrong for people with MS and other spinal disorders. If there is partial weakness, trying exercises that require too much resistance or doing too many fatiguing repetitions may lead to injuries such as sprained ankles, etc. Exercise programs must be individualized according to the person's level of training and type of underlying neurologic problems. However, exercise is strongly recommended for people with MS and should be for people with TM also.

In fact, a recent study of 46 patients with mild to moderate disability from MS who could all walk, some showed that an aerobic exercise program of three supervised training sessions per week for 15 weeks had significant benefits including improved fitness and strength and reduced body fat. A 5-minute warm-up period was included and care was taken to control the air temperature and to prevent overheating by fans. In addition to the obvious benefits, the exercise group also showed some benefits in bowel and bladder function, fatigue and depression. This study was reported in the April 1996 issue of Annals of Neurology.

You may find it useful to read about the stretching exercises described in Dr. Schapiro's book or to ask your physician for a referral to see a physical therapist to help design an individual exercise program. Obviously, you should consult with your personal physician for recommendations regarding exercise. However, I would say that people with TM should not be scared away from exercise by worsening of tingling in the legs, etc. It is unwise to exercise to the point of significant pain as your body is probably trying to tell you that you are injuring it. The guide here is "start slow, and go slow."

Could you speculate as to why TM impacts one particular area of the spine and not another? Is it a random process? Could there be any influence from a physical episode such as a strain or a blow to that area?

I don't think that I can speculate in any meaningful way about why one area of the spine is affected in TM and not another. It has been noted that the thoracic spine is most frequently affected, followed by the cervical and then lower levels. There have been attempts to link many neurologic illnesses to trauma including multiple sclerosis, amyotrophic lateral sclerosis (Lou Gherig's disease), Parkinson's disease, etc. However, there has never been good evidence to back up these proposals and trauma would seem to be an unlikely cause for most episodes of TM. It should be noted that the spinal cord can suffer injury from trauma with resultant high signal lesion in the cord which could mimick TM. Preexisting canal stenosis (not enough room in the canal for the spinal cord) could also predispose to spinal injury with trauma.

Is there a causal relationship between TM and seizures - any relationship?

By definition, TM normally affects only the spinal cord. Seizures are caused by abnormal discharges in the brain. Therefore, TM should not be a cause of seizures. However, there are processes of inflammation that may affect both the brain and the spinal cord at the same time. In those cases, the TM would be caused by inflammation of the spinal cord and the seizures by inflammation or injury to the cerebrum (part of the brain).
Reference: Randall T. Schapiro, MD. Symptom Management in Multiple Sclerosis. New York: Demos Medical Publishing Co., Inc., 1998.

Member Questions and Answers from Norman J. Uretsky, PhD

Norman J. Uretsky, Ph.D. is a Professor of Pharmacology in the College of Pharmacy at The Ohio State University. Dr. Uretsky's research interests include neuropharmacology, neurotransmitter release in animal behavior and neurological diseases. If you have questions for Dr. Uretsky regarding medications, please send those to Sandy Siegel; we will attempt to have your questions addressed in the next newsletter.

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 medications or treatment should be made in consultation with your physician who is best suited to make appropriate medical recommendations for you.

Do antidepressants interfere with libido and ability to achieve orgasm? If so, why do antidepressants have this effect? Are there classes of antidepressants that have less effect on libido and orgasm than others?

There are several antidepressant drugs that are used clinically. These drugs can relieve depression in a majority of patients, but are associated with certain unpleasant side effects. One side effect produced by most antidepressant drugs currently in use is impairment in sexual functioning. This effect not only leads to a reduced quality of life but has been known to cause patients to become noncompliant and refuse to take their medication.

In order to determine whether an antidepressant drug interferes with sexual function, it is necessary to distinguish between the effects of a drug and those produced by depression itself. This is because both depression, as well as antidepressant drugs, can produce sexual dysfunction and, in particular, a loss of sexual desire. In fact, depressed patients, taking antidepressant drugs, often do not complain about sexual dysfunction simply because their sex drive is reduced by the disease. In addition, patients who experience drug-induced sexual dysfunction usually don't spontaneously complain about this impairment and will only mention this problem if they are directly questioned. It has been suggested that this is the reason why the incidence of sexual impairment associated with antidepressant drugs is reported to be lower in the Physicians' Desk Reference than in the results of clinical studies, where questions about sexual dysfunction are usually asked of the subjects.

Data from several studies indicate that most antidepressant drugs are associated with sexual dysfunction. Thus, tricyclic antidepressants (e.g., imipramine -Tofranil, amitriptyline - Elavil, etc.), monoamine-oxidase inhibitors (e.g., phenelzine-Nardil), selective serotonin reuptake inhibitors (e.g., fluoxetine - Prozac, sertraline - Zoloft, etc.), and selective norepinephrine and serotonin reuptake inhibitors (e.g., venlafaxine -Effexor) are reported to produce a decreased sex drive, erectile dysfunction, delayed orgasm, inability to achieve orgasm, impaired or painful ejaculation, and/or penile or clitoral anesthesia. The antidepressant drug, trazodone (Desyrel), has been associated with the condition called priapism (prolonged painful erection requiring immediate medical attention) although the incidence of this adverse effect is rare (1 in 6000).

A variety of strategies have been developed to deal with the problem of sexual dysfunction caused by antidepressant drugs. One approach has been for the patient to take a "drug holiday." That is, the patient discontinues taking the drug for 2-3 days before the anticipated sexual activity. Such an approach has been useful in treating sexual dysfunction caused by the selective serotonin reuptake inhibitors, sertraline (Zoloft) and paroxetine (Paxil). However, it has not been successful in patients taking fluoxetine (Prozac) because the active metabolite of the drug remains in the blood for long periods of time and is present even after the drug holiday. Another problem with this procedure is that the temporary discontinuation of paroxetine (Paxil) and sertraline (Zoloft) can produce a transient withdrawal reaction. An approach, recommended from case studies, is adding drugs to the antidepressant regimen. Thus, cyproheptadine (which blocks serotonin receptors), yohimbine (which blocks noradrenergic receptors), or amantadine (Symmetrel) or methylphenidate (Ritalin) (which activates brain dopamine receptors) have all been reported to be effective in reducing sexual dysfunction induced by the selective serotonin reuptake inhibitors. However, one problem with this approach is that these adjunct drugs, like all drugs, can, themselves, produce unpleasant side effects. Probably a better strategy is to change antidepressant drugs to one that is less commonly associated with impairment in sexual function. In general, three antidepressants currently available are associated with a relatively low incidence of sexual dysfunction (although they produce other side effects). These are bupropion (Wellbutrin, Zyban), nefazodone (Serzone), and mirtazapine (Remeron). Studies have shown that switching to one of these antidepressant drugs can produce a marked improvement in sexual functioning.

The mechanism by which antidepressant drugs produce impairments in sexual functioning is unclear. Certain inferences, however, can be made. In general, drugs that increase serotonin transmission in the brain produce dysfunctional symptoms (described above), suggesting that activation of central serotonin receptors may mediate sexual dysfunction. Since antidepressant drugs that both increase serotonin transmission and block specific serotonin-2 receptors (nefazodone & mirtazapine) are less commonly associated with sexual dysfunction, the activation of these particular receptors may mediate the dysfunctional effects. This concept is supported by the low incidence of sexual dysfunction associated with bupropion, which increases dopamine and norepinephrine but not serotonin transmission in the brain.

Is aspartame a neurotoxin and is it possible that aspartame can cause MS type symptoms?

Aspartame is an artificial sweetener and it is also found in some diet soft drinks. There have been many reports published on aspartame and I am not aware of any documented problems. There have been a number of diseases that have been attributed to aspartame, including epilepsy, multiple sclerosis, brain cancer, Alzheimer's disease and diabetes. The evidence, however, does not support any relationship. The FDA reports that the product is safe, and the Multiple Sclerosis Foundation and the Canadian Diabetes Association also report that the product is safe. Methanol, which can be toxic, is one of the metabolites of aspartame, but it is toxic only at a certain dose. There is no evidence that the quantity of methanol produced from taking aspartame is sufficient to be toxic.