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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.
References
- 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.
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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.
Administration
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.
References
- 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.
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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.
References
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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).
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4. 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.
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5. 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."
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6. 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.
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7. 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.
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8. How do illnesses, such as colds, fever and flu impact TM?
There are two ways to interpret this question. The first possible relationship is that viral illnesses are well known precipitants of post-infectious TM. Somehow the viral infection sets off an autoimmune response directed at the spinal cord with resultant inflammation and injury within spinal cord tissue. Recurrent transverse myelitis has been reported; therefore, there is a very small theoretical risk that viral infection might set off a recurrence of post-infectious TM. However, this is very small and it is more likely that worsening of symptoms with a cold or fever would occur by the mechanism described in the next paragraph.
The other way to interpret this question is how do colds, fever and flu impact upon the patient with a past episode of TM who is now stable with residual neurologic problems from spinal cord injury. We know from studies of people with multiple sclerosis that fever may have profound effects on neurologic function in areas of the brain and spinal cord with demyelination (injury to the myelin or insulation material wrapped around nerve fibers). In normal myelinated nerves, small increases in temperature will speed up conduction of electrical nerve impulses. However, an increase in temperature such as a fever may cause failure (or block) of conduction of nerve impulses in demyelinated nerve fibers. In fact, decades ago before MRIs and other sophisticated tests, MS was often diagnosed with the aid of the "hot bath test". The patient was placed in a hot bath to raise body temperature and then reexamined to see if new neurologic problems developed. It is commonplace for a person with MS who is walking with a cane to become temporarily paralyzed in the legs if they develop a high fever. This phenomenon is not specific for MS but may occur in any injury to the central nervous system and especially when there is prominent demyelination as there often is in TM.
This means that a person with TM may experience a worsening of lower extremity weakness or numbness, etc. when they have a fever. People who have experienced this worsening with fever should try to bring fever down with Tylenol or aspirin if there are no contraindications to taking these agents and get with their physician to determine what is causing the fever. A worsening of neurologic function in the setting of a fever is usually not a new episode of transverse myelitis just the result of the stress of the fever on a neurologic system without the usual reserves to tolerate the stress.
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9. For how long can the healing process continue and in what degrees?
Again, there are few good studies that report on the healing process and outcome in large numbers of people with TM. Berman et al reported that out of 59 patients with TM, 22 had good recovery, 20 had fair recovery and 14 had poor recovery. They observed that recovery usually began within 4 weeks to 3 months after the onset of symptoms. If no signs of improvement were seen within 3 months, significant recovery was unlikely to occur.
Reference:
Berman M, Feldman S, Alter M, et al. Acute transverse myelitis: incidence and etiological considerations. Neurology 1981;31:966.
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10. Is there a way to prevent this (TM) from happening again, i.e., diet, stress reduction, vitamins, etc.?
For most people, the cause of TM is unknown or idiopathic. Therefore, there is no evidence available that diet, stress reduction or vitamins would decrease the risk of an exacerbation of TM. Of course, there is much that we do not know about the immune system. There are some studies that suggest that stress may have adverse effects on the immune system. However, it is virtually impossible to construct a stress-free life that is rich and fulfilling. For that reason, it would seem prudent for those with TM to follow the same recommendations for a healthy life-style that are given for all: adequate rest, regular exercise, a good diet, moderation in alcohol intake, no smoking, etc. There is no dietary or vitamin supplement that has been proven to heal nervous system injury so beware those who promote expensive regimens.
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11. So many people who have TM complain about fatigue. What possible explanations are there for this symptom?
Fatigue is one of the most common complaints in clinical medicine. The cause of abnormal fatigue is poorly understood in most clinical conditions. The only ways that we have to measure fatigue are through subjective rating scales in which the person reports how fatigued he or she is. There are several different types of fatigue, which include 1) a sense of low energy, 2) abnormal mental fatigue, 3) fatigability in physical activities, 4) delayed recovery after fatiguing exercise. There are very few studies on fatigue and TM, so we should look at what is known or hypothesized about fatigue in other diseases that injure the spinal cord such as MS, spinal cord trauma, and degenerative diseases of the spinal cord. The types of fatigue that would be most expected to occur in a person with TM would be the third and fourth types. With injury to the spinal cord, there is a breakdown in the pathway for nervous system activation of muscles. In order to move your right toe, upper motor neuron cells in the motor cortex on the left side of the brain must be activated and send a signal through nerve fibers along a pathway which crosses to the right side in the brainstem and then courses down through the spinal cord to the lower levels of the spinal cord. These fibers make connections with lower motor neurons in the spinal cord, which then send fibers to the muscle. These fibers spritz out chemicals that travel short distances to the muscle fibers and cause them to contract.
One theory about motor fatigue in spinal cord injury is that it is due to an increase in energy demands caused by the inefficiency that is caused by weakness. What this means is that if your legs are weak, you have to work harder than a person with normal strength to walk and this requires more oxygen consumption and more work for your heart and lungs. Some studies suggest that this increased inefficiency is especially present if you have significant spasticity (or abnormally increased muscle tone) which must be fought against to move a limb. Some studies have suggested that the muscles themselves function poorly after an upper motor neuron injury with weak muscle contraction and quick fatigue.
Another possible contribution to fatigue is the fact that nerve fibers within the spinal cord that have been injured do not transmit electrical signals as well as normal fibers. One type of injury is demyelination. Nerve fibers are normally surrounded by an insulation material known as myelin. In inflammatory conditions such as TM and MS, the myelin is injured. This may lead to a type of "short-circuiting" of electrical flow across channels which results in weakened nerve firing and thus fatigue.
Another contribution to fatigue may be that people with significant leg weakness may become deconditioned and have poor physical fitness. That part of fatigue might be lessened by physical training and physical therapy.
There is no cure for fatigue. Even though the mechanism of fatigue is not well understood, there are several measures that may be tried. Rest and conservation of energy for those times when it is most needed are important strategies. Fatiguing tasks should be performed in the morning before fatigue sets in for most people with TM. It is sometimes helpful to analyze daily routines to see if tasks are performed efficiently. Moderate physical exercise and condition will result in gradual benefits for most.
Several medications have been tried for fatigue in MS; they could also be tried for people with TM. Amantadine is an antiviral medication that has been shown to have some benefits for fatigue in MS. It is given in doses of 100 mg in the morning and the afternoon and is tolerated well by most people. Pemoline is another stimulant that has been used with some success for fatigue in MS. Of course, other illnesses that might cause fatigue should be considered such as hypothyroidism, sleep disturbances of various kinds, depression and others.
References:
- Miller RG, Green AT, Moussavi RS et al. Excessive muscular fatigue in patients with spastic paraparesis. Neurology 40:1271, 1990.
- Olgiati R, Jacquet J and Prampero PE. Energy cost of walking and exertional dyspnea in multiple sclerosis. Am. Rev. Respir. Dis. 134:1005,1986.
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12. Are there eye problems or vision problems that can occur as a symptom of having TM?
No. By definition TM is a disorder of the spinal cord and cannot affect vision. Vision is affected by disorders of the eye, optic nerve, or optic pathways that radiate to the visual cortex that is located in the back of the brain (occipital lobe). However, there is a disorder that is related to TM named acute disseminated encephalomyelitis (ADEM). This is a monophasic inflammation of white matter in multiple areas of the central nervous system including brain, brainstem, optic nerves and spinal cord. It is triggered by the same things as post-infectious/post-vaccinal transverse myelitis. Some researchers propose that TM is just a form fruste (a partial form in which not all of the elements of the syndrome are present) or isolated, limited form of ADEM. So it is possible that one might develop an acute problem with spinal cord, vision or eye movement abnormalities as part of the same process. Spinal cord and optic nerve demyelination may also occur simultaneously or in close temporal relationship in one form of multiple sclerosis known as Devic's syndrome.
There are many other nervous system disorders that might affect vision. If there is a disturbance of vision, obviously this should be evaluated by an ophthalmologist. It is difficult in this setting to review all of the possible problems with vision. Briefly, double vision or diplopia suggests a disorder of the brainstem that is directly above the spinal cord and links the spinal cord with the rest of the brain or with the nerves or muscles that move the eyes. One cause of loss of vision in one eye is inflammation of the optic nerve that brings messages from the retina of that eye back to the brain. If either of these things should occur, then this suggests an underlying process that is affecting several levels of the nervous system, not just the spinal cord. Some possibilities might be multiple sclerosis, sarcoidosis, systemic lupus erythematosis, infections, vitamin B12 deficiency, or less likely, cancer.
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13. Should a person with TM be concerned about receiving a flu vaccination or any other type of vaccination?
This is a difficult question. The reason is that acute disseminated encephalomyelitis (ADEM) or TM may occur as an immune response to vaccination. ADEM is a monophasic inflammatory disease of white matter of the central nervous system (brain and spinal cord). Epidemiology of ADEM and, to some degree, TM is discussed in the chapter by Tselis and Lisak referenced below. ADEM and TM can occur after immunization with vaccines against measles, diphtheria/tetanus, rubella and pertussis. But when you consider the very large number of vaccinations given against these diseases and the small incidence of ADEM/TM that occurs, many would think that the incidence is rare enough to suggest a coincidence rather than causality. They discuss reports of ADEM after influenza shots.
Given these uncertainties, the only possible answer is that one must weigh the potential risks versus the benefits. One moderate view would be that vaccination should certainly be avoided during any phase of active worsening and in those in whom the initial episode of TM followed an influenza vaccination by a short period of time. Certainly, the benefits of influenza vaccination probably exceed the small risks in people who have significant risk factors for death or severe illness from the flu (e.g., severe emphysema or other lung disease, etc.).
Reference:
Acute Disseminated Encephalomyelitis. Tselis AC and Lisak RP in Antel J, Birnbaum G and Hartung H. Clinical Immunology. Malden MA: Blackwell Science, Inc., 1998. Pp118-119.
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14. Should a person who has been diagnosed with TM who experiences recurring symptoms or an intensification of existing symptoms be tested for MS?
Recurrent idiopathic transverse myelitis has been reported (Tippett 1991) and does not necessarily mean that there is underlying MS. However, recurrent exacerbations of myelopathy or spinal cord dysfunction should prompt reevaluation. Myelitis due to an underlying autoimmune disease is more likely to recur than idiopathic transverse myelitis. This would include systemic lupus erythematosis, Sjogren's syndrome, or multiple sclerosis. Relentlessly progressive spinal cord dysfunction should prompt consideration of a spinal cord mass lesion such as tumor or abscess, MS, or a paraneoplastic disorder (immune attacks on the spinal cord related to an underlying cancer).
Other neurologic symptoms occurring after the initial spinal cord attack that might suggest multiple sclerosis or another underlying inflammatory central nervous system disease would include visual loss, double vision, trouble with speech or swallowing, vertigo or seizures.
In most follow-up studies of people who present with transverse myelitis, the majority do not develop MS. However, if there are abnormal lesions in the white matter of the brain, the risk of subsequently developing MS is increased. Those with myelitis who have total paralysis of both legs (complete TM) are more unlikely to develop MS than those who had incomplete TM (weakness or sensory loss without complete paralysis).
References:
- Tippett DS, Fishman PS, Panitch HS. Relapsing transverse myelitis. Neurology 1991;41:703-706.
- Christensen PB, Wermuth L, Hinge HH, Bomers K. Clinical course and long-term prognosis of acute transverse myelopathy. Acta Neurol Scand 1990;81:431-435.
- Ropper AH, Poskanzer DC. The prognosis of acute and subacute traumatic myelopathy based on early signs and symptoms. Ann Neurol 1978;4:51-59.
- Ford B, Tampieri D, Francis G. Long-term follow-up of acute transverse myelopathy. Neurology. 1992;42:250-252.
- Miller DH, Ormerod IEC, Rudge P, et al. The early risk of multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord. Ann Neurol. 1989;26:635-639.
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15. 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.
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16. 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 toproduce 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. Chronice 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.
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17. 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:
- 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.
- 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.
- 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)
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