Symptom Management in Multiple Sclerosis Randall T. Schapiro, MD For ordering information or subscriptions please contact: Nancy Campbell Medical Journals Department of Little, Brown and Company Boston, MA 02108 (617)859-5636 Copyright (c) 1994 by the American Neurological Association -------------------------------------------------------------------------------------------------------------------- Presently, the course of multiple sclerosis (MS) can be altered little, if at all. Appropriate symptom management, however, can change the course of lives and allow for more comfortable, healthier living despite significant disease. Symptoms in MS are divided into three broad categories. Those that result from actual demyelination include de- creased vision, weakness, spasticity, bladder problems, ataxia, numbness, and decreased cognition. Secondary symptoms spring from the primary; these symptoms include contr=ures, urinary tract infections, megacolon, decubiti, decreased bony calcification, and muscle atrophy. Tertiary symptoms are the unavoidable psychological, vocational, and social problems that occur with chronic disease. This article reviews standard therapies, but the emphasis is on newer management solutions that may not have reached their full potential, though they add to the development of an appropriate life-management plan for persons with MS. The pharmacological approach to symptom management is emphasized, while understanding that rehabilitation and medications cannot be separated in the real life alleviation of MS symptoms. Schapiro RT. Symptom management in multiple sclerosis. Ann Neurol 1994;36:S1230-S129 -------------------------------------------------------------------------------------------------------------------- It is difficult to discuss symptom management without rehabilitation, but because Dr Mertin is discussing the rehabilitation of multiple sclerosis (MS) patients, this will be limited to a more purely neurological approach. The Serenity Prayer is particularly appropriate to the area of symptom management in MS. It says "God grant me the courage to change the things I can change, the serenity to accept those I cannot change, and the wisdom to know the difference. But, God grant me the courage not to give up on what I think is right, even though it may appear to be hopeless." God grant me the courage to change the things I can change. In managing MS, that is the byword, to change the things we can change. We need to be realistic and look for things that will help improve somebody's lot in life. In managing patients with disease, there are four possibilities of change. (1) Disease may be prevented, (2) the patient sometimes cured, (3) sometimes re- stored back to health, but, in the end, (4) symptom management becomes important. Symptoms may be divided into the following three broad categories: (1) primary Symptoms, (2) secondary symptoms, and (3) tertiary symptoms. Primary symptoms occur because of frank loss of myelin within the central nervous system. They include such things as spasticity, weakness, ataxia, tremor, numbness, cognitive problems, visual difficulties,-and balance problems, and the list goes on and on. Secondary symptoms occur because of the primary symptoms. If a person has a spastic leg that is immo- bile, a contracture will develop about the joint. If the person's bladder is not working very well, a urinary tract infection may occur. If immobility is present, pressure sores may occur, bones get thin, and break, and muscles can atrophy. These are secondary symptoms. Tertiary symproms occur because of the psychologi- cal problems that occur because of the chronic disease process. These include psychological, social, voca- tional, personal, marital, and the list goes on in that regard as well. People with MS not only have spasticiry but with that, they often have spasms. There are standard ways to treat these particular problems. They include the use of baclofen (Lioresal), which is commonly pre- scribed and commonly misused. The biggest mistake with Loresal is not to use enough of it and not to tell patients that they should not give up on it until the dose is raised to an appropriate level. The biggest prob- lem with getting it to an appropriate level is that spas- ticity is often traded for weakness and that is a difficult trade to make. That is particularly true with the use of dantrolene (Dantrium). Dantrotene works with a different mecha- nism, but it appears to be far more potent in MS and is better reserved for cerebral palsy. But, in some peo- ple who do not respond to baclofen, Dantrolene will often be a way to loosen those spastic muscles. Diazepam (VaLium) is very effective but results in somnolence, and thus, it is very difficult to get people on enough diazepain to relieve their spasticity without forcing them to sleep the day away. There are a number of other spasticiry, spasm mea- surement "tools." Clonazeparn (Klonapin) is a relative of diazepain and is very, very useful, especially noctur- nauy for people who have nighttime spasms. Those spasms often occur even with sleep, allowing a restless night without good sleep. Thus, the spasms contribute to fatigue the next day. Therefore, it is a very good nighttime antispasticity medicine. Carbamazepine (Tegretol) is not the greatest anti- spasticity medicine, but for flexor spasms and extensor spasms that may occur with the spasticity, carbarnaze- pine can be very useful. Tizanadine is used in Europe and a clinical trial has just been completed in the United States. The results of that are yet to be published. Botulinum toxin (Botox) is an invasive way to de- crease muscle tone. With more experience, it will be- come more useful. Over time, it will likely become more readily available to decrease muscle tone in those people who have unmanageable tone. There are a number of reports on the use of mari- juana for spasticiry. These are all anecdotal. The drug Marinol, used for nausea in cancer chemotherapy, is basically cannibus and, in fact, does have some anti-spas- ticity properties but is not any better than the routine spasticity medications that are available. Intrathecal baclofen has made a significant contribu- tion to the management of severe spasticity. Med- tronic's programmable pump is placed into the abdo- men with a tube that goes into the spinal canal intrathecally. The neurosurgical placement of this is not difficult, although it is real surgery. Liquid baclofen then is placed into this pump. In micrograms, the amount of spasticity can be regulated. This pump has been sensational for patients who have severe flexor and extensor spasms with severe spasticity that throws them out of their wheelchairs. It makes a significant difference in wheelchair positioning. Potentially ambulatory patients, following the im- plantation, may become ambulatory because stiffness may be controlled, allowing use of strength. In cases of intractable spasticiry, this is a very important man- agement tool. Paroxysmal spasms or paroxysmal symptoms seen in MS are rather unique to that disease. Whether trigemi- nal neuralgia or tonic paroxysmal spasms of the arms or legs, carbamazepine (Tegrecol) is effective almost all of the time. In those cases in which it is not, phenytoin (Dilantin) may be effective. But, uniquely, there are a couple of other drugs to use in circumstances in which the standard ones fail. Valproic acid (Depikote) and corticosteroids appear to allow these spasms to abate. Tremor is one of the most difficult symptoms to treat. There is no good rehabilitative approach for tremor, although in some of the more recently pub- Eshed articles there are mechanical devices being de- veloped that appear hopeful. The best drug for tremor has been propranolol (Inderal), which is extremely ef- fective for familiar, essential tremor bur may also be effective in the kind of action tremor coming from the cerebellar disease of MS. Primidone (Mysoline)has been found to be effective in this regard as well, how- ever, is very fatiguing. Clonazepam (Klonapin) helps decrease the tremor, although it also appears to act by producing sedation and by calming. The antihistamine hydroxazine (Atarax, Vistarit) likewise works in this manner. There are some more unique treatments for tremor that have been reported to be of value. Acetazolamine (Diarnox), a diuretic, and isoniazide (INH) in high dos- ages have been shown to be of some value in some kinds of tremor. It is surprising that a sleeping pill that was taken off the market because it was so habit form- ing, glutethemide (Doriden), has been used in some studies in action tremor in MS and traumatic brain injury, a rather unique way to approach a very difficult problem. The bladder is a major problem in MS. There are a variety of antichohnergic medicines that slow the spas- tic bladder. The large failure to empty the bladder may be managed with urechohne, but it, unfortunately, usu- ally does not work and is almost a waste of time. Self- catheterization has become the standard in the large f@ure to empty the bladder. But there are a number of unique ways to treat blad- der problems. Some bladders are dyssynergic. The sphincter closes as the bladder tightens. This dyssyner- gia creates a great difficulty, particularly in males who have MS because the pressures build up within the bladder and may allow urine to flow up the ureter to the kidney. In reality, despite some academic studies, this very rarely happens. Upper tract problems in MS are rare. There are -blocking agents, the antihyper- tensive agents (terazosin, phenoxybenzamine, cloni- dine), which appear to allow this dyssynergia to be less and allow urination to occur more efficiently. Sometimes a patient has severe urgency of urination and, after elimination, dribbling occurs. This is with apparently good emptying of the bladder. A little- known fact is that cold pills, such as Ornade or Dristan tighten sphincters and may be very useful in that partic- ular circumstance, allowing the person to be continent. Vasopressin has been around for a long tune and now is available in a nasal spray. That slows the pro- duction of urine during a particular time. Thus, a person with severe nocturia can get a good night's sleep by decreasing the production of urine during the night. Obviously, compensation occurs the next day. It is im- portant to understand that much of what goes in has to come out, but the timing is important. The downside of using the vasopressin nasal spray is the cost of it. While costly, it is effective. Newer antibiotics have allowed management of in- fection in the urinary system with relatively minor dif- ficulty. The use of a Foley catheter, therefore, has become somewhat easier. Foley catheters have traditionally been frowned upon. Physicians who say, "never put in a Foley catheter," have not taken care of lot of people who have MS. Those with MS who have significant ataxia of the arms and are wet and breaking down from skin problems may find a Foley catheter necessary and extremely lifesaving. Foley cath- erers can be very, very helpful in these difficult circum- stances. Artificial sphincters may evencuauy obviate permanent catheter use and there are studies now looking at that. In the meantime, self-catheterizadon is a very impor- tant tool. There are a number of different self-catheters that are on the market. Some even come packaged in a serile bag. Self-catheterization is a clean technique, not a sterile technique. But this allows the person to do it even more cleanly. The catheter is in the bag and it can then be placed into the urethra without having to touch it. Condom catheters fit over the penis and attach to a tube. For the most part, they are difficult to use be- cause they fall off so frequently. But some condom catheters do work better than others and we should be aware of them. Bowel problems are common problems in MS as well. The average neurologist does not spend much rime worrying about bowel problems. This is some- thing that can be created and something that should be understood. The time of day plays a big role in having a bowel movement. There is a reflex promoting a bowel movement after a meal. Babies express that routinely. After their meal, their diapers fill. Adults have learned to wait, but that reflex, the gastrocolic reflex, is still present. With constipation a bowel movement occurs easier after a meal. If that fails, a bulk former is added. There are many on the market. A personal favorite is Perdiem. Some bulk formers can be used to regulate the bowel. Metarnucil is especially appropriate for that. If the stool is too loose, increase the bulk former and decrease the liquid associated with them. If the stool is constipated, increase the liquid with the bulk former. If that does not work, add a glycerin suppository. That will be on the third day. If char does not work, after a meal, go to a more aggressive approach with a stimu- lant and even digital stimulation. There is a product called the Tberavac Mini Enema. This is a neat little device that looks like a mini enema. It is about 2 in. in length. The patient simply cuts off the tip of the tube, inserts the tube and squeezes. It is a very lubricating, very mile, gentle mini enema. To move the bowels from above, Lactulose works best. If there is no action from below, the oral dose of Lactulose is adjusted accordingly. There is a Foley type of bag available, called the Bard recad bag. It is glued to the anal region for the person who is incontinent. They can fill the bag and it can be taken off cleanly without the upset of incontinence. It can be a lifesaver for a family that is trying to take care of a very disabled loved one. Sex. There are some standard treatments for sexual dysfunction, but where is the line between standard and unique? When a male or female is having sexual difficulties, the first thing looked at is an alternative means of expressing one's sexuality, be that by caress- ing or by oral sexuality, or by any other means that would seem appropriate within their relationship. Beyond that in the male, penile implantation used to be the only alternative. There are a number of im- plants that have been made available that worked very successfully in the late 1970s and early 1980s. Over time injection intercavemously into the tissue of the penis of a vasodilating agent became popular. Papaver- ine was the first of that type of agent. This has become fairly standard management in most MS programs. Pa- paverine has its ups and downs. Sometimes the ups stay up and it can be difficult to control. It has become clear that in some people, papavetine must be com- bined with Regitine and/or with prostagiandin. This dual or triple therapy appears to work with better con- trol of the erection. The vascularity of the erectile de- vice is what allows for the erection. People who learn to give themselves the injection into the shaft of the penis feel it is very effective and natural. It is probably the most natural erection next to doing it without the medication help. But, for those who cannot bring themselves to injecting their penis, there are vacuum devices that are available. A number of different companies make them, but the principle is all the same. Rubber bands fit over the tube such that the tube then goes over the penis and a vacuum is created, which allows the erection to occur. The rubber band slips off onto the penis and holds the erection, allowing intercourse. Too often, the sexual difficulties of the female with MS are ignored despite the majority of MS occurring in women. They also have some sex- ual difficulties. Often it is a probes with lubrication. KY jelly is a very good lubricant, but there are vaginal lubricants that can be placed into the vagina. Packets of lubricants, called Replens, during simulation, will break open and provide for some natural lubrication. Often the female with MS will state that they have lost sensation in the vaginal area. Vibrators are avail- able to enhance the sensation. Neurologists should know where to buy a vibrator. Strength is not an easy subject to discuss regarding MS. It is particularly difficult because it is very difficult to strengthen a muscle that is made weak by demyelin- ation within the central nervous system. Thus, there is no standard way to strengthen that muscle. However, in the future, the central nervous system may be by- passed by putting pads on affected muscles and by trig- gering a mechanism attached to a walker. The pads put electricity into the muscles, which is brought together by a computer worn about the belt and allows differen- tial contraction and relaxation of muscles resulting in people walking. This is already being done for spinal transaction; this is functional electric stimulation. Stud- ies are now being done in MS for this technique. Pharmacologically, 4-aminopyridine and 3,4-diami- nopyridine appear to be "strength producing." Dr Dusan Stefoski in the United States has been working with Dr Floyd Davis and other people in Europe on this. This may turn into a really important prospect. Cooling is a simple way to help demyelinated nerves to work more efficiently. That is something known diagnostically in MS. People who have MS do poorly after a hot bath. Now there are cooling vests, which in fact, will allow people to function more efficiently, especially if they are sensitive to heat. Fatigue is a major problem in MS. There are a num- ber of medicines that have been used standardly. Amantidine (Symmetret) has become the standard. Pemeline (Cylert) is a favorite of others. Methylpheni- date (Ritlin) was certainly one that was used for many many years. Prozac is also effective for this particular kind of fatigue. Cooling can also be quite effective in particular individuals. Aerobic exercise, if done prop- erly, can help with lassitude as well. Pain occurs in about 80% of people with MS. Sig- nificant pain occurs in about 20% of people with MS. MS can be a very painful disease. Carbamazepine (Teg- retol), phenytoin (Dilantin), and an-ticriptyline (Elavil) are used standardly for people who have pain in MS. The phenothiazine, Taractin, can be helpful when ev- erything else fails. Zostrix HP is a cream that gives a counterirritant effect. If a person can tolerate that counterirritant, they often feel improved from their pain. Sometimes placing a tight wrap over the painful area, whether it is a glove or a leg stocking, is helpful and even acupuncture and medication can be help- ful for creaunent of pain in MS. Swollen ankles are common in MS. Too often doc- tors treat this with diuretics that never solve the prob- lem. They work initially, the fluid then recurs, and the person is stuck on the diuretic. The reason it does not work is related to the reason the swollen ankles are present in the first place. The kneading action of their muscles to their blood vessels is not occurring and the fluid is leaking and accumulating by gravity. It cannot be mobilized. The fluid mobilized with the diuretic is the intravascular fluid; thus, a person can become "dehydrated" with excess fluid in their extremities. Ele- vating the legs helps by pushing the fluid back into the body and allowing more area for it to be absorbed. Support stockings can be of value, but there is a newer product. For years alternating compression wraps have been helpful in the hospital. There is now a stocking, the jobst pump. It is a zippered stocking measured to fit. The stocking is placed over the swollen legs, zip- pered up with a jacket placed over the stocking. Within this jacket is a pump. This pump device then is attached to the jacket and then the pump alternates contraction with relaxation giving a rather natural kneading process to the muscles. This allows the fluid to get back into the circulation and be carried away. Massage can do the same thing but is time consuming and not practical on a long-term basis. Dizziness. There are drugs for dizziness, i.e., Dram- amine and Antivert. There are other drugs that are more effective. All of the Valium-like derivatives are direct vestibular suppressants; thus, oxazepam (Serax) and clonazeparn (Klonopin) are extremely felpfile for dizziness and Transderm scopolamine amy be useful in a particular individual. Double vision is something common in MS. 0ften prisms are given. Sometimes an eye is patched. Patch- ing eyes does not allow compensation to develolp. If allowed, brains will compensate for diplopia over a pe- riod of time. Patching eyes for driving or when reading is appropriate. Otherwise, eyes not patched will even- tuaffy see single again. Cognitive problems in MS are something notable for which there is no useful medication. Despite that, there are a number of symptoms that we can treat in MS to make our patiens' lives better. There are stan- dard treatments and there are more unique treatment; all can help make patients' lives more fulfilling. QUESTION (Lemanne Metz, Calgary): I would like to ask Dr Schapiro if he has any experience using Periac- tin for spasticity; and also in our clinic we have just added two psychiatrists managing mood and cognitive problems, which has made a huge difference to the patients that we have been dealing with so far, and I am wondering what you do along that line in your clinic. ANSWER (Dr Schapiro): In answer to your first quc tion, I have never used Periactin for spasticity. We used it for itching and I have used it for migraine head- aches that sometimes occur in people with MS and I do not know why it would have any effect on spasticicy in particular, but I would be interested to hear. (Louanne Metz)-. There are a number of trials looking at it in cord patients, not MS patients, spinal cord injury patients, and we use it; it is almost one of our first-line drugs in spasticity in walkers. They do not get weak, they usually tolerate it, it either works or it doesn't work, it has been a very helpful drug. Weight gain in women tends to be more of a problem, the men do not have too much difficulty. (Dr Schapiro): It is certainly something to try. In terms of psychiatry and psychology, is that what you were asking? (Louranne Metz): Psychiatry (Dr. Schapiro): We use psychiatrists sparingly when it is appropriate for our patients to be seen for so-called medical management of mental health disease. The psychologists primarily are our mental health workers along with social workers. They have the time to help. QUESTION (Dr Scheinberg): We were also asked the question whether or not the solo practicing free- standing neurologist was better, Don (Don Silberberg), than the center. ANSWER (Dr Schapiro): Quality of life measurements are probably one of the things that we sadly lack in looking at multiple sclerosis. When we do such things as rehabilitation, symptom management, things of that nature, often it is difficult to measure the outcome entirely. You can measure residual urine, but it is dif- cult to get a good quantifiable number and yet the person's quality of life has improved; so one of the major ongoing tasks of the MS Society right now is to look for appropriate ways to measure quality of life, and I think when we get the appropriate tool, which is within the year, I would bet then I think we can proceed on to look at other outcome studies, looking at some of the management strategies that we have been using over the years, to see if we can in fact show improvement in people's qualities of lives. In terms of MS centers versus the single practitioner, I personally think that a lot has to do with the person who has MS. If they have a complicated kind of MS that requires the skills of a lot of different health professionals, I think that there is no question in my mind that they will do better in an MS center that is rehabilitatively oriented, that can took at their whole circumstance and put together a management strategy. If they in fact have mild or benign MS and they are doing perfectly fine and are adjusted, I think anybody probably could manage them appropriately if they are kind and consid- erate and listen to them, because that is the major thing that they are looking for. COMMENT (Dr D. Paty): Well, I would like to make a statement on that regard following up on George Ellson's presentation earlier today, and that is we are entering a time when clinical studies in multiple sciero- sis are going to become more important rather than less important and we justify our MS center in Vancou- ver not necessarily because we deliver better medical care, we think we do, but we justify it primarily on the fact that we are studying the disease systematically and therefore we not only want that experience of the broad spectrum of patients with multiple sclerosis, but we need those patients, all of us do, for our studies in the future because, as George pointed out, patient material is going to become more and more scarce in the future for doing the various studies that we vitally need to do to answer some of these very important questions. QUESTION (Dr R Vorkinhagen, Vancouver): I wonder if Dr Schapiro has any comments about the use of magnesium for spasms. ANSWER (Dr Schapiro): I do not have comments about the use of magnesium for spasms except that it would make sense to me that it might be of value if we are in a temporary circumstance for spasms, more than Periactin makes sense, but that does not mean that Periactin does not work under those circumstances. QUESTION (Dr T. Tuncbay, Turkey): All along the conferences or the meeting I noticed one thing. We all talk about the MS patients, adult MS patients. How about the children, for instance, I see, sometimes, a 10-year-old child. Are we going to approach to the point, exactly the way we do for the adults, or we should have some different view for the children as far as the therapy is concerned, the rehabilitation is concerned, or the other parts of the MS? ANSWER (Dr Schapiro): You are talking about chil- dren who have MS, not children of parents who have MS. I think the one thing about rehabilitation and I think Dr Mertens would back me up on this is that we do not have a set way in which we handle every single person. We develop a unique treatment plan for that particular person's unique set of problems and that is the hallmark of a rehabilitation goal oriented plan and certainly the problems of a child are very different from the problems of an adult, but the problems of a young adult are different from the problems of an older adult, and I think we have to look at each one of those and develop a life management plan for each one of chose as an individual and not have an algorithm that we just follow for everybody. COMMENT (Dr Scheinberg): This is the problem of having these MS centers where you have a number of specialists around. They all feel that their needs have to be satisfied. We more or less put these patients into beds and I think this is the point that Randy was mak- ing, that if the patient is too long you cut their legs off, if they are too short you stretch them, but you basically cannot run a clinic this way. (Dr Schapiro): I don't know what he just said, but it sounded good. QUESTION (Judy Soderberg, Minneapolis, Minnesota): I was wondering if panel members could comment on seizures secondary to multiple sclerosis. ANSWER (Dr Schapiro): A sensitive topic, Judy, as you know. Judy is director of our day program in Min- neapolis, and our day program has a lot of very signif- cantly disabled people with MS who come for mainte- nance rehabihtadon once a week with the prospect that, hopefully, we can prevent some difficulties; and we are obtaining outcome studies from that group of people, and I would be happy to share that dam with you at some time. However, she raises the question because a number of those people have gone into sta- tus epflepticus at various times and clearly when that person goes into status they are harder to treat than the average person who goes into status for other rea- sons and the prognosis after they come out of status does not appear to be as good as people who go into status for other reasons as well. I have made the com- ment to her that you can almost see which people are going to do that and she made the comment to me then, why do you not prophylactically treat them with anticonvulsants before they go into status and I have never had the guts quite to do that. It is clear from epidemiological studies that about 1% of the popula- tion in general have seizures and it is probably abouc double that in the MS population in general and proba- bly in the Achievement Centre population it is proba- bly 10 times that, so probably about 10% of the people who have significant MS will have a problem with sei- zures. When it happens we treat them, but it would be nice to do a prospective study looking at factors that would give us an indication that people might be hav- ing a seizure in the future so that we could get ahead of it. QUESTION (Sue Forwell, Vancouver): I too am pardcu- larly interested in outcome measures in rehabilitation. I found it quite interesting, what you said, Dr Schapiro, that the MS Society is looking at developing tools about measures and I would like to hear a bit more about that; and my agenda in asking the question is that I think that there are tools that are used in other sciences, particularly the social sciences, that do investi- gate quality of life issues quite readily in terms of quali- tative methods, and perhaps we could look at anthro- pology or the historians at gathering information using ethnographic methods or case methods to look at qual- iry of life issues. I was discussing one night, I think, with a neurologist, Claude, from Switzerland about us- ing the FIM scale to look at measures, and I thought wouldn't it be interesting if we actually had no idea about scales and looked at a completely different way of measuring outcome instead of reducing it to a num- ber. Anyway, I would like your comment on that. ANSWER (Dr Schapiro): While I am thinking of it, we utilize the FIL scale regularly and have found it singularly unhelpful for measuring quality of life in people with MS. Clearly our patients do not change that much on the FIM scale, but they certainly do change in their ability to do a lot of things; the scale just is not quite sensitive enough. And specifically the quality of life issue, the Consortium of MD Centers, which I will remind everybody is meeting across the street and everybody is welcome to attend the wine and cheese party afterwards, last year put together a subcommittee on health services research, which has gotten a grant from MS Society. That subcommittee is a Canadian-United States amalgamation of people of many different disciplines, mostly psycholgists and health services researchers, and they have looked at a lot of different tools that are already available from a number of different sources. I don't know how far anthropologically they have gone, but they have gone in many different directions and submitted then a pro- posal to be funded by the MS Society to do some testing in that arena and that proposal now has been modified in order to make it appropriately fundable It is our hope at the end of all of this that we will have a usable tool, not just a tool, but a usable tool that will in fact look at various aspects of quality of life with some accuracy that we can then apply to various cir- cumstances in the area of rehabilitation and MS living in general. And so it is a hot topic and hopefully, this time maybe next year, there will be some studies that could be reported upon at the Consortium of MS Cen- tres meeting in Minneapolis in September of 1994, and we would Eke you all to come there at at that time. QUESTION (Dr Scheinberg): Randy, now that you have gotten your plug in for Minnesota, perhaps for the nonfe@nists here could you describe the FIM scale? ANSWER (Dr Schapiro):FIM, not FEM, Functional Independence Measurement Scale. It is a scale that looks at various activities of daily living and physical measurements and, basically, can you do it indepen- dendy, do you need assistive devices to do it, down the line to cannot do it at all, and things of that nature, and you score those individually and you get a total score. It works extremely well for stroke following, and there is stroke registry, a national stroke resistry, that follows these scores and works well for amalgamat- ing data. As I say, in MS it has not been, in our hands, at least as useful as it is in stroke, where people are in the hospital for 2 months and have big changes in their FIM scores. QUESTION (Dr Gujeo, Hungary): Fatigue is one of the greatest daily problems of persons with MS. Can you tell us a little bit more about pemoline treatment? ANSWER (Dr Schapiro): There have been a number of studies about pemoline, which is called Cylert in the United States. It is a stimulant which has the advantage of not requiring a narcotic refill and call-in in the United Scares that Ritalin has. There are a number of studies that show that it helps this lassitude kind of fatigue. You know there are four different kinds of fatigue that we have in MS. There is normal fatigue, what I call a short-circuiting fatigue when the demye- linated nerve poops out basically, there is the fatigue of depression, and then there is this overwhelming just tired fatigue that I was talking about today. There are studies that show very clearly that pemoline is of value in that kind of fatigue, but I do not like it as well as Prozac because it is a stimulant type of action so people will feel kind of a high on it rather than a natural feel- ing of being unfatigued, but it does work and we do use it. COMMENT (Dr Scheinberg): One of the advantages is the technical advantage of Cylert over Ritalin and the drugs such as the speed, is that pemoline in New York does not require a triplicate prescription whereas Rit- alin and Dexadrine do, but these are all drugs in the same category and pemoline does not cause physio- logic dependence and you do nor have a withdrawal reaction when you come off of it. It is a drug that works I think equally well to some of the other drugs that are used, but the use of Prozac, Randy, does lead you into then the next problem, is to manage the con- stipation that occurs. (Dr Schapiro): We have not been faced so much with constipation, but I tell my patients if they feel like killing their husbands while they are on Prozac that they should call Donahue first, make sure they get on television, and then call me next, but that is an "in joke" in the United States. COMMENT (Dr P. Ketelaer, Brussels, Belgium): I just want to comment a little bit about the outcome mea- surements in MS and that is a primary goal we have also in our proposal, which was introduced to the Euro- pean con-ununity and for which we received a 3-year financial support from the European community, and one of the goals is also on the assessment, outcome assessment scales. So you see, we are fairly in accor- dance with what is being done here in the United States and Canada, and we had gmdy two workshops last year and the previous year on these scales because that is the major problem to solve in order to come to outcome measurements. (Dr Schapiro): I might add that I think that the COSTAR and the European data base program are essential to these outcome studies. I think without those kinds of programs we are never going to have outcome studies. ----------------------------------------------------------- Copyright (c) 1994 by the American Neurological Association For ordering information or subscriptions please contact: Nancy Campbell Medical Journals Department of Little, Brown and Company Boston, MA 02108 (617)859-5636 ----------------------------------------------------------- This information provided by the Center for Neurologic Study. Please visit us at http://www.cnsonline.org