Multiple Sclerosis
Multiple sclerosis, or MS, is an autoimmune disease that progressively impairs the central nervous system. The body's immune system attacks the protective insulation of nerve fibers, known as myelin, causing a buildup of plaques and the eventual scarring and hardening of multiple nerve fibers. This process is known as sclerosis, hence the name of the disease. Once nerve pathways become damaged, nerve impulses direct muscle movement to slow down or to stop altogether.

MS usually strikes between the ages of 15 to 60, with most cases occurring between 20 and 40 years of age. It affects women twice as often as men, and is most prevalent in the northern United States, Canada, and upper Europe, where the climate tends to be temperate. Overall, an estimated 350,000 Americans suffer from MS, which is considered to be incurable by conventional physicians, who also have little understanding about its causes.

Symptoms 
As the buildup of plaque scars or strips the myelin sheath away from nerve fibers, nerve transmission becomes impaired, and the symptoms of MS begin to appear. They include loss of muscle control, problems with balance and gait, blurry or double vision, chronic pain, chronic fatigue, heightened sensitivity to heat and cold (especially heat, which can worsen other symptoms), and painful tingling sensations in the hands and/or feet. In advanced cases, patients can experience difficulty speaking, spastic movements, and weakness in the arms, hands, legs, and/or feet. Full or partial paralysis can also occur, and severe fatigue can make normal activities extremely difficult to carry out. Urinary incontinence or a frequent need to urinate can develop. In some cases, MS patients need to use a wheelchair; although in many cases, patients are able to continue living and working as before, but with increasing degrees of difficulty. A rarer symptom of MS is alexia, a sudden inability to understand written language.

MS tends to go into remission and then flare up again, intensifying and worsening with each episode. In some cases the progression of MS is swift, leading to serious degeneration within a few months or years, whereas others may experience less severe attacks that can occur on and off over many decades. No two cases of MS are exactly alike, making effective treatment extremely difficult. For this reason, it is essential that proper individualized treatment begin as early as possible following the initial appearance of MS symptoms.

Causes
Although conventional medicine claims that multiple sclerosis is caused by demyelination (the breakdown of the myelin sheath caused by the buildup of plaques), holistic health practitioners maintain that there are many other potential causes, as well. This view is strengthened by the fact that major symptoms of MS can be present even when there is little myelin damage; and, in some cases, major dymelination only produces minor symptoms. What follows is an overview of the other most common potential causes of MS.

Candidiasis: Candidiasis, also known as candida, is caused by systemic overgrowth of a type of yeast, Candidiasis albicans, beyond its normal location in the lower intestinal tract. Left unchecked, candidiasis can greatly exacerbate MS symptoms, as was first documented by William G. Crook, M.D., author of The Yeast Connection. According to Dr. Crook, cases of MS in which candidiasis is a factor can be greatly improved once the spread of Candida albicans is halted and then reversed.

Dental Amalgam Fillings: Dental amalgam fillings contain mercury, a highly toxic substance that can be leeched out from fillings in the form of mercury vapors that settle in the body's tissues and organs. Over time, as mercury continues to accumulate in the body, a host of serious health problems can occur, including MS or symptoms that are virtually indistinguishable from it. People with MS have been shown to have mercury levels in their cerebrospinal fluid that are much as 700 percent greater than healthy people.

The health problems mercury causes are due to its ability to attach itself to the DNA in the body's cells and cell membranes, distorting them and impairing their ability to properly function. As this cellular distortion occurs, the body's immune system acts as if the affected cells are foreign invaders and begins attacking them. In the process, myelin can be destroyed. In addition, the mercury vapors can interfere with the body's enzyme functions and cause the chronic fatigue that is often a symptom of MS. According to Hal Huggins, DDS, a leader in the field of biological (holistic) dentistry, and a renowned expert in mercury toxicity, many cases of MS have been completely reversed once mercury amalgams are properly replaced and the body is detoxified.

Poor Diet: Since 1950, when Roy Swank, MD, of Oregon Health Sciences University, first discovered that MS patients had higher than normal concentrations of saturated fat intake from the foods they ate, holistic health practitioners have pointed to poor diet as a major potential contributing factor for multiple sclerosis. This is particularly so among people who eat a standard Western diet high in dairy products, meats, and commercially processed foods that contain high amounts of unhealthy, saturated fats, but are low in unsaturated fats containing essential fatty acids (EFAs). EFAs are vital for the optimum health of both the brain and the nervous system, and are found in fresh fruits and vegetables, oily fish, and olive and seed oils, all of which are often lacking in the diets of MS patients. The lack of such foods and the EFAs they contain can set the stage for demyelination.

Electromagnetic Fields: Electromagnetic fields (EMFs) are generated when electric currents flow through wire coils. This type of low-level radiation can cause a variety of health problems because of how EMFs can negatively impact the body's bioenergetic balance and damage enzymes that regulate growth. EMFs can also negatively affect the body's pineal gland, as well as upset the balance and production of the hormones melatonin and serotonin, both of which are essential for optimum brain and nerve function. Research has shown that MS patients usually exhibit lower than normal levels of both these hormones, as well as calcification of the pineal gland. In addition, EMFs can interfere with the how the body's cells divide and multiply.

You are exposed to EMFs every time you use an appliance that runs on electricity. These include computers, fluorescent lights, microwave ovens, televisions, and video terminals. Cell phones, electrical poles, and many types of motors that can also create unhealthy EMF exposure.

Environmental Toxins: Environmental toxins can cause or exacerbate MS in a variety of ways, including impairing and interrupting the body's metabolic processes. In addition, environmental toxins can act directly to damage the myelin covering that protects nerve fibers. They can also distort cells and cell membranes, triggering an autoimmune response that can cause nerve damage and MS symptoms. Among the offending toxins are chemicals found in commercially processed foods, toxins contained in tap water, carbon monoxide, diesel exhaust, fumes and vapors released from gas water heaters, commercial solvents, aerosol sprays, and chemicals contained in the chipboard and foam used to make furniture and carpets.

Food Allergies and Sensitivities: People with multiple sclerosis often suffer from food allergies or sensitivities, which can greatly exacerbate their MS symptoms. The most common foods that trigger food allergies and sensitivities include coffee and caffeine products, corn, dairy products, food additives and preservatives, fungi such as mushrooms, gluten (a food ingredient in barley, oats, rye, spelt, and wheat), ketchup, milk, sugar, vinegar, wheat, and wine. However, any food can potentially act as an allergy trigger.

Genetic Predisposition: MS is not considered a hereditary disease. Even so, the disease does appear to be related to genetic predisposition. First generation descendents or relatives of people with MS have a 30 to 50 greater risk of developing the disease than people born into families where there is no history of multiple sclerosis. If your relatives have MS, you should be screened as early as possible.

Infections: Infection can greatly exacerbate MS symptoms, and may also play a role in causing it. Researchers, for example, have found that viral infections such as the Epstein Barr Virus, not only reduce the level of essential fatty acids in the brain to levels commonly found in MS patients, but infections can also interfere with the body's ability to properly utilize essential fatty acids, weakening the immune system and possibly triggering autoimmune reactions that can result in demyelination. Based on such findings, holistic health practitioners warn that people who suffered from viral infections, especially Epstein Barr Virus or mononucleosis (which can be trigged by Epstein Barr) in childhood or adolescence, may be more susceptible to developing MS later on in life.

Other infectious agents known as stealth pathogens may also play a role in the development of MS, as well as exacerbate its symptoms. Stealth pathogens are types of bacteria with cell walls that lack proper structure, giving them the ability to easily transport DNA between the cells of the human body. Stealth pathogens can also fuse together. Both of these outcomes can trigger immune responses that can cause a variety of autoimmune diseases, including MS.

Another type of bacteria that can cause or contribute to MS is Borrelia mylophora. If this bacteria gains a foothold in the body, it can infiltrate the nervous system. In white blood cells' fervent effort to eliminate Borrelia mylophora, the immune system can also destroy surrounding myelin, causing MS. Borrelia mylophora is very similar to Borrelia burgdorferi, one of the causes of Lyme disease, and some researchers speculate that Lyme disease itself is also a cause of MS because of its similar affects on the body's immune and nervous systems. For more information about the link between MS and Lyme disease, see Could Lyme Disease Become MS? and Researcher Reveals Possible Connection with Lyme and MS.

"Leaky Gut" Syndrome: "leaky gut" syndrome is caused by food allergies and/or candidiasis causing a breach in the intestinal wall, allowing toxins to flood into the bloodstream. As this happens, the immune system attempts to correct the problem by launching an attack on these invaders. In the commotion, however, immune cells and antibodies may also attack healthy cells, including those that comprise myelin. The stress placed on the body by "leaky gut" syndrome can exacerbate the symptoms of people who already have MS, and also make people with MS more susceptible to additional pathogens, such as bacteria, viruses, and unhealthy yeasts.

Nutritional Deficiencies: Even when MS patients follow a healthy, balanced diet, they can often be deficient in vital nutrients because they have difficulty assimilating them. The most common nutrient deficiencies in MS patients are vitamin B1, vitamin B6, vitamin B12, biotin, folic acid, magnesium, manganese, selenium, and zinc, along with various amino acids and essential fatty acids.

According to the late Hans Neiper, MS, a pioneering researcher and holistic physician in Germany, lack of calcium AEP, also known as colamine phosphate, can significantly increase the risk of MS. Calcium AEP is required for the body to produce the electrical charges on the myelin surface and on nerve cell membranes that are necessary for proper function of the central nervous system. Lack of calcium AEP not only interferes with the production of these electrical charges, Dr. Nieper maintained, but it also causes cells membranes to become too porous, allowing toxins and immune cells passage into the body's nerve cells, creating an autoimmune reaction and the destruction of myelin.

Stress and Trauma: Many cases of MS are often initially triggered by prolonged emotional stress or physical trauma. Moreover, the initial symptoms of MS will often first manifest at the part of the body that suffered an injury.

Treatment
While conventional physicians consider multiple sclerosis to be incurable, holistic physicians are often able to slow and reverse its progression. Early diagnosis, followed immediately by a comprehensive treatment program addressing all of the factors that can cause MS, provides the best hope for a successful outcome—the end result is often a complete cure. As patients follow their prescribed treatment protocols and make necessary changes to their diet and lifestyle, at the very least, noticeable improvements are achieved, enabling them to have much greater control over their symptoms.

MS affects each person differently and requires an individualized treatment program in order to be properly dealt with. For this reason, holistic practitioners recommend that in-depth testing be conducted to fully determine the factors involved in each patient's condition. Testing can include a mineral sweat test to evaluate each patient's overall mineral status as well as possible heavy mineral poisoning. This test is simple to perform and involves the application of a specific type of plaque on the patient's back. The patient is then engaged in physical activity that causes him or her to moderately perspire for an hour. Perspiration is collected in the plaque and then analyzed.

Other recommended tests include nutrient and antioxidant assessment, adrenal stress test, complete blood count testing, a biochemistry panel, glucose tolerance testing, and stool analysis to determine the health of the patient's digestive system and ability to assimilate nutrients.

Screening for food and environmental allergies is also important.

Once the underlying causative factors are assessed, a proper treatment program can be created. Typically, it will include the following therapeutic approaches:

Aromatherapy: Adding juniper or rosemary essential oils to extra virgin olive oil (5 percent essential oil to 95 percent olive oil) and then massaging your body with this blend can help ease MS symptoms.

Ayurvedic Medicine: The Ayurvedic herb ashwaghanda can often be helpful in alleviating symptoms of MS because of its adaptogenic properties that help to restore balance to various body systems, including the immune and nervous systems.

Bee Venom Therapy: Bee venom therapy, also known as apitherapy, involves the injection of honeybee venom by hypodermic needle, or by applied bee stings. In the latter case, trained physicians hold honeybees with tweezers, placing them over patients' bodies, where the bees then sting them. The bee stings can last for only a few seconds or for as much as five minutes, depending on the dosage of bee venom that is determined to be necessary.

Over 1,500 scientific papers on bee venom therapy have been published in Europe and Asia attesting to the healing benefits of bee stings. According to the practitioners of the therapy, bee venom therapy can begin to ease MS symptoms after as little as 20 to 40 bee stings, with most patients achieving significant reversals of their symptoms, including complete remission, within six to 18 months. The therapy works by first stimulating the immune system, both at the site of the bee sting, and systemically throughout the body. Then, as the venom enters the body, it produces anti-inflammatory effects that are 100 times greater than cortisone shots. Bee venom also acts as a potent antioxidant.

Caution: Approximately 2 percent of the population is allergic to bee venom. If you fall into this category, you should avoid bee venom therapy because of the risk of severe allergic reactions and anaphylactic shock.

Biological Dentistry: If you suffer from MS due to dental amalgam fillings, you should consider having them removed and replaced with biologically compatible fillings. According to Dr. Hal Huggins, individuals should undergo a serum biocompatibility blood test to determine what materials are biologically compatible with their body. He cautions that some replacement filling materials can over-stimulate or depress immune function, and that others contain aluminum, another toxic metal that should be avoided.

For best results, amalgam removal and replacement should be individualized based on each person's unique biochemistry. Then, once the fillings have been removed and replaced, treatment should be followed by a detoxification program to help rid the body of stored mercury in tissues and organs. Dr. Huggins recommends that nutritional support, along with acupressure and massage therapy, be part of such a detoxification program, depending on each patient's specific needs. Following detoxification, specific individualized, dietary guidelines and nutritional supplements are used to further enhance recovery.

Dr. Huggins has treated hundreds of MS patients using the above protocol, and achieved significant benefit in 85 percent of his cases, including wheelchair-bound MS patients recovering their ability to walk.

Detoxification Therapies: Detoxifying the body of toxins and improving the health and function of the lymphatic system can significantly reduce MS symptoms. Useful detoxification strategies include colonics, dry skin brushing, enemas, far-infrared and steam saunas (under your physician's supervision), fasting, herbal wraps, lymphatic massage, and light beam therapy. For more information on detoxification, see Cleansing and Detoxification.

Diet: MS patients should emphasize an organic, whole foods diet that is low on saturated fats and includes plenty of fresh organic fruits and vegetables. According to Dr. Swank, who has been exploring the link between diet and MS for more than 50 years, saturated fat intake should be limited to not more than 15 grams each day, which is the equivalent of three teaspoons per day. Ideally, all sources of saturated fats, such as dairy products, meats, and commercially processed and packaged foods, should be avoided. Instead, emphasis should be on foods high in essential fatty acids and polyunsaturated and monounsaturated fats, which are contained in fresh fruits and vegetables; oily fish, such as bluefish, bass, salmon, sardines, and trout; and olive, flaxseed, safflower, and sunflower oils. For additional benefit, Dr. Swank recommends supplementing with between four to ten teaspoons of unsaturated oils each day.

Other foods to include in your daily meals are mung beans and mung bean sprouts, millet, free-range poultry, and organic nuts and seeds, while avoiding alcohol, chocolate, dairy products, eggs, commercially prepared and fast foods, fermented foods, hydrogenated oils and solid fats, margarine, milk, red meats, salt, shellfish, sugar, and yeast, as well as hydrolyzed vegetable proteins and food additives and preservatives.

Energy Medicine: One of the most effective ways to screen for all of the underlying causes of MS is a technique known as electrodermal screening, or EDS. Electrodermal screening is a noninvasive diagnostic technique that measures the electrical output of specific points on the hands, face, or feet that correlate to acupuncture meridian points at the beginning or end of energy meridians. The electrical signals given off at these points provide information about the health status of the body's organs and organ systems, and can also be used to detect the presence of toxins, energy and hormonal imbalances, and harmful microorganisms. In the hands of a highly skilled practitioner, EDS can often detect hidden contributing factors for MS, even when other sophisticated testing methods fail to do so because of the fact that both health and disease are first and foremost the results of balanced or imbalanced energy.

Energy medicine can also be used to protect MS patients from harmful EMFs. One of the most useful devices for doing so is a Teslar watch, named after the brilliant inventor Nikola Tesla, which protects against harmful EMF frequencies while producing a healthy EMF signal similar to the earth's resonance of 7-9 Hz to enable the body to operate within its own natural frequency range.

Environmental Medicine: Practitioners of environmental medicine test MS patients for dietary and environmental allergies—such as chemicals, dust, heavy metals, mold, and pollen—that can contribute to and exacerbate MS symptoms. Food allergies are determined via blood testing, elimination diets, and electrodermal screening (see Energy Medicine above). To conduct an elimination diet, remove suspected offending foods from your diet and see if your symptoms are reduced within a few days. If so, you should avoid such foods completely for 60-90 days. After this period you may begin to slowly re-introduce them into your diet if symptoms do not return.

Environmental allergies can be diagnosed using electrodermal screening and/or a technique known as maximum tolerated intradermal dose testing. The latter test is conducted by the injection of suspected substances into the skin. If an allergic reaction occurs, patients can often become desensitized to such substances by injecting them in the largest dose that does not cause a reaction. In the case of stored toxins, a detoxification regimen can be devised to help eliminate them. It is not unusual for MS patients to experience a complete remission of their symptoms once offending foods and environmental substances are eliminated.

Enzyme Therapy: The use of pancreatic enzymes can improve MS symptoms, often quite dramatically. This natural approach for treating MS is widely used in both Germany and Mexico.

The reason pancreatic enzyme therapy can be so helpful is because of the enzyme's ability to digest or destroy circulating immune complexes (CICs). CICs are undigested food particles that remain in the blood, triggering an autoimmune reaction that can lead to the destruction of myelin. As they are digested or destroyed by pancreatic enzymes, the autoimmune reaction ceases, often leading to an improvement in MS symptoms, and greater periods of respite before MS symptoms flare up again. To enhance this treatment approach, you can also supplement with essential fatty acids and selenium.

Histamine Therapy: Histamine, a compound created from the amino acid histidine, is released during allergic reactions. Since the 1950s, researchers have known that histamine can relieve MS symptoms due to the various reactions it causes in the body, such as contraction of smooth muscles, dilation of blood vessels, and improved secretion of gastric acid.

Histamine can be applied topically and absorbed through the skin. When administered to MS patients, research shows that they typically exhibit improved bladder control, cognitive function, and muscle strength, as well as a reduction in the levels of fatigue that often accompany MS. Concurrent with these improvements are an increase of blood flow to the brain, improved digestion, and a cessation of inappropriate immune responses. In some cases, there is also a regrowth of myelin tissue.

Hydrotherapy: Hydrotherapy is the application of water, ice, steam and hot and cold temperatures to maintain and restore health. Treatments include full body immersion, steam baths, saunas, sitz baths, colonic irrigation and the application of hot and/or cold compresses. Hydrotherapy is effective for treating a wide range of conditions and can easily be used in the home as part of a self-care program. Many Naturopathic Physicians, Physical Therapists and Day Spas use Hydrotherapy as part of treatment. We suggest several at-home hydrotherapy treatments. Please seek the advice of your alternative health care practitioner before undergoing these procedures to make sure they are appropriate for you.

Hyperbaric Oxygen Therapy: Hyperbaric oxygen therapy, or HBOT, involves the placement of patients inside a sealed oxygen chamber. Once inside, patients sit comfortably as the atmospheric pressure is elevated to saturate the body's tissues with oxygen. In addition to increasing the oxygen supply to the body's tissues, HBOT can help enhance immune function and reduce inflammation, heal damaged blood vessels and improve blood circulation, and, most importantly, stimulate the production of new myelin.

Physicians in England who administered HBOT to approximately 4,000 MS patients reported that nearly half of them experienced significant benefits, including improved control over their symptoms, less fatigue and pain, and improvements in their balance, bladder control, coordination, upper and lower limb movements, speech, and vision.

According to Richard A. Neubauer, and HBOT expert and author of the book Hyperbaric Oxygen Therapy, an average of 20 HBOT sessions per year are enough to prevent a return of MS symptoms, with best results being obtained when HBOT is administered as soon as possible after MS symptoms first begin.

Juice Therapy: Short fasts using organic fruit and vegetable juices can help alleviate symptoms.

Lifestyle: Exercise can help MS patients in a variety of ways, including helping to balance immune response, improving mood, and keeping muscles toned and supple. The best forms of exercise for MS patients include walking, gentle aerobic exercise, and yoga.

Stopping smoking and reducing your exposure to secondhand smoke is advised. Research has found that MS patients who smoke experience an immediate deterioration of their motor function, most likely because of how nicotine negatively affects the central nervous system.

In addition, you should also avoid the use of electric heating pads, chlorinated water, and fluoride, which is found in tap water and commercial mouthwashes and toothpastes, all of which can exacerbate MS symptoms.

Magnet Therapy: Though MS can be exacerbated by electromagnetic fields (EMFs), magnet therapy that employs weak pulsed magnetic fields can be very helpful in soothing MS symptoms. Among the MS symptoms that are improved by pulsed magnet therapy are alexia, bladder incontinence, fatigue, and spasticity.

Mind Body Medicine: Mind/body medicine can help MS patients cope with stress, which can significantly increase MS symptoms. Mind/body approaches can be as simple as taking a short, restful nap each day or breathing deeply through the belly periodically for five to ten minutes at a time. Other useful mind/body medicine techniques include biofeedback, guided imagery and visualization, hypnosis, and meditation.

Nutritional Supplements: Proper nutritional supplementation is essential for MS patients. This includes supplementing with essential fatty acids, especially omega-3 oils such as alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), evening primrose oil, and flaxseeds and flaxseed oil.

Many holistic physicians also recommend oil instillation in conjunction with a chamomile enema. The purpose of the enema, which involves taking chamomile tea into the lower bowel via an enema bag, is to clean out the colon and to relax the intestinal muscles, which can often spasm in cases of MS. Following the enema, 3 tablespoons of either organic, cold-pressed flax, sunflower, or walnut oil is inserted into the colon using a syringe tipped with a catheter. This enables the body to quickly absorb the essential fatty acids the oil contains through the intestinal walls. For best results, both the enema and oil instillation should be administered each night for three weeks. Afterwards, the dose can be reduced to 1 1/2 to 2 teaspoons and can be administered three times a week.

In addition to essential fatty acids, the following nutrients are also recommended for MS patients: beta-carotene and carotenoids; bioflavonoids; B-complex vitamins, along with vitamin B1, B3, B5, B6, and B12; vitamin C; vitamin D; vitamin E; folic acid; calcium AEP; coenzyme Q10 (CoQ10); magnesium; selenium; and zinc. Other helpful supplements include alpha lipoic acid; aspartic acid; dimethylsulfoxide (DMSO); gamma-aminobutyric acid (GABA); glutamic acid; glycine; methylsufonylmethane (MSM); and the amino acids carnitine, choline, cysteine, glutathione, and methione.

5-HTP (5-hydroxy-tryptophan), which aids in the body's production of the hormones melatonin and serotonin, is also recommended for MS patients.

Action Plan for Miltiple Sclerosis:
  1. If you suspect you suffer from multiple sclerosis, seek diagnosis as soon as possible, as early diagnosis can dramatically improve the likelihood of a successful treatment outcome. An excellent means of diagnosing MS is electrodermal screening, which can often detect disease symptoms far earlier than conventional testing methods, and which can also detect hidden causative factors that other tests are unable to find.

  2. A healthy diet is essential for dealing successfully with MS. Emphasize a diet that is low in saturated fats and abundant in essential fatty acids. Eat plenty of fresh, organic fruits and vegetables, oily fish, free-range poultry, and olive, flaxseed, safflower, and sunflower oils. Organic nuts and seeds, millet, mung beans, and mung bean sprouts are also recommended.

  3. Avoid alcohol, chocolate, dairy products, eggs, fast and commercially prepared foods, fermented foods, hydrogenated oils and solid fats, margarine, red meats, salt, shellfish, sugar, and yeast, as well as hydrolyzed vegetable proteins and food additives and preservatives.

  4. For additional benefit, supplement with four to ten teaspoons of unsaturated oils each day.

  5. Recommended nutritional supplements for MS include B complex vitamins, vitamin B2, vitamin B3, vitamin B6, vitamin B12, beta carotene and other carotenoids, bioflavonoids, vitamin C, vitamin D, vitamin E, calcium AEP, magnesium, selenium, and zinc.

  6. Other useful supplements include alpha lipoic acid, CoQ10, DMSO, MSM, and the amino acids carnitine, choline, cysteine, glutathione, and methionine.

  7. Test for and eliminate all foods and environmental factors that can cause allergies and sensitivities.

  8. To reduce the burden of toxins in your body, consider a program of detoxification therapy, ideally under the supervision of your physician.

  9. If you have mercury-containing dental amalgam fillings, have them removed and replaced with new fillings made from materials with which you are biocompatible.

  10. Avoid exposure to unhealthy electromagnetic fields (EMFs) caused by electricity flowing through the coils of electrical wires and common home and office appliances and equipment, as well as cell phones and many types of motors. To protect yourself from unhealthy EMFs, consider wearing a Teslar watch and receiving weak pulsed magnet therapy.

  11. Be sure to minimize your stress levels using mind/body medicine techniques such as biofeedback, guided imagery and visualization, hypnosis, meditation, and relaxation exercises such as deep breathing.

  12. A restful nap each day can also help reduce your MS symptoms.

  13.  Regularly engage in an exercise program of gentle aerobics or walking to keep your muscles toned and supple.

  14. To increase oxygenation of tissues and to stimulate the repair of myelin, consider hyperbaric oxygen therapy (HBOT).

Reports
Index
Multiple Sclerosis Treatment
MS Treatment: When The Body Fights Against Itself

The Sum is Equal to the Whole: Individualizing MS Treatment

Mobility Matters: Assisted Devices for People with MS
The Buzz About Bee Venom Therapy for MS and Arthritis
Beyond Just Tired: Figuring Out MS-Related Fatigue
Let There Be Light
Yoga Matters: Exercise for MS
A Quicker Predictor for MS
Cognitive Impairment in Multiple Sclerosis
Cracking the Clinical Trials Code
What's Happening to Me?: Invisible MS
Unraveling the Mystery of Autoimmunity
Epstein-Barr Virus: Does It Increase the Risk for MS?


Multiple Sclerosis Treatment   By: Dina A. Jacobs, MD & Steven L. Galetta, MD
What's the Best Way to Stay Healthy and Avoid Attacks?
Avoid heat
There are several things you can do to feel better if you have MS. First, try to avoid the triggers that make you feel worse. Although heat does not further damage the nervous system, it may bring out old symptoms that you haven't had in a while, as well as deplete your energy levels. As such, it is generally a good idea to avoid overexerting yourself on hot and humid days and stay as cool as possible in the summer months. While taking hot showers or baths will not cause damage to your nervous system, the previously damaged neurons do not function quite as efficiently while your body temperature is up, thus making you notice your old symptoms, such as weakness and visual problems.

Good sleep habits
It is extremely important to develop good sleep habits. While none of us does well with sleep-deprivation, it is particularly important in people with MS, because it may affect how well you function the next day. While not proven to cause MS flares in general, sleep-deprivation, getting run down, and stress may affect how your body's immune system works in ways we don't yet understand.

Diet
People often ask if there is a special diet that they can follow to stay well. While there are no vitamins or special foods proven to prevent flares, we do recommend that people eat a well-balanced diet. If people find it difficult to eat a well-balanced diet, it is a good idea to take a daily multi-vitamin to get the vitamins and minerals that they may be missing. People should avoid aggressive weight-loss plans and fasting, as that may limit their energy level.

Calcium supplements
Osteoporosis (thinning of the bones) can be a particular problem in MS. Women, who comprise the majority of people with MS, are at a general increased risk of developing osteoporosis. In addition, decreased weight-bearing activity, which is often a problem in MS, can increase your risk. Finally, the long-term use of steroids (over months and years, not in the short term) can lead to osteoporosis as well. It is particularly important to get an adequate amount of calcium in your diet. If you can't do so by eating enough dairy products, then you should take a calcium supplement.

Another question people often ask is how to exercise. In general, physical activity is a good thing in MS. It keeps people flexible, helps to prevent spasms, and keeps up muscle mass. But, as with anything else, too much of a good thing can be bad. Overexertion can lead to problems with fatigue and muscle weakness. You can stick to whatever exercise regimen worked for you in the past, but remember that you must pay special attention to your body signals. If you're feeling like you're pushing yourself too hard, then ease up. It is also important to discuss your exercise regimen with your doctor first. If you weren't a runner before you were diagnosed, then it may not be the best time to start. Swimming is an excellent exercise: it keeps you flexible, is a great cardiovascular workout, builds muscle mass, and keeps your body temperature low while you exercise. Physical therapists are great at helping you to plan an exercise regimen that works for you.

Pregnancy and MS
Although whether or not you should become pregnant is a question you need to ask your doctor, and more importantly yourself, there are some general words of wisdom that may help. It used to be a widely held notion that women with MS shouldn't get pregnant. In general, that is not currently accepted. Again, it is important to tailor that thought to your own level of disease and what you think you can manage in terms of energy levels and the difficulty of child-rearing. For example, you may want to have a small family, but again that is a personal decision, and one to take into consideration in thinking how much your energy will allow. For the most part, pregnancy does not lead to increased disability in MS. In fact, recent studies have shown that there are actually fewer exacerbations during pregnancy. However, there do tend to be more attacks in the post-partum period (especially between three and six months after delivery), although not drastically more than the general MS population. Overall, there is no change in the level of disability. It is a good idea to restart immunomodulating therapy as soon after delivery as possible. These medications are not used during pregnancy, as the effects to the fetus are unknown, and should be stopped several months (we advise three) prior to conception. If you are planning to conceive, you should discuss these issues with your neurologist and gynecologist. Again, this is a very personal decision, and one that should be tailored to your level of disease and to your lifestyle.

Conclusion
As you can see, multiple sclerosis is a variable disease. The exact cause of MS remains unknown, but many factors are thought to play a role in its development. We now have several medications available to treat the symptoms of MS and to prevent them from developing. Your experience with MS may be quite different from other people with whom you speak. It is important to keep that in perspective and to bring up any questions you might have with your physician.


MS Treatment: When The Body Fights Against Itself   By: William Stuart, MD
There are approximately 350,000 people in the United States and 2.5 million people worldwide living with multiple sclerosis (MS), a disease for which there is no known cure. MS can affect any area of the nervous system, and cause a wide variety of symptoms such as visual problems, weakness, or numbness.

Though there is no cure for MS, there are a number of effective treatments available that can slow the progression of the disease. Some of the medications most widely used to slow MS progression, such as Betaseron, Avonex, and Rebif, are called interferons. These drugs have proven to be some of the most effective medications for relapsing MS. Over time, however, people taking an interferon medication may produce "antibodies", or proteins that fight foreign substances in the body. These antibodies begin to fight against the interferon medication, and neutralize its effectiveness.

The development of antibodies poses an interesting problem for doctors and patients as they create what will often be a life-long treatment plan for an incurable disease. "There isn't any such thing as treating MS for a year or two years; this is a 40- to 50-year disease," says Dr. Bill Stuart, Medical Director of the MS Center of Atlanta. "You want to pick a drug that you can use for an extended period of time."

Below, Dr. Stuart describes the balancing act of choosing an MS treatment plan, and the role that the development of antibodies plays in making that plan.

What are antibodies?
WILLIAM STUART, MD: Antibodies are protein substances that the body develops in response to some offending antigen (a different substance), whether it's outside the body or inside the body. The antigen provokes the body's response to develop an antibody, which then protects the body.

What is the concern about the interferon medications creating antibodies?
The concern is that these neutralizing antibodies will render the drugs ineffective in controlling the disease.

The medications we use to treat MS -- with the exception of Copaxone - are interferons, which produce antibodies. The body recognizes the drugs as foreign substances that it doesn't want there. And the drugs that we have available -- Betaseron, Avonex and Rebif, all of which are interferons - have varying degrees of antibody production. These range from about 40-45% in Betaseron to 25% in Rebif and 2-5% in Avonex.

How do these antibodies develop?
The injection of a substance, such as an interferon, into the body, can stimulate the body to produce antibodies by other cells in the body. It is like coming into contact with a virus, which stimulates the immune system to react and create antibodies. Once those antibodies are there, the capacity for them to be there -- even though they may change in levels from time-to-time -- is permanent.

How long does is take MS patients to have clinically significant levels of antibodies?
Between a year and two years is when you generally start to see some problem with antibody formation. We're seeing, though, in some of our long-term treatment patients, that the antibodies may develop seven or eight years into treatment. At least, that's when they are recognized. The patients begin to fail the benefits of treatment and you check the antibodies and they're positive.

Do we know for sure whether antibodies decrease the effectiveness of MS treatments?

Yes, I think it is known for sure that the presence of antibodies has an impact on the effectiveness of the drugs. It isn't known for sure what the extent of their effect is, but I think the data about antibodies that has come from the existing phase III trials is enough to raise concern.

How do antibodies affect your decisions about treating patients?
You want to pick a drug that you can use for an extended period of time. I look for the drug that is going to provoke the least amount of problems so that the patient's compliance in taking it long-term will be good. I think it is very important to consider the production of antibodies in determining which drug to use, particularly if there is any truth to the issue that the presence of the antibodies to one drug may counteract the effectiveness of another drug.

We talk to our patients about the potential development of antibodies, and we describe it as one of the issues involved in long-term treatment. It's important that they understand it, and it factors into their treatment decisions.

How does this information affect your patients?
MS is a very difficult disease to monitor. We expect progression, even under the best of circumstances. We know that none of the drugs are completely effective. If the patient is progressing, then it's hard to know whether it's driven by neutralization from the antibodies or if the drug that they're taking just isn't quite effective enough. So you have to send off a specimen for antibody testing to find out.

This isn't always easy to get reimbursed for, and it's a fairly expensive test, so you can't do this every week or every month.

Do you think that all patients should be tested for the presence of neutralizing antibodies?
I'm increasingly coming to the conclusion that we should test it more frequently and if we could get coverage for the test, we probably would do it maybe twice a year as a routine on patients who are taking interferons, because the incidence is relatively high.

What's the bottom line for MS patients?
Patients need to know about neutralizing antibodies. It is an issue under significant discussion and needs further investigation. And they need to know that antibodies may be one of the reasons that their medication isn't working effectively. It has to be factored into the long-term, 10-, 20-, 30-year decision-making regarding their treatment.


The Sum is Equal to the Whole: Individualizing MS Treatment   By: Christine Haran
Multiple sclerosis (MS) is an insidious disease where destructive lesions in the brain and spinal cord interfere with practically every physical process in the body. No two people have the exact same set of symptoms, which can range from the annoying to the disabling. And that's why many MS specialists are saying that the management of MS symptoms should also vary from person to person.

In MS, the body mistakenly attacks its own myelin, the fatty tissue that insulates the nerves in the central nervous system, leading to attacks or flare-ups of MS symptoms. Disease-modifying drugs are given to decrease the frequency of those attacks and to slow down the progression of the disease.

"But treating the pathology of MS does not necessarily translate into treating symptoms of the disease," says Heidi Crayton, MD, co-director of the Multiple Sclerosis Center at the Georgetown University Multiple Sclerosis Center in Washington, DC. "I believe it is when people's symptoms aren't being addressed that they stop taking their disease-modifying drug, because they don't feel any better."

Treating MS symptoms can help people not only stay on their disease-modifying drugs but also feel better. And effective symptom management, Dr. Crayton says, starts with good doctor-patient communication. In an MS center, the neurologist will oversee symptom management, but outside of a center, the neurologist might refer a patient to other specialists or to the primary care doctor.
 
What are the most common MS symptoms?
Most people have symptoms from their MS that affect their quality of life on a day-to-day basis. Probably the most common symptoms are fatigue, spasticity, bladder and bowel dysfunction, cognitive dysfunction (problems with thinking and remembering), sexual dysfunction and pain. The symptoms can occur by themselves or in conjunction with other symptoms and when they build up, MS becomes a lot more disabling.

How do you approach the treatment of such a wide range of symptoms?
Doctors and patients often get very overwhelmed and are not quite sure where to start. It really is a kind of a negative feedback loop. For instance, if somebody's fatigued and depressed, they're not very likely to exercise. And, as the level of exercise decreases, spasticity increases and so does constipation. And if you're more spastic and constipated, you have a full colon, so you usually develop bladder problems. And if you have bladder problems, you're probably not getting good sleep. And if you're not getting good sleep, then you usually experience cognitive deficits. And cognitive deficits feed into fatigue and depression. So it is a very vicious cycle and you just have to dive in.

I ask the patient whether or not they want a symptom treated; that's a very important step that we don't always pay attention to. For example, there have been situations where I treated spasticity, stiffness usually in the legs and sometimes the arms, in people who are very weak. But I found out that the treatment ended up disabling that person even more, because somebody with absolutely no strength in their legs sometimes relies on stiffness to be able to stand up or to support their bodies. So sometimes when I would treat spasticity, I would take that support away and then they'd have noodle legs. So, I've certainly learned that if it's not really bothering the patient, then it shouldn't be treated.

How do you treat spasticity when it is bothersome?
Spasticity involves increased muscle tone, jerkiness or spasms. It often gets worse as muscles get weaker. Sometimes, it's very painful to have very tight, contracted muscles. Some patients refer to it as their "sewing-machine" leg because it kind of bounces around. It can very bothersome, especially at night.

Management of spasticity first starts with movement because muscles that don't move become more spastic. So I recommend that people stretch in the morning and evening. For people who are in a wheelchair, passive range-of-motion exercises, where someone else is lifting your limb, is wonderful. Also, yoga and working in the water can be very helpful for managing spasticity.

How do you treat bladder problems?
There are three different kinds of MS bladder problems. The bladder is ultimately just a big muscle. Some people have spasticity of their bladder, which means that when a little bit of urine comes down from the kidneys, their bladder starts to contract very quickly and they feel like they have to get to the bathroom right away.

The other kind of bladder is one that becomes a big, floppy muscle. Normally, our brain receives the first signal that there is urine in the bladder at about 250 cc's, but we can override that and still hold it. Well, these people don't get that signal. Their bladder fills and fills until it just spills over. Those people then become incontinent, which can be very disabling. Then there are people who have a combination of symptoms and they are tied to the bathroom.

Depending on which of those issues is the prominent one, we do have some things that we can implement. When the bladder is spastic, we can use medicines that quiet down that irritability and spasticity. In people who have a difficult time getting urine out, pressing on the bladder can help to completely empty it. Sometimes, people have to start using a catheter and many patients, when they hear that, feel like that's the beginning of the end. I try to explain that it can be very liberating once they're the ones who are able to control the function of their bladder. It is relatively simple to learn how to do.

How do you treat bowel problems?
We most commonly think about that in terms of constipation, but some people have difficulty with loose or explosive stools. A lot of people have bladder problems, so they don't want to drink water. But for your bowel function to be optimal, you need two liters of water a day and 30 g of fiber. For somebody who has to pee every five minutes, when they hear "two liters," they say, "You're crazy." And I say, "You know, there are going to be times when you're home and close to the bathroom and, at those times, you need to catch up on your fluid intake." After all, fiber with no fluid equals cement, so you can end up making the problem much worse.

For people with loose stool or explosive stool, the treatment is actually the same—fiber—which sounds very counterintuitive. But bulking up the stool helps the sphincter function better. There are medicines that we can use as well, but we try to start with fluid and fiber.

How do you treat fatigue?
About 92 percent of patients with MS experience fatigue and it can be something that they experience to a low degree or to a disabling degree. Even doing the activities of daily living, just to get themselves ready to go to work, can leave them so wiped out that they really can't function. Fatigue can lead to cognitive symptoms such as forgetfulness, difficulty concentrating and the ability to multitask. Sometimes, it's the most difficult symptom because people often don't have a visible physical disability, so family members and coworkers don't understand why they can't be productive.

The very first thing to do with fatigue is start with sleep. Sometimes it takes time to delve into why somebody may not be getting good sleep. It may be because they have spasms of their legs. It may be because they're waking up to go to the bathroom every five minutes. It may be because they're just having a hard time quieting their brain down.

The other thing that is sometimes missed is other medical issues. It's always important to check somebody's thyroid status. Some medicines, such as beta-blockers for high blood pressure, antiplasticty medicines or other medicines, can make people feel fatigued.

After all of those things are sifted through and somebody is able to get good sleep and they're still fatigued, we do have medications such as stimulants and amphetamines. For patients of mine who don't have problems with their bladder, caffeine is a wonderful drug, so they'll have a cup of coffee at 3 pm. Exercise is also important. Energy really does produce energy, so it is an effective way to help combat fatigue.

Do you see a lot of depression?
Yes, there's a high incidence of depression with MS. Part of it is just the disease process itself and some of it is difficulty with dealing with having a disabling disease. It also tends to co-occur with pain or fatigue. But there still is such a stigma in our society about depression that people often feel that they're just not doing a good enough job coping with their disease, so they are hesitant to discuss it and get help for it. But MS support groups, talk therapy or antidepressants can make a big difference.

How can people cope with sexual dysfunction?
I think sexual dysfunction is experienced by just about everybody with MS and nobody talks about it. Sometimes medicines are the issue. For example, people who fail to achieve orgasm often experience that as a side effect of other medicines. For men, sometimes it's because their spinal cord is involved, which can result in erectile dysfunction. And, of course, that's relatively simple nowadays to treat with the whole host of erectile dysfunction products that are on the market. Another problem that can occur in men is increased or decreased sensation in the entire genital region and that's more difficult to overcome.

Women can experience a lack of sensation or too much sensation as well. And both men and women can be so incredibly hypersensitive that any kind of touch is painful. For women, sometimes the issue is vaginal dryness and we can often work around that with lubricants and estrogen creams.

Very often, psychological factors come into play with fear of a spouse hurting their spouse with MS who might have some muscle weakness. An anxiety-provoking issue for people with MS is loss of bladder control. A lot of these things can be overcome with communication between partners or by introducing sex aids to really help heighten sexual experience. Of course, we also have to remember that intimacy is often more than sex.

What is your advice to people who want to better control their symptoms?
The most important thing is that symptoms have to be communicated. And symptom management has to be just as important as disease management. People don't have to live their days feeling bad because of their MS. There's a lot that can be done in terms of symptom management. But sometimes it really comes down to patient self-education, so that patients can really be their own best advocates.

Redefining Intimacy in People with Multiple Sclerosis
If you don't believe in the importance of good sex within an intimate relationship, just check out the cover of any woman's magazine in the supermarket. For couples that are coping with multiple sclerosis (MS), both physical symptoms and their emotional repercussions can make a healthy sex life challenging.
Below, Fred Foley, PhD, director of psychosocial services at the Gimbel Multiple Sclerosis Comprehensive Care Center in Teaneck, N.J., talks about how couples can reclaim an intimate relationship by learning about new ways to enjoy each other.

How common are sexual problems in MS?
Multiple sclerosis can cause a variety of symptoms and interfere in a variety of bodily functions. About 80 percent of persons with MS describe some kind of sexual problem at some point in the course of their disease. That may sound very high, but in the general American population, 35 to 40 percent of people report at least occasional sexual dysfunction.

What kind of sexual dysfunction occurs?
When we were first studying sexual dysfunction in MS, we realized that there could be many different types of dysfunctions. The first category is primary sexual dysfunction, which includes problems directly due to lesions in the spinal cord and the brain. A typical primary problem would be a section of the spinal cord that would cause complete lack of sensation in the pelvic area.

The second type of sexual dysfunction is secondary sexual dysfunction, which are problems that affect sexuality that are indirectly caused by MS symptoms, such as a tingling or burning sensation in the arms or legs that interferes with your pleasure when your partner touches you.

The third type of sexual dysfunction is tertiary sexual dysfunction in MS. That includes psychosocial and cultural aspects of sexuality. For example, if MS affects a woman with body image concerns, it could take the joy out of giving and receiving in a sexual relationship. It could be very inhibiting.

What sexual problems do women with MS experience?
The studies on the frequency of sexual problems in MS show that women complain mostly of a loss of libido or sex drive. That's the number-one complaint, followed by vaginal dryness and loss or impairment of the ability to orgasm. Since MS can also impair the nerves that nourish the vagina and vaginal tissues, then there can also be a loss of muscle control and ability to respond to sexual stimuli. Also changes in sensation in the genitals can occur in both men and women.

How is vaginal dryness treated?
Once we have made sure there is no other problem or medication impairing sexual function, we would advise the woman to use water-soluble lubricants, such as K-Y Jelly or Astroglide, but not petroleum-based lubricants such as Vaseline since they can sometimes leave residuals that can lead to bladder infections.

When we were first advising women to use lubricants, they would sometimes come back and say "It's not working." I finally began asking them how much they were using and realized they weren't using adequate amounts. If there is a significant amount of dryness and irritation present, you'll have to use a lot of the stuff. I recommend incorporating the application into the love-making, into the play; have your partner warm it up to body temperature for you.

How is low libido in women treated?
We recently completed a study that found that women's concept of sexuality and their sexual identities are more complex than that of men with multiple sclerosis. So we often make our interventions for women more relationship focused and make sure that here is a counseling component.

What kind of sexual problems are seen in men?
The most common complaint sexually for men with MS is erectile dysfunction. That is, the inability to develop and maintain an adequate erection for sexual behavior. There are also other sexual problems that men have such as impaired sensation and loss of the capacity to orgasm.

How can people cope with changes in sensation?
If we find that sensation is diminished in the genital area, the solution is to increase stimulation to that area. In woman, oral sex is sometimes more stimulating than traditional vaginal penetration. For vaginal intercourse, we may advise partners on how to change their sexual techniques to provide more stimulation or to use vibrators.
 
For people with altered sensations what formerly felt like a light touch or pleasurable sensation to the genitals can now feel like burning or itching, kind of like the sensation you would feel if your foot fell asleep. We sometimes advise patients dampen the sensations either with medicines that can be prescribed by their MS physician or by applying a cold pack to the genital area.

How can other symptoms of MS interfere with sex?
Spasticity is a fairly common symptom that could impair the ability to position oneself for sexual activities. Education about changing the timing of when they administer their antispasticity medicines frequently resolves the problem.

Bladder dysfunction is a very common MS symptom. Some individuals, particularly women, tend to lose bladder control when they have an orgasm. So advising them how to how to deal with their bladder issues whether through medicines or self-catheterization or going to the bathroom prior to intercourse, or just educating their partners and themselves to approach it together goes a long way in reducing the embarrassment and the emotional difficulty.

Since many people with MS experience pain, we want to make sure that we properly assess and treat it since most people aren't feeling particularly sexy when they're in significant pain.

How can men and women cope with difficulty achieving orgasm?
Difficulty achieving orgasm is a fairly common complaint in both men and women in MS. It can be caused by many different problems. We may want to review the medications that the person is taking. While the disease-modifying medicines in MS do not cause sexual side effects, some of the symptomatic medicines for depression or bladder dysfunction, in particular, can cause some sexual problems.

If that doesn't work, counseling can help them accept what they cannot change and learn how to enjoy their partners even with reduced or altered sexual functioning. The capacity is always there for people to give and receive pleasure no matter how severe the disease.

To what degree does the disease make it difficult for people to remain intimate with each other?
Maintaining one's intimate relationship requires flexibility, creativity and imagination, otherwise life can be all work and no play. In a couple I recently worked with, the man had MS. He had severe MS-related fatigue, so by the end of the day he had very little energy for sexual activity. In the past, the couple would have sexual activity in the evening. Counseling taught them to be a little more flexible and to engage in sexual and intimate activities at other times.

When should couples seek help?

You need to get educated about the nature of sexual problems in people with MS and become empowered to approach your MS health care team. Be creative with your partner and yourself with trial and error strategies. We find that if you talk about sex and intimacy with your health care team and your partner, you have already overcome the single biggest obstacle to getting adequate treatment for sexual problems in MS.

Say you've been experiencing a little tingling in your arm and decided to make a doctor's appointment. Chances are you're not expecting a diagnosis of multiple sclerosis (MS). But if your medical team determines that your vague symptoms are due to this neurological disease, then they are likely to recommend starting treatment right away.
Although people with MS—particularly those with mild symptoms—are sometimes reluctant to embark on a life-long medication regimen, studies show that early treatment not only helps prevent and minimize MS attacks, but may also lessen the long-term impact of MS. Below, Karen Blitz-Shabbir, DO, director of the North Shore MS Center at Long Island Jewish Hospital System in New York, discusses the benefits of early treatment.

Do people with MS experience symptoms constantly?

Generally speaking, when MS patients are diagnosed, they have a relapsing-remitting form of this disease, which means they can have some symptoms and then the symptoms can go away. Some of the symptoms can be quiescent for 10 or 20 or 30 years, and we call this a remission.

But the interesting thing is, if you follow these patients' MRIs, their disease is not quiescent. We see new lesions that are coming, we see old lesions that are going. This means that the disease is actually quite active. What I think and what a lot of physicians think now is that it is this silent, constant bombardment of the nervous system that eventually doesn't allow the nervous system to bounce back. That's why, much later on in the disease, a lot of patients develop disabilities.

If we can shut this bombardment down with early treatment and continued treatment, we give our patients the best chance of a very good course with this disease.
 
What is the benefit of early treatment?
I would say the buzzword now with MS is early treatment and staying on treatment. That's because what we know about this disease from MRI shows that even when the patient is not experiencing symptoms, the disease is active and we think that has long-term consequences. There have been several studies to date showing that early treatment is not only effective, but it changes the course of the disease. If you get treated later, you never quite catch up.

Are some patients hesitant about starting treatment early?

By early treatment, I mean you should be diagnosed and treated almost in the same breath. Sometimes patients don't want to do that. They don't want to take injectable therapies, they don't want to stop denying this disease. But the interesting thing is that the patients who are protected actually do better and feel better because they have this umbrella of protection.

I have a great story about a patient of mine who was diagnosed and didn't come back to see me because I really pushed treatment, and she didn't want to do it. She called me a year later, stating that she's numb on the entire right side, and she's crying. I said, "Don't worry, we'll take care of it, we'll treat you." And she says to me, "That's not the problem. Every single morning for the past one year, I've woken up worrying, 'Should I be on treatment? Shouldn't I be on treatment? Am I making a mistake?' And now I realize I've made a mistake." And from that point forward, she felt protected and she was on treatment and, psychologically, she did much better.

Will some patients do well without treatment?

There are a small percentage of patients who actually do well whether you treat them or not, but it's important to note that that's a small number of the patients. Only 5 or 10 percent of patients truly have a benign course to this disease. Although we all want to think we have the benign course, number one, we can't predict who really does have the benign course and, number two, the odds are not with you.


Mobility Matters: Assisted Devices for People with MS   By Christine Haran
Being able to move from one place to another is a capability most of us take for granted. But difficulty walking is one of the most common challenges faced by people with multiple sclerosis (MS), a common neurological disorder. But that doesn't mean people with MS have to give up their activities: Assisted devices ranging from foot orthotics to power wheelchairs can help restore independence in people with mobility limitations.

Problems with walking, or gait, can arise from a number of MS symptoms, such as muscle weakness or stiffness, numbness and poor balance. Fatigue, which is overwhelmingly debilitating in many people with MS, and vision loss, can also affect mobility. Because MS symptoms vary so much, the degree of limitation is also different from person to person. And depending upon the type of MS someone has, symptoms can become progressively worse or come and go over time.

"There's no way to predict how someone is going to feel," explains Dorothy Northrop, director of clinical programs for the National Multiple Sclerosis Society. "In the morning, you might be able to do something that you can't do in the evening. It's like a moving target, which makes it very challenging. You have to always be adapting to find a way to function and do the things that you want to do."

Assessing What You Need
That's where assisted devices come in. But some people with MS must first overcome their own psychological barrier to using devices that may seem to stigmatize them as being weak. "Sometimes people feel like they're giving in if they accept the use of a device, even though it's going to enable them to continue to do things," Northrop says. "It's a hard line to cross, so it's something that people have to build themselves up to."

Once someone with MS and their physician decides that an assisted device would be helpful, the physician will probably refer them to a physical therapist or occupational therapist. These specialists will analyze gait and evaluate muscle strength, coordination and other factors that affect mobility before recommending and fitting a device.

"When we look at a patient we look at their entire being," says Mary Ann Baraibar, an occupational therapist who is a member of the MS Specialty Team at Fairview Homecare and Hospice in Minnesota. "Some of the things that need to be taken into consideration are their type of MS, their physical ability, their cognitive ability, their home environment, and their family dynamic."

Assisted Device Options
While some people might just need a brace, others may require an electric scooter. Among the simplest mobility devices are foot orthotics, such as a brace called an ankle-foot orthotic, or AFO, sometimes worn by people who need a little help with balance. People with poor balance, muscle weakness or stiffness, or those who have numbness in the foot, which can cause the foot to drag—a condition called "foot drop"—might benefit from a cane or crutch. A walker with four legs and wheels provides the next level of stability by allowing the person to hold onto something continually. Certain walkers have seats, which can be particularly helpful to people with fatigue.

Motorized scooters, which are essentially chairs and handlebars perched on a platform on three or four wheels, have become increasing popular, Northrop says. She surmises that's because scooters tend to be less cumbersome and more socially acceptable than wheelchairs. As with other devices, people may bring out their scooter on an as-needed basis. "People with MS might use scooters for particular occasions such as weddings, vacation or holiday shopping," she says.


People who don't have the strength to hold up their upper body or to reposition themselves may require a wheelchair rather than a scooter. While some wheelchairs are manual, others are electric and are usually steered with a joystick. According to Baraibar, it's often important to have a tilt feature on the wheelchair seat so that people can shift their weight and avoid skin breakdown and pressure sores. It's also crucial to fit the chair properly, she says, so the skin doesn't rub.

Even when one has decided what type of device is most appropriate, there are many varieties from which to choose. The devices come in different materials, which vary in weight: The optimal weight of a wheelchair, for example, might depend on one's size and even the type of floor one has at home. Some scooters, along with some canes and crutches and even wheelchairs, can be collapsed so people can store the devices when they're not needed.

Insurance is another consideration many people with MS have to factor into choosing an assisted device. Getting coverage can be particularly hard for people whose symptoms come and go, or for people who need assisted devices because of fatigue, which is hard to measure. Northrop recommends that the physician or physical therapist provide a detailed explanation of one's need for the device to the insurance company. And Baraibar says that there are programs that can help people with MS find financial assistance, so they can get the devices they need to be able to continue being as active and independent as possible.


The Buzz About Bee Venom Therapy for MS and Arthritis   By Christine Haran
Bees are creatures that people usually work fairly hard to avoid. Despite their small size, these fuzzy flying insects can cause considerable pain with their stingers—and occasionally severe allergic reactions. But many people with multiple sclerosis (MS) have taken an interest in bee venom, and some even arrange to be stung in an effort to treat their symptoms.

People who practice apitherapy, or the medical use of honeybee products, believe that bee venom can be used to treat MS, as well as arthritis, inflammation from injuries and other conditions. Its popularity has led to the proliferation of journals devoted to bee venom, alternative medicine practioners and beekeepers offering bee venom injections or simply a hive of bees, and companies selling bee venom products. Yet little research has been conducted in the United States, and experts caution that its safety and effectiveness have not been established.

Joseph A. Bellanti, MD, a professor of pediatrics and microbiology-immunology and director of the International Center for Interdisciplinary Studies of Immunology at Georgetown University Medical Center in Washington, DC, has just concluded the first Phase I study of the safety of honey-bee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis. Below, Dr. Bellanti discusses the future of bee venom therapy for this debilitating autoimmune disorder.
 
Do you know where the idea of using bee venom as a therapy came from?

The use of bee venom goes back to antiquity, to the time of the ancient Greeks. And bee venom has been advocated not only for multiple sclerosis but also for rheumatoid arthritis. There may be some products of the immune system that are produced by the stinging insect or by the injection of these venoms that ameliorates these diseases. It's all anecdotal, and it's never been studied critically. I think ours is the only study that attempted to use the scientific method to critically examine the question.

Why you did you decide to study bee venom extract in people with MS?

There have been a lot of anecdotal reports suggesting that bee venom may be an effective treatment for multiple sclerosis. So there's been a lot of media exposure and a large underground movement of patients who go to zealous lay practitioners who subject multiple sclerosis patients to multiple and repeated bee stings. Since we felt that this practice entailed a real risk of possible allergic reactions, some of which could be fatal, as well as the emotional and economic burdens of chasing false hopes, we felt properly conducted studies of safety and efficacy were needed.

What did your study involve?

With funding from the Multiple Sclerosis Association of America (MSAA) and the collaboration of my Georgetown colleagues, neurologist Dr. John Richert, and my fellows, we treated a group of patients with multiple sclerosis with a commercially available and prepared extract that had a definable concentration of bee venom. We could then do a very carefully controlled dose-related response study, starting with very small doses and gradually increasing. Our main concern, of course, was to maintain safety.

One of the entry criteria was that the diagnosis be primary or secondary progressive multiple sclerosis. There are various types of multiple sclerosis, some of which occur in peaks and waves, and others that have a steadier progressive course. The reason that we chose the stable progressive patients was to try to eliminate the variations in disease expression that could be unrelated to the treatment. Another requirement was that they not be receiving any other immunomodulatory treatment such as steroids or interferon.

The patients were given a diary card to record any symptoms experienced, the dates of the onset of these symptoms and any other pertinent information. We also performed blood counts, urinalyses and chemical tests, to make sure that there were no adverse effects that were resulting from the treatment.

We ended the study with nine patients, among whom the mean age was about 45 years of age and the mean duration of the disease was about 14 years. It was a safety study, primarily, and our one-year results indicated that there were no serious adverse effects observed during the study. There were some minor localized reactions because the injections were given at multiple injection sites twice a week.
 
Four patients had to drop out of the study because of exacerbations of their disease or because of possible progression of the disease. We didn't think that this was related to the bee venom but, to be on the safe side, we discontinued their treatment at the first sign of neurological worsening. Three of the remaining five improved, which would be 60 percent, but the numbers are too small to draw any definitive conclusions about whether this is an effective treatment. We certainly would not recommend this as a form of treatment yet, but it's an encouraging study and it opens up the possibility for some additional studies that could be performed at multiple centers.

What symptoms were relieved?

Many of them had pain and stiffness or tingling or weakness of their extremities. The participants who improved felt that this form of treatment increased strength or decreased pain. One woman thought that there was improvement in pain and swelling of her joints and in her muscles around her joints. We, however, could not objectively quantify improvements in symptoms such as pain and tingling.  

How might bee venom improve MS symptoms?

We really don't know. We think that the pathogenesis of multiple sclerosis is related to the demyelinization of the coverings of the nerves. If you view a nerve as an electrical cord that conducts an electrical current, the myelin is the insulation. In this disease, there is a stripping away of the covering of the electrical wire so that the current that's passed in the nerve is short-circuited and that contributes to the symptoms of the disease.

Why this happens we're not entirely sure, but it appears to be related to a viral infection, and in a genetically susceptible host, his or her immune response is being directed against their own tissues; in this case, against the nerves. If this treatment works, it is somehow preventing that attack. One of the proteins in bee venom has been shown to increase nerve conduction velocity, and this could be how it works.

Why is it dangerous to receive bee venom therapy outside of a controlled study?

We would not advocate the use of whole bee venom of stinging insects. I think the dosing is very erratic and potentially dangerous. When you're giving this material through stinging insects, you don't know how much venom is being administered. We knew exactly how much we were giving.

But even with this type of study, there is a potential danger whenever you administer a protein such as venom extract to a patient. Allergists treat patients with allergic disease with extracts all the time. They safeguard against any adverse reactions by using very small doses and then gradually increasing them and watching the patient very carefully after every injection for a period of about 20 or 30 minutes. The one danger that we worry about most is an allergic reaction called anaphylaxis, in which there is a swelling of the tissues. Swelling could lead to low blood pressure, respiratory failure and shock . Fortunately, we didn't encounter this, but there is that potential danger.

What is your advice to people with MS who are interested in bee venom therapy?

I would encourage them to be followed by their physician or their neurologist and use the appropriate standard treatments, which are basically interferon and other preparations that influence the immune system, such as steroids and immunosuppressive drugs. I would not recommend this form of therapy until we accumulate more data.

Our hope is that we can continue to do research at academic centers exploring these new techniques and new procedures. But these studies should be done, as best we can, using the scientific method of carefully conducting careful research, where we can draw proper conclusions.


Beyond Just Tired: Figuring Out MS-Related Fatigue   By Christine Haran
Fatigue affects up to 87 percent of people with MS, and about 40 percent say it is their most disabling symptom—and one that interferes with their work and social lives. Although the cause of MS-related fatigue is not fully understood, a study recently published in the Archives of Neurology found that nerve cell dysfunction is associated with fatigue in MS. This was determined by measuring nerve cell damage or loss with magnetic resonance spectroscopy (MRI). The extra work the brain has to do to compensate for this brain injury, the study authors write, results in a feeling of fatigue.

Below, Heidi Crayton, MD, co-director of the Multiple Sclerosis Center at Georgetown University Hospital in Washington, DC, discusses how people with MS can cope with fatigue.

Do most people with MS experience fatigue?

The majority of people with MS, regardless of their degree of disability, report that fatigue is huge symptom. And their fatigue is certainly not simple tiredness. It's whole-body washout. People describe feeling completely wrung out like a rag. It can be a physical as well as a mental fatigue; people are just incapable of performing at the level that they're used to. Lassitude is probably the closest word in the English language that comes close to MS fatigue.

Is there a way that fatigue is measured in MS?

Yes, when we try to objectively measure fatigue in clinical trials, we use several scales. They measure how much fatigue affects people's activities of daily living, the typical duration of their fatigue, and if it impacts them psychologically, physically, cognitively.

I think fatigue probably interferes more with daily living and one's ability to have a job than physical disability does. A workplace can make accommodations for someone's physical disability, but it's very difficult to make accommodations for somebody's cognitive deficits, which are often the result of fatigue. The ability to multitask goes down. Memory declines, and without those skills, sometimes it's very difficult to maintain a job. Fatigue also contributes to the loss of relationships.

Is fatigue often one of the first signs of MS?

Oftentimes people present very early on with fatigue as their sole symptom. I think it occurs a lot more frequently than we think because people are misdiagnosed with chronic fatigue syndrome or said to be distressed or working too hard. It's usually attributed to something else.

Is fatigue due to the disease process itself?
Yes, there is evidence that MS-related fatigue is associated with the disease process itself. There has been evidence for decreased blood sugar metabolism in certain areas of the brain in MS patients who experience fatigue. The recent study in the Archives of Neurology supports that theory. There was also evidence of nerve cell destruction in the brains of MS patients who suffered from fatigue. In the future, we may be able to use neuroprotective agents to prevent or slow this destruction to have a greater impact on the treatment of MS fatigue.

Does heat exacerbate fatigue?
Certainly most, though not all, MS patients report that their symptoms either worsen or they have a feeling of increased fatigue when they overheat. Heat slows down nerve conduction, and people with MS already have abnormal nerve conduction. Even as little as a half a degree increased body temperature can create problems, and that increase could be from fever, working out or environmental temperature increase.

How do you know if the fatigue is MS related?
People can experience fatigue as a relapse, or as an exacerbation, of MS, or they can just have it as an everyday baseline symptom that can be pretty steady. Or sometimes people have daily fatigue at a certain level that can then increase during the period of a flare-up or an exacerbation.

But fatigue, depression and cognitive deficits are so intimately related it's very difficult sometimes to sift out the primary problem. Most people who are fatigued experience cognitive problems. And depression can actually present as fatigue. So it can be very difficult to see if fatigue is the primary problem or whether a sleep disturbance due to depression is the primary problem or even if other medical non-MS related issues are to blame.

Sometimes people who have MS aren't always treated as if they have a whole body and may have other medical issues. We always have to make sure that the fatigue is not caused by some other medical problem, such as a thyroid condition, or medicines that they're taking for other conditions.

Why is fatigue often so hard for friends and family to understand?
Oftentimes fatigue doesn't correlate with physical disability, so it's something that people on the outside are not really able to observe. We often think of fatigue as being tiredness. So people might think: "Oh, why don't you just take a nap and get over it?" Unless you've really experienced true fatigue itself, it's very difficult to really understand what that concept means.

Is MS-related fatigue sometimes under-recognized by health professionals?
Most definitely; probably more so in women than in men. It's often attributed to overworking or to stress, so people get patted on the back and are told to take it easy and things will get better.

I think that the general primary care doc especially is not very attuned to the impact that fatigue plays with MS. But even some neurologists aren't attuned to it.

How can people living with MS manage fatigue?
I highly encourage vigorous physical activity, as long as people can tolerate it, which seems kind of counterintuitive. But getting people moving with exercise and getting some element of aerobic activity in their life is very important. For people who do become a little symptomatic if they overheat, I have them put cold towels around their neck or make sure that the room that they do their aerobics class in, or their gym, is air conditioned, or that they have a fan on them.

If people do become symptomatic after working out because they've overheated, immediately cooling their bodies down afterwards can quiet those symptoms. They can just get into a cool shower or put ice packs on their neck or their wrists.

The intensity of the exercise should be tailored to what a patient is able to do. If they have limited range of motion or they are very physically disabled, then we're talking about a totally different exercise program than one for somebody who has absolutely no problem with their arms or legs.

But even somebody who is confined to a wheelchair often has a lot of strength in their upper extremities, and you can still get your heart rate up by using your upper extremities. There are just some modifications that need to be made, but there is usually something that you can find that can help people out in terms of exercise.

Are there any other behavioral strategies for avoiding or minimizing fatigue?
If it's at all possible, I recommend that people incorporate a little bit of a rest time sometime in the afternoon. I think that really helps a lot with rejuvenating and increasing energy levels and decreasing fatigue for the remainder of the day.

What is your advice to someone who has MS and fatigue?
They should really be aggressive about having their fatigue treated. People often feel like fatigue is something that's in their control, and they sometimes don't even bring it up to their physician. But it's a real and sometimes very disabling symptom. It's not in their head. And there is really a lot that can be done for it.

Most of what we do for MS is to increase the quality of life. We don't have any cures for this disease right now, so our number-one goal is to slow down the progression of the disease process and to treat the symptoms—such as fatigue—that are getting in the way of somebody having a great quality of life.


Let There Be Light   By Christine Haran
While you may still hear secret stories about women covered in baby oil and lying on a crinkly bed of aluminum foil, sun worship has been discouraged for the last 30 years. But there's still a bright side to sunshine: Light therapy is used to treat medical conditions such as psoriasis and depression and may even prevent autoimmune disease such as multiple sclerosis (MS).

Researchers have long suspected that the vitamin D in ultraviolet sunlight protects people from developing MS. This theory was first floated when scientists observed that the number of MS cases increases as the distance from the equator increases. Because ultraviolet rays (UV) from sunlight triggers vitamin D production in the skin, people at northern latitudes sometimes have a vitamin D deficiency due to the low levels of sunlight. Exposure is also affected by the time of day, weather and sunscreen usage.
 
"The hypothesis has been that vitamin D could reduce the risk of MS, but for a long time there was no data," says Alberto Ascherio, MD, DrPH, an associate professor of nutrition and epidemiology at the Harvard School of Public Health.

A recent study coauthored by Dr. Ascherio and published in Neurology has provided some evidence. The researchers examined the use of vitamin D supplements in 187,563 women and found that women who took a vitamin D supplement, usually as part of a multivitamin, had a 40 percent lower risk of MS than women who did not use supplements. Future studies will also examine the amount of vitamin D women receive from sunlight.

Although it's not fully understood how vitamin D might protect people from MS, Dr. Ascherio says that the vitamin may reduce the immune response against myelin, which is the protective nerve coating that is damaged by MS.

While the connection between sunshine and MS is still being established, ultraviolet light has proven to be an effective treatment for the skin condition psoriasis, which can cause painful and itchy plaques.


Yoga Matters: Exercise for MS   By Christine Haran
In the last few years, yoga has resurfaced as an exercise, not to mention fashion, craze. One of the remarkable things about this historic Indian form of exercise and relaxation is that is can be tailored to the fantastically fit or those with physical limitations. And a number of studies have shown that yoga may have specific health benefits for people with joint pain, insomnia and even those with certain lung diseases. A study funded by the National Center for Complementary and Alternative Medicine at the National Institutes of Health recently examined its benefits in people with multiple sclerosis (MS).

Lead researcher Barry Oken, MD, director of the Oregon Center for Complementary and Alternative Medicine in Neurological Disorders in Portland, was interested in providing health professionals with data that would allow them to recommend specific exercise strategies. His study randomized 69 people with MS to one of three groups for six months. One group attended a weekly yoga group and the second group went to a weekly aerobic exercise group run by a physical therapist; the exercise involved riding at stationary bicycle in class and at home. The third group maintained their normal state of activity.

Below, Dr. Oken discusses his study's finding that people in both the yoga and aerobic exercise groups experienced less fatigue, and what people with MS should keep in mind when choosing an exercise program.
 
Why did you decide to look at the benefits of yoga in MS patients?

I thought that yoga might be beneficial in terms of cognitive function in multiple sclerosis, where there are significant cognitive problems, such as difficulty concentrating. So cognitive function was the primary outcome measure in the study, and the all the quality of life measures such as fatigue and mood were secondary outcome measures.

Yoga and aerobic exercise have a lot of similar properties, but yoga might offer some other plusses. Yoga has a stress reduction or relaxation component, which may be helpful for people with MS or other conditions. For example, you concentrate on your breathing. People who are doing aerobic exercise may be doing that as well, but it may not be quite as overt. Yoga also improves joint flexibility through stretching, which is not as important in most exercise routines. Joint flexibility may be good in arthritis and other kinds of joint symptoms.

There are also yoga poses where there is significant strengthening of, for example, the shoulder girdle muscles, which is not happening if somebody is running or doing an exercise bicycle. And yoga improves balance.

What did the yoga classes involve?

We chose to do a 90-minute Iyangar yoga class because Iyangar lends itself to easy adaptability with props. A lot of the patients needed chairs, blankets and other props in order to be able to do the poses because they had problems with balance and strength.

After a fair amount of work, we designed a series of poses that we thought would be feasible for people with MS. There were more restorative or rest poses than there would be in a standard class, and poses weren't maintained for as long as they might be in a normal class; poses were only held for about 10 to 30 seconds. The class was pretty structured, with each week being fairly similar to the previous week.

What did the study find?

There was no improvement in cognitive measures, actually. The changes were in the measures of fatigue. Statistically, the improvements in fatigue were equivalent in the bicycling and yoga groups.

Fatigue in MS is a major issue. More than three-quarters of people who have MS have significant fatigue. There are a couple of causes of this fatigue. Some people who are depressed may complain of fatigue, and depression is not uncommon in multiple sclerosis. But even people who are not depressed—and those who do have not significant physical disability—have problems with fatigue, to the point that there are prescription medications that are used to treat the fatigue in MS.

The results of our study, however, might have been partly due to the class structure. There was a bit of a support group atmosphere because it was a group of people with MS who were doing this exercise class together.

Do you think exercise should be recommended to people with MS?

Ten years ago, doctors were recommending that people with MS not exercise. At this point, I think the recommendation should be that people with MS should engage in some kind of exercise program, be it aerobic exercise, such as the stationary bicycle, or yoga. The reason we stress the stationary bicycle is that, unlike walking, it is a physical exercise that people with MS can continue fairly readily as the disease progresses. And swimming is sometimes impractical.

While our yoga results may be translatable to somebody with MS taking a general yoga class, I'm not sure of it. Certainly, the yoga class attended by someone with MS has to be fairly tailored to them. So I'm not sure people who have significant symptoms from MS should just go into the corner yoga studio. The National Multiple Sclerosis Society has been interested in yoga and has been recommending it, and there is the sense that people with MS want yoga classes. We published the design of the class so yoga teachers could have access to what a class specifically designed for people with MS should look like.

Personal trainers working with people with MS on aerobic exercise need to be fully attuned to limitations as well. For example, overheating is an issue in MS. MS damages myelin, a protective coating that covers the nerves. As best we know, electrical conduction in the nerves doesn't function as well when you lose the myelin covering of the nerves. And so, the body is more sensitive to high temperature changes than it would be if there was good myelin covering of the nerve.

Still, I think people with MS should engage in some form of physical activity, be it aerobic exercise or yoga, or whatever exercise they think they can maintain for a number of years.


A Quicker Predictor for MS   By Christine Haran
As with many chronic medical conditions, there is a lot of guesswork involved in making a diagnosis of multiple sclerosis (MS). Lesions in the brain and spinal cord cause a wide range of neurological symptoms depending on where the damage occurs. These symptoms are initially experienced as a sudden "attack" that may last for hours or days. But not everyone who has experiences will go on to have additional attacks; and a diagnosis of MS is only definitive when an individual has two or more attacks. Although brain imaging is sometimes used after the first attack to try to predict a diagnosis by detecting lesions, a blood test might be a simpler way to identify people with the disease.

In a recent New England Journal of Medicine (NEJM) study, Austrian researchers found that a blood test measuring two antibodies, which are substances that the immune system produces, which, in MS, may attack the myelin, a protective coating that insulates the nerves. The test was given to 103 participants who had had one neurological episode, as well as brain imaging and spinal fluid tests that indicated that they had a high risk of MS. Researchers found that 95 percent of patients with both antibodies were eventually diagnosed with MS; 83 percent with one antibody were later diagnosed; and only 23 percent with neither antibodies went on to be diagnosed.

Amit Bar-Or, MD, FRCPC, an assistant professor in neurology and neurosurgery at the Montreal Neurological Institute and an associate in microbiology and immunology at McGill University in Montreal, Canada, contributed to an editorial that accompanied the NEJM article. Below, Dr. Bar-Or discusses the need for a reliable MS blood test and how it might affect treatment decisions.

How is MS is traditionally diagnosed?

Most patients will come to attention of their doctors when they have their first neurological episode, which may involve a range of different symptoms or signs. This first episode is called a clinically isolated syndrome.

The part of the nervous system that is involved in an attack will determine what kind of symptoms or signs a patient has. These may include loss of vision, problems with weakness, incoordination of the limbs, unsteadiness of gait, or a loss of sensation or a tingling sensation in the limbs, trunk or face.

A proportion of these patients will eventually end up with a diagnosis of multiple sclerosis and a proportion of them will end up having just that clinically isolated syndrome. The challenge of seeing a patient with a single episode is trying to help them understand how likely they are to end up with a diagnosis of MS.

What diagnostic tests are available for MS?
What has been most helpful in identifying people who will transition to an MS diagnosis is a type of brain imaging called magnetic resonance imaging (MRI). Research shows that if you look at an MRI of the brain at the time of the first episode, the presence or absence of lesions associated with demyelination can be helpful in predicting the likelihood of eventually having a second attack, and consequently a multiple sclerosis diagnosis.

If you have an isolated event, such as optic neuritis, which is an inflammation of the optic nerve, but your brain scan is quite normal looking, then you are at a relatively low risk of developing MS. Depending on the study, the risk may be as low as 10 percent. If you have an MRI with multiple lesions that suggest demyelination at the time of that same single episode, your likelihood of eventually developing MS is about 80 percent.

That difference is quite substantial in terms of trying to plan treatment, but it's still not as close to perfect prediction as one would like to get. So there is a great interest in identifying additional, easy-to-measure and reliable parameters early on that could predict who will end up with MS and who will not, or whether individuals are likely to have a more aggressive course of MS or a milder course of MS.

Why is a blood test such an attractive concept?

If it turns out to be validated, a blood test is a very simple thing to do. It's minimally invasive and relatively inexpensive. Theoretically, the test could be given to people when they have their first isolated syndrome and help guide the team in terms of predicting the eventual development of MS. It could also help in terms of considering instituting therapies early on, or following patients more proactively, as opposed to just waiting until they come back with another episode.
 
What are the blood tests measuring?

The blood tests are measuring antibodies that are produced by the immune system and recognize myelin. People have known for a long time that many MS patients have an unusual antibody response within the central nervous system. We've known about that because we measured what are called oligoclonal bands in the spinal fluid. Oligoclonal bands represent antibodies, yet it has been very difficult to understand whether these antibodies are actively participating in the disease process.

Myelin is one of the components thought to be a target of attack in the brain. In this study, the blood test measured antibodies that targeted two particular proteins within the myelin, one being myelin basic protein (MBP) and the other one being myelin oligodendrocyte glycoprotein (MOG). Those two proteins have been considered potential targets in MS for a long time.

This study showed that if you identify antibodies directed against these particular targets, you might have additional information in terms of predictive value. The study still doesn't tell us whether or not these antibodies are causing damage or whether they just represent a marker of immune system activity. It is also possible that someone could have these antibodies but not have MS, or neurological symptoms.

How could the test affect treatment?

Given that there are many countries where it is possible to prescribe immune modulators for MS when patients have only a single attack, this kind of information can be helpful in allowing people to have discussions about MS therapies early on.

This is important because we now recognize that people with MS have perhaps tenfold more underlying MS activity than what is apparent during clinical attacks. We believe that those attacks are likely to be associated with damage to the central nervous system. The reason that patients don't necessarily experience deficits early on is because there is reserve built into the nervous system, just as there is with any other organ of the body. So as you're waiting and considering the institution of therapy, more damage may be occurring, which is a reason for considering early intervention. And for that decision you want to have early and accurate diagnosis.

What questions still need to be addressed?

One would want to see these results validated in another study. I think it's important to mention that there are other publications out there, including some fairly recent ones, that suggest that antibodies against these same targets—the MBP and the MOG—are not likely to be important in MS. Part of our challenge is to understand how to reconcile these observations.

 What these conflicting results may be reflecting is the involvement of these antibodies at different stages of MS. For instance, the antibodies may play more of a role earlier on, whereas later in MS, the antibodies may be harder to detect and not necessarily that helpful.

The other thing of interest is how this antibody test relates to the predictive value of magnetic resonance imaging. Is the combination of MRI and the antibody test going to be helpful? Or will they be overlapping in terms of their predictive ability?

I think that groups will start to apply a similar assay to their patient populations and follow them prospectively. And so there will be information coming out over the next couple of years. Obviously the longer you wait to confirm results, the more confident you feel. It will probably take two to three years to sort out whether this could be a test of predictive value.

Another initiative is prospectively following the pediatric population with MS. We are adding this blood test to other measures, such as MRI and comprehensive immunological studies. The pediatric population offers a unique opportunity to understand the predictive value of tests done early on in the disease process.

Are you aware of any other potential early detection methods that are being studied now?

There is an initiative that is driven by the Immune Tolerance Network, supported in part by the National Institutes of Health, which is trying to develop ways of looking at T cell and other responses in MS. This test would hopefully be able to discriminate between normal individuals and those with MS, and could potentially be used in patients with MS to follow their disease as well as response to therapies.


Cognitive Impairment in Multiple Sclerosis   By: Stephen M. Rao, PhD
What is Cognitive Impairment?
Cognition is another word for thinking. It includes many different functions, including our abilities to pay attention, learn and remember information, solve problems, and use language to express our ideas. Almost everything we do involves some aspect of cognition, from walking our dog to solving a complex math problem. Impairment of cognitive functions can occur as a result of brain disease or damage. Conditions that frequently cause impairments of cognition include Alzheimer's disease, head trauma, and stroke. Most people think of multiple sclerosis (MS) as a physically disabling disease. In recent years, it has become apparent that this illness can also affect the way the mind works and, in particular, how the brain performs cognitive tasks.

How Common is Cognitive Impairment in MS?
Approximately one-half of persons with MS experience some degree of cognitive impairment. Of the MS patients with cognitive dysfunction, most (80 percent) exhibit relatively mild symptoms such as difficulties remembering lists of food items to buy in the supermarket or performing tasks in distracting environments. Most patients can learn ways to compensate for these nuisance symptoms (see below). The remaining 20 percent experience more serious cognitive problems that may interfere with their ability to work and engage in everyday activities such as cooking and driving.

Causes of Cognitive Impairment in MS
Many factors can cause cognitive impairment. Stress, anxiety, and depression can decrease our ability to remember, pay attention, and solve problems. Similar impairments can occur as a side effect of some types of medications. We are also quite aware that our ability to pay attention and retrieve information declines as we get older. But, in MS, the cause of cognitive dysfunction is directly related to changes that occur in the brain. MS produces changes, called lesions, in the white matter of the brain. These lesions affect the way electrical impulses are transmitted across nerve cells. The lesions can be visualized with magnetic resonance imaging (MRI). Almost all patients with MS have some brain lesions on MRI scans. Research has shown that the degree and type of cognitive impairment observed in MS patients is related to the amount and location of the lesions in the brain. Thus patients with a small number of lesions may not experience any cognitive dysfunction, whereas persons with a large number of lesions are at high risk for experiencing cognitive problems.

How Do Cognitive Impairments in MS Differ From Other Conditions Such as Alzheimer's Disease?
For most patients with MS-related cognitive impairment, the deficits are mild and do not necessarily progress for long periods of time, if at all. This contrasts with Alzheimer's disease, where afflicted individuals experience severe cognitive deficits that invariably get worse with time.

MS and Alzheimer's patients also differ in the way memory and language functions are affected. In the area of memory, patients with Alzheimer's disease experience difficulties storing new information. As a result, they may not benefit from receiving reminders from others or from using notes to aid their recall. In contrast, persons with MS can store new memories and are capable of learning new information, but have problems spontaneously retrieving this information. MS patients are capable of benefiting from reminders and visual aids. Alzheimer's patients can experience severe problems in using language to communicate (called aphasia); it is very rare for an MS patient to have language or communication problems.

Diagnosing Cognitive Impairment
Cognitive impairments are typically diagnosed as part of a neuropsychological examination. Neuropsychology is a subspecialty field within clinical psychology that is devoted to the diagnosis and treatment of cognitive dysfunction. A clinical neuropsychologist will administer a battery of cognitive tests and compare the results to a normative sample of healthy individuals of the same age and educational level as the person being evaluated. This examination can be lengthy (three to five hours), but it can provide information and useful recommendations to the patient, family, and treating physician. Such an evaluation is often requested by the patient's physician, although occasionally a patient may contact a neuropsychologist directly.

Are Cognitive Impairments an Inevitable Part of MS?
Some MS patients experience cognitive dysfunction very early in their disease, whereas other persons may never experience such problems. Over a three year period, approximately 20 percent of persons with MS will experience the emergence of new cognitive symptoms or a worsening of their existing cognitive symptoms. The patients who experience a worsening of cognitive symptoms tend to be the patients who acquire new brain lesions. It should be noted that there is very little relationship between the degree of physical disability and the degree of cognitive impairment. As a result, a person with significant physical symptoms (problems with walking, coordination, visual or tactile sensory disturbance, bowel or bladder dysfunction) may experience no problems with cognition, but a person with little outward signs of physical disability may have significant cognitive problems. Likewise, an acute worsening or exacerbation of physical symptoms may not affect cognitive functions, and vice versa.

How to Cope With Cognitive Impairments
Most patients can compensate for their memory problems by relying more on visual cues such as post-it notes, calendars, date books, and day planners. An electronic organizer, such as a Palm Pilot, or a handheld tape recorder can be particularly helpful. Making lists will help to organize and prioritize information, errands, tasks and other details and will aid recall. It is important to check items off as you accomplish them. There's also nothing wrong with requesting relatives and loved ones to call you with reminders about upcoming events and appointments. Exercising the mind—reading newspapers and books, playing cards, doing crossword puzzles, engaging in stimulating conversation—can also be helpful. For people with attention problems, directing concentration on a single task is preferable to doing too many things at once. When engaging in tasks requiring intense concentration, try to avoid noisy or distracting environments.

For MS individuals with more severe cognitive problems, cognitive retraining programs are available through most medical centers. Typically these programs are conducted by rehabilitation specialists from a variety of disciplines, including clinical neuropsychologists, speech pathologists, and occupational therapists.

Summary
Approximately one-half of MS patients experience some form of cognitive impairment, primarily in the areas of attention, memory, and problem solving. The primary cause of the cognitive impairment is the buildup of MS lesions in the brain. In most patients, the problems are minor and can be compensated for by making changes in the home and work environments. More severe cognitive problems can be treated with cognitive retraining programs. Cognitive dysfunction can occur early in the disease, but is not inevitable. The diagnosis of cognitive dysfunction is typically made by a clinical neuropsychologist. Proven treatments of cognitive dysfunction with medicines are not available, although drug testing is currently underway. Prevention of cognitive dysfunction can be achieved with disease-modifying treatments designed to alter the body's immune system to prevent the build-up of new MS lesions in the brain. If you have MS and think you may be experiencing problems with cognition, it is important to discuss this with your physician.


Cracking the Clinical Trials Code  
By: Frederick Munschauer III, & Jeffrey Greenstein, MDs
New treatments for disease are constantly being tested in clinical trials, and a lot of patients pay close attention to their results, hoping to learn about the latest medication that will change their lives. But the data from these trials is easy to misinterpret, and it can lead to unnecessary fears or false hopes. Below, clinical trial experts Drs. Jeffrey Greenstein and Frederick Munschauer discuss how patients can best evaluate clinical trials, and steer clear of disappointment and confusion.

What is a clinical trial?

DR. FREDERICK MUNSCHAUER: A clinical trial is a very well-designed experiment whose purpose is to test the safety and efficacy of a drug. This is done by selecting patients who are relatively similar, and randomly assigning some to the drug being tested and some to a placebo (sugar pill containing no medication). The group is followed over a period of months or years, to see whether the group of patients taking the drug does better than the patients taking the placebo. If the patients on the drug do better, we must evaluate whether the rate at which they are improving compared to the placebo group is statistically significant, or if it is just chance. That's a clinical trial. It represents a major achievement of medicine, and it's the only way to really evaluate both the safety and efficacy of a drug.

Could you describe the different phases of a clinical trial?
DR. JEFFREY GREENSTEIN: There are actually four phases of a clinical trial. The first phase tests the drug in people who are healthy, to see whether or not there are adverse side effects. In phase II, we begin to use the drug in a person with a disease that we hope to treat. In phase II, we're primarily interested in whether or not the drug is safe to use, but we're also hoping to glean some information as to whether or not there may be potential efficacy. However, we can't prove efficacy in this phase because it's usually too small a study to give us what we call "statistical power."

Then we move on to the phase III study, which is really the gold standard of proving whether or not a drug actually works. These are the kinds of studies that determine whether or not a drug is truly effective, and have been done in the drugs, for example, that are marketed and FDA-approved for the use of treatment in MS.
 
Finally, we go on to phase IV studies. These are so-called "post-marketing studies." The drug is, by this time, approved by the FDA, and now we're concerned about it's long-term safety. A phase III study may run for two or three years, but a phase IV study can go much longer. During phase IV, we're looking for long-term effects of the drug, including any adverse effects that weren't discovered in earlier phases.

How do you establish dosage for a clinical trial?
DR. JEFFREY GREENSTEIN: Dosage is usually established in the phase I and the phase II studies. We look for a dosage that is both effective and safe. We do this by initially testing a range of doses, some too low to be effective, and some that are as high as can be tolerated, and some in between. Then we select a dose based on these tests.

How does a patient evaluate a clinical study when they hear about it in the news or from their doctor?
DR. FREDERICK MUNSCHAUER: It's very difficult for patients. Even physicians sometimes have difficulty evaluating a phase III clinical trial. If you hear about a trial in the media, try to determine whether it is a new agent being tried on mice or whether it's an agent being studied on a large number of individuals with the disease. That's the first question. What people are looking for is a double-blinded, placebo controlled, prospective trial. Those are words to look for.

"Double-blind" means that neither the patient nor the physician taking care of the patient, know whether the agent that's being administered to the patient is the real drug or a placebo. A placebo is like a sugar pill. It is a medication that has no known effect, but no toxicity, either. So that's what we refer to as a placebo control.

"Prospective" means that you identify a group of patients and you start them on one of these two treatments, the placebo or active drug, and you follow them over time and watch to see whether or not the agent that you feel is the active agent, the real drug, has a beneficial effect in treating the disease.

What about the size of the trial? If you have a drug, and one person gets better normally, and then after taking the drug, two people get better, it's 100 percent improvement, but does that really count with such a small sample size?
DR. JEFFREY GREENSTEIN: No. In going to phase III studies, we try to define how large a difference we might be able to measure. For the most part we look at things like a 30 percent or a 50 percent difference in outcome between the drug being studied and placebo, not 100 percent difference. The statisticians calculate the number of patients needed to show the difference, if in fact that difference actually occurred during the study. They also define a number of different statistical methods that tell us whether the results of the study have occurred by chance or really are reflective of true therapeutic benefit from a treatment that's been tried. You have to do better than chance.

Are these clinical trials designed with pharmaceutical marketing objectives in mind?
DR. FREDERICK MUNSCHAUER: A lot of clinical trials are done on agents which have little or no commercial value. But, yes, the pharmaceutical companies design innovative drugs that they hope will treat a disease, and that they won't go broke making.

You do need to evaluate the process by which any drug is held to be an effective therapy. Testing a drug on twenty people is not science and should not be taken as science. That's very different from a study that's supported either by the pharmaceutical industry or the National Institute of Health, since these groups use the kinds of rigorous scientific methods we are outlining here.

What's Happening to Me?: Invisible MS   By: Frederick Munschauer III & Gina Gunkel MDs
There are approximately 350,000 people in the United States today living with multiple sclerosis, an incurable condition that attacks the nervous system. Common symptoms of MS, like weakness, cognitive impairment, fatigue or numbness, are not always apparent to the objective observer, which at times may feel like a blessing, other times a curse. Living with "invisible" symptoms can be isolating and lonely, and can even confuse treatment decisions.
Patient Gina Gunkel and neurologist Dr. Rick Munschauer talk about the difficulties of treating and living with the symptoms of MS that can't be seen.

First, what is this whole invisible MS syndrome? Is it a syndrome?

DR. FREDERICK MUNSCHAUER: I think it certainly is. Multiple sclerosis can affect an individual in so many ways. It can slow down your thinking, it can blur your vision, it can make you feel just a little bit dizzy, lightheaded. It can be a painful disease. You can have numbness and tingling and burning, and yet look beautiful, just like you. I think that when we deal with these symptoms, it's very important to have somebody with MS when they're not feeling well express it, because they need to get the people who live with them and work with them aware that they're not having a very good day. It's also very important that they tell their doctor, because there's very good therapy to treat a lot of these symptoms.

Gina, is it hard to make people understand when you're not feeling well?

GINA GUNKEL: Yes, especially when they can't see why you feel bad, I think it's very difficult. You try to express to people, "Oh, I have this big blind spot in front of my eye," and they don't really understand. "But you look so well. What's the problem?" they say. "Oh, I can't walk around the mall a few times. I'm too tired." "But you look so well." It really is a problem.

Is this a chronic condition? I mean, do you feel tired all the time?
GINA GUNKEL: No, no. It varies. But the thing is that usually there's always something that's going on that's brewing, and nobody can tell. It's not even that no one can tell, it's just you have to constantly remind your family and friends, "That might be pushing it over the line. I really need to take it easy," and they say, "Why?"

Is there some kind of education that the doctor can do in some of the doctor's visits with the family members?
DR. FREDERICK MUNSCHAUER: I think so. I think physicians can take a greater responsibility in trying to teach people how to deal with MS. For instance, when people are having symptoms, they may be more irritable. They may have a shorter fuse. They may not be able to control their emotions as well as they usually do, and it's very important for somebody with MS to just turn to somebody and say, "Look, my leg is burning now, so I don't feel quite well, and just give me a little wider berth." The bladder problems, also. I mean, you can be in the middle of a conversation and just have to go to the bathroom, and you can be so embarrassed that you have to go and yet know that if you don't go immediately then you're going to be in an even greater social problem. Just saying to someone, "Excuse me, but I have MS and I need to find a bathroom," I think that can help.

How does a person know if their medications are working or not? If they look good, they may think that their medications are actually doing a good job, but they still may not be feeling great inside.

DR. FREDERICK MUNSCHAUER: That's very true. For instance, let's take fatigue, which is a very difficult symptom to deal with on a daily basis. There are medications that can help. The medications, unfortunately, do not completely remove the symptom, but we hope to get control of it. Burning, painful tingling can be characteristic of MS. There are medicines that help. Some of these medicines have their own side effects that can make you miserable, too, but I think it's important for you to get an idea of how the symptoms are affecting you, and then to address them with your physician so that the physician can prescribe the appropriate medications that can allow you to lead a happier, more fulfilled life with less of the invisible symptoms that erode a sense of well-being and happiness.

If the symptoms are invisible, the doctor's not necessarily going to pick them up in an exam, so you have to communicate with the doctor. Is that really important?
GINA GUNKEL: Absolutely. The other interesting part about invisible MS, especially with people that are newly diagnosed, is that psychologically a lot of people stay in denial longer because they don't have to confront it with other people. I think people with invisible MS take a lot longer time to come to terms with their illness and their diagnosis.

What's the harm in that?

DR. FREDERICK MUNSCHAUER: There are good treatments for MS. You need to be on drugs that decrease the inflammation, because over long periods of time, you will do better and have fewer impairments. There's no reason to suffer in silence with MS, and therapies can address the symptoms to make them more bearable. People can, with MS, lead tremendously productive, vibrant lives. But to do that, you have to acknowledge your symptoms, acknowledge your limitations and work with your family and your healthcare providers to get a handle on it. That's the key.
 
Any last words to other sufferers?
GINA GUNKEL: So many people with invisible MS feel, "Maybe the doctor made a mistake. Maybe I really don't have MS," especially if they're intermittent symptoms, and it's really, really important to get on therapy right away because it will have long-term effects that will be beneficial. But in order to take that step, you have to be able to say "I have MS".


Unraveling the Mystery of Autoimmunity
Everybody wants to have a strong immune system. The immune system is the body's own personal Department of Defense, protecting its health and integrity from invading armies of harmful viruses and bacteria. Its specialized cells, called lymphocytes, normally do a fine job of keeping illness at bay, but sometimes they slip up, sending us home with the flu.

Even with all the smart weaponry at its command, the immune system can sometimes go awry, attacking targets inside the very body it was designed to protect. This is the explanation behind over 80 suspected autoimmune diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis and juvenile diabetes.

Noel Rose, MD, Professor in the Department of Pathology at Johns Hopkins School of Medicine and Director of the Johns Hopkins Center for Autoimmune Disease Research, has spent the better part of his distinguished career following the common thread that weaves these diseases together. In the following remarks, he shows how autoimmune diseases of the skin, joints, nerves and pancreas are fundamentally linked.

What is autoimmunity?
Traditionally, the immune response has been understood as the body's method of defending itself against disease, which it does by identifying and destroying foreign invading microorganisms. By contrast, autoimmunity involves an immune response to something within the body itself.
 
How does the immune system distinguish between what belongs in our bodies and what doesn't?
The job of the immune system is to produce antibodies against antigens which cause harm. In fact, our immune systems accomplish that task very well. Not only do we produce antibodies to newly emerging infectious agents but also to molecules produced in the laboratory that may be used in certain types of medications. So why don't we normally produce antibodies to molecules in our own bodies? The answer lies in the complex mechanisms that govern self-recognition and self-tolerance.

We all produce lymphocytes that are potentially capable of recognizing and even attacking "self." Normally, these cells are either deleted very early or they're held in check by regulatory controls. When these safeguards fail us, so-called autoantibodies develop. All of us have autoantibodies - antibodies in our blood that react with something in our own bodies.

Are you saying that autoantibodies and autoimmunity are normal?
Autoimmunity is mostly harmless. Some immunologists even believe it may be helpful. Autoantibodies may help to remove worn out or dead cells, but firm evidence for this is not yet at hand. Clearly, though, an autoimmune reaction can go too far, and that's where the problem begins.

What is autoimmune disease?
The definition of an autoimmune disease is sometimes very hard to pin down. There is no universal agreement on which diseases are autoimmune and which are not autoimmune. Autoimmunity may be present in the disease, but may not be actually causing it.

What causes some people to develop autoimmune diseases in the first place?
The tendency to develop an autoimmune disease has roots in both genetics and the environment. Autoimmune diseases are different from other genetically determined diseases that we're more familiar with, like sickle cell anemia, where there's a single gene and either you have it or you don't. In autoimmune disease, there's an accumulation of a number of different genes that, when added together, give a heightened probability that you will develop an autoimmune disease. About a third of the risk of developing an autoimmune disease is inherited. That means the other 66% is environmental. Even if you inherit a genetic predisposition, the autoimmune disease will not occur unless there's an environmental trigger.

What are some conditions that are now considered autoimmune diseases?
Interestingly, back in the 1960s, many of us suspected that Type 1 diabetes might be an autoimmune disease, but we couldn't really find substantial evidence to support our suspicions. Later, it emerged that the autoimmune form of diabetes is the insulin-dependent form, sometimes called juvenile diabetes or Type 1, which affects about 10% of patients with diabetes. So that was a major surprise.

According to the current view, psoriasis is now considered an autoimmune disease involving an immune response that results in lesions in the skin. For example, they may have been exposed to an infection, and the infecting organism may have had an antigen - a substance that resembles a component of the skin. Whether psoriasis is caused by an internal or external stimulus, the upshot is that there is an immune response to something in the skin.

 Another example is rheumatoid arthritis, a very common disease. Patients with rheumatoid arthritis have autoantibodies. We still don't know for certain whether the autoimmunity we see in the disease is actually causing the disease. That having been said, virtually all of us now accept rheumatoid arthritis as an autoimmune disease. Still, there's a little uncertainty in the back of our minds that there could be a virus, or something else, that's causing the disease, and that the autoimmunity is merely an accompaniment.

Is it important to establish the ultimate cause of rheumatoid arthritis in order to treat it effectively?
At present, the ultimate cause is not a matter of overwhelming importance, because what we treat are its symptoms. The kinds of drugs we use today block the substances that are produced during an immune response, substances that are actually causing the pathology of the disease. These drugs work. It's not relevant whether the immune response that we're blocking is actually a true autoimmune response or whether it's a response to a hypothetical virus that we've never found.

Finding the actual cause of the autoimmune disease will probably become more of an issue in the future years. We hope to see a whole new generation of treatments based on a more advanced understanding of autoimmunity as an underlying disease process.

Once a patient has a full-blown autoimmune disease, what are today's preferred methods of treatment?
In some cases, we can treat an autoimmune disease by replacing a lost function. That's what we do when we give insulin for diabetes or thyroid hormone for Hashimoto's thyroiditis. When these symptomatic remedies fail, however, we must turn to immunosuppression in order to down-regulate the entire immune system. Obviously, this approach is hazardous, because it makes people susceptible to infection, plus most immunosuppressant drugs have severe side effects. They're a last resort. Most physicians give them with great reluctance.

We would much prefer to have a more targeted type of therapy - one that turns down the disease-inducing, damaging autoimmune response without interfering with general immune function. Some of the newer biologic drugs are an improvement over traditional immunosuppressants, since they focus on the inflammatory consequences of the autoimmune reaction. But they still may have adverse effects in heightening susceptibility to certain types of infection.
 
How would you assess the pace of medical discovery in the field of autoimmunity? Is substantial progress being made?
We're getting closer and closer to the root cause of autoimmune disease. My vision is that someday we'll identify the substance that gets the harmful autoimmune disease process going. The goal is to make people unresponsive to their own excessive autoimmune response. We need to learn a lot more about how to identify these offending antigens in people and how to make people immunologically unresponsive. The fact that we can do it in animals shows that it's possible.


Epstein-Barr Virus: Does It Increase the Risk for MS?   By Christine Haran
Viruses that linger in the body long after the symptoms of an infection have subsided have been linked to a number of different diseases and conditions. It's well known, for example, that the Epstein-Barr virus (EBV) causes infectious mononucleosis, a disease that is often acquired during adolescence. But few people realize that this common virus has also been linked to some cancers and, recently, multiple sclerosis (MS). MS is a chronic, progressive disease of the central nervous system, with a wide range of symptoms that typically come and go over time. MS, which is primarily diagnosed in young adults, is classified as an autoimmune disease. In MS, cells of the immune system mistakenly attack myelin, a coating that surrounds nerves in the brain and spinal cord. When this protective coating is damaged, messages cannot be transmitted properly between the brain and the spinal cord and the rest of the body.

Confirming that EBV increases risk for MS would provide researchers with a better understanding of the disease. Dr. Alberto Ascherio, an associate professor of nutrition and epidemiology at the Harvard School of Public Health, is one of researchers who has recently highlighted the potential link between EBV and MS. He is the senior author of a study, conducted with the Walter Reed Army Institute of Research, and published in the March 26th issue of The Journal of the American Medical Association. In the study, Dr. Ascherio and his colleagues analyzed blood samples of people who later developed MS and those of people who did not develop the disease. The blood samples were analyzed for anti-EBV antibodies. Antibodies are produced by the immune system in response to viral infections and their presence in the blood attests to a presence of a viral infection. Dr. Ascherio found that the risk of developing MS for individuals with the highest levels of the anti-EBV antibodies was 30 times higher than those of individuals with the lowest levels. Below, Dr. Ascherio explains EBV and its potential link to MS and other conditions, as well as how such a link could affect MS prevention and treatment.

What is the Epstein-Barr virus (EBV) and how prevalent is it?
EBV is a ubiquitous virus mostly transmitted through saliva, which infects about 95 percent of the adult population in the United States. When the virus infects children it usually doesn't cause any symptoms. But when people are infected during the adolescence or adulthood, it can cause infectious mononucleosis.

Is EBV a risk factor for cancers?
The association is well established for Burkitt lymphoma, a cancer that is seen most commonly in some parts of Africa, and for nasopharyngeal carcinoma, which is common in Asia. Virtually all the cases of these diseases in this region are related to EBV. The relationship with Hodgkin's disease is more speculative: Some cases of Hodgkin's disease are EBV positive and others are EBV negative.

Why did you decide to investigate a potential link to multiple sclerosis (MS)?
The geographical and age distribution of infectious mononucleosis and MS are very similar. It was noted more than 20 years ago that both diseases are rare in the equatorial and tropical region; the incidence increases when you get it to higher latitude. EBV and MS also tend to affect the same population group: Caucasians are at higher risk than people of Asian or African descent. And both diseases occur at slightly younger age in women than in men.

So all these similarities supported an investigation. The original hypothesis was that MS could be sort of a rare reaction to EBV, specifically when the EBV infection occurs later in life. People who have a history of infectious mononucleosis have been found to have a three- or fourfold increase in risk of MS.

What did you find when you looked at the Nurses' Health Studies for a link between MS and EBV?
We took advantage of two large studies, the Nurses' Health Studies, which followed more than 200,000 women for many years. We looked at the blood samples collected before the onset of MS in women who developed MS and compared the antibody titers, or the amount of anti-EBV antibodies in the blood, to women of the same age who did not develop MS.
 
We found a strong association between the antibody levels and the risk of developing MS. But MS is a relatively rare disease so there weren't many samples in these large studies. We had only 18 women in that study with blood collected before MS onset. But in spite of the small number of cases, we found a strong, significant association between EBV and MS.

Did this new study involve more participants?
Yes, the Department of Defense keeps these amazing facilities where they have blood samples from more than three million Army personnel. So we were able to find out which people in that population developed MS over the years and then to go back and retrieve their stored blood samples.

These study results went beyond our original results in several ways. One important thing we looked at was the length of the interval between the blood collection and the onset of neurological symptoms. In the Nurses' Health Studies, the interval was relatively short, generally less than two years. So in those situations, you cannot exclude the possibility that the elevated antibody levels among women who will develop MS would, in fact, just be an early sign of MS.

But we were interested to see how long before the onset of neurological symptoms you could see a significant elevation in anti-EBV antibodies. And in this study, we had enough numbers and a long follow-up; the overall interval was an average of four years, but we did analysis with blood collected five to 10 years before. And we found the same strong association: High levels of these antibodies measured in blood in healthy young adults may predict a 30-fold increase in risk of MS five to 10 years later. This clearly indicates that the elevation in anti-EBV antibodies is very unlikely to be a consequence of MS.

Why might EBV cause MS?
At this point we can only speculate, but the prevailing hypothesis would be that the immune response to EBV may include immune cells or antibodies that may cross-react with some protein in the body. In some people, who are probably genetically predisposed, the immune cells that are meant to recognize EBV, and to control EBV infection, happen to also recognize some protein in the myelin and/or in the brain and cause damage. But there is no direct proof that this is true. So this is something that needs to be investigated.

What kind of studies and information do you need to confirm your findings?
When trying to establish causality between an infectious agent and a complex disease, it's not as straightforward to design a study as it could seem because we are not looking at a one-to-one relationship as is the case with simple infectious diseases. If you are infected by the measles virus, for example, you get the measles. What we are looking at here is a complex cascade of genetic and environmental factors that are possibly interacting. And the fact that the EBV is ubiquitous has made this more difficult.

We would like to see if there are interactions between the EBV infection and an individual's genetic background. But more compellingly, people should start looking at immune cells in people with MS and see if the immune cells that regulate EBV infections are different in number or reactivity among people with MS than people without MS.

Could this potentially lead to different kinds of immunotherapies for MS?
If we find that the virus plays an important role in MS, it will open up a new area for drug research that may include antiviral drugs. Because today, the anti-virus drugs that are available are not very effective against EBV. It could also help to identify more precisely what type of immune cells or antibodies may be involved in causing MS. And, of course, a vaccine remains a possibility. If it turns out that MS and EBV are causally related, then a vaccine that prevents or reduces EBV infection could have a role in preventing MS as well.

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