What is it?

            Degenerative Myelopathy (DM) of German Shepherds is an autoimmune disease. In autoimmune diseases, the patient's own immune system attacks some part of its body. In DM, the myelin and axons are attacked. (Myelin is the insulation around nerve fibers leaving the nerve cell. Axons are long nerve fibers that go from nerve cells to muscles and other parts. They carry the signals from the nerve to the muscles.) It is similar to Multiple Sclerosis in humans. Belgian Shepherds, Old English Sheep Dogs, Rhodesian Ridgebacks, Weimaraners and, probably, Great Pyrenees seem to suffer from the same problem, and can be helped by the same things that help German Shepherds. Many other breeds can suffer from myelopathy. Since we're not sure whether the cause is the same, we don't know if they  can respond as well to these treatments.

            DM is usually first seen in adult dogs between the ages of 5 and 14 years of age. It is diagnosed mainly by the clinical signs: a progressive weakness and ataxia of the hindquarters, which may come and go, or just get steadily worse. Muscles of the lower back and hindlegs are smaller than normal. Many dogs also have hip dysplasia and/or arthritis of the spine, which complicates the picture. Conventional treatment for these problems (such as Rimadyl or corticosteroids) may initially cause an improvement, but they don't necessarily help the myelopathy. DM begins in the spinal cord in the middle of the back, and is most severe there. It also affects other areas of the central nervous system, including the brain stem and sub-cortical white matter of the brain. The cause is most likely a combination of inherited weakness, plus environmental and toxic factors that lead to its development.

            Due to some triggering factor, immune-complexes circulate. These immune-complexes lead to damage to the cells lining the blood vessels in the central nervous system. Later, fibrin is deposited in the spaces around the blood vessels. When it breaks down, inflammatory cells migrate into this area. (Aminocaproic acid helps decrease the breakdown.)

            The inflammatory cells release prostaglandins and cytokines. These chemicals activate tissue enzyme, contributing to the formation of free radicals which, in turn, lead to tissue damage.
            Vitamins C and E help decrease prostaglandin and cytokine release. Anti-oxidants in general and acetylcysteine help decrease damage from the free radicals.

            Conventional medicine has little to offer patients with DM. Use of exercise, certain vitamins and selected drugs have delayed or prevented progression of DM in many dogs. While these treatments are aimed at suppressing the clinical signs, little has been done to prevent the development of this autoimmune disease.

            In DM, cerebrospinal fluid shows elevated protein in the lumbar area, and elevated acetylcholinesterase. There are no signs of myelopathy that can be detected in a plain X ray. A myelogram also will not show anything, and signs can worsen after it's done. An EMG will show the presence of spinal cord disease, but is not specific for myelopathy.

            Treatment

            The treatment of DM involves four basic approaches:

                1) medication
                2) exercise
                3) supplements
                4) other supportive measures

            This combination corrects those aspects of the immune dysfunction which we can treat, based upon the belief that DM is an immune-mediated inflammatory disease. This combined treatment has been up to 80% effective in patients diagnosed at the University of Florida. The chances of successful treatment are improved if the therapy is begun early in the course of DM rather than later. A response to the drugs should occur within the first 7-10 days. There is no other medications that have been found to provide any real benefits in the long term treatment of DM.

            Medication:

            There are 2 medications which, when used together, can prevent progression or result in clinical remission of DM in up to 80% of affected dogs. These medications are aminocaproic acid (EACA) and n-acetylcysteine (NAC). EACA is usually best given as the solution, using the generic product. This product, while designed for injection, can be mixed with chicken broth to make it palatable and easy to give by mouth.

            EACA

            Mix 2 parts of aminocaproic acid solution (250 mg/ml) with 1 part chicken broth. Give 3 ml of this mixture by mouth, 3 times a day. It is reported to be at least as effective as tablets, and possibly more effective. The generic form is much cheaper than the tablets. The generic form of EACA solution can be obtained from American Regent, (800) 645-1706 (outside of NY). Your local pharmacy can order it from them. Another way is to have a compounding pharmacy make the solution from chemical grade EACA.

            The only side effect reported from EACA is occasional gastrointestinal irritation. The only known drug interaction is with estrogen compounds; but, only in high doses.

           NAC

            Acetylcysteine is a potent anti-oxidant which has powerful neuroprotective effects. Give 25 mg/kg 3 times a day for 2 weeks. Then, we give the 3 doses every other day. The N-acetylcysteine comes as a 20% solution and must be diluted with chicken broth (or other compatible substitute) to 5%. (1 part NAC mixed with 3 parts chicken broth.) Otherwise, it will cause stomach upset. This new treatment is expensive unless purchased through compounding pharmacies.

            NAC can produce vomiting and may increase the bleeding time. The gi upset is probably from the the sodium content of the pharmaceutical product, from the buffer required to keep it at a pH of 7.4. Dilution with chicken broth will help decrease the side effects. Fresh ginger given 30 minutes before the NAC, and giving the NAC with food, often helps.

            Hydergiene

            This drug really can cause digestive upset and diarrhea and is pretty expensive, besides. In really advanced cases it may be worth trying, because it appears to help regeneration of nerve cells and fibers. The dose is 2.5 mg 3 times a day for 2 weeks. If there is no problem with vomiting, diarrhea, or decreased appetite, the dose can be increased to 5 mg 3 times a day. It should be given for at least 3 months, if it doesn't make your dog too sick. You can get a somewhat cheaper generic form from Westlab Pharmacy (1-800-4WESTLA).

            Exercise:

            Many of the goals of treatment in DM are obtainable through regular exercise. Exercise is extremely important in maintaining the well being of affected dogs, maximizing muscle tone and maintaining good circulation and conditioning. This is best achieved by an increasing schedule of alternative day exercise. Running loose on the owner's property is not adequate; regular periods of programmed continuous exercise are the most important. It is equally important that the patient with DM be allowed to rest on the day when exercise is not programmed. This will allow strained muscles and tendons to heal and increase the build up of muscle strength. The dogs do not have to be confined, only that they are not encouraged to do strenuous exercise on the "off" day. I recommend starting with 5-10 minutes of
            walking or swimming every other day for 2 weeks. Then, increase the length of exercise time to a goal of 30 minutes twice a week and a long walk of 1 hour once a week. If your dog already exceeds this limits, that is fine. However, remember to provide a day of easier exercise between vigorous workouts. This is particularly important as the patient gets older.

            Two forms of exercise seem the most useful: walking and swimming. Swimming generally increases muscle tone and allows movement without stress on joints. Walking, on the other hand, helps build strength. In older patients, particularly those with arthritis, gradually building the exercise program is important. In addition, allowing a day of rest between heavy workouts can help the patient recover faster from the exercise.

            If the patient exhibits muscle or joint stiffness on the day following vigorous exercise, try ginger, garlic, mustard and feverfew to reduce inflammation. Acupuncture and Chinese herbs can also be helpful. Alternately, carprofen (Rimadyl 2 mg/kg twice a day) or acetaminophen (5 mg/kg up to 3 times a day) may help make the patient more comfortable. Many DM patients have remained functional because of exercise alone. We use to think that hospitalization was harmful to patients. We now know it is the lack of exercise which is harmful. Make sure your pet gets their exercise if they are hospitalized or kenneled for any period of time.

           Supplements:

            Vitamins

            B-Complex:

            Dogs with DM don't absorb B vitamins as well. B-50 or even B-100 vitamins can help.
           Vitamin E:

            There is also a decreased absorption and tissue binding of vitamin E in dogs with myelopathy. Vitamin E is a potent antioxidant which reduces fat oxidation and increases the production of HDL cholesterol. At higher doses it also decreases production of prostaglandins and leukotreines by reducing cyclooxygenase and lipooxygenases activities. This makes it a potent anti-inflammatory drug, and it helps slow the progression of DM.

            It reduces platelet function and prolongs the bleeding time slightly in healthy individuals, so care must be taken in dogs with bleeding disorders. Other than that, there are no known side-effects in dogs with vitamin E at levels less than 4000-6000 IU per day.

            The most potent form is d-alpha tocopherol. This is better than dl-alpha or mixed tocopherols. Healthy shepherds should be given 400 to 800 IU per day. Dogs with DM should receive up to 2000 IU per day.

           Vitamin C:

            Vitamin C is a water-soluble antioxidant that works with fat-soluble vitamin E and helps regenerate it. Although dogs manufacture their own vitamin C, under stress or disease, the blood level drops and they need more. Vitamin C can cause oxalate stones in dogs that are prone to them. It also causes soft stool or diarrhea in high doses. Sodium (not calcium) ascorbate is a form that decreases the likelihood of this happening. Start at 500 mg twice a day and gradually increase to bowel tolerance (soft stool or diarrhea). Back down to the dose that is not quite enough to cause a soft stool.

            Selenium:

            Selenium is a mineral which has antioxidant properties similar to vitamin E. Vitamin E can partly replace the requirement for selenium in the body, but selenium cannot substitute for vitamin E. In addition, selenium does not cross the blood-brain barrier like vitamin E does. A combination of E and selenium works better than either one alone. In too high doses, it will cause selenium poisoning. A maximum of 200 micrograms per day is safe for large dogs.

            Membrane stabilizers

            Omega-3 fatty acids:

            Omega-3 fatty acids like EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the constituents of fish oils that act as anti-inflammatory agents. They help dogs with arthritis and may help dogs with DM. Like vitamin E, they reduce platelet function, but dogs compensate for it within 8 weeks. Ground flax seed or flax oil is another source.

            Omega-3 fatty acids gradually replace the omega-2-series fatty acids over time. Cellular stimulation then produces 3-series prostaglandins and thromboxanes. The 3-series thromboxanes don't cause inflammation and reduce blood flow like the 2-series thromboxanes. Large dogs shouId receive 1000 mg of fish oil capsule per day.

            Gammalinolenic acid:

            Borage oil, evening primrose oil or black currant oil, are natural sources of gammalinolenic acid, a fatty acid which is hard to get in the diet. GLA is an effective anti-inflammatory agent.
            It is good for skin conditions, arthritis, and autoimmune disorders. It takes six to eight weeks to see changes after adding GLA to the diet. Large dogs should receive 500 mg of GLA twice a day, either as borage oil, evening primrose oil or as black currant oil.

            Soybean Lecithin:

            Lecithin is a fat-like substance found in the cells of the body. It helps the body use and absorb fats better. Add 1-2 tsp of soybean lecithin granules to the food twice a day.

            Coenzyme Q-10

            Coenzyme Q-10, also called Co-Q-10, is a natural substance that assists in oxidative metabolism. It improves the utilization of oxygen at the cellular level, and patients with heart, muscle and nerve problems are often helped by it--sometimes dramatically. It's expensive, but can be worth it for dogs with DM. 60 to 100 mg per day should help.

           The following is from

                                R.M. Clemmons, DVM, PhD Associate Professor of Neurology & Neurosurgery

                              Small Animal Clinical Sciences
 
 
 

            Tonic herbs (natural remedies)

           Ginkgo leaves:

            One tonic I recommend is an herbal preparation made from the leaves of the ginkgo tree (Ginkgo bilboa). Recently extracts of ginkgo leaves have attracted much attention from researchers because of their ability to increase blood flow to the brain. You can buy capsules of these extracts in most health-food stores, although different brands vary considerably in their content of active ingredients (ginkgocides). Ginkgo is nontoxic. For DM dogs, give 1 capsule twice a day.

            Ginseng: (males only)

            Two species of ginseng are available: Oriental ginseng (Panax ginseng) and American ginseng (Panax quinquefolium). Both are full of compounds (ginsenosides) that work on the pituitary-adrenal axis, increasing resistance to stress and affecting metabolism, skin and muscle tone, and hormonal balance. Oriental ginseng is more of a stimulant and can raise blood pressure in some people, so I recommend using only the American species for dogs.
            Ginseng probably has little to offer young dogs, but may provide an increase in vitality to older one. I recommend using 1 capsule of American ginseng once or twice a day in male dogs over 6 years of age. (Obviously, this includes male GSD who have DM!)

            Dong quai: (females only)

            Dong quai is a Chinese herbal remedy made from the root of Angelica sinensis, a large plant in the carrot family. It is often called "female ginseng," because it is a general tonic for women and the female reproductive system in much the same way that ginseng acts as a tonic for men and the male reproductive system. Dong quai is available in the form of encapsulated extracts. It is a good general remedy for female dogs who lack energy. I  recommend using 1 capsule of dong quai once or twice a day for female dogs over 5 years of the age.

           Green tea:

            Green tea is a good general tonic and has some cholesterol lowering effects. It also contains theophylline which can help boost energy. It is available as a capsular extract or you can  make green tea and add it to the diet. I recommend 1 capsule (or cup) twice a day for DM dogs.

            Grape seed extract:

            A great deal of recent evidence supports the value of grape seed extract in reducing free radicals and decreasing the chances of developing chronic diseases. It is best to use standardized extracts. Alternatively, your dog can drink 1 cup of "purple" grape juice or eat 5-6 red grapes (peel and seeds included) a day. The dose of the extract is 1 capsule (50 mg) daily for DM dogs.

            Siberian Ginseng:

            Siberian ginseng is derived from the root of a large, spiny shrub (Eleutherococcus senticosus) found in Siberia and northern China. It is a relative of true ginseng, but has entirely different properties. Siberian ginseng has "adaptogenic" properties and reduces physiologic responses to stress. Scientific investigations suggest it increases physical performance and endurance and improves immune function. For dogs with DM, given 1 capsule twice a day.

            Bromelain/Curcumin:

            Bromelain is an extract of pineapple stems which has the property of decreasing circulating immune-complexes. As such, there is no Western medicine which is its equal. Since many of the complications and the direct initiation of the immune damage may be caused by the elevated immune-complexes in DM, bromelain may be an important key in helping to control the progression of DM. Curcumin (the yellow pigment of turmeric plants) is a potent anti-inflammatory agent. Bromelain and curcumin have a synergistic effect whereby they assist the absorption of each other from the gastrointestinal tract, increasing their potency.
            As such, they should be given together. Many health food stores carry combinations of bromelain and curcumin. For dogs with DM, give 400-500 mg of bromelain with 500-400 mg of curcumin twice a day. (Curcumin is found in low concentrations in the spices turmeric and yellow mustard. As such, it is possible to replace the "capsule" form by adding 1-2 Tbs of turmeric and 1-2 tsp of dry yellow mustard to the diet.)

           Feverfew:

            Feverfew is a natural NSAID compound without the side-effects of prescription drugs. It can be used in dogs with pain or arthritis to help reduce inflammation and discomfort. I do not recommend it for routine use; but, if your dog has pain from arthritis, give 1 capsule every 8-12 hours as needed. You can use this for 5 days out of the week, safely.

            Note: WestLab Pharmacy has developed a palatable vitamin/mineral/herb product (Antiox-Q) which contains bovine cartilage, coenzyme Q, vitamin E, GLA, omega fatty acids, selenium, ginkgo, bromelain, curcumin, olive oil and B complex. This product contains the correct dosage of these compounds and only needs the addition of vitamin C, the ginsengs, green tea and grape seed to be complete.

           Diet

            Although we find deficient levels of certain vitamins in dogs afflicted with DM, supplementation with those vitamins has not resulted in more than mild reduction in the rate of progression of the clinical signs. On the other hand, diet itself may have a powerful influence on the development of the disease. The current treatment of DM is designed to suppress the immune disease, but does nothing to correct the immune alterations which led to the disease state. Diet might help in correcting this defect and allow the immune system in DM dogs to stabilize. The principles of dietary therapy are outlined here, including a "home-made" diet. For those who cannot "cook" for their dog, the basic diet should be supplemented with the additional ingredients list below. It is best to choose a dog food which  is close in protein content and is as "natural" as possible. Wild dogs were not meat eaters.
            They ate bodies, including intestinal contents (often laden with plants and plant materials). Dogs have evolved so that eating animal fats and protein do not cause them to suffer the same problems as human beings when eating these sources of saturated fats.

            By cooking for your dog, you can select healthy products which do not have preservatives and additives which might be harmful. In addition, you have the option to use organically grown foods. If the dietary approach is successful, DM patients may not need to use other medications to prevent further deterioration. It is also possible that this diet might prevent the development of DM in dogs who are presently healthy.

                Basic diet: (based upon 1 serving size for 30-50 pounds body weight)
                    2 oz Boneless Pork Center Loin Chop (boiled, baked or fried in olive oil)

                    4 oz Tofu (soybean curd)

                    8 oz Long Grain Brown Rice (3 oz cooked in 6 oz water)

                    2 tsp Extra Virgin Olive Oil

                    ¼ cup Molasses

                    2 Whole Carrots (boiled and then cut up)

                    1 cup Spinach (cooked)

                    4 Tbs Green Bell Pepper (chopped and steamed)

                    4 Broccoli Spears (boiled and then cut up)

            This diet (1 serving for 30-50 pounds body weight) provides approximately 1160-1460 calories per serving. You can substitute poultry meats, beef and lamb for the pork chop. This will alter the composition slightly, mainly by added additional fat. The weight of meat is based upon boneless weight. Most of the items can be prepared in a microwave. Based upon your dogs body weight, you will need to make more or less. For example, if your dog weighs 80 pounds, multiply all the ingredients by 1.5 (can be as high as 2.5 times, though), keeping their relative proportions. This is a starting point. You can also make this portion of the diet  in advance, aliquot it into appropriate quantities and freeze it for later use. Just before feeding time, remove the diet from the freezer and thaw in hot (or boiling) water or microwave to defrost. To complete the diet, add (amount per serving) before serving:

                    1 tsp Dry Ground Ginger

                    2 Raw Garlic Cloves (crushed)

                    ½ tsp Dry Mustard

                    1 tsp Bone Meal

            Using the above diet, approximately 1 serving equals 1 can of commercial dog food. The exact requirements for your dog can be approximated by substituting the diet on that basis. You should weigh your dog each week, if losing weight, increase the amount of the diet given. If gaining weight, cut back on the amount given. Eventually, the correct amount will be clear. The reason why the amount has such a broad range in that ideas about the daily caloric requirements vary. Since many German Shepherds have sensitive stomachs, it may be wise to phase in the new diet by mixing it with their existing food until they have adapted. Start by mixing the diet with their existing food in equal amounts. After 1 week increase the diet to 75% of their food. After another week, switch completely over to the diet. This diet is balanced and high in most of the vitamins and minerals which your dog will need. Any shortcomings will be corrected with the supplements given below as part of the treatment.

            Note: The general purpose of the diet is to provide excellent quality of ingredients with protein coming from Soybean curd (tofu). Tofu contains many valuable flavonoids and other ingredients which promote health. If you decide to use a commercial food, you may want to use a Soybean Concentrate which contains these ingredients, but lacks the extra protein.
            Alternatively, you can add tofu to the diet (5-6 oz/day) and add honey or molasses to it (¼ cup) to make it taste better. Reduce the commercial diet by 25-33% and monitor your dogs weight, reducing or increasing the commercial diet accordingly. The addition of raw garlic is to provide garlic's anti-inflammatory action and (since it is raw) to provide an antibiotic action. Raw garlic is anti-bacterial and anti-fungal. This action is lost when garlic is cooked or dried. Dry ginger is also a good anti-inflammatory. Together with garlic, dry ginger can replace the need for aspirin-like (NSAID) drugs. Fresh ginger or pickled ginger are also good      anti-emetic compounds, calming the stomach. Mustard provides ingredients which support improve digestion and bowel function. So, raw garlic, dry ginger (occasionally using fresh or pickled ginger) and dry mustard should be added to the food, even if it is commercial. These will not unbalance the commercial food, providing important drug properties without the side-effects of "non-natural" drugs. Using the vegetables, the diet also provides many nutrient and vitamins which are not found in commercial dog food. If commercial dog food is given, giving extra Soy Concentrate, Soy Lecithin and Beta-Carotene to the diet will improve the commercial food. They are not needed, if you feed the above diet. The diet provides a balanced, moderate protein and fat diet which is high in many essential nutrients. The only commercial food which fulfills many of the goals is Nature's Recipe Canine Vegetarian Diet, available from many specialty pet supply stores.

            Other Supportive Measures:

           Heartworm medication:

            Since the monthly heartworm medications (Heartgard, Heartgard plus and Interceptor) increase immune responsiveness, we do not recommend using these products. Instead, we  recommend plain diethylcarbamazine (DEC or Filaribits) which must be given daily. I do not recommend Filaribits plus (some dogs experience liver problems using it). If you dog is currently taking a monthly heartworm preventative, you must give one last dose and start the daily medication the next day. This is because the medications work at different points in the heartworm "life-cycle".

           Flea prevention:

            Many of the old and new flea product can cause problems when certain neurologic conditions are present. As such, we recommend using boron, pyrethrums and Precor as the main control methods. Of the new medications, Frontline Spray may be safe to use.

           Acupuncture:

            The traditional Chinese art of insertion of needles into various specific points of the body ( with injection of small amounts of fluid or electrical stimulation) has been shown to provide analgesia and relief from acute and chronic pain. This has the advantage of having none of the side-effects of analgesic drugs. In addition, acupuncture can do no harm. In DM, acupuncture alone slows the condition, but does not stop the progress. One the other hand, DM patients who have concurrent arthritis may benefit from acupuncture therapy.

           Dietary Cartilage:

            Recent studies have shown that glycosaminoglycans and chondroitin sulfate may help reduce pain and inflammation from osteoarthritis, help regenerate normal joint cartilage, normalize joint fluid, and assist in the healing process. 500 mg of glucosamine sulfate (not HCl) with 400 mg chondroitin sulfate twice daily is helpful. Another alternative is bovine gelatin (Knox  gelatin or Knox Nutrajoint) which can be added to the food (1-2 packages per feeding).

            Stress Reduction:

            DM progresses at different rates and "stress" plays a role in its advancement. Minimizing stressful situations is important where possible. While anesthesia does not appear to cause problems with DM; in the past, even minor invasive surgical procedures can result in a marked increase in clinical signs of DM. Unfortunately, the worsening caused by surgical stress can be irreversible. Due to the advent of N-acetylcysteine therapy and being more attentive to the continued exercise of hospitalized DM patients, we now have been successful in performing many surgical procedures in these dogs. These have included cervical and       thoracolumbar disc surgery and total hip replacement. Before aggressive surgeries are considered, it is best to determine that the patients neurologic status is stable.
            Post-operative physical therapy remains crucial in getting patients on their feet quickly.

            Note: If your dog already has DM, you should consider treatment with the above natural products and more traditional aminocaproic acid and acetylcysteine medications. Use the aminocaproic acid and acetylcysteine for the first 2 months of therapy and then see if they can be withdrawn (without signs of deterioration). If so, then continue with the natural approach from that point on.
 
 

           The Future for DM:

            The key to DM in the future is likely to be prevention. While it may be necessary to wait for the next generation of GSD to see whether the principles laid down here work, they can do no harm. Science is only beginning to understand the fragile nature of DNA and how natural healing can be hampered by dietary and environmental toxins. The body is endowed with a tremendous capacity to heal, if we do nothing to interfere with this process. We are the keepers of our pet's health. We must empower ourselves to accept this responsibility.
            Conventional medicine falls short in the treatment of DM, leading to the need to pursue other forms of treatment. For more information about the positive aspects of spontaneous healing, read the book by Andrew Weil, MD: Spontaneous Healing, Ballantine Books, New York, 1995.