Revised 2012
German Shepherd Dog Myelopathy, also known as DM for Degenerative (chronic and progressive) Myelopathy (spinal cord disease), or CDRM in the UK, is the first disorder that comes to mind when German Shepherd Dogs and spinal lesions are spoken of together. Almost peculiar to Shepherds, the first symptoms are usually seen at more than 5 years of age and typically last 5 to 30 or so months, perhaps a bit longer if aggressive measures are taken to forestall euthanasia. All accounts to date concede that there is great variation in age of onset: the youngest case reported to Glasgow researcher Pamela Johnston in the course of her studies for her doctorate at the University of Glasgow, Scotland was five years old, and the eldest 14 years, while the majority were about nine years old at first presentation. Most early signs are seen at or shortly after about 6 years of age, if the observer is experienced and keenly looking for it. In my experience, many cases drag on for 2 years, a few go three or more years, and several I have seen last little over 6 months.
Thanks to that excellent research recently done by Johnston, we now have a better understanding of the disease, although no more hope than before regarding its prognosis. I have taken the liberty to edit her work, rephrasing where helpful to the organization of this article and clarifying for the lay reader. Where I have repeated her work verbatim or nearly so, I use a different inset-page width and italics, which I trust anyone reprinting this will honor. My comments within her paragraphs are in brackets. Some typically British spellings in Johnston’s dissertation have been retained. You will also see, in place of “DM”, the frequent use of the abbreviation CDRM, which stands for Chronic Degenerative Radiculomyelopathy. As her study was “dedicated solely to the investigation of CDRM in GSDs”, the most populous breed in the world, “it would provide the largest database so far collected on this disorder.”
Chronic degenerative radiculomyelopathy (CDRM) is a well-recognised neuro-degenerative disease of unknown aetiology which affected large breed dogs, primarily the German Shepherd Dog (GSD). There were other progressive neurodegenerative conditions which had been reported in a number of different dog breeds, but these conditions were too dissimilar to CDRM to warrant discussion in this thesis. CDRM affects selected areas of the spinal cord and brain stem. The underlying aim of the Glasgow study was to improve the clinical knowledge of CDRM by regularly examining a large group of affected dogs. The most common presenting sign(s), the age at onset, and whether there was any previously unreported sex predisposition were of particular interest. Additional aims were to tabulate rates of degeneration and note the most commonly seen clinical “syndrome.” This project is the first to study a large number of affected dogs repeatedly throughout the course of disease. The previously reported clinical signs have been confirmed and the relationship between age of onset and rate of deterioration has been addressed for which no definite correlation was found.
First described as a specific, separate disease in 1973, it gets its common name from the fact that German Shepherd Dogs are affected most often (studies report a range from 56% to 82% in this breed) and relatively often (one estimate is that 20% of the breed population develop clinical signs of DM at some stage in their lives). GSDs are not the only breed affected. It is much less common in a few other large or medium-size breeds and large breed crosses such as German Shepherd Dog, Irish Setter, Collie cross, Rough Collie, Rhodesian Ridgeback, and Labrador cross.
Dr. R. M. Clemmons, neurology professor at University of Florida’s veterinary school, feels that the peculiar syndrome seen in our breed is also seen only (and even then rarely) in the Belgian Shepherd and the Old English Sheepdog, and he has believed that what is seen in other breeds may well be a different disorder. Those other degenerative myelopathies are probably not caused by the same immune-system-related deficiency as we have in the GSD, he thinks. The president of the Kerry Blue Terrier Club reported DM in her breed, and there has been another indication that Auburn University was about to publish a study of a disorder that appears to be DM in Bernese Mountain Dogs. It is important to remember, though, that while other breeds apparently get some spinal myelopathies that are also degenerative, the DM of the GSD, at least, is probably an autoimmune disease. Dr. Dennis O’Brien from the University of Missouri has been working with the PWCCA (Pembroke Welsh Corgi Club of America) Genetics Committee, according to correspondence from Dr. Sylvia Lueck of Lacey, WA. A $45,000 grant proposal was submitted to the AKC Canine Health Foundation with support from the PWCCA to do a 2-year study, with 9 investigators, on DM in Pembrokes. Researchers include Dr. O’Brien and principal investigator Dr. Joan Coates of Texas A & M who had been doing a DM project in German Shepherd Dogs. The Corgi project was to be different, quite a bit more involved, Dr. Lueck says. Three major projects (DNA fingerprinting, epidemiologic data collection and a leflunomide trial) were proposed. At the time I corresponded with Dr. Lueck, she was unable to get any response regarding cooperation from the GSD Club of America.
CLINICAL SIGNS
“Diagnosis” (purposely put in quotation marks here) is by process of elimination, since regular neurological tests aren’t satisfactory, except perhaps for the presence of a brain fluid protein in the lumbar area of the cord. True diagnosis is only possible upon autopsy. Your best bet for a clue while the dog is living would be to consult an experienced breeder who’s been through it with his own dog or dogs, read the literature (this is a good start), and consult your vet for confirmation and medication. He will see what you have seen, including some of the following.
Initially, the dog does not seem to realize what position his rear legs are in; soon he will begin to drag his toenails and the top part of his paws, and may tremble as if palsied. The dog sooner or later begins to atrophy in the haunches and croup. He may “dance” with the rear limbs because he does not realize how high he is stepping. Proprioception is the ability of the animal to recognize the location of his limbs, and this is increasingly lost in the afflicted dog. He will get his hocks “tangled up” (one hooked behind the other) and trip over them or drag both. Later, he will have more difficulty getting up and “steering” the rear quarters. Eventually, he will be unable to get up on all four legs, and by this time most owners will have decided upon euthanasia. There were only two cases in the U.K. study, that were maintained for two years after first signs of thoracic limb involvement, such as stumbling in front; these had both been in a “K-9 Kart” for more than 12 months, their back halves being supported by the wheeled contraption. My own cut-off date for euthanasia is when a dog can no longer get up and squat to defecate. Everyone has to decide on his own deadline, but you must have a plan and stick to it, or the event will be even harder on you.
It is not possible to diagnose CDRM definitively in life. A presumptive diagnosis [best guess] could be made, however, based on typical history and clinical signs. Clinical signs of CDRM had been well documented. The dogs showed a slowly progressive pelvic limb ataxia and paresis with loss of proprioception. Initially they scuffed the middle two toes of one or both hind feet. Subsequently they developed problems with circling and with stairs, especially going down; they often scuffed, misjudged distances and showed hypermetria (ataxia in which intended movements overreach the intended goal). The dogs were often affected asymmetrically [more or earlier in one limb than the other] although both pelvic limbs were usually involved. Disuse muscle atrophy developed over the trunk and hindquarters several months after disease onset. With time, prolonged scuffing resulted in excoriation and ulceration of the feet. Eventually the disease resulted in marked paraparesis; the dogs could not rise without assistance and would pull themselves along with their thoracic limbs. A degree of faecal and urinary incontinence would often develop late in the disease. Dogs maintained beyond this stage could show thoracic limb signs. It had been reported that brain stem involvement eventually occurred (Clemmons, 1992) which could result in a number of signs including asymmetrical tetraparesis, cranial nerve abnormalities and altered mental status. The clinical signs were inexorably progressive and whilst they may have stabilised for short periods of time, improvement did not occur. Typically, the signs, which developed as the disease progressed, were as follows: wearing of the nails became increasingly noticeable and more persistent; all dogs started to have problems turning, developing a tendency for the hindquarters to fall to the outside on a turn. These difficulties were more obvious on slippery surfaces and on stairs. Most cases were still keen to exercise at this stage. Crossing of the pelvic limbs then developed, where one leg would get caught behind the other, which often resulted in the dog falling over. Collapsing to one side when walking in a straight line followed. Eventually, after a period of six to 18 months, the dogs were unable to rise to a standing position, so pulled themselves along with their thoracic limbs.
In the brain, the lateral vestibular nucleus (LVN) is the one most commonly affected in CDRM. The axons of all these cells pass to the spinal cord in the vestibulospinal tract. Cerebello-vestibular fibres from the cerebellar cortex provide a feedback mechanism between the vestibular nuclei and the cerebellum. Maintenance of equilibrium or orientation of the body in the vestibular righting reflex is largely reflex activity governed primarily by general proprioceptive impulses from muscles, tendons and joints in the trunk and limbs, and special proprioceptive nerve endings which initiate impulses conveyed via the vestibular nerve to the vestibular nuclei. The LVN, by way of that vestibulospinal tract, exerts a facilitatory effect on spinal reflexes that control muscle tone, especially to maintain appropriate posture or strength of supporting and balancing movements. This is compromised in the case of DM, and the dog is unable to sense that its rear feet are not in the right place or doing the right thing, and likewise is unable to exercise normal control over them. These tracts have an effect on the spinal cord nuclei supplying the antigravity (i.e. the postural and extensor) muscles. [Thus, the DM-affected dog will tend to gallop or bunny-hop rather than trot or walk with as much extension of the hocks as previously or normally.] A failure in the normal activity of the vestibular system due to DM or other lesions may cause disequilibrium, staggering, postural changes, falling or rolling to the same side, and other reactions. [Most owners choose euthanasia long before these symptoms appear.]
METHODS
[From Johnston’s work]: A full case history was obtained from the owner and referring veterinary surgeon and the relevant details were recorded. All cases underwent full systemic examination, full physical assessment, and neurological examination and the following functions were found to be the most useful in the assessment of CDRM.
Gait was assessed initially for lameness, coordination and weakness with the animal moving in a straight line on a flat surface. This was observed from the side, in front and behind the animal. This was followed by assessment of gait during circling or when going up and down stairs.
“The wheelbarrow” [in which the dog is picked up at either end and made to walk on the other two legs] and hopping tests were used primarily to detect weakness of limbs and to highlight any asymmetry between limbs.
Neurological tests used to evaluate the sensory modality of proprioception also required adequate motor function by the animal to perform properly. Conscious proprioception and motor function were assessed by paw position, reflex step, and hip sway tests. The hip sway test was carried out by holding the dog either side of the midline in the flank region and gently moving the dog over to one side then the other. A dog with normal proprioception will immediately move the relevant foot such that the body is properly supported. Proprioception was severely affected either unilaterally or bilaterally, depending to some extent on the duration of disease.
Muscle tone was assessed by passive flexion and extension of the limb; muscle bulk and symmetry were assessed by palpation; and the local spinal reflexes (patellar reflex and pedal reflex) were assessed in the pelvic limbs with the dog in lateral recumbency. The pedal reflex was tested to evaluate flexor muscle group strength and to assess cutaneous sensory fields in the distal limb. In the thoracic limbs a similar examination was made. Joints were examined for the presence of musculoskeletal disease.
Mentation [mental activity] and posture were noted and the owners questioned about any change in behaviour or attitude. The presence or absence of conscious pain perception was noted. Additional signs of importance were a lack of any spinal pain and no evidence of faecal or urinary incontinence (except very late in the course of the disease).
The clinical signs indicated both motor (paresis) and sensory deficits (abnormal proprioception) and suggested that the major abnormalities occurred within the T3 to L3 region of the spinal cord. Based on these and other findings, an attempt was made to localise the lesion to this region.
ACTUAL DIAGNOSIS
Previous studies had identified the major clinical signs of pelvic limb ataxia and weakness to have resulted from degeneration of tracts in the white matter portions of the spinal cord.
Autopsy will not help you or your dog, but would find the obvious demyelination (loss of the insulating sheath) of the spinal cord, destruction of some large axons (nerve cells leading from the cord to smaller branch nerves), and abnormal cells (or certain cells in abnormal locations). Similar signs may be seen in the brain’s white matter, and plasma cell infiltrates in the kidneys and intestines give further evidence of the immune system failure at the root of this disease.
PATHOLOGY
It had been reported that brain stem involvement eventually occurred (Clemmons, 1992) which could result in a number of signs including asymmetrical tetraparesis, cranial nerve abnormalities, and altered mental status. The pathology in the spinal cord had been described in detail by a number of authors. Lesions were considered to be typical of Wallerian-type degeneration and affected both the axon and myelin sheath. Observed clinical asymmetry correlates with pathological asymmetry. This loss of axons and myelin sheaths is seen in many cervical and cranial thoracic segments, but occasional axon and myelin sheath loss is also noted in the lumbar and sacral cord segments. In an area of the cord known as the lateral funiculus, the corticospinal tract is most severely affected in the caudal thoracic segments. In the thoracic cord, Clemmons saw vacuolation, swollen axons, and other things that represented degenerate and regenerate axons. The present study [Johnston] also identified significant brain pathology. The intermediate horn [column of cells] is the region in the grey matter of the cord that is most often affected in CDRM, but most agreed that the white matter areas of the spinal cord were the most consistently affected, with degeneration involving both axons and myelin, often with an associated gliosis. The caudal thoracic segments were consistently the most severely affected. Only one author suggested that there was evidence of axonal regeneration in the spinal cord (Clemmons, 1989), the same author mentioned the possibility of changes occurring in unspecified white matter areas of the brain. Detailed examination of the brains of affected dogs revealed novel (not seen in other disorders) pathological changes in specific brain nuclei. Such changes included neurones with eccentric nuclei, chromatolytic neurones and neuronal loss often with an associated gliosis. These changes affected the red nucleus, lateral vestibular nucleus and lateral (dentate) nucleus to varying extents. Such changes were found consistently in CDRM dogs but only rarely in dogs with focal spinal cord lesions. Furthermore, gliosis in the red nucleus was found only in the dogs with CDRM.
Dogs with DM often develop lick granulomas, which are ulcerations or (if you are lucky) callous-like reactions of the skin to extremely frequent licking, sometimes chewing, at the location of a supposed itch. It is probably a case of the limb feeling as if it has “fallen asleep,” to put it into terms familiar to human experience. The tingling sensation caused by incomplete and erroneous signals by the nerves serving that place is much like the irritation caused by an ant bite, or hairs out of place, or anything in between. In trying to lick it away, the dog actually softens and wears away the hair and skin. The best I could do for my dog was prick a vitamin E capsule, squeeze out a little for topical application to the granuloma, pop the rest into his mouth, and then give him some distraction such as go for a walk. These ulcers on the feet or elsewhere don’t easily respond, but the battle must be waged if the dog’s life and comfort are to be prolonged. If vitamin E does help in immune system insufficiency, it may be temporary, though it is more often just “managed” or covered up, or it may be worth the effort. It may limit itself to just one or two symptoms such as the biting/nibbling/licking.
Symptoms and histological changes of canine DM are very similar to those in human multiple sclerosis (MS) but most scientists do not admit to the probability of a genetic relationship. Still, I cannot help but suspect that most of these various canine immune-system deficiencies might be related: DM, demodex sensitivity, hormone and endocrine gland irregularities, corneal dystrophy, cauda equina, some allergies, pannus, and other problems, and perhaps even some human ailments. A big problem is that so many gene-mediated disorders of these types also have a large environmental component.
Since DM is so similar to multiple sclerosis, many thought it worth trying the nutritional approaches used by some who treat that human disorder. Wheat germ oil contains octocosanol, a fatty or waxy high molecular-weight alcohol also given to patients with encephalitis and cerebral palsy, and also contains linoleic acid (as do several vegetable oils). But one fatty acid, docosahexanoic acid, is not at all abundant in normal diets, yet seems to be the first one depleted from the nerves’ myelin sheaths in such disorders as MS. In many diets for MS patients, foods such as sardines and mackerel are emphasized, because they are among the very few foods that can supply this compound. Of course, vitamin B complex high in inositol, B6, B12, and choline frequently is also highly recommended as an adjunct to vitamin E for nerve-muscle disorders. Since only a percentage of patients with MS or DM respond satisfactorily to a vitamin-only approach, the concomitant use of drugs and exercise perhaps should always be prescribed. As of this writing, there were three FDA-approved drugs for MS that not only help manage symptoms but also appear to “impact disease course” in relapsing MS, according to the National Multiple Sclerosis Society. They are Copaxone (Teva Marion), Avonex (Biogen), and Zanaflex (Athena Neurosciences). Your vet would have to decide whether or not he wanted to “go off-label,” since these have not (yet) been approved for dogs.
For several years, there was no generally accepted treatment, but as breeders became aware of the benefits of high vitamin E dosages in other immune-related disorders, the veterinary profession began to look into its efficacy and the relation to the immune system. When I first encountered it, I imagined that I got an extra one or two years useful life out of one of my dogs by giving him 800 units (IU) a day, plus vitamin C for its synergistic effect. Years later Clemmons and others claimed that 2000 IU of vitamin E daily, 500 mg of vitamin C twice a day, and a high-strength vitamin B complex twice a day was the best dosage. Vitamin E is an important nutrient with a number of physiologic and pharmacological effects. As an antioxidant it helps reduce oxidation of fats and increases the production of HDL cholesterol. At higher doses it decreases production of prostaglandins and has anti-inflammatory action. There are no known side-effects to vitamin E at levels less than 4000-6000 IU per day (except in cats, where levels above 100 IU/day can create hepatolipidosis. In DM, low serum and tissue concentrations of vitamin E have been observed, although recent research by Johnston indicates this may be equivocal. I recommend that vitamin E be given to older German Shepherd Dogs for a variety of benefits. Dr. Clemmons recommended the vitamin E be dropped temporarily to about 100 IU if the dog has to be given aspirin for any reason during the treatment, and recommends that daily DEC (diethylcarbamazine) replace the monthly heartworm medications ivermectin (Heartgard, Heartgard Plus, Ivomec brands) and Interceptor (a different antifilarial drug) because these increase immune responsiveness; also use the DEC in place of styrid caracide or Filaribits, he says. Personally, I would simply stop all use of heartworm medication, because the dog with DM probably isn’t going to last as long as it takes for a case of heartworm to become life threatening, anyway. Flea control should possibly be limited to Precor™ for the house, and carbamates or pyrethrin/pyrethrum on the dog.
Chemical-pharmacological treatment has largely been via the use of aminocaproic acid, something my friend Wayne Riser (founder of OFA) told me about in the late-1960s—he recommended it for pain relief in hip dysplasia patients. More recently, acetylcysteine three times a day has found acceptance. To Clemmons, it appeared the best treatment is a combination of all three approaches (these two and the vitamin therapy), along with exercise. According to some, alternate-day dosage with a steroid such as prednisone, plus acetylcysteine, added to the aminocaproic acid and vitamin formula, is enough to keep the dog owner very busy and tied to the home, but it might offer a chance at reducing progression, thus prolonging life considerably more than in the past. More recently, Clemmons has been quoted as saying that steroids are no longer recommended for DM dogs. He found that steroids lead to muscle wasting. Therefore, giving steroids to a dog with DM is like pouring gasoline onto a fire. A dog with DM that is given steroids will lose muscle mass much more rapidly than one that is not on steroids. Hydergine, a prescription drug derived from ergot fungus, is being studied, since it seems to promote nerve regeneration. For dogs with advanced DM, Dr. Clemmons suggested trying 5 mg three times a day for at least three months. There is still some disagreement among researchers as to both the nature and the preferred treatment of DM, but the work by Johnston is the most comprehensive and detailed, and she indicates that these approaches are, at best, dubious in reputed value.
Unpublished reports from the U.K. indicate that, of the dogs diagnosed with DM, 88% of those still walking at 12 months and 80% of those walking at 18 months after symptoms were recognized, were being treated with aminocaproic acid, at least.
I mentioned exercise, and this is the third of what might be considered a four-part fight against the disease. Every other day, the dog perhaps should be given 30 minutes of aerobic activity such as vigorous walking or swimming; if you start late, build up to the strenuous level gradually. If your dog can’t do the most, do less, but make it regular and stretch the limits where you can. The alternating days of relaxation are important for repair and renewal. If the dog acts sore, give him the analgesic prescribed by your vet (after he has “read up” on the interactions of medications in regard to DM).
NUTRITION AND “ALTERNATIVE MEDICINE” CLAIMS
The fourth part in the semi-holistic Clemmons approach is stress reduction. The vitamin C, that anti-stress vitamin, is in his recommendations for a good reason, but take steps to avoid stressful situations, including surgery. If the dog needs surgery, make sure he gets the acetylcysteine as well.
The approach to treatment of DM that has been proposed by Dr. Clemmons is what he calls “integrative treatment.” It combines conventional pharmaceutical treatment with “alternative medicine” or “supportive therapy.” Paraphrasing some of his comments might be helpful here. Conventional drug therapy (medicines) has been of little lasting help to patients with DM. However, the combination of exercise, vitamins, and certain drugs (he says) has delayed the progression of DM in many dogs. Treatment has been directed at suppression of symptoms, and since until recently the actual cause or causes of this autoimmune disease were not known, little had been done in the way of finding out how to prevent it. We now know that the genetic component is the major factor. Saying that Degenerative Myelopathy is an autoimmune disease means that the animal’s immune system attacks its own cells; in this case, the central nervous system. The myelin insulation sheath around the nerves and axons (fibers) is gradually destroyed. It’s worst in the thoraco-lumbar area of the spinal cord, but can also affect the brain stem and other nerve tissue.
“Integrative” or supportive treatment of DM, as promoted by Clemmons at the University of Florida vet school, suggests the use of dietary alternatives and supplements to combat the immune system, and is derived from an approach to treating Multiple Sclerosis. You probably know at least one person with MS, and can recognize the similarity in symptoms. It has been postulated that besides the vitamins E and C, the drugs, and the exercise mentioned above, avoidance of toxins such as is found in pesticides and lawn chemicals, and perhaps in some processed foods, is possibly helpful. Clemmons recommends “stress formula” B-complex containing 100 mg of most of the B vitamin components. Or use yeast as a good source of these B-complex vitamins, trace minerals, and some protein. It is relatively inexpensive; try half a tablespoon mixed in each meal. If your dog gets flatulence from this, as most do, use a discount or mail-order vitamin B complex pill instead.
Antioxidant vitamins E and C are synergistic; i.e., they work together better than they do separately. While dogs produce vitamin C, those with DM may need more than they can manufacture. In excess, it also can cause flatulence. Tolerance in the intestines may be for as much as 3000 mg per day, but up to 1000 mg twice a day should be enough unless it causes diarrhea. Selenium also is synergistic, helping vitamin E to be more effective. It can be toxic to medium-size dogs if given at more than 200 µg (micrograms) of selenium per day. I take 200 µg whenever I feel I’m not getting much western grain (good source of selenium) in my daily diet (which is rarely, such as when I’m out of the country for an extended time), and I weigh twice as much as my largest German Shepherd Dog. I keep it in the house to give it (100 micrograms daily) along with vitamin E to my old stud dog in an attempt to control prostate enlargement.
Clemmons says that “Omega-3 fatty acids such as EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) are constituents of fish oils that act as anti-inflammatory agents and may be worth trying if your dog has an autoimmune disorder or arthritis.” If so, fortunate is the owner who can give an afflicted dog a couple of cooked sardines or a small piece of salmon as a daily, natural source of such fatty acids. A 1000-mg fish oil capsule, tablespoon of ground flax seeds, or flaxseed or wheat germ oil supplement can do about the same thing. If you are really “into” the health-food store shopping, 500 mg twice a day of GLA (gammalinolenic acid), a fatty acid found in evening primrose and black currant oils, is an alternative anti-inflammatory without the side effects of most anti-inflammatory drugs. All of the above should be considered as optional adjuncts to conventional treatment with the drugs, vitamins, and exercise, not replacements for them. Johnston found none of these therapies to be effective, however:
Clemmons (1992) suggested, among other ideas, the presence of an 85kDa antigen in dogs with CDRM. However, no other authors have mentioned such a possibility. He has also made numerous other observations and conclusions that have not been duplicated by other researchers, so one must look with care at his “data” until verified in the scientific community. His treatment regimen has also been controversial, as the claims made therein have not been substantiated elsewhere. High doses of vitamin E (2000 IU/day), high-potency B vitamin complex, and epsilon aminocaproic acid (EACA) had all been used as treatments (Clemmons, 1989 & 1992) although their efficacy appeared questionable. Since EACA has anti-protease activity, Clemmons considered that it would therefore be helpful in CDRM, as it would presumably block the final step in the inflammatory pathway, thus helping to prevent tissue destruction. There was no further evidence suggesting that any of the therapies suggested by Clemmons were beneficial in the treatment of CDRM, which was still considered untreatable. All authors agreed that maintenance of regular exercise and optimal body weight seemed beneficial to affected dogs. Clemmons has been the only author in the scientific literature who suggested a treatment regime would be effective which included vitamin E, vitamin B, and EACA; this was not confirmed by other workers in the field. Clemmons in 1989 and 1992 suggested that a combination of vitamins, evening primrose oil, and essential fatty acids might slow the rate of neuro-degeneration in cases of CDRM. These claims remained to be substantiated, although a number of owners have decided to give their dogs these therapies. The rate of deterioration in the studies reported by Johnston was not obviously altered in the cases given the vitamins and evening primrose oil therapies.
Clinical and pathological similarities between CDRM and neurodegenerative disorders due to vitamin E deficiency in horses and humans had implicated vitamin E as a potential factor in the aetiology of CDRM. This stimulated a study of serum vitamin E concentrations. Data presented in this thesis suggests that affected GSDs do not have significantly lower serum vitamin E concentrations than other breeds of dog. In contrast, GSDs with CDRM appear to have elevated levels of serum vitamin E in comparison with the general canine population. [That may be because owners are supplementing.]
[Johnston found that]: The significance of the possible involvement of vitamin B 12 must be questioned, as the study this idea was based on did not include a control population of unaffected dogs. CDRM may occur due to the abnormal absorption of some other nutrient(s) such as vitamin E, or the reported biochemical abnormalities might be occurring secondary to (a result of) the neurologic dysfunction. It has been postulated that since “ataxia with vitamin E deficiency” (AVED) in man responds to the administration of high doses of vitamin E, and that loss of axons and myelin sheaths had been associated with chronic vitamin E deficiency in rats and rhesus monkeys as well as humans, the deficiency of this free radical scavenger that protects neuronal cell membranes from peroxidation could lead to increased membrane fragility and ultimately neuronal cell death. Barclay and Haines (1994) suggested that an immune-mediated spinal cord destruction might be occurring, because they found immunohistochemical evidence in the spinal cords of affected dogs which was not present in the normal dog. Further, the pathogenesis for this or a similar condition in horses is not understood.
As the owners in the U.K. study represented a highly motivated population, the inevitable result was that the vast majority of cases seen were on the dietary supplements (26/34). A further problem with analysing this information was the fact that dogs with CDRM do deteriorate such that they have periods of deterioration interspersed with periods of no apparent deterioration. Thus in the short term, the supplements could have appeared to slow down the degeneration depending on the precise timing of the initiation of therapy. However, as the dogs were being objectively reassessed at Glasgow on a regular basis throughout the clinical course of disease, any such discrepancies should have been minimized.
Analysis of vitamin E concentrations for dogs in the preliminary investigation using the two-sample t-test, suggested that there was no significant difference between vitamin E concentrations in GSDs with CDRM and non-GSDs unaffected by CDRM. Williams et al (1985) investigated a small number of GSDs with CDRM (n=7) and found that they had a slightly lower serum vitamin E concentration than control dogs. These latter authors consider that the GSDs with CDRM also had an enteropathy which could cause improper absorption of essential nutrients. Williams (1984) investigated the possible involvement of vitamin B 12 deficiency but ruled this out as a possible cause of CDRM. Serum vitamin E concentrations, when measured, were lowered in neurological disorders in other species which had been attributed to vitamin E deficiency. Work done in other species had suggested that serum vitamin E concentration was decreased quite considerably before any associated disease occurred. The data presented in this work, in the light of findings associated with vitamin E deficiency and disease in the dog and other species, suggested that deficiency of vitamin E is unlikely to be a primary factor in the aetiology of CDRM.
