NAVIGATION


Scientists Seek Better Understanding of Degenerative Myelopathy

Used with permission from the Purina Pro Club Boxer Update, Nestle Purina PetCare Company

Degenerative myelopathy (DM), a potentially debilitating neurological condition that can eventually paralyze its victims, can occur with relative frequency in Boxers. Unfortunately, the cause of DM remains unknown, although researchers in both clinical and basic sciences are working to find answers.

What is particularly frustrating is that signs of the condition -- progressive spinal weakness and paralysis -- do not usually appear until later in life, after a dog has been used in a breeding program.

Understanding DM
Degenerative myelopathy has been described as a degenerative neurological condition. Because there is no screening test, DM is considered a "rule-out" condition in which other mimicking conditions, such as a disc condition or tumors, must be eliminated, leaving DM as the conclusion. At present, a definitive identification of DM can only be determined post-mortem.

Signs usually appear when a dog is between 5 and 9 years old. It begins with a loss of coordination in the hind legs. The dog may wobble or drag its feet. The condition generally results in rear leg paralysis in approximately three to six months, foreleg paralysis in about another three to six months, and respiratory failure approximately three to six months later.

No pain appears to be associated with the paralysis, other than the dog wanting to continue life as before but being unable to. Both sexes appear to be equally affected.

DM is reported with the most frequency in the German Shepherd Dog breed, based on statistics of dogs presenting to veterinary teaching hospitals with the condition. Roy Berghaus, D.V.M., M.S., a graduate student in the Department of Population Health and Reproduction in the College of Veterinary Medicine at the University of California-Davis, analyzed DM cases from the Veterinary Medical Database from a 10-year period and found that 2 percent of German Shepherds were identified as having DM, but only 0.19 percent of dogs in general. Other breeds with a significantly higher prevalence than that of the general population were Cardigan Welsh Corgis, with a 1.51 percent occurrence rate; Chesapeake Bay Retrievers, with 0.83 percent; Irish Setters with 0.68 percent; Boxers with 0.59 percent; and Collies with 0.38 percent.

"One thing to keep in mind," Berghaus says, "is that dogs presenting to veterinary teaching hospitals are not necessarily representative of the general population of dogs, and the prevalence of DM in the general population is probably different."

DM Theories
Different approaches are being taken to learn more about the condition. Much of the activity has taken place at the University of Florida in Gainesville and at Texas A&M University in College Station.

In Texas, Joan R. Coates, D.V.M., M.S., assistant professor in the Department of Small Animal Medicine and Surgery, heads DM studies. Coates says her research shows that DM is a noninflammatory condition.

As a study co-investigator with Dr. Phil March of the College of the pathology reflects primary axonal degeneration -- a deterioration of the white fatty material that sheaths the nerve fiber bundles and the nerve processes. In addition, she says astrogliosis, which is a proliferation of the support cells of the central nervous system, is present. She says DM presents similarities to oxidative stress, which is characterized by the release of free radicals and results in cellular degeneration.

In Florida, Roger M. Clemmons, D.V.M., Ph.D., associate professor of neurology and neurosurgery in the College of Veterinary Medicine, has a different assessment. "I have looked at hundreds of dogs with DM over the last 30 years, all of them client-owned," he says. His research has largely focused on DM in German Shepherd Dogs, and he suggests that DM in German Shepherd Dogs is an immune-mediated inflammatory condition that leads to free radical production and progressive spinal cord damage. Recent studies, he says, have found that there are increased levels of two specific proteins in the cerebrospinal fluid of German Shepherds with DM: interleukin 6 and ubiquitin.

"The former is a marker of immune-mediated inflammation, and the latter is a marker of free radical damage to the leptomeninges (the two innermost layers of the membranes surrounding the brain and spinal cord between which cerebrospinal fluid circulates), suggesting our clinical approach is on track," Clemmons says. "We also found that there are markers in the immune complexes of German Shepherds with DM that suggest the inflammation underlies the condition. Again, these changes are not specific, since they can occur in other inflammatory central nervous system conditions. We continue to look for genetic markers as part of our ongoing research."

Managing DM
"Our treatment, which includes diet, exercise, supplements and medications, is directed at the underlying processes and designed to slow or stop the progression of clinical signs," Clemmons says. "Mostly, I propose neuroprotectant medications to attempt to control the condition. We have found that we can sometimes double the life expectancy of patients and make it so that many do not progress or die from DM. They are not young patients, and so they do still get other problems." In early identified cases, he says, the effectiveness rate has been 80 percent. In advanced cases, however, there has not been as much success. "Sadly, it does not work in every case. On the other hand, we also see many cases that some would call German Shepherd DM that are not and require other specific therapy."

Future Outlook
A combination of genetic, environmental and toxic factors likely lead to the development of DM, Clemmons suggests. "If a dog doesn't have the right genetic pattern, then it's unlikely it will get it," he says. "This is what we are looking for now. Certainly we see siblings and parent-offspring relationships, but it is not a condition like most others, since dogs don't get it until much later in life. Moreover, not all dogs get it. So there may be environmental factors that also play a role in the condition."

Meanwhile, Coates has expanded her DM research with a new grant supported by the Pembroke Welsh Corgi Club of America and the AKC Canine Health Foundation. Although this project focuses on Pembroke Welsh Corgis, Coates plans to continue collecting DNA and pedigree information from other affected breeds for genetic studies.

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