Christina Vitale, DVM, ACVIM (Neurology)
Degenerative myelopathy (DM) is a progressive canine spinal cord disease characterized by axon and myelin degeneration, with the white matter tracks of the thoracolumbar spinal cord most severely affected. As the disease progresses, lesions will also appear in the lumbosacral and cervical spinal cord, and clinical signs will follow this progression. DM is purely a degenerative process; there is no inflammatory component.
The only way to obtain a definitive diagnosis of DM is with histopathologic examination of the spinal cord at postmortem. During life, however, we can achieve a presumptive diagnosis of DM by exclusion of other myelopathies. Following a complete neurologic examination and general health evaluation as indicated for each patient, advanced diagnostic including an MRI (ideal) or myelogram and cerebrospinal fluid (CSF) analysis should be performed. The advanced imaging will help to rule out other nonpainful myelopathies, including neoplasia and myelitis, as well as compressive myelopathies, such as intervertebral disc disease, extradural neoplasia, and intradural-extramedullary neoplasia. The cerebrospinal fluid analysis will help rule out inflammatory myelopathies. In dogs with DM, the results of both the advanced imaging and CSF analysis should be normal. It is not uncommon to see evidence of intervertebral disc degeneration with varying degrees of extrusion or protrusion, however the degree of epidural fat and cerebrospinal fluid attenuation can be evaluated to determine the likely clinical significance of these lesions. A lack of spinal pain will also support the fact that these lesions may be clinically insignificant. Electromyography and nerve conduction studies are also indicated to help with diagnosis in some cases.
Thanks to combined efforts by the University of Missouri and the Broad Institute of MIT/Harvard, a mutation in the superoxide dismutase 1 (SOD-1) gene has been discovered in dogs affected with DM. This same gene is mutated in human patients with familial amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. A test for the presence of this mutated gene is now available and being offered through the OFA. The test can be done either on an EDTA blood sample or a cheek swab, and it will reveal if the patient is homozygous for the normal SOD-1 gene, homozygous for the mutated SOD-1 gene, or heterozygous.
Homozygous normal gene (clear) – It is highly unlikely that a patient’s signs are due to DM if this is the test result. It is also unlikely that this dog will develop DM in the future.
Heterozygous (carrier) – It is still unlikely that this patient’s signs are due to DM and unlikely that they will develop DM in the future.
Homozygous affected/mutated gene (affected) – If the clinical signs are consistent with those of DM, and if the advanced imaging and CSF analysis are normal, it is likely (but not definitive) that this dog has DM. It is also possible that a dog with this test result could develop DM in the future. At this point, all dogs that have been studied with a confirmed diagnosis of DM have had this test result. However, numerous dogs with this test result have not had, nor have they developed DM. Therefore, the terminology of “affected” that is used for this category can be misleading.
Though familiarity with the test is imperative in order to reach meaningful conclusions, care must be taken to ensure that the owners are counseled by a veterinarian not only familiar with the test itself, but also familiar with the patient being tested and that particular patient’s clinical signs.
In addition to the DNA test being used to aid in presumptive diagnoses in dogs exhibiting clinical signs, it is also being used for screening by many breeders. At this time, researchers are not recommending removal of dogs with carrier or affected test results from the breeding population, but they are encouraging breeders to consider a test result as one factor when planning an optimally balanced breeding. Since this test is still relatively new, the total number of dogs with a DNA test and postmortem spinal cord examination is not high, and this should be considered when interpreting results. While presence of the mutation is clearly a risk factor in development of the disease, there are certainly other, currently undefined risk factors involved. This test provides a helpful piece of information, but histopathologic evaluation of the spinal cord is still the only way to reach a definitive diagnosis of DM.
Researchers are aggressively pursuing this disease in many breeds to rapidly increase this pool of data, and, consequently, some dogs may be eligible for free DNA testing. The Canine Genetic Disease Network is an excellent resource for both veterinarians and clients: it provides a summary of the disease, a link to the OFA website for sample submission, guidelines on which dogs are eligible for free testing, and information for breeders. The website is http://www.caninegeneticdiseases. net/DM/mainDM.htm.
If you have any questions about DNA test results in your patients, please contact a VSA neurologist to discuss the case with you and/or your client.