Dogs with degenerative myelopathy (DM) show an insidious, progressive ataxia and paresis of the pelvic limbs that ultimately leads to paraplegia and euthanasia (Go to video clip. Note progression of ataxia to inability to ambulate in the pelvic limbs).  Neuroanatomic localization early in the disease course indicates a lesion between the third thoracic (T3) and third lumbar (L3) spinal cord segments.  Progressive asymmetric pelvic limb ataxia and paresis, and lack of paraspinal hyperesthesia are key clinical features of DM.  Pelvic limb hyporeflexia is observed less commonly.  This clinical manifestation reflects nerve root involvement and the disease is termed canine degenerative radiculomyelopathy.   Dogs often lose the ability to ambulate in the pelvic limbs within 4 to 6 months from the time of diagnosis.  Thoracic limb function, and urinary and fecal continence usually are spared until end-stage disease.  Age of onset of neurologic signs usually is 5 years or older with a mean age of 9 years however, younger dogs also have been affected.  The clinical course of DM can vary from 6 months to 1 year or longer after the suspected diagnosis.  There is no sex predilection. Although the German Shepherd Dog (GSD) is the most commonly affected breed,  other breeds with predilection include Pembroke (Fig. 1)  and Cardigan Welsh Corgi, Chesapeake Bay Retriever, Rhodesian Ridgeback, Irish Setter, Boxer, Collie dog and Standard Poodle.

Tentative antemortem diagnosis presently is based upon ruling out other diseases causing progressive myelopathy.  Common differentials include intervertebral disc disease, inflammatory disease, and spinal cord neoplasia.  Hip dysplasia and degenerative lumbosacral stenosis often can be confused with DM, but the neurologic findings are different, if a careful examination is performed.  Neurodiagnostic techniques for evaluation of spinal cord disease include CSF analysis, electrodiagnostic testing, myelography, computed tomography and magnetic resonance imaging.  Imaging and additional diagnostic procedures will rule-out other diseases that cause progressive myelopathy.

Definitive diagnosis of DM is determined postmortem by histopathologic examination of the spinal cord (Fig. 2).  Neuropathologic lesions involve the spinal cord myelin and axons in all funiculi. Vacuolated axons and myelin sheaths are most extensive in the thoracic spinal cord.  Astroglial proliferation is prominent in severely affected areas.  Lesions have been described as discontinuous, bilateral, and asymmetrical.  However, more recent evidence describes lesion distribution as symmetric and continuous in dogs that survive for long periods with DM.

Until a cause of DM is known, it is difficult to recommend an appropriate treatment regimen.  Aminocaproic acid, an antiprotease agent, has been advocated for long-term management of DM, but no published clinical data is available to support drug efficacy.  Although vitamin deficiencies can cause spinal cord degeneration in some species, therapy with parenteral cobalamin or oral tocopherol did not affect neurologic progression in a study of DM affected dogs. ( DA Williams, unpublished data)   DL-Methionine supplementation to DM affected dogs also did not alter disease progression. (JR Coates, unpublished data)  Combination therapies with an exercise regimen have been advocated for treatment of DM.  Physical therapy using range of motion and isometric exercises helps to maintain limb mobility and muscle strength. When the dog loses mobility in the pelvic limbs, a wheel cart may assist with patient mobility.  Long term prognosis however is poor. 

NEW STUDY ON DEGENERATIVE MYELOPATHY IN THE BOXER DOG

AKC Canine Health Foundation Grant #821 (2007-2009)
Phenotypic Characterization and Mapping Genes Associated with Canine Degenerative Myelopathy in the Boxer

Degenerative myelopathy (DM) is a disease of the spinal cord causing progressive paraparesis.  Though most commonly reported in German Shepherds, high disease prevalence is also exists in other breeds, such as Cardigan and Pembroke Welsh Corgis, Rhodesian Ridgebacks, and Boxer dogs.  The increased risk in specific breeds suggests a significant genetic predisposition and adds power to mapping any genetic risk factors.  The purpose of this proposal is to map genes associated with DM in the Boxer dog and other breeds.  We propose characterizing the phenotype in the Boxer dog using sequential antemortem neurodiagnostic testing, and neuropathology. A small subset of 10 Boxer dogs will be further characterized directly by the principal investigator, to determine if the phenotype and clinical progression is identical to that seen in Welsh Corgi.

Genome-wide association mapping will be performed to identify a genomic locus associated with DM in 50-100 affected and 50-100 old healthy boxers using the ~20,000 SNP array. If as expected the same phenotype is seen in Boxers as in the Pembroke Welsh Corgis and Rhodesian Ridgebacks, disease haplotypes are likely to be shared between these breeds. We will thus fine map using Boxers as well as smaller numbers of affected and control Pembroke Welsh Corgis and Rhodesian Ridgebacks. We expect to narrow the region to contain only 1-2 genes.  This project will allow for more rapid development of genetic tests to identify carrier and affected dogs of DM and thus eliminate the genotype of this late-onset disease from the population.  Early, accurate distinction of DM from other neurological disease will facilitate therapeutic trials. 

DNA samples are currently being banked on affected and related breeds affected by Degenerative myelopathy.

For information on sample submission go to the following website:  www.caninegeneticdiseases.net