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RESEARCH PROJECTS

Orthopaedic Pathology and Genetic Associations in Cervical Stenotic Myelopathy

James N. MacLeod, VMD, PhD
jnmacleod@uky.edu
(859) 218-1099

Photo of horses in fieldCervical stenotic myelopathy is a disease that affects both the neurologic and musculoskeletal system of horses.    The disease is characterized by a structural narrowing of the vertebral canal in the neck that can produce severe neurological deficits through compression of the cervical spinal cord.  Lesions are classified as either dynamic or static, based on myelogram.  With dynamic lesions, compression of the spinal cord only occurs during neck flexion.  Static lesions result from compression of the spinal cord regardless of neck position.  Horses with dynamic lesions are typically 8-18 months of age and the location of the compression is usually C3-5.  Static lesions tend to occur at 1-4 years of age and in the caudal cervical vertebra from C5-7. While the exact etiology and pathogenesis are not well understood, it is thought to be a multi-factorial disease with genetics, high planes of nutrition, trauma, rapid growth, and decreased copper/increased zinc levels all potentially playing a role.

The breed examined in this study will be limited to Thoroughbreds.  The objective is to elucidate the role of genetics along with normal and abnormal bone and cartilage formation in the onset and progression of this disease.  Comparison of the articular processes and cranial and caudal epiphyseal growth plates of cervical vertebrae from affected and control horses will be analyzed using detailed gross and histological examinations.    Lesions consistent with osteochondrosis will be graded on gross and histological levels using a standardized scale.  Postmortem Magnetic Resonance Imaging (MRI) will be performed on all affected and control horses (see image on left below).  The procedure will enable a detailed in situ inspection of the cervical vertebrae, cervical spinal cord, and associated soft tissue structures.  Alterations in subchondral bone, as well as structural changes in articular and physeal cartilage will be assessed.  MicroCT imaging will allow for detailed bone structure and matrix analysis (see image on right below).

MRI image
MicroCT image

Genomic DNA will be isolated and purified.  Genotyping will be performed using a 54,602 element equine-specific single nucleotide polymorphism (SNP) array.  Linkage disequilibrium between affected and control horses will be evaluated by comparing SNP haplotypes with the disease phenotype to identify any quantitative trait loci (QTL) associations.  Fine mapping within identified QTL regions with additional SNPs will be completed to prioritize candidate genes.  Results of this study will enhance understanding of the etiology and pathogenesis of cervical stenotic myelopathy, advance MRI imaging and molecular diagnostic technologies, and provide a scientific foundation for research on improved management and therapeutic practices for this prevalent and serious disease.

Cervical stenotic myelopathy is a prevalent disease and represented 31% of the postmortem neurologic cases performed at the University of Kentucky Livestock Disease Diagnostic Center over the 3 year period of 2000 through 2002.  Thoroughbreds accounted for a full 79% of these cases.  A diagnosis of cervical stenotic myelopathy often carries a guarded to poor prognosis in terms of the horse’s future potential for racing or any other athletic career.  Medical therapies have limited efficacy and a surgical option involving vertebral fusion is considered in only a subset of cases.  Euthanasia is a frequent outcome in affected horses due to both humane and safety considerations.  Taken together, cervical stenotic myelopathy is a major neurological disease of Thoroughbreds and has a substantial financial and emotional impact on owners and the industry.

SNP Chip
SNP Chip (www.illumina.com)

 

Maxwell H.Gluck Equine Research Center
Department of Veterinary Science, University of Kentucky
Lexington, Kentucky 40546-0099

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