NEUROMUSCULAR CASE OF THE MONTH - JULY 2000

Muscular dystrophy in a 6 month old male mixed breed dog
Contributed by Dr. Steven Peterson
Veterinary Specialists of Nevada
Sparks, NV 89434

Clinical History The dog (Fig. 1) was adopted from the Humane Society at 6 to 8 weeks of age. The owner reported that the dog did not run like a "normal" dog, was always weak with poor exercise tolerance, fatigued quickly with any activity, and hopped in the rear limbs with increased activity (See Video Clip). The dog would lay down while eating and drinking (Fig. 2). Physical Examination The dog was slow to rise from a laying position and would walk around the room but sit and lay quickly. Cardiovascular, respiratory, and cranial nerve evaluations were normal. The mouth did not open fully and was painful when forced open. Atrophy of the temporalis muscle was noted. Spinal reflexes were intact and no specific neurological deficits were found. A conformational abnormality with extreme "cow hocked" posture in the tarsi was observed. All joints had normal range of motion although the hips were thought to be slightly painful with full extension.

Figure 1. Figure 2.

Diagnostic Testing
Thoracic radiographs - No abnormalities noted. Megaesophagus was not observed.

CBC, serum chemistry analysis including T4, and urinalysis - The only significant abnormalities were elevated creatine kinase (CK) and AST (SGOT)
    CK - 4711 (10-200 IU/L)
    AST (SGOT) - 870 (5-55 IU/L)

Joint fluid analysis - No abnormalities

Assessment
A primary muscle disorder was suspected based on the presence of exercise intolerance, muscle atrophy, and elevation of serum CK concentration. Peripheral nerve disease was thought to be less likely since the spinal reflexes were normal, and a disorder of neuromuscular transmission was unlikely since muscle atrophy and elevation of serum CK was present. Differential diagnosis for primary muscle disease in a young dog should include inflammatory myopathies with an infectious etiology (Toxoplasma, Neospora) and inherited myopathies including the muscular dystrophies. A muscle biopsy was performed to differentiate these possibilities.

Muscle Biopsy Fresh and fixed biopsies were submitted from multiple muscles including the temporalis, vastus lateralis and triceps muscles. Prominent abnormalities included large groups of necrotic fibers undergoing phagocytosis with numerous calcific deposits (Fig. 3, arrows denote calcific deposits), clusters of basophilic regenerating fibers and endomysial fibrosis. Perimysial and endomysial fibrosis were most prominent in the temporalis muscle biopsy. The pathological changes within all muscle biopsies were consistent with a non-inflammatory myopathy of a dystrophic nature. Immunofluorescence analysis was performed to further define the dystrophic nature of this myopathy. Monoclonal antibodies against dystrophin, dystroglycan, sarcoglycan, spectrin, and laminin were used to determine the presence or absence of these membrane associated proteins (Fig. 4).   Almost complete absence of staining for dystrophin, dystroglycan, and sarcoglycan was observed in the dystrophic dog with normal staining following incubation with antibodies against the control proteins spectrin (not shown) and laminin. Rare revertant fibers were positively stained for dystrophin (arrow). Antibodies stained all myofibers from a control dog. (Immunohistochemistry performed by Dr. Ling Liu and Dr. Eva Engvall, Burnham Institute, La Jolla, CA).

Figure 3. Fresh frozen biopsy from the vastus lateralis muscle (H&E) Figure 4. Immunohistochemical analysis for dystrophin and related proteins

Conclusion
The pathological changes within the muscle biopsy and the immunohistochemical staining showing absence of the membrane protein dystrophin are diagnostic of a dystrophinopathy in this mixed breed male dog similar to that described in the Golden Retriever. No treatment is currently available for these disorders. This case should alert clinicians to the possibility of muscular dystrophies in mixed breed dogs and in young dogs presenting with conformational abnormalities and exercise intolerance.

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