How do I diagnose and manage degenerative myelopathy in German Shepherds, including genetic testing?

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Presumptive antemortem diagnosis of degenerative myelopathy (DM) in German Shepherd Dogs (GSDs) rests on three pillars: compatible clinical signs, SOD1 homozygosity on genetic testing, and exclusion of other thoracolumbar myelopathies by spinal MRI and cerebrospinal fluid (CSF) analysis. Definitive diagnosis requires postmortem histopathology of the spinal cord. 1710 The clinical presentation is characteristic but not pathognomonic. DM begins as insidious, asymmetric general proprioceptive ataxia and upper motor neuron spastic paraparesis of the pelvic limbs, progressing to lower motor neuron paraplegia, then flaccid tetraplegia, and ultimately respiratory failure if euthanasia is not elected. 2510 In GSDs allowed to progress without euthanasia, death from respiratory failure occurs approximately 3 years after disease onset. 5 Genetic testing for the SOD1:c.118G>A missense mutation is the cornerstone of the diagnostic workup. The mutation is inherited in an autosomal recessive pattern with incomplete penetrance; homozygosity for the A allele (A/A genotype) confers high risk for clinical DM, while heterozygotes (G/A) rarely develop clinical signs. 210 In GSD populations, the A allele frequency has been reported at 0.220 in Japan, 0.23 in Uruguay, 0.15 in Paraguay, and 0.121 in Brazil (where no A/A homozygotes were identified in the sampled population). 369 Among A/A dogs older than 10 years, clinical progression rate reaches 100% in both Japanese and South American GSD populations. 36 A second mutation, SOD1:c.52A>T, has been identified only in Bernese Mountain Dogs and is not relevant to GSDs. 910 The majority of neurologists require genetic testing for the SOD1 mutation to support a presumptive DM diagnosis; 82 of 189 neurologist respondents also require spinal MRI. 1 Spinal MRI is essential to exclude structural differentials — intervertebral disc extrusion, spinal neoplasia, and other compressive myelopathies — because DM lesions are not visible on conventional M