A six-year-old male neutered Great Dane presented for assessment of acute, progressive, non-painful, non-ambulatory, non-lateralizing tetraparesis, hyporexia, and urinary tract infection (UTI). The dog had a one-month history of UTI treated with four antibiotics, including a ten-day course of nitrofurantoin after urine culture. The lesion was localized as a generalized neuromuscular problem or concurrent C1-5 and L4-S3 myelopathies. Serum biochemistry was unremarkable, treatment with edrophonium yielded a decompensated gait, and three-view thoracic radiographs were negative for megaesophagus. Cervical and lumbar magnetic resonance imaging demonstrated mild osseous cervical spondylomyelopathy with minimal spinal cord compression at C4-5 and C6-7 and intervertebral disc degeneration with mild C2-3 foraminal stenosis and no compressive radiculopathy at C3-T4 and L7-S1. No underlying cause for the neuromuscular signs was identified. Acetylcholine receptor antibody test was negative for myasthenia gravis, and cessation of nitrofurantoin combined with four days of supportive care resulted in complete resolution of the neurologic deficits.