NEUROMUSCULAR CASE OF THE MONTH - MARCH 2002

Progressive paraparesis in 6 year old MC Saint Bernard
Contributed by Dr. Don Levesque
Veterinary Neurological Center
Las Vegas, NV 89188


Clinical History
The dog was presented with paraparesis that progressed over a 2-3 week period. Spinal survey radiography performed by the referring veterinarian showed marked lumbar spondylosis and articular facet degenerative joint disease. Hip dysplasia associated with osteoarthritis was also described. The dog also had chronic bowel problems, that according to the owner, had been treated with 1250 mg metronidazole daily for over a year.


Physical and Neurological Examination
No specific abnormalities were identified on general physical examination. Upon presentation, the dog could not support weight on its rear limbs without assistance. Voluntary movement was present with assistance and support. The dog improved within 12 hours of diazepam therapy resulting in consideration of metronidazole toxicity. While the dog did not show classic cerebellar or vestibular signs of metronidazole toxicity, the improvement in such a short period of time could have been due to early signs of central toxicity. Following diazepam therapy, a dysmetric rear limb gait was present with reduced hock flexion (See video clip). The dog would frequently collapse in the rear quarters. The forelimb gait appeared normal. Mentation was also considered normal and no cranial nerve abnormalities were identified. Predominant abnormalities identified on the neurological examination included absent conscious proprioception and hopping in the pelvic limb, weak withdrawal reflexes bilaterally in the pelvic limb, and slowed patellar reflexes. Neurolocalization was determined to be the L4-S2 spinal segments possibly associated with a peripheral neuropathy


Diagnostic Testing
CBC, serum chemistry, and urinalysis – No significant abnormalities

Thyroid profile – Normal T4(RIA), T4 (equilibrium dialysis) and TSH

Electrophysiology: Electromyography (EMG) showed absent insertional potentials in the rear limb interosseous muscles bilaterally. No EMG abnormalities were identified in the more proximal rear limb muscles. The forelimb muscles were also normal except for the interosseous muscles which showed marked denervation (fibrillation) potentials. Motor nerve conduction velocities were considered normal in both the proximal sciatic (greater trochanter to stifle) and ulnar (elbow to carpus) nerves. Distal sciatic nerve conduction velocities could not be recorded due to a conduction block. A distal axonopathy was suggested based on the electrophysiological findings.

Muscle and Nerve Biopsies: A biopsy was submitted from the right cranial tibial muscle (Fig. 1). There was a marked variation in myofiber size with small groups of atrophic fibers and scattered pyknotic nuclear clumps. Endomysial fibrosis was present in areas of most marked atrophy. Fiber type grouping was also observed (not shown). These findings supported chronic axonal degeneration. A biopsy from the right tibial nerve was plastic embedded and evaluated in 1 µm sections. There was a moderate depletion of large myelinated nerve fibers with scattered small, thinly myelinated fibers suggestive of regeneration. Resolving endoneurial edema separated the remaining nerve fibers.



Figure 1. Cranial tibial
muscle (H&E stain)


Figure 2. Tibial nerve
(Toluidine blue stain)

Conclusion
The neurological examination, electrophysiological findings, and results of muscle and nerve biopsy evaluations were supportive of a peripheral neuropathy. Given the history in this dog of daily treatment with metronidazole for over 1 year, a toxic polyneuropathy is a possible etiology. Although the dosage of metronidazole used was within an appropriate range, the drug was used over a long period of time. The toxic effects of the drug are a result of binding to neuronal RNA and inhibition of protein synthesis resulting in axonal degeneration. Purkinjie cell lesions develop after prolonged use. The dog was euthanitized without a necropsy. Cases of a predominantly sensory peripheral neuropathy have developed in human patients treated for several months. Electrophysiologic studies and nerve biopsy in humans suggested a primary axonal pathology.

Bradley WG, Karlsson IJ, Rassol CG. Metronidazole neuropathy. Br Med J 1977; 2:260.

Coxon A, Pallis CA. Metronidazole neuropathy. J Neurol Neurosurg Psychiatry 1976; 39:403.

Evans J, Levesque D, Plummer S et al. The use of diazepam in the treatment of metronidazole toxicosis in the dog. J Vet Int Med 2002; 16:368a


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