Multisystem Axonopathy and Neuronopathy in Golden Retriever Dogs

Central axonopathies are uncommon in dogs. Several terms have been used to describe these diseases, such as axonopathy, leukomyelopathy, axonal degeneration, and neuroaxonal degeneration. The majority of reported cases were breed-specific with peculiar clinical and pathological features seen in each breed. The association of central axonopathy and motor neuronal degeneration has not been reported. We report a progressive multisystem central axonopathy and motor neuronopathy in 3 Golden Retriever littermates with unique clinical and pathological features. Dog 1 was a 3-month-old female intact Golden Retriever dog referred to the Small Animal Clinic of the Ontario Veterinary College (OVC) with a 6-week history of pelvic limb weakness. The owners noticed that the dog appeared smaller than the other littermates and that her pelvic limb musculature was underdeveloped. She had difficulty in getting up, and when resting in lateral recumbency had fine muscle tremors in the limb muscles. The clinical signs progressed to involve the thoracic limbs with generalized weakness observed 2 weeks before presentation. On physical examination, no other abnormalities were detected except for generalized muscle atrophy. On neurological examination, short-strided tetraparesis, with no evidence of proprioceptive ataxia, was observed. The postural reactions (proprioceptive positioning and hopping) were adequate, as were the cranial nerve reflexes and responses. The flexor and patellar reflexes were mildly decreased. Resting, high-frequency, low-amplitude muscle tremors were seen in all limbs. These tremors could be elicited by palpation of the limb muscles. Based on the findings of lower motor neuron (LMN) tetraparesis, absence of proprioceptive ataxia, normal postural reactions, and mildly decreased reflexes, a neuromuscular disease was suspected. CBC, biochemistry profile, and urinalysis were performed. Abnormalities on the biochemistry profile were a creatine kinase (CK) activity of 517U/L (reference range, 40–255U/L) and a globulin concentration of 17 g/L (reference range, 21–42 g/L). No cause for the mild hypoglobulinemia was identified and it was assumed to be associated with the young age of the dog. No abnormalities were identified on the CBC or urinalysis. Electromyography, nerve conduction studies, and nerve and muscle biopsies were proposed, but declined by the owners. The dog continued to deteriorate and was re-evaluated at 6 months of age. At that time, the dog was markedly tetraparetic and the patellar reflexes were no longer present. Some extensor muscle tone was still present. Euthanasia and necropsy were performed. Two other littermates had a similar history and presentation. Dog 2, a male intact Golden Retriever, began to show signs of weakness and tremors at 15 weeks of age. By 5 months of age, severe generalized muscle atrophy and fatigue were obvious. CBC and biochemistry profile at that time were normal. The dog was referred and examined at 8 months of age. The neurological examination identified a kyphotic posture (Fig 1), generalized muscle atrophy, neuromuscular type (short-stride) tetraparesis, absence of ataxia, mildly decreased spinal reflexes, and head and body tremors. The nature of the tremors was suggestive of muscle weakness and not intentional tremors as seen with cerebellar disorders. Cranial nerve examination and postural reactions were adequate. CBC and biochemistry profile did not identify any clinically relevant abnormalities. Serum and whole blood were submitted for metabolic screening for amino acids, organic acids, and carbohydrates to investigate a possible metabolic or storage disease. Results of these tests were within reference limits. Euthanasia and necropsy were performed. Dog 3, a male intact Golden Retriever littermate, was presented to the OVC at 8 months of age. Weakness and body tremors were first observed when the dog was 3 months old. At presentation, the dog was markedly tetraAbbreviations: