NEUROMUSCULAR CASE OF THE MONTH - SEPTEMBER 1999

Progressive lower motor neuron weakness in a
10 year old male castrated DSH
Contributed by Drs. Dr. Jason Berg and Dr. Richard Joseph
The Animal Medical Center
510 E. 62nd St.
New York, NY 10021

Clinical History
The cat was presented with a 1 month history of progressive weakness in the rear limbs, decreased jumping, decreased ambulation, crouched posture and flexion of the hocks. A previous diagnosis of intestinal lymphoma was made in April 1998. He had been treated with a multidrug chemotherapy protocol which included vincristine, L-asparaginase, cyclophosphamide, adriamycin, methotrexate, and prednisone. The cat had a complete remission and remained in good health with regular chemotherapy visits for the next 16 months before the current presentation.

Physical and Neurological Examination No specific abnormalities were observed on general physical examination. Neurological examination showed the cat was alert with appropriate mentation. Cranial nerve evaluation and conscious proprioception were normal. There was a short-strided gait with the rear limbs worse than the forelimbs, sliding out of the rear limbs, inability to jump, plantigrade stance, and weakness. Cranial tibial  and patellar reflexes were 1+ bilaterally. Withdrawal was normal. Pain was elicited on caudal thigh muscle palpation. Atrophy of the rear limb musculature was prominent (Fig. 1). Neurolocalization was to the peripheral nerve or muscle.

Figure 1. Note atrophy of rear limb musculature

Diagnostic Tests CBC, Serum chemistries - Normal Toxoplasma IgG - Negative Chest radiographs - Normal Electromyography - Positive sharp waves and fibrillation potentials severe in distal muscles and mild in proximal and axial muscles with the rear limbs more active than the forelimbs (Fig.2A). Motor nerve conduction velocities were within the reference range at 97 m/sec in the forelimb and 78 m/sec in the rear limb with a normal configuration (Fig. 2B). The differential diagnosis included infectious, immune-mediated, paraneoplastic, toxic, drug induced (vincristine), primary neoplastic infiltration, or degenerative etiologies. Muscle and Nerve Biopsies - Pathological changes within the muscle biopsy were compatible with denervation and included angular atrophied fibers occurring singularly and in large groups without fiber type grouping. Scattered necrotic fibers undergoing phagocytosis were also present. A fixed nerve biopsy evaluated in plastic embedded sections showed infiltrative lymphoma (Fig. 3).

Figure 2A. Electromyogram showing positive sharp waves and fibrillation potentials within the distal rear limb musculature. Figure 2B. Nerve conduction velocity was within the reference range with normal configuration. Figure 3. Infiltrative lymphoma (asterisk) and replacement of nerve fibers were observed within the biopsy from the peroneal nerve. Several foamy macrophages (left facing arrowhead) and remyelinating nerve fibers (upward facing arrowhead) were identified. Plastic embedded sections (1 um) were stained with toluidine blue-basic fuschin.

Conclusion
Reinduction of chemotherapy with L-aspariginase and cyclophosphamide was initiated. A moderate clinical improvement was observed within 3 weeks following reinduction with less flexion, more mobility, and a more upright stance. Direct infiltration of nerve roots and peripheral nerves by lymphocytic cells is not uncommon in human lymphoma, particularly the non-Hodgkin types. In a retrospective study of 145 cases of malignant lymphoma in humans, there was histologic evidence of peripheral nerve infiltration by malignant cells in almost 40% of the patients.

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Reference
McLeod JG. Peripheral neuropathy associated with lymphomas, leukemias, and polycythemia vera. In: Dyck PJ and Thomas PK (ed). Peripheral Neuropathy, W.B. Saunders Co, Philadelphia, 1993, 1591-1598. (Extensive reference list)

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