Progressive lower motor neuron weakness in a 10 year old male castrated DSH

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.

Case Update

After diagnosis of sciatic nerve lymphoma, the cat was re-induced with a new chemotherapy protocol. L-asparaginase was administered and a protocol including two cycles of weekly cyclophosphamide, adriamycin, and vincristine were given on a rotational basis. A CBC was performed prior to each chemotherapy administration. The only abnormality noted was a mild waxing and waning regenerative anemia. The corticosteroid was changed from prednisone to dexamethasone. After six weeks the treatment frequency was reduced to once every two weeks. At this point the protocol was modified with adriamycin replaced by cytosar arabinoside. Clinically the cat had improved dramatically and regained the ability to jump on furniture and remain standing while consuming a meal. Posture was much improved with the previous plantigrade stance disappearing almost entirely. The deep tendon reflexes and withdrawal reflex were considered normal. Ten months after diagnosis the cat began to lose weight and have chronic diarrhea. Reoccurrence of hind limb weakness was not observed. The cat underwent endoscopy with biopsy of the stomach and duodenum. The biopsies revealed recurrent lymphoma in the duodenum. The cat was again re-induced with L-asparaginase and the chemotherapy protocol was changed. The new protocol included mustragen, vincristine, procarbazine and prednisone. Due to anorexia the procarbazine was discontinued. At the time of this writing the cat was 13 months from the diagnosis of peripheral nerve lymphoma and stable. Review of pathology records from the Animal Medical Center from 1995-2000 revealed five additional cats identified with peripheral nerve involvement and concurrent systemic lymphoma. Unfortunately all the diagnoses were made at necropsy. This report should raise the awareness of the possibility of peripheral nerve lymphoma in other cats that present with lower motor neuron signs. Update provided by Drs. Jason Berg and Richard Joseph.

References

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)