Paraneoplastic syndromes are nonmetastatic complications of cancer. They can affect all parts of the nervous system, including the brain, cranial nerves, spinal cord, dorsal root ganglia, peripheral nerves, and the neuromuscular junction. They are thought to be immunologically mediated and are unrelated to metabolic or nutritional disorders, infection, stroke, or complications of therapy (eg, chemotherapy). Although the exact pathogenesis is unclear, similarities between antigens expressed by tumors and neural tissues (molecular mimicry) may lead to effects against neural tissue by immune cells targeting the tumor.
Paraneoplastic syndromes affecting the CNS are rare in animals, but lack of awareness may have led to a low detection rate. A case involving the spinal cord was described in an 8-yr-old, male German Shepherd with a history of acute pelvic limb paralysis. Clinical signs included progressive loss of motor function, conscious proprioceptive deficits, loss of superficial and deep pain sensation over the trunk and pelvic limbs, and Schiff-Sherrington-like hyperextension in the thoracic limbs. Hepatocellular carcinoma with metastasis to the lungs, liver, spleen, and lymph nodes was found on necropsy. Severe necrotizing myelopathy was present throughout the gray and white matter of the thoracic spinal cord, including spongy degeneration, gliosis, demyelination, axonal swelling and degeneration, and neuronal necrosis. In a second case, a range of neurologic deficits in a 17-mo-old, male Poodle was attributed to hyperviscosity syndrome secondary to macroglobulinemia-associated lymphocytic leukemia.
Dogs with thymoma may develop paraneoplastic myasthenia gravis (MG). In one review of canine thymoma, 47% of the dogs had MG, 33% had nonthymic cancer (including pheochromocytoma, mammary adenocarcinoma, or pulmonary adenocarcinoma), and 20% had concurrent signs of polymyositis. Dogs with thymoma-associated MG may also produce autoantibodies to several neuromuscular antigens, including ryanodine (a skeletal muscle calcium-release channel receptor) and the muscle protein titin.
An association between myositis (eg, dermatomyositis and polymyositis) and malignant neoplasia in people has been well established. Dogs with malignant tumors such as bronchogenic carcinoma, myeloid leukemia, or tonsillar carcinoma may also have muscular necrosis and low-grade myositis, but the frequency of this potentially paraneoplastic association is unknown.
While the frequency of peripheral neuropathy in animals with cancer is also uncertain, certain types of cancer, such as bronchogenic carcinoma, mammary adenocarcinoma, malignant melanoma, insulinoma, osteosarcoma, lymphoma, thyroid adenocarcinoma and mast cell tumor, may facilitate development of peripheral nerve lesions. Histopathologic findings can include paranodal-segmental demyelination, remyelination, axonal degeneration, and myelin globules. The incidence of neuropathy may vary with the type of malignancy. Dogs with multiple myeloma may also develop peripheral neuropathy.
Clinical signs may include reduced or absent spinal or cranial reflexes, flaccid weakness, reduced muscle tone, paralysis of limb or head muscles, and, after 1–2 wk, neurogenic muscle atrophy. Dysphonia may also be present.
Dogs and cats with clinical signs of nervous system disease (or with myositis or necrotizing myopathy confirmed by histopathology) that fail to respond to therapy or that relapse should be carefully checked for malignancy. Testing may include chest radiography, sonography, CT, or MRI as indicated. Such vigilance may detect tumors at a more treatable stage.
Last full review/revision July 2011 by Kyle G. Braund, BVSc, MVSc, PhD, FRCVS, DACVIM (Neurology)