Neurologic Complications of Bladder Cancer

Abstract & Commentary

Source: Anderson TS, et al. Neurologic complications of bladder carcinoma: A review of 359 cases. Cancer. 2003;97: 2267-2272.

Among 359 patients with bladder cancer confirmed by tissue diagnosis and seen between 1962 and 2001 at the University of Kentucky Medical Center, 14% (n = 52) developed neurological complications. Overall, 5% developed neurologic metastases, with 2% each experiencing lumbosacral plexopathy (n = 7) or epidural spinal cord compression (n = 6), and 1% (n = 4) developing brain metastases. In 1 patient, brain metastases preceded diagnosis of the bladder cancer by 3 months. Nonmetastatic complications were the more common and included metabolic encephalopathy in 24 (7%), peripheral neuropathy in 9 (2.5%), stroke in 6 (1.7%), and seizures in 5 (1.4%). One patient each was diagnosed with normal pressure hydrocephalus, subdural hematoma, and glioblastoma multiforme. Back pain was the most frequent neurologic complaint (n = 32, 9%), but in 25% (n = 8) it was unrelated to the cancer and in another 34% (n = 11) it was due to purely bony metastases. No patient developed infectious or carcinomatous meningitis. At autopsy, 67% of bladder cancer patients show metastases, usually to the liver (39%), lung (38%), or bone (28%). For the neurologist, however, local spread is more common than distant metastases. Back pain and metabolic encephalopathy, the latter usually due to renal failure, remain the most common incentives for neurologic consultation in such patients.

Commentary

Paraneoplastic neurological syndromes may also, on rare occasions, occur with bladder carcinoma. Presumably a protein, normally restricted to the nervous system, is expressed by the tumor, inducing an immune response with production of onconeural antibodies both against the tumor and the nervous tissue. Evidence suggests that cytotoxic T cells are also involved. Among 34 patients with type 2 antineuronal nuclear autoantibody (ANNA-2 or "anti-Ri"), cancer was found in 24 (86%), including lung (n = 10), breast (n = 9), and 1 each with cervical and bladder cancer.1 Opsoclonus-myoclonus was the predominant neurologic syndrome in the latter, presenting 1 year after cancer diagnosis, with other symptoms and signs comprising trochlear nerve palsy, tremor, dizziness, and memory problems. Dermatomyositis is also reported with transitional cell bladder carcinoma, and a causal relationship was suggested when treatment of the cancer resulted in resolution of the dermatomyositis.2 Anti-Yo antibody (anti-Purkinje cell cytoplasmic antibody, APCA-1), paraneoplastic cerebellar degeneration, and bladder cancer comprise another syndrome. Tumor tissue demonstrated the presence of Yo antigen and antibody titers fell with removal of the tumor.3 Lastly, among 12 patients with antineuronal nicotinic ganglionic acetylcholine receptor (AchR) antibodies, 5 had subacute autonomic neuropathy, 1 each with cancer of lung, rectum, or bladder. Neither healthy subjects nor 62 patients with myasthenia gravis and muscle AChR antibodies were positive for ganglionic AChR antibodies, implicating the latter in this paraneoplastic association.4 — Michael Rubin, MD. Dr. Rubin, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.

References

1. Pittock SJ, et al. Ann Neurol. 2003;53:580-587.

2. Mallon E, et al. Clin Exp Dermatol. 1999;24:94-96.

3. Greenlee JE, et al. Ann Neurol. 1999;45:805-809.

4. Vernino S, et al. Neurology. 1998;50:1806-1813.