Paraneoplastic Syndrome - Neurological Complications

10/19/00 (Del Rio / Mooney)

Group: Monday Residents

Presenting Resident: Dr. Steve Mooney

RE: 56 year old African-American female with breast mass and ataxia.

Question: Does breast cancer have paraneoplastic involvement in the cerebellum?

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Unique Identifier: 99235151

Authors: Dalmau J. Gultekin HS. Posner JB.

Institution: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA. dalmauj@mskcc.org

Abstract: Since 1965 when the first paraneoplastic antineuronal antibody was reported by Wilkinson and Zeromski (55), the number of immunological responses detected in association with paraneoplastic syndromes of the nervous system has steadily increased. These responses are characterized by the presence of antineuronal antibodies in serum and CSF and/or infiltrates of T-cells in the tumor and nervous system. A few syndromes are mediated by antibodies; they include those resulting from dysfunction of the neuromuscular junction at the pre- or post-synaptic level (Lambert-Eaton myasthenic syndrome, myasthenia gravis) or ion channel dysfunction in the peripheral nervous system (i.e, Voltage-gated potassium channel and neuromyotonia). In most other paraneoplastic syndromes, including those involving the central nervous system, the pathogenic role of highly specific antineuronal antibodies (anti-Hu, anti-Yo, etc.) has not been established; nevertheless these antibodies should be regarded as useful markers of specific paraneoplastic syndromes and tumors. Moreover, there is increasing evidence that in some of these syndromes T-cell mediated mechanisms can cause the neurologic dysfunction and contribute to tumor rejection. Some paraneoplastic syndromes are caused by the tumor secretion of antibodies (macroglobulinemia and MAG antibodies), hormones, and cytokines. In other instances, the tumor may compete with the nervous system for an essential substrate (glucose, tryptophan) and result in neurologic dysfunction. [References: 56]

Link Directly to Fulltext article in Ovid

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Unique Identifier: 99213419

Authors: Dalmau JO. Posner JB.

Institution: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Abstract: The fact that a small cancer hidden in the chest, abdomen, or pelvis could destroy or damage portions of the nervous system, such as cerebellar Purkinje cells or cholinergic synapses, has intrigued neurologists since paraneoplastic syndromes were first described. In 1965, when little was known about their pathogenesis, a full issue of the journal Brain and an international symposium were devoted to paraneoplastic disorders. In this decade, the discovery of several paraneoplastic antibodies that react with both the nervous system and the causal cancer has rekindled interest in these syndromes (Table). Several other factors make these rare syndromes of clinical and scientific interest. A recent review by Dalmau and Posner contains a more comprehensive bibliography of paraneoplastic syndromes. [References: 17]

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Unique Identifier: 92005277

Authors: Waterhouse DM. Natale RB. Cody RL.

Institution: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0374.

Abstract: Of the remote effects of cancer on the neurologic system, paraneoplastic cerebellar degeneration (PCD), characterized by global cerebellar dysfunction, is second only to paraneoplastic neuropathies in frequency. Recent evidence, including the finding of anti-Purkinje cell (now termed anti-Yo) antibodies directed against specific protein antigens shared by Purkinje's and tumor cells, supports an autoimmune etiology for this disorder. Increasingly, a link between breast cancer and PCD is being recognized. The authors report a case, as well as a comprehensive overview, of 62 women with breast cancer and PCD, identified through a Medline (National Library of Medicine, Washington, DC) computer search (1966 to 1991) and comprehensive reference follow-up of the medical literature. The current understanding of the pathophysiology of PCD, with particular emphasis upon those features both salient and unique to breast cancer, is discussed. Whereas PCD will affect only a small number of patients with breast cancer, recognition of this syndrome is important. Anti-Purkinje cell (anti-Yo) antibody titers are now commercially available through several reference laboratories, and a serum anti-Purkinje cell antibody titer will assist in establishing the diagnosis. Presence of consistent symptoms and elevated titers of anti-Yo antibodies should prompt a search for an otherwise occult, and potentially treatable, malignancy. Only therapy initiated early in the patient's course appears to be of benefit. Finally, investigations into the pathogenesis of this syndrome may shed further light upon other diseases presumed secondary to autoimmune dysfunction. [References: 43]