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Paraneoplastic cerebellar degeneration (PCD) is characterized by the rapid development of a severe pancerebellar dysfunction. The postmortem study shows extensive loss of Purkinje neurons with relative preservation of other cerebellar neurons. Inflammatory infiltrates in the deep cerebellar nuclei and brainstem are also identified in some patients. PCD has mostly been reported in association with gynecologic tumors, breast cancer, lung cancer, particularly small cell lung carcinoma (SCLC), and Hodgkin's lymphoma. The clinical picture is similar in all patients with PCD independent of the associated tumor. The patient subacutely develops truncal and appendicular ataxia, and dysarthria. Ataxia is initially asymmetric in 40% of the patients. After a few months symptoms stabilize, leaving the patient severely disabled. Most of the patients have diplopia, horizontal nystagmus, and half of them have rotatory or downbeating nystagmus. Signs and symptoms of involvement of other areas of the neuraxis are common but usually mild. CT and MRI studies are normal or demonstrate cerebellar atrophy particularly in the latter stages of the disease.
Anti-Yo antibodies are present in the great majority of patients with PCD and cancer of the ovary, breast, or other gynecological malignancies. In two thirds of anti-Yo PCD patients the neurological symptoms develop before the diagnosis of the tumor.
Anti-Tr antibodies are markers of patients with PCD and Hodgkin disease. Unlike anti-Yo antibodies, anti-Tr antibodies usually disappear after treatment of the tumor or, in a few patients, are only found in the CSF. Anti-Tr antibodies are found in a few patients with a subacute cerebelar syndrome, identical to PCD who never develop Hodhkin’s disease or solid tumors.
Anti-voltage-gated calcium channel (VGCC) antibodies are present in near 40% of patients with PCD and lung cancer, usually SCLC. About half of these patients present a coincident Lambert Eaton myasthenic syndrome (LEMS).
Anti-Hu antibodies are reported in 23% of patients with PCD and lung cancer. These patients rarely harbour VGCC antibodies. The frequency of anti-Hu antibodies is much higher in those patients who present a cerebellar syndrome, lung cancer, and symptoms of involvement of other areas of the nervous system (paraneoplastic encephalomyelitis).
A few patients with PCD and lung cancer present anti-CV2(CRMP5), anti-Zic4 or anti-Ma antibodies.
As in many paraneoplastic neurological syndromes of the central nervous system, PCD rarely improves with treatment. The best chance to at least stabilize the syndrome is to induce a complete response of the tumor. Immunotherapy rarely is effective but a trial with intravenous immunoglobulins, steroids or plasmapheresis is indicated because there are a few patient who improved. Patients with anti-Tr antibodies are more likely to improve than those with anti-Hu or anti-Yo antibodies.
1. Peterson K, Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration: a clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992;42:1931-37.
2. Graus F, Lang B, Pozo-Rosich P, et al. P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 2002;59:764-6.
3. MasonWP, Graus F, Lang B, et al. Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton mysthenic syndrome. Brain 1997;120:1279-300.
4. Shams’ili S, Grefkens J, de Leeuw B, et al. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies:analysis of 50 patients. Brain 2003;126:1409-18.
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Updated 2009-09-15
