Paraneoplastic cerebellar degeneration

The term classical PNS is reserved for the PNS in which the association with cancer is common and includes encephalomyelitis, limbic encephalitis, paraneoplastic cerebellar degeneration, and paraneoplastic opsoclonus myoclonus (OM), as well as sensory neuronopathy (SN), chronic gastrointestinal pseudo-obstruction, Lambert Eaton myasthenic syndrome (LEMS), and dermatomyositis [14]. This chapter does not include dermatomyositis. 

The cdr2 antigen, the target antigen of the Yo antibodies in paraneoplastic cerebellar degeneration, is located in the cytoplasma. The cdr2 protein is a neuronal signaling protein, and is, like the Ma proteins, normally expressed... 

Fig. 1. Examples of positive immunostaining. (A) Cytoplasmic staining of rat Purkinje cells by human serum diluted 1 1000, from an individual with paraneoplastic cerebellar degeneration and Yo antibodies. (B) Serum from an individual with paraneoplastic encephalomyelitis and Hu antibodies, diluted 1 500, showing nuclear staining of rat Purkinje cells. (C) Serum from the same individual as in (B), staining the neuronal nuclei of dorsal ganglion from rat, with nucleolar sparing.

Corradi JP, Yang C, Darnell JC, Dalmau J, Darnell RB. A post-transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues. J Neurosci 1997 17(4) 1406-1415. 

Mason WP, Graus F, Lang B, Honnorat J, Delattre JY, Valldeoriola F, et al. Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome. Brain 1997 120(Pt. 8) 1279-1300. 

Shams ili S, Grefkens J, de Leeuw B, van den Bent M, Hooijkaas H, van der Holt B, et al. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies Analysis of 50 patients. Brain 2003 126(Pt. 6) 1409-1418. 

Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A. P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 2002 59(5) 764-766. 

Bernal F, Shams ili S, Rojas I, Sanchez-Valle R, Saiz A, Dalmau J, et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin s disease. Neurology 2003 60(2) 230-234. 

Graus F, Dalmau J, Valldeoriola F, Ferrer I, Rene R, Marin C, et al. Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin s disease. J Neuroimmunol 1997 74(1—2) 55—61. 

Rojas I, Graus F, Keime-Guibert F, Rene R, Delattre JY, Ramon JM, et al. Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology 2000 55(5) 713-715. 

Fukuda T, Motomura M, Nakao Y, Shiraishi H, Yoshimura T, Iwanaga K, et al. Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome. Ann Neurol 2003 53(1) 21-28. 

Frings M, Antoch G, Knorn P, Freudenberg L, Bier U, Timmann D, et al. Strategies in detection of the primary tumour in anti-Yo associated paraneoplastic cerebellar degeneration. J Neurol 2005 252(2) 197-201. 

Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992 42(10) 1931—1937. 

Furneaux HM, Rosenblum MK, Dalmau J, Wong E, Woodruff P, Graus F, et al. Selective expression of Purkinje-cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration. N Engl J Med 1990 322(26) 1844—1851. 

Verschuuren J, Chuang L, Rosenblum MK, Lieberman F, Pryor A, Posner JB, et al. Inflammatory infiltrates and complete absence of Purkinje cells in anti-Yo-associated paraneoplastic cerebellar degeneration. Acta Neuropathol (Berl) 1996 91 (5) 519—525. 

Stich O, Graus F, Rasiah C, Rauer S. Qualitative evidence of anti-Yo-specific intrathecal antibody synthesis in patients with paraneoplastic cerebellar degeneration. J Neuroimmu-nol 2003 141(1-2) 165-169. 

Tanaka K, Tanaka M, Igarashi S, Onodera O, Miyatake T, Tsuji S. Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice. Clin Neurol Neurosurg 1995 97(1) 101-105. 

Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000 47(1) 9 17. 

Tanaka M, Tanaka K, Tokiguchi S, Shinozawa K, Tsuji S. Cytotoxic T cells against a peptide of Yo protein in patients with paraneoplastic cerebellar degeneration and anti-Yo antibody. J Neurol Sci 1999 168(1) 28—31. 

Albert ML, Darnell JC, Bender A, Francisco LM, Bhardwaj N, Darnell RB. Tumor-specific killer cells in paraneoplastic cerebellar degeneration. Nat Med 1998 4(11) 1321-1324. 

Sutton IJ, Steele J, Savage CO, Winer JB, Young LS. An interferon-gamma ELISPOT and immunohistochemical investigation of cytotoxic T lymphocyte-mediated tumour immunity in patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies. J Neuroimmunol 2004 150(l-2) 98-106. 

Peltola J, Hietaharju A, Rantala I, Lehtinen T, Haapasalo H. A reversible neuronal antibody (anti-Tr) associated paraneoplastic cerebellar degeneration in Hodgkin s disease. Acta Neurol Scand 1998 98(5) 360-363. 

Anderson NE, Rosenblum MK, Posner JB (1988) Paraneoplastic cerebellar degeneration Clinical-immunological correlations. Arm. Neurol, 24, 559-567. 

Cunningham J, Graus F, Anderson N, Posner JB (1986) Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration. Neurology. 36. 1163-1168. 

Dropcho EJ, Chen Y-T, Posner JB, Old LJ (1987) Cloning of a brain protein identified by autoantibodies from a patient with paraneoplastic cerebellar degeneration. Proc. Natl Acad. Scl USA, 84, 4552-4556. 

Furneaux HM, Dropcho EJ, Barbut D, Chen Y-T, Rosenblum MK, Old LJ, Posner JB (1989) Characterization of a cDNA encoding a 34-kDa Purkinje neuron protein recognized by sera from patients with paraneoplastic cerebellar degeneration. Proc. Nati Acad. Sci. USA, 86, 2873-2877. 

Greenlee JE, Sun M (1985) Immunofluorescent labeling of nonhuman cerebellar tissue with sera from patients with systemic cancer and paraneoplastic cerebellar degeneration. Acta Neuropath. Berlin. 67, 226-229. 

Jaeckle K, Graus F, Houghton A, Cardon-Cardo C (1985) Auto-immune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen. Ann. Neurol, 18, 592-600. 

Rodriguez M, Truh LI, O Neill BP, Lennon VA (1988) Autoimmune paraneoplastic cerebellar degeneration Ultrastructural localization of antibody-binding sites in Purkinje cells. Neurology. 38, 1380-1386. 

Tanaka K, Yamazaki M, Sato S, Toyoshima I, Yamamoto A, Miyatake T (1986) Antibodies to brain proteins in paraneoplastic cerebellar degeneration. Neurology, 36, 1169-1172. 

Tsukamoto T, Yamamoto H, Iwasaki Y. (1989). Antineural autoantibodies in patients with paraneoplastic cerebellar degeneration. Arch. Neurol.. 46. 1225-1229. 

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