Paraneoplastic neurologic disorders

Abstract

Paraneoplastic neurologic syndromes (PNS) are manifestations of cancers located outside the central nervous system. They appears before the diagnosis of cancer in most of the patients. Frequency among all cancer patients is 0.01%. They show close association with some kinds of cancer. These disorders occure due to stimulation of immune response by some proteins which are formed by a tumor, against both tumor and the nervous system. For diagnosis, cancer associated with paraneoplastic syndrome should be detected and antibody should be demonstrated. Neurologists should be aware of these syndromes so that appropriate diagnostic and treatment options can be applied sooner. Because the tumor examination and treatment plan should be made following the diagnosis.

Keywords

• Cancer
• Diagnosis
• Paraneoplastic syndromes
• Pathophysiology
• Treatment

References

1. Albert, M.L., Darnell, J.C., Bender, A., Francisco, L.M., Bhardwaj, N., Darnell, R.B., 1998. Tumor-specific killer cells in paraneoplastic cerebellar degeneration. Nature Med. 4, 1321-1324.
2. Amoura, Z., Duhaut, P., Huong, D.L., Wechsler, B., Costedoat-Chalumeau, N., Francès, C., Cacoub, P., Papo, T., Cormont, S., Touitou, Y., Grenier, P., Valeyre, D., Piette, J.C., 2005. Tumor antigen markers for the detection of solid cancers in inflammatory myopathies. Cancer Epidemiol Biomarkers Prev. 14, 1279-1282.
3. Ances, B.M., Vitaliani, R., Taylor, R.A., Liebeskind, D.S., Voloschin, A., Houghton, D.J., Galetta, S.L., Dichter, M., Alavi, A., Rosenfeld, M.R., Dalmau, J., 2005. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 128, 1764–1777.
4. Antoine, J.C., Camdessanche, J.P., 2007. Peripheral nervous system involvement in patients with cancer. Lancet Neurol. 6, 75- 86.
5. Antoine, J.C., Honnorat, J., Camdessanché, J.P., Magistris, M., Absi, L., Mosnier, J.F., Petiot, P., Kopp, N., Michel, D., 2001. Paraneoplastic anti-CV2 antibodies react with peripheral nerve and are associated with a mixed axonal and demyelinating peripheral neuropathy. Ann Neurol. 49, 214-221.
6. Antoine, J.C., Honnorat, J., Vocanson, C., Koenig, F., Aguera, M., Belin, M.F., Michel, D., 1993. Posterior uveitis, paraneoplastic encephalomyelitis and auto-antibodies reacting with developmental protein of brain and retina. J. Neurol. Sci. 117, 215-223.
7. Armstrong, M.B., Robertson, P.L., Castle, V.P., 2005. Delayed, recurrent opsoclonus-myoclonus syndrome responding to plasmapheresis. Pediatric Neurol. 33, 365- 367.
8. Bataller, L., Dalmau, J., 2003. Paraneoplastic neurologic syndromes: Approaches to diagnosis and treatment. Sem. In. Neurol. 23, 215-224.

9. Bataller, L., Dalmau, J., 2004. Neuro-ophthalmology and paraneoplastic syndromes. Curr. Opin. Neurol. 17, 3- 8.
10. Bataller, L., Graus, F., Saiz, A., Vilchez, J.J., Spanish Opsoclonus-Myoclonus Study Group, 2001. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. Brain. 124, 437– 443.
11. Bataller, L., Kleopa, K.A., Wu, G.F., Rossi, J.E., Rosenfeld, M.R., Dalmau, J., 2007. Autoimmune limbic encephalitis in 39 patients: Immunophenotypes and outcomes. J. Neurol. Neurosurg. Psychiatry. 78, 381- 385.
12. Bradley, W.G., 2008, Neurology in Clinical Practice, fifth edition, Part 3, Philadelphia. pp. 1405-1415.
13. Camdessanche, J.P., Antoine, J.C., Honnorat, J., Vial, C., Petiot, P., Convers, P., Michel, D., 2002. Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. Brain. 125, 166-175.
14. Chalk, C.H., Murray, N.M., Newsom-Davis, J., O’Neill, J.H., Spiro, S.G., 1990. Response of Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. Neurology. 40, 1552-1556. 213 Chiò, A., Brignolio, F., Meineri, P., Rosso, M.G., Tribolo, A., Schiffer, D., 1988. Motor neuron disease and malignancies: Results of a population-based study. J. Neurol. 235, 374 –375.
15. Dalmau, J., Graus, F., Rosenblum, M.K., Posner, J.B., 1992. Anti-Hu associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore). 71, 59-72.
16. Dalmau, J., Graus, F., Villarejo, A., Posner, J.B., Blumenthal, D., Thiessen, B., Saiz, A., Meneses, P., Rosenfeld, M.R., 2004. Clinical analysis of anti-Ma2 associated encephalitis. Brain. 127, 1831-1844.
17. Damek, D.M., 2005. Paraneoplastic retinopathy/optic neuropathy. Curr. Treat. Options Neurol. 7, 57– 67.
18. Darnell, R.B., Posner, J.B., 2003. Paraneoplastic syndromes involving the nervous system. N. Eng. J. Med. 349, 1543–1554.
19. Folli, F., Solimena, M., Cofiell, R., Austoni, M., Tallini, G., Fassetta, G., Bates, D., Cartlidge, N., Bottazzo, G.F., Piccolo, G., Camilli, P.D., 1993. Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N. Engl. J. Med. 328, 546-551. Graus, F., Dalmau, J., 2007. Paraneoplastic neurological syndromes: Diagnosis and treatment. Curr. Opin. Neurol. 20, 732-737.
20. Graus, F., Dalmau, J., 2012. Paraneoplastic neurological syndromes: Diagnosis and treatment. Curr. Opin. Neurol. 25, 795-801.
21. Graus, F., Keime-Guibert, F., Reñe, R., Benyahia, B., Ribalta, T., Ascaso, C., Escaramis, G., Delattre, J.Y., 2001. Anti-Hu-associated paraneoplastic encephalomyelitis: Analysis of 200 patients. Brain. 124, 1138-1148.
22. Gultekin, S.H., Rosenfeld, M.R., Voltz, R., Eichen, J., Posner, J.B., Dalmau, J., 2000. Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 123, 1481-1494.
23. Hammack, J., Kotanides, H., Rosenblum, M.K., Posner, J.B., 1992. Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin’s disease. Neurol. 42, 1938-1943.
24. Hill, C.L., Zhang, Y., Sigurgeirsson, B., Pukkala, E., Mellemkjaer, L., Airio, A., Evans, S., Felson, D., 2001. Frequency of specific cancer types in dermatomyositis and polymyositis: A population-based study. Lancet. 357, 96-100.
25. Honnorat, J., Antoine, J.C., 2007. Paraneoplastic neurological syndromes. Orphanet. J. Rare Dis. 2, 22.
26. Jacobson, D.M., Adamus, G., 2001. Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon cancer. Am. J. Ophthalmol. 131, 806-808.
27. Khwaja, S., Sripathi, N., Ahmad, B.K., Lennon, V.A., 1998. Paraneoplastic motor neuron disease with type 1 purkinje cell antibodies. Muscle Nerve. 21, 943-945.
28. Kurtzke, J.F., Beebe, G.W., 1980. Epidemiology of amyotrophic lateral sclerosis: 1. a case control comparison based on ALS deaths. Neurology. 30, 453–462.
29. Levine, T., Pestronk, A., Florence, J., Al-Lozi, M.T., Lopate, G., Miller, T., Ramneantu, I., Waheed, W., Stambuk, M., Stone, M.J., Choksi, R., 200 Peripheral neuropathies in Waldenström’s macroglobulinaemia. J. Neurol. Neurosurg. Psychiatry. 77, 224-228. Mareska, M., Gutmann, L., 2004. Lambert-Eaton myasthenic syndrome. Semin. Neurol. 24, 149 –153.
30. Molinuevo, J.L., Graus, F., Serrano, C., Reñe, R., Guerrero, A., Illa, I., 1998. Utility of anti-Hu antibodies in the diagnosis of paraneoplastic sensory neuropathy. Ann Neurol. 44, 976–980.
31. Newsom-Davis, J., 2004. Lambert-Eaton myasthenic syndrome. Rev. Neurol. (Paris). 160,177-180.
32. O’Neill, J.H., Murray, N.M., Newsom-Davis, J., 1988. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain. 111, 577-596. Peterson, K., Rosenblum, M.K., Kotanides, H., Posner, J.B., 1992. Paraneoplastic cerebellar degeneration I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurol. 42, 1931–1937.
33. Petzold, G.C., Marcucci, M., Butler, M.H., van Landeghem, F.K., Einhaupl, K.M., Solimena, M., Valdueza, J.M., De Camilli, P., 2004. Rhabdomyolysis and paraneoplastic stiff-man syndrome with amphiphysin autoimmunity. Ann Neurol. 55, 286-290.
34. Phuphanich, S., Brock, C., 2007. Neurologic improvement after high-dose intravenous immunoglobulin therapy in patients with paraneoplastic cerebellar degeneration associated with anti-Purkinje cell antibody. J. Neurooncol. 81, 67- 69.
35. Pranzatelli, M.R., Tate, E.D., Travelstead, A.L., Barbosa, J., Bergamini, R.A., Civitello, L., Franz, D.N., Greffe, B.S., Hanson, R.D., Hurwitz, C.A., Kalinyak, K.A., Kelfer, H., Khakoo, Y., Mantovani, J.F., Nicholson, S.H., Sanders, J.M., Wnegwe, S., 2006. Rituximab (anti-CD20) adjunctive therapy for opsoclonus–myoclonus syndrome. J. Pediatr. Hematol. Oncol. 28, 585-593.
36. Rosenfeld, M.R., Dalmau, J., 2010. Update on paraneoplastic neurologic disorders. The Oncologist. 15, 603-617.
37. Rowland, L.P., Shceider, N.A., 2001. Amyotrophic lateral sclerosis. N. Engl. J. Med. 344, 1688 –1700.
38. Rudnick, E., Khakoo, Y., Antunes, N.L., Seeger, R.C., Brodeur, G.M., Shimada, H., Gerbing, R.B., Stram, D.O., Matthay, K.K., 2001. Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: Clinical outcome and antineural antibodies-a report from the Children’s Cancer Group study. Med. Pediatr. Oncol. 36, 612–622.
39. Sadeghian, H., Vernino, S., 2010. Progress in the management of paraneoplastic neurological disorders. Ther. Adv. Neurol. Disord. 3, 43-52.
40. Sanders, D.B., Massey, J.M., Sanders, L.L., Edwards, L.J., 2000. A randomized trial of 3,4- diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology. 54, 603– 607.
41. Sigurgeirsson, B., Lindelöf, B., Edhag, O., Allander, E., 1992. Risk of cancer in patients with dermatomyositis or polymyositis. N. Engl. J. Med. 326, 363-367.
42. Stich, O., Kleer, B., Rauer, S., 2007. Absence of paraneoplastic antineuronal antibodies in sera of 145 patients with motor neuron disease. J Neurol Neurosurg Psychiatry. 78, 883-885.
43. Targoff, I.N., Mamyrova, G., Trieu, E.P., Perurena, O., Koneru, B., O’Hanlon, T.P., Miller, F.W., Rider, L.G., 2006. Childhood Myositis Heterogeneity Study Group; International Myositis Collaborative Study Group A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis. Rheum. 54, 3682-3689.
44. Tate, E.D., Allison, T.J., Pranzatelli, M.R., Verhulst, S.J., 2005. Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus syndrome. J. Pediatr. Oncol. Nurs. 22, 8-19.
45. Toothaker, T.B., Rubin, M., 2009. Paraneoplastic neurological syndromes: A review. Neurologist. 15, 21-33.
46. Tüzün E, Dalmau J., 2007. Limbic encephalitis and variants: Classification, diagnosis and treatment. Neurologist. 13, 261-271.
47. Tüzün, E., 2010. Neurological involvement in navigating the paraneoplastic syndromes. Klinik Gelisim. 23.1, 71-77.
48. Verma, A., Berger, J.R., Snodgrass, S., Petito, C., 1996. Motor neuron disease: A paraneoplastic process associated with anti-Hu antibody and small-cell lung carcinoma. Ann Neurol. 40, 112–116.
49. Widdess-Walsh, P., Tavee, J.O., Schuele, S., Stevens, G.H., 2003. Response to intravenous immunoglobulin in anti-Yo associated paraneoplastic cerebellar degeneration: Case report and review of the literature. J. Neurooncol. 63, 187-190.
50. Wong, A., 2007. An update on opsoclonus. Curr. Opin. Neurol. 20, 25-31.