PARANEOPLASTİK NÖROLOJİK SENDROMLAR 

Tanım: Bu sendromlar kanser hastalarının yaklaşık %1‘ini etkiler ve %50 vakada kanser tanısından önce bulunabilir. Majör sendromlar etkilenen santral sinir sistemi anatomisine göre sınıflandırılır; uluslararası çalışma grubu konsensus bildirgesinde, daha doğru bir tanı için immünohistokimya ve Western Blot kombinasyonunu önerilmektedir. Başlıca paraneoplastik nörolojik sendromlar; Paraneoplastik serebellar dejenerasyon (PCD), küçük hücreli akciğer kanseri hastalarında görülen paraneoplastik ensefalomyelit (PEM), Paraneoplastik opsoklonus/myoklonus (POM) ve paraneoplastik katı-adam (stifff person) sendromudur. 

Gerekçe: PCD ve PEM için otoimmün özellikte olduklarının varsayılmaları ve spesifik beyin omurilik sıvısı ve serum antikorlarıyla (sırasıyla anti-Yo ve anti-Hu) ilişkili olmaları nedeniyle tedavilerinde terapötik plazmaferez kullanımını gündeme getirmektedir. 

İşlem: TPD, DFPP, CF, IA 

İşlenen Volüm: 1-1,5 TPH 

Sıklığı: TPD: günlük ya da gün aĢırı; DFPP / CF /IA: haftalık iki kez 

Replasman Sıvısı: Albümin, albümin/serum fizyolojik 

Uygulama sayı ve/veya süresi: TPD uygulanan hastalar için 2 haftaya kadar ulaşan sürede 5 ila 6 işlem. Eğer cevap yoksa ek tedavi önerilmemektedir. DFPP / CF / IA tedavisi:3 haftalık süre için haftada 2 kez uygulanan 6 iĢlemden oluşmaktadır. 

YARARLANILAN LİTERATÜRLER

*Dalmau J, Posner JB. Neurologic paraneoplastic antibodies (anti-Yo; anti-Hu; anti-Ri): the case for a nomenclature based on antibody and antigen specificity. Neurology 1994;44:2241–2246. 

*Dalmau JO, Posner JB. Paraneoplastic syndromes affecting the nervous system. Semin Oncol 1997;24:318–328. 

*Dropcho EJ. Autoimmune central nervous system paraneoplastic disorders: mechanisms, diagnosis, and therapeutic options. Ann Neurol 1995;37 (Suppl 1):S102–S113. 

*Graus F, Abos J, Roquer J, Mazzara R, Pereira A. Effect of plasmapheresis on serum and CSF autoantibody levels in CNS paraneoplastic syndromes. Neurology 1990;40:1621–1623.

*Graus F, Vega F, Delattre JY, Bonaventura I, Rene R, Arbaiza D, Tolosa E. Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. Neurology 1992;42(3 Pt 1):536–540. 

*Hinton RC. Paraneoplastic neurologic syndromes. Hematol Oncol Clin North Am 1996;10:909–925. 

*Lennon VA. The case for a descriptive generic nomenclature: clarification of immunostaining criteria for PCA-1, ANNA-1, and ANNA-2 autoantibodies. Neurology 1994;44:2412–2415. 

*Uchuya M, Graus F, Vega F, Rene R, Delattre JY. Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal autoantibodies. J Neurol Neurosurg Psychiatry 1996;60:388–392. 

*Cher LM, Hochberg FH, Teruya J, Nitschke M, Valenzuela RF, Schmahmann JD, Herbert M, Rosas HD, Stowell C. Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption. Cancer 1995;75:1678–1683. 

*David YB, Warner E, Levitan M, Sutton DM, Malkin MG, Dalmau JO. Autoimmune paraneoplastic cerebellar degeneration in ovarian carcinoma patients treated with plasmapheresis and immunoglobulin. A case report. Cancer 1996;78:2153–2156. 

*Greenlee JE, Lipton HL. Anticerebellar antibodies in serum and cerebrospinal fluid of a patient with oat cell carcinoma of the lung and paraneoplastic cerebellar degeneration. Ann Neurology 1986;19:82–85. 

*Anderson NE, Posner JB. Antineuronal autoantibodies in neurologic paraneoplastic syndromes. Ann NY Acad Sci 1988; 540:440–441. 

*Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology 1988;38:1391–1398.

*Weissman DE, Gottschall JL. Complete remission of paraneoplastic sensorimotor neuropathy: a case associated with smallcell lung cancer responsive to chemotherapy, plasma exchange, and radiotherapy. J Clin Apher 1989;5:3–6. 

*Furneaux HF, Reich L, Posner JB. Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990;40:1085–1091. 

*Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu— associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine 1992;71:59–72. 

*Hammack J, Kotanides H, Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin‘s disease. Neurology 1992;42:1938–1943. 

*Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs‘ syndrome). Report of five cases and literature review. Brain 1993;116 (Pt 2):453–469. 

*Batchelor TT, Platten M, Hochberg FH. Immunoadsorption therapy for paraneoplastic syndromes. J Neurooncol 1998;40: 131–136. 

*van den Berg JS, van Engelen BG, Boerman RH, de Baets MH. Acquired neuromyotonia: superiority of plasma Exchange over high-dose intravenous human immunoglobulin. J Neurol 1999;246:623–625. 

*Rojas I, Graus F, Keime-Guibert F, Rene R, Delattre JY, Ramon JM, Dalmau J, Posner JB. Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology 2000;55:713–715. 

*Rickman OB, Parisi JE, Yu Z, Lennon VA, Vernino S. Fulminant autoimmune cortical encephalitis associated with thymoma treated with plasma exchange. Mayo Clinic Proc 2000; 75:1321–1326.

*Hayat GR, Kulkantrakorn K, Campbell WW, Giuliani MJ. Neuromyotonia: autoimmune pathogenesis and response to immune modulating therapy. J Neurol Sci 2000;181:38–43. 

*Yiu VW, Kovithavongs T, McGonigle LF, Ferreira P. Plasmapheresis as an effective treatment for opsoclonus-myoclonus syndrome. Pediatr Neurol 2001;24:72–74. 

*Sillevis Smitt P, Grefkens J, de Leeuw B, van den Bent M, van Putten W, Hooijkaas H, Vecht C. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/ sensory neuronopathy. J Neurol 2002;249:745–753. 

*Shams‘ili S, Grefkens J, de Leeuw B, van den Bent M, Hooijkaas H, van der Holt B, Vecht C, Sillevis Smitt P. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain 2003;126 (Pt 6):1409–1418. 

*Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 2003;349:1543–1554. 

*BlochMH, HwangWC, Baehring JM, Chambers SK. Paraneoplastic limbic encephalitis: ovarian cancer presenting as an amnesic syndrome. Obstet Gynecol 2004;104 (5 Pt 2):1174–1177. 

*R SS, Mani PJ. Opsoclonus myoclonus syndrome: response to plasmapheresis. Indian Pediatr 2004;41:499–502. 

*Vernino S, O‘Neill BP, Marks RS, O‘Fallon JR, Kimmel DW. Immunomodulatory treatment trial for paraneoplastic neurological disorders. Neuro Oncol 2004;6:55–62. 

*Armstrong MB, Robertson PL, Castle VP. Delayed, recurrent opsoclonus-myoclonus syndrome responding to plasmapheresis. Pediatr Neurol 2005;33:365–367. 

*Taniguchi Y, Tanji C, Kawai T, Saito H, Marubayashi S, Yorioka N. A case report of plasmapheresis in paraneoplastic cerebellar ataxia associated with anti-Tr antibody. Ther Apher Dial 2006;10:90–93.

*Vedeler CA, Antoine JC, Giometto B, Graus F, Grisold W, Hart IK, Honnorat J, Sillevis Smitt PA, Verschuuren JJ, Voltz R. Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol 2006;13:682–690. 

*Graus F, Dalmau J. Paraneoplastic neurological syndromes: diagnosis and treatment. Curr Opin Neurol 2007;20:732–737. 

*Landtblom AM, Lindvall B, Ledin T, Berlin G. A case report of plasmapheresis treatment in a patient with paraneoplastic cerebellar degeneration and high anti-yo antibody titers. Ther Apher Dial 2008;12:82–85. 

*Kaestner F, Mostert C, Behnken A, Boeckermann I, Ternes F, Diedrich M, Zavorotnyy M, Arolt V, Weckesser M, Rothermundt M. Therapeutic strategies for catatonia in paraneoplastic encephalitis. World J Biol Psychiatry 2008;9:236–240.