The spectrum of CNS clinical manifestations in patients with small cell lung carcinoma presented through two case reports
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Neurology Department of General Hospital of Serres, Greece
Pneumonology Department of General Hospital of Serres, Greece
Antonis Antoniadis   

Director of Pneumonology Clinic General Hospital of Serres, Greece
Pneumon 2019;32(1-2):34–42
Lung cancer is one of the most common neoplasms in the world. In particular, small cell lung carcinoma (SCLC) is one of the most aggressive neoplasms with poor prognosis. Central and peripheral nervous system involvement is very common in this type of cancer due to cerebral metastases, spinal cord compression or even complications from treatment (either chemotherapy or immunotherapy). Paraneoplastic neurological syndromes and hypercoagulability syndrome are two complicated conditions which connect small cell carcinoma and nervous system. In this article, an extensive reference is made to the two latter situations through the description of two incidents: one with subacute cerebellar degeneration and one with hypercoagulable syndrome and multiple ischemic strokes in patients with SCLC.
American Cancer Society. Cancer Facts & Figures 2018.
Small Cell Lung Cancer Treatment (PDQ®): Health Professional Version. National Cancer Institute. April 20,2014.
Jackman DM, Johnson BE. Small-cell lung cancer. Lancet 2005; 366:1385-96.
Mason WP, Graus F, Lang B, et al. Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome. Brain 1997;120:1279–300.
Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 antiYo antibody-positive patients. Neurology 1992;42:1931–37.
Dalmau J, Gonzalez RG, Lerwill MF. Case records of the Massachusetts General Hospital: case 4-2007—a 56-year-old woman with rapidly progressive vertigo and ataxia. N Engl J Med 2007;356:612–20.
Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J. Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol 2001;50:339–48.
Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001;49:146–54.
Choi KD, Kim JS, Park SH, Kim YK, Kim SE, Smitt PS. Cerebellar hypermetabolism in paraneoplastic cerebellar degeneration. J Neurol Neurosurg Psychiatry 2006;77:525–28.
Verschuuren J, Chuang L, Rosenblum MK, et al. Inflammatory infiltrates and complete absence of Purkinje cells in anti-Yoassociated paraneoplastic cerebellar degeneration. Acta Neuropathol (Berl) 1996;91:519–25.
Rojas I, Graus F, Keime-Guibert F, et al. Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology 2000;55:713–15.
Bernal F, Shams’ili S, Rojas I, et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology 2003;60:230–34.
Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000;47:297–305.
Chan KH, Vernino S, Lennon VA. ANNA-3 anti-neuronal nuclear antibody: marker of lung cancerrelated autoimmunity. Ann Neurol 2001;50:301–11.
Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry 2000;68:479–82.
Kim SG, Hong JM, Kim HY, et al. Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea. Stroke 2010; 41:798–801.
Chaturvedi S, Ansell J, Recht L. Should cerebral ischemic events in cancer patients be considered a manifestation of hypercoagulability? Stroke 1994; 25:1215–8.
Zhang YY, Cordato D, Shen Q, Sheng AZ, Hung WT, Chan DK. Risk factor, pattern, etiology and outcome in ischemic stroke patients with cancer: a nested case-control study. Cerebrovasc Dis 2007; 23:181–7.
Hong CT, Tsai LK, Jeng JS. Patterns of acute cerebral infarcts in patients with active malignancy using diffusion-weighted imaging. Cerebrovasc Dis 2009; 28:411–6.
Uemura J, Kimura K, Sibazaki K, Inoue T, Iguchi Y, Yamashita S. Acute stroke patients have occult malignancy more often than expected. Eur Neurol 2010; 64:140–44.
Falanga A, Gordon SG. Isolation and characterization of cancer procoagulant: a cysteine proteinase from malignant tissue. Biochemistry 1985; 24:5558–67.
Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia 2002; 4:465–73.
Butenas S, Orfeo T, Mann KG. Tissue factor in coagulation: Which? Where? When? Arterioscler Thromb Vasc Biol 2009; 29:1989–96.
Jander S, Sitzer M, Wendt A, et al. Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization. Stroke 2001; 32:850–54.
Bick RL. Cancer-associated thrombosis. N Engl J Med 2003; 349:109–11.
Robert F. The potential benefits of low-molecular-weight heparins in cancer patients. J Hematol Oncol 2010; 3:3.
Cramer SC, Rordorf G, Maki JH, et al. Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study. Stroke 2004; 35:46–50.
Eliasson A, Bergqvist D, Björck M, Acosta S, Sternby NH, Ogren M. Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23,796 consecutive autopsies. J Thromb Haemost 2006; 4:1897–902.
el-Shami K, Griffiths E, Streiff M. Nonbacterial thrombotic endocarditis in cancer patients: pathogenesis, diagnosis, and treatment. Oncologist 2007; 12:518–23.
Dutta T, Karas MG, Segal AZ, Kizer JR. Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cerebral ischemia. Am J Cardiol 2006; 97:894–8.
Kooiker JC, MacLean JM, Sumi SM. Cerebral embolism, marantic endocarditis, and cancer. Arch Neurol 1976; 33:260–64.
Singhal AB, Topcuoglu MA, Buonanno FS. Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis:a diffusion-weighted magnetic resonance imaging study. Stroke 2002; 33:1267–73.
Chen H, Cebula H, Schott R, Dietemann JL, Froelich S. Glioblastoma multiforme presenting with ischemic stroke: case report and review of the literature. J Neuroradiol 2011; 38:304–7.
Obeid M, Ulane C, Rosenfeld S. Pearls & Oy-sters: Large vessel ischemic stroke secondary to glioblastoma multiforme. Neurology 2010; 74:e50–e51.
Rogers LR. Cerebrovascular complications in patients with cancer. Semin Neurol 2010; 30:311–9.
Kase CS. Intracerebral hemorrhage: non-hypertensive causes. Stroke 1986; 17:590–95.
Mitomi M, Kimura K, Iguchi Y, Hayashida A, Nishimura H, Irei I, et al. A case of stroke due to tumor emboli associated with metastatic cardiac liposarcoma. Intern Med. 2011; 50:1489–1491.
Reynen K, Köckeritz U, Strasser RH. Metastases to the heart. Ann Oncol 2004; 15:375–81.
Foreman NK, Mahmoud HH, Rivera GK, Crist WM. Recurrent cerebrovascular accident with Lasparaginase rechallenge. Med Pediatr Oncol 1992; 20:532–4.
Ortín X, Rodríguez-Luaces M, Calabuig M, Font L. Stroke in a multiple myeloma patient treated with thalidomide. J Stroke Cerebrovasc Dis 2006; 15:283–5.
Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom K, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers. Clin Chem 2010; 56:e1–e48.
Sturgeon CM, Duffy MJ, Stenman UH, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 2008; 54:e11–e79.
Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349:146–53.
Hull RD, Pineo GF, Brant RF, et al. Long-term low-molecularweight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 2006; 119:1062–72.