Based on the test results and clinical manifestation, the final diagnosis was “pulmonary adenocarcinoma and paraneoplastic GBS.” He was treated with methylprednisolone at 80 mg Qd for 10 consecutive days, which only resulted in improvement in arms (MRC grade 4), and the symptoms of the legs did not improve (MRC grade 2). The dose was then adjusted to 40 mg Qd for another 10 consecutive days, followed by oral prednisone 10 mg Qd for 3 months. Given his age and poor general condition, although there was no metastasis, the patient and his family members still chose to discharged from hospital automatically without any surgery or chemotherapy. A follow up was performed 3 months after his discharge, and his symptoms did not worsen. However, the patient experienced systemic weakness again after 6 months; he became completely bedridden and gave up re-admission treatment (Table 2).
GBS is an acute immune-mediated peripheral nerve dysfunction that is usually provoked by an antecedent infection, such as Campylobacter jejunitis or influenza, which was characterized by ascending motor weakness of the extremities that can ascend to the diaphragm, up to 20% of patients develop severe disability and approximately 5% die. In this case, the patient exhibited progressive bilateral and relatively symmetric weakness of the limbs, elevated protein and anti-GM1 IgG antibodies in CSF, and peripheral nerve severe demyelination, which fulfilled the criteria for GBS. Paraneoplastic peripheral neuropathy main lesions is subacute sensory neuropathy. And sensory motor neuropathy, such as GBS, is less frequently observed. Graus et al suggested a diagnostic criteria for PNS: the presence of cancer, the classical syndrome, and well characterized onconeural antibody. In this case, despite the absence of onconeural antibodies, our patient was relatively old and confirmed to have pulmonary adenocarcinoma with simultaneously detected GBS, and so was considered to be a paraneoplastic syndrome, rather than pure GBS.
The exact mechanism of PNS is not well known. PNS is considered to involve an immune response, including severe cross-immunoreaction directed at the tumor and peripheral nerves. Our patient had definite pulmonary adenocarcinoma, so the testing for onconeural antibodies was not carried out. After all, not all patients have well characterized antibodies of PNS, and patients with atypical syndromes or undetected cancer are common. However, he exhibited a positive titer for anti-GM1 IgG antibodies. It may be associated with the immune disorder caused by lung cancer. One research showed that gangliosides may represent onconeural antigens in patients with PNS, whose expression in neoplastic tissue may elicit autoimmune responses against neural structures. The reported case may support this hypothesis.
Researchers have confirmed the presence of ANAs in patients with malignant diseases several decades ago. Large sample, controlled studies of cancer patients’ serum and noncancer subjects’, showed that ANAs were highly elevated in cancer patients. Our patient presented a high ANA titers of 1:10,000; we believed that the ANA may be related to lung cancer. Although the clinical significance of cancer-associated positive ANAs is known little, it seems that ANAs occur more frequently in cancer patients with musculoskeletal symptoms and connective tissue paraneoplastic syndromes. According to this case, for patients with positive ANA results, unless there is evidence for connective tissue disease, the association with PNS should be considered.
CEA and CYFRA are considered as reliable markers of chemotherapy for non-SCLC. Both CEA and CYFRA levels increased in our patient. However, NSE—the most valuable serum tumor marker for SCLC patients—also increased in this case. Therefore, further studies are required to determine the significance of NSE.
There are 2 current, nonspecific approaches to manage PNS, treating the potential tumor to remove antigen source and inhibiting the immune response. Timely and effective treatment of primary tumors is the best way to stabilize PNS. And immunoregulation by corticosteroid, immunosuppressant, anti-CD20 monoclonal antibodies, intravenous immunoglobulin, and plasma exchange constitutes an important part of the treatment. In this case, the patient gave up surgery and chemotherapy. Notably, treatment with methylprednisolone was effective, which further supported the immunological cause.
In conclusion, we herein report the first case of an 80-year-old man who developed pulmonary adenocarcinoma GBS, which is very difficult to diagnose and treat. We suggest that elderly patients with GBS should not be considered as simple GBS and should be thoroughly examined to exclude systemic diseases, especially PNS. In addition, the elderly should be screened regularly for tumor markers. Further studies into the PNS mechanisms regulating the immune response are warranted.
Conceptualization: Yuhuan Wang, Sijia Yang.
Data curation: Yuhuan Wang, Sijia Yang, Liang Fang, Gang Jiang, Xiaoyan Ding, He Wei.
Formal analysis: Yuhuan Wang, Sijia Yang.
Investigation: Gang Jiang, Xiaoyan Ding, He Wei.
Project administration: Min Liu.
Resources: Min Liu.
Supervision: Min Liu.
Validation: Min Liu.
Visualization: Yuhuan Wang, Sijia Yang, Liang Fang, Yang Liu, Min Liu.
Writing – original draft: Yuhuan Wang, Sijia Yang.
Writing – review & editing: Yuhuan Wang, Sijia Yang, Liang Fang, Yang Liu.
. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes
. Orphanet J Rare Dis 2007;2:22.
. Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008;7:327–40.
. McClelland MT. Paraneoplastic syndromes related to lung cancer. Clin J Oncol Nurs 2010;14:357–64.
. Elrington GM, Murray NM, Spiro SG, et al. Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients. J Neurol Neurosurg Psychiatry 1991;54:764–7.
. Kim MH, Hwang MS, Park YK, et al. Paraneoplastic Guillain–Barré syndrome
in small cell lung cancer. Case Rep Oncol 2015;8:295–300.
. Yuki N, Hartung HP. Guillain–Barré syndrome
. N Engl J Med 2012;366:2294–304.
. Asbury AK. Diagnostic considerations in Guillain–Barré syndrome
. Ann Neurol 1981;9(suppl):1–5.
. Koike H, Tanaka F, Sobue G. Paraneoplastic neuropathy: wide-ranging clinicopathological manifestations. Curr Opin Neurol 2011;24:504–10.
. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes
. J Neurol Neurosurg Psychiatry 2004;75:1135–40.
. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc 2010;85:838–54.
. De Toni L, Marconi S, Nardelli E, et al. Gangliosides act as onconeural antigens in paraneoplastic neuropathies. J Neuroimmunol 2004;156:178–87.
. Burnham TK. Antinuclear antibodies in patients with malignancies. Lancet 1972;2:436.
. Solans-Laque R, Perez-Bocanegra C, Salud-Salvia A, et al. Clinical significance of antinuclear antibodies in malignant diseases: association with rheumatic and connective tissue paraneoplastic syndromes. Lupus 2004;13:159–64.
. Edelman MJ, Hodgson L, Rosenblatt PY, et al. CYFRA 21-1 as a prognostic and predictive marker in advanced non-small-cell lung cancer in a prospective trial: CALGB 150304. J Thorac Oncol 2012;7:649–54.
. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 2003;349:1543–54.
Keywords:Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
Guillain–Barré syndrome; paraneoplastic neurological syndromes; pulmonary adenocarcinoma