Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report

Sreter,Katherina   Bernadette; Barisic,Blazenka; Barisic Kutija,Marija; Kukulj,Suzana; Samarzija,Miroslav

doi:10.3892/mco.2017.1248

Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report

Authors:
- Katherina Bernadette Sreter
- Blazenka Barisic
- Marija Barisic Kutija
- Suzana Kukulj
- Miroslav Samarzija
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Affiliations: Department of Clinical Immunology, Pulmonology and Rheumatology, University Hospital Centre ‘Sestre Milosrdnice’, 10000 Zagreb, Croatia, Department of Allergy and Chronic Obstructive Pulmonary Disease, Clinic for Respiratory Diseases ‘Jordanovac’, University Hospital Centre Zagreb, 10000 Zagreb, Croatia, Department of Ophthalmology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia, Department of Mediastinal Tumours, Clinic for Respiratory Diseases ‘Jordanovac’, University Hospital Centre Zagreb, 10000 Zagreb, Croatia, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Published online on: May 8, 2017 https://doi.org/10.3892/mco.2017.1248
Pages: 921-924

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Abstract

Adie's syndrome (AS) and paraneoplastic sensorimotor neuropathy with cerebellar ataxia (PSN CA) are extremely rare, rapidly progressive, autoimmune diseases associated with the development of antibodies against neuronal‑specific Hu proteins that are abnormally expressed in small‑cell lung cancer (SCLC). We herein present the unique case of a 55‑year‑old obese woman, previous heavy smoker, who, during treatment with standard cisplatin‑etoposide chemotherapy for limited‑stage SCLC, developed simultaneous AS and worsening symptoms consistent with PSN CA that led to significant neurological disability and severe axonal electrophysiological pattern on nerve conduction studies. Serology confirmed the presence of low‑titre type 1 antineuronal nuclear antibodies (ANNA‑1), previously referred to as anti‑Hu antibodies. Following plasmapheresis, immunosuppressive therapy and physical rehabilitation, the neurological symptoms progressively improved. The tumour completely regressed, with no recurrence detected on subsequent radiological examinations. The aim of this case was to highlight the importance of a multidisciplinary team approach for early recognition and rapid treatment of paraneoplastic neurological syndromes (PNS) as key to achieving significant recovery and marked improvement of the neurological deficit. This report extends the literature by confirming earlier studies showing that the presence of serum ANNA‑1 in SCLC, an aggressive type of pulmonary carcinoma that is challenging to treat, may portend a more favourable prognosis and response to chemotherapy. Thus, patients with SCLC and new‑onset neurological symptoms should be tested for ANNA‑1. The role of a multimodality approach to treating PNS is also emphasized.

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1	Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, et al: SEER Cancer Statistics Review, 1975–2013. November. 2015, National Cancer Institute; Bethesda, MD: http://seer.cancer.gov/csr/1975_2013/based on SEER data submission, posted to the SEER web site. April 25–2016
2	Worden FP and Kalemkerian GP: Therapeutic advances in small cell lung cancer. Expert Opin Investig Drugs. 9:565–579. 2000. View Article : Google Scholar : PubMed/NCBI
3	Kalemkerian GP: Advances in pharmacotherapy of small cell lung cancer. Expert Opin Pharmacother. 15:2385–2396. 2014. View Article : Google Scholar : PubMed/NCBI
4	Darnell RB and Posner JB: Paraneoplastic syndromes involving the nervous system. N Engl J Med. 349:1543–1554. 2003. View Article : Google Scholar : PubMed/NCBI
5	Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, Ishii T, Dobashi H and Matsunaga T: Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 5:197–223. 2014. View Article : Google Scholar : PubMed/NCBI
6	Dalmau J, Graus F, Rosenblum MK and Posner JB: Anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore). 71:59–72. 1992. View Article : Google Scholar : PubMed/NCBI
7	Mawhinney E, Gray OM, McVerry F and McDonnell GV: Paraneoplastic sensorimotor neuropathy associated with regression of small cell lung carcinoma. BMJ Case Reports. 2010:pii: bcr0120091486. 2010. View Article : Google Scholar : PubMed/NCBI
8	Roberts WK, Deluca IJ, Thomas A, Fak J, Williams T, Buckley N, Dousmanis AG, Posner JB and Darnell RB: Patients with lung cancer and paraneoplastic Hu syndrome harbour HuD-specific type 2 CD8+ T cells. J Clin Invest. 119:2042–2051. 2009.PubMed/NCBI
9	Gozzard P and Maddison P: Which antibody and which cancer in which paraneoplastic syndromes? Pract Neurol. 10:260–270. 2010. View Article : Google Scholar : PubMed/NCBI
10	Pignolet BS, Gebauer CM and Liblau RS: Immunopathogenesis of paraneoplastic neurological syndromes associated with anti-Hu antibodies: A beneficial antitumor immune response going awry. Oncoimmunology. 2:e273842013. View Article : Google Scholar : PubMed/NCBI
11	Bruno MK, Winterkorn JM, Edgar MA, Kamal A and Stübgen JP: Unilateral Adie pupil as sole ophthalmic sign of anti-Hu paraneoplastic syndrome. J Neuroophthalmol. 20:248–249. 2000. View Article : Google Scholar : PubMed/NCBI
12	Harriman DG and Garland H: The pathology of Adie's syndrome. Brain. 91:401–418. 1968. View Article : Google Scholar : PubMed/NCBI
13	Hersh B, Dalmau J, Dangond F, Gultekin S, Geller E and Wen PY: Paraneoplastic opsoclonus-myoclonus associated with anti-Hu antibody. Neurology. 44:1754–1755. 1994. View Article : Google Scholar : PubMed/NCBI
14	Yin L, Qu H and Chen Q: Proliferative response of peripheral blood mononuclear cells in anti-Hu antibody-associated patients with paraneoplastic neurological syndrome and their depressant effect on small cell lung cancer cells. Mol Med Rep. 11:1595–1600. 2015.PubMed/NCBI
15	Graus F, Dalmou J, Reñé R, Tora M, Malats N, Verschuuren JJ, Cardenal F, Viñolas N, del Muro J Garcia, Vadell C, et al: Anti-Hu antibodies in patients with small-cell lung cancer: Association with complete response to therapy and improved survival. J Clin Oncol. 15:2866–2872. 1997. View Article : Google Scholar : PubMed/NCBI
16	Douglas CA and Ellershaw J: Anti-Hu antibodies may indicate a positive response to chemotherapy in paraneoplastic syndrome secondary to small cell lung cancer. Palliat Med. 17:638–639. 2003. View Article : Google Scholar : PubMed/NCBI
17	Kazarian M, Calbo J, Proost N, Carpenter CL, Berns A and Laird-Offringa IA: Immune response in lung cancer mouse model mimics human anti-Hu reactivity. J Neuroimmunol. 217:38–45. 2009. View Article : Google Scholar : PubMed/NCBI
18	Dalmau J, Graus F, Cheung NK, Rosenblum MK, Ho A, Cañete A, Delattre JY, Thompson SJ and Posner JB: Major histocompatibility proteins, anti-Hu antibodies and paraneoplastic encephalomyelitis in neuroblastoma and small cell lung cancer. Cancer. 75:99–109. 1995. View Article : Google Scholar : PubMed/NCBI
19	Smitt P Sillevis, Grefkens J, de Leeuw B, van den Bent M, van Putten W, Hooijkaas H and Vecht C: Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. 249:745–753. 2002. View Article : Google Scholar : PubMed/NCBI
20	Aguirre-Cruz L, Charuel JL, Carpentier AF, Benyahia B, Delattre JY and Musset L: Clinical relevance of non-neuronal auto-antibodies in patients with anti-Hu or anti-Yo paraneoplastic diseases. J Neurooncol. 71:39–41. 2005. View Article : Google Scholar : PubMed/NCBI
21	Maddison P and Lang B: Paraneoplastic neurological autoimmunity and survival in small-cell lung cancer. J Neuroimmunol. 201–202. 159–162. 2008.
22	Tsou JA, Kazarian M, Patel A, Galler JS, Laird-Offringa IA, Carpenter CL and London SJ: Low level anti-Hu reactivity: A risk marker for small cell lung cancer? Cancer Detect Prev. 32:292–299. 2009. View Article : Google Scholar : PubMed/NCBI
23	Gill S, Murray N, Dalmau J and Thiessen B: Paraneoplastic sensory neuronopathy and spontaneous regression of small cell lung cancer. Can J Neurol Sci. 30:269–271. 2003. View Article : Google Scholar : PubMed/NCBI
24	Pujol JL, Godard AL, Jacot W and Labauge P: Spontaneous complete remission of a non-small cell lung cancer associated with anti-Hu antibody syndrome. J Thorac Oncol. 2:168–170. 2007. View Article : Google Scholar : PubMed/NCBI
25	Kazarian M and Laird-Offringa IA: Small-cell lung cancer-associated autoantibodies: Potential applications to cancer diagnosis, early detection, and therapy. Mol Cancer. 10:332011. View Article : Google Scholar : PubMed/NCBI
26	Voltz RD, Posner JB, Dalmau J and Graus F: Paraneoplastic encephalomyelitis: An update of the effects of the anti-Hu immune response on the nervous system and tumour. J Neurol Neurosurg Psychiatry. 63:133–136. 1997. View Article : Google Scholar : PubMed/NCBI
27	Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis G and Delattre JY: Anti-Hu-associated paraneoplastic encephalomyelitis: Analysis of 200 patients. Brain. 124:1138–1148. 2001. View Article : Google Scholar : PubMed/NCBI
28	List M, Jamous F, Gupta A and Huntington M: Anti-Hu positive antibodies and small cell carcinoma: A single center review. S D Med. 68:251–255. 2015.PubMed/NCBI
29	Keime-Guibert F, Graus F, Fleury A, René R, Honnorat J, Broet P and Delattre JA: Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide and methylprednisolone. J Neurol Neurosurg Psychiatry. 68:479–482. 2000. View Article : Google Scholar : PubMed/NCBI
30	Greenlee JE, Clawson SA, Hill KE, Wood B, Clardy SL, Tsunoda I, Jaskowski TD and Carlson NG: Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures. J Neuroinflammation. 11:1602014. View Article : Google Scholar : PubMed/NCBI
31	Roberts WK, Deluca IJ, Thomas A, Fak J, Williams T, Buckley N, Dousmanis AG, Posner JB and Darnell RB: Patients with lung cancer and paraneoplastic Hu syndrome harbor HuD-specific type 2 CD8+T cells. J Clin Invest. 119:2042–2051. 2009.PubMed/NCBI
32	Antoine JC: Peripheral neuropathies associated with antibodies directed to intracellular neural antigens. Rev Neurol (Paris). 170:570–576. 2014. View Article : Google Scholar : PubMed/NCBI
33	Pignolet BS, Gebauer CM and Liblau RS: Immunopathogenesis of paraneoplastic neurological syndromes associated with anti-Hu antibodies: A beneficial antitumor immune response going awry. Oncoimmunology. 2:e273842013. View Article : Google Scholar : PubMed/NCBI