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Immunophenotypical characterization of paraneoplastic neurological syndrome patients: a multicentric study

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Abstract

Paraneoplastic neurological syndromes (PNS) are a group of rare and severe immune-mediated disorders that affect the nervous system in patients with cancer. The best way to diagnose a paraneoplastic neurological disorder is to identify anti-onconeural protein antibodies that are specifically associated with various cancers. The aim of this multicentric study was to clinically and immunologically characterize patients with PNS and study their association with cancer. Patients suspected to have PNS were enrolled from various clinical centres and were characterized immunologically. This study population consisted of 112 patients. Onset of PNS was mainly subacute (76%). PNS patients had various neurological disorders and symptoms. PNS developed before the diagnosis of cancer in 28 definite PNS patients and in six suspected PNS patients. The most frequent autoantibodies detected in PNS patients were anti-Hu and anti-Yo. One definite PNS patient with cerebellar syndrome had anti-Tr antibody and seven patients had atypical antibodies. The literature associates these antibodies with various neurological disorders and cancers. Our observations confirm the important role of autoantibodies in PNS and their importance for the early diagnosis of cancer in PNS patients.

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References

  • Antoine JC and Camdessanchè JP 2007 Peripheral nervous system involvement in patients with cancer. Lancet Neurol. 6 75–86

    Article  Google Scholar 

  • Antoine JC and Camdessanché JP 2013 Treatment options in paraneoplastic disorders of the peripheral nervous system. Curr. Treat. Options Neurol. 15 210–223

    Article  Google Scholar 

  • Armangué T, Sabater L, Torres-Vega E, Martínez-Hernández E, Ariño H, Petit-Pedrol M, Planagumà J, Bataller L, Dalmau J and Graus F 2016 Clinical and immunological features of opsoclonus-myoclonus syndrome in the era of neuronal cell surface antibodies. JAMA Neurol. 73 417–424

    Article  Google Scholar 

  • Asztely F and Kumlien E 2012 The diagnosis and treatment of limbic encephalitis. Acta Neurol. Scand. 126 365–375

    Article  CAS  Google Scholar 

  • Berger B, Bischler P, Dersch R, Hottenrott T, Rauer S and Stich O 2015 “Non-classical” paraneoplastic neurological syndromes associated with well-characterized antineuronal antibodies as compared to “classical” syndromes—More frequent than expected. J. Neurol. Sci. 352 58–61

    Article  Google Scholar 

  • Bernal F, Shams’ili S, Rojas I, Sanchez-Valle R, Saiz A, Dalmau J, Honnorat J, Sillevis Smitt P and Graus F 2003 Anti-Tr antibodies as markers of paraneoplasticcerebellar degeneration and Hodgkin’s disease. Neurology 60 230–234

    Article  CAS  Google Scholar 

  • Blaes F 2012 Paraneoplastic neurological syndromes-diagnosis and management. Curr. Pharm. Des. 18 4518–4525

    Article  CAS  Google Scholar 

  • Blyakhman I and Chakravarthy K 2019 Updated review and treatment recommendations on paraneoplastic neurologic syndromes and chronic pain. Pain Physician 22 433–445

    PubMed  Google Scholar 

  • Chan AM and Baehring JM 2019 Paraneoplastic neurological syndromes: a single institution 10-year case series. J. Neurooncol. 141 431–439

    Article  Google Scholar 

  • Dalmau J, Graus F, Villarejo A, Posner JB, Blumenthal D, Thiessen B, Saiz A, Meneses P and Rosenfeld MR 2004 Clinical analysis of anti-Ma2-associated encephalitis. Brain 127 1831–1844

    Article  Google Scholar 

  • Dalmau J and Rosenfeld MR 2008 Paraneoplastic syndromes of the CNS. Lancet Neurol. 7 327–340

    Article  Google Scholar 

  • Darnell RB and Posner JB 2003 Paraneoplastic syndromes involving the nervous system. N. Engl. J. Med. 349 1543–1554

    Article  CAS  Google Scholar 

  • Dankó K, Ponyi A, Molnar AP, András C and Constantin T 2009 Paraneoplastic myopathy. Curr. Opin. Rheumatol. 21 594–598

    Article  Google Scholar 

  • Daroff RB, Jankovic J, Mazziotta JC and Pomeroy SL 2016 Bradley’s neurology in clinical practice, 7th edition, (London, Elsevier)

    Google Scholar 

  • Dean S, McCracken J, Kosmider S and Herath D 2018 Lambert-Eaton myasthenic syndrome developing post-diagnosis of small-cell lung cancer. Intern. Med. J. 48 1541–1542

    Article  Google Scholar 

  • England JD and Asbury AK 2004 Peripheral neuropathy. Lancet 363 2151–2161

    Article  Google Scholar 

  • Gordon L and Dinkin M 2019 Paraneoplastic syndromes in neuro-ophthalmology. Continuum (Minneap. Minn.) 25 1401–1421

  • Graus F and Dalmau J 2019 Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 16 535–548

    Article  CAS  Google Scholar 

  • Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, Honnorat J,Smitt PS, Vedeler Ch, Verschuuren JJ, Vincent A and Voltz R 2004 Recommended diagnostic criteria for paraneoplastic neurological syndromes. J. Neurol. Neurosurg. Psychiatry 75 1135–1140

    Article  CAS  Google Scholar 

  • Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis, G and Delattre JY 2001 Anti-Hu-associated paraneoplastic encephalomyelitis: Analysis of 200 patients. Brain 124 1138–1144

    Article  CAS  Google Scholar 

  • Gutmann L, Crosby TW, Takamori M and Martin JD 1972 The Eaton-Lambert syndrome and autoimmune disorders. Am. J. Med. 53 354–356

    Article  CAS  Google Scholar 

  • Honnorat J and Antoine JC 2007 Paraneoplastic neurological syndromes. Orphanet J. Rare Dis. 2 22

    Article  Google Scholar 

  • Kanikannan MA, Sirisha Y, Uppin MS, Jabeen SA, Kandadai RM, Sundaram C, Raghunadharao D and Borgohain R 2015 Incidence and spectrum of paraneoplastic neurological syndromes: Single center study. J. Neurooncol. 125 197–206

    Article  Google Scholar 

  • Kazarian M and Laird-Offringa IA 2011 Small-cell lung cancer-associated autoantibodies: Potential applications to cancer diagnosis, early detection, and therapy. Mol. Cancer. 10 33

    Article  CAS  Google Scholar 

  • Lancaster E 2017 Paraneoplastic disorders. Continuum (Minneap. Minn.) 6 1653–1679

  • Longo V, Brunetti O, Azzariti A, Galetta D, Nardulli P, Leonetti F and Silvestris N 2019 Strategies to improve cancer immune checkpoint inhibitors efficacy, other than abscopal effect: A systematic review. Cancers 11 539

    Article  CAS  Google Scholar 

  • Lukacs S, Szabo N and Woodhams S 2012 Rare association of anti-hu antibody positive paraneoplastic neurological syndrome and transitional cell bladder carcinoma. Case Rep. Urol. 2012 724940

    CAS  PubMed  PubMed Central  Google Scholar 

  • McKeon A, Tracy JA, Pittock SJ, Parisi JE, Klein CJ and Lennon VA 2011 Purkinje cell cytoplasmic autoantibody type 1 accompaniments: The cerebellum and beyond. Arch. Neurol. 68 1282–1289

    Article  Google Scholar 

  • Mélé N, Berzero G, Maisonobe T, Salachas F, Nicolas G, Weiss N, Beaudonnet G, Ducray F, Psimaras D and Lenglet T 2018 Motor neuron disease of paraneoplastic origin: a rare but treatable condition. J. Neurol. 265 1590–1599

    Article  Google Scholar 

  • Murinson BB and Guarnaccia JB 2008 Stiff-person syndrome with amphiphysin antibodies: Distinctive features of a rare disease. Neurology 71 1955–1958

    Article  CAS  Google Scholar 

  • Ortega Suero G, Sola-Valls N, Escudero D, Saiz A and Graus F 2018 Anti-Ma and anti-Ma2-associated paraneoplastic neurological syndromes. Neurology 33 18–27

    CAS  Google Scholar 

  • Rosenfeld MR and Dalmau J 2018 Paraneoplastic neurologic syndromes. Neurol. Clin. 36 675–685

    Article  Google Scholar 

  • Sæther SG, Schou M and Kondziella D 2017 What is the significance of onconeural antibodies for psychiatric symptomatology? A systematic review. BMC Psychiatry 17 161

    Article  Google Scholar 

  • Van Coevorden-Hameete MH, Titulaer MJ, Schreurs MW, de Graaff E, Sillevis Smitt PA and Hoogenraad CC 2016 Detection and characterization of autoantibodies to neuronal cell-surface antigens in the central nervous system. Front. Mol. Neurosci. 9 37

    PubMed  PubMed Central  Google Scholar 

  • Venkatraman A and Opal P 2016 Paraneoplastic cerebellar degeneration with anti-Yo antibodies – A review. Ann. Clin. Transl. Neurol. 3 655–663

    Article  CAS  Google Scholar 

  • Vincent A 2005 Antibodies associated with paraneoplastic neurological disorders. Neurol. Sci. 26 s3–s4

    Article  Google Scholar 

  • Zaborowski MP and Michalak S 2013 Cell-mediated immune responses in paraneoplastic neurological syndromes. Clin. Dev. Immunol. 2013 630602

    Article  Google Scholar 

  • Zidan A, Fein A and Zuchowski K 2019 The use, misuse and abuse of paraneoplastic panels in neurological disorders. A retrospective study. Clin. Neurol. Neurosurg. 186 105545

    Article  Google Scholar 

  • Zis P, Paladini A, Piroli A, McHugh PC, Varrassi G and Hadjivassiliou M 2017 Pain as a first manifestation of paraneoplastic neuropathies: A systematic review and meta-analysis. Pain Ther. 6 143–151

    Article  Google Scholar 

  • Zoccarato M, Gastaldi M, Zuliani L, Biagioli T, Brogi M, et al. 2017 Diagnostics of paraneoplastic neurological syndromes. Neurol. Sci. 38 237–242

    Article  Google Scholar 

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Acknowledgements

We would like to thank Marco L. Rossi for his support and encouragement in this study.

Funding

PNS-Euronetwork supported by the European Commission (QLGT-CT-2002-01756; LSSM-CT-2005 518174).

Author information

Authors and Affiliations

  1. UOC Neurology and Stroke Unit, ASST Lecco, Merate, LC, Italy

    Lorenzo Lorusso

  2. MAGI EUREGIO, Bolzano, Italy

    Vincenza Precone & Matteo Bertelli

  3. Department of Neurology, The Walton Centre, Liverpool, UK

    Ian K Hart

  4. Department of Neurology, Santa Chiara Hospital, Trento, Italy

    Bruno Giometto

  5. Department of Medicine (DIMED), University of Padua, OU Endocrinology, Padua, Italy

    Raffaele Pezzani

  6. Department of Neurology, Hospital Centre Emile Mayrisch, Esch-sur-Alzette, Luxemburg

    Gaelle K Ngonga

  7. MAGI’S Lab, Rovereto, TN, Italy

    Stefano Paolacci & Matteo Bertelli

  8. Department of Neurology, Simone Veil Hospital, Eaubonne, France

    Daniela Ferrari

  9. Laboratory of Cellular Pathophysiology and Clinical Immunology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

    Giovanni Ricevuti

  10. The Clatterbridge Cancer Centre, NHS Foundation Trust, Liverpool, UK

    Ernie Marshall

  11. EBTNA-LAB, Rovereto, TN, Italy

    Matteo Bertelli

Authors
  1. Lorenzo Lorusso
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  2. Vincenza Precone
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  3. Ian K Hart
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  4. Bruno Giometto
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  5. Raffaele Pezzani
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  6. Gaelle K Ngonga
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  7. Stefano Paolacci
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  8. Daniela Ferrari
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  9. Giovanni Ricevuti
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  10. Ernie Marshall
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  11. Matteo Bertelli
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Corresponding author

Correspondence to Stefano Paolacci.

Additional information

This paper is dedicated to the memory of the late Prof. Ian Kirkland Hart (1958–2008).

Corresponding editor: Aurnab Ghose

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Lorusso, L., Precone, V., Hart, I.K. et al. Immunophenotypical characterization of paraneoplastic neurological syndrome patients: a multicentric study. J Biosci 46, 13 (2021). https://doi.org/10.1007/s12038-020-00128-0

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  • DOI: https://doi.org/10.1007/s12038-020-00128-0

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