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Journal of Neurology

, Volume 267, Issue 1, pp 26–35 | Cite as

Epidemiology of paraneoplastic neurological syndromes: a population-based study

  • Alberto VogrigEmail author
  • Gian Luigi Gigli
  • Samantha Segatti
  • Elisa Corazza
  • Alessandro Marini
  • Andrea Bernardini
  • Francesca Valent
  • Martina Fabris
  • Francesco Curcio
  • Francesco Brigo
  • Donatella Iacono
  • Paolo Passadore
  • Michele Rana
  • Jérôme Honnorat
  • Mariarosaria Valente
Original Communication

Abstract

Background

The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy.

Methods

We performed a 9-year (2009–2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated.

Results

We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26–90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009–2011), 0.81/100,000 person-years (2012–2014) to 1.22/100,000 person-years (2015–2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001).

Conclusions

This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.

Keywords

Paraneoplastic syndromes Epidemiology Incidence Prevalence Encephalitis Autoimmune 

Notes

Author contributions

Study concept and design: AV. Acquisition of data: AV, SS, EC, AM, AB, MF, PP and MR. Analysis and interpretation of data: AV, GLG, SS, EC, AM, AB, FV, MF, FC, FB, DI, PP, MR, JH and MV. Drafting of the manuscript: AV. Critical revision of the manuscript for important intellectual content: AV, GLG, SS, EC, AM, AB, FV, MF, FC, FB, DI, PP, MR, JH and MV. Study supervision: GLG and MV. All authors read and approved the final manuscript.

Funding

No targeted funding reported.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

All procedures were performed in accordance with the institutional ethics committee and the Declaration of Helsinki.

Supplementary material

415_2019_9544_MOESM1_ESM.docx (19 kb)
Supplementary file1 (DOCX 18 kb)

References

  1. 1.
    Darnell RB, Posner JB (2003) Paraneoplastic syndromes involving the nervous system. N Engl J Med 349:1543–1554.  https://doi.org/10.1056/NEJMra023009 CrossRefPubMedGoogle Scholar
  2. 2.
    Honnorat J, Antoine J-C (2007) Paraneoplastic neurological syndromes. Orphanet J Rare Dis 2:22.  https://doi.org/10.1186/1750-1172-2-22 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Dalmau J, Graus F (2018) Antibody-mediated encephalitis. N Engl J Med 378:840–851.  https://doi.org/10.1056/NEJMra1708712 CrossRefPubMedGoogle Scholar
  4. 4.
    Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404.  https://doi.org/10.1016/S1474-4422(15)00401-9 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Vogrig A, Joubert B, Ducray F et al (2018) Glioblastoma as differential diagnosis of autoimmune encephalitis. J Neurol 265:669–677.  https://doi.org/10.1007/s00415-018-8767-1 CrossRefPubMedGoogle Scholar
  6. 6.
    Graus F, Delattre JY, Antoine JC et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75:1135–1140.  https://doi.org/10.1136/jnnp.2003.034447 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bettini M, Chaves M, Cristiano E et al (2017) Incidence of autoimmune myasthenia gravis in a health maintenance organization in Buenos Aires, Argentina. Neuroepidemiology 48:119–123.  https://doi.org/10.1159/000477733 CrossRefPubMedGoogle Scholar
  8. 8.
    Breiner A, Widdifield J, Katzberg HD et al (2016) Epidemiology of myasthenia gravis in Ontario, Canada. Neuromuscul Disord 26:41–46.  https://doi.org/10.1016/j.nmd.2015.10.009 CrossRefPubMedGoogle Scholar
  9. 9.
    Martinka I, Fulova M, Spalekova M, Spalek P (2018) Epidemiology of myasthenia gravis in Slovakia in the years 1977–2015. Neuroepidemiology 50:153–159.  https://doi.org/10.1159/000487886 CrossRefPubMedGoogle Scholar
  10. 10.
    Popperud TH, Boldingh MI, Brunborg C et al (2017) Juvenile myasthenia gravis in Norway: a nationwide epidemiological study. Eur J Paediatr Neurol 21:312–317.  https://doi.org/10.1016/j.ejpn.2016.09.001 CrossRefPubMedGoogle Scholar
  11. 11.
    Monaco S, Turri E, Zanusso G, Maistrello B (2004) Treatment of inflammatory and paraproteinemic neuropathies. Curr Drug Targets Immune Endocr Metabol Disord 4:141–148CrossRefGoogle Scholar
  12. 12.
    Naing NN (2000) Easy way to learn standardization: direct and indirect methods. Malays J Med Sci 7:10–15PubMedPubMedCentralGoogle Scholar
  13. 13.
    Keyfitz N (1966) Finite approximations in demography. Popul Stud (Camb) 19:281–295.  https://doi.org/10.1080/00324728.1966.10406017 CrossRefGoogle Scholar
  14. 14.
    Vogrig A, Joubert B, André-Obadia N et al (2019) Seizure specificities in patients with antibody-mediated autoimmune encephalitis. Epilepsia 60:1508–1525.  https://doi.org/10.1111/epi.16282 CrossRefPubMedGoogle Scholar
  15. 15.
    Kanikannan MA, Sirisha Y, Uppin MS et al (2015) Incidence and spectrum of paraneoplastic neurological syndromes: single center study. J Neurooncol 125:197–206.  https://doi.org/10.1007/s11060-015-1898-7 CrossRefPubMedGoogle Scholar
  16. 16.
    Chan AM, Baehring JM (2019) Paraneoplastic neurological syndromes: a single institution 10-year case series. J Neurooncol 141:431–439.  https://doi.org/10.1007/s11060-018-03053-3 CrossRefPubMedGoogle Scholar
  17. 17.
    Hayat MJ, Howlader N, Reichman ME, Edwards BK (2007) Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program. Oncologist 12:20–37.  https://doi.org/10.1634/theoncologist.12-1-20 CrossRefPubMedGoogle Scholar
  18. 18.
    Ducray F, Graus F, Vigliani MC et al (2010) Delayed onset of a second paraneoplastic neurological syndrome in eight patients. J Neurol Neurosurg Psychiatry 81:937–939.  https://doi.org/10.1136/jnnp.2009.190199 CrossRefPubMedGoogle Scholar
  19. 19.
    Dubey D, Pittock SJ, Kelly CR et al (2018) Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 83:166–177.  https://doi.org/10.1002/ana.25131 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Talbott EO, Malek AM, Lacomis D (2016) The epidemiology of amyotrophic lateral sclerosis. Handb Clin Neurol 138:225–238.  https://doi.org/10.1016/B978-0-12-802973-2.00013-6 CrossRefPubMedGoogle Scholar
  21. 21.
    Zarei S, Carr K, Reiley L et al (2015) A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int.  https://doi.org/10.4103/2152-7806.169561 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Giometto B, Grisold W, Vitaliani R et al (2010) Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch Neurol 67:330–335.  https://doi.org/10.1001/archneurol.2009.341 CrossRefPubMedGoogle Scholar
  23. 23.
    Vogrig A, Ferrari S, Tinazzi M et al (2015) Anti-Ma-associated encephalomyeloradiculopathy in a patient with pleural mesothelioma. J Neurol Sci 350:105–106.  https://doi.org/10.1016/j.jns.2015.01.028 CrossRefPubMedGoogle Scholar
  24. 24.
    Dalmau J (2004) Clinical analysis of anti-Ma2-associated encephalitis. Brain 127:1831–1844.  https://doi.org/10.1093/brain/awh203 CrossRefPubMedGoogle Scholar
  25. 25.
    Vogrig A, Joubert B, Maureille A et al (2018) Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome. J Neurol 266:398–410.  https://doi.org/10.1007/s00415-018-9143-x CrossRefPubMedGoogle Scholar
  26. 26.
    Vogrig A, Fouret M, Joubert B et al (2019) Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors. Neurol Neuroimmunol Neuroinflamm 6:e604.  https://doi.org/10.1212/NXI.0000000000000604 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Maureille A, Fenouil T, Joubert B et al (2018) Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis. J Neurol.  https://doi.org/10.1007/s00415-018-9132-0 CrossRefPubMedGoogle Scholar
  28. 28.
    Vogrig A, Pauletto G, Belgrado E et al (2018) Effect of thymectomy on refractory autoimmune status epilepticus. J Neuroimmunol 317:90–94.  https://doi.org/10.1016/j.jneuroim.2018.01.009 CrossRefPubMedGoogle Scholar
  29. 29.
    Camdessanché J-P, Jousserand G, Ferraud K et al (2009) The pattern and diagnostic criteria of sensory neuronopathy: a case-control study. Brain 132:1723–1733.  https://doi.org/10.1093/brain/awp136 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Shams’ili S, Grefkens J, de Leeuw B et al (2003) Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain 126:1409–1418CrossRefGoogle Scholar
  31. 31.
    McKeon A, Tracy JA, Pittock SJ et al (2011) Purkinje cell cytoplasmic autoantibody type 1 accompaniments: the cerebellum and beyond. Arch Neurol 68:1282–1289.  https://doi.org/10.1001/archneurol.2011.128 CrossRefPubMedGoogle Scholar
  32. 32.
    Ventura L, Giorgi D, Giordano L et al (2015) Mammographic breast cancer screening in Italy: 2011–2012 survey. Epidemiol Prev 39:21–29PubMedGoogle Scholar
  33. 33.
    Vogrig A, Zanoni T, Moretto G (2016) Nystagmus and lower extremity hyperalgesia after colectomy. JAMA 316:1488–1489.  https://doi.org/10.1001/jama.2016.13658 CrossRefPubMedGoogle Scholar
  34. 34.
    Do L-D, Chanson E, Desestret V et al (2017) Characteristics in limbic encephalitis with anti-adenylate kinase 5 autoantibodies. Neurology 88:514–524.  https://doi.org/10.1212/WNL.0000000000003586 CrossRefPubMedGoogle Scholar
  35. 35.
    Spatola M, Petit-Pedrol M, Simabukuro MM et al (2017) Investigations in GABAA receptor antibody-associated encephalitis. Neurology 88:1012–1020.  https://doi.org/10.1212/WNL.0000000000003713 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Gaig C, Graus F, Compta Y et al (2017) Clinical manifestations of the anti-IgLON5 disease. Neurology 88:1736–1743.  https://doi.org/10.1212/WNL.0000000000003887 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hara M, Ariño H, Petit-Pedrol M et al (2017) DPPX antibody–associated encephalitis: main syndrome and antibody effects. Neurology 88:1340–1348.  https://doi.org/10.1212/WNL.0000000000003796 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Mandel-Brehm C, Dubey D, Kryzer TJ et al (2019) Kelch-like protein 11 antibodies in seminoma-associated paraneoplastic encephalitis. N Engl J Med 381:47–54.  https://doi.org/10.1056/NEJMoa1816721 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alberto Vogrig
    • 1
    • 2
    • 3
    • 4
    Email author
  • Gian Luigi Gigli
    • 1
    • 5
    • 6
  • Samantha Segatti
    • 5
  • Elisa Corazza
    • 5
  • Alessandro Marini
    • 5
  • Andrea Bernardini
    • 5
  • Francesca Valent
    • 7
  • Martina Fabris
    • 8
  • Francesco Curcio
    • 5
    • 8
  • Francesco Brigo
    • 9
    • 10
  • Donatella Iacono
    • 11
  • Paolo Passadore
    • 12
  • Michele Rana
    • 13
  • Jérôme Honnorat
    • 2
    • 3
    • 4
  • Mariarosaria Valente
    • 1
    • 5
  1. 1.Clinical Neurology UnitSanta Maria della Misericordia University HospitalUdineItaly
  2. 2.French Reference Center of Paraneoplastic Neurological SyndromeHospices Civils de Lyon, Hôpital NeurologiqueLyonFrance
  3. 3.SynatAc TeamNeuroMyoGene Institute, INSERM U1217/CNRS UMR5310LyonFrance
  4. 4.University Claude Bernard Lyon 1, Université de LyonLyonFrance
  5. 5.Department of Medicine (DAME)University of Udine Medical SchoolUdineItaly
  6. 6.Department of Mathematics, Informatics and Physics (DMIF)University of UdineUdineItaly
  7. 7.Institute of Hygiene and Clinical EpidemiologySanta Maria della Misericordia University HospitalUdineItaly
  8. 8.Department of Laboratory Medicine, Institute of Clinical PathologySanta Maria della Misericordia University HospitalUdineItaly
  9. 9.Department of Neuroscience, Biomedicine and Movement SciencesUniversity of VeronaVeronaItaly
  10. 10. Department of NeurologyHospital Franz TappeinerMeranoItaly
  11. 11.Department of OncologySanta Maria della Misericordia University HospitalUdineItaly
  12. 12.Neurology UnitHospital of PordenonePordenoneItaly
  13. 13.Neurology UnitHospital of GoriziaGoriziaItaly

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