Journal of Neuro-Oncology

, Volume 141, Issue 2, pp 431–439 | Cite as

Paraneoplastic neurological syndromes: a single institution 10-year case series

  • Amy M. Chan
  • Joachim M. BaehringEmail author
Clinical Study



Given its rare incidence, there are few epidemiological case series on paraneoplastic neurologic syndromes (PNS).


We present a 10-year series compiled in the Section of Neuro-Oncology, Yale Cancer Center between 2002 and 2012.


Twenty-five cases met the PNS Euro-network criteria for definitive PNS. Most (64%; 16/25) had no known neoplasm. Cerebrospinal fluid pleocytosis declined logarithmically over time. Neuroimaging abnormalities were seen in 88% of cases (15/17), but with delayed onset. Therapeutic benefit correlated strongly to pre-treatment modified Rankin Scale (mRS) (p < 0.01), but not with time elapsed between syndrome onset to treatment (p = 0.8), first immunotherapy modality (corticosteroids: n = 10; IVIG: n = 10; PLEX: n = 3; p = 0.37), or number of immunotherapy modalities provided (p = 0.17). PNS-related mortality was high (24%; 6/25). Nonetheless, 16% (3/18; 7 living patients censored) survived over 6 times the anticipated median expected by tumor type and stage.


PNS are rare, at an estimated incidence of 3.1 cases per million-person-years. Detection of CSF pleocytosis and MRI abnormalities depend on time of analysis. While PNS-related mortality was high, immunotherapy benefit correlated strongly with pre-treatment mRS and long-term survival is possible.


Paraneoplastic Neurologic Syndrome Presentation Treatment Outcome 



Paraneoplastic syndrome


Onconeural antibodies


Cerebro spinal fluid


Limbic encephalitis


Subacute cerebellar degeneration


Sensory neuronopathy






Brainstem encephalitis


Lambert–Eaton myasthenic syndrome




Small cell lung cancer


modified Rankin Scale




Intravenous immunoglobulin


Plasma exchange


Non-small cell lung cancer


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent requirement was waived by the Institutional Review Board (minimal risk; majority of patients had died at the time the study was initiated).


  1. 1.
    Guichard M, Cabanne F, Tommasi M et al (1956) Polyneuropathies in cancer patients and paraneoplastic polyneuropathies. Lyon Med 41:309–329Google Scholar
  2. 2.
    Sillevis Smitt P, Manley G, Posner J (1995) Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause neurologic disease in mice. Neurology 45:1873–1878CrossRefGoogle Scholar
  3. 3.
    Graus F, Dalmau J (2007) Paraneoplastic neurological syndromes: diagnosis and treatment. Curr Opin Neurol 20:732–737Google Scholar
  4. 4.
    Dalmau J, Rosenfeld M (2008) Paraneoplastic syndromes of the CNS. Lancet Neurol 7:327–340CrossRefGoogle Scholar
  5. 5.
    Younes-Mhenni S, Janier M, Cinotti L et al (2004) FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes. Brain 127(Pt 10):2331–2338CrossRefGoogle Scholar
  6. 6.
    Kanikannan M, Sirisha Y, Uppin M et al (2015) Incidence and spectrum of paraneoplastic neurological syndromes: single center study. J Neurooncol 125(1):197–206CrossRefGoogle Scholar
  7. 7.
    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(3):330–335. (published Online First: 2010/03/10)CrossRefGoogle Scholar
  8. 8.
    Graus F, Delattre J, Antoine J et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75:1135–1140CrossRefGoogle Scholar
  9. 9.
    Keime-Guibert F, Graus F, Fleury A et al (2000) Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry 68:479–482CrossRefGoogle Scholar
  10. 10.
  11. 11.
    Titulaer M, McCracken L, Gabilondo I et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12(2):157–165CrossRefGoogle Scholar
  12. 12.
    Irani S, Alexander S, Waters P et al (2010) Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 133(9):2734–2748CrossRefGoogle Scholar
  13. 13.
    Lai M, Huijbers M, Lancaster E et al (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9(8):776–785CrossRefGoogle Scholar
  14. 14.
    Saiz A, Blanco Y, Sabater L et al (2008) Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 131(Pt 10):2553–2563CrossRefGoogle Scholar
  15. 15.
    Dalmau J, Graus F, Rosenblum M et al (1992) Anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuronopathy: a clinical study of 71 patients. Medicine (Baltim) 71:59–72CrossRefGoogle Scholar
  16. 16.
    Peterson K, Rosenblum M, Posner J (1992) Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 42:1931–1937CrossRefGoogle Scholar
  17. 17.
    Yu Z, Kryzer T, Griesmann G et al (2001) CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 49:146–154CrossRefGoogle Scholar
  18. 18.
    Dalmau J, Graus F, Villarejo A et al (2004) Clinical analysis of anti-Ma2-associated encephalitis. Brain 127:1831–1844CrossRefGoogle Scholar
  19. 19.
    Bernal F, Shams’ili S, Rojas I et al (2003) Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology 60:230–234CrossRefGoogle Scholar
  20. 20.
    Pittock SJLC, Lennon VA (2003) Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 53:580–587CrossRefGoogle Scholar
  21. 21.
    Psimaras D, Carpentier A, Rossi C, PNS Euronetwork (2010) Cerebrospinal fluid study in paraneoplastic syndromes. J Neurol Neurosurg Psychiatry 81(1):42–45CrossRefGoogle Scholar
  22. 22.
    Blumenthal D, Salzman K, Digre K et al (2006) Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis. Neurology 67:146–149CrossRefGoogle Scholar
  23. 23.
    Graus F, Ribalta T, Campo E et al (1990) Immunohistochemical analysis of the immune reaction in the nervous system in paraneoplastic encephalomyelitis. Neurology 40(2):219–222CrossRefGoogle Scholar
  24. 24.
    Vernino S, O’Neill B, Marks R et al (2004) Immunomodulatory treatment trial for paraneoplastic neurological disorders. Neurooncology 6:55–62Google Scholar
  25. 25.
    van Broekhoven F, de Graaf M, Bromberg J et al (2010) Human chorionic gonadotropin treatment of anti-Hu-associated paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 81:1341–1344CrossRefGoogle Scholar
  26. 26.
    Shams’ili S, de Beukelaar J, Gratama J et al (2006) An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes. J Neurol 253:16–20CrossRefGoogle Scholar
  27. 27.
    Graus F, Keime-Guibert F, Rene R et al (2001) Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 124:1138–1148CrossRefGoogle Scholar
  28. 28.
    Sillevis Smitt P, Grefkens J, de Leeuw B et al (2002) Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol 249:745–753CrossRefGoogle Scholar
  29. 29.
    Poepel A, Jarius S, Heukamp LC et al (2007) Neurological course of long-term surviving patients with SCLC and anti-Hu syndrome. J Neurol Sci 263(1–2):145–148CrossRefGoogle Scholar
  30. 30.
    Vedeler C, Antoine J, Giometto B, Paraneoplastic Neurological Syndrome Euronetwork et al (2006) Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol 7:682–690CrossRefGoogle Scholar
  31. 31.
    Rosenfeld M, Dalmau J (2013) Diagnosis and management of paraneoplastic neurologic disorders. Curr Treat Options Oncol 4:528–538CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyYale School of MedicineNew HavenUSA
  2. 2.Department of NeurosurgeryYale School of MedicineNew HavenUSA

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