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Onco-neural antibodies and tumor type determine survival and neurological symptoms in paraneoplastic neurological syndromes with Hu or CV2/CRMP5 antibodies
  1. Jerome Honnorat (jerome.honnorat{at}chu-lyon.fr)
  1. Hopital Neurologique, France
    1. Stéphanie Cartalat-Carel (stephanie.cartalat-carel{at}chu-lyon.fr)
    1. Hopital Neurologique, France
      1. Damien Ricard (damien.ricard{at}m4x.org)
      1. Hôpital du Val-de-Grace, France
        1. Jean-Philippe Camdessanché (j.philippe.camdessanche{at}chu-st-etienne.fr)
        1. Hopital Bellevue, France
          1. Antoine F Carpentier (antoine.carpentier{at}avc.aphp.fr)
          1. Hopital de la Pitié-Salpêtrière, France
            1. Véronique Rogemond (rogemond{at}lyon.inserm.fr)
            1. Inserm U842, France
              1. François Chapuis (francois.chapuis{at}chu-lyon.fr)
              1. Hospices Civils de Lyon, France
                1. Michèle Aguera (micheleaguera{at}free.fr)
                1. Inserm U842, France
                  1. Evelyne Decullier (evelyne.decullier{at}chu-lyon.fr)
                  1. Hospices Civils de Lyon, France
                    1. Anne-Marie Duchemin (duchemin.1{at}osu.edu)
                    1. Ohio State University, United States
                      1. Francesc Graus (fgraus{at}clinic.ub.es)
                      1. Hospital Clinic Barcelona, Spain
                        1. Jean-Christophe Antoine (j.christophe.antoine{at}chu-st-etienne.fr)
                        1. Hopital de Bellevue, France

                          Abstract

                          Objective: Anti-Hu antibodies (Hu-Ab) and anti-CV2/CRMP5 antibodies (CV2/CRMP5-Ab) have been identified in association with paraneoplastic neurological disorders. However, it is not clear whether these antibodies are associated with specific neurological symptoms or are only markers of anti-cancer immune reaction.

                          Methods: To address this question, we compared 37 patients with CV2/CRMP5-Ab and 324 patients with Hu-Ab.

                          Results: Whereas the age and sex ratio were the same between the two groups, the distribution of neurological symptoms was not. Patients with CV2/CRMP5-Ab presented more frequently cerebellar ataxia, chorea, uveo/retinal symptoms and myasthenic syndrome (Lambert-Eaton myasthenic syndrome LEMS or myasthenia gravis). They also had better Rankin score. On the opposite, dysautonomia, brainstem encephalitis and peripheral neuropathy were more frequent in patients with Hu-Ab. Limbic encephalitis occurred similarly in both groups. Small cell lung cancer (SCLC) was the most frequently associated tumor in both groups of patients while malignant thymoma was observed only in patients with CV2/CRMP5-Ab. In particular, patients with CV2/CRMP5-Ab and thymoma developed more frequently myasthenic syndrome while patients with SCLC developed more frequently neuropathies. Chorea and myasthenic syndrome were only seen in patients with CV2/CRMP5-Ab. The median survival time was significantly longer in patients with CV2/CRMP5-Ab and this effect was not dependent on the type of tumor.

                          Interpretation: Our data demonstrate that in patients with paraneoplastic neurological syndromes, the neurological symptoms and survival vary with both the type of associated onco-neural antibody and the type of tumor.

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