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Early intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with onconeural antibodies
  1. Giulia Berzero1,2,
  2. Evgenia Karantoni1,
  3. Caroline Dehais1,
  4. François Ducray3,
  5. Laure Thomas3,
  6. Géraldine Picard3,
  7. Véronique Rogemond3,
  8. Gaëlle Candelier1,
  9. Jean-Philippe Camdessanché4,5,6,
  10. Jean-Christophe Antoine4,6,5,
  11. Jérôme De Seze7,
  12. Amélie Liou-Schischmanoff8,
  13. Jérôme Honnorat3,6,5,
  14. Jean-Yves Delattre1,9,
  15. Dimitri Psimaras1
  1. 1Service de Neurologie 2-Mazarin, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  2. 2Neuroscience Consortium, University of Pavia, Monza Policlinico, and Pavia Mondino, Italy
  3. 3Centre de Référence National pour les Syndromes Neurologiques Paranéoplasiques, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Lyon, France
  4. 4Service de Neurologie, Hôpital Nord, CHU Saint-Etienne, Saint-Etienne, France
  5. 5Université Claude Bernard Lyon 1, F-69372, Université de Lyon, Lyon, France
  6. 6Institut NeuroMyoGene, INSERMU1217/CNRS UMR 5310, Lyon, France
  7. 7Service de Neurologie, Hôpital Civil, Strasbourg, France
  8. 8Service Pharmacie, Pôle SPEPS, Hôpitaux Universitaires Pitié Salpetrière–Charles Foix, Paris, France
  9. 9Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière (CRICM), UMRS 975, Université Pierre et Marie Curie - Paris VI, Paris, France
  1. Correspondence to Dr Dimitri Psimaras, Service de Neurologie 2-Mazarin, AP-HP Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, Paris 75013, France; dimitri.psimaras{at}

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Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer, characterised by relentless progression. The mainstay of PNS treatment is the achievement of tumour remission,1 while immunotherapy provides only little additional benefit.2 3 However, in historical series, immunotherapy was initiated over 6 months after neurological onset and, at that stage, neuronal loss is already extensive and irreversible.

Among available immunotherapies, intravenous immunoglobulin (IVIg) has been used in single cases4 and in one retrospective series,3 showing some efficacy when administered timely.4 Based on these findings, we designed a prospective study to assess the efficacy and safety of early IVIg treatment in patients with PNS.


Study design

This prospective, multicentre, non-comparative, phase II clinical study was performed by the ‘Centre de Reference Français des Syndromes Neurologiques Paranéoplasiques’. Written informed consent was obtained from all participants. This trial is registered at (NCT02343211).


Inclusion criteria were: (1) diagnosis of ‘definite’ PNS5; (2) anti-Hu, anti-Yo, or anti-CV2/CRMP5 antibodies in the serum and/or in the cerebrospinal fluid; (3) neurological symptom onset within 6 months; (4) modified Rankin Score (mRS) 2 or 3; (5) neurological deterioration over the last 3 weeks. Exclusion criteria were: (1) other concomitant immunotherapy; (2) absolute contraindications to IVIg (hypersensitivity to IVIg, selective IgA deficiency); (3) thrombophilia; (4) renal insufficiency (creatinine clearance <30 mL/min).


Enrolled patients received three cycles of IVIg (Privigen, 2 g/kg, every 4 weeks), followed by an interim evaluation. If the patient was stable or improved according to the primary outcome measure, three additional IVIg cycles were administered. If the patient deteriorated, IVIg was discontinued. Final evaluation was …

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