Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

doi:10.1212/NXI.0000000000001014

. 2021 May 18;8(4):e1014.

doi: 10.1212/NXI.0000000000001014. Print 2021 Jul.

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

Francesc Graus¹, Alberto Vogrig¹, Sergio Muñiz-Castrillo¹, Jean-Christophe G Antoine¹, Virginie Desestret¹, Divyanshu Dubey¹, Bruno Giometto¹, Sarosh R Irani¹, Bastien Joubert¹, Frank Leypoldt¹, Andrew McKeon¹, Harald Prüss¹, Dimitri Psimaras¹, Laure Thomas¹, Maarten J Titulaer¹, Christian A Vedeler¹, Jan J Verschuuren¹, Josep Dalmau¹, Jerome Honnorat²

Affiliations

¹ From the Neuroimmunology Program (F.G., J.D.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique (A.V., S.M.-C., J.-C.G.A., V.D., B.J., L.T., J.H.), Hôpital Neurologique, Hospices Civils de Lyon; SynatAc Team (A.V., S.M.-C., V.D., B.J., L.T., J.H.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon; Université Claude Bernard Lyon 1 (A.V., S.M.-C., V.D., B.J., L.T., J.H.), Université de Lyon; Service de Neurologie (J.-C.G.A.), CHU de Saint-Etienne, France; Department of Neurology (D.D., A.M.), Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Neurology Unit (B.G.), Trento Hospital, Azienda Provinciale per I Servizi Sanitari (APSS) di Trento, Italy; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom; Neuroimmunology Section (F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel/Lübeck; German Center for Neurodegenerative Diseases (DZNE) Berlin (H.P.), and Department of Neurology and Experimental Neurology (H.P.), Charité-Universitätsmedizin Berlin, Germany; Centre de Compétence des Syndromes Neurologiques Paranéoplasiques et Encéphalites Autoimmunes (D.P.), Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Department of Neurology 2 Mazarin (D.P.), and INSERM U 1127 (D.P.), CNRS UMR 7225, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière Groupe, Hospitalier Pitié-Salpêtriêre et Université Pierre et Marie Curie-Paris 6, AP-HP, France; Department of Neurology (M.J.T.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Clinical Medicine (C.A.V.), University of Bergen; Department of Neurology (C.A.V.), Haukeland University Hospital; Neuro-SysMed-Centre of Excellence for Experimental Therapy in Neurology (C.A.V.), Departments of Neurology and Clinical Medicine, Bergen, Norway; and Neurology Department (J.J.V.), Leiden University Medical Center, the Netherlands.
² From the Neuroimmunology Program (F.G., J.D.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique (A.V., S.M.-C., J.-C.G.A., V.D., B.J., L.T., J.H.), Hôpital Neurologique, Hospices Civils de Lyon; SynatAc Team (A.V., S.M.-C., V.D., B.J., L.T., J.H.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon; Université Claude Bernard Lyon 1 (A.V., S.M.-C., V.D., B.J., L.T., J.H.), Université de Lyon; Service de Neurologie (J.-C.G.A.), CHU de Saint-Etienne, France; Department of Neurology (D.D., A.M.), Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Neurology Unit (B.G.), Trento Hospital, Azienda Provinciale per I Servizi Sanitari (APSS) di Trento, Italy; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom; Neuroimmunology Section (F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel/Lübeck; German Center for Neurodegenerative Diseases (DZNE) Berlin (H.P.), and Department of Neurology and Experimental Neurology (H.P.), Charité-Universitätsmedizin Berlin, Germany; Centre de Compétence des Syndromes Neurologiques Paranéoplasiques et Encéphalites Autoimmunes (D.P.), Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Department of Neurology 2 Mazarin (D.P.), and INSERM U 1127 (D.P.), CNRS UMR 7225, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière Groupe, Hospitalier Pitié-Salpêtriêre et Université Pierre et Marie Curie-Paris 6, AP-HP, France; Department of Neurology (M.J.T.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Clinical Medicine (C.A.V.), University of Bergen; Department of Neurology (C.A.V.), Haukeland University Hospital; Neuro-SysMed-Centre of Excellence for Experimental Therapy in Neurology (C.A.V.), Departments of Neurology and Clinical Medicine, Bergen, Norway; and Neurology Department (J.J.V.), Leiden University Medical Center, the Netherlands. jerome.honnorat@chu-lyon.fr.

PMID: 34006622
PMCID: PMC8237398
DOI: 10.1212/NXI.0000000000001014

Free PMC article

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

Francesc Graus et al. Neurol Neuroimmunol Neuroinflamm. 2021.

Free PMC article

. 2021 May 18;8(4):e1014.

doi: 10.1212/NXI.0000000000001014. Print 2021 Jul.

Authors

Affiliations

¹ From the Neuroimmunology Program (F.G., J.D.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique (A.V., S.M.-C., J.-C.G.A., V.D., B.J., L.T., J.H.), Hôpital Neurologique, Hospices Civils de Lyon; SynatAc Team (A.V., S.M.-C., V.D., B.J., L.T., J.H.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon; Université Claude Bernard Lyon 1 (A.V., S.M.-C., V.D., B.J., L.T., J.H.), Université de Lyon; Service de Neurologie (J.-C.G.A.), CHU de Saint-Etienne, France; Department of Neurology (D.D., A.M.), Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Neurology Unit (B.G.), Trento Hospital, Azienda Provinciale per I Servizi Sanitari (APSS) di Trento, Italy; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom; Neuroimmunology Section (F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel/Lübeck; German Center for Neurodegenerative Diseases (DZNE) Berlin (H.P.), and Department of Neurology and Experimental Neurology (H.P.), Charité-Universitätsmedizin Berlin, Germany; Centre de Compétence des Syndromes Neurologiques Paranéoplasiques et Encéphalites Autoimmunes (D.P.), Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Department of Neurology 2 Mazarin (D.P.), and INSERM U 1127 (D.P.), CNRS UMR 7225, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière Groupe, Hospitalier Pitié-Salpêtriêre et Université Pierre et Marie Curie-Paris 6, AP-HP, France; Department of Neurology (M.J.T.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Clinical Medicine (C.A.V.), University of Bergen; Department of Neurology (C.A.V.), Haukeland University Hospital; Neuro-SysMed-Centre of Excellence for Experimental Therapy in Neurology (C.A.V.), Departments of Neurology and Clinical Medicine, Bergen, Norway; and Neurology Department (J.J.V.), Leiden University Medical Center, the Netherlands.
² From the Neuroimmunology Program (F.G., J.D.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique (A.V., S.M.-C., J.-C.G.A., V.D., B.J., L.T., J.H.), Hôpital Neurologique, Hospices Civils de Lyon; SynatAc Team (A.V., S.M.-C., V.D., B.J., L.T., J.H.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon; Université Claude Bernard Lyon 1 (A.V., S.M.-C., V.D., B.J., L.T., J.H.), Université de Lyon; Service de Neurologie (J.-C.G.A.), CHU de Saint-Etienne, France; Department of Neurology (D.D., A.M.), Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Neurology Unit (B.G.), Trento Hospital, Azienda Provinciale per I Servizi Sanitari (APSS) di Trento, Italy; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom; Neuroimmunology Section (F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel/Lübeck; German Center for Neurodegenerative Diseases (DZNE) Berlin (H.P.), and Department of Neurology and Experimental Neurology (H.P.), Charité-Universitätsmedizin Berlin, Germany; Centre de Compétence des Syndromes Neurologiques Paranéoplasiques et Encéphalites Autoimmunes (D.P.), Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Department of Neurology 2 Mazarin (D.P.), and INSERM U 1127 (D.P.), CNRS UMR 7225, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière Groupe, Hospitalier Pitié-Salpêtriêre et Université Pierre et Marie Curie-Paris 6, AP-HP, France; Department of Neurology (M.J.T.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Clinical Medicine (C.A.V.), University of Bergen; Department of Neurology (C.A.V.), Haukeland University Hospital; Neuro-SysMed-Centre of Excellence for Experimental Therapy in Neurology (C.A.V.), Departments of Neurology and Clinical Medicine, Bergen, Norway; and Neurology Department (J.J.V.), Leiden University Medical Center, the Netherlands. jerome.honnorat@chu-lyon.fr.

PMID: 34006622
PMCID: PMC8237398
DOI: 10.1212/NXI.0000000000001014

Abstract

Objective: The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS.

Methods: A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project.

Results: The panel proposed to substitute "classical syndromes" with the term "high-risk phenotypes" for cancer and introduce the concept of "intermediate-risk phenotypes." The term "onconeural antibody" was replaced by "high risk" (>70% associated with cancer) and "intermediate risk" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided.

Conclusions: The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.

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Comment in

The Pursuit of Precision in Paraneoplastic Neurologic Disease.
Abbatemarco JR, Clardy SL. Abbatemarco JR, et al. Neurol Neuroimmunol Neuroinflamm. 2021 May 13;8(4):e1015. doi: 10.1212/NXI.0000000000001015. Print 2021 Jul. Neurol Neuroimmunol Neuroinflamm. 2021. PMID: 33986129 Free PMC article. No abstract available.

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References

1. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007;2(1):22. - PMC - PubMed
1. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(3):1543-1554. - PubMed
1. Vogrig A, Gigli GL, Segatti S, et al. . Epidemiology of paraneoplastic neurological syndromes: a population-based study. J Neurol. 2019;267(1):26-35. - PubMed
1. Hébert J, Riche B, Vogrig A, et al. . Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France. Neurol Neuroimmunol Neuroinflamm. 2020;7(6):e883. - PMC - PubMed
1. Graus F, Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2019;16(9):535-548. - PubMed

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[1] Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007;2(1):22. - PMC - PubMed

[2] Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007;2(1):22. - PMC - PubMed

[3] Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(3):1543-1554. - PubMed

[4] Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(3):1543-1554. - PubMed

[5] Vogrig A, Gigli GL, Segatti S, et al. . Epidemiology of paraneoplastic neurological syndromes: a population-based study. J Neurol. 2019;267(1):26-35. - PubMed

[6] Vogrig A, Gigli GL, Segatti S, et al. . Epidemiology of paraneoplastic neurological syndromes: a population-based study. J Neurol. 2019;267(1):26-35. - PubMed

[7] Hébert J, Riche B, Vogrig A, et al. . Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France. Neurol Neuroimmunol Neuroinflamm. 2020;7(6):e883. - PMC - PubMed

[8] Hébert J, Riche B, Vogrig A, et al. . Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France. Neurol Neuroimmunol Neuroinflamm. 2020;7(6):e883. - PMC - PubMed

[9] Graus F, Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2019;16(9):535-548. - PubMed

[10] Graus F, Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2019;16(9):535-548. - PubMed

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Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

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Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

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