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Original research
Unclassified clinical presentations of chronic inflammatory demyelinating polyradiculoneuropathy
  1. Pietro Emiliano Doneddu1,2,
  2. Houseyin Akyil1,
  3. Fiore Manganelli3,
  4. Chiara Briani4,
  5. Dario Cocito5,
  6. Luana Benedetti6,
  7. Anna Mazzeo7,
  8. Raffaella Fazio8,
  9. Massimiliano Filosto9,
  10. Giuseppe Cosentino10,11,
  11. Vincenzo Di Stefano12,
  12. Giovanni Antonini13,
  13. Girolama Alessandra Marfia14,
  14. Maurizio Inghilleri15,
  15. Gabriele Siciliano16,
  16. Angelo Maurizio Clerici17,
  17. Marinella Carpo18,
  18. Angelo Schenone6,19,
  19. Marco Luigetti20,21,
  20. Giuseppe Lauria22,23,
  21. Sabrina Matà24,
  22. Tiziana Rosso25,
  23. Giacomo Maria Minicuci26,
  24. Marta Lucchetta27,
  25. Guido Cavaletti28,
  26. Giuseppe Liberatore1,
  27. Emanuele Spina3,
  28. Marta Campagnolo4,
  29. Erdita Peci5,
  30. Francesco Germano6,
  31. Luca Gentile7,
  32. Camilla Strano8,
  33. Stefano Cotti Piccinelli9,
  34. Elisa Vegezzi10,
  35. Luca Leonardi13,
  36. Giorgia Mataluni14,
  37. Marco Ceccanti15,
  38. Erika Schirinzi16,
  39. Marina Romozzi21,
  40. Eduardo Nobile-Orazio1,23
  41. Italian CIDP Database study group
    1. 1 Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy
    2. 2 Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy
    3. 3 Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Napoli, Italy
    4. 4 Department of Neuroscience, University of Padova, Padova, Italy
    5. 5 SSD Patologie Neurologiche Specialistiche, AOU San Luigi, Torino, Italy
    6. 6 IRCCS Ospedale Policlinico San Martino, Genova, Italy
    7. 7 Department of Clinical and Experimental Medicine, Unit of Neurology, University of Messina, Messina, Italy
    8. 8 Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milano, Italy
    9. 9 Department of Clinical and Experimental Sciences, NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy
    10. 10 IRCCS Mondino Foundation, Pavia, Italy
    11. 11 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
    12. 12 Department of Biomedicine, Neuroscience, and advanced Diagnostic (BiND), University of Palermo, Palermo, Italy
    13. 13 Unit of Neuromuscular Diseases, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Sant'Andrea Hospital, Rome, Italy
    14. 14 Dysimmune Neuropathies Unit, Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy
    15. 15 Department of Neurology and Psychiatry, 'Sapienza' University of Rome, Rome, Italy
    16. 16 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
    17. 17 Neurology Unit, Circolo & Macchi Foundation Hospital, University of Insubria, Varese, Italy
    18. 18 ASST Bergamo Ovest-Ospedale Treviglio, Milan, Italy
    19. 19 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy
    20. 20 UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
    21. 21 Università Cattolica del Sacro Cuore. Sede di Roma, Roma, Italy
    22. 22 Unit of Neuroalgology, IRCCS Foundation ’Carlo Besta’ Neurological Institute, Milano, Italy
    23. 23 Department of Medical Biotechnology and Translational Medicine, Milan University, Milano, Italy
    24. 24 Dipartimento Neuromuscoloscheletrico e degli organi di Senso, Neurology Unit, University Hospital Careggi, Firenze, Italy
    25. 25 UOC di Neurologia, Ospedale San Bassiano, Vicenza, Italy
    26. 26 Ospedale di Vicenza, Vicenza, Italy
    27. 27 UOC Neurologia, Ospedale Santa Maria della Misericordia, Rovigo, Italy
    28. 28 School of Medicine and surgery and experimental Neurology Unit, University of Milan-Bicocca, Milano, Italy
    1. Correspondence to Eduardo Nobile-Orazio, Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Rozzano, Lombardia, Italy; eduardo.nobile{at}unimi.it

    Abstract

    Background To assess the ability of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) clinical criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to include within their classification the whole spectrum of clinical heterogeneity of the disease and to define the clinical characteristics of the unclassifiable clinical forms.

    Methods The 2021 EAN/PNS clinical criteria for CIDP were applied to 329 patients fulfilling the electrodiagnostic (and in some cases also the supportive) criteria for the diagnosis of CIDP. Clinical characteristics were reviewed for each patient not strictly fulfilling the clinical criteria (‘unclassifiable’).

    Results At study inclusion, 124 (37.5%) patients had an unclassifiable clinical presentation, including 110 (89%) with a typical CIDP-like clinical phenotype in whom some segments of the four limbs were unaffected by weakness (‘incomplete typical CIDP’), 10 (8%) with a mild distal, symmetric, sensory or sensorimotor polyneuropathy confined to the lower limbs with cranial nerve involvement (‘cranial nerve predominant CIDP’) and 4 (1%) with a symmetric sensorimotor polyneuropathy limited to the proximal and distal areas of the lower limbs (‘paraparetic CIDP’). Eighty-one (65%) patients maintained an unclassifiable presentation during the entire disease follow-up while 13 patients progressed to typical CIDP. Patients with the unclassifiable clinical forms compared with patients with typical CIDP had a milder form of CIDP, while there was no difference in the distribution patterns of demyelination.

    Conclusions A proportion of patients with CIDP do not strictly fulfil the 2021 EAN/PNS clinical criteria for diagnosis. These unclassifiable clinical phenotypes may pose diagnostic challenges and thus deserve more attention in clinical practice and research.

    • NEUROMUSCULAR
    • NEUROIMMUNOLOGY
    • NEUROPATHY

    Data availability statement

    Anonymised data used for this study are available on reasonable request from the corresponding author.

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    Data availability statement

    Anonymised data used for this study are available on reasonable request from the corresponding author.

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    Footnotes

    • Collaborators Italian CIDP Database study group: Pietro Emiliano Doneddu, Alberto De Lorenzo, Giuseppe Liberatore, and Eduardo Nobile-Orazio from Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Clinical and Research Institute and, Department of Medical Biotechnology and Translational Medicine, Milan University, Milan, Italy; Dario Cocito from SSD Patologie Neurologiche Specialistiche, AOU San Luigi Gonzaga, Turin, Italy; Fiore Manganelli, Emanuele Spina, Enrica Pisano, and Lucio Santoro from the Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples 'Federico II', Naples, Italy; Daniele Velardo, Camilla Strano and Raffaella Fazio from the Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy; Marta Ruiz, Mario Cacciavillani, Francesca Castellani, and Chiara Briani from the Neurology Unit, Department of Neuroscience, University of Padua, Padua, Italy; Stefano Cotti Piccinelli, Filomena Caria and Massimiliano Filosto from the NeMO-Brescia Clinical CenterCentre for Neuromuscular Diseases, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Elisa Bianchi and Ettore Beghi from IRCCS-Istituto Mario Negri, Milan, Italy; Elena Pinuccia Verrengia and Stefano Jann from the Department of Neuroscience, Niguarda Ca' Granda Hospital, Milan, Italy; Antonio Toscano, Luca Gentile, Massimo Russo, and Anna Mazzeo from the Department of Clinical and Experimental Medicine, Unit of Neurology, University of Messina, Messina, Italy; Luca Leonardi and Giovanni Antonini from the Unit of Neuromuscular Diseases, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Sant'Andrea Hospital, Rome, Italy; Giuseppe Cosentino, Ilaria Callegari and Andrea Cortese from Translational Neurophysiology Research Unit, IRCCS Mondino Foundation, Pavia, Italy and Department of Brain and BehavioralBehavioural Sciences, University of Pavia, Pavia, Italy; Giorgia Mataluni and Girolama Alessandra Marfia from the Disimmune Neuropathies Unit, Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy; Angelo Maurizio Clerici from the Neurology Unit, Circolo & Macchi Foundation Hospital, Insubria University, DBSV, Varese, Italy; Federica Scrascia and Marinella Carpo from the ASST Bergamo Ovest-Ospedale Treviglio, Treviglio, Italy; Angelo Schenone, from the Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa and IRCCS San Martino Hospital, Genoa, Italy; Luana Benedetti and Corrado Cabona from IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Alessandro Beronio from Ospedale Sant'Andrea, La Spezia, Italy; Erika Schirinzi and Gabriele Siciliano from the Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Marco Luigetti from Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Neurologia, and Università Cattolica del Sacro Cuore, Sede di Roma, Roma, Italy; Patrizia Dacci and Giuseppe Lauria from the Unit of Neuroalgology, IRCCS Foundation 'Carlo Besta' Neurological Institute, Milan, Italy; Tiziana Rosso from the Azienda UL.SS. 8 Asolo, Castelfranco Veneto, Italy; Claudia Balducci and Guido Cavaletti from the School of Medicine and Surgery and Experimental Neurology Unit, University of Milano-Bicocca, Monza, Italy; Mario Sabatelli from Centro Clinico NEMO Adulti, Universita’ Cattolica del Sacro Cuore, Roma, Italy; Erdita Peci from the Department of Neuroscience, University of Turin, Turin, Italy.

    • Contributors PED contributed to the conception of the research project, performed the statistical analysis, wrote the first draft of the report, reviewed the report and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. HA, FM, CB, DC, LB, AM, RF, MF, GC, VDS, GA, GAM, MI, GS, AMC, MC, AS, ML, GL, SM, TR, GMM, ML, GC, GL, ES, MC, EP, FG, LG, CS, SCP, EV, LL, GM, MC, ES and MR contributed to the conception, organisation and execution of the research project, reviewed and commented on the statistical analysis and the report. EN-O conceived, organised and designed the study, reviewed and commented on the statistical analysis, reviewed the report.

    • Funding The study was supported by Regione Lombardia, Italy ('A Database from Lombardia on CIDP'), by a Grant from Ministero della Salute, Ricerca Finalizzata (Progetto RF-2016–02361887), and by the GBS-CIDP Foundation International (USA). The study was also supported by unrestricted grants from Kedrion Biopharma (Italy), CSL Behring (Italy) and Humanitas Clinical and Research Institute (Milan, Italy).

    • Disclaimer The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    • Competing interests PED has received travel grants to attend scientific meetings from CSL Behring and Kedrion. Fiore Manganelli reports personal fees for scientific events from CSL Behring and has received travel grants to attend scientific meetings from CSL Behring and Kedrion. Dario Cocito has received honoraria for lecturing from Shire, CSL Behring, and Kedrion and travel grants to attend scientific meeting from Shire, Kedrion and CSL Behring. RF has served on scientific advisory boards for CSL Behring and has received travel grants from Kedrion and CSL Behring to attend scientific meeting. CB has served on scientific advisory boards for Pfizer, Alnylam, and Akcea, and has received travel grants from Kedrion and CSL Behring to attend scientific meeting. AM has received travel grants from Kedrion and CSL Behring to attend scientific meeting. MF has served on scientific advisory boards for CSL Behring, Sanofi and Amicus and has received travel grants from Sanofi, Biogen, Kedrion and CSL Behring to attend scientific meeting. GC has received travel grants to attend scientific meetings from CSL Behring and Kedrion. ML has received travel grants to attend scientific meetings from Kedrion. GAM has received travel grants to attend scientific meetings from CSL Behring and Kedrion. GL has received travel grants to attend scientific meetings from CSL Behring and Kedrion. EP has received travel grants to attend scientific meetings from CSL Behring. TR has received travel grants to attend scientific meetings from CSL Behring. EN-O reports personal fees for Advisory or Scientific Board from ArgenX—Belgium, Takeda—Italy and USA, CSL-Behring—Italy and USA, Janssen—USA, Kedrion—Italy, LFB—France, Roche—Switzerland, Sanofi—USA. The other authors declare no conflict of interest.

    • Provenance and peer review Not commissioned; externally peer reviewed.