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Original research
Epileptic phenotypes in autoimmune encephalitis: from acute symptomatic seizures to autoimmune-associated epilepsy
  1. Sara Matricardi1,
  2. Sara Casciato2,
  3. Silvia Bozzetti3,4,
  4. Sara Mariotto3,
  5. Andrea Stabile5,
  6. Elena Freri6,
  7. Francesco Deleo5,
  8. Stefano Sartori7,8,
  9. Margherita Nosadini7,8,
  10. Irene Pappalardo9,
  11. Stefano Meletti10,11,
  12. Giada Giovannini10,11,
  13. Elisabetta Zucchi10,11,
  14. Carlo Di Bonaventura12,
  15. Giancarlo Di Gennaro2,
  16. Sergio Ferrari3,
  17. Luigi Zuliani13,
  18. Marco Zoccarato14,
  19. Alberto Vogrig15,
  20. Simona Lattanzi16,
  21. Roberto Michelucci17,
  22. Antonio Gambardella18,
  23. Edoardo Ferlazzo19,20,
  24. Lucia Fusco21,
  25. Tiziana Granata6,
  26. Flavio Villani9
  27. On behalf of the Immune Epilepsies Study Group of the Italian League Against Epilepsy
    1. 1Child Neurology and Psychiatry Unit, Children’s Hospital “G. Salesi”, Ospedali Riuniti Ancona, Polytechnic University of Marche, Ancona, Italy
    2. 2IRCCS Neuromed, Pozzilli, Italy
    3. 3Neurology Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
    4. 4Department of Neurology/Stroke Unit, San Maurizio Hospital, Bolzano, Italy
    5. 5Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
    6. 6Department of Paediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
    7. 7Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy
    8. 8Neuroimmunology Group, Paediatric Research Institute "Città della Speranza", Padova, Italy
    9. 9Division of Clinical Neurophysiology and Epilepsy Centre, IRCCS Ospedale Policlinico San Martino, Genova, Italy
    10. 10Dept of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
    11. 11Neurology Dept, Azienda Ospedaliera-Universitaria di Modena, Modena, Italy
    12. 12Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy
    13. 13Neurology Unit, Vicenza, Italy
    14. 14Neurology Unit O.S.A. - Azienda Ospedale Università Padova, Padova, Italy
    15. 15Department of Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy
    16. 16Neurological Clinic, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
    17. 17IRCCS - Istituto delle Scienze Neurologiche di Bologna, Unit of Neurology, Bologna, Italy
    18. 18Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy
    19. 19Regional Epilepsy Center, BMM Great Metropolitan Hospital, Reggio Calabria, Italy
    20. 20Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
    21. 21Department of Neuroscience, Bambino Gesù Children's Hospital, Rome, Italy
    22. 22Italian League Against Epilepsy, Rome, Italy
    1. Correspondence to Dr Sara Matricardi, Child Neurology and Psychiatry Unit, Children’s Hospital “G. Salesi”, Ospedali Riuniti Ancona, Polytechnic University of Marche, Ancona 60123, Italy; sara.matricardi{at}yahoo.it; Dr Tiziana Granata; Tiziana.Granata{at}istituto-besta.it

    Abstract

    Objective To describe the clinical and paraclinical findings, treatment options and long-term outcomes in autoimmune encephalitis (AE), with a close look to epilepsy.

    Methods In this retrospective observational cohort study, we enrolled patients with new-onset seizures in the context of AE. We compared clinical and paraclinical findings in patients with and without evidence of antibodies.

    Results Overall, 263 patients (138 females; median age 55 years, range 4–86) were followed up for a median time of 30 months (range 12–120). Antineuronal antibodies were detected in 63.50%.

    Antibody-positive patients had multiple seizure types (p=0.01) and prevalent involvement of temporal regions (p=0.02). A higher prevalence of episodes of SE was found in the antibody-negative group (p<0.001).

    Immunotherapy was prescribed in 88.60%, and effective in 61.80%. Independent predictors of favourable outcome of the AE were early immunotherapy (p<0.001) and the detection of antineuronal surface antibodies (p=0.01).

    Autoimmune-associated epilepsy was the long-term sequela in 43.73%, associated with cognitive and psychiatric disturbances in 81.73%. Independent predictors of developing epilepsy were difficult to treat seizures at onset (p=0.04), a high number of antiseizure medications (p<0.001), persisting interictal epileptiform discharges at follow-up (p<0.001) and poor response to immunotherapy during the acute phase (p<0.001).

    Conclusions The recognition of seizures secondary to AE represents a rare chance for aetiology-driven seizures management. Early recognition and treatment at the pathogenic level may reduce the risk of long-term irreversible sequelae. However, the severity of seizures at onset is the major risk factor for the development of chronic epilepsy.

    This study provides class IV evidence for management recommendations.

    • EPILEPSY
    • AUTOIMMUNE ENCEPHALITIS

    Data availability statement

    Data are available on reasonable request.

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • Twitter @SaraMatricardi, @stefano.meletti@unimore.it, @@_mzoccarato, @flaviovillani

    • Collaborators Collaborators: Immune Epilepsies Study Group of the Italian League Against Epilepsy (LICE) Collaborators: Umberto Aguglia, Vincenzo Belcastro, Luana Benedetti, Simone Beretta, Stefania Maria Bova, Claudia Cagnetti, Susanna Casellato, Lorenzo Celli, Elisabetta Cesaroni, Eduard Cesnick, Giangennaro Coppola, Edvige Correnti, Giuseppe Didato, Giuseppe D’Orsi, Elena Fallica, Alessandra Ferrari, Alessandro Ferretti, Carlo Andrea Galimberti, Annateresa Giallonardo, Loretta Giuliano, Angela La Neve, Claudio Liguori, Carla Marini, Federico Massa, Massimo Mastrangelo, Laura Mumoli, Carlotta Mutti, Francesca Felicia Operto, Elena Pasini, Chiara Pastori, Daniela Passarelli, Giada Pauletto, Chiara Pizzanelli, Francesca Ragona, Patrizia Riguzzi, Romana Rizzi, Marta Elena Santarone, Delia Simula, Vito Sofia, Maria Tappatà, Elena Tartara, Francesca Vanadia, Alberto Verrotti, Laura Tassi, Lucia Zinno.

    • Contributors SM is responsible for the overall content as the guarantor. SM, TG, EF, SL, FD and FV conceptualised and designed the study. SM, SC, FD, EF, SL, AS, SS, MN, CDB, GDG, IP, SM, GG, EZ, SB, SM, SF, LZ, MZ, AV, RM, AG, EF, LF, and FV selected and enrolled patients, critically reviewing all medical charts and records. SM, TG, FD, SM, SB, SL and FV were involved with the dataset and analysis. SM, TG and FV drafted the manuscript. All collaborators of the Immune Epilepsies Study Group of the Italian League Against Epilepsy (LICE) are responsible for each case data collection and diagnostic process. All authors and collaborators edited the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.