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Original research
Epileptic seizures of suspected autoimmune origin: a multicentre retrospective study
  1. Silvia Bozzetti1,
  2. Fabio Rossini2,
  3. Sergio Ferrari1,
  4. Rachele Delogu3,
  5. Gaetano Cantalupo4,
  6. Fabio Marchioretto5,
  7. Giampietro Zanette6,
  8. Tiziano Zanoni7,
  9. Marco Turatti1,
  10. Giuseppina Vitale8,
  11. Morena Cadaldini9,
  12. Francesca Rossi10,
  13. Luca Di Tizio11,
  14. Carmela Zuco12,
  15. Giorgia Teresa Maniscalco13,
  16. Fabio Soldani14,
  17. Salvatore Monaco1,
  18. Eugen Trinka2,
  19. Romana Hoeftberger15,
  20. Sara Mariotto1
  1. 1 Department of Neuroscience, Biomedicine and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy
  2. 2 Department of Neurology, Christian Doppler Medical Centre and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
  3. 3 Department of Clinical and Experimental Medicine, Neurology Unit, University of Sassari, Sassari, Italy
  4. 4 Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
  5. 5 Neurology Unit, Sacro Cuore – Don Calabria, Negrar, Verona, Italy
  6. 6 Department of Neurology, Pederzoli Hospital Private Clinic SpA, Peschiera del Garda, Veneto, Italy
  7. 7 Neurology Unit, AOUI Verona, Verona, Italy
  8. 8 Neurology Unit, Ospedale Garibaldi, Catania, Italy
  9. 9 Neurology Unit, AULSS6 Euganea, Ospedali Riuniti Padova Sud, Padova, Italy
  10. 10 Neurology Unit, Mater Salutis Hospital, Legnago, Italy
  11. 11 Intensive Care Unit, SS Annunziata Hospital, Chieti, Italy
  12. 12 Neurology Unit, Ospedale C. Poma, Mantova, Italy
  13. 13 Department of Neurological Sciences, University of Naples Federico II, Napoli, Italy
  14. 14 Department of Diagnostics and Public Health, Infectious Disease Unit, University of Verona, Verona, Italy
  15. 15 Department of Neurology, Medical University of Vienna, Division of Neuropathology and Neurochemistry, Vienna, Austria
  1. Correspondence to Dr Sara Mariotto, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37129 Verona, Italy; sara.mariotto{at}gmail.com

Abstract

Objective To analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy (APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores.

Methods We retrospectively collected clinical and paraclinical data of 92 patients referred to the Neurology Units of Verona and Salzburg between January 2014 and July 2019 with new-onset epilepsy, status epilepticus or chronic epilepsy of unknown aetiology. Fixed and live cell-based assays, tissue-based assays, immunoblot, and live rat hippocampal cell cultures were performed in paired serum/cerebrospinal fluid (CSF) to detect antineuronal and antiglial antibodies. The APE2 and RITE2 scores were then calculated and compared with clinical and laboratory data.

Results Autoantibodies were detected in 29/92 patients (31.5%), with multiple positivity observed in 6/29 cases. The APE2 score (median 5, range 1–15) significantly correlated with antibody positivity (p=0.014), especially for the presence of neuropsychiatric symptoms (p<0.01), movement disorders (p<0.01), dysautonomia (p=0.03), faciobrachial dyskinesias (p=0.03) and cancer history (p<0.01). Status epilepticus was significantly more frequent in antibody-negative patients (p<0.01). Among the items of the RITE2 score, early initiation of immunotherapy correlated with a good treatment response (p=0.001), whereas a cancer history was significantly more common among non-responders (p<0.01). Persistence of neuropsychiatric symptoms and seizures correlated with antiepileptic maintenance after at least 1 year.

Conclusions This is the first study that independently validates the APE2 and RITE2 scores and includes the largest cohort of patients whose paired serum and CSF samples have been tested for autoantibodies possibly associated with autoimmune epilepsy.

  • epilepsy
  • autoimmune encephalitis
  • neuroimmunology
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Footnotes

  • RH and SM are joint senior authors.

  • RH and SM contributed equally.

  • Contributors SB: design and conceptualisation of the study, sample collection, cooperation in the analysis and interpretation of autoantibody tests, collection and interpretation of clinical data, data generation and interpretation and drafting the manuscript. RD, GC, FM, GZ, TZ, MT, GV, MC, FR, LDT, CZ and GTM: collection and interpretation of clinical data. FS: statistical analysis. SF and FR: collection and interpretation of clinical data, data generation and interpretation and revising the manuscript for intellectual content. ET and SalM: interpretation of clinical data and revising the manuscript for intellectual content. RH: design and conceptualisation of the study, coordination and validation of the analysis and interpretation of autoantibody tests, and revising the manuscript for intellectual content. SarM: design and conceptualisation of the study, collection and interpretation of clinical and laboratory data, data generation and interpretation, and revising the manuscript for intellectual content.

  • Funding This work was partly supported by grants from the 'Jubiläumsfonds der Österreichischen Nationalbank', project 16919.

  • Competing interests SB, RD, GC, FM, GZ, TZ, MT, GV, MC, FarR, LDT, CZ, GTM, FS, FrR, ET, SalM and RH: report no disclosures. SF received support for attending scientific meetings by Shire, Sanofi Genzyme and Euroimmun. SarM received support for attending scientific meetings by Merck and Euroimmun and received speaker honoraria from Biogen.

  • Patient consent for publication Not required.

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article.

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