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NMDA-receptor encephalitis in Denmark from 2009 to 2019: a national cohort study

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Abstract

Background

To describe the national Danish N-methyl-d-aspartate receptor encephalitis (NMDARE) cohort.

Methods

All NMDAR immunoglobulin G (IgG) positive cases in Denmark from 2009 to 2019 were included. Medical information was assessed retrospectively for clinical phenotype, workup, treatment and outcome.

Results

Seventy-seven patients were NMDAR IgG positive in serum/CSF. Fifty-five fulfilled the criteria of NMDARE, 18 did not and 4 had missing data. Incidence was 0.17/100,000 persons per year in 2018, and incidence rates increased since 2009. Of the 55 NMDARE patients (median age 27; 60% female), 9 had post-herpes simplex (HSE) NMDARE and 7 had a tumor (four teratomas). MRI was normal in 51% of patients. Brain FDG PET was performed in 17 patients, and was abnormal in 47% of patients with a normal MRI. First-line therapy was administered to 91%, and 24% required second-line therapy. Maintenance therapy during recovery was given 84% of patients, with no effect on relapse-risk. ICU admission occurred in 29%. Poor outcome (mRS > 2) was reported in 27% and dependent on age and etiology. Patients > 45 years had a poorer outcome (71% vs 8%, p < 0.0001), more frequently post-HSE NMDARE (47% vs 3%, p < 0.0001) and underlying malignancies (18% vs 0%).

Conclusion

The incidence of NMDARE in Denmark is currently 0.17/100,000 persons per year, and has increased since 2009. NMDARE patients in Denmark display a higher median age, lower female:male ratio, a less frequent tumor association and need for ICU admission. Maintenance therapy did not reduce relapse rate. Poor outcome was seen with higher age, likely related to underlying etiology.

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Data availability statement

Anonymized patient data, the statistical analysis plan and supplementary data not published within this article will be made available for purposes of replicating results by request from any qualified investigator.

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Acknowledgements

This research was conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation. Authors acknowledge the Autoimmune Laboratory at the Dept. of Clinical Immunology, Odense University Hospital and the Autoimmune Laboratory at Statens Serum Institut, Denmark. In addition, all the involved hospitals who kindly provided clinical information on patients.

Funding

MSN received grant support by Odense University Hospital and the Faculty of Health Sciences, University of Southern Denmark. No award/grant number.

Author information

Authors and Affiliations

  1. Department of Neurology, Odense University Hospital, J.B. Winsløws Vej 4, 5000, Odense C, Denmark

    Mette Scheller Nissen & Morten Blaabjerg

  2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Mette Scheller Nissen, Anna Christine Nilsson, Matias Ryding & Morten Blaabjerg

  3. Brain Research-Inter Disciplinary Guided Excellence (BRIDGE), Odense, Denmark

    Mette Scheller Nissen, Matias Ryding & Morten Blaabjerg

  4. Department of Neurology, Telemark Hospital, Skien, Norway

    Maren Synnøve Ørvik

  5. Department of Clinical Immunology, Odense University Hospital, Odense, Denmark

    Anna Christine Nilsson

  6. Danish National Biobank, Statens Serum Institut, Copenhagen, Denmark

    Magnus Lydolph

  7. Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Morten Blaabjerg

Authors
  1. Mette Scheller Nissen
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Contributions

Design and conceptualization: MB and MSN. Acquisition of data: MSN, MSØ, MR, ACN, and ML. Analysis and interpretation of the data: MSN and MB. Drafting and revising the manuscript: MSN, MSØ, ACN, MR, ML, and MB.

Corresponding authors

Correspondence to Mette Scheller Nissen or Morten Blaabjerg.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Standard protocol approvals, registrations, and patient consents

Approval was obtained from the Danish Data Protection Agency and the Danish Medical Authorities (3–3013-3124/1), who granted a waiver for patient consent.

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Nissen, M.S., Ørvik, M.S., Nilsson, A.C. et al. NMDA-receptor encephalitis in Denmark from 2009 to 2019: a national cohort study. J Neurol 269, 1618–1630 (2022). https://doi.org/10.1007/s00415-021-10738-9

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  • DOI: https://doi.org/10.1007/s00415-021-10738-9

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