Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;27(3):1479-1489.
doi: 10.1038/s41380-021-01396-4. Epub 2022 Jan 19.

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany

Dominique Endres  1   2 , Eva Lüngen  1   2 , Alkomiet Hasan  3   4 , Michael Kluge  5 , Sabrina Fröhlich  6   7 , Jan Lewerenz  8 , Tom Bschor  9 , Ida Sibylle Haußleiter  10 , Georg Juckel  10 , Florian Then Bergh  11 , Barbara Ettrich  11 , Lisa Kertzscher  5 , Tatiana Oviedo-Salcedo  4 , Robert Handreka  12 , Martin Lauer  13 , Klaas Winter  14 , Norbert Zumdick  15 , Anna Drews  16 , Jost Obrocki  17 , Yavor Yalachkov  18 , Anna Bubl  19 , Felix von Podewils  20 , Udo Schneider  21 , Kristina Szabo  22 , Margarete Mattern  23 , Alexandra Philipsen  24 , Katharina Domschke  2   25 , Klaus-Peter Wandinger  26 , Alexandra Neyazi  27 , Oliver Stich  28   29 , Harald Prüss  30   31 , Frank Leypoldt #  26   32 , Ludger Tebartz van Elst #  33   34
Affiliations

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany

Dominique Endres et al. Mol Psychiatry. 2022 Mar.

Abstract

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

PubMed Disclaimer

Conflict of interest statement

AH: is editor of the German and WFBSP guidelines schizophrenia. He has been invited to scientific meetings by Lundbeck, Janssen, and Pfizer, and he received paid speakerships from Desitin, Janssen, Otsuka, and Lundbeck. He was member of Roche, Otsuka, Lundbeck, and Janssen advisory boards. MK: lecture fees or travel grants within the last 3 years: Haema, Janssen-Cilag, Servier. JL: received speaker fees or travel compensation from UCB, Bayer, Roche, Teva and the Cure Huntington’s Disease Initiative (CHDI). His institution has been reimbursed for his role as a principal investigator in trials for UCB and CHDI. His research is funded by the European Huntington’s Disease Initiative and Ministry for Education and Research Baden-Württemberg outside the submitted work, as well as the German Ministry for Education and Research (BMBF). He works for an academic institution, which also offers commercial antibody testing. YY: has been supported by travel grants from Novartis and Sanofi Genzyme, has received an honorarium for active participation in an advisory board by Sanofi Genzyme as well as speaking honoraria by Roche and Sanofi Genzyme. FvP: has received fees as speaker or consultant from Bial, Desitin, Eisai, GW Pharma, Arvelle, and UCB Pharma. AP: has served on advisory boards, given lectures, performed phase 3 studies, or received travel grants within the last 3 years from Boehringer, Janssen-Cilag, MEDICE Arzneimittel Putter GmbH and Co KG, and Shire/Takeda and has authored books and articles on ADHD published by Elsevier, Hogrefe, Schattauer, Kohlhammer, Karger, Springer, Thieme, and Oxford University Press. KD: Steering Committee Neurosciences, Janssen. AN: has received lecture fees from Novartis. FL: consulting activities/lecture fees for/from Biogen, Grifols, Teva, Roche, Merck, Fresenius. LTvE: advisory boards, lectures, or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag, Novartis, Shire, UCB, GSK, Servier, Janssen and Cyberonics. Other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Syndromal findings (presented here is the predominant psychiatric syndrome for each patient).
AE autoimmune encephalitis. The group of patients with paranoid-hallucinatory syndromes includes all patients with catatonic syndromes.
Fig. 2
Fig. 2. Autoantibody findings.
Inflammatory CSF pathologies are coded here only if patients had no additional neuronal antibodies. For a small subgroup of patients only response to immunomodulatory treatment was documented. *Anti-Yo antibodies were tested in one patient using an immunoblot and in indirect immunofluorescence, in the second anti-Yo positive patient, these antibodies were positive in two immunoblots. **Unfortunately, the antibody measurement method in the anti-Zic4 positive patient was not documented. AE autoimmune encephalitis, CSF cerebrospinal fluid.
See this image and copyright information in PMC

Comment in

References

    1. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15:391–404. doi: 10.1016/S1474-4422(15)00401-9.. - DOI - PMC - PubMed
    1. Kayser MS, Titulaer MJ, Gresa-Arribas N, Dalmau J. Frequency and characteristics of isolated psychiatric episodes in anti–N-methyl-d-aspartate receptor encephalitis. JAMA Neurol. 2013;70:1133–9. doi: 10.1001/jamaneurol.2013.3216.. - DOI - PMC - PubMed
    1. Endres D, Maier V, Leypoldt F, Wandinger KP, Lennox B, Pollak TA, et al. Autoantibody-associated psychiatric syndromes: a systematic literature review resulting in 145 cases. Psychol Med. 2020:1–12. 10.1017/S0033291720002895. - PMC - PubMed
    1. Endres D, Meixensberger S, Dersch R, Feige B, Stich O, Venhoff N, et al. Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis. Transl Psychiatry. 2020;10:279. doi: 10.1038/s41398-020-00967-3.. - DOI - PMC - PubMed
    1. Endres D, Prüss H, Rauer S, Süß P, Venhoff N, Feige B, et al. Probable autoimmune catatonia with antibodies against cilia on hippocampal granule cells and highly suspicious cerebral FDG-PET findings. Biol Psychiatry. 2020;S0006-3223:31982–1. doi: 10.1016/j.biopsych.2019.12.020. - DOI - PubMed

Publication types

Supplementary concepts