Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study

IntroductionAnti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a neuropsychiatric disorder with additional psychiatric features caused by NMDA-R immunoglobulin G (IgG) antibodies in cerebrospinal fluid (CSF). This report presents the follow-up of a patient in whom we assumed mild NMDA-R enc...

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Main Authors: Katharina von Zedtwitz, Judith Weiser, Raphael J. Dressle, Simon J. Maier, Bernd Feige, Kathrin Nickel, Nils Venhoff, Katharina Domschke, Joachim Brumberg, Sebastian Rauer, Ludger Tebartz van Elst, Luciana Hannibal, Harald Prüss, Alexander Rau, Dominique Endres
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Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1630357/full
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author Katharina von Zedtwitz
Judith Weiser
Raphael J. Dressle
Simon J. Maier
Bernd Feige
Kathrin Nickel
Nils Venhoff
Katharina Domschke
Katharina Domschke
Joachim Brumberg
Sebastian Rauer
Ludger Tebartz van Elst
Luciana Hannibal
Harald Prüss
Harald Prüss
Alexander Rau
Dominique Endres
author_facet Katharina von Zedtwitz
Judith Weiser
Raphael J. Dressle
Simon J. Maier
Bernd Feige
Kathrin Nickel
Nils Venhoff
Katharina Domschke
Katharina Domschke
Joachim Brumberg
Sebastian Rauer
Ludger Tebartz van Elst
Luciana Hannibal
Harald Prüss
Harald Prüss
Alexander Rau
Dominique Endres
author_sort Katharina von Zedtwitz
collection DOAJ
description IntroductionAnti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a neuropsychiatric disorder with additional psychiatric features caused by NMDA-R immunoglobulin G (IgG) antibodies in cerebrospinal fluid (CSF). This report presents the follow-up of a patient in whom we assumed mild NMDA-R encephalitis in the first psychotic episode.Case studyA patient with a prior episode of an acute polymorphic psychotic syndrome relapsed five and a half years later following a severe COVID-19 infection. Serum NMDA-R antibodies were again detected with a titer of max. 1:320 using fixed-cell-based assays, but conventional magnetic resonance imaging (MRI), electroencephalography (EEG), and CSF findings were largely normal. NMDA-R antibody levels in serum decreased to 1:80 after approximately one month without immunotherapy. [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) still revealed pronounced metabolism of the association cortices (clearly more pronounced in the first episode with an encephalitis-like pattern at that time). Advanced MRI analyses including diffusion microstructure imaging (DMI) showed frontal and thalamic microstructural alterations compatible with edematization (but also far less accentuated than in the first episode). Further advanced antibody tests of CSF (approx. 1 month after symptom onset) using a live-cell-based and different tissue-based assays were negative for NMDA-R IgG antibodies. Research mass spectrometry of the CSF identified neurotransmitter-precursor shortages, increased turnover of tryptophan into quinolinic acid, and low-glucose/lactate levels. Immunotherapy (performed after the initial assumption of an autoimmune cause) with steroids led to clinical improvement of residual symptoms. After approximately three months, NMDA-R IgG serum antibodies were no longer detectable; however, FDG-PET/DMI follow-up revealed no relevant changes.DiscussionThe international consensus criteria for a probable/definite diagnosis of NMDA-R encephalitis or autoimmune psychosis were not fulfilled, especially as no NMDA-R IgG antibodies were identified in CSF using different antibody assays and EEG/CSF routine findings were inconspicuous. NMDA-R encephalitis was therefore not diagnosed (as initially suspected). Independent of the NMDA-R IgG antibodies, there were possible signs of an autoimmune process. For a better understanding of similar patients, multimodal diagnostic approaches including complementary antibody tests could be promising.
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spelling doaj-art-e2c2d5a3227b43fe876aae09c20011cf2025-08-25T04:10:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16303571630357Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case studyKatharina von Zedtwitz0Judith Weiser1Raphael J. Dressle2Simon J. Maier3Bernd Feige4Kathrin Nickel5Nils Venhoff6Katharina Domschke7Katharina Domschke8Joachim Brumberg9Sebastian Rauer10Ludger Tebartz van Elst11Luciana Hannibal12Harald Prüss13Harald Prüss14Alexander Rau15Dominique Endres16Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Center for Mental Health (DZPG), Partner Site Berlin, Berlin/Potsdam, GermanyDepartment of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Neurodegenerative Diseases (DZNE) Berlin/Potsdam, Berlin, GermanyDepartment of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyIntroductionAnti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a neuropsychiatric disorder with additional psychiatric features caused by NMDA-R immunoglobulin G (IgG) antibodies in cerebrospinal fluid (CSF). This report presents the follow-up of a patient in whom we assumed mild NMDA-R encephalitis in the first psychotic episode.Case studyA patient with a prior episode of an acute polymorphic psychotic syndrome relapsed five and a half years later following a severe COVID-19 infection. Serum NMDA-R antibodies were again detected with a titer of max. 1:320 using fixed-cell-based assays, but conventional magnetic resonance imaging (MRI), electroencephalography (EEG), and CSF findings were largely normal. NMDA-R antibody levels in serum decreased to 1:80 after approximately one month without immunotherapy. [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) still revealed pronounced metabolism of the association cortices (clearly more pronounced in the first episode with an encephalitis-like pattern at that time). Advanced MRI analyses including diffusion microstructure imaging (DMI) showed frontal and thalamic microstructural alterations compatible with edematization (but also far less accentuated than in the first episode). Further advanced antibody tests of CSF (approx. 1 month after symptom onset) using a live-cell-based and different tissue-based assays were negative for NMDA-R IgG antibodies. Research mass spectrometry of the CSF identified neurotransmitter-precursor shortages, increased turnover of tryptophan into quinolinic acid, and low-glucose/lactate levels. Immunotherapy (performed after the initial assumption of an autoimmune cause) with steroids led to clinical improvement of residual symptoms. After approximately three months, NMDA-R IgG serum antibodies were no longer detectable; however, FDG-PET/DMI follow-up revealed no relevant changes.DiscussionThe international consensus criteria for a probable/definite diagnosis of NMDA-R encephalitis or autoimmune psychosis were not fulfilled, especially as no NMDA-R IgG antibodies were identified in CSF using different antibody assays and EEG/CSF routine findings were inconspicuous. NMDA-R encephalitis was therefore not diagnosed (as initially suspected). Independent of the NMDA-R IgG antibodies, there were possible signs of an autoimmune process. For a better understanding of similar patients, multimodal diagnostic approaches including complementary antibody tests could be promising.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1630357/fullautoimmuneinflammationbrainimmunotherapyautoimmune encephalitis
spellingShingle Katharina von Zedtwitz
Judith Weiser
Raphael J. Dressle
Simon J. Maier
Bernd Feige
Kathrin Nickel
Nils Venhoff
Katharina Domschke
Katharina Domschke
Joachim Brumberg
Sebastian Rauer
Ludger Tebartz van Elst
Luciana Hannibal
Harald Prüss
Harald Prüss
Alexander Rau
Dominique Endres
Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study
Frontiers in Immunology
autoimmune
inflammation
brain
immunotherapy
autoimmune encephalitis
title Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study
title_full Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study
title_fullStr Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study
title_full_unstemmed Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study
title_short Case Report: Acute polymorphic psychosis and NMDA-R IgG antibodies in serum: a follow-up case study
title_sort case report acute polymorphic psychosis and nmda r igg antibodies in serum a follow up case study
topic autoimmune
inflammation
brain
immunotherapy
autoimmune encephalitis
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1630357/full
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