Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis
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Abstract
Objectives To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP).
Methods This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed.
Results One hundred five patients were included; their median age was 30 (range 14–75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features).
Conclusions NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.
Glossary
- AP=
- autoimmune psychosis;
- CBA=
- cell-based assay;
- CI=
- confidence interval;
- DSM=
- Diagnostic and Statistical Manual of Mental Disorders;
- FEP=
- first episode psychosis;
- IgG=
- immunoglobulin G;
- IQR=
- interquartile range;
- NMDAR=
- NMDA receptor;
- NMDAR-abs=
- NMDAR antibodies;
- WBC=
- white blood cells
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 16
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- Received December 2, 2020.
- Accepted in final form March 26, 2021.
- © 2021 American Academy of Neurology
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Letters: Rapid online correspondence
- Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis
- Mar Guasp, Neurologist, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona
- Josep Dalmau, Neurologist, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, ICREA
Submitted February 17, 2022 - Reader Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis
- Ludger Tebartz van Elst, Professor of Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine University of Freiburg
- Kimon Runge, Psychiatrist, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine University of Freiburg
- Dominique Endres, Psychiatrist, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine University of Freiburg
- Marion Leboyer, Professor of Psychiatry, INSERM, IMRB, Translational Neuropsychiatry, University of Paris Est Créteil
- Janet L. Cunningham, Associate professor at Department of Neuroscience, Psychiatry, Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
Submitted November 11, 2021 - Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis
- Josep Dalmau, Neurologist, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
- Mar Guasp, Neurologist, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
- Francesc Graus, Neurologist, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Submitted September 09, 2021 - Reader Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis
- Thomas Pollak, NIHR Clinical Lecturer, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
- Harald Prüss, Professor of Neurology, Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Karl Bechter, Professor of Psychiatry, Department for Psychiatry and Psychotherapy II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany
- Souhel Najjar, Chair of Neurology, Department of Neurology, Zucker School of Medicine at Hofstra/Northwell, Lenox Hill Hospital, New York, USA
- Angela Vincent, Emeritus Professor of Neuroimmunology, Nuffield Department of Clinical Neurosciences, University of Oxford, UK
Submitted August 16, 2021
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