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Blood and CSF anti-neuronal antibodies testing in psychotic syndromes: a retrospective analysis from a tertiary psychiatric hospital

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Abstract

A Consensus of Psychoimmunology Experts (Pollak et al., 2019) established a set of red flags and proposed diagnostic criteria for psychosis of autoimmune origin (AIP). Previous studies on AIP are limited by the scarcity of CSF analysis, preventing the valorization of blood anti-neuronal antibodies (Ab). The aims of this study are to determine the relative frequency and characterize AIP in a cohort of psychotic patients that underwent CSF workup. This work is a retrospective study in a tertiary psychiatric hospital. Clinical and paraclinical data were collected from medical records, and patients were classified according to Pollak et al. (2019) criteria. From 68 patients, ten (14.7%) had positive anti-neuronal antibodies (Ab): n = 5 in CSF and blood (n = 4 anti-NMDAr, n = 1 -GAD65), and n = 5 in blood only (n = 1 anti-GABAb, n = 1 -GAD65, n = 1 -SOX1, n = 1 -NMDAr, n = 1 -zic4). After 5- (2–10)-year follow-up, n = 6/68 (8.8%) had AIP diagnosis in context of autoimmune encephalitis (AE), and the remaining (n = 4/10, blood-only Ab) alternative diagnoses (n = 2 dementia, n = 1 schizophrenia, n = 1 intellectual disability). Ten of the 13 patients that fulfilled criteria for possible AIP were mimics, and only three AE had criteria for probable AIP. All AIP developed neurological manifestations (mostly cognitive dysfunction); EEG was usually abnormal (66.7%), and all had normal MRI. We found statistically significant associations between AIP/AE and systemic autoimmune disease, presentation with seizures and EEG abnormalities. All AE developed neurological symptoms alongside psychosis. Ab positivity occurred predominantly in AE but also in other neuropsychiatric disorders. Clinical suspicion based on the knowledge of the described presentations of established Ab is crucial in the psychotic patient approach.

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References

  1. Honnorat J, Plazat LO. Autoimmune encephalitis and psychiatric disorders. Rev Neurol (Paris). 2018;174(4):228–36.

    Article  CAS  PubMed  Google Scholar 

  2. Bost C, Pascual O, Honnorat J. Autoimmune encephalitis in psychiatric institutions: current perspectives. Neuropsychiatr Dis Treat. 2016;12:2775–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tebartz van Elst L, Bechter K, Prüss H, Hasan A, Steiner JH, Leypoldt F, et al. Autoantibody-associated schizophreniform psychoses: pathophysiology, diagnostics, and treatment. Nervenarzt. 2019;90(7):745–61.

    Article  PubMed  Google Scholar 

  4. 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;52(6):1–12.

    Google Scholar 

  5. Hansen N, Lüdecke D, Maier HB, Steiner J, Neyazi AN. Psychiatrische Autoimmunenzephalitis – Diagnose und therapeutische Ansätze. psychu2d. 2023;17(01):13–28.

    Google Scholar 

  6. Pollak TA, Lennox BR, Müller S, Benros ME, Prüss H, Tebartz van Elst L, et al. Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry. 2020;7(1):93–108.

    Article  PubMed  Google Scholar 

  7. 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(4):391–404.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pollak TA, McCormack R, Peakman M, Nicholson TR, David AS. Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med. 2014;44(12):2475–87.

    Article  CAS  PubMed  Google Scholar 

  9. Chen CH, Cheng MC, Liu CM, Liu CC, Lin KH, Hwu HG. Seroprevalence survey of selective anti-neuronal autoantibodies in patients with first-episode schizophrenia and chronic schizophrenia. Schizophr Res. 2017;190:28–31.

    Article  PubMed  Google Scholar 

  10. Sæther SG, Schou M, Kondziella D. What is the significance of onconeural antibodies for psychiatric symptomatology? A systematic review. BMC Psychiatry. 2017;17(1):161.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Colijn MA, Ismail Z. Clinically relevant anti-neuronal cell surface antibodies in schizophrenia spectrum Disorders. Neuropsychobiology. 2019;78(2):70–8.

    Article  CAS  PubMed  Google Scholar 

  12. Blackman G, Lim MF, Pollak T, Al-Diwani A, Symmonds M, Mazumder A, et al. The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data. J Neurol. 2022;269(10):5302–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Asgari S, Gashirai M, Smith J, Alusi S. Seronegative autoimmune limbic encephalitis with psychiatric symptoms. Prog Neurol Psychiatry. 2022;26(1):14–7.

    Article  Google Scholar 

  14. The ICD-10 classification of mental and behavioural disorders [Internet]. 2019. https://icd.who.int/browse10/2019/en. Accessed 8 Nov 2023.

  15. Guasp M, Giné-Servén E, Maudes E, Rosa-Justicia M, Martínez-Hernández E, Boix-Quintana E, et al. Clinical, neuroimmunologic, and CSF investigations in first episode psychosis. Neurology. 2021;97(1):e61–75.

    Article  PubMed  Google Scholar 

  16. Graus F, Dalmau J. Autoimmune encephalitis or autoimmune psychosis? Eur Neuropsychopharmacol. 2021;50:112–4.

    Article  CAS  PubMed  Google Scholar 

  17. Wang J, Liu X, Lian J, Zheng H, Cai D, Cai H, et al. Autoimmune antibodies in first-episode psychosis with red flags: a hospital-based case-control study protocol. Front Psychiatry. 2022;13:976159.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Guasp M, Dalmau J. Searching for neuronal antibodies in psychiatric diseases: uncertain findings and implications. Neurology. 2023;101(15):656–60.

    Article  CAS  PubMed  Google Scholar 

  19. Dalmau J, Guasp M, Graus F. Author response: clinical, neuroimmunologic, and CSF investigations in first episode psychosis. Neurology. 2021;97(21):1010.

    Article  PubMed  Google Scholar 

  20. Endres D, Lüngen E, Hasan A, Kluge M, Fröhlich S, Lewerenz J, et al. Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany. Mol Psychiatry. 2022;27(3):1479–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Araújo MV, Monteiro RB, Samões R, Norton A, Correia AP. Persistently positive anti-NMDA receptor antibodies in chronic psychotic disorder: foe or innocent bystander? Psychiatry Clin Neurosci. 2021;75(8):269–70.

    Article  PubMed  Google Scholar 

  22. 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(9):1133–9.

    Article  PubMed  Google Scholar 

  23. Endres D, Matysik M, Feige B, Venhoff N, Schweizer T, Michel M, et al. Diagnosing organic causes of schizophrenia spectrum disorders: findings from a one-year cohort of the Freiburg Diagnostic Protocol in Psychosis (FDPP). Diagnostics. 2020;10(9):691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Doss S, Wandinger K-P, Hyman BT, Panzer JA, Synofzik M, Dickerson B, et al. High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types. Ann Clin Transl Neurol. 2014;1(10):822–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Giannoccaro MP, Gastaldi M, Rizzo G, Jacobson L, Vacchiano V, Perini G, et al. Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder. Brain Behav Immun. 2021;96:106–12.

    Article  CAS  PubMed  Google Scholar 

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Joana Lopes—conceptualization (equal), data curation (equal), formal analysis, methodology (equal), writing – original draft preparation; Maria João Malaquias—conceptualization (equal), data curation (equal), methodology (equal), writing – review &; editing (lead); Joana Freita—data curation (equal); Rodrigo Valido—data curation (equal); Paula Carneiro—writing – review &; editing (equal); Esmeralda Neves writing – review &; editing (equal); Ana Maria Moreira writing – review &; editing (equal); Raquel Samões writing – review &; editing (equal); Ernestina Santos writing – review; editing (equal); Ana Paula Correia—conceptualization (equal), writing – review &; editing (lead).

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Correspondence to Joana Lopes.

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This study was approved by the institutional ethics review board, and informed consent was waived (reference 000204 HML 21/JAN/22). The work was carried out in accordance with the code of ethics of the World Medical Association (declaration of Helsinki).

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Lopes, J., Malaquias, M.J., Freitas, J. et al. Blood and CSF anti-neuronal antibodies testing in psychotic syndromes: a retrospective analysis from a tertiary psychiatric hospital. Immunol Res (2024). https://doi.org/10.1007/s12026-024-09457-w

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