Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-05-14T14:53:43.368Z Has data issue: false hasContentIssue false
  • English
  • Français

Characterisation and outcome of neuropsychiatric symptoms in patients with anti-NMDAR encephalitis

Published online by Cambridge University Press:  20 January 2020

Miguel Restrepo-Martinez Open the ORCID record for Miguel Restrepo-Martinez [Opens in a new window] ,
Jesus Ramirez-Bermudez Open the ORCID record for Jesus Ramirez-Bermudez [Opens in a new window] ,
Leo Bayliss  and
Mariana Espinola-Nadurille
Miguel Restrepo-Martinez
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
Jesus Ramirez-Bermudez
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
Leo Bayliss
Affiliation:
Department of Neuropsychiatry and Neurology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
Mariana Espinola-Nadurille*
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Department of neurology and neurosurgery, Médica Sur, Mexico
*
Author for correspondence: Mariana Espinola-Nadurille, Email: menadu2002@yahoo.com.mx
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms.

Objective:

To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE.

Methods:

This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale.

Results:

24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259).

Conclusions:

Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

Keywords

anti-N-methyl-D-aspartate receptor encephalitisneuropsychiatrydifferentialdiagnosispsychoneuroimmunology
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 2 , April 2020 , pp. 92 - 98
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Al-Diwani, A, Handel, A, Townsend, L, Pollak, T, Leite, MI, Harrison, PJ, Lennox, BR, Okai, D, Manohar, SG and Irani, SR (2019) The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry 6, 235–246. doi: 10.1016/S2215-0366(19)30001-X.CrossRefGoogle ScholarPubMed
American Psychiatric Association and American Psychiatric Association (ed) (2013) Diagnostic and Statistical Manual of Mental disorders: DSM-5, 5th Edn.Washington, DC: American Psychiatric Association.Google Scholar
Bach, LJ (2014) Long term rehabilitation management and outcome of anti-NMDA receptor encephalitis. NeuroRehabilitation 35, 863–875.CrossRefGoogle ScholarPubMed
Barry, H, Byrne, S, Barrett, E, Murphy, KC and Cotter, DR (2015) Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bulletin 39, 19–23. doi: 10.1192/pb.bp.113.045518.CrossRefGoogle ScholarPubMed
Barry, H, Hardiman, O, Healy, DG, Keogan, M, Moroney, J, Molnar, PP, Cotter, DR and Murphy, KC (2011) Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis. British Journal of Psychiatry 199, 508–509. doi: 10.1192/bjp.bp.111.092197.CrossRefGoogle ScholarPubMed
Bush, G, Fink, M, Petrides, G, Dowling, F and Francis, A (1996) Catatonia. I. Rating scale and standardized examination. Acta Psychiatrica Scandinavica 93, 129–136. doi: 10.1111/j.1600-0447.1996.tb09814.x.CrossRefGoogle ScholarPubMed
Cummings, JL (1997) The neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 48, 10S–16S. doi: 10.1212/WNL.48.5_Suppl_6.10S.CrossRefGoogle ScholarPubMed
Dalmau, J, Gleichman, AJ, Hughes, EG, Rossi, JE, Peng, X, Lai, M, Dessain, SK, Rosenfeld, MR, Balice-Gordon, R and Lynch, DR (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. The Lancet Neurology 7, 1091–1098. doi: 10.1016/S1474-4422(08)70224-2.CrossRefGoogle ScholarPubMed
Espinola-Nadurille, M, Bautista-Gomez, P, Flores, J, Rivas-Alonso, V, Perez-Esparza, R, Solís-Vivanco, R and Vargas-Cañas, S (2018) Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis. Arquivos de Neuro-Psiquiatria 76, 2–5. doi: 10.1590/0004-282x20170179.CrossRefGoogle ScholarPubMed
Espinola-Nadurille, M, Flores-Rivera, J, Rivas-Alonso, V, Vargas-Cañas, S, Fricchione Gregory, L, Bayliss, L, Martinez-Juarez, IE, Hernandez-Vanegas, LE, Porcayo-Liborio, S, Martinez-Hernandez, R, Bautista-Gomez, P, Solis-Vivanco, R, Perez-Esparza, R, A Bustamante-Gomez, P, Restrepo-Martinez, M and Ramirez-Bermudez, J (2019) Catatonia in patients with anti-NMDA receptor encephalitis. Psychiatry and Clinical Neurosciences pcn.12867. doi: 10.1111/pcn.12867.CrossRefGoogle ScholarPubMed
Fink, M (1999) Delirious mania. Bipolar Disorder 1, 54–60. doi: 10.1034/j.1399-5618.1999.10112.x.CrossRefGoogle ScholarPubMed
Finke, C, Kopp, UA, Prüss, H, Dalmau, J, Wandinger, K-P and Ploner, CJ (2012) Cognitive deficits following anti-NMDA receptor encephalitis. Journal of Neurology, Neurosurgery, and Psychiatry 83, 195–198. doi: 10.1136/jnnp-2011-300411.CrossRefGoogle ScholarPubMed
Gable, MS, Sheriff, H, Dalmau, J, Tilley, DH and Glaser, CA (2012) The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clinical Infectious Diseases 54, 899–904. doi: 10.1093/cid/cir1038.CrossRefGoogle ScholarPubMed
Graus, F, Titulaer, MJ, Balu, R, Benseler, S, Bien, CG, Cellucci, T, Cortese, I, Dale, RC, Gelfand, JM, Geschwind, M, Glaser, CA, Honnorat, J, Höftberger, R, Iizuka, T, Irani, SR, Lancaster, E, Leypoldt, F, Prüss, H, Rae-Grant, A, Reindl, M, Rosenfeld, MR, Rostásy, K, Saiz, A, Venkatesan, A, Vincent, A, Wandinger, K-P, Waters, P and Dalmau, J (2016) A clinical approach to diagnosis of autoimmune encephalitis. The Lancet Neurology 15, 391–404. doi: 10.1016/S1474-4422(15)00401-9.CrossRefGoogle ScholarPubMed
Grover, S (2012) Assessment scales for delirium: a review. World Journal of Psychiatry 2, 58. doi: 10.5498/wjp.v2.i4.58.CrossRefGoogle ScholarPubMed
Gurrera, RJ (2018) Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms. Psychological Medicine 49, 2709–2716. Cambridge University Press. doi: 10.1017/S0033291718003665.CrossRefGoogle ScholarPubMed
Herken, J and Prüss, H (2017) Red flags: clinical signs for identifying autoimmune encephalitis in psychiatric patients. Frontiers in Psychiatry 8, 25. doi: 10.3389/fpsyt.2017.00025.CrossRefGoogle ScholarPubMed
Inouye, SK, Kosar, CM, Tommet, D, Schmitt, EM, Puelle, MR, Saczynski, JS, Marcantonio, ER and Jones, RN (2014) The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts. Annals of Internal Medicine 160, 526. doi: 10.7326/M13-1927.CrossRefGoogle ScholarPubMed
Lennox, BR, Coles, AJ and Vincent, A (2012) Antibody-mediated encephalitis: a treatable cause of schizophrenia. British Journal of Psychiatry 200, 92–94. doi: 10.1192/bjp.bp.111.095042.CrossRefGoogle ScholarPubMed
Maat, P, de Graaff, E, van Beveren, NM, Hulsenboom, E, Verdijk, RM, Koorengevel, K, van Duijn, M, Hooijkaas, H, Hoogenraad, C and Sillevis Smitt, PA (2013) Psychiatric phenomena as initial manifestation of encephalitis by anti-NMDAR antibodies. Acta Neuropsychiatrica 25, 128–136. doi: 10.1111/acn.12013.CrossRefGoogle ScholarPubMed
Maneta, E and Garcia, G (2014) Psychiatric manifestations of anti-NMDA receptor encephalitis: neurobiological underpinnings and differential diagnostic implications. Psychosomatics 55, 37–44. doi: 10.1016/j.psym.2013.06.002.CrossRefGoogle ScholarPubMed
McKeon, GL, Robinson, GA, Ryan, AE, Blum, S, Gillis, D, Finke, C and Scott, JG (2018) Cognitive outcomes following anti-N-methyl-D-aspartate receptor encephalitis: a systematic review. Journal of Clinical and Experimental Neuropsychology 40, 234–252. doi: 10.1080/13803395.2017.1329408.CrossRefGoogle ScholarPubMed
McKeon, GL, Scott, JG, Spooner, DM, Ryan, AE, Blum, S, Gillis, D, Langguth, D and Robinson, GA (2016) Cognitive and social functioning deficits after anti-N-methyl-D-aspartate receptor encephalitis: an exploratory case series. Journal of the International Neuropsychological Society 22, 828–838.CrossRefGoogle Scholar
Nóbrega, PR, Pitombeira, MS, Mendes, LS, Krueger, MB, Santos, CF, Morais, NMDM, Simabukuro, MM, Maia, FM and Braga-Neto, P (2019) Clinical features and inflammatory markers in autoimmune encephalitis associated with antibodies against neuronal surface in Brazilian patients. Frontiers in Neurology 10, 472. doi: 10.3389/fneur.2019.00472.CrossRefGoogle ScholarPubMed
Pedraza, OL, Salazar, AM, Sierra, FA, Soler, D, Castro, J, Castillo, P, Hernández, A and Piñeros, C (2016) Reliability, criterion and discriminant validity of the Montreal Cognitive Assessment Test (MoCA) in a group of adults from Bogotá. Acta Medica Colombian 41, 8.Google Scholar
Restrepo-Martínez, M, Chacón-González, J, Bayliss, L, Ramírez-Bermúdez, J, Lewis, FG and Nadurille, M (2019) Delirious mania as a neuropsychiatric presentation in patients with anti-NMDAr encephalitis. Psychosomatics (in press). doi: 10.1016/j.psym.2019.03.002.Google Scholar
Restrepo Martínez, M, Paola Bautista, G, Espínola-Nadurille, M and Bayliss, L (2019) Banderas rojas para sospechar encefalitis anti-NMDAr en un primer episodio psicótico: reporte de dos casos. Revista Colombiana de Psiquiatría 48, 127–130. doi: 10.1016/j.rcp.2017.10.002.CrossRefGoogle Scholar
Titulaer, MJ, McCracken, L, Gabilondo, I, Armangué, T, Glaser, C, Iizuka, T, Honig, LS, Benseler, SM, Kawachi, I, Martinez-Hernandez, E, Aguilar, E, Gresa-Arribas, N, Ryan-Florance, N, Torrents, A, Saiz, A, Rosenfeld, MR, Balice-Gordon, R, Graus, F and Dalmau, J (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. The Lancet Neurology 12, 157–165. doi: 10.1016/S1474-4422(12)70310-1.CrossRefGoogle ScholarPubMed
Warren, N, Siskind, D and O’Gorman, C (2018) Refining the psychiatric syndrome of anti- N -methyl- d -aspartate receptor encephalitis. Acta Psychiatrica Scandinavica 138, 401–408. doi: 10.1111/acps.12941.CrossRefGoogle ScholarPubMed
Yudofsky, SC, Kopecky, HJ, Kunik, M, Silver, JM and Endicott, J (1997) The Overt Agitation Severity Scale for the objective rating of agitation. The Journal of Neuropsychiatry and Clinical Neurosciences 9, 541–548. doi: 10.1176/jnp.9.4.541.Google ScholarPubMed
Zhang, L, Wu, M-Q, Hao, Z-L, Chiang, SMV, Shuang, K, Lin, M-T, Chi, X-S, Fang, J-J, Zhou, D and Li, J-M (2017) Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: a systematic review of reported cases. Epilepsy & Behavior 68, 57–65. doi: 10.1016/j.yebeh.2016.12.019.CrossRefGoogle ScholarPubMed