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Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms

Published online by Cambridge University Press:  18 December 2018

Ronald J. Gurrera Open the ORCID record for Ronald J. Gurrera [Opens in a new window]
Ronald J. Gurrera*
Affiliation:
VA Boston Healthcare System, Boston, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA
*
Author for correspondence: Ronald J. Gurrera, E-mail: [email protected]; [email protected]
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Abstract

Background

Anti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.

Methods

A systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.

Results

Two hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.

Conclusions

Clinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

Keywords

anti-NMDAdiagnosisencephalitisNMDA receptor
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 16 , December 2019 , pp. 2709 - 2716
Copyright
Copyright © Cambridge University Press 2018 

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References

Braakman, HMH, Moers-Hornikx, VMP, Arts, BMG, Hupperts, RMM and Nicolai, J (2010) Pearls & Oysters: electroconvulsive therapy in anti-NMDA receptor encephalitis. Neurology 75, e44–e46.Google Scholar
Caroff, SN and Campbell, C (2015) Risk of neuroleptic malignant syndrome in patients with NMDAR encephalitis. Neurological Sciences 36, 479–480.Google Scholar
Dalmau, J (2016) NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: the 2016 Cotzias Lecture. Neurology 87, 2471–2482.Google Scholar
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.Google Scholar
Dalmau, J, Lancaster, E, Martinez-Hernandez, E, Rosenfeld, MR and Balice-Gordon, R (2011) Clinical experience and laboratory investigations in patients with anit-NMDAR encephalitis. The Lancet. Neurology 10, 63–74.Google Scholar
Gabilondo, I, Saiz, A, Galán, L, González, V, Jadraque, R, Sabater, L, Sans, A, Sempere, A, Vela, A, Villalobos, F, Viñals, M, Villoslada, P and Graus, F (2011) Analysis of relapses in anti-NMDAR encephalitis. Neurology 77, 996–999.Google Scholar
Gable, MS, Gavali, S, Radner, A, Tilley, DH, Lee, B, Dyner, L, Collins, A, Dengel, A, Dalmau, J and Glaser, CA (2009) Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. European Journal of Clinical Microbiology & Infectious Diseases 28, 1421–1429.Google Scholar
Granerod, J, Ambrose, HE, Davies, NWS, Clewley, JP, Walsh, A, Morgan, D, Cunningham, R, Zuckerman, M, Mutton, KJ, Solomon, T, Ward, KN, Lunn, MPT, Irani, SR, Vincent, A, Brown, DWG and Crowcroft, NS, on behalf of the UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. The Lancet. Infectious Diseases 10, 835–844.Google Scholar
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.Google Scholar
Heekin, RD, Catalano, MC, Frontera, AT and Catalano, G (2015) Anti-NMDA receptor encephalitis in a patient with previous psychosis and neurological abnormalities: a diagnostic challenge. Case Reports in Psychiatry 2015, article ID 253891, http://dx.doi.org/10.1155/2015/253891.Google Scholar
Hopkins, SA, Moodley, KK and Chan, D (2013) Autoimmune limbic encephalitis presenting as relapsing psychosis. BMJ Case Reports 2013, published online: August 30; doi: 10.1136/bcr-2013-010461.Google Scholar
Howard, CM, Kass, JS, Bandi, VDP and Guntupalli, KK (2014) Challenges in providing critical care for patients with anti-N-methyl-D-aspartate receptor encephalitis. Chest 145, 1143–1147.Google Scholar
Huang, C, Kang, Y, Zhang, B, Li, B, Qiu, C, Liu, S, Ren, H, Yang, Y, Liu, X, Li, T and Guo, W (2015) Anti-N-methyl-D-aspartate encephalitis in a patient with a 7-year history of being diagnosed as schizophrenia: complexities in diagnosis and treatment. Neuropsychiatric Disease and Treatment 11, 1437–1442.Google Scholar
Irani, SR, Bera, K, Waters, P, Zuliani, L, Maxwell, S, Zandi, MS, Friese, MA, Galea, I, Kullmann, DM, Beeson, D, Lang, B, Bien, CG and Vincent, A (2010) N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 133, 1655–1667.Google Scholar
Kayser, MS and Dalmau, J (2016) Anti-NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophrenia Research 176, 36–40.Google Scholar
Kayser, MS, Titulaer, MJ, Gresa-Arribas, N and Dalmau, J (2013) Frequency and characteristics of isolated psychiatric episodes in anti-N-methyl-D-aspartate receptor encephalitis. JAMA Neurology 70, 1133–1139.Google Scholar
Koksal, A, Baybas, S, Mutluay, B, Altunkaynak, Y and Keskek, A (2015) A case of NMDAR encephalitis misdiagnosed as postpartum psychosis and neuroleptic malignant syndrome. Neurological Sciences 36, 1257–1258.Google Scholar
Lancaster, E, Martinez-Hernandez, E and Dalmau, J (2011) Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 77, 179–189.Google Scholar
Lejuste, F, Thomas, L, Picard, G, Desestret, V, Ducray, F, Rogemond, V, Psimaras, D, Antoine, J-C, Delattre, J-Y, Groc, L, Leboyer, M and Honnorat, J (2016) Neuroleptic intolerance in patients with anti NMDAR encephalitis. Neurology. Neuroimmunology & Neuroinflammation 3, e280.Google Scholar
Leypoldt, F, Armangue, T and Dalmau, J (2015) Autoimmune encephalopathies. Annals of the New York Academy of Sciences 1338, 94–114.Google Scholar
Lim, J-A, Lee, S-T, Jung, K-H, Kim, S, Shin, J-W, Moon, J, Byun, J-I, Kim, T-J, Shin, Y-W, Lee, K-J, Kim, Y-S, Park, K-I, Lee, SK and Chu, K (2014) Anti-N-methyl-D-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. Journal of Clinical Neurology (Seoul, Korea) 10, 157–161.Google Scholar
Maneta, E and Garcia, G (2014) Psychiatric manifestations of anti-NMDA receptor encephalitis: neurobiological underpinnings and differential diagnostic implications. Psychosomatics 55, 37–44.Google Scholar
Peer, M, Prüss, H, Ben-Dayan, I, Paul, F, Arzy, S and Finke, C (2017) Functional connectivity of large-scale brain networks in patients with anti-NMDA receptor encephalitis: an observational study. The Lancet. Psychiatry 4, 768–774.Google Scholar
Punja, M, Pomerleau, AC, Devlin, JJ, Morgan, BW, Schier, JG and Schwartz, MD (2013) Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth considering in the differential diagnosis of delirium. Clinical Toxicology 51, 794–797.Google Scholar
Schmitt, SE, Pargeon, K, Frechette, ES, Hirsch, LJ, Dalmau, J and Friedman, D (2012) Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 79, 1094–1100.Google Scholar
Slettedal, IÖ, Dahl, HM, Sandvig, I, Dalmau, J and Strømme, P (2012) Young girl with psychosis, cognitive failure and seizures. Tidsskrift for den Norske lægeforening: tidsskrift for praktisk medicin, ny række 132, 2073–2076.Google 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.Google Scholar
Yoshimura, B, Yada, Y, Horigome, T and Kishi, Y (2015) Anti-N-methyl-D-aspartate receptor encephalitis presenting with intermittent catatonia. Psychosomatics 56, 313–315.Google Scholar
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