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Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study

Published online by Cambridge University Press:  10 May 2022

M. Espinola-Nadurille Open the ORCID record for M. Espinola-Nadurille [Opens in a new window] ,
M. Restrepo-Martínez Open the ORCID record for M. Restrepo-Martínez [Opens in a new window] ,
L. Bayliss Open the ORCID record for L. Bayliss [Opens in a new window] ,
E. Flores-Montes ,
V. Rivas-Alonso Open the ORCID record for V. Rivas-Alonso [Opens in a new window] ,
S. Vargas-Cañas Open the ORCID record for S. Vargas-Cañas [Opens in a new window] ,
L. Hernández Open the ORCID record for L. Hernández [Opens in a new window] ,
I. Martínez-Juarez Open the ORCID record for I. Martínez-Juarez [Opens in a new window] ,
A. Gonzalez-Aguilar Open the ORCID record for A. Gonzalez-Aguilar [Opens in a new window]  and
R. Solis-Vivanco Open the ORCID record for R. Solis-Vivanco [Opens in a new window]
...Show all authors
M. Espinola-Nadurille
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
M. Restrepo-Martínez
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
L. Bayliss
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
E. Flores-Montes
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
V. Rivas-Alonso
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
S. Vargas-Cañas
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
L. Hernández
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
I. Martínez-Juarez
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
A. Gonzalez-Aguilar
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
R. Solis-Vivanco
Affiliation:
Laboratory of Cognitive and Clinical Neurophysiology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
G. L. Fricchione
Affiliation:
Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
J. Flores-Rivera
Affiliation:
Department of Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
J. Ramirez-Bermudez*
Affiliation:
Department of Neuropsychiatry, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico
*
Author for correspondence: J. Ramirez-Bermudez, E-mail: [email protected]
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Abstract

Background

Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments.

Methods

A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF.

Results

After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia–delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia.

Conclusions

Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia–delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Keywords

Anti-NMDAR encephalitisautoimmune encephalitisautoimmune psychosiscatatoniadeliriumneurologyneuropsychiatrypsychiatrypsychosis
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 9 , July 2023 , pp. 4266 - 4274
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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