Examining the Features of Neuroleptic Malignant Syndrome in Anti-NMDA Receptor Encephalitis: A Case-Control Study

Jesus Ramirez-Bermudez; Miguel Restrepo-Martinez; Mariana Espinola-Nadurille; Victoria Martinez-Angeles; Juan Carlos Lopez-Hernandez; Laura E Hernandez-Vanegas; Francisco Martinez-Carrillo; Ramiro Ruiz-Garcia; Veronica Rivas-Alonso; Jose Flores-Rivera; Thomas A Pollak

doi:10.1016/j.jaclp.2023.12.002

Examining the Features of Neuroleptic Malignant Syndrome in Anti-NMDA Receptor Encephalitis: A Case-Control Study

J Acad Consult Liaison Psychiatry. 2023 Dec 25:S2667-2960(23)00853-4. doi: 10.1016/j.jaclp.2023.12.002. Online ahead of print.

Affiliations

¹ Departments of Neuropsychiatry, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico. Electronic address: jesusramirezb@yahoo.com.mx.
² Departments of Neuropsychiatry, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico.
³ Department of Neurological Emergencies, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico.
⁴ Department of Clinical Neurology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico.
⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London.

PMID: 38151160
DOI: 10.1016/j.jaclp.2023.12.002

Abstract

Background: Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis.

Methods: This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions.

Results: A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics.

Conclusions: Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.

Keywords: anti-NMDAR encephalitis; antipsychotics; autoimmune encephalitis; autoimmune psychosis; neuroleptic malignant syndrome; neuropsychiatry.